2	30705973	Further, approximately 74%-88% of patients with MG have anti-acetylcholine receptor (AChR) antibodies that bind to postsynaptic membrane and induce complement-mediated injury.	('antibodies', 'Var', (91, 101))	('AChR', 'Gene', (85, 89))	('induce', 'Reg', (141, 147))	('patients', 'Species', '9606', (34, 42))	('complement-mediated', 'CPA', (148, 167))
4	30705973	Herein, we report the case of refractory thymoma-associated generalized MG with anti-AChR and anti-striational antibodies.	('anti-striational', 'Var', (94, 110))	('anti-AChR', 'Var', (80, 89))	('thymoma', 'Disease', 'MESH:D013945', (41, 48))	('thymoma', 'Disease', (41, 48))	('thymoma', 'Phenotype', 'HP:0100522', (41, 48))	('generalized MG', 'Disease', (60, 74))
33	30705973	Presence of these antibodies is associated with severe manifestations of MG including complications of myositis and cardiomyositis.	('myositis and cardiomyositis', 'Disease', 'MESH:D009220', (103, 130))	('myositis', 'Phenotype', 'HP:0100614', (103, 111))	('associated', 'Reg', (32, 42))	('myositis', 'Phenotype', 'HP:0100614', (122, 130))	('Presence', 'Var', (0, 8))
59	27167980	PBMC from 6 thymoma patients with autoantibodies to IL-12/23 p40 (thymoma positive), 4 thymoma patients without autoantibodies (thymoma negative), three HIES adults with confirmed STAT3 deficiency (V637M, R417S, G618D) and 16 adult controls were isolated using Ficoll (GE Health, UK) according to manufacturer protocol.	('HIES', 'Disease', (153, 157))	('thymoma', 'Phenotype', 'HP:0100522', (12, 19))	('R417S', 'Mutation', 'p.R417S', (205, 210))	('thymoma', 'Disease', (66, 73))	('thymoma', 'Disease', 'MESH:D013945', (128, 135))	('thymoma', 'Phenotype', 'HP:0100522', (66, 73))	('R417S', 'Var', (205, 210))	('STAT3 deficiency', 'Disease', (180, 196))	('STAT3 deficiency', 'Disease', 'MESH:D007153', (180, 196))	('thymoma', 'Disease', 'MESH:D013945', (87, 94))	('patients', 'Species', '9606', (20, 28))	('thymoma', 'Disease', (128, 135))	('HIES', 'Disease', 'MESH:D007589', (153, 157))	('V637M', 'Mutation', 'rs113994139', (198, 203))	('V637M', 'Var', (198, 203))	('thymoma', 'Phenotype', 'HP:0100522', (128, 135))	('IL-12/23', 'Gene', (52, 60))	('G618D', 'Mutation', 'p.G618D', (212, 217))	('p40', 'Gene', '3578', (61, 64))	('thymoma', 'Disease', 'MESH:D013945', (12, 19))	('thymoma', 'Disease', (87, 94))	('thymoma', 'Phenotype', 'HP:0100522', (87, 94))	('p40', 'Gene', (61, 64))	('patients', 'Species', '9606', (95, 103))	('thymoma', 'Disease', 'MESH:D013945', (66, 73))	('thymoma', 'Disease', (12, 19))	('G618D', 'Var', (212, 217))
90	27167980	Further observations on other immunodeficiencies with similar clinical features and/or systemic Th17 deficiencies are required to better understand the role of innate and conventional T cell compartments in the protection against infectious disease.	('immunodeficiencies', 'Disease', 'MESH:D007153', (30, 48))	('immunodeficiencies', 'Disease', (30, 48))	('immunodeficiencies', 'Phenotype', 'HP:0002721', (30, 48))	('infectious disease', 'Disease', (230, 248))	('deficiencies', 'Var', (101, 113))	('infectious disease', 'Disease', 'MESH:D003141', (230, 248))
131	30507309	The combination of NICs and lambdaHU had higher sensitivity and specificity than did those of conventional qualitative CT image analysis during the combined phases.	('CT', 'Chemical', 'MESH:D002251', (119, 121))	('NICs', 'Chemical', '-', (19, 23))	('sensitivity', 'MPA', (48, 59))	('higher', 'PosReg', (41, 47))	('NICs', 'Var', (19, 23))
271	31143343	Several studies revealed that using antibiotics should be used with caution, there are specific antibiotics that may cause muscle weakness due to their ability to produce partial neuromuscular blockade through inhibiting acetylcholine release from the presynaptic membrane.	('muscle weakness', 'Disease', (123, 138))	('partial neuromuscular blockade', 'MPA', (171, 201))	('acetylcholine', 'Chemical', 'MESH:D000109', (221, 234))	('muscle weakness', 'Phenotype', 'HP:0001324', (123, 138))	('inhibiting', 'NegReg', (210, 220))	('muscle weakness', 'Disease', 'MESH:D018908', (123, 138))	('antibiotics', 'Var', (96, 107))
392	29984771	Resection of the thymoma led to the improvement of the neurologic symptoms typical of PERM, as well as a reduction in the GlyR-Ab titers.	('GlyR-Ab', 'Chemical', '-', (122, 129))	('PERM', 'Disease', (86, 90))	('Resection', 'Var', (0, 9))	('thymoma', 'Disease', 'MESH:D013945', (17, 24))	('thymoma', 'Disease', (17, 24))	('improvement', 'PosReg', (36, 47))	('neurologic symptoms', 'MPA', (55, 74))	('reduction', 'NegReg', (105, 114))	('thymoma', 'Phenotype', 'HP:0100522', (17, 24))	('GlyR-Ab titers', 'MPA', (122, 136))
402	29984771	PDGFR alpha is mutated in about 5% of GISTs that are negative for c-kit mutations and therefore has constitutive kinase activity.	('PDGFR alpha', 'Gene', (0, 11))	('constitutive kinase activity', 'MPA', (100, 128))	('GIST', 'Phenotype', 'HP:0100723', (38, 42))	('mutated', 'Var', (15, 22))	('PDGFR alpha', 'Gene', '5156', (0, 11))
403	29984771	Since PDGFR alpha and beta can function as a heterodimer, it is conceivable that an autoimmune reaction to PDGFRs might occur in the presence of a GIST expressing a mutant PDGFR alpha.	('PDGFR alpha', 'Gene', (172, 183))	('PDGFR', 'Gene', '5159', (172, 177))	('mutant', 'Var', (165, 171))	('PDGFR alpha', 'Gene', (6, 17))	('GIST', 'Phenotype', 'HP:0100723', (147, 151))	('autoimmune reaction', 'Phenotype', 'HP:0002960', (84, 103))	('PDGFR', 'Gene', (6, 11))	('PDGFR', 'Gene', '5159', (6, 11))	('PDGFR alpha', 'Gene', '5156', (6, 17))	('PDGFR alpha', 'Gene', '5156', (172, 183))	('PDGFR', 'Gene', (107, 112))	('function', 'Reg', (31, 39))	('PDGFR', 'Gene', '5159', (107, 112))	('PDGFR', 'Gene', (172, 177))
405	29984771	Knockout of PDGF-B and PDGFR beta in mice was lethal to embryos, which showed microaneurysms and severe edema.	('edema', 'Disease', 'MESH:D004487', (104, 109))	('edema', 'Phenotype', 'HP:0000969', (104, 109))	('PDGF-B', 'Gene', (12, 18))	('microaneurysms', 'Disease', (78, 92))	('PDGFR beta', 'Gene', (23, 33))	('edema', 'Disease', (104, 109))	('PDGF-B', 'Gene', '18591', (12, 18))	('Knockout', 'Var', (0, 8))	('microaneurysms', 'Disease', 'MESH:D000071071', (78, 92))	('mice', 'Species', '10090', (37, 41))
431	30010142	Since 2001 and 2011, two new subgroups of patients have been characterized with autoantibodies against other components of the NMJ: respectively, the muscle-specific kinase (MuSK) and the low-density lipoprotein-related protein 4 (LRP4).	('autoantibodies', 'Var', (80, 94))	('muscle-specific kinase', 'Gene', '4593', (150, 172))	('lipoprotein-related protein 4', 'Gene', '4038', (200, 229))	('LRP4', 'Gene', (231, 235))	('muscle-specific kinase', 'Gene', (150, 172))	('patients', 'Species', '9606', (42, 50))	('lipoprotein-related protein 4', 'Gene', (200, 229))
446	30010142	MG with anti-MuSK antibodies corresponds to about 5% of the MG patients (Table 1).	('anti-MuSK', 'Protein', (8, 17))	('anti-MuSK antibodies', 'Phenotype', 'HP:0030210', (8, 28))	('MuSK antibodies', 'Phenotype', 'HP:0030210', (13, 28))	('patients', 'Species', '9606', (63, 71))	('antibodies', 'Var', (18, 28))
506	30010142	The results of the MG thymectomy trial (MGTX) confirm the fact that transsternal thymectomy, associated with prednisone, allows a decrease in prednisone requirement in non-thymomatous patients when compared with prednisone alone, and a general alleviation of the disease burden over time.	('prednisone', 'Chemical', 'MESH:D011241', (212, 222))	('patients', 'Species', '9606', (184, 192))	('thymoma', 'Disease', 'MESH:D013945', (172, 179))	('decrease', 'NegReg', (130, 138))	('prednisone requirement', 'MPA', (142, 164))	('transsternal', 'Var', (68, 80))	('prednisone', 'Chemical', 'MESH:D011241', (142, 152))	('thymoma', 'Disease', (172, 179))	('thymoma', 'Phenotype', 'HP:0100522', (172, 179))	('prednisone', 'Chemical', 'MESH:D011241', (109, 119))
534	30010142	Moreover the use of an anti-CD40L antibody is an effective treatment to suppress EAMG even when it is given during the chronic stage of disease.	('EAMG', 'Chemical', '-', (81, 85))	('EAMG', 'Disease', (81, 85))	('anti-CD40L', 'Var', (23, 33))
581	30010142	Moreover, antibodies against IL-6 suppress EAMG in the rat model when administrated either during the acute or the chronic phase of disease.	('EAMG', 'CPA', (43, 47))	('IL-6', 'Gene', (29, 33))	('EAMG', 'Chemical', '-', (43, 47))	('rat', 'Species', '10116', (78, 81))	('antibodies', 'Var', (10, 20))	('suppress', 'NegReg', (34, 42))	('rat', 'Species', '10116', (55, 58))
593	30010142	Numerous studies on EAMG models have clearly shown that inhibition of complement pathways effectively and specifically diminish the NMJ destruction induced by anti-AChR antibodies.	('anti-AChR antibodies', 'Protein', (159, 179))	('complement pathways', 'Pathway', (70, 89))	('NMJ', 'Disease', (132, 135))	('diminish', 'NegReg', (119, 127))	('inhibition', 'Var', (56, 66))	('EAMG', 'Chemical', '-', (20, 24))
595	30010142	Moreover, increased complement consumption was detected in MG patients with high AChR antibody concentrations.	('complement consumption', 'MPA', (20, 42))	('rat', 'Species', '10116', (102, 105))	('AChR antibody', 'Protein', (81, 94))	('high', 'Var', (76, 80))	('patients', 'Species', '9606', (62, 70))	('increased', 'PosReg', (10, 19))
641	27855632	The variables used for classification were sex, age of onset, disease duration, presence of thymoma or thymic hyperplasia, positivity for AChR-Ab or anti-muscle-specific tyrosine kinase antibody, positivity for other concurrent autoantibodies, and disease condition at worst and current.	('positivity', 'Var', (123, 133))	('thymic hyperplasia', 'Phenotype', 'HP:0010516', (103, 121))	('thymoma or thymic hyperplasia', 'Disease', (92, 121))	('AChR-Ab', 'Chemical', '-', (138, 145))	('thymoma', 'Phenotype', 'HP:0100522', (92, 99))	('AChR-Ab', 'Gene', (138, 145))	('thymoma or thymic hyperplasia', 'Disease', 'MESH:D013952', (92, 121))
663	27855632	The other variables evaluated were: sex; age of onset; disease duration; presence of thymoma; presence of thymic hyperplasia in thymectomized cases; positivity for AChR-Ab or MuSK-Ab; and positivity for other concurrent autoantibodies (Table 2).	('AChR-Ab', 'Chemical', '-', (164, 171))	('AChR-Ab', 'Protein', (164, 171))	('thymic hyperplasia', 'Disease', 'MESH:D013952', (106, 124))	('thymoma', 'Disease', (85, 92))	('thymoma', 'Phenotype', 'HP:0100522', (85, 92))	('thymic hyperplasia', 'Phenotype', 'HP:0010516', (106, 124))	('positivity', 'Var', (149, 159))	('MuSK-Ab', 'Chemical', '-', (175, 182))	('thymic hyperplasia', 'Disease', (106, 124))	('MuSK-Ab', 'Gene', (175, 182))
681	27855632	Patients with MuSK-Ab also showed worst severity at the same level as thymoma-associated MG patients, although this result was not statistically significant because of the small number of patients.	('MuSK-Ab', 'Var', (14, 21))	('thymoma-associated MG', 'Disease', (70, 91))	('patients', 'Species', '9606', (92, 100))	('patients', 'Species', '9606', (188, 196))	('Patients', 'Species', '9606', (0, 8))	('thymoma', 'Phenotype', 'HP:0100522', (70, 77))	('MuSK-Ab', 'Chemical', '-', (14, 21))
810	24379993	The 2004 WHO classification considers three morphological types of thymoma according to genetic alterations (microsatellite instability, 6q25, 5q21-22 mutations): A, B (B1, B2, and B3), and AB.	('thymoma', 'Phenotype', 'HP:0100522', (67, 74))	('B (B1, B2, and B3', 'Gene', '931;2925;680', (166, 183))	('5q21-22 mutations', 'Var', (143, 160))	('microsatellite instability', 'Var', (109, 135))	('thymoma', 'Disease', 'MESH:D013945', (67, 74))	('thymoma', 'Disease', (67, 74))
866	24379993	Our hypothesis is also highlighted by the clinical and molecular data reported by Aigner, who showed the presence of LKM-3 and UGT 1 antibody (UDP glutamyl-transferase involved in AIH) in the patient's serum, liver, and thymoma tissue.	('patient', 'Species', '9606', (192, 199))	('UGT 1', 'Gene', (127, 132))	('thymoma', 'Disease', 'MESH:D013945', (220, 227))	('thymoma', 'Disease', (220, 227))	('LKM-3', 'Var', (117, 122))	('presence', 'Reg', (105, 113))	('thymoma', 'Phenotype', 'HP:0100522', (220, 227))	('UGT 1', 'Gene', '7361', (127, 132))
946	33506159	Anti-PIT-1 hypophysitis (anti-PIT-1 antibody syndrome) is characterized by acquired growth hormone (GH), prolactin (PRL), and thyrotropin (TSH) deficiencies associated with autoimmunity to PIT-1.	('PIT-1', 'Gene', (30, 35))	('deficiencies', 'Var', (144, 156))	('growth hormone', 'Gene', (84, 98))	('PRL', 'Gene', (116, 119))	('TSH', 'Chemical', 'MESH:D013972', (139, 142))	('PIT-1 antibody syndrome', 'Disease', 'MESH:D000069281', (30, 53))	('growth hormone', 'Gene', '2688', (84, 98))	('prolactin', 'Gene', (105, 114))	('prolactin', 'Gene', '5617', (105, 114))	('PIT-1', 'Gene', (5, 10))	('PIT-1', 'Gene', '5449', (189, 194))	('PIT-1 hypophysitis', 'Disease', 'MESH:C536528', (5, 23))	('autoimmunity', 'Phenotype', 'HP:0002960', (173, 185))	('PIT-1', 'Gene', '5449', (5, 10))	('PIT-1 antibody syndrome', 'Disease', (30, 53))	('PIT-1', 'Gene', (189, 194))	('PIT-1', 'Gene', '5449', (30, 35))	('PIT-1 hypophysitis', 'Disease', (5, 23))	('PRL', 'Gene', '5617', (116, 119))	('GH', 'Gene', '2688', (100, 102))
1011	33506159	Generally, ectopic antigen presentation in tumors evokes disruption of immune tolerance, causing autoimmunity.	('autoimmunity', 'Phenotype', 'HP:0002960', (97, 109))	('evokes', 'Reg', (50, 56))	('tumor', 'Phenotype', 'HP:0002664', (43, 48))	('immune tolerance', 'CPA', (71, 87))	('ectopic', 'Var', (11, 18))	('tumors', 'Disease', (43, 49))	('tumors', 'Phenotype', 'HP:0002664', (43, 49))	('causing', 'Reg', (89, 96))	('tumors', 'Disease', 'MESH:D009369', (43, 49))
1012	33506159	In previous cases of anti-PIT-1 hypophysitis, ectopic expression of PIT-1 in thymoma tissue has eventually led to the production of autoreactive PIT-1-specific CTLs as well as circulating autoantibodies.	('PIT-1', 'Gene', '5449', (145, 150))	('PIT-1 hypophysitis', 'Disease', 'MESH:C536528', (26, 44))	('thymoma', 'Disease', (77, 84))	('PIT-1', 'Gene', (68, 73))	('led to', 'Reg', (107, 113))	('thymoma', 'Phenotype', 'HP:0100522', (77, 84))	('ectopic expression', 'Var', (46, 64))	('PIT-1 hypophysitis', 'Disease', (26, 44))	('PIT-1', 'Gene', '5449', (26, 31))	('PIT-1', 'Gene', (145, 150))	('PIT-1', 'Gene', '5449', (68, 73))	('thymoma', 'Disease', 'MESH:D013945', (77, 84))	('PIT-1', 'Gene', (26, 31))
1017	33506159	These data also suggest that anti-PIT-1 hypophysitis is a form of paraneoplastic syndrome that may be associated with several malignancies, including breast cancer and gastric cancer, because ectopic expression of PIT-1 has been reported in these tumors.	('tumor', 'Phenotype', 'HP:0002664', (247, 252))	('tumors', 'Disease', (247, 253))	('breast cancer', 'Phenotype', 'HP:0003002', (150, 163))	('ectopic', 'Var', (192, 199))	('cancer', 'Phenotype', 'HP:0002664', (176, 182))	('PIT-1', 'Gene', '5449', (34, 39))	('gastric cancer', 'Disease', 'MESH:D013274', (168, 182))	('breast cancer', 'Disease', 'MESH:D001943', (150, 163))	('tumors', 'Disease', 'MESH:D009369', (247, 253))	('breast cancer', 'Disease', (150, 163))	('PIT-1', 'Gene', (34, 39))	('malignancies', 'Disease', 'MESH:D009369', (126, 138))	('associated', 'Reg', (102, 112))	('PIT-1', 'Gene', '5449', (214, 219))	('gastric cancer', 'Phenotype', 'HP:0012126', (168, 182))	('paraneoplastic syndrome', 'Disease', (66, 89))	('malignancies', 'Disease', (126, 138))	('PIT-1', 'Gene', (214, 219))	('cancer', 'Phenotype', 'HP:0002664', (157, 163))	('tumors', 'Phenotype', 'HP:0002664', (247, 253))	('PIT-1 hypophysitis', 'Disease', 'MESH:C536528', (34, 52))	('paraneoplastic syndrome', 'Disease', 'MESH:D010257', (66, 89))	('gastric cancer', 'Disease', (168, 182))	('PIT-1 hypophysitis', 'Disease', (34, 52))
1025	32215054	Suitable indications of eculizumab for patients with refractory generalized myasthenia gravis Eculizumab is a humanized monoclonal antibody that targets complement protein C5 and inhibits terminal complement-mediated damage at the neuromuscular junction.	('myasthenia gravis', 'Disease', (76, 93))	('men', 'Species', '9606', (203, 206))	('men', 'Species', '9606', (159, 162))	('patients', 'Species', '9606', (39, 47))	('inhibits', 'NegReg', (179, 187))	('complement protein C5', 'Protein', (153, 174))	('myasthenia gravis', 'Disease', 'MESH:D009157', (76, 93))	('human', 'Species', '9606', (110, 115))	('Eculizumab', 'Var', (94, 104))	('myasthenia', 'Phenotype', 'HP:0003473', (76, 86))	('Eculizumab', 'Chemical', 'MESH:C481642', (94, 104))
1044	32215054	In this disease, the complement-mediated pathological membrane changes reduce the efficiency of neurotransmission at the neuromuscular junction, resulting in the characteristic muscle weakness and fatigability.	('reduce', 'NegReg', (71, 77))	('fatigability', 'CPA', (197, 209))	('muscle weakness', 'Phenotype', 'HP:0001324', (177, 192))	('muscle weakness', 'Disease', 'MESH:D018908', (177, 192))	('muscle weakness', 'Disease', (177, 192))	('changes', 'Var', (63, 70))	('men', 'Species', '9606', (27, 30))
1046	32215054	Patients with refractory gMG might also have frequent exacerbations, which can be life-threatening, require admission to a hospital or intensive care, and cause episodes of respiratory failure that require mechanical ventilation.	('respiratory failure', 'Disease', (173, 192))	('respiratory failure', 'Disease', 'MESH:D012131', (173, 192))	('exacerbations', 'MPA', (54, 67))	('refractory gMG', 'Var', (14, 28))	('Patients', 'Species', '9606', (0, 8))	('MG', 'Chemical', 'MESH:D008274', (26, 28))	('episodes of respiratory failure', 'Phenotype', 'HP:0004885', (161, 192))	('cause', 'Reg', (155, 160))	('respiratory failure', 'Phenotype', 'HP:0002878', (173, 192))	('respiratory failure that require mechanical ventilation', 'Phenotype', 'HP:0004887', (173, 228))
1148	32215054	In addition, a single missense C5 heterozygous mutation (c.2654G>A) was identified as a poor responder to eculizumab in patients with paroxysmal nocturnal hemoglobinuria.	('hemoglobinuria', 'Phenotype', 'HP:0003641', (155, 169))	('paroxysmal nocturnal hemoglobinuria', 'Disease', 'MESH:D006457', (134, 169))	('patients', 'Species', '9606', (120, 128))	('c.2654G>A', 'Var', (57, 66))	('c.2654G>A', 'Mutation', 'c.2654G>A', (57, 66))	('paroxysmal nocturnal hemoglobinuria', 'Disease', (134, 169))	('paroxysmal nocturnal hemoglobinuria', 'Phenotype', 'HP:0004818', (134, 169))	('eculizumab', 'Chemical', 'MESH:C481642', (106, 116))
1183	30697585	MG onset was defined as the earlier of 2 dates: (1) the date of development of weakness with increased fatigability of skeletal muscles (e.g., fluctuating diplopia, ptosis, or skeletal muscle power) or (2) the date of detection of abnormality on RNS or an SFEMG in weakened muscles.	('weakness', 'Disease', (79, 87))	('diplopia', 'Phenotype', 'HP:0000651', (155, 163))	('fatigability', 'MPA', (103, 115))	('weakness', 'Disease', 'MESH:D018908', (79, 87))	('ptosis', 'Disease', (165, 171))	('ptosis', 'Phenotype', 'HP:0000508', (165, 171))	('diplopia', 'Disease', 'MESH:D004172', (155, 163))	('increased fatigability', 'Phenotype', 'HP:0003388', (93, 115))	('diplopia', 'Disease', (155, 163))	('abnormality', 'Var', (231, 242))	('fatigability of skeletal muscles', 'Phenotype', 'HP:0030197', (103, 135))	('ptosis', 'Disease', 'MESH:C564553', (165, 171))
1203	30697585	Four thymomatous patients with normal RNS tests on extremities presented with rapid progression of weakness with acute markedly elevated serum CK levels (1,008-10,226 IU/L) at IM development (rhabdomyolysis-like features) and required ventilator support.	('thymoma', 'Disease', 'MESH:D013945', (5, 12))	('markedly elevated serum CK levels', 'Phenotype', 'HP:0030234', (119, 152))	('weakness', 'Disease', (99, 107))	('thymoma', 'Disease', (5, 12))	('rhabdomyolysis', 'Disease', 'MESH:D012206', (192, 206))	('weakness', 'Disease', 'MESH:D018908', (99, 107))	('IM', 'Phenotype', 'HP:0009071', (176, 178))	('thymoma', 'Phenotype', 'HP:0100522', (5, 12))	('CK', 'Gene', '51727', (143, 145))	('rhabdomyolysis', 'Disease', (192, 206))	('patients', 'Species', '9606', (17, 25))	('rhabdomyolysis', 'Phenotype', 'HP:0003201', (192, 206))	('1,008-10,226', 'Var', (154, 166))	('elevated serum CK', 'Phenotype', 'HP:0003236', (128, 145))	('elevated', 'PosReg', (128, 136))
1210	30697585	The serum testing for autoantibodies demonstrated anti-AChR Ab (9/10), MSAs (0/9), and anti-titin Ab (6/8).	('MSA', 'Chemical', '-', (71, 74))	('titin', 'Gene', '7273', (92, 97))	('anti-AChR', 'Var', (50, 59))	('titin', 'Gene', (92, 97))	('MSAs', 'Disease', (71, 75))
1282	30697585	However, a previous report has shown that genetic polymorphisms of CTLA-4 are associated with thymomatous MG patients.	('associated', 'Reg', (78, 88))	('patients', 'Species', '9606', (109, 117))	('thymomatous MG', 'Disease', 'MESH:D000080343', (94, 108))	('CTLA-4', 'Gene', (67, 73))	('thymomatous MG', 'Disease', (94, 108))	('genetic polymorphisms', 'Var', (42, 63))	('thymoma', 'Phenotype', 'HP:0100522', (94, 101))
1354	28275751	Type B2 is most frequently observed thymoma type in patients with MG. Okumura et al.	('thymoma', 'Phenotype', 'HP:0100522', (36, 43))	('thymoma type', 'Disease', 'MESH:D013945', (36, 48))	('MG.', 'Var', (66, 69))	('thymoma type', 'Disease', (36, 48))	('patients', 'Species', '9606', (52, 60))
1361	28275751	Though earlier studies reported presence of MG as an indicator of poor prognosis, recent publications have demonstrated that presence of MG may not affect prognosis or that, in fact, these thymoma patients may have a better prognosis.	('thymoma', 'Gene', '7063', (189, 196))	('patients', 'Species', '9606', (197, 205))	('presence', 'Var', (125, 133))	('thymoma', 'Gene', (189, 196))	('thymoma', 'Phenotype', 'HP:0100522', (189, 196))
1364	28275751	detected an association between MG and early Masaoka stage, which was explained by early diagnosis of thymoma as result of MG. Elmaci et al.	('thymoma', 'Gene', (102, 109))	('MG.', 'Var', (123, 126))	('thymoma', 'Gene', '7063', (102, 109))	('thymoma', 'Phenotype', 'HP:0100522', (102, 109))	('early Masaoka stage', 'Disease', (39, 58))
1569	25189481	Although complete surgical resection is the mainstay of treatment of TETs and is the most important predictor of long-term survival, debulking is also reported to provide palliation and prolong survival for selected patients incapable of being rendered completely disease-free.	('patients', 'Species', '9606', (216, 224))	('debulking', 'Var', (133, 142))	('palliation', 'Disease', (171, 181))
1710	27956763	An increase in the level of IgA, IgG, IgM, CD3+T, CD4+T, CD4+T/CD8+T, WBC, CRP, and NK-cell in the IN group was observed after thymectomy, while a decrease was seen with regard to prealbumin and albumin (p < 0.05).	('IgG', 'MPA', (33, 36))	('CRP', 'Gene', (75, 78))	('CRP', 'Gene', '1401', (75, 78))	('CD4+T/CD8+T', 'Var', (57, 68))	('CD3+T', 'MPA', (43, 48))	('CD4+T', 'MPA', (50, 55))	('IgA', 'MPA', (28, 31))	('increase', 'PosReg', (3, 11))
1716	27956763	The immunonutrients are glutamine, arginine, and polyunsaturated fatty acids (omega-3), among others, which can improve the immunity and nutrition effectively.	('polyunsaturated', 'Var', (49, 64))	('improve', 'PosReg', (112, 119))	('nutrition', 'CPA', (137, 146))	('immunity', 'CPA', (124, 132))	('arginine', 'Chemical', 'MESH:D001120', (35, 43))	('omega-3', 'Chemical', 'MESH:D015525', (78, 85))	('glutamine', 'Chemical', 'MESH:D005973', (24, 33))	('polyunsaturated fatty acids', 'Chemical', 'MESH:D005231', (49, 76))
1733	27956763	Arginine, as the important component part of immune nutriment, stimulates anabolic hormone release, improves nitrogen balance, and has immunostimulatory and thymotrophic functions.	('nitrogen balance', 'MPA', (109, 125))	('Arginine', 'Chemical', 'MESH:D001120', (0, 8))	('anabolic hormone release', 'MPA', (74, 98))	('Arginine', 'Var', (0, 8))	('improves', 'PosReg', (100, 108))	('stimulates', 'PosReg', (63, 73))
1784	24171048	Studies on paraneoplastic syndromes such as pure red cell aplasia with thymoma show that auto-antibodies or auto-reactive T lymphocytes could directly or indirectly inhibit erythropoiesis, so that the loss of B cell function could be secondary to the immune destruction.	('aplasia with thymoma', 'Phenotype', 'HP:0005359', (58, 78))	('erythropoiesis', 'MPA', (173, 187))	('pure red cell aplasia', 'Disease', (44, 65))	('loss of B cell', 'Phenotype', 'HP:0005365', (201, 215))	('paraneoplastic syndromes', 'Disease', 'MESH:D010257', (11, 35))	('thymoma', 'Phenotype', 'HP:0100522', (71, 78))	('paraneoplastic syndromes', 'Disease', (11, 35))	('auto-antibodies', 'Var', (89, 104))	('pure red cell aplasia', 'Disease', 'MESH:D012010', (44, 65))	('thymoma', 'Gene', '7063', (71, 78))	('thymoma', 'Gene', (71, 78))	('pure red cell aplasia', 'Phenotype', 'HP:0012410', (44, 65))	('inhibit', 'NegReg', (165, 172))
1866	30411854	The GP + E group had a significantly higher overall response rate (75% vs. 42.9%; P = 0.028), and median progression-free survival (PFS) and overall survival (OS) of 19 and 76 months, respectively.	('GP + E', 'Var', (4, 10))	('GP + E', 'Chemical', 'MESH:C062053', (4, 10))	('higher', 'PosReg', (37, 43))	('progression-free survival', 'CPA', (105, 130))
1894	30411854	Twenty-four (53.3%) patients received GP + E, including 10 (22.2%) thymoma and 14 (31.1%) thymic carcinoma patients.	('GP + E', 'Chemical', 'MESH:C062053', (38, 44))	('thymic carcinoma', 'Disease', 'MESH:D013945', (90, 106))	('carcinoma', 'Phenotype', 'HP:0030731', (97, 106))	('thymoma', 'Phenotype', 'HP:0100522', (67, 74))	('patients', 'Species', '9606', (20, 28))	('thymic carcinoma', 'Disease', (90, 106))	('GP + E', 'Var', (38, 44))	('patients', 'Species', '9606', (107, 115))	('thymoma', 'Disease', 'MESH:D013945', (67, 74))	('thymoma', 'Disease', (67, 74))
1899	30411854	The GP + E group had a significantly higher ORR (75% vs. 42.9%; P = 0.028).	('GP + E', 'Var', (4, 10))	('GP + E', 'Chemical', 'MESH:C062053', (4, 10))	('higher', 'PosReg', (37, 43))	('ORR', 'MPA', (44, 47))
1903	30411854	In the GP + E group, the median PFS was 19 months (95% CI 15.7-22.3) and the median OS was 76 months (Fig 2).	('GP + E', 'Var', (7, 13))	('PFS', 'MPA', (32, 35))	('GP + E', 'Chemical', 'MESH:C062053', (7, 13))
1936	24517958	Further investigation revealed for resection margin-positive patients; S + RT had higher OS than S alone (P = 0.006).	('S + RT', 'Var', (71, 77))	('patients', 'Species', '9606', (61, 69))	('higher', 'PosReg', (82, 88))	('OS', 'Chemical', '-', (89, 91))
1957	24517958	Positive surgical margins predicted for worse OS (hazard ratio [HR] = 7.1, P = 0.004, Table 2).	('Positive', 'Var', (0, 8))	('OS', 'Chemical', '-', (46, 48))	('worse OS', 'Disease', (40, 48))
1966	24517958	The margin-positive stages II and III thymoma patients treated with S + RT had higher OS than S alone (log-rank test, P = 0.006); whereas, margin-negative stages II and III thymoma patients did not demonstrate any significant differences between S + RT versus S alone (log-rank test, P = 0.733).	('S + RT', 'Var', (68, 74))	('III thymoma', 'Disease', (169, 180))	('patients', 'Species', '9606', (46, 54))	('III thymoma', 'Disease', 'MESH:D013945', (169, 180))	('OS', 'Chemical', '-', (86, 88))	('patients', 'Species', '9606', (181, 189))	('III thymoma', 'Disease', (34, 45))	('III thymoma', 'Disease', 'MESH:D013945', (34, 45))	('higher', 'PosReg', (79, 85))	('thymoma', 'Phenotype', 'HP:0100522', (38, 45))	('thymoma', 'Phenotype', 'HP:0100522', (173, 180))
1967	24517958	No statically significant differences in PFS were observed between S + RT versus S alone in margin-positive (log-rank test, P = 0.467) or margin-negative (log-rank test, P = 0.847) stage II and III thymoma.	('III thymoma', 'Disease', (194, 205))	('thymoma', 'Phenotype', 'HP:0100522', (198, 205))	('III thymoma', 'Disease', 'MESH:D013945', (194, 205))	('stage II', 'Disease', (181, 189))	('S + RT', 'Var', (67, 73))
1976	24517958	Our study using Cox regression modeling showed that positive surgical margin predicted worse overall survival (hazard ratio=7.1; P=0.004).	('overall survival', 'MPA', (93, 109))	('worse', 'NegReg', (87, 92))	('Cox', 'Gene', '1351', (16, 19))	('positive', 'Var', (52, 60))	('Cox', 'Gene', (16, 19))
1977	24517958	Our study using Cox regression modeling showed that positive surgical margin was an independent factor associated with worse OS (HR = 7.1, P = 0.004).	('OS', 'Chemical', '-', (125, 127))	('positive surgical margin', 'Var', (52, 76))	('Cox', 'Gene', '1351', (16, 19))	('worse OS', 'Disease', (119, 127))	('Cox', 'Gene', (16, 19))
1980	24517958	We found that for resection marginpositive stages II and III thymoma, S + RT resulted in a higher OS than S alone (P = 0.006); for resection margin-negative stages II and III thymoma, no statistically significant differences were observed between S + RT versus S alone (P = 0.733).	('thymoma', 'Phenotype', 'HP:0100522', (175, 182))	('higher', 'PosReg', (91, 97))	('III thymoma', 'Disease', (57, 68))	('III thymoma', 'Disease', 'MESH:D013945', (57, 68))	('S + RT', 'Var', (70, 76))	('thymoma', 'Phenotype', 'HP:0100522', (61, 68))	('III thymoma', 'Disease', (171, 182))	('OS', 'Chemical', '-', (98, 100))	('III thymoma', 'Disease', 'MESH:D013945', (171, 182))
2016	24725416	We conclude that dysgeusia shared a common pathological background with MG. MG has a clear autoimmune substrate with a primary pathogenic role for the thymus.	('MG. MG', 'Var', (72, 78))	('dysgeusia', 'Phenotype', 'HP:0031249', (17, 26))	('dysgeusia', 'Disease', 'MESH:D004408', (17, 26))	('dysgeusia', 'Disease', (17, 26))
2060	33142021	This study arises from the analysis of a large cohort of patients affected by thymoma-associated myasthenia gravis with antiacetylcholine receptor antibodies.	('myasthenia', 'Phenotype', 'HP:0003473', (97, 107))	('patients', 'Species', '9606', (57, 65))	('acetylcholine', 'Chemical', 'MESH:D000109', (124, 137))	('thymoma', 'Phenotype', 'HP:0100522', (78, 85))	('thymoma-associated myasthenia gravis', 'Disease', (78, 114))	('thymoma-associated myasthenia gravis', 'Disease', 'MESH:D009157', (78, 114))	('antiacetylcholine', 'Var', (120, 137))	('antiacetylcholine receptor antibodies', 'Phenotype', 'HP:0030208', (120, 157))
2065	33142021	Neuromyotonia was diagnosed according to the presence of typical electromyography abnormalities and/or autoantibodies against LGI1/CASPR2.	('Neuromyotonia', 'Disease', (0, 13))	('Neuromyotonia', 'Disease', 'MESH:D020386', (0, 13))	('CASPR2', 'Gene', '26047', (131, 137))	('LGI1', 'Gene', '9211', (126, 130))	('LGI1', 'Gene', (126, 130))	('electromyography abnormalities', 'Phenotype', 'HP:0003457', (65, 95))	('autoantibodies', 'Var', (103, 117))	('CASPR2', 'Gene', (131, 137))
2102	33381454	Different studies showed that PD1/PDL1 inhibitors are effective in advanced TETs and contributed to the approval of Pembrolizumab for thymic carcinoma.	('inhibitors', 'Var', (39, 49))	('carcinoma', 'Phenotype', 'HP:0030731', (141, 150))	('PDL1', 'Gene', '29126', (34, 38))	('Pembrolizumab', 'Chemical', 'MESH:C582435', (116, 129))	('PDL1', 'Gene', (34, 38))	('PD1', 'Gene', '5133', (30, 33))	('thymic carcinoma', 'Disease', (134, 150))	('thymic carcinoma', 'Disease', 'MESH:D013953', (134, 150))	('PD1', 'Gene', (30, 33))
2117	33381454	Thyroid dysfunction was also shown, with FT4 >7.7 ng/dl (normal range 0.9 to 1.7 ng/dl) and TSH 0.013 mcUI/ml (normal range 0.3 to 4.2 mcUI/ml).	('Thyroid dysfunction', 'Disease', 'MESH:D013959', (0, 19))	('Thyroid dysfunction', 'Disease', (0, 19))	('TSH 0.013 mcUI/ml', 'Var', (92, 109))	('FT4 >', 'Var', (41, 46))
2170	33381454	Since PD1 is a crucial inhibitory receptor, its blockade might revert T-cell exhaustion, unleash the immune response and potentially lead to the hepatic damage.	('PD1', 'Gene', (6, 9))	('immune response', 'CPA', (101, 116))	('hepatic damage', 'Disease', 'MESH:D056486', (145, 159))	('unleash', 'Reg', (89, 96))	('T-cell exhaustion', 'Phenotype', 'HP:0005435', (70, 87))	('T-cell exhaustion', 'CPA', (70, 87))	('lead to', 'Reg', (133, 140))	('hepatic damage', 'Disease', (145, 159))	('blockade', 'Var', (48, 56))	('revert', 'NegReg', (63, 69))	('PD1', 'Gene', '5133', (6, 9))
2175	33381454	Thus, it is mandatory to better refine the druggable focuses, decreasing the incidence of undesired effects exerted by immune-system modulation and novel bullets striking the non-cancerous neighborhood.	('cancerous neighborhood', 'Disease', 'MESH:D009369', (179, 201))	('cancer', 'Phenotype', 'HP:0002664', (179, 185))	('novel', 'Var', (148, 153))	('decreasing', 'NegReg', (62, 72))	('cancerous neighborhood', 'Disease', (179, 201))
2187	30302151	On the other hand, regarding postoperative drainage, duration of chest tube drainage and length of hospital stay, VATS thymectomy yielded better results and the differences were significant.	('chest tube drainage', 'Disease', (65, 84))	('VATS', 'Var', (114, 118))	('better', 'PosReg', (138, 144))	('chest tube drainage', 'Disease', 'MESH:D002637', (65, 84))
2222	30302151	Likewise, duration of chest tube drainage and length of hospital stay were shorter in the VATS group than the open thymectomy group, and the difference was statistically significant (p = 0.039 and p = 0.018).	('VATS', 'Var', (90, 94))	('shorter', 'NegReg', (75, 82))	('duration', 'MPA', (10, 18))	('chest tube drainage', 'Disease', 'MESH:D002637', (22, 41))	('chest tube drainage', 'Disease', (22, 41))
2231	30302151	According to these reports, VATS thymectomy demonstrated a superior outcome in terms of hospital stay, intraoperative blood loss, and cosmetic satisfaction when compared with open access surgery.	('intraoperative blood loss', 'Disease', (103, 128))	('VATS', 'Var', (28, 32))	('intraoperative blood loss', 'Disease', 'MESH:D016063', (103, 128))
2247	30302151	There are numerous studies confirming that VATS thymectomy results in less post-operative pain compared with open procedures.	('less', 'NegReg', (70, 74))	('pain', 'Phenotype', 'HP:0012531', (90, 94))	('pain', 'Disease', 'MESH:D010146', (90, 94))	('pain', 'Disease', (90, 94))	('VATS', 'Var', (43, 47))
2251	30302151	Our data suggest that VATS thymectomy has some advantages over open surgery, including shorter length of hospital stay, less postoperative drainage and shorter duration of chest tube drainage.	('chest tube drainage', 'Disease', 'MESH:D002637', (172, 191))	('chest tube drainage', 'Disease', (172, 191))	('VATS', 'Var', (22, 26))
2345	25528459	In other situations, thymectomy may precipitate a clinical deterioration or even create a new disease, suggesting a protective role of the thymus against autoimmunity.	('thymectomy', 'Var', (21, 31))	('autoimmunity', 'Disease', 'MESH:D001327', (154, 166))	('autoimmunity', 'Disease', (154, 166))	('new disease', 'Disease', (90, 101))	('autoimmunity', 'Phenotype', 'HP:0002960', (154, 166))	('precipitate', 'Reg', (36, 47))	('create', 'Reg', (81, 87))	('clinical', 'MPA', (50, 58))
2384	25574416	The association with cryoablation produced a significant improvement of her symptoms; she died of lung metastases 41 months later.	('improvement', 'PosReg', (57, 68))	('cryoablation', 'Var', (21, 33))	('lung metastases', 'Disease', (98, 113))	('symptoms', 'MPA', (76, 84))	('lung metastases', 'Disease', 'MESH:D009362', (98, 113))
2401	18545673	These denote alternative splicing in MG-thymoma tumors compared to healthy human thymus and to in-house and Affymetrix datasets from colon cancer and healthy tissues.	('colon cancer', 'Phenotype', 'HP:0003003', (133, 145))	('colon cancer', 'Disease', 'MESH:D015179', (133, 145))	('thymoma', 'Phenotype', 'HP:0100522', (40, 47))	('tumors', 'Phenotype', 'HP:0002664', (48, 54))	('cancer', 'Phenotype', 'HP:0002664', (139, 145))	('colon cancer', 'Disease', (133, 145))	('alternative splicing', 'Var', (13, 33))	('human', 'Species', '9606', (75, 80))	('MG-thymoma tumors', 'Disease', (37, 54))	('tumor', 'Phenotype', 'HP:0002664', (48, 53))	('MG-thymoma tumors', 'Disease', 'MESH:D013945', (37, 54))
2407	18545673	Changes in gene expression, and particularly in alternative splicing patterns are often disease-associated, and aberrant alternative splicing (hyper-splicing) is one of the characteristics of cancer cells, as well as of inflammation and autoimmune muscle diseases.	('alternative splicing patterns', 'MPA', (48, 77))	('autoimmune muscle diseases', 'Disease', (237, 263))	('autoimmune muscle diseases', 'Disease', 'MESH:D001327', (237, 263))	('cancer', 'Disease', (192, 198))	('cancer', 'Disease', 'MESH:D009369', (192, 198))	('inflammation', 'Disease', 'MESH:D007249', (220, 232))	('aberrant alternative splicing', 'Var', (112, 141))	('inflammation', 'Disease', (220, 232))	('Changes', 'Reg', (0, 7))	('cancer', 'Phenotype', 'HP:0002664', (192, 198))
2418	18545673	At the functional level, alternative hyper-splicing can modify tumor properties, since gene products may play roles in multiple, often seemingly unrelated, routes.	('tumor', 'Disease', (63, 68))	('alternative hyper-splicing', 'Var', (25, 51))	('tumor', 'Phenotype', 'HP:0002664', (63, 68))	('tumor', 'Disease', 'MESH:D009369', (63, 68))	('modify', 'Reg', (56, 62))
2420	18545673	First, we analyzed our in-house MG-thymoma study and the Affymetrix colon cancer exon microarray data set, which identified tumor-specific alternative splicing events relevant to both tumors or specific to one of them.	('tumor', 'Disease', 'MESH:D009369', (184, 189))	('MG-thymoma', 'Disease', (32, 42))	('tumor', 'Phenotype', 'HP:0002664', (124, 129))	('colon cancer', 'Phenotype', 'HP:0003003', (68, 80))	('colon cancer', 'Disease', 'MESH:D015179', (68, 80))	('tumor', 'Phenotype', 'HP:0002664', (184, 189))	('tumor', 'Disease', (124, 129))	('cancer', 'Phenotype', 'HP:0002664', (74, 80))	('tumors', 'Disease', (184, 190))	('tumors', 'Disease', 'MESH:D009369', (184, 190))	('alternative', 'Var', (139, 150))	('tumor', 'Disease', (184, 189))	('tumors', 'Phenotype', 'HP:0002664', (184, 190))	('colon cancer', 'Disease', (68, 80))	('MG-thymoma', 'Disease', 'MESH:D013945', (32, 42))	('thymoma', 'Phenotype', 'HP:0100522', (35, 42))	('tumor', 'Disease', 'MESH:D009369', (124, 129))
2421	18545673	In-depth analyses of exon-specific alterations involved several key transcripts from the tumor-related, immune function and muscle-characteristic GO categories and the MG-related ACHE gene, which is ubiquitously expressed, undergoes alternative splicing at both termini (3' and 5') and contributes to many different biological processes.	('ACHE', 'Gene', (179, 183))	('tumor', 'Disease', 'MESH:D009369', (89, 94))	('rat', 'Species', '10116', (39, 42))	('alternative splicing', 'Var', (233, 253))	('contributes', 'Reg', (286, 297))	('ACHE', 'Gene', '43', (179, 183))	('tumor', 'Phenotype', 'HP:0002664', (89, 94))	('tumor', 'Disease', (89, 94))
2424	18545673	Combined ad-hoc and post-hoc statistics with in-depth analysis of key transcripts and FISH, RT-PCR and mass spectrometry followed by peptide sequencing validation revealed pronounced alternative hyper-splicing in several gene categories modified in MG-thymoma tumors.	('MG-thymoma tumors', 'Disease', 'MESH:D013945', (249, 266))	('thymoma', 'Phenotype', 'HP:0100522', (252, 259))	('alternative hyper-splicing', 'Var', (183, 209))	('tumor', 'Phenotype', 'HP:0002664', (260, 265))	('MG-thymoma tumors', 'Disease', (249, 266))	('tumors', 'Phenotype', 'HP:0002664', (260, 266))
2426	18545673	Together, these findings support the notion of a major contribution of alternative hyper-splicing to MG-thymoma features, opening new venues for diagnosis and treatment of specific tumor types, and revealed specific tumor-type alternative splicing signatures reflecting MG-thymoma and colon cancer properties.	('colon cancer', 'Disease', (285, 297))	('tumor', 'Disease', (216, 221))	('MG-thymoma', 'Disease', (101, 111))	('tumor', 'Disease', (181, 186))	('MG-thymoma', 'Disease', 'MESH:D013945', (270, 280))	('tumor', 'Phenotype', 'HP:0002664', (181, 186))	('MG-thymoma', 'Disease', (270, 280))	('alternative', 'Var', (71, 82))	('thymoma', 'Phenotype', 'HP:0100522', (273, 280))	('tumor', 'Disease', 'MESH:D009369', (216, 221))	('colon cancer', 'Phenotype', 'HP:0003003', (285, 297))	('tumor', 'Disease', 'MESH:D009369', (181, 186))	('MG-thymoma', 'Disease', 'MESH:D013945', (101, 111))	('tumor', 'Phenotype', 'HP:0002664', (216, 221))	('thymoma', 'Phenotype', 'HP:0100522', (104, 111))	('cancer', 'Phenotype', 'HP:0002664', (291, 297))	('colon cancer', 'Disease', 'MESH:D015179', (285, 297))
2471	18545673	It exhibited alternative splicing in MG-thymoma tumors compared to healthy thymuses but not between colon cancers to normal colons (Text S3).	('colon cancers', 'Disease', (100, 113))	('thymoma', 'Phenotype', 'HP:0100522', (40, 47))	('cancer', 'Phenotype', 'HP:0002664', (106, 112))	('colon cancers', 'Phenotype', 'HP:0003003', (100, 113))	('tumors', 'Phenotype', 'HP:0002664', (48, 54))	('cancers', 'Phenotype', 'HP:0002664', (106, 113))	('colon cancers', 'Disease', 'MESH:D015179', (100, 113))	('alternative splicing', 'Var', (13, 33))	('colon cancer', 'Phenotype', 'HP:0003003', (100, 112))	('MG-thymoma tumors', 'Disease', (37, 54))	('tumor', 'Phenotype', 'HP:0002664', (48, 53))	('MG-thymoma tumors', 'Disease', 'MESH:D013945', (37, 54))
2483	18545673	FISH for AChE-R protein variant indicated a significant increase in the number of stained cells in the MG-thymomic section compared to healthy thymus (Figure 5A).	('variant', 'Var', (24, 31))	('increase', 'PosReg', (56, 64))	('AChE', 'Gene', (9, 13))	('AChE', 'Gene', '43', (9, 13))
2503	18545673	Our findings highlighted hyper-splicing in tumor-related, immune function and muscle-specific transcripts with distinct patterns from those of colon cancer or healthy thymus and included parent-child relationships in the GO hierarchy, which specifically highlighted biologically significant categories and transcripts.	('child', 'Species', '9606', (194, 199))	('colon cancer', 'Phenotype', 'HP:0003003', (143, 155))	('tumor', 'Disease', 'MESH:D009369', (43, 48))	('cancer', 'Phenotype', 'HP:0002664', (149, 155))	('colon cancer', 'Disease', 'MESH:D015179', (143, 155))	('tumor', 'Phenotype', 'HP:0002664', (43, 48))	('colon cancer', 'Disease', (143, 155))	('hyper-splicing', 'Var', (25, 39))	('tumor', 'Disease', (43, 48))
2506	18545673	Changes in the expression of these proteins can affect the alternative splicing of an undefined number of cellular transcripts and might account for some of the known splicing changes in cancer.	('affect', 'Reg', (48, 54))	('cancer', 'Disease', 'MESH:D009369', (187, 193))	('cancer', 'Disease', (187, 193))	('splicing', 'MPA', (167, 175))	('expression', 'MPA', (15, 25))	('Changes', 'Var', (0, 7))	('cancer', 'Phenotype', 'HP:0002664', (187, 193))
2508	18545673	Specific changes related to MG-thymoma included HLA-DRB1, associated with a haplotype predictive of MG susceptibility in female with specific gene variants.	('variants', 'Var', (147, 155))	('MG-thymoma', 'Disease', 'MESH:D013945', (28, 38))	('MG-thymoma', 'Disease', (28, 38))	('HLA-DRB1', 'Gene', (48, 56))	('HLA-DRB1', 'Gene', '3123', (48, 56))	('thymoma', 'Phenotype', 'HP:0100522', (31, 38))	('changes', 'Reg', (9, 16))
2514	18545673	Indeed, antibodies against structural muscle proteins, among them myosin, were detected by others in the sera of MG patients, and myosin mutations are associated with colon cancer.	('colon cancer', 'Phenotype', 'HP:0003003', (167, 179))	('myosin', 'Gene', '79784', (130, 136))	('associated', 'Reg', (151, 161))	('patients', 'Species', '9606', (116, 124))	('colon cancer', 'Disease', 'MESH:D015179', (167, 179))	('mutations', 'Var', (137, 146))	('myosin', 'Gene', (66, 72))	('cancer', 'Phenotype', 'HP:0002664', (173, 179))	('colon cancer', 'Disease', (167, 179))	('myosin', 'Gene', '79784', (66, 72))	('myosin', 'Gene', (130, 136))
2613	32189468	Postoperative chemotherapy was suggested for patients with Masaoka stage IV or R2 resection.	('patients', 'Species', '9606', (45, 53))	('Masaoka stage IV', 'Disease', (59, 75))	('R2 resection', 'Var', (79, 91))
2678	31828474	The majority of patients (approximately 80%) have antibodies against the nicotinic acetylcholine receptor (AChR), while in a small subset of patients antibodies against muscle-specific receptor tyrosine kinase (MuSK), lipoprotein-related protein 4 (LRP4) or other postsynaptic structures of the neuromuscular junction are detected.	('MuSK', 'Gene', (211, 215))	('LRP4', 'Gene', '4038', (249, 253))	('antibodies', 'Var', (50, 60))	('acetylcholine', 'Chemical', 'MESH:D000109', (83, 96))	('MuSK', 'Gene', '4593', (211, 215))	('muscle-specific receptor tyrosine kinase', 'Gene', (169, 209))	('muscle-specific receptor tyrosine kinase', 'Gene', '4593', (169, 209))	('patients', 'Species', '9606', (16, 24))	('LRP4', 'Gene', (249, 253))	('lipoprotein-related protein 4', 'Gene', '4038', (218, 247))	('patients', 'Species', '9606', (141, 149))	('lipoprotein-related protein 4', 'Gene', (218, 247))
2691	31828474	Diagnostic criteria for myasthenia gravis consisted of typical myasthenic symptoms in combination with myasthenia gravis-related antibodies, or in seronegative patients either pathological repetitive nerve stimulation with a decrement over 10%, a positive edrophonium chloride test, or documented clinical improvement following pyridostigmine treatment.	('men', 'Species', '9606', (313, 316))	('pyridostigmine', 'Chemical', 'MESH:D011729', (328, 342))	('pathological', 'Var', (176, 188))	('myasthenia gravis', 'Disease', (24, 41))	('myasthenia gravis', 'Disease', (103, 120))	('decrement', 'NegReg', (225, 234))	('myasthenia', 'Phenotype', 'HP:0003473', (24, 34))	('myasthenia', 'Phenotype', 'HP:0003473', (103, 113))	('edrophonium chloride', 'Chemical', 'MESH:D004491', (256, 276))	('men', 'Species', '9606', (230, 233))	('men', 'Species', '9606', (348, 351))	('myasthenic symptoms', 'Phenotype', 'HP:0003473', (63, 82))	('myasthenic symptoms', 'Disease', 'MESH:D051271', (63, 82))	('patients', 'Species', '9606', (160, 168))	('myasthenia gravis', 'Disease', 'MESH:D009157', (24, 41))	('myasthenia gravis', 'Disease', 'MESH:D009157', (103, 120))	('men', 'Species', '9606', (290, 293))	('edrophonium chloride test', 'MPA', (256, 281))	('myasthenic symptoms', 'Disease', (63, 82))
2715	31828474	Additionally, male sex was also associated with treatment failure in the multivariate analysis (p = 0.011, OR 6.05, 95% CI 1.51-24.15), but not in the univariate analysis (p = 0.26).	('men', 'Species', '9606', (53, 56))	('treatment failure', 'CPA', (48, 65))	('male sex', 'Var', (14, 22))
2770	29867917	Most of these individuals suffer from X-linked agammaglobulinemia (XLA) which occurs due to mutations in the gene encoding Bruton's tyrosine kinase (BTK), an enzyme essential for B-cell development.	('BTK', 'Gene', '695', (149, 152))	('suffer', 'Reg', (26, 32))	('X-linked agammaglobulinemia', 'Disease', (38, 65))	("Bruton's tyrosine kinase", 'Gene', (123, 147))	('mutations', 'Var', (92, 101))	('X-linked agammaglobulinemia', 'Disease', 'MESH:C537409', (38, 65))	("Bruton's tyrosine kinase", 'Gene', '695', (123, 147))	('BTK', 'Gene', (149, 152))	('agammaglobulinemia', 'Phenotype', 'HP:0004432', (47, 65))
2806	29867917	Reflecting the heterogeneity of these conditions, the single patient with protective vaccine responses, in retrospect had an atypical presentation for CVID with early-onset chronic mucocutaneous candidiasis, and subsequent adult-onset hypogammaglobulinemia, was identified to have a gain-of-function (GOF) STAT1 mutation, which is not typically associated with PAD.	('chronic mucocutaneous candidiasis', 'Disease', (173, 206))	('CVID', 'Disease', (151, 155))	('gain-of-function', 'PosReg', (283, 299))	('mutation', 'Var', (312, 320))	('patient', 'Species', '9606', (61, 68))	('CVID', 'Disease', 'MESH:D017074', (151, 155))	('chronic mucocutaneous candidiasis', 'Disease', 'MESH:D002178', (173, 206))	('hypogammaglobulinemia', 'Phenotype', 'HP:0004313', (235, 256))	('chronic mucocutaneous candidiasis', 'Phenotype', 'HP:0002728', (173, 206))	('STAT1', 'Gene', (306, 311))	('hypogammaglobulinemia', 'Disease', (235, 256))	('STAT1', 'Gene', '6772', (306, 311))	('mucocutaneous candidiasis', 'Phenotype', 'HP:0002728', (181, 206))	('hypogammaglobulinemia', 'Disease', 'MESH:D000361', (235, 256))
2809	29867917	This included 21 XLA patients with hemizygous BTK mutations.	('mutations', 'Var', (50, 59))	('BTK', 'Gene', (46, 49))	('patients', 'Species', '9606', (21, 29))	('BTK', 'Gene', '695', (46, 49))
2811	29867917	Of the CVID patients, 4 had NFkappaB1 deficiency, and 3 were heterozygous for the (C104R) variant in TNFSRF13B, encoding TACI, a known risk-factor for the development of CVID.	('patients', 'Species', '9606', (12, 20))	('TNFSRF13B', 'Gene', (101, 110))	('CVID', 'Disease', (7, 11))	('CVID', 'Disease', 'MESH:D017074', (7, 11))	('C104R', 'Var', (83, 88))	('TACI', 'Gene', '23495', (121, 125))	('CVID', 'Disease', (170, 174))	('C104R', 'Mutation', 'rs34557412', (83, 88))	('CVID', 'Disease', 'MESH:D017074', (170, 174))	('NFkappaB1', 'Protein', (28, 37))	('TACI', 'Gene', (121, 125))
2812	29867917	One of these patients also harbored a pathogenic mutation in TCF3 (E555K), which causes an autosomal dominant form of agammaglobulinemia.	('TCF3', 'Gene', (61, 65))	('causes', 'Reg', (81, 87))	('patients', 'Species', '9606', (13, 21))	('agammaglobulinemia', 'Disease', 'MESH:D000361', (118, 136))	('E555K', 'Var', (67, 72))	('agammaglobulinemia', 'Disease', (118, 136))	('pathogenic', 'Reg', (38, 48))	('E555K', 'Mutation', 'rs879255271', (67, 72))	('agammaglobulinemia', 'Phenotype', 'HP:0004432', (118, 136))	('TCF3', 'Gene', '6929', (61, 65))
2813	29867917	In addition, we identified NFKB2 mutations in three CVID and two IgGSCD patients, who had marked autoimmune clinical manifestations.	('NFKB2', 'Gene', '4791', (27, 32))	('CVID', 'Disease', (52, 56))	('mutations', 'Var', (33, 42))	('CVID', 'Disease', 'MESH:D017074', (52, 56))	('NFKB2', 'Gene', (27, 32))	('patients', 'Species', '9606', (72, 80))
2858	29867917	In this cohort, patients who were later identified to have a genetic contribution to their disease, had a shorter time to a clinical diagnosis (Table 2).	('shorter', 'NegReg', (106, 113))	('patients', 'Species', '9606', (16, 24))	('genetic', 'Var', (61, 68))
2860	29867917	In addition, molecular tests may help identify patients-at-risk for certain disease complications, as in the case of NFKB2 mutations which are associated with a high risk of central adrenal insufficiency.	('associated', 'Reg', (143, 153))	('NFKB2', 'Gene', '4791', (117, 122))	('central adrenal insufficiency', 'Disease', (174, 203))	('patients', 'Species', '9606', (47, 55))	('central adrenal insufficiency', 'Phenotype', 'HP:0011734', (174, 203))	('central adrenal insufficiency', 'Disease', 'MESH:D000309', (174, 203))	('adrenal insufficiency', 'Phenotype', 'HP:0000846', (182, 203))	('NFKB2', 'Gene', (117, 122))	('mutations', 'Var', (123, 132))
2861	29867917	Further highlighting the complexities of clinical presentation in PID, we have described a patient who was initially misdiagnosed with CVID, but later found to have a STAT1 GOF mutation after his diagnosis was reconsidered in light of early-onset mucocutaneous candidiasis.	('STAT1', 'Gene', '6772', (167, 172))	('mutation', 'Var', (177, 185))	('mucocutaneous candidiasis', 'Disease', 'MESH:D002178', (247, 272))	('GOF', 'PosReg', (173, 176))	('mucocutaneous candidiasis', 'Phenotype', 'HP:0002728', (247, 272))	('mucocutaneous candidiasis', 'Disease', (247, 272))	('CVID', 'Disease', (135, 139))	('PID', 'Gene', (66, 69))	('STAT1', 'Gene', (167, 172))	('patient', 'Species', '9606', (91, 98))	('CVID', 'Disease', 'MESH:D017074', (135, 139))	('PID', 'Gene', '9219', (66, 69))
2862	29867917	We also identified one individual with digenic disease due to a pathogenic E555K variant in TCF3 and C104R variant in TNFRSF13B.	('TNFRSF13B', 'Gene', '23495', (118, 127))	('C104R', 'Mutation', 'rs34557412', (101, 106))	('TNFRSF13B', 'Gene', (118, 127))	('pathogenic', 'Reg', (64, 74))	('E555K', 'Var', (75, 80))	('TCF3', 'Gene', '6929', (92, 96))	('C104R', 'Var', (101, 106))	('TCF3', 'Gene', (92, 96))	('digenic disease', 'Disease', (39, 54))	('E555K', 'Mutation', 'rs879255271', (75, 80))
2863	29867917	We have previously reported another kindred affected by PAD and autoimmune disease; the proband harbored a novel non-sense TCF3 mutation and the C104R variant in TNFRSF13B, with a resultant CVID-like disorder and systemic lupus erythematosus.	('kin', 'Gene', (36, 39))	('TNFRSF13B', 'Gene', (162, 171))	('systemic lupus erythematosus', 'Phenotype', 'HP:0002725', (213, 241))	('TCF3', 'Gene', (123, 127))	('C104R', 'Mutation', 'rs34557412', (145, 150))	('autoimmune disease', 'Disease', (64, 82))	('CVID-like disorder', 'Disease', (190, 208))	('kin', 'Gene', '22944', (36, 39))	('systemic lupus erythematosus', 'Disease', 'MESH:D008180', (213, 241))	('C104R', 'Var', (145, 150))	('autoimmune disease', 'Phenotype', 'HP:0002960', (64, 82))	('autoimmune disease', 'Disease', 'MESH:D001327', (64, 82))	('TCF3', 'Gene', '6929', (123, 127))	('mutation', 'Var', (128, 136))	('systemic lupus erythematosus', 'Disease', (213, 241))	('TNFRSF13B', 'Gene', '23495', (162, 171))	('CVID-like disorder', 'Disease', 'MESH:D017074', (190, 208))
2864	29867917	We are not aware of other reports of digenic PAD due to the more common pathogenic TCF3 E555K variant in combination with an additional genetic risk-factor.	('TCF3', 'Gene', '6929', (83, 87))	('TCF3', 'Gene', (83, 87))	('E555K', 'Var', (88, 93))	('E555K', 'Mutation', 'rs879255271', (88, 93))	('digenic PAD', 'Disease', (37, 48))
2866	29867917	Nevertheless diagnostic rates could increase to 30% for CVID patients selected for sequencing on the basis of certain clinical or laboratory features.	('sequencing', 'Var', (83, 93))	('increase', 'PosReg', (36, 44))	('patients', 'Species', '9606', (61, 69))	('CVID', 'Disease', (56, 60))	('CVID', 'Disease', 'MESH:D017074', (56, 60))
2875	29867917	Importantly, two IGSCD patients in our cohort harbored NFKB2 mutations, which may have predisposed these patients to the more severe clinical phenotype.	('patients', 'Species', '9606', (105, 113))	('patients', 'Species', '9606', (23, 31))	('NFKB2', 'Gene', '4791', (55, 60))	('mutations', 'Var', (61, 70))	('IGSCD', 'Phenotype', 'HP:0032135', (17, 22))	('NFKB2', 'Gene', (55, 60))
2898	24294607	The vast majority of genetic factors that have been implicated in autoimmune disease susceptibility are common variants, predominantly, single nucleotide polymorphisms (SNPs) rather than insertion/deletion polymorphisms or microsatellites.	('single nucleotide polymorphisms', 'Var', (136, 167))	('autoimmune disease', 'Disease', 'MESH:D001327', (66, 84))	('autoimmune disease', 'Disease', (66, 84))	('autoimmune disease', 'Phenotype', 'HP:0002960', (66, 84))
2904	24294607	As probably expected, the study detected the strongest association in the Human Leukocyte Antigen (HLA) Class I locus (rs7750641) which, after imputation and conditional analyses of the broad HLA region, led to the determination of HLA-B*08 allele as the main risk allele (Table 1).	('HLA', 'Gene', '3119', (192, 195))	('rs7750641', 'DBSNP_MENTION', 'None', (119, 128))	('HLA', 'Gene', (232, 235))	('HLA', 'Gene', (99, 102))	('HLA', 'Gene', (192, 195))	('HLA-B', 'Gene', (232, 237))	('rs7750641', 'Var', (119, 128))	('HLA-B', 'Gene', '3106', (232, 237))	('HLA', 'Gene', '3119', (232, 235))	('Human', 'Species', '9606', (74, 79))	('HLA', 'Gene', '3119', (99, 102))
2908	24294607	This GWAS, also, verified the association between MG with thymus hyperplasia and the rs2476601 SNP in the PTPN22 locus (discussed below) which has been reported in previous studies.	('rs2476601', 'DBSNP_MENTION', 'None', (85, 94))	('PTPN22', 'Gene', '26191', (106, 112))	('thymus hyperplasia', 'Disease', (58, 76))	('thymus hyperplasia', 'Disease', 'MESH:D013952', (58, 76))	('thymus hyperplasia', 'Phenotype', 'HP:0010516', (58, 76))	('rs2476601', 'Var', (85, 94))	('PTPN22', 'Gene', (106, 112))
2910	24294607	Applying imputation around the TNIP1 locus, a strong association was demonstrated with the rs2233290 SNP, causing a proline to alanine substitution at position 151 of the coding region.	('proline to alanine substitution at position 151', 'Var', (116, 163))	('TNIP1', 'Gene', '10318', (31, 36))	('rs2233290', 'Var', (91, 100))	('rs2233290', 'DBSNP_MENTION', 'None', (91, 100))	('TNIP1', 'Gene', (31, 36))	('causing', 'Reg', (106, 113))	('proline to alanine substitution at position 151', 'SUBSTITUTION', 'None', (116, 163))
2933	24294607	The 59 ATA-positive patients appeared to be associated with the DR7 allele, whilst a negative association was observed in the case of the DR3 allele (Table 1), revealing a reverse outcome from the one noticed in MG patients with thymus hyperplasia and in ATA-negative patients who were associated with DR3 (Table 1), as well.	('associated', 'Reg', (44, 54))	('patients', 'Species', '9606', (215, 223))	('DR3', 'Gene', '8718', (138, 141))	('DR7', 'Var', (64, 67))	('thymus hyperplasia', 'Disease', (229, 247))	('ATA', 'Chemical', '-', (7, 10))	('ATA', 'Chemical', '-', (255, 258))	('thymus hyperplasia', 'Phenotype', 'HP:0010516', (229, 247))	('thymus hyperplasia', 'Disease', 'MESH:D013952', (229, 247))	('DR3', 'Gene', '8718', (302, 305))	('patients', 'Species', '9606', (20, 28))	('DR3', 'Gene', (138, 141))	('patients', 'Species', '9606', (268, 276))	('DR3', 'Gene', (302, 305))
2937	24294607	Overall, 27 markers, most of them microsatellites, covering the entire region of HLA complex, were genotyped.	('HLA', 'Gene', (81, 84))	('HLA', 'Gene', '3119', (81, 84))	('microsatellites', 'Var', (34, 49))
2940	24294607	More recent data derived from an association study of 1,472 SNPs covering the overall MHC region, in a cohort of 438 MG cases from Sweden, determined the Class I HLA locus as the most susceptible in MG. More specifically, the strongest association was detected in the case of rs2523674 SNP mapped 3.5 kb downstream of the HLA complex protein 5 (HCP5) gene, while the imputed HLA-C*0701 allele was also associated, in an independent way (Table 1).	('HLA', 'Gene', (375, 378))	('HCP5', 'Gene', '10866', (345, 349))	('HLA', 'Gene', (162, 165))	('HCP5', 'Gene', (345, 349))	('HLA', 'Gene', '3119', (375, 378))	('HLA', 'Gene', (322, 325))	('HLA-C', 'Gene', '3107', (375, 380))	('rs2523674', 'DBSNP_MENTION', 'None', (276, 285))	('HLA', 'Gene', '3119', (162, 165))	('rs2523674', 'Var', (276, 285))	('HLA-C', 'Gene', (375, 380))	('HLA complex protein 5', 'Gene', (322, 343))	('HLA', 'Gene', '3119', (322, 325))	('HLA complex protein 5', 'Gene', '10866', (322, 343))
2941	24294607	Although this study scrutinized a large set of genetic variants across the vast MHC region, it disregarded the heterogeneous clinical and biological profiles of the disease that could lead to distinct HLA association signals.	('variants', 'Var', (55, 63))	('HLA', 'Gene', (201, 204))	('HLA', 'Gene', '3119', (201, 204))
2964	24294607	The missense SNP rs2476601 (1858C>T), which leads to an arginine to tryptophan substitution (R620W), has been reproducibly associated with multiple autoimmune diseases, MG included, as reviewed in.	('associated', 'Reg', (123, 133))	('rs2476601', 'Var', (17, 26))	('autoimmune disease', 'Phenotype', 'HP:0002960', (148, 166))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (148, 167))	('rs2476601', 'DBSNP_MENTION', 'None', (17, 26))	('autoimmune diseases', 'Disease', 'MESH:D001327', (148, 167))	('R620W', 'Var', (93, 98))	('1858C>T', 'Var', (28, 35))	('R620W', 'SUBSTITUTION', 'None', (93, 98))	('1858C>T', 'SUBSTITUTION', 'None', (28, 35))	('arginine', 'Chemical', 'MESH:D001120', (56, 64))	('leads to', 'Reg', (44, 52))	('autoimmune diseases', 'Disease', (148, 167))	('tryptophan', 'Chemical', 'MESH:D014364', (68, 78))
2965	24294607	As a matter of fact, a meta-analysis, conducted recently on the association of rs2476601 with a plethora of autoimmune diseases, established the correlation of this variant with rheumatoid arthritis, MG, lupus, type I diabetes, and several other diseases, but not with a cluster of diseases affecting the skin, the gastrointestinal tract, or immune privileged areas, such as psoriasis, Crohn's disease, multiple sclerosis, and so forth.	('arthritis', 'Phenotype', 'HP:0001369', (189, 198))	('psoriasis', 'Phenotype', 'HP:0003765', (375, 384))	('rs2476601', 'Var', (79, 88))	('type I diabetes', 'Phenotype', 'HP:0100651', (211, 226))	('psoriasis', 'Disease', 'MESH:D011565', (375, 384))	('rheumatoid arthritis', 'Disease', (178, 198))	('multiple sclerosis', 'Disease', (403, 421))	('psoriasis', 'Disease', (375, 384))	('plethora', 'Phenotype', 'HP:0001050', (96, 104))	('rheumatoid arthritis', 'Disease', 'MESH:D001172', (178, 198))	('autoimmune diseases', 'Disease', 'MESH:D001327', (108, 127))	('multiple sclerosis', 'Disease', 'MESH:D009103', (403, 421))	('rs2476601', 'DBSNP_MENTION', 'None', (79, 88))	("Crohn's disease", 'Phenotype', 'HP:0100280', (386, 401))	('autoimmune diseases', 'Disease', (108, 127))	("Crohn's disease", 'Disease', 'MESH:D003424', (386, 401))	('correlation', 'Interaction', (145, 156))	("Crohn's disease", 'Disease', (386, 401))	('type I diabetes', 'Disease', 'MESH:D003922', (211, 226))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (108, 127))	('type I diabetes', 'Disease', (211, 226))	('autoimmune disease', 'Phenotype', 'HP:0002960', (108, 126))	('rheumatoid arthritis', 'Phenotype', 'HP:0001370', (178, 198))	('lupus', 'Disease', (204, 209))	('association', 'Interaction', (64, 75))
2969	24294607	This observation is inconsistent with the results of decreased IL-2 levels, demonstrated by Vang and coworkers, in patients with type I autoimmune diabetes carrying the 620W allele.	('type I autoimmune diabetes', 'Phenotype', 'HP:0100651', (129, 155))	('patients', 'Species', '9606', (115, 123))	('IL-2', 'Gene', (63, 67))	('IL-2', 'Gene', '3558', (63, 67))	('620W', 'Var', (169, 173))	('type I autoimmune diabetes', 'Disease', 'MESH:D003922', (129, 155))	('decreased', 'NegReg', (53, 62))	('type I autoimmune diabetes', 'Disease', (129, 155))
2970	24294607	An association study of the R620W variant in Hungarian and German MG patients proved that the PTPN22 1858T allele was associated with MG predisposition, only, in the subgroup of nonthymoma patients with detectable ATA (Table 2), leading to conflicting conclusions compared to the French MG study, in which the association was established in the exactly opposite case of non-thymoma patients lacking ATA.	('ATA', 'Chemical', '-', (214, 217))	('patients', 'Species', '9606', (382, 390))	('thymoma', 'Phenotype', 'HP:0100522', (181, 188))	('thymoma', 'Disease', 'MESH:D013945', (181, 188))	('R620W', 'Var', (28, 33))	('thymoma', 'Disease', 'MESH:D013945', (374, 381))	('R620W', 'SUBSTITUTION', 'None', (28, 33))	('ATA', 'Chemical', '-', (399, 402))	('MG predisposition', 'Disease', (134, 151))	('PTPN22', 'Gene', (94, 100))	('thymoma', 'Disease', (181, 188))	('thymoma', 'Disease', (374, 381))	('PTPN22', 'Gene', '26191', (94, 100))	('associated', 'Reg', (118, 128))	('patients', 'Species', '9606', (69, 77))	('patients', 'Species', '9606', (189, 197))	('thymoma', 'Phenotype', 'HP:0100522', (374, 381))
2971	24294607	Another study in German Caucasian MG patients was the first to uncover a strong association between +1858T genotypes and thymoma-related MG (Table 2).	('thymoma', 'Phenotype', 'HP:0100522', (121, 128))	('patients', 'Species', '9606', (37, 45))	('+1858T', 'Var', (100, 106))	('thymoma', 'Disease', 'MESH:D013945', (121, 128))	('thymoma', 'Disease', (121, 128))
2972	24294607	It is worth mentioning that the intratumorous IL-2 expression levels were found to be reduced in patients bearing the +1858T allele.	('reduced', 'NegReg', (86, 93))	('expression levels', 'MPA', (51, 68))	('IL-2', 'Gene', '3558', (46, 50))	('+1858T', 'Var', (118, 124))	('IL-2', 'Gene', (46, 50))	('patients', 'Species', '9606', (97, 105))
2974	24294607	Instead, the rs2488457 SNP which resides in the PTPN22 promoter region (-1123G>C) appeared to be associated with MG characterized by low titer anti-AChR antibodies (Table 2).	('-1123G>C', 'SUBSTITUTION', 'None', (72, 80))	('PTPN22', 'Gene', (48, 54))	('PTPN22', 'Gene', '26191', (48, 54))	('-1123G>C', 'Var', (72, 80))	('rs2488457', 'Var', (13, 22))	('associated', 'Reg', (97, 107))	('rs2488457', 'DBSNP_MENTION', 'None', (13, 22))
2975	24294607	A meta-analysis of the four above studies performed on allele frequencies of the PTPN22 rs2476601 verified the association of the T allele with nonthymomatous MG.	('PTPN22', 'Gene', '26191', (81, 87))	('thymoma', 'Disease', 'MESH:D013945', (147, 154))	('thymoma', 'Disease', (147, 154))	('thymoma', 'Phenotype', 'HP:0100522', (147, 154))	('association', 'Interaction', (111, 122))	('rs2476601', 'Var', (88, 97))	('PTPN22', 'Gene', (81, 87))	('rs2476601', 'DBSNP_MENTION', 'None', (88, 97))
2977	24294607	To begin with, one of the most important associations is that of the rs16862847 SNP located at the promoter region of the CHRNA1:encoding the alpha-subunit of the muscle AChR pentameric channel:which has been constantly associated with MG, as discussed in detail in.	('associations', 'Reg', (41, 53))	('rs16862847', 'Var', (69, 79))	('associated', 'Reg', (220, 230))	('CHRNA1', 'Gene', (122, 128))	('CHRNA1', 'Gene', '1134', (122, 128))	('rs16862847', 'DBSNP_MENTION', 'None', (69, 79))
2980	24294607	In addition to previous studies reporting a probable association between the +49A/G coding variant and the subset of thymoma-related MG, the involvement of SNPs located at the promoter region of CTLA-4 has also been evaluated.	('CTLA-4', 'Gene', '1493', (195, 201))	('thymoma', 'Disease', 'MESH:D013945', (117, 124))	('thymoma', 'Disease', (117, 124))	('+49A/G', 'SUBSTITUTION', 'None', (77, 83))	('CTLA-4', 'Gene', (195, 201))	('+49A/G', 'Var', (77, 83))	('thymoma', 'Phenotype', 'HP:0100522', (117, 124))
2981	24294607	Two SNPs, at positions -1772T/C and -1661A/G upstream of CTLA-4, were shown to be associated with MG in a group of 165 MG patients of Swedish origin.	('CTLA-4', 'Gene', '1493', (57, 63))	('associated with', 'Reg', (82, 97))	('-1772T/C', 'Var', (23, 31))	('CTLA-4', 'Gene', (57, 63))	('-1661A/G', 'Var', (36, 44))	('-1772T/C', 'SUBSTITUTION', 'None', (23, 31))	('patients', 'Species', '9606', (122, 130))	('-1661A/G', 'SUBSTITUTION', 'None', (36, 44))
2982	24294607	Because of their location within regulatory elements:the NF-1 and c/EBP binding sites:these polymorphisms plausibly have an effect on gene transcription or even splicing, as implied by the increased levels of sCD152, in -1772T/C heterozygote MG patients.	('NF-1', 'Gene', (57, 61))	('polymorphisms', 'Var', (92, 105))	('patients', 'Species', '9606', (245, 253))	('c/EBP', 'Gene', '1050', (66, 71))	('c/EBP', 'Gene', (66, 71))	('effect', 'Reg', (124, 130))	('CD152', 'Gene', '1493', (210, 215))	('splicing', 'MPA', (161, 169))	('-1772T/C', 'Var', (220, 228))	('NF-1', 'Gene', '4763', (57, 61))	('-1772T/C', 'SUBSTITUTION', 'None', (220, 228))	('CD152', 'Gene', (210, 215))	('gene transcription', 'MPA', (134, 152))	('increased', 'PosReg', (189, 198))
2985	24294607	The rs2737713 polymorphism which leads to a phenylalanine to tyrosine substitution (F19Y) in the LGALS8 locus, encoding galectin-8, appeared to be moderately associated with MG. A previous study of the same research group examined two SNPs in the 5' upstream sequence of the galectin-1 gene (LGALS1), along with two SNPs in regulatory regions of the interleukin receptor 2beta gene (IL2Rbeta) which resides in the 22q13 chromosomal region, too.	('LGALS8', 'Gene', (97, 103))	('F19Y', 'Var', (84, 88))	('galectin-1', 'Gene', '3956', (275, 285))	('associated', 'Reg', (158, 168))	('galectin-8', 'Gene', (120, 130))	('IL2Rbeta', 'Gene', (383, 391))	('rs2737713', 'DBSNP_MENTION', 'None', (4, 13))	('F19Y', 'SUBSTITUTION', 'None', (84, 88))	('galectin-8', 'Gene', '3964', (120, 130))	('IL2Rbeta', 'Gene', '3559', (383, 391))	('galectin-1', 'Gene', (275, 285))	('tyrosine', 'Chemical', 'MESH:D014443', (61, 69))	('LGALS8', 'Gene', '3964', (97, 103))	('LGALS1', 'Gene', (292, 298))	('phenylalanine', 'Chemical', 'MESH:D010649', (44, 57))	('LGALS1', 'Gene', '3956', (292, 298))	('rs2737713', 'Var', (4, 13))
2986	24294607	A strong association was identified between MG and the haplotype formed by SNPs rs4820293 and rs743777 of LGALS1 and IL2Rbeta, respectively, but functional studies did not verify an impact of rs4820293-different genotypes on gene expression.	('rs4820293', 'Var', (192, 201))	('LGALS1', 'Gene', '3956', (106, 112))	('rs4820293', 'DBSNP_MENTION', 'None', (192, 201))	('rs4820293', 'DBSNP_MENTION', 'None', (80, 89))	('IL2Rbeta', 'Gene', '3559', (117, 125))	('rs4820293', 'Var', (80, 89))	('rs743777', 'Var', (94, 102))	('LGALS1', 'Gene', (106, 112))	('IL2Rbeta', 'Gene', (117, 125))	('rs743777', 'DBSNP_MENTION', 'None', (94, 102))
2988	24294607	In this survey, three missense variants in the IL4Ralpha (I75V, S503P, and Q576R) which are thought to disrupt the signal transduction of interleukin-4 (IL-4) were selected.	('IL-4', 'Gene', (153, 157))	('Q576R', 'Var', (75, 80))	('IL-4', 'Gene', '3565', (153, 157))	('I75V', 'Var', (58, 62))	('IL4Ralpha', 'Gene', '3566', (47, 56))	('interleukin-4', 'Gene', '3565', (138, 151))	('I75V', 'SUBSTITUTION', 'None', (58, 62))	('disrupt', 'NegReg', (103, 110))	('signal transduction', 'MPA', (115, 134))	('IL4Ralpha', 'Gene', (47, 56))	('S503P', 'SUBSTITUTION', 'None', (64, 69))	('interleukin-4', 'Gene', (138, 151))	('Q576R', 'SUBSTITUTION', 'None', (75, 80))	('S503P', 'Var', (64, 69))
2996	24294607	A recent study in Han Chinese MG cases attempted to assess the contribution of two SNPs, rs3761548 (-3279A/C) and rs2280883 (IVS9+459A/G), in the FOXP3 gene to MG susceptibility.	('rs2280883', 'Var', (114, 123))	('-3279A/C', 'Var', (100, 108))	('IVS9+459A/G', 'SUBSTITUTION', 'None', (125, 136))	('rs3761548', 'Var', (89, 98))	('FOXP3', 'Gene', (146, 151))	('rs3761548', 'DBSNP_MENTION', 'None', (89, 98))	('IVS9+459A/G', 'Var', (125, 136))	('-3279A/C', 'SUBSTITUTION', 'None', (100, 108))	('FOXP3', 'Gene', '50943', (146, 151))	('rs2280883', 'DBSNP_MENTION', 'None', (114, 123))
3011	32110228	Paraneoplastic neurological syndromes (PNS) associated with anti-CV2/collapsin response mediator protein (CRMP) 5 antibodies are rare and often precede the cancer itself.	('collapsin response mediator protein (CRMP) 5', 'Gene', '56896', (69, 113))	('Paraneoplastic neurological syndromes', 'Disease', 'MESH:D020361', (0, 37))	('cancer', 'Disease', (156, 162))	('CV2', 'Gene', (65, 68))	('cancer', 'Disease', 'MESH:D009369', (156, 162))	('Paraneoplastic neurological syndromes', 'Disease', (0, 37))	('PNS', 'Disease', (39, 42))	('neurological syndrome', 'Phenotype', 'HP:0000707', (15, 36))	('cancer', 'Phenotype', 'HP:0002664', (156, 162))	('PNS', 'Disease', 'MESH:D020361', (39, 42))	('antibodies', 'Var', (114, 124))	('CV2', 'Gene', '168667', (65, 68))
3039	32110228	Onconeural antibodies are classified into 3 main categories: (a) well-characterized antibodies with a strong cancer association (anti-amphiphysin, anti-CV2 [CRMP5], anti-Hu [ANNA-1], anti-Ma2, anti-recoverin, anti-Ri [ANNA-2], and anti-Yo [PCA-1]), (b) partially characterized antibodies (ANNA-3, anti-mGluR1, anti-Tr, anti-Zic4, PCA-2), and (c) antibodies occurring in both cancer- and non-cancer-associated syndromes (anti-acetylcholine receptor [AchR], anti-nicotinic AchR, anti-VGCC, anti-VGKC).	('cancer', 'Disease', 'MESH:D009369', (109, 115))	('Zic4', 'Gene', '84107', (324, 328))	('cancer', 'Phenotype', 'HP:0002664', (375, 381))	('mGluR1', 'Gene', (302, 308))	('Ma2', 'Gene', (188, 191))	('cancer', 'Disease', (391, 397))	('CRMP5', 'Gene', (157, 162))	('cancer', 'Phenotype', 'HP:0002664', (391, 397))	('Zic4', 'Gene', (324, 328))	('CV2', 'Gene', (152, 155))	('PCA-1', 'Gene', '100750225', (240, 245))	('Ma2', 'Gene', '10687', (188, 191))	('cancer', 'Disease', 'MESH:D009369', (375, 381))	('CV2', 'Gene', '168667', (152, 155))	('PCA-1', 'Gene', (240, 245))	('cancer', 'Disease', (109, 115))	('PCA-2', 'Gene', '103164619', (330, 335))	('cancer', 'Disease', 'MESH:D009369', (391, 397))	('cancer', 'Phenotype', 'HP:0002664', (109, 115))	('CRMP5', 'Gene', '56896', (157, 162))	('anti-acetylcholine', 'Var', (420, 438))	('PCA-2', 'Gene', (330, 335))	('mGluR1', 'Gene', '2911', (302, 308))	('cancer', 'Disease', (375, 381))
3049	32110228	Antibodies associated with limbic encephalitis are anti-Hu, anti-Ma2, anti-amphiphysin and anti-CV2/CRMP5.	('encephalitis', 'Disease', (34, 46))	('CV2', 'Gene', (96, 99))	('Ma2', 'Gene', '10687', (65, 68))	('encephalitis', 'Disease', 'MESH:D004660', (34, 46))	('associated', 'Reg', (11, 21))	('CRMP5', 'Gene', (100, 105))	('anti-Hu', 'Var', (51, 58))	('CRMP5', 'Gene', '56896', (100, 105))	('encephalitis', 'Phenotype', 'HP:0002383', (34, 46))	('anti-amphiphysin', 'Var', (70, 86))	('CV2', 'Gene', '168667', (96, 99))	('Ma2', 'Gene', (65, 68))
3066	32110228	Treatment of PNS of the CNS in general is challenging, particularly for disorders associated with antibodies against intracellular antigens which probably cause neuronal damage by cytotoxic T-cell mechanisms.	('antibodies', 'Var', (98, 108))	('neuronal damage', 'Disease', (161, 176))	('PNS', 'Disease', (13, 16))	('PNS', 'Disease', 'MESH:D020361', (13, 16))	('neuronal damage', 'Disease', 'MESH:D009410', (161, 176))
3110	28242989	However, Tc-99m MIBI uptake has been reported in both malignant and benign thymomas.	('malignant', 'Disease', (54, 63))	('Tc-99', 'Chemical', '-', (9, 14))	('benign thymomas', 'Disease', 'MESH:D013945', (68, 83))	('thymoma', 'Phenotype', 'HP:0100522', (75, 82))	('MIBI', 'Chemical', 'MESH:C055887', (16, 20))	('Tc-99m', 'Var', (9, 15))	('benign thymomas', 'Disease', (68, 83))
3121	23765114	Of two patients with PIK3CA or AKT1 mutations, one was treated with an mTOR inhibitor-based regimen and achieved 26% regression with a TTF of 17 months.	('AKT1', 'Gene', '207', (31, 35))	('PIK3CA', 'Gene', (21, 27))	('mutations', 'Var', (36, 45))	('mTOR', 'Gene', '2475', (71, 75))	('TTF', 'Chemical', '-', (135, 138))	('AKT1', 'Gene', (31, 35))	('mTOR', 'Gene', (71, 75))	('PIK3CA', 'Gene', '5290', (21, 27))	('patients', 'Species', '9606', (7, 15))	('regression', 'NegReg', (117, 127))
3133	23765114	Of 12 patients assessed for a PIK3CA mutation (7 by NGS; 6 by single gene PCR sequencing, including one of whom was also assessed by NGS), one patient (8%; case #16, Table 2) had a PIK3CA mutation (S553T) in exon 9.	('PIK3CA', 'Gene', (30, 36))	('patient', 'Species', '9606', (143, 150))	('patient', 'Species', '9606', (6, 13))	('PIK3CA', 'Gene', '5290', (30, 36))	('S553T', 'Mutation', 'rs1285828931', (198, 203))	('PIK3CA', 'Gene', (181, 187))	('PIK3CA', 'Gene', '5290', (181, 187))	('patients', 'Species', '9606', (6, 14))	('S553T', 'Var', (198, 203))
3134	23765114	One of the 13 patients (8%) assessed for an EGFR mutation (7 by NGS; 8 by single gene PCR-based sequencing including 2 who also had NGS) had a mutation (case #4, Table 2; T785I in exon 20) in the sample obtained five years prior to referral.	('T785I', 'Var', (171, 176))	('EGFR', 'Gene', '1956', (44, 48))	('EGFR', 'Gene', (44, 48))	('T785I', 'Mutation', 'rs587780591', (171, 176))	('patients', 'Species', '9606', (14, 22))
3135	23765114	Of interest no EGFR mutation was found by NGS in the sample obtained from a separate site, one year after referral.	('EGFR', 'Gene', '1956', (15, 19))	('EGFR', 'Gene', (15, 19))	('mutation', 'Var', (20, 28))
3136	23765114	Twelve patients assessed for a KRAS mutation, 9 for an NRAS mutation, and 9 for a BRAF mutation, were all wild-type.	('KRAS', 'Gene', (31, 35))	('BRAF', 'Gene', '673', (82, 86))	('NRAS', 'Gene', '4893', (55, 59))	('KRAS', 'Gene', '3845', (31, 35))	('BRAF', 'Gene', (82, 86))	('NRAS', 'Gene', (55, 59))	('patients', 'Species', '9606', (7, 15))	('mutation', 'Var', (36, 44))
3139	23765114	One patient (case #4, Table 2) had an APC mutation (E1536), TP53 mutation (R282W) and MCL1 amplification.	('R282W', 'Var', (75, 80))	('APC', 'Disease', 'MESH:D011125', (38, 41))	('patient', 'Species', '9606', (4, 11))	('TP53', 'Gene', '7157', (60, 64))	('MCL1', 'Gene', '4170', (86, 90))	('APC', 'Disease', (38, 41))	('R282W', 'Mutation', 'rs28934574', (75, 80))	('E1536', 'Var', (52, 57))	('TP53', 'Gene', (60, 64))	('MCL1', 'Gene', (86, 90))
3140	23765114	A second patient (case #8, Table 2) had a RET mutation (E768Q) and CDKN2A/B deletion.	('RET', 'Gene', '5979', (42, 45))	('CDKN2A/B', 'Gene', '1029;1030', (67, 75))	('E768Q', 'Var', (56, 61))	('CDKN2A/B', 'Gene', (67, 75))	('RET', 'Gene', (42, 45))	('patient', 'Species', '9606', (9, 16))	('E768Q', 'Mutation', 'p.E768Q', (56, 61))
3141	23765114	MCL1 amplification was identified in a third patient (case #11, Table 2) and an AKT1 mutation (E17K) in a fourth patient (case #17, Table 2).	('patient', 'Species', '9606', (113, 120))	('E17K', 'Var', (95, 99))	('MCL1', 'Gene', '4170', (0, 4))	('AKT1', 'Gene', '207', (80, 84))	('MCL1', 'Gene', (0, 4))	('patient', 'Species', '9606', (45, 52))	('AKT1', 'Gene', (80, 84))	('E17K', 'Mutation', 'rs121434592', (95, 99))
3155	23765114	One of two patients (cases #16 and 17, Table 2) with a mutation in the PI3K/AKT/mTOR axis was treated with an mTOR-based regimen and achieved 26% regression with a TTF of 17 months (case #17, Table 2).	('mTOR', 'Gene', (110, 114))	('mTOR', 'Gene', '2475', (110, 114))	('AKT', 'Gene', '207', (76, 79))	('regression', 'NegReg', (146, 156))	('mTOR', 'Gene', (80, 84))	('mTOR', 'Gene', '2475', (80, 84))	('TTF', 'Chemical', '-', (164, 167))	('AKT', 'Gene', (76, 79))	('mutation', 'Var', (55, 63))	('patients', 'Species', '9606', (11, 19))
3160	23765114	The median TTF was significantly longer in nine patients (one patient [case #; Table ] was not included in the paired analysis as the patient did not receive prior systemic therapy for advanced cancer) treated on mTOR inhibitor combinations (11.6 months, 95% CI, 0.0-30.9 months) compared to median TTF on their last standard therapy prior to referral to the phase I clinic (2.3 months, 95% CI, 1.7-2.9 months; p=0.024; Figure 2B).	('TTF', 'Chemical', '-', (11, 14))	('mTOR', 'Gene', (213, 217))	('combinations', 'Var', (228, 240))	('TTF', 'MPA', (11, 14))	('cancer', 'Disease', (194, 200))	('TTF', 'Chemical', '-', (299, 302))	('patient', 'Species', '9606', (62, 69))	('cancer', 'Phenotype', 'HP:0002664', (194, 200))	('patient', 'Species', '9606', (48, 55))	('patient', 'Species', '9606', (134, 141))	('patients', 'Species', '9606', (48, 56))	('mTOR', 'Gene', '2475', (213, 217))	('longer', 'PosReg', (33, 39))	('cancer', 'Disease', 'MESH:D009369', (194, 200))
3173	23765114	For instance, one of 12 patients (8%) harbored a PIK3CA mutation; one of 13 (8%), an EGFR mutation; one of seven (14%), a RET mutation; and one of seven (14%), an AKT1 mutation.	('RET', 'Gene', '5979', (122, 125))	('EGFR', 'Gene', (85, 89))	('EGFR', 'Gene', '1956', (85, 89))	('RET', 'Gene', (122, 125))	('AKT1', 'Gene', '207', (163, 167))	('PIK3CA', 'Gene', (49, 55))	('AKT1', 'Gene', (163, 167))	('patients', 'Species', '9606', (24, 32))	('PIK3CA', 'Gene', '5290', (49, 55))	('mutation', 'Var', (56, 64))	('mutation', 'Var', (90, 98))
3177	23765114	One of the five patients (case #17, Table 2) had an AKT1 mutation, and achieved tumor regression of 26% that lasted 17 months.	('mutation', 'Var', (57, 65))	('tumor', 'Disease', 'MESH:D009369', (80, 85))	('AKT1', 'Gene', '207', (52, 56))	('tumor', 'Phenotype', 'HP:0002664', (80, 85))	('patients', 'Species', '9606', (16, 24))	('tumor', 'Disease', (80, 85))	('AKT1', 'Gene', (52, 56))
3186	23765114	One patient (case #4, Table 2) showed an EGFR mutation in sample tissue obtained five years prior to referral.	('EGFR', 'Gene', (41, 45))	('EGFR', 'Gene', '1956', (41, 45))	('mutation', 'Var', (46, 54))	('patient', 'Species', '9606', (4, 11))
3188	23765114	Other aberrations included mutations in APC, a tumor suppressor gene often altered in colorectal cancer, or in p53.	('mutations', 'Var', (27, 36))	('APC', 'Disease', 'MESH:D011125', (40, 43))	('colorectal cancer', 'Disease', 'MESH:D015179', (86, 103))	('APC', 'Disease', (40, 43))	('p53', 'Gene', (111, 114))	('p53', 'Gene', '7157', (111, 114))	('colorectal cancer', 'Phenotype', 'HP:0003003', (86, 103))	('tumor', 'Disease', 'MESH:D009369', (47, 52))	('colorectal cancer', 'Disease', (86, 103))	('cancer', 'Phenotype', 'HP:0002664', (97, 103))	('tumor', 'Phenotype', 'HP:0002664', (47, 52))	('tumor', 'Disease', (47, 52))
3189	23765114	MCL1 amplification implicated in antiapoptic activity, and loss of CDKN2A/B, a gene that encodes inhibition of cyclin-dependent kinases were also seen (Table 2).	('antiapoptic activity', 'MPA', (33, 53))	('amplification', 'Var', (5, 18))	('CDKN2A/B', 'Gene', '1029;1030', (67, 75))	('MCL1', 'Gene', '4170', (0, 4))	('MCL1', 'Gene', (0, 4))	('CDKN2A/B', 'Gene', (67, 75))	('loss', 'NegReg', (59, 63))
3197	23765114	Diverse actionable molecular aberrations were seen in our patients including, but not limited to, mutations in PIK3CA (1 of 12 tested; 8%); EGFR (1 of 13; 8%); RET (1 of 7; 14%); and AKT1 (1 of 7; 14%).	('EGFR', 'Gene', (140, 144))	('AKT1', 'Gene', '207', (183, 187))	('PIK3CA', 'Gene', (111, 117))	('mutations', 'Var', (98, 107))	('AKT1', 'Gene', (183, 187))	('RET', 'Gene', '5979', (160, 163))	('patients', 'Species', '9606', (58, 66))	('PIK3CA', 'Gene', '5290', (111, 117))	('EGFR', 'Gene', '1956', (140, 144))	('RET', 'Gene', (160, 163))
3198	23765114	Other aberrations were also observed: TP53 mutation, APC mutation, MCL1 amplification, and, CDK2A/B deletion.	('MCL1', 'Gene', (67, 71))	('amplification', 'Var', (72, 85))	('APC', 'Disease', 'MESH:D011125', (53, 56))	('APC', 'Disease', (53, 56))	('MCL1', 'Gene', '4170', (67, 71))	('TP53', 'Gene', (38, 42))	('mutation', 'Var', (43, 51))	('CDK2A/B', 'Gene', (92, 99))	('TP53', 'Gene', '7157', (38, 42))
3228	20421818	High EGFR immunoreactivity is seen in more aggressive thymic neoplasms as classified according to the 2004 WHO, but regardless of classification, the presence of EGFR in tumor cells (1+, 2+, and 3+) is associated with improved performance free survival (PFS) and a trend for better OS.	('tumor', 'Disease', 'MESH:D009369', (170, 175))	('aggressive thymic neoplasms', 'Disease', 'MESH:D013953', (43, 70))	('thymic neoplasms', 'Phenotype', 'HP:0100521', (54, 70))	('tumor', 'Phenotype', 'HP:0002664', (170, 175))	('neoplasms', 'Phenotype', 'HP:0002664', (61, 70))	('EGFR', 'Gene', (162, 166))	('tumor', 'Disease', (170, 175))	('performance free survival', 'CPA', (227, 252))	('1+', 'Var', (183, 185))	('presence', 'Var', (150, 158))	('aggressive thymic neoplasms', 'Disease', (43, 70))	('improved', 'PosReg', (218, 226))
3277	20421818	Patients with high C-kit expression had an inferior PFS then those with low C-kit expression (Figure 2).	('C-kit', 'Gene', (76, 81))	('C-kit', 'Gene', (19, 24))	('C-kit', 'Gene', '3815', (76, 81))	('C-kit', 'Gene', '3815', (19, 24))	('high', 'Var', (14, 18))	('Patients', 'Species', '9606', (0, 8))	('PFS', 'MPA', (52, 55))
3280	20421818	After adjusting for the presence of liver metastasis, EGFR positivity (hazard ratio = 0.16, 95% confidence interval: [0.06 - 0.43], p = 0.0004) and low C-kit expression (hazard ratio = 0.08, 95% confidence interval: [0.02-0.35], p = 0.0008) remained significant predictors of PFS.	('C-kit', 'Gene', (152, 157))	('C-kit', 'Gene', '3815', (152, 157))	('expression', 'MPA', (158, 168))	('positivity', 'Var', (59, 69))	('PFS', 'Disease', (276, 279))	('liver metastasis', 'Disease', 'MESH:D009362', (36, 52))	('EGFR', 'Gene', (54, 58))	('liver metastasis', 'Disease', (36, 52))	('low', 'NegReg', (148, 151))
3281	20421818	OS (Figure 3) for patients with EGFR positivity (median 64.3 months [43.4 -93.3 months]) tended to be better than that of patients without EGFR expression (median 39.9 months [15.2-Inf mos], log-rank test p value 0.058).	('positivity', 'Var', (37, 47))	('patients', 'Species', '9606', (122, 130))	('EGFR', 'Gene', (32, 36))	('patients', 'Species', '9606', (18, 26))
3282	20421818	Those with high C-kit expression tended toward an inferior OS, but the difference was not statistically significant (log-rank test p = 0.12).	('C-kit', 'Gene', (16, 21))	('inferior OS', 'CPA', (50, 61))	('C-kit', 'Gene', '3815', (16, 21))	('high', 'Var', (11, 15))
3283	20421818	The median OS (Figure 4) for patients with high C-kit expression was 34.6 months (16.0-Inf) compared with 63.6 months (43.4 - 88.0 months) for those with low expression.	('C-kit', 'Gene', (48, 53))	('patients', 'Species', '9606', (29, 37))	('C-kit', 'Gene', '3815', (48, 53))	('high', 'Var', (43, 47))
3296	20421818	Our study confirms other reports demonstrating a high percentage of EGFR positivity in thymic epithelial tumors.	('epithelial tumors', 'Disease', (94, 111))	('epithelial tumors', 'Disease', 'MESH:D002277', (94, 111))	('positivity', 'Var', (73, 83))	('tumor', 'Phenotype', 'HP:0002664', (105, 110))	('tumors', 'Phenotype', 'HP:0002664', (105, 111))	('EGFR', 'Gene', (68, 72))
3302	20421818	Our results demonstrate that the presence of EGFR immunostaining in tumor cells (+1, 2, and 3) was associated with a significantly better PFS with a trend toward improved OS.	('tumor', 'Disease', (68, 73))	('EGFR', 'Gene', (45, 49))	('improved', 'PosReg', (162, 170))	('presence', 'Var', (33, 41))	('tumor', 'Disease', 'MESH:D009369', (68, 73))	('PFS', 'MPA', (138, 141))	('better', 'PosReg', (131, 137))	('tumor', 'Phenotype', 'HP:0002664', (68, 73))
3303	20421818	In addition, the presence of C-kit immunoreactivity was associated with a significantly worse PFS.	('PFS', 'Disease', (94, 97))	('C-kit', 'Gene', (29, 34))	('C-kit', 'Gene', '3815', (29, 34))	('presence', 'Var', (17, 25))	('worse', 'NegReg', (88, 93))
3311	20421818	Further studies are needed to define the frequency of mutations on these markers, whether such mutations carry therapeutic predictive capabilities, and the importance of these pathways on carcinogenesis and drug resistance.	('carcinogenesis', 'Disease', (188, 202))	('carcinogenesis', 'Disease', 'MESH:D063646', (188, 202))	('mutations', 'Var', (54, 63))	('drug resistance', 'Phenotype', 'HP:0020174', (207, 222))
3407	32358402	Deficiencies in T lymphocyte function may induce autoimmune diseases such as myasthenia gravis, erythropoiesis, systemic lupus erythematosus, inflammatory myopathy, and thyroid disease.	('as', 'Gene', '112935892', (181, 183))	('autoimmune diseases', 'Disease', 'MESH:D001327', (49, 68))	('induce', 'Reg', (42, 48))	('thyroid disease', 'Disease', (169, 184))	('T lymphocyte', 'Protein', (16, 28))	('autoimmune diseases', 'Disease', (49, 68))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (49, 68))	('thyroid disease', 'Phenotype', 'HP:0000820', (169, 184))	('systemic lupus erythematosus', 'Disease', (112, 140))	('myasthenia gravis', 'Disease', 'MESH:D009157', (77, 94))	('thyroid disease', 'Disease', 'MESH:D013959', (169, 184))	('inflammatory myopathy', 'Phenotype', 'HP:0009071', (142, 163))	('autoimmune disease', 'Phenotype', 'HP:0002960', (49, 67))	('myopathy', 'Phenotype', 'HP:0003198', (155, 163))	('myopathy', 'Disease', (155, 163))	('as', 'Gene', '112935892', (74, 76))	('systemic lupus erythematosus', 'Phenotype', 'HP:0002725', (112, 140))	('Deficiencies', 'Var', (0, 12))	('systemic lupus erythematosus', 'Disease', 'MESH:D008180', (112, 140))	('myasthenia gravis', 'Disease', (77, 94))	('as', 'Gene', '112935892', (64, 66))	('as', 'Gene', '112935892', (79, 81))	('myasthenia', 'Phenotype', 'HP:0003473', (77, 87))	('erythropoiesis', 'Disease', (96, 110))	('myopathy', 'Disease', 'MESH:D009135', (155, 163))
3467	31891634	In this study, we excluded the following ICD-O-3 histology codes according to the SEER guideline: 9050-9055 (mesothelioma), 9060-9091 (germ cell tumor), 9140 (Kaposi sarcoma), and 9550-9992 (lymphomas, leukemias, myelomas, lymphoreticular, and immunoproliferative diseases).	('9060-9091', 'Var', (124, 133))	('9550-9992', 'Var', (180, 189))	('9140', 'Var', (153, 157))	('Kaposi sarcoma', 'Disease', 'MESH:D012514', (159, 173))	('myelomas', 'Disease', 'MESH:D009101', (213, 221))	('9050-9055', 'Var', (98, 107))	('lymphomas', 'Disease', (191, 200))	('sarcoma', 'Phenotype', 'HP:0100242', (166, 173))	('tumor', 'Disease', (145, 150))	('Kaposi sarcoma', 'Disease', (159, 173))	('immunoproliferative diseases', 'Disease', 'MESH:D007160', (244, 272))	('immunoproliferative diseases', 'Disease', (244, 272))	('tumor', 'Disease', 'MESH:D009369', (145, 150))	('myelomas', 'Disease', (213, 221))	('lymphoreticular', 'Disease', (223, 238))	('leukemias', 'Disease', 'MESH:D007938', (202, 211))	('Kaposi sarcoma', 'Phenotype', 'HP:0100726', (159, 173))	('mesothelioma', 'Disease', (109, 121))	('leukemias', 'Phenotype', 'HP:0001909', (202, 211))	('germ cell tumor', 'Phenotype', 'HP:0100728', (135, 150))	('O-3', 'Chemical', 'MESH:D013481', (45, 48))	('mesothelioma', 'Disease', 'MESH:D008654', (109, 121))	('tumor', 'Phenotype', 'HP:0002664', (145, 150))	('lymphomas', 'Disease', 'MESH:D008223', (191, 200))	('lymphomas', 'Phenotype', 'HP:0002665', (191, 200))	('leukemias', 'Disease', (202, 211))
3468	31891634	Then, we used the ICD-O-3 histology code to identify cases of thymoma (8581-8585), thymic carcinoma (8020, 8023, 8033, 8070, 8082, 8123, 8140, 8200, 8260, 8310, 8430, 8480, 8560, 8576, and 8586), thymic neuroendocrine tumor (8013, 8041, 8045, 8240, and 8249), and other types of tumor (with different codes) according to the WHO Classification of Tumors of Endocrine Organs 4th edition.	('tumor', 'Phenotype', 'HP:0002664', (279, 284))	('8013', 'Var', (225, 229))	('carcinoma', 'Phenotype', 'HP:0030731', (90, 99))	('Tumors', 'Phenotype', 'HP:0002664', (347, 353))	('tumor', 'Disease', (218, 223))	('8020', 'Var', (101, 105))	('thymic neuroendocrine tumor', 'Disease', (196, 223))	('neuroendocrine tumor', 'Phenotype', 'HP:0100634', (203, 223))	('Tumor', 'Phenotype', 'HP:0002664', (347, 352))	('8581-8585', 'Var', (71, 80))	('tumor', 'Disease', 'MESH:D009369', (218, 223))	('8586', 'Var', (189, 193))	('Tumors of Endocrine', 'Disease', 'MESH:D004701', (347, 366))	('O-3', 'Chemical', 'MESH:D013481', (22, 25))	('tumor', 'Disease', (279, 284))	('tumor', 'Phenotype', 'HP:0002664', (218, 223))	('thymic carcinoma', 'Disease', (83, 99))	('thymoma', 'Gene', '7063', (62, 69))	('thymoma', 'Phenotype', 'HP:0100522', (62, 69))	('tumor', 'Disease', 'MESH:D009369', (279, 284))	('thymic neuroendocrine tumor', 'Disease', 'MESH:D018358', (196, 223))	('8070', 'Var', (119, 123))	('thymoma', 'Gene', (62, 69))	('Tumors of Endocrine', 'Disease', (347, 366))	('thymic carcinoma', 'Disease', 'MESH:D013945', (83, 99))
3571	31289591	On multivariate analysis, greater than or equal to 50% abutment of the circumference of an adjacent vessel on CT was statistically associated with an incomplete resection or late stage thymomas.	('greater than', 'Var', (26, 38))	('thymomas', 'Disease', (185, 193))	('thymomas', 'Disease', 'MESH:D013945', (185, 193))	('incomplete resection', 'CPA', (150, 170))	('associated', 'Reg', (131, 141))	('thymoma', 'Phenotype', 'HP:0100522', (185, 192))
3676	30038930	The risk of reactivation is increased in settings of T-cell-mediated immune dysfunction, which may be the result of T-cell exhaustion, deterioration, or deletion.	('deletion', 'Var', (153, 161))	('reactivation', 'MPA', (12, 24))	('immune dysfunction', 'Disease', (69, 87))	('T-cell exhaustion', 'Phenotype', 'HP:0005435', (116, 133))	('immune dysfunction', 'Disease', 'MESH:D007154', (69, 87))
3680	30038930	Although the precise mechanism remains unknown, we hypothesize that our patient's immune dysfunction was most likely due to defective expression of the autoimmune regulator (AIRE) in thymoma resulting in deficient selection and functional T-cell deficits, despite a normal absolute CD4+ T-cell count.	('immune dysfunction', 'Disease', (82, 100))	('autoimmune regulator', 'Gene', (152, 172))	('autoimmune regulator', 'Gene', '326', (152, 172))	('absolute CD4+ T-cell count', 'Phenotype', 'HP:0005407', (273, 299))	('patient', 'Species', '9606', (72, 79))	('selection', 'CPA', (214, 223))	('defective', 'Var', (124, 133))	('CD4', 'Gene', '920', (282, 285))	('thymoma', 'Gene', '7063', (183, 190))	('thymoma', 'Phenotype', 'HP:0100522', (183, 190))	('expression', 'MPA', (134, 144))	('CD4', 'Gene', (282, 285))	('AIRE', 'Gene', (174, 178))	('thymoma', 'Gene', (183, 190))	('AIRE', 'Gene', '326', (174, 178))	('T-cell deficits', 'Phenotype', 'HP:0005435', (239, 254))	('immune dysfunction', 'Disease', 'MESH:D007154', (82, 100))	('functional T-cell deficits', 'CPA', (228, 254))	('deficient', 'NegReg', (204, 213))
3804	24457247	Laboratory workup showed transaminitis (AST 377 U/L, upper limit of normal (ULN) 34 U/L; ALT 357 U/L, ULN 41 U/L) elevated creatine kinase (CK 1462 U/L, ULN 252 U/L), and lactate dehydrogenase (LDH 947 U/L, ULN 226 U/L), no serological evidence of hepatitis A, B or C infection and absence of anti-smooth muscle and anti-nuclear antibodies.	('lactate dehydrogenase', 'MPA', (171, 192))	('hepatitis A, B or C infection', 'Disease', 'MESH:D006509', (248, 277))	('LDH 947 U/L', 'Var', (194, 205))	('hepatitis', 'Phenotype', 'HP:0012115', (248, 257))	('CK', 'Gene', '51727', (140, 142))	('creatine kinase', 'MPA', (123, 138))	('elevated creatine kinase', 'Phenotype', 'HP:0003236', (114, 138))	('transaminitis', 'Disease', (25, 38))	('AST', 'Gene', (40, 43))	('elevated', 'PosReg', (114, 122))	('ALT 357 U/L', 'Var', (89, 100))	('AST', 'Gene', '26503', (40, 43))
3893	21819556	Laboratory toxicity was defined as white cell count <=3.0 x109/L, neutrophils <=1.5 x109/L, or platelets <=100 x109/L, or AST, ALT and GGT > 2-fold the upper limit of normal.	('AST', 'Gene', (122, 125))	('ALT', 'MPA', (127, 130))	('neutrophils', 'CPA', (66, 77))	('AST', 'Gene', '26503', (122, 125))	('toxicity', 'Disease', 'MESH:D064420', (11, 19))	('white cell count', 'CPA', (35, 51))	('toxicity', 'Disease', (11, 19))	('platelets', 'CPA', (95, 104))	('Laboratory', 'Disease', (0, 10))	('<=100 x109/L', 'Var', (105, 117))	('GGT', 'Gene', '728441', (135, 138))	('GGT', 'Gene', (135, 138))
3912	21819556	The average daily prednisone dose per kilogram bodyweight at month 12 was also lower in the MTX-group being on average 0.15 mg/kg prednisone (SD +- 0.08) daily as compared with that in the AZA-group of 0.31 mg/kg (SD +- 0.22)(mean Delta 0.16; 95% CI 0.29; 0.03; p = 0.019).	('MTX-group', 'Var', (92, 101))	('AZA', 'Chemical', 'MESH:D001379', (189, 192))	('prednisone', 'Chemical', 'MESH:D011241', (18, 28))	('lower', 'NegReg', (79, 84))	('MTX', 'Chemical', 'MESH:D008727', (92, 95))	('prednisone', 'Chemical', 'MESH:D011241', (130, 140))
3950	21819556	This study represents the "real-life" situation in that a spectrum of patients with generalized MG were recruited including AChR-Ab-negative and thymoma-associated variants: two less prevalent MG subgroups often associated with severe disease requiring immunosuppression.	('thymoma', 'Phenotype', 'HP:0100522', (145, 152))	('variants', 'Var', (164, 172))	('generalized', 'Disease', (84, 95))	('patients', 'Species', '9606', (70, 78))
3959	33674910	Molecular pathology of thymomas: implications for diagnosis and therapy Thymomas exhibit a unique genomic landscape, comprising the lowest on average total mutational burden among adult human cancers; a unique point mutation in the GTF2I gene in WHO type A and AB thymomas (and rarely others); almost unique KMT2A-MAML2 translocations in rare WHO type B2 and B3 thymomas; a unique YAP1-MAML2 translocation in almost all metaplastic thymomas; and unique miRNA profiles in relation to GTF2I mutational status and WHO histotypes.	('YAP1', 'Gene', '10413', (381, 385))	('thymoma', 'Phenotype', 'HP:0100522', (362, 369))	('cancers', 'Phenotype', 'HP:0002664', (192, 199))	('KMT2A', 'Gene', '4297', (308, 313))	('AB thymomas', 'Disease', (261, 272))	('cancers', 'Disease', (192, 199))	('thymomas', 'Disease', 'MESH:D013945', (362, 370))	('thymoma', 'Phenotype', 'HP:0100522', (432, 439))	('thymomas', 'Disease', (23, 31))	('cancer', 'Phenotype', 'HP:0002664', (192, 198))	('YAP1', 'Gene', (381, 385))	('AB thymomas', 'Disease', 'MESH:D013945', (261, 272))	('thymomas', 'Disease', 'MESH:D013945', (432, 440))	('thymomas', 'Disease', (362, 370))	('GTF2I', 'Gene', '2969', (232, 237))	('MAML2', 'Gene', (314, 319))	('thymoma', 'Phenotype', 'HP:0100522', (264, 271))	('MAML2', 'Gene', (386, 391))	('thymomas', 'Disease', (432, 440))	('GTF2I', 'Gene', (232, 237))	('KMT2A', 'Gene', (308, 313))	('thymomas', 'Disease', 'MESH:D013945', (264, 272))	('cancers', 'Disease', 'MESH:D009369', (192, 199))	('GTF2I', 'Gene', '2969', (483, 488))	('MAML2', 'Gene', '84441', (314, 319))	('MAML2', 'Gene', '84441', (386, 391))	('GTF2I', 'Gene', (483, 488))	('thymomas', 'Disease', (264, 272))	('point mutation', 'Var', (210, 224))	('thymoma', 'Phenotype', 'HP:0100522', (23, 30))	('Thymoma', 'Phenotype', 'HP:0100522', (72, 79))	('human', 'Species', '9606', (186, 191))	('thymomas', 'Disease', 'MESH:D013945', (23, 31))
3960	33674910	While most thymomas can be diagnosed solely on the basis of morphological features, mutational analyses can solve challenging differential diagnostic problems.	('thymoma', 'Phenotype', 'HP:0100522', (11, 18))	('thymomas', 'Disease', (11, 19))	('thymomas', 'Disease', 'MESH:D013945', (11, 19))	('mutational', 'Var', (84, 94))
3988	33674910	CD247 hypoexpression entails susceptibility to infections and, hypothetically, the increased prevalence of non-thymic cancers in thymoma patients.	('hypoexpression', 'Var', (6, 20))	('cancers', 'Disease', (118, 125))	('cancers', 'Disease', 'MESH:D009369', (118, 125))	('CD247', 'Gene', '919', (0, 5))	('susceptibility to infections', 'Phenotype', 'HP:0002719', (29, 57))	('thymoma', 'Disease', (129, 136))	('CD247', 'Gene', (0, 5))	('infections', 'Disease', 'MESH:D007239', (47, 57))	('thymoma', 'Phenotype', 'HP:0100522', (129, 136))	('patients', 'Species', '9606', (137, 145))	('cancer', 'Phenotype', 'HP:0002664', (118, 124))	('infections', 'Disease', (47, 57))	('susceptibility', 'Reg', (29, 43))	('cancers', 'Phenotype', 'HP:0002664', (118, 125))	('thymoma', 'Disease', 'MESH:D013945', (129, 136))
3994	33674910	Also, gains and losses were commonly large-scale alterations such as whole chromosome or chromosome arm losses and gains, with losses of chromosome 6 material (harboring the FOXC1 tumor suppressor gene at 6p25.3) and gains in 1q as the most common structural abnormalities across all histotypes.	('FOXC1 tumor', 'Disease', 'MESH:D009369', (174, 185))	('chromosome arm', 'CPA', (89, 103))	('gains', 'PosReg', (115, 120))	('tumor', 'Phenotype', 'HP:0002664', (180, 185))	('structural abnormalities', 'Disease', 'MESH:C566527', (248, 272))	('FOXC1 tumor', 'Disease', (174, 185))	('losses', 'NegReg', (127, 133))	('gains in', 'Var', (217, 225))	('losses', 'NegReg', (104, 110))	('structural abnormalities', 'Disease', (248, 272))
3995	33674910	One of the most prevalent somatic mutations of thymomas is a single nucleotide hot-spot mutation (c.74146970T>A; p.L424H) in the general transcription factor IIi gene (GTF2I).	('p.L424H', 'Mutation', 'p.L424H', (113, 120))	('GTF2I', 'Gene', (168, 173))	('c.74146970T>A', 'Mutation', 'c.74146970T>A', (98, 111))	('thymoma', 'Phenotype', 'HP:0100522', (47, 54))	('c.74146970T>A;', 'Var', (98, 112))	('GTF2I', 'Gene', '2969', (168, 173))	('thymomas', 'Disease', (47, 55))	('thymomas', 'Disease', 'MESH:D013945', (47, 55))
3997	33674910	Less common recurrent alterations concern gain-of-function mutations of HRAS (mainly in type A and AB thymomas) and NRAS (in type A and B thymomas), and loss-of-function mutations of TP53 (in type B thymomas and TCs).	('TP53', 'Gene', '7157', (183, 187))	('B thymomas', 'Disease', 'MESH:D013945', (197, 207))	('type B thymomas', 'Disease', (192, 207))	('thymoma', 'Phenotype', 'HP:0100522', (138, 145))	('type B thymomas', 'Disease', 'MESH:D013945', (192, 207))	('B thymomas', 'Disease', (136, 146))	('B thymomas', 'Disease', 'MESH:D013945', (100, 110))	('loss-of-function', 'NegReg', (153, 169))	('NRAS', 'Gene', '4893', (116, 120))	('AB thymomas', 'Disease', (99, 110))	('TP53', 'Gene', (183, 187))	('gain-of-function', 'PosReg', (42, 58))	('thymoma', 'Phenotype', 'HP:0100522', (199, 206))	('mutations', 'Var', (59, 68))	('AB thymomas', 'Disease', 'MESH:D013945', (99, 110))	('B thymomas', 'Disease', 'MESH:D013945', (136, 146))	('HRAS', 'Gene', '3265', (72, 76))	('mutations', 'Var', (170, 179))	('HRAS', 'Gene', (72, 76))	('NRAS', 'Gene', (116, 120))	('thymoma', 'Phenotype', 'HP:0100522', (102, 109))	('type A', 'Disease', (88, 94))
3998	33674910	The enrichment of C>T mutations within CpG di-nucleotides is an age-related signature that fits well with the age of thymoma patients.	('fits', 'Disease', (91, 95))	('thymoma', 'Disease', 'MESH:D013945', (117, 124))	('C>T mutations', 'Var', (18, 31))	('di-nucleotides', 'Chemical', 'MESH:D015226', (43, 57))	('thymoma', 'Disease', (117, 124))	('fits', 'Disease', 'MESH:D012640', (91, 95))	('thymoma', 'Phenotype', 'HP:0100522', (117, 124))	('patients', 'Species', '9606', (125, 133))
3999	33674910	KIT mutations and oncogenic driver mutations or translocations that are characteristic of lung and other cancers have not been observed.	('translocations', 'Var', (48, 62))	('cancers', 'Phenotype', 'HP:0002664', (105, 112))	('cancers', 'Disease', (105, 112))	('cancers', 'Disease', 'MESH:D009369', (105, 112))	('KIT', 'Gene', '3815', (0, 3))	('cancer', 'Phenotype', 'HP:0002664', (105, 111))	('mutations', 'Var', (4, 13))	('KIT', 'Gene', (0, 3))
4001	33674910	While a single TC among the 10 tested carcinomas showed microsatellite instability (MSI) due to a pathogenic nonsense mutation (E37*) in the MHL1 gene, none of the 107 tested thymomas exhibited this oncogenic feature.	('carcinomas', 'Disease', 'MESH:D009369', (38, 48))	('carcinomas', 'Disease', (38, 48))	('E37*', 'Var', (128, 132))	('E37*', 'SUBSTITUTION', 'None', (128, 132))	('pathogenic', 'Reg', (98, 108))	('microsatellite instability', 'Disease', 'MESH:D053842', (56, 82))	('carcinomas', 'Phenotype', 'HP:0030731', (38, 48))	('thymomas', 'Disease', 'MESH:D013945', (175, 183))	('thymoma', 'Phenotype', 'HP:0100522', (175, 182))	('microsatellite instability', 'Disease', (56, 82))	('MHL1', 'Gene', (141, 145))	('thymomas', 'Disease', (175, 183))
4005	33674910	2) vaguely resembles spindle cell areas in type A and AB thymomas, GTF2I mutations were consistently absent.	('AB thymomas', 'Disease', (54, 65))	('GTF2I', 'Gene', (67, 72))	('thymoma', 'Phenotype', 'HP:0100522', (57, 64))	('GTF2I', 'Gene', '2969', (67, 72))	('absent', 'NegReg', (101, 107))	('mutations', 'Var', (73, 82))	('AB thymomas', 'Disease', 'MESH:D013945', (54, 65))
4007	33674910	Recurrent KMT2A-MAML2 translocations were recently identified in 6% of clinically aggressive type B2 and B3 thymomas and a single case of combined TC (B3 thymoma with small TC component).	('thymoma', 'Disease', 'MESH:D013945', (154, 161))	('thymoma', 'Disease', (154, 161))	('identified', 'Reg', (51, 61))	('thymomas', 'Disease', (108, 116))	('thymomas', 'Disease', 'MESH:D013945', (108, 116))	('thymoma', 'Phenotype', 'HP:0100522', (154, 161))	('thymoma', 'Disease', 'MESH:D013945', (108, 115))	('translocations', 'Var', (22, 36))	('KMT2A', 'Gene', (10, 15))	('thymoma', 'Disease', (108, 115))	('MAML2', 'Gene', (16, 21))	('KMT2A', 'Gene', '4297', (10, 15))	('thymoma', 'Phenotype', 'HP:0100522', (108, 115))	('MAML2', 'Gene', '84441', (16, 21))
4008	33674910	The translocations variably involved exons 8, 9, 10, or 11 of KMT2A and exon 2 of MAML2, and are highly characteristic of type B2 and B3 thymomas, because they were previously found only in very rare leukemias, myelodysplastic syndromes, and one plasmacytoma but not in any other tumor among over 250.000 cases sequenced by Foundation Medicine, including 266 thymic carcinomas.	('translocations', 'Var', (4, 18))	('leukemias', 'Disease', (200, 209))	('carcinomas', 'Phenotype', 'HP:0030731', (366, 376))	('plasmacytoma', 'Phenotype', 'HP:0011857', (246, 258))	('KMT2A', 'Gene', '4297', (62, 67))	('myelodysplastic syndromes', 'Phenotype', 'HP:0002863', (211, 236))	('myelodysplastic syndromes', 'Disease', (211, 236))	('thymoma', 'Phenotype', 'HP:0100522', (137, 144))	('tumor', 'Disease', (280, 285))	('thymomas', 'Disease', 'MESH:D013945', (137, 145))	('MAML2', 'Gene', (82, 87))	('myelodysplastic syndromes', 'Disease', 'MESH:D009190', (211, 236))	('tumor', 'Disease', 'MESH:D009369', (280, 285))	('leukemias', 'Disease', 'MESH:D007938', (200, 209))	('KMT2A', 'Gene', (62, 67))	('thymomas', 'Disease', (137, 145))	('MAML2', 'Gene', '84441', (82, 87))	('thymic carcinomas', 'Disease', (359, 376))	('leukemias', 'Phenotype', 'HP:0001909', (200, 209))	('involved', 'Reg', (28, 36))	('tumor', 'Phenotype', 'HP:0002664', (280, 285))	('thymic carcinomas', 'Disease', 'MESH:D013953', (359, 376))
4009	33674910	The function of the respective fusion proteins in thymomas is currently unclear, but might be oncogenic drivers, since 7 of the 11 cases did not harbor any concurrent mutations, while the four others showed only single additional mutations/variants in TP53, ARID1A, SFB1, and the TERT promoter.	('TERT', 'Gene', '7015', (280, 284))	('ARID1A', 'Gene', '8289', (258, 264))	('SFB1', 'Gene', (266, 270))	('ARID1A', 'Gene', (258, 264))	('mutations/variants', 'Var', (230, 248))	('TP53', 'Gene', '7157', (252, 256))	('thymoma', 'Phenotype', 'HP:0100522', (50, 57))	('thymomas', 'Disease', 'MESH:D013945', (50, 58))	('TERT', 'Gene', (280, 284))	('thymomas', 'Disease', (50, 58))	('TP53', 'Gene', (252, 256))
4010	33674910	Furthermore, KMT2A (also known as MLL) is a known oncogenic driver in translocations with other partner genes in sarcomas and leukemias.	('translocations', 'Var', (70, 84))	('MLL', 'Gene', (34, 37))	('sarcomas and leukemias', 'Disease', 'MESH:D012509', (113, 135))	('MLL', 'Gene', '4297', (34, 37))	('KMT2A', 'Gene', (13, 18))	('KMT2A', 'Gene', '4297', (13, 18))	('leukemias', 'Phenotype', 'HP:0001909', (126, 135))	('sarcomas', 'Phenotype', 'HP:0100242', (113, 121))
4014	33674910	3) or combined SMARCA4/SMARCA2 deficiency.	('SMARCA4', 'Gene', '6597', (15, 22))	('SMARCA2', 'Gene', (23, 30))	('SMARCA2', 'Gene', '6595', (23, 30))	('deficiency', 'Var', (31, 41))	('SMARCA4', 'Gene', (15, 22))
4027	33674910	However, no recurrent genetic alterations were identified even in heavily pretreated thymomas, while TC frequently showed mutations in potential oncogenic driver genes with a role in chromatin remodeling (e.g., SMARCA4), histone modification (BAP1, SETD2, ASXL1), and DNA methylation (TET2, DNMT3a34, WT1).	('WT1', 'Gene', '7490', (301, 304))	('BAP1', 'Gene', (243, 247))	('TET2', 'Gene', (285, 289))	('thymomas', 'Disease', (85, 93))	('thymomas', 'Disease', 'MESH:D013945', (85, 93))	('SETD2', 'Gene', '29072', (249, 254))	('SETD2', 'Gene', (249, 254))	('ASXL1', 'Gene', '171023', (256, 261))	('SMARCA4', 'Gene', '6597', (211, 218))	('thymoma', 'Phenotype', 'HP:0100522', (85, 92))	('SMARCA4', 'Gene', (211, 218))	('ASXL1', 'Gene', (256, 261))	('mutations', 'Var', (122, 131))	('BAP1', 'Gene', '8314', (243, 247))	('DNA', 'MPA', (268, 271))	('TET2', 'Gene', '54790', (285, 289))	('histone modification', 'MPA', (221, 241))	('WT1', 'Gene', (301, 304))
4028	33674910	Mutations in these genes appear worth testing as biomarkers in TCs, as they constitute promising biomarkers in advanced renal cell carcinomas treated with sunitinib, sorafenib, and everolimus, i.e., drugs that are used in advanced TCs (reviewed in).	('carcinomas', 'Phenotype', 'HP:0030731', (131, 141))	('sorafenib', 'Chemical', 'MESH:D000077157', (166, 175))	('renal cell carcinomas', 'Disease', 'MESH:C538614', (120, 141))	('sunitinib', 'Chemical', 'MESH:D000077210', (155, 164))	('renal cell carcinomas', 'Phenotype', 'HP:0005584', (120, 141))	('Mutations', 'Var', (0, 9))	('everolimus', 'Chemical', 'MESH:D000068338', (181, 191))	('renal cell carcinomas', 'Disease', (120, 141))
4031	33674910	A GTF2I (p.L424H) mutation strongly argues for the diagnosis of type A over a focally spindly type B3 thymoma or a metaplastic thymoma.	('p.L424H', 'Mutation', 'p.L424H', (9, 16))	('GTF2I', 'Gene', (2, 7))	('type A', 'Disease', (64, 70))	('thymoma', 'Disease', 'MESH:D013945', (127, 134))	('thymoma', 'Disease', (127, 134))	('thymoma', 'Disease', 'MESH:D013945', (102, 109))	('p.L424H', 'Var', (9, 16))	('GTF2I', 'Gene', '2969', (2, 7))	('thymoma', 'Disease', (102, 109))	('thymoma', 'Phenotype', 'HP:0100522', (127, 134))	('thymoma', 'Phenotype', 'HP:0100522', (102, 109))
4036	33674910	The diagnostic relevance of the recently described KMT2A-MAML2 translocations in aggressive type B2 and B3 thymomas needs confirmation.	('thymoma', 'Phenotype', 'HP:0100522', (107, 114))	('translocations', 'Var', (63, 77))	('KMT2A', 'Gene', '4297', (51, 56))	('thymomas', 'Disease', (107, 115))	('thymomas', 'Disease', 'MESH:D013945', (107, 115))	('KMT2A', 'Gene', (51, 56))	('MAML2', 'Gene', '84441', (57, 62))	('MAML2', 'Gene', (57, 62))
4050	32051380	Approximately 85% of all MG patients have an autoantibody against the nicotinic acetylcholine receptor (AChR) in their serum.	('autoantibody', 'Var', (45, 57))	('AChR', 'Gene', (104, 108))	('acetylcholine', 'Chemical', 'MESH:D000109', (80, 93))	('MG', 'Disease', 'MESH:D000080343', (25, 27))	('patients', 'Species', '9606', (28, 36))
4057	32051380	An international, randomized, and controlled trial involving 126 adult MG patients with anti-AChR antibody showed a distinct benefit of thymectomy in patients <50 years old at onset compared with those >=50 years old.	('MG', 'Disease', 'MESH:D000080343', (71, 73))	('anti-AChR antibody', 'Var', (88, 106))	('thymectomy', 'Disease', (136, 146))	('patients', 'Species', '9606', (74, 82))	('patients', 'Species', '9606', (150, 158))	('benefit', 'PosReg', (125, 132))	('antibody', 'Var', (98, 106))
4059	32051380	We herein report a case in which anti-LRP4 antibody-positive MG was complicated by a thymoma, and surgical resection of this thymoma successfully ameliorated the patient's symptoms.	('LRP4', 'Gene', (38, 42))	('thymoma', 'Disease', 'MESH:D013945', (85, 92))	('thymoma', 'Phenotype', 'HP:0100522', (125, 132))	('thymoma', 'Disease', (85, 92))	('LRP4', 'Gene', '4038', (38, 42))	('thymoma', 'Phenotype', 'HP:0100522', (85, 92))	('antibody-positive', 'Var', (43, 60))	('thymoma', 'Disease', 'MESH:D013945', (125, 132))	('patient', 'Species', '9606', (162, 169))	('MG', 'Disease', 'MESH:D000080343', (61, 63))	('thymoma', 'Disease', (125, 132))
4079	32051380	MG patients with anti-LRP4 antibodies were mainly female, and their symptoms were relatively mild with predominant ocular muscle involvement.	('LRP4', 'Gene', '4038', (22, 26))	('MG', 'Disease', 'MESH:D000080343', (0, 2))	('antibodies', 'Var', (27, 37))	('patients', 'Species', '9606', (3, 11))	('LRP4', 'Gene', (22, 26))
4128	27346413	Patients who received PORT had a younger median age, were more likely of male gender, had a higher rate of myasthenia gravis, higher proportion of stage III disease, larger tumors, more likely WHO type B1, B2 or B3 histology than A or AB and less likely to having received chemotherapy.	('myasthenia gravis', 'Disease', (107, 124))	('myasthenia gravis', 'Disease', 'MESH:D009157', (107, 124))	('tumor', 'Phenotype', 'HP:0002664', (173, 178))	('Patients', 'Species', '9606', (0, 8))	('stage III disease', 'Disease', (147, 164))	('myasthenia', 'Phenotype', 'HP:0003473', (107, 117))	('tumors', 'Disease', 'MESH:D009369', (173, 179))	('tumors', 'Disease', (173, 179))	('tumors', 'Phenotype', 'HP:0002664', (173, 179))	('B2 or B3 histology', 'Var', (206, 224))
4168	27346413	When analyzing subgroups with different histologic subtypes, the patient group with stage III, WHO type B1, B2 or B3, thymomas had the greatest benefit with PORT.	('B2 or B3', 'Var', (108, 116))	('thymoma', 'Phenotype', 'HP:0100522', (118, 125))	('benefit', 'PosReg', (144, 151))	('thymomas', 'Disease', 'MESH:D013945', (118, 126))	('thymomas', 'Disease', (118, 126))	('patient', 'Species', '9606', (65, 72))
4389	23125865	Expression of the Autoimmune Regulator Gene and Its Relevance to the Mechanisms of Central and Peripheral Tolerance The autoimmune polyendocrine syndrome type 1 (APS-1) is a monogenic disease due to pathogenic variants occurring in the autoimmune regulator (AIRE) gene.	('variants', 'Var', (210, 218))	('autoimmune polyendocrine syndrome type 1 (APS-1)', 'Disease', 'MESH:C538275', (120, 168))	('AIRE', 'Gene', (258, 262))	('autoimmune regulator', 'Gene', (236, 256))	('Autoimmune Regulator', 'Gene', '326', (18, 38))	('autoimmune regulator', 'Gene', '326', (236, 256))	('pathogenic', 'Reg', (199, 209))	('Autoimmune Regulator', 'Gene', (18, 38))
4390	23125865	Dysregulation of thymic AIRE expression in genetically transmitted and acquired diseases other than APS-1 may contribute to further forms of autoimmunity.	('autoimmunity', 'Disease', (141, 153))	('Dysregulation', 'Var', (0, 13))	('autoimmunity', 'Disease', 'MESH:D001327', (141, 153))	('APS-1', 'Gene', '326', (100, 105))	('APS-1', 'Gene', (100, 105))	('contribute', 'Reg', (110, 120))	('autoimmunity', 'Phenotype', 'HP:0002960', (141, 153))
4392	23125865	Pathogenic variants in the autoimmune regulator (AIRE) gene cause the autoimmune polyendocrine syndrome type 1 (APS-1), also called autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), an autosomal recessive disease characterized by immunological disturbances such as difficulty to eradicate surface candidiasis and autoimmunity to various organs, mainly endocrine glands.	('autoimmunity', 'Disease', 'MESH:D001327', (336, 348))	('autoimmunity', 'Phenotype', 'HP:0002960', (336, 348))	('AIRE', 'Gene', (49, 53))	('APECED', 'Gene', '326', (196, 202))	('autosomal recessive disease', 'Disease', (208, 235))	('variants', 'Var', (11, 19))	('candidiasis', 'Disease', (320, 331))	('candidiasis', 'Disease', (162, 173))	('ectodermal dystrophy', 'Phenotype', 'HP:0000968', (174, 194))	('candidiasis', 'Disease', 'MESH:D002177', (320, 331))	('candidiasis', 'Disease', 'MESH:D002177', (162, 173))	('autosomal recessive disease', 'Disease', 'MESH:D030342', (208, 235))	('autoimmune regulator', 'Gene', '326', (27, 47))	('autoimmune polyendocrine syndrome type 1 (APS-1)', 'Disease', 'MESH:C538275', (70, 118))	('autoimmunity', 'Disease', (336, 348))	('autoimmune regulator', 'Gene', (27, 47))	('autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy', 'Disease', 'MESH:D016884', (132, 194))	('cause', 'Reg', (60, 65))	('immunological disturbances', 'Phenotype', 'HP:0002715', (253, 279))	('APECED', 'Gene', (196, 202))
4420	23125865	Such cells were able to induce the deletion of CD8+ T-cell clones bearing TCRs specific for antigens encoded by Aire-dependent genes: the clones had been transferred into irradiated mice reconstituted with beta 2-microglobulin-deficient (beta 2-m -/-) bone marrow to ensure that only radioresistant stromal cells of the secondary lymphoid organs could interact with them.	('beta 2-microglobulin', 'Gene', (206, 226))	('CD8', 'Gene', (47, 50))	('CD8', 'Gene', '925', (47, 50))	('mice', 'Species', '10090', (182, 186))	('beta 2-m', 'Gene', '12010', (206, 214))	('beta 2-microglobulin', 'Gene', '12010', (206, 226))	('deletion', 'Var', (35, 43))	('beta 2-m', 'Gene', (238, 246))	('beta 2-m', 'Gene', '12010', (238, 246))
4425	23125865	AIRE expression is confined to a final stage of cell maturation, as shown in vitro and in vivo by the postmitotic status of murine Aire+ mTECs; in addition, Aire+ mTECs show a very limited life span.	('life span', 'CPA', (189, 198))	('murine', 'Species', '10090', (124, 130))	('Aire+', 'Var', (157, 162))
4427	23125865	This led the researchers to suggest that, in human field, the condition of heterozygosity for pathogenic AIRE variants could confer a risk for the onset of sporadic autoimmune diseases, when acting in synergy with other susceptibility factors.	('autoimmune diseases', 'Disease', 'MESH:D001327', (165, 184))	('risk', 'Reg', (134, 138))	('variants', 'Var', (110, 118))	('human', 'Species', '9606', (45, 50))	('autoimmune diseases', 'Disease', (165, 184))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (165, 184))	('autoimmune disease', 'Phenotype', 'HP:0002960', (165, 183))	('AIRE', 'Gene', (105, 109))
4434	23125865	Impairment in various steps of T-cell maturation may cause the disease: the most frequent defect is caused by pathogenic variants in the recombinase-activating genes 1 and 2 (RAG-1 and RAG-2, resp.).	('caused', 'Reg', (100, 106))	('RAG-1', 'Gene', '5896', (175, 180))	('variants', 'Var', (121, 129))	('RAG-2', 'Gene', (185, 190))	('RAG-2', 'Gene', '5897', (185, 190))	('RAG-1', 'Gene', (175, 180))
4439	23125865	A reasonable interpretation of what happens in these conditions leads to suppose that the thymi of the patients bearing genetically transmitted defects of the molecules involved in the developmental steps of T lymphocytes (with privileged reference to the construction of TCR diversity), show abnormalities of TEC differentiation, and consequently of AIRE expression, that are proportional to the timing of intervention of the same factors; hypomorphic variants of the related genes would result in more subtle disturbances.	('defects', 'Var', (144, 151))	('expression', 'MPA', (356, 366))	('hypomorphic variants', 'Var', (441, 461))	('patients', 'Species', '9606', (103, 111))	('TEC differentiation', 'CPA', (310, 329))
4440	23125865	Thymomas are rare tumors derived from TECs that are often associated with autoimmune diseases, mainly myasthenia gravis, caused by Abs to the acetylcholine receptor (AChR).	('caused by', 'Reg', (121, 130))	('autoimmune diseases', 'Disease', (74, 93))	('Thymomas', 'Disease', 'MESH:D013945', (0, 8))	('Thymoma', 'Phenotype', 'HP:0100522', (0, 7))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (74, 93))	('Thymomas', 'Disease', (0, 8))	('autoimmune disease', 'Phenotype', 'HP:0002960', (74, 92))	('myasthenia', 'Phenotype', 'HP:0003473', (102, 112))	('myasthenia gravis', 'Disease', (102, 119))	('tumors', 'Disease', (18, 24))	('tumors', 'Disease', 'MESH:D009369', (18, 24))	('tumors', 'Phenotype', 'HP:0002664', (18, 24))	('autoimmune diseases', 'Disease', 'MESH:D001327', (74, 93))	('Abs to', 'Var', (131, 137))	('myasthenia gravis', 'Disease', 'MESH:D009157', (102, 119))	('tumor', 'Phenotype', 'HP:0002664', (18, 23))
4455	23125865	Rag -/- mouse recalls the most frequent defect causing Omenn syndrome: as reported, RAG/Rag proteins are indispensable to create TCR diversity and an adequate T-cell repertoire; the consequence of their deficiency is an impaired thymocyte maturation, with a block at DN3 stage.	('recalls', 'Disease', (14, 21))	('Omenn syndrome', 'Disease', 'MESH:C538564', (55, 69))	('Omenn syndrome', 'Disease', (55, 69))	('deficiency', 'Var', (203, 213))	('thymocyte maturation', 'CPA', (229, 249))	('mouse', 'Species', '10090', (8, 13))	('impaired', 'NegReg', (220, 228))	('recalls', 'Disease', 'MESH:D008569', (14, 21))
4458	23125865	As well as in human field, following studies suggest that the degree of thymic abnormalities, Aire expression included, depends on how precociously the factors damaged by pathogenic variants of the encoding genes act in the construction of TCR diversity.	('thymic abnormalities', 'Phenotype', 'HP:0000777', (72, 92))	('human', 'Species', '9606', (14, 19))	('variants', 'Var', (182, 190))	('thymic abnormalities', 'Disease', 'MESH:D013953', (72, 92))	('thymic abnormalities', 'Disease', (72, 92))
4506	22007295	Some MG patients with anti-MuSK antibodies are hypersensitive to an increase in acetylcholine concentration.	('antibodies', 'Var', (32, 42))	('anti-MuSK antibodies', 'Phenotype', 'HP:0030210', (22, 42))	('MuSK', 'Gene', (27, 31))	('acetylcholine', 'Chemical', 'MESH:D000109', (80, 93))	('MuSK antibodies', 'Phenotype', 'HP:0030210', (27, 42))	('hypersensitive', 'Disease', 'MESH:D004342', (47, 61))	('MuSK', 'Gene', '4593', (27, 31))	('increase', 'PosReg', (68, 76))	('hypersensitive', 'Disease', (47, 61))	('acetylcholine concentration', 'MPA', (80, 107))	('patients', 'Species', '9606', (8, 16))
4535	22007295	For milder MG, the risk of progressive multifocal leucoencephalopathy and other potential long-term side effects probably outweigh its therapeutic potential.	('milder', 'Var', (4, 10))	('multifocal leucoencephalopathy', 'Disease', (39, 69))	('multifocal leucoencephalopathy', 'Disease', 'None', (39, 69))	('progressive multifocal leucoencephalopathy', 'Phenotype', 'HP:0006980', (27, 69))
4551	22007295	For MG patients with anti-MuSK antibodies, the majority of evidence points to no therapeutic effect of thymectomy.	('MuSK antibodies', 'Phenotype', 'HP:0030210', (26, 41))	('MuSK', 'Gene', '4593', (26, 30))	('MuSK', 'Gene', (26, 30))	('anti-MuSK antibodies', 'Phenotype', 'HP:0030210', (21, 41))	('antibodies', 'Var', (31, 41))	('patients', 'Species', '9606', (7, 15))
4750	31791411	Patients who were potential candidates for first-line CT-guided RFA were as follows: (1) patients with stage I thymomas according to the Masaoka staging system; (2) patients with an East Coast Oncology Group (ECOG) performance status value <=2; (3) patients who were not considered high-risk for anesthesia and surgery; (4) patients with normal coagulation function without bleeding tendency; and (5) patients who strongly refused any other further treatment but voluntarily accepted RFA after being informed of the potential risks and benefits.	('patients', 'Species', '9606', (324, 332))	('thymoma', 'Phenotype', 'HP:0100522', (111, 118))	('patients', 'Species', '9606', (249, 257))	('Oncology', 'Phenotype', 'HP:0002664', (193, 201))	('thymomas', 'Disease', (111, 119))	('patients', 'Species', '9606', (401, 409))	('thymomas', 'Disease', 'MESH:D013945', (111, 119))	('Patients', 'Species', '9606', (0, 8))	('bleeding', 'Disease', 'MESH:D006470', (374, 382))	('patients', 'Species', '9606', (89, 97))	('patients', 'Species', '9606', (165, 173))	('bleeding tendency', 'Phenotype', 'HP:0001892', (374, 391))	('<=2', 'Var', (240, 243))	('bleeding', 'Disease', (374, 382))
4893	26915359	Based on c-Kit gene mutant status, drugs that inhibit c-Kit, such as imatinib, sorafenib, and sunitinib, may provide better results.	('sorafenib', 'Chemical', 'MESH:D000077157', (79, 88))	('c-Kit', 'Gene', (54, 59))	('inhibit', 'NegReg', (46, 53))	('sunitinib', 'Chemical', 'MESH:D000077210', (94, 103))	('c-Kit', 'Gene', '3815', (54, 59))	('c-Kit', 'Gene', (9, 14))	('mutant', 'Var', (20, 26))	('c-Kit', 'Gene', '3815', (9, 14))	('imatinib', 'Chemical', 'MESH:D000068877', (69, 77))
4931	26173602	After the pathological diagnosis of thymic lesion, tests for the presence of autoantibodies were positive for antinuclear antibodies, rheumatic factor, and anti-SSA/Ro antibodies.	('rheumatic', 'Disease', 'MESH:D012216', (134, 143))	('rheumatic', 'Disease', (134, 143))	('thymic lesion', 'Disease', (36, 49))	('thymic lesion', 'Disease', 'MESH:D013953', (36, 49))	('antinuclear antibodies', 'Protein', (110, 132))	('antinuclear antibodies', 'Phenotype', 'HP:0003493', (110, 132))	('positive for antinuclear antibodies', 'Phenotype', 'HP:0003493', (97, 132))	('anti-SSA/Ro', 'Var', (156, 167))
4954	26173602	Lymphoid markers revealed organized mixed distribution of CD3+, CD5+, CD20+, and CD79+ cells and did not show monoclonal proliferation of B cells or T cells (Fig.	('CD79+ cells', 'Var', (81, 92))	('CD20', 'Gene', '54474', (70, 74))	('CD20', 'Gene', (70, 74))	('CD5', 'Gene', (64, 67))	('CD3+', 'Var', (58, 62))	('CD5', 'Gene', '921', (64, 67))
5004	25889429	The results of the present study provide a perspective on lncRNA expression in MG. We identify a subset of aberrant lncRNAs and mRNAs as potential biomarkers for the diagnosis of MG.	('ncRNA', 'Gene', (59, 64))	('aberrant', 'Var', (107, 115))	('ncRNA', 'Gene', (117, 122))	('ncRNA', 'Gene', '220202', (59, 64))	('ncRNA', 'Gene', '220202', (117, 122))
5008	25889429	Muscle weakness and fatigue, as hallmarks of MG, indicate improper signaling between T and B cells, resulting in the elicitation of an antibody-mediated autoimmune response against the acetylcholine receptor (AChR) located at neuromuscular junctions.	('AChR', 'Gene', (209, 213))	('Muscle weakness', 'Phenotype', 'HP:0001324', (0, 15))	('fatigue', 'Disease', (20, 27))	('acetylcholine', 'Chemical', 'MESH:D000109', (185, 198))	('improper', 'Var', (58, 66))	('elicitation', 'Reg', (117, 128))	('fatigue', 'Phenotype', 'HP:0012378', (20, 27))	('fatigue', 'Disease', 'MESH:D005221', (20, 27))	('autoimmune response', 'Phenotype', 'HP:0002960', (153, 172))	('Muscle weakness', 'Disease', (0, 15))	('Muscle weakness', 'Disease', 'MESH:D018908', (0, 15))
5041	25889429	We selected the top 100 and 200 reliability prediction terms(according to the P-value and enrichment) for co-expressed and aberrant lncRNA genes, respectively (Figure 2).	('ncRNA', 'Gene', '220202', (133, 138))	('aberrant', 'Var', (123, 131))	('ncRNA', 'Gene', (133, 138))
5057	25889429	Among these, 4 lncRNAs (oebiotech_11658, oebiotech_12721, oebiotech_21725 and oebiotech_21831) had 8 cis genes, and the lncRNA with the highest aberrant expression, lncRNA oebiotech_11933, had 3 cis genes (C1orf74, G0S2 and TRAF3IP3).	('G0S2', 'Gene', (215, 219))	('ncRNA', 'Gene', '220202', (121, 126))	('oebiotech_21831', 'Var', (78, 93))	('ncRNA', 'Gene', '220202', (166, 171))	('TRAF3IP3', 'Gene', (224, 232))	('ncRNA', 'Gene', (16, 21))	('C1orf74', 'Gene', '148304', (206, 213))	('oebiotech_21725', 'Var', (58, 73))	('C1orf74', 'Gene', (206, 213))	('ncRNA', 'Gene', '220202', (16, 21))	('ncRNA', 'Gene', (166, 171))	('G0S2', 'Gene', '50486', (215, 219))	('TRAF3IP3', 'Gene', '80342', (224, 232))	('ncRNA', 'Gene', (121, 126))
5058	25889429	The aberrantly expressed lncRNA A_24_P927716 had 2 cis genes (ACSL1 and LOC731424).	('ncRNA', 'Gene', (26, 31))	('ACSL1', 'Gene', '2180', (62, 67))	('LOC731424', 'Var', (72, 81))	('ncRNA', 'Gene', '220202', (26, 31))	('ACSL1', 'Gene', (62, 67))
5077	25889429	Figure 6A shows the core TF-lncRNA-target gene relationship for MG patients with thymoma versus healthy controls, containing 8 lncRNAs with disrupted expression (lncRNAs oebiotech_24272, oebiotech_23755, oebiotech_18319, oebiotech_13727, oebiotech_08281, A_21_P0008564, A_21_P0006010 and A_21_P0001906), 27 target genes and 1 core TF CTCF in this core map.	('ncRNA', 'Gene', (128, 133))	('ncRNA', 'Gene', (29, 34))	('CTCF', 'Gene', (334, 338))	('thymoma', 'Disease', (81, 88))	('patients', 'Species', '9606', (67, 75))	('ncRNA', 'Gene', '220202', (163, 168))	('ncRNA', 'Gene', '220202', (128, 133))	('A_21_P0001906', 'Var', (288, 301))	('thymoma', 'Phenotype', 'HP:0100522', (81, 88))	('ncRNA', 'Gene', '220202', (29, 34))	('thymoma', 'Disease', 'MESH:D013945', (81, 88))	('CTCF', 'Gene', '10664', (334, 338))	('A_21_P0006010', 'Var', (270, 283))	('ncRNA', 'Gene', (163, 168))
5079	25889429	Figure 6C shows the core TF-lncRNA-target gene relationship in MG patients with thymoma versus MG patients without thymoma, containing 8 lncRNA with disrupted expression (lncRNAs oebiotech_22642, oebiotech_18319, oebiotech_18319, oebiotech_09353, oebiotech_06898, oebiotech_00715, A_21_P0010245, and A_21_P0009360), 27 target genes and1 core TF CTCF in this core map.	('ncRNA', 'Gene', (29, 34))	('ncRNA', 'Gene', '220202', (29, 34))	('CTCF', 'Gene', (345, 349))	('ncRNA', 'Gene', (138, 143))	('ncRNA', 'Gene', (172, 177))	('thymoma', 'Disease', (115, 122))	('ncRNA', 'Gene', '220202', (138, 143))	('ncRNA', 'Gene', '220202', (172, 177))	('thymoma', 'Phenotype', 'HP:0100522', (115, 122))	('A_21_P0010245', 'Var', (281, 294))	('expression', 'MPA', (159, 169))	('thymoma', 'Disease', 'MESH:D013945', (80, 87))	('thymoma versus MG', 'Disease', (80, 97))	('thymoma versus MG', 'Disease', 'MESH:D013945', (80, 97))	('patients', 'Species', '9606', (98, 106))	('A_21_P0009360', 'Var', (300, 313))	('CTCF', 'Gene', '10664', (345, 349))	('thymoma', 'Disease', (80, 87))	('patients', 'Species', '9606', (66, 74))	('thymoma', 'Phenotype', 'HP:0100522', (80, 87))	('thymoma', 'Disease', 'MESH:D013945', (115, 122))
5117	25889429	The increased expression of cytokines and chemokines, such as IL-8, CXCL1, CXCL3, CXCL3, and CXCL5, was observed among the oebiotech_11658, oebiotech_12721, oebiotech_21831, oebiotech_11933, and oebiotech_22652 'cis' genes, suggesting that these lncRNAs may regulate the expression of these cytokines and chemokines.	('CXCL3', 'Gene', (75, 80))	('CXCL1', 'Gene', '2919', (68, 73))	('expression', 'MPA', (271, 281))	('CXCL3', 'Gene', (82, 87))	('CXCL1', 'Gene', (68, 73))	('IL-8', 'Gene', '3576', (62, 66))	('CXCL5', 'Gene', (93, 98))	('ncRNA', 'Gene', (247, 252))	('expression', 'MPA', (14, 24))	('regulate', 'Reg', (258, 266))	('CXCL3', 'Gene', '2921', (82, 87))	('CXCL3', 'Gene', '2921', (75, 80))	('oebiotech_11658', 'Var', (123, 138))	('CXCL5', 'Gene', '6374', (93, 98))	('ncRNA', 'Gene', '220202', (247, 252))	('increased', 'PosReg', (4, 13))	('IL-8', 'Gene', (62, 66))
5123	25889429	In the present study, we identified a subset of aberrant lncRNAs to distinguish MG patients with or without thymoma compared with healthy individuals.	('thymoma', 'Phenotype', 'HP:0100522', (108, 115))	('thymoma', 'Disease', 'MESH:D013945', (108, 115))	('aberrant', 'Var', (48, 56))	('ncRNA', 'Gene', (58, 63))	('thymoma', 'Disease', (108, 115))	('patients', 'Species', '9606', (83, 91))	('ncRNA', 'Gene', '220202', (58, 63))
5167	20181983	Because thymic tumors can support thymocyte development, aberrant T-cell generation has been suggested as a cause.	('T-cell generation', 'CPA', (66, 83))	('tumors', 'Phenotype', 'HP:0002664', (15, 21))	('thymic tumor', 'Phenotype', 'HP:0100521', (8, 20))	('aberrant T-cell', 'Phenotype', 'HP:0002843', (57, 72))	('thymocyte development', 'CPA', (34, 55))	('tumor', 'Phenotype', 'HP:0002664', (15, 20))	('tumors', 'Disease', 'MESH:D009369', (15, 21))	('aberrant', 'Var', (57, 65))	('tumors', 'Disease', (15, 21))
5168	20181983	The autoimmune polyglandular syndrome type 1 (APS1), a monogenic syndrome of pleomorphic autoimmunity characterized by the clinical triad of hypoparathyroidism, hypoadrenalism, and candidiasis, arises from defects in the AIRE (auto-immune regulator) gene, which mediates the expression of tissue-specific self-antigens by medullary thymic epithelial cells.	('hypoparathyroidism', 'Disease', (141, 159))	('candidiasis', 'Disease', (181, 192))	('pleomorphic autoimmunity', 'Disease', (77, 101))	('autoimmune polyglandular syndrome type 1', 'Gene', '326', (4, 44))	('candidiasis', 'Disease', 'MESH:D002177', (181, 192))	('pleomorphic autoimmunity', 'Disease', 'MESH:D008228', (77, 101))	('autoimmunity', 'Phenotype', 'HP:0002960', (89, 101))	('arises from', 'Reg', (194, 205))	('hypoadrenalism', 'Disease', (161, 175))	('hypoparathyroidism', 'Phenotype', 'HP:0000829', (141, 159))	('AIRE', 'Gene', '326', (221, 225))	('AIRE', 'Gene', (221, 225))	('defects', 'Var', (206, 213))	('APS1', 'Gene', (46, 50))	('autoimmune polyglandular syndrome type 1', 'Gene', (4, 44))	('hypoadrenalism', 'Disease', 'MESH:D000309', (161, 175))	('APS1', 'Gene', '326', (46, 50))	('hypoadrenalism', 'Phenotype', 'HP:0000846', (161, 175))	('hypoparathyroidism', 'Disease', 'MESH:D007011', (141, 159))
5241	33729676	Furthermore, patients with low LDH (<=373 IU/L) at baseline and myasthenia gravis concurrence showed significantly better OS (p = 0.001 and p = 0.008, respectively) (Figure 3).	('LDH', 'MPA', (31, 34))	('myasthenia gravis', 'Disease', 'MESH:D009157', (64, 81))	('patients', 'Species', '9606', (13, 21))	('myasthenia', 'Phenotype', 'HP:0003473', (64, 74))	('<=373 IU/L', 'Var', (36, 46))	('low', 'NegReg', (27, 30))	('better', 'PosReg', (115, 121))	('myasthenia gravis', 'Disease', (64, 81))
5244	33729676	In the analysis for RFS, Masaoka stages (HR 2.291, 95% CI: 1.088-4.822; p = 0.029) and surgical resection (HR 3.221, 95% CI: 1.446-7.175; p = 0.004) were statistically significantly associated with risk of relapse (Table 3).	('relapse', 'Disease', (206, 213))	('associated', 'Reg', (182, 192))	('RFS', 'Disease', (20, 23))	('RFS', 'Disease', 'MESH:D005198', (20, 23))	('Masaoka', 'Disease', (25, 32))	('surgical resection', 'Var', (87, 105))
5279	33729676	demonstrated that high serum LDH (>225 IU/L) was an independent predictor of decreased PFS in 95 patients with thymic carcinoma.	('thymic carcinoma', 'Disease', (111, 127))	('thymic carcinoma', 'Disease', 'MESH:D013953', (111, 127))	('LDH', 'Protein', (29, 32))	('PFS', 'Disease', (87, 90))	('carcinoma', 'Phenotype', 'HP:0030731', (118, 127))	('>225 IU/L', 'Var', (34, 43))	('decreased', 'NegReg', (77, 86))	('patients', 'Species', '9606', (97, 105))
5294	31819103	A significant advantage in Freedom-from-Recurrence and/or Cause-specific survival (CSS) was evident for patients with high Advanced-Lung- Cancer-Inflammation-Index, low CRP-Fibrinogen-Score (CFS), low Glasgow-Prognostic-Score (GPS), low high-sensitivity-modified GPS, low TET-adapted GPS (TET-aGPS) and low Systemic-Immune-Inflammation Index.	('Cancer-Inflammation', 'Disease', 'MESH:D009369', (138, 157))	('Glasgow-Prognostic-Score', 'Protein', (201, 225))	('CRP', 'Gene', (169, 172))	('aGPS', 'Gene', '8540', (293, 297))	('low', 'Var', (197, 200))	('high-sensitivity-modified GPS', 'Protein', (237, 266))	('CRP', 'Gene', '1401', (169, 172))	('aGPS', 'Gene', (293, 297))	('low', 'NegReg', (233, 236))	('Cancer-Inflammation', 'Disease', (138, 157))	('TET-adapted GPS', 'MPA', (272, 287))	('advantage', 'PosReg', (14, 23))	('low', 'NegReg', (165, 168))	('low CRP-Fibrinogen', 'Phenotype', 'HP:0011900', (165, 183))	('Freedom-from-Recurrence', 'CPA', (27, 50))	('low', 'NegReg', (268, 271))	('Cancer', 'Phenotype', 'HP:0002664', (138, 144))	('patients', 'Species', '9606', (104, 112))
5327	31819103	The majority of all patients with paraneoplastic MG (94.7%) were scored with CFS 0, whereas only 73% of all patients without MG had CFS 0.	('paraneoplastic MG', 'Disease', 'MESH:D000080343', (34, 51))	('CFS', 'Var', (77, 80))	('paraneoplastic MG', 'Disease', (34, 51))	('patients', 'Species', '9606', (20, 28))	('patients', 'Species', '9606', (108, 116))
5336	31819103	GPS 0 was associated with significantly better FFR (p = 0.001) compared to patients scored with GPS 1 + 2, however there was no difference for CSS (p = 0.823), respectively.	('GPS 0', 'Var', (0, 5))	('GPS 1', 'Gene', (96, 101))	('patients', 'Species', '9606', (75, 83))	('FFR', 'Gene', (47, 50))	('GPS 1', 'Gene', '2873', (96, 101))	('FFR', 'Gene', '738', (47, 50))	('better', 'PosReg', (40, 46))
5340	31819103	Univariable analysis revealed significantly worse CSS in patients with TC (HR = 11.1; p < 0.001), high CFS (HR = 5.94; p = 0.002), high Masaoka-Koga tumor stage (HR = 5.52; p = 0.003), high GPS (HR = 4.90; p = 0.040), high HS-mGPS (HR = 4.87; p = 0.041), high TET-aGPS (HR = 5.18; p = 0.014) and low ALI (HR = 3.47; p = 0.049), respectively.	('worse', 'NegReg', (44, 49))	('tumor', 'Disease', 'MESH:D009369', (149, 154))	('aGPS', 'Gene', (264, 268))	('HS-mGPS', 'Disease', 'MESH:C567159', (223, 230))	('patients', 'Species', '9606', (57, 65))	('high', 'Var', (98, 102))	('tumor', 'Phenotype', 'HP:0002664', (149, 154))	('high', 'Var', (185, 189))	('tumor', 'Disease', (149, 154))	('CSS', 'CPA', (50, 53))	('HS-mGPS', 'Disease', (223, 230))	('aGPS', 'Gene', '8540', (264, 268))
5343	31819103	Regarding FFR, univariable analyses showed that the risk of recurrence was significantly increased in men (HR = 2.37; p = 0.02), in patients with TC (HR = 4.45; p < 0.001), resection status R1 + R2 (HR = 3.55; p = 0.029), in patients with absence of MG (HR = 3.77; p = 0.029), in patients with Masaoka-Koga stage III-IV (HR = 4.86; p < 0.001), low ALI (HR = 2.92; p = 0.038), high CFS (HR = 4.56; p = 0.001), high GPS (HR = 5.13; p = 0.009) and high TET-aGPS (HR = 3.17; p = 0.009).	('resection status R1 + R2', 'Var', (173, 197))	('FFR', 'Gene', '738', (10, 13))	('aGPS', 'Gene', (454, 458))	('patients', 'Species', '9606', (280, 288))	('high GPS', 'CPA', (409, 417))	('patients', 'Species', '9606', (225, 233))	('aGPS', 'Gene', '8540', (454, 458))	('increased', 'PosReg', (89, 98))	('FFR', 'Gene', (10, 13))	('men', 'Species', '9606', (102, 105))	('patients', 'Species', '9606', (132, 140))	('high', 'Var', (376, 380))
5344	31819103	Multivariable analyses remained statistically significant for patients with TC (HR = 28.24; p < 0.001), for patients with incomplete resection status R1 + R2 (HR = 13.96; p = 0.003) and for patients with Masaoka-Koga stage III-IV (HR = 4.78; 0.042), while none of the clinical composite scores represented an independent predictive factor for FFR (Table 3).	('patients', 'Species', '9606', (190, 198))	('FFR', 'Gene', (343, 346))	('FFR', 'Gene', '738', (343, 346))	('R1 + R2', 'Var', (150, 157))	('patients', 'Species', '9606', (108, 116))	('patients', 'Species', '9606', (62, 70))
5345	31819103	Univariable analysis for thymoma revealed significantly worse CSS in patients with resection status R1 + R2 (HR = 14; p = 0.009) and high Masaoka-Koga tumor stage (HR = 9.7; p = 0.049), respectively.	('tumor', 'Phenotype', 'HP:0002664', (151, 156))	('thymoma', 'Disease', 'MESH:D013945', (25, 32))	('R1 + R2', 'Var', (100, 107))	('tumor', 'Disease', (151, 156))	('worse', 'NegReg', (56, 61))	('thymoma', 'Disease', (25, 32))	('thymoma', 'Phenotype', 'HP:0100522', (25, 32))	('CSS', 'MPA', (62, 65))	('patients', 'Species', '9606', (69, 77))	('tumor', 'Disease', 'MESH:D009369', (151, 156))
5347	31819103	Regarding FFR, univariable analyses showed that the risk of recurrence was significantly increased in men (HR = 3.01; p = 0.048), resection status R1 + R2 (HR = 4.57; p = 0.021), in patients with Masaoka-Koga stage III-IV (HR = 6.68; p = 0.001), and high GPS (HR = 85.9; p = 0.002).	('FFR', 'Gene', '738', (10, 13))	('resection status R1 + R2', 'Var', (130, 154))	('patients', 'Species', '9606', (182, 190))	('increased', 'PosReg', (89, 98))	('FFR', 'Gene', (10, 13))	('men', 'Species', '9606', (102, 105))
5354	31819103	Patients with CRP (>0.3 mg/dL) showed significantly worse CSS (HR 4.9; p = 0.042) as well as a worse FFR (HR 3.5; p = 0.013).	('CRP', 'Gene', '1401', (14, 17))	('FFR', 'Gene', (101, 104))	('worse', 'NegReg', (52, 57))	('FFR', 'Gene', '738', (101, 104))	('Patients', 'Species', '9606', (0, 8))	('CSS', 'MPA', (58, 61))	('>0.3 mg/dL', 'Var', (19, 29))	('CRP', 'Gene', (14, 17))
5358	31819103	The HS-mGPS was composed of previously described variables albumin (<35 g/L) and CRP (>0.3 mg/L).	('albumin', 'Gene', (59, 66))	('CRP', 'Gene', (81, 84))	('albumin', 'Gene', '213', (59, 66))	('HS-mGPS', 'Disease', 'MESH:C567159', (4, 11))	('CRP', 'Gene', '1401', (81, 84))	('HS-mGPS', 'Disease', (4, 11))	('<35 g/L', 'Var', (68, 75))
5386	31819103	ALI > 18, representing lower systemic inflammation was associated with better outcome in patients with NSCLC.	('NSCLC', 'Disease', (103, 108))	('NSCLC', 'Disease', 'MESH:D002289', (103, 108))	('ALI > 18', 'Var', (0, 8))	('patients', 'Species', '9606', (89, 97))	('NSCLC', 'Phenotype', 'HP:0030358', (103, 108))	('inflammation', 'Disease', 'MESH:D007249', (38, 50))	('inflammation', 'Disease', (38, 50))
5423	31819103	In our cohort 355 did not reveal a significant difference among low and high SII regarding CSS and FFR.	('FFR', 'Gene', '738', (99, 102))	('low', 'Var', (64, 67))	('CSS', 'Disease', (91, 94))	('FFR', 'Gene', (99, 102))
5487	31608319	Mutations in general transcription factor IIi (GTF2I) are unique to TETs and are rarely observed in other malignancies.	('malignancies', 'Disease', 'MESH:D009369', (106, 118))	('GTF2I', 'Gene', (47, 52))	('TETs', 'Disease', 'MESH:C536905', (68, 72))	('malignancies', 'Disease', (106, 118))	('GTF2I', 'Gene', '2969', (47, 52))	('Mutations', 'Var', (0, 9))	('TETs', 'Disease', (68, 72))
5513	31608319	Mutations in the GTF2I oncogene were found predominantly in type A and AB thymoma, which is consistent with previously published data.	('type A', 'Disease', (60, 66))	('found', 'Reg', (37, 42))	('thymoma', 'Phenotype', 'HP:0100522', (74, 81))	('AB thymoma', 'Disease', 'MESH:D013945', (71, 81))	('Mutations', 'Var', (0, 9))	('GTF2I', 'Gene', (17, 22))	('AB thymoma', 'Disease', (71, 81))	('GTF2I', 'Gene', '2969', (17, 22))
5515	31608319	An independent effort at developing a molecular classification of TETs was conducted by Lee and colleagues by using information on DNA mutations, mRNA expression and somatic copy number alterations from the TCGA data set.	('mRNA expression', 'MPA', (146, 161))	('TETs', 'Disease', 'MESH:C536905', (66, 70))	('TETs', 'Disease', (66, 70))	('mutations', 'Var', (135, 144))	('DNA', 'Gene', (131, 134))
5516	31608319	Four molecular subgroups were identified with the following molecular characteristics: tumors with GTF2I mutations, GTF2I-wild type tumors with expression of genes associated with T-cell signaling, and tumors with chromosomal stability and instability.	('tumor', 'Phenotype', 'HP:0002664', (87, 92))	('GTF2I', 'Gene', (116, 121))	('tumors', 'Disease', 'MESH:D009369', (202, 208))	('tumors', 'Phenotype', 'HP:0002664', (87, 93))	('mutations', 'Var', (105, 114))	('GTF2I', 'Gene', '2969', (99, 104))	('GTF2I', 'Gene', (99, 104))	('tumors', 'Phenotype', 'HP:0002664', (132, 138))	('tumors', 'Disease', (87, 93))	('type tumors', 'Disease', 'MESH:D009369', (127, 138))	('tumors', 'Phenotype', 'HP:0002664', (202, 208))	('tumor', 'Phenotype', 'HP:0002664', (132, 137))	('tumors', 'Disease', 'MESH:D009369', (87, 93))	('tumors', 'Disease', (132, 138))	('tumor', 'Phenotype', 'HP:0002664', (202, 207))	('tumors', 'Disease', (202, 208))	('GTF2I', 'Gene', '2969', (116, 121))	('tumors', 'Disease', 'MESH:D009369', (132, 138))	('type tumors', 'Disease', (127, 138))
5520	31608319	Recurrent mutations in 7 of 9 epigenetic regulatory genes, including BAP1, ASXL1, SETD2, SMARCA4, DNMT3A, TET2, and WT1, were detected in 16 (34%) cases of thymic carcinoma but were absent in thymoma samples.	('thymoma', 'Disease', 'MESH:D013945', (192, 199))	('SETD2', 'Gene', (82, 87))	('WT1', 'Gene', (116, 119))	('DNMT3A', 'Gene', '1788', (98, 104))	('BAP1', 'Gene', '8314', (69, 73))	('SETD2', 'Gene', '29072', (82, 87))	('WT1', 'Gene', '7490', (116, 119))	('ASXL1', 'Gene', '171023', (75, 80))	('thymoma', 'Disease', (192, 199))	('thymoma', 'Phenotype', 'HP:0100522', (192, 199))	('TET2', 'Gene', (106, 110))	('thymic carcinoma', 'Disease', (156, 172))	('SMARCA4', 'Gene', '6597', (89, 96))	('BAP1', 'Gene', (69, 73))	('ASXL1', 'Gene', (75, 80))	('DNMT3A', 'Gene', (98, 104))	('carcinoma', 'Phenotype', 'HP:0030731', (163, 172))	('TET2', 'Gene', '54790', (106, 110))	('thymic carcinoma', 'Disease', 'MESH:D013945', (156, 172))	('mutations', 'Var', (10, 19))	('detected', 'Reg', (126, 134))	('SMARCA4', 'Gene', (89, 96))	('epigenetic regulatory genes', 'Gene', (30, 57))
5525	31608319	Dysregulation of collagen metabolism in the tumor microenvironment has been previously shown to have variable effects on tumor growth at various stages of cancer development.	('tumor', 'Phenotype', 'HP:0002664', (121, 126))	('Dysregulation', 'Var', (0, 13))	('cancer', 'Phenotype', 'HP:0002664', (155, 161))	('effects', 'Reg', (110, 117))	('tumor', 'Disease', (121, 126))	('tumor', 'Disease', 'MESH:D009369', (44, 49))	('collagen metabolism', 'MPA', (17, 36))	('tumor', 'Phenotype', 'HP:0002664', (44, 49))	('tumor', 'Disease', (44, 49))	('cancer', 'Disease', (155, 161))	('cancer', 'Disease', 'MESH:D009369', (155, 161))	('tumor', 'Disease', 'MESH:D009369', (121, 126))
5533	31608319	The cytosine deaminase activity of apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) correlated strongly with mutational heterogeneity.	('cytosine deaminase activity', 'MPA', (4, 31))	('catalytic', 'MPA', (73, 82))	('apolipoprotein B', 'Protein', (35, 51))	('cytosine', 'Chemical', 'MESH:D003596', (4, 12))	('mutational', 'Var', (134, 144))	('mRNA editing enzyme', 'Enzyme', (52, 71))
5542	31608319	In contrast, C19MC expression was absent in type B thymomas.	('type B thymomas', 'Disease', 'MESH:D013945', (44, 59))	('thymoma', 'Phenotype', 'HP:0100522', (51, 58))	('type B thymomas', 'Disease', (44, 59))	('C19MC', 'Var', (13, 18))
5544	31608319	Enkner and colleagues also observed overexpression of C19MC in type A thymomas and absence of expression in thymic carcinomas.	('thymic carcinomas', 'Disease', (108, 125))	('carcinoma', 'Phenotype', 'HP:0030731', (115, 124))	('overexpression', 'PosReg', (36, 50))	('carcinomas', 'Phenotype', 'HP:0030731', (115, 125))	('thymic carcinomas', 'Disease', 'MESH:D013945', (108, 125))	('type A thymomas', 'Disease', 'MESH:D013945', (63, 78))	('type A thymomas', 'Disease', (63, 78))	('thymoma', 'Phenotype', 'HP:0100522', (70, 77))	('A thymomas', 'Phenotype', 'HP:0100522', (68, 78))	('C19MC', 'Var', (54, 59))
5546	31608319	C14MC appears to have tumor suppressor properties in gastrointestinal stromal tumor and glioma.	('gastrointestinal stromal tumor', 'Phenotype', 'HP:0100723', (53, 83))	('tumor', 'Disease', 'MESH:D009369', (22, 27))	('gastrointestinal stromal tumor', 'Disease', (53, 83))	('tumor', 'Disease', 'MESH:D009369', (78, 83))	('glioma', 'Phenotype', 'HP:0009733', (88, 94))	('glioma', 'Disease', (88, 94))	('tumor', 'Phenotype', 'HP:0002664', (22, 27))	('tumor', 'Phenotype', 'HP:0002664', (78, 83))	('C14MC', 'Var', (0, 5))	('gastrointestinal stromal tumor', 'Disease', 'MESH:D046152', (53, 83))	('glioma', 'Disease', 'MESH:D005910', (88, 94))	('tumor', 'Disease', (22, 27))	('tumor', 'Disease', (78, 83))
5570	31608319	An acquired defect in CD247 in naive T-cells has been described in patients with lymphocyte-rich thymomas, which causes T-cell receptor hyporesponsiveness and cutaneous anergy.	('CD247', 'Gene', (22, 27))	('thymoma', 'Phenotype', 'HP:0100522', (97, 104))	('hyporesponsiveness', 'Disease', (136, 154))	('cutaneous anergy', 'Disease', (159, 175))	('patients', 'Species', '9606', (67, 75))	('cutaneous anergy', 'Phenotype', 'HP:0002965', (159, 175))	('causes', 'Reg', (113, 119))	('thymomas', 'Disease', (97, 105))	('defect', 'Var', (12, 18))	('thymomas', 'Disease', 'MESH:D013945', (97, 105))	('T-cell receptor hyporesponsiveness', 'Phenotype', 'HP:0002930', (120, 154))	('hyporesponsiveness', 'Disease', 'MESH:C566417', (136, 154))	('CD247', 'Gene', '919', (22, 27))
5573	31608319	Acquired immunodeficiency caused by anti-cytokine antibodies can increase the risk for development of opportunistic infections.	('Acquired immunodeficiency', 'Disease', (0, 25))	('immunodeficiency', 'Phenotype', 'HP:0002721', (9, 25))	('opportunistic infections', 'Disease', (102, 126))	('opportunistic infections', 'Phenotype', 'HP:0031690', (102, 126))	('opportunistic infections', 'Disease', 'MESH:D009894', (102, 126))	('anti-cytokine antibodies', 'Var', (36, 60))	('Acquired immunodeficiency', 'Disease', 'MESH:D000163', (0, 25))
5579	31608319	XPO1 is involved in nuclear export of tumor suppressor proteins, including p53 and inhibition of XPO1 in TET cells has been shown to induce anti-tumor activity in vitro.	('tumor', 'Phenotype', 'HP:0002664', (38, 43))	('tumor', 'Disease', (38, 43))	('tumor', 'Disease', 'MESH:D009369', (145, 150))	('induce', 'PosReg', (133, 139))	('tumor', 'Phenotype', 'HP:0002664', (145, 150))	('XPO1', 'Gene', '7514', (0, 4))	('XPO1', 'Gene', (0, 4))	('tumor', 'Disease', (145, 150))	('p53', 'Gene', (75, 78))	('tumor', 'Disease', 'MESH:D009369', (38, 43))	('p53', 'Gene', '7157', (75, 78))	('XPO1', 'Gene', '7514', (97, 101))	('inhibition', 'Var', (83, 93))	('XPO1', 'Gene', (97, 101))
5583	31608319	Mutations in p53 were also associated with worse overall survival (OS) compared with p53-wild-type tumors (median survival 19 versus 106 months; P=0.0003).	('tumors', 'Phenotype', 'HP:0002664', (99, 105))	('overall survival', 'MPA', (49, 65))	('p53', 'Gene', (85, 88))	('type tumors', 'Disease', 'MESH:D009369', (94, 105))	('type tumors', 'Disease', (94, 105))	('Mutations', 'Var', (0, 9))	('p53', 'Gene', (13, 16))	('tumor', 'Phenotype', 'HP:0002664', (99, 104))	('p53', 'Gene', '7157', (85, 88))	('p53', 'Gene', '7157', (13, 16))	('worse', 'NegReg', (43, 48))
5584	31608319	A negative impact of p53 mutations on survival was also detected in 123 TET cases derived from the TCGA database.	('negative', 'NegReg', (2, 10))	('mutations', 'Var', (25, 34))	('p53', 'Gene', '7157', (21, 24))	('p53', 'Gene', (21, 24))
5586	31608319	Presence of a p53 mutation was also associated with a shorter time to disease relapse (median disease-free survival was 9.7 months versus not evaluable in p53-wild-type cases due to a low frequency of relapse).	('p53', 'Gene', (155, 158))	('p53', 'Gene', '7157', (155, 158))	('p53', 'Gene', (14, 17))	('p53', 'Gene', '7157', (14, 17))	('disease relapse', 'CPA', (70, 85))	('mutation', 'Var', (18, 26))	('shorter', 'NegReg', (54, 61))	('Presence', 'Var', (0, 8))
5587	31608319	Presence of a GTF2I mutation and enrichment of genes involved in T-cell signaling are associated with favorable disease-free survival and OS in contrast to tumors with chromosomal instability.	('chromosomal instability', 'Phenotype', 'HP:0040012', (168, 191))	('mutation', 'Var', (20, 28))	('tumor', 'Phenotype', 'HP:0002664', (156, 161))	('tumors', 'Disease', 'MESH:D009369', (156, 162))	('GTF2I', 'Gene', (14, 19))	('tumors', 'Phenotype', 'HP:0002664', (156, 162))	('tumors', 'Disease', (156, 162))	('Presence', 'Var', (0, 8))	('GTF2I', 'Gene', '2969', (14, 19))
5588	31608319	Other prognostic markers under investigation include expression of the genes SOX2 and CA9, which are reported to be associated with shorter survival in TET patients and the methylation status of the genes KSR1, ELF3, ILRN and RAG1, which have variable effects on OS.	('patients', 'Species', '9606', (156, 164))	('RAG1', 'Gene', (226, 230))	('CA9', 'Gene', (86, 89))	('RAG1', 'Gene', '5896', (226, 230))	('ELF3', 'Gene', '1999', (211, 215))	('CA9', 'Gene', '768', (86, 89))	('methylation status', 'Var', (173, 191))	('KSR1', 'Gene', '8844', (205, 209))	('ELF3', 'Gene', (211, 215))	('shorter', 'NegReg', (132, 139))	('SOX2', 'Gene', (77, 81))	('KSR1', 'Gene', (205, 209))	('SOX2', 'Gene', '6657', (77, 81))	('ILRN', 'Gene', (217, 221))
5682	25789744	Fatal Yellow Fever Vaccine-Associated Viscerotropic Disease : Oregon, September 2014 In September 2014, a previously healthy Oregon woman in her 60s went to a hospital emergency department with malaise, dyspnea, vomiting, and diarrhea of 3-5 days' duration.	('woman', 'Species', '9606', (132, 137))	('diarrhea', 'Phenotype', 'HP:0002014', (226, 234))	('malaise', 'Phenotype', 'HP:0012378', (194, 201))	('vomiting', 'Phenotype', 'HP:0002013', (212, 220))	('Fever', 'Phenotype', 'HP:0001945', (13, 18))	('diarrhea', 'Disease', (226, 234))	('dyspnea', 'Disease', 'MESH:D004417', (203, 210))	('diarrhea', 'Disease', 'MESH:D003967', (226, 234))	('malaise', 'Disease', (194, 201))	('vomiting', 'Disease', (212, 220))	('vomiting', 'Disease', 'MESH:D014839', (212, 220))	('Yellow Fever', 'Disease', (6, 18))	('dyspnea', 'Phenotype', 'HP:0002094', (203, 210))	('September', 'Var', (88, 97))	('Yellow Fever', 'Disease', 'MESH:D015004', (6, 18))	('malaise', 'Disease', 'MESH:D005221', (194, 201))	('dyspnea', 'Disease', (203, 210))
5730	25611232	Other potential mechanisms include the increased frequency of mutations in thymoma-derived T cells due to high turnover rate of cortical thymocytes and reduced numbers of T regulatory cells, which have inhibitory effects on antigen-specific activation of naive autologous T cells.	('thymoma', 'Phenotype', 'HP:0100522', (75, 82))	('reduced', 'NegReg', (152, 159))	('T regulatory cells', 'CPA', (171, 189))	('thymoma', 'Disease', 'MESH:D013945', (75, 82))	('mutations', 'Var', (62, 71))	('thymoma', 'Disease', (75, 82))
5731	25611232	In a subset of patients, defects in autoimmune regulatory (AIRE) gene may play a role.	('patients', 'Species', '9606', (15, 23))	('defects', 'Var', (25, 32))	('AIRE', 'Gene', '326', (59, 63))	('AIRE', 'Gene', (59, 63))
5733	25611232	AIRE mutations underlie the APECED syndrome (autoimmune polyendocrinopathy candidiasis ectodermal dystrophy) which shares autoimmune manifestations and anti-interferon autoantibodies with thymoma associated autoimmune syndromes.	('autoimmune polyendocrinopathy candidiasis ectodermal dystrophy', 'Disease', 'MESH:D016884', (45, 107))	('APECED syndrome', 'Disease', 'MESH:D016884', (28, 43))	('APECED syndrome', 'Disease', (28, 43))	('thymoma', 'Disease', 'MESH:D013945', (188, 195))	('autoimmune manifestations', 'Phenotype', 'HP:0002960', (122, 147))	('thymoma', 'Disease', (188, 195))	('underlie', 'Reg', (15, 23))	('AIRE', 'Gene', (0, 4))	('mutations', 'Var', (5, 14))	('thymoma', 'Phenotype', 'HP:0100522', (188, 195))	('AIRE', 'Gene', '326', (0, 4))	('polyendocrinopathy candidiasis', 'Phenotype', 'HP:0005411', (56, 86))	('ectodermal dystrophy', 'Phenotype', 'HP:0000968', (87, 107))
5735	25611232	The association between autoimmune manifestations with response is possibly due to modulation of thymic immune mileu by cixutumumab or an egress of dysfunctional T cells to the periphery as a result of tumor shrinkage.	('dysfunctional T', 'Disease', (148, 163))	('dysfunctional T', 'Disease', 'MESH:D006331', (148, 163))	('tumor', 'Disease', (202, 207))	('association', 'Interaction', (4, 15))	('autoimmune manifestations', 'Phenotype', 'HP:0002960', (24, 49))	('cixutumumab', 'Var', (120, 131))	('cixutumumab', 'Chemical', 'MESH:C557414', (120, 131))	('tumor', 'Disease', 'MESH:D009369', (202, 207))	('tumor', 'Phenotype', 'HP:0002664', (202, 207))
5814	27992479	Incomplete resection significantly influences survival, with a 5-year survival rate of 55% and 48% in R1- and R2-resected tumors, respectively, in contrast to 70% in R0 tumors.	('tumors', 'Phenotype', 'HP:0002664', (122, 128))	('tumors', 'Disease', (122, 128))	('tumors', 'Disease', 'MESH:D009369', (122, 128))	('survival', 'MPA', (46, 54))	('tumors', 'Disease', 'MESH:D009369', (169, 175))	('tumor', 'Phenotype', 'HP:0002664', (169, 174))	('influences', 'Reg', (35, 45))	('tumors', 'Phenotype', 'HP:0002664', (169, 175))	('tumor', 'Phenotype', 'HP:0002664', (122, 127))	('R2-resected', 'Var', (110, 121))	('tumors', 'Disease', (169, 175))	('R1-', 'Var', (102, 105))
5870	27992479	At study start, six patients were positive for antibodies against the AChR but showed no clinically relevant symptoms of myasthenia gravis (Table 2).	('myasthenia gravis', 'Disease', (121, 138))	('antibodies', 'Var', (47, 57))	('positive', 'Reg', (34, 42))	('AChR', 'Gene', (70, 74))	('myasthenia gravis', 'Disease', 'MESH:D009157', (121, 138))	('patients', 'Species', '9606', (20, 28))	('myasthenia', 'Phenotype', 'HP:0003473', (121, 131))
5999	32277368	While it is well-recognized that these diseases may occur in the absence of a thymoma, the presence of a thymoma has been associated with a worse prognosis, which in some part, appears to be dependent on thymoma WHO classification and Masaoka staging.	('thymoma', 'Phenotype', 'HP:0100522', (204, 211))	('thymoma', 'Phenotype', 'HP:0100522', (105, 112))	('thymoma', 'Phenotype', 'HP:0100522', (78, 85))	('absence of a thymoma', 'Phenotype', 'HP:0005359', (65, 85))	('thymoma', 'Gene', '7063', (204, 211))	('presence', 'Var', (91, 99))	('thymoma', 'Gene', '7063', (105, 112))	('thymoma', 'Gene', '7063', (78, 85))	('thymoma', 'Gene', (204, 211))	('thymoma', 'Gene', (105, 112))	('thymoma', 'Gene', (78, 85))
6000	32277368	noted that among different WHO thymoma classes, class B2 is most commonly associated with autoimmune and paraneoplastic disorders, whereas class AB thymomas are least commonly associated.	('thymoma', 'Gene', '7063', (31, 38))	('thymoma', 'Gene', (31, 38))	('thymoma', 'Gene', '7063', (148, 155))	('thymomas', 'Disease', (148, 156))	('class B2', 'Var', (48, 56))	('thymoma', 'Gene', (148, 155))	('thymomas', 'Disease', 'MESH:D013945', (148, 156))	('thymoma', 'Phenotype', 'HP:0100522', (31, 38))	('paraneoplastic disorders', 'Disease', 'MESH:D010257', (105, 129))	('paraneoplastic disorders', 'Disease', (105, 129))	('associated', 'Reg', (74, 84))	('thymoma', 'Phenotype', 'HP:0100522', (148, 155))
6006	32277368	Multiple theories on the pathogenesis and development of autoimmune disease/paraneoplastic syndromes in the context of thymoma have been postulated, primarily focusing on an underlying dysregulation of normal thymic function, in turn affecting positive and negative selection processes and defects in central tolerance.	('affecting', 'Reg', (234, 243))	('neoplastic syndrome', 'Phenotype', 'HP:0002664', (80, 99))	('autoimmune disease', 'Disease', 'MESH:D001327', (57, 75))	('autoimmune disease', 'Phenotype', 'HP:0002960', (57, 75))	('central tolerance', 'CPA', (301, 318))	('dysregulation', 'Var', (185, 198))	('thymoma', 'Gene', '7063', (119, 126))	('paraneoplastic syndromes', 'Disease', 'MESH:D010257', (76, 100))	('thymoma', 'Phenotype', 'HP:0100522', (119, 126))	('paraneoplastic syndromes', 'Disease', (76, 100))	('thymoma', 'Gene', (119, 126))	('autoimmune disease', 'Disease', (57, 75))
6013	32277368	This theory is supported by the presence of autoantibodies in thymomas associated with myasthenia gravis and other autoimmune diseases.	('myasthenia gravis', 'Disease', (87, 104))	('thymomas', 'Disease', (62, 70))	('thymomas', 'Disease', 'MESH:D013945', (62, 70))	('autoimmune disease', 'Phenotype', 'HP:0002960', (115, 133))	('myasthenia gravis', 'Disease', 'MESH:D009157', (87, 104))	('autoimmune diseases', 'Disease', 'MESH:D001327', (115, 134))	('autoantibodies', 'Var', (44, 58))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (115, 134))	('myasthenia', 'Phenotype', 'HP:0003473', (87, 97))	('thymoma', 'Phenotype', 'HP:0100522', (62, 69))	('autoimmune diseases', 'Disease', (115, 134))	('associated', 'Reg', (71, 81))
6164	26320843	Apart from the "thymic stemness" alteration on chromosome 6q25, thymic squamous cell carcinomas share other similarities with type B3 thymomas, namely gain of chromosome 1q and loss of chromosome 6.	('thymomas', 'Disease', (134, 142))	('thymomas', 'Disease', 'MESH:D013945', (134, 142))	('gain', 'PosReg', (151, 155))	('squamous cell carcinomas', 'Phenotype', 'HP:0002860', (71, 95))	('squamous cell carcinoma', 'Phenotype', 'HP:0002860', (71, 94))	('thymoma', 'Phenotype', 'HP:0100522', (134, 141))	('loss', 'Var', (177, 181))	('carcinoma', 'Phenotype', 'HP:0030731', (85, 94))	('squamous cell carcinomas', 'Disease', 'MESH:D002294', (71, 95))	('carcinomas', 'Phenotype', 'HP:0030731', (85, 95))	('squamous cell carcinomas', 'Disease', (71, 95))
6302	33537838	Here, we cover (a) tolerance-inducing cell types, whether thymic epithelial or tuft cells, or dendritic, B- or thymic myoid cells; (b) tolerance-inducing mechanisms and their failure in relation to thymic anatomic compartments, and with special emphasis on human monogenic and polygenic autoimmune diseases and the related thymic pathologies, if known; (c) polymorphisms and mutations of tolerance-related genes with an impact on positive selection (e.g.	('autoimmune diseases', 'Phenotype', 'HP:0002960', (287, 306))	('mutations', 'Var', (375, 384))	('human', 'Species', '9606', (257, 262))	('polymorphisms', 'Var', (357, 370))	('autoimmune diseases', 'Disease', 'MESH:D001327', (287, 306))	('autoimmune diseases', 'Disease', (287, 306))
6308	33537838	It also prevents human autoimmune diseases (HAIDs) through both negative selection (by which most autoreactive alpha/beta-T-cells are deleted) and generation of FOXP3+ regulatory T-cells (Tregs) that restrain those autoreactive T-cells that inevitably escape negative selection and seed the periphery.	('FOXP3+', 'Var', (161, 167))	('autoimmune diseases', 'Disease', (23, 42))	('human', 'Species', '9606', (17, 22))	('negative selection', 'CPA', (64, 82))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (23, 42))	('HAIDs', 'Disease', 'None', (44, 49))	('Tregs', 'Chemical', '-', (188, 193))	('HAIDs', 'Disease', (44, 49))	('autoimmune diseases', 'Disease', 'MESH:D001327', (23, 42))	('prevents', 'NegReg', (8, 16))
6311	33537838	the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED, alias autoimmune polyglandular syndrome type 1, APS1) due to autoimmune regulator (AIRE) mutations, the immunodysregulation polyendocrinopathy and enteropathy X-linked (IPEX) syndrome) resulting from FOXP3 mutations and 'leaky' (subtotal) immunodeficiency syndromes due to primary T-cell or stromal cell developmental defects.	('APECED', 'Gene', '326', (77, 83))	('autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome', 'Disease', 'MESH:D016884', (4, 75))	('immunodeficiency', 'Phenotype', 'HP:0002721', (324, 340))	("'leaky'", 'Disease', (305, 312))	('mutations', 'Var', (174, 183))	('enteropathy', 'Phenotype', 'HP:0002242', (232, 243))	('immunodeficiency syndromes', 'Disease', (324, 350))	('APS1', 'Gene', (133, 137))	('mutations', 'Var', (291, 300))	('alias autoimmune polyglandular syndrome', 'Disease', (85, 124))	('immunodysregulation polyendocrinopathy and enteropathy X-linked (IPEX) syndrome', 'Disease', 'MESH:C580192', (189, 268))	('ectodermal dystrophy', 'Phenotype', 'HP:0000968', (46, 66))	('autoimmune regulator', 'Gene', (146, 166))	('autoimmune regulator', 'Gene', '326', (146, 166))	('FOXP3', 'Gene', (285, 290))	('alias autoimmune polyglandular syndrome', 'Disease', 'MESH:D016884', (85, 124))	('APECED', 'Gene', (77, 83))	('APS1', 'Gene', '326', (133, 137))	('immunodeficiency syndromes', 'Disease', 'MESH:D007153', (324, 350))
6315	33537838	Identifying AIRE mutations as the cause of the APECED syndrome has deepened the understanding of negative selection.	('AIRE', 'Gene', (12, 16))	('cause', 'Reg', (34, 39))	('APECED syndrome', 'Disease', (47, 62))	('APECED syndrome', 'Disease', 'MESH:D016884', (47, 62))	('mutations', 'Var', (17, 26))
6333	33537838	Patients with inactivating AIRE mutations develop APECED due to autoimmune T- and B-cell responses that damage many organs, preferentially the adrenal cortex and parathyroid glands.	('APECED', 'Gene', '326', (50, 56))	('damage', 'Reg', (104, 110))	('APECED', 'Gene', (50, 56))	('AIRE', 'Gene', (27, 31))	('Patients', 'Species', '9606', (0, 8))	('mutations', 'Var', (32, 41))	('inactivating', 'Var', (14, 26))
6334	33537838	In contrast to AIRE-deficient mice, nearly all APECED patients show neutralizing autoantibodies to type I interferons and TH17 interleukins, and loss of Th17 and Th22 cells, which correlate with the characteristic mucocutaneous candidiasis, which is often the first sign of APECED.	('AIRE-deficient', 'Disease', 'MESH:D016884', (15, 29))	('Th17', 'Protein', (153, 157))	('mice', 'Species', '10090', (30, 34))	('patients', 'Species', '9606', (54, 62))	('neutralizing', 'MPA', (68, 80))	('APECED', 'Gene', '326', (47, 53))	('APECED', 'Gene', '326', (274, 280))	('APECED', 'Gene', (47, 53))	('loss', 'Var', (145, 149))	('AIRE-deficient', 'Disease', (15, 29))	('APECED', 'Gene', (274, 280))	('candidiasis', 'Disease', 'MESH:D002177', (228, 239))	('mucocutaneous candidiasis', 'Phenotype', 'HP:0002728', (214, 239))	('candidiasis', 'Disease', (228, 239))
6337	33537838	AIRE polymorphisms have been associated with sporadic vitiligo and rheumatoid arthritis (RA) but not with other common autoimmune diseases such as T1D.	('rheumatoid arthritis', 'Phenotype', 'HP:0001370', (67, 87))	('autoimmune diseases', 'Disease', (119, 138))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (119, 138))	('sporadic vitiligo and rheumatoid arthritis', 'Disease', 'MESH:D001172', (45, 87))	('AIRE', 'Gene', (0, 4))	('RA', 'Disease', 'MESH:D001172', (89, 91))	('vitiligo', 'Phenotype', 'HP:0001045', (54, 62))	('associated', 'Reg', (29, 39))	('arthritis', 'Phenotype', 'HP:0001369', (78, 87))	('autoimmune diseases', 'Disease', 'MESH:D001327', (119, 138))	('polymorphisms', 'Var', (5, 18))
6338	33537838	mutations of PRKDC) can cause APECED-like syndromes.	('PRKDC', 'Gene', (13, 18))	('APECED', 'Gene', '326', (30, 36))	('cause', 'Reg', (24, 29))	('PRKDC', 'Gene', '5591', (13, 18))	('APECED', 'Gene', (30, 36))	('mutations', 'Var', (0, 9))
6345	33537838	Transplantation of Fezf2-/- thymi into nude mice elicits organ infiltrates and autoantibodies that are different from those in AIRE-/- mice.	('elicits', 'Reg', (49, 56))	('nude mice', 'Species', '10090', (39, 48))	('organ infiltrates', 'CPA', (57, 74))	('Fezf2-/-', 'Var', (19, 27))	('mice', 'Species', '10090', (135, 139))	('mice', 'Species', '10090', (44, 48))
6347	33537838	In mice, Chd4 induces the expression of a small set of unique genes.	('expression', 'MPA', (26, 36))	('mice', 'Species', '10090', (3, 7))	('induces', 'Reg', (14, 21))	('Chd4', 'Var', (9, 13))
6353	33537838	Similarly, a polymorphism in the IRF8-binding site in the promoter of the AIRE-driven gene encoding the acetylcholine receptor (AChR) alpha-subunit has been linked to reduced AChR expression in the thymus and the risk of very early-onset myasthenia gravis.	('polymorphism', 'Var', (13, 25))	('AChR', 'Gene', (175, 179))	('myasthenia', 'Phenotype', 'HP:0003473', (238, 248))	('IRF8', 'Gene', (33, 37))	('myasthenia gravis', 'Disease', 'MESH:D009157', (238, 255))	('expression', 'MPA', (180, 190))	('myasthenia gravis', 'Disease', (238, 255))	('acetylcholine', 'Chemical', 'MESH:D000109', (104, 117))	('IRF8', 'Gene', '3394', (33, 37))	('reduced', 'NegReg', (167, 174))
6381	33537838	cDC1s are generated intrathymically from immature precursors recruited to the thymus by mTEC-derived CCL21s, while other DCs are attracted from the periphery as mature cells by mTEC-derived chemokines, some of which require toll-like receptor 9 (TLR9)/MYD-88 signalling for production.	('MYD-88', 'Gene', '4615', (252, 258))	('mTEC-derived', 'Var', (88, 100))	('MYD-88', 'Gene', (252, 258))	('toll-like receptor 9', 'Gene', (224, 244))	('TLR9', 'Gene', (246, 250))	('CCL21', 'Gene', (101, 106))	('CCL21', 'Gene', '6366', (101, 106))	('TEC', 'Chemical', '-', (178, 181))	('TEC', 'Chemical', '-', (89, 92))	('toll-like receptor 9', 'Gene', '54106', (224, 244))	('TLR9', 'Gene', '54106', (246, 250))
6392	33537838	A defect at this level elicits Treg deficiency and autoimmunity.	('defect', 'Var', (2, 8))	('elicits', 'Reg', (23, 30))	('autoimmunity', 'Phenotype', 'HP:0002960', (51, 63))	('deficiency', 'Disease', (36, 46))	('Treg', 'Chemical', '-', (31, 35))	('deficiency', 'Disease', 'MESH:D007153', (36, 46))
6393	33537838	Subsequently, CD4+ CD8-- single positive thymocytes develop in the medulla through further epigenetic modifications, establishment of the 'Treg-specific demethylated region, TSDR' and binding of transcription factors (e.g.	('Treg', 'Chemical', '-', (139, 143))	('CD8', 'Gene', (19, 22))	('CD8', 'Gene', '925', (19, 22))	('binding', 'Interaction', (184, 191))	('epigenetic modifications', 'Var', (91, 115))
6402	33537838	For example, IPEX syndrome (analogous to murine scurfy syndrome) results from different mutations across the FOXP3 gene, showing that Tregs are indispensable to prevent T1D (even perinatally), inflammatory bowel disease and allergies, although the clinical variability of IPEX correlates poorly with the type of FOXP3 mutation.	('IPEX', 'Gene', (13, 17))	('scurfy', 'Gene', '20371', (48, 54))	('IPEX syndrome', 'Disease', (13, 26))	('mutations', 'Var', (88, 97))	('results from', 'Reg', (65, 77))	('T1D', 'Disease', (169, 172))	('allergies', 'Disease', 'MESH:D004342', (224, 233))	('IPEX', 'Gene', '50943', (13, 17))	('Tregs', 'Chemical', '-', (134, 139))	('IPEX syndrome', 'Disease', 'MESH:C580192', (13, 26))	('IPEX', 'Gene', (272, 276))	('inflammatory bowel disease', 'Phenotype', 'HP:0002037', (193, 219))	('inflammatory bowel disease', 'Disease', (193, 219))	('inflammatory bowel disease', 'Disease', 'MESH:D015212', (193, 219))	('scurfy', 'Gene', (48, 54))	('allergies', 'Phenotype', 'HP:0012393', (224, 233))	('IPEX', 'Gene', '50943', (272, 276))	('allergies', 'Disease', (224, 233))	('murine', 'Species', '10090', (41, 47))	('FOXP3', 'Gene', (109, 114))
6403	33537838	Other mutations in CD25, CTLA4, LRBA, BACH2 and STAT3 cause 'IPEX-like syndromes' due to Treg dysfunction.	('CD25', 'Gene', (19, 23))	('STAT3', 'Gene', (48, 53))	('cause', 'Reg', (54, 59))	('BACH2', 'Gene', (38, 43))	('IPEX', 'Gene', (61, 65))	('CTLA4', 'Gene', '1493', (25, 30))	('IPEX', 'Gene', '50943', (61, 65))	('LRBA', 'Gene', (32, 36))	('Treg', 'Chemical', '-', (89, 93))	('CTLA4', 'Gene', (25, 30))	('Treg dysfunction', 'Disease', (89, 105))	('STAT3', 'Gene', '6774', (48, 53))	('LRBA', 'Gene', '987', (32, 36))	('mutations', 'Var', (6, 15))	('BACH2', 'Gene', '60468', (38, 43))
6405	33537838	In addition, genetic variants in Treg-related loci associate with some common sporadic autoimmune diseases.	('associate', 'Reg', (51, 60))	('Treg', 'Chemical', '-', (33, 37))	('genetic variants', 'Var', (13, 29))	('autoimmune diseases', 'Disease', 'MESH:D001327', (87, 106))	('autoimmune diseases', 'Disease', (87, 106))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (87, 106))	('Treg-related loci', 'Gene', (33, 50))
6413	33537838	Homozygosity for the rs54457782 SNP of PSMB11 has been associated with altered B5t function of the protein in cTECs and an elevated risk of Sjogren syndrome in one study.	('PSMB11', 'Gene', (39, 45))	('TEC', 'Chemical', '-', (111, 114))	('associated', 'Reg', (55, 65))	('rs54457782', 'Mutation', 'rs54457782', (21, 31))	('B5t function of the', 'MPA', (79, 98))	('altered', 'Reg', (71, 78))	('PSMB11', 'Gene', '122706', (39, 45))	('rs54457782', 'Var', (21, 31))	('Sjogren syndrome', 'Disease', 'MESH:D012859', (140, 156))	('Sjogren syndrome', 'Disease', (140, 156))
6414	33537838	Deletion of Prss16 in cTECs clearly protects NOD mice against T1D, presumably by affecting processing of pancreatic islet cell TRAs.	('T1D', 'Disease', (62, 65))	('TRA', 'Gene', '6955', (127, 130))	('affecting', 'Reg', (81, 90))	('mice', 'Species', '10090', (49, 53))	('protects', 'Reg', (36, 44))	('TEC', 'Chemical', '-', (23, 26))	('Prss16', 'Gene', (12, 18))	('TRA', 'Gene', (127, 130))	('Prss16', 'Gene', '54373', (12, 18))	('Deletion', 'Var', (0, 8))
6416	33537838	Polymorphisms of the C-type lectin CLEC16A gene show associations with T1D, multiple sclerosis (MS), systemic lupus (SLE), celiac disease, RA and JIA.	('multiple sclerosis', 'Disease', 'MESH:D009103', (76, 94))	('celiac disease', 'Disease', (123, 137))	('JIA', 'Disease', (146, 149))	('SLE', 'Disease', (117, 120))	('RA', 'Disease', 'MESH:D001172', (139, 141))	('CLEC16A', 'Gene', '23274', (35, 42))	('SLE', 'Disease', 'MESH:D008180', (117, 120))	('Polymorphisms', 'Var', (0, 13))	('systemic lupus', 'Disease', 'MESH:D008180', (101, 115))	('celiac disease', 'Phenotype', 'HP:0002608', (123, 137))	('T1D', 'Disease', (71, 74))	('systemic lupus', 'Disease', (101, 115))	('multiple sclerosis', 'Disease', (76, 94))	('CLEC16A', 'Gene', (35, 42))	('associations', 'Reg', (53, 65))	('systemic lupus', 'Phenotype', 'HP:0002725', (101, 115))
6418	33537838	In a similar scenario, 'autoimmunizing positive selection' (complemented by defective negative selection) might be operative in thymomas (see below), and in patients with ZAP70 mutations: while inactivating mutations of ZAP70 cause severe immunodeficiency, hypomorphic mutations lead to positive selection of autoreactive thymocytes.	('ZAP70', 'Gene', (220, 225))	('ZAP70', 'Gene', '7535', (171, 176))	('positive selection', 'CPA', (287, 305))	('severe immunodeficiency', 'Phenotype', 'HP:0004430', (232, 255))	('thymomas', 'Disease', (128, 136))	('mutations', 'Var', (177, 186))	('inactivating mutations', 'Var', (194, 216))	('ZAP70', 'Gene', '7535', (220, 225))	('ZAP70', 'Gene', (171, 176))	('lead to', 'Reg', (279, 286))	('patients', 'Species', '9606', (157, 165))	('hypomorphic mutations', 'Var', (257, 278))	('immunodeficiency', 'Disease', 'MESH:D007153', (239, 255))	('thymomas', 'Disease', 'MESH:D013945', (128, 136))	('immunodeficiency', 'Phenotype', 'HP:0002721', (239, 255))	('immunodeficiency', 'Disease', (239, 255))	('thymoma', 'Phenotype', 'HP:0100522', (128, 135))
6419	33537838	Since attenuated ZAP70 signalling also attenuates negative selection and selection of Tregs, autoimmunity arises, leading to bullous pemphigoid, colitis and proteinuria in patients.	('leading to', 'Reg', (114, 124))	('attenuated', 'Var', (6, 16))	('negative selection', 'CPA', (50, 68))	('proteinuria', 'Phenotype', 'HP:0000093', (157, 168))	('colitis', 'Disease', 'MESH:D003092', (145, 152))	('colitis', 'Disease', (145, 152))	('ZAP70', 'Gene', '7535', (17, 22))	('proteinuria', 'Disease', 'MESH:D011507', (157, 168))	('bullous pemphigoid', 'Disease', (125, 143))	('attenuates', 'NegReg', (39, 49))	('colitis', 'Phenotype', 'HP:0002583', (145, 152))	('Tregs', 'Chemical', '-', (86, 91))	('autoimmunity', 'Phenotype', 'HP:0002960', (93, 105))	('patients', 'Species', '9606', (172, 180))	('ZAP70', 'Gene', (17, 22))	('proteinuria', 'Disease', (157, 168))
6420	33537838	Nucleotide variants of TAGAP that encode a thymocyte GAP protein are associated with various HAIDs, likely reflecting attenuated thymocyte migration from the cortex to the medulla.	('thymocyte migration from the', 'CPA', (129, 157))	('HAIDs', 'Disease', (93, 98))	('Nucleotide variants', 'Var', (0, 19))	('TAGAP', 'Gene', (23, 28))	('associated', 'Reg', (69, 79))	('TAGAP', 'Gene', '117289', (23, 28))	('attenuated', 'NegReg', (118, 128))	('HAIDs', 'Disease', 'None', (93, 98))
6421	33537838	Finally, associations of SNPs of SATB1 with colitis, psoriasis and MS have been linked to SATB1's role in Treg development in the thymic cortex.	('psoriasis', 'Disease', 'MESH:D011565', (53, 62))	('colitis', 'Phenotype', 'HP:0002583', (44, 51))	('linked', 'Reg', (80, 86))	('psoriasis', 'Phenotype', 'HP:0003765', (53, 62))	('SATB1', 'Gene', (90, 95))	('Treg', 'Chemical', '-', (106, 110))	('colitis', 'Disease', 'MESH:D003092', (44, 51))	('SNPs', 'Var', (25, 29))	('psoriasis', 'Disease', (53, 62))	('associations', 'Interaction', (9, 21))	('colitis', 'Disease', (44, 51))	('Treg development', 'CPA', (106, 122))	('SATB1', 'Gene', '6304', (90, 95))	('SATB1', 'Gene', (33, 38))	('SATB1', 'Gene', '6304', (33, 38))
6429	33537838	Defects of thymocyte adhesion, migration and egress from the thymus are typically associated with a combined (T-/B-cell) immunodeficiency, as exemplified by mutations of MST1 and CORO1A.	('thymocyte adhesion', 'CPA', (11, 29))	('associated', 'Reg', (82, 92))	('Defects', 'NegReg', (0, 7))	('immunodeficiency', 'Phenotype', 'HP:0002721', (121, 137))	('migration', 'CPA', (31, 40))	('MST1', 'Gene', '4485', (170, 174))	('immunodeficiency', 'Disease', 'MESH:D007153', (121, 137))	('MST1', 'Gene', (170, 174))	('mutations', 'Var', (157, 166))	('immunodeficiency', 'Disease', (121, 137))	('CORO1A', 'Gene', '11151', (179, 185))	('CORO1A', 'Gene', (179, 185))	('egress', 'CPA', (45, 51))
6431	33537838	In MTS1 mutant thymi, some T-cells typically escape to the periphery, where rarely oligoclonal or even monoclonal lymphoproliferations, organ infiltrates and autoantibody-mediated cytopenias develop.	('MTS1', 'Gene', '1029', (3, 7))	('mutant', 'Var', (8, 14))	('cytopenias', 'Disease', 'MESH:D006402', (180, 190))	('cytopenias', 'Disease', (180, 190))	('MTS1', 'Gene', (3, 7))
6432	33537838	In CORO1A mutations, the egress defect is generally so severe that autoimmunity is generally prevented.	('autoimmunity', 'Phenotype', 'HP:0002960', (67, 79))	('CORO1A', 'Gene', '11151', (3, 9))	('egress defect', 'MPA', (25, 38))	('CORO1A', 'Gene', (3, 9))	('mutations', 'Var', (10, 19))
6433	33537838	Thymi with defects in egress due to mutations of MTS1 and CORA1A usually retain their corticomedullary architecture.	('egress', 'CPA', (22, 28))	('MTS1', 'Gene', '1029', (49, 53))	('mutations', 'Var', (36, 45))	('defects', 'NegReg', (11, 18))	('RA', 'Disease', 'MESH:D001172', (60, 62))	('corticomedullary architecture', 'CPA', (86, 115))	('MTS1', 'Gene', (49, 53))
6434	33537838	The generally mild defect in MTS1 mutations shifts the balance towards a higher proportion of mature thymocytes, while the massive block to egress in CORO1A mutated thymi leads to 'giant PVS' with accumulations of mature T-cells.	('CORO1A', 'Gene', '11151', (150, 156))	('leads to', 'Reg', (171, 179))	('accumulations', 'PosReg', (197, 210))	("'giant", 'PosReg', (180, 186))	('MTS1', 'Gene', (29, 33))	('CORO1A', 'Gene', (150, 156))	('MTS1', 'Gene', '1029', (29, 33))	('mutated', 'Var', (157, 164))	('egress', 'MPA', (140, 146))	('mutations', 'Var', (34, 43))
6439	33537838	Female gender and the HLA-DR3 B8 A1 haplotype are strong risk factors, B8 appearing the strongest, though roles of other loci are less clear (Table 1).	('HLA', 'Gene', (22, 25))	('haplotype', 'Var', (36, 45))	('HLA', 'Gene', '3117', (22, 25))
6462	33537838	With rare exceptions, levels of mRNA encoding the AChR alpha-subunit are higher in TAMG(+) thymomas than in TAMG(-) thymomas, hinting at immunisation there rather than tolerance induction, unlike in the normal thymus.	('thymomas', 'Disease', 'MESH:D013945', (116, 124))	('thymomas', 'Disease', 'MESH:D013945', (91, 99))	('TAMG', 'Chemical', '-', (83, 87))	('thymoma', 'Phenotype', 'HP:0100522', (91, 98))	('TAMG(+', 'Var', (83, 89))	('TAMG', 'Chemical', '-', (108, 112))	('mRNA encoding', 'MPA', (32, 45))	('levels', 'MPA', (22, 28))	('thymoma', 'Phenotype', 'HP:0100522', (116, 123))	('thymomas', 'Disease', (91, 99))	('thymomas', 'Disease', (116, 124))	('higher', 'PosReg', (73, 79))
6467	33537838	autoantibodies against IL-17s and/ or IL-22 and loss of the cytokine-producing cells.	('loss', 'NegReg', (48, 52))	('IL-17', 'Gene', '3605', (23, 28))	('IL-22', 'Gene', '50616', (38, 43))	('IL-22', 'Gene', (38, 43))	('IL-17', 'Gene', (23, 28))	('autoantibodies', 'Var', (0, 14))
6469	33537838	The differences between these syndromes include the rarity in APECED patients of MG or of almost any neurological disorder or autoantibody; they may partly reflect the contrasting effects of AIRE mutations present since conception in APECED versus the focal acquisition of a neoplastic AIRE-deficient clone of thymic epithelial cells in adult thymoma patients who already have an established normal peripheral immune repertoire.	('neurological disorder', 'Disease', (101, 122))	('MG', 'Disease', 'MESH:D000080343', (81, 83))	('thymoma', 'Disease', (343, 350))	('neurological disorder', 'Phenotype', 'HP:0000707', (101, 122))	('neurological disorder', 'Disease', 'MESH:D009422', (101, 122))	('patients', 'Species', '9606', (69, 77))	('thymoma', 'Phenotype', 'HP:0100522', (343, 350))	('APECED', 'Gene', (62, 68))	('APECED', 'Gene', '326', (62, 68))	('neoplastic AIRE-deficient', 'Disease', (275, 300))	('thymoma', 'Disease', 'MESH:D013945', (343, 350))	('APECED', 'Gene', '326', (234, 240))	('patients', 'Species', '9606', (351, 359))	('APECED', 'Gene', (234, 240))	('neoplastic AIRE-deficient', 'Disease', 'MESH:D016884', (275, 300))	('mutations', 'Var', (196, 205))
6570	28674368	Subsequently, SPS was established as an autoimmune disorder, most frequently associated with antibodies against GAD.	('autoimmune disorder', 'Phenotype', 'HP:0002960', (40, 59))	('SPS', 'Disease', (14, 17))	('autoimmune disorder', 'Disease', (40, 59))	('GAD', 'Gene', (112, 115))	('antibodies', 'Var', (93, 103))	('autoimmune disorder', 'Disease', 'MESH:D001327', (40, 59))	('GAD', 'Gene', '2571', (112, 115))	('associated', 'Reg', (77, 87))
6740	26632723	Although pathogenic bacterium is the most common pathogen in all GS patients, opportunistic pathogens associated with cell-mediated immunodeficiency including CMV (41.7%) and P. jirovecii (16.7%), frequently caused opportunistic infections in hospitalized GS patients in this study.	('P. jirovecii', 'Var', (175, 187))	('patients', 'Species', '9606', (259, 267))	('immunodeficiency', 'Phenotype', 'HP:0002721', (132, 148))	('opportunistic infections', 'Disease', (215, 239))	('opportunistic infections', 'Phenotype', 'HP:0031690', (215, 239))	('immunodeficiency', 'Disease', 'MESH:D007153', (132, 148))	('caused', 'Reg', (208, 214))	('GS', 'Disease', 'MESH:D011125', (256, 258))	('opportunistic infections', 'Disease', 'MESH:D009894', (215, 239))	('immunodeficiency', 'Disease', (132, 148))	('patients', 'Species', '9606', (68, 76))	('P. jirovecii', 'Species', '42068', (175, 187))	('GS', 'Disease', 'MESH:D011125', (65, 67))
6741	26632723	CMV often appeared to cause intestinal infection, and P. jirovecii led to pulmonary infection.	('cause', 'Reg', (22, 27))	('intestinal infection', 'Disease', 'MESH:D007410', (28, 48))	('P. jirovecii', 'Species', '42068', (54, 66))	('pulmonary infection', 'Disease', (74, 93))	('pulmonary infection', 'Phenotype', 'HP:0006532', (74, 93))	('intestinal infection', 'Disease', (28, 48))	('led to', 'Reg', (67, 73))	('pulmonary infection', 'Disease', 'MESH:D008171', (74, 93))	('P. jirovecii', 'Var', (54, 66))
6807	25240293	The 5-year survival rate was around 50% for type B3 thymoma, while it was 90% for types B1, AB and A.	('AB', 'Disease', 'MESH:D049290', (92, 94))	('thymoma', 'Phenotype', 'HP:0100522', (52, 59))	('type B3', 'Var', (44, 51))	('thymoma', 'Disease', 'MESH:D013945', (52, 59))	('thymoma', 'Disease', (52, 59))
6861	23074376	A recheck of the thyroid function tests 20 days after the operation revealed TSH 22 mIU/ml, corrected calcium 8.8 mg/dl, and phosphate 2.4 mg/dl.	('corrected calcium', 'MPA', (92, 109))	('TSH', 'Var', (77, 80))	('TSH', 'Chemical', '-', (77, 80))	('calcium', 'Chemical', 'MESH:D002118', (102, 109))	('phosphate', 'Chemical', 'MESH:D010710', (125, 134))
6982	26087886	Based on mouse model, we confirmed that miR-15b knockdown could increase IL-15 expression in healthy mice, while miR-15b overexpression could inhibit IL-15 expression in EAMG mice.	('expression', 'Species', '29278', (79, 89))	('mice', 'Species', '10090', (175, 179))	('IL-15', 'Gene', (150, 155))	('inhibit', 'NegReg', (142, 149))	('overexpression', 'PosReg', (121, 135))	('expression', 'MPA', (79, 89))	('EAMG', 'Chemical', '-', (170, 174))	('expression', 'Species', '29278', (125, 135))	('mouse', 'Species', '10090', (9, 14))	('miR-15b', 'Gene', (40, 47))	('miR-15b', 'Gene', (113, 120))	('increase', 'PosReg', (64, 72))	('expression', 'Species', '29278', (156, 166))	('mice', 'Species', '10090', (101, 105))	('expression', 'MPA', (156, 166))	('IL-15', 'Gene', (73, 78))	('knockdown', 'Var', (48, 57))
6994	26087886	miR-15b is also an miRNA significantly and consistently downregulated in different clinical phenotypes of MG.	('MG', 'Disease', 'MESH:D000080343', (106, 108))	('miR-15b', 'Var', (0, 7))	('downregulated', 'NegReg', (56, 69))
7015	26087886	Il-15 concentration in human serum and in mouse serum and EDL muscle tissue were measured by using an ELISA kit (USCN Life Science, SEA061Hu and SEA061Mu) according to the manufacturer's instructions.	('Il-15', 'Gene', (0, 5))	('mouse', 'Species', '10090', (42, 47))	('Il-15', 'Gene', '3600', (0, 5))	('SEA061Hu', 'Var', (132, 140))	('human', 'Species', '9606', (23, 28))	('SEA061Mu', 'Var', (145, 153))
7026	26087886	To verify the putative binding site, HEK293T cells or C2C12 cells were co-transfected with either 100nM miR-15b mimics or miR-NC mimics and 200 ng of plasmid.	('HEK293T', 'CellLine', 'CVCL:0063', (37, 44))	('miR-15b', 'Gene', (104, 111))	('C2C12 cells', 'CellLine', 'CVCL:0188', (54, 65))	('mimics', 'Var', (112, 118))
7031	26087886	In both serum and EDL muscle level, miR-15b was significantly lower in EAMG mice than in healthy controls (Figure 1C, 1D).	('miR-15b', 'Gene', (36, 43))	('EAMG', 'Chemical', '-', (71, 75))	('lower', 'NegReg', (62, 67))	('mice', 'Species', '10090', (76, 80))	('EAMG', 'Var', (71, 75))
7032	26087886	For IL-15 expression, the average concentration (mean +-SD) in serum (pg/ml) and muscle (pg/mg tissue protein) of EAMG mice were 431.6+-36.1 and 11.4+-2.4, respectively, which were significantly higher than in healthy mice (264.0+-15.4 and 4.4+-1.3, respectively) (Figure 1E, 1F).	('mice', 'Species', '10090', (119, 123))	('IL-15', 'Gene', (4, 9))	('EAMG', 'Chemical', '-', (114, 118))	('higher', 'PosReg', (195, 201))	('expression', 'MPA', (10, 20))	('expression', 'Species', '29278', (10, 20))	('EAMG', 'Var', (114, 118))	('mice', 'Species', '10090', (218, 222))
7034	26087886	To further explore whether miR-15b can module IL-15 expression, primary EDL muscle cells were used for analysis.	('expression', 'Species', '29278', (52, 62))	('IL-15', 'Gene', (46, 51))	('miR-15b', 'Var', (27, 34))	('expression', 'MPA', (52, 62))
7035	26087886	First, primary EDL muscle cells from EMAG mice and healthy mice were transfected for overexpression and knockdown of miR-15b, respectively.	('mice', 'Species', '10090', (59, 63))	('miR-15b', 'Gene', (117, 124))	('mice', 'Species', '10090', (42, 46))	('expression', 'Species', '29278', (89, 99))	('knockdown', 'Var', (104, 113))
7037	26087886	In primary EMAG mouse, EDL muscle cells, miR-15b overexpression led to significantly decreased IL-15 expression at both mRNA (Figure 2C) and protein (Figure 2E) level.	('decreased', 'NegReg', (85, 94))	('IL-15', 'Gene', (95, 100))	('expression', 'Species', '29278', (53, 63))	('expression', 'Species', '29278', (101, 111))	('mouse', 'Species', '10090', (16, 21))	('overexpression', 'PosReg', (49, 63))	('expression', 'MPA', (101, 111))	('miR-15b', 'Var', (41, 48))
7038	26087886	In contrast, miR-15b knockdown in primary healthy mouse EDL muscle cells resulted in significantly increased IL-15 expression at mRNA (Figure 2D) and protein level (Figure 2F).	('IL-15', 'Gene', (109, 114))	('mouse', 'Species', '10090', (50, 55))	('expression', 'Species', '29278', (115, 125))	('expression', 'MPA', (115, 125))	('miR-15b', 'Gene', (13, 20))	('increased', 'PosReg', (99, 108))	('knockdown', 'Var', (21, 30))
7039	26087886	Therefore, these results suggest that miR-15b can modulate IL-15 expression.	('modulate', 'Reg', (50, 58))	('IL-15', 'Gene', (59, 64))	('expression', 'Species', '29278', (65, 75))	('expression', 'MPA', (65, 75))	('miR-15b', 'Var', (38, 45))
7042	26087886	Dual luciferase assay showed that miR-15b could significantly abrogate luciferase activity of the reporter with wild-type sequence, but had no inhibitive effect on the vector with mutant sequence in both HEK293T and C2C12 cells (Figure 3D, 3E).	('miR-15b', 'Var', (34, 41))	('HEK293T', 'CellLine', 'CVCL:0063', (204, 211))	('luciferase', 'Enzyme', (71, 81))	('C2C12 cells', 'CellLine', 'CVCL:0188', (216, 227))	('activity', 'MPA', (82, 90))	('abrogate', 'NegReg', (62, 70))
7050	26087886	Based on a mouse model, we confirmed that miR-15b knockdown can increase IL-15 expression in skeletal muscle of healthy mice, while miR-15b overexpression can inhibit IL-15 expression in EAMG mice.	('expression', 'Species', '29278', (79, 89))	('expression', 'Species', '29278', (144, 154))	('mice', 'Species', '10090', (120, 124))	('mice', 'Species', '10090', (192, 196))	('expression', 'MPA', (79, 89))	('EAMG', 'Chemical', '-', (187, 191))	('miR-15b', 'Gene', (132, 139))	('mouse', 'Species', '10090', (11, 16))	('knockdown', 'Var', (50, 59))	('overexpression', 'PosReg', (140, 154))	('increase', 'PosReg', (64, 72))	('expression', 'Species', '29278', (173, 183))	('expression', 'MPA', (173, 183))	('IL-15', 'Gene', (73, 78))	('inhibit', 'NegReg', (159, 166))	('miR-15b', 'Gene', (42, 49))
7056	26087886	IL-15 neutralization by using IL-15-specific antibodies contributed to reduced severity of psoriasis in a human psoriasis xenograft model.	('human', 'Species', '9606', (106, 111))	('IL-15', 'Gene', (0, 5))	('psoriasis', 'Disease', 'MESH:D011565', (112, 121))	('psoriasis', 'Disease', 'MESH:D011565', (91, 100))	('severity', 'MPA', (79, 87))	('IL-15-specific', 'Gene', (30, 44))	('psoriasis', 'Disease', (112, 121))	('psoriasis', 'Phenotype', 'HP:0003765', (112, 121))	('reduced', 'NegReg', (71, 78))	('psoriasis', 'Disease', (91, 100))	('psoriasis', 'Phenotype', 'HP:0003765', (91, 100))	('neutralization', 'Var', (6, 20))
7057	26087886	In an in vivo model, blocking IL-15 also prevented the induction of allergen-specific T cells and associated allergic inflammation .	('IL-15', 'Gene', (30, 35))	('blocking', 'Var', (21, 29))	('prevented', 'NegReg', (41, 50))	('allergic inflammation', 'Disease', (109, 130))	('allergen-specific T cells', 'CPA', (68, 93))	('allergic inflammation', 'Disease', 'MESH:D007249', (109, 130))
7174	33805310	reported a better, but not statistically significant survival rate in B1-B2 vs. B3 thymomas.	('thymomas', 'Disease', 'MESH:D013945', (83, 91))	('thymomas', 'Disease', (83, 91))	('B1-B2', 'Var', (70, 75))	('thymoma', 'Phenotype', 'HP:0100522', (83, 90))
7186	33805310	reporting a significantly better survival in surgical resections (also debulking) versus other treatments; R0-R1 thymoma patients showed a better survival rate than R2 patients, which in turn, showed a better survival rate than those treated differently, even if not statistically significant.	('thymoma', 'Disease', 'MESH:D013945', (113, 120))	('R0-R1', 'Var', (107, 112))	('thymoma', 'Disease', (113, 120))	('survival', 'MPA', (146, 154))	('thymoma', 'Phenotype', 'HP:0100522', (113, 120))	('patients', 'Species', '9606', (168, 176))	('better', 'PosReg', (139, 145))	('patients', 'Species', '9606', (121, 129))
7299	33569912	13 ,  16 ,  28 ,  29 ,  30 ,  31   The operative time and intraoperative blood loss in the CRT + surgery group were significantly longer than that in the surgery group, which may be due to the formation of connective tissue around the thymoma by chemoradiotherapy, making it more difficult to separate the tumors.	('thymoma', 'Disease', (235, 242))	('longer', 'PosReg', (130, 136))	('tumor', 'Phenotype', 'HP:0002664', (306, 311))	('tumors', 'Disease', (306, 312))	('tumors', 'Disease', 'MESH:D009369', (306, 312))	('thymoma', 'Phenotype', 'HP:0100522', (235, 242))	('tumors', 'Phenotype', 'HP:0002664', (306, 312))	('intraoperative blood loss', 'Disease', (58, 83))	('CRT + surgery', 'Var', (91, 104))	('intraoperative blood loss', 'Disease', 'MESH:D016063', (58, 83))	('thymoma', 'Disease', 'MESH:D013945', (235, 242))
7342	26429871	T cell clonality screening by TCRgamma PCR was positive for a clonal TCRbeta gene rearrangement.	('rearrangement', 'Var', (82, 95))	('TCRbeta', 'Gene', '6957', (69, 76))	('TCRbeta', 'Gene', (69, 76))
7345	26429871	FISH analysis utilizing probes specific for aberrations commonly associated with myelodysplasia (MDS) and for rearrangements of the TCR alpha/delta locus (14q11) were performed.	('MDS', 'Disease', (97, 100))	('MDS', 'Disease', 'MESH:D009190', (97, 100))	('MDS', 'Phenotype', 'HP:0002863', (97, 100))	('myelodysplasia', 'Disease', 'MESH:D009190', (81, 95))	('rearrangements', 'Var', (110, 124))	('associated', 'Reg', (65, 75))	('myelodysplasia', 'Disease', (81, 95))	('TCR alpha/delta', 'Gene', (132, 147))	('myelodysplasia', 'Phenotype', 'HP:0002863', (81, 95))
7381	26429871	It is believed that dysregulated activation signaling and impaired Fas-induced dealth signaling complex (DISC) formation, which renders LGL CD8+ T cells resistant to Fas-mediated apoptosis, enable them to proliferate and contribute to pathogenesis of LGL.	('dysregulated', 'Var', (20, 32))	('contribute', 'Reg', (221, 231))	('Fas', 'Chemical', 'MESH:C038178', (166, 169))	('enable', 'PosReg', (190, 196))	('activation', 'PosReg', (33, 43))	('CD8', 'Gene', (140, 143))	('proliferate', 'CPA', (205, 216))	('CD8', 'Gene', '925', (140, 143))	('LGL', 'Disease', (251, 254))	('impaired', 'NegReg', (58, 66))	('Fas', 'Chemical', 'MESH:C038178', (67, 70))
7605	31827799	Concordance between antibodies was lower for PD-L1 staining on immune cells with no significant difference between TB3 and TC except on E1L3N antibody.	('Concordance', 'MPA', (0, 11))	('E1L3N', 'Var', (136, 141))	('lower', 'NegReg', (35, 40))	('TB3', 'Chemical', '-', (115, 118))	('PD-L1', 'Gene', (45, 50))
7640	31827799	Sections were deparaffinized, rehydrated and heated for antigen retrieval, 20 min in high buffer (DAKO) (PD-L1 SP142, PD-L1 E1L3N, and PD-L2), and 64 min CC1 (PD1 and CD8).	('PD-L2', 'Gene', (135, 140))	('PD-L2', 'Gene', '80380', (135, 140))	('SP142', 'Chemical', '-', (111, 116))	('CD8', 'Gene', (167, 170))	('CD8', 'Gene', '925', (167, 170))	('CC1', 'Gene', '6358', (154, 157))	('CC1', 'Gene', (154, 157))	('PD-L1 E1L3N', 'Var', (118, 129))	('PD-L1 SP142', 'Var', (105, 116))
7652	31827799	PD-L1 expression was found positive using a 50% threshold in approximatively half of the patients with reproducible results across the antibodies: 51% with 22C3 pharm DX assay, 52% with E1L3N antibody on Dako Autostainer, 51% with SP142 antibody on Dako Autostainer, 53% with SP263 CA on Ventana Benchmark Ultra.	('SP263', 'Chemical', '-', (276, 281))	('SP142', 'Chemical', '-', (231, 236))	('SP263 CA', 'Var', (276, 284))	('patients', 'Species', '9606', (89, 97))	('E1L3N', 'Var', (186, 191))	('Dako', 'Chemical', '-', (204, 208))	('Dako', 'Chemical', '-', (249, 253))
7671	31827799	As expected, survival was superior in TB3 when compared to TC (p = 0.04, Fig.	('TB3', 'Chemical', '-', (38, 41))	('superior', 'PosReg', (26, 34))	('TB3', 'Var', (38, 41))	('survival', 'CPA', (13, 21))
7674	31827799	In the subgroup of TB3, PD-L1 expression was significantly associated with a better PFS no matter which antibody was used (Fig.	('expression', 'Var', (30, 40))	('PFS', 'Disease', (84, 87))	('PD-L1', 'Gene', (24, 29))	('TB3', 'Chemical', '-', (19, 22))
7675	31827799	PFS was almost double in patients with PDL1 expression regardless the antibody used for PD-L1 detection and the cut-off (1% vs. 50%).	('PDL1', 'Gene', (39, 43))	('PFS', 'MPA', (0, 3))	('expression', 'Var', (44, 54))	('patients', 'Species', '9606', (25, 33))	('PDL1', 'Gene', '29126', (39, 43))
7682	31827799	PD-L1 high scores were more frequent in TETs than in thymic controls (68.1% versus 17.6%).	('PD-L1', 'Gene', (0, 5))	('TETs', 'Chemical', 'MESH:C010349', (40, 44))	('TETs', 'Disease', (40, 44))	('high scores', 'Var', (6, 17))
7690	31827799	found no impact of PD-L1 expression on survival but high PD-L1 was associated with advanced Masaoka staging and high-grade histology in surgically treated thymoma ).	('high-grade histology', 'CPA', (112, 132))	('PD-L1', 'Gene', (57, 62))	('thymoma', 'Disease', 'MESH:D013945', (155, 162))	('Masaoka', 'Disease', (92, 99))	('associated', 'Reg', (67, 77))	('high', 'Var', (52, 56))	('thymoma', 'Disease', (155, 162))	('thymoma', 'Phenotype', 'HP:0100522', (155, 162))
7691	31827799	In patients with advanced thymic carcinoma, the median PFS was higher in the low PD-L1 group vs the high PD-L1 group (23.5 vs 13.3 months).	('thymic carcinoma', 'Disease', (26, 42))	('low', 'Var', (77, 80))	('carcinoma', 'Phenotype', 'HP:0030731', (33, 42))	('thymic carcinoma', 'Disease', 'MESH:D013953', (26, 42))	('PFS', 'MPA', (55, 58))	('patients', 'Species', '9606', (3, 11))	('higher', 'PosReg', (63, 69))
7692	31827799	reported that PD-L1 expression was more common in thymomas compared to thymic carcinoma and was associated with longer overall survival (Arbour KC, PLoS One 2017) in line with our findings.	('thymic carcinoma', 'Disease', (71, 87))	('thymic carcinoma', 'Disease', 'MESH:D013953', (71, 87))	('thymoma', 'Phenotype', 'HP:0100522', (50, 57))	('carcinoma', 'Phenotype', 'HP:0030731', (78, 87))	('expression', 'Var', (20, 30))	('common', 'Reg', (40, 46))	('thymomas', 'Disease', 'MESH:D013945', (50, 58))	('overall survival', 'MPA', (119, 135))	('PD-L1', 'Gene', (14, 19))	('thymomas', 'Disease', (50, 58))	('longer', 'PosReg', (112, 118))
7807	30572538	This survival benefit of reducing the tumor burden, decompressing the spinal stenosis to alleviate radiculopathy, and facilitating subsequent chemotherapy and radiation therapy.	('radiculopathy', 'Disease', 'MESH:D011843', (99, 112))	('tumor', 'Disease', (38, 43))	('spinal stenosis', 'Phenotype', 'HP:0003416', (70, 85))	('tumor', 'Phenotype', 'HP:0002664', (38, 43))	('radiculopathy', 'Disease', (99, 112))	('decompressing', 'Var', (52, 65))	('tumor', 'Disease', 'MESH:D009369', (38, 43))	('spinal stenosis', 'Disease', 'MESH:D013130', (70, 85))	('spinal stenosis', 'Disease', (70, 85))
7963	28123839	IHC revealed positivity for B-cell markers CD20 and CD45, findings suggestive, but not diagnostic, of B-cell lymphoma.	('positivity', 'Var', (13, 23))	('CD20', 'Gene', '54474', (43, 47))	('CD45', 'Gene', (52, 56))	('CD20', 'Gene', (43, 47))	('lymphoma', 'Disease', 'MESH:D008223', (109, 117))	('lymphoma', 'Phenotype', 'HP:0002665', (109, 117))	('CD45', 'Gene', '5788', (52, 56))	('cell lymphoma', 'Phenotype', 'HP:0012191', (104, 117))	('lymphoma', 'Disease', (109, 117))	('B-cell lymphoma', 'Phenotype', 'HP:0012191', (102, 117))
7977	28123839	Patients with the much less common and more aggressive DLBCL variant present with fever, dyspnea, cough, and constitutional symptoms.	('DLBCL', 'Gene', (55, 60))	('fever', 'Disease', 'MESH:D005334', (82, 87))	('dyspnea', 'Phenotype', 'HP:0002094', (89, 96))	('fever', 'Disease', (82, 87))	('cough', 'Phenotype', 'HP:0012735', (98, 103))	('variant', 'Var', (61, 68))	('Patients', 'Species', '9606', (0, 8))	('dyspnea', 'Disease', (89, 96))	('fever', 'Phenotype', 'HP:0001945', (82, 87))	('constitutional symptoms', 'Disease', (109, 132))	('cough', 'Disease', (98, 103))	('dyspnea', 'Disease', 'MESH:D004417', (89, 96))	('constitutional symptoms', 'Phenotype', 'HP:0025142', (109, 132))
8069	23742015	Eosinophil deficiency can be regarded as having several origins: first, as a spontaneous occurrence in human diseases; second, as a result of genetic manipulations in experimental animals; and third, as an effect of pharmacological agents specifically designed to reduce eosinophil numbers.	('Eosinophil deficiency', 'Disease', 'MESH:D004802', (0, 21))	('man', 'Species', '9606', (105, 108))	('man', 'Species', '9606', (150, 153))	('Eosinophil deficiency', 'Disease', (0, 21))	('human', 'Species', '9606', (103, 108))	('manipulations', 'Var', (150, 163))	('Eosinophil deficiency', 'Phenotype', 'HP:0031891', (0, 21))	('reduce eosinophil numbers', 'Phenotype', 'HP:0031891', (264, 289))
8142	23742015	One strain was engineered by deletion of a high-affinity GATA-binding site in the GATA-1 promoter.	('deletion', 'Var', (29, 37))	('GATA-binding', 'Protein', (57, 69))	('GATA', 'Chemical', '-', (57, 61))	('GATA', 'Chemical', '-', (82, 86))	('GATA-1', 'Gene', '2623', (82, 88))	('GATA-1', 'Gene', (82, 88))
8144	23742015	Deletion of the GATA-binding site within the gene's promoter led to selective loss of the eosinophil lineage, and these mice have been used to determine the role of the eosinophil in disease models, including asthma.	('asthma', 'Disease', (209, 215))	('mice', 'Species', '10090', (120, 124))	('asthma', 'Phenotype', 'HP:0002099', (209, 215))	('GATA', 'Chemical', '-', (16, 20))	('eosinophil lineage', 'CPA', (90, 108))	('loss', 'NegReg', (78, 82))	('asthma', 'Disease', 'MESH:D001249', (209, 215))	('Deletion', 'Var', (0, 8))
8176	23742015	Furthermore, because anti-IL-5 antibody therapy profoundly reduces the numbers of blood and tissue eosinophils, but does not deplete them completely, treatment with these agents is not entirely comparable to the mouse models and patients described above.	('patients', 'Species', '9606', (229, 237))	('reduces', 'NegReg', (59, 66))	('anti-IL-5', 'Var', (21, 30))	('mouse', 'Species', '10090', (212, 217))
8248	30961527	In ANCA-associated vasculitis, abnormalities in the number and function of regulatory T cells have been observed, and peripheral immune tolerance abnormality in regulatory T cells is one of the pathogeneses of ANCA-associated vasculitis.	('vasculitis', 'Disease', 'MESH:D014657', (226, 236))	('vasculitis', 'Disease', (19, 29))	('vasculitis, abnormalities in the number', 'Disease', 'MESH:D014657', (19, 58))	('vasculitis', 'Disease', (226, 236))	('abnormality', 'Var', (146, 157))	('ANCA', 'Chemical', '-', (210, 214))	('vasculitis', 'Disease', 'MESH:D014657', (19, 29))	('vasculitis', 'Phenotype', 'HP:0002633', (19, 29))	('ANCA', 'Chemical', '-', (3, 7))	('vasculitis', 'Phenotype', 'HP:0002633', (226, 236))
8249	30961527	In contrast, thymoma-associated autoimmune diseases may be caused by abnormalities of central immune tolerance due to the induction of autoreactive T-cell clones in abnormal thymic tissue or to the suppression of regulatory T cells.	('abnormalities', 'Var', (69, 82))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (32, 51))	('thymoma', 'Disease', 'MESH:D013945', (13, 20))	('thymoma', 'Disease', (13, 20))	('autoimmune disease', 'Phenotype', 'HP:0002960', (32, 50))	('autoimmune diseases', 'Disease', 'MESH:D001327', (32, 51))	('central immune tolerance', 'CPA', (86, 110))	('thymoma', 'Phenotype', 'HP:0100522', (13, 20))	('caused by', 'Reg', (59, 68))	('autoimmune diseases', 'Disease', (32, 51))
8380	33374432	This considering that a correlation of the rate of lymph node metastases with the WHO classification and TNM staging system has been reported, with a higher incidence of lymphatic spread in B2-B3 thymomas and in TNM stage III tumors.	('B2-B3', 'Var', (190, 195))	('thymomas', 'Disease', 'MESH:D013945', (196, 204))	('tumors', 'Phenotype', 'HP:0002664', (226, 232))	('higher', 'PosReg', (150, 156))	('metastases', 'Disease', 'MESH:D009362', (62, 72))	('III tumors', 'Disease', 'MESH:D009369', (222, 232))	('thymoma', 'Phenotype', 'HP:0100522', (196, 203))	('III tumors', 'Disease', (222, 232))	('tumor', 'Phenotype', 'HP:0002664', (226, 231))	('thymomas', 'Disease', (196, 204))	('metastases', 'Disease', (62, 72))	('lymphatic spread', 'CPA', (170, 186))
8404	32015469	Compared with non-dRT, dRT significantly improved 5-year overall survival (OS, P = 0.003), progression-free survival (PFS, P = 0.008), and freedom from locoregional failure (FFLF, P < 0.001).	('LF', 'Disease', 'MESH:D009364', (176, 178))	('improved', 'PosReg', (41, 49))	('freedom', 'CPA', (139, 146))	('dRT', 'Var', (23, 26))	('overall survival', 'CPA', (57, 73))	('locoregional failure', 'Disease', 'MESH:D009364', (152, 172))	('locoregional failure', 'Disease', (152, 172))	('progression-free survival', 'CPA', (91, 116))
8406	32015469	On multivariate analysis, dRT was an independent prognostic factor for OS (hazard ratio [HR]: 2.37, P = 0.024), PFS (HR: 2.40, P = 0.004), and FFLF (HR: 3.83, P = 0.001).	('PFS', 'Disease', (112, 115))	('dRT', 'Var', (26, 29))	('LF', 'Disease', 'MESH:D009364', (145, 147))
8450	32015469	Patients who received dRT had improved OS and PFS compared with patients who did not receive dRT (Fig.	('patients', 'Species', '9606', (64, 72))	('dRT', 'Var', (22, 25))	('Patients', 'Species', '9606', (0, 8))	('PFS', 'CPA', (46, 49))	('improved', 'PosReg', (30, 38))
8455	32015469	The 5- and 10-year PFS rates were 37.3% and 37.3%, respectively, among patients who underwent both DS and dRT and 34.8% and 18%, respectively, among patients who did not undergo both DS and dRT (P = 0.149).	('patients', 'Species', '9606', (71, 79))	('PFS', 'CPA', (19, 22))	('patients', 'Species', '9606', (149, 157))	('dRT', 'Var', (106, 109))
8456	32015469	Table 2 showed that tumor size >7 cm (P = 0.014), B2 or B3 subtype (P = 0.002), absence of dRT (P = 0.008), and unimodal treatment (P = 0.038) were found to be associated with worse OS, and tumor size >7 cm (P = 0.019), B2 or B3 subtype (P = 0.004), and absence of dRT (P = 0.003) were found to be associated with worse PFS on univariate analysis.	('absence', 'Var', (80, 87))	('tumor', 'Disease', 'MESH:D009369', (190, 195))	('tumor', 'Phenotype', 'HP:0002664', (190, 195))	('worse OS', 'Disease', (176, 184))	('tumor', 'Disease', 'MESH:D009369', (20, 25))	('tumor', 'Disease', (190, 195))	('tumor', 'Phenotype', 'HP:0002664', (20, 25))	('tumor', 'Disease', (20, 25))
8457	32015469	On multivariate analysis (Table 3), tumor size >7 cm (hazard ratio [HR]: 2.37, 95% confidence interval [CI]: 1.09-5.15, P = 0.029), B2 or B3 subtype (HR: 0.38, 95% CI: 0.19-0.74, P = 0.005), and absence of dRT (HR: 2.12, 95% CI: 1.10-4.06, P = 0.024) were associated with worse OS, while tumor size >7 cm (HR: 2.55, 95% CI: 1.29-5.04, P = 0.007) and absence of dRT (HR: 2.40, 95% CI: 1.33-4.38, P = 0.004) were associated with worse PFS.	('tumor', 'Disease', (288, 293))	('tumor', 'Disease', 'MESH:D009369', (36, 41))	('tumor', 'Disease', 'MESH:D009369', (288, 293))	('absence', 'Var', (350, 357))	('tumor', 'Phenotype', 'HP:0002664', (36, 41))	('tumor', 'Phenotype', 'HP:0002664', (288, 293))	('tumor', 'Disease', (36, 41))
8464	32015469	The 5- and 10-year FFLF rates were significantly higher in the dRT group (79.6% and 48.5%, respectively) than in the non-dRT group (23.6% and 8.8%, respectively; P < 0.001).	('dRT', 'Var', (63, 66))	('higher', 'PosReg', (49, 55))	('LF', 'Disease', 'MESH:D009364', (21, 23))
8466	32015469	Table 4 showed that tumor size >7 cm (P = 0.011), B2 or B3 subtype (P = 0.002), and absence of dRT (P < 0.001) were found to be associated with worse FFLF, and tumor size >7 cm (P = 0.014) and B2 or B3 subtype (P < 0.001) were found to be associated with worse FFDM on univariate analysis.	('absence', 'Var', (84, 91))	('LF', 'Disease', 'MESH:D009364', (152, 154))	('tumor', 'Disease', 'MESH:D009369', (160, 165))	('dRT', 'Gene', (95, 98))	('tumor', 'Disease', 'MESH:D009369', (20, 25))	('tumor', 'Phenotype', 'HP:0002664', (160, 165))	('tumor', 'Phenotype', 'HP:0002664', (20, 25))	('tumor', 'Disease', (160, 165))	('tumor', 'Disease', (20, 25))
8467	32015469	On multivariate analysis (Table 5), tumor size >7 cm (HR: 5.63, 95% CI: 1.99-15.91, P = 0.001), great-vessel invasion (HR: 2.36, 95% CI: 1.09-5.12, P = 0.029), and absence of dRT (HR: 3.83, 95% CI: 1.76-8.31, P = 0.001) were associated with worse FFLF, and tumor size >7 cm (HR: 4.38, 95% CI: 1.79-15.01, P = 0.002), B2 or B3 subtype (HR: 0.14, 95% CI: 0.05-0.37, P < 0.001), and great-vessel invasion (HR: 4.09, 95% CI: 1.50-11.12, P = 0.006) were associated with worse FFDM.	('tumor', 'Phenotype', 'HP:0002664', (257, 262))	('tumor', 'Disease', (257, 262))	('worse', 'Disease', (241, 246))	('absence', 'Var', (164, 171))	('tumor', 'Disease', 'MESH:D009369', (36, 41))	('LF', 'Disease', 'MESH:D009364', (249, 251))	('great-vessel invasion', 'CPA', (380, 401))	('tumor', 'Phenotype', 'HP:0002664', (36, 41))	('tumor', 'Disease', 'MESH:D009369', (257, 262))	('tumor', 'Disease', (36, 41))
8496	32015469	In addition to radiotherapy, our study found that tumor size <=7 cm was associated with improved OS, PFS, FFLF, and FFDM, which implies that tumor size may be an important prognostic predictor for incompletely resected or unresectable thymoma.	('tumor', 'Disease', 'MESH:D009369', (141, 146))	('thymoma', 'Disease', (235, 242))	('LF', 'Disease', 'MESH:D009364', (108, 110))	('tumor', 'Phenotype', 'HP:0002664', (141, 146))	('<=7', 'Var', (61, 64))	('PFS', 'Disease', (101, 104))	('tumor', 'Disease', (141, 146))	('tumor', 'Disease', 'MESH:D009369', (50, 55))	('thymoma', 'Phenotype', 'HP:0100522', (235, 242))	('tumor', 'Phenotype', 'HP:0002664', (50, 55))	('improved', 'PosReg', (88, 96))	('tumor', 'Disease', (50, 55))	('thymoma', 'Disease', 'MESH:D013945', (235, 242))
8509	32015469	Multivariate analysis showed that dRT was an independent predictor of OS, PFS, and FFLF.	('PFS', 'Disease', (74, 77))	('dRT', 'Var', (34, 37))	('LF', 'Disease', 'MESH:D009364', (85, 87))
8513	24260492	Association of the DNMT3B -579G>T Polymorphism with Risk of Thymomas in Patients with Myasthenia Gravis Increasing evidence suggests a contribution of epigenetic processes in promoting cancer and autoimmunity.	('Thymomas', 'Disease', (60, 68))	('Myasthenia Gravis', 'Disease', 'MESH:D009157', (86, 103))	('cancer', 'Phenotype', 'HP:0002664', (185, 191))	('-579G>T', 'Var', (26, 33))	('DNMT3B', 'Gene', (19, 25))	('DNMT3B', 'Gene', '1789', (19, 25))	('Myasthenia Gravis', 'Disease', (86, 103))	('autoimmunity', 'Phenotype', 'HP:0002960', (196, 208))	('-579G>T', 'SUBSTITUTION', 'None', (26, 33))	('cancer', 'Disease', 'MESH:D009369', (185, 191))	('Myasthenia', 'Phenotype', 'HP:0003473', (86, 96))	('Association', 'Interaction', (0, 11))	('cancer', 'Disease', (185, 191))	('Patients', 'Species', '9606', (72, 80))	('Thymoma', 'Phenotype', 'HP:0100522', (60, 67))
8514	24260492	Myasthenia gravis (MG) is an autoimmune disease mediated, in approximately 80% of the patients, by antibodies against the nicotinic acetylcholine receptor (AChR+).	('autoimmune disease', 'Disease', 'MESH:D001327', (29, 47))	('antibodies', 'Var', (99, 109))	('autoimmune disease', 'Phenotype', 'HP:0002960', (29, 47))	('Myasthenia gravis', 'Disease', (0, 17))	('Myasthenia gravis', 'Disease', 'MESH:D009157', (0, 17))	('mediated', 'Reg', (48, 56))	('acetylcholine', 'Chemical', 'MESH:D000109', (132, 145))	('AChR+', 'Gene', (156, 161))	('Myasthenia', 'Phenotype', 'HP:0003473', (0, 10))	('autoimmune disease', 'Disease', (29, 47))	('patients', 'Species', '9606', (86, 94))
8516	24260492	In the present study we investigated if a common polymorphism (-579G>T: rs1569686) in the promoter of the DNMT3B gene coding for the DNA methyltransferase 3B, an enzyme that mediates DNA methylation, increases the risk to develop MG or MG-associated thymomas.	('DNA methyltransferase 3B', 'Gene', (133, 157))	('-579G>T', 'SUBSTITUTION', 'None', (63, 70))	('thymoma', 'Phenotype', 'HP:0100522', (250, 257))	('increases', 'PosReg', (200, 209))	('DNMT3B', 'Gene', (106, 112))	('DNMT3B', 'Gene', '1789', (106, 112))	('DNA methyltransferase 3B', 'Gene', '1789', (133, 157))	('rs1569686', 'Var', (72, 81))	('thymomas', 'Disease', (250, 258))	('rs1569686', 'DBSNP_MENTION', 'None', (72, 81))	('thymomas', 'Disease', 'MESH:D013945', (250, 258))	('-579G>T', 'Var', (63, 70))
8523	24260492	Increasing evidence suggests a contribution of epigenetic modifications in complex diseases such as cancer and autoimmune disorders.	('epigenetic modifications', 'Var', (47, 71))	('cancer', 'Phenotype', 'HP:0002664', (100, 106))	('autoimmune disorders', 'Disease', (111, 131))	('contribution', 'Reg', (31, 43))	('autoimmune disorders', 'Phenotype', 'HP:0002960', (111, 131))	('cancer', 'Disease', (100, 106))	('cancer', 'Disease', 'MESH:D009369', (100, 106))	('autoimmune disorders', 'Disease', 'MESH:D001327', (111, 131))
8525	24260492	Most of the studies performed so far in autoimmune diseases have focused on DNA methylation impairments in systemic lupus erythematosus and rheumatoid arthritis.	('autoimmune diseases', 'Disease', (40, 59))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (40, 59))	('systemic lupus erythematosus', 'Disease', (107, 135))	('arthritis', 'Phenotype', 'HP:0001369', (151, 160))	('autoimmune disease', 'Phenotype', 'HP:0002960', (40, 58))	('systemic lupus erythematosus', 'Phenotype', 'HP:0002725', (107, 135))	('rheumatoid arthritis', 'Phenotype', 'HP:0001370', (140, 160))	('autoimmune diseases', 'Disease', 'MESH:D001327', (40, 59))	('systemic lupus erythematosus', 'Disease', 'MESH:D008180', (107, 135))	('impairments', 'Var', (92, 103))	('rheumatoid arthritis', 'Disease', (140, 160))	('rheumatoid arthritis', 'Disease', 'MESH:D001172', (140, 160))
8531	24260492	The goal of the present study was to investigate if a common polymorphism (-579G>T: rs1569686) in the promoter of the DNMT3B gene coding for the DNA methyltransferase 3B, one of the key de novo enzymes mediating DNA methylation, increases the risk to develop MG or MG-associated thymomas.	('DNMT3B', 'Gene', (118, 124))	('DNA methyltransferase 3B', 'Gene', '1789', (145, 169))	('DNMT3B', 'Gene', '1789', (118, 124))	('-579G>T', 'Var', (75, 82))	('thymomas', 'Disease', (279, 287))	('thymomas', 'Disease', 'MESH:D013945', (279, 287))	('rs1569686', 'DBSNP_MENTION', 'None', (84, 93))	('increases', 'Reg', (229, 238))	('-579G>T', 'SUBSTITUTION', 'None', (75, 82))	('DNA methyltransferase 3B', 'Gene', (145, 169))	('thymoma', 'Phenotype', 'HP:0100522', (279, 286))	('rs1569686', 'Var', (84, 93))
8532	24260492	The selected polymorphism has been suggested to impair DNA methylation of tumor suppressor genes, therefore impairing their expression levels, and for this reason it was investigated as a susceptibility factor for several cancer types.	('polymorphism', 'Var', (13, 25))	('cancer', 'Disease', 'MESH:D009369', (222, 228))	('tumor', 'Disease', 'MESH:D009369', (74, 79))	('impairing', 'NegReg', (108, 117))	('expression levels', 'MPA', (124, 141))	('cancer', 'Disease', (222, 228))	('tumor', 'Phenotype', 'HP:0002664', (74, 79))	('impair', 'NegReg', (48, 54))	('tumor', 'Disease', (74, 79))	('DNA methylation', 'MPA', (55, 70))	('cancer', 'Phenotype', 'HP:0002664', (222, 228))
8533	24260492	A meta-analysis of published studies revealed that the mutant allele (T) is associated with increased risk of cancer compared to the wild type one (G).	('cancer', 'Disease', (110, 116))	('cancer', 'Disease', 'MESH:D009369', (110, 116))	('mutant', 'Var', (55, 61))	('cancer', 'Phenotype', 'HP:0002664', (110, 116))
8534	24260492	Moreover, DNMT3B promoter polymorphisms have been associated with global DNA methylation and are increasingly investigated in other complex diseases than cancer.	('polymorphisms', 'Var', (26, 39))	('global DNA methylation', 'MPA', (66, 88))	('cancer', 'Disease', (154, 160))	('cancer', 'Disease', 'MESH:D009369', (154, 160))	('DNMT3B', 'Gene', '1789', (10, 16))	('cancer', 'Phenotype', 'HP:0002664', (154, 160))	('associated', 'Reg', (50, 60))	('DNMT3B', 'Gene', (10, 16))
8535	24260492	Indeed, clinical studies showed association with wide-spread DNA methylation and suicide attempts in psychiatric patients, with increased risk of early-onset schizophrenia, with risk of giving birth to a child with Down syndrome, as well as with increased risk of the autoimmune disease oral lichen planus, and with the progression of joint destruction in rheumatoid arthritis.	('rheumatoid arthritis', 'Disease', (356, 376))	('rheumatoid arthritis', 'Disease', 'MESH:D001172', (356, 376))	('autoimmune disease oral lichen planus', 'Disease', 'MESH:D008010', (268, 305))	('child', 'Species', '9606', (204, 209))	('risk of giving birth', 'Phenotype', 'HP:0001622', (178, 198))	('patients', 'Species', '9606', (113, 121))	('schizophrenia', 'Disease', (158, 171))	('psychiatric', 'Disease', 'MESH:D001523', (101, 112))	('psychiatric', 'Disease', (101, 112))	('suicide attempts', 'Phenotype', 'HP:0100716', (81, 97))	('rheumatoid arthritis', 'Phenotype', 'HP:0001370', (356, 376))	('methylation', 'Var', (65, 76))	('schizophrenia', 'Disease', 'MESH:D012559', (158, 171))	('autoimmune disease', 'Phenotype', 'HP:0002960', (268, 286))	('schizophrenia', 'Phenotype', 'HP:0100753', (158, 171))	('association', 'Interaction', (32, 43))	('arthritis', 'Phenotype', 'HP:0001369', (367, 376))	('autoimmune disease oral lichen planus', 'Disease', (268, 305))
8553	24260492	Allele and genotype frequencies generated by the DNMT3B -579G>T polymorphism in patients and controls are shown in Tables 2 and 3, respectively .	('DNMT3B', 'Gene', (49, 55))	('-579G>T', 'Var', (56, 63))	('patients', 'Species', '9606', (80, 88))	('-579G>T', 'SUBSTITUTION', 'None', (56, 63))	('DNMT3B', 'Gene', '1789', (49, 55))
8559	24260492	We also compared allele and genotype frequencies generated by the DNMT3B -579G>T polymorphism in MG patients stratified according to disease age at onset (<=45 years vs. > 45 years), to disease severity (less severe forms: Grade I + IIA vs. more severe forms: Grade IIB + III + IV), or to the presence/absence of associated autoimmune diseases (associated AID vs. no associated AID).	('age', 'Gene', '5973', (141, 144))	('AID', 'Disease', 'None', (356, 359))	('AID', 'Disease', (378, 381))	('AID', 'Disease', (356, 359))	('autoimmune disease', 'Phenotype', 'HP:0002960', (324, 342))	('AID', 'Disease', 'None', (378, 381))	('autoimmune diseases', 'Disease', 'MESH:D001327', (324, 343))	('AID', 'Phenotype', 'HP:0002960', (356, 359))	('DNMT3B', 'Gene', '1789', (66, 72))	('-579G>T', 'SUBSTITUTION', 'None', (73, 80))	('AID', 'Phenotype', 'HP:0002960', (378, 381))	('patients', 'Species', '9606', (100, 108))	('age', 'Gene', (141, 144))	('autoimmune diseases', 'Disease', (324, 343))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (324, 343))	('-579G>T', 'Var', (73, 80))	('DNMT3B', 'Gene', (66, 72))
8561	24260492	In order to shed some light on the role of epigenetics in both MG and MG-associated diseases, we analyzed the DNMT3B -579G>T polymorphism in a large population of MG patients of Italian descent.	('-579G>T', 'Var', (117, 124))	('DNMT3B', 'Gene', (110, 116))	('DNMT3B', 'Gene', '1789', (110, 116))	('-579G>T', 'SUBSTITUTION', 'None', (117, 124))	('patients', 'Species', '9606', (166, 174))
8564	24260492	Present data are in agreement with a literature meta-analysis suggesting an increased risk of cancer associated with the presence of the DNMT3B -579T allele.	('presence', 'Var', (121, 129))	('cancer', 'Phenotype', 'HP:0002664', (94, 100))	('DNMT3B', 'Gene', '1789', (137, 143))	('DNMT3B', 'Gene', (137, 143))	('cancer', 'Disease', (94, 100))	('cancer', 'Disease', 'MESH:D009369', (94, 100))
8570	24260492	Their results were in accordance with Chen and coworkers, who found that tumor suppressor genes and DNA repair genes, including hMLH1, RASSF1A, MGMT, p16/INK4, DAPK, FHIT, RAR2, CDH1, and APC, are frequently hypermethylated in thymic epithelial tumours, all found to be methylated in almost 20 to 40% of the cases.	('INK4', 'Gene', (154, 158))	('tumor', 'Phenotype', 'HP:0002664', (73, 78))	('RAR2', 'Gene', (172, 176))	('RAR2', 'Gene', '142684', (172, 176))	('MGMT', 'Gene', '4255', (144, 148))	('hypermethylated', 'Var', (208, 223))	('FHIT', 'Gene', '2272', (166, 170))	('APC', 'Disease', 'MESH:D011125', (188, 191))	('APC', 'Disease', (188, 191))	('epithelial tumours', 'Disease', (234, 252))	('DAPK', 'Gene', (160, 164))	('p16', 'Gene', (150, 153))	('CDH1', 'Gene', '999', (178, 182))	('tumor', 'Disease', (73, 78))	('p16', 'Gene', '1029', (150, 153))	('epithelial tumours', 'Disease', 'MESH:D002277', (234, 252))	('DAPK', 'Gene', '1612', (160, 164))	('MGMT', 'Gene', (144, 148))	('RASSF1A', 'Gene', '11186', (135, 142))	('tumours', 'Phenotype', 'HP:0002664', (245, 252))	('CDH1', 'Gene', (178, 182))	('tumor', 'Disease', 'MESH:D009369', (73, 78))	('INK4', 'Gene', '1029', (154, 158))	('hMLH1', 'Gene', (128, 133))	('tumour', 'Phenotype', 'HP:0002664', (245, 251))	('RASSF1A', 'Gene', (135, 142))	('FHIT', 'Gene', (166, 170))	('hMLH1', 'Gene', '4292', (128, 133))
8572	24260492	The functional role of the DNMT3B -579G>T polymorphism is not yet completely elucidated.	('-579G>T', 'Var', (34, 41))	('DNMT3B', 'Gene', (27, 33))	('DNMT3B', 'Gene', '1789', (27, 33))	('-579G>T', 'SUBSTITUTION', 'None', (34, 41))
8573	24260492	Some authors suggest that it can directly impair promoter activity and gene expression levels, and others observed a linkage disequilibrium between rs1569686 and other DNMT3B promoter polymorphisms, namely -149C>T (rs2424913) and -283T>C (rs6058870), which have been functionally associated with promoter activity and gene expression levels.	('rs6058870', 'DBSNP_MENTION', 'None', (239, 248))	('gene expression levels', 'MPA', (71, 93))	('-149C>T', 'SUBSTITUTION', 'None', (206, 213))	('-283T>C', 'SUBSTITUTION', 'None', (230, 237))	('rs2424913', 'DBSNP_MENTION', 'None', (215, 224))	('impair', 'NegReg', (42, 48))	('rs1569686', 'DBSNP_MENTION', 'None', (148, 157))	('-283T>C', 'Var', (230, 237))	('rs6058870', 'Var', (239, 248))	('DNMT3B', 'Gene', (168, 174))	('rs2424913', 'Var', (215, 224))	('DNMT3B', 'Gene', '1789', (168, 174))	('rs1569686', 'Var', (148, 157))	('age', 'Gene', (121, 124))	('promoter activity', 'MPA', (49, 66))	('-149C>T', 'Var', (206, 213))	('age', 'Gene', '5973', (121, 124))
8574	24260492	Taken overall, results from those studies coupled with the evidence of an association of the DNMT3B -579G>T polymorphism with various types of cancer, suggest that this polymorphism might either have a functional role on gene expression levels, or be a tag SNP of functional haplotypes.	('DNMT3B', 'Gene', '1789', (93, 99))	('cancer', 'Phenotype', 'HP:0002664', (143, 149))	('DNMT3B', 'Gene', (93, 99))	('-579G>T', 'SUBSTITUTION', 'None', (100, 107))	('cancer', 'Disease', (143, 149))	('cancer', 'Disease', 'MESH:D009369', (143, 149))	('-579G>T', 'Var', (100, 107))	('association', 'Interaction', (74, 85))	('gene expression levels', 'MPA', (221, 243))
8580	24260492	By contrast, several studies revealed global or gene specific hypomethylation, impaired activities of enzymes such as DNMTs or methyl CpG binding proteins, histone tail modifications, and/or changes in non coding RNAs, in autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, Sjogren's syndrome, psoriasis, multiple sclerosis, and systemic sclerosis, among others, suggesting that further studies are needed to elucidate the possible contribution of epigenetics to the pathogenesis of MG.	('rheumatoid arthritis', 'Phenotype', 'HP:0001370', (280, 300))	('systemic lupus erythematosus', 'Disease', 'MESH:D008180', (250, 278))	('systemic sclerosis', 'Disease', 'MESH:D012595', (357, 375))	('multiple sclerosis', 'Disease', (333, 351))	("Sjogren's syndrome", 'Disease', 'MESH:D012859', (302, 320))	("Sjogren's syndrome", 'Disease', (302, 320))	('autoimmune diseases', 'Disease', 'MESH:D001327', (222, 241))	('arthritis', 'Phenotype', 'HP:0001369', (291, 300))	('autoimmune diseases', 'Disease', (222, 241))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (222, 241))	('autoimmune disease', 'Phenotype', 'HP:0002960', (222, 240))	('rheumatoid arthritis', 'Disease', (280, 300))	('multiple sclerosis', 'Disease', 'MESH:D009103', (333, 351))	('systemic sclerosis', 'Disease', (357, 375))	('psoriasis', 'Phenotype', 'HP:0003765', (322, 331))	('systemic lupus erythematosus', 'Disease', (250, 278))	('rheumatoid arthritis', 'Disease', 'MESH:D001172', (280, 300))	('changes', 'Var', (191, 198))	('psoriasis', 'Disease', 'MESH:D011565', (322, 331))	('psoriasis', 'Disease', (322, 331))	('systemic lupus erythematosus', 'Phenotype', 'HP:0002725', (250, 278))
8582	24260492	At best of our knowledge the present is the first investigation of DNMT3B promoter polymorphisms in MG patients.	('polymorphisms', 'Var', (83, 96))	('DNMT3B', 'Gene', '1789', (67, 73))	('patients', 'Species', '9606', (103, 111))	('DNMT3B', 'Gene', (67, 73))
8583	24260492	Our study suggests that the presence of the DNMT3B -579T allele might represent a risk factor for the development of MG-associated thymomas, particularly in carriers of the homozygous TT genotype, while it probably does not have effect on other MG subtypes.	('presence', 'Var', (28, 36))	('thymoma', 'Phenotype', 'HP:0100522', (131, 138))	('risk', 'Reg', (82, 86))	('DNMT3B', 'Gene', (44, 50))	('DNMT3B', 'Gene', '1789', (44, 50))	('thymomas', 'Disease', (131, 139))	('thymomas', 'Disease', 'MESH:D013945', (131, 139))
8635	31214197	Approximately 80% of patients with PNP have circulating anti-Dsg3 IgG, and other autoantibodies against desmosomal cadherins (e.g., Dsg1, Dsc1, Dsc2, and Dsc3) have been detected in some patients with PNP (19-42%).	('Dsg1', 'Gene', (132, 136))	('patients', 'Species', '9606', (187, 195))	('Dsc3', 'Gene', (154, 158))	('Dsg1', 'Gene', '1828', (132, 136))	('PNP', 'Disease', (35, 38))	('Dsc1', 'Gene', (138, 142))	('Dsc1', 'Gene', '1823', (138, 142))	('patients', 'Species', '9606', (21, 29))	('Dsc2', 'Gene', (144, 148))	('anti-Dsg3', 'Var', (56, 65))	('Dsc2', 'Gene', '1824', (144, 148))	('Dsc3', 'Gene', '1825', (154, 158))
8662	31214197	A recent study showed that antibodies to A2ML1, which act as a protease inhibitor, decrease the adhesion of cultured normal human keratinocytes by activating plasmin.	('activating', 'Reg', (147, 157))	('rat', 'Species', '10116', (132, 135))	('adhesion of cultured normal human keratinocytes', 'CPA', (96, 143))	('antibodies', 'Var', (27, 37))	('plasmin', 'Gene', (158, 165))	('decrease', 'NegReg', (83, 91))	('human', 'Species', '9606', (124, 129))	('A2ML1', 'Gene', (41, 46))	('A2ML1', 'Gene', '144568', (41, 46))	('plasmin', 'Gene', '5340', (158, 165))
8671	31214197	Thus, anti-Dsg3 antibody might contribute to the pathogenesis of bronchiolitis obliterans.	('bronchiolitis obliterans', 'Disease', 'MESH:D001989', (65, 89))	('bronchiolitis obliterans', 'Disease', (65, 89))	('anti-Dsg3', 'Var', (6, 15))	('bronchiolitis', 'Phenotype', 'HP:0011950', (65, 78))	('bronchiolitis obliterans', 'Phenotype', 'HP:0011946', (65, 89))	('contribute', 'Reg', (31, 41))
8672	31214197	In a recent study, mice treated with anti-epiplakin antibodies showed loss of cell-cell adhesion in the respiratory epithelium, suggesting that anti-epiplakin antibody may play a pathogenic role in bronchiolitis obliterans, although epiplakin is located within the subcellular area of epithelial cells.	('anti-epiplakin', 'Var', (37, 51))	('loss', 'NegReg', (70, 74))	('bronchiolitis obliterans', 'Phenotype', 'HP:0011946', (198, 222))	('cell-cell adhesion in the respiratory epithelium', 'CPA', (78, 126))	('rat', 'Species', '10116', (109, 112))	('bronchiolitis', 'Phenotype', 'HP:0011950', (198, 211))	('bronchiolitis obliterans', 'Disease', 'MESH:D001989', (198, 222))	('pathogenic', 'Reg', (179, 189))	('antibodies', 'Var', (52, 62))	('play', 'Reg', (172, 176))	('bronchiolitis obliterans', 'Disease', (198, 222))	('mice', 'Species', '10090', (19, 23))
8683	31214197	With regard to CD4+ T cell-mediated immunity, adoptive transfer of Dsg3-specific CD4+ T cells into RAG2-/- mice was found to cause interface dermatitis as a result of cell-mediated immunity, and interferon-gamma from CD4+ T cells was shown as a crucial inducer of this interface dermatitis.	('Dsg3-specific', 'Gene', (67, 80))	('dermatitis', 'Disease', 'MESH:D003872', (279, 289))	('dermatitis', 'Disease', (279, 289))	('dermatitis', 'Disease', 'MESH:D003872', (141, 151))	('dermatitis', 'Disease', (141, 151))	('cell-mediated immunity', 'CPA', (167, 189))	('dermatitis', 'Phenotype', 'HP:0011123', (141, 151))	('RAG2', 'Gene', (99, 103))	('dermatitis', 'Phenotype', 'HP:0011123', (279, 289))	('interferon-gamma', 'Gene', '15978', (195, 211))	('cause', 'Reg', (125, 130))	('CD4+ T cells', 'Var', (81, 93))	('RAG2', 'Gene', '19374', (99, 103))	('mice', 'Species', '10090', (107, 111))	('interferon-gamma', 'Gene', (195, 211))
8707	31214197	Although the role of Tregs in PNP has not been studied, recent studies in FOXP3-/- scurfy mice revealed that the absence of Tregs leads to autoimmune bullous skin diseases mediated by anti-BP230 antibodies.	('bullous skin', 'Phenotype', 'HP:0008066', (150, 162))	('BP230', 'Gene', '13518', (189, 194))	('leads to', 'Reg', (130, 138))	('autoimmune bullous skin diseases', 'Disease', (139, 171))	('absence', 'Var', (113, 120))	('absence of Tregs', 'Phenotype', 'HP:0030336', (113, 129))	('autoimmune bullous skin diseases', 'Phenotype', 'HP:0001019', (139, 171))	('mice', 'Species', '10090', (90, 94))	('Tregs', 'Protein', (124, 129))	('autoimmune bullous skin diseases', 'Disease', 'MESH:D012872', (139, 171))	('BP230', 'Gene', (189, 194))
8708	31214197	Similar to the findings of the mouse study, bullous pemphigoid, characterized by anti-BP180 and anti-BP230 autoantibodies, reportedly developed in a pediatric patient with immune dysregulation, polyendocrinopathy, enteropathy, and X-linked (IPEX) syndrome caused by FOXP3 mutation.	('enteropathy', 'Disease', (214, 225))	('polyendocrinopathy', 'Disease', 'MESH:D016884', (194, 212))	('developed', 'Reg', (134, 143))	('bullous pemphigoid', 'Disease', (44, 62))	('BP230', 'Gene', (101, 106))	('enteropathy', 'Phenotype', 'HP:0002242', (214, 225))	('polyendocrinopathy', 'Disease', (194, 212))	('immune dysregulation', 'Phenotype', 'HP:0002958', (172, 192))	('mouse', 'Species', '10090', (31, 36))	('BP230', 'Gene', '13518', (101, 106))	('caused by', 'Reg', (256, 265))	('mutation', 'Var', (272, 280))	('X-linked (IPEX) syndrome', 'Disease', 'MESH:C580192', (231, 255))	('patient', 'Species', '9606', (159, 166))	('FOXP3', 'Gene', (266, 271))	('enteropathy', 'Disease', 'MESH:C538273', (214, 225))
8716	31214197	Tumor-specific neoantigens result from the mutation of tumors.	('Tumor', 'Phenotype', 'HP:0002664', (0, 5))	('tumor', 'Phenotype', 'HP:0002664', (55, 60))	('mutation', 'Var', (43, 51))	('tumors', 'Phenotype', 'HP:0002664', (55, 61))	('neoantigens', 'MPA', (15, 26))	('result from', 'Reg', (27, 38))	('tumors', 'Disease', 'MESH:D009369', (55, 61))	('tumors', 'Disease', (55, 61))
8717	31214197	Neoantigens mimicking self-antigens derived from desmosomal and hemidesmosomal proteins have not been investigated in neoplasms to date, although studies have shown that several proteins including Dsg3, BP180, BP230, and alpha6beta4 integrin are overexpressed in epithelial-origin carcinoma.	('neoplasms', 'Phenotype', 'HP:0002664', (118, 127))	('BP180', 'Var', (203, 208))	('BP230', 'Gene', (210, 215))	('neoplasm', 'Phenotype', 'HP:0002664', (118, 126))	('alpha6beta4 integrin', 'Protein', (221, 241))	('carcinoma', 'Disease', 'MESH:D002277', (281, 290))	('BP230', 'Gene', '13518', (210, 215))	('carcinoma', 'Phenotype', 'HP:0030731', (281, 290))	('neoplasms', 'Disease', 'MESH:D009369', (118, 127))	('neoplasms', 'Disease', (118, 127))	('overexpressed', 'PosReg', (246, 259))	('Dsg3', 'Gene', (197, 201))	('carcinoma', 'Disease', (281, 290))
8777	26766736	A substantial differentiator was a large microRNA cluster on chr19q13.42 that was significantly overexpressed in all A and AB tumours and whose expression was virtually absent in the other thymomas and normal tissues.	('tumour', 'Phenotype', 'HP:0002664', (126, 132))	('thymomas', 'Disease', (189, 197))	('thymomas', 'Disease', 'MESH:D013945', (189, 197))	('AB tumours', 'Disease', (123, 133))	('tumours', 'Phenotype', 'HP:0002664', (126, 133))	('overexpressed', 'PosReg', (96, 109))	('chr19q13.42', 'Var', (61, 72))	('AB tumours', 'Disease', 'MESH:D009369', (123, 133))	('thymoma', 'Phenotype', 'HP:0100522', (189, 196))
8780	26766736	A large microRNA cluster on chr19q13.42 is a transcriptional hallmark of type A and AB thymomas.	('thymoma', 'Phenotype', 'HP:0100522', (87, 94))	('chr19q13.42', 'Var', (28, 39))	('type A', 'Disease', (73, 79))	('AB thymomas', 'Disease', 'MESH:D013945', (84, 95))	('AB thymomas', 'Disease', (84, 95))
8810	26766736	All A and AB samples were classified into the group positive for C19MC cluster, whereas the B1, B2, and B3 samples were present in the C19MC-negative group.	('C19MC', 'Chemical', '-', (65, 70))	('C19MC', 'Chemical', '-', (135, 140))	('B1, B2, and B3', 'Gene', '931;3383;680', (92, 106))	('positive', 'Reg', (52, 60))	('C19MC cluster', 'Var', (65, 78))
8812	26766736	Previous work in hepatocellular carcinoma has demonstrated that the C19MC cluster causes activation of the PI3K/AKT pathway by inhibition of the PI3K antagonist PTEN, and also of the cell cycle inhibitor p21.	('hepatocellular carcinoma', 'Disease', (17, 41))	('C19MC', 'Var', (68, 73))	('PTEN', 'Gene', '5728', (161, 165))	('carcinoma', 'Phenotype', 'HP:0030731', (32, 41))	('AKT', 'Gene', '207', (112, 115))	('p21', 'Gene', '1026', (204, 207))	('p21', 'Gene', (204, 207))	('C19MC', 'Chemical', '-', (68, 73))	('activation', 'PosReg', (89, 99))	('inhibition', 'NegReg', (127, 137))	('PTEN', 'Gene', (161, 165))	('AKT', 'Gene', (112, 115))	('hepatocellular carcinoma', 'Disease', 'MESH:D006528', (17, 41))	('hepatocellular carcinoma', 'Phenotype', 'HP:0001402', (17, 41))
8817	26766736	In congruence with the pathway analysis, we observed significantly higher activated phospho-AKT in the C19MC-positive thymomas as compared with the C19MC-negative tumours (P<0.0001) as well as the expected downregulation of PTEN in the C19MC-positive thymomas as compared with the C19MC-negative tumours (P<0.0001).	('thymomas', 'Disease', 'MESH:D013945', (251, 259))	('tumour', 'Phenotype', 'HP:0002664', (163, 169))	('thymomas', 'Disease', (118, 126))	('downregulation', 'NegReg', (206, 220))	('tumours', 'Phenotype', 'HP:0002664', (296, 303))	('tumours', 'Disease', 'MESH:D009369', (296, 303))	('thymomas', 'Disease', (251, 259))	('C19MC', 'Chemical', '-', (103, 108))	('tumour', 'Phenotype', 'HP:0002664', (296, 302))	('C19MC-positive', 'Var', (236, 250))	('AKT', 'Gene', (92, 95))	('PTEN', 'Gene', (224, 228))	('C19MC', 'Chemical', '-', (148, 153))	('C19MC', 'Chemical', '-', (236, 241))	('PTEN', 'Gene', '5728', (224, 228))	('thymoma', 'Phenotype', 'HP:0100522', (118, 125))	('tumours', 'Disease', (163, 170))	('AKT', 'Gene', '207', (92, 95))	('thymomas', 'Disease', 'MESH:D013945', (118, 126))	('thymoma', 'Phenotype', 'HP:0100522', (251, 258))	('C19MC', 'Chemical', '-', (281, 286))	('tumours', 'Phenotype', 'HP:0002664', (163, 170))	('higher activated', 'PosReg', (67, 83))	('tumours', 'Disease', 'MESH:D009369', (163, 170))	('tumours', 'Disease', (296, 303))	('C19MC-positive', 'Var', (103, 117))
8818	26766736	To provide additional support that the C19MC cluster induces activation of the PI3K pathway, we performed an in vitro experiment using the only known existing human Thymoma AB cell line, IU-TAB1.	('C19MC cluster', 'Var', (39, 52))	('Thymoma AB', 'Disease', (165, 175))	('Thymoma', 'Phenotype', 'HP:0100522', (165, 172))	('activation', 'PosReg', (61, 71))	('human', 'Species', '9606', (159, 164))	('C19MC', 'Chemical', '-', (39, 44))	('PI3K pathway', 'Pathway', (79, 91))	('Thymoma AB', 'Disease', 'MESH:D013945', (165, 175))
8823	26766736	Upregulation of p-AKT, p-MTOR, p-70 S6K, and p-4E-BP1 was also observed with mir-517a alone.	('Upregulation', 'PosReg', (0, 12))	('p-4E-BP1', 'Var', (45, 53))	('mir-517a', 'Gene', '574479', (77, 85))	('p-70 S6K', 'Gene', '6198', (31, 39))	('AKT', 'Gene', (18, 21))	('mir-517a', 'Gene', (77, 85))	('p-70 S6K', 'Gene', (31, 39))	('MTOR', 'Gene', (25, 29))	('AKT', 'Gene', '207', (18, 21))	('MTOR', 'Gene', '2475', (25, 29))
8825	26766736	As seen in Figure 5, we observe significant sensitivity of this cell line to these inhibitors, with PF-04691502 and BEZ235 demonstrating the best reduction in cell viability at an IC50 of 118 and 210 nM, respectively.	('BEZ235', 'Chemical', 'MESH:C531198', (116, 122))	('PF-04691502', 'Var', (100, 111))	('PF-04691502', 'Chemical', 'MESH:C570662', (100, 111))	('cell viability', 'CPA', (159, 173))	('BEZ235', 'Var', (116, 122))	('reduction', 'NegReg', (146, 155))
8831	26766736	In a similarly classified set of tumours, ETMRs (embryonal tumours with multilayered rosettes), 12 out of 12 ETMRs demonstrated overexpression of C19MC driven by a fusion of the TTYH1 gene promoter (tweety family member 1) with C19MC, suggesting that a translocation along with amplification drives expression in these rare tumours.	('fusion', 'Var', (164, 170))	('tumours', 'Phenotype', 'HP:0002664', (59, 66))	('tumours', 'Disease', 'MESH:D009369', (59, 66))	('rosettes', 'Phenotype', 'HP:0031925', (85, 93))	('tumour', 'Phenotype', 'HP:0002664', (59, 65))	('tumours', 'Disease', (33, 40))	('tumour', 'Phenotype', 'HP:0002664', (33, 39))	('TTYH1', 'Gene', (178, 183))	('tumours', 'Disease', (324, 331))	('tumours', 'Phenotype', 'HP:0002664', (33, 40))	('embryonal tumours', 'Disease', 'MESH:D009373', (49, 66))	('tumours', 'Disease', 'MESH:D009369', (33, 40))	('C19MC', 'Chemical', '-', (228, 233))	('C19MC', 'Var', (146, 151))	('embryonal tumours', 'Disease', (49, 66))	('tumours', 'Phenotype', 'HP:0002664', (324, 331))	('tumours', 'Disease', 'MESH:D009369', (324, 331))	('TTYH1', 'Gene', '57348', (178, 183))	('overexpression', 'PosReg', (128, 142))	('C19MC', 'Chemical', '-', (146, 151))	('tumour', 'Phenotype', 'HP:0002664', (324, 330))	('tumours', 'Disease', (59, 66))
8832	26766736	Overexpression of this cluster is similarly seen in thyroid adenomas, parathyroid adenomas, hepatic mesenchymal hamartomas, hepatocellular carcinomas, and in a subset of tamoxifen-resistant breast cancers, mediated by a variety of mechanisms including gene amplification, chromosomal translocations, and hypomethylation.	('parathyroid adenomas', 'Disease', 'MESH:D010282', (70, 90))	('hepatocellular carcinoma', 'Phenotype', 'HP:0001402', (124, 148))	('thyroid adenomas', 'Phenotype', 'HP:0000854', (74, 90))	('hepatic mesenchymal hamartomas', 'Disease', 'MESH:D006222', (92, 122))	('gene amplification', 'Var', (252, 270))	('hepatic mesenchymal hamartomas', 'Disease', (92, 122))	('hypomethylation', 'Var', (304, 319))	('cancers', 'Phenotype', 'HP:0002664', (197, 204))	('hepatocellular carcinomas', 'Disease', 'MESH:D006528', (124, 149))	('cancer', 'Phenotype', 'HP:0002664', (197, 203))	('breast cancers', 'Disease', 'MESH:D001943', (190, 204))	('tamoxifen', 'Chemical', 'MESH:D013629', (170, 179))	('parathyroid adenomas', 'Phenotype', 'HP:0002897', (70, 90))	('breast cancers', 'Disease', (190, 204))	('hamartomas', 'Phenotype', 'HP:0010566', (112, 122))	('thyroid adenomas', 'Disease', (52, 68))	('hepatocellular carcinomas', 'Phenotype', 'HP:0001402', (124, 149))	('carcinoma', 'Phenotype', 'HP:0030731', (139, 148))	('carcinomas', 'Phenotype', 'HP:0030731', (139, 149))	('thyroid adenomas', 'Disease', 'MESH:D013964', (52, 68))	('breast cancers', 'Phenotype', 'HP:0003002', (190, 204))	('hepatocellular carcinomas', 'Disease', (124, 149))	('parathyroid adenomas', 'Disease', (70, 90))	('thyroid adenomas', 'Disease', 'MESH:D013964', (74, 90))	('thyroid adenomas', 'Phenotype', 'HP:0000854', (52, 68))	('chromosomal translocations', 'Var', (272, 298))
8834	26766736	Of further interest to thymoma, it has been recently hypothesised that C19MC exosomes are potent immunomodulators that may suppress immune function in the tumour microenvironment.	('C19MC', 'Var', (71, 76))	('thymoma', 'Disease', (23, 30))	('suppress immune function', 'Phenotype', 'HP:0002721', (123, 147))	('thymoma', 'Phenotype', 'HP:0100522', (23, 30))	('tumour', 'Phenotype', 'HP:0002664', (155, 161))	('tumour', 'Disease', 'MESH:D009369', (155, 161))	('suppress', 'NegReg', (123, 131))	('C19MC', 'Chemical', '-', (71, 76))	('thymoma', 'Disease', 'MESH:D013945', (23, 30))	('tumour', 'Disease', (155, 161))
8837	26766736	Although overactivation of this pathway is common in many cancers, the mean of activation varies, but in many cases is achieved via somatic mutations in PIK3CA or PTEN.	('PIK3CA', 'Gene', '5290', (153, 159))	('cancer', 'Phenotype', 'HP:0002664', (58, 64))	('PTEN', 'Gene', (163, 167))	('cancers', 'Phenotype', 'HP:0002664', (58, 65))	('PTEN', 'Gene', '5728', (163, 167))	('cancers', 'Disease', 'MESH:D009369', (58, 65))	('mutations', 'Var', (140, 149))	('cancers', 'Disease', (58, 65))	('overactivation', 'PosReg', (9, 23))	('PIK3CA', 'Gene', (153, 159))
8840	26766736	Further protein-level data in our validation cohort demonstrated elevated p-AKT and decreased PTEN in our C19MC-positive tumours.	('AKT', 'Gene', '207', (76, 79))	('tumours', 'Disease', 'MESH:D009369', (121, 128))	('tumours', 'Disease', (121, 128))	('PTEN', 'Gene', (94, 98))	('tumour', 'Phenotype', 'HP:0002664', (121, 127))	('PTEN', 'Gene', '5728', (94, 98))	('AKT', 'Gene', (76, 79))	('C19MC-positive', 'Var', (106, 120))	('elevated', 'PosReg', (65, 73))	('tumours', 'Phenotype', 'HP:0002664', (121, 128))	('C19MC', 'Chemical', '-', (106, 111))	('decreased', 'NegReg', (84, 93))
8847	26766736	Because C19MC expression is largely restricted to type A and AB thymomas, measurement of this microRNA cluster as a routine molecular diagnostic in thymoma tissues may be well warranted and potentially superior to histological subtyping by microscopy.	('thymoma', 'Disease', 'MESH:D013945', (64, 71))	('AB thymomas', 'Disease', (61, 72))	('thymoma', 'Disease', (64, 71))	('thymoma', 'Phenotype', 'HP:0100522', (64, 71))	('C19MC', 'Chemical', '-', (8, 13))	('thymoma', 'Disease', 'MESH:D013945', (148, 155))	('thymoma', 'Disease', (148, 155))	('C19MC', 'Var', (8, 13))	('AB thymomas', 'Disease', 'MESH:D013945', (61, 72))	('thymoma', 'Phenotype', 'HP:0100522', (148, 155))
8849	26766736	Outcomes from our clinical trial, as well as studies of the C19MC cluster with PI3K pathway inhibitors in other cancer types, will help to shed light on the utility of C19MC as a therapeutic biomarker.	('C19MC', 'Chemical', '-', (168, 173))	('cancer', 'Disease', (112, 118))	('cancer', 'Disease', 'MESH:D009369', (112, 118))	('C19MC', 'Var', (168, 173))	('C19MC', 'Chemical', '-', (60, 65))	('cancer', 'Phenotype', 'HP:0002664', (112, 118))
8913	25396312	Several antibodies (Abs) have been described in MG. Pathogenic Abs bind to extracellular determinants of postsynaptic membrane proteins, and cause morphologic and functional alterations that interfere with neuromuscular transmission (NMT).	('Ab', 'Chemical', '-', (20, 22))	('interfere', 'NegReg', (191, 200))	('neuromuscular transmission', 'MPA', (206, 232))	('bind', 'Reg', (67, 71))	('Ab', 'Chemical', '-', (63, 65))	('cause', 'Reg', (141, 146))	('Abs', 'Var', (63, 66))
8926	25396312	a reduced number of acetylcholine vesicles released by nerve depolarization, generally caused by Abs to the P/Q-type voltage-gated calcium channel (VGCC) on motor nerve membrane.	('acetylcholine', 'Chemical', 'MESH:D000109', (20, 33))	('nerve', 'Var', (55, 60))	('calcium', 'Chemical', 'MESH:D002118', (131, 138))	('depolarization', 'NegReg', (61, 75))	('VGCC', 'Gene', (148, 152))	('reduced', 'NegReg', (2, 9))	('Abs', 'NegReg', (97, 100))	('Ab', 'Chemical', '-', (97, 99))	('acetylcholine vesicles released', 'MPA', (20, 51))
8936	25396312	NMT with or without CNS alterations can occur as a paraneoplastic disease, generally in association with thymoma and with MG as frequent co-morbidity.	('alterations', 'Var', (24, 35))	('NMT', 'Disease', (0, 3))	('thymoma', 'Phenotype', 'HP:0100522', (105, 112))	('paraneoplastic disease', 'Disease', 'MESH:D010257', (51, 73))	('thymoma', 'Gene', '7063', (105, 112))	('paraneoplastic disease', 'Disease', (51, 73))	('CNS', 'Gene', (20, 23))	('thymoma', 'Gene', (105, 112))	('occur', 'Reg', (40, 45))
8957	25396312	While LGI1 Abs are more common in autoimmune non-paraneoplastic encephalitis, patients with thymoma more often have antibodies to Caspr2.	('Caspr2', 'Gene', (130, 136))	('non-paraneoplastic encephalitis', 'Phenotype', 'HP:0007030', (45, 76))	('encephalitis', 'Phenotype', 'HP:0002383', (64, 76))	('antibodies', 'Var', (116, 126))	('LGI1', 'Gene', '9211', (6, 10))	('thymoma', 'Phenotype', 'HP:0100522', (92, 99))	('LGI1', 'Gene', (6, 10))	('Caspr2', 'Gene', '26047', (130, 136))	('patients', 'Species', '9606', (78, 86))	('Ab', 'Chemical', '-', (11, 13))	('autoimmune non-paraneoplastic encephalitis', 'Disease', (34, 76))	('autoimmune non-paraneoplastic encephalitis', 'Disease', 'MESH:C535841', (34, 76))	('thymoma', 'Gene', '7063', (92, 99))	('common', 'Reg', (24, 30))	('thymoma', 'Gene', (92, 99))
8967	25396312	A recent serologic analysis of 27 patients with Morvan's syndrome reported patients with Abs to Caspr2 (n=6), LGI1 (n=3), or both Caspr2 and LGI1 (n=15); thymoma was found in approximately 50% of patients with Caspr2 antibodies but in no patients with only LGI1 antibodies.	('Ab', 'Chemical', '-', (89, 91))	('LGI1', 'Gene', (257, 261))	('thymoma', 'Phenotype', 'HP:0100522', (154, 161))	('patients', 'Species', '9606', (196, 204))	('antibodies', 'Var', (217, 227))	('LGI1', 'Gene', '9211', (141, 145))	('thymoma', 'Gene', '7063', (154, 161))	('Caspr2', 'Gene', '26047', (96, 102))	('thymoma', 'Gene', (154, 161))	('LGI1', 'Gene', '9211', (257, 261))	("Morvan's syndrome", 'Disease', 'MESH:D013595', (48, 65))	('Caspr2', 'Gene', (130, 136))	('patients', 'Species', '9606', (75, 83))	('LGI1', 'Gene', (110, 114))	('patients', 'Species', '9606', (34, 42))	('Caspr2', 'Gene', (210, 216))	("Morvan's syndrome", 'Disease', (48, 65))	('patients', 'Species', '9606', (238, 246))	('Caspr2', 'Gene', '26047', (130, 136))	('LGI1', 'Gene', '9211', (110, 114))	('LGI1', 'Gene', (141, 145))	('Caspr2', 'Gene', (96, 102))	('Caspr2', 'Gene', '26047', (210, 216))
8980	25396312	Anti-Hu (anti-ANNA1) is associated with several different PNDs, and most of these have rarely been seen in patients with thymic tumors including sensory neuronopathy, encephalitis/brainstem encephalitis, autonomic neuropathy.	('autonomic neuropathy', 'Disease', 'MESH:D009422', (204, 224))	('encephalitis', 'Phenotype', 'HP:0002383', (190, 202))	('thymic tumors', 'Disease', (121, 134))	('Anti-Hu', 'Var', (0, 7))	('thymic tumors', 'Disease', 'MESH:D013953', (121, 134))	('thymic tumor', 'Phenotype', 'HP:0100521', (121, 133))	('encephalitis/brainstem encephalitis', 'Disease', (167, 202))	('autonomic neuropathy', 'Disease', (204, 224))	('encephalitis', 'Phenotype', 'HP:0002383', (167, 179))	('PNDs', 'Disease', 'None', (58, 62))	('encephalitis/brainstem encephalitis', 'Disease', 'MESH:D004660', (167, 202))	('tumor', 'Phenotype', 'HP:0002664', (128, 133))	('PNDs', 'Disease', (58, 62))	('neuropathy', 'Phenotype', 'HP:0009830', (214, 224))	('tumors', 'Phenotype', 'HP:0002664', (128, 134))	('sensory neuronopathy', 'Disease', 'MESH:D009134', (145, 165))	('patients', 'Species', '9606', (107, 115))	('sensory neuronopathy', 'Disease', (145, 165))
9036	24705787	Aberrant expression of RAGE or RAGE ligands in human patients with malignancies has been reported in e.g.	('human', 'Species', '9606', (47, 52))	('reported', 'Reg', (89, 97))	('patients', 'Species', '9606', (53, 61))	('Aberrant', 'Var', (0, 8))	('malignancies', 'Disease', (67, 79))	('malignancies', 'Disease', 'MESH:D009369', (67, 79))
9105	24705787	The concentration of HMGB1 in serum was significantly increased in patients with TETs (HMGB1 [ng/ml] 2.1+-0.3 vs. 1.1+-0.2; p = 0.008; fig.	('concentration', 'MPA', (4, 17))	('patients', 'Species', '9606', (67, 75))	('HMGB1', 'Gene', (21, 26))	('TETs', 'Var', (81, 85))	('increased', 'PosReg', (54, 63))	('TETs', 'Chemical', 'MESH:C010349', (81, 85))
9132	24705787	The knockout of p53 in HCT116 cells increased the expression of cytosolic HMGB1 and induced autophagy.	('induced', 'Reg', (84, 91))	('HCT116', 'CellLine', 'CVCL:0291', (23, 29))	('p53', 'Gene', (16, 19))	('knockout', 'Var', (4, 12))	('increased', 'PosReg', (36, 45))	('autophagy', 'CPA', (92, 101))	('p53', 'Gene', '7157', (16, 19))	('HMGB1', 'Gene', (74, 79))	('expression', 'MPA', (50, 60))
9137	24705787	In patients with colorectal cancer the coexpression of RAGE and HMGB1 was associated with invasion and metastasis.	('colorectal cancer', 'Phenotype', 'HP:0003003', (17, 34))	('cancer', 'Phenotype', 'HP:0002664', (28, 34))	('coexpression', 'Var', (39, 51))	('HMGB1', 'Gene', (64, 69))	('colorectal cancer', 'Disease', (17, 34))	('patients', 'Species', '9606', (3, 11))	('colorectal cancer', 'Disease', 'MESH:D015179', (17, 34))	('associated', 'Reg', (74, 84))
9170	24705787	Evidence that cTEC mediate positive selection stems from experiments in mice whose MHC class II genes were deleted by targeted disruption.	('MHC class II genes', 'Gene', (83, 101))	('cTEC', 'Chemical', '-', (14, 18))	('deleted', 'Var', (107, 114))	('mice', 'Species', '10090', (72, 76))
9187	24705787	S100+ (CD1a+, CD207+, CD11c+) positive dendritic cells were described in juvenile and immature Hassall's corpuscles of postnatal human thymus.	('CD11c', 'Gene', (22, 27))	('CD207', 'Gene', (14, 19))	('CD1a', 'Gene', '909', (7, 11))	('CD1a', 'Gene', (7, 11))	('human', 'Species', '9606', (129, 134))	('S100+', 'Var', (0, 5))	('CD207', 'Gene', '50489', (14, 19))	('CD11c', 'Gene', '3687', (22, 27))
9228	33489209	A 63-year-old gentleman, known to have hypertension was referred to hematology clinic in November 2018, after he was detected to have high hemoglobin (20.3 mg/dL, normal <16.5 mg/dL) with high hematocrit (62.6%, normal 35%-45%), erythrocytes (7.2 x 106/microL, normal 3.8-4.8), leukocytes (14.3 x 103/microL, normal 4-10), and thrombocytes (674 x 103/microL, normal 150-400).	('hypertension', 'Disease', (39, 51))	('674 x 103/microL', 'Var', (341, 357))	('hypertension', 'Phenotype', 'HP:0000822', (39, 51))	('14.3 x 103/microL', 'Var', (290, 307))	('high hemoglobin', 'Phenotype', 'HP:0001900', (134, 149))	('high hematocrit', 'Phenotype', 'HP:0001899', (188, 203))	('hypertension', 'Disease', 'MESH:D006973', (39, 51))
9277	33489209	Patients with PV positive for JAK2 mutation can develop MG as a paraneoplastic syndrome, in the absence of thymoma.	('thymoma', 'Phenotype', 'HP:0100522', (107, 114))	('paraneoplastic syndrome', 'Disease', (64, 87))	('JAK2', 'Gene', '3717', (30, 34))	('develop', 'PosReg', (48, 55))	('paraneoplastic syndrome', 'Disease', 'MESH:D010257', (64, 87))	('Patients', 'Species', '9606', (0, 8))	('JAK2', 'Gene', (30, 34))	('MG', 'Disease', 'MESH:D000080343', (56, 58))	('mutation', 'Var', (35, 43))	('absence of thymoma', 'Phenotype', 'HP:0005359', (96, 114))	('thymoma', 'Disease', 'MESH:D013945', (107, 114))	('thymoma', 'Disease', (107, 114))
9287	31156543	Antibodies against these channels cause a heterogeneous group of diseases, such as Lambert-Eaton syndrome, Isaacs' syndrome and myasthenia gravis.	('myasthenia gravis', 'Disease', (128, 145))	("Isaacs' syndrome", 'Disease', (107, 123))	('Lambert-Eaton syndrome', 'Disease', (83, 105))	('Antibodies', 'Var', (0, 10))	('Lambert-Eaton syndrome', 'Disease', 'MESH:D015624', (83, 105))	('myasthenia gravis', 'Disease', 'MESH:D009157', (128, 145))	('cause', 'Reg', (34, 39))	('myasthenia', 'Phenotype', 'HP:0003473', (128, 138))
9311	31156543	Antibodies of VGKCs in peripheral nervous system cause autoimmune neuromyotonia disorders, such as Isaacs' syndrome, and in central nervous system lead to Morvan syndrome and limbic encephalitis.	('VGKCs', 'Gene', (14, 19))	('encephalitis', 'Disease', (182, 194))	('Morvan syndrome', 'Disease', 'OMIM:201300', (155, 170))	('Antibodies', 'Var', (0, 10))	('autoimmune neuromyotonia disorders', 'Disease', (55, 89))	('encephalitis', 'Disease', 'MESH:D004660', (182, 194))	("Isaacs' syndrome", 'Disease', (99, 115))	('Morvan syndrome', 'Disease', (155, 170))	('autoimmune neuromyotonia disorders', 'Disease', 'MESH:D020386', (55, 89))	('encephalitis', 'Phenotype', 'HP:0002383', (182, 194))	('myotonia', 'Phenotype', 'HP:0002486', (71, 79))	('cause', 'Reg', (49, 54))
9339	31156543	In MG, antibodies against AChRs lead to a decreased safety margin of neuromuscular transmission, so that slight depletion of ACh results in failure of post-synaptic depolarization for many muscle fibers.	('ACh', 'Chemical', 'MESH:D000109', (26, 29))	('failure of post-synaptic depolarization', 'Phenotype', 'HP:0007688', (140, 179))	('decreased', 'NegReg', (42, 51))	('AChRs', 'Gene', (26, 31))	('depletion', 'MPA', (112, 121))	('antibodies', 'Var', (7, 17))	('ACh', 'Chemical', 'MESH:D000109', (125, 128))	('safety margin', 'MPA', (52, 65))	('failure', 'NegReg', (140, 147))
9340	31156543	Similarly, in LEMS, antibodies against VGCC compromise the safety margin which results in radically decrease ACh release at all times.	('compromise', 'NegReg', (44, 54))	('ACh release', 'MPA', (109, 120))	('antibodies', 'Var', (20, 30))	('safety margin', 'MPA', (59, 72))	('decrease', 'NegReg', (100, 108))	('VGCC', 'Protein', (39, 43))	('ACh', 'Chemical', 'MESH:D000109', (109, 112))
9341	31156543	Antibodies against VGCCs and AChRs usually cause similar symptoms, such as skeletal muscle weakness, to list the main feature, due to insufficient AChs released from presynaptic membrane or reduced functional AChR density on post-synaptic membrane, respectively.	('AChs released from presynaptic membrane', 'MPA', (147, 186))	('ACh', 'Chemical', 'MESH:D000109', (147, 150))	('AChRs', 'Gene', (29, 34))	('cause', 'Reg', (43, 48))	('VGCCs', 'Gene', (19, 24))	('Antibodies', 'Var', (0, 10))	('skeletal muscle weakness', 'Disease', 'MESH:D018908', (75, 99))	('skeletal muscle weakness', 'Disease', (75, 99))	('functional AChR density on post-synaptic membrane', 'MPA', (198, 247))	('reduced', 'NegReg', (190, 197))	('muscle weakness', 'Phenotype', 'HP:0001324', (84, 99))	('ACh', 'Chemical', 'MESH:D000109', (29, 32))	('ACh', 'Chemical', 'MESH:D000109', (209, 212))	('insufficient', 'NegReg', (134, 146))
9342	31156543	While antibodies against VGKCs often lead to serial symptoms as a result of redundant AChs released from the nerve terminal, such as muscle stiffness and cramps.	('cramps', 'Disease', (154, 160))	('serial symptoms', 'Disease', (45, 60))	('VGKCs', 'Gene', (25, 30))	('muscle stiffness', 'Disease', (133, 149))	('cramps', 'Disease', 'MESH:D009120', (154, 160))	('ACh', 'Chemical', 'MESH:D000109', (86, 89))	('lead to', 'Reg', (37, 44))	('antibodies', 'Var', (6, 16))	('muscle stiffness', 'Disease', 'None', (133, 149))	('muscle stiffness', 'Phenotype', 'HP:0003552', (133, 149))	('AChs', 'Protein', (86, 90))
9343	31156543	LEMS is an autoimmune neuromuscular junction channelopathy caused by antibodies against VGCCs.	('VGCCs', 'Gene', (88, 93))	('autoimmune neuromuscular junction channelopathy', 'Disease', (11, 58))	('LEMS', 'Disease', (0, 4))	('autoimmune neuromuscular junction channelopathy', 'Disease', 'MESH:D053447', (11, 58))	('antibodies', 'Var', (69, 79))	('caused by', 'Reg', (59, 68))
9370	31156543	Traditionally, antibodies against P/Q-type VGCCs are detected in 85-90% of patients with LEMS, in some reports even with up to 100% in LEMS patients with SCLC, which suggests a high specificity of LEMS diagnosis.	('patients', 'Species', '9606', (75, 83))	('VGCCs', 'Protein', (43, 48))	('SCLC', 'Disease', (154, 158))	('LEMS', 'Disease', (89, 93))	('detected', 'Reg', (53, 61))	('patients', 'Species', '9606', (140, 148))	('SCLC', 'Disease', 'MESH:D018288', (154, 158))	('antibodies', 'Var', (15, 25))	('SCLC', 'Phenotype', 'HP:0030357', (154, 158))
9379	31156543	Two studies showed antibody against SOX1 presents in 64-67% of patients with SCLC-LEMS, compared to 0-5% in NT-LEMS patients.	('SCLC-LEMS', 'Disease', 'MESH:D018288', (77, 86))	('patients', 'Species', '9606', (116, 124))	('SOX1', 'Gene', '6656', (36, 40))	('NT-LEMS', 'Chemical', '-', (108, 115))	('antibody', 'Var', (19, 27))	('SOX1', 'Gene', (36, 40))	('patients', 'Species', '9606', (63, 71))	('SCLC', 'Phenotype', 'HP:0030357', (77, 81))	('SCLC-LEMS', 'Disease', (77, 86))
9384	31156543	Intriguingly, antibodies against AChRs can also be detected in a small part of LEMS, while these specific antibodies have no diagnostic value.	('antibodies', 'Var', (14, 24))	('detected', 'Reg', (51, 59))	('ACh', 'Chemical', 'MESH:D000109', (33, 36))	('AChRs', 'Gene', (33, 38))
9408	31156543	Since LEMS is caused by the antibodies against VGCCs, treatment suppressing the immune system is effective.	('VGCCs', 'Protein', (47, 52))	('suppressing the immune system', 'Phenotype', 'HP:0002721', (64, 93))	('antibodies', 'Var', (28, 38))	('LEMS', 'Disease', (6, 10))	('caused by', 'Reg', (14, 23))	('men', 'Species', '9606', (59, 62))
9442	31156543	LGI1 antibody seems to be more strongly associated with limbic encephalitis than Isaacs' syndrome and less seropositive in Isaacs' syndrome compared with CASPR2 antibody.	('LGI1', 'Gene', '9211', (0, 4))	('antibody', 'Var', (5, 13))	('LGI1', 'Gene', (0, 4))	('CASPR2', 'Gene', (154, 160))	("encephalitis than Isaacs' syndrome", 'Disease', (63, 97))	('encephalitis', 'Phenotype', 'HP:0002383', (63, 75))	("encephalitis than Isaacs' syndrome", 'Disease', 'MESH:D020386', (63, 97))	('associated with', 'Reg', (40, 55))	('CASPR2', 'Gene', '26047', (154, 160))
9487	31156543	The immune response against epitopes expressed on abnormal thymic cells spills over to components at NMJ, mostly like AChR, which causes symptoms of MG. MG is mainly caused by antibodies against AChR or other proteins on the post-synaptic membrane, with a characteristic of impaired signal transduction, muscle weakness, and fatigability.	('caused by', 'Reg', (166, 175))	('ACh', 'Chemical', 'MESH:D000109', (195, 198))	('muscle weakness', 'Disease', 'MESH:D018908', (304, 319))	('signal transduction', 'MPA', (283, 302))	('ACh', 'Chemical', 'MESH:D000109', (118, 121))	('muscle weakness', 'Phenotype', 'HP:0001324', (304, 319))	('fatigability', 'Disease', (325, 337))	('antibodies', 'Var', (176, 186))	('muscle weakness', 'Disease', (304, 319))	('AChR', 'Protein', (195, 199))
9490	31156543	Antibodies against AChR alpha subunit are more pathogenic than those against other subunits, such as beta, delta, gamma, and epsilon.	('AChR', 'Gene', (19, 23))	('pathogenic', 'Reg', (47, 57))	('Antibodies', 'Var', (0, 10))	('ACh', 'Chemical', 'MESH:D000109', (19, 22))
9497	31156543	In LRP4 immunized mice, LRP4 antibodies induce muscular weakness through disruption of the interaction between LRP4 and agrin, and thereby inhibit AChR-mediated neuromuscular signal transmission.	('LRP4', 'Gene', (24, 28))	('antibodies', 'Var', (29, 39))	('ACh', 'Chemical', 'MESH:D000109', (147, 150))	('disruption', 'NegReg', (73, 83))	('inhibit', 'NegReg', (139, 146))	('AChR-mediated neuromuscular signal transmission', 'MPA', (147, 194))	('mice', 'Species', '10090', (18, 22))	('weakness', 'Disease', (56, 64))	('weakness', 'Disease', 'MESH:D018908', (56, 64))	('muscular weakness', 'Phenotype', 'HP:0001324', (47, 64))	('interaction', 'Interaction', (91, 102))	('LRP4', 'Protein', (111, 115))	('induce', 'Reg', (40, 46))	('agrin', 'Protein', (120, 125))
9515	31156543	By inhibiting AChE through neostigmine, the amount of AChs is significantly increased in the synaptic cleft, and AChs are capable of binding to the AChRs for a longer period, resulting improved neuromuscular transmission.	('AChE', 'Gene', '43', (14, 18))	('improved', 'PosReg', (185, 193))	('ACh', 'Chemical', 'MESH:D000109', (14, 17))	('inhibiting', 'NegReg', (3, 13))	('ACh', 'Chemical', 'MESH:D000109', (148, 151))	('AChs', 'Var', (113, 117))	('neostigmine', 'Protein', (27, 38))	('AChRs', 'Protein', (148, 153))	('neostigmine', 'Chemical', 'MESH:D009388', (27, 38))	('AChE', 'Gene', (14, 18))	('ACh', 'Chemical', 'MESH:D000109', (113, 116))	('ACh', 'Chemical', 'MESH:D000109', (54, 57))	('neuromuscular transmission', 'MPA', (194, 220))	('binding', 'Interaction', (133, 140))
9523	31156543	The classic electrophysiologic demonstration of an NMJ transmission defect is the documentation of a decremental response of the CMAP to slow (2-3 Hz) motor repetitive nerve stimulation.	('men', 'Species', '9606', (86, 89))	('NMJ', 'Gene', (51, 54))	('decremental response', 'MPA', (101, 121))	('defect', 'Var', (68, 74))	('men', 'Species', '9606', (106, 109))
9578	30276969	Tumors were classified into three categories according to International Classification of Disease (ICD-O-3) codes: TNETs (8150-8157, 8240-8246, and 8249), thymoma (8580-8585), and thymic carcinoma (8070, 8123, 8430, 8082, 8310, 8033, 8260, 8200, 8480, 8140, 8023, 8560, 8576, 8586, 8588, and 8589).	('8560', 'Var', (264, 268))	('8310', 'Var', (222, 226))	('Tumors', 'Phenotype', 'HP:0002664', (0, 6))	('8430', 'Var', (210, 214))	('TNETs', 'Disease', (115, 120))	('8586', 'Var', (276, 280))	('8576', 'Var', (270, 274))	('8480', 'Var', (246, 250))	('8240-8246', 'Var', (133, 142))	('Tumors', 'Disease', (0, 6))	('8589', 'Var', (292, 296))	('ICD', 'Disease', (99, 102))	('thymic carcinoma', 'Disease', (180, 196))	('thymoma', 'Disease', 'MESH:D013945', (155, 162))	('ICD', 'Disease', 'OMIM:252500', (99, 102))	('8082', 'Var', (216, 220))	('Tumors', 'Disease', 'MESH:D009369', (0, 6))	('8150-8157', 'Var', (122, 131))	('8140', 'Var', (252, 256))	('8580-8585', 'Var', (164, 173))	('thymic carcinoma', 'Disease', 'MESH:D013945', (180, 196))	('carcinoma', 'Phenotype', 'HP:0030731', (187, 196))	('thymoma', 'Phenotype', 'HP:0100522', (155, 162))	('thymoma', 'Disease', (155, 162))	('8070', 'Var', (198, 202))
9616	30276969	The OS rate was higher in the PORT group than that in the control group (yes vs. no, five-year OS 67.6% vs.54.6%; P = 0.036) (Fig 4a,b).	('PORT', 'Var', (30, 34))	('higher', 'PosReg', (16, 22))	('OS', 'Chemical', '-', (4, 6))	('OS', 'Chemical', '-', (95, 97))
9621	30276969	In subgroup analysis, PORT improved both OS and CSS in patients with M-K stage III-IV and improved OS in patients with M-K stage IIB.	('OS', 'Chemical', '-', (41, 43))	('CSS', 'Chemical', '-', (48, 51))	('patients', 'Species', '9606', (105, 113))	('improved', 'PosReg', (27, 35))	('M-K', 'Var', (69, 72))	('improved', 'PosReg', (90, 98))	('patients', 'Species', '9606', (55, 63))	('OS', 'Chemical', '-', (99, 101))	('CSS', 'MPA', (48, 51))
9692	28072685	Testing for c-kit mutation was performed to exclude thymic carcinoma and to consider a targeted agent; exons 9, 11, 13, and 17 were unidentified.	('carcinoma', 'Disease', (59, 68))	('mutation', 'Var', (18, 26))	('carcinoma', 'Disease', 'MESH:D002277', (59, 68))	('carcinoma', 'Phenotype', 'HP:0030731', (59, 68))	('c-kit', 'Gene', '3815', (12, 17))	('c-kit', 'Gene', (12, 17))
9893	33936037	Therefore, it's necessary to optimize dose to minimize the irAEs induced by PD-1 antibody while maintaining clinical effectiveness.	('minimize', 'NegReg', (46, 54))	('antibody', 'Var', (81, 89))	('irAEs', 'Disease', (59, 64))	('PD-1', 'Gene', (76, 80))	('PD-1', 'Gene', '5133', (76, 80))
9907	33174672	It is a rare syndrome that progressively decreases inhibition of the central nervous system due to blockade of glutamic acid decarboxylase (GAD) causing increased muscle activity.	('GAD', 'Gene', '2571', (140, 143))	('muscle activity', 'MPA', (163, 178))	('decreases', 'NegReg', (41, 50))	('increased', 'PosReg', (153, 162))	('blockade', 'Var', (99, 107))	('glutamic acid decarboxylase', 'Gene', '2571', (111, 138))	('increased muscle', 'Phenotype', 'HP:0003712', (153, 169))	('glutamic acid decarboxylase', 'Gene', (111, 138))	('GAD', 'Gene', (140, 143))	('inhibition of the central nervous system', 'MPA', (51, 91))
9915	33174672	The diagnosis of SPS requires a high index of suspicion as there is no formal diagnostic criteria; however, the following are features generally considered necessary to make the diagnosis: Stiffness in the axial and limb muscles resulting in impairment of ambulation; presence of superimposed episodic spasms that are precipitated by sudden movement, noise, or emotional upset; a positive therapeutic response to oral diazepam or findings of continuous motor-unit activity on electromyography (EMG) that are abolished by intravenous diazepam; and an absence of other neurologic disorders that may explain the clinical features7, 8.	('impairment of ambulation', 'Disease', (242, 266))	('MG', 'Chemical', 'MESH:D008274', (495, 497))	('SPS', 'Disease', 'MESH:C535540', (17, 20))	('diazepam', 'Chemical', 'MESH:D003975', (418, 426))	('men', 'Species', '9606', (248, 251))	('SPS', 'Disease', (17, 20))	('impairment of ambulation', 'Disease', 'MESH:D020233', (242, 266))	('neurologic disorders', 'Disease', (567, 587))	('neurologic disorders', 'Disease', 'MESH:D009422', (567, 587))	('men', 'Species', '9606', (345, 348))	('neurologic disorders', 'Phenotype', 'HP:0000707', (567, 587))	('Stiffness', 'Var', (189, 198))	('diazepam', 'Chemical', 'MESH:D003975', (533, 541))	('episodic spasms', 'Disease', 'MESH:C580065', (293, 308))	('emotional upset', 'Phenotype', 'HP:0000712', (361, 376))	('episodic spasms', 'Disease', (293, 308))
9996	32701070	Lynch syndrome is most frequently caused by mutations in the mismatch repair genes MLH1, MSH2, MSH6, and PMS2, leading to microsatellite instability.	('PMS2', 'Gene', '5395', (105, 109))	('MSH6', 'Gene', '2956', (95, 99))	('MSH2', 'Gene', (89, 93))	('MLH1', 'Gene', '4292', (83, 87))	('MSH2', 'Gene', '4436', (89, 93))	('Lynch syndrome', 'Disease', (0, 14))	('MLH1', 'Gene', (83, 87))	('mutations', 'Var', (44, 53))	('PMS2', 'Gene', (105, 109))	('MSH6', 'Gene', (95, 99))	('microsatellite instability', 'MPA', (122, 148))	('Lynch syndrome', 'Disease', 'MESH:D003123', (0, 14))	('caused', 'Reg', (34, 40))
10061	30186552	In more severe forms, weakness of the bulbar muscles can cause dysphasia and dysarthria.	('dysphasia and dysarthria', 'Disease', 'MESH:D004401', (63, 87))	('cause', 'Reg', (57, 62))	('dysarthria', 'Phenotype', 'HP:0001260', (77, 87))	('weakness', 'Var', (22, 30))	('weakness of the bulbar muscles', 'Phenotype', 'HP:0001283', (22, 52))	('dysphasia', 'Phenotype', 'HP:0002357', (63, 72))
10093	25915571	In 8% of patients with thyroid-associated ophtalmopathy, AChR antibodies are found, possibly due to common autoimmune targets in the eye muscle and/or genetic factors.	('patients', 'Species', '9606', (9, 17))	('ophtalmopathy', 'Disease', (42, 55))	('ophtalmopathy', 'Disease', 'None', (42, 55))	('found', 'Reg', (77, 82))	('antibodies', 'Var', (62, 72))	('AChR', 'Gene', (57, 61))
10098	25915571	Furthermore, ATD and DM (both type 1 and 2) occur more frequently in patients with AChR antibodies than in those without such antibodies.	('DM', 'Phenotype', 'HP:0000819', (21, 23))	('DM', 'Disease', 'MESH:D009223', (21, 23))	('AChR', 'Gene', (83, 87))	('ATD', 'Disease', (13, 16))	('patients', 'Species', '9606', (69, 77))	('antibodies', 'Var', (88, 98))
10101	25915571	Nevertheless, both SLE and ATD are more frequent in the LOMG subgroup than in control populations, especially Hashimoto's disease.	('SLE', 'Phenotype', 'HP:0002725', (19, 22))	('frequent', 'Reg', (40, 48))	("Hashimoto's disease", 'Disease', 'MESH:D050031', (110, 129))	("Hashimoto's disease", 'Disease', (110, 129))	('ATD', 'Disease', (27, 30))	('SLE', 'Disease', 'MESH:D008180', (19, 22))	('SLE', 'Disease', (19, 22))	('LOMG', 'Var', (56, 60))
10127	25915571	A possible association between anti-Kv1.4 antibodies and cardiac involvement, especially myocarditis, was recently described, the disease characterized by heart failure and arrhythmias together with limb and paraspinal muscle weakness.	('arrhythmias', 'Disease', 'MESH:D001145', (173, 184))	('arrhythmias', 'Disease', (173, 184))	('myocarditis', 'Disease', (89, 100))	('heart failure', 'Disease', 'MESH:D006333', (155, 168))	('Kv1.4', 'Gene', (36, 41))	('myocarditis', 'Phenotype', 'HP:0012819', (89, 100))	('heart failure', 'Phenotype', 'HP:0001635', (155, 168))	('cardiac involvement', 'Disease', 'MESH:D006331', (57, 76))	('Kv1.4', 'Gene', '3739', (36, 41))	('arrhythmias', 'Phenotype', 'HP:0011675', (173, 184))	('heart failure', 'Disease', (155, 168))	('paraspinal muscle weakness', 'Disease', (208, 234))	('antibodies', 'Var', (42, 52))	('muscle weakness', 'Phenotype', 'HP:0001324', (219, 234))	('myocarditis', 'Disease', 'MESH:D009205', (89, 100))	('paraspinal muscle weakness', 'Disease', 'MESH:D018908', (208, 234))	('cardiac involvement', 'Disease', (57, 76))
10146	25915571	D-penicillamine can induce both AChR and MuSK antibody-positive MG, a rare phenomenon which is reversible after discontinuation of the treatment.	('induce', 'Reg', (20, 26))	('D-penicillamine', 'Chemical', 'MESH:D010396', (0, 15))	('MuSK antibody', 'Phenotype', 'HP:0030210', (41, 54))	('MuSK', 'Gene', (41, 45))	('MuSK', 'Gene', '4593', (41, 45))	('D-penicillamine', 'Var', (0, 15))	('AChR', 'Gene', (32, 36))
10148	25915571	LRP4 autoantibodies are reported in up to 50% of MG patients without AChR or MuSK antibodies, and even in a few patients with MuSK-MG.	('LRP4', 'Gene', (0, 4))	('MuSK', 'Gene', (77, 81))	('MuSK', 'Gene', '4593', (77, 81))	('LRP4', 'Gene', '4038', (0, 4))	('MuSK', 'Gene', '4593', (126, 130))	('patients', 'Species', '9606', (112, 120))	('MuSK', 'Gene', (126, 130))	('MuSK-MG', 'CellLine', 'CVCL:1698', (126, 133))	('autoantibodies', 'Var', (5, 19))	('patients', 'Species', '9606', (52, 60))	('MuSK antibodies', 'Phenotype', 'HP:0030210', (77, 92))
10151	25915571	However, LRP4 antibodies have been found in Lambert Eaton myasthenic syndrome and neuromyelitis optica.	('neuromyelitis optica', 'Disease', 'MESH:D009471', (82, 102))	('myasthenic syndrome', 'Phenotype', 'HP:0003473', (58, 77))	('neuromyelitis optica', 'Disease', (82, 102))	('Eaton myasthenic syndrome', 'Disease', (52, 77))	('Eaton myasthenic syndrome', 'Disease', 'MESH:D015624', (52, 77))	('LRP4', 'Gene', (9, 13))	('antibodies', 'Var', (14, 24))	('LRP4', 'Gene', '4038', (9, 13))	('found', 'Reg', (35, 40))
10165	25915571	EOMG and other autoimmune disorders are associated with the HLA A1-B8-DR3-DQ2 haplotype.	('autoimmune disorders', 'Disease', 'MESH:D001327', (15, 35))	('HLA', 'Gene', '3117', (60, 63))	('autoimmune disorder', 'Phenotype', 'HP:0002960', (15, 34))	('haplotype', 'Var', (78, 87))	('HLA', 'Gene', (60, 63))	('EOMG', 'Disease', (0, 4))	('autoimmune disorders', 'Phenotype', 'HP:0002960', (15, 35))	('EOMG', 'Chemical', '-', (0, 4))	('autoimmune disorders', 'Disease', (15, 35))	('associated', 'Reg', (40, 50))
10178	25915571	The protein tyrosine phosphatase non-receptor 22 (PTPN22) R620W gene polymorphism is a general risk factor for autoimmune diseases with an increased production of auto-antibodies and predisposes MG and EOMG in particular for additional autoimmune diseases.	('protein tyrosine phosphatase non-receptor 22', 'Gene', (4, 48))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (111, 130))	('EOMG', 'Chemical', '-', (202, 206))	('predisposes', 'Reg', (183, 194))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (236, 255))	('protein tyrosine phosphatase non-receptor 22', 'Gene', '26191', (4, 48))	('EOMG', 'Disease', (202, 206))	('autoimmune diseases', 'Disease', 'MESH:D001327', (111, 130))	('R620W', 'Var', (58, 63))	('R620W', 'Mutation', 'rs2476601', (58, 63))	('risk factor', 'Reg', (95, 106))	('autoimmune disease', 'Phenotype', 'HP:0002960', (236, 254))	('autoimmune diseases', 'Disease', 'MESH:D001327', (236, 255))	('PTPN22', 'Gene', (50, 56))	('autoimmune diseases', 'Disease', (111, 130))	('PTPN22', 'Gene', '26191', (50, 56))	('autoimmune disease', 'Phenotype', 'HP:0002960', (111, 129))	('autoimmune diseases', 'Disease', (236, 255))
10180	25915571	The lack of association of PTPN22 R620W polymorphism with MuSK-MG and antibody negative-MG subgroups emphasizes the different genetic background for MG subgroups.	('PTPN22', 'Gene', (27, 33))	('R620W', 'Var', (34, 39))	('R620W', 'Mutation', 'rs2476601', (34, 39))	('PTPN22', 'Gene', '26191', (27, 33))	('MuSK-MG', 'Disease', (58, 65))	('MuSK-MG', 'CellLine', 'CVCL:1698', (58, 65))	('association', 'Interaction', (12, 23))
10182	25915571	CTLA4 gene polymorphisms are associated with MG and also other autoimmune diseases such as type 1 DM, ATD, SLE, RA and celiac disease.	('SLE', 'Disease', 'MESH:D008180', (107, 110))	('SLE', 'Disease', (107, 110))	('CTLA4', 'Gene', (0, 5))	('DM', 'Disease', 'MESH:D009223', (98, 100))	('RA', 'Disease', 'MESH:D001172', (112, 114))	('SLE', 'Phenotype', 'HP:0002725', (107, 110))	('polymorphisms', 'Var', (11, 24))	('autoimmune diseases', 'Disease', 'MESH:D001327', (63, 82))	('autoimmune diseases', 'Disease', (63, 82))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (63, 82))	('associated', 'Reg', (29, 39))	('celiac disease', 'Disease', (119, 133))	('autoimmune disease', 'Phenotype', 'HP:0002960', (63, 81))	('RA', 'Phenotype', 'HP:0001370', (112, 114))	('celiac disease', 'Phenotype', 'HP:0002608', (119, 133))	('DM', 'Phenotype', 'HP:0000819', (98, 100))	('CTLA4', 'Gene', '1493', (0, 5))	('ATD', 'Disease', (102, 105))	('celiac disease', 'Disease', 'MESH:D002446', (119, 133))
10216	26324168	In the present case, we preferred the anterolateral approach because the incision could be extended to either a posterolateral approach in the case of adhesions to the inferior pulmonary vein, or a hemiclamshell approach in case of adhesions to the superior vena cava.	('inferior pulmonary vein', 'Disease', (168, 191))	('inferior pulmonary vein', 'Disease', 'MESH:D000071078', (168, 191))	('superior vena cava', 'Phenotype', 'HP:0031041', (249, 267))	('adhesions', 'Var', (151, 160))
10229	22138614	We reviewed 13 studies that evaluated the diagnostic role of thymic epithelial tumors with [18F]FDG-PET.	('FDG', 'Chemical', 'MESH:D019788', (96, 99))	('thymic epithelial tumors', 'Disease', 'MESH:C536905', (61, 85))	('epithelial tumor', 'Phenotype', 'HP:0031492', (68, 84))	('thymic epithelial tumors', 'Disease', (61, 85))	('[18F]FDG-PET', 'Var', (91, 103))	('tumors', 'Phenotype', 'HP:0002664', (79, 85))	('tumor', 'Phenotype', 'HP:0002664', (79, 84))
10231	22138614	However, [18F]FDG-PET may not be useful for differentiating low-risk thymoma and high-risk thymoma.	('thymoma', 'Disease', (91, 98))	('[18F]FDG-PET', 'Var', (9, 21))	('FDG', 'Chemical', 'MESH:D019788', (14, 17))	('thymoma', 'Phenotype', 'HP:0100522', (91, 98))	('thymoma', 'Disease', 'MESH:D013945', (69, 76))	('thymoma', 'Disease', (69, 76))	('thymoma', 'Disease', 'MESH:D013945', (91, 98))	('thymoma', 'Phenotype', 'HP:0100522', (69, 76))
10232	22138614	One paper reported that [18F]FDG-PET has a predictive significance for treatment and prognosis in thymic epithelial tumors.	('thymic epithelial tumors', 'Disease', (98, 122))	('epithelial tumor', 'Phenotype', 'HP:0031492', (105, 121))	('thymic epithelial tumors', 'Disease', 'MESH:C536905', (98, 122))	('FDG', 'Chemical', 'MESH:D019788', (29, 32))	('tumor', 'Phenotype', 'HP:0002664', (116, 121))	('tumors', 'Phenotype', 'HP:0002664', (116, 122))	('[18F]FDG-PET', 'Var', (24, 36))
10241	22138614	The purpose of this study is to systematically review the available literature regarding the diagnostic performance of [18F]FDG-PET in patients with thymic epithelial tumors, which may contribute to the development of guidelines for the usefulness of PET.	('patients', 'Species', '9606', (135, 143))	('FDG', 'Chemical', 'MESH:D019788', (124, 127))	('FDG-PET', 'Gene', (124, 131))	('thymic epithelial tumors', 'Disease', (149, 173))	('tumor', 'Phenotype', 'HP:0002664', (167, 172))	('tumors', 'Phenotype', 'HP:0002664', (167, 173))	('[18F]', 'Var', (119, 124))	('thymic epithelial tumors', 'Disease', 'MESH:C536905', (149, 173))	('epithelial tumor', 'Phenotype', 'HP:0031492', (156, 172))
10243	22138614	We performed a systematic search of the MEDLINE and PubMed databases to identify all clinical trials regarding the relationship between [18F]FDG-PET and thymic epithelial tumors.	('thymic epithelial tumors', 'Disease', (153, 177))	('epithelial tumor', 'Phenotype', 'HP:0031492', (160, 176))	('thymic epithelial tumors', 'Disease', 'MESH:C536905', (153, 177))	('FDG', 'Chemical', 'MESH:D019788', (141, 144))	('tumor', 'Phenotype', 'HP:0002664', (171, 176))	('[18F]FDG-PET', 'Var', (136, 148))	('tumors', 'Phenotype', 'HP:0002664', (171, 177))
10244	22138614	The search strategy included articles published between January 1995 and August 2011 using the following keywords: "PET" or "positron emission tomography"; "positron emission tomography/computer tomography" or "PET/CT"; "[18F]FDG" or "fluorodeoxyglucose"; "thymic epithelial tumor", "thymoma", "thymic carcinoma" or "thymic".	('thymoma', 'Disease', (284, 291))	('PET/CT"; "[', 'Var', (211, 222))	('carcinoma', 'Phenotype', 'HP:0030731', (302, 311))	('tumor', 'Phenotype', 'HP:0002664', (275, 280))	('thymoma', 'Phenotype', 'HP:0100522', (284, 291))	('glucose', 'Chemical', 'MESH:D005947', (246, 253))	('thymic carcinoma', 'Disease', (295, 311))	('epithelial tumor', 'Disease', (264, 280))	('epithelial tumor', 'Phenotype', 'HP:0031492', (264, 280))	('thymic carcinoma', 'Disease', 'MESH:D013945', (295, 311))	('FDG', 'Chemical', 'MESH:D019788', (226, 229))	('thymoma', 'Disease', 'MESH:D013945', (284, 291))	('epithelial tumor', 'Disease', 'MESH:D002277', (264, 280))
10245	22138614	We selected all published reports that clearly described the diagnostic performance of [18F]FDG-PET in patients with thymic epithelial tumors.	('tumor', 'Phenotype', 'HP:0002664', (135, 140))	('tumors', 'Phenotype', 'HP:0002664', (135, 141))	('thymic epithelial tumors', 'Disease', 'MESH:C536905', (117, 141))	('thymic epithelial tumors', 'Disease', (117, 141))	('FDG', 'Chemical', 'MESH:D019788', (92, 95))	('epithelial tumor', 'Phenotype', 'HP:0031492', (124, 140))	('patients', 'Species', '9606', (103, 111))	('FDG-PET', 'Gene', (92, 99))	('[18F]', 'Var', (87, 92))
10268	22138614	In monitoring treatment by [18F]FDG-PET, one study documented that [18F]FDG-PET was useful for monitoring response after treatment (chemotherapy or radiation) in inoperable thymic epithelial tumors.	('FDG', 'Chemical', 'MESH:D019788', (72, 75))	('FDG', 'Chemical', 'MESH:D019788', (32, 35))	('[18F]FDG-PET', 'Var', (67, 79))	('tumor', 'Phenotype', 'HP:0002664', (191, 196))	('thymic epithelial tumors', 'Disease', (173, 197))	('thymic epithelial tumors', 'Disease', 'MESH:C536905', (173, 197))	('tumors', 'Phenotype', 'HP:0002664', (191, 197))	('epithelial tumor', 'Phenotype', 'HP:0031492', (180, 196))
10275	22138614	The results of this study indicate that cellular uptake of [18F]FDG is mediated by Glut1 and that the expression of Glut1 protein is regulated by HIF-1alpha.	('Glut1', 'Gene', '6513', (116, 121))	('mediated', 'Reg', (71, 79))	('expression', 'MPA', (102, 112))	('Glut1', 'Gene', '6513', (83, 88))	('[18F]FDG', 'Var', (59, 67))	('HIF-1alpha', 'Gene', (146, 156))	('HIF-1alpha', 'Gene', '3091', (146, 156))	('Glut1', 'Gene', (116, 121))	('FDG', 'Chemical', 'MESH:D019788', (64, 67))	('cellular uptake', 'CPA', (40, 55))	('Glut1', 'Gene', (83, 88))
10276	22138614	One of 12 studies examined the diagnostic significance of [11C]methionine (MET)-PET in thymic epithelial tumors  and another study examined [11C]acetate (AC)-PET.	('[11C', 'Chemical', 'MESH:C000615233', (140, 144))	('AC', 'Chemical', 'MESH:C438206', (154, 156))	('MET', 'Chemical', '-', (75, 78))	('[11C', 'Chemical', 'MESH:C000615233', (58, 62))	('tumor', 'Phenotype', 'HP:0002664', (105, 110))	('thymic epithelial tumors', 'Disease', 'MESH:C536905', (87, 111))	('thymic epithelial tumors', 'Disease', (87, 111))	('[11C]methionine', 'Var', (58, 73))	('tumors', 'Phenotype', 'HP:0002664', (105, 111))	('epithelial tumor', 'Phenotype', 'HP:0031492', (94, 110))
10282	22138614	This is the first review to evaluate the clinical significance of [18F]FDG-PET in patients with thymic epithelial tumors.	('[18F]', 'Var', (66, 71))	('tumor', 'Phenotype', 'HP:0002664', (114, 119))	('patients', 'Species', '9606', (82, 90))	('FDG-PET', 'Gene', (71, 78))	('thymic epithelial tumors', 'Disease', (96, 120))	('FDG', 'Chemical', 'MESH:D019788', (71, 74))	('thymic epithelial tumors', 'Disease', 'MESH:C536905', (96, 120))	('tumors', 'Phenotype', 'HP:0002664', (114, 120))	('epithelial tumor', 'Phenotype', 'HP:0031492', (103, 119))
10292	22138614	Moreover, the overall survival after treatment tended to be longer in patients with partial metabolic response compared with those with non-partial metabolic response.	('longer', 'PosReg', (60, 66))	('patients', 'Species', '9606', (70, 78))	('overall survival', 'MPA', (14, 30))	('partial metabolic response', 'Var', (84, 110))
10299	22138614	Biologically, the expression of Glut1 plays a crucial role in the accumulation of [18F]FDG within tumor cells.	('[18F]FDG', 'Var', (82, 90))	('FDG', 'Chemical', 'MESH:D019788', (87, 90))	('tumor', 'Disease', 'MESH:D009369', (98, 103))	('Glut1', 'Gene', (32, 37))	('tumor', 'Phenotype', 'HP:0002664', (98, 103))	('tumor', 'Disease', (98, 103))	('Glut1', 'Gene', '6513', (32, 37))
10310	22138614	However, [18F]FDG-PET may not be useful for distinguishing these groups, because [18F]FDG accumulation overlaps in low-risk thymoma and high-risk thymoma.	('FDG', 'Chemical', 'MESH:D019788', (86, 89))	('thymoma', 'Phenotype', 'HP:0100522', (146, 153))	('[18F]FDG', 'Var', (81, 89))	('FDG', 'Chemical', 'MESH:D019788', (14, 17))	('thymoma', 'Phenotype', 'HP:0100522', (124, 131))	('thymoma', 'Disease', 'MESH:D013945', (146, 153))	('thymoma', 'Disease', 'MESH:D013945', (124, 131))	('thymoma', 'Disease', (124, 131))	('thymoma', 'Disease', (146, 153))
10311	22138614	[18F]FDG-PET may have an important role in predicting response to treatment and prognosis in thymic epithelial tumors.	('tumor', 'Phenotype', 'HP:0002664', (111, 116))	('[18F]', 'Var', (0, 5))	('tumors', 'Phenotype', 'HP:0002664', (111, 117))	('epithelial tumor', 'Phenotype', 'HP:0031492', (100, 116))	('FDG', 'Chemical', 'MESH:D019788', (5, 8))	('thymic epithelial tumors', 'Disease', 'MESH:C536905', (93, 117))	('thymic epithelial tumors', 'Disease', (93, 117))
10317	19861435	All thymic tumors were profiled for mutations in genes encoding components of the EGFR and KIT signaling pathways, assessed for EGFR and KIT expression by immunohistochemistry (IHC), and analyzed by array-based comparative genomic hybridization (aCGH).	('thymic tumors', 'Disease', 'MESH:D013953', (4, 17))	('EGFR', 'Gene', (82, 86))	('tumor', 'Phenotype', 'HP:0002664', (11, 16))	('tumors', 'Phenotype', 'HP:0002664', (11, 17))	('EGFR', 'Gene', '1956', (128, 132))	('EGFR', 'Gene', (128, 132))	('mutations', 'Var', (36, 45))	('thymic tumors', 'Disease', (4, 17))	('EGFR', 'Gene', '1956', (82, 86))	('thymic tumor', 'Phenotype', 'HP:0100521', (4, 16))
10320	19861435	One thymoma and one thymic carcinoma harbored KRAS mutations (G12A and G12V, respectively), and one thymoma had a G13V HRAS mutation.	('thymic carcinoma harbored KRAS', 'Disease', 'MESH:D013945', (20, 50))	('thymoma', 'Phenotype', 'HP:0100522', (100, 107))	('carcinoma', 'Phenotype', 'HP:0030731', (27, 36))	('thymoma', 'Gene', (4, 11))	('G12A', 'Mutation', 'rs121913529', (62, 66))	('G13V', 'Mutation', 'rs104894226', (114, 118))	('G12V', 'Var', (71, 75))	('thymoma', 'Gene', (100, 107))	('thymic carcinoma harbored KRAS', 'Disease', (20, 50))	('thymoma', 'Gene', '7063', (4, 11))	('G12V', 'Mutation', 'rs121913529', (71, 75))	('HRAS', 'Gene', '3265', (119, 123))	('G12A', 'Var', (62, 66))	('thymoma', 'Phenotype', 'HP:0100522', (4, 11))	('HRAS', 'Gene', (119, 123))	('thymoma', 'Gene', '7063', (100, 107))
10322	19861435	Two thymic carcinomas harbored somatic KIT mutations (V560del and H697Y).	('thymic carcinomas', 'Disease', 'MESH:D013945', (4, 21))	('H697Y', 'Mutation', 'rs763308199', (66, 71))	('H697Y', 'Var', (66, 71))	('V560del', 'Var', (54, 61))	('thymic carcinomas', 'Disease', (4, 21))	('carcinomas', 'Phenotype', 'HP:0030731', (11, 21))	('carcinoma', 'Phenotype', 'HP:0030731', (11, 20))	('V560del', 'Mutation', 'p.560delV', (54, 61))
10323	19861435	In cell viability assays, the V560del mutant was associated with similar sensitivities to imatinib and sunitinib, while the H697Y mutant displayed greater sensitivity to sunitinib.	('V560del', 'Mutation', 'p.560delV', (30, 37))	('sunitinib', 'Chemical', 'MESH:D000077210', (103, 112))	('imatinib', 'Chemical', 'MESH:D000068877', (90, 98))	('H697Y', 'Mutation', 'rs763308199', (124, 129))	('sunitinib', 'Chemical', 'MESH:D000077210', (170, 179))	('V560del', 'Var', (30, 37))	('H697Y', 'Var', (124, 129))	('sensitivities to imatinib', 'MPA', (73, 98))
10331	19861435	For example, compared to thymomas, thymic carcinomas display many more chromosomal gains and losses and exclusively harbor somatic mutations in the kinase encoded by KIT.	('thymic carcinomas', 'Disease', (35, 52))	('carcinomas', 'Phenotype', 'HP:0030731', (42, 52))	('mutations', 'Var', (131, 140))	('losses', 'NegReg', (93, 99))	('chromosomal gains', 'CPA', (71, 88))	('thymomas', 'Disease', 'MESH:D013945', (25, 33))	('KIT', 'Gene', (166, 169))	('thymic carcinomas', 'Disease', 'MESH:D013945', (35, 52))	('thymoma', 'Phenotype', 'HP:0100522', (25, 32))	('carcinoma', 'Phenotype', 'HP:0030731', (42, 51))	('thymomas', 'Disease', (25, 33))
10333	19861435	Some thymic malignancies harbor mutations in RAS genes, which have been previously associated with resistance to EGFR-directed therapies.	('thymic malignancies', 'Disease', 'MESH:D013953', (5, 24))	('thymic malignancies', 'Disease', (5, 24))	('mutations', 'Var', (32, 41))	('associated', 'Reg', (83, 93))	('EGFR', 'Gene', '1956', (113, 117))	('EGFR', 'Gene', (113, 117))	('RAS genes', 'Gene', (45, 54))
10362	19861435	All samples were analyzed for a total of 74 Sequenom assays, designed to detect 101 known somatic mutations in genes of the EGFR signaling pathway: EGFR, KRAS, HRAS, NRAS, BRAF, PIK3CA, AKT1, ERBB2, and MEK1 (Supplemental Table 1).	('NRAS', 'Gene', '4893', (166, 170))	('MEK1', 'Gene', '5604', (203, 207))	('ERBB2', 'Gene', (192, 197))	('KRAS', 'Gene', '3845', (154, 158))	('EGFR', 'Gene', '1956', (124, 128))	('PIK3CA', 'Gene', (178, 184))	('EGFR', 'Gene', '1956', (148, 152))	('AKT1', 'Gene', '207', (186, 190))	('ERBB2', 'Gene', '2064', (192, 197))	('men', 'Species', '9606', (215, 218))	('KRAS', 'Gene', (154, 158))	('NRAS', 'Gene', (166, 170))	('HRAS', 'Gene', '3265', (160, 164))	('HRAS', 'Gene', (160, 164))	('MEK1', 'Gene', (203, 207))	('BRAF', 'Gene', '673', (172, 176))	('AKT1', 'Gene', (186, 190))	('BRAF', 'Gene', (172, 176))	('EGFR', 'Gene', (148, 152))	('EGFR', 'Gene', (124, 128))	('mutations', 'Var', (98, 107))	('PIK3CA', 'Gene', '5290', (178, 184))
10375	19861435	Ba/F3 cells harboring the KITV560del and KITH697Y mutations were generated using the QuikChange II XL site-directed Mutagenesis Kit (Stratagene Agilent Technologies), as previously described (See Supplemental Methods).	('KITV560del', 'Mutation', 'c.560delKITV', (26, 36))	('men', 'Species', '9606', (202, 205))	('KITH697Y', 'Var', (41, 49))	('H697Y', 'Mutation', 'rs763308199', (44, 49))	('KITV560del', 'Var', (26, 36))
10393	19861435	High EGFR staining was significantly associated with stage III-IV tumors (p=0.023, Chi-square test).	('tumor', 'Phenotype', 'HP:0002664', (66, 71))	('High', 'Var', (0, 4))	('tumors', 'Disease', (66, 72))	('EGFR', 'Gene', '1956', (5, 9))	('tumors', 'Disease', 'MESH:D009369', (66, 72))	('tumors', 'Phenotype', 'HP:0002664', (66, 72))	('associated', 'Reg', (37, 47))	('EGFR', 'Gene', (5, 9))
10394	19861435	We then profiled tumors for the presence of mutations in genes encoding components of the EGFR signaling pathway that are known to be mutated at specific recurrent nucleotide positions in human cancers.	('tumors', 'Phenotype', 'HP:0002664', (17, 23))	('human', 'Species', '9606', (188, 193))	('cancers', 'Phenotype', 'HP:0002664', (194, 201))	('tumors', 'Disease', (17, 23))	('tumors', 'Disease', 'MESH:D009369', (17, 23))	('EGFR', 'Gene', '1956', (90, 94))	('cancers', 'Disease', 'MESH:D009369', (194, 201))	('cancer', 'Phenotype', 'HP:0002664', (194, 200))	('cancers', 'Disease', (194, 201))	('EGFR', 'Gene', (90, 94))	('mutations', 'Var', (44, 53))	('tumor', 'Phenotype', 'HP:0002664', (17, 22))
10395	19861435	Somatic RAS mutations were found in 3 (7%) of 45 tumors (Table 2): a heterozygous G to C substitution at nucleotide position 35 in exon 1 of KRAS, resulting in a alanine for glycine amino acid substitution at position 12 (G12A) in a type B2 thymoma (case 28); a heterozygous G to T substitution at nucleotide position 35 in exon 1 of KRAS, resulting in a valine for glycine amino acid substitution at position 12 (G12V) in a thymic carcinoma (case 41); and a heterozygous G to T mutation at position 38 in exon 1 of HRAS, resulting in a valine for glycine amino acid substitution at position 13 (G13V), in a type A thymoma (case 3) (Figure 1).	('KRAS', 'Gene', (141, 145))	('valine for glycine amino acid substitution at position 13', 'Mutation', 'rs104894226', (537, 594))	('tumor', 'Phenotype', 'HP:0002664', (49, 54))	('G13V', 'Mutation', 'rs104894226', (596, 600))	('in a', 'Reg', (532, 536))	('tumors', 'Disease', (49, 55))	('type B2 thymoma', 'Disease', (233, 248))	('thymoma', 'Phenotype', 'HP:0100522', (241, 248))	('thymoma', 'Phenotype', 'HP:0100522', (615, 622))	('type A thymoma', 'Disease', (608, 622))	('valine for glycine amino acid substitution at position 12', 'Mutation', 'rs121913529', (355, 412))	('G12A', 'Mutation', 'rs121913529', (222, 226))	('KRAS', 'Gene', '3845', (334, 338))	('tumors', 'Disease', 'MESH:D009369', (49, 55))	('substitution', 'Var', (282, 294))	('KRAS', 'Gene', (334, 338))	('G to T mutation', 'Var', (472, 487))	('alanine for glycine amino acid substitution at position 12', 'Mutation', 'rs121913529', (162, 220))	('G12V', 'Mutation', 'rs121913529', (414, 418))	('thymic carcinoma', 'Disease', (425, 441))	('KRAS', 'Gene', '3845', (141, 145))	('mutations', 'Var', (12, 21))	('HRAS', 'Gene', '3265', (516, 520))	('type A thymoma', 'Disease', 'MESH:D013945', (608, 622))	('tumors', 'Phenotype', 'HP:0002664', (49, 55))	('G to T mutation at position 38', 'Mutation', 'rs104894226', (472, 502))	('substitution', 'Var', (89, 101))	('G to T substitution at nucleotide position 35', 'Mutation', 'rs121913529', (275, 320))	('HRAS', 'Gene', (516, 520))	('thymic carcinoma', 'Disease', 'MESH:D013945', (425, 441))	('G to C substitution at nucleotide position 35', 'Mutation', 'rs121913529', (82, 127))	('type B2 thymoma', 'Disease', 'MESH:D013945', (233, 248))	('carcinoma', 'Phenotype', 'HP:0030731', (432, 441))
10399	19861435	Moreover, KIT staining by IHC has been reported to be frequent in thymic carcinoma.	('thymic carcinoma', 'Disease', 'MESH:D013945', (66, 82))	('frequent', 'Reg', (54, 62))	('KIT staining', 'Var', (10, 22))	('thymic carcinoma', 'Disease', (66, 82))	('carcinoma', 'Phenotype', 'HP:0030731', (73, 82))
10401	19861435	Direct sequencing of exons that encode the KIT kinase and transmembrane domains revealed that 2 (4%) of the 45 tumors, both thymic carcinomas, harbored KIT mutations (Table 2).	('carcinoma', 'Phenotype', 'HP:0030731', (131, 140))	('carcinomas', 'Phenotype', 'HP:0030731', (131, 141))	('harbored', 'Reg', (143, 151))	('thymic carcinomas', 'Disease', 'MESH:D013945', (124, 141))	('mutations', 'Var', (156, 165))	('tumor', 'Phenotype', 'HP:0002664', (111, 116))	('KIT', 'Gene', (152, 155))	('tumors', 'Disease', (111, 117))	('tumors', 'Disease', 'MESH:D009369', (111, 117))	('tumors', 'Phenotype', 'HP:0002664', (111, 117))	('thymic carcinomas', 'Disease', (124, 141))
10402	19861435	One tumor, CD5-positive, contained a heterozygous deletion of nucleotides 1678 to 1680 in exon 11 of KIT, resulting in a deletion of valine at position 560 (V560del) (Figure 1).	('tumor', 'Disease', (4, 9))	('CD5', 'Gene', '921', (11, 14))	('V560del', 'Mutation', 'p.560delV', (157, 164))	('KIT', 'Gene', (101, 104))	('valine', 'MPA', (133, 139))	('tumor', 'Disease', 'MESH:D009369', (4, 9))	('valine', 'Chemical', 'MESH:D014633', (133, 139))	('tumor', 'Phenotype', 'HP:0002664', (4, 9))	('deletion', 'Var', (121, 129))	('CD5', 'Gene', (11, 14))
10403	19861435	The other mutation, found in a CD5-negative tumor, was a heterozygous C to T mutation at position 2089 in exon 14 of KIT, resulting in a tyrosine for histidine amino acid substitution at position 697 (H697Y) (Figure 1).	('tyrosine for histidine amino acid substitution at position 697', 'Mutation', 'rs763308199', (137, 199))	('CD5', 'Gene', (31, 34))	('KIT', 'Gene', (117, 120))	('CD5', 'Gene', '921', (31, 34))	('tumor', 'Disease', 'MESH:D009369', (44, 49))	('tyrosine', 'Var', (137, 145))	('C to T mutation at position 2089', 'Mutation', 'rs763308199', (70, 102))	('tumor', 'Phenotype', 'HP:0002664', (44, 49))	('H697Y', 'Mutation', 'rs763308199', (201, 206))	('in a', 'Reg', (132, 136))	('tumor', 'Disease', (44, 49))
10404	19861435	KIT V560G, KIT del557-558) have been found in GISTs sensitive to imatinib, and this exact mutation was previously observed in a case of thymic carcinoma responding to imatinib.	('imatinib', 'Chemical', 'MESH:D000068877', (65, 73))	('KIT del557-558', 'Var', (11, 25))	('V560G', 'Var', (4, 9))	('thymic carcinoma', 'Disease', (136, 152))	('sensitive to imatinib', 'MPA', (52, 73))	('V560G', 'Mutation', 'rs121913521', (4, 9))	('thymic carcinoma', 'Disease', 'MESH:D013945', (136, 152))	('carcinoma', 'Phenotype', 'HP:0030731', (143, 152))	('imatinib', 'Chemical', 'MESH:D000068877', (167, 175))	('KIT', 'Gene', (0, 3))
10405	19861435	The KIT H697Y has not been previously reported in any cancer (COSMIC).	('cancer', 'Disease', 'MESH:D009369', (54, 60))	('cancer', 'Disease', (54, 60))	('H697Y', 'Mutation', 'rs763308199', (8, 13))	('H697Y', 'Var', (8, 13))	('cancer', 'Phenotype', 'HP:0002664', (54, 60))
10407	19861435	To confirm that the V560del mutation is associated with imatinib sensitivity, and to study the H697Y mutation, we generated stable Ba/F3 transfectants expressing the mutant alleles.	('V560del', 'Var', (20, 27))	('imatinib', 'Chemical', 'MESH:D000068877', (56, 64))	('V560del', 'Mutation', 'p.560delV', (20, 27))	('imatinib sensitivity', 'MPA', (56, 76))	('H697Y', 'Mutation', 'rs763308199', (95, 100))	('associated', 'Reg', (40, 50))
10409	19861435	Ba/F3-KITV560del and Ba/F3-KITH697Y cells grew in the absence of IL-3, demonstrating that these mutations confer gain-of-function (data not shown).	('H697Y', 'Mutation', 'rs763308199', (30, 35))	('KITV560del', 'Mutation', 'c.560delKITV', (6, 16))	('gain-of-function', 'PosReg', (113, 129))	('mutations', 'Var', (96, 105))
10412	19861435	Although the latter GI50 was still below 1000nM for imatinib, a cut-off reported for resistance to this drug in GISTs, these data suggest that sunitinib may be a more effective KIT inhibitor than imatinib in KIT-mutant thymic carcinomas.	('carcinomas', 'Phenotype', 'HP:0030731', (226, 236))	('sunitinib', 'Chemical', 'MESH:D000077210', (143, 152))	('imatinib', 'Chemical', 'MESH:D000068877', (52, 60))	('thymic carcinomas', 'Disease', 'MESH:D013945', (219, 236))	('KIT-mutant', 'Var', (208, 218))	('carcinoma', 'Phenotype', 'HP:0030731', (226, 235))	('imatinib', 'Chemical', 'MESH:D000068877', (196, 204))	('thymic carcinomas', 'Disease', (219, 236))
10434	19861435	Copy number data analysis revealed that compared to squamous lung cancers, chromosomal aberrations were more frequent and occurred in different and larger loci in thymic carcinomas (Supplemental Figure 3).	('lung cancer', 'Phenotype', 'HP:0100526', (61, 72))	('carcinoma', 'Phenotype', 'HP:0030731', (170, 179))	('thymic carcinomas', 'Disease', (163, 180))	('squamous lung cancers', 'Disease', (52, 73))	('cancer', 'Phenotype', 'HP:0002664', (66, 72))	('squamous lung cancers', 'Disease', 'MESH:D008175', (52, 73))	('lung cancers', 'Phenotype', 'HP:0100526', (61, 73))	('cancers', 'Phenotype', 'HP:0002664', (66, 73))	('carcinomas', 'Phenotype', 'HP:0030731', (170, 180))	('thymic carcinomas', 'Disease', 'MESH:D013945', (163, 180))	('occurred', 'Reg', (122, 130))	('men', 'Species', '9606', (188, 191))	('chromosomal aberrations', 'Var', (75, 98))	('chromosomal aberrations', 'Phenotype', 'HP:0040012', (75, 98))
10439	19861435	First, mutational analysis of genes encoding components of the EGFR signaling pathway led to the identification of RAS mutations in 3 (7%) out of 45 thymic epithelial tumors.	('EGFR', 'Gene', '1956', (63, 67))	('epithelial tumors', 'Disease', 'MESH:D002277', (156, 173))	('EGFR', 'Gene', (63, 67))	('RAS', 'Gene', (115, 118))	('tumor', 'Phenotype', 'HP:0002664', (167, 172))	('mutations', 'Var', (119, 128))	('tumors', 'Phenotype', 'HP:0002664', (167, 173))	('epithelial tumors', 'Disease', (156, 173))	('mutational', 'Var', (7, 17))	('epithelial tumor', 'Phenotype', 'HP:0031492', (156, 172))
10441	19861435	In our study, 2 RAS mutant tumors were thymomas (type A and B2) which are low-grade, and the other tumor was a thymic carcinoma, which is high-grade.	('thymic carcinoma', 'Disease', (111, 127))	('tumor', 'Disease', (99, 104))	('tumor', 'Phenotype', 'HP:0002664', (27, 32))	('thymic carcinoma', 'Disease', 'MESH:D013945', (111, 127))	('tumor', 'Disease', (27, 32))	('thymomas', 'Disease', 'MESH:D013945', (39, 47))	('thymoma', 'Phenotype', 'HP:0100522', (39, 46))	('tumors', 'Disease', (27, 33))	('tumors', 'Disease', 'MESH:D009369', (27, 33))	('tumors', 'Phenotype', 'HP:0002664', (27, 33))	('carcinoma', 'Phenotype', 'HP:0030731', (118, 127))	('tumor', 'Disease', 'MESH:D009369', (99, 104))	('RAS', 'Gene', (16, 19))	('tumor', 'Phenotype', 'HP:0002664', (99, 104))	('thymomas', 'Disease', (39, 47))	('tumor', 'Disease', 'MESH:D009369', (27, 32))	('mutant', 'Var', (20, 26))
10442	19861435	KRAS mutations predict for primary resistance to anti-EGFR directed therapies (i.e.	('KRAS', 'Gene', (0, 4))	('mutations', 'Var', (5, 14))	('predict', 'Reg', (15, 22))	('EGFR', 'Gene', '1956', (54, 58))	('EGFR', 'Gene', (54, 58))	('KRAS', 'Gene', '3845', (0, 4))
10444	19861435	HRAS mutations occur much more rarely in epithelial cancers.	('HRAS', 'Gene', (0, 4))	('cancer', 'Phenotype', 'HP:0002664', (52, 58))	('epithelial cancers', 'Disease', 'MESH:D000077216', (41, 59))	('mutations', 'Var', (5, 14))	('epithelial cancers', 'Disease', (41, 59))	('HRAS', 'Gene', '3265', (0, 4))	('cancers', 'Phenotype', 'HP:0002664', (52, 59))
10445	19861435	Cells expressing activated or mutant HRAS (T24 cell line) have also been reported to be resistant to gefitinib.	('HRAS', 'Gene', '3265', (37, 41))	('resistant', 'MPA', (88, 97))	('gefitinib', 'Chemical', 'MESH:D000077156', (101, 110))	('mutant', 'Var', (30, 36))	('HRAS', 'Gene', (37, 41))
10451	19861435	As both RAS mutant tumors were strongly positive for EGFR staining, the data also suggest that IHC staining for EGFR is not useful as an eligibility marker for anti-EGFR therapies.	('EGFR', 'Gene', (112, 116))	('tumors', 'Disease', (19, 25))	('EGFR', 'Gene', (165, 169))	('tumors', 'Disease', 'MESH:D009369', (19, 25))	('tumor', 'Phenotype', 'HP:0002664', (19, 24))	('mutant', 'Var', (12, 18))	('EGFR', 'Gene', '1956', (53, 57))	('EGFR', 'Gene', '1956', (112, 116))	('EGFR', 'Gene', (53, 57))	('tumors', 'Phenotype', 'HP:0002664', (19, 25))	('positive', 'Reg', (40, 48))	('EGFR', 'Gene', '1956', (165, 169))
10452	19861435	The second finding is the presence of KIT mutations in 2 of 45 thymic tumors.	('thymic tumors', 'Disease', 'MESH:D013953', (63, 76))	('presence', 'Reg', (26, 34))	('tumor', 'Phenotype', 'HP:0002664', (70, 75))	('KIT', 'Gene', (38, 41))	('tumors', 'Phenotype', 'HP:0002664', (70, 76))	('mutations', 'Var', (42, 51))	('thymic tumor', 'Phenotype', 'HP:0100521', (63, 75))	('thymic tumors', 'Disease', (63, 76))
10453	19861435	One was a V560 deletion in exon 11, and the other was a novel H697Y mutation in exon 14.	('H697Y', 'Mutation', 'rs763308199', (62, 67))	('H697Y', 'Var', (62, 67))	('V560 deletion', 'Var', (10, 23))
10454	19861435	In contrast to RAS mutations, KIT mutations were found exclusively in thymic carcinomas.	('thymic carcinomas', 'Disease', (70, 87))	('thymic carcinomas', 'Disease', 'MESH:D013945', (70, 87))	('carcinoma', 'Phenotype', 'HP:0030731', (77, 86))	('KIT', 'Gene', (30, 33))	('carcinomas', 'Phenotype', 'HP:0030731', (77, 87))	('mutations', 'Var', (34, 43))	('found', 'Reg', (49, 54))
10455	19861435	Previously, out of 106 thymic tumors collectively tested, only 3 cases of KIT mutation have been reported in the literature; all these mutations also occurred in thymic carcinomas.	('tumors', 'Phenotype', 'HP:0002664', (30, 36))	('carcinoma', 'Phenotype', 'HP:0030731', (169, 178))	('carcinomas', 'Phenotype', 'HP:0030731', (169, 179))	('mutations', 'Var', (135, 144))	('thymic carcinomas', 'Disease', 'MESH:D013945', (162, 179))	('thymic tumor', 'Phenotype', 'HP:0100521', (23, 35))	('thymic tumors', 'Disease', (23, 36))	('thymic tumors', 'Disease', 'MESH:D013953', (23, 36))	('tumor', 'Phenotype', 'HP:0002664', (30, 35))	('occurred', 'Reg', (150, 158))	('thymic carcinomas', 'Disease', (162, 179))
10456	19861435	This mutation is associated with sensitivity to KIT inhibitors, based upon multiple lines of evidence: 1) we showed in vitro that the growth of mutant-bearing Ba/F3 cells is readily inhibited by treatment with imatinib and sunitinib; 2) the patient whose tumor harbored this mutation responded to treatment with imatinib, and 3) this mutation has also been found in an imatinib-sensitive GIST.	('sunitinib', 'Chemical', 'MESH:D000077210', (223, 232))	('tumor', 'Disease', (255, 260))	('men', 'Species', '9606', (302, 305))	('tumor', 'Phenotype', 'HP:0002664', (255, 260))	('mutant-bearing', 'Var', (144, 158))	('patient', 'Species', '9606', (241, 248))	('mutation', 'Var', (275, 283))	('men', 'Species', '9606', (200, 203))	('imatinib', 'Chemical', 'MESH:D000068877', (369, 377))	('inhibited', 'NegReg', (182, 191))	('imatinib', 'Chemical', 'MESH:D000068877', (312, 320))	('tumor', 'Disease', 'MESH:D009369', (255, 260))	('imatinib', 'Chemical', 'MESH:D000068877', (210, 218))
10457	19861435	Another KIT-mutant case of thymic carcinoma reported in the literature harbored an L576P mutation in exon 11.	('L576P', 'Mutation', 'rs121913513', (83, 88))	('L576P', 'Var', (83, 88))	('thymic carcinoma', 'Disease', (27, 43))	('carcinoma', 'Phenotype', 'HP:0030731', (34, 43))	('thymic carcinoma', 'Disease', 'MESH:D013945', (27, 43))
10459	19861435	The third mutation reported is a D820E mutation in exon 17, exhibited by a thymic carcinoma responding to sorafenib.	('D820E', 'Var', (33, 38))	('D820E', 'Mutation', 'rs1057519711', (33, 38))	('thymic carcinoma', 'Disease', (75, 91))	('carcinoma', 'Phenotype', 'HP:0030731', (82, 91))	('sorafenib', 'Chemical', 'MESH:D000077157', (106, 115))	('thymic carcinoma', 'Disease', 'MESH:D013945', (75, 91))
10460	19861435	The D820Y KIT mutation is known to be associated with imatinib resistance and sorafenib sensitivity in GIST.	('D820Y', 'Mutation', 'rs1057519710', (4, 9))	('associated', 'Reg', (38, 48))	('imatinib resistance', 'MPA', (54, 73))	('imatinib', 'Chemical', 'MESH:D000068877', (54, 62))	('sorafenib', 'Chemical', 'MESH:D000077157', (78, 87))	('D820Y KIT', 'Var', (4, 13))	('sensitivity', 'MPA', (88, 99))
10461	19861435	Finally, we show here that the KIT H697Y mutation, identified in exon 14 (which was not sequenced in previous studies) is associated in vitro with greater sensitivity to sunitinib vs. imatinib.	('greater', 'PosReg', (147, 154))	('KIT', 'Gene', (31, 34))	('H697Y', 'Mutation', 'rs763308199', (35, 40))	('H697Y', 'Var', (35, 40))	('sunitinib', 'Chemical', 'MESH:D000077210', (170, 179))	('imatinib', 'Chemical', 'MESH:D000068877', (184, 192))	('sensitivity to sunitinib', 'MPA', (155, 179))
10463	19861435	The rarity of KIT mutations in unselected thymic tumors and the greater sensitivity of the H697Y mutant to sunitinib could explain the absence of responses observed in 2 recent phase II trials with imatinib, where patients were selected either by histologic type (B3 thymomas and thymic carcinomas), or using KIT staining by IHC.	('thymic tumor', 'Phenotype', 'HP:0100521', (42, 54))	('thymic tumors', 'Disease', 'MESH:D013953', (42, 55))	('patients', 'Species', '9606', (214, 222))	('tumor', 'Phenotype', 'HP:0002664', (49, 54))	('sunitinib', 'Chemical', 'MESH:D000077210', (107, 116))	('tumors', 'Phenotype', 'HP:0002664', (49, 55))	('imatinib', 'Chemical', 'MESH:D000068877', (198, 206))	('thymoma', 'Phenotype', 'HP:0100522', (267, 274))	('carcinoma', 'Phenotype', 'HP:0030731', (287, 296))	('carcinomas', 'Phenotype', 'HP:0030731', (287, 297))	('H697Y', 'Mutation', 'rs763308199', (91, 96))	('H697Y', 'Var', (91, 96))	('thymic tumors', 'Disease', (42, 55))	('thymomas and thymic carcinomas', 'Disease', 'MESH:D013945', (267, 297))	('mutations', 'Var', (18, 27))
10485	19861435	We were also able to identify additional differential alterations present in thymic tumors (chromosome 12 gains, and chromosome 2p, 6, 7, 14 losses).	('tumor', 'Phenotype', 'HP:0002664', (84, 89))	('chromosome', 'Var', (92, 102))	('thymic tumors', 'Disease', (77, 90))	('tumors', 'Phenotype', 'HP:0002664', (84, 90))	('thymic tumor', 'Phenotype', 'HP:0100521', (77, 89))	('gains', 'PosReg', (106, 111))	('thymic tumors', 'Disease', 'MESH:D013953', (77, 90))	('losses', 'NegReg', (141, 147))
10486	19861435	Consistent with these findings, we did not identify mutations in TP53 in thymic carcinomas, although such mutations are frequent (55%) in lung squamous cell carcinomas.	('mutations', 'Var', (52, 61))	('carcinoma', 'Phenotype', 'HP:0030731', (80, 89))	('carcinomas', 'Phenotype', 'HP:0030731', (157, 167))	('lung squamous cell carcinomas', 'Disease', (138, 167))	('TP53', 'Gene', '7157', (65, 69))	('TP53', 'Gene', (65, 69))	('carcinomas', 'Phenotype', 'HP:0030731', (80, 90))	('thymic carcinomas', 'Disease', 'MESH:D013945', (73, 90))	('squamous cell carcinomas', 'Phenotype', 'HP:0002860', (143, 167))	('lung squamous cell carcinomas', 'Disease', 'MESH:D002294', (138, 167))	('carcinoma', 'Phenotype', 'HP:0030731', (157, 166))	('squamous cell carcinoma', 'Phenotype', 'HP:0002860', (143, 166))	('thymic carcinomas', 'Disease', (73, 90))
10655	23725376	Loss of heterozygosity (LOH) on chromosome 6 is the most frequent genetic abnormality in thymoma.	('thymoma', 'Disease', 'MESH:D013945', (89, 96))	('Loss of heterozygosity', 'Var', (0, 22))	('thymoma', 'Disease', (89, 96))	('thymoma', 'Phenotype', 'HP:0100522', (89, 96))	('genetic abnormality', 'Disease', 'MESH:D030342', (66, 85))	('genetic abnormality', 'Disease', (66, 85))
10658	23725376	There are five hotspots of frequent deletions indicating that several putative tumor suppressor genes on chromosome 6 are involved in the development of thymic epithelial tumor.	('epithelial tumor', 'Phenotype', 'HP:0031492', (160, 176))	('deletions', 'Var', (36, 45))	('tumor', 'Disease', (79, 84))	('involved', 'Reg', (122, 130))	('tumor', 'Phenotype', 'HP:0002664', (171, 176))	('tumor', 'Disease', 'MESH:D009369', (171, 176))	('thymic epithelial tumor', 'Disease', 'MESH:C536905', (153, 176))	('tumor', 'Disease', 'MESH:D009369', (79, 84))	('tumor', 'Disease', (171, 176))	('thymic epithelial tumor', 'Disease', (153, 176))	('tumor', 'Phenotype', 'HP:0002664', (79, 84))
10661	23725376	This primary adenocarcinoma of the thymus with intestinal differentiation shows homozygous deletion of part of the HLA- locus in chromosomal region 6p21.32 confirmed by CGH array.	('adenocarcinoma of the thymus', 'Disease', (13, 41))	('carcinoma', 'Phenotype', 'HP:0030731', (18, 27))	('deletion', 'Var', (91, 99))	('HLA- locus', 'Gene', (115, 125))	('adenocarcinoma of the thymus', 'Phenotype', 'HP:0100521', (13, 41))	('primary adenocarcinoma', 'Disease', 'MESH:D000230', (5, 27))	('primary adenocarcinoma', 'Disease', (5, 27))	('adenocarcinoma of the thymus', 'Disease', 'MESH:D000230', (13, 41))
10744	23493352	It may provide additional support for a diagnosis by identifying tumor-specific genetic signatures, help in prognostication and even in determining the best therapeutic options.	('tumor', 'Disease', (65, 70))	('help', 'Reg', (100, 104))	('tumor', 'Disease', 'MESH:D009369', (65, 70))	('genetic', 'Var', (80, 87))	('tumor', 'Phenotype', 'HP:0002664', (65, 70))
10765	20966748	Immunodeficiency secondary to anti-cytokine autoantibodies Anti-cytokine autoantibodies are an important and emerging mechanism of disease pathogenesis.	('Immunodeficiency', 'Phenotype', 'HP:0002721', (0, 16))	('Immunodeficiency', 'Disease', (0, 16))	('Immunodeficiency', 'Disease', 'MESH:D007153', (0, 16))	('anti-cytokine autoantibodies', 'Var', (30, 58))
10766	20966748	We will review the clinical and laboratory features of syndromes in which immunodeficiency is caused by or associated with neutralizing anti-cytokine autoantibodies.	('caused by', 'Reg', (94, 103))	('neutralizing', 'Var', (123, 135))	('immunodeficiency', 'Phenotype', 'HP:0002721', (74, 90))	('immunodeficiency', 'Disease', (74, 90))	('immunodeficiency', 'Disease', 'MESH:D007153', (74, 90))
10782	20966748	Other defects impacting the same metabolic pathway have similar susceptibilities, including STAT1, IL-12p40, IL-12Rb1, and NEMO.	('metabolic pathway', 'Pathway', (33, 50))	('NEMO', 'Gene', (123, 127))	('p40', 'Gene', (104, 107))	('NEMO', 'Gene', '8517', (123, 127))	('impacting', 'Reg', (14, 23))	('IL-12Rb1', 'Gene', (109, 117))	('p40', 'Gene', '3578', (104, 107))	('STAT1', 'Gene', (92, 97))	('STAT1', 'Gene', '6772', (92, 97))	('defects', 'Var', (6, 13))	('IL-12Rb1', 'Gene', '3594', (109, 117))
10783	20966748	The first cases of immunodeficiency caused by autoantibodies to IFN-gamma were described in 2004.	('immunodeficiency', 'Phenotype', 'HP:0002721', (19, 35))	('immunodeficiency', 'Disease', (19, 35))	('caused', 'Reg', (36, 42))	('autoantibodies', 'Var', (46, 60))	('immunodeficiency', 'Disease', 'MESH:D007153', (19, 35))	('IFN-gamma', 'Gene', '3458', (64, 73))	('IFN-gamma', 'Gene', (64, 73))
10792	20966748	There are 3 distinct forms of PAP, each demonstrating abnormalities of surfactant metabolism that result in accumulation of acellular periodic acid-Schiff (PAS) positive proteinaceous material in pulmonary alveoli and development of large foamy, monocyte-like alveolar macrophages (reviewed by Trapnell et al.).	('pulmonary alveoli', 'Disease', 'MESH:D008171', (196, 213))	('acellular', 'MPA', (124, 133))	('PAS', 'Chemical', '-', (156, 159))	('accumulation', 'PosReg', (108, 120))	('development', 'CPA', (218, 229))	('abnormalities', 'Var', (54, 67))	('pulmonary alveoli', 'Disease', (196, 213))	('periodic acid-Schiff', 'Chemical', '-', (134, 154))	('PAP', 'Disease', (30, 33))
10793	20966748	Primary PAP, the most severe form, results from mutations in the GM-CSF receptor and generally leads to respiratory failure and death shortly after birth.	('death', 'Disease', (128, 133))	('Primary PAP', 'Disease', (0, 11))	('respiratory failure', 'Disease', (104, 123))	('GM-CSF receptor', 'Gene', (65, 80))	('respiratory failure', 'Disease', 'MESH:D012131', (104, 123))	('results from', 'Reg', (35, 47))	('respiratory failure', 'Phenotype', 'HP:0002878', (104, 123))	('death', 'Disease', 'MESH:D003643', (128, 133))	('leads to', 'Reg', (95, 103))	('mutations', 'Var', (48, 57))
10795	20966748	Anti-GM-CSF autoantibodies in patients with PAP contribute to a range of defects in alveolar macrophage function including chemotaxis, adhesion, phagocytosis, microbicidal activity, and phagolysosome fusion.	('Anti-GM-CSF', 'Protein', (0, 11))	('Anti-GM-CSF autoantibodies', 'Phenotype', 'HP:0020050', (0, 26))	('alveolar macrophage function', 'CPA', (84, 112))	('adhesion', 'CPA', (135, 143))	('autoantibodies', 'Var', (12, 26))	('phagolysosome fusion', 'CPA', (186, 206))	('microbicidal activity', 'CPA', (159, 180))	('phagocytosis', 'CPA', (145, 157))	('patients', 'Species', '9606', (30, 38))	('chemotaxis', 'CPA', (123, 133))	('PAP', 'Disease', (44, 47))	('defects', 'NegReg', (73, 80))
10796	20966748	Evidence from GM-CSF receptor-deficient mice suggests that GM-CSF induces PU.1, a gene critical to both surfactant homeostasis and TLR signaling, which potentially explains both surfactant accumulation and infection susceptibility seen in PAP.	('induces', 'Reg', (66, 73))	('infection', 'Disease', (206, 215))	('infection', 'Disease', 'MESH:D007239', (206, 215))	('GM-CSF', 'Var', (59, 65))	('mice', 'Species', '10090', (40, 44))	('PU.1', 'Gene', '20375', (74, 78))	('PU.1', 'Gene', (74, 78))
10805	20966748	APECED is a rare, autosomal recessive disorder caused by mutations in the autoimmune regulator (AIRE) gene that is characterized by a classic triad of CMC, hypoparathyroidism, and Addison's disease (reviewed by Perheentupa).	("Addison's disease", 'Disease', (180, 197))	('hypoparathyroidism', 'Disease', (156, 174))	('hypoparathyroidism', 'Phenotype', 'HP:0000829', (156, 174))	('hypoparathyroidism', 'Disease', 'MESH:D007011', (156, 174))	('CMC', 'Disease', (151, 154))	('autoimmune regulator', 'Gene', '326', (74, 94))	('AIRE', 'Gene', (96, 100))	('caused by', 'Reg', (47, 56))	('autoimmune regulator', 'Gene', (74, 94))	('mutations', 'Var', (57, 66))	("Addison's disease", 'Disease', 'MESH:D000224', (180, 197))	('AIRE', 'Gene', '326', (96, 100))	("Addison's disease", 'Phenotype', 'HP:0008207', (180, 197))	('autosomal recessive disorder', 'Disease', 'MESH:D030342', (18, 46))	('APECED', 'Gene', '326', (0, 6))	('CMC', 'Phenotype', 'HP:0002728', (151, 154))	('autosomal recessive disorder', 'Disease', (18, 46))	('APECED', 'Gene', (0, 6))
10824	20966748	Pathogenic autoantibodies are common in thymoma, most often in the form of myasthenia gravis caused by anti-acetylcholine receptor antibodies.	('thymoma', 'Disease', (40, 47))	('acetylcholine receptor antibodies', 'Phenotype', 'HP:0030208', (108, 141))	('myasthenia', 'Phenotype', 'HP:0003473', (75, 85))	('thymoma', 'Phenotype', 'HP:0100522', (40, 47))	('anti-acetylcholine', 'Var', (103, 121))	('caused', 'Reg', (93, 99))	('myasthenia gravis', 'Disease', (75, 92))	('myasthenia gravis', 'Disease', 'MESH:D009157', (75, 92))	('thymoma', 'Disease', 'MESH:D013945', (40, 47))
10838	20966748	Hyper-IgE syndrome, characterized by recurrent staphylococcal skin abscesses, is due to mutations in STAT3, the critical signal transduction molecule for IL-6 and IL-10 responses.	('Hyper-IgE syndrome', 'Disease', (0, 18))	('STAT3', 'Gene', '6774', (101, 106))	('Hyper-IgE syndrome', 'Disease', 'MESH:D007589', (0, 18))	('recurrent staphylococcal skin', 'Phenotype', 'HP:0007499', (37, 66))	('IL-10', 'Gene', (163, 168))	('skin abscesses', 'Phenotype', 'HP:0031292', (62, 76))	('STAT3', 'Gene', (101, 106))	('abscess', 'Phenotype', 'HP:0025615', (67, 74))	('due', 'Reg', (81, 84))	('mutations', 'Var', (88, 97))	('IL-6', 'Gene', (154, 158))	('IL-10', 'Gene', '3586', (163, 168))	('staphylococcal skin abscesses', 'Disease', (47, 76))	('IL-6', 'Gene', '3569', (154, 158))	('abscesses', 'Phenotype', 'HP:0025615', (67, 76))
10860	33718203	In the validation set, the NECT-based clinical RM (AUC = 0.770 for low-risk thymoma, 0.689 for high-risk thymoma, and 0.783 for thymic carcinoma; ACC = 0.569) performed better than the CECT-based clinical-semantic RM (AUC = 0.785 for low-risk thymoma, 0.576 for high-risk thymoma, and 0.774 for thymic carcinoma; ACC = 0.483).	('thymoma', 'Disease', 'MESH:D013945', (105, 112))	('thymoma', 'Disease', (243, 250))	('thymic carcinoma', 'Disease', (295, 311))	('thymoma', 'Phenotype', 'HP:0100522', (243, 250))	('thymoma', 'Disease', 'MESH:D013945', (272, 279))	('thymoma', 'Disease', (76, 83))	('thymoma', 'Disease', (105, 112))	('thymoma', 'Phenotype', 'HP:0100522', (76, 83))	('carcinoma', 'Phenotype', 'HP:0030731', (135, 144))	('thymoma', 'Phenotype', 'HP:0100522', (105, 112))	('carcinoma', 'Phenotype', 'HP:0030731', (302, 311))	('thymoma', 'Disease', (272, 279))	('better', 'PosReg', (169, 175))	('thymoma', 'Phenotype', 'HP:0100522', (272, 279))	('thymic carcinoma', 'Disease', 'MESH:D013953', (128, 144))	('thymic carcinoma', 'Disease', 'MESH:D013953', (295, 311))	('0.783', 'Var', (118, 123))	('thymoma', 'Disease', 'MESH:D013945', (243, 250))	('thymoma', 'Disease', 'MESH:D013945', (76, 83))	('thymic carcinoma', 'Disease', (128, 144))
10914	33718203	In the training set, the NECT-based RM achieved AUCs of 0.739 (for low-risk thymoma), 0.783 (for high-risk thymoma), and 0.759 (for thymic carcinoma) and an ACC of 0.644 ( Table 2 ,  Figure 3 ).	('thymoma', 'Disease', (76, 83))	('thymoma', 'Phenotype', 'HP:0100522', (107, 114))	('thymoma', 'Phenotype', 'HP:0100522', (76, 83))	('carcinoma', 'Phenotype', 'HP:0030731', (139, 148))	('thymoma', 'Disease', 'MESH:D013945', (76, 83))	('0.783', 'Var', (86, 91))	('0.759', 'Var', (121, 126))	('thymoma', 'Disease', 'MESH:D013945', (107, 114))	('thymoma', 'Disease', (107, 114))	('thymic carcinoma', 'Disease', (132, 148))	('thymic carcinoma', 'Disease', 'MESH:D013953', (132, 148))
10915	33718203	In contrast, the CECT-based RM achieved AUCs of 0.679 (for low-risk thymoma), 0.688 (for high-risk thymoma), and 0.721 (for thymic carcinoma) and an ACC of 0.576.	('0.721', 'Var', (113, 118))	('thymoma', 'Disease', 'MESH:D013945', (99, 106))	('carcinoma', 'Phenotype', 'HP:0030731', (131, 140))	('thymoma', 'Disease', 'MESH:D013945', (68, 75))	('thymoma', 'Disease', (68, 75))	('thymoma', 'Disease', (99, 106))	('0.688', 'Var', (78, 83))	('thymoma', 'Phenotype', 'HP:0100522', (68, 75))	('thymoma', 'Phenotype', 'HP:0100522', (99, 106))	('thymic carcinoma', 'Disease', (124, 140))	('thymic carcinoma', 'Disease', 'MESH:D013953', (124, 140))
10916	33718203	In the validation set, similar results were found, where the NECT-based RM achieved AUCs of 0.686 (for low-risk thymoma), 0.601 (for high-risk thymoma), and 0.632 (for thymic carcinoma) and an ACC of 0.483 ( Table 3 ).	('thymoma', 'Disease', 'MESH:D013945', (112, 119))	('0.632', 'Var', (157, 162))	('thymoma', 'Disease', (112, 119))	('0.601', 'Var', (122, 127))	('thymoma', 'Disease', 'MESH:D013945', (143, 150))	('thymoma', 'Phenotype', 'HP:0100522', (112, 119))	('thymoma', 'Disease', (143, 150))	('thymoma', 'Phenotype', 'HP:0100522', (143, 150))	('thymic carcinoma', 'Disease', (168, 184))	('carcinoma', 'Phenotype', 'HP:0030731', (175, 184))	('thymic carcinoma', 'Disease', 'MESH:D013953', (168, 184))
10917	33718203	In contrast, the CECT-based RM achieved AUCs of 0.611 (for low-risk thymoma), 0.574 (for high-risk thymoma), and 0.626 (for thymic carcinoma) and an ACC of 0.448.	('thymoma', 'Disease', 'MESH:D013945', (99, 106))	('carcinoma', 'Phenotype', 'HP:0030731', (131, 140))	('0.626', 'Var', (113, 118))	('thymoma', 'Disease', 'MESH:D013945', (68, 75))	('thymoma', 'Disease', (68, 75))	('thymoma', 'Disease', (99, 106))	('0.574', 'Var', (78, 83))	('thymoma', 'Phenotype', 'HP:0100522', (68, 75))	('thymoma', 'Phenotype', 'HP:0100522', (99, 106))	('thymic carcinoma', 'Disease', (124, 140))	('thymic carcinoma', 'Disease', 'MESH:D013953', (124, 140))
10918	33718203	In the training set, the NECT-based clinical RM exhibited AUCs of 0.746 (for low-risk thymoma), 0.808 (for high-risk thymoma), and 0.813 (for thymic carcinoma) and an ACC of 0.659.	('thymic carcinoma', 'Disease', 'MESH:D013953', (142, 158))	('carcinoma', 'Phenotype', 'HP:0030731', (149, 158))	('0.808', 'Var', (96, 101))	('thymoma', 'Disease', 'MESH:D013945', (117, 124))	('thymoma', 'Disease', 'MESH:D013945', (86, 93))	('thymoma', 'Disease', (86, 93))	('0.813', 'Var', (131, 136))	('thymoma', 'Phenotype', 'HP:0100522', (86, 93))	('thymoma', 'Disease', (117, 124))	('thymic carcinoma', 'Disease', (142, 158))	('thymoma', 'Phenotype', 'HP:0100522', (117, 124))
10919	33718203	Moreover, the CECT-based clinical RM exhibited AUCs of 0.690 (for low-risk thymoma), 0.717 (for high-risk thymoma), and 0.768 (for thymic carcinoma) and an ACC of 0.553.	('thymic carcinoma', 'Disease', (131, 147))	('0.768', 'Var', (120, 125))	('thymic carcinoma', 'Disease', 'MESH:D013953', (131, 147))	('carcinoma', 'Phenotype', 'HP:0030731', (138, 147))	('thymoma', 'Disease', 'MESH:D013945', (106, 113))	('thymoma', 'Phenotype', 'HP:0100522', (75, 82))	('thymoma', 'Disease', (106, 113))	('thymoma', 'Phenotype', 'HP:0100522', (106, 113))	('0.717', 'Var', (85, 90))	('thymoma', 'Disease', 'MESH:D013945', (75, 82))	('thymoma', 'Disease', (75, 82))
10920	33718203	Similarly, in the validation set, the NECT-based clinical RM exhibited AUCs of 0.687 (for low-risk thymoma), 0.699 (for high-risk thymoma), and 0.689 (for thymic carcinoma) and an ACC of 0.483.	('thymoma', 'Disease', 'MESH:D013945', (99, 106))	('thymoma', 'Disease', 'MESH:D013945', (130, 137))	('thymoma', 'Disease', (130, 137))	('0.699', 'Var', (109, 114))	('thymoma', 'Disease', (99, 106))	('thymoma', 'Phenotype', 'HP:0100522', (130, 137))	('thymoma', 'Phenotype', 'HP:0100522', (99, 106))	('0.689', 'Var', (144, 149))	('thymic carcinoma', 'Disease', (155, 171))	('thymic carcinoma', 'Disease', 'MESH:D013953', (155, 171))	('carcinoma', 'Phenotype', 'HP:0030731', (162, 171))
10921	33718203	The CECT-based clinical RM exhibited AUCs of 0.538 (for low-risk thymoma), 0.644 (for high-risk thymoma), and 0.679 (for thymic carcinoma) and an ACC of 0.448.	('thymoma', 'Phenotype', 'HP:0100522', (65, 72))	('carcinoma', 'Phenotype', 'HP:0030731', (128, 137))	('thymoma', 'Disease', 'MESH:D013945', (65, 72))	('thymoma', 'Disease', 'MESH:D013945', (96, 103))	('thymoma', 'Disease', (96, 103))	('thymoma', 'Disease', (65, 72))	('thymoma', 'Phenotype', 'HP:0100522', (96, 103))	('0.644', 'Var', (75, 80))	('0.679', 'Var', (110, 115))	('thymic carcinoma', 'Disease', (121, 137))	('thymic carcinoma', 'Disease', 'MESH:D013953', (121, 137))
10922	33718203	In the training set, the NECT-based clinical-semantic RM exhibited AUCs of 0.880 (for low-risk thymoma), 0.850 (for high-risk thymoma), and 0.939 (for thymic carcinoma) and an ACC of 0.750.	('0.850', 'Var', (105, 110))	('thymoma', 'Disease', (95, 102))	('thymoma', 'Disease', 'MESH:D013945', (126, 133))	('thymoma', 'Phenotype', 'HP:0100522', (95, 102))	('thymoma', 'Disease', (126, 133))	('0.939', 'Var', (140, 145))	('thymoma', 'Phenotype', 'HP:0100522', (126, 133))	('carcinoma', 'Phenotype', 'HP:0030731', (158, 167))	('thymic carcinoma', 'Disease', (151, 167))	('thymic carcinoma', 'Disease', 'MESH:D013953', (151, 167))	('thymoma', 'Disease', 'MESH:D013945', (95, 102))
10923	33718203	Moreover, the CECT-based clinical-semantic RM exhibited AUCs of 0.835 (for low-risk thymoma), 0.813 (for high-risk thymoma), and 0.946 (for thymic carcinoma) and an ACC of 0.705.	('thymoma', 'Phenotype', 'HP:0100522', (115, 122))	('thymoma', 'Phenotype', 'HP:0100522', (84, 91))	('0.813', 'Var', (94, 99))	('thymic carcinoma', 'Disease', (140, 156))	('thymic carcinoma', 'Disease', 'MESH:D013953', (140, 156))	('thymoma', 'Disease', 'MESH:D013945', (115, 122))	('0.946', 'Var', (129, 134))	('thymoma', 'Disease', (115, 122))	('carcinoma', 'Phenotype', 'HP:0030731', (147, 156))	('thymoma', 'Disease', 'MESH:D013945', (84, 91))	('thymoma', 'Disease', (84, 91))
10924	33718203	Similarly, in the validation set, the NECT-based clinical-semantic RM exhibited AUCs of 0.770 (for low-risk thymoma), 0.689 (for high-risk thymoma), and 0.783 (for thymic carcinoma) and an ACC of 0.569.	('0.689', 'Var', (118, 123))	('thymoma', 'Disease', (139, 146))	('thymoma', 'Phenotype', 'HP:0100522', (139, 146))	('thymoma', 'Disease', 'MESH:D013945', (108, 115))	('thymic carcinoma', 'Disease', (164, 180))	('thymic carcinoma', 'Disease', 'MESH:D013953', (164, 180))	('carcinoma', 'Phenotype', 'HP:0030731', (171, 180))	('thymoma', 'Disease', (108, 115))	('0.783', 'Var', (153, 158))	('thymoma', 'Disease', 'MESH:D013945', (139, 146))	('thymoma', 'Phenotype', 'HP:0100522', (108, 115))
10925	33718203	The CECT-based clinical-semantic RM exhibited AUCs of 0.785 (for low-risk thymoma), 0.576 (for high-risk thymoma), and 0.774 (for thymic carcinoma) and an ACC of 0.483.	('thymoma', 'Disease', 'MESH:D013945', (74, 81))	('thymoma', 'Disease', 'MESH:D013945', (105, 112))	('thymoma', 'Disease', (105, 112))	('thymoma', 'Disease', (74, 81))	('thymoma', 'Phenotype', 'HP:0100522', (105, 112))	('thymic carcinoma', 'Disease', (130, 146))	('thymoma', 'Phenotype', 'HP:0100522', (74, 81))	('carcinoma', 'Phenotype', 'HP:0030731', (137, 146))	('thymic carcinoma', 'Disease', 'MESH:D013953', (130, 146))	('0.774', 'Var', (119, 124))	('0.576', 'Var', (84, 89))
10971	33547763	DRB1*07 carriers and non-carriers did not differ in disease severity and response to therapy.	('DRB1', 'Gene', (0, 4))	('carriers', 'Var', (8, 16))	('DRB1', 'Gene', '3123', (0, 4))
10974	33547763	Myasthenia gravis (MG) is caused by antibodies (Abs) to post-synaptic proteins at the motor end-plate.	('antibodies', 'Var', (36, 46))	('caused by', 'Reg', (26, 35))	('Myasthenia gravis', 'Disease', (0, 17))	('Myasthenia gravis', 'Disease', 'MESH:D009157', (0, 17))	('Myasthenia', 'Phenotype', 'HP:0003473', (0, 10))	('post-synaptic proteins', 'Protein', (56, 78))
11020	33547763	Using the same approach, we could confirm the association results for DRB1*07 (frequencies in simulated controls between 0.075 and 0.182, 0.125 in the whole control cohort and 0.234 in LOMG; p-values from 6.83x10-6 to 0.2335, 93 out of 100 < 0.05) and, to a lesser extent, for DQB1*02 (frequencies in simulated controls between 0.107 and 0.220, 0.125 in the whole control cohort and 0.224 in LOMG; p-values from 0.0017 to 1.00, 42 out of 100 P-values < 0.05).	('DRB1', 'Gene', '3123', (70, 74))	('DQB1', 'Gene', '3119', (277, 281))	('LOMG', 'Phenotype', 'HP:0007081', (185, 189))	('DRB1', 'Gene', (70, 74))	('LOMG', 'Phenotype', 'HP:0007081', (392, 396))	('DQB1', 'Gene', (277, 281))	('0.224', 'Var', (383, 388))	('0.234', 'Var', (176, 181))	('0.182', 'Var', (131, 136))
11040	33547763	In the former, conducted in U.S. patients, there was an association with TNFRSF11A (rs4263037) and with rs9271871 in the DRB1-DQA1 intergenic region.	('DRB1', 'Gene', (121, 125))	('rs9271871', 'Mutation', 'rs9271871', (104, 113))	('patients', 'Species', '9606', (33, 41))	('DRB1', 'Gene', '3123', (121, 125))	('rs4263037', 'Var', (84, 93))	('DQA1', 'Gene', '3117', (126, 130))	('rs9271871', 'Var', (104, 113))	('association', 'Interaction', (56, 67))	('rs4263037', 'Mutation', 'rs4263037', (84, 93))	('TNFRSF11A', 'Gene', (73, 82))	('TNFRSF11A', 'Gene', '8792', (73, 82))	('DQA1', 'Gene', (126, 130))
11062	33547763	Renton and co-workers found that the association of the TNFRSF11A single nucleotide polymorphism with MG increased in parallel with age of onset.	('TNFRSF11A', 'Gene', '8792', (56, 65))	('association', 'Interaction', (37, 48))	('single nucleotide polymorphism', 'Var', (66, 96))	('TNFRSF11A', 'Gene', (56, 65))
11069	33547763	When clinical characteristics were analyzed, DRB1*07 carriers and non-carriers did not differ in disease severity, comorbidities, and response to therapies by univariate analysis.	('carriers', 'Var', (53, 61))	('DRB1', 'Gene', (45, 49))	('DRB1', 'Gene', '3123', (45, 49))
11070	33547763	Furthermore, in our cohort, titin Abs were not associated with a more severe disease course, in line with other studies performed in non-Scandinavian populations, 41  questioning their utility as a negative prognostic marker.	('titin', 'Gene', (28, 33))	('Abs', 'Var', (34, 37))	('titin', 'Gene', '7273', (28, 33))
11126	29977769	Our case developed bacteremia caused by E. coli, S. pneumoniae and P. aeruginosa.	('S. pneumoniae', 'Var', (49, 62))	('bacteremia', 'Disease', 'MESH:D016470', (19, 29))	('bacteremia', 'Disease', (19, 29))	('S. pneumoniae', 'Species', '1313', (49, 62))	('P. aeruginosa', 'Species', '287', (67, 80))	('E. coli', 'Species', '562', (40, 47))	('bacteremia', 'Phenotype', 'HP:0031864', (19, 29))	('pneumonia', 'Phenotype', 'HP:0002090', (52, 61))	('P. aeruginosa', 'Var', (67, 80))
11154	29668640	Immunohistochemistry results were presented as follows: positivity for Keratin (broad-spectrum), P63 (+) and Ki-67 (+20%), negative for TTF-1, P53, PLAP, TDT, LCA, CD1a, and VIM.	('TTF-1', 'Gene', (136, 141))	('TTF-1', 'Gene', '7270', (136, 141))	('TDT', 'Gene', '1791', (154, 157))	('P63 (+) and Ki-67', 'Gene', '8626', (97, 114))	('VIM', 'Gene', '7431', (174, 177))	('CD1a', 'Gene', '909', (164, 168))	('positivity', 'Var', (56, 66))	('LCA', 'Gene', '5788', (159, 162))	('TDT', 'Gene', (154, 157))	('P53', 'Gene', (143, 146))	('CD1a', 'Gene', (164, 168))	('P53', 'Gene', '7157', (143, 146))	('VIM', 'Gene', (174, 177))	('PLAP', 'Gene', (148, 152))	('Keratin', 'Protein', (71, 78))	('PLAP', 'Gene', '250', (148, 152))	('LCA', 'Gene', (159, 162))
11314	28190926	In humans, cortical and medullary thymic epithelial cells yield different expression patterns of cytokeratin: medullary thymic epithelial cells express cytokeratin 5 and cytokeratin 14, whereas cortical thymic epithelial cells express cytokeratin 8 and cytokeratin 18, .	('cytokeratin 18', 'Gene', (253, 267))	('cytokeratin 18', 'Gene', '3875', (253, 267))	('cytokeratin', 'Var', (170, 181))	('humans', 'Species', '9606', (3, 9))	('cytokeratin 5', 'Gene', (152, 165))	('cytokeratin 5', 'Gene', '3852', (152, 165))
11319	26481746	Single-fiber Electromyography in the Extensor Digitorum Communis for the Predictive Prognosis of Ocular Myasthenia Gravis: A Retrospective Study of 102 Cases Single-fiber electromyography (SFEMG) abnormality in the extensor digitorum communis (EDC) was reported in ocular myasthenia gravis (OMG), which indicated subclinical involvement beyond extraocular muscles in OMG patients.	('MG', 'Disease', 'MESH:D000080343', (192, 194))	('Ocular Myasthenia Gravis', 'Disease', 'MESH:D009157', (97, 121))	('abnormality', 'Var', (196, 207))	('MG', 'Disease', 'MESH:D000080343', (368, 370))	('patients', 'Species', '9606', (371, 379))	('Ocular Myasthenia Gravis', 'Disease', (97, 121))	('MG', 'Disease', 'MESH:D000080343', (292, 294))	('SFEMG', 'Chemical', '-', (189, 194))	('myasthenia', 'Phenotype', 'HP:0003473', (272, 282))	('ocular myasthenia gravis', 'Disease', (265, 289))	('reported', 'Reg', (253, 261))	('ocular myasthenia gravis', 'Disease', 'MESH:D009157', (265, 289))	('Myasthenia', 'Phenotype', 'HP:0003473', (104, 114))
11339	26481746	As subclinical abnormality could be found, would an abnormal jitter predict the prognosis of OMG?	('predict', 'Reg', (68, 75))	('abnormal', 'Var', (52, 60))	('jitter', 'MPA', (61, 67))	('MG', 'Disease', 'MESH:D000080343', (94, 96))
11375	26481746	Total 55 OMG developed generalized myasthenia gravis (GMG) in the follow-up, 47 of 84 patients in the abnormal SFEMG group while 8 of 18 in the normal SFEMG group.	('SFEMG', 'Chemical', '-', (151, 156))	('myasthenia gravis', 'Disease', (35, 52))	('SFEMG', 'Chemical', '-', (111, 116))	('MG', 'Disease', 'MESH:D000080343', (154, 156))	('myasthenia gravis', 'Disease', 'MESH:D009157', (35, 52))	('MG', 'Disease', 'MESH:D000080343', (10, 12))	('MG', 'Disease', 'MESH:D000080343', (55, 57))	('MG', 'Disease', 'MESH:D000080343', (114, 116))	('myasthenia', 'Phenotype', 'HP:0003473', (35, 45))	('abnormal', 'Var', (102, 110))	('patients', 'Species', '9606', (86, 94))
11382	26481746	Since a gold diagnostic standard is not available in MG, abnormal SFEMG in accordance with clinical fatigue could contribute to the diagnosis.	('fatigue', 'Disease', 'MESH:D005221', (100, 107))	('SFEMG', 'Chemical', '-', (66, 71))	('fatigue', 'Disease', (100, 107))	('fatigue', 'Phenotype', 'HP:0012378', (100, 107))	('MG', 'Disease', 'MESH:D000080343', (69, 71))	('abnormal', 'Var', (57, 65))	('MG', 'Disease', 'MESH:D000080343', (53, 55))	('contribute', 'Reg', (114, 124))
11394	26481746	Since there is no reliable parameter at present to predict the tendency for OMG patients to develop GMG, we suspected that the SFEMG abnormality in EDC muscle might imply an OMG patient to be "subclinical GMG" from a clinical neurophysiology point of view.	('MG', 'Disease', 'MESH:D000080343', (130, 132))	('MG', 'Disease', 'MESH:D000080343', (77, 79))	('patients', 'Species', '9606', (80, 88))	('abnormality', 'Var', (133, 144))	('patient', 'Species', '9606', (178, 185))	('MG', 'Disease', 'MESH:D000080343', (206, 208))	('imply', 'Reg', (165, 170))	('MG', 'Disease', 'MESH:D000080343', (175, 177))	('MG', 'Disease', 'MESH:D000080343', (101, 103))	('patient', 'Species', '9606', (80, 87))	('SFEMG', 'Chemical', '-', (127, 132))
11505	32869520	Data were acquired from the following four registers, provided by the National Board of Health and Welfare in Sweden (Socialstyrelsen):   Patients with (a) classification codes for MG; ICD-9 code 358A or ICD-10 code G70.0, in the NPR and/or (b) two or more prescriptions of pyridostigmine (ATC N07AA02) or ambenonium (ATC N07AA30) in SPDR were considered to have an MG diagnosis, in accordance with the MG identification method validated in a Swedish setting by Fang et al.	('ATC N07AA30', 'Var', (318, 329))	('pyridostigmine', 'Chemical', 'MESH:D011729', (274, 288))	('ATC N07AA02', 'Var', (290, 301))	('Patients', 'Species', '9606', (138, 146))	('ambenonium', 'Chemical', 'MESH:D000549', (306, 316))
11516	32869520	TOMG: All patients with a thymoma, as identified by ICD-10 code D15.0, D38.4, or C37.9 in the NPR or in the CR registers.	('thymoma', 'Disease', (26, 33))	('TOMG', 'Chemical', '-', (0, 4))	('thymoma', 'Phenotype', 'HP:0100522', (26, 33))	('D15.0', 'Var', (64, 69))	('D38.4', 'Var', (71, 76))	('C37.9', 'Var', (81, 86))	('patients', 'Species', '9606', (10, 18))	('thymoma', 'Disease', 'MESH:D013945', (26, 33))
11559	29485186	Biochemical abnormalities included azotemia (BUN 57 mg/dL; [RI], 10-30 mg/dL; creatinine 3.7 mg/dL; [RI], 0.5-1.5 mg/dL; hyperphosphatemia 8.9 mg/dL; [RI], 3.2-6.0 mg/dL), decreased bicarbonate (16.0 mEq/L; [RI], 19-25 mEq/L), hypoalbuminemia (2.1 g/dL; [RI], 2.7-4.0 g/dL), hypercholesterolemia (436 mg/dL; [RI], 132-300 mg/dL), hyperbilirubinemia (0.66 mg/dL; [RI], <0.1-0.6 mg/dL), mildly increased ALP (192 U/L; [RI], 20-150 U/L), and mild electrolyte alterations (sodium 135 mEq/L; [RI], 141-151 mEq/L; chloride 108 mEq/L; [RI], 112-121 mEq/L; calcium 8.9 mg/dL; [RI], 9.7-11.3 mg/dL).	('hyperphosphatemia', 'Phenotype', 'HP:0002905', (121, 138))	('hypercholesterolemia', 'Disease', 'MESH:D006937', (275, 295))	('hypoalbuminemia', 'Disease', 'MESH:D034141', (227, 242))	('ALP', 'Gene', (402, 405))	('creatinine', 'Chemical', 'MESH:D003404', (78, 88))	('hyperbilirubinemia', 'Disease', (330, 348))	('increased', 'PosReg', (392, 401))	('hypercholesterolemia', 'Disease', (275, 295))	('hypoalbuminemia', 'Disease', (227, 242))	('increased ALP', 'Phenotype', 'HP:0003155', (392, 405))	('azotemia', 'Disease', 'MESH:D053099', (35, 43))	('hypoalbuminemia', 'Phenotype', 'HP:0003073', (227, 242))	('ALP', 'Gene', '403548', (402, 405))	('decreased bicarbonate', 'Phenotype', 'HP:0032066', (172, 193))	('azotemia', 'Disease', (35, 43))	('hyperphosphatemia', 'Disease', 'MESH:D054559', (121, 138))	('electrolyte alterations', 'Phenotype', 'HP:0003111', (444, 467))	('hyperbilirubinemia', 'Disease', 'MESH:D006932', (330, 348))	('hyperbilirubinemia', 'Phenotype', 'HP:0002904', (330, 348))	('azotemia', 'Phenotype', 'HP:0002157', (35, 43))	('electrolyte alterations', 'MPA', (444, 467))	('decreased', 'NegReg', (172, 181))	('436 mg/dL', 'Var', (297, 306))	('hyperphosphatemia', 'Disease', (121, 138))	('mildly increased ALP', 'Phenotype', 'HP:0008180', (385, 405))	('hypercholesterolemia', 'Phenotype', 'HP:0003124', (275, 295))
11720	21151207	Similar to membranous nephropathy, ablation of the tumor frequently achieves remission of MCD; therefore, factors produced by cancer cells may contribute to the pathogenesis of paraneoplastic MCD.	('MCD', 'Phenotype', 'HP:0012579', (90, 93))	('MCD', 'Phenotype', 'HP:0012579', (192, 195))	('ablation', 'Var', (35, 43))	('tumor', 'Disease', (51, 56))	('cancer', 'Disease', (126, 132))	('paraneoplastic MCD', 'Disease', 'MESH:D012514', (177, 195))	('tumor', 'Disease', 'MESH:D009369', (51, 56))	('cancer', 'Phenotype', 'HP:0002664', (126, 132))	('MCD', 'Gene', (90, 93))	('MCD', 'Gene', '4582', (90, 93))	('membranous nephropathy', 'Disease', (11, 33))	('MCD', 'Gene', (192, 195))	('MCD', 'Gene', '4582', (192, 195))	('tumor', 'Phenotype', 'HP:0002664', (51, 56))	('membranous nephropathy', 'Phenotype', 'HP:0012578', (11, 33))	('cancer', 'Disease', 'MESH:D009369', (126, 132))	('paraneoplastic MCD', 'Disease', (177, 195))	('contribute', 'Reg', (143, 153))	('nephropathy', 'Phenotype', 'HP:0000112', (22, 33))	('membranous nephropathy', 'Disease', 'MESH:D007674', (11, 33))
11735	21151207	Although this study was reported before the discovery of anti-neutrophil cytoplasmic antibodies (ANCAs), an assessment of renal pathology revealed pauci-immune crescentic glomerulonephritis, consistent with vasculitis.	('vasculitis', 'Disease', (207, 217))	('nephritis', 'Phenotype', 'HP:0000123', (180, 189))	('crescentic glomerulonephritis', 'Phenotype', 'HP:0008653', (160, 189))	('vasculitis', 'Phenotype', 'HP:0002633', (207, 217))	('men', 'Species', '9606', (114, 117))	('glomerulonephritis', 'Disease', 'MESH:D005921', (171, 189))	('vasculitis', 'Disease', 'MESH:D014657', (207, 217))	('glomerulonephritis', 'Phenotype', 'HP:0000099', (171, 189))	('glomerulonephritis', 'Disease', (171, 189))	('anti-neutrophil', 'Var', (57, 72))
11811	21151207	The Val617Phe mutation in JAK2, which causes abnormal cell proliferation, is present in more than 90% of patients with polycythemia vera and in nearly half of those with essential thrombocythemia or primary myelofibrosis.	('polycythemia vera', 'Disease', 'MESH:D011087', (119, 136))	('myelofibrosis', 'Disease', 'MESH:D055728', (207, 220))	('patients', 'Species', '9606', (105, 113))	('Val617Phe', 'Var', (4, 13))	('JAK2', 'Gene', '3717', (26, 30))	('thrombocythemia', 'Disease', 'MESH:D013922', (180, 195))	('Val617Phe', 'Mutation', 'rs77375493', (4, 13))	('polycythemia vera', 'Disease', (119, 136))	('thrombocythemia', 'Disease', (180, 195))	('JAK2', 'Gene', (26, 30))	('myelofibrosis', 'Phenotype', 'HP:0011974', (207, 220))	('thrombocythemia', 'Phenotype', 'HP:0001894', (180, 195))	('polycythemia', 'Phenotype', 'HP:0001901', (119, 131))	('abnormal cell proliferation', 'Phenotype', 'HP:0031377', (45, 72))	('rat', 'Species', '10116', (66, 69))	('myelofibrosis', 'Disease', (207, 220))
11814	21151207	Plasma and urine levels of platelet-derived growth factor (PDGF) are elevated in patients with myeloproliferative neoplasms and PDGF has been shown to enhance mesangial proliferation and fibrosis.	('myeloproliferative neoplasms', 'Disease', 'MESH:D009196', (95, 123))	('rat', 'Species', '10116', (176, 179))	('PDGF', 'Var', (128, 132))	('neoplasms', 'Phenotype', 'HP:0002664', (114, 123))	('enhance', 'PosReg', (151, 158))	('mesangial proliferation', 'Phenotype', 'HP:0012574', (159, 182))	('neoplasm', 'Phenotype', 'HP:0002664', (114, 122))	('patients', 'Species', '9606', (81, 89))	('mesangial proliferation', 'CPA', (159, 182))	('myeloproliferative neoplasms', 'Disease', (95, 123))	('myeloproliferative neoplasm', 'Phenotype', 'HP:0005547', (95, 122))	('fibrosis', 'Disease', 'MESH:D005355', (187, 195))	('fibrosis', 'Disease', (187, 195))	('myeloproliferative neoplasms', 'Phenotype', 'HP:0005547', (95, 123))	('elevated', 'PosReg', (69, 77))	('rat', 'Species', '10116', (107, 110))
11830	21151207	Monocytes may be involved in pathogenesis of paraneoplastic glomerulonephritis since monocyte counts are higher in patients with nephrotic range proteinuria than in those without.. Of note, severe monocytosis causes marked lysozymuria, which may present as nephrotic range proteinuria.	('proteinuria', 'Disease', (145, 156))	('monocytosis', 'Var', (197, 208))	('proteinuria', 'Disease', 'MESH:D011507', (145, 156))	('paraneoplastic glomerulonephritis', 'Disease', (45, 78))	('proteinuria', 'Disease', (273, 284))	('nephrotic', 'Disease', 'MESH:D009404', (129, 138))	('proteinuria', 'Disease', 'MESH:D011507', (273, 284))	('nephrotic range proteinuria', 'Phenotype', 'HP:0012593', (257, 284))	('proteinuria', 'Phenotype', 'HP:0000093', (145, 156))	('nephrotic', 'Disease', (129, 138))	('nephrotic', 'Disease', 'MESH:D009404', (257, 266))	('glomerulonephritis', 'Phenotype', 'HP:0000099', (60, 78))	('proteinuria', 'Phenotype', 'HP:0000093', (273, 284))	('monocytosis', 'Phenotype', 'HP:0012311', (197, 208))	('nephrotic range proteinuria', 'Phenotype', 'HP:0012593', (129, 156))	('patients', 'Species', '9606', (115, 123))	('lysozymuria', 'Disease', (223, 234))	('nephrotic', 'Disease', (257, 266))	('paraneoplastic glomerulonephritis', 'Disease', 'MESH:D005921', (45, 78))	('severe monocytosis', 'Var', (190, 208))	('nephritis', 'Phenotype', 'HP:0000123', (69, 78))
11859	21151207	Mitomycin C is associated with a 2-10% risk of thrombotic microangiopathy; this risk increases considerably for cumulative doses of >= 40 mg/m2.	('thrombotic microangiopathy', 'Disease', 'MESH:D057049', (47, 73))	('Mitomycin C', 'Chemical', 'MESH:D016685', (0, 11))	('Mitomycin', 'Var', (0, 9))	('thrombotic microangiopathy', 'Disease', (47, 73))
11881	21151207	This notion is supported by studies in Buffalo/Mna rats, in which TH2 polarization induces thymoma-associated MCD and FSGS.	('FSGS', 'Gene', (118, 122))	('thymoma', 'Disease', (91, 98))	('MCD', 'Phenotype', 'HP:0012579', (110, 113))	('rats', 'Species', '10116', (51, 55))	('MCD', 'Gene', (110, 113))	('thymoma', 'Phenotype', 'HP:0100522', (91, 98))	('TH2 polarization', 'Var', (66, 82))	('MCD', 'Gene', '4582', (110, 113))	('FSGS', 'Phenotype', 'HP:0000097', (118, 122))	('induces', 'Reg', (83, 90))	('FSGS', 'Gene', '81', (118, 122))	('thymoma', 'Disease', 'MESH:D013945', (91, 98))
11991	32132638	Enhancements in cytokine production and the cytotoxicity of T cells by the anti-PD-1 antibody were significantly greater in B3/C.	('anti-PD-1', 'Var', (75, 84))	('cytotoxicity of T', 'Disease', 'MESH:D064420', (44, 61))	('Enhancements', 'PosReg', (0, 12))	('cytotoxicity of T', 'Disease', (44, 61))	('cytokine production', 'MPA', (16, 35))	('greater', 'PosReg', (113, 120))
12000	32132638	The anti-PD-1 blocking antibody exerts beneficial effects in a limited population of cancer patients.	('anti-PD-1', 'Var', (4, 13))	('cancer', 'Disease', 'MESH:D009369', (85, 91))	('patients', 'Species', '9606', (92, 100))	('cancer', 'Disease', (85, 91))	('beneficial effects', 'PosReg', (39, 57))	('cancer', 'Phenotype', 'HP:0002664', (85, 91))
12002	32132638	Clinical trials on immune checkpoint inhibitors are ongoing, and acceptable clinical efficacies of the anti-PD-1 antibody have been reported for TETs.	('TETs', 'Disease', 'MESH:C536905', (145, 149))	('TETs', 'Disease', (145, 149))	('anti-PD-1', 'Var', (103, 112))
12026	32132638	2a), the rates of Tim-3+ and CD103+ in CD4 and CD8 single-positive T cells were significantly higher in B3/C than in non-B3/C (Fig.	('Tim-3', 'Gene', (18, 23))	('CD8', 'Gene', (47, 50))	('Tim-3', 'Gene', '84868', (18, 23))	('CD103', 'Gene', '3682', (29, 34))	('CD8', 'Gene', '925', (47, 50))	('B3/C', 'Var', (104, 108))	('CD4', 'Gene', (39, 42))	('CD103', 'Gene', (29, 34))	('higher', 'PosReg', (94, 100))
12028	32132638	The rate of 4-1BB+ in CD4 single-positive T cells was significantly higher in B3/C than in non-B3/C (Fig.	('B3/C', 'Var', (78, 82))	('rate', 'MPA', (4, 8))	('higher', 'PosReg', (68, 74))	('4-1BB', 'Gene', '3604', (12, 17))	('CD4', 'Gene', (22, 25))	('4-1BB', 'Gene', (12, 17))
12029	32132638	The rate of OX40+ in CD8 single-positive T cells was higher in B3/C than in non-B3/C (Fig.	('higher', 'PosReg', (53, 59))	('CD8', 'Gene', (21, 24))	('rate', 'MPA', (4, 8))	('CD8', 'Gene', '925', (21, 24))	('B3/C', 'Var', (63, 67))	('OX40', 'Gene', '7293', (12, 16))	('OX40', 'Gene', (12, 16))
12030	32132638	The rate of CD4+CD25++, namely, regulatory T cells, in CD4 single-positive T cells was also significantly higher in B3/C (Fig.	('CD25', 'Gene', (16, 20))	('B3/C', 'Var', (116, 120))	('regulatory T cells', 'CPA', (32, 50))	('higher', 'PosReg', (106, 112))	('CD25', 'Gene', '3559', (16, 20))
12032	32132638	As expected, the proportion of CD4+CD8+ double-positive T cells was significantly lower in B3/C than in non-B3/C (Supplementary Fig.	('B3/C', 'Var', (91, 95))	('CD8', 'Gene', (35, 38))	('CD8', 'Gene', '925', (35, 38))	('lower', 'NegReg', (82, 87))
12033	32132638	Similarly, the proportions of CD4 and CD8 single-positive T cells were also higher in B3/C than in non-B3/C (Supplementary Fig.	('CD4', 'Protein', (30, 33))	('CD8', 'Gene', (38, 41))	('CD8', 'Gene', '925', (38, 41))	('higher', 'PosReg', (76, 82))	('B3/C', 'Var', (86, 90))
12036	32132638	Moreover, the ability of CD8 single-positive T cells to produce IFN-gamma, TNF-alpha, and IL-2 was significantly greater in B3/C than in non-B3/C (Fig.	('TNF-alpha', 'Gene', (75, 84))	('IFN-gamma', 'Gene', (64, 73))	('CD8', 'Gene', (25, 28))	('IL-2', 'Gene', '3558', (90, 94))	('CD8', 'Gene', '925', (25, 28))	('IL-2', 'Gene', (90, 94))	('TNF-alpha', 'Gene', '7124', (75, 84))	('ability', 'MPA', (14, 21))	('greater', 'PosReg', (113, 120))	('IFN-gamma', 'Gene', '3458', (64, 73))	('B3/C', 'Var', (124, 128))
12044	32132638	Similar to the results obtained for cytotoxicity, IFN-gamma secretion from CD8 single-positive T cells was higher in B3/C than in non-B3/C (Fig.	('CD8', 'Gene', '925', (75, 78))	('IFN-gamma', 'Gene', '3458', (50, 59))	('IFN-gamma', 'Gene', (50, 59))	('B3/C', 'Var', (117, 121))	('higher', 'PosReg', (107, 113))	('CD8', 'Gene', (75, 78))
12045	32132638	The expression levels of perforin and granzyme B in CD8 single-positive T cells were also higher in B3/C than in non-B3/C (Supplementary Fig.	('expression levels', 'MPA', (4, 21))	('granzyme B', 'Gene', (38, 48))	('B3/C', 'Var', (100, 104))	('granzyme B', 'Gene', '3002', (38, 48))	('higher', 'PosReg', (90, 96))	('CD8', 'Gene', (52, 55))	('CD8', 'Gene', '925', (52, 55))
12046	32132638	In a quantitative multiplex analysis, the cytokine production of IL-2, IL-4, IL-6, and IFN-gamma was significantly greater in B3/C than in non-B3/C (Supplementary Fig.	('IL-4', 'Gene', (71, 75))	('IFN-gamma', 'Gene', (87, 96))	('cytokine production', 'MPA', (42, 61))	('IFN-gamma', 'Gene', '3458', (87, 96))	('IL-2', 'Gene', '3558', (65, 69))	('IL-6', 'Gene', (77, 81))	('IL-2', 'Gene', (65, 69))	('IL-4', 'Gene', '3565', (71, 75))	('greater', 'PosReg', (115, 122))	('B3/C', 'Var', (126, 130))	('IL-6', 'Gene', '3569', (77, 81))
12050	32132638	Similar to the bulk results, the effects of nivolumab on the cytotoxicity of CD8 single-positive T cells were slightly stronger in B3/C than in non-B3/C (Supplementary Fig.	('CD8', 'Gene', (77, 80))	('CD8', 'Gene', '925', (77, 80))	('stronger', 'PosReg', (119, 127))	('nivolumab', 'Chemical', 'MESH:D000077594', (44, 53))	('cytotoxicity', 'CPA', (61, 73))	('B3/C', 'Var', (131, 135))
12051	32132638	S10A), and cytokine production levels were also higher in B3/C than in non-B3/C in the IFN-gamma secretion assay (Supplementary Fig.	('IFN-gamma', 'Gene', '3458', (87, 96))	('cytokine production levels', 'MPA', (11, 37))	('IFN-gamma', 'Gene', (87, 96))	('S10A', 'Var', (0, 4))	('higher', 'PosReg', (48, 54))	('S10A', 'SUBSTITUTION', 'None', (0, 4))	('B3/C', 'Var', (58, 62))
12064	32132638	Although PD-1 expression by T cells did not markedly differ between B3/C and non-B3/C, the rate of PD-1 + Tim-3+ in CD4 and CD8 single-positive T cells was significantly higher in B3/C than in non-B3/C.	('higher', 'PosReg', (170, 176))	('Tim-3', 'Gene', '84868', (106, 111))	('CD8', 'Gene', (124, 127))	('B3/C and non-B3/C', 'Gene', '28908', (68, 85))	('CD8', 'Gene', '925', (124, 127))	('B3/C', 'Var', (180, 184))	('Tim-3', 'Gene', (106, 111))
12074	32132638	Based on these analyses, we found that T cells in B3/C showed a stronger anti-tumor immune response to nivolumab than those in non-B3/C.	('stronger', 'PosReg', (64, 72))	('tumor', 'Disease', 'MESH:D009369', (78, 83))	('tumor', 'Phenotype', 'HP:0002664', (78, 83))	('nivolumab', 'Chemical', 'MESH:D000077594', (103, 112))	('tumor', 'Disease', (78, 83))	('B3/C', 'Var', (50, 54))
12075	32132638	Clinical trials on immune checkpoint inhibitors for TETs are ongoing, and an acceptable clinical efficacy has been reported for the anti-PD-1 antibody for TETs.	('TETs', 'Disease', 'MESH:C536905', (52, 56))	('TETs', 'Disease', (52, 56))	('TETs', 'Disease', (155, 159))	('anti-PD-1', 'Var', (132, 141))	('TETs', 'Disease', 'MESH:C536905', (155, 159))
12080	32132638	In conclusion, the characteristics of CD4 and CD8 single-positive T cells in B3 thymoma and thymic carcinoma are favorable for anti-tumor immunity.	('CD8', 'Gene', '925', (46, 49))	('CD4', 'Gene', (38, 41))	('thymoma', 'Phenotype', 'HP:0100522', (80, 87))	('tumor', 'Disease', 'MESH:D009369', (132, 137))	('thymic carcinoma', 'Disease', (92, 108))	('tumor', 'Phenotype', 'HP:0002664', (132, 137))	('single-positive', 'Var', (50, 65))	('tumor', 'Disease', (132, 137))	('thymic carcinoma', 'Disease', 'MESH:D013945', (92, 108))	('carcinoma', 'Phenotype', 'HP:0030731', (99, 108))	('CD8', 'Gene', (46, 49))	('thymoma', 'Disease', 'MESH:D013945', (80, 87))	('thymoma', 'Disease', (80, 87))
12136	27580949	In case of thymomas greater than 2 cm and without fat tissue surrounding the thymic capsule, the manipulation of the tumor may cause seeding of tumor cells that are responsible for local and pleural recurrences.	('tumor', 'Disease', (144, 149))	('tumor', 'Phenotype', 'HP:0002664', (117, 122))	('seeding', 'CPA', (133, 140))	('tumor', 'Disease', (117, 122))	('cause', 'Reg', (127, 132))	('thymomas', 'Disease', (11, 19))	('thymomas', 'Disease', 'MESH:D013945', (11, 19))	('pleural', 'Disease', 'MESH:D010995', (191, 198))	('tumor', 'Disease', 'MESH:D009369', (144, 149))	('thymoma', 'Phenotype', 'HP:0100522', (11, 18))	('tumor', 'Phenotype', 'HP:0002664', (144, 149))	('pleural', 'Disease', (191, 198))	('tumor', 'Disease', 'MESH:D009369', (117, 122))	('manipulation', 'Var', (97, 109))
12201	27580949	A case report shows that a patient with EGFR mutation fails to respond to gefitinib.	('patient', 'Species', '9606', (27, 34))	('EGFR', 'Gene', '1956', (40, 44))	('mutation', 'Var', (45, 53))	('EGFR', 'Gene', (40, 44))	('gefitinib', 'Chemical', 'MESH:D000077156', (74, 83))
12249	27165426	The rate of thymoma comorbidity with MG was determined by identifying cases with thymoma (KCD codes: C37, malignant thymoma; D150, thymoma, benign; D384, thymoma, uncertain) among the incident MG cases.	('thymoma', 'Disease', (154, 161))	('thymoma', 'Phenotype', 'HP:0100522', (12, 19))	('thymoma', 'Disease', (116, 123))	('thymoma', 'Phenotype', 'HP:0100522', (154, 161))	('thymoma', 'Phenotype', 'HP:0100522', (116, 123))	('thymoma', 'Disease', (131, 138))	('thymoma', 'Phenotype', 'HP:0100522', (131, 138))	('thymoma', 'Disease', (81, 88))	('thymoma', 'Phenotype', 'HP:0100522', (81, 88))	('thymoma comorbidity', 'Disease', 'MESH:D013945', (12, 31))	('C37', 'Var', (101, 104))	('malignant thymoma', 'Disease', 'MESH:D013945', (106, 123))	('D150', 'Var', (125, 129))	('thymoma', 'Disease', 'MESH:D013945', (12, 19))	('thymoma comorbidity', 'Disease', (12, 31))	('thymoma', 'Disease', 'MESH:D013945', (154, 161))	('thymoma', 'Disease', 'MESH:D013945', (116, 123))	('thymoma', 'Disease', 'MESH:D013945', (131, 138))	('malignant thymoma', 'Disease', (106, 123))	('thymoma', 'Disease', (12, 19))	('thymoma', 'Disease', 'MESH:D013945', (81, 88))
12300	24213242	It must be emphasized that the trials included in this analysis predominantly utilized less conformal radiation techniques and had a large proportion of patients with N0 status (approximately 25%) and that many patients did not undergo adequate staging.	('less', 'NegReg', (87, 91))	('N0 status', 'Var', (167, 176))	('patients', 'Species', '9606', (211, 219))	('patients', 'Species', '9606', (153, 161))
12305	24213242	Finally, investigators from Vanderbilt University Medical Center assessed the impact of extranodal extension (ECE) in patients receiving PORT, and found that the survival benefit with PORT was present with negative ECE but not with positive ECE.	('ECE', 'Gene', (241, 244))	('ECE', 'Gene', '1889', (241, 244))	('survival', 'MPA', (162, 170))	('ECE', 'Gene', (110, 113))	('ECE', 'Gene', '1889', (110, 113))	('ECE', 'Gene', (215, 218))	('ECE', 'Gene', '1889', (215, 218))	('patients', 'Species', '9606', (118, 126))	('PORT', 'Var', (184, 188))
12428	33028413	The results can be explained by that decreased diffusion space of water protons in the extracellular and intracellular dimensions due to enlarged nuclei, hyperchromatism, and hypercellularity in high risk thymoma and thymic carcinoma.	('enlarged', 'PosReg', (137, 145))	('thymoma', 'Phenotype', 'HP:0100522', (205, 212))	('hyperchromatism', 'Disease', (154, 169))	('men', 'Species', '9606', (121, 124))	('hyperchromatism', 'Disease', 'None', (154, 169))	('diffusion space of water protons', 'MPA', (47, 79))	('thymoma and thymic carcinoma', 'Disease', 'MESH:D013953', (205, 233))	('water', 'Chemical', 'MESH:D014867', (66, 71))	('hypercellularity', 'Var', (175, 191))	('carcinoma', 'Phenotype', 'HP:0030731', (224, 233))	('decreased', 'NegReg', (37, 46))
12439	33028413	On the other hand, type B1 and B2 thymomas belonged to the lymphocyte-rich thymomas, and type B1 thymoma showed the lowest ECV because of its dense lymphocystic population.	('thymomas', 'Disease', (34, 42))	('thymoma', 'Phenotype', 'HP:0100522', (97, 104))	('thymomas', 'Disease', 'MESH:D013945', (34, 42))	('thymoma', 'Disease', 'MESH:D013945', (34, 41))	('thymoma', 'Phenotype', 'HP:0100522', (75, 82))	('thymoma', 'Disease', (97, 104))	('thymomas', 'Disease', 'MESH:D013945', (75, 83))	('thymoma', 'Disease', (34, 41))	('type B1', 'Var', (89, 96))	('thymoma', 'Disease', 'MESH:D013945', (97, 104))	('thymoma', 'Phenotype', 'HP:0100522', (34, 41))	('thymoma', 'Disease', 'MESH:D013945', (75, 82))	('thymoma', 'Disease', (75, 82))	('thymomas', 'Disease', (75, 83))
12479	32668077	1 ,  2 ,  18 ,  19 ,  20 ,  21 ,  22 ,  23 ,  24 ,  25 ,  26   Myasthenia gravis is defined in humans as skeletal muscle weakness and fatigability caused by autoantibodies against components of the NMJ of skeletal muscle.	('fatigability', 'Disease', (134, 146))	('muscle weakness', 'Phenotype', 'HP:0001324', (114, 129))	('skeletal muscle weakness', 'Disease', (105, 129))	('skeletal muscle weakness', 'Disease', 'MESH:D018908', (105, 129))	('humans', 'Species', '9606', (95, 101))	('Myasthenia gravis', 'Disease', (63, 80))	('Myasthenia gravis', 'Disease', 'MESH:D009157', (63, 80))	('Myasthenia', 'Phenotype', 'HP:0003473', (63, 73))	('autoantibodies', 'Var', (157, 171))	('caused by', 'Reg', (147, 156))
12569	32668077	72 ,  73 ,  74 ,  75 ,  76 ,  77  Over 30 mutations have been identified in humans, and affect proteins involved in NMJ structure, function, or repair.	('affect', 'Reg', (88, 94))	('proteins', 'Protein', (95, 103))	('function', 'MPA', (131, 139))	('humans', 'Species', '9606', (76, 82))	('mutations', 'Var', (42, 51))
12572	32668077	72 ,  73 ,  74 ,  75  For some mutations, however, the location of the affected protein or proteins is unknown, meaning that these CMSs cannot presently be classified, and are referred to as "other".	('mutations', 'Var', (31, 40))	('CMSs', 'Disease', (131, 135))	('CMSs', 'Disease', 'None', (131, 135))
12581	32668077	11 ,  63 ,  66 ,  71  It involves a missense mutation in exon 6 of the choline acetyltransferase (CHAT) gene the normal function of which is the synthesis of acetylcholine (ACh), and is inherited in an autosomal recessive manner.	('choline acetyltransferase', 'Gene', (71, 96))	('choline acetyltransferase', 'Gene', '486775', (71, 96))	('synthesis of', 'MPA', (145, 157))	('ACh', 'Chemical', 'MESH:D000109', (173, 176))	('CHAT', 'Disease', 'None', (98, 102))	('missense mutation in', 'Var', (36, 56))	('CHAT', 'Disease', (98, 102))	('acetylcholine', 'Chemical', 'MESH:D000109', (158, 171))
12586	32668077	12 ,  13  These CMSs involve a mutation in the collagen-like tail subunit of asymmetric acetylcholinesterase (COLQ) gene, which anchors acetylcholinesterase (AChE) to the basal lamina of the NMJ.	('collagen-like tail subunit of asymmetric acetylcholinesterase', 'Gene', '101093134', (47, 108))	('anchors acetylcholinesterase', 'MPA', (128, 156))	('COLQ', 'Gene', (110, 114))	('mutation', 'Var', (31, 39))	('-like tail', 'Phenotype', 'HP:0002825', (55, 65))	('CMSs', 'Disease', (16, 20))	('CMSs', 'Disease', 'None', (16, 20))
12589	32668077	8  Administration of pyridostigmine bromide results in worsening of skeletal muscle weakness and fatigability.	('pyridostigmine', 'Var', (21, 35))	('skeletal muscle weakness', 'Disease', (68, 92))	('muscle weakness', 'Phenotype', 'HP:0001324', (77, 92))	('skeletal muscle weakness', 'Disease', 'MESH:D018908', (68, 92))	('worsening of skeletal muscle weakness', 'Phenotype', 'HP:0003323', (55, 92))	('pyridostigmine bromide', 'Chemical', 'MESH:D011729', (21, 43))	('worsening', 'NegReg', (55, 64))	('fatigability', 'CPA', (97, 109))
12599	32668077	68  Both of these CMSs are associated with a mutation in the cholinergic receptor nicotinic epsilon subunit (CHRNE) gene, which codes for the epsilon subunit of the AChR.	('AChR', 'Gene', (165, 169))	('CMSs', 'Disease', (18, 22))	('CMSs', 'Disease', 'None', (18, 22))	('AChR', 'Gene', '751106', (165, 169))	('associated', 'Reg', (27, 37))	('cholinergic receptor nicotinic epsilon subunit', 'Gene', (61, 107))	('mutation', 'Var', (45, 53))	('cholinergic receptor nicotinic epsilon subunit', 'Gene', '479471', (61, 107))	('CHRNE', 'Gene', (109, 114))
12602	32668077	9  In the Heideterrier, a nonsynonymous mutation in exon 31 is reported in 1 dog with skeletal muscle weakness and fatigability.	('dog', 'Species', '9615', (77, 80))	('muscle weakness', 'Phenotype', 'HP:0001324', (95, 110))	('skeletal muscle weakness', 'Disease', (86, 110))	('nonsynonymous mutation in', 'Var', (26, 51))	('skeletal muscle weakness', 'Disease', 'MESH:D018908', (86, 110))
12609	32668077	1 ,  8 ,  9 ,  10 ,  11 ,  13  Although a decremental response frequently is observed upon RNS in most CMSs, 8 ,  9 ,  10  there is a CMS in cats in which RNS often can be normal, 12 ,  13  and a CMS in dogs in which a preceding high frequency conditioning train usually is required before observation of a decremental response.	('CMSs', 'Disease', (103, 107))	('CMSs', 'Disease', 'None', (103, 107))	('dogs', 'Species', '9615', (203, 207))	('cats', 'Species', '9685', (141, 145))	('RNS', 'Var', (91, 94))
12611	32668077	8 ,  9 ,  10 ,  11 ,  12 ,  13  With the recent identification of the genetic mutations responsible for some CMSs in dogs and cats, it is now clear that the causative gene plays a pivotal role as to which symptomatic treatment benefits a given CMS.	('dogs', 'Species', '9615', (117, 121))	('mutations', 'Var', (78, 87))	('CMSs', 'Disease', (109, 113))	('cats', 'Species', '9685', (126, 130))	('CMSs', 'Disease', 'None', (109, 113))
12616	32668077	10  Similarly, COLQ-associated CMSs in humans respond positively to beta2-adrenergic receptor agonists such as albuterol and ephedrine, which are thought to stabilize the NMJ and decrease dispersion of AChRs.	('ephedrine', 'Var', (125, 134))	('albuterol', 'Chemical', 'MESH:D000420', (111, 120))	('AChR', 'Gene', (202, 206))	('humans', 'Species', '9606', (39, 45))	('CMSs', 'Disease', (31, 35))	('CMSs', 'Disease', 'None', (31, 35))	('decrease', 'NegReg', (179, 187))	('ephedrine', 'Chemical', 'MESH:D004809', (125, 134))	('beta2-adrenergic receptor', 'Gene', (68, 93))	('beta2-adrenergic receptor', 'Gene', '154', (68, 93))	('NMJ', 'MPA', (171, 174))	('COLQ-associated', 'Disease', (15, 30))	('AChR', 'Gene', '751106', (202, 206))
12620	32668077	78   Given the shared pathogenesis, and similarities in the response to a given symptomatic treatment among CMSs in humans, dogs, and cats with shared causative mutations, it is logical to consider similar treatments in dogs and cats as those used in humans for a given CMS, which emphasizes the importance of correctly classifying CMSs in dogs and cats.	('cats', 'Species', '9685', (229, 233))	('CMSs', 'Disease', (108, 112))	('CMSs', 'Disease', 'None', (108, 112))	('dogs', 'Species', '9615', (340, 344))	('cats', 'Species', '9685', (349, 353))	('dogs', 'Species', '9615', (220, 224))	('humans', 'Species', '9606', (116, 122))	('cats', 'Species', '9685', (134, 138))	('dogs', 'Species', '9615', (124, 128))	('mutations', 'Var', (161, 170))	('humans', 'Species', '9606', (251, 257))	('CMSs', 'Disease', (332, 336))	('CMSs', 'Disease', 'None', (332, 336))
12654	26839727	Genetic studies show a possible role of Transmembrane Activator and CAML interactor (TACI) mutation in B-cells and plasma cells in pathogenesis of both CVID and GS.	('Transmembrane Activator and CAML interactor', 'Gene', '23495', (40, 83))	('mutation', 'Var', (91, 99))	('TACI', 'Gene', '23495', (85, 89))	('CVID', 'Disease', (152, 156))	('TACI', 'Gene', (85, 89))	('CVID', 'Disease', 'MESH:D017074', (152, 156))	('GS', 'Disease', 'MESH:D011125', (161, 163))
12716	31666013	Associations of BAFF rs2893321 polymorphisms with myasthenia gravis susceptibility Myasthenia gravis (MG) is an autoimmune diseases characterized by fatigue and weakness of skeletal muscles.	('autoimmune diseases', 'Phenotype', 'HP:0002960', (112, 131))	('Associations', 'Interaction', (0, 12))	('fatigue', 'Disease', (149, 156))	('fatigue', 'Phenotype', 'HP:0012378', (149, 156))	('weakness of skeletal muscles', 'Disease', (161, 189))	('Myasthenia gravis', 'Disease', (83, 100))	('Myasthenia', 'Phenotype', 'HP:0003473', (83, 93))	('BAFF', 'Gene', '10673', (16, 20))	('myasthenia', 'Phenotype', 'HP:0003473', (50, 60))	('rs2893321', 'Mutation', 'rs2893321', (21, 30))	('MG', 'Disease', 'MESH:D009157', (102, 104))	('myasthenia gravis', 'Disease', 'MESH:D009157', (50, 67))	('fatigue', 'Disease', 'MESH:D005221', (149, 156))	('polymorphisms', 'Var', (31, 44))	('BAFF', 'Gene', (16, 20))	('weakness of skeletal muscles', 'Disease', 'MESH:D018908', (161, 189))	('myasthenia gravis', 'Disease', (50, 67))	('autoimmune diseases', 'Disease', 'MESH:D001327', (112, 131))	('Myasthenia gravis', 'Disease', 'MESH:D009157', (83, 100))	('autoimmune diseases', 'Disease', (112, 131))
12718	31666013	The current study aimed to investigate the association between single nucleotide polymorphism rs2893321 in BAFF with MG susceptibility in Chinese Han population.	('single nucleotide polymorphism rs2893321', 'Var', (63, 103))	('rs2893321', 'Var', (94, 103))	('rs2893321', 'Mutation', 'rs2893321', (94, 103))	('BAFF', 'Gene', '10673', (107, 111))	('BAFF', 'Gene', (107, 111))	('MG', 'Disease', 'MESH:D009157', (117, 119))
12722	31666013	Additionally, rs2893321 was found to be associated with gender and age in patients with MG. Genetic variations of rs2893321 in BAFF might be associated with susceptibility to MG in the Chinese Han population.	('susceptibility', 'Reg', (157, 171))	('rs2893321', 'Mutation', 'rs2893321', (14, 23))	('rs2893321', 'Var', (114, 123))	('patients', 'Species', '9606', (74, 82))	('MG', 'Disease', 'MESH:D009157', (88, 90))	('variations', 'Var', (100, 110))	('MG', 'Disease', 'MESH:D009157', (175, 177))	('associated', 'Reg', (141, 151))	('rs2893321', 'Mutation', 'rs2893321', (114, 123))	('BAFF', 'Gene', '10673', (127, 131))	('BAFF', 'Gene', (127, 131))
12732	31666013	Evidence shows that dysregulation of BAFF contributes to autoimmune disorders, including rheumatoid arthritis, systemic lupus erythematosus, and primary biliary cirrhosis.	('systemic lupus erythematosus', 'Disease', 'MESH:D008180', (111, 139))	('autoimmune disorders', 'Phenotype', 'HP:0002960', (57, 77))	('rheumatoid arthritis', 'Disease', (89, 109))	('rheumatoid arthritis', 'Disease', 'MESH:D001172', (89, 109))	('BAFF', 'Gene', '10673', (37, 41))	('systemic lupus erythematosus', 'Disease', (111, 139))	('autoimmune disorders', 'Disease', 'MESH:D001327', (57, 77))	('arthritis', 'Phenotype', 'HP:0001369', (100, 109))	('primary biliary cirrhosis', 'Disease', 'MESH:D008105', (145, 170))	('cirrhosis', 'Phenotype', 'HP:0001394', (161, 170))	('dysregulation', 'Var', (20, 33))	('primary biliary cirrhosis', 'Phenotype', 'HP:0002613', (145, 170))	('systemic lupus erythematosus', 'Phenotype', 'HP:0002725', (111, 139))	('contributes', 'Reg', (42, 53))	('rheumatoid arthritis', 'Phenotype', 'HP:0001370', (89, 109))	('primary biliary cirrhosis', 'Disease', (145, 170))	('autoimmune disorders', 'Disease', (57, 77))	('BAFF', 'Gene', (37, 41))
12735	31666013	Specifically, BAFF polymorphisms are associated with the phenotypes and occurrence of autoimmune diseases.	('polymorphisms', 'Var', (19, 32))	('BAFF', 'Gene', '10673', (14, 18))	('BAFF', 'Gene', (14, 18))	('autoimmune diseases', 'Disease', 'MESH:D001327', (86, 105))	('autoimmune diseases', 'Disease', (86, 105))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (86, 105))	('associated', 'Reg', (37, 47))
12736	31666013	The variant, single nucleotide polymorphism (SNP) rs2893321 of the BAFF gene, has been reported to be a susceptible genetic variant for the development of Graves' disease and autoimmune thyroid diseases.	('autoimmune thyroid diseases', 'Disease', (175, 202))	("Graves' disease", 'Disease', 'MESH:D006111', (155, 170))	('thyroid diseases', 'Phenotype', 'HP:0000820', (186, 202))	('single nucleotide polymorphism', 'Var', (13, 43))	('autoimmune thyroid diseases', 'Disease', 'MESH:D013967', (175, 202))	('rs2893321', 'Mutation', 'rs2893321', (50, 59))	("Graves' disease", 'Phenotype', 'HP:0100647', (155, 170))	('BAFF', 'Gene', '10673', (67, 71))	('BAFF', 'Gene', (67, 71))	("Graves' disease", 'Disease', (155, 170))	('men', 'Species', '9606', (147, 150))
12754	31666013	As shown in Table 1, we observed significant differences in genotype frequencies of BAFF rs2893321 between the MG group and the control group (chi2 = 6.088, P = .048).	('rs2893321', 'Mutation', 'rs2893321', (89, 98))	('rs2893321', 'Var', (89, 98))	('BAFF', 'Gene', '10673', (84, 88))	('BAFF', 'Gene', (84, 88))	('MG', 'Disease', 'MESH:D009157', (111, 113))
12755	31666013	Frequency of genotype GG in MG patients (18.1%) was significantly elevated compared to control group (10.8%) (P < 0.05).	('MG', 'Disease', 'MESH:D009157', (28, 30))	('genotype', 'Var', (13, 21))	('patients', 'Species', '9606', (31, 39))	('elevated', 'PosReg', (66, 74))
12757	31666013	As shown in Table 2, rs2893321 genotype frequencies were significantly different between women in the MG group and those in the control group (chi2 = 6.145, P = .046).	('rs2893321', 'Mutation', 'rs2893321', (21, 30))	('women', 'Species', '9606', (89, 94))	('MG', 'Disease', 'MESH:D009157', (102, 104))	('rs2893321', 'Var', (21, 30))	('different', 'Reg', (71, 80))
12760	31666013	As shown in Table 3, the rs2893321 genotype frequencies in the EOMG group showed significant differences between the MG and control groups (chi2 = 6.058, P = .048).	('rs2893321', 'Var', (25, 34))	('rs2893321', 'Mutation', 'rs2893321', (25, 34))	('MG', 'Disease', 'MESH:D009157', (117, 119))	('differences', 'Reg', (93, 104))	('MG', 'Disease', 'MESH:D009157', (65, 67))
12761	31666013	Frequency of genotype AA in EOMG patients (43.0%) was significantly elevated compared to control group (34.2%) (P < 0.05).	('elevated', 'PosReg', (68, 76))	('genotype', 'Var', (13, 21))	('MG', 'Disease', 'MESH:D009157', (30, 32))	('patients', 'Species', '9606', (33, 41))
12765	31666013	In the current study, the single nucleotide polymorphism rs2893321 of the BAFF gene was found to be associated with susceptibility to MG in a Chinese Han population.	('susceptibility', 'Reg', (116, 130))	('MG', 'Disease', 'MESH:D009157', (134, 136))	('associated', 'Reg', (100, 110))	('single nucleotide polymorphism rs2893321', 'Var', (26, 66))	('rs2893321', 'Var', (57, 66))	('BAFF', 'Gene', '10673', (74, 78))	('rs2893321', 'Mutation', 'rs2893321', (57, 66))	('BAFF', 'Gene', (74, 78))
12768	31666013	No associations were found between the rs2893321 polymorphism and MG patients with or without thymoma or MG patients who were AChR antibody negative or positive.	('MG', 'Disease', 'MESH:D009157', (105, 107))	('patients', 'Species', '9606', (69, 77))	('thymoma', 'Disease', (94, 101))	('thymoma', 'Disease', 'MESH:D013945', (94, 101))	('rs2893321', 'Var', (39, 48))	('MG', 'Disease', 'MESH:D009157', (66, 68))	('patients', 'Species', '9606', (108, 116))	('rs2893321', 'Mutation', 'rs2893321', (39, 48))	('thymoma', 'Phenotype', 'HP:0100522', (94, 101))
12769	31666013	BAFF stimulates the biological functions of B cells, and dysregulation of BAFF can affect the development of MG.	('affect', 'Reg', (83, 89))	('dysregulation', 'Var', (57, 70))	('BAFF', 'Gene', '10673', (0, 4))	('BAFF', 'Gene', (0, 4))	('stimulates', 'PosReg', (5, 15))	('MG', 'Disease', 'MESH:D009157', (109, 111))	('biological functions of B cells', 'CPA', (20, 51))	('men', 'Species', '9606', (101, 104))	('BAFF', 'Gene', '10673', (74, 78))	('BAFF', 'Gene', (74, 78))
12770	31666013	The genetic variant of BAFF is associated with systemic lupus erythematosus, Graves' disease, chronic lymphocytic leukemia, and other autoimmune diseases.	('autoimmune diseases', 'Disease', (134, 153))	("Graves' disease", 'Phenotype', 'HP:0100647', (77, 92))	('chronic lymphocytic leukemia', 'Disease', 'MESH:D015451', (94, 122))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (134, 153))	("Graves' disease", 'Disease', (77, 92))	('chronic lymphocytic leukemia', 'Phenotype', 'HP:0005550', (94, 122))	('leukemia', 'Phenotype', 'HP:0001909', (114, 122))	('systemic lupus erythematosus', 'Disease', 'MESH:D008180', (47, 75))	('associated', 'Reg', (31, 41))	("Graves' disease", 'Disease', 'MESH:D006111', (77, 92))	('systemic lupus erythematosus', 'Disease', (47, 75))	('autoimmune diseases', 'Disease', 'MESH:D001327', (134, 153))	('genetic variant', 'Var', (4, 19))	('chronic lymphocytic leukemia', 'Disease', (94, 122))	('BAFF', 'Gene', '10673', (23, 27))	('BAFF', 'Gene', (23, 27))	('systemic lupus erythematosus', 'Phenotype', 'HP:0002725', (47, 75))
12771	31666013	However, no study has investigated the connection between BAFF polymorphisms and MG.	('BAFF', 'Gene', '10673', (58, 62))	('BAFF', 'Gene', (58, 62))	('MG', 'Disease', 'MESH:D009157', (81, 83))	('polymorphisms', 'Var', (63, 76))
12772	31666013	In our study, the results demonstrated that the frequencies of the AA genotype of rs2893321 were significantly higher in patients with MG than in the healthy controls, which suggests that rs2893321 might be associated with MG susceptibility in this ethnic Chinese Han population.	('rs2893321', 'Mutation', 'rs2893321', (188, 197))	('rs2893321', 'Gene', (82, 91))	('MG', 'Disease', 'MESH:D009157', (135, 137))	('MG', 'Disease', 'MESH:D009157', (223, 225))	('associated', 'Reg', (207, 217))	('higher', 'PosReg', (111, 117))	('rs2893321', 'Mutation', 'rs2893321', (82, 91))	('rs2893321', 'Var', (188, 197))	('patients', 'Species', '9606', (121, 129))
12774	31666013	In this study, rs2893321 was found to be closely associated with MG patients who were younger than 50 years and female.	('associated', 'Reg', (49, 59))	('rs2893321', 'Var', (15, 24))	('patients', 'Species', '9606', (68, 76))	('rs2893321', 'Mutation', 'rs2893321', (15, 24))	('MG', 'Disease', 'MESH:D009157', (65, 67))
12776	31666013	Additionally, no significant differences in genotype or allele frequency of rs2893321 were observed among MG patients with or without thymoma or MG patients who were AChR antibody positive and negative.	('MG', 'Disease', 'MESH:D009157', (145, 147))	('patients', 'Species', '9606', (148, 156))	('thymoma', 'Disease', (134, 141))	('patients', 'Species', '9606', (109, 117))	('rs2893321', 'Var', (76, 85))	('thymoma', 'Phenotype', 'HP:0100522', (134, 141))	('rs2893321', 'Mutation', 'rs2893321', (76, 85))	('MG', 'Disease', 'MESH:D009157', (106, 108))	('thymoma', 'Disease', 'MESH:D013945', (134, 141))
12780	31666013	Our study indicated the genotype frequency of rs2893321 was different in EOMG patients compared with healthy control, which suggested rs2893321 in BAFF might be a susceptible genetic variant in EOMG patients.	('BAFF', 'Gene', '10673', (147, 151))	('BAFF', 'Gene', (147, 151))	('rs2893321', 'Var', (46, 55))	('MG', 'Disease', 'MESH:D009157', (75, 77))	('patients', 'Species', '9606', (78, 86))	('rs2893321', 'Var', (134, 143))	('rs2893321', 'Mutation', 'rs2893321', (46, 55))	('MG', 'Disease', 'MESH:D009157', (196, 198))	('patients', 'Species', '9606', (199, 207))	('rs2893321', 'Mutation', 'rs2893321', (134, 143))
12787	31666013	These results suggest that sex hormones affected BAFF gene expression and that the genetic variant of rs2893321 in BAFF was significantly associated with susceptibility to MG in women.	('rs2893321', 'Mutation', 'rs2893321', (102, 111))	('susceptibility', 'Reg', (154, 168))	('BAFF', 'Gene', '10673', (49, 53))	('BAFF', 'Gene', (49, 53))	('associated', 'Reg', (138, 148))	('expression', 'MPA', (59, 69))	('rs2893321', 'Var', (102, 111))	('BAFF', 'Gene', (115, 119))	('women', 'Species', '9606', (178, 183))	('MG', 'Disease', 'MESH:D009157', (172, 174))	('BAFF', 'Gene', '10673', (115, 119))
12788	31666013	This study demonstrate the association between BAFF polymorphisms and MG.	('BAFF', 'Gene', (47, 51))	('MG', 'Disease', 'MESH:D009157', (70, 72))	('BAFF', 'Gene', '10673', (47, 51))	('polymorphisms', 'Var', (52, 65))
12789	31666013	In a Chinese Han population, rs2893321 was found to be associated with MG susceptibility, specifically in women with the condition and in patients who were younger than 50 years.	('MG', 'Disease', 'MESH:D009157', (71, 73))	('associated', 'Reg', (55, 65))	('rs2893321', 'Var', (29, 38))	('women', 'Species', '9606', (106, 111))	('rs2893321', 'Mutation', 'rs2893321', (29, 38))	('patients', 'Species', '9606', (138, 146))
12926	29945642	Slides were preincubated in 20% normal goat serum, and then incubated with antibodies against pan-cytokeratin (AE1/AE3; 1:100; Dako, Carpinteria, CA), CK5/6(1:50, Dako, Carpinteria, CA), p63 (1:50; Dako, Carpinteria, CA), TdT (1:100, Dako, Carpinteria, CA), CD20(1:50, Dako, Carpinteria, CA), CD117(1:200; Dako, Carpinteria, CA) and CD5 (1:20; Thermo Fisher Scientific, Fremont, CA).	('AE1/AE3', 'Gene', (111, 118))	('CD5', 'Gene', '921', (333, 336))	('p63', 'Gene', '8626', (187, 190))	('CK5/6(1:50', 'Gene', '3852', (151, 161))	('AE1/AE3', 'Gene', '6521;6508', (111, 118))	('goat', 'Species', '9925', (39, 43))	('CD117', 'Gene', '3815', (293, 298))	('CD20', 'Gene', '54474', (258, 262))	('CD20', 'Gene', (258, 262))	('CD117', 'Gene', (293, 298))	('p63', 'Gene', (187, 190))	('TdT', 'Gene', (222, 225))	('1:100', 'Var', (227, 232))	('CD5', 'Gene', (333, 336))	('TdT', 'Gene', '1791', (222, 225))
12998	29945642	demonstrated that the immunohistochemistry was also in accordance with this hypothesis, the epithelial lining of Hassall corpuscles and MTCs showed similar staining for AE1/AE3, CK13, p63, CK5/6 and D2-40.	('CK5/6', 'Gene', (189, 194))	('AE1/AE3', 'Gene', (169, 176))	('D2-40', 'Var', (199, 204))	('MTC', 'Gene', (136, 139))	('p63', 'Gene', '8626', (184, 187))	('AE1/AE3', 'Gene', '6521;6508', (169, 176))	('CK13', 'Gene', '3860', (178, 182))	('CK13', 'Gene', (178, 182))	('p63', 'Gene', (184, 187))	('CK5/6', 'Gene', '3852', (189, 194))	('MTC', 'Gene', '4489', (136, 139))
13066	28458876	Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant tumor syndrome arising from mutations of the MEN 1 tumor suppressor gene on chromosome 11q13.	('mutations', 'Var', (97, 106))	('tumor', 'Phenotype', 'HP:0002664', (69, 74))	('autosomal dominant tumor syndrome', 'Disease', (50, 83))	('MEN 1', 'Gene', (114, 119))	('MEN 1', 'Gene', '4221', (114, 119))	('tumor', 'Disease', (69, 74))	('Multiple endocrine neoplasia type 1', 'Gene', (0, 35))	('endocrine neoplasia', 'Phenotype', 'HP:0100568', (9, 28))	('Multiple endocrine neoplasia type 1', 'Gene', '4221', (0, 35))	('MEN 1', 'Gene', (37, 42))	('tumor', 'Disease', 'MESH:D009369', (120, 125))	('MEN 1', 'Gene', '4221', (37, 42))	('neoplasia', 'Phenotype', 'HP:0002664', (19, 28))	('tumor', 'Phenotype', 'HP:0002664', (120, 125))	('autosomal dominant tumor syndrome', 'Disease', 'MESH:D030342', (50, 83))	('tumor', 'Disease', 'MESH:D009369', (69, 74))	('tumor', 'Disease', (120, 125))
13097	28458876	examined possible genotype-phenotype correlation in thymic carcinoid from MEN 1 and reported a high prevalence of truncating MEN 1 mutation in patients with thymic carcinoid.	('carcinoid', 'Phenotype', 'HP:0100570', (59, 68))	('truncating', 'MPA', (114, 124))	('carcinoid', 'Phenotype', 'HP:0100570', (164, 173))	('MEN 1', 'Gene', (125, 130))	('MEN 1', 'Gene', '4221', (125, 130))	('MEN 1', 'Gene', (74, 79))	('MEN 1', 'Gene', '4221', (74, 79))	('patients', 'Species', '9606', (143, 151))	('mutation', 'Var', (131, 139))
13161	20573206	Any errors occurring during this process can cause dissemination of aberrant nodules that are responsible for most atypical thymomas.	('atypical thymomas', 'Disease', 'MESH:D013945', (115, 132))	('errors', 'Var', (4, 10))	('dissemination', 'MPA', (51, 64))	('atypical thymomas', 'Disease', (115, 132))	('cause', 'Reg', (45, 50))	('thymoma', 'Phenotype', 'HP:0100522', (124, 131))
13164	20573206	It also confirmed the presence of CD3+, CD5+ T lymphocytes and the absence of immature T-lymphocyte markers.	('CD5', 'Gene', '921', (40, 43))	('CD5', 'Gene', (40, 43))	('CD3+', 'Var', (34, 38))
13167	20573206	Any errors occurring during this phase can cause dissemination of aberrant nodules that are responsible for most uncommon thymomas.	('errors', 'Var', (4, 10))	('cause', 'Reg', (43, 48))	('thymomas', 'Disease', 'MESH:D013945', (122, 130))	('dissemination', 'MPA', (49, 62))	('thymoma', 'Phenotype', 'HP:0100522', (122, 129))	('thymomas', 'Disease', (122, 130))
13226	27802446	Overall distributions of HLA-B*61 and C*05 were more frequent in MG patients (7.4 vs. 2.0% and 14.8 vs. 6.8%, respectively) than in non-MG patients.	('MG', 'Disease', 'MESH:D000080343', (136, 138))	('HLA-B', 'Gene', '3106', (25, 30))	('patients', 'Species', '9606', (139, 147))	('HLA-B', 'Gene', (25, 30))	('patients', 'Species', '9606', (68, 76))	('C*05', 'Var', (38, 42))	('MG', 'Disease', 'MESH:D000080343', (65, 67))
13228	27802446	In patients seropositive for anti-AchR antibodies, the frequencies of HLA-B*50 and C*05 were higher.	('higher', 'PosReg', (93, 99))	('HLA-B', 'Gene', '3106', (70, 75))	('HLA-B', 'Gene', (70, 75))	('anti-AchR antibodies', 'Protein', (29, 49))	('patients', 'Species', '9606', (3, 11))	('C*05', 'Var', (83, 87))
13230	27802446	In addition, HLA-A*01, A*31, B*08, and DRB1*14 were higher among patients with thymic hyperplasia, whereas DQB1*03 was lower.	('A*31', 'Var', (23, 27))	('thymic hyperplasia', 'Disease', (79, 97))	('thymic hyperplasia', 'Phenotype', 'HP:0010516', (79, 97))	('DQB1', 'Gene', (107, 111))	('HLA-A', 'Gene', '3105', (13, 18))	('B*08', 'Var', (29, 33))	('thymic hyperplasia', 'Disease', 'MESH:D013952', (79, 97))	('DRB1', 'Gene', '3123', (39, 43))	('HLA-A', 'Gene', (13, 18))	('DRB1', 'Gene', (39, 43))	('higher', 'PosReg', (52, 58))	('patients', 'Species', '9606', (65, 73))	('DQB1', 'Gene', '3119', (107, 111))
13283	27802446	The overall distribution of HLA alleles B*61 and C*05 was more frequent in MG patients (Table 2); however, these differences lost significance after correction of the p values (Pc = 1.248 and Pc = 0.936, respectively).	('B*61', 'Var', (40, 44))	('patients', 'Species', '9606', (78, 86))	('HLA', 'Gene', '3117', (28, 31))	('C*05', 'Var', (49, 53))	('HLA', 'Gene', (28, 31))	('MG', 'Disease', 'MESH:D000080343', (75, 77))
13289	27802446	In the present study, the frequencies of HLA-B*61 and C*05 were higher in the MG patients than in the controls.	('MG', 'Disease', 'MESH:D000080343', (78, 80))	('HLA-B', 'Gene', (41, 46))	('C*05', 'Var', (54, 58))	('higher', 'PosReg', (64, 70))	('HLA-B', 'Gene', '3106', (41, 46))	('patients', 'Species', '9606', (81, 89))
13300	27802446	In the present study, both the patients with ocular weakness at disease onset and those seropositive for anti-AchR antibodies had significantly higher frequencies of HLA-B*50 and C*05 alleles than did the controls, but all of these differences lost significance after correction for multiple comparisons.	('ocular weakness at disease', 'Disease', 'MESH:D018908', (45, 71))	('HLA-B', 'Gene', '3106', (166, 171))	('ocular weakness at disease', 'Disease', (45, 71))	('HLA-B', 'Gene', (166, 171))	('anti-AchR', 'Gene', (105, 114))	('higher', 'PosReg', (144, 150))	('patients', 'Species', '9606', (31, 39))	('antibodies', 'Var', (115, 125))
13308	27802446	reported that the TNF-2 polymorphism at the TNF-308 promoter position was associated with HLA-B*50, and among HLA-B*50-positive individuals TNF-2 was strongly correlated with ocular Behcet's disease.	('TNF', 'Gene', '7124', (44, 47))	('polymorphism', 'Var', (24, 36))	('TNF', 'Gene', (18, 21))	('HLA-B', 'Gene', (90, 95))	('HLA-B', 'Gene', (110, 115))	('TNF', 'Gene', '7124', (140, 143))	('HLA-B', 'Gene', '3106', (90, 95))	('HLA-B', 'Gene', '3106', (110, 115))	("ocular Behcet's disease", 'Disease', (175, 198))	('correlated with', 'Reg', (159, 174))	('TNF', 'Gene', '7124', (18, 21))	('TNF', 'Gene', (44, 47))	('associated', 'Reg', (74, 84))	('TNF', 'Gene', (140, 143))
13314	27802446	In the other study of Turkish patients with MG, the higher frequencies of the HLA alleles A*02, B*8, and DRB1*03 were associated with EOMG.	('MG', 'Disease', 'MESH:D000080343', (136, 138))	('MG', 'Disease', 'MESH:D000080343', (44, 46))	('HLA', 'Gene', '3117', (78, 81))	('B*8', 'Var', (96, 99))	('DRB1', 'Gene', (105, 109))	('DRB1', 'Gene', '3123', (105, 109))	('HLA', 'Gene', (78, 81))	('patients', 'Species', '9606', (30, 38))	('EOMG', 'Chemical', '-', (134, 138))	('associated with', 'Reg', (118, 133))	('A*02', 'Var', (90, 94))
13402	33767014	Although most reports suggested no difference between total thymectomy and partial thymectomy, multi-institutional studies with large numbers of patients revealed a higher local recurrence rate after partial thymectomy, particularly for stage II disease, which is difficult (if not impossible) to assess preoperatively.	('patients', 'Species', '9606', (145, 153))	('stage II disease', 'Disease', 'MESH:D058625', (237, 253))	('stage II disease', 'Disease', (237, 253))	('partial thymectomy', 'Var', (200, 218))	('local recurrence', 'CPA', (172, 188))
13471	28449028	Masaoka-Koga Stage III-IV, incomplete resection and non-thymoma histology were identified to have a significant impact on increasing recurrences and worsening survival in an ESTS cohort study (2030 patients).	('survival', 'MPA', (159, 167))	('non-thymoma', 'Disease', 'MESH:D013945', (52, 63))	('increasing', 'PosReg', (122, 132))	('recurrences', 'CPA', (133, 144))	('incomplete resection', 'Var', (27, 47))	('worsening', 'NegReg', (149, 158))	('non-thymoma', 'Disease', (52, 63))	('thymoma', 'Phenotype', 'HP:0100522', (56, 63))
13504	27123063	Furthermore, DLET and one-lung ventilation may result in a variety of complications, including hoarseness, hypoxaemia, tracheobronchial injury, vocal cord injury and re-expansion or oxidative stress.	('DLET', 'Var', (13, 17))	('tracheobronchial injury', 'Disease', (119, 142))	('hoarseness', 'Phenotype', 'HP:0001609', (95, 105))	('vocal cord injury', 'Disease', (144, 161))	('oxidative stress', 'Disease', (182, 198))	('tracheobronchial injury', 'Disease', 'MESH:C566362', (119, 142))	('oxidative stress', 'Phenotype', 'HP:0025464', (182, 198))	('lung ventilation', 'Phenotype', 'HP:0002107', (26, 42))	('result in', 'Reg', (47, 56))	('hypoxaemia', 'Disease', 'MESH:D000860', (107, 117))	('hoarseness', 'Disease', (95, 105))	('hypoxaemia', 'Disease', (107, 117))	('re-expansion', 'Disease', (166, 178))	('vocal cord injury', 'Disease', 'MESH:D014826', (144, 161))
13507	27123063	In addition, the artificial pneumothorax with CO2 insufflation may result in deteriorative changes, such as circulatory failure, ventricular arrhythmias and contralateral pneumothorax.	('result', 'Reg', (67, 73))	('contralateral pneumothorax', 'Disease', (157, 183))	('ventricular arrhythmias', 'Disease', 'MESH:D001145', (129, 152))	('circulatory failure', 'Disease', 'MESH:D012769', (108, 127))	('ventricular arrhythmias', 'Phenotype', 'HP:0004308', (129, 152))	('arrhythmias', 'Phenotype', 'HP:0011675', (141, 152))	('pneumothorax', 'Phenotype', 'HP:0002107', (28, 40))	('insufflation', 'Disease', (50, 62))	('CO2', 'Var', (46, 49))	('ventricular arrhythmias', 'Disease', (129, 152))	('artificial pneumothorax', 'Disease', (17, 40))	('circulatory failure', 'Disease', (108, 127))	('insufflation', 'Disease', 'None', (50, 62))	('pneumothorax', 'Phenotype', 'HP:0002107', (171, 183))	('CO2', 'Chemical', 'MESH:D002245', (46, 49))	('deteriorative', 'MPA', (77, 90))
13517	26193470	We compared the PDT lung cancer patients with those receiving chemotherapy or target therapy (n = 51) and found that the PDT group had better survival than non-PDT patients (mean survival time: 39.0 versus 17.6 months; P = .047).	('survival', 'MPA', (142, 150))	('patients', 'Species', '9606', (32, 40))	('cancer', 'Phenotype', 'HP:0002664', (25, 31))	('PDT lung cancer', 'Disease', 'MESH:D008175', (16, 31))	('lung cancer', 'Phenotype', 'HP:0100526', (20, 31))	('PDT', 'Var', (121, 124))	('better', 'PosReg', (135, 141))	('patients', 'Species', '9606', (164, 172))	('PDT lung cancer', 'Disease', (16, 31))
13612	31700740	Negative selection ensures T-cell non-reactivity to self-antigens, thereby preventing development of autoimmunity.	('autoimmunity', 'Disease', (101, 113))	('T-cell', 'CPA', (27, 33))	('autoimmunity', 'Disease', 'MESH:D001327', (101, 113))	('Negative selection', 'Var', (0, 18))	('preventing', 'NegReg', (75, 85))	('autoimmunity', 'Phenotype', 'HP:0002960', (101, 113))
13704	31473641	Historically, neurologic symptoms found in the setting of positive antibodies to CASPR2 receptor or LGI1 were considered to be part of the 'classical' syndrome highly suggestive of limbic encephalitis.	('encephalitis', 'Phenotype', 'HP:0002383', (188, 200))	('CASPR2', 'Gene', (81, 87))	('LGI1', 'Gene', '9211', (100, 104))	('LGI1', 'Gene', (100, 104))	('CASPR2', 'Gene', '26047', (81, 87))	('encephalitis', 'Disease', 'MESH:D004660', (188, 200))	('encephalitis', 'Disease', (188, 200))	('antibodies', 'Var', (67, 77))
13713	31473641	Prior literature reported association between limbic encephalitis due to thymoma and VGKC antibodies, but as more case reports come forth, the list of 'responsible' autoantibodies has continually developed to include even more different biomarkers, as evidenced by the extensive list of antibodies tested in the expanded autoimmune encephalitis panel both in the serum and CSF for this patient.	('encephalitis', 'Disease', 'MESH:D004660', (332, 344))	('thymoma', 'Phenotype', 'HP:0100522', (73, 80))	('encephalitis', 'Disease', (332, 344))	('encephalitis', 'Phenotype', 'HP:0002383', (53, 65))	('VGKC', 'Gene', (85, 89))	('autoimmune encephalitis', 'Disease', 'MESH:C535841', (321, 344))	('patient', 'Species', '9606', (386, 393))	('encephalitis', 'Phenotype', 'HP:0002383', (332, 344))	('autoimmune encephalitis', 'Disease', (321, 344))	('encephalitis', 'Disease', (53, 65))	('thymoma', 'Disease', 'MESH:D013945', (73, 80))	('thymoma', 'Disease', (73, 80))	('encephalitis', 'Disease', 'MESH:D004660', (53, 65))	('antibodies', 'Var', (90, 100))	('association', 'Interaction', (26, 37))
13738	28180106	The clinical diagnosis was cT1aN0M0 primary lung cancer of the salivary gland type or a spindle cell tumor showing epithelial differentiation; subsequently, thoracoscopic RUL lobectomy and mediastinal lymph node dissection were performed.	('lung cancer', 'Phenotype', 'HP:0100526', (44, 55))	('primary lung cancer', 'Disease', (36, 55))	('cancer', 'Phenotype', 'HP:0002664', (49, 55))	('cT1aN0M0', 'Var', (27, 35))	('tumor', 'Disease', (101, 106))	('primary lung cancer', 'Disease', 'MESH:D008175', (36, 55))	('tumor', 'Phenotype', 'HP:0002664', (101, 106))	('tumor', 'Disease', 'MESH:D009369', (101, 106))
13847	21139832	Immunohistochemically, a Pan-CK and CK19 expression could be identified (Figure 4B) as well as a concomitant infiltrate of partly CD3-positive lymphocytes (Figure 4C).	('CK19', 'Gene', '3880', (36, 40))	('CK19', 'Gene', (36, 40))	('Pan-CK', 'Var', (25, 31))
13885	32569233	Thymic pathological changes can activate the autoimmune response towards acetylcholine receptor, whereas thymusectomy will reduce the sources of abnormal immunity.	('acetylcholine', 'Chemical', 'MESH:D000109', (73, 86))	('autoimmune response', 'Phenotype', 'HP:0002960', (45, 64))	('Thymic', 'Disease', (0, 6))	('sources of abnormal immunity', 'MPA', (134, 162))	('reduce', 'NegReg', (123, 129))	('autoimmune response towards acetylcholine receptor', 'MPA', (45, 95))	('activate', 'PosReg', (32, 40))	('changes', 'Var', (20, 27))	('pathological changes', 'Var', (7, 27))
13896	32569233	Patients will be included when meet the following items: onset within 5 years; age 18 to 65 years; acetylcholine-receptor-antibody level over 1.00 nmol/L or 0.50 to 0.99 nmol/L if edrophonium test is positive, repetitive nerve stimulation or single-fiber electromyography is abnormal; fit the MG recommendations for clinical research standards of II to IV.	('0.50', 'Var', (157, 161))	('edrophonium', 'Chemical', 'MESH:D004491', (180, 191))	('acetylcholine-receptor-antibody level', 'Phenotype', 'HP:0030208', (99, 136))	('Patients', 'Species', '9606', (0, 8))	('acetylcholine-receptor-antibody level', 'MPA', (99, 136))	('acetylcholine', 'Chemical', 'MESH:D000109', (99, 112))
13913	29850635	Aberrant Peripheral Immune Function in a Good Syndrome Patient Good's syndrome (GS) is often accompanied by recurrent respiratory infections and chronic diarrhea.	('diarrhea', 'Disease', (153, 161))	('chronic diarrhea', 'Phenotype', 'HP:0002028', (145, 161))	('respiratory infections', 'Disease', (118, 140))	('Aberrant', 'Var', (0, 8))	("Good's syndrome", 'Disease', (63, 78))	('GS', 'Disease', 'MESH:D011125', (80, 82))	('recurrent respiratory infection', 'Phenotype', 'HP:0002205', (108, 139))	('accompanied', 'Reg', (93, 104))	('respiratory infections', 'Phenotype', 'HP:0011947', (118, 140))	('respiratory infections', 'Disease', 'MESH:D012131', (118, 140))	('recurrent respiratory infections', 'Phenotype', 'HP:0002205', (108, 140))	('respiratory infection', 'Phenotype', 'HP:0011947', (118, 139))	("Good's syndrome", 'Disease', 'MESH:D010300', (63, 78))	('diarrhea', 'Phenotype', 'HP:0002014', (153, 161))	('diarrhea', 'Disease', 'MESH:D003967', (153, 161))
13941	29850635	PBMCs (1 x 106) isolated from the GS patient and healthy donors were labeled with CFSE (0.5 muM; Invitrogen) and incubated with anti-CD3 (2 mug/mL) and anti-CD28 (2 mug/mL) (eBioscience, San Diego, CA, USA) at 37 C incubator for 5 days.	('GS', 'Disease', 'MESH:D011125', (34, 36))	('anti-CD28', 'Var', (152, 161))	('patient', 'Species', '9606', (37, 44))	('anti-CD3', 'Var', (128, 136))
13965	29850635	Accordingly, the percentage of Vdelta1 T cells in this patient was higher than that in the HCs (43.9% versus 19.12 +- 17.20%) (Figure 2(c)).	('HCs', 'Chemical', '-', (91, 94))	('higher', 'PosReg', (67, 73))	('patient', 'Species', '9606', (55, 62))	('Vdelta1', 'Var', (31, 38))
13999	29850635	We separately measured the IL-17A produced by CD4+ T cells, CD8+ T cells, and gammadeltaT cells but did not detect any obvious differences between the cells from our GS patient and those from HCs.	('IL-17A', 'Gene', (27, 33))	('HCs', 'Chemical', '-', (192, 195))	('CD8', 'Gene', '925', (60, 63))	('GS', 'Disease', 'MESH:D011125', (166, 168))	('IL-17A', 'Gene', '3605', (27, 33))	('patient', 'Species', '9606', (169, 176))	('CD4+ T', 'Var', (46, 52))	('CD8', 'Gene', (60, 63))
14118	17261634	The number of OT1-GFP cells infiltrating EG7 was, as expected, higher than the number infiltrating EL4, especially at day 6 after adoptive transfer (327 +- 50 cells/mm2 versus 27 +- 2 cells/mm2) (Fig.	('EL4', 'Gene', '111979', (99, 102))	('EG7', 'Var', (41, 44))	('rat', 'Species', '10116', (92, 95))	('rat', 'Species', '10116', (34, 37))	('higher', 'PosReg', (63, 69))	('EL4', 'Gene', (99, 102))
14129	17261634	As shown in Videos S1 and S2 (available at http://www.jem.org/cgi/content/full/jem.20061890/DC1), during the early phase of rejection OT1-GFP moved actively in EL4 tumors but had reduced motility in EG7 tumors.	('tumor', 'Phenotype', 'HP:0002664', (203, 208))	('OT1-GFP', 'Var', (134, 141))	('tumors', 'Disease', (203, 209))	('tumors', 'Disease', (164, 170))	('tumors', 'Disease', 'MESH:D009369', (203, 209))	('EG7 tumors', 'Disease', (199, 209))	('tumors', 'Disease', 'MESH:D009369', (164, 170))	('tumors', 'Phenotype', 'HP:0002664', (164, 170))	('tumors', 'Phenotype', 'HP:0002664', (203, 209))	('EG7 tumors', 'Disease', 'MESH:D009369', (199, 209))	('motility', 'MPA', (187, 195))	('EL4', 'Gene', '111979', (160, 163))	('tumor', 'Phenotype', 'HP:0002664', (164, 169))	('reduced', 'NegReg', (179, 186))	('EL4', 'Gene', (160, 163))
14133	17261634	The migration trajectories were more restrained in the EG7 compared with the EL4 tumors (confinement ratios of 0.4 +- 0.2 versus 0.6 +- 0.2).	('EL4', 'Gene', (77, 80))	('tumors', 'Disease', (81, 87))	('tumors', 'Disease', 'MESH:D009369', (81, 87))	('rat', 'Species', '10116', (101, 104))	('restrained', 'NegReg', (37, 47))	('migration trajectories', 'CPA', (4, 26))	('rat', 'Species', '10116', (7, 10))	('EG7', 'Var', (55, 58))	('tumor', 'Phenotype', 'HP:0002664', (81, 86))	('EL4', 'Gene', '111979', (77, 80))	('tumors', 'Phenotype', 'HP:0002664', (81, 87))
14134	17261634	Consistently, the arrest coefficient was higher in EG7 (33 +- 17%) than in EL4 (13 +- 17%) tumors.	('tumors', 'Disease', (91, 97))	('tumors', 'Disease', 'MESH:D009369', (91, 97))	('tumors', 'Phenotype', 'HP:0002664', (91, 97))	('EG7', 'Var', (51, 54))	('tumor', 'Phenotype', 'HP:0002664', (91, 96))	('higher', 'PosReg', (41, 47))	('EL4', 'Gene', (75, 78))	('EL4', 'Gene', '111979', (75, 78))	('arrest coefficient', 'MPA', (18, 36))
14140	17261634	The GFP-expressing tumors behaved like their GFP-negative counterparts in terms of tumor growth and rejection after transfer of OT1 cells.	('tumors', 'Disease', (19, 25))	('tumors', 'Disease', 'MESH:D009369', (19, 25))	('tumor', 'Phenotype', 'HP:0002664', (83, 88))	('tumor', 'Disease', 'MESH:D009369', (19, 24))	('tumor', 'Disease', (83, 88))	('rejection', 'CPA', (100, 109))	('tumor', 'Phenotype', 'HP:0002664', (19, 24))	('GFP-expressing', 'Var', (4, 18))	('tumor', 'Disease', (19, 24))	('tumors', 'Phenotype', 'HP:0002664', (19, 25))	('tumor', 'Disease', 'MESH:D009369', (83, 88))
14141	17261634	During the early phase of tumor rejection, tumor cells formed a dense network of bright living cells in both EL4-GFP and EG7-GFP tumors, similar to that observed in the absence of OT1 cells (Fig.	('EG7-GFP', 'Var', (121, 128))	('EL4', 'Gene', (109, 112))	('tumors', 'Disease', (129, 135))	('tumors', 'Disease', 'MESH:D009369', (129, 135))	('tumors', 'Phenotype', 'HP:0002664', (129, 135))	('tumor', 'Disease', 'MESH:D009369', (26, 31))	('tumor', 'Disease', 'MESH:D009369', (43, 48))	('tumor', 'Disease', 'MESH:D009369', (129, 134))	('tumor', 'Phenotype', 'HP:0002664', (129, 134))	('tumor', 'Phenotype', 'HP:0002664', (43, 48))	('tumor', 'Disease', (26, 31))	('tumor', 'Phenotype', 'HP:0002664', (26, 31))	('tumor', 'Disease', (129, 134))	('tumor', 'Disease', (43, 48))	('EL4', 'Gene', '111979', (109, 112))
14260	17261634	Cell suspensions were prepared in PBS 0.5% BSA, and cells were labeled with anti-CD69-biotin followed by streptavidin-PercP-Cy5.5, anti-CD62L-allophycocyanin, anti-CD44-PE, or anti-Vbeta5-PE (Becton Dickinson).	('CD62L', 'Gene', (136, 141))	('PercP-Cy5', 'Chemical', '-', (118, 127))	('CD69', 'Gene', (81, 85))	('CD62L', 'Gene', '6402', (136, 141))	('PBS', 'Chemical', 'MESH:D007854', (34, 37))	('CD44', 'Gene', '960', (164, 168))	('anti-Vbeta5-PE', 'Var', (176, 190))	('CD44', 'Gene', (164, 168))	('CD69', 'Gene', '969', (81, 85))
14309	31516798	This disease is mediated by the anti-acetylcholine receptor (ACh) antibody (Ab) or rarely by muscle-specific tyrosine kinase (MuSK) Ab, lipoprotein-related protein 4 (LRP4), or agrin.	('LRP4', 'Gene', '4038', (167, 171))	('mediated', 'Reg', (16, 24))	('lipoprotein-related protein 4', 'Gene', (136, 165))	('MuSK', 'Gene', '4593', (126, 130))	('anti-acetylcholine', 'Var', (32, 50))	('muscle-specific tyrosine kinase', 'Gene', (93, 124))	('MuSK', 'Gene', (126, 130))	('muscle-specific tyrosine kinase', 'Gene', '4593', (93, 124))	('agrin', 'Gene', '375790', (177, 182))	('LRP4', 'Gene', (167, 171))	('lipoprotein-related protein 4', 'Gene', '4038', (136, 165))	('agrin', 'Gene', (177, 182))
14386	25890208	Previous series studies revealed intraoperative adhesion of noninvasive thymomas had a significantly higher recurrent rate.	('higher', 'PosReg', (101, 107))	('thymomas', 'Disease', (72, 80))	('noninvasive', 'Disease', (60, 71))	('recurrent rate', 'CPA', (108, 122))	('thymomas', 'Disease', 'MESH:D013945', (72, 80))	('thymoma', 'Phenotype', 'HP:0100522', (72, 79))	('adhesion', 'Var', (48, 56))
14395	19449311	We have previously demonstrated that on double positive (DP) thymocytes the ligation of CD8 in the absence of TCR engagement results in apoptosis and have postulated this is a mechanism to remove thymocytes that have failed positive selection.	('CD8', 'Gene', '925', (88, 91))	('apoptosis', 'CPA', (136, 145))	('rat', 'Species', '10116', (26, 29))	('ligation', 'Var', (76, 84))	('results in', 'Reg', (125, 135))	('DP', 'Chemical', '-', (57, 59))	('CD8', 'Gene', (88, 91))
14398	19449311	Decreasing LAT expression and mutation of tyrosine residues of LAT reduced apoptosis upon crosslinking of CD8.	('mutation of tyrosine residues', 'Var', (30, 59))	('Decreasing', 'NegReg', (0, 10))	('CD8', 'Gene', (106, 109))	('apoptosis', 'CPA', (75, 84))	('CD8', 'Gene', '925', (106, 109))	('LAT', 'Gene', (63, 66))	('reduced', 'NegReg', (67, 74))	('expression', 'MPA', (15, 25))	('LAT', 'Protein', (11, 14))	('tyrosine', 'Chemical', 'MESH:D014443', (42, 50))
14399	19449311	Our results identify novel functions for both CD8 and LAT that are independent of TCR signal transduction and suggest a mechanism for signal transduction leading to apoptosis upon CD8 crosslinking.	('CD8', 'Gene', '925', (46, 49))	('apoptosis', 'CPA', (165, 174))	('leading to', 'Reg', (154, 164))	('crosslinking', 'Var', (184, 196))	('CD8', 'Gene', (46, 49))	('CD8', 'Gene', (180, 183))	('CD8', 'Gene', '925', (180, 183))
14402	19449311	Apoptosis of thymocytes can also be triggered by corticosteroids or by ligation of CD24, CD45, or Thy-1, however the role of these events in thymic selection is yet to be established.. We have previously described a novel mechanism for apoptosis of immature DP thymocytes through the ligation of CD8.	('apoptosis', 'CPA', (236, 245))	('ligation', 'Var', (284, 292))	('Thy-1', 'Gene', (98, 103))	('DP', 'Chemical', '-', (258, 260))	('CD8', 'Gene', (296, 299))	('Thy-1', 'Gene', '21838', (98, 103))	('CD8', 'Gene', '925', (296, 299))	('CD24', 'Gene', (83, 87))	('CD45', 'Gene', '19264', (89, 93))	('CD24', 'Gene', '12484', (83, 87))	('CD45', 'Gene', (89, 93))
14406	19449311	The ligation of CD8, in the absence of TCR engagement, results in apoptosis of a proportion of DP thymocytes and we hypothesize that this maybe a mechanism to remove DP thymocytes that have failed positive selection.	('results in', 'Reg', (55, 65))	('DP', 'Chemical', '-', (95, 97))	('ligation', 'Var', (4, 12))	('apoptosis', 'CPA', (66, 75))	('DP', 'Chemical', '-', (166, 168))	('CD8', 'Gene', (16, 19))	('CD8', 'Gene', '925', (16, 19))
14411	19449311	CD8beta is palmitoylated on a cysteine residue in its cytoplasmic tail and partitions CD8 heterodimers into lipid rafts.	('CD8', 'Gene', (86, 89))	('CD8', 'Gene', (0, 3))	('cysteine', 'Chemical', 'MESH:D003545', (30, 38))	('lipid', 'Chemical', 'MESH:D008055', (108, 113))	('CD8', 'Gene', '925', (0, 3))	('CD8', 'Gene', '925', (86, 89))	('CD8beta', 'Gene', (0, 7))	('CD8beta', 'Gene', '12526', (0, 7))	('partitions', 'MPA', (75, 85))	('palmitoylated', 'Var', (11, 24))
14420	19449311	Only the five C-terminal tyrosines (Y127, Y132, Y171, Y191 and Y226) undergo detectable phosphorylation upon TCR engagement.	('Y226', 'Var', (63, 67))	('phosphorylation', 'MPA', (88, 103))	('Y132', 'Var', (42, 46))	('Y127', 'Var', (36, 40))	('tyrosines', 'Chemical', 'MESH:D014443', (25, 34))	('Y171', 'Var', (48, 52))	('undergo', 'Reg', (69, 76))	('Y132', 'Chemical', '-', (42, 46))	('Y191', 'Var', (54, 58))
14424	19449311	We found that upon ligation of CD8 the association of LAT with CD8 was increased and LAT was phosphorylated on several regulatory tyrosine residues.	('ligation', 'Var', (19, 27))	('CD8', 'Gene', (31, 34))	('phosphorylated', 'MPA', (93, 107))	('CD8', 'Gene', (63, 66))	('CD8', 'Gene', '925', (31, 34))	('increased', 'PosReg', (71, 80))	('tyrosine', 'Chemical', 'MESH:D014443', (130, 138))	('CD8', 'Gene', '925', (63, 66))	('association', 'Interaction', (39, 50))
14425	19449311	In addition, the expression and phosphorylation of LAT was required for apoptosis to occur following the ligation of CD8 while Lck did not play a role.	('ligation', 'Var', (105, 113))	('CD8', 'Gene', (117, 120))	('CD8', 'Gene', '925', (117, 120))
14426	19449311	In this study we present a model in which ligation of CD8 initiates a novel biochemical signaling pathway that leads to apoptosis and provides an explanation for the preferential association of LAT with CD8 during thymocyte development.	('CD8', 'Gene', '925', (54, 57))	('initiates', 'Reg', (58, 67))	('apoptosis', 'CPA', (120, 129))	('biochemical signaling pathway', 'Pathway', (76, 105))	('leads to', 'Reg', (111, 119))	('CD8', 'Gene', (203, 206))	('CD8', 'Gene', '925', (203, 206))	('CD8', 'Gene', (54, 57))	('ligation', 'Var', (42, 50))
14440	19449311	To determine if separate crosslinking of CD8alpha or CD8beta induced apoptosis 3H6 cells were treated with anti-CD8alpha or anti-CD8beta antibodies and anti-rat IgG (Fig.	('anti-CD8alpha', 'Var', (107, 120))	('IgG', 'Gene', (161, 164))	('CD8beta', 'Gene', (53, 60))	('CD8beta', 'Gene', '12526', (53, 60))	('CD8beta', 'Gene', '12526', (129, 136))	('H6', 'CellLine', 'CVCL:J418', (80, 82))	('rat', 'Species', '10116', (157, 160))	('CD8beta', 'Gene', (129, 136))	('rat', 'Species', '10116', (20, 23))	('IgG', 'Gene', '16059', (161, 164))
14441	19449311	Anti-CD8alpha and anti-CD8beta both induced apoptosis in 70% of 3H6 cells following crosslinking as determined by the binding of annexin-V.	('induced', 'Reg', (36, 43))	('apoptosis', 'CPA', (44, 53))	('Anti-CD8alpha', 'Var', (0, 13))	('CD8beta', 'Gene', (23, 30))	('H6', 'CellLine', 'CVCL:J418', (65, 67))	('CD8beta', 'Gene', '12526', (23, 30))
14453	19449311	The ligation of CD8 results in a slight increase in the association of CD8alpha with Lck.	('CD8', 'Gene', '925', (71, 74))	('Lck', 'Disease', (85, 88))	('increase', 'PosReg', (40, 48))	('ligation', 'Var', (4, 12))	('association', 'Interaction', (56, 67))	('CD8', 'Gene', (16, 19))	('CD8', 'Gene', '925', (16, 19))	('CD8', 'Gene', (71, 74))
14454	19449311	This result suggests that a small pool of Lck is recruited to CD8alpha upon crosslinking of CD8 and may be involved in coupling the apoptotic signals from CD8 to downstream pathways.	('CD8', 'Gene', (92, 95))	('CD8', 'Gene', (62, 65))	('crosslinking', 'Var', (76, 88))	('CD8', 'Gene', '925', (92, 95))	('CD8', 'Gene', '925', (62, 65))	('involved', 'Reg', (107, 115))	('CD8', 'Gene', (155, 158))	('CD8', 'Gene', '925', (155, 158))	('coupling', 'MPA', (119, 127))	('apoptotic signals', 'MPA', (132, 149))	('recruited', 'PosReg', (49, 58))
14455	19449311	Lck is regulated by reversible phosphorylation of 2 tyrosine residues Y394 and Y505.	('Y505', 'Chemical', '-', (79, 83))	('Y394', 'Chemical', '-', (70, 74))	('tyrosine', 'Chemical', 'MESH:D014443', (52, 60))	('Y394', 'Var', (70, 74))	('Y505', 'Var', (79, 83))
14456	19449311	Lck autophosphorylates Y394 leading to a conformational change in the activation loop of Lck.	('Y394', 'Chemical', '-', (23, 27))	('conformational change in the activation loop', 'MPA', (41, 85))	('Y394', 'Var', (23, 27))	('Lck', 'Gene', (89, 92))
14457	19449311	An increase in phosphorylation of Y394 is indicative of an increase in Lck kinase activity.	('Lck kinase', 'Enzyme', (71, 81))	('Y394', 'Var', (34, 38))	('increase', 'PosReg', (59, 67))	('activity', 'MPA', (82, 90))	('Y394', 'Chemical', '-', (34, 38))	('increase', 'PosReg', (3, 11))	('phosphorylation', 'MPA', (15, 30))
14458	19449311	Lck is also negatively regulated by phosphorylation of a conserved C-terminal tyrosine residue, Y505.	('Lck', 'Gene', (0, 3))	('Y505', 'Chemical', '-', (96, 100))	('Y505', 'Var', (96, 100))	('tyrosine', 'Chemical', 'MESH:D014443', (78, 86))	('negatively', 'NegReg', (12, 22))
14459	19449311	When phosphorylated, Y505 binds to the SH2 domain in the same Lck molecule forcing Lck into an inactive conformation.	('Lck', 'MPA', (83, 86))	('Y505', 'Var', (21, 25))	('Y505', 'Chemical', '-', (21, 25))
14468	19449311	To verify that PP2 inhibits the activity of src-family kinases in our system, MHC-/- thymocytes were treated with either PP2, or PP3 (a pharmacologically inactive control for PP2), or were left untreated.	('PP2', 'Gene', '18169', (15, 18))	('PP2', 'Gene', (175, 178))	('src', 'Gene', '20779', (44, 47))	('PP3', 'Var', (129, 132))	('src', 'Gene', (44, 47))	('PP2', 'Gene', (121, 124))	('activity', 'MPA', (32, 40))	('PP2', 'Gene', '18169', (175, 178))	('PP2', 'Gene', (15, 18))	('inhibits', 'NegReg', (19, 27))	('PP2', 'Gene', '18169', (121, 124))
14472	19449311	Thymocytes from MHC-/- mice were pretreated with PP2 or PP3 and then incubated with antibody to CD8 under crosslinking conditions.	('PP3', 'Var', (56, 59))	('PP2', 'Gene', (49, 52))	('CD8', 'Gene', (96, 99))	('CD8', 'Gene', '925', (96, 99))	('PP2', 'Gene', '18169', (49, 52))	('mice', 'Species', '10090', (23, 27))
14478	19449311	Upon the ligation of CD8 there is a dramatic increase in the amount of LAT that is associated with CD8alpha.	('ligation', 'Var', (9, 17))	('CD8', 'Gene', (99, 102))	('CD8', 'Gene', '925', (99, 102))	('CD8', 'Gene', (21, 24))	('CD8', 'Gene', '925', (21, 24))	('LAT', 'MPA', (71, 74))	('increase', 'PosReg', (45, 53))
14482	19449311	Ligation of CD8 increases tyrosine phosphorylation of LAT within 1 minute with a sustained increase in phosphorylation until 30 minutes.	('CD8', 'Gene', '925', (12, 15))	('Ligation', 'Var', (0, 8))	('tyrosine', 'Chemical', 'MESH:D014443', (26, 34))	('LAT', 'Protein', (54, 57))	('phosphorylation', 'MPA', (103, 118))	('increases', 'PosReg', (16, 25))	('tyrosine phosphorylation', 'MPA', (26, 50))	('CD8', 'Gene', (12, 15))
14486	19449311	3 N-terminal tyrosine residues Y37, Y45, and Y110 did not become phosphorylated following the ligation of CD8.	('Y110', 'Var', (45, 49))	('CD8', 'Gene', (106, 109))	('CD8', 'Gene', '925', (106, 109))	('Y37', 'Var', (31, 34))	('tyrosine', 'Chemical', 'MESH:D014443', (13, 21))	('Y45', 'Var', (36, 39))
14487	19449311	3 C-terminal tyrosine residues; Y127 Y 132 and Y 191became phosphorylated following ligation of CD8 but with varying kinetics and intensity.	('phosphorylated', 'MPA', (59, 73))	('Y 191became', 'Var', (47, 58))	('Y127 Y 132', 'Var', (32, 42))	('CD8', 'Gene', (96, 99))	('Y127 Y', 'Mutation', 'p.Y127Y', (32, 38))	('CD8', 'Gene', '925', (96, 99))	('tyrosine', 'Chemical', 'MESH:D014443', (13, 21))
14488	19449311	Phosphorylation of Y110Y127 and Y226 results in the formation of binding sites for the small adaptor molecule Grb2 while phosphorylation of Y132 creates a binding site for PLCgamma1.	('Y132', 'Var', (140, 144))	('binding', 'Interaction', (65, 72))	('Grb2', 'Gene', (110, 114))	('binding', 'Interaction', (155, 162))	('Y226', 'Var', (32, 36))	('Y110Y127', 'Var', (19, 27))	('Y132', 'Chemical', '-', (140, 144))	('PLCgamma1', 'Gene', (172, 181))	('PLCgamma1', 'Gene', '18803', (172, 181))	('Grb2', 'Gene', '14784', (110, 114))
14489	19449311	The final residue, Y171, appears to have a high level of phosphorylation in unstimulated cells that is maintained following the ligation of CD8.	('phosphorylation', 'MPA', (57, 72))	('CD8', 'Gene', (140, 143))	('CD8', 'Gene', '925', (140, 143))	('Y171', 'Var', (19, 23))
14490	19449311	These data demonstrates that the ligation of CD8 on DP thymocytes induces the phosphorylation on specific tyrosine residues of LAT and that these residues are within the binding sites for Grb2, Gads, and PLCgamma1.	('rat', 'Species', '10116', (18, 21))	('PLCgamma1', 'Gene', (204, 213))	('PLCgamma1', 'Gene', '18803', (204, 213))	('induces', 'Reg', (66, 73))	('ligation', 'Var', (33, 41))	('DP', 'Chemical', '-', (52, 54))	('CD8', 'Gene', (45, 48))	('Grb2', 'Gene', '14784', (188, 192))	('CD8', 'Gene', '925', (45, 48))	('tyrosine', 'Chemical', 'MESH:D014443', (106, 114))	('Grb2', 'Gene', (188, 192))	('phosphorylation on specific tyrosine residues', 'MPA', (78, 123))
14499	19449311	The experiments described above demonstrated that the expression of LAT is required for apoptosis following ligation of CD8 and that LAT exhibits an increase in tyrosine phosphorylation upon crosslinking of CD8.	('CD8', 'Gene', '925', (207, 210))	('tyrosine phosphorylation', 'MPA', (161, 185))	('increase', 'PosReg', (149, 157))	('CD8', 'Gene', (120, 123))	('CD8', 'Gene', '925', (120, 123))	('rat', 'Species', '10116', (39, 42))	('tyrosine', 'Chemical', 'MESH:D014443', (161, 169))	('ligation', 'Var', (108, 116))	('CD8', 'Gene', (207, 210))
14501	19449311	A study by Zhu et al examined the effect of phenyalanine substitutions for the tyrosine residues of LAT on TCR signaling in a Jurkat T cell line that did not express LAT.	('tyrosine', 'Chemical', 'MESH:D014443', (79, 87))	('phenyalanine substitutions', 'Var', (44, 70))	('LAT', 'Gene', (100, 103))	('phenyalanine', 'Chemical', '-', (44, 56))	('a Jurkat', 'CellLine', 'CVCL:0065', (124, 132))	('TCR signaling', 'MPA', (107, 120))
14502	19449311	They established that the human equivalents of the 4 c-terminal tyrosine residues (Y132 Y171 Y191 and Y226) are important for TCR signaling and thymocyte development.	('thymocyte development', 'CPA', (144, 165))	('Y132 Y171 Y191', 'Var', (83, 97))	('tyrosine', 'Chemical', 'MESH:D014443', (64, 72))	('Y226', 'Var', (102, 106))	('Y132', 'Chemical', '-', (83, 87))	('human', 'Species', '9606', (26, 31))
14503	19449311	We sought to determine if the apoptotic signal induced by the ligation of CD8 utilized a similar pattern of LAT phosphorylation.	('CD8', 'Gene', '925', (74, 77))	('CD8', 'Gene', (74, 77))	('ligation', 'Var', (62, 70))
14504	19449311	We created a panel of stable cell lines that express tyrosine to phenylalanine mutated forms of human LAT (mut-hLAT) expressed in the LATkd-3H6 cell line.	('phenylalanine', 'Chemical', 'MESH:D010649', (65, 78))	('H6', 'CellLine', 'CVCL:J418', (141, 143))	('human', 'Species', '9606', (96, 101))	('tyrosine', 'Chemical', 'MESH:D014443', (53, 61))	('tyrosine to phenylalanine', 'Var', (53, 78))	('hLAT', 'Gene', (111, 115))	('hLAT', 'Gene', '27040', (111, 115))
14507	19449311	The LATkd-3H6 cells have a ~90% decrease in the amount of murine LAT (mLAT) protein that is expressed, therefore, the majority of the LAT protein that is expressed is the mut-hLAT.	('mLAT', 'Gene', (70, 74))	('hLAT', 'Gene', (175, 179))	('H6', 'CellLine', 'CVCL:J418', (11, 13))	('mLAT', 'Gene', '16797', (70, 74))	('murine', 'Species', '10090', (58, 64))	('hLAT', 'Gene', '27040', (175, 179))	('LATkd-3H6', 'Var', (4, 13))	('decrease', 'NegReg', (32, 40))	('amount', 'MPA', (48, 54))
14509	19449311	Probing western blots using an antibody that reacts with both mLAT and mut-hLAT proteins demonstrated that expression of mut-hLAT protein restored the total LAT protein level to approximately 4 fold the level of endogenous murine LAT expressed in 3H6 cells (Fig 5B).	('protein', 'Var', (130, 137))	('hLAT', 'Gene', (75, 79))	('LAT protein level', 'MPA', (157, 174))	('mLAT', 'Gene', '16797', (62, 66))	('restored', 'PosReg', (138, 146))	('hLAT', 'Gene', '27040', (75, 79))	('H6', 'CellLine', 'CVCL:J418', (248, 250))	('hLAT', 'Gene', (125, 129))	('murine', 'Species', '10090', (223, 229))	('expression', 'Var', (107, 117))	('rat', 'Species', '10116', (96, 99))	('mLAT', 'Gene', (62, 66))	('hLAT', 'Gene', '27040', (125, 129))
14512	19449311	3H6, LATkd-3H6 and LATkd-3H6 cells that expressed either wildtype (WT) or mutant (mut) human LAT were treated with CD8alpha antibody under crosslinking conditions and apoptosis was measured by the binding of annexin-V (Figure 5C).	('H6', 'CellLine', 'CVCL:J418', (1, 3))	('human', 'Species', '9606', (87, 92))	('H6', 'CellLine', 'CVCL:J418', (26, 28))	('H6', 'CellLine', 'CVCL:J418', (12, 14))	('binding', 'Interaction', (197, 204))	('mutant', 'Var', (74, 80))
14513	19449311	Crosslinking of CD8 resulted in the induction of apoptosis in 40% of 3H6 cells and18% of LATkd-3H6 cells.	('H6', 'CellLine', 'CVCL:J418', (96, 98))	('Crosslinking', 'Var', (0, 12))	('induction', 'Reg', (36, 45))	('H6', 'CellLine', 'CVCL:J418', (70, 72))	('CD8', 'Gene', (16, 19))	('apoptosis', 'CPA', (49, 58))	('CD8', 'Gene', '925', (16, 19))
14516	19449311	The expression of the Delta1-9LAT mut-hLAT did not restore the susceptibility to CD8 mediated apoptosis indicating that phosphorylation of at least some of the tyrosine residues of LAT is necessary for apoptosis.	('CD8', 'Gene', (81, 84))	('Delta1-9LAT', 'Var', (22, 33))	('CD8', 'Gene', '925', (81, 84))	('hLAT', 'Gene', (38, 42))	('tyrosine', 'Chemical', 'MESH:D014443', (160, 168))	('hLAT', 'Gene', '27040', (38, 42))
14525	19449311	Mice deficient in ZAP-70 have normal thymic development through the pre-TCR/beta-selection stage but are unable to progress through positive and negative selection and are arrested at the DP stage.	('DP', 'Chemical', '-', (188, 190))	('thymic development', 'CPA', (37, 55))	('Mice', 'Species', '10090', (0, 4))	('ZAP-70', 'Gene', (18, 24))	('deficient', 'Var', (5, 14))
14528	19449311	Following crosslinking of CD8, the proportion of apoptotic cells in ZAP-70-/- thymocytes was similar to the levels obtained when MHC-/- or C57BL/6 thymocytes were treated in a similar manner.	('crosslinking', 'Var', (10, 22))	('ZAP-70-/-', 'Var', (68, 77))	('CD8', 'Gene', '925', (26, 29))	('CD8', 'Gene', (26, 29))
14530	19449311	Zap-70 has been shown to phosphorylate the 5 c-terminal tyrosine of LAT including Y132, Y171 and Y191.	('tyrosine', 'Chemical', 'MESH:D014443', (56, 64))	('Y132', 'Var', (82, 86))	('Zap-70', 'Gene', (0, 6))	('Y132', 'Chemical', '-', (82, 86))	('Y191', 'Var', (97, 101))	('Zap-70', 'Gene', '22637', (0, 6))	('Y171', 'Var', (88, 92))
14531	19449311	The ligation of CD8 induced an increase in the phosphorylation of Y191 (data not shown) in a similar pattern to MHC-/- thymocytes.	('phosphorylation', 'MPA', (47, 62))	('Y191', 'Var', (66, 70))	('ligation', 'Var', (4, 12))	('CD8', 'Gene', (16, 19))	('CD8', 'Gene', '925', (16, 19))	('increase', 'PosReg', (31, 39))
14532	19449311	In contrast, thymocytes from Zap-70-/- mice did not have an increase in phosphorylation on Y132 in response to ligation of CD8 compared to MHC-/- thymocytes (Fig 6C).	('ligation', 'Var', (111, 119))	('CD8', 'Gene', (123, 126))	('mice', 'Species', '10090', (39, 43))	('CD8', 'Gene', '925', (123, 126))	('phosphorylation', 'MPA', (72, 87))	('Y132', 'Chemical', '-', (91, 95))	('Zap-70', 'Gene', (29, 35))	('Zap-70', 'Gene', '22637', (29, 35))
14533	19449311	This data demonstrates that Zap-70 is responsible for the increase in phosphorylation of LAT on Y132.	('Y132', 'Var', (96, 100))	('increase', 'PosReg', (58, 66))	('LAT', 'Protein', (89, 92))	('Zap-70', 'Gene', (28, 34))	('Zap-70', 'Gene', '22637', (28, 34))	('phosphorylation', 'MPA', (70, 85))	('Y132', 'Chemical', '-', (96, 100))	('rat', 'Species', '10116', (17, 20))
14534	19449311	Since Zap-70 is not required for apoptosis, this implies that phosphorylation of Y132 of LAT is also not involved in CD8-mediated apoptosis.	('LAT', 'Gene', (89, 92))	('Zap-70', 'Gene', (6, 12))	('Y132', 'Chemical', '-', (81, 85))	('CD8', 'Gene', (117, 120))	('Zap-70', 'Gene', '22637', (6, 12))	('CD8', 'Gene', '925', (117, 120))	('involved', 'Reg', (105, 113))	('Y132', 'Var', (81, 85))
14543	19449311	The percentage of CD4+CD8+ DP thymocytes is slightly lower in ITK-/- (81.7) and RLK-/-ITK-/- (80.2%) mice compared to C57BL/6 mice (85%).	('ITK-/-', 'Var', (62, 68))	('mice', 'Species', '10090', (126, 130))	('RLK', 'Gene', '22165', (80, 83))	('CD4', 'Gene', (18, 21))	('DP', 'Chemical', '-', (27, 29))	('CD4', 'Gene', '12504', (18, 21))	('mice', 'Species', '10090', (101, 105))	('RLK', 'Gene', (80, 83))	('CD8', 'Gene', (22, 25))	('lower', 'NegReg', (53, 58))	('CD8', 'Gene', '925', (22, 25))
14545	19449311	Thymocytes from MHC-/-, C57BL/6, ITK-/-, and RLK-/-ITK-/- mice were crosslinked with CD8alpha antibody and apoptosis was measured by binding of annexin-V (Fig.	('C57BL/6', 'Var', (24, 31))	('RLK', 'Gene', (45, 48))	('mice', 'Species', '10090', (58, 62))	('RLK', 'Gene', '22165', (45, 48))	('binding', 'Interaction', (133, 140))
14547	19449311	The ligation of CD8 induced the phosphorylation of LAT on Y132 and Y191 indicating that ITK and RLK are not involved in the phosphorylation of LAT during apoptosis (Fig 6F).	('CD8', 'Gene', (16, 19))	('Y191', 'Var', (67, 71))	('Y132', 'Var', (58, 62))	('RLK', 'Gene', (96, 99))	('Y132', 'Chemical', '-', (58, 62))	('RLK', 'Gene', '22165', (96, 99))	('phosphorylation', 'MPA', (32, 47))	('ligation', 'Var', (4, 12))	('LAT', 'Protein', (51, 54))	('CD8', 'Gene', '925', (16, 19))
14549	19449311	In this study we investigated the initial events of the biochemical signaling pathway in DP thymocytes that links the ligation of CD8 on the cell surface to apoptosis.	('ligation', 'Var', (118, 126))	('DP', 'Chemical', '-', (89, 91))	('CD8', 'Gene', '925', (130, 133))	('CD8', 'Gene', (130, 133))
14551	19449311	In this report we focused on the phosphorylation events initiated by CD8 ligation.	('CD8', 'Gene', '925', (69, 72))	('CD8', 'Gene', (69, 72))	('ligation', 'Var', (73, 81))
14555	19449311	Other investigators have suggested that expression of CD8alphaalpha and CD8alphabeta represent alternate differentiation.	('CD8alphaalpha', 'Chemical', '-', (54, 67))	('CD8alphaalpha', 'Var', (54, 67))	('CD8alphabeta', 'Gene', (72, 84))
14560	19449311	In our experiments the ligation of CD8 resulted in a large increase in the amount of CD8alpha associated with LAT while the association of CD8alpha with Lck was only slightly increased (Figure 3, 4).	('CD8', 'Gene', (139, 142))	('CD8', 'Gene', '925', (139, 142))	('CD8', 'Gene', (85, 88))	('CD8', 'Gene', '925', (85, 88))	('ligation', 'Var', (23, 31))	('CD8', 'Gene', (35, 38))	('CD8', 'Gene', '925', (35, 38))	('increase', 'PosReg', (59, 67))
14564	19449311	Overall our observations are consistent with a signaling model in which the ligation of the CD8 that is associated with LAT and/or the CD8 that is not associated with either Lck or LAT, results in the increased association of LAT with CD8alpha and the induction of the apoptotic signaling cascade.	('CD8', 'Gene', (92, 95))	('CD8', 'Gene', '925', (135, 138))	('CD8', 'Gene', (235, 238))	('increased', 'PosReg', (201, 210))	('CD8', 'Gene', '925', (235, 238))	('CD8', 'Gene', '925', (92, 95))	('LAT', 'Protein', (226, 229))	('association', 'Interaction', (211, 222))	('CD8', 'Gene', (135, 138))	('apoptotic signaling cascade', 'Pathway', (269, 296))	('induction', 'Reg', (252, 261))	('ligation', 'Var', (76, 84))
14565	19449311	The ligation of Lck-associated CD8 is not required for apoptosis but is involved in TCR signaling.	('CD8', 'Gene', (31, 34))	('CD8', 'Gene', '925', (31, 34))	('involved', 'Reg', (72, 80))	('Lck-associated', 'Gene', (16, 30))	('ligation', 'Var', (4, 12))
14566	19449311	This proposed model might explain why the ligation of CD8 activated several signaling molecules, including ZAP-70, MAP kinases, AKT, and ROS, (data not shown) even though these molecules are not required for the apoptosis initiated by the ligation of CD8.	('CD8', 'Gene', '925', (54, 57))	('MAP kinases', 'Pathway', (115, 126))	('ligation', 'Var', (42, 50))	('CD8', 'Gene', (251, 254))	('CD8', 'Gene', '925', (251, 254))	('ZAP-70', 'Protein', (107, 113))	('CD8', 'Gene', (54, 57))	('activated', 'PosReg', (58, 67))	('ROS', 'Pathway', (137, 140))	('AKT', 'Pathway', (128, 131))	('ROS', 'Chemical', '-', (137, 140))
14569	19449311	This adds an additional layer of complexity to the outcome of the phosphorylation of LAT if the engagement of CD8 results in the phosphorylation of these same 4 tyrosine residues during positive selection.	('results in', 'Reg', (114, 124))	('phosphorylation', 'MPA', (129, 144))	('engagement', 'Var', (96, 106))	('CD8', 'Gene', (110, 113))	('tyrosine', 'Chemical', 'MESH:D014443', (161, 169))	('CD8', 'Gene', '925', (110, 113))
14574	19449311	In general, the ligation of CD8 induced a slow increase in phosphorylation that peaked at 30 minutes after crosslinking.	('CD8', 'Gene', (28, 31))	('ligation', 'Var', (16, 24))	('phosphorylation', 'MPA', (59, 74))	('increase', 'PosReg', (47, 55))	('CD8', 'Gene', '925', (28, 31))
14575	19449311	In contrast, the ligation of CD3 and CD8 induces a rapid phosphorylation response that peaked at 1 minute after crosslinking and then gradually declined.	('CD3', 'Gene', '12503', (29, 32))	('phosphorylation response', 'MPA', (57, 81))	('CD8', 'Gene', (37, 40))	('CD8', 'Gene', '925', (37, 40))	('ligation', 'Var', (17, 25))	('CD3', 'Gene', (29, 32))
14587	19449311	Thymocytes are also susceptible to the induction of apoptosis by the ligation of molecules such as Thy-1, CD24 and CD45.	('CD45', 'Gene', (115, 119))	('CD45', 'Gene', '19264', (115, 119))	('Thy-1', 'Gene', '21838', (99, 104))	('Thy-1', 'Gene', (99, 104))	('CD24', 'Gene', (106, 110))	('CD24', 'Gene', '12484', (106, 110))	('ligation', 'Var', (69, 77))
14588	19449311	Our studies indicate that ligation of CD8 can also induce apoptosis in a proportion of DP thymocytes.	('induce', 'Reg', (51, 57))	('DP', 'Chemical', '-', (87, 89))	('CD8', 'Gene', (38, 41))	('ligation', 'Var', (26, 34))	('CD8', 'Gene', '925', (38, 41))	('apoptosis', 'CPA', (58, 67))
14590	19449311	The crosslinking of CD45, CD24, and Thy-1 with antibodies induces apoptosis of thymocytes and the characterization of the pathways initiated by cross-linking of these molecules has suggested that there are both similar and distinct events.	('Thy-1', 'Gene', (36, 41))	('induces', 'Reg', (58, 65))	('CD24', 'Gene', (26, 30))	('apoptosis', 'CPA', (66, 75))	('CD24', 'Gene', '12484', (26, 30))	('Thy-1', 'Gene', '21838', (36, 41))	('CD45', 'Gene', (20, 24))	('CD45', 'Gene', '19264', (20, 24))	('crosslinking', 'Var', (4, 16))
14597	19449311	The ligation of CD8 induces a unique pattern of phosphorylation on LAT that utilizes the same tyrosine residues as TCR signaling, but with different kinetics and intensities.	('tyrosine', 'Chemical', 'MESH:D014443', (94, 102))	('induces', 'Reg', (20, 27))	('phosphorylation', 'MPA', (48, 63))	('CD8', 'Gene', '925', (16, 19))	('ligation', 'Var', (4, 12))	('CD8', 'Gene', (16, 19))	('tyrosine residues', 'MPA', (94, 111))
14600	19449311	C57BL/6 and B6.MHC-/- (Abetab-/- and beta2M-/-) were purchased from Taconic Farms (Germantown, NY).	('beta2M', 'Gene', (37, 43))	('C57BL/6', 'Var', (0, 7))	('beta2M', 'Gene', '12010', (37, 43))
14602	19449311	B6.CD8beta-/- mice were obtained from Dr. Alfred Singer (National Institutes of Health, Bethesda MD); B6.ZAP-70-/- mice were obtained from Dr. Arthur Weiss (University of California, San Francisco, San Francisco CA); and B6.ITK-/- and B6.	('mice', 'Species', '10090', (14, 18))	('B6.ITK-/-', 'Var', (221, 230))	('CD8beta', 'Gene', (3, 10))	('mice', 'Species', '10090', (115, 119))	('CD8beta', 'Gene', '12526', (3, 10))
14618	19449311	Plasmids encoding myc-tagged human LAT either wildtype (WTLAT) or mutants Delta1-9LAT, Delta1-5LAT, and Delta6-9LAT in pMSCVGFP were obtained from Dr. Weiguo Zhang (Duke University) and cloned into the pMSCVpuro retroviral vector.	('Delta1-5LAT', 'Var', (87, 98))	('Delta1-9LAT', 'Var', (74, 85))	('mutants Delta1-9LAT', 'Var', (66, 85))	('human', 'Species', '9606', (29, 34))	('Delta6-9LAT', 'Var', (104, 115))
14642	20551960	Each patient was required to fulfil the following criteria: 15-70 years of age; Eastern Cooperative Oncology Group (ECOG) performance status, 0-2; and adequate organ function, that is, leukocyte count >=4000/mul, platelet count >=105/mul, haemoglobin >=10.0 g per 100 ml, serum creatinine <1.5 mg per 100 ml, creatinine clearance >=60 ml min-1, serum bilirubin <1.5 mg per 100 ml, serum alanine aminotransferase and aspartate aminotransferase less than double the upper limit of the institutional normal range, PaO2 >=70 mm Hg and predicted post-operative forced expiratory volume in 1 s to be 50% or more of the age-, sex- and height-predicted vital capacity.	('>=105/mul', 'Var', (228, 237))	('patient', 'Species', '9606', (5, 12))	('min-1', 'Gene', '966', (338, 343))	('>=4000/mul', 'Var', (201, 211))	('alanine aminotransferase', 'Gene', (387, 411))	('>=10.0', 'Var', (251, 257))	('forced expiratory', 'MPA', (556, 573))	('serum bilirubin', 'MPA', (345, 360))	('alanine aminotransferase', 'Gene', '2875', (387, 411))	('creatinine clearance', 'MPA', (309, 329))	('min-1', 'Gene', (338, 343))	('Oncology', 'Phenotype', 'HP:0002664', (100, 108))	('forced expiratory volume in 1 s', 'Phenotype', 'HP:0032342', (556, 587))	('less', 'NegReg', (443, 447))	('>=60', 'Var', (330, 334))	('aspartate aminotransferase', 'MPA', (416, 442))
14775	32300521	Post-Contrast sagittal images exhibited some irregularity between the interface of the mass and the superior vena cava, suggestive of adherence to the outer aspect of the vessel adventitia.	('vessel adventitia', 'Disease', 'MESH:C536223', (171, 188))	('irregularity', 'Var', (45, 57))	('vessel adventitia', 'Disease', (171, 188))	('superior vena cava', 'Phenotype', 'HP:0031041', (100, 118))
14886	31832410	In the lymphoid stroma, B lymphocytes were mainly CD20-positive, while the number of mature T lymphocytes varied in different parts of the lesion but were mainly positive for CD3 and CD5.	('CD5', 'Gene', (183, 186))	('lymphoid stroma', 'Disease', (7, 22))	('lymphoid stroma', 'Disease', 'MESH:D008224', (7, 22))	('CD5', 'Gene', '921', (183, 186))	('CD20', 'Gene', '54474', (50, 54))	('CD20', 'Gene', (50, 54))	('CD3', 'Var', (175, 178))
14901	31832410	After a comprehensive analysis of these studies, we observed some polygonal tumor-like epithelial cells with a certain amount of type B2 thymomaism, which is similar to type B2 thymomas.	('thymoma', 'Disease', 'MESH:D013945', (137, 144))	('thymoma', 'Phenotype', 'HP:0100522', (177, 184))	('tumor', 'Phenotype', 'HP:0002664', (76, 81))	('tumor', 'Disease', (76, 81))	('thymoma', 'Disease', (137, 144))	('thymoma', 'Phenotype', 'HP:0100522', (137, 144))	('type B2', 'Var', (129, 136))	('thymomas', 'Disease', (177, 185))	('thymomas', 'Disease', 'MESH:D013945', (177, 185))	('thymoma', 'Disease', 'MESH:D013945', (177, 184))	('thymoma', 'Disease', (177, 184))	('tumor', 'Disease', 'MESH:D009369', (76, 81))
15145	29191778	With regards to MG, 10-20% of patients with MG have thymoma and 30% of patients with thymoma either present with or develop MG. Myasthenia gravis is a result of autoantibodies against the neuromuscular junction, with the most common being acetylcholine receptor (AChR) antibodies.	('thymoma', 'Disease', 'MESH:D013945', (85, 92))	('autoantibodies', 'Var', (161, 175))	('thymoma', 'Phenotype', 'HP:0100522', (52, 59))	('thymoma', 'Disease', (85, 92))	('patients', 'Species', '9606', (71, 79))	('result', 'Reg', (151, 157))	('thymoma', 'Phenotype', 'HP:0100522', (85, 92))	('patients', 'Species', '9606', (30, 38))	('thymoma', 'Disease', 'MESH:D013945', (52, 59))	('Myasthenia gravis', 'Disease', (128, 145))	('thymoma', 'Disease', (52, 59))	('Myasthenia gravis', 'Disease', 'MESH:D009157', (128, 145))	('Myasthenia', 'Phenotype', 'HP:0003473', (128, 138))	('AChR', 'Gene', (263, 267))
15147	29191778	There are specific antibodies associated with MG that co-exist with AChR antibodies and increase the likelihood of a coexisting thymoma and may herald more severe disease, including antibodies against titin, a large intracellular protein important for muscle contractility, and against ryanodine receptor (RyR), a calcium channel in the sarcoplasmic reticulum.	('ryanodine receptor', 'Gene', (286, 304))	('titin', 'Gene', '7273', (201, 206))	('RyR', 'Gene', (306, 309))	('antibodies', 'Var', (182, 192))	('ryanodine receptor', 'Gene', '6261', (286, 304))	('herald', 'Reg', (144, 150))	('RyR', 'Gene', '6261', (306, 309))	('thymoma', 'Disease', 'MESH:D013945', (128, 135))	('thymoma', 'Disease', (128, 135))	('titin', 'Gene', (201, 206))	('thymoma', 'Phenotype', 'HP:0100522', (128, 135))
15306	26713298	In this retrospective study with long-term clinical outcomes, 86.9 +- 50.3 months follow-up duration, we demonstrated that transsternal thymectomy, along with postoperative prednisolone and pyridostigmine in MG patients was associated with favorable outcomes regardless of pathologic features, thymoma versus thymus hyperplasia.	('pyridostigmine', 'Chemical', 'MESH:D011729', (190, 204))	('patients', 'Species', '9606', (211, 219))	('thymoma versus thymus hyperplasia', 'Disease', (294, 327))	('thymus hyperplasia', 'Phenotype', 'HP:0010516', (309, 327))	('thymoma versus thymus hyperplasia', 'Disease', 'MESH:D013945', (294, 327))	('thymoma', 'Phenotype', 'HP:0100522', (294, 301))	('prednisolone', 'Chemical', 'MESH:D011239', (173, 185))	('transsternal', 'Var', (123, 135))	('MG', 'Disease', 'MESH:D000080343', (208, 210))
15343	26713298	In another study comparing VATS and transsternal thymectomy in 60 nonthymomatous MG patients, it has been demonstrated that VATS thymectomy was more advantageous due to shorter hospital stay, less tissue injury, better cosmetic results, and equivalent CSR rate compared with classic transsternal thymectomy.	('VATS', 'Var', (124, 128))	('patients', 'Species', '9606', (84, 92))	('CSR', 'CPA', (252, 255))	('nonthymomatous MG', 'Disease', 'MESH:D000080343', (66, 83))	('thymoma', 'Phenotype', 'HP:0100522', (69, 76))	('nonthymomatous MG', 'Disease', (66, 83))
15347	26713298	In addition, transsternal thymectomy was associated with high rates of CSR and PR among this cohort of MG patients.	('MG', 'Disease', 'MESH:D000080343', (103, 105))	('transsternal', 'Var', (13, 25))	('CSR', 'Disease', (71, 74))	('patients', 'Species', '9606', (106, 114))
15382	25385331	In mice, mucous cell increases can be induced by various experimental methods, including the ovalbumin-induced allergic asthma model; genetic modifications and exposure to various noxious agents such as bacterial toxins, allergens and particulates, viruses, and certain carcinogens.	('asthma', 'Phenotype', 'HP:0002099', (120, 126))	('genetic modifications', 'Var', (134, 155))	('ovalbumin', 'Gene', '282665', (93, 102))	('mice', 'Species', '10090', (3, 7))	('ovalbumin', 'Gene', (93, 102))	('allergic asthma', 'Disease', 'MESH:D004342', (111, 126))	('allergic asthma', 'Disease', (111, 126))
15422	25385331	One early change seen, within 15 minutes of administration of L-norepinephrine, was an increase in the number of cell-to-cell hernias in which a portion of the cytoplasm of a smooth muscle cell within the tunica media invaginated into an adjacent smooth muscle cell, and this change is evident on light microscopy as vacuolation (Figure 2E, arrows).	('rat', 'Species', '10116', (52, 55))	('hernias', 'Disease', 'MESH:D006547', (126, 133))	('hernias', 'Disease', (126, 133))	('L-norepinephrine', 'Var', (62, 78))	('L-norepinephrine', 'Chemical', 'MESH:D009638', (62, 78))	('hernias', 'Phenotype', 'HP:0100790', (126, 133))
15428	25385331	Nitrative stress was found to be a prominent feature of PDE inhibitors, and more recent studies showed that nitric oxide (NO) was involved in vascular injury both due to PDE inhibitors and fenoldopam mesylate.	('fenoldopam', 'Chemical', 'MESH:D018818', (189, 199))	('Nitrative stress', 'Phenotype', 'HP:0025464', (0, 16))	('involved', 'Reg', (130, 138))	('vascular injury', 'Disease', (142, 157))	('inhibitors', 'Var', (174, 184))	('vascular injury', 'Disease', 'MESH:D057772', (142, 157))	('nitric oxide', 'MPA', (108, 120))	('rat', 'Species', '10116', (3, 6))	('PDE', 'Gene', (170, 173))	('nitric oxide', 'Chemical', 'MESH:D009569', (108, 120))
15433	25385331	It is likely that these alterations in the endothelial cell junctions results in the subintimal deposition of plasma proteins within the vascular wall at injured sites.	('rat', 'Species', '10116', (28, 31))	('alterations', 'Var', (24, 35))	('results in', 'Reg', (70, 80))	('subintimal deposition of plasma proteins', 'MPA', (85, 125))
15471	25385331	Exocrine pancreatic injury induced in the rat by non-invasive methods (administration of cerulein, cyanohydroxybutene and large amounts of select amino acids such as L-arginine, L-ornithine) is characterized by inflammation, lobular atrophy, acinar cell death, acinar cell vacuolar degeneration, and/or replacement of exocrine tissue by fibrosis and adipose tissue.	('inflammation', 'Disease', 'MESH:D007249', (211, 223))	('death', 'Disease', (254, 259))	('L-ornithine', 'Var', (178, 189))	('lobular atrophy', 'Disease', 'MESH:D018275', (225, 240))	('fibrosis', 'Disease', 'MESH:D005355', (337, 345))	('fibrosis', 'Disease', (337, 345))	('rat', 'Species', '10116', (79, 82))	('cerulein', 'Chemical', 'MESH:D002108', (89, 97))	('inflammation', 'Disease', (211, 223))	('acinar cell vacuolar degeneration', 'Disease', (261, 294))	('L-ornithine', 'Chemical', 'MESH:D009952', (178, 189))	('L-arginine', 'Chemical', 'MESH:D001120', (166, 176))	('death', 'Disease', 'MESH:D003643', (254, 259))	('pancreatic injury', 'Disease', (9, 26))	('pancreatic injury', 'Disease', 'MESH:D010195', (9, 26))	('acinar cell vacuolar degeneration', 'Disease', 'MESH:C536522', (261, 294))	('rat', 'Species', '10116', (288, 291))	('lobular atrophy', 'Disease', (225, 240))	('cyanohydroxybutene', 'Chemical', '-', (99, 117))	('rat', 'Species', '10116', (42, 45))
15518	25385331	The six-month Tg.rasH2 mouse study has gained scientific and regulatory acceptance as a potential replacement for the standard 2-year carcinogenicity mouse bioassay; this model was created by microinjecting the human c-Ha-ras gene into C57BL/6 x BALBc F2 zygotes.	('Tg', 'Chemical', '-', (14, 16))	('c-Ha-ras', 'Gene', (217, 225))	('microinjecting', 'Var', (192, 206))	('mouse', 'Species', '10090', (23, 28))	('human', 'Species', '9606', (211, 216))	('c-Ha-ras', 'Gene', '15461', (217, 225))	('mouse', 'Species', '10090', (150, 155))
15558	25385331	The mRNA of the human c-Ha-ras gene was detected in femoral muscle from the Tg.rasH2 mice by RT-PCR, suggesting that integration of the c-Ha-ras gene plays a crucial role in the pathogenesis of skeletal myopathy in the rasH2 mice.	('mice', 'Species', '10090', (85, 89))	('skeletal myopathy', 'Disease', (194, 211))	('c-Ha-ras', 'Gene', (136, 144))	('Tg', 'Chemical', '-', (76, 78))	('myopathy', 'Phenotype', 'HP:0003198', (203, 211))	('skeletal myopathy', 'Phenotype', 'HP:0003756', (194, 211))	('c-Ha-ras', 'Gene', '15461', (22, 30))	('c-Ha-ras', 'Gene', '15461', (136, 144))	('mice', 'Species', '10090', (225, 229))	('rat', 'Species', '10116', (122, 125))	('skeletal myopathy', 'Disease', 'MESH:D009135', (194, 211))	('human', 'Species', '9606', (16, 21))	('c-Ha-ras', 'Gene', (22, 30))	('integration', 'Var', (117, 128))
15735	25385331	The voting results for the diagnoses were: Craniopharyngeal dysplasia (8%); Craniopharyngeal derivatives (9%); Aberrant craniopharyngeal structures (27%, preferred OWG diagnosis); Craniopharyngeal cysts (6%); Craniopharyngeal duct hyperplasia (33%); Craniopharyngeal duct metaplasia (8%); Craniopharyngioma (7%); Other (2%).	('dysplasia', 'Disease', 'MESH:D004476', (60, 69))	('duct metaplasia', 'Disease', 'MESH:D008679', (267, 282))	('Craniopharyngioma', 'Phenotype', 'HP:0030062', (289, 306))	('duct metaplasia', 'Disease', (267, 282))	('Craniopharyngioma', 'Disease', 'MESH:D003397', (289, 306))	('Aberrant', 'Var', (111, 119))	('Craniopharyngioma', 'Disease', (289, 306))	('duct hyperplasia', 'Disease', (226, 242))	('dysplasia', 'Disease', (60, 69))	('duct hyperplasia', 'Disease', 'MESH:D006965', (226, 242))	('Craniopharyngeal cysts', 'Disease', (180, 202))
15801	27566187	In this study, 27% of patients in the MIT group underwent partial thymectomy compared with 9% of patients in the OT group.	('OT', 'Chemical', '-', (113, 115))	('patients', 'Species', '9606', (22, 30))	('partial thymectomy', 'Disease', (58, 76))	('MIT', 'Chemical', '-', (38, 41))	('MIT', 'Var', (38, 41))	('patients', 'Species', '9606', (97, 105))
15860	28123518	On the basis of the WHO classification, thymic carcinomas were present in 25 patients (25/66, 37.9%), type B3 thymomas in 18 (18/66, 27.3%), type B2+B3 thymomas in 8 (8/66, 12.1%), type B2 thymomas in 10 (10/66, 15.2%), type B1+B2 thymomas in 3 (3/66, 4.5%) and type A thymomas in 2 (2/66, 3.0%).	('thymic carcinomas', 'Disease', 'MESH:D013945', (40, 57))	('A thymomas', 'Disease', 'MESH:D013945', (267, 277))	('thymomas', 'Disease', 'MESH:D013945', (189, 197))	('thymomas', 'Disease', (110, 118))	('thymic carcinomas', 'Disease', (40, 57))	('thymomas', 'Disease', 'MESH:D013945', (269, 277))	('type B3', 'Var', (102, 109))	('thymomas', 'Disease', (189, 197))	('B2+B3', 'Gene', (146, 151))	('thymomas', 'Disease', (269, 277))	('patients', 'Species', '9606', (77, 85))	('carcinoma', 'Phenotype', 'HP:0030731', (47, 56))	('A thymomas', 'Phenotype', 'HP:0100522', (267, 277))	('carcinomas', 'Phenotype', 'HP:0030731', (47, 57))	('type B2', 'Var', (181, 188))	('A thymomas', 'Disease', (267, 277))	('thymoma', 'Phenotype', 'HP:0100522', (152, 159))	('thymoma', 'Phenotype', 'HP:0100522', (231, 238))	('B1+B2', 'Gene', '28905;3383', (225, 230))	('thymomas', 'Disease', 'MESH:D013945', (152, 160))	('thymomas', 'Disease', 'MESH:D013945', (231, 239))	('thymoma', 'Phenotype', 'HP:0100522', (110, 117))	('thymoma', 'Phenotype', 'HP:0100522', (269, 276))	('B1+B2', 'Gene', (225, 230))	('thymomas', 'Disease', 'MESH:D013945', (110, 118))	('B2+B3', 'Gene', '28907;680', (146, 151))	('thymomas', 'Disease', (152, 160))	('thymomas', 'Disease', (231, 239))	('thymoma', 'Phenotype', 'HP:0100522', (189, 196))
15935	24455488	In contrast, mutations in the epithelial growth factor receptor are quite uncommon in thymic malignancies and seem to be limited to a small proportion of Asian patients.	('patients', 'Species', '9606', (160, 168))	('malignancies', 'Disease', 'MESH:D009369', (93, 105))	('epithelial growth factor receptor', 'Gene', (30, 63))	('mutations', 'Var', (13, 22))	('malignancies', 'Disease', (93, 105))
16052	21600006	described the first case of a carcinoma with an activating KIT mutation and suggested that screening for activating KIT mutations may identify KIT-expressing carcinomas that could benefit from imatinib.	('carcinomas', 'Disease', (158, 168))	('activating', 'Reg', (48, 58))	('carcinomas', 'Disease', 'MESH:D002277', (158, 168))	('carcinoma', 'Disease', (158, 167))	('KIT-expressing', 'MPA', (143, 157))	('imatinib', 'Chemical', 'MESH:D000068877', (193, 201))	('mutation', 'Var', (63, 71))	('carcinoma', 'Disease', 'MESH:D002277', (158, 167))	('carcinoma', 'Disease', 'MESH:D002277', (30, 39))	('mutations', 'Var', (120, 129))	('carcinoma', 'Phenotype', 'HP:0030731', (30, 39))	('carcinoma', 'Phenotype', 'HP:0030731', (158, 167))	('carcinomas', 'Phenotype', 'HP:0030731', (158, 168))	('carcinoma', 'Disease', (30, 39))
16064	20123959	In contrast, the subsequent endocrine features are clearly autoimmune, resulting from defects in thymic self-tolerance induction caused by mutations in the autoimmune regulator (AIRE).	('autoimmune regulator', 'Gene', (156, 176))	('mutations', 'Var', (139, 148))	('autoimmune regulator', 'Gene', '326', (156, 176))	('AIRE', 'Gene', (178, 182))	('AIRE', 'Gene', '326', (178, 182))	('thymic self-tolerance induction', 'CPA', (97, 128))	('self-tolerance', 'Phenotype', 'HP:0100716', (104, 118))	('defects', 'NegReg', (86, 93))
16068	20123959	We independently found autoantibodies against these Th17-produced cytokines in rare thymoma patients with CMC.	('autoantibodies', 'Var', (23, 37))	('patients', 'Species', '9606', (92, 100))	('thymoma', 'Phenotype', 'HP:0100522', (84, 91))	('found', 'Reg', (17, 22))	('thymoma', 'Disease', 'MESH:D013945', (84, 91))	('thymoma', 'Disease', (84, 91))
16074	20123959	CMC and impaired Th17 production are also prominent in the autosomal dominant hyper-IgE syndrome caused by STAT3 mutations and in patients with defective CARD9 or dectin-1.	('STAT3', 'Gene', (107, 112))	('CARD9', 'Gene', (154, 159))	('CARD9', 'Gene', '64170', (154, 159))	('hyper-IgE syndrome', 'Disease', 'MESH:D007589', (78, 96))	('caused', 'Reg', (97, 103))	('CMC', 'Disease', (0, 3))	('patients', 'Species', '9606', (130, 138))	('hyper-IgE syndrome', 'Disease', (78, 96))	('dectin-1', 'Gene', (163, 171))	('mutations', 'Var', (113, 122))	('Th17 production', 'MPA', (17, 32))	('dectin-1', 'Gene', '64581', (163, 171))	('STAT3', 'Gene', '6774', (107, 112))
16101	20123959	Remarkably, we detected serum autoantibodies against IL-17A, IL-17F, and/or IL-22 in the great majority of the 162 patients, with diverse AIRE mutations.	('patients', 'Species', '9606', (115, 123))	('IL-17A', 'Gene', (53, 59))	('IL-17A', 'Gene', '3605', (53, 59))	('detected', 'Reg', (15, 23))	('IL-17F', 'Gene', (61, 67))	('AIRE', 'Gene', (138, 142))	('AIRE', 'Gene', '326', (138, 142))	('IL-22', 'Gene', '50616', (76, 81))	('IL-17F', 'Gene', '112744', (61, 67))	('IL-22', 'Gene', (76, 81))	('mutations', 'Var', (143, 152))
16103	20123959	In sharp contrast, their levels were low or undetectable in healthy subjects and unaffected relatives heterozygous for AIRE mutations.	('AIRE', 'Gene', '326', (119, 123))	('AIRE', 'Gene', (119, 123))	('mutations', 'Var', (124, 133))
16109	20123959	We therefore use neutralizing titers against IL-22 for optimal quantification and sensitivity in most subsequent analyses.	('IL-22', 'Gene', '50616', (45, 50))	('IL-22', 'Gene', (45, 50))	('neutralizing', 'Var', (17, 29))
16135	20123959	If so, the autoantibodies against IL-17 and IL-22 might prove to be useful predictors of CMC susceptibility that could be assessed in prospective serial studies in AIRE mutant siblings of APECED probands (or thymoma patients).	('IL-17', 'Gene', (34, 39))	('thymoma', 'Disease', 'MESH:D013945', (208, 215))	('IL-17', 'Gene', '3605', (34, 39))	('thymoma', 'Disease', (208, 215))	('IL-22', 'Gene', '50616', (44, 49))	('CMC', 'Disease', (89, 92))	('AIRE', 'Gene', (164, 168))	('thymoma', 'Phenotype', 'HP:0100522', (208, 215))	('IL-22', 'Gene', (44, 49))	('patients', 'Species', '9606', (216, 224))	('AIRE', 'Gene', '326', (164, 168))	('mutant', 'Var', (169, 175))	('APECED', 'Gene', '326', (188, 194))	('APECED', 'Gene', (188, 194))
16138	20123959	At one extreme, every p.R257X homozygote (61 from Finland, 5 from Slovenia, and 2 from Norway) had CMC and was positive against IL-22, and 64 were also positive against IL-17F.	('IL-22', 'Gene', (128, 133))	('p.R257X', 'Mutation', 'rs121434254', (22, 29))	('CMC', 'Disease', (99, 102))	('IL-17F', 'Gene', (169, 175))	('p.R257X', 'Var', (22, 29))	('positive', 'Reg', (111, 119))	('IL-17F', 'Gene', '112744', (169, 175))	('positive', 'Reg', (152, 160))	('Slovenia', 'Disease', (66, 74))	('Slovenia', 'Disease', 'None', (66, 74))	('IL-22', 'Gene', '50616', (128, 133))
16139	20123959	In contrast, among 20 c.967_979del13 homozygous patients (13 from Norway, 6 from USA, and 1 from Pakistan), 7 were negative against IL-17F and 1 against IL-22, and these also included the 7 without CMC.	('IL-22', 'Gene', (153, 158))	('IL-17F and 1', 'Gene', '112744;3553', (132, 144))	('c.967_979del13', 'Mutation', 'c.967_979del13', (22, 36))	('patients', 'Species', '9606', (48, 56))	('negative', 'NegReg', (115, 123))	('c.967_979del13', 'Var', (22, 36))	('IL-22', 'Gene', '50616', (153, 158))
16140	20123959	Moreover, autoantibodies and CMC were both rare in a unique family with a dominant-negative p.G228W substitution that cosegregates mainly with autoimmune thyroiditis and autoantibodies to type I IFNs.	('IFN', 'Gene', '3439', (195, 198))	('thyroiditis', 'Phenotype', 'HP:0100646', (154, 165))	('p.G228W', 'Mutation', 'rs121434257', (92, 99))	('autoimmune thyroiditis', 'Disease', (143, 165))	('p.G228W', 'Var', (92, 99))	('IFN', 'Gene', (195, 198))	('autoimmune thyroiditis', 'Disease', 'MESH:D013967', (143, 165))
16154	20123959	Clinically, APECED is highly variable, including in the CMC onset age (even in p.R257X homozygotes), so there must be multiple predisposing factors, whether genetic, immunological, or environmental.	('p.R257X', 'Var', (79, 86))	('APECED', 'Gene', '326', (12, 18))	('APECED', 'Gene', (12, 18))	('CMC', 'Disease', (56, 59))	('p.R257X', 'Mutation', 'rs121434254', (79, 86))
16161	20123959	Even more importantly, this susceptibility is likewise phenocopied in patients with autoantibodies against IFN-gamma.	('patients', 'Species', '9606', (70, 78))	('autoantibodies', 'Var', (84, 98))	('IFN-gamma', 'Gene', '3458', (107, 116))	('IFN-gamma', 'Gene', (107, 116))
16214	31781423	A myelodysplastic syndrome was excluded by morphological evaluation, cytogenetic analysis, and mutational analysis, which revealed a normal karyotype and the absence of EZH2, GATA2, and TET2 mutations.	('GATA2', 'Gene', (175, 180))	('TET2', 'Gene', '54790', (186, 190))	('absence', 'NegReg', (158, 165))	('TET2', 'Gene', (186, 190))	('mutations', 'Var', (191, 200))	('myelodysplastic syndrome', 'Phenotype', 'HP:0002863', (2, 26))	('GATA2', 'Gene', '2624', (175, 180))	('EZH2', 'Gene', '2146', (169, 173))	('myelodysplastic syndrome', 'Disease', (2, 26))	('EZH2', 'Gene', (169, 173))	('myelodysplastic syndrome', 'Disease', 'MESH:D009190', (2, 26))
16253	31781423	For this reason, our first goal was to exclude a myelodysplastic syndrome secondary to chemotherapy and radiotherapy treatments: no morphological changes suggestive of MDS were observed, the karyotype was normal, and also the mutations associated with myelodysplasia and rare forms of sideroblastic anemia associated with immunodeficiency such as TET2, GATA2, TRNT1, were negative.	('sideroblastic anemia', 'Disease', (285, 305))	('TET2', 'Gene', (347, 351))	('myelodysplastic syndrome', 'Disease', (49, 73))	('myelodysplasia', 'Disease', (252, 266))	('immunodeficiency', 'Disease', 'MESH:D007153', (322, 338))	('MDS', 'Disease', 'MESH:D009190', (168, 171))	('TRNT1', 'Gene', '51095', (360, 365))	('TRNT1', 'Gene', (360, 365))	('immunodeficiency', 'Phenotype', 'HP:0002721', (322, 338))	('MDS', 'Disease', (168, 171))	('myelodysplastic syndrome', 'Phenotype', 'HP:0002863', (49, 73))	('myelodysplasia', 'Phenotype', 'HP:0002863', (252, 266))	('TET2', 'Gene', '54790', (347, 351))	('myelodysplastic syndrome', 'Disease', 'MESH:D009190', (49, 73))	('myelodysplasia', 'Disease', 'MESH:D009190', (252, 266))	('anemia', 'Phenotype', 'HP:0001903', (299, 305))	('GATA2', 'Gene', '2624', (353, 358))	('sideroblastic anemia', 'Disease', 'MESH:D000756', (285, 305))	('mutations', 'Var', (226, 235))	('GATA2', 'Gene', (353, 358))	('sideroblastic anemia', 'Phenotype', 'HP:0001924', (285, 305))	('immunodeficiency', 'Disease', (322, 338))
16350	31218940	The outcome in this case was supported by our previous studies, whereby FMT relieved patients' economic burden and stopped or reduced the need for use of some medications.	('economic burden', 'MPA', (95, 110))	('relieved', 'NegReg', (76, 84))	('patients', 'Species', '9606', (85, 93))	('FMT', 'Var', (72, 75))	('reduced', 'NegReg', (126, 133))	('need for use of some medications', 'MPA', (138, 170))
16375	30816514	There are various mechanisms by which the pathogenesis of thymoma occurs, including epigenetic alterations, which are a hallmark of cancer due to their role in carcinogenesis initiation.	('cancer', 'Disease', (132, 138))	('thymoma', 'Gene', (58, 65))	('epigenetic alterations', 'Var', (84, 106))	('carcinogenesis initiation', 'Disease', (160, 185))	('cancer', 'Phenotype', 'HP:0002664', (132, 138))	('thymoma', 'Phenotype', 'HP:0100522', (58, 65))	('carcinogenesis initiation', 'Disease', 'MESH:D063646', (160, 185))	('thymoma', 'Gene', '7063', (58, 65))	('cancer', 'Disease', 'MESH:D009369', (132, 138))
16376	30816514	Recent evidence has indicated that miR-145-5p is an important epigenetic regulation factor that may be involved in tumor progression and treatment response in thymic epithelial tumors.	('epithelial tumors', 'Disease', 'MESH:D002277', (166, 183))	('tumor', 'Phenotype', 'HP:0002664', (115, 120))	('tumors', 'Phenotype', 'HP:0002664', (177, 183))	('tumor', 'Disease', (115, 120))	('tumor', 'Disease', 'MESH:D009369', (177, 182))	('tumor', 'Phenotype', 'HP:0002664', (177, 182))	('involved', 'Reg', (103, 111))	('epithelial tumors', 'Disease', (166, 183))	('tumor', 'Disease', (177, 182))	('epithelial tumor', 'Phenotype', 'HP:0031492', (166, 182))	('miR-145-5p', 'Var', (35, 45))	('tumor', 'Disease', 'MESH:D009369', (115, 120))
16379	30816514	Previous research has also provided evidence that DNA hypermethylation in promoter regions and global DNA hypomethylation serve an important role in the tumorigenesis of thymic epithelial tumors.	('tumor', 'Disease', (188, 193))	('tumor', 'Disease', 'MESH:D009369', (153, 158))	('hypomethylation', 'Var', (106, 121))	('tumors', 'Phenotype', 'HP:0002664', (188, 194))	('epithelial tumors', 'Disease', (177, 194))	('epithelial tumor', 'Phenotype', 'HP:0031492', (177, 193))	('epithelial tumors', 'Disease', 'MESH:D002277', (177, 194))	('tumor', 'Disease', (153, 158))	('tumor', 'Phenotype', 'HP:0002664', (153, 158))	('tumor', 'Disease', 'MESH:D009369', (188, 193))	('tumor', 'Phenotype', 'HP:0002664', (188, 193))
16380	30816514	Specific DNA methylation aberrations, which are associated with different thymic epithelial tumor histotypes or thymomas accompanied by MG, have previously been identified.	('epithelial tumor', 'Disease', (81, 97))	('associated', 'Reg', (48, 58))	('methylation', 'Var', (13, 24))	('epithelial tumor', 'Phenotype', 'HP:0031492', (81, 97))	('thymoma', 'Phenotype', 'HP:0100522', (112, 119))	('tumor', 'Phenotype', 'HP:0002664', (92, 97))	('epithelial tumor', 'Disease', 'MESH:D002277', (81, 97))	('thymomas', 'Disease', 'MESH:D013945', (112, 120))	('thymomas', 'Disease', (112, 120))
16381	30816514	However, the function of aberrant DNA methylation in thymomas is less clear.	('aberrant', 'Var', (25, 33))	('thymomas', 'Disease', (53, 61))	('thymoma', 'Phenotype', 'HP:0100522', (53, 60))	('thymomas', 'Disease', 'MESH:D013945', (53, 61))
16408	30816514	A total of 19,118 probes were found to be significantly differentially methylated (Deltabeta>0.2 and adjusted P<0.05), including 119 hypermethylated and 18,999 hypomethylated DMCs.	('DMCs', 'Chemical', '-', (175, 179))	('hypomethylated', 'Reg', (160, 174))	('Deltabeta', 'Chemical', '-', (83, 92))	('hypermethylated', 'Var', (133, 148))
16414	30816514	Significant differences were observed between the hypo- and hypermethylated DMCs according to the functional genomic distribution, as well as the CpG content and neighborhood context (Fig.	('DMCs', 'Chemical', '-', (76, 80))	('differences', 'Reg', (12, 23))	('hypo-', 'Var', (50, 55))	('hypermethylated', 'Var', (60, 75))
16424	30816514	In total, 10,014 CpGs were differentially methylated at Deltabeta>0.2 and P<0.001 between type A and B thymoma subjects, which consisted of 3,998 hypermethylated and 6,016 hypomethylated DMCs.	('DMCs', 'Chemical', '-', (187, 191))	('hypermethylated', 'Var', (146, 161))	('thymoma', 'Gene', '7063', (103, 110))	('Deltabeta', 'Chemical', '-', (56, 65))	('thymoma', 'Gene', (103, 110))	('CpGs', 'Chemical', 'MESH:C015772', (17, 21))	('thymoma', 'Phenotype', 'HP:0100522', (103, 110))
16432	30816514	Considering that aberrant DNA methylation may cause gene expression alterations in thymomas, methylation and expression data of type A and B thymomas from the GEO database were analyzed.	('gene expression alterations', 'MPA', (52, 79))	('aberrant', 'Var', (17, 25))	('thymomas', 'Disease', (83, 91))	('thymomas', 'Disease', 'MESH:D013945', (83, 91))	('thymomas', 'Disease', (141, 149))	('thymomas', 'Disease', 'MESH:D013945', (141, 149))	('B thymomas', 'Disease', 'MESH:D013945', (139, 149))	('B thymomas', 'Disease', (139, 149))	('DNA', 'Protein', (26, 29))	('cause', 'Reg', (46, 51))	('thymoma', 'Phenotype', 'HP:0100522', (141, 148))	('thymoma', 'Phenotype', 'HP:0100522', (83, 90))
16433	30816514	Differential methylation analysis showed that a total of 377 hypermethylated DMCs between type A and B thymomas were located in proximal promoters (TSS1500 and TSS200), which were associated with 319 genes.	('hypermethylated', 'Reg', (61, 76))	('DMCs', 'Chemical', '-', (77, 81))	('TSS1500', 'Var', (148, 155))	('B thymomas', 'Disease', 'MESH:D013945', (101, 111))	('B thymomas', 'Disease', (101, 111))	('thymoma', 'Phenotype', 'HP:0100522', (103, 110))	('TSS200', 'Var', (160, 166))
16434	30816514	In addition, a total of 658 hypomethylated DMCs between type A and B thymomas were located in proximal promoters, which were associated with 530 genes.	('DMCs', 'Chemical', '-', (43, 47))	('B thymomas', 'Disease', 'MESH:D013945', (67, 77))	('B thymomas', 'Disease', (67, 77))	('hypomethylated', 'Var', (28, 42))	('thymoma', 'Phenotype', 'HP:0100522', (69, 76))
16438	30816514	Furthermore, functional annotation showed that the seven genes that were hypermethylated with a lower expression were highly involved in five KEGG pathways: 'Insulin signaling pathway', 'Fc gamma R-mediated phagocytosis', 'Fc epsilon RI singling pathway', 'CAMs' and 'focal adhesion' (Table IV).	('Fc epsilon RI', 'Gene', '2205', (223, 236))	('KEGG pathways', 'Pathway', (142, 155))	("'Insulin signaling pathway'", 'Pathway', (157, 184))	('Fc epsilon RI', 'Gene', (223, 236))	('involved', 'Reg', (125, 133))	('hypermethylated', 'Var', (73, 88))
16442	30816514	For the seven genes that were hypermethylated with low expression, the AUC of ICAM3 (0.717), APBB1IP (0.748), IFI16 (0.745), PARVG (0.762), CCM2 (0.703), INPP5D (0.741) and SP110 (0.738) was >0.7, as shown in Fig.	('APBB1IP', 'Gene', (93, 100))	('0.762', 'Var', (132, 137))	('ICAM3', 'Gene', '3385', (78, 83))	('PARVG', 'Gene', (125, 130))	('0.703', 'Var', (146, 151))	('SP110', 'Gene', '3431', (173, 178))	('PARVG', 'Gene', '64098', (125, 130))	('0.717', 'Var', (85, 90))	('IFI16', 'Gene', '3428', (110, 115))	('APBB1IP', 'Gene', '54518', (93, 100))	('CCM2', 'Gene', '83605', (140, 144))	('INPP5D', 'Gene', '3635', (154, 160))	('IFI16', 'Gene', (110, 115))	('INPP5D', 'Gene', (154, 160))	('SP110', 'Gene', (173, 178))	('ICAM3', 'Gene', (78, 83))	('0.748', 'Var', (102, 107))	('CCM2', 'Gene', (140, 144))	('0.745', 'Var', (117, 122))
16448	30816514	Using Deltabeta>0.2 and P<0.001, 121 DMCs were identified between the MG- and non-MG-thymoma subjects, including 22 hypermethylated and 99 hypomethylated DMCs.	('Deltabeta', 'Chemical', '-', (6, 15))	('hypomethylated', 'Var', (139, 153))	('hypermethylated', 'Var', (116, 131))	('thymoma', 'Phenotype', 'HP:0100522', (85, 92))	('DMCs', 'Chemical', '-', (37, 41))	('DMCs', 'Chemical', '-', (154, 158))	('non-MG-thymoma', 'Disease', 'MESH:D013945', (78, 92))	('non-MG-thymoma', 'Disease', (78, 92))
16452	30816514	Epigenetic changes, particularly changes in DNA methylation, are important markers and widely studied in a variety of cancer types.	('cancer', 'Disease', (118, 124))	('DNA methylation', 'MPA', (44, 59))	('changes', 'Reg', (33, 40))	('cancer', 'Disease', 'MESH:D009369', (118, 124))	('cancer', 'Phenotype', 'HP:0002664', (118, 124))	('Epigenetic changes', 'Var', (0, 18))
16454	30816514	A previous report showed that epigenetic events have been implicated in thymomas.	('thymomas', 'Disease', (72, 80))	('epigenetic events', 'Var', (30, 47))	('thymomas', 'Disease', 'MESH:D013945', (72, 80))	('thymoma', 'Phenotype', 'HP:0100522', (72, 79))	('implicated', 'Reg', (58, 68))
16462	30816514	The present study provided a more extensive list of candidate differentially methylated genes, which may be associated with thymomas.	('differentially methylated genes', 'Var', (62, 93))	('thymomas', 'Disease', (124, 132))	('thymomas', 'Disease', 'MESH:D013945', (124, 132))	('associated', 'Reg', (108, 118))	('thymoma', 'Phenotype', 'HP:0100522', (124, 131))
16463	30816514	Further studies are required to evaluate the gene expression alterations in thymomas regulated by aberrant DNA methylation.	('thymomas', 'Disease', 'MESH:D013945', (76, 84))	('aberrant', 'Var', (98, 106))	('thymomas', 'Disease', (76, 84))	('thymoma', 'Phenotype', 'HP:0100522', (76, 83))
16468	30816514	Differential methylation analysis identified 3,998 hypermethylated and 6,016 hypomethylated DMCs between type A and B thymoma subjects.	('thymoma', 'Phenotype', 'HP:0100522', (118, 125))	('thymoma', 'Gene', '7063', (118, 125))	('thymoma', 'Gene', (118, 125))	('DMCs', 'Chemical', '-', (92, 96))	('hypermethylated', 'Var', (51, 66))
16472	30816514	Therefore, the present results underlined the importance of aberrant DNA methylation in different subtypes of thymoma.	('thymoma', 'Gene', '7063', (110, 117))	('DNA', 'Protein', (69, 72))	('thymoma', 'Gene', (110, 117))	('thymoma', 'Phenotype', 'HP:0100522', (110, 117))	('aberrant', 'Var', (60, 68))
16478	30816514	In conclusion, the present study reported the dysregulated DNA methylation involved in thymoma using the Illumina 850K methylation microarray.	('thymoma', 'Gene', '7063', (87, 94))	('thymoma', 'Phenotype', 'HP:0100522', (87, 94))	('thymoma', 'Gene', (87, 94))	('dysregulated', 'Var', (46, 58))
16483	30897085	The PIK3/Akt/mTOR pathway plays a key role in various cancers; interestingly, several phase I/II studies have reported a positive effect of mTOR inhibitors in disease control in thymoma patients.	('thymoma', 'Disease', 'MESH:D013945', (178, 185))	('cancers', 'Phenotype', 'HP:0002664', (54, 61))	('PIK3', 'Gene', (4, 8))	('cancers', 'Disease', (54, 61))	('Akt', 'Gene', (9, 12))	('cancers', 'Disease', 'MESH:D009369', (54, 61))	('thymoma', 'Disease', (178, 185))	('PIK3', 'Gene', '5294', (4, 8))	('thymoma', 'Phenotype', 'HP:0100522', (178, 185))	('mTOR', 'Gene', (13, 17))	('cancer', 'Phenotype', 'HP:0002664', (54, 60))	('mTOR', 'Gene', '2475', (13, 17))	('mTOR', 'Gene', (140, 144))	('inhibitors', 'Var', (145, 155))	('mTOR', 'Gene', '2475', (140, 144))	('patients', 'Species', '9606', (186, 194))	('Akt', 'Gene', '207', (9, 12))
16487	30897085	Interestingly, we report the activation of Akt, mTOR and P70S6 proteins in primary thymic epithelial cells maintained for short period of time after their derivation from seven AB and B thymomas.	('mTOR', 'Gene', '2475', (48, 52))	('activation', 'PosReg', (29, 39))	('mTOR', 'Gene', (48, 52))	('Akt', 'Gene', '207', (43, 46))	('thymoma', 'Phenotype', 'HP:0100522', (186, 193))	('Akt', 'Gene', (43, 46))	('thymomas', 'Disease', (186, 194))	('thymomas', 'Disease', 'MESH:D013945', (186, 194))	('P70S6', 'Var', (57, 62))
16499	30897085	Sequencing of 197 cancer-related genes revealed the presence of non-synonymous somatic mutations in over 60% thymic carcinomas and barely 15% thymomas.	('non-synonymous somatic mutations', 'Var', (64, 96))	('thymic carcinomas', 'Disease', (109, 126))	('thymomas', 'Disease', (142, 150))	('thymomas', 'Disease', 'MESH:D013945', (142, 150))	('cancer', 'Phenotype', 'HP:0002664', (18, 24))	('carcinoma', 'Phenotype', 'HP:0030731', (116, 125))	('carcinomas', 'Phenotype', 'HP:0030731', (116, 126))	('thymic carcinomas', 'Disease', 'MESH:D013945', (109, 126))	('cancer', 'Disease', (18, 24))	('cancer', 'Disease', 'MESH:D009369', (18, 24))	('thymoma', 'Phenotype', 'HP:0100522', (142, 149))
16500	30897085	The most frequent mutations (26% of thymic carcinomas) were located in the p53 tumor suppressor gene.	('tumor', 'Phenotype', 'HP:0002664', (79, 84))	('tumor', 'Disease', (79, 84))	('carcinoma', 'Phenotype', 'HP:0030731', (43, 52))	('thymic carcinomas', 'Disease', (36, 53))	('carcinomas', 'Phenotype', 'HP:0030731', (43, 53))	('p53', 'Gene', (75, 78))	('p53', 'Gene', '7157', (75, 78))	('tumor', 'Disease', 'MESH:D009369', (79, 84))	('thymic carcinomas', 'Disease', 'MESH:D013945', (36, 53))	('mutations', 'Var', (18, 27))
16501	30897085	GTF2I was confirmed as an oncogene associated with type A thymoma, and mutations in HRAS, NRAS, and TP53 were identified in thymomas.	('TP53', 'Gene', '7157', (100, 104))	('NRAS', 'Gene', (90, 94))	('thymomas', 'Disease', 'MESH:D013945', (124, 132))	('thymomas', 'Disease', (124, 132))	('TP53', 'Gene', (100, 104))	('type A thymoma', 'Disease', (51, 65))	('associated', 'Reg', (35, 45))	('identified', 'Reg', (110, 120))	('GTF2I', 'Gene', (0, 5))	('NRAS', 'Gene', '4893', (90, 94))	('HRAS', 'Gene', '3265', (84, 88))	('type A thymoma', 'Disease', 'MESH:D013945', (51, 65))	('mutations', 'Var', (71, 80))	('thymoma', 'Phenotype', 'HP:0100522', (58, 65))	('HRAS', 'Gene', (84, 88))	('thymoma', 'Phenotype', 'HP:0100522', (124, 131))	('GTF2I', 'Gene', '2969', (0, 5))
16503	30897085	Mutations of genes encoding regulatory subunit of PIK3 have been reported in a tumorigenic thymic carcinoma cell line, using targeted exome sequencing, predicting the efficacy of PIK3 inhibitors.	('tumor', 'Phenotype', 'HP:0002664', (79, 84))	('PIK3', 'Gene', (179, 183))	('thymic carcinoma', 'Disease', (91, 107))	('tumor', 'Disease', (79, 84))	('carcinoma', 'Phenotype', 'HP:0030731', (98, 107))	('PIK3', 'Gene', '5294', (179, 183))	('thymic carcinoma', 'Disease', 'MESH:D013945', (91, 107))	('Mutations', 'Var', (0, 9))	('PIK3', 'Gene', (50, 54))	('tumor', 'Disease', 'MESH:D009369', (79, 84))	('PIK3', 'Gene', '5294', (50, 54))
16517	30897085	After 20 min rehydration in PBS, cells were incubated for one hour at room temperature with the BM4048 mouse monoclonal anti-cytokeratin (Acris) or mouse monoclonal anti-vimentin (Sigma) antibodies diluted in PBS supplemented with 1% bovine serum albumin as recommended.	('PBS', 'Chemical', 'MESH:D007854', (209, 212))	('vimentin', 'Gene', '7431', (170, 178))	('bovine', 'Species', '9913', (234, 240))	('mouse', 'Species', '10090', (103, 108))	('mouse', 'Species', '10090', (148, 153))	('vimentin', 'Gene', (170, 178))	('PBS', 'Chemical', 'MESH:D007854', (28, 31))	('BM4048', 'Var', (96, 102))
16522	30897085	Primary thymic epithelial cells (5000 cells/well) derived from patients #3147 (AB type), #3146 (B2 type) and #3149 (B2/B3 type) were incubated in "TEC medium" in 96 well plates for twelve hours then treated with 1, 10 or 100 nM rapamycin (Sigma).	('rapamycin', 'Chemical', 'MESH:D020123', (228, 237))	('#3149', 'Var', (109, 114))	('TEC medium', 'Chemical', '-', (147, 157))	('#3146', 'Var', (89, 94))	('patients', 'Species', '9606', (63, 71))
16525	30897085	Primary thymic epithelial cells (5.104 cells/well) derived from thymomas #3146 (B2), #3147 (AB) and #3149 (B2/B3) were incubated in "TEC medium" in 6 well plates for twelve hours then treated with 100 nM rapamycin (Sigma) or 10 muM cisplatin (Promega).	('TEC medium', 'Chemical', '-', (133, 143))	('rapamycin', 'Chemical', 'MESH:D020123', (204, 213))	('thymoma', 'Phenotype', 'HP:0100522', (64, 71))	('#3147', 'Var', (85, 90))	('#3149', 'Var', (100, 105))	('thymomas', 'Disease', (64, 72))	('cisplatin', 'Chemical', 'MESH:D002945', (232, 241))	('thymomas', 'Disease', 'MESH:D013945', (64, 72))
16528	30897085	Mutations of PIK3CA, PIK3R1 and GTF2i have been analyzed using primers in exons 1 to 21 for PIK3CA (GenBank NM06218.3), exons 5 to 16 for PIK3R1 (GenBank NM181523) and exons 5-15 for GTF2I (GenBank NM001518.4) gene (Table 2).	('PIK3CA', 'Gene', (13, 19))	('PIK3R1', 'Gene', '5295', (21, 27))	('PIK3CA', 'Gene', '5290', (92, 98))	('GTF2I', 'Gene', '2969', (183, 188))	('PIK3R1', 'Gene', (21, 27))	('PIK3R1', 'Gene', '5295', (138, 144))	('GTF2i', 'Gene', (32, 37))	('PIK3R1', 'Gene', (138, 144))	('PIK3CA', 'Gene', '5290', (13, 19))	('Mutations', 'Var', (0, 9))	('GTF2i', 'Gene', '2969', (32, 37))	('PIK3CA', 'Gene', (92, 98))	('GTF2I', 'Gene', (183, 188))
16531	30897085	From January 2015 to December 2017, twelve patients (8 males and 4 females, mean age of 66.67 +- 8.99 years (46-83)) who have undergone surgery (Table 1) for thymic epithelial tumors (3154, 2635, 2646, 2836, 3147, 3148, 3152, 3146, 3149, 3150, 2637) or for pleural relapse of a type A thymoma removed 25 months before the surgery (3153) have been included in our study (Table 1).	('thymoma', 'Phenotype', 'HP:0100522', (285, 292))	('pleural', 'Disease', 'MESH:D010995', (257, 264))	('tumor', 'Phenotype', 'HP:0002664', (176, 181))	('thymic epithelial tumors', 'Disease', (158, 182))	('thymic epithelial tumors', 'Disease', 'MESH:C536905', (158, 182))	('type A thymoma', 'Disease', (278, 292))	('patients', 'Species', '9606', (43, 51))	('pleural', 'Disease', (257, 264))	('type A thymoma', 'Disease', 'MESH:D013945', (278, 292))	('epithelial tumor', 'Phenotype', 'HP:0031492', (165, 181))	('3154', 'Var', (184, 188))	('tumors', 'Phenotype', 'HP:0002664', (176, 182))
16534	30897085	According to the WHO pathological classification, tumors were of type AB for 6 patients (2635, 2646, 2836, 3147, 3148, and 3152), B2 for 3 patients (3146, 3149, 3150) and thymic carcinoma for patient 2637 (Table 1).	('3146', 'Var', (149, 153))	('patient', 'Species', '9606', (192, 199))	('tumors', 'Disease', 'MESH:D009369', (50, 56))	('patients', 'Species', '9606', (139, 147))	('2836', 'Var', (101, 105))	('thymic carcinoma', 'Disease', (171, 187))	('2635', 'Var', (89, 93))	('patient', 'Species', '9606', (79, 86))	('patients', 'Species', '9606', (79, 87))	('thymic carcinoma', 'Disease', 'MESH:D013945', (171, 187))	('carcinoma', 'Phenotype', 'HP:0030731', (178, 187))	('tumor', 'Phenotype', 'HP:0002664', (50, 55))	('tumors', 'Phenotype', 'HP:0002664', (50, 56))	('tumors', 'Disease', (50, 56))	('patient', 'Species', '9606', (139, 146))	('3147', 'Var', (107, 111))
16541	30897085	A screening of PIK3 and GTF2I mutations was performed on all tumors.	('PIK3', 'Gene', '5294', (15, 19))	('tumors', 'Disease', (61, 67))	('tumors', 'Disease', 'MESH:D009369', (61, 67))	('GTF2I', 'Gene', (24, 29))	('mutations', 'Var', (30, 39))	('tumor', 'Phenotype', 'HP:0002664', (61, 66))	('PIK3', 'Gene', (15, 19))	('tumors', 'Phenotype', 'HP:0002664', (61, 67))	('GTF2I', 'Gene', '2969', (24, 29))
16542	30897085	Among the 12 tumors, only patient 3149 (B2/ B3 thymoma) carried a non-conservative A/C transversion localized on position 56 of exon 2 of PIK3CA (Fig 2A).	('patient', 'Species', '9606', (26, 33))	('thymoma', 'Disease', 'MESH:D013945', (47, 54))	('A/C transversion', 'Var', (83, 99))	('tumors', 'Disease', (13, 19))	('tumors', 'Disease', 'MESH:D009369', (13, 19))	('tumors', 'Phenotype', 'HP:0002664', (13, 19))	('thymoma', 'Disease', (47, 54))	('thymoma', 'Phenotype', 'HP:0100522', (47, 54))	('PIK3CA', 'Gene', (138, 144))	('B2/ B3', 'Gene', '680', (40, 46))	('B2/ B3', 'Gene', (40, 46))	('tumor', 'Phenotype', 'HP:0002664', (13, 18))	('PIK3CA', 'Gene', '5290', (138, 144))
16543	30897085	We also detected a GTF2I mutation for tumor 3154, reported as a micronodular thymoma with lymphoid stroma, a rare presentation of type A thymoma (Fig 2B).	('tumor', 'Phenotype', 'HP:0002664', (38, 43))	('tumor', 'Disease', (38, 43))	('thymoma', 'Disease', (77, 84))	('thymoma', 'Disease', 'MESH:D013945', (137, 144))	('type A thymoma', 'Disease', 'MESH:D013945', (130, 144))	('GTF2I', 'Gene', (19, 24))	('thymoma', 'Phenotype', 'HP:0100522', (77, 84))	('mutation', 'Var', (25, 33))	('thymoma', 'Disease', (137, 144))	('lymphoid stroma', 'Disease', (90, 105))	('thymoma', 'Disease', 'MESH:D013945', (77, 84))	('GTF2I', 'Gene', '2969', (19, 24))	('tumor', 'Disease', 'MESH:D009369', (38, 43))	('thymoma', 'Phenotype', 'HP:0100522', (137, 144))	('lymphoid stroma', 'Disease', 'MESH:D008223', (90, 105))	('type A thymoma', 'Disease', (130, 144))
16555	30897085	We focused our analysis on cell cultures derived from AB (# 3147), B2 (# 3146) and B2/ B3 (#3149) thymomas at early passages because these cells had good proliferative abilities (~24 hours doubling time), a prerequisite for the study of rapamycin inhibition over a 72-hour period.	('thymomas', 'Disease', 'MESH:D013945', (98, 106))	('B2/ B3', 'Gene', '680', (83, 89))	('#3149', 'Var', (91, 96))	('proliferative abilities', 'CPA', (154, 177))	('# 3146', 'Var', (71, 77))	('thymoma', 'Phenotype', 'HP:0100522', (98, 105))	('B2/ B3', 'Gene', (83, 89))	('rapamycin', 'Chemical', 'MESH:D020123', (237, 246))	('thymomas', 'Disease', (98, 106))
16558	30897085	The activation of mTOR was reduced by ~90%, ~30% and ~ 50% in thymic epithelial cells respectively derived from AB (3147), B2 (3146) and B2/B3 thymomas (Fig 5).	('reduced', 'NegReg', (27, 34))	('thymomas', 'Disease', (143, 151))	('mTOR', 'Gene', (18, 22))	('mTOR', 'Gene', '2475', (18, 22))	('thymomas', 'Disease', 'MESH:D013945', (143, 151))	('activation', 'MPA', (4, 14))	('thymoma', 'Phenotype', 'HP:0100522', (143, 150))	('B2 (3146', 'Var', (123, 131))
16571	30897085	Besides PIK3 regulatory subunits mutations, copy number gain of the anti-apoptotic molecule BCL2 was observed at comparative genomic hybridization of such cell lines, while in vitro siRNA knockdown reduced cell proliferation, and in vivo exposure to a pan-BCL2 inhibitor led to an inhibition of xenograft growth, via a mechanism involving the PIK3/AKT/mTOR pathway.	('AKT', 'Gene', '207', (348, 351))	('BCL2', 'Gene', (256, 260))	('PIK3', 'Gene', '5294', (343, 347))	('PIK3', 'Gene', (343, 347))	('inhibition', 'NegReg', (281, 291))	('cell proliferation', 'CPA', (206, 224))	('gain', 'PosReg', (56, 60))	('mutations', 'Var', (33, 42))	('AKT', 'Gene', (348, 351))	('mTOR', 'Gene', '2475', (352, 356))	('BCL2', 'Gene', '596', (92, 96))	('PIK3', 'Gene', (8, 12))	('mTOR', 'Gene', (352, 356))	('reduced', 'NegReg', (198, 205))	('BCL2', 'Gene', '596', (256, 260))	('xenograft growth', 'CPA', (295, 311))	('PIK3', 'Gene', '5294', (8, 12))	('BCL2', 'Gene', (92, 96))
16572	30897085	Exposure of thymic carcinoma cells to HSP90 inhibitors led to cell cycle arrest and apoptosis, and blocked invasiveness, through the downregulation of HSP90 oncogenic clients, including insulin-like growth factor 1 receptor (IGF-1R), a transmembrane tyrosine kinase receptor frequently overexpressed in thymic carcinomas, CDK4, and PIK3/ Akt.	('PIK3', 'Gene', '5294', (332, 336))	('IGF-1R', 'Gene', '3480', (225, 231))	('CDK4', 'Gene', (322, 326))	('IGF-1R', 'Gene', (225, 231))	('thymic carcinoma', 'Disease', 'MESH:D013945', (303, 319))	('Akt', 'Gene', (338, 341))	('apoptosis', 'CPA', (84, 93))	('arrest', 'Disease', 'MESH:D006323', (73, 79))	('carcinoma', 'Phenotype', 'HP:0030731', (310, 319))	('carcinomas', 'Phenotype', 'HP:0030731', (310, 320))	('HSP90', 'Gene', (38, 43))	('CDK4', 'Gene', '1019', (322, 326))	('blocked invasiveness', 'CPA', (99, 119))	('HSP90', 'Gene', (151, 156))	('downregulation', 'NegReg', (133, 147))	('insulin-like growth factor 1 receptor', 'Gene', (186, 223))	('Akt', 'Gene', '207', (338, 341))	('thymic carcinoma', 'Disease', (12, 28))	('thymic carcinomas', 'Disease', 'MESH:D013945', (303, 320))	('HSP90', 'Gene', '3320', (38, 43))	('HSP90', 'Gene', '3320', (151, 156))	('thymic carcinomas', 'Disease', (303, 320))	('cell cycle arrest', 'Phenotype', 'HP:0011018', (62, 79))	('inhibitors', 'Var', (44, 54))	('thymic carcinoma', 'Disease', 'MESH:D013945', (12, 28))	('carcinoma', 'Phenotype', 'HP:0030731', (19, 28))	('insulin-like growth factor 1 receptor', 'Gene', '3480', (186, 223))	('arrest', 'Disease', (73, 79))	('PIK3', 'Gene', (332, 336))
16573	30897085	Taken together, these data were of significant therapeutic relevance: while pictilisib is mostly developed in breast cancers, which more frequently harbor PIK3 alterations, phase II trials dedicated to thymic epithelial tumors were conducted with the IGF-1R inhibitor cixutumumab, the mTOR inhibitor everolimus, and the CDK inhibitor milciclib [INS], reporting on clinical antitumor activity in advanced, refractory cases.	('tumor', 'Disease', (220, 225))	('thymic epithelial tumors', 'Disease', (202, 226))	('breast cancers', 'Phenotype', 'HP:0003002', (110, 124))	('tumor', 'Disease', 'MESH:D009369', (220, 225))	('tumor', 'Disease', (377, 382))	('tumors', 'Phenotype', 'HP:0002664', (220, 226))	('PIK3', 'Gene', (155, 159))	('epithelial tumor', 'Phenotype', 'HP:0031492', (209, 225))	('PIK3', 'Gene', '5294', (155, 159))	('tumor', 'Disease', 'MESH:D009369', (377, 382))	('mTOR', 'Gene', (285, 289))	('tumor', 'Phenotype', 'HP:0002664', (220, 225))	('cancer', 'Phenotype', 'HP:0002664', (117, 123))	('thymic epithelial tumors', 'Disease', 'MESH:C536905', (202, 226))	('alterations', 'Var', (160, 171))	('IGF-1R', 'Gene', '3480', (251, 257))	('cancers', 'Phenotype', 'HP:0002664', (117, 124))	('IGF-1R', 'Gene', (251, 257))	('tumor', 'Phenotype', 'HP:0002664', (377, 382))	('everolimus', 'Chemical', 'MESH:D000068338', (300, 310))	('mTOR', 'Gene', '2475', (285, 289))	('cixutumumab', 'Chemical', 'MESH:C557414', (268, 279))	('breast cancers', 'Disease', 'MESH:D001943', (110, 124))	('breast cancers', 'Disease', (110, 124))
16586	30897085	Beside the deregulation of the Akt/ mTOR pathway, we have identified for the first time PIK3CA mutation in a type B2/B3 thymoma, which may participate to the deregulation of the Akt-mTOR pathway, among others.	('mTOR', 'Gene', (182, 186))	('mTOR', 'Gene', '2475', (182, 186))	('Akt', 'Gene', (31, 34))	('PIK3CA', 'Gene', '5290', (88, 94))	('participate', 'Reg', (139, 150))	('mTOR', 'Gene', (36, 40))	('Akt', 'Gene', '207', (178, 181))	('thymoma', 'Disease', (120, 127))	('mTOR', 'Gene', '2475', (36, 40))	('thymoma', 'Disease', 'MESH:D013945', (120, 127))	('Akt', 'Gene', '207', (31, 34))	('thymoma', 'Phenotype', 'HP:0100522', (120, 127))	('PIK3CA', 'Gene', (88, 94))	('Akt', 'Gene', (178, 181))	('mutation', 'Var', (95, 103))
16588	30897085	Interestingly, only one of our cases harbored a GTF2I mutations, that was associated at RPPA analysis in this cohort, with lower expression of the apoptosis, cell cycle, DNA damage response, hormone receptor signaling, breast hormone signaling, RAS/MAPK, RTK, and TSC/mTOR pathways.	('mTOR', 'Gene', '2475', (268, 272))	('cell cycle', 'CPA', (158, 168))	('mTOR', 'Gene', (268, 272))	('expression', 'MPA', (129, 139))	('RAS/MAPK', 'Pathway', (245, 253))	('lower', 'NegReg', (123, 128))	('mutations', 'Var', (54, 63))	('RTK', 'Pathway', (255, 258))	('apoptosis', 'CPA', (147, 156))	('GTF2I', 'Gene', (48, 53))	('breast hormone signaling', 'Pathway', (219, 243))	('DNA', 'MPA', (170, 173))	('hormone', 'CPA', (191, 198))	('GTF2I', 'Gene', '2969', (48, 53))
16593	29750002	Immunohistochemically, the epithelial tumor cells reacted positively for cytokeratin AE1/AE3, and some reacted positively for p63, which is expressed in normal thymic epithelial cells.	('reacted', 'Reg', (50, 57))	('tumor', 'Phenotype', 'HP:0002664', (38, 43))	('p63', 'Var', (126, 129))	('epithelial tumor', 'Phenotype', 'HP:0031492', (27, 43))	('AE1', 'Gene', '24779', (85, 88))	('reacted positively', 'Reg', (103, 121))	('AE3', 'Gene', '24781', (89, 92))	('AE3', 'Gene', (89, 92))	('AE1', 'Gene', (85, 88))
16809	33975604	A previous retrospective study developed a radiomics model using LR analysis and realized high diagnostic performance; it reported that the AUCs for differentiating high-risk thymomas from low-risk thymomas were 0.89 for mean0c and 0.87 for a combination of mean0u and entropy.	('mean0c', 'Var', (221, 227))	('thymoma', 'Phenotype', 'HP:0100522', (198, 205))	('thymomas', 'Disease', (198, 206))	('thymomas', 'Disease', (175, 183))	('thymoma', 'Phenotype', 'HP:0100522', (175, 182))	('thymomas', 'Disease', 'MESH:D013945', (198, 206))	('thymomas', 'Disease', 'MESH:D013945', (175, 183))
16835	33192293	Epigenetic modifications, and particularly the gene silencing resulting from hypermethylation of tumor suppressor and DNA repair genes, play a pivotal role in tumor development and progression (Costa-Pinheiro et al.,).	('tumor', 'Disease', 'MESH:D009369', (97, 102))	('tumor', 'Phenotype', 'HP:0002664', (97, 102))	('tumor', 'Phenotype', 'HP:0002664', (159, 164))	('tumor', 'Disease', (97, 102))	('tumor', 'Disease', (159, 164))	('DNA repair genes', 'Gene', (118, 134))	('gene', 'MPA', (47, 51))	('Epigenetic modifications', 'Var', (0, 24))	('hypermethylation', 'Var', (77, 93))	('tumor', 'Disease', 'MESH:D009369', (159, 164))
16837	33192293	However, the study compared very few samples (Bi et al.,), so that larger studies are required to epigenetically characterize those tumors and their different histological subtypes, as well as to understand the links between the epigenetic modifications observed in TAMG tissues and the severity of the MG symptoms.	('tumor', 'Phenotype', 'HP:0002664', (132, 137))	('TAMG', 'Chemical', '-', (266, 270))	('tumors', 'Phenotype', 'HP:0002664', (132, 138))	('tumors', 'Disease', (132, 138))	('tumors', 'Disease', 'MESH:D009369', (132, 138))	('epigenetic modifications', 'Var', (229, 253))
16839	33192293	Collectively, those studies have shown that hypermethylation of those genes is more frequent in thymic carcinomas than in thymomas, but most of those studies did not clarify if thymoma samples were from patients with TAMG or from patients without MG, while others included very few TAMG-associated thymomas, making it not possible to correlate the observed methylation levels with tumor stage, histology, or MG symptoms; in addition, no data were often available from adjacent normal thymic tissues in order to compare the methylation levels between pathological and healthy samples.	('thymoma', 'Disease', (298, 305))	('thymoma', 'Disease', 'MESH:D013945', (122, 129))	('thymoma', 'Phenotype', 'HP:0100522', (298, 305))	('thymic carcinomas', 'Disease', 'MESH:D013953', (96, 113))	('thymoma', 'Disease', (177, 184))	('thymomas', 'Disease', 'MESH:D013945', (298, 306))	('tumor', 'Phenotype', 'HP:0002664', (381, 386))	('carcinomas', 'Phenotype', 'HP:0030731', (103, 113))	('TAMG', 'Chemical', '-', (282, 286))	('thymoma', 'Phenotype', 'HP:0100522', (177, 184))	('thymoma', 'Disease', (122, 129))	('patients', 'Species', '9606', (203, 211))	('thymoma', 'Phenotype', 'HP:0100522', (122, 129))	('thymomas', 'Disease', (298, 306))	('TAMG', 'Chemical', '-', (217, 221))	('thymomas', 'Disease', 'MESH:D013945', (122, 130))	('hypermethylation', 'Var', (44, 60))	('thymomas', 'Disease', (122, 130))	('thymoma', 'Disease', 'MESH:D013945', (298, 305))	('tumor', 'Disease', (381, 386))	('patients', 'Species', '9606', (230, 238))	('thymic carcinomas', 'Disease', (96, 113))	('thymoma', 'Disease', 'MESH:D013945', (177, 184))	('tumor', 'Disease', 'MESH:D009369', (381, 386))
16841	33192293	The study revealed an increased prevalence of aneuploidy among MG+ thymomas, but the MG status was not associated with any methylation signature (Radovich et al.,).	('thymomas', 'Disease', 'MESH:D013945', (67, 75))	('thymoma', 'Phenotype', 'HP:0100522', (67, 74))	('Rad', 'Gene', (146, 149))	('Rad', 'Gene', '6236', (146, 149))	('aneuploidy', 'Disease', (46, 56))	('MG+', 'Var', (63, 66))	('thymomas', 'Disease', (67, 75))	('aneuploidy', 'Disease', 'MESH:D000782', (46, 56))
16861	33192293	Negative controls are DNA samples from patients with colorectal cancer that showed hypomethylation (promoter methylation levels ranging from 1-5%) of the investigated genes in both cancer and adjacent healthy mucosa (Supplementary Figure 1).	('cancer', 'Phenotype', 'HP:0002664', (181, 187))	('patients', 'Species', '9606', (39, 47))	('cancer', 'Disease', (64, 70))	('cancer', 'Disease', 'MESH:D009369', (64, 70))	('colorectal cancer', 'Disease', 'MESH:D015179', (53, 70))	('hypomethylation', 'Var', (83, 98))	('cancer', 'Disease', 'MESH:D009369', (181, 187))	('colorectal cancer', 'Phenotype', 'HP:0003003', (53, 70))	('cancer', 'Disease', (181, 187))	('cancer', 'Phenotype', 'HP:0002664', (64, 70))	('colorectal cancer', 'Disease', (53, 70))
16874	33192293	All the investigated genes were largely demethylated in thymomas, and no correlation with the demographic (age and gender) or clinical data (tumor histology and grade) was observed (Supplementary Table 1).	('tumor', 'Disease', 'MESH:D009369', (141, 146))	('tumor', 'Phenotype', 'HP:0002664', (141, 146))	('thymoma', 'Phenotype', 'HP:0100522', (56, 63))	('thymomas', 'Disease', 'MESH:D013945', (56, 64))	('thymomas', 'Disease', (56, 64))	('tumor', 'Disease', (141, 146))	('demethylated', 'Var', (40, 52))
16879	33192293	Collectively, previous studies in TETs have shown that these genes are frequently hypermethylated in thymic carcinomas, but studies investigating their methylation levels in thymomas have provided conflicting and inconclusive results.	('thymic carcinomas', 'Disease', 'MESH:D013953', (101, 118))	('carcinomas', 'Phenotype', 'HP:0030731', (108, 118))	('thymoma', 'Phenotype', 'HP:0100522', (174, 181))	('thymomas', 'Disease', (174, 182))	('hypermethylated', 'Var', (82, 97))	('thymomas', 'Disease', 'MESH:D013945', (174, 182))	('thymic carcinomas', 'Disease', (101, 118))
16898	33192293	Previous studies in Asian samples have shown that MLH1, MGMT, CDKN2A, and RASSF1A genes are hypomethylated in thymomas as compared with thymic carcinomas or neuroendocrine tumors (Hirabayashi et al.,; Suzuki et al.,; Chen et al.,; Mokhtar et al.,; Kajiura et al.,).	('RASSF1A', 'Gene', (74, 81))	('MLH1', 'Gene', '4292', (50, 54))	('carcinomas', 'Phenotype', 'HP:0030731', (143, 153))	('MLH1', 'Gene', (50, 54))	('tumor', 'Phenotype', 'HP:0002664', (172, 177))	('MGMT', 'Gene', (56, 60))	('RASSF1A', 'Gene', '11186', (74, 81))	('thymomas', 'Disease', (110, 118))	('thymomas', 'Disease', 'MESH:D013945', (110, 118))	('MGMT', 'Gene', '4255', (56, 60))	('tumors', 'Phenotype', 'HP:0002664', (172, 178))	('CDKN2A', 'Gene', '1029', (62, 68))	('hypomethylated', 'Var', (92, 106))	('thymic carcinomas or neuroendocrine tumors', 'Disease', 'MESH:D013953', (136, 178))	('CDKN2A', 'Gene', (62, 68))	('thymic carcinomas or neuroendocrine tumors', 'Disease', (136, 178))	('thymoma', 'Phenotype', 'HP:0100522', (110, 117))	('neuroendocrine tumors', 'Phenotype', 'HP:0100634', (157, 178))
16921	33178562	Other significant negatives in the evaluation for hepatitis included negative antinuclear antibody; anti-M2; anti-smooth muscle; and anti-LKM.	('anti-LKM', 'Var', (133, 141))	('negative antinuclear antibody', 'Phenotype', 'HP:0003493', (69, 98))	('antinuclear antibody', 'Protein', (78, 98))	('negative', 'NegReg', (69, 77))	('hepatitis', 'Disease', (50, 59))	('hepatitis', 'Phenotype', 'HP:0012115', (50, 59))	('anti-M2', 'Var', (100, 107))	('hepatitis', 'Disease', 'MESH:D056486', (50, 59))	('anti-smooth', 'Var', (109, 120))
16987	33178562	describes the first patient affected with GS to carry 2 missense mutations in BAFF-R, P21R/H159Y, associated with low BAFF-R expression and low B-cell counts.	('P21R', 'Var', (86, 90))	('BAFF-R', 'Gene', (118, 124))	('P21R', 'SUBSTITUTION', 'None', (86, 90))	('BAFF-R', 'Gene', '115650', (78, 84))	('H159Y', 'Var', (91, 96))	('H159Y', 'SUBSTITUTION', 'None', (91, 96))	('expression', 'MPA', (125, 135))	('missense mutations', 'Var', (56, 74))	('patient', 'Species', '9606', (20, 27))	('BAFF-R', 'Gene', (78, 84))	('low', 'NegReg', (114, 117))	('BAFF-R', 'Gene', '115650', (118, 124))
17012	33178562	Lower serum bactericidal activity to H. pylori have been observed in primary antibody deficiency disorders like XLA and CVID, leading some to postulate that hypogammaglobulinemic states, causes immune dysregulation and predisposes to chronic infections like H. pylori.	('hypogammaglobulinemic states', 'Phenotype', 'HP:0004313', (157, 185))	('immune', 'MPA', (194, 200))	('XLA', 'Disease', (112, 115))	('Lower', 'NegReg', (0, 5))	('H. pylori', 'Disease', (258, 267))	('H. pylori', 'Species', '210', (37, 46))	('predisposes to', 'Reg', (219, 233))	('serum bactericidal activity', 'MPA', (6, 33))	('H. pylori', 'Species', '210', (258, 267))	('immune dysregulation', 'Phenotype', 'HP:0002958', (194, 214))	('chronic infections', 'Phenotype', 'HP:0031035', (234, 252))	('hypogammaglobulinemic', 'Var', (157, 178))	('causes', 'Reg', (187, 193))	('CVID', 'Disease', (120, 124))	('infections', 'Disease', 'MESH:D007239', (242, 252))	('CVID', 'Disease', 'MESH:D017074', (120, 124))	('infections', 'Disease', (242, 252))	('antibody deficiency', 'Phenotype', 'HP:0004313', (77, 96))	('primary antibody deficiency disorders', 'Disease', 'MESH:D000081207', (69, 106))	('primary antibody deficiency disorders', 'Disease', (69, 106))
17044	32264857	Myasthenia gravis (MG) is a neuromuscular junction disease that is mostly associated with autoimmune antibodies, such as anti-acetylcholine receptor (AChR)-antibody (Ab).	('anti-acetylcholine', 'Var', (121, 139))	('acetylcholine', 'Chemical', 'MESH:D000109', (126, 139))	('autoimmune antibodies', 'Phenotype', 'HP:0002960', (90, 111))	('neuromuscular junction disease', 'Disease', 'MESH:D020511', (28, 58))	('associated', 'Reg', (74, 84))	('Myasthenia gravis', 'Disease', (0, 17))	('Myasthenia gravis', 'Disease', 'MESH:D009157', (0, 17))	('Myasthenia', 'Phenotype', 'HP:0003473', (0, 10))	('neuromuscular junction disease', 'Disease', (28, 58))
17075	32264857	She had HLA-A*11:01/24:02, B*39:01/51:01, C*07:02/14:02, DRB1*04:5/11:01, DRB3*02:02, DRB4*01:03, DQA1*03:03/05:05, DQB1*03:01/04:01, DPA1*01:03/02:02, and DPB1*02:01/05:01 (Table 3).	('HLA-A', 'Gene', (8, 13))	('B*39:01/51:01', 'Var', (27, 40))	('C*07:02/14:02', 'Var', (42, 55))	('DQB1', 'Gene', '3119', (116, 120))	('DPB1', 'Gene', '3115', (156, 160))	('DQA1*03:03/05:05', 'Var', (98, 114))	('DPA1*01:03/02:02', 'Var', (134, 150))	('DRB1', 'Gene', (57, 61))	('DRB4', 'Gene', (86, 90))	('DRB1', 'Gene', '3123', (57, 61))	('DRB3*02:02', 'Var', (74, 84))	('DRB4', 'Gene', '3126', (86, 90))	('DPB1', 'Gene', (156, 160))	('DQB1', 'Gene', (116, 120))	('HLA-A', 'Gene', '3105', (8, 13))
17089	32264857	reported a case of APS-2 similar to the current case; their patient had AD, HT and AIH with MG without thymoma and with no bronchial asthma but had HLA-A23, B52/62, and DR11/15.	('AD', 'Phenotype', 'HP:0008207', (72, 74))	('patient', 'Species', '9606', (60, 67))	('bronchial asthma', 'Disease', 'MESH:D001249', (123, 139))	('DR11', 'Gene', '55717', (169, 173))	('APS-2', 'Gene', (19, 24))	('bronchial asthma', 'Phenotype', 'HP:0002099', (123, 139))	('DR11', 'Gene', (169, 173))	('bronchial asthma', 'Disease', (123, 139))	('APS-2', 'Gene', '170685', (19, 24))	('thymoma', 'Disease', 'MESH:D013945', (103, 110))	('AD', 'Disease', 'MESH:D000544', (72, 74))	('B52/62', 'Var', (157, 163))	('HT', 'Phenotype', 'HP:0000872', (76, 78))	('HLA-A', 'Gene', '3105', (148, 153))	('thymoma', 'Disease', (103, 110))	('HLA-A', 'Gene', (148, 153))	('AD', 'Disease', (72, 74))	('thymoma', 'Phenotype', 'HP:0100522', (103, 110))
17109	29472706	ATM kinase has been established as a central player in DNA double-strand break repair and its deficiency causes ataxia telangiectasia, a rare, multi-system disease with no cure.	('causes', 'Reg', (105, 111))	('multi-system disease', 'Disease', (143, 163))	('ataxia telangiectasia', 'Disease', (112, 133))	('telangiectasia', 'Phenotype', 'HP:0001009', (119, 133))	('ataxia telangiectasia', 'Disease', 'MESH:D001260', (112, 133))	('deficiency', 'Var', (94, 104))	('multi-system disease', 'Disease', 'MESH:C564969', (143, 163))	('ataxia', 'Phenotype', 'HP:0001251', (112, 118))
17115	29472706	Mutations in the ataxia telangiectasia mutated (ATM) gene cause ataxia telangiectasia (A-T) syndrome, a rare disease that exhibits cancer predisposition, neurodegeneration, immunodeficiency, and premature aging of the skin and hair.	('immunodeficiency', 'Phenotype', 'HP:0002721', (173, 189))	('neurodegeneration', 'Phenotype', 'HP:0002180', (154, 171))	('telangiectasia', 'Phenotype', 'HP:0001009', (24, 38))	('cancer', 'Disease', 'MESH:D009369', (131, 137))	('neurodegeneration', 'Disease', 'MESH:D019636', (154, 171))	('telangiectasia', 'Phenotype', 'HP:0001009', (71, 85))	('Mutations', 'Var', (0, 9))	('ATM', 'Gene', (48, 51))	('ataxia', 'Phenotype', 'HP:0001251', (17, 23))	('ataxia telangiectasia (A-T) syndrome', 'Disease', 'MESH:D001260', (64, 100))	('immunodeficiency', 'Disease', (173, 189))	('neurodegeneration', 'Disease', (154, 171))	('cancer', 'Disease', (131, 137))	('ataxia', 'Phenotype', 'HP:0001251', (64, 70))	('cause', 'Reg', (58, 63))	('cancer', 'Phenotype', 'HP:0002664', (131, 137))	('ataxia telangiectasia mutated', 'Gene', '11920', (17, 46))	('ataxia telangiectasia mutated', 'Gene', (17, 46))	('immunodeficiency', 'Disease', 'MESH:D007153', (173, 189))
17119	29472706	The majority of A-T patients have mutations in ATMgene that result in complete loss of the protein.	('loss', 'NegReg', (79, 83))	('A-T', 'Disease', 'MESH:D001260', (16, 19))	('protein', 'Protein', (91, 98))	('ATMgene', 'Gene', (47, 54))	('patients', 'Species', '9606', (20, 28))	('A-T', 'Disease', (16, 19))	('mutations', 'Var', (34, 43))
17128	29472706	The possibility of reinserting ATM protein or correcting point mutations as soon as the disease is diagnosed can be predicted to be of great benefit for A-T patients; however, whether and to what extent A-T phenotypes can be rescued, once ATM functions are restored, need to be tested in preclinical experiments.	('A-T', 'Disease', (153, 156))	('A-T', 'Disease', (203, 206))	('A-T', 'Disease', 'MESH:D001260', (153, 156))	('patients', 'Species', '9606', (157, 165))	('correcting', 'Var', (46, 56))	('A-T', 'Disease', 'MESH:D001260', (203, 206))	('point mutations', 'Var', (57, 72))
17143	29472706	More consistently, transgenic MEFs, treated overnight with 1 muM 4-OHT before gamma-irradiation, activated an Atm-dependent signaling cascade similarly to Atm+/- MEFs (Fig.	('Atm', 'Gene', (110, 113))	('Atm', 'Gene', (155, 158))	('MEFs', 'CellLine', 'CVCL:9115', (30, 34))	('transgenic', 'Var', (19, 29))	('transgenic', 'Species', '10090', (19, 29))	('MEFs', 'CellLine', 'CVCL:9115', (162, 166))	('4-OHT', 'Chemical', 'MESH:C032278', (65, 70))	('Atm', 'Gene', '11920', (155, 158))	('Atm', 'Gene', '11920', (110, 113))	('activated', 'PosReg', (97, 106))
17153	29472706	Analysis of T-cell development revealed that the percentage of CD4-positive cells was partially recovered after tamoxifen in transgenic mice compared with knockout mice, but not in transgenic mice that were not treated with tamoxifen (Fig.	('mice', 'Species', '10090', (136, 140))	('CD4', 'Gene', (63, 66))	('transgenic', 'Var', (125, 135))	('mice', 'Species', '10090', (192, 196))	('tamoxifen', 'Chemical', 'MESH:D013629', (112, 121))	('mice', 'Species', '10090', (164, 168))	('CD4', 'Gene', '12504', (63, 66))	('tamoxifen', 'Chemical', 'MESH:D013629', (224, 233))	('transgenic mice', 'Species', '10090', (125, 140))	('transgenic mice', 'Species', '10090', (181, 196))
17167	29472706	Notably, transgenic males were able to fertilize females and to give pups within 2 months of continuous breeding after tamoxifen treatment (Fig.	('transgenic', 'Species', '10090', (9, 19))	('transgenic', 'Var', (9, 19))	('tamoxifen', 'Chemical', 'MESH:D013629', (119, 128))	('fertilize', 'CPA', (39, 48))
17191	29472706	5e, right panels) did not reveal major differences in the cerebella and in Purkinje cell morphology and number between Atm+/+ and Atm TgERT2-LBDAtm-/- mice suggesting that transgene expression preserved cerebella integrity in an Atm knockout background.	('Atm', 'Gene', (144, 147))	('mice', 'Species', '10090', (151, 155))	('cerebella integrity', 'CPA', (203, 222))	('Atm', 'Gene', '11920', (229, 232))	('Atm', 'Gene', '11920', (119, 122))	('ERT2', 'Gene', '26417', (136, 140))	('Atm', 'Gene', '11920', (130, 133))	('Atm', 'Gene', (229, 232))	('transgene', 'Var', (172, 181))	('Atm', 'Gene', '11920', (144, 147))	('ERT2', 'Gene', (136, 140))	('Atm', 'Gene', (130, 133))	('Atm', 'Gene', (119, 122))
17195	29472706	A-T is a highly pleiotropic autosomal recessive human disorder that is caused by mutations in the ATM gene, located on the long arm of chromosome 11 (q22-23).	('autosomal recessive human disorder', 'Disease', 'MESH:D030342', (28, 62))	('ATM', 'Gene', (98, 101))	('caused by', 'Reg', (71, 80))	('autosomal recessive human disorder', 'Disease', (28, 62))	('A-T', 'Disease', (0, 3))	('mutations', 'Var', (81, 90))	('A-T', 'Disease', 'MESH:D001260', (0, 3))
17202	29472706	Interestingly, we found that Atm reactivation in the meiotic phase was sufficient to restore male fertility, providing novel biological insights with potential implications in the reproductive medicine.	('Atm', 'Gene', '11920', (29, 32))	('reactivation', 'Var', (33, 45))	('male fertility', 'CPA', (93, 107))	('Atm', 'Gene', (29, 32))	('restore', 'PosReg', (85, 92))
17221	29472706	To explain the later cerebellar phenotype it has been proposed that defective Atm might permit specific neuronal cell population, such as Purkinje cells to accumulate mutations that lead to functional deficits later in life.	('Atm', 'Gene', '11920', (78, 81))	('mutations', 'Var', (167, 176))	('Atm', 'Gene', (78, 81))
17247	29472706	DNA-PK inhibitor (NU7026:10 muM, Sigma) and ATM inhibitor (Kudo55933:10 muM, SelleckChem, Huston, TX, USA) were added to the medium 1 h before bleomycin (5 nM), NCS (500ng/ml, Sigma), and gamma-irradiation (10 Gy) and cells were collected 1 h later, if not indicated.	('bleomycin', 'Chemical', 'MESH:D001761', (143, 152))	('Kudo55933', 'Chemical', '-', (59, 68))	('DNA-PK', 'Gene', (0, 6))	('NU7026', 'Chemical', 'MESH:C479235', (18, 24))	('NU7026:10', 'Var', (18, 27))	('DNA-PK', 'Gene', '19090', (0, 6))
17251	29472706	Primary antibodies were used overnight at the following dilutions: anti-mouse Atm S1987p (1:500), produced by immunization with the synthetic peptide SPTFEEGSpQGTTISS (Becton Dickinson), anti-Smc1 S957p (1:500, Rockland Immunochemicals, Limerick, PA, USA), anti-p53 S15p (1:500, Cell Signaling, Danvers, MA, USA), anti-p53 (1:1000, Santa Cruz, Dallas, TX, USA), anti-gammaH2AX (1: 1000 Upstate Biotechnology), and anti-Kap-1 S824p (1:700, Bethyl Labs, Montgomery, TX, USA), anti-tubulin (1:10,000, Sigma), anti-Actin (1:2000, Sigma), anti-Histone H3 (1:1000, Abcam, Cambridge, UK).	('p53', 'Gene', '22060', (319, 322))	('1:700', 'Var', (432, 437))	('p53', 'Gene', (262, 265))	('anti-Kap-1', 'Var', (414, 424))	('Biotec', 'Chemical', '-', (394, 400))	('gammaH2AX', 'Gene', '15270', (367, 376))	('mouse', 'Species', '10090', (72, 77))	('Atm', 'Gene', '11920', (78, 81))	('Smc1', 'Gene', '24061', (192, 196))	('p53', 'Gene', '22060', (262, 265))	('p53', 'Gene', (319, 322))	('Smc1', 'Gene', (192, 196))	('anti-Histone', 'Var', (534, 546))	('anti-Actin', 'Protein', (506, 516))	('anti-tubulin', 'Protein', (474, 486))	('gammaH2AX', 'Gene', (367, 376))	('Atm', 'Gene', (78, 81))
17263	29472706	Single-cell suspensions of thymocytes were stained for 20 min with anti-CD4-PE, anti-CD8-FITC, or anti-TCR-beta-APC antibodies (1:50; Miltenyi Biotec, Bologna, Italy) at 4  C. Dead cells were stained with SYTOX  Blue (Thermo Fisher Scientific-Life Technologies, Waltham, MA, USA).	('CD8-FITC', 'Chemical', '-', (85, 93))	('anti-CD8-FITC', 'Var', (80, 93))	('Biotec', 'Chemical', '-', (143, 149))	('SYTOX  Blue', 'Chemical', '-', (205, 216))	('CD4', 'Gene', (72, 75))	('CD4', 'Gene', '12504', (72, 75))
17274	27623618	Myasthenia gravis (MG) is an organ-specific, autoimmune disorder, which is generally mediated by anti-acetylcholine receptor (AChR) or, less frequently, by anti-muscle-specific receptor tyrosine kinase (MuSK) antibodies (Ab) at the neuromuscular junction.	('autoimmune disorder', 'Disease', (45, 64))	('MG', 'Disease', 'MESH:D000080343', (19, 21))	('autoimmune disorder', 'Disease', 'MESH:D001327', (45, 64))	('anti-acetylcholine', 'Var', (97, 115))	('mediated', 'Reg', (85, 93))	('Myasthenia gravis', 'Disease', (0, 17))	('Myasthenia gravis', 'Disease', 'MESH:D009157', (0, 17))	('Myasthenia', 'Phenotype', 'HP:0003473', (0, 10))	('autoimmune disorder', 'Phenotype', 'HP:0002960', (45, 64))	('acetylcholine', 'Chemical', 'MESH:D000109', (102, 115))
17306	27623618	Titin-Ab and RyR-Ab have a 70 % positive predictive value, and 95 % sensitivity and specificity for a thymoma in MG.	('MG', 'Disease', 'MESH:D000080343', (113, 115))	('thymoma', 'Disease', 'MESH:D013945', (102, 109))	('Titin', 'Gene', '7273', (0, 5))	('thymoma', 'Disease', (102, 109))	('Titin', 'Gene', (0, 5))	('RyR-Ab', 'Var', (13, 19))	('thymoma', 'Phenotype', 'HP:0100522', (102, 109))
17313	27623618	Considering that titin-Ab and RyR-Ab have been mostly associated with invasive/malignant types of thymoma, in the presence of such antibodies in MG or GrM-MG patients, the employment of a thymectomy technique that assures complete resection is decisive for the prognosis.	('thymoma', 'Disease', 'MESH:D013945', (98, 105))	('thymoma', 'Disease', (98, 105))	('titin', 'Gene', (17, 22))	('GrM-MG', 'Disease', (151, 157))	('thymoma', 'Phenotype', 'HP:0100522', (98, 105))	('RyR-Ab', 'Var', (30, 36))	('MG', 'Disease', 'MESH:D000080343', (155, 157))	('GrM-MG', 'Disease', 'MESH:D000080343', (151, 157))	('MG', 'Disease', 'MESH:D000080343', (145, 147))	('patients', 'Species', '9606', (158, 166))	('associated', 'Reg', (54, 64))	('titin', 'Gene', '7273', (17, 22))
17422	22792269	The Dlc1 gene has multiple transcriptional isoforms and we have previously established a mouse strain containing a gene trap (gt) insertion, which specifically reduces the expression of the 6.1 kb isoform (isoform 2).	('gt', 'Gene', (126, 128))	('Dlc1', 'Gene', (4, 8))	('insertion', 'Var', (130, 139))	('expression', 'MPA', (172, 182))	('reduces', 'NegReg', (160, 167))	('mouse', 'Species', '10090', (89, 94))
17427	22792269	We have found tumour specific selective hypermethylation of the Dlc1 isoform 2 promoter and reduction of the corresponding protein expression in thymic lymphoma (TL) and thymic epithelial carcinoma (TEC) derived from the thymic tumours.	('tumour', 'Disease', (228, 234))	('thymic epithelial carcinoma', 'Disease', (170, 197))	('reduction', 'NegReg', (92, 101))	('hypermethylation', 'Var', (40, 56))	('tumour', 'Phenotype', 'HP:0002664', (14, 20))	('tumour', 'Disease', 'MESH:D009369', (14, 20))	('thymic tumours', 'Disease', 'MESH:D013953', (221, 235))	('lymphoma', 'Phenotype', 'HP:0002665', (152, 160))	('protein expression', 'MPA', (123, 141))	('tumour', 'Disease', (14, 20))	('epithelial carcinoma', 'Phenotype', 'HP:0031492', (177, 197))	('thymic epithelial carcinoma', 'Disease', 'MESH:C536905', (170, 197))	('thymic lymphoma', 'Disease', 'MESH:D013953', (145, 160))	('carcinoma', 'Phenotype', 'HP:0030731', (188, 197))	('tumours', 'Phenotype', 'HP:0002664', (228, 235))	('Dlc1', 'Gene', (64, 68))	('thymic tumours', 'Disease', (221, 235))	('thymic lymphoma', 'Disease', (145, 160))	('tumour', 'Phenotype', 'HP:0002664', (228, 234))	('tumour', 'Disease', 'MESH:D009369', (228, 234))
17431	22792269	The Dlc1 gene has been found frequently deleted or, down regulated by promoter hypermethylation in breast, lung, liver, colon and prostate tumours.	('tumours', 'Phenotype', 'HP:0002664', (139, 146))	('Dlc1', 'Gene', (4, 8))	('down regulated', 'NegReg', (52, 66))	('liver', 'Disease', (113, 118))	('lung', 'Disease', (107, 111))	('tumour', 'Phenotype', 'HP:0002664', (139, 145))	('colon and prostate tumours', 'Disease', 'MESH:D015179', (120, 146))	('breast', 'Disease', (99, 105))	('promoter hypermethylation', 'Var', (70, 95))
17432	22792269	A recent study using representational oligonucleotide microarray analysis has shown heterozygous deletion of Dlc1 locus in ~50% of liver, breast and lung tumours and 70% of colon cancers.	('tumour', 'Phenotype', 'HP:0002664', (154, 160))	('tumours', 'Phenotype', 'HP:0002664', (154, 161))	('oligonucleotide', 'Chemical', 'MESH:D009841', (38, 53))	('cancer', 'Phenotype', 'HP:0002664', (179, 185))	('colon cancers', 'Disease', (173, 186))	('breast and lung tumours', 'Disease', 'MESH:D008175', (138, 161))	('colon cancers', 'Phenotype', 'HP:0003003', (173, 186))	('cancers', 'Phenotype', 'HP:0002664', (179, 186))	('Dlc1', 'Gene', (109, 113))	('colon cancers', 'Disease', 'MESH:D015179', (173, 186))	('liver', 'Disease', (131, 136))	('deletion', 'Var', (97, 105))
17433	22792269	In vitro studies have shown that transfection of the Dlc1 gene can inhibit cell growth, abolish in vivo tumour formation and induce apoptosis.	('apoptosis', 'CPA', (132, 141))	('transfection', 'Var', (33, 45))	('inhibit', 'NegReg', (67, 74))	('tumour', 'Disease', (104, 110))	('cell growth', 'CPA', (75, 86))	('induce', 'Reg', (125, 131))	('tumour', 'Phenotype', 'HP:0002664', (104, 110))	('tumour', 'Disease', 'MESH:D009369', (104, 110))	('abolish', 'NegReg', (88, 95))	('Dlc1', 'Gene', (53, 57))
17436	22792269	We have previously established a mouse strain containing a gene trap insertion, which specifically reduces the expression of the 6.1 kb transcriptional isoform (isoform 2) of Dlc1, thus creating a hypomorph.	('Dlc1', 'Gene', (175, 179))	('insertion', 'Var', (69, 78))	('expression', 'MPA', (111, 121))	('mouse', 'Species', '10090', (33, 38))	('reduces', 'NegReg', (99, 106))
17442	22792269	Therefore, it is hypothesized that activation of the Rho pathway through loss of the Dlc1 RhoGAP expression will complement the Ras oncogene in cell transformation in vivo.	('RhoGAP', 'Gene', '75404', (90, 96))	('Rho pathway', 'Pathway', (53, 64))	('loss', 'Var', (73, 77))	('RhoGAP', 'Gene', (90, 96))
17453	22792269	This revealed significantly lower survival in the heterozygous KD gene trapped mice compared with K+ mice (P value = 0.0077, Figure 3A).	('lower', 'NegReg', (28, 33))	('survival', 'CPA', (34, 42))	('mice', 'Species', '10090', (79, 83))	('KD gene trapped', 'Var', (63, 78))	('mice', 'Species', '10090', (101, 105))
17479	22792269	To determine that the tumours were due to the activation of K-Ras2G12D allele, we extracted cellular RNA from the primary tumours and the tumour cell lines and then performed pyrosequencing based mutation analysis for K-Ras2G12D mutation (Figure 6).	('tumour', 'Disease', 'MESH:D009369', (122, 128))	('tumour', 'Disease', 'MESH:D009369', (22, 28))	('tumours', 'Phenotype', 'HP:0002664', (22, 29))	('tumours', 'Disease', 'MESH:D009369', (22, 29))	('tumour', 'Disease', (22, 28))	('tumours', 'Phenotype', 'HP:0002664', (122, 129))	('tumour', 'Disease', (122, 128))	('tumour', 'Phenotype', 'HP:0002664', (138, 144))	('tumours', 'Disease', (22, 29))	('tumours', 'Disease', 'MESH:D009369', (122, 129))	('primary tumours', 'Disease', (114, 129))	('primary tumours', 'Disease', 'MESH:D009369', (114, 129))	('tumour', 'Phenotype', 'HP:0002664', (22, 28))	('tumour', 'Disease', 'MESH:D009369', (138, 144))	('tumours', 'Disease', (122, 129))	('K-Ras2G12D mutation', 'Var', (218, 237))	('tumour', 'Phenotype', 'HP:0002664', (122, 128))	('tumour', 'Disease', (138, 144))
17480	22792269	All the primary tumours showed expression of the mutant K-Ras2 allele (Figure 6F).	('K-Ras2', 'Gene', '16653', (56, 62))	('mutant', 'Var', (49, 55))	('K-Ras2', 'Gene', (56, 62))	('primary tumours', 'Disease', 'MESH:D009369', (8, 23))	('tumour', 'Phenotype', 'HP:0002664', (16, 22))	('tumours', 'Phenotype', 'HP:0002664', (16, 23))	('primary tumours', 'Disease', (8, 23))
17481	22792269	However, the expression of the mutant allele was less than 50% in the primary tumours as revealed by the pyrogram, presumably due to normal cell infiltration (Figure 6D & E).	('tumours', 'Phenotype', 'HP:0002664', (78, 85))	('mutant', 'Var', (31, 37))	('primary tumours', 'Disease', (70, 85))	('primary tumours', 'Disease', 'MESH:D009369', (70, 85))	('tumour', 'Phenotype', 'HP:0002664', (78, 84))
17482	22792269	In the tumour cell lines the mutant and wild type allele were expressed at equal levels indicating absence of normal cell contamination (Figure 6F).	('tumour', 'Disease', (7, 13))	('tumour', 'Phenotype', 'HP:0002664', (7, 13))	('mutant', 'Var', (29, 35))	('tumour', 'Disease', 'MESH:D009369', (7, 13))
17487	22792269	The frequency of methylation in the primary tumour also matched with the methylation pattern observed in the cell line DNA.	('tumour', 'Disease', 'MESH:D009369', (44, 50))	('methylation', 'Var', (17, 28))	('tumour', 'Disease', (44, 50))	('tumour', 'Phenotype', 'HP:0002664', (44, 50))
17488	22792269	Deletion of Dlc1 locus has been reported to be responsible for loss of protein expression in different human tumours.	('tumours', 'Phenotype', 'HP:0002664', (109, 116))	('tumour', 'Phenotype', 'HP:0002664', (109, 115))	('human', 'Species', '9606', (103, 108))	('tumours', 'Disease', 'MESH:D009369', (109, 116))	('tumours', 'Disease', (109, 116))	('protein expression', 'MPA', (71, 89))	('Dlc1', 'Gene', (12, 16))	('loss', 'NegReg', (63, 67))	('Deletion', 'Var', (0, 8))
17489	22792269	The LOH analysis revealed no significant loss at the Dlc1 locus in the majority of tumours; however, we have found microsatellite size alteration for the D8Mit293 marker in one tumour as well as the corresponding cell line DNA (Figure 8C).	('tumour', 'Disease', (83, 89))	('tumours', 'Disease', (83, 90))	('tumour', 'Disease', 'MESH:D009369', (177, 183))	('tumour', 'Disease', (177, 183))	('alteration', 'Reg', (135, 145))	('D8Mit293', 'Var', (154, 162))	('microsatellite', 'Var', (115, 129))	('tumour', 'Phenotype', 'HP:0002664', (83, 89))	('tumour', 'Disease', 'MESH:D009369', (83, 89))	('tumours', 'Phenotype', 'HP:0002664', (83, 90))	('tumour', 'Phenotype', 'HP:0002664', (177, 183))	('Mit293', 'CellLine', 'CVCL:0045', (156, 162))	('tumours', 'Disease', 'MESH:D009369', (83, 90))
17499	22792269	To determine if the T-lymphoma cells with lower Dlc1 levels showed increased extravasation and migration, a transendothalial migration assay was carried out (Figure 10).	('extravasation', 'MPA', (77, 90))	('Dlc1', 'Gene', (48, 52))	('lymphoma', 'Phenotype', 'HP:0002665', (22, 30))	('lower', 'Var', (42, 47))	('T-lymphoma', 'Disease', (20, 30))	('increased', 'PosReg', (67, 76))	('migration', 'CPA', (95, 104))	('T-lymphoma', 'Disease', 'MESH:D016399', (20, 30))	('T-lymphoma', 'Phenotype', 'HP:0012190', (20, 30))
17506	22792269	The aberrant use of one promoter over another in genes, such as TGFB3, LEF1 and CYP19A1, is directly linked to cancerous cell growth (reviewed by).	('CYP19A1', 'Gene', '13075', (80, 87))	('cancerous', 'Disease', (111, 120))	('aberrant', 'Var', (4, 12))	('cancer', 'Phenotype', 'HP:0002664', (111, 117))	('LEF1', 'Gene', (71, 75))	('CYP19A1', 'Gene', (80, 87))	('cancerous', 'Disease', 'MESH:D009369', (111, 120))	('TGFB3', 'Gene', (64, 69))	('TGFB3', 'Gene', '21809', (64, 69))	('linked', 'Reg', (101, 107))	('LEF1', 'Gene', '16842', (71, 75))
17515	22792269	The Dlc1 genetrap alone is unable to induce tumours however, in presence of K-Ras2G12D mutation, it increases tumour and metastasis frequencies compared with K-Ras2G12D mutation only mice, indicating an additive effect.	('tumours', 'Phenotype', 'HP:0002664', (44, 51))	('tumours', 'Disease', 'MESH:D009369', (44, 51))	('tumour', 'Disease', 'MESH:D009369', (44, 50))	('increases', 'PosReg', (100, 109))	('tumour', 'Disease', (44, 50))	('tumours', 'Disease', (44, 51))	('K-Ras2G12D mutation', 'Var', (76, 95))	('mice', 'Species', '10090', (183, 187))	('tumour', 'Phenotype', 'HP:0002664', (110, 116))	('tumour', 'Disease', 'MESH:D009369', (110, 116))	('tumour', 'Phenotype', 'HP:0002664', (44, 50))	('tumour', 'Disease', (110, 116))
17531	22792269	This suggests that the novel exon 1 of isoform 3 may change either localization or the RhoGap activity of Dlc1.	('Dlc1', 'Gene', (106, 110))	('RhoGap', 'Gene', '75404', (87, 93))	('RhoGap', 'Gene', (87, 93))	('exon', 'Var', (29, 33))	('change', 'Reg', (53, 59))	('localization', 'MPA', (67, 79))
17533	22792269	The usual mechanisms for down regulation of Dlc1 protein in tumours is either deletion of the Dlc1 locus or hypermethylation of the Dlc1 promoter.	('down regulation', 'NegReg', (25, 40))	('hypermethylation', 'Var', (108, 124))	('tumours', 'Disease', 'MESH:D009369', (60, 67))	('tumours', 'Disease', (60, 67))	('deletion', 'Var', (78, 86))	('Dlc1', 'Gene', (94, 98))	('tumour', 'Phenotype', 'HP:0002664', (60, 66))	('Dlc1', 'Gene', (44, 48))	('tumours', 'Phenotype', 'HP:0002664', (60, 67))
17534	22792269	Somatic mutations are rare for the coding region of Dlc1 gene in different tumours, reviewed by and so far there is no report on the association of existing single nucleotide polymorphisms in Dlc1 with the outcome of the disease.	('single nucleotide polymorphisms', 'Var', (157, 188))	('Dlc1', 'Gene', (192, 196))	('association', 'Interaction', (133, 144))	('tumours', 'Disease', 'MESH:D009369', (75, 82))	('tumours', 'Disease', (75, 82))	('Dlc1', 'Gene', (52, 56))	('tumours', 'Phenotype', 'HP:0002664', (75, 82))	('tumour', 'Phenotype', 'HP:0002664', (75, 81))
17539	22792269	Thus, our results indicate that in the K-Ras2 induced thymic tumours, selective methylation of the promoter of Dlc1 isoform 2 may lead to a malignant phenotype in thymus.	('malignant phenotype', 'CPA', (140, 159))	('lead to', 'Reg', (130, 137))	('thymic tumours', 'Disease', (54, 68))	('tumours', 'Phenotype', 'HP:0002664', (61, 68))	('K-Ras2', 'Gene', '16653', (39, 45))	('Dlc1', 'Gene', (111, 115))	('tumour', 'Phenotype', 'HP:0002664', (61, 67))	('methylation', 'Var', (80, 91))	('thymic tumours', 'Disease', 'MESH:D013953', (54, 68))	('K-Ras2', 'Gene', (39, 45))
17548	22792269	Alteration in anyone of these Rho mediated functions could increase the metastatic potential of T lymphoma cells.	('T lymphoma', 'Disease', (96, 106))	('Alteration', 'Var', (0, 10))	('lymphoma', 'Phenotype', 'HP:0002665', (98, 106))	('T lymphoma', 'Phenotype', 'HP:0012190', (96, 106))	('T lymphoma', 'Disease', 'MESH:D016399', (96, 106))	('increase', 'PosReg', (59, 67))
17551	22792269	p21 deficiency contributes to the development of a wide variety of tumour types in mice, which include skin, colon, intestine, pituitary, thyroid, mammary gland, salivary gland, connective tissue and histiocytic sarcomas.	('colon', 'Disease', (109, 114))	('pituitary', 'Disease', (127, 136))	('tumour', 'Phenotype', 'HP:0002664', (67, 73))	('sarcomas', 'Disease', 'MESH:D012509', (212, 220))	('tumour', 'Disease', 'MESH:D009369', (67, 73))	('skin', 'Disease', (103, 107))	('salivary gland', 'Disease', (162, 176))	('sarcomas', 'Phenotype', 'HP:0100242', (212, 220))	('sarcomas', 'Disease', (212, 220))	('p21', 'Gene', (0, 3))	('tumour', 'Disease', (67, 73))	('mice', 'Species', '10090', (83, 87))	('intestine', 'Disease', (116, 125))	('deficiency', 'Var', (4, 14))	('contributes', 'Reg', (15, 26))	('p21', 'Gene', '12575', (0, 3))	('thyroid', 'Disease', (138, 145))	('mammary gland', 'Disease', (147, 160))	('connective tissue', 'Disease', (178, 195))
17555	22792269	In brief, our finding indicates that Dlc1 isoform 2 undergoes selective hypermethylation in oncogenic K-Ras2 induced thymic tumours and significantly decrease the overall survival in mice.	('thymic tumours', 'Disease', 'MESH:D013953', (117, 131))	('decrease', 'NegReg', (150, 158))	('mice', 'Species', '10090', (183, 187))	('hypermethylation', 'Var', (72, 88))	('K-Ras2', 'Gene', (102, 108))	('tumour', 'Phenotype', 'HP:0002664', (124, 130))	('tumours', 'Phenotype', 'HP:0002664', (124, 131))	('thymic tumours', 'Disease', (117, 131))	('K-Ras2', 'Gene', '16653', (102, 108))
17563	22792269	Eight week Dlcgt/wt; K-Ras2G12D/wt and the K-Ras2G12D/wt mice were injected with 1x108 plaque forming units of AdCre virus/0.2 ml phosphate buffered saline (PBS) via the tail vein.	('mice', 'Species', '10090', (57, 61))	('phosphate buffered saline', 'Chemical', '-', (130, 155))	('K-Ras2G12D/wt', 'Var', (43, 56))	('PBS', 'Disease', 'MESH:D011535', (157, 160))	('PBS', 'Disease', (157, 160))
17580	22792269	Six microsatellite markers, namely D8Mit293, D8Mit225, Dlc1, and D8Mit226, D8Mit97, and D8Mit194 were used, which spans 1.9 Mb chromosomal region around Dlc1 locus (based on Build 37 assembly by NCBI).	('D8Mit225', 'Var', (45, 53))	('D8Mit194', 'Var', (88, 96))	('D8Mit226', 'Var', (65, 73))	('D8Mit97', 'Var', (75, 82))	('D8Mit293', 'Var', (35, 43))	('Dlc1', 'Gene', (153, 157))	('Mit293', 'CellLine', 'CVCL:0045', (37, 43))
17688	29932785	Recently, antibodies towards the lipoprotein receptor like protein-4 (LRP4) have been found in patients with MG, but thus far their pathogenicity has not been unequivocally established.	('found', 'Reg', (86, 91))	('LRP4', 'Gene', (70, 74))	('antibodies', 'Var', (10, 20))	('patients', 'Species', '9606', (95, 103))
17701	29932785	AChE inhibition increases the available acetylcholine for binding to the AChR thereby increasing the endplate potential and improving a compromise of the safety factor.	('improving', 'PosReg', (124, 133))	('AChR', 'Protein', (73, 77))	('acetylcholine', 'MPA', (40, 53))	('binding', 'Interaction', (58, 65))	('inhibition', 'Var', (5, 15))	('of', 'Gene', '6688', (147, 149))	('increases', 'PosReg', (16, 25))	('increasing', 'PosReg', (86, 96))	('compromise', 'MPA', (136, 146))	('endplate', 'MPA', (101, 109))	('acetylcholine', 'Chemical', 'MESH:D000109', (40, 53))
17708	29932785	Third, AChR antibodies may inhibit activation of the AChR through blocking of the ACh binding site or inhibition of ion channel opening.	('antibodies', 'Var', (12, 22))	('AChR', 'Protein', (7, 11))	('blocking', 'NegReg', (66, 74))	('ion channel opening', 'MPA', (116, 135))	('ACh', 'Protein', (82, 85))	('activation', 'MPA', (35, 45))	('inhibition', 'NegReg', (102, 112))	('of', 'Gene', '6688', (46, 48))	('of', 'Gene', '6688', (75, 77))	('inhibit', 'NegReg', (27, 34))	('of', 'Gene', '6688', (113, 115))
17714	29932785	Antibodies to LRP4 are predominantly IgG1 and appear to induce weakness by disrupting the interaction between LRP4-agrin signaling and by complement-activation.	('LRP4', 'Gene', (14, 18))	('Antibodies', 'Var', (0, 10))	('disrupting', 'NegReg', (75, 85))	('weakness', 'Disease', (63, 71))	('weakness', 'Disease', 'MESH:D018908', (63, 71))	('men', 'Species', '9606', (144, 147))	('interaction', 'Interaction', (90, 101))	('LRP4-agrin signaling', 'MPA', (110, 130))
17715	29932785	Antibodies to LRP-4 have been detected in about 18% of patients without AChR and MuSK antibodies in a large multicenter analysis from Europe, while a study from China indicated a frequency of 4%.	('MuSK antibodies', 'Phenotype', 'HP:0030210', (81, 96))	('Antibodies', 'Var', (0, 10))	('of', 'Gene', '6688', (52, 54))	('LRP-4', 'Gene', (14, 19))	('of', 'Gene', '6688', (189, 191))	('detected', 'Reg', (30, 38))	('patients', 'Species', '9606', (55, 63))
17746	29932785	Morphometric analysis does not reveal significant differences between LOMG and normal thymus from age matched controls.	('age', 'Gene', '5973', (98, 101))	('LOMG', 'Var', (70, 74))	('age', 'Gene', (98, 101))
17748	29932785	A diversity of autoantibodies, including anti-titin and anti-RyR, are found in the circulation of LOMG patients.	('anti-RyR', 'Var', (56, 64))	('of', 'Gene', '6688', (95, 97))	('anti-titin', 'Var', (41, 51))	('of', 'Gene', '6688', (12, 14))	('patients', 'Species', '9606', (103, 111))	('LOMG', 'Disease', (98, 102))
17787	29932785	Purine synthesis is inhibited by azathioprine leading to inhibition of rapidly dividing cells, including lymphocytes involved in the autoimmune response.	('autoimmune response', 'Phenotype', 'HP:0002960', (133, 152))	('of', 'Gene', '6688', (68, 70))	('Purine', 'Chemical', 'MESH:C030985', (0, 6))	('azathioprine', 'Chemical', 'MESH:D001379', (33, 45))	('inhibition', 'NegReg', (57, 67))	('rapidly dividing cells', 'CPA', (71, 93))	('inhibited', 'NegReg', (20, 29))	('azathioprine', 'Var', (33, 45))	('Purine synthesis', 'MPA', (0, 16))
17803	29932785	Cyclosporine increases risk of osteoporosis.	('osteoporosis', 'Disease', 'MESH:D010024', (31, 43))	('osteoporosis', 'Disease', (31, 43))	('of', 'Gene', '6688', (28, 30))	('Cyclosporine', 'Var', (0, 12))	('osteoporosis', 'Phenotype', 'HP:0000939', (31, 43))	('Cyclosporine', 'Chemical', 'MESH:D016572', (0, 12))
17820	29932785	Cyclophosphamide inhibits lymphocyte replication but also has more broader immunomodulatory effects including modulation of Th2/Th1 ratios, altered cytokine production, and enhanced proliferation and survival of certain lymphocyte populations, and modulation of dendritic cell activity.	('inhibits', 'NegReg', (17, 25))	('modulation', 'Reg', (110, 120))	('proliferation', 'CPA', (182, 195))	('altered', 'Reg', (140, 147))	('lymphocyte replication', 'CPA', (26, 48))	('of', 'Gene', '6688', (209, 211))	('Cyclophosphamide', 'Chemical', 'MESH:D003520', (0, 16))	('of', 'Gene', '6688', (121, 123))	('cytokine production', 'MPA', (148, 167))	('of', 'Gene', '6688', (259, 261))	('Th2/Th1 ratios', 'MPA', (124, 138))	('enhanced', 'PosReg', (173, 181))	('Cyclophosphamide', 'Var', (0, 16))	('survival', 'CPA', (200, 208))	('modulation', 'Reg', (248, 258))
17845	29932785	A deficiency of eculizumab is its inactivity among patients with a genetic variant of the C5 epitope to which it binds, and its general complement inhibition in an immunosuppressed population.	('A deficiency of eculizumab', 'Disease', 'MESH:D007153', (0, 26))	('men', 'Species', '9606', (142, 145))	('of', 'Gene', '6688', (13, 15))	('variant', 'Var', (75, 82))	('of', 'Gene', '6688', (83, 85))	('inactivity', 'MPA', (34, 44))	('patients', 'Species', '9606', (51, 59))	('inhibition', 'NegReg', (147, 157))	('complement', 'MPA', (136, 146))	('A deficiency of eculizumab', 'Disease', (0, 26))	('binds', 'Interaction', (113, 118))
17858	29932785	EN101 is an antisense oligodeoxynucleotide that acts at the mRNA level and selectively reduces the enzymatic isoform of AChE-R, which is generated with injury to the NMJ produced by MG.	('EN101', 'Var', (0, 5))	('of', 'Gene', '6688', (117, 119))	('oligodeoxynucleotide', 'Chemical', 'MESH:D009838', (22, 42))	('reduces', 'NegReg', (87, 94))	('of', 'Gene', '6688', (111, 113))
17870	29932785	The disruption of FcRn-IgG interaction results in IgG catabolism and lowering of serum IgG levels.	('of', 'Gene', '6688', (78, 80))	('IgG catabolism', 'MPA', (50, 64))	('serum IgG levels', 'MPA', (81, 97))	('interaction', 'Interaction', (27, 38))	('FcRn-IgG', 'Protein', (18, 26))	('disruption', 'Var', (4, 14))	('lowering', 'NegReg', (69, 77))	('lowering of serum IgG', 'Phenotype', 'HP:0004315', (69, 90))	('of', 'Gene', '6688', (15, 17))
17876	29932785	The first attempts to induce tolerance involved administration of denatured Torpedo AChR, which reduced severity of EAMG in rabbits and rodents.	('denatured', 'Var', (66, 75))	('EAMG', 'Chemical', '-', (116, 120))	('EAMG', 'Disease', (116, 120))	('of', 'Gene', '6688', (63, 65))	('rabbits', 'Species', '9986', (124, 131))	('of', 'Gene', '6688', (113, 115))	('reduced', 'NegReg', (96, 103))
18154	31452756	It has been suggested that 'SPT before thymoma' arises from the dysfunction of cortical thymic epithelial cells in nascent thymoma without clinical symptoms.	('thymoma', 'Gene', (123, 130))	('SPT', 'Gene', (28, 31))	('SPT', 'Gene', '189', (28, 31))	('thymoma', 'Phenotype', 'HP:0100522', (39, 46))	('thymoma', 'Gene', '7063', (39, 46))	('thymoma', 'Phenotype', 'HP:0100522', (123, 130))	('thymoma', 'Gene', (39, 46))	('thymoma', 'Gene', '7063', (123, 130))	('dysfunction', 'Var', (64, 75))
18176	31452756	Sun et al have suggested that Fas and FasL polymorphisms may modify SPT risk in oropharyngeal or other types of H&N SCC.	('polymorphisms', 'Var', (43, 56))	('SCC', 'Gene', (116, 119))	('SPT', 'Gene', '189', (68, 71))	('FasL', 'Gene', '356', (38, 42))	('SPT', 'Gene', (68, 71))	('FasL', 'Gene', (38, 42))	('oropharyngeal', 'Disease', (80, 93))	('modify', 'Reg', (61, 67))	('SCC', 'Gene', '6317', (116, 119))	('Fas', 'Gene', (30, 33))	('H&N', 'Chemical', '-', (112, 115))
18267	23382114	Patients who were previously treated for advanced disease with at least one platinum-based chemotherapy were treated with cixutumumab, an insulin-like growth factor receptor 1 (IGF1R) inhibitor (NCT00965250) or belinostat, an histone deacetylase (HDAC) inhibitor (NCT00589290).	('histone deacetylase', 'Gene', '9734', (226, 245))	('IGF1R', 'Gene', (177, 182))	('platinum', 'Chemical', 'MESH:D010984', (76, 84))	('belinostat', 'Chemical', 'MESH:C487081', (211, 221))	('histone deacetylase', 'Gene', (226, 245))	('IGF1R', 'Gene', '3480', (177, 182))	('Patients', 'Species', '9606', (0, 8))	('NCT00965250', 'Var', (195, 206))	('HDAC', 'Gene', (247, 251))	('cixutumumab', 'Chemical', 'MESH:C557414', (122, 133))	('HDAC', 'Gene', '9734', (247, 251))
18307	23382114	Whereas some investigators reported the usefulness of [18F]-FDG PET/CT, a marked overlap in uptake among high and low-risk thymomas was also observed.	('thymomas', 'Disease', (123, 131))	('thymoma', 'Phenotype', 'HP:0100522', (123, 130))	('[18F]-FDG', 'Var', (54, 63))	('thymomas', 'Disease', 'MESH:D013945', (123, 131))
18363	33327647	As SQAP led to increased tumor oxygenation in mice, it was considered that the radiosensitizing effect of this agent was to enhance the oxygen-dependent effects of radiotherapy in tumors.	('tumor', 'Disease', 'MESH:D009369', (180, 185))	('tumor', 'Phenotype', 'HP:0002664', (25, 30))	('SQAP', 'Chemical', 'MESH:C000605760', (3, 7))	('oxygen', 'Chemical', 'MESH:D010100', (136, 142))	('oxygen-dependent effects', 'MPA', (136, 160))	('tumor', 'Phenotype', 'HP:0002664', (180, 185))	('tumor', 'Disease', (25, 30))	('enhance', 'PosReg', (124, 131))	('tumors', 'Phenotype', 'HP:0002664', (180, 186))	('tumor', 'Disease', (180, 185))	('increased', 'PosReg', (15, 24))	('oxygen', 'Chemical', 'MESH:D010100', (31, 37))	('SQAP', 'Var', (3, 7))	('tumors', 'Disease', (180, 186))	('tumors', 'Disease', 'MESH:D009369', (180, 186))	('mice', 'Species', '10090', (46, 50))	('tumor', 'Disease', 'MESH:D009369', (25, 30))
18488	29552309	Patients with preoperative radiotherapy had lower OS and DSS than patients with PORT or without radiotherapy (P = 0.007 and P < 0.001, respectively).	('lower', 'NegReg', (44, 49))	('DSS', 'Gene', (57, 60))	('radiotherapy', 'Var', (27, 39))	('Patients', 'Species', '9606', (0, 8))	('DSS', 'Gene', '5376', (57, 60))	('OS', 'Chemical', '-', (50, 52))	('patients', 'Species', '9606', (66, 74))
18525	29552309	In thymoma in Masaoka Stages II-IV, surgically treated patients with PORT had significantly better OS than those without PORT (P = 0.015).	('thymoma', 'Gene', (3, 10))	('thymoma', 'Phenotype', 'HP:0100522', (3, 10))	('PORT', 'Var', (69, 73))	('patients', 'Species', '9606', (55, 63))	('thymoma', 'Gene', '7063', (3, 10))	('OS', 'Chemical', '-', (99, 101))	('better', 'PosReg', (92, 98))
18616	28614249	Also, there has recently been evidence for a potential role of RVATS in the treatment of lung cancer; in lobectomy, RVATS was associated with shorter hospital stay, shorter chest tube duration, and less blood loss compared with open lobectomy.	('blood loss', 'Disease', (203, 213))	('lung cancer', 'Disease', (89, 100))	('lung cancer', 'Phenotype', 'HP:0100526', (89, 100))	('shorter', 'NegReg', (142, 149))	('blood loss', 'Disease', 'MESH:D006473', (203, 213))	('cancer', 'Phenotype', 'HP:0002664', (94, 100))	('lung cancer', 'Disease', 'MESH:D008175', (89, 100))	('RVATS', 'Var', (116, 121))
18633	28614249	Patients undergoing RVATS spent significantly less time hospitalized than patients undergoing sternotomy [-4.06 days (95% CI -7.98 to -0.13); P = .046].	('Patients', 'Species', '9606', (0, 8))	('less', 'NegReg', (46, 50))	('patients', 'Species', '9606', (74, 82))	('RVATS', 'Var', (20, 25))
18646	28614249	Patients undergoing RVATS spent significantly less time in hospital than patients undergoing sternotomy.	('Patients', 'Species', '9606', (0, 8))	('less', 'NegReg', (46, 50))	('patients', 'Species', '9606', (73, 81))	('RVATS', 'Var', (20, 25))
18654	28614249	The results of our meta-analyses show that patients undergoing RVATS spent less time in hospital than patients treated by open surgery.	('patients', 'Species', '9606', (43, 51))	('RVATS', 'Var', (63, 68))	('less', 'NegReg', (75, 79))	('patients', 'Species', '9606', (102, 110))
18938	27684864	There was no diabetic mellitus and negative results for complement 3 (143 mg/dL), complement 4 (35.1 mg/dL), syphilis test, hepatitis B, hepatitis C, Immunoglobulin G (898 mg/dL), Immunoglobulin A (288 mg/dL), and Immunoglobulin M (129 mg/dL).	('syphilis test', 'Disease', (109, 122))	('diabetic mellitus', 'Disease', (13, 30))	('hepatitis', 'Phenotype', 'HP:0012115', (124, 133))	('288 mg/dL', 'Var', (198, 207))	('hepatitis B, hepatitis C', 'Disease', 'MESH:D006509', (124, 148))	('diabetic mellitus', 'Phenotype', 'HP:0000819', (13, 30))	('898 mg/dL', 'Var', (168, 177))	('hepatitis', 'Phenotype', 'HP:0012115', (137, 146))	('diabetic mellitus', 'Disease', 'MESH:D003920', (13, 30))
19006	27267746	Among them, type B2 and B3 tumours are considered to be "high-risk" thymomas, whereas type A, AB, and B1 tumours are considered "low-risk" thymomas".	('tumours', 'Phenotype', 'HP:0002664', (105, 112))	('tumour', 'Phenotype', 'HP:0002664', (27, 33))	('tumours', 'Disease', 'MESH:D009369', (105, 112))	('thymoma', 'Phenotype', 'HP:0100522', (139, 146))	('tumours', 'Disease', (105, 112))	('tumours', 'Phenotype', 'HP:0002664', (27, 34))	('type B2', 'Var', (12, 19))	('thymoma', 'Phenotype', 'HP:0100522', (68, 75))	('thymomas', 'Disease', 'MESH:D013945', (68, 76))	('tumour', 'Phenotype', 'HP:0002664', (105, 111))	('tumours', 'Disease', 'MESH:D009369', (27, 34))	('thymomas', 'Disease', (139, 147))	('tumours', 'Disease', (27, 34))	('thymomas', 'Disease', (68, 76))	('thymomas', 'Disease', 'MESH:D013945', (139, 147))
19047	27267746	Local recurrence at the site of the primary tumour after surgical resection was noted only in patients with thymomas (type B3 in one, B2 in two, B1 in one, and AB in one patient), and not in patients with thymic carcinoma (p=0.05).	('patients', 'Species', '9606', (191, 199))	('patients', 'Species', '9606', (94, 102))	('thymoma', 'Phenotype', 'HP:0100522', (108, 115))	('type B3', 'Var', (118, 125))	('primary tumour', 'Disease', (36, 50))	('thymic carcinoma', 'Disease', 'MESH:D013945', (205, 221))	('thymomas', 'Disease', (108, 116))	('thymomas', 'Disease', 'MESH:D013945', (108, 116))	('patient', 'Species', '9606', (170, 177))	('carcinoma', 'Phenotype', 'HP:0030731', (212, 221))	('primary tumour', 'Disease', 'MESH:D009369', (36, 50))	('patient', 'Species', '9606', (94, 101))	('patient', 'Species', '9606', (191, 198))	('tumour', 'Phenotype', 'HP:0002664', (44, 50))	('thymic carcinoma', 'Disease', (205, 221))
19118	33436376	cTfh increased with elevated expression of inducible T-cell costimulator (ICOS) in patients with MG. cTfh shifted to Th2 and Th17 over Th1 in MG. ICOShighcTfh produced significantly higher levels of interleukin (IL)-21, IL-4, and IL-17A than ICOSlow cTfh only in patients with MG.	('interleukin (IL)-21', 'Gene', '59067', (199, 218))	('cTfh', 'Chemical', '-', (0, 4))	('interleukin (IL)-21', 'Gene', (199, 218))	('Th2', 'Chemical', '-', (117, 120))	('ICOShighcTfh', 'Chemical', '-', (146, 158))	('higher', 'PosReg', (182, 188))	('Th1', 'Gene', (135, 138))	('MG', 'Disease', 'MESH:D000080343', (97, 99))	('IL-17A', 'Gene', (230, 236))	('Th1', 'Gene', '51497', (135, 138))	('ICOShighcTfh', 'Var', (146, 158))	('cTfh', 'Chemical', '-', (101, 105))	('Th1', 'Gene', (125, 128))	('MG', 'Disease', 'MESH:D000080343', (142, 144))	('patients', 'Species', '9606', (83, 91))	('inducible T-cell costimulator', 'Gene', '29851', (43, 72))	('Th1', 'Gene', '51497', (125, 128))	('MG', 'Disease', 'MESH:D000080343', (277, 279))	('inducible T-cell costimulator', 'Gene', (43, 72))	('cTfh', 'Chemical', '-', (250, 254))	('cTfh', 'Chemical', '-', (154, 158))	('patients', 'Species', '9606', (263, 271))	('IL-17A', 'Gene', '3605', (230, 236))
19121	33436376	Alternation of cTfh is a key feature in the development of MG and may become a biomarker for disease severity and therapeutic efficacy.	('cTfh', 'Chemical', '-', (15, 19))	('cTfh', 'Gene', (15, 19))	('Alternation', 'Var', (0, 11))	('MG', 'Disease', 'MESH:D000080343', (59, 61))
19129	33436376	Evidence shows that Tfh in PB and secondary lymph nodes can be divided into Tfh1, Tfh2, and Tfh17-like total helper T cells and that Tfh2 and Tfh17 more strongly induce antibody production.	('Tfh', 'Chemical', '-', (92, 95))	('Tfh', 'Chemical', '-', (82, 85))	('Tfh17', 'Chemical', '-', (92, 97))	('induce', 'PosReg', (162, 168))	('Tfh', 'Chemical', '-', (20, 23))	('Tfh', 'Chemical', '-', (142, 145))	('antibody', 'CPA', (169, 177))	('Tfh2', 'Chemical', '-', (82, 86))	('Tfh2', 'Chemical', '-', (133, 137))	('Tfh', 'Chemical', '-', (76, 79))	('Tfh2', 'Var', (133, 137))	('Tfh17', 'Chemical', '-', (142, 147))	('Tfh', 'Chemical', '-', (133, 136))
19152	33436376	The frequency of cTfh2 and cTfh17 within CD4 T cells was significantly higher in patients with MG than in HS (5.7% in patients with MG vs 4.2% in HS, p = 0.023, and 0.73% in patients with MG vs 0.21% in HS, p < 0.001, respectively) (figure 1E).	('higher', 'PosReg', (71, 77))	('CD4', 'Gene', (41, 44))	('MG', 'Disease', 'MESH:D000080343', (95, 97))	('cTfh2', 'Chemical', '-', (17, 22))	('MG', 'Disease', 'MESH:D000080343', (188, 190))	('CD4', 'Gene', '920', (41, 44))	('patients', 'Species', '9606', (81, 89))	('cTfh2', 'Var', (17, 22))	('patients', 'Species', '9606', (174, 182))	('MG', 'Disease', 'MESH:D000080343', (132, 134))	('cTfh17', 'Chemical', '-', (27, 33))	('cTfh17', 'Var', (27, 33))	('patients', 'Species', '9606', (118, 126))
19189	33436376	The frequency of cTfh1 and cTfh2 within CD4 T cells decreased after treatment (p = 0.1 and 0.04, respectively) (figure e-4, A and B, links.lww.com/NXI/A378).	('CD4 T cells decreased', 'Phenotype', 'HP:0005407', (40, 61))	('cTfh2', 'Chemical', '-', (27, 32))	('decreased', 'NegReg', (52, 61))	('cTfh2', 'Var', (27, 32))	('CD4', 'Gene', (40, 43))	('T cells decreased', 'Phenotype', 'HP:0005403', (44, 61))	('cTfh1', 'Var', (17, 22))	('cTfh', 'Chemical', '-', (17, 21))	('CD4', 'Gene', '920', (40, 43))	('cTfh', 'Chemical', '-', (27, 31))
19212	33436376	We reported on enhanced cytokine production by ICOShigh cTfh in a human pathologic condition.	('cytokine production', 'MPA', (24, 43))	('cTfh', 'Chemical', '-', (56, 60))	('human', 'Species', '9606', (66, 71))	('enhanced', 'PosReg', (15, 23))	('ICOShigh cTfh', 'Var', (47, 60))
19242	33094573	In fact, a recent study suggested that the diagnostic power of 18F-FDG PET/CT for anterior mediastinal mass is high, but its negative predictive value is higher.	('anterior mediastinal mass', 'Disease', (82, 107))	('18F-FDG PET/CT', 'Var', (63, 77))	('18F-FDG', 'Chemical', '-', (63, 70))
19340	31683962	TaqMan  Gene Expression Assays, including IL10 (Hs00174086_m1), PD-L1 (CD274: Hs00204257_m1), and beta-actin (Hs99999903_m1), were purchased from Thermo Fisher Scientific.	('Hs99999903_m1', 'Var', (110, 123))	('IL10', 'Gene', (42, 46))	('IL10', 'Gene', '3586', (42, 46))	('CD274', 'Gene', (71, 76))	('PD-L1', 'Gene', (64, 69))	('Hs00174086_m1', 'Var', (48, 61))	('PD-L1', 'Gene', '29126', (64, 69))	('CD274', 'Gene', '29126', (71, 76))
19361	31683962	The counts were higher in the type B1-3 thymomas than in types A, AB, or C (Figure 6).	('higher', 'PosReg', (16, 22))	('thymoma', 'Phenotype', 'HP:0100522', (40, 47))	('thymomas', 'Disease', 'MESH:D013945', (40, 48))	('thymomas', 'Disease', (40, 48))	('type B1-3', 'Var', (30, 39))
19371	31683962	These data also supported the potential of PD1/PD-L1 blockades as a promising treatment for aggressive thymomas, such as type B2 or B3.	('type B2', 'Disease', (121, 128))	('PD-L1', 'Gene', (47, 52))	('men', 'Species', '9606', (83, 86))	('aggressive thymomas', 'Disease', 'MESH:D013945', (92, 111))	('PD1', 'Gene', '5133', (43, 46))	('blockades', 'Var', (53, 62))	('PD-L1', 'Gene', '29126', (47, 52))	('PD1', 'Gene', (43, 46))	('aggressive thymomas', 'Disease', (92, 111))	('thymoma', 'Phenotype', 'HP:0100522', (103, 110))
19387	31683962	Overall, our study suggests that the application of immunotherapy in TET treatment would be lucrative, since PD-L1 positivity was diffuse, strong, and present in a large number of TETs (53.9%), as confirmed in previous reports.	('men', 'Species', '9606', (78, 81))	('PD-L1', 'Gene', (109, 114))	('positivity', 'Var', (115, 125))	('PD-L1', 'Gene', '29126', (109, 114))
19395	31683962	Apart from PD-1/PD-L1 blockade therapy, recent studies have identified a missense mutation (chromosome 7 c.74146970T>A) in the GTF2I gene at a high frequency in TETs.	('c.74146970T>A', 'Mutation', 'c.74146970T>A', (105, 118))	('PD-1/PD-L1 blockade', 'Disease', (11, 30))	('GTF2I', 'Gene', (127, 132))	('PD-1/PD-L1 blockade', 'Disease', 'MESH:D010300', (11, 30))	('c.74146970T>A', 'Var', (105, 118))	('GTF2I', 'Gene', '2969', (127, 132))
19430	27387303	Detection of the EGFR mutation in each specimen was performed using a peptide nucleic acid-locked nucleic acid (PNA-LNA) PCR clamp assay (SRL Inc., Tokyo, Japan).	('mutation', 'Var', (22, 30))	('EGFR', 'Gene', '1956', (17, 21))	('EGFR', 'Gene', (17, 21))
19448	27387303	On the other hand, there were no EGFR gene mutations found in the TC and B3 specimens.	('mutations', 'Var', (43, 52))	('EGFR', 'Gene', '1956', (33, 37))	('EGFR', 'Gene', (33, 37))
19484	27387303	However, no EGFR mutations were detected in the B3 and TC specimens.	('EGFR', 'Gene', '1956', (12, 16))	('EGFR', 'Gene', (12, 16))	('mutations', 'Var', (17, 26))
19485	27387303	Several previous reports have also noted that EGFR mutations are rare in thymic malignancies.	('mutations', 'Var', (51, 60))	('thymic malignancies', 'Disease', 'MESH:D013953', (73, 92))	('EGFR', 'Gene', '1956', (46, 50))	('EGFR', 'Gene', (46, 50))	('thymic malignancies', 'Disease', (73, 92))
19574	21396119	The patients that underwent EPP (n = 4) had better local recurrence free survival compared to the patients that did not have an EPP (n = 7) (5-year: 75% vs. 16%, 10-year: 75% vs. 0%).	('better', 'PosReg', (44, 50))	('EPP', 'Var', (28, 31))	('patients', 'Species', '9606', (98, 106))	('patients', 'Species', '9606', (4, 12))	('local recurrence free survival', 'CPA', (51, 81))
19647	33889210	Patients that were MG+ had better OS rates versus MG- counterparts (p < 0.05, Figure 1d).	('Patients', 'Species', '9606', (0, 8))	('MG+', 'Var', (19, 22))	('OS rates', 'MPA', (34, 42))	('better', 'PosReg', (27, 33))
19664	33889210	Interestingly, our data suggest that MG+ patients had better OS versus MG- counterparts (Figure 1d).	('MG+', 'Var', (37, 40))	('patients', 'Species', '9606', (41, 49))	('better', 'PosReg', (54, 60))
19667	33889210	More recently, a large retrospective study found that MG+ had a slight protective effect on OS among thymoma patients.	('MG+', 'Var', (54, 57))	('patients', 'Species', '9606', (109, 117))	('thymoma', 'Phenotype', 'HP:0100522', (101, 108))	('thymoma', 'Gene', '7063', (101, 108))	('thymoma', 'Gene', (101, 108))
19672	33889210	Unexpectedly, our data report a statistically significant difference in OS regarding MG status, with better rates of OS at 5 and 10 years for MG+ patients.	('better rates', 'PosReg', (101, 113))	('MG+', 'Var', (142, 145))	('patients', 'Species', '9606', (146, 154))
19782	27900082	Based on the clinical diagnosis of T4N0M0 lung cancer, sequential chemoradiotherapy with two cycles of mytomycin C, vindecine and cisplatin (MVC regimen), and radiotherapy of 60 Gy was administered.	('vindecine', 'Chemical', '-', (116, 125))	('lung cancer', 'Disease', (42, 53))	('lung cancer', 'Phenotype', 'HP:0100526', (42, 53))	('cisplatin', 'Chemical', 'MESH:D002945', (130, 139))	('cancer', 'Phenotype', 'HP:0002664', (47, 53))	('T4N0M0', 'Var', (35, 41))	('mytomycin C', 'Chemical', 'MESH:D016685', (103, 114))	('lung cancer', 'Disease', 'MESH:D008175', (42, 53))
19875	21461350	Considering the possibility of drug resistance, based on the past history of treatment with antituberculosis drugs twice, a 6-drug ATT regimen that included rifampicin (450 mg), isoniazid (300 mg), ethambutol (800 mg), pyrazinamide (1250 mg), streptomycin (0.75 gm), and levofloxacin (750 mg) along with pyridoxine was started.	('isoniazid', 'Chemical', 'MESH:D007538', (178, 187))	('450', 'Var', (169, 172))	('levofloxacin', 'Chemical', 'MESH:D064704', (271, 283))	('drug resistance', 'Phenotype', 'HP:0020174', (31, 46))	('ethambutol', 'Chemical', 'MESH:D004977', (198, 208))	('streptomycin', 'Chemical', 'MESH:D013307', (243, 255))	('300', 'Var', (189, 192))	('pyridoxine', 'Chemical', 'MESH:D011736', (304, 314))	('pyrazinamide', 'Chemical', 'MESH:D011718', (219, 231))	('rifampicin', 'Chemical', 'MESH:D012293', (157, 167))	('1250', 'Var', (233, 237))
19961	32705358	reported that elevation of serum IgE was more frequently observed in lymph nodes of patients with IgG4-RD compared with those with MCD, and high levels of IL-6 and CRP may be important differential diagnostic markers for MCD apart from IgG4-RD.	('IL-6', 'Gene', '3569', (155, 159))	('patients', 'Species', '9606', (84, 92))	('MCD', 'Gene', (221, 224))	('serum IgE', 'MPA', (27, 36))	('CRP', 'Gene', (164, 167))	('elevation', 'PosReg', (14, 23))	('IgG4-RD', 'Var', (98, 105))	('MCD', 'Gene', (131, 134))	('MCD', 'Gene', '4582', (131, 134))	('CRP', 'Gene', '1401', (164, 167))	('MCD', 'Gene', '4582', (221, 224))	('IL-6', 'Gene', (155, 159))
20095	20880069	Mammography revealed breast cancer or infiltrated lymph nodes in 83% of patients with PCD, anti-Yo antibodies and breast cancer.	('PCD', 'Disease', 'MESH:D007619', (86, 89))	('anti-Yo', 'Var', (91, 98))	('cancer', 'Phenotype', 'HP:0002664', (28, 34))	('breast cancer', 'Disease', 'MESH:D001943', (21, 34))	('cancer', 'Phenotype', 'HP:0002664', (121, 127))	('breast cancer', 'Disease', (21, 34))	('PCD', 'Disease', (86, 89))	('breast cancer', 'Phenotype', 'HP:0003002', (21, 34))	('breast cancer', 'Disease', 'MESH:D001943', (114, 127))	('revealed', 'Reg', (12, 20))	('breast cancer', 'Phenotype', 'HP:0003002', (114, 127))	('breast cancer', 'Disease', (114, 127))	('patients', 'Species', '9606', (72, 80))
20103	20880069	Five other prospective cohort studies compared MRI with mammography and US in women with a life-time risk for breast cancer over 20-25% showed similar results: sensitivity was 77-100% for MRI, 16-40% for mammography and 16-40% for US.	('MRI', 'Var', (188, 191))	('cancer', 'Phenotype', 'HP:0002664', (117, 123))	('women', 'Species', '9606', (78, 83))	('breast cancer', 'Disease', 'MESH:D001943', (110, 123))	('breast cancer', 'Disease', (110, 123))	('breast cancer', 'Phenotype', 'HP:0003002', (110, 123))
20106	20880069	The optimal modality to screen the ovaries will depend on the expected tumour: carcinoma in anti-Yo, anti-Ri and anti-amphiphysin-related PNS and teratoma in anti-NMDAR related PNS.	('tumour', 'Disease', (71, 77))	('ovaries', 'Disease', 'MESH:D010051', (35, 42))	('teratoma', 'Phenotype', 'HP:0009792', (146, 154))	('carcinoma', 'Disease', (79, 88))	('anti-amphiphysin-related', 'Var', (113, 137))	('teratoma', 'Disease', 'MESH:D013724', (146, 154))	('carcinoma', 'Disease', 'MESH:D002277', (79, 88))	('ovaries', 'Disease', (35, 42))	('tumour', 'Phenotype', 'HP:0002664', (71, 77))	('teratoma', 'Disease', (146, 154))	('carcinoma', 'Phenotype', 'HP:0030731', (79, 88))	('tumour', 'Disease', 'MESH:D009369', (71, 77))
20126	20880069	This study showed that it has additional value to obtain tissue (biopsy or orchiectomy, unilateral or even bilateral) in young male patients (<50 years) with anti-Ma2 antibodies, deteriorating neurological disease and microcalcifications on US.	('antibodies', 'Var', (167, 177))	('Ma2', 'Gene', '10687', (163, 166))	('deteriorating', 'NegReg', (179, 192))	('deteriorating neurological disease', 'Phenotype', 'HP:0002344', (179, 213))	('neurological disease', 'Disease', (193, 213))	('neurological disease', 'Disease', 'MESH:D019636', (193, 213))	('neurological disease', 'Phenotype', 'HP:0000707', (193, 213))	('microcalcifications', 'CPA', (218, 237))	('patients', 'Species', '9606', (132, 140))	('Ma2', 'Gene', (163, 166))
20234	29217782	In contrast, "autoimmune PRCA" mediated by antibodies is less common, and most antierythroid antibodies would typically result in immune hemolytic anemia.	('immune hemolytic anemia', 'Phenotype', 'HP:0001890', (130, 153))	('anemia', 'Phenotype', 'HP:0001903', (147, 153))	('PRCA', 'Phenotype', 'HP:0012410', (25, 29))	('result in', 'Reg', (120, 129))	('hemolytic anemia', 'Disease', 'MESH:D000743', (137, 153))	('hemolytic anemia', 'Phenotype', 'HP:0001878', (137, 153))	('antierythroid', 'Var', (79, 92))	('hemolytic anemia', 'Disease', (137, 153))
20258	29217782	The distributions of MGUS, hypogammaglobulinemia, presence of T-cell receptor (TCR) rearrangement, median CD4/CD8 ratio, median CD16/CD56 ratio, and Vbeta expansion are listed in Table 1.	('CD4', 'Gene', (106, 109))	('CD56', 'Gene', (133, 137))	('presence of T-cell receptor', 'Phenotype', 'HP:0005354', (50, 77))	('CD16', 'Gene', (128, 132))	('T-cell receptor', 'Gene', '6962', (62, 77))	('hypogammaglobulinemia', 'Disease', (27, 48))	('CD4', 'Gene', '920', (106, 109))	('T-cell receptor', 'Gene', (62, 77))	('presence', 'Var', (50, 58))	('TCR', 'Gene', '6962', (79, 82))	('CD8', 'Gene', (110, 113))	('hypogammaglobulinemia', 'Disease', 'MESH:D000361', (27, 48))	('CD16', 'Gene', '2214', (128, 132))	('rearrangement', 'Var', (84, 97))	('CD56', 'Gene', '4684', (133, 137))	('TCR', 'Gene', (79, 82))	('CD8', 'Gene', '925', (110, 113))	('hypogammaglobulinemia', 'Phenotype', 'HP:0004313', (27, 48))
20260	29217782	The CD4/CD8 ratio was significantly lower among the LGL/PRCA group (0.2) compared to the idiopathic group with and without thymoma (0.9 and 1.5; P=0.0064) (Online Supplementary Figure S2).	('lower', 'NegReg', (36, 41))	('CD4', 'Gene', (4, 7))	('thymoma', 'Disease', 'MESH:D013945', (123, 130))	('LGL/PRCA', 'Var', (52, 60))	('CD4', 'Gene', '920', (4, 7))	('thymoma', 'Disease', (123, 130))	('thymoma', 'Phenotype', 'HP:0100522', (123, 130))	('CD8', 'Gene', (8, 11))	('PRCA', 'Phenotype', 'HP:0012410', (56, 60))	('CD8', 'Gene', '925', (8, 11))
20261	29217782	The STAT3 mutation in the LGL/PRCA patients were positive in 5/11 patients tested, whereas 17 patients tested negative in the idiopathic group.	('patients', 'Species', '9606', (94, 102))	('PRCA', 'Phenotype', 'HP:0012410', (30, 34))	('positive', 'Reg', (49, 57))	('mutation', 'Var', (10, 18))	('STAT3', 'Gene', '6774', (4, 9))	('LGL/PRCA', 'Gene', (26, 34))	('patients', 'Species', '9606', (35, 43))	('STAT3', 'Gene', (4, 9))	('patients', 'Species', '9606', (66, 74))
20264	29217782	Alterations found in genes affected in MDS were present in five typical idiopathic aPRCA patients and were considered to be of germline origin (Online Supplementary Table S7).	('Alterations', 'Var', (0, 11))	('MDS', 'Phenotype', 'HP:0002863', (39, 42))	('patients', 'Species', '9606', (89, 97))	('aPRCA', 'Disease', (83, 88))	('MDS', 'Disease', (39, 42))	('MDS', 'Disease', 'MESH:D009190', (39, 42))	('PRCA', 'Phenotype', 'HP:0012410', (84, 88))
20303	29217782	The presence of STAT3 mutations may support this notion, as STAT3 mutant clonal cells are usually a subfraction of clonally TCR-rearranged cytotoxic lymphocytes (CTL) as determined by quantitative analyses of TCR Vbeta-chain sequencing (data not shown).	('TCR', 'Gene', (124, 127))	('mutant', 'Var', (66, 72))	('TCR', 'Gene', '6962', (209, 212))	('STAT3', 'Gene', '6774', (16, 21))	('STAT3', 'Gene', '6774', (60, 65))	('STAT3', 'Gene', (16, 21))	('TCR', 'Gene', '6962', (124, 127))	('TCR', 'Gene', (209, 212))	('STAT3', 'Gene', (60, 65))
20335	29031952	PLGA pellets loaded with 50% w/w 5-FU exhibited comparable, and significantly enhanced, antitumor activity (as measured by tumor volumes and survival) in vivo in a thymoma and colon cancer model, respectively, when compared to an equivalent bolus dose (120 mg/kg) of soluble 5-FU.	('cancer', 'Phenotype', 'HP:0002664', (182, 188))	('tumor', 'Disease', (123, 128))	('tumor', 'Disease', 'MESH:D009369', (92, 97))	('tumor', 'Disease', 'MESH:D009369', (123, 128))	('5-FU', 'Chemical', 'MESH:D005472', (275, 279))	('tumor', 'Phenotype', 'HP:0002664', (92, 97))	('tumor', 'Phenotype', 'HP:0002664', (123, 128))	('thymoma', 'Phenotype', 'HP:0100522', (164, 171))	('5-FU', 'Var', (33, 37))	('thymoma and colon cancer', 'Disease', 'MESH:D013945', (164, 188))	('tumor', 'Disease', (92, 97))	('colon cancer', 'Phenotype', 'HP:0003003', (176, 188))	('5-FU', 'Chemical', 'MESH:D005472', (33, 37))	('enhanced', 'PosReg', (78, 86))
20352	29031952	PLGA pellets loaded with 50% w/w 5-FU were capable of imparting significant antitumor activity against two independent tumor types (thymoma (EL4) and colon carcinoma (CT26)) in vivo when subcutaneously injected proximal to palpable tumors.	('thymoma', 'Phenotype', 'HP:0100522', (132, 139))	('tumor', 'Phenotype', 'HP:0002664', (80, 85))	('EL4', 'Gene', '111979', (141, 144))	('tumor', 'Phenotype', 'HP:0002664', (119, 124))	('tumors', 'Disease', 'MESH:D009369', (232, 238))	('colon carcinoma', 'Disease', (150, 165))	('tumor', 'Disease', (232, 237))	('5-FU', 'Chemical', 'MESH:D005472', (33, 37))	('colon carcinoma', 'Disease', 'MESH:D015179', (150, 165))	('CT26', 'CellLine', 'CVCL:7254', (167, 171))	('carcinoma', 'Phenotype', 'HP:0030731', (156, 165))	('tumor', 'Disease', 'MESH:D009369', (232, 237))	('tumor', 'Disease', (80, 85))	('EL4', 'Gene', (141, 144))	('5-FU', 'Var', (33, 37))	('tumors', 'Phenotype', 'HP:0002664', (232, 238))	('thymoma', 'Disease', 'MESH:D013945', (132, 139))	('tumor', 'Disease', 'MESH:D009369', (80, 85))	('tumor', 'Disease', (119, 124))	('tumor', 'Phenotype', 'HP:0002664', (232, 237))	('tumor', 'Disease', 'MESH:D009369', (119, 124))	('thymoma', 'Disease', (132, 139))	('tumors', 'Disease', (232, 238))
20415	29031952	With 5-FU being a mildly hydrophilic molecule (approximately 12 mg/ml in water at pH 7 ), an increase in percent 5-FU in the formulation therefore likely increased the hydrophilicity of the formulation and accordingly enhanced the rate of water absorption, polymer hydrolysis and erosion, and consequently, the 5-FU release rate.	('enhanced', 'PosReg', (218, 226))	('5-FU', 'Chemical', 'MESH:D005472', (311, 315))	('water', 'Chemical', 'MESH:D014867', (239, 244))	('polymer hydrolysis', 'CPA', (257, 275))	('increase', 'PosReg', (93, 101))	('water absorption', 'MPA', (239, 255))	('5-FU', 'Chemical', 'MESH:D005472', (113, 117))	('hydrophilicity', 'MPA', (168, 182))	('polymer', 'Chemical', 'MESH:D011108', (257, 264))	('5-FU', 'Var', (113, 117))	('5-FU release rate', 'MPA', (311, 328))	('erosion', 'CPA', (280, 287))	('increased', 'PosReg', (154, 163))	('5-FU', 'Chemical', 'MESH:D005472', (5, 9))	('water', 'Chemical', 'MESH:D014867', (73, 78))
20416	29031952	PLGA pellets loaded with 30% 5-FU (w/w) showed a tri-phasic release pattern with a small initial burst release within one day followed by a diffusion-predominate release until day 14.	('diffusion-predominate', 'MPA', (140, 161))	('5-FU', 'Var', (29, 33))	('5-FU', 'Chemical', 'MESH:D005472', (29, 33))	('tri-phasic release pattern', 'MPA', (49, 75))
20438	29031952	When delivered in solution form, 5-FU significantly reduced lymphocyte counts (Figure 5E) and granulocyte counts (Figure 5F) within the first week of treatment compared to untreated mice (p < 0.05) while there were no significant differences in lymphocyte nor granulocyte counts between mice treated with 5-FU-loaded PLGA pellets and mice receiving no treatment (Figures 5E & 5F).	('5-FU', 'Chemical', 'MESH:D005472', (305, 309))	('reduced', 'NegReg', (52, 59))	('mice', 'Species', '10090', (334, 338))	('mice', 'Species', '10090', (182, 186))	('reduced lymphocyte counts', 'Phenotype', 'HP:0001888', (52, 77))	('mice', 'Species', '10090', (287, 291))	('granulocyte counts', 'CPA', (94, 112))	('lymphocyte counts', 'CPA', (60, 77))	('5-FU', 'Var', (33, 37))	('5-FU', 'Chemical', 'MESH:D005472', (33, 37))
20441	29031952	Although an independent study performed by another group showed the negative impact of 5-FU on mouse weight, the impact was only marginal and thus the results were largely in agreement with the study presented here.	('negative', 'NegReg', (68, 76))	('5-FU', 'Var', (87, 91))	('5-FU', 'Chemical', 'MESH:D005472', (87, 91))	('mouse weight', 'CPA', (95, 107))	('mouse', 'Species', '10090', (95, 100))
20464	27844328	The sequencing of 50 genes detected nonsynonymous mutations in 16 carcinomas affecting ALK, ATM, CDKN2A, ERBB4, FGFR3, KIT, NRAS and TP53.	('carcinoma', 'Phenotype', 'HP:0030731', (66, 75))	('CDKN2A', 'Gene', (97, 103))	('carcinomas', 'Phenotype', 'HP:0030731', (66, 76))	('carcinomas', 'Disease', (66, 76))	('FGFR3', 'Gene', (112, 117))	('carcinomas', 'Disease', 'MESH:D002277', (66, 76))	('ALK', 'Gene', '238', (87, 90))	('KIT', 'Gene', (119, 122))	('nonsynonymous mutations', 'Var', (36, 59))	('ALK', 'Gene', (87, 90))	('RB', 'Disease', 'MESH:D012175', (106, 108))
20465	27844328	Only two B3 thymomas had a mutation in noncoding regions of the SMARCB1 and STK11 gene respectively.	('thymoma', 'Phenotype', 'HP:0100522', (12, 19))	('thymomas', 'Disease', (12, 20))	('mutation', 'Var', (27, 35))	('STK11', 'Gene', (76, 81))	('thymomas', 'Disease', 'MESH:D013945', (12, 20))	('SMARCB1', 'Gene', (64, 71))
20467	27844328	Fluorescence in situ hybridization detected in 38 % of carcinomas a CDKN2A, in 32 % a TP53 and in 8 % an ATM gene deletion, whereas only one B3 thymoma exhibited a CDKNA deletion, and none of the type A thymomas showed a gene loss.	('detected', 'Reg', (35, 43))	('carcinomas', 'Phenotype', 'HP:0030731', (55, 65))	('carcinomas', 'Disease', 'MESH:D002277', (55, 65))	('type A thymomas', 'Disease', 'MESH:D013945', (196, 211))	('carcinoma', 'Phenotype', 'HP:0030731', (55, 64))	('CDKN2A', 'Gene', (68, 74))	('carcinomas', 'Disease', (55, 65))	('type A thymomas', 'Disease', (196, 211))	('thymoma', 'Disease', (144, 151))	('thymoma', 'Disease', 'MESH:D013945', (144, 151))	('thymoma', 'Disease', 'MESH:D013945', (203, 210))	('A thymomas', 'Phenotype', 'HP:0100522', (201, 211))	('thymoma', 'Phenotype', 'HP:0100522', (144, 151))	('thymoma', 'Disease', (203, 210))	('thymoma', 'Phenotype', 'HP:0100522', (203, 210))	('deletion', 'Var', (114, 122))
20468	27844328	Sequencing of the total miRNA pool of 5 type A thymomas and 5 thymic carcinomas identified the C19MC miRNA cluster as highly expressed in type A thymomas, but completely silenced in thymic carcinomas.	('type A thymomas', 'Disease', (40, 55))	('C19MC', 'Var', (95, 100))	('type A thymomas', 'Disease', 'MESH:D013945', (40, 55))	('A thymomas', 'Phenotype', 'HP:0100522', (143, 153))	('carcinomas', 'Phenotype', 'HP:0030731', (69, 79))	('thymic carcinomas', 'Disease', 'MESH:D013945', (182, 199))	('A thymomas', 'Phenotype', 'HP:0100522', (45, 55))	('carcinomas', 'Phenotype', 'HP:0030731', (189, 199))	('thymic carcinomas', 'Disease', 'MESH:D013945', (62, 79))	('thymoma', 'Phenotype', 'HP:0100522', (47, 54))	('type A thymomas', 'Disease', (138, 153))	('type A thymomas', 'Disease', 'MESH:D013945', (138, 153))	('thymic carcinomas', 'Disease', (182, 199))	('carcinoma', 'Phenotype', 'HP:0030731', (69, 78))	('carcinoma', 'Phenotype', 'HP:0030731', (189, 198))	('thymic carcinomas', 'Disease', (62, 79))	('thymoma', 'Phenotype', 'HP:0100522', (145, 152))
20469	27844328	Furthermore, the miRNA cluster C14MC was downregulated in thymic carcinomas.	('C14MC', 'Var', (31, 36))	('carcinoma', 'Phenotype', 'HP:0030731', (65, 74))	('carcinomas', 'Phenotype', 'HP:0030731', (65, 75))	('thymic carcinomas', 'Disease', 'MESH:D013945', (58, 75))	('downregulated', 'NegReg', (41, 54))	('thymic carcinomas', 'Disease', (58, 75))	('miRNA', 'Protein', (17, 22))
20470	27844328	Among non-clustered miRNAs, the upregulation of miR-21, miR-9-3 and miR-375 and the downregulation of miR-34b, miR-34c, miR-130a and miR-195 in thymic carcinomas were most significant.	('miR-375', 'Chemical', '-', (68, 75))	('miR-34', 'Chemical', '-', (102, 108))	('carcinomas', 'Phenotype', 'HP:0030731', (151, 161))	('thymic carcinomas', 'Disease', 'MESH:D013945', (144, 161))	('miR-195', 'Gene', '406971', (133, 140))	('miR-21', 'Gene', (48, 54))	('upregulation', 'PosReg', (32, 44))	('miR-375', 'Var', (68, 75))	('miR-195', 'Gene', (133, 140))	('miR-34', 'Chemical', '-', (111, 117))	('miR-34b', 'Gene', (102, 109))	('miR-130a', 'Chemical', '-', (120, 128))	('carcinoma', 'Phenotype', 'HP:0030731', (151, 160))	('thymic carcinomas', 'Disease', (144, 161))	('miR-130a', 'Var', (120, 128))	('miR-34c', 'Var', (111, 118))	('miR-9-3', 'Gene', (56, 63))	('downregulation', 'NegReg', (84, 98))
20478	27844328	Mutation of the tyrosine kinase KIT was the only known targetable alteration in thymic carcinoma, but it is present in only 6-12 % of cases.	('carcinoma', 'Phenotype', 'HP:0030731', (87, 96))	('thymic carcinoma', 'Disease', 'MESH:D013945', (80, 96))	('Mutation', 'Var', (0, 8))	('thymic carcinoma', 'Disease', (80, 96))
20479	27844328	Recently, whole exome and targeted gene panel sequencing of TETs identified a specific missense mutation in GTF2I in type A thymomas and common mutations in TP53 and epigenetic regulatory genes in thymic carcinomas.	('GTF2I', 'Gene', (108, 113))	('carcinoma', 'Phenotype', 'HP:0030731', (204, 213))	('thymic carcinomas', 'Disease', (197, 214))	('missense mutation', 'Var', (87, 104))	('type A thymomas', 'Disease', 'MESH:D013945', (117, 132))	('carcinomas', 'Phenotype', 'HP:0030731', (204, 214))	('type A thymomas', 'Disease', (117, 132))	('A thymomas', 'Phenotype', 'HP:0100522', (122, 132))	('thymoma', 'Phenotype', 'HP:0100522', (124, 131))	('thymic carcinomas', 'Disease', 'MESH:D013945', (197, 214))
20510	27844328	Four carcinomas exhibited a missense mutation in the tumor suppressor CDKN2A, which was thus the second most frequently mutated gene.	('missense mutation', 'Var', (28, 45))	('tumor', 'Disease', 'MESH:D009369', (53, 58))	('carcinoma', 'Phenotype', 'HP:0030731', (5, 14))	('tumor', 'Phenotype', 'HP:0002664', (53, 58))	('carcinomas', 'Phenotype', 'HP:0030731', (5, 15))	('exhibited', 'Reg', (16, 25))	('tumor', 'Disease', (53, 58))	('CDKN2A', 'Gene', (70, 76))	('carcinomas', 'Disease', (5, 15))	('carcinomas', 'Disease', 'MESH:D002277', (5, 15))
20511	27844328	Two carcinomas each harbored a missense mutation in the fibroblast growth factor receptor 3 (FGFR3) and the receptor tyrosine kinase KIT.	('carcinomas', 'Phenotype', 'HP:0030731', (4, 14))	('carcinomas', 'Disease', 'MESH:D002277', (4, 14))	('carcinomas', 'Disease', (4, 14))	('receptor tyrosine kinase', 'Gene', (108, 132))	('harbored', 'Reg', (20, 28))	('missense mutation', 'Var', (31, 48))	('receptor tyrosine kinase', 'Gene', '5979', (108, 132))	('FGFR3', 'Gene', (93, 98))	('carcinoma', 'Phenotype', 'HP:0030731', (4, 13))
20512	27844328	The receptor tyrosine kinases ALK and ERBB4, the serine/threonine kinase ATM, and the GTPase NRAS were mutated in one thymic carcinoma each (Tables 1 and 2).	('receptor tyrosine kinase', 'Gene', (4, 28))	('mutated', 'Var', (103, 110))	('ALK', 'Gene', (30, 33))	('receptor tyrosine kinase', 'Gene', '5979', (4, 28))	('thymic carcinoma', 'Disease', 'MESH:D013945', (118, 134))	('carcinoma', 'Phenotype', 'HP:0030731', (125, 134))	('serine/threonine kinase ATM', 'Enzyme', (49, 76))	('RB', 'Disease', 'MESH:D012175', (39, 41))	('ALK', 'Gene', '238', (30, 33))	('GTPase NRAS', 'Gene', (86, 97))	('thymic carcinoma', 'Disease', (118, 134))
20515	27844328	One was a point mutation in the 3' untranslated region at position -17 of the tumor suppressor SMARCB1.	('tumor', 'Disease', 'MESH:D009369', (78, 83))	('tumor', 'Phenotype', 'HP:0002664', (78, 83))	('SMARCB1', 'Gene', (95, 102))	('tumor', 'Disease', (78, 83))	('point mutation in', 'Var', (10, 27))
20516	27844328	The other represented a deletion of two nucleotides +16 and +17 upstream of the exon-intron boundary of exon 4 of the tumor suppressor STK11.	('tumor', 'Phenotype', 'HP:0002664', (118, 123))	('tumor', 'Disease', (118, 123))	('tumor', 'Disease', 'MESH:D009369', (118, 123))	('deletion', 'Var', (24, 32))
20517	27844328	Three (17 %) of the 18 type A thymomas harbored a non-synonymous mutation in the HRAS oncogene (Tables 1 and 2).	('type A thymomas', 'Disease', 'MESH:D013945', (23, 38))	('A thymomas', 'Phenotype', 'HP:0100522', (28, 38))	('HRAS', 'Gene', (81, 85))	('type A thymomas', 'Disease', (23, 38))	('thymoma', 'Phenotype', 'HP:0100522', (30, 37))	('non-synonymous mutation', 'Var', (50, 73))	('harbored', 'Reg', (39, 47))
20529	27844328	Motivated by the two thymic carcinomas with an FGFR3 mutation and the one carcinoma with an ALK mutation, we also performed FISH for these two genes.	('carcinomas', 'Phenotype', 'HP:0030731', (28, 38))	('FGFR3', 'Gene', (47, 52))	('mutation', 'Var', (53, 61))	('ALK', 'Gene', (92, 95))	('carcinoma', 'Disease', (28, 37))	('thymic carcinomas', 'Disease', 'MESH:D013945', (21, 38))	('carcinoma', 'Phenotype', 'HP:0030731', (28, 37))	('carcinoma', 'Disease', 'MESH:D002277', (74, 83))	('carcinoma', 'Phenotype', 'HP:0030731', (74, 83))	('ALK', 'Gene', '238', (92, 95))	('carcinoma', 'Disease', (74, 83))	('carcinoma', 'Disease', 'MESH:D002277', (28, 37))	('thymic carcinomas', 'Disease', (21, 38))
20533	27844328	C19MC miRNAs were highly expressed in 4 of the 5 type A thymomas and completely silenced in all 5 thymic carcinomas (Fig.	('thymic carcinomas', 'Disease', 'MESH:D013945', (98, 115))	('C19MC', 'Var', (0, 5))	('thymic carcinomas', 'Disease', (98, 115))	('type A thymomas', 'Disease', 'MESH:D013945', (49, 64))	('carcinoma', 'Phenotype', 'HP:0030731', (105, 114))	('A thymomas', 'Phenotype', 'HP:0100522', (54, 64))	('type A thymomas', 'Disease', (49, 64))	('carcinomas', 'Phenotype', 'HP:0030731', (105, 115))	('thymoma', 'Phenotype', 'HP:0100522', (56, 63))
20534	27844328	C14MC transcripts were also significantly downregulated in thymic carcinomas, but the cluster was not completely silenced (Fig.	('carcinoma', 'Phenotype', 'HP:0030731', (66, 75))	('carcinomas', 'Phenotype', 'HP:0030731', (66, 76))	('thymic carcinomas', 'Disease', 'MESH:D013945', (59, 76))	('downregulated', 'NegReg', (42, 55))	('C14MC', 'Var', (0, 5))	('thymic carcinomas', 'Disease', (59, 76))
20536	27844328	On the contrary miR-34b, miR-34c, miR-130a and miR-195 were of low abundance in thymic carcinomas, but strongly expressed in type A thymomas (Fig.	('thymic carcinomas', 'Disease', (80, 97))	('thymoma', 'Phenotype', 'HP:0100522', (132, 139))	('miR-34b', 'Var', (16, 23))	('miR-34', 'Chemical', '-', (25, 31))	('miR-34c', 'Var', (25, 32))	('carcinomas', 'Phenotype', 'HP:0030731', (87, 97))	('thymic carcinomas', 'Disease', 'MESH:D013945', (80, 97))	('type A thymomas', 'Disease', 'MESH:D013945', (125, 140))	('miR-130a', 'Chemical', '-', (34, 42))	('A thymomas', 'Phenotype', 'HP:0100522', (130, 140))	('miR-130a', 'Var', (34, 42))	('type A thymomas', 'Disease', (125, 140))	('miR-34', 'Chemical', '-', (16, 22))	('expressed', 'Reg', (112, 121))	('miR-195', 'Gene', (47, 54))	('miR-195', 'Gene', '406971', (47, 54))	('carcinoma', 'Phenotype', 'HP:0030731', (87, 96))
20549	27844328	In thymic carcinomas, but not in type A and B3 thymomas, a lack of p16INK4A expression was largely associated with CDKN2A mutation or gene deletion (data not shown).	('CDKN2A', 'Gene', (115, 121))	('gene deletion', 'Var', (134, 147))	('lack', 'NegReg', (59, 63))	('p16INK4A', 'Gene', (67, 75))	('mutation', 'Var', (122, 130))	('carcinomas', 'Phenotype', 'HP:0030731', (10, 20))	('thymic carcinomas', 'Disease', 'MESH:D013945', (3, 20))	('p16INK4A', 'Gene', '1029', (67, 75))	('thymoma', 'Phenotype', 'HP:0100522', (47, 54))	('expression', 'MPA', (76, 86))	('thymic carcinomas', 'Disease', (3, 20))	('thymomas', 'Disease', 'MESH:D013945', (47, 55))	('carcinoma', 'Phenotype', 'HP:0030731', (10, 19))	('associated', 'Reg', (99, 109))	('thymomas', 'Disease', (47, 55))
20559	27844328	It encodes p16INK4A and p14ARF by alternative splicing.	('p14ARF', 'Var', (24, 30))	('p16INK4A', 'Gene', '1029', (11, 19))	('p16INK4A', 'Gene', (11, 19))
20560	27844328	p16INK4A inhibits cell cycle progression by blocking cyclin dependent kinases 4 and 6, whereas p14ARF activates the TP53 tumor suppressor.	('cyclin', 'Enzyme', (53, 59))	('cell cycle progression', 'CPA', (18, 40))	('TP53', 'Gene', (116, 120))	('tumor', 'Phenotype', 'HP:0002664', (121, 126))	('tumor', 'Disease', (121, 126))	('p16INK4A', 'Gene', (0, 8))	('activates', 'PosReg', (102, 111))	('inhibits', 'NegReg', (9, 17))	('block', 'Disease', 'MESH:D006327', (44, 49))	('block', 'Disease', (44, 49))	('p14ARF', 'Var', (95, 101))	('p16INK4A', 'Gene', '1029', (0, 8))	('tumor', 'Disease', 'MESH:D009369', (121, 126))
20561	27844328	Inhibitors for these kinases are currently being investigated in clinical trials for various malignancies and might constitute a therapeutic option also for thymic carcinomas.	('thymic carcinomas', 'Disease', 'MESH:D013945', (157, 174))	('thymic carcinomas', 'Disease', (157, 174))	('Inhibitors', 'Var', (0, 10))	('malignancies', 'Disease', 'MESH:D009369', (93, 105))	('carcinoma', 'Phenotype', 'HP:0030731', (164, 173))	('malignancies', 'Disease', (93, 105))	('carcinomas', 'Phenotype', 'HP:0030731', (164, 174))
20563	27844328	In our study, however, CDKN2A gene loss or mutation did not correlate with a worse outcome in thymic carcinomas.	('thymic carcinomas', 'Disease', (94, 111))	('carcinoma', 'Phenotype', 'HP:0030731', (101, 110))	('mutation', 'Var', (43, 51))	('loss', 'NegReg', (35, 39))	('CDKN2A', 'Gene', (23, 29))	('carcinomas', 'Phenotype', 'HP:0030731', (101, 111))	('thymic carcinomas', 'Disease', 'MESH:D013945', (94, 111))
20565	27844328	A TP53 protein overexpression, which is often caused by TP53 mutation, has been reported in a cohort of 25 thymic carcinomas to be associated with a worse disease free survival.	('overexpression', 'PosReg', (15, 29))	('carcinoma', 'Phenotype', 'HP:0030731', (114, 123))	('mutation', 'Var', (61, 69))	('TP53 protein', 'Protein', (2, 14))	('carcinomas', 'Phenotype', 'HP:0030731', (114, 124))	('thymic carcinomas', 'Disease', 'MESH:D013945', (107, 124))	('TP53', 'Gene', (56, 60))	('thymic carcinomas', 'Disease', (107, 124))
20566	27844328	In our study with 31 evaluable thymic carcinomas TP53 gene loss or mutation was, however, not a prognostic marker for disease free or overall survival.	('carcinomas TP53 gene loss', 'Disease', (38, 63))	('mutation', 'Var', (67, 75))	('thymic carcinomas', 'Disease', 'MESH:D013945', (31, 48))	('carcinomas', 'Phenotype', 'HP:0030731', (38, 48))	('carcinomas TP53 gene loss', 'Disease', 'MESH:D025063', (38, 63))	('carcinoma', 'Phenotype', 'HP:0030731', (38, 47))	('thymic carcinomas', 'Disease', (31, 48))
20568	27844328	Mutated KIT constitutes a therapeutic target for kinase inhibitors such as imatinib.	('Mutated', 'Var', (0, 7))	('imatinib', 'Chemical', 'MESH:D000068877', (75, 83))	('KIT', 'Gene', (8, 11))
20569	27844328	KIT mutation is rare in thymic carcinoma, but so far the only known molecular target based on few, but encouraging case reports.	('mutation', 'Var', (4, 12))	('thymic carcinoma', 'Disease', (24, 40))	('KIT', 'Gene', (0, 3))	('thymic carcinoma', 'Disease', 'MESH:D013945', (24, 40))	('carcinoma', 'Phenotype', 'HP:0030731', (31, 40))
20570	27844328	In our series two carcinomas with KIT mutations that predict sensitivity to imatinib were present.	('carcinoma', 'Phenotype', 'HP:0030731', (18, 27))	('imatinib', 'Chemical', 'MESH:D000068877', (76, 84))	('carcinomas', 'Phenotype', 'HP:0030731', (18, 28))	('carcinomas', 'Disease', (18, 28))	('carcinomas', 'Disease', 'MESH:D002277', (18, 28))	('mutations', 'Var', (38, 47))	('KIT', 'Gene', (34, 37))
20572	27844328	FGFR genes are deregulated in solid tumors by amplification, translocation or mutation.	('translocation', 'Var', (61, 74))	('solid tumors', 'Disease', (30, 42))	('deregulated', 'PosReg', (15, 26))	('amplification', 'Var', (46, 59))	('mutation', 'Var', (78, 86))	('solid tumors', 'Disease', 'MESH:D009369', (30, 42))	('tumor', 'Phenotype', 'HP:0002664', (36, 41))	('FGFR genes', 'Gene', (0, 10))	('tumors', 'Phenotype', 'HP:0002664', (36, 42))
20573	27844328	FGFR3 mutations are particulary frequent in bladder cancer, where they are associated with low grade, early stage, and better survival.	('cancer', 'Phenotype', 'HP:0002664', (52, 58))	('bladder cancer', 'Phenotype', 'HP:0009725', (44, 58))	('FGFR3', 'Gene', (0, 5))	('bladder cancer', 'Disease', 'MESH:D001749', (44, 58))	('bladder cancer', 'Disease', (44, 58))	('mutations', 'Var', (6, 15))	('frequent', 'Reg', (32, 40))
20574	27844328	We observed a FGFR3 missense mutation in two thymic carcinomas.	('missense mutation', 'Var', (20, 37))	('carcinoma', 'Phenotype', 'HP:0030731', (52, 61))	('carcinomas', 'Phenotype', 'HP:0030731', (52, 62))	('thymic carcinomas', 'Disease', 'MESH:D013945', (45, 62))	('FGFR3', 'Gene', (14, 19))	('thymic carcinomas', 'Disease', (45, 62))
20575	27844328	Thus, inhibition of FGFR3 might represent a novel target in a subset of thymic carcinomas.	('carcinomas', 'Phenotype', 'HP:0030731', (79, 89))	('FGFR3', 'Gene', (20, 25))	('thymic carcinomas', 'Disease', 'MESH:D013945', (72, 89))	('inhibition', 'Var', (6, 16))	('carcinoma', 'Phenotype', 'HP:0030731', (79, 88))	('thymic carcinomas', 'Disease', (72, 89))
20576	27844328	ALK is a receptor tyrosine kinase that, when altered by chromosomal inversion, translocation, amplification or mutation, plays an oncogenic role in certain cancers.	('altered', 'Reg', (45, 52))	('amplification', 'Var', (94, 107))	('cancers', 'Phenotype', 'HP:0002664', (156, 163))	('cancers', 'Disease', (156, 163))	('cancers', 'Disease', 'MESH:D009369', (156, 163))	('plays', 'Reg', (121, 126))	('translocation', 'Var', (79, 92))	('receptor tyrosine kinase', 'Gene', '5979', (9, 33))	('ALK', 'Gene', (0, 3))	('cancer', 'Phenotype', 'HP:0002664', (156, 162))	('receptor tyrosine kinase', 'Gene', (9, 33))	('mutation', 'Var', (111, 119))	('ALK', 'Gene', '238', (0, 3))
20577	27844328	Best known are ALK gene alterations in anaplastic large cell lymphoma, lung adenocarcinoma, inflammatory myofibroblastic tumor and neuroblastoma.	('ALK', 'Gene', (15, 18))	('cell lymphoma', 'Disease', (56, 69))	('neuroblastoma', 'Disease', (131, 144))	('alterations', 'Var', (24, 35))	('lung adenocarcinoma', 'Phenotype', 'HP:0030078', (71, 90))	('tumor', 'Phenotype', 'HP:0002664', (121, 126))	('lymphoma', 'Phenotype', 'HP:0002665', (61, 69))	('lung adenocarcinoma', 'Disease', (71, 90))	('tumor', 'Disease', (121, 126))	('ALK', 'Gene', '238', (15, 18))	('cell lymphoma', 'Phenotype', 'HP:0012191', (56, 69))	('carcinoma', 'Phenotype', 'HP:0030731', (81, 90))	('neuroblastoma', 'Phenotype', 'HP:0003006', (131, 144))	('lung adenocarcinoma', 'Disease', 'MESH:D000077192', (71, 90))	('cell lymphoma', 'Disease', 'MESH:D016399', (56, 69))	('myofibroblastic tumor', 'Phenotype', 'HP:0020135', (105, 126))	('neuroblastoma', 'Disease', 'MESH:D009447', (131, 144))	('tumor', 'Disease', 'MESH:D009369', (121, 126))
20584	27844328	Therapy of colon and breast cancer with anti-EGFR and anti-ERBB2 antibodies, respectively, and of EGFR mutated lung adenocarcinoma with tyrosine kinase inhibitors is well established.	('EGFR', 'Gene', (98, 102))	('lung adenocarcinoma', 'Phenotype', 'HP:0030078', (111, 130))	('carcinoma', 'Phenotype', 'HP:0030731', (121, 130))	('mutated', 'Var', (103, 110))	('cancer', 'Phenotype', 'HP:0002664', (28, 34))	('lung adenocarcinoma', 'Disease', (111, 130))	('breast cancer', 'Phenotype', 'HP:0003002', (21, 34))	('lung adenocarcinoma', 'Disease', 'MESH:D000077192', (111, 130))	('RB', 'Disease', 'MESH:D012175', (60, 62))	('colon and breast cancer', 'Disease', 'MESH:D001943', (11, 34))
20585	27844328	ERBB4 mutations have been identified in lung, breast and gastric cancer and melanoma.	('melanoma', 'Disease', (76, 84))	('melanoma', 'Disease', 'MESH:D008545', (76, 84))	('cancer', 'Phenotype', 'HP:0002664', (65, 71))	('lung', 'Disease', (40, 44))	('gastric cancer', 'Phenotype', 'HP:0012126', (57, 71))	('RB', 'Disease', 'MESH:D012175', (1, 3))	('identified', 'Reg', (26, 36))	('mutations', 'Var', (6, 15))	('breast and gastric cancer', 'Disease', 'MESH:D013274', (46, 71))	('melanoma', 'Phenotype', 'HP:0002861', (76, 84))
20586	27844328	Several of these ERBB4 mutations were shown to be oncogenic in melanoma models and could be inhibited by treatment with lapatinib.	('RB', 'Disease', 'MESH:D012175', (18, 20))	('oncogenic', 'CPA', (50, 59))	('melanoma models', 'Disease', (63, 78))	('mutations', 'Var', (23, 32))	('melanoma models', 'Disease', 'MESH:D008545', (63, 78))	('lapatinib', 'Chemical', 'MESH:D000077341', (120, 129))	('melanoma', 'Phenotype', 'HP:0002861', (63, 71))
20587	27844328	ERBB4 mutated thymic carcinoma might also be inhibited by EGFR family blockers such as lapatinib and afatinib.	('block', 'Disease', (70, 75))	('thymic carcinoma', 'Disease', 'MESH:D013945', (14, 30))	('block', 'Disease', 'MESH:D006327', (70, 75))	('lapatinib', 'Chemical', 'MESH:D000077341', (87, 96))	('EGFR', 'Gene', (58, 62))	('thymic carcinoma', 'Disease', (14, 30))	('afatinib', 'Chemical', 'MESH:D000077716', (101, 109))	('RB', 'Disease', 'MESH:D012175', (1, 3))	('carcinoma', 'Phenotype', 'HP:0030731', (21, 30))	('mutated', 'Var', (6, 13))
20593	27844328	One thymic carcinoma harbored a NRAS and three type A thymomas a HRAS mutation.	('type A thymomas', 'Disease', 'MESH:D013945', (47, 62))	('A thymomas', 'Phenotype', 'HP:0100522', (52, 62))	('thymoma', 'Phenotype', 'HP:0100522', (54, 61))	('type A thymomas', 'Disease', (47, 62))	('HRAS', 'Gene', (65, 69))	('NRAS', 'Disease', (32, 36))	('thymic carcinoma', 'Disease', (4, 20))	('mutation', 'Var', (70, 78))	('thymic carcinoma', 'Disease', 'MESH:D013945', (4, 20))	('carcinoma', 'Phenotype', 'HP:0030731', (11, 20))
20596	27844328	C19MC overexpression has been reported in embryonal pediatric brain tumors caused by fusion with TTYH1 or focal genomic amplification.	('fusion', 'Var', (85, 91))	('C19MC', 'Var', (0, 5))	('tumors', 'Phenotype', 'HP:0002664', (68, 74))	('TTYH1', 'Protein', (97, 102))	('embryonal pediatric brain tumors', 'Disease', 'MESH:D001932', (42, 74))	('embryonal pediatric brain tumors', 'Disease', (42, 74))	('caused by', 'Reg', (75, 84))	('overexpression', 'PosReg', (6, 20))	('brain tumors', 'Phenotype', 'HP:0030692', (62, 74))	('tumor', 'Phenotype', 'HP:0002664', (68, 73))	('focal genomic amplification', 'Var', (106, 133))
20598	27844328	C19MC overexpression in type A and AB thymomas has recently been reported by Radovich M. et al., who suggested that one of the key functions of the cluster is the activation of the PI3K/AKT pathway.	('C19MC', 'Var', (0, 5))	('activation', 'PosReg', (163, 173))	('PI3K/AKT pathway', 'Pathway', (181, 197))	('AB thymomas', 'Disease', 'MESH:D013945', (35, 46))	('AB thymomas', 'Disease', (35, 46))	('thymoma', 'Phenotype', 'HP:0100522', (38, 45))
20600	27844328	C14MC miRNA expression was decreased in thymic carcinomas as compared to type A thymomas, but still present to some degree, with not all miRNAs of the cluster affected.	('thymic carcinomas', 'Disease', 'MESH:D013945', (40, 57))	('thymoma', 'Phenotype', 'HP:0100522', (80, 87))	('decreased', 'NegReg', (27, 36))	('thymic carcinomas', 'Disease', (40, 57))	('carcinoma', 'Phenotype', 'HP:0030731', (47, 56))	('C14MC', 'Var', (0, 5))	('carcinomas', 'Phenotype', 'HP:0030731', (47, 57))	('type A thymomas', 'Disease', 'MESH:D013945', (73, 88))	('A thymomas', 'Phenotype', 'HP:0100522', (78, 88))	('type A thymomas', 'Disease', (73, 88))
20601	27844328	Infering from published work suggesting that C14MC functions as a large tumor suppressor cluster in GIST and glioma we assume that the downregulation of C14MC miRNAs might exert a tumor promoting effect in thymic carcinomas.	('tumor', 'Disease', 'MESH:D009369', (180, 185))	('glioma', 'Phenotype', 'HP:0009733', (109, 115))	('tumor', 'Phenotype', 'HP:0002664', (72, 77))	('C14MC', 'Var', (153, 158))	('tumor', 'Phenotype', 'HP:0002664', (180, 185))	('tumor', 'Disease', (72, 77))	('GIST', 'Disease', (100, 104))	('thymic carcinomas', 'Disease', 'MESH:D013945', (206, 223))	('carcinomas', 'Phenotype', 'HP:0030731', (213, 223))	('tumor', 'Disease', (180, 185))	('glioma', 'Disease', (109, 115))	('tumor', 'Disease', 'MESH:D009369', (72, 77))	('carcinoma', 'Phenotype', 'HP:0030731', (213, 222))	('downregulation', 'NegReg', (135, 149))	('thymic carcinomas', 'Disease', (206, 223))	('glioma', 'Disease', 'MESH:D005910', (109, 115))
20602	27844328	Among the non-clustered miRNAs with significant differences in expression between type A thymomas and thymic carcinomas, the low expression of miR-34b, miR-34c, miR-130a and miR-195 in thymic carcinomas was most pronounced.	('thymic carcinomas', 'Disease', (102, 119))	('carcinoma', 'Phenotype', 'HP:0030731', (192, 201))	('carcinomas', 'Phenotype', 'HP:0030731', (192, 202))	('miR-34b', 'Var', (143, 150))	('thymomas and thymic carcinomas', 'Disease', 'MESH:D013945', (89, 119))	('thymoma', 'Phenotype', 'HP:0100522', (89, 96))	('A thymomas', 'Phenotype', 'HP:0100522', (87, 97))	('miR-130a', 'Chemical', '-', (161, 169))	('miR-130a', 'Var', (161, 169))	('miR-195', 'Gene', '406971', (174, 181))	('thymic carcinomas', 'Disease', 'MESH:D013945', (185, 202))	('carcinoma', 'Phenotype', 'HP:0030731', (109, 118))	('thymic carcinomas', 'Disease', (185, 202))	('miR-34', 'Chemical', '-', (152, 158))	('carcinomas', 'Phenotype', 'HP:0030731', (109, 119))	('miR-195', 'Gene', (174, 181))	('miR-34', 'Chemical', '-', (143, 149))	('type A thymomas', 'Disease', (82, 97))	('type A thymomas', 'Disease', 'MESH:D013945', (82, 97))	('miR-34c', 'Var', (152, 159))	('thymic carcinomas', 'Disease', 'MESH:D013945', (102, 119))
20604	27844328	In non-small cell lung cancer (NSCLC) immune evasion of the tumor via PD-L1 is mediated by miR-34.	('mediated by', 'Reg', (79, 90))	('PD-L1', 'Gene', '29126', (70, 75))	('non-small cell lung cancer', 'Phenotype', 'HP:0030358', (3, 29))	('NSCLC', 'Disease', (31, 36))	('tumor', 'Disease', 'MESH:D009369', (60, 65))	('miR-34', 'Var', (91, 97))	('NSCLC', 'Disease', 'MESH:D002289', (31, 36))	('miR-34', 'Chemical', '-', (91, 97))	('lung cancer', 'Phenotype', 'HP:0100526', (18, 29))	('tumor', 'Phenotype', 'HP:0002664', (60, 65))	('non-small cell lung cancer', 'Disease', 'MESH:D002289', (3, 29))	('cancer', 'Phenotype', 'HP:0002664', (23, 29))	('tumor', 'Disease', (60, 65))	('non-small cell lung cancer', 'Disease', (3, 29))	('NSCLC', 'Phenotype', 'HP:0030358', (31, 36))	('PD-L1', 'Gene', (70, 75))	('small cell lung cancer', 'Phenotype', 'HP:0030357', (7, 29))
20608	27844328	Among the non-clustered miRNAs overexpressed in thymic carcinoma as compared to type A thymoma miR21, miR-9-3 and miR-375 were most significant.	('thymoma', 'Phenotype', 'HP:0100522', (87, 94))	('thymic carcinoma', 'Disease', 'MESH:D013945', (48, 64))	('miR-375', 'Var', (114, 121))	('miR-9-3', 'Var', (102, 109))	('miR21', 'Var', (95, 100))	('carcinoma', 'Phenotype', 'HP:0030731', (55, 64))	('overexpressed', 'PosReg', (31, 44))	('A thymoma', 'Disease', 'MESH:D013945', (85, 94))	('miR-375', 'Chemical', '-', (114, 121))	('A thymoma', 'Disease', (85, 94))	('thymic carcinoma', 'Disease', (48, 64))
20610	27844328	In contrast to our findings in thymic carcinomas miR-9-3 has been reported to be repressed by methylation in NSCLC.	('thymic carcinomas', 'Disease', (31, 48))	('NSCLC', 'Disease', 'MESH:D002289', (109, 114))	('thymic carcinomas', 'Disease', 'MESH:D013945', (31, 48))	('carcinomas', 'Phenotype', 'HP:0030731', (38, 48))	('NSCLC', 'Phenotype', 'HP:0030358', (109, 114))	('methylation', 'Var', (94, 105))	('carcinoma', 'Phenotype', 'HP:0030731', (38, 47))	('NSCLC', 'Disease', (109, 114))
20620	27844328	The authors furthermore described HER3 positivity in 45.8 % of the carcinomas.	('HER3', 'Gene', (34, 38))	('HER3', 'Gene', '2065', (34, 38))	('carcinomas', 'Disease', 'MESH:D002277', (67, 77))	('carcinoma', 'Phenotype', 'HP:0030731', (67, 76))	('carcinomas', 'Phenotype', 'HP:0030731', (67, 77))	('carcinomas', 'Disease', (67, 77))	('positivity', 'Var', (39, 49))
20621	27844328	detected HER2 positivity in nine of 17 thymic carcinomas, but no HER2 gene amplification could be demonstrated by FISH.	('HER2', 'Gene', '2064', (65, 69))	('carcinoma', 'Phenotype', 'HP:0030731', (46, 55))	('thymic carcinomas', 'Disease', (39, 56))	('HER2', 'Gene', (9, 13))	('HER2', 'Gene', '2064', (9, 13))	('carcinomas', 'Phenotype', 'HP:0030731', (46, 56))	('positivity', 'Var', (14, 24))	('thymic carcinomas', 'Disease', 'MESH:D013945', (39, 56))	('HER2', 'Gene', (65, 69))
20625	27844328	Tumors with MET overexpression, gene amplification and exon 14 skipping mutations are candidates for MET targeted therapies in clinical trials.	('overexpression', 'PosReg', (16, 30))	('gene amplification', 'Var', (32, 50))	('exon', 'Var', (55, 59))	('Tumors', 'Disease', (0, 6))	('Tumors', 'Disease', 'MESH:D009369', (0, 6))	('Tumors', 'Phenotype', 'HP:0002664', (0, 6))	('skipping', 'NegReg', (63, 71))
20627	27844328	Aberrations in the PI3K/mTOR/AKT pathway are common in solid tumors.	('common', 'Reg', (45, 51))	('solid tumors', 'Disease', (55, 67))	('solid tumors', 'Disease', 'MESH:D009369', (55, 67))	('tumor', 'Phenotype', 'HP:0002664', (61, 66))	('tumors', 'Phenotype', 'HP:0002664', (61, 67))	('Aberrations', 'Var', (0, 11))	('mTOR', 'Gene', (24, 28))	('mTOR', 'Gene', '2475', (24, 28))
20643	27844328	In thymic carcinomas a lack of p16INK4A protein expression was largely associated with CDKNA gene deletion.	('carcinomas', 'Phenotype', 'HP:0030731', (10, 20))	('expression', 'MPA', (48, 58))	('deletion', 'Var', (98, 106))	('thymic carcinomas', 'Disease', 'MESH:D013945', (3, 20))	('p16INK4A', 'Gene', (31, 39))	('thymic carcinomas', 'Disease', (3, 20))	('lack', 'NegReg', (23, 27))	('carcinoma', 'Phenotype', 'HP:0030731', (10, 19))	('p16INK4A', 'Gene', '1029', (31, 39))	('associated', 'Reg', (71, 81))	('CDKNA gene', 'Disease', (87, 97))
20644	27844328	In type A thymomas that lacked CDKN2A deletions and type B3 thymomas that rarely (7 %) exhibited CDKN2A deletion a different mechanism must predominate.	('thymomas', 'Disease', (10, 18))	('thymomas', 'Disease', 'MESH:D013945', (10, 18))	('type A thymomas', 'Disease', 'MESH:D013945', (3, 18))	('thymoma', 'Phenotype', 'HP:0100522', (60, 67))	('A thymomas', 'Phenotype', 'HP:0100522', (8, 18))	('type A thymomas', 'Disease', (3, 18))	('deletions', 'Var', (38, 47))	('thymomas', 'Disease', (60, 68))	('thymomas', 'Disease', 'MESH:D013945', (60, 68))	('CDKN2A', 'Gene', (31, 37))	('thymoma', 'Phenotype', 'HP:0100522', (10, 17))
20645	27844328	CDKN2A promoter methylation is a known alternative mechanism of p16I INK4A silencing and may dominate in type A and B3 thymomas.	('dominate', 'Reg', (93, 101))	('thymomas', 'Disease', (119, 127))	('silencing', 'NegReg', (75, 84))	('thymoma', 'Phenotype', 'HP:0100522', (119, 126))	('p16I', 'Var', (64, 68))	('thymomas', 'Disease', 'MESH:D013945', (119, 127))
20651	27844328	Furthermore, PD-L1 high TETs were associated with a more aggressive histology and worse prognosis.	('aggressive histology', 'CPA', (57, 77))	('PD-L1', 'Gene', (13, 18))	('high TETs', 'Var', (19, 28))	('PD-L1', 'Gene', '29126', (13, 18))
20659	27844328	ROS1 is a tyrosine kinase that is aberrantly activated by translocation in a subset of lung carcinomas and cholangiocarcinomas.	('translocation', 'Var', (58, 71))	('ROS1', 'Gene', (0, 4))	('carcinoma', 'Phenotype', 'HP:0030731', (92, 101))	('ROS1', 'Gene', '6098', (0, 4))	('lung carcinomas and cholangiocarcinomas', 'Disease', 'MESH:D018281', (87, 126))	('carcinomas', 'Phenotype', 'HP:0030731', (92, 102))	('carcinoma', 'Phenotype', 'HP:0030731', (116, 125))	('carcinomas', 'Phenotype', 'HP:0030731', (116, 126))	('activated', 'PosReg', (45, 54))
20661	27844328	ROS1 positivity by immunohistochemistry is a surrogate marker for the presence of a ROS1 translocation.	('translocation', 'Var', (89, 102))	('ROS1', 'Gene', '6098', (84, 88))	('ROS1', 'Gene', (0, 4))	('ROS1', 'Gene', '6098', (0, 4))	('ROS1', 'Gene', (84, 88))
20665	27844328	In summary, our data show genetic differences between type A and B3 thymomas and thymic carcinomas with respect to cancer gene mutations and miRNA expression.	('miRNA expression', 'MPA', (141, 157))	('cancer', 'Disease', (115, 121))	('thymomas and thymic carcinomas', 'Disease', 'MESH:D013945', (68, 98))	('thymoma', 'Phenotype', 'HP:0100522', (68, 75))	('cancer', 'Phenotype', 'HP:0002664', (115, 121))	('carcinoma', 'Phenotype', 'HP:0030731', (88, 97))	('carcinomas', 'Phenotype', 'HP:0030731', (88, 98))	('mutations', 'Var', (127, 136))	('cancer', 'Disease', 'MESH:D009369', (115, 121))
20667	24482655	FK506 attenuates thymic output in patients with myasthenia gravis Myasthenia gravis (MG) is an antibody-mediated, T-cell-dependent autoimmune disease.	('myasthenia gravis', 'Disease', (48, 65))	('autoimmune disease', 'Disease', 'MESH:D001327', (131, 149))	('attenuates', 'NegReg', (6, 16))	('autoimmune disease', 'Phenotype', 'HP:0002960', (131, 149))	('FK506', 'Var', (0, 5))	('FK506', 'Chemical', 'MESH:D016559', (0, 5))	('myasthenia gravis', 'Disease', 'MESH:D009157', (48, 65))	('myasthenia', 'Phenotype', 'HP:0003473', (48, 58))	('patients', 'Species', '9606', (34, 42))	('autoimmune disease', 'Disease', (131, 149))	('Myasthenia', 'Phenotype', 'HP:0003473', (66, 76))	('Myasthenia gravis', 'Disease', (66, 83))	('Myasthenia gravis', 'Disease', 'MESH:D009157', (66, 83))	('thymic output', 'MPA', (17, 30))
20668	24482655	The production of these antibodies in B-cells depends on AChR-specific CD4+ T-cells and the thymus gland seems to play a significant role in the pathogenesis of MG. Altered thymic T-cell export seems to be associated with a pathological mechanism in myasthenia gravis.	('myasthenia', 'Phenotype', 'HP:0003473', (250, 260))	('associated', 'Reg', (206, 216))	('thymic T-cell export', 'MPA', (173, 193))	('Altered', 'Var', (165, 172))	('myasthenia gravis', 'Disease', (250, 267))	('CD4', 'Gene', (71, 74))	('CD4', 'Gene', '920', (71, 74))	('myasthenia gravis', 'Disease', 'MESH:D009157', (250, 267))
20731	24482655	The patients with myasthenia gravis took FK506 for at least 6 months.	('myasthenia gravis', 'Disease', 'MESH:D009157', (18, 35))	('FK506', 'Chemical', 'MESH:D016559', (41, 46))	('patients', 'Species', '9606', (4, 12))	('FK506', 'Var', (41, 46))	('myasthenia', 'Phenotype', 'HP:0003473', (18, 28))	('myasthenia gravis', 'Disease', (18, 35))
20753	24482655	It is confirmed in many institutions that low-dose FK506 is effective in myasthenia gravis.	('myasthenia gravis', 'Disease', (73, 90))	('myasthenia gravis', 'Disease', 'MESH:D009157', (73, 90))	('myasthenia', 'Phenotype', 'HP:0003473', (73, 83))	('FK506', 'Var', (51, 56))	('FK506', 'Chemical', 'MESH:D016559', (51, 56))
20792	22720235	As depicted in Figure 1A and B, the vaccination with EG-7/alphaGC significantly reduced the growth of solid tumors and induced prolonged survival in comparison to those of EG-7/veh group.	('solid tumors', 'Disease', (102, 114))	('survival', 'CPA', (137, 145))	('growth', 'MPA', (92, 98))	('tumor', 'Phenotype', 'HP:0002664', (108, 113))	('EG-7/alphaGC', 'Var', (53, 65))	('prolonged', 'PosReg', (127, 136))	('reduced', 'NegReg', (80, 87))	('solid tumors', 'Disease', 'MESH:D009369', (102, 114))	('tumors', 'Phenotype', 'HP:0002664', (108, 114))
20793	22720235	Tumors affect myelopoiesis and induce the expansion of CD11b+Gr-1+ myeloid-derived suppressor cell (MDSC) in the bone marrow, blood, spleen.	('Tumor', 'Phenotype', 'HP:0002664', (0, 5))	('Tumors', 'Disease', (0, 6))	('CD11b+Gr-1+', 'Var', (55, 66))	('Tumors', 'Disease', 'MESH:D009369', (0, 6))	('Tumors', 'Phenotype', 'HP:0002664', (0, 6))	('myelopoiesis', 'CPA', (14, 26))	('affect', 'Reg', (7, 13))
20794	22720235	Of note, we also observed a great decrease of CD11b+Gr-1+ population in the spleen of EG-7/alphaGC vaccinated mice (< 4%) compared with that of EG-7/veh group (> 20%) (Fig.	('mice', 'Species', '10090', (110, 114))	('EG-7/alphaGC', 'Var', (86, 98))	('CD11b+Gr-1+', 'MPA', (46, 57))	('decrease', 'NegReg', (34, 42))
20809	22720235	As depicted in Figure 3B, the CD8+ T cells from the EG-7/alphaGC vaccinated mice induced a significantly higher percentage of caspase-3 cleavage in the target cells than those from the EG-7/veh vaccinated mice.	('higher', 'PosReg', (105, 111))	('caspase-3', 'Gene', '12367', (126, 135))	('mice', 'Species', '10090', (76, 80))	('mice', 'Species', '10090', (205, 209))	('caspase-3', 'Gene', (126, 135))	('EG-7/alphaGC', 'Var', (52, 64))
20819	22720235	When we analyzed splenocytes six hours after the injection, we observed that CD1d-tetramer+ cells in mice receiving T/alphaGC produced IFNgamma+ whereas the same population in mice receiving T/veh did not produce IFNgamma (Fig.	('IFNgamma', 'Gene', (135, 143))	('IFNgamma', 'Gene', '15978', (135, 143))	('mice', 'Species', '10090', (176, 180))	('mice', 'Species', '10090', (101, 105))	('IFNgamma', 'Gene', (213, 221))	('T/alphaGC', 'Var', (116, 125))	('IFNgamma', 'Gene', '15978', (213, 221))
20849	22720235	We utilized bm-1 mouse whose cells are able to load SIINFEKL onto their MHC I, but the resulting complex cannot be recognized by OT-I TCR due to a mutation in the H-2K region.	('TCR', 'Gene', '328483', (134, 137))	('mouse', 'Species', '10090', (17, 22))	('H-2K region', 'Gene', (163, 174))	('SIINFEKL', 'Disease', (52, 60))	('mutation', 'Var', (147, 155))	('TCR', 'Gene', (134, 137))	('SIINFEKL', 'Disease', 'None', (52, 60))
20867	22720235	T cells were isolated from C57BL/6(WT), B7-/- (B7.1-/-B7.2-/-), B7h-/- or B7B7h-/- and loaded with alphaGC and SIINFEKL ex vivo.	('SIINFEKL', 'Disease', 'None', (111, 119))	('SIINFEKL', 'Disease', (111, 119))	('B7h-/-', 'Var', (64, 70))	('B7B7h-/-', 'Var', (74, 82))
20871	22720235	In the present study, we showed that vaccination with conventional CD4 T cells presenting both CD1d-alphaGC and MHC class I-restricted peptide triggered iNKT cell activation and generated an antigen-specific cytotoxic T lymphocyte response in vivo.	('activation', 'PosReg', (163, 173))	('iNKT cell', 'CPA', (153, 162))	('peptide', 'Chemical', 'MESH:D010455', (135, 142))	('antigen-specific cytotoxic T lymphocyte response', 'CPA', (191, 239))	('CD1d-alphaGC', 'Var', (95, 107))
20901	22720235	C57BL/6, OT-I, C57BL/6bm1 (bm-1), IL-4-/-, IFNgamma-/-, IL-12p35-/-, CD80-/-CD86-/- (B7-/-) mice were purchased from The Jackson Laboratory (Bar Harbor, ME).	('IFNgamma', 'Gene', (43, 51))	('IL-12p35', 'Gene', (56, 64))	('IL-4', 'Gene', (34, 38))	('CD80', 'Gene', (69, 73))	('IFNgamma', 'Gene', '15978', (43, 51))	('C57BL/6bm1', 'Var', (15, 25))	('IL-4', 'Gene', '16189', (34, 38))	('CD86', 'Gene', (76, 80))	('CD86', 'Gene', '12524', (76, 80))	('mice', 'Species', '10090', (92, 96))	('CD80', 'Gene', '12519', (69, 73))	('IL-12p35', 'Gene', '16159', (56, 64))
21017	32374079	To our knowledge, this is the first study to construct a lncRNAs classifier consisting of ADAMTS9-AS1, HSD52, LINC00968 and LINC01697, for predicting recurrence probability in patients with TETs.	('LINC01697', 'Var', (124, 133))	('patients', 'Species', '9606', (176, 184))	('ncRNA', 'Gene', '54719', (58, 63))	('LINC00968', 'Gene', (110, 119))	('AS1', 'Gene', (98, 101))	('LINC00968', 'Gene', '100507632', (110, 119))	('ncRNA', 'Gene', (58, 63))	('AS1', 'Gene', '5729', (98, 101))	('ADAMTS9', 'Gene', '56999', (90, 97))	('HSD52', 'Gene', (103, 108))	('HSD52', 'Gene', '729467', (103, 108))	('ADAMTS9', 'Gene', (90, 97))
21035	32374079	In our study, we found WHO histological types was not a significant association with recurrence among patients with TETs, which is in agreement with previous trials.26, 27 Nevertheless, several published trials reported that WHO histological types were an independent risk factor for TETs patients in predicting RFS.28, 29 Masaoka stage was significantly associated with recurrence among patients with TETs in univariate cox analysis, whereas not in multivariate cox analysis.	('RFS.28', 'Var', (312, 318))	('patients', 'Species', '9606', (289, 297))	('Masaoka stage', 'Disease', (323, 336))	('patients', 'Species', '9606', (102, 110))	('associated', 'Reg', (355, 365))	('patients', 'Species', '9606', (388, 396))	('recurrence', 'Disease', (371, 381))
21107	29924013	Upon MRI, leiomyosarcomas are seen with enhancement and have the appearance of water molecule diffusion confined in the diffusion-weighted imaging (DWI) sequence.	('sarcoma', 'Phenotype', 'HP:0100242', (17, 24))	('enhancement', 'PosReg', (40, 51))	('water molecule diffusion', 'MPA', (79, 103))	('leiomyosarcomas', 'Phenotype', 'HP:0100243', (10, 25))	('water', 'Chemical', 'MESH:D014867', (79, 84))	('leiomyosarcomas', 'Disease', 'MESH:D007890', (10, 25))	('men', 'Species', '9606', (47, 50))	('leiomyosarcoma', 'Phenotype', 'HP:0100243', (10, 24))	('leiomyosarcomas', 'Disease', (10, 25))	('MRI', 'Var', (5, 8))	('sarcomas', 'Phenotype', 'HP:0100242', (17, 25))
21155	29862111	's study showed the tumor group CSR value and the hyperplasia group CSR value of 1.0398 +- 0.0244 and 0.4964 +- 0.1841, respectively.	('0.4964 +-', 'Var', (102, 111))	('hyperplasia', 'Disease', (50, 61))	('tumor', 'Disease', 'MESH:D009369', (20, 25))	('tumor', 'Phenotype', 'HP:0002664', (20, 25))	('hyperplasia', 'Disease', 'MESH:D006965', (50, 61))	('tumor', 'Disease', (20, 25))
21207	33633666	Vitamin D Receptor Polymorphism and Myasthenia Gravis in Chinese Han Population Myasthenia gravis (MG) is an autoimmune disease in which antibodies bind to acetylcholine receptors (AChR) or other functional molecules in the postsynaptic membrane at the neuromuscular junction.	('Vitamin D Receptor', 'Gene', '7421', (0, 18))	('Myasthenia Gravis', 'Disease', (36, 53))	('Myasthenia gravis', 'Disease', (80, 97))	('bind', 'Interaction', (148, 152))	('autoimmune disease', 'Disease', (109, 127))	('Myasthenia gravis', 'Disease', 'MESH:D009157', (80, 97))	('Myasthenia', 'Phenotype', 'HP:0003473', (36, 46))	('acetylcholine', 'Chemical', 'MESH:D000109', (156, 169))	('autoimmune disease', 'Disease', 'MESH:D001327', (109, 127))	('autoimmune disease', 'Phenotype', 'HP:0002960', (109, 127))	('Myasthenia Gravis', 'Disease', 'MESH:D009157', (36, 53))	('acetylcholine', 'MPA', (156, 169))	('Vitamin D Receptor', 'Gene', (0, 18))	('Polymorphism', 'Var', (19, 31))	('Myasthenia', 'Phenotype', 'HP:0003473', (80, 90))
21209	33633666	The immunomodulatory actions of 1,25(OH)2D3 are mediated by its binding to a vitamin D receptor (VDR).	('binding', 'Interaction', (64, 71))	('VDR', 'Gene', (97, 100))	('vitamin D receptor', 'Gene', '7421', (77, 95))	('1,25(OH)2D3', 'Chemical', 'MESH:D002117', (32, 43))	('vitamin D receptor', 'Gene', (77, 95))	('VDR', 'Gene', '7421', (97, 100))	('1,25(OH)2D3', 'Var', (32, 43))
21210	33633666	In the study, we undertook a case-control study to explore the association between VDR gene polymorphism and the susceptibility and severity of MG patients.	('VDR', 'Gene', (83, 86))	('association', 'Interaction', (63, 74))	('VDR', 'Gene', '7421', (83, 86))	('patients', 'Species', '9606', (147, 155))	('polymorphism', 'Var', (92, 104))
21214	33633666	In the analysis of subgroups with a comprehensive classification, the frequencies of alleles and genotypes in rs731236 showed significant differences between adult non-thymoma AChRAb negative MG subgroup and the control group, as well as the adult non-thymoma AChRAb positive MG group.	('AChRAb', 'Chemical', '-', (260, 266))	('rs731236', 'Var', (110, 118))	('thymoma', 'Phenotype', 'HP:0100522', (252, 259))	('negative', 'NegReg', (183, 191))	('differences', 'Reg', (138, 149))	('thymoma', 'Phenotype', 'HP:0100522', (168, 175))	('rs731236', 'Mutation', 'rs731236', (110, 118))	('AChRAb', 'Chemical', '-', (176, 182))
21215	33633666	In the Chinese Han population, rs731236 was found to be possibly associated with adult non-thymoma AChRAb negative MG patients, although this needs further confirmation.	('adult non-thymoma AChRAb negative', 'Disease', (81, 114))	('AChRAb', 'Chemical', '-', (99, 105))	('thymoma', 'Phenotype', 'HP:0100522', (91, 98))	('associated', 'Reg', (65, 75))	('rs731236', 'Mutation', 'rs731236', (31, 39))	('patients', 'Species', '9606', (118, 126))	('rs731236', 'Var', (31, 39))
21220	33633666	Moreover, 1,25(OH)2D3 inhibits proliferation and differentiation of plasma cells.	('inhibits', 'NegReg', (22, 30))	('1,25(OH)2D3', 'Var', (10, 21))	('1,25(OH)2D3', 'Chemical', 'MESH:D002117', (10, 21))
21221	33633666	The immunomodulatory actions of 1,25(OH)2D3 are mediated by its binding to VDR.	('binding', 'Interaction', (64, 71))	('1,25(OH)2D3', 'Chemical', 'MESH:D002117', (32, 43))	('VDR', 'Gene', (75, 78))	('VDR', 'Gene', '7421', (75, 78))	('1,25(OH)2D3', 'Var', (32, 43))
21227	33633666	VDR genes' polymorphism has been associated with many autoimmune disorders such as autoimmune thyroid disease, idiopathic inflammatory myopathy, multiple sclerosis, type 1 diabetes mellitus, and systemic lupus erythematosus.	('autoimmune thyroid disease', 'Disease', 'MESH:D013967', (83, 109))	('multiple sclerosis', 'Disease', 'MESH:D009103', (145, 163))	('systemic lupus erythematosus', 'Phenotype', 'HP:0002725', (195, 223))	('type 1 diabetes', 'Phenotype', 'HP:0100651', (165, 180))	('diabetes mellitus', 'Disease', 'MESH:D003920', (172, 189))	('myopathy', 'Phenotype', 'HP:0003198', (135, 143))	('systemic lupus erythematosus', 'Disease', 'MESH:D008180', (195, 223))	('autoimmune disorders', 'Disease', (54, 74))	('diabetes mellitus', 'Phenotype', 'HP:0000819', (172, 189))	('idiopathic inflammatory myopathy', 'Disease', 'MESH:D009220', (111, 143))	('VDR', 'Gene', (0, 3))	('thyroid disease', 'Phenotype', 'HP:0000820', (94, 109))	('autoimmune disorders', 'Disease', 'MESH:D001327', (54, 74))	('autoimmune disorders', 'Phenotype', 'HP:0002960', (54, 74))	('polymorphism', 'Var', (11, 23))	('autoimmune thyroid disease', 'Disease', (83, 109))	('multiple sclerosis', 'Disease', (145, 163))	('systemic lupus erythematosus', 'Disease', (195, 223))	('diabetes mellitus', 'Disease', (172, 189))	('idiopathic inflammatory myopathy', 'Disease', (111, 143))	('VDR', 'Gene', '7421', (0, 3))	('associated', 'Reg', (33, 43))	('inflammatory myopathy', 'Phenotype', 'HP:0009071', (122, 143))
21228	33633666	Our previous study found that VDR gene Tru9I (rs757343) polymorphism was associated with risk of MG in females older than 15 years.	('rs757343) polymorphism', 'Var', (46, 68))	('polymorphism', 'Var', (56, 68))	('associated', 'Reg', (73, 83))	('VDR', 'Gene', (30, 33))	('rs757343', 'Mutation', 'rs757343', (46, 54))	('VDR', 'Gene', '7421', (30, 33))
21229	33633666	In this study, we undertook a case-control study to further explore the association between VDR gene polymorphisms and the susceptibility and severity of MG patients in a systematic way.	('association', 'Interaction', (72, 83))	('patients', 'Species', '9606', (157, 165))	('VDR', 'Gene', (92, 95))	('polymorphisms', 'Var', (101, 114))	('VDR', 'Gene', '7421', (92, 95))
21241	33633666	SNPs were selected systematically, including the functional loci [rs4516035 (5' near gene), rs2228570 (exon 2), rs9729 (3'UTR)], hot SNPs [rs1544410, rs731236, rs7975232, rs757343, rs2238136 ], and tag SNPs (rs3847987, rs10875692, rs2107301, rs2239186, rs2853564, rs11574027, rs7136534, rs739837, and rs2239181).	('rs11574027', 'Var', (264, 274))	('[rs4516035', 'Var', (65, 75))	('rs757343', 'Mutation', 'rs757343', (171, 179))	('rs2107301', 'Mutation', 'rs2107301', (231, 240))	('rs7136534', 'Mutation', 'rs7136534', (276, 285))	('rs4516035', 'Mutation', 'rs4516035', (66, 75))	('rs2239181', 'Mutation', 'rs2239181', (301, 310))	('rs1544410', 'Mutation', 'rs1544410', (139, 148))	('rs739837', 'Mutation', 'rs739837', (287, 295))	('rs3847987', 'Var', (208, 217))	('rs7136534', 'Var', (276, 285))	('rs2239186', 'Var', (242, 251))	('rs2239181', 'Var', (301, 310))	('rs2238136', 'Mutation', 'rs2238136', (181, 190))	('rs10875692', 'Var', (219, 229))	('rs2107301', 'Var', (231, 240))	('rs731236', 'Mutation', 'rs731236', (150, 158))	('rs2853564', 'Var', (253, 262))	('rs2239186', 'Mutation', 'rs2239186', (242, 251))	('rs731236', 'Var', (150, 158))	('rs7975232', 'Var', (160, 169))	('[rs1544410', 'Var', (138, 148))	('rs10875692', 'Mutation', 'rs10875692', (219, 229))	('rs2853564', 'Mutation', 'rs2853564', (253, 262))	('rs9729', 'Mutation', 'rs9729', (112, 118))	('rs2228570', 'Mutation', 'rs2228570', (92, 101))	('rs7975232', 'Mutation', 'rs7975232', (160, 169))	('rs739837', 'Var', (287, 295))	('rs11574027', 'Mutation', 'rs11574027', (264, 274))	('rs2238136 ]', 'Var', (181, 192))	('rs757343', 'Var', (171, 179))	('rs2228570', 'Var', (92, 101))	('rs3847987', 'Mutation', 'rs3847987', (208, 217))	('rs9729', 'Var', (112, 118))
21243	33633666	Rs1544410 and rs2107301 were genotyped by using improved multiplex ligation detection reaction (iMLDR) technique (Shanghai Genesky Biotechnologies Inc. China).	('rs2107301', 'Var', (14, 23))	('Rs1544410', 'Mutation', 'Rs1544410', (0, 9))	('Rs1544410', 'Var', (0, 9))	('rs2107301', 'Mutation', 'rs2107301', (14, 23))
21258	33633666	The G allele frequency in rs731236 was significantly higher in the adult non-thymoma AChRAb negative MG subgroup than that in the control group (Pbon = 0.032, OR = 2.42) and in the adult non-thymoma AChRAb positive MG group (Pbon = 0.032, OR = 2.90) (Table 2).	('thymoma', 'Phenotype', 'HP:0100522', (191, 198))	('higher', 'PosReg', (53, 59))	('AChRAb', 'Chemical', '-', (85, 91))	('thymoma', 'Phenotype', 'HP:0100522', (77, 84))	('AChRAb', 'Chemical', '-', (199, 205))	('rs731236', 'Mutation', 'rs731236', (26, 34))	('rs731236', 'Var', (26, 34))
21261	33633666	The G allele frequency in rs731236 was significantly higher in the double negative group than those in the control group (Pbon = 0.016, OR = 2.65).	('rs731236', 'Mutation', 'rs731236', (26, 34))	('rs731236', 'Var', (26, 34))	('double', 'Var', (67, 73))	('higher', 'PosReg', (53, 59))
21262	33633666	There were no significant differences in allele frequency in rs731236 between the MuSK positive and the double negative group, as well as between the MuSK positive and the control group (Supplementary Table 2).	('MuSK', 'Gene', '4593', (82, 86))	('MuSK', 'Gene', '4593', (150, 154))	('MuSK', 'Gene', (82, 86))	('MuSK', 'Gene', (150, 154))	('rs731236', 'Mutation', 'rs731236', (61, 69))	('rs731236', 'Var', (61, 69))
21264	33633666	Block 1 was constructed by rs9729, rs3847987, rs739837, rs731236, rs7975232, rs10875692, and rs757343, and block 2 was constructed by rs11574027 and rs7136534.	('rs757343', 'Var', (93, 101))	('rs739837', 'Var', (46, 54))	('rs7975232', 'Mutation', 'rs7975232', (66, 75))	('rs11574027', 'Var', (134, 144))	('rs9729', 'Var', (27, 33))	('rs11574027', 'Mutation', 'rs11574027', (134, 144))	('rs3847987', 'Var', (35, 44))	('rs7136534', 'Mutation', 'rs7136534', (149, 158))	('rs731236', 'Var', (56, 64))	('rs739837', 'Mutation', 'rs739837', (46, 54))	('rs757343', 'Mutation', 'rs757343', (93, 101))	('rs3847987', 'Mutation', 'rs3847987', (35, 44))	('rs7136534', 'Var', (149, 158))	('rs10875692', 'Var', (77, 87))	('rs9729', 'Mutation', 'rs9729', (27, 33))	('rs731236', 'Mutation', 'rs731236', (56, 64))	('rs7975232', 'Var', (66, 75))	('rs10875692', 'Mutation', 'rs10875692', (77, 87))
21266	33633666	Block 1 was constructed by rs9729, rs3847987, rs739837, rs731236, rs7975232, rs10875692, rs757343, and rs1544410, and block 2 was constructed by rs11574027 and rs7136534.	('rs739837', 'Var', (46, 54))	('rs7136534', 'Mutation', 'rs7136534', (160, 169))	('rs11574027', 'Var', (145, 155))	('rs7136534', 'Var', (160, 169))	('rs3847987', 'Var', (35, 44))	('rs1544410', 'Var', (103, 112))	('rs10875692', 'Var', (77, 87))	('rs757343', 'Var', (89, 97))	('rs731236', 'Mutation', 'rs731236', (56, 64))	('rs731236', 'Var', (56, 64))	('rs739837', 'Mutation', 'rs739837', (46, 54))	('rs9729', 'Mutation', 'rs9729', (27, 33))	('rs7975232', 'Var', (66, 75))	('rs10875692', 'Mutation', 'rs10875692', (77, 87))	('rs757343', 'Mutation', 'rs757343', (89, 97))	('rs7975232', 'Mutation', 'rs7975232', (66, 75))	('rs9729', 'Var', (27, 33))	('rs1544410', 'Mutation', 'rs1544410', (103, 112))	('rs3847987', 'Mutation', 'rs3847987', (35, 44))	('rs11574027', 'Mutation', 'rs11574027', (145, 155))
21275	33633666	The rs731236 was found to be located in a CpG imposing a direct cis effect on site-specific and regional methylation.	('rs731236', 'Var', (4, 12))	('methylation', 'MPA', (105, 116))	('rs731236', 'Mutation', 'rs731236', (4, 12))
21276	33633666	Children carrying the C allele for TaqI were more likely to develop asthma, and interleukin-10 levels were significantly low in asthmatics with the TC genotype for TaqI due to a decrease in expression of VDR.	('interleukin-10', 'Gene', (80, 94))	('Children', 'Species', '9606', (0, 8))	('asthma', 'Disease', (68, 74))	('TaqI', 'Gene', (164, 168))	('VDR', 'Gene', (204, 207))	('decrease', 'NegReg', (178, 186))	('asthma', 'Disease', (128, 134))	('C allele', 'Var', (22, 30))	('expression', 'MPA', (190, 200))	('develop', 'PosReg', (60, 67))	('VDR', 'Gene', '7421', (204, 207))	('asthma', 'Disease', 'MESH:D001249', (128, 134))	('asthma', 'Phenotype', 'HP:0002099', (68, 74))	('interleukin-10', 'Gene', '3586', (80, 94))	('low', 'NegReg', (121, 124))	('asthma', 'Phenotype', 'HP:0002099', (128, 134))	('asthma', 'Disease', 'MESH:D001249', (68, 74))
21277	33633666	Therefore, it is presumed that rs731236 can affect the expression of VDR, and thus affect the expression of cytokines, thereby exerting immunomodulatory effects.	('affect', 'Reg', (83, 89))	('VDR', 'Gene', '7421', (69, 72))	('expression', 'MPA', (55, 65))	('rs731236', 'Mutation', 'rs731236', (31, 39))	('affect', 'Reg', (44, 50))	('expression of cytokines', 'MPA', (94, 117))	('VDR', 'Gene', (69, 72))	('rs731236', 'Var', (31, 39))
21278	33633666	rs731236 was also found to be associated with allergic diseases, autoimmune thyroid disease, and multiple sclerosis.	('associated', 'Reg', (30, 40))	('autoimmune thyroid disease', 'Disease', 'MESH:D013967', (65, 91))	('allergic diseases', 'Disease', (46, 63))	('multiple sclerosis', 'Disease', 'MESH:D009103', (97, 115))	('allergic diseases', 'Disease', 'MESH:D004342', (46, 63))	('rs731236', 'Mutation', 'rs731236', (0, 8))	('autoimmune thyroid disease', 'Disease', (65, 91))	('thyroid disease', 'Phenotype', 'HP:0000820', (76, 91))	('rs731236', 'Var', (0, 8))	('multiple sclerosis', 'Disease', (97, 115))
21284	33633666	Previous studies found that rs7975232, rs731236, and rs1544410 variants were in strong linkage disequilibrium, and we also performed haplotype analysis.	('rs7975232', 'Mutation', 'rs7975232', (28, 37))	('rs731236', 'Var', (39, 47))	('rs731236', 'Mutation', 'rs731236', (39, 47))	('rs1544410', 'Var', (53, 62))	('rs7975232', 'Var', (28, 37))	('rs1544410', 'Mutation', 'rs1544410', (53, 62))
21285	33633666	We found that rs9729, rs3847987, rs739837, rs731236, rs7975232, rs10875692, and rs757343 were in high linkage disequilibrium, but there were no significant differences in haplotype frequencies between MG and the control group, which suggested that these haplotypes were not significantly related to the susceptibility of MG.	('rs739837', 'Var', (33, 41))	('rs10875692', 'Mutation', 'rs10875692', (64, 74))	('rs757343', 'Var', (80, 88))	('rs7975232', 'Var', (53, 62))	('rs731236', 'Mutation', 'rs731236', (43, 51))	('rs9729', 'Var', (14, 20))	('rs731236', 'Var', (43, 51))	('rs7975232', 'Mutation', 'rs7975232', (53, 62))	('rs739837', 'Mutation', 'rs739837', (33, 41))	('rs757343', 'Mutation', 'rs757343', (80, 88))	('rs3847987', 'Var', (22, 31))	('rs9729', 'Mutation', 'rs9729', (14, 20))	('rs10875692', 'Var', (64, 74))	('rs3847987', 'Mutation', 'rs3847987', (22, 31))
21287	33633666	Our previous research found that VDR gene Tru9I (rs757343) polymorphism may be associated with risk of MG in females older than 15 years.	('associated', 'Reg', (79, 89))	('polymorphism', 'Var', (59, 71))	('rs757343', 'Mutation', 'rs757343', (49, 57))	('VDR', 'Gene', (33, 36))	('rs757343) polymorphism', 'Var', (49, 71))	('VDR', 'Gene', '7421', (33, 36))
21288	33633666	Therefore, we recruited a new cohort with a larger sample size, selected SNPs of VDR gene in a systematic strategy, and performed Logistic analysis.	('SNPs', 'Var', (73, 77))	('VDR', 'Gene', (81, 84))	('VDR', 'Gene', '7421', (81, 84))
21290	33633666	Our study mainly explores the association between vitamin D receptor gene polymorphism and the susceptibility and maximal severity of MG.	('polymorphism', 'Var', (74, 86))	('vitamin D receptor', 'Gene', '7421', (50, 68))	('vitamin D receptor', 'Gene', (50, 68))	('association', 'Interaction', (30, 41))
21295	33633666	In conclusion, in the Chinese Han population, rs731236 was found to be possibly associated with adult non-thymoma AChRAb negative MG patients.	('rs731236', 'Mutation', 'rs731236', (46, 54))	('patients', 'Species', '9606', (133, 141))	('rs731236', 'Var', (46, 54))	('thymoma', 'Phenotype', 'HP:0100522', (106, 113))	('associated', 'Reg', (80, 90))	('AChRAb', 'Chemical', '-', (114, 120))
21347	33458585	These antibodies are either clinically silent or they cause MG, myositis, neuro-myotonia, encephalitis, autonomic neuropathy, subacute hearing loss and even encephalitis .	('cause', 'Reg', (54, 59))	('hearing loss', 'Disease', (135, 147))	('myositis', 'Disease', (64, 72))	('myotonia', 'Phenotype', 'HP:0002486', (80, 88))	('encephalitis', 'Phenotype', 'HP:0002383', (157, 169))	('hearing loss', 'Disease', 'MESH:D034381', (135, 147))	('encephalitis', 'Disease', 'MESH:D004660', (90, 102))	('encephalitis', 'Disease', (90, 102))	('antibodies', 'Var', (6, 16))	('neuro-myotonia, encephalitis, autonomic neuropathy', 'Disease', 'MESH:D009422', (74, 124))	('myositis', 'Phenotype', 'HP:0100614', (64, 72))	('neuropathy', 'Phenotype', 'HP:0009830', (114, 124))	('hearing loss', 'Phenotype', 'HP:0000365', (135, 147))	('encephalitis', 'Disease', 'MESH:D004660', (157, 169))	('encephalitis', 'Disease', (157, 169))	('encephalitis', 'Phenotype', 'HP:0002383', (90, 102))	('myositis', 'Disease', 'MESH:D009220', (64, 72))
21402	31655916	The TNM classification was p-T1aN0M0 stage I, while it was stage II in accordance with the Masaoka staging system.	('TNM', 'Gene', (4, 7))	('p-T1aN0M0', 'Var', (27, 36))	('TNM', 'Gene', '10178', (4, 7))
21411	31655916	The diagnosis was thymic LELC, classified as p-T1aN0M0 stage I in the TNM classification and stage II according to the Masaoka staging system.	('thymic LELC', 'Disease', (18, 29))	('thymic LELC', 'Disease', 'MESH:D013945', (18, 29))	('TNM', 'Gene', '10178', (70, 73))	('p-T1aN0M0', 'Var', (45, 54))	('TNM', 'Gene', (70, 73))
21452	21785709	The presence of striational antibodies is associated with more severe disease in all MG subgroups.	('severe disease', 'Disease', (63, 77))	('associated with', 'Reg', (42, 57))	('presence', 'Var', (4, 12))	('severe disease', 'Disease', 'MESH:D056729', (63, 77))	('striational antibodies', 'Protein', (16, 38))
21477	21785709	Generally, anti-titin antibody is detected in 20-40% of all MG patients, anti-RyR in 13-38%, and anti-Kv1.4 in 12-15%.	('detected', 'Reg', (34, 42))	('anti-RyR', 'Var', (73, 81))	('Kv1.4', 'Gene', (102, 107))	('MG', 'Disease', 'MESH:D000080343', (60, 62))	('titin', 'Gene', '7273', (16, 21))	('Kv1.4', 'Gene', '3739', (102, 107))	('titin', 'Gene', (16, 21))	('patients', 'Species', '9606', (63, 71))
21479	21785709	The disease onset age is eldest in MG patients with anti-titin antibodies and youngest in those with anti-Kv1.4 antibodies.	('Kv1.4', 'Gene', (106, 111))	('titin', 'Gene', '7273', (57, 62))	('MG', 'Disease', 'MESH:D000080343', (35, 37))	('Kv1.4', 'Gene', '3739', (106, 111))	('antibodies', 'Var', (63, 73))	('patients', 'Species', '9606', (38, 46))	('titin', 'Gene', (57, 62))
21485	21785709	Since common characteristics of MG patients with anti-titin and anti-RyR antibodies have been described, the clinical picture may be common across different ethnic groups and immunogenetic backgrounds.	('MG', 'Disease', 'MESH:D000080343', (32, 34))	('anti-RyR', 'Var', (64, 72))	('titin', 'Gene', '7273', (54, 59))	('patients', 'Species', '9606', (35, 43))	('titin', 'Gene', (54, 59))
21495	21785709	Anti-RyR antibodies cause allosteric inhibition of RyR function in vitro, inhibiting Ca2+ release from the sarcoplasmic reticulum.	('inhibiting', 'NegReg', (74, 84))	('Ca2+', 'Chemical', 'MESH:D000069285', (85, 89))	('Anti-RyR', 'Protein', (0, 8))	('antibodies', 'Var', (9, 19))	('Ca2+ release from the sarcoplasmic reticulum', 'MPA', (85, 129))
21497	21785709	In this regard, a 27-year-old MG patient, who was positive for anti-RyR antibody, but not anti-AChR, was proven to be impaired E-C coupling.	('impaired', 'NegReg', (118, 126))	('MG', 'Disease', 'MESH:D000080343', (30, 32))	('patient', 'Species', '9606', (33, 40))	('anti-RyR antibody', 'Var', (63, 80))	('E-C', 'CPA', (127, 130))
21500	21785709	Autoantibodies to neuronal VGKC are known to be associated with acquired neuromyotonia, Morvan's syndrome, and autoimmune nonparaneoplastic limbic encephalitis.	("Morvan's syndrome", 'Disease', 'MESH:D013595', (88, 105))	('neuromyotonia', 'Disease', 'MESH:D020386', (73, 86))	('associated', 'Reg', (48, 58))	('encephalitis', 'Phenotype', 'HP:0002383', (147, 159))	("Morvan's syndrome", 'Disease', (88, 105))	('VGKC', 'Gene', (27, 31))	('nonparaneoplastic limbic encephalitis', 'Phenotype', 'HP:0007030', (122, 159))	('autoimmune nonparaneoplastic limbic encephalitis', 'Disease', (111, 159))	('VGKC', 'Gene', '3752', (27, 31))	('autoimmune nonparaneoplastic limbic encephalitis', 'Disease', 'MESH:C531729', (111, 159))	('Autoantibodies', 'Var', (0, 14))	('neuromyotonia', 'Disease', (73, 86))
21516	21785709	In addition, the autoantibodies for C-terminal regions in RyR1 are frequently detected in T-MG and may contribute to muscle dysfunction via the impairment of Ca2+ release.	('muscle dysfunction', 'Disease', 'MESH:D018908', (117, 135))	('MG', 'Disease', 'MESH:D000080343', (92, 94))	('Ca2+', 'Chemical', 'MESH:D000069285', (158, 162))	('RyR1', 'Gene', (58, 62))	('Ca2+ release', 'MPA', (158, 170))	('impairment', 'MPA', (144, 154))	('RyR1', 'Gene', '6261', (58, 62))	('detected', 'Reg', (78, 86))	('contribute to', 'Reg', (103, 116))	('muscle dysfunction', 'Disease', (117, 135))	('autoantibodies', 'Var', (17, 31))
21521	21785709	When the disease severity is compared between different striational antibodies, MG patients with anti-Kv1.4 antibodies show more severe symptoms than those with anti-titin antibodies.	('titin', 'Gene', '7273', (166, 171))	('Kv1.4', 'Gene', (102, 107))	('titin', 'Gene', (166, 171))	('Kv1.4', 'Gene', '3739', (102, 107))	('MG', 'Disease', 'MESH:D000080343', (80, 82))	('antibodies', 'Var', (108, 118))	('patients', 'Species', '9606', (83, 91))
21522	21785709	Similarly, it is also reported that MG patients with anti-RyR antibodies have more severe manifestations than those with anti-titin antibodies.	('titin', 'Gene', (126, 131))	('patients', 'Species', '9606', (39, 47))	('titin', 'Gene', '7273', (126, 131))	('anti-RyR antibodies', 'Var', (53, 72))	('MG', 'Disease', 'MESH:D000080343', (36, 38))
21524	21785709	In addition, patients with anti-RyR antibodies have high rates of bulbar, respiratory, and neck involvement at MG onset.	('antibodies', 'Var', (36, 46))	('bulbar', 'Disease', (66, 72))	('patients', 'Species', '9606', (13, 21))	('anti-RyR', 'Protein', (27, 35))	('MG', 'Disease', 'MESH:D000080343', (111, 113))	('respiratory', 'Disease', (74, 85))
21539	21785709	We also confirmed that some MG patients with anti-Kv1.4 antibodies had a risk for lethal arrhythmias including ventricular tachycardia, sick sinus syndrome, and complete atrial ventricular block (Figure 1).	('ventricular tachycardia', 'Disease', (111, 134))	('Kv1.4', 'Gene', (50, 55))	('sick sinus syndrome', 'Disease', 'MESH:D012804', (136, 155))	('Kv1.4', 'Gene', '3739', (50, 55))	('arrhythmias', 'Disease', 'MESH:D001145', (89, 100))	('sick sinus syndrome', 'Phenotype', 'HP:0011704', (136, 155))	('sick sinus syndrome', 'Disease', (136, 155))	('ventricular tachycardia', 'Disease', 'MESH:D017180', (111, 134))	('atrial ventricular block', 'Disease', 'MESH:C563984', (170, 194))	('antibodies', 'Var', (56, 66))	('MG', 'Disease', 'MESH:D000080343', (28, 30))	('atrial ventricular block', 'Disease', (170, 194))	('arrhythmias', 'Disease', (89, 100))	('patients', 'Species', '9606', (31, 39))	('arrhythmias', 'Phenotype', 'HP:0011675', (89, 100))	('sinus syndrome', 'Phenotype', 'HP:0000246', (141, 155))	('tachycardia', 'Phenotype', 'HP:0001649', (123, 134))	('ventricular tachycardia', 'Phenotype', 'HP:0004756', (111, 134))
21555	21785709	Although 20 years have passed since the discovery of anti-titin antibodies in MG patient, the detection of striational antibodies is not routinely tested in the clinical management by all neurologist.	('titin', 'Gene', (58, 63))	('MG', 'Disease', 'MESH:D000080343', (78, 80))	('patient', 'Species', '9606', (81, 88))	('antibodies', 'Var', (64, 74))	('titin', 'Gene', '7273', (58, 63))
21567	32126176	Adaptive immune dysregulation plays an integral role in the development and progression of many malignancies, most notably in the setting of a high mutational burden or other immunogenic features, which are particularly common in melanoma.	('immune dysregulation', 'Phenotype', 'HP:0002958', (9, 29))	('malignancies', 'Disease', 'MESH:D009369', (96, 108))	('mutational', 'Var', (148, 158))	('malignancies', 'Disease', (96, 108))	('melanoma', 'Phenotype', 'HP:0002861', (230, 238))	('melanoma', 'Disease', (230, 238))	('melanoma', 'Disease', 'MESH:D008545', (230, 238))
21591	32126176	Antibodies that block these inhibitory receptors or "immune checkpoints" bolster the anti-tumor response by promoting T-cell activation and function and increasing immune exposure to tumor specific antigens.	('immune exposure', 'MPA', (164, 179))	('Antibodies', 'Var', (0, 10))	('function', 'CPA', (140, 148))	('tumor', 'Disease', 'MESH:D009369', (183, 188))	('promoting', 'PosReg', (108, 117))	('tumor', 'Phenotype', 'HP:0002664', (90, 95))	('tumor', 'Disease', (90, 95))	('T-cell activation', 'CPA', (118, 135))	('bolster', 'PosReg', (73, 80))	('tumor', 'Phenotype', 'HP:0002664', (183, 188))	('tumor', 'Disease', (183, 188))	('tumor', 'Disease', 'MESH:D009369', (90, 95))	('increasing', 'PosReg', (153, 163))
21596	32126176	While iRAEs have been reported in up to 90% of patients treated with anti-CTLA4 agents and 70% of those treated with anti-PD1/PDL1, grade 3 or 4 toxicities occur in an estimated 27% and 16% respectively.	('PDL1', 'Gene', '29126', (126, 130))	('toxicities', 'Disease', (145, 155))	('anti-CTLA4', 'Var', (69, 79))	('PDL1', 'Gene', (126, 130))	('patients', 'Species', '9606', (47, 55))	('iRAEs', 'Disease', (6, 11))	('toxicities', 'Disease', 'MESH:D064420', (145, 155))
21628	32126176	The GRIN2A gene, which encodes for a subunit of the NMDA receptor is frequently expressed and mutated in melanoma and could represent a shared antigen involved in paraneoplastic autoimmune encephalitis.	('mutated', 'Var', (94, 101))	('melanoma', 'Phenotype', 'HP:0002861', (105, 113))	('melanoma', 'Disease', (105, 113))	('melanoma', 'Disease', 'MESH:D008545', (105, 113))	('NMDA', 'Chemical', 'MESH:D016202', (52, 56))	('paraneoplastic autoimmune encephalitis', 'Disease', (163, 201))	('encephalitis', 'Phenotype', 'HP:0002383', (189, 201))	('GRIN2A', 'Gene', (4, 10))	('paraneoplastic autoimmune encephalitis', 'Disease', 'MESH:C535841', (163, 201))	('GRIN2A', 'Gene', '2903', (4, 10))
21630	32126176	Mouse models involving a neo-self-antigen expressed in both Purkinje cells and implanted tumor cells demonstrated significant cerebellar inflammation and T-cell infiltration after exposure to anti-CTLA4 antibodies.	('T-cell infiltration', 'CPA', (154, 173))	('cerebellar inflammation', 'Disease', (126, 149))	('cerebellar inflammation', 'Disease', 'MESH:D007249', (126, 149))	('tumor', 'Disease', 'MESH:D009369', (89, 94))	('antibodies', 'Var', (203, 213))	('cerebellar inflammation', 'Phenotype', 'HP:0002383', (126, 149))	('anti-CTLA4 antibodies', 'Var', (192, 213))	('Mouse', 'Species', '10090', (0, 5))	('anti-CTLA4', 'Gene', (192, 202))	('tumor', 'Phenotype', 'HP:0002664', (89, 94))	('tumor', 'Disease', (89, 94))
21631	32126176	Cerebellar inflammation was present in 84% (27/32) of mice treated with anti-CTLA4 but was not found in any controls that were not exposed to anti-CTLA4 or in any non-neo-antigen expressing models that were treated with ICI.	('inflammation', 'Disease', (11, 23))	('anti-CTLA4', 'Var', (72, 82))	('Cerebellar inflammation', 'Phenotype', 'HP:0002383', (0, 23))	('mice', 'Species', '10090', (54, 58))	('inflammation', 'Disease', 'MESH:D007249', (11, 23))
21647	32126176	Some authors have postulated that disruption of the blood brain barrier in patients with CNS metastases who undergo stereotactic radiosurgery (SRS) may increase the risk for immune-related CNS complications.	('SRS', 'Disease', 'MESH:C536678', (143, 146))	('metastases', 'Disease', (93, 103))	('SRS', 'Disease', (143, 146))	('immune-related CNS', 'Disease', (174, 192))	('patients', 'Species', '9606', (75, 83))	('disruption', 'Var', (34, 44))	('metastases', 'Disease', 'MESH:D009362', (93, 103))	('CNS', 'Disease', (89, 92))
21654	32126176	Rituximab can be considered in patients with features typical for autoimmune encephalitis, such as positive CSF autoantibody testing, new onset seizures, or characteristic T2 hyperintensities of the medial temporal lobes or in those with no improvement despite 1-2 weeks of appropriate therapy.	('seizures', 'Disease', 'MESH:D012640', (144, 152))	('Rituximab', 'Chemical', 'MESH:D000069283', (0, 9))	('encephalitis', 'Phenotype', 'HP:0002383', (77, 89))	('T2 hyperintensities', 'Var', (172, 191))	('seizures', 'Disease', (144, 152))	('seizures', 'Phenotype', 'HP:0001250', (144, 152))	('patients', 'Species', '9606', (31, 39))	('autoimmune encephalitis', 'Disease', 'MESH:C535841', (66, 89))	('autoimmune encephalitis', 'Disease', (66, 89))
21679	32126176	While some cases involve exacerbation of known myasthenia, most represent a de novo syndrome.. Antibodies to the acetylcholine receptor are identified in ~85% of patients with generalized myasthenia gravis yet are more frequently negative in patients with ICI-associated MG.	('patients', 'Species', '9606', (162, 170))	('myasthenia', 'Disease', 'MESH:D020294', (188, 198))	('myasthenia', 'Phenotype', 'HP:0003473', (47, 57))	('myasthenia', 'Disease', (47, 57))	('myasthenia', 'Disease', (188, 198))	('myasthenia', 'Phenotype', 'HP:0003473', (188, 198))	('MG', 'Chemical', 'MESH:D008274', (271, 273))	('myasthenia gravis', 'Disease', (188, 205))	('Antibodies', 'Var', (95, 105))	('myasthenia', 'Disease', 'MESH:D020294', (47, 57))	('identified', 'Reg', (140, 150))	('myasthenia gravis', 'Disease', 'MESH:D009157', (188, 205))	('acetylcholine', 'Chemical', 'MESH:D000109', (113, 126))	('patients', 'Species', '9606', (242, 250))
21746	32126176	Like non-ICI associated GBS, most cases can be categorized as an acute inflammatory demyelinating polyneuropathy (AIDP) although rare variants, including Miller-Fisher syndrome, have also been reported in association with ICI.	('ICI', 'Disease', (222, 225))	('variants', 'Var', (134, 142))	('Miller-Fisher syndrome', 'Disease', (154, 176))	('polyneuropathy', 'Phenotype', 'HP:0001271', (98, 112))	('neuropathy', 'Phenotype', 'HP:0009830', (102, 112))	('association', 'Reg', (205, 216))	('AIDP', 'Phenotype', 'HP:0007131', (114, 118))	('inflammatory demyelinating polyneuropathy', 'Disease', 'MESH:D020275', (71, 112))	('acute inflammatory demyelinating polyneuropathy', 'Phenotype', 'HP:0007131', (65, 112))	('inflammatory demyelinating polyneuropathy', 'Disease', (71, 112))
21758	32126176	BRAF inhibitors have many known immunomodulatory effects in metastatic melanoma and could theoretically potentiate an anti-tumor response that also aberrantly targets neural tissue.	('tumor', 'Disease', (123, 128))	('inhibitors', 'Var', (5, 15))	('melanoma', 'Phenotype', 'HP:0002861', (71, 79))	('melanoma', 'Disease', (71, 79))	('BRAF', 'Gene', '673', (0, 4))	('melanoma', 'Disease', 'MESH:D008545', (71, 79))	('potentiate', 'PosReg', (104, 114))	('tumor', 'Disease', 'MESH:D009369', (123, 128))	('BRAF', 'Gene', (0, 4))	('tumor', 'Phenotype', 'HP:0002664', (123, 128))
21783	32126176	One can speculate that a viral infection or reactivation would produce CNS inflammation, which would be countered by expression of PD-L1 on the inflamed cells.	('viral infection', 'Disease', 'MESH:D001102', (25, 40))	('produce', 'Reg', (63, 70))	('PD-L1', 'Gene', '29126', (131, 136))	('reactivation', 'Var', (44, 56))	('viral infection', 'Disease', (25, 40))	('inflammation', 'Disease', 'MESH:D007249', (75, 87))	('inflammation', 'Disease', (75, 87))	('PD-L1', 'Gene', (131, 136))
21784	32126176	Blockade of PD-1 or PD-L1 however, would allow inflammation to persist unchecked, further worsening the clinical presentation.	('Blockade', 'Var', (0, 8))	('worsening', 'PosReg', (90, 99))	('PD-L1', 'Gene', '29126', (20, 25))	('PD-L1', 'Gene', (20, 25))	('clinical', 'MPA', (104, 112))	('inflammation', 'Disease', (47, 59))	('inflammation', 'Disease', 'MESH:D007249', (47, 59))	('PD-1', 'Gene', (12, 16))
21892	30454002	Many studies demonstrated that high NLR value is predictive of reduced overall survival (OS), cancer-related survival, DFS, progression-free survival, and enhanced resistance to therapies in a multitude of solid neoplasms.	('NLR', 'MPA', (36, 39))	('reduced', 'NegReg', (63, 70))	('progression-free survival', 'CPA', (124, 149))	('resistance to therapies', 'CPA', (164, 187))	('solid neoplasms', 'Disease', (206, 221))	('solid neoplasms', 'Disease', 'MESH:D018250', (206, 221))	('neoplasms', 'Phenotype', 'HP:0002664', (212, 221))	('enhanced', 'PosReg', (155, 163))	('cancer', 'Phenotype', 'HP:0002664', (94, 100))	('overall survival', 'CPA', (71, 87))	('OS', 'Chemical', '-', (89, 91))	('high', 'Var', (31, 35))	('DFS', 'CPA', (119, 122))	('cancer', 'Disease', (94, 100))	('cancer', 'Disease', 'MESH:D009369', (94, 100))
21920	30454002	The proportion of patients older than the median age (61 years) was significantly higher (p = 0.021) in the high-NLR-Group (69%) than in the low-NLR-Group (40%).	('high-NLR-Group', 'Var', (108, 122))	('higher', 'PosReg', (82, 88))	('patients', 'Species', '9606', (18, 26))
21929	30454002	However, following stratification of the patients according to TNM stage, DFS rates for patients in the low-NLR-Group were significantly higher (p = 0.043) than those in the high-NLR-Group both in I-II stages (Fig.	('low-NLR-Group', 'Var', (104, 117))	('DFS', 'MPA', (74, 77))	('TNM', 'Gene', '10178', (63, 66))	('patients', 'Species', '9606', (88, 96))	('higher', 'PosReg', (137, 143))	('patients', 'Species', '9606', (41, 49))	('TNM', 'Gene', (63, 66))
21944	30454002	Patients with NLR >=1.96 had significantly shorter OS, recurrence-free survival, disease-specific survival, disease-related survival, and showed higher cumulative incidence of recurrence.	('disease-related', 'CPA', (108, 123))	('NLR >=1.96', 'Var', (14, 24))	('OS', 'Chemical', '-', (51, 53))	('disease-specific survival', 'CPA', (81, 106))	('Patients', 'Species', '9606', (0, 8))	('recurrence-free survival', 'CPA', (55, 79))	('higher', 'PosReg', (145, 151))	('shorter', 'NegReg', (43, 50))
22203	22590574	The muscle fatigability is mediated by pathogenic autoantibodies against the muscle acetylcholine receptors (AChR-abs) detectable in the majority of patients (80-85%).	('muscle fatigability', 'Phenotype', 'HP:0003750', (4, 23))	('patients', 'Species', '9606', (149, 157))	('muscle fatigability', 'CPA', (4, 23))	('autoantibodies', 'Var', (50, 64))	('acetylcholine', 'Chemical', 'MESH:D000109', (84, 97))
22204	22590574	Among the remaining patients without AChR-abs, 10-50% have antibodies to the muscle specific kinase (MuSK).	('muscle specific kinase', 'Gene', '4593', (77, 99))	('muscle specific kinase', 'Gene', (77, 99))	('antibodies', 'Var', (59, 69))	('patients', 'Species', '9606', (20, 28))	('MuSK', 'Gene', '4593', (101, 105))	('MuSK', 'Gene', (101, 105))
22257	22590574	Haplotype analysis of the DRB1*15:01 versus other HLA-B alleles showed the strongest LD with B*07 (D' = 0.5, r2 = 0.2).	('B*07', 'Var', (93, 97))	('DRB1', 'Gene', '3123', (26, 30))	('HLA-B', 'Gene', (50, 55))	('DRB1', 'Gene', (26, 30))	('HLA-B', 'Gene', '3106', (50, 55))
22263	22590574	Novel negative associations were seen with HLA-A*02 (pnc = 4.6x10-4, pc = 3.7x10-3), C*05 (pnc = 4.6x10-3, pc = 0.06) and DRB1*13:01(pnc = 3.1x10-3, pc = 0.1), however, only A*02 was significant associated after correction.	('HLA-A', 'Gene', (43, 48))	('negative', 'NegReg', (6, 14))	('C*05', 'Var', (85, 89))	('DRB1', 'Gene', '3123', (122, 126))	('DRB1', 'Gene', (122, 126))	('HLA-A', 'Gene', '3105', (43, 48))
22315	21860784	Thymomas lacking this ability do not induce MG. Thymomas with histological similarities to medullary thymic tissue or thymomas lacking developing T cells are seldom associated with MG. Other thymoma characteristics that can cause reduced self-tolerance include defective epithelial expression of the autoimmune regulator (AIRE) gene and/or of major histocompatibility complex class II molecules, absence of myoid cells, failure to generate FOXP3(+) regulatory T cells, and genetic polymorphisms affecting T-cell signalling.	('Thymomas', 'Disease', 'MESH:D013945', (0, 8))	('Thymoma', 'Phenotype', 'HP:0100522', (0, 7))	('Thymomas', 'Disease', 'MESH:D013945', (48, 56))	('thymomas', 'Disease', (118, 126))	('Thymoma', 'Phenotype', 'HP:0100522', (48, 55))	('defective', 'Var', (261, 270))	('thymoma', 'Disease', 'MESH:D013945', (191, 198))	('FOXP3', 'Gene', (440, 445))	('rat', 'Species', '10116', (435, 438))	('Thymomas', 'Disease', (0, 8))	('Thymomas', 'Disease', (48, 56))	('T-cell signalling', 'MPA', (505, 522))	('thymoma', 'Disease', 'MESH:D013945', (118, 125))	('thymoma', 'Disease', (191, 198))	('reduced', 'NegReg', (230, 237))	('thymoma', 'Phenotype', 'HP:0100522', (191, 198))	('autoimmune regulator', 'Gene', (300, 320))	('autoimmune regulator', 'Gene', '326', (300, 320))	('FOXP3', 'Gene', '50943', (440, 445))	('thymoma', 'Disease', (118, 125))	('thymoma', 'Phenotype', 'HP:0100522', (118, 125))	('AIRE', 'Gene', (322, 326))	('AIRE', 'Gene', '326', (322, 326))	('thymomas', 'Disease', 'MESH:D013945', (118, 126))	('self-tolerance', 'CPA', (238, 252))
22333	21860784	There is also a rat model with thymoma and MG with RyR antibodies but no AChR antibodies, indicating that RyR antibodies may cause MG symptoms irrespective of AChR antibodies.	('rat', 'Species', '10116', (16, 19))	('AChR', 'Gene', (73, 77))	('thymoma', 'Disease', 'MESH:D013945', (31, 38))	('thymoma', 'Phenotype', 'HP:0100522', (31, 38))	('cause', 'Reg', (125, 130))	('thymoma', 'Disease', (31, 38))	('AChR', 'Gene', (159, 163))	('AChR', 'Gene', '170945', (73, 77))	('MG symptoms', 'Disease', (131, 142))	('AChR', 'Gene', '170945', (159, 163))	('RyR antibodies', 'Var', (106, 120))
22335	21860784	Neck weakness at MG onset is a distinctive feature of patients with RyR antibodies, while respiratory symptoms are also found in patients with titin antibodies with and without RyR antibodies.	('Neck weakness', 'Disease', (0, 13))	('respiratory symptoms', 'Phenotype', 'HP:0011947', (90, 110))	('titin', 'Gene', (143, 148))	('patients', 'Species', '9606', (54, 62))	('rat', 'Species', '10116', (95, 98))	('patients', 'Species', '9606', (129, 137))	('Neck weakness', 'Disease', 'MESH:D018908', (0, 13))	('Neck weakness', 'Phenotype', 'HP:0000467', (0, 13))	('titin', 'Gene', '7273', (143, 148))	('RyR antibodies', 'Var', (68, 82))
22346	21860784	The presence of titin and RyR antibodies is associated with more severe disease in thymoma MG and in late-onset MG.	('late-onset MG', 'Disease', (101, 114))	('RyR antibodies', 'Protein', (26, 40))	('titin', 'Gene', '7273', (16, 21))	('thymoma MG', 'Disease', (83, 93))	('thymoma MG', 'Disease', 'MESH:D013945', (83, 93))	('titin', 'Gene', (16, 21))	('presence', 'Var', (4, 12))	('thymoma', 'Phenotype', 'HP:0100522', (83, 90))	('associated with', 'Reg', (44, 59))
22371	21860784	Tacrolimus, which is an immunosuppressant and enhancer of RyR-related sarcoplasmic calcium release, may be especially beneficial in MG patients with RyR antibodies that in theory might block the RyR interfering with its function.	('patients', 'Species', '9606', (135, 143))	('Tacrolimus', 'Chemical', 'MESH:D016559', (0, 10))	('RyR', 'Gene', (149, 152))	('RyR', 'MPA', (195, 198))	('antibodies', 'Var', (153, 163))	('block', 'NegReg', (185, 190))	('calcium', 'Chemical', 'MESH:D002118', (83, 90))
22511	25648096	Immunoreactivity to CD5 is a distinctive feature of CASTLE, with 82% and 100% sensitivity and specificity, respectively.	('CD5', 'Gene', (20, 23))	('Immunoreactivity', 'Var', (0, 16))	('CASTLE', 'Disease', (52, 58))	('CD5', 'Gene', '921', (20, 23))
22566	26273358	Thy0517 are polygonal adherent cell lines, complying with tumor cell morphology and with apparent nuclear membrane and nucleolus by microscopic observation (Fig 1e), excluding contact-inhibition.	('tumor', 'Phenotype', 'HP:0002664', (58, 63))	('tumor', 'Disease', (58, 63))	('Thy0517', 'Var', (0, 7))	('tumor', 'Disease', 'MESH:D009369', (58, 63))
22575	26273358	As shown by immunohistochemistry and immunocytochemistry, the cell lines, human thymoma, and nude mice tumors were positive for expressions of cytokeratin CK7, CK8/18, CK19, CK-pan, CD24, BCL-2, P63, Vimentin, epithelial membrane antigen (EMA), and COX2 (Fig 3a-j).	('CK19', 'Gene', (168, 172))	('tumor', 'Phenotype', 'HP:0002664', (103, 108))	('tumors', 'Disease', (103, 109))	('P63', 'Gene', (195, 198))	('COX2', 'Gene', '17709', (249, 253))	('CD24', 'Gene', (182, 186))	('CK-pan', 'Gene', (174, 180))	('tumors', 'Disease', 'MESH:D009369', (103, 109))	('nude mice', 'Species', '10090', (93, 102))	('COX2', 'Gene', (249, 253))	('Vimentin', 'Protein', (200, 208))	('thymoma', 'Phenotype', 'HP:0100522', (80, 87))	('tumors', 'Phenotype', 'HP:0002664', (103, 109))	('thymoma', 'Gene', '7063', (80, 87))	('BCL-2', 'Gene', (188, 193))	('epithelial membrane antigen (EMA),', 'Gene', '107924', (210, 244))	('cytokeratin CK7', 'Protein', (143, 158))	('CK8/18', 'Var', (160, 166))	('thymoma', 'Gene', (80, 87))	('human', 'Species', '9606', (74, 79))
22589	26273358	In 1992, a cell line named Ty-82 from a 22-year-old female with undifferentiated thymic carcinoma and t(15;19)(q12;p13) chromosome translocation was established.	('carcinoma', 'Phenotype', 'HP:0030731', (88, 97))	('undifferentiated thymic carcinoma', 'Disease', 'MESH:D002277', (64, 97))	('undifferentiated thymic carcinoma', 'Disease', (64, 97))	('Ty-82', 'Chemical', '-', (27, 32))	('t(15;19)(q12;p13', 'Var', (102, 118))	('t(15;19)(q12;p13)', 'STRUCTURAL_ABNORMALITY', 'None', (102, 119))
22600	26273358	The doubling time of Thy0517 (37 hours) is greater than thymoma cell line IU-TAB-1 (48 hours), but lower than thymic carcinoma cell line ThyL-6 (26.3 hours).	('Thy0517', 'Var', (21, 28))	('thymic carcinoma', 'Disease', 'MESH:D013945', (110, 126))	('carcinoma', 'Phenotype', 'HP:0030731', (117, 126))	('lower', 'NegReg', (99, 104))	('thymoma', 'Gene', '7063', (56, 63))	('thymoma', 'Gene', (56, 63))	('doubling', 'MPA', (4, 12))	('thymic carcinoma', 'Disease', (110, 126))	('thymoma', 'Phenotype', 'HP:0100522', (56, 63))
22602	26273358	The IU-TAB-1 cell line exhibits epithelial markers (pan-cytokeratin), CD29, CD9, CD58, CD24, P63, and epithelial cell adhesion molecule (EpCAM) without showing C-Kit (CD117) and EGFR markers.	('epithelial cell adhesion molecule', 'Gene', (102, 135))	('CD58', 'Gene', '965', (81, 85))	('EpCAM', 'Gene', '4072', (137, 142))	('CD58', 'Gene', (81, 85))	('epithelial cell adhesion molecule', 'Gene', '4072', (102, 135))	('C-Kit', 'Gene', (160, 165))	('CD9', 'Gene', '928', (76, 79))	('CD24', 'Var', (87, 91))	('C-Kit', 'Gene', '3815', (160, 165))	('CD29', 'Gene', '3688', (70, 74))	('P63', 'Var', (93, 96))	('CD117', 'Gene', (167, 172))	('CD117', 'Gene', '3815', (167, 172))	('CD9', 'Gene', (76, 79))	('EpCAM', 'Gene', (137, 142))	('CD29', 'Gene', (70, 74))
22603	26273358	In contrast, Thy0517 cell line expresses p63, EGFR, BCL-2, Vimentin, and several epithelial markers including pan-cytokeratin, CK7, CK8/18, CK19, EMA, but no expression of lymphocyte antigen CD99 and TdT.	('p63', 'Gene', (41, 44))	('CD99', 'Gene', '4267', (191, 195))	('CK8/18', 'Var', (132, 138))	('CK19', 'Var', (140, 144))	('TdT', 'Gene', (200, 203))	('BCL-2', 'Gene', (52, 57))	('CK7', 'Var', (127, 130))	('EGFR', 'Gene', (46, 50))	('p63', 'Gene', '8626', (41, 44))	('TdT', 'Gene', '1791', (200, 203))	('EMA', 'CPA', (146, 149))	('CD99', 'Gene', (191, 195))
22605	26273358	However, the cell line expresses CD24 scattered, which has been considered as a kind of cancer stem cell marker in malignant mesothelioma, colon, ovarian, gastric and hepatic cancers.	('cancer', 'Disease', (88, 94))	('malignant mesothelioma', 'Disease', (115, 137))	('cancer', 'Disease', 'MESH:D009369', (88, 94))	('gastric and hepatic cancers', 'Disease', 'MESH:D013274', (155, 182))	('malignant mesothelioma', 'Phenotype', 'HP:0100001', (115, 137))	('cancer', 'Disease', (175, 181))	('cancer', 'Disease', 'MESH:D009369', (175, 181))	('colon', 'Disease', 'MESH:D015179', (139, 144))	('ovarian', 'Disease', (146, 153))	('cancers', 'Phenotype', 'HP:0002664', (175, 182))	('malignant mesothelioma', 'Disease', 'MESH:C562839', (115, 137))	('cancer', 'Phenotype', 'HP:0002664', (88, 94))	('colon', 'Disease', (139, 144))	('cancer', 'Phenotype', 'HP:0002664', (175, 181))	('CD24', 'Var', (33, 37))
22612	32218504	Among the six WHO subtypes (Type A, AB, B1, B2, and B3 thymoma and thymic carcinoma), the mean CEmax values and most of the perfusion and spectral parameter values of Type A and Type AB were significantly higher than those of the other subtypes (all P < 0.05), and there was no difference among Type B1, B2 and B3 (all P > 0.05).	('Type A', 'Var', (167, 173))	('thymoma and thymic carcinoma', 'Disease', 'MESH:D013945', (55, 83))	('higher', 'PosReg', (205, 211))	('CEmax values', 'MPA', (95, 107))	('carcinoma', 'Phenotype', 'HP:0030731', (74, 83))	('B1, B2 and B3', 'Gene', '28905;28907;680', (300, 313))	('B1, B2, and B3', 'Gene', '28905;3383;680', (40, 54))	('thymoma', 'Phenotype', 'HP:0100522', (55, 62))
22635	32218504	According to the histological and immunohistochemical results, with regard to WHO pathological subtypes, there were 9 (10.2%) Type A, 8 (9.1%) Type AB, 13 (14.8%) Type B1, 16 (18.2%) Type B2, 11 (12.5%) Type B3, and 31 (35.2%) TC patients (Table 1).	('patients', 'Species', '9606', (230, 238))	('Type B1', 'Var', (163, 170))	('Type B2', 'Var', (183, 190))	('Type AB', 'Var', (143, 150))
22670	32218504	The specificity of NICv values in differentiating HRT* from TC was 100% and was higher than that (88.0%) of ICv.	('NICv values', 'Var', (19, 30))	('HRT*', 'Disease', (50, 54))	('ICv', 'Chemical', '-', (108, 111))	('ICv', 'Chemical', '-', (20, 23))
22706	32218504	Normalized iodine concentrations (NICs) and lambdaHU were calculated separately using the following formula: NIC = ICtumour/ICThoracic aorta or aortic arch; lambdaHU = (CT40keV-CT80keV)/40.	('CT40keV-CT80keV)/40', 'Var', (169, 188))	('iodine', 'Chemical', 'MESH:D007455', (11, 17))	('tumour', 'Phenotype', 'HP:0002664', (117, 123))	('tumour', 'Disease', 'MESH:D009369', (117, 123))	('tumour', 'Disease', (117, 123))
22746	31616725	The thymus plays an important role in the growth and differentiation of T lymphocytes and its disorder can cause a spectrum of autoimmune diseases due to disturbance in cell-mediated immunity including synthesis of anti-AChR leading to MG.	('disturbance', 'Reg', (154, 165))	('autoimmune diseases', 'Disease', 'MESH:D001327', (127, 146))	('MG', 'Disease', 'MESH:D009157', (236, 238))	('autoimmune diseases', 'Disease', (127, 146))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (127, 146))	('anti-AChR', 'Protein', (215, 224))	('cause', 'Reg', (107, 112))	('spectrum', 'Disease', (115, 123))	('disorder', 'Var', (94, 102))
22764	30339550	Low-risk (type A, AB, and B1) thymomas or early-stage (stages I and II) thymic epithelial tumors (TETs) are usually treated with surgery, and high-risk (type B2 and B3) thymomas or advanced stage (stages III and IV) TETs frequently require a multimodality approach, whereas lymphomas are managed with chemotherapy.	('thymoma', 'Phenotype', 'HP:0100522', (169, 176))	('thymomas', 'Disease', 'MESH:D013945', (169, 177))	('lymphomas', 'Phenotype', 'HP:0002665', (274, 283))	('lymphoma', 'Phenotype', 'HP:0002665', (274, 282))	('thymoma', 'Phenotype', 'HP:0100522', (30, 37))	('tumor', 'Phenotype', 'HP:0002664', (90, 95))	('type B2', 'Var', (153, 160))	('epithelial tumors', 'Disease', (79, 96))	('lymphomas', 'Disease', 'MESH:D008223', (274, 283))	('thymomas', 'Disease', 'MESH:D013945', (30, 38))	('tumors', 'Phenotype', 'HP:0002664', (90, 96))	('thymomas', 'Disease', (169, 177))	('lymphomas', 'Disease', (274, 283))	('epithelial tumors', 'Disease', 'MESH:D002277', (79, 96))	('thymomas', 'Disease', (30, 38))
22895	29318185	It has been reported that MG patients with corticosteroids treatment had a 1.46-fold increased risk of developing diabetes mellitus as compared with non-MG cohort; while those without corticosteroids had no increase risk of DM.	('patients', 'Species', '9606', (29, 37))	('diabetes mellitus', 'Phenotype', 'HP:0000819', (114, 131))	('corticosteroids', 'Var', (43, 58))	('diabetes mellitus', 'Disease', (114, 131))	('DM', 'Disease', 'MESH:D009223', (224, 226))	('diabetes mellitus', 'Disease', 'MESH:D003920', (114, 131))	('steroids', 'Chemical', 'MESH:D013256', (191, 199))	('steroids', 'Chemical', 'MESH:D013256', (50, 58))
22926	28216655	These data strongly suggest that the aberrant expression of PIT-1 in the thymoma plays a causal role in the development of this syndrome.	('PIT-1', 'Gene', (60, 65))	('thymoma', 'Phenotype', 'HP:0100522', (73, 80))	('causal', 'Reg', (89, 95))	('aberrant expression', 'Var', (37, 56))	('PIT-1', 'Gene', '5449', (60, 65))	('thymoma', 'Disease', 'MESH:D013945', (73, 80))	('thymoma', 'Disease', (73, 80))
22932	28216655	It also regulates the expression of growth hormone (GH), prolactin (PRL), and thyroid-stimulating hormone (TSH) and mutations in PIT-1 gene cause congenital GH, PRL, and TSH deficiencies.	('PRL', 'Gene', (68, 71))	('prolactin', 'Gene', '5617', (57, 66))	('growth hormone', 'Gene', (36, 50))	('prolactin', 'Gene', (57, 66))	('PIT-1', 'Gene', '5449', (129, 134))	('cause', 'Reg', (140, 145))	('PRL', 'Gene', (161, 164))	('growth hormone', 'Gene', '2688', (36, 50))	('PRL', 'Gene', '5617', (68, 71))	('PRL', 'Gene', '5617', (161, 164))	('GH', 'Gene', '2688', (157, 159))	('mutations', 'Var', (116, 125))	('GH', 'Gene', '2688', (52, 54))	('TSH deficiencies', 'Disease', (170, 186))	('TSH deficiencies', 'Disease', 'MESH:D007037', (170, 186))	('PIT-1', 'Gene', (129, 134))
22941	28216655	Although the precise mechanisms remain unknown, it has been suggested that the aberrant expression of the antigen, acetylcholine receptor (AChR) in the tumor cells and a defect in the negative selection in thymoma may play a role in the development of autoimmunity.	('tumor', 'Disease', 'MESH:D009369', (152, 157))	('tumor', 'Phenotype', 'HP:0002664', (152, 157))	('role', 'Reg', (225, 229))	('aberrant', 'Var', (79, 87))	('play', 'Reg', (218, 222))	('thymoma', 'Disease', 'MESH:D013945', (206, 213))	('autoimmunity', 'Phenotype', 'HP:0002960', (252, 264))	('tumor', 'Disease', (152, 157))	('autoimmunity', 'Disease', (252, 264))	('defect', 'NegReg', (170, 176))	('thymoma', 'Disease', (206, 213))	('AChR', 'Gene', (139, 143))	('negative selection', 'CPA', (184, 202))	('thymoma', 'Phenotype', 'HP:0100522', (206, 213))	('expression', 'MPA', (88, 98))	('autoimmunity', 'Disease', 'MESH:D001327', (252, 264))
22961	28216655	Since it has been reported that the aberrant expression of AChR is associated with autoimmunity to AChR in MG, we analyzed the expression of PIT-1 protein in the thymoma tissue.	('autoimmunity', 'Phenotype', 'HP:0002960', (83, 95))	('autoimmunity', 'Disease', 'MESH:D001327', (83, 95))	('AChR', 'Gene', (59, 63))	('expression', 'MPA', (45, 55))	('associated', 'Reg', (67, 77))	('PIT-1', 'Gene', (141, 146))	('aberrant', 'Var', (36, 44))	('thymoma', 'Disease', 'MESH:D013945', (162, 169))	('thymoma', 'Disease', (162, 169))	('PIT-1', 'Gene', '5449', (141, 146))	('autoimmunity', 'Disease', (83, 95))	('thymoma', 'Phenotype', 'HP:0100522', (162, 169))
22966	28216655	Furthermore, immunohistochemical analysis showed an aberrant expression of PIT-1 in the neoplastic cortical thymic epithelial cells in patient 1 (Fig.	('patient', 'Species', '9606', (135, 142))	('PIT-1', 'Gene', '5449', (75, 80))	('aberrant', 'Var', (52, 60))	('PIT-1', 'Gene', (75, 80))	('expression', 'MPA', (61, 71))
22974	28216655	These data strongly suggest that thymoma that aberrantly expressed PIT-1 plays an essential role in the development of this disease.	('thymoma', 'Disease', (33, 40))	('aberrantly expressed', 'Var', (46, 66))	('thymoma', 'Phenotype', 'HP:0100522', (33, 40))	('PIT-1', 'Gene', '5449', (67, 72))	('thymoma', 'Disease', 'MESH:D013945', (33, 40))	('PIT-1', 'Gene', (67, 72))
22978	28216655	In anti-PIT-1 antibody syndrome, it is speculated that the aberrant expression of PIT-1 evoked positive selection for PIT-1-reactive T cells and the defect in negative selection in thymoma tissue induced breakdown in immune tolerance for PIT-1.	('PIT-1', 'Gene', (82, 87))	('antibody syndrome', 'Disease', 'MESH:D007153', (14, 31))	('PIT-1', 'Gene', '5449', (8, 13))	('aberrant', 'Var', (59, 67))	('PIT-1', 'Gene', (118, 123))	('PIT-1', 'Gene', '5449', (118, 123))	('thymoma', 'Disease', 'MESH:D013945', (181, 188))	('PIT-1', 'Gene', '5449', (238, 243))	('PIT-1', 'Gene', '5449', (82, 87))	('thymoma', 'Disease', (181, 188))	('antibody syndrome', 'Disease', (14, 31))	('thymoma', 'Phenotype', 'HP:0100522', (181, 188))	('PIT-1', 'Gene', (238, 243))	('PIT-1', 'Gene', (8, 13))
22980	28216655	Recently, it has been reported that mutations of epigenetic regulatory genes are common in thymic neoplasms, suggesting that epigenetic changes such as histone modification, chromatin remodeling, and DNA methylation pathways may occur and cause a dysregulated expression of silencing gene in thymoma.	('cause', 'Reg', (239, 244))	('dysregulated expression of silencing', 'MPA', (247, 283))	('neoplasms', 'Phenotype', 'HP:0002664', (98, 107))	('thymoma', 'Disease', 'MESH:D013945', (292, 299))	('thymic neoplasms', 'Disease', 'MESH:D013953', (91, 107))	('histone', 'MPA', (152, 159))	('mutations', 'Var', (36, 45))	('thymoma', 'Disease', (292, 299))	('thymic neoplasms', 'Disease', (91, 107))	('thymoma', 'Phenotype', 'HP:0100522', (292, 299))	('thymic neoplasms', 'Phenotype', 'HP:0100521', (91, 107))
22981	28216655	It is possible that such epigenetic changes cause the aberrant expression of PIT-1 in the thymoma tissue of anti-PIT-1 antibody syndrome.	('PIT-1', 'Gene', (77, 82))	('cause', 'Reg', (44, 49))	('PIT-1', 'Gene', (113, 118))	('PIT-1', 'Gene', '5449', (77, 82))	('expression', 'MPA', (63, 73))	('PIT-1', 'Gene', '5449', (113, 118))	('antibody syndrome', 'Disease', (119, 136))	('thymoma', 'Disease', 'MESH:D013945', (90, 97))	('epigenetic changes', 'Var', (25, 43))	('thymoma', 'Disease', (90, 97))	('antibody syndrome', 'Disease', 'MESH:D007153', (119, 136))	('thymoma', 'Phenotype', 'HP:0100522', (90, 97))
22985	28216655	Anti-AChR antibodies are the most common type of the pathogenesis of MG. Anti-AChR antibody activates the classical complement pathway, formation of the membrane attack complex initiated by activated C3, causes severe structural injury of endplates and lyses the postsynaptic membrane.	('classical complement pathway', 'Pathway', (106, 134))	('injury of endplates', 'Disease', (229, 248))	('lyses the postsynaptic membrane', 'CPA', (253, 284))	('Anti-AChR antibody', 'Var', (73, 91))	('activates', 'PosReg', (92, 101))	('causes', 'Reg', (204, 210))	('injury of endplates', 'Disease', 'MESH:C566415', (229, 248))
22997	28216655	Most of the patients reveal autoantibodies against the common antigens between the tumor and central nervous system.	('tumor', 'Phenotype', 'HP:0002664', (83, 88))	('patients', 'Species', '9606', (12, 20))	('tumor', 'Disease', (83, 88))	('tumor', 'Disease', 'MESH:D009369', (83, 88))	('autoantibodies', 'Var', (28, 42))
23053	25616178	Myasthenia gravis (MG) is more frequent in type B1-3 thymomas (35-49%) than in type A and AB (25-26%).	('MG', 'Disease', 'MESH:D000080343', (19, 21))	('thymoma', 'Phenotype', 'HP:0100522', (53, 60))	('thymomas', 'Disease', 'MESH:D013945', (53, 61))	('Myasthenia gravis', 'Disease', (0, 17))	('Myasthenia gravis', 'Disease', 'MESH:D009157', (0, 17))	('type B1-3', 'Var', (43, 52))	('Myasthenia', 'Phenotype', 'HP:0003473', (0, 10))	('thymomas', 'Disease', (53, 61))
23082	25616178	The effect on recurrence is seen in stages I + II thymoma and for type AB versus B1, B2, and B3.	('thymoma', 'Gene', (50, 57))	('thymoma', 'Gene', '7063', (50, 57))	('type AB', 'Var', (66, 73))	('thymoma', 'Phenotype', 'HP:0100522', (50, 57))
23181	22171357	Over the next 10 years or so, many clinical studies on patients with compromised ventilation were undertaken, many with anaesthetist Laurie Loh, who subsequently moved with JND to Oxford (Supplementary materials B10, B11, B13, B14, B15, B24 and B25).	('B14', 'Gene', (227, 230))	('man', 'Species', '9606', (30, 33))	('B13', 'Gene', '4698', (222, 225))	('B15', 'Gene', (232, 235))	('B11', 'Var', (217, 220))	('men', 'Species', '9606', (194, 197))	('B14', 'Gene', '4700', (227, 230))	('B13', 'Gene', (222, 225))	('man', 'Species', '9606', (110, 113))	('B10', 'Gene', '5169', (212, 215))	('patients', 'Species', '9606', (55, 63))	('B10', 'Gene', (212, 215))	('B15', 'Gene', '4710', (232, 235))
23192	22171357	Within a few weeks, the first muscle biopsies began to arrive at UCL; endplate recordings were made by visiting postdoc Yushi Ito who confirmed that alpha-bungarotoxin inhibited human muscle neuromuscular transmission and that the miniature endplate potentials were indeed substantially reduced in amplitude at myasthenia gravis endplates.	('myasthenia gravis endplates', 'Phenotype', 'HP:0004576', (311, 338))	('miniature endplate potentials', 'MPA', (231, 260))	('human', 'Species', '9606', (178, 183))	('myasthenia', 'Phenotype', 'HP:0003473', (311, 321))	('inhibited', 'NegReg', (168, 177))	('reduced', 'NegReg', (287, 294))	('myasthenia gravis', 'Disease', (311, 328))	('human muscle neuromuscular transmission', 'MPA', (178, 217))	('alpha-bungarotoxin', 'Var', (149, 167))	('myasthenia gravis', 'Disease', 'MESH:D009157', (311, 328))
23208	22171357	The results in seven patients, including one with congenital myasthenia who had no detectable AChR antibodies and did not improve clinically, otherwise showed a remarkable inverse correlation:not only as the AChR antibodies fell following the exchanges, but also as they subsequently rose (Supplementary material B19).	('men', 'Species', '9606', (296, 299))	('myasthenia', 'Phenotype', 'HP:0003473', (61, 71))	('congenital myasthenia', 'Disease', (50, 71))	('fell', 'NegReg', (224, 228))	('patients', 'Species', '9606', (21, 29))	('B19', 'Gene', '59271', (313, 316))	('exchanges', 'Var', (243, 252))	('B19', 'Gene', (313, 316))	('congenital myasthenia', 'Disease', 'MESH:D020294', (50, 71))	('AChR', 'Gene', (208, 212))
23211	22171357	It was many years before JND and Jackie Palace performed the seminal trial of prednisolone alone versus prednisolone plus azathioprine (Supplementary material B212) demonstrating that azathioprine reduced the maintenance dose of prednisolone required to achieve clinical remission, but that this effect took 10 months to be evident.	('B21', 'Gene', '9267', (159, 162))	('men', 'Species', '9606', (142, 145))	('prednisolone', 'Chemical', 'MESH:D011239', (104, 116))	('B21', 'Gene', (159, 162))	('azathioprine', 'Chemical', 'MESH:D001379', (184, 196))	('reduced', 'NegReg', (197, 204))	('azathioprine', 'Var', (184, 196))	('man', 'Species', '9606', (7, 10))	('prednisolone', 'Chemical', 'MESH:D011239', (229, 241))	('azathioprine', 'Chemical', 'MESH:D001379', (122, 134))	('rat', 'Species', '10116', (172, 175))	('prednisolone', 'Chemical', 'MESH:D011239', (78, 90))	('maintenance dose of prednisolone', 'MPA', (209, 241))
23217	22171357	Despite several publications from other groups claiming no convincing effect, careful analysis showed a clear influence of thymectomy alone on AChR antibody levels, which declined on average by ~50% over a year in patients with hyperplastic thymi (Supplementary material B53), but not in thymoma patients, as predicted from their poorer clinical response.	('patients', 'Species', '9606', (214, 222))	('men', 'Species', '9606', (254, 257))	('hyperplastic thymi', 'Phenotype', 'HP:0010516', (228, 246))	('AChR antibody levels', 'MPA', (143, 163))	('hyperplastic', 'Var', (228, 240))	('patients', 'Species', '9606', (296, 304))	('thymoma', 'Phenotype', 'HP:0100522', (288, 295))	('declined', 'NegReg', (171, 179))	('thymoma', 'Gene', '7063', (288, 295))	('thymoma', 'Gene', (288, 295))
23245	22171357	Some years later, clinical training fellow Jeremy Farrar (now Director of the Oxford University Clinical Research Unit in Ho Chi Mingh City, Vietnam), supervised by Nick Willcox, was able to recombine the heavy and light chain genes from messenger RNA expressed in the thymus of a patient with myasthenia gravis and demonstrate the diverse germ-line gene origins of the antibodies (Supplementary material B191).	('Willcox', 'Chemical', '-', (170, 177))	('rat', 'Species', '10116', (323, 326))	('patient', 'Species', '9606', (281, 288))	('B19', 'Gene', '59271', (405, 408))	('recombine', 'Var', (191, 200))	('myasthenia', 'Phenotype', 'HP:0003473', (294, 304))	('B19', 'Gene', (405, 408))	('myasthenia gravis', 'Disease', (294, 311))	('men', 'Species', '9606', (388, 391))	('myasthenia gravis', 'Disease', 'MESH:D009157', (294, 311))
23247	22171357	These had shown that the antibodies could inhibit acetylcholine or alpha-bungarotoxin binding to rodent receptors, and reduce the surface expression of AChRs on cultured cell lines by a process known as antigenic modulation:cross-linking and internalization of the receptors followed by their degradation.	('alpha-bungarotoxin', 'Protein', (67, 85))	('degradation', 'MPA', (293, 304))	('reduce', 'NegReg', (119, 125))	('binding', 'Interaction', (86, 93))	('antibodies', 'Var', (25, 35))	('surface expression', 'MPA', (130, 148))	('acetylcholine', 'MPA', (50, 63))	('acetylcholine', 'Chemical', 'MESH:D000109', (50, 63))	('internalization', 'MPA', (242, 257))	('inhibit', 'NegReg', (42, 49))	('AChRs', 'Gene', (152, 157))
23287	22171357	Indeed, postdoc Ian Matthews with visiting clinical fellow Hiro Shiono, together with Glasgow immunologists Gary Sims and David Stott, subsequently showed that the IgGs cloned from the thymic B cells were highly mutated (Supplementary material B278).	('men', 'Species', '9606', (227, 230))	('mutated', 'Var', (212, 219))	('IgGs', 'Gene', (164, 168))
23290	22171357	As a result of a collaboration between David Beeson, Henri-Jean Garchon (Paris) and Bruno Kyewski (Heidelberg), a predisposing polymorphism of the AChR alpha subunit gene was found to influence AChR expression in the epithelial cells, particularly under the influence of a protein called the Autoimmune Regulator (AIRE; see below; Giraud et al., 2006).	('polymorphism', 'Var', (127, 139))	('AIRE', 'Gene', '326', (314, 318))	('expression', 'MPA', (199, 209))	('AChR alpha', 'Gene', (147, 157))	('AIRE', 'Gene', (314, 318))	('Autoimmune Regulator', 'Gene', '326', (292, 312))	('AChR alpha', 'Gene', '1134', (147, 157))	('AChR', 'Gene', (194, 198))	('rat', 'Species', '10116', (24, 27))	('Autoimmune Regulator', 'Gene', (292, 312))	('influence', 'Reg', (184, 193))
23299	22171357	Visiting clinical fellow Norbert Sommer found that AChR-reactive T cells were present in both patients and controls (Supplementary material B137), probably indicating incomplete deletion of autoreactive T cells in the thymus.	('patients', 'Species', '9606', (94, 102))	('B13', 'Gene', '4698', (140, 143))	('deletion', 'Var', (178, 186))	('men', 'Species', '9606', (123, 126))	('B13', 'Gene', (140, 143))
23302	22171357	One AChR-specific T-cell clone from an HLA-DR3/4 heterozygous early-onset myasthenia gravis patient's thymus demonstrated a role for a recurring 86Gly Val dimorphism in the presenting HLA Class II molecules (a collaboration with John Bell and Paul Wordsworth in the Human Immunology Group at the Weatherall Institute of Molecular Medicine; Supplementary material B134).	('patient', 'Species', '9606', (92, 99))	('86Gly Val dimorphism', 'Var', (145, 165))	('myasthenia', 'Phenotype', 'HP:0003473', (74, 84))	('B13', 'Gene', '4698', (363, 366))	('DR3', 'Gene', (43, 46))	('DR3', 'Gene', '8718', (43, 46))	('myasthenia gravis', 'Disease', (74, 91))	('rat', 'Species', '10116', (116, 119))	('myasthenia gravis', 'Disease', 'MESH:D009157', (74, 91))	('B13', 'Gene', (363, 366))	('men', 'Species', '9606', (346, 349))	('rat', 'Species', '10116', (217, 220))	('Human', 'Species', '9606', (266, 271))
23311	22171357	Overall, the eight native AChR-specific clones that were identified all recognized extracellular AChR epitopes and were presented to the different T-cell receptors often by 'minor' Class II molecules (HLA-DQ, -DP and -DR52a) rather than the HLA-DR molecules that associate strongly with myasthenia gravis.	('myasthenia gravis', 'Disease', 'MESH:D009157', (287, 304))	('myasthenia', 'Phenotype', 'HP:0003473', (287, 297))	('extracellular', 'MPA', (83, 96))	('rat', 'Species', '10116', (225, 228))	('HLA-DQ', 'Var', (201, 207))	('presented', 'Interaction', (120, 129))	('myasthenia gravis', 'Disease', (287, 304))	('AChR', 'Gene', (97, 101))
23324	22171357	Whereas four patients, including two brothers, had reduced AChRs, not dissimilar to those in many patients with myasthenia gravis, one patient had completely normal AChR numbers despite very small miniature endplate potential amplitudes [later identified by postdoc Richard Webster as harbouring an AChR alpha gene (CHRNA1) mutation causing abnormally small AChR channel openings].	('mutation', 'Var', (324, 332))	('patient', 'Species', '9606', (135, 142))	('CHRNA1', 'Gene', '1134', (316, 322))	('patient', 'Species', '9606', (98, 105))	('myasthenia', 'Phenotype', 'HP:0003473', (112, 122))	('patient', 'Species', '9606', (13, 20))	('patients', 'Species', '9606', (13, 21))	('small miniature endplate', 'Phenotype', 'HP:0003402', (191, 215))	('patients', 'Species', '9606', (98, 106))	('AChR alpha', 'Gene', (299, 309))	('myasthenia gravis', 'Disease', (112, 129))	('CHRNA1', 'Gene', (316, 322))	('myasthenia gravis', 'Disease', 'MESH:D009157', (112, 129))	('man', 'Species', '9606', (93, 96))	('miniature endplate potential amplitudes', 'MPA', (197, 236))	('AChR alpha', 'Gene', '1134', (299, 309))
23327	22171357	As the genes encoding human proteins were cloned and the primary sequences determined (Supplementary materials B109 and B149), research assistant Rebecca Croxen and clinical fellow Phil Nicolls were able to identify mutations in AChR and rapsyn genes.	('men', 'Species', '9606', (93, 96))	('B10', 'Gene', '5169', (111, 114))	('B14', 'Gene', '4700', (120, 123))	('B14', 'Gene', (120, 123))	('B10', 'Gene', (111, 114))	('rapsyn', 'Gene', (238, 244))	('AChR', 'Gene', (229, 233))	('mutations', 'Var', (216, 225))	('human', 'Species', '9606', (22, 27))	('rapsyn', 'Gene', '5913', (238, 244))
23328	22171357	She obtained a detailed description of the consequences of the different genetic defects on AChR expression and function using patch and cell recordings from Xenopus oocytes, or from HEK (human embryonic kidney) 293 cells transfected with the mutant or wild-type genes.	('genetic defects', 'Disease', (73, 88))	('embryonic kidney', 'Disease', 'MESH:D007674', (194, 210))	('human', 'Species', '9606', (188, 193))	('293 cells', 'CellLine', 'CVCL:0045', (212, 221))	('HEK', 'CellLine', 'CVCL:M624', (183, 186))	('Xenopus', 'Species', '8355', (158, 165))	('genetic defects', 'Disease', 'MESH:D030342', (73, 88))	('embryonic kidney', 'Disease', (194, 210))	('AChR', 'Gene', (92, 96))	('expression', 'MPA', (97, 107))	('mutant', 'Var', (243, 249))	('function', 'MPA', (112, 120))
23329	22171357	Novel alpha subunit mutations were identified and characterized in the Slow Channel Syndrome (Supplementary material B190) and the adult AChR-specific epsilon subunit gene was found to be a major target for CMS-associated mutations, probably, as suggested by Andrew Engel and colleagues, because loss of the epsilon subunit could be partially compensated by maintaining expression of foetal AChR (that has the gamma subunit instead of epsilon).	('CMS', 'Disease', 'MESH:C536089', (207, 210))	('men', 'Species', '9606', (100, 103))	('Slow Channel Syndrome', 'Disease', (71, 92))	('Slow Channel Syndrome', 'Disease', 'MESH:D020294', (71, 92))	('CMS', 'Disease', (207, 210))	('mutations', 'Var', (222, 231))	('B19', 'Gene', (117, 120))	('B19', 'Gene', '59271', (117, 120))	('mutations', 'Var', (20, 29))
23330	22171357	The gene mutations were located throughout the length of the epsilon subunit coding sequence, and along with the first identification of AChR promoter sequence mutations, were shown to cause reduced AChR expression and thus underlie AChR deficiency syndromes (Supplementary materials B216, B227 and B239).	('mutations', 'Var', (160, 169))	('deficiency syndromes', 'Disease', 'MESH:D013577', (238, 258))	('mutations', 'Var', (9, 18))	('AChR', 'Gene', (199, 203))	('expression', 'MPA', (204, 214))	('reduced', 'NegReg', (191, 198))	('B22', 'Gene', '4715', (290, 293))	('B21', 'Gene', '9267', (284, 287))	('B23', 'Gene', '4869', (299, 302))	('B21', 'Gene', (284, 287))	('men', 'Species', '9606', (266, 269))	('B22', 'Gene', (290, 293))	('B23', 'Gene', (299, 302))	('deficiency syndromes', 'Disease', (238, 258))	('AChR', 'Gene', (137, 141))	('underlie', 'Reg', (224, 232))
23331	22171357	However, AChR epsilon mutations did not explain all of the patients with reduced endplate AChR expression, and mutations in rapsyn, the protein that anchors AChRs at the neuromuscular junction, were also identified.	('mutations', 'Var', (111, 120))	('rapsyn', 'Gene', (124, 130))	('endplate', 'MPA', (81, 89))	('reduced', 'NegReg', (73, 80))	('patients', 'Species', '9606', (59, 67))	('reduced endplate AChR', 'Phenotype', 'HP:0003402', (73, 94))	('expression', 'MPA', (95, 105))	('rapsyn', 'Gene', '5913', (124, 130))
23333	22171357	Georgina Burke, working in the clinic with JND, was able to identify different clinical phenotypes in these two forms of AChR deficiency with respect to ophthalmoplegia, arthrogryposis, squint and apnoeas, enabling targeted gene screening (Supplementary material B256).	('ophthalmoplegia', 'Phenotype', 'HP:0000602', (153, 168))	('apnoeas', 'Disease', 'MESH:D001049', (197, 204))	('arthrogryposis', 'Phenotype', 'HP:0002804', (170, 184))	('apnoeas', 'Disease', (197, 204))	('deficiency', 'Var', (126, 136))	('squint', 'Phenotype', 'HP:0000486', (186, 192))	('ophthalmoplegia', 'Disease', (153, 168))	('arthrogryposis', 'Disease', (170, 184))	('men', 'Species', '9606', (246, 249))	('AChR', 'Gene', (121, 125))	('ophthalmoplegia', 'Disease', 'MESH:D009886', (153, 168))	('arthrogryposis', 'Disease', 'MESH:D001176', (170, 184))	('squint and apnoeas', 'Phenotype', 'HP:0002104', (186, 204))	('squint', 'Disease', (186, 192))
23335	22171357	The clinical and experimental work has flourished with the important identification of limb-girdle myasthenic syndrome associated with mutations in the recently-discovered DOK7 gene, the clinical correlates (Supplementary materials B67 and B275), and the realisation that treatment with ephedrine or other beta-2 adrenergic receptor agonists such as salbutamol can lead to dramatic patient improvements in this now commonly recognized CMS.	('beta-2 adrenergic receptor', 'Gene', '154', (306, 332))	('improvements', 'PosReg', (390, 402))	('beta-2 adrenergic receptor', 'Gene', (306, 332))	('patient', 'Species', '9606', (382, 389))	('associated', 'Reg', (119, 129))	('CMS', 'Disease', 'MESH:C536089', (435, 438))	('men', 'Species', '9606', (397, 400))	('mutations', 'Var', (135, 144))	('limb-girdle myasthenic syndrome', 'Disease', 'MESH:D049288', (87, 118))	('ephedrine', 'Chemical', 'MESH:D004809', (287, 296))	('CMS', 'Disease', (435, 438))	('men', 'Species', '9606', (23, 26))	('salbutamol', 'Chemical', 'MESH:D000420', (350, 360))	('men', 'Species', '9606', (214, 217))	('men', 'Species', '9606', (277, 280))	('DOK7', 'Gene', '285489', (172, 176))	('myasthenic syndrome', 'Phenotype', 'HP:0003473', (99, 118))	('DOK7', 'Gene', (172, 176))	('limb-girdle myasthenic syndrome', 'Disease', (87, 118))
23338	22171357	John Ealing, MRC clinical training fellow, joined the group to show that DNA hammerhead ribozymes could be used to repair or change AChR gene sequences (in collaboration with Professor Matthew Wood, Oxford), and had considerable success in vitro.	('rat', 'Species', '10116', (163, 166))	('AChR gene', 'Gene', (132, 141))	('repair', 'Var', (115, 121))	('DNA hammerhead', 'Phenotype', 'HP:0001765', (73, 87))	('change', 'Reg', (125, 131))	('MRC', 'CellLine', 'CVCL:0440', (13, 16))
23356	22171357	Engel and a succession of his visiting Japanese clinical fellows demonstrated beautifully the normal clustering of the presynaptic active zone particles that are voltage-gated calcium channels, and their disorganization/disappearance over time, indicating internalization and destruction of the protein:analogous to the antigenic modulation shown earlier in myasthenia gravis:which correlated with the electrophysiological defects seen in Oxford (Supplementary materials B47, B84, B85, B86, B104 and B110).	('calcium', 'Chemical', 'MESH:D002118', (176, 183))	('rat', 'Species', '10116', (72, 75))	('B86', 'Var', (486, 489))	('B110', 'Var', (500, 504))	('B10', 'Gene', (491, 494))	('myasthenia gravis', 'Disease', (358, 375))	('B85', 'Var', (481, 484))	('B84', 'Var', (476, 479))	('B47', 'Gene', '2886', (471, 474))	('men', 'Species', '9606', (453, 456))	('myasthenia gravis', 'Disease', 'MESH:D009157', (358, 375))	('B10', 'Gene', '5169', (491, 494))	('myasthenia', 'Phenotype', 'HP:0003473', (358, 368))	('B47', 'Gene', (471, 474))
23374	22171357	When the same IgG preparations were applied to cerebellar granular cells in culture, however, the electrophysiological responses became less dependent on P/Q-type voltage-gated calcium channels, with an increase in the contributions of other voltage-gated calcium channels (Supplementary material B213).	('B21', 'Gene', '9267', (297, 300))	('rat', 'Species', '10116', (23, 26))	('calcium', 'Chemical', 'MESH:D002118', (177, 184))	('calcium', 'Chemical', 'MESH:D002118', (256, 263))	('B21', 'Gene', (297, 300))	('P/Q-type', 'Var', (154, 162))	('men', 'Species', '9606', (280, 283))
23386	22171357	In fact, IgG from patients with muscle specific kinase antibodies did not directly affect AChR function in vitro.	('affect', 'Reg', (83, 89))	('AChR function', 'CPA', (90, 103))	('patients', 'Species', '9606', (18, 26))	('antibodies', 'Var', (55, 65))
23408	22171357	From then, apart from a continued interest in respiratory function in different diseases (Supplementary materials B24, B25, B114, B126 and B145), most of his focus was on neuromuscular junction disorders.	('neuromuscular junction disorders', 'Disease', (171, 203))	('men', 'Species', '9606', (96, 99))	('B14', 'Gene', (139, 142))	('B12', 'Gene', (130, 133))	('B12', 'Gene', '4709', (130, 133))	('B114', 'Var', (124, 128))	('B14', 'Gene', '4700', (139, 142))	('neuromuscular junction disorders', 'Disease', 'MESH:D020511', (171, 203))	('rat', 'Species', '10116', (51, 54))
23415	22171357	The clinical features of patients with CMS that David Beeson identified, including many with Dok-7 mutations, were characterized (Supplementary material B275), and Georgina Burke documented useful clinical clues to the diagnoses of AChR and rapsyn deficiencies (Supplementary materials B246 and B256).	('men', 'Species', '9606', (183, 186))	('CMS', 'Disease', 'MESH:C536089', (39, 42))	('men', 'Species', '9606', (268, 271))	('CMS', 'Disease', (39, 42))	('Dok-7', 'Gene', (93, 98))	('mutations', 'Var', (99, 108))	('patients', 'Species', '9606', (25, 33))	('rapsyn deficiencies', 'Disease', 'MESH:D007153', (241, 260))	('Dok-7', 'Gene', '285489', (93, 98))	('man', 'Species', '9606', (83, 86))	('rapsyn deficiencies', 'Disease', (241, 260))	('men', 'Species', '9606', (136, 139))	('AChR', 'Gene', (232, 236))
23421	22171357	After his retirement, despite a little more time with his family, JND switched focus to clinical trials in a characteristically effective manner, helping to promote better and more comprehensive reporting of their results (Supplementary material B242) and establishing with US colleagues Gil Wolfe, Henry Kaminski, Fred Jaretski and Gary Cutter, among others, the first blinded randomized clinical trial of thymectomy in myasthenia gravis which is still recruiting today (Supplementary materials B254, B276, B280 and H).	('men', 'Species', '9606', (478, 481))	('B276', 'Var', (502, 506))	('myasthenia gravis', 'Disease', (421, 438))	('men', 'Species', '9606', (16, 19))	('B28', 'Gene', '54069', (508, 511))	('men', 'Species', '9606', (229, 232))	('man', 'Species', '9606', (138, 141))	('myasthenia gravis', 'Disease', 'MESH:D009157', (421, 438))	('myasthenia', 'Phenotype', 'HP:0003473', (421, 431))	('B28', 'Gene', (508, 511))
23465	26886206	Antibodies against LRP4 are predominantly of the complement-binding IgG1 and 2 type and are able to inhibit the LRP4-agrin interaction and thus alter AChR clustering in muscle cells.	('AChR', 'Protein', (150, 154))	('men', 'Species', '9606', (55, 58))	('Antibodies', 'Var', (0, 10))	('LRP4', 'Gene', '4038', (112, 116))	('agrin', 'Gene', '375790', (117, 122))	('LRP4', 'Gene', '4038', (19, 23))	('agrin', 'Gene', (117, 122))	('alter', 'Reg', (144, 149))	('LRP4', 'Gene', (19, 23))	('LRP4', 'Gene', (112, 116))	('interaction', 'Interaction', (123, 134))	('inhibit', 'NegReg', (100, 107))
23466	26886206	Antibodies against agrin are able to inhibit agrin-induced MuSK phosphorylation and AChR clustering in muscle cells.	('Antibodies', 'Var', (0, 10))	('agrin', 'Gene', '375790', (45, 50))	('inhibit', 'NegReg', (37, 44))	('MuSK', 'Gene', '4593', (59, 63))	('MuSK', 'Gene', (59, 63))	('AChR clustering', 'CPA', (84, 99))	('agrin', 'Gene', (45, 50))	('agrin', 'Gene', '375790', (19, 24))	('agrin', 'Gene', (19, 24))
23505	26886206	(c) More than 50 % share common expansions in the peripheral T cell repertoire with TAMG patients.	('patients', 'Species', '9606', (89, 97))	('peripheral T cell repertoire', 'CPA', (50, 78))	('TAMG', 'Chemical', '-', (84, 88))	('expansions', 'Var', (32, 42))
23506	26886206	Hence, immunological parallels between LOMG and TAMG are so close that it appears that aberrations in the aged thymus in LOMG mimic thymoma behavior without definite neoplasia, leading to export and possibly even activation of non-tolerant T cells.	('thymoma', 'Phenotype', 'HP:0100522', (132, 139))	('thymoma behavior', 'Disease', 'MESH:D013945', (132, 148))	('thymoma behavior', 'Disease', (132, 148))	('neoplasia', 'Disease', (166, 175))	('LOMG', 'Chemical', '-', (39, 43))	('TAMG', 'Chemical', '-', (48, 52))	('aberrations', 'Var', (87, 98))	('mimic', 'Reg', (126, 131))	('non-tolerant T cells', 'CPA', (227, 247))	('neoplasia', 'Disease', 'MESH:D009369', (166, 175))	('activation', 'PosReg', (213, 223))	('neoplasia', 'Phenotype', 'HP:0002664', (166, 175))	('LOMG', 'Chemical', '-', (121, 125))	('export', 'CPA', (188, 194))	('aged thymus', 'Phenotype', 'HP:0010516', (106, 117))
23542	26886206	In case of an estimated therapy duration of longer than 3 months using a dosage of >7.5 mg prednisolone equivalent, patients should be treated with calcium (1000-1500 mg/d) and vitamin D (400-800 IE/d) to prevent osteoporosis.	('calcium', 'Chemical', 'MESH:D002118', (148, 155))	('osteoporosis', 'Disease', 'MESH:D010024', (213, 225))	('400-800', 'Var', (188, 195))	('osteoporosis', 'Disease', (213, 225))	('patients', 'Species', '9606', (116, 124))	('osteoporosis', 'Phenotype', 'HP:0000939', (213, 225))	('vitamin D', 'Chemical', 'MESH:D014807', (177, 186))	('prednisolone', 'Chemical', 'MESH:D011239', (91, 103))
23565	26886206	Testing for TMTP activity or TPMT genotype can be performed prior to treatment initiation: (a) patients completely lacking TMPT activity (frequency 1:300) or those homozygous for distinct TPMT single nucleotide polymorphisms cannot be treated with AZA.	('TPMT', 'Gene', '7172', (29, 33))	('AZA', 'Chemical', 'MESH:D001379', (248, 251))	('TPMT', 'Gene', '7172', (188, 192))	('patients', 'Species', '9606', (95, 103))	('TPMT', 'Gene', (29, 33))	('single nucleotide polymorphisms', 'Var', (193, 224))	('men', 'Species', '9606', (74, 77))	('lacking', 'NegReg', (115, 122))	('TMPT activity', 'MPA', (123, 136))	('TPMT', 'Gene', (188, 192))
23582	26886206	Methotrexate (MTX) has been used for several decades now as a treatment for MG. MTX competitively inhibits dihydrofolate reductase (DHFR) with an affinity of about 1000-fold that of dihydrofolate.	('MTX', 'Var', (80, 83))	('DHFR', 'Gene', '1719', (132, 136))	('dihydrofolate reductase', 'Gene', (107, 130))	('MTX', 'Chemical', 'MESH:D008727', (80, 83))	('men', 'Species', '9606', (67, 70))	('dihydrofolate', 'Chemical', 'MESH:C010920', (182, 195))	('Methotrexate', 'Chemical', 'MESH:D008727', (0, 12))	('inhibits', 'NegReg', (98, 106))	('dihydrofolate reductase', 'Gene', '1719', (107, 130))	('dihydrofolate', 'Chemical', 'MESH:C010920', (107, 120))	('DHFR', 'Gene', (132, 136))	('MTX', 'Chemical', 'MESH:D008727', (14, 17))
23606	26886206	In a multicenter, open cohort study in 79 patients with MG, low-dosage TCM (0.1 mg/day/kg bodyweight) could replace combination therapy consisting of CSA and prednisolon and provide good clinical stabilization including regression of nAChR-Ab titers.	('low-dosage', 'Var', (60, 70))	('nAChR', 'Gene', '1137', (234, 239))	('regression', 'MPA', (220, 230))	('prednisolon', 'Chemical', '-', (158, 169))	('nAChR', 'Gene', (234, 239))	('TCM', 'Chemical', 'MESH:D016559', (71, 74))	('CSA', 'Gene', '1161', (150, 153))	('patients', 'Species', '9606', (42, 50))	('CSA', 'Gene', (150, 153))
23613	26886206	A meta-analysis was recently performed of 15 uncontrolled observational studies including a total of 168 patients [125 females and 43 males; 91 MG patients with AChR antibodies, 70 MG patients with MuSK antibodies, and 7 MG patients without AChR or MuSK antibodies ("double seronegative")].	('MuSK', 'Gene', '4593', (249, 253))	('antibodies', 'Var', (166, 176))	('MuSK', 'Gene', (198, 202))	('patients', 'Species', '9606', (105, 113))	('MuSK antibodies', 'Phenotype', 'HP:0030210', (249, 264))	('MuSK', 'Gene', '4593', (198, 202))	('patients', 'Species', '9606', (184, 192))	('MuSK antibodies', 'Phenotype', 'HP:0030210', (198, 213))	('patients', 'Species', '9606', (147, 155))	('patients', 'Species', '9606', (224, 232))	('MuSK', 'Gene', (249, 253))
23635	26886206	Clinical experience with other therapeutic monoclonal antibodies now in broader use in multiple sclerosis such as anti-CD52/alemtuzumab and anti-IL2R/daclizumab are sparce in patients with MG and should be considered in individual rare cases only.	('anti-CD52/alemtuzumab', 'Var', (114, 135))	('IL2R', 'Gene', (145, 149))	('sclerosis', 'Disease', 'MESH:D012598', (96, 105))	('patients', 'Species', '9606', (175, 183))	('IL2R', 'Gene', '3559', (145, 149))	('alemtuzumab', 'Chemical', 'MESH:D000074323', (124, 135))	('sclerosis', 'Disease', (96, 105))	('daclizumab', 'Chemical', 'MESH:D000077561', (150, 160))
23696	26224649	Ablation of beta-catenin in Keratin 5 (K5)-expressing mTECs results in thymic atrophy, mainly due to a defective IL-7 niche in beta-catenin-deficient mTEC derivatives that are unable to support early thymocyte development.	('beta-catenin', 'Gene', '12387', (12, 24))	('beta-catenin', 'Gene', '12387', (127, 139))	('Ablation', 'Var', (0, 8))	('beta-catenin', 'Gene', (12, 24))	('atrophy', 'Disease', 'MESH:D001284', (78, 85))	('K5', 'Gene', (39, 41))	('IL-7', 'Gene', (113, 117))	('Keratin 5', 'Gene', (28, 37))	('IL-7', 'Gene', '16196', (113, 117))	('Keratin 5', 'Gene', '110308', (28, 37))	('atrophy', 'Disease', (78, 85))	('defective', 'NegReg', (103, 112))	('beta-catenin', 'Gene', (127, 139))	('thymic', 'Disease', (71, 77))
23701	26224649	Early thymoma lesions driven by the  N64Ctnnb1/ERT2 transgene are frequently identified at the cortical-medullary junction (CMJ) of the transgenic thymi.	('N64Ctnnb1/ERT2', 'Var', (37, 51))	('thymoma lesions', 'Disease', 'MESH:D013945', (6, 21))	('thymoma lesions', 'Disease', (6, 21))	('transgenic', 'Species', '10090', (136, 146))	('thymoma', 'Phenotype', 'HP:0100522', (6, 13))
23704	26224649	The thymoma lesions express K5,  Np63 (alpha and beta isoforms), and beta5t, which is a protease subunit used as a differential diagnostic marker of human type B3 thymomas.	('thymoma', 'Phenotype', 'HP:0100522', (163, 170))	('beta5t', 'Gene', (69, 75))	('thymoma lesions', 'Disease', 'MESH:D013945', (4, 19))	('beta5t', 'Gene', '122706', (69, 75))	('thymomas', 'Disease', (163, 171))	('thymomas', 'Disease', 'MESH:D013945', (163, 171))	('human', 'Species', '9606', (149, 154))	('thymoma lesions', 'Disease', (4, 19))	('Np63', 'Var', (33, 37))	('thymoma', 'Phenotype', 'HP:0100522', (4, 11))
23705	26224649	Consistent with expression patterns found in human thymomas,  N64Ctnnb1/ERT2-mediated thymomas showed loss of AIRE and downregulation of p21.	('p21', 'Gene', '644914', (137, 140))	('N64Ctnnb1/ERT2-mediated', 'Var', (62, 85))	('thymomas', 'Disease', (51, 59))	('downregulation', 'NegReg', (119, 133))	('thymomas', 'Disease', 'MESH:D013945', (51, 59))	('thymomas', 'Disease', (86, 94))	('AIRE', 'Gene', (110, 114))	('human', 'Species', '9606', (45, 50))	('thymomas', 'Disease', 'MESH:D013945', (86, 94))	('AIRE', 'Gene', '326', (110, 114))	('loss', 'NegReg', (102, 106))	('thymoma', 'Phenotype', 'HP:0100522', (86, 93))	('thymoma', 'Phenotype', 'HP:0100522', (51, 58))	('p21', 'Gene', (137, 140))
23706	26224649	Moreover, histologic characteristics of  N64Ctnnb1/ERT2 transgene-induced thymomas have a squamoid appearance and loose connective tissue in the perivascular space resembling that of human type B3 thymomas (or atypical thymomas).	('thymomas', 'Disease', (219, 227))	('thymoma', 'Phenotype', 'HP:0100522', (197, 204))	('thymomas', 'Disease', 'MESH:D013945', (219, 227))	('N64Ctnnb1/ERT2', 'Var', (41, 55))	('thymoma', 'Phenotype', 'HP:0100522', (74, 81))	('thymomas', 'Disease', (197, 205))	('human', 'Species', '9606', (183, 188))	('thymomas', 'Disease', 'MESH:D013945', (74, 82))	('thymomas', 'Disease', (74, 82))	('thymomas', 'Disease', 'MESH:D013945', (197, 205))	('thymoma', 'Phenotype', 'HP:0100522', (219, 226))	('perivascular space', 'Phenotype', 'HP:0012520', (145, 163))
23710	26224649	Interestingly, specific ablation of beta-catenin in prostate basal cells blocks basal-to-luminal differentiation, indicating a critical role of beta-catenin in this process (Figure 1B).	('beta-catenin', 'Gene', (144, 156))	('basal-to-luminal differentiation', 'CPA', (80, 112))	('beta-catenin', 'Gene', (36, 48))	('beta-catenin', 'Gene', '12387', (144, 156))	('blocks', 'NegReg', (73, 79))	('ablation', 'Var', (24, 32))	('beta-catenin', 'Gene', '12387', (36, 48))
23718	26224649	We further demonstrate that loss of beta-catenin suppresses basal-derived prostate cancer progression but is dispensable for luminal-derived prostate cancer.	('cancer', 'Phenotype', 'HP:0002664', (150, 156))	('loss', 'Var', (28, 32))	('prostate cancer', 'Disease', (74, 89))	('prostate cancer', 'Disease', 'MESH:D011471', (141, 156))	('cancer', 'Phenotype', 'HP:0002664', (83, 89))	('prostate cancer', 'Phenotype', 'HP:0012125', (141, 156))	('beta-catenin', 'Gene', (36, 48))	('prostate cancer', 'Disease', 'MESH:D011471', (74, 89))	('prostate cancer', 'Phenotype', 'HP:0012125', (74, 89))	('suppresses', 'NegReg', (49, 59))	('prostate cancer', 'Disease', (141, 156))	('beta-catenin', 'Gene', '12387', (36, 48))
23721	26224649	Aberrant beta-catenin activation in the K5-expressing epithelial derivatives of the thymus and prostate gland promotes tumor progression.	('tumor', 'Disease', (119, 124))	('Aberrant', 'Var', (0, 8))	('beta-catenin', 'Gene', (9, 21))	('activation', 'PosReg', (22, 32))	('promotes', 'PosReg', (110, 118))	('tumor', 'Disease', 'MESH:D009369', (119, 124))	('beta-catenin', 'Gene', '12387', (9, 21))	('tumor', 'Phenotype', 'HP:0002664', (119, 124))
24127	25499804	A large number of DCs is related to better survival in a variety of malignant tumors such as melanoma, breast carcinoma, hepatocellular carcinoma, and lung adenocarcinoma.	('lung adenocarcinoma', 'Disease', 'MESH:D000077192', (151, 170))	('melanoma', 'Disease', 'MESH:D008545', (93, 101))	('malignant tumors', 'Disease', 'MESH:D018198', (68, 84))	('tumor', 'Phenotype', 'HP:0002664', (78, 83))	('hepatocellular carcinoma', 'Disease', (121, 145))	('lung adenocarcinoma', 'Phenotype', 'HP:0030078', (151, 170))	('carcinoma', 'Phenotype', 'HP:0030731', (136, 145))	('better', 'PosReg', (36, 42))	('tumors', 'Phenotype', 'HP:0002664', (78, 84))	('malignant tumors', 'Disease', (68, 84))	('breast carcinoma', 'Disease', 'MESH:D001943', (103, 119))	('melanoma', 'Phenotype', 'HP:0002861', (93, 101))	('melanoma', 'Disease', (93, 101))	('carcinoma', 'Phenotype', 'HP:0030731', (110, 119))	('hepatocellular carcinoma', 'Phenotype', 'HP:0001402', (121, 145))	('lung adenocarcinoma', 'Disease', (151, 170))	('breast carcinoma', 'Phenotype', 'HP:0003002', (103, 119))	('DCs', 'Var', (18, 21))	('hepatocellular carcinoma', 'Disease', 'MESH:D006528', (121, 145))	('breast carcinoma', 'Disease', (103, 119))	('carcinoma', 'Phenotype', 'HP:0030731', (161, 170))
24225	21152329	Feature signs and symptoms include weakness in the muscles that control eye and eyelid movements (ocular myasthenia), facial expression, chewing, swallowing (dysphagia), slurred speech (dysarthria) that is often associated with a nasal tone (dystonia) due to weakness of the velar muscles, and generalized muscle weakness that may involve the extremities and trunk.	('dysphagia', 'Phenotype', 'HP:0002015', (158, 167))	('ocular myasthenia', 'Disease', 'MESH:D009157', (98, 115))	('eyelid movements', 'Disease', 'MESH:D009069', (80, 96))	('dystonia', 'Phenotype', 'HP:0001332', (242, 250))	('myasthenia', 'Phenotype', 'HP:0003473', (105, 115))	('weakness', 'Var', (35, 43))	('slurred speech', 'Phenotype', 'HP:0001350', (170, 184))	('muscle weakness', 'Phenotype', 'HP:0001324', (306, 321))	('associated', 'Reg', (212, 222))	('nasal tone', 'Disease', (230, 240))	('chewing', 'Disease', (137, 144))	('dysarthria', 'Phenotype', 'HP:0001260', (186, 196))	('dysphagia', 'Disease', (158, 167))	('facial expression', 'Disease', (118, 135))	('swallowing', 'Disease', (146, 156))	('slurred speech', 'Disease', (170, 184))	('eyelid movements', 'Disease', (80, 96))	('generalized muscle weakness', 'Phenotype', 'HP:0003324', (294, 321))	('ocular myasthenia', 'Disease', (98, 115))
24248	33438140	Compared to AChR-MG, DSP-MG had greater bulbar dysfunction (47.1% vs 18.6%, P = 0.04), higher incidence of myasthenia crisis (41.2% vs 14.8%, P = 0.04), more severe Myasthenia Gravis Foundation of America classification at maximum worsening, greater autoantibody abnormalities (70.6% vs 33.3%, P = 0.015), greater need for immunosuppressant treatment (58.8% vs 3.7%, P < 0.001), and worse prognosis with less remission (11.8% vs 55.6%, P = 0.001).	('Myasthenia Gravis', 'Disease', (165, 182))	('bulbar dysfunction', 'Disease', 'MESH:D010244', (40, 58))	('DSP-MG', 'Var', (21, 27))	('autoantibody abnormalities', 'Disease', 'MESH:D050031', (250, 276))	('myasthenia crisis', 'Disease', (107, 124))	('autoantibody abnormalities', 'Disease', (250, 276))	('Myasthenia', 'Phenotype', 'HP:0003473', (165, 175))	('greater', 'PosReg', (242, 249))	('myasthenia', 'Phenotype', 'HP:0003473', (107, 117))	('myasthenia crisis', 'Disease', 'MESH:D020294', (107, 124))	('bulbar dysfunction', 'Disease', (40, 58))	('Myasthenia Gravis', 'Disease', 'MESH:D009157', (165, 182))
24262	33438140	DSP-MG patients had greater bulbar palsy dysfunction, a higher incidence of myasthenia crisis, higher MGFA classification at maximum worsening, more autoantibody abnormalities, greater need for immunosuppressants, and a lower rate of pharmacologic remission.	('autoantibody abnormalities', 'Disease', 'MESH:D050031', (149, 175))	('bulbar palsy dysfunction', 'Disease', (28, 52))	('myasthenia crisis', 'Disease', 'MESH:D020294', (76, 93))	('autoantibody abnormalities', 'Disease', (149, 175))	('greater', 'PosReg', (20, 27))	('higher', 'PosReg', (95, 101))	('DSP-MG', 'Var', (0, 6))	('MGFA', 'Chemical', '-', (102, 106))	('bulbar palsy dysfunction', 'Disease', 'MESH:D010244', (28, 52))	('myasthenia crisis', 'Disease', (76, 93))	('bulbar palsy', 'Phenotype', 'HP:0001283', (28, 40))	('MGFA classification', 'MPA', (102, 121))	('patients', 'Species', '9606', (7, 15))	('myasthenia', 'Phenotype', 'HP:0003473', (76, 86))
24282	33438140	MuSK-MG also has worse prognosis than AChR-MG as a result of drug insensitivity and more aggressive disease course.	('MuSK-MG', 'Var', (0, 7))	('aggressive disease', 'Disease', 'MESH:D001523', (89, 107))	('aggressive disease', 'Disease', (89, 107))	('MuSK-MG', 'CellLine', 'CVCL:1698', (0, 7))	('drug insensitivity', 'Phenotype', 'HP:0008189', (61, 79))
24361	31452699	After functional annotation analysis, it was determined that the DEGs were enriched in 'ribosome', 'oxidative phosphorylation', 'spliceosome', 'DNA replication' and 'cell cycle', which indicated that the DEGs may affect cell growth and have an important role in the occurrence and development of thymoma.	('DEGs', 'Var', (204, 208))	('thymoma', 'Disease', 'MESH:D013945', (296, 303))	('thymoma', 'Disease', (296, 303))	('thymoma', 'Phenotype', 'HP:0100522', (296, 303))	('cell growth', 'CPA', (220, 231))	('affect', 'Reg', (213, 219))
24416	30191163	6) revealed a tissue made-up by bands of sclerosis and average size lymphocytes with T-immature phenotype (precursor T cell, CD3+, CD5+/-, CD4+, CD8+, TdT+), associated also with irregular oval shape epithelial cells (CKAE1-AE3+, Calretinin-).	('CKAE1-AE3', 'Gene', (218, 227))	('CD3+', 'Var', (125, 129))	('CD8', 'Gene', (145, 148))	('CKAE1-AE3', 'Gene', '6508', (218, 227))	('CD4', 'Gene', (139, 142))	('CD5', 'Gene', (131, 134))	('sclerosis', 'Disease', 'MESH:D012598', (41, 50))	('CD8', 'Gene', '925', (145, 148))	('CD5', 'Gene', '921', (131, 134))	('CD4', 'Gene', '920', (139, 142))	('sclerosis', 'Disease', (41, 50))
24491	29682176	Finally, CTLA-4 gene polymorphisms have been associated to increased susceptibility to multiple types of cancer such as breast, melanoma gastric and colon cancers and cervical carcinomas.	('carcinoma', 'Phenotype', 'HP:0030731', (176, 185))	('carcinomas', 'Phenotype', 'HP:0030731', (176, 186))	('cancer', 'Phenotype', 'HP:0002664', (155, 161))	('cancer', 'Disease', (105, 111))	('cancer', 'Disease', 'MESH:D009369', (105, 111))	('breast', 'Disease', (120, 126))	('CTLA-4', 'Gene', (9, 15))	('colon cancers', 'Phenotype', 'HP:0003003', (149, 162))	('melanoma', 'Phenotype', 'HP:0002861', (128, 136))	('cancers', 'Phenotype', 'HP:0002664', (155, 162))	('polymorphisms', 'Var', (21, 34))	('cancer', 'Phenotype', 'HP:0002664', (105, 111))	('melanoma gastric and colon cancers and cervical carcinomas', 'Disease', 'MESH:D013274', (128, 186))	('cancer', 'Disease', (155, 161))	('cancer', 'Disease', 'MESH:D009369', (155, 161))
24517	29682176	In regard to CTLA-4 expression, patients were divided into two groups showing low < 0.5 (n = 15 specimens) and high > 0.5 (n = 48 specimens) CTLA-4 level.	('high > 0.5', 'Var', (111, 121))	('CTLA-4', 'MPA', (141, 147))	('patients', 'Species', '9606', (32, 40))
24519	29682176	In addition, atypical histological type thymoma (OS = 65.73 months) (Figure 5B) showed a significant (p = 0.0055) reduced survival respect to typical thymoma (OS = 188.22 months) confirming that high CTLA-4 expression in atypical thymoma (Figure 1D) is associated with negative prognosis.	('thymoma', 'Gene', (230, 237))	('OS', 'Chemical', '-', (49, 51))	('thymoma', 'Phenotype', 'HP:0100522', (40, 47))	('reduced', 'NegReg', (114, 121))	('CTLA-4', 'Gene', (200, 206))	('OS', 'Chemical', '-', (159, 161))	('thymoma', 'Phenotype', 'HP:0100522', (150, 157))	('thymoma', 'Gene', '7063', (40, 47))	('high', 'Var', (195, 199))	('thymoma', 'Gene', '7063', (150, 157))	('type thymoma', 'Disease', 'MESH:D013945', (35, 47))	('thymoma', 'Phenotype', 'HP:0100522', (230, 237))	('thymoma', 'Gene', (150, 157))	('type thymoma', 'Disease', (35, 47))	('thymoma', 'Gene', (40, 47))	('thymoma', 'Gene', '7063', (230, 237))
24531	29682176	In particular, single nucleotide polymorphisms (SNPs) of CTLA-4 seem to be associated with the manifestation of MG in patients with thymoma.	('associated with', 'Reg', (75, 90))	('thymoma', 'Phenotype', 'HP:0100522', (132, 139))	('thymoma', 'Gene', '7063', (132, 139))	('CTLA-4', 'Gene', (57, 63))	('thymoma', 'Gene', (132, 139))	('single nucleotide polymorphisms', 'Var', (15, 46))	('patients', 'Species', '9606', (118, 126))
24532	29682176	SNPs in position 49 in patients expressing high CTLA-4 levels, in particular SNP +49 A/A and SNP +49 A/G showed a bad prognosis and reduced OS.	('+49 A/G', 'Mutation', 'rs231775', (97, 104))	('patients', 'Species', '9606', (23, 31))	('reduced', 'NegReg', (132, 139))	('SNP +49 A/A', 'Var', (77, 88))	('OS', 'Chemical', '-', (140, 142))	('SNP +49 A/G', 'Var', (93, 104))
24545	29682176	In a multivariate Cox proportional hazards regression model, high CTLA-4 levels both in total and atypical thymoma, as well as age > 60 and tumor dimension > 5 cm, confirm their significance as negative prognostic factor for survival.	('thymoma', 'Phenotype', 'HP:0100522', (107, 114))	('CTLA-4', 'Gene', (66, 72))	('thymoma', 'Gene', '7063', (107, 114))	('high', 'Var', (61, 65))	('tumor', 'Disease', 'MESH:D009369', (140, 145))	('thymoma', 'Gene', (107, 114))	('tumor', 'Phenotype', 'HP:0002664', (140, 145))	('negative', 'NegReg', (194, 202))	('tumor', 'Disease', (140, 145))
24550	29682176	The presence of Treg in tumor microenvironment has been associated with poor outcomes in patients with cancers.	('tumor', 'Phenotype', 'HP:0002664', (24, 29))	('cancers', 'Disease', 'MESH:D009369', (103, 110))	('cancer', 'Phenotype', 'HP:0002664', (103, 109))	('tumor', 'Disease', (24, 29))	('patients', 'Species', '9606', (89, 97))	('cancers', 'Phenotype', 'HP:0002664', (103, 110))	('presence', 'Var', (4, 12))	('tumor', 'Disease', 'MESH:D009369', (24, 29))	('cancers', 'Disease', (103, 110))
24564	29682176	Regarding the use of IPI, thymoma patients showing high CTLA-4 expression could be benefit of immunotherapy with IPI.	('CTLA-4', 'Gene', (56, 62))	('thymoma', 'Phenotype', 'HP:0100522', (26, 33))	('IPI', 'Chemical', 'MESH:D000074324', (113, 116))	('expression', 'MPA', (63, 73))	('IPI', 'Chemical', 'MESH:D000074324', (21, 24))	('thymoma', 'Gene', '7063', (26, 33))	('high', 'Var', (51, 55))	('patients', 'Species', '9606', (34, 42))	('thymoma', 'Gene', (26, 33))
24595	29682176	CTLA-4 Cytotoxic T lymphocyte antigen 4 OS Overall Survival MG Myasthenia Gravis Teff effector T cells Treg regulatory T cells PBMCs Peripheral Blood Mononuclear Cells PMA Phorbol 12-Myristate 13-acetate qRT-PCR Quantitative real time polymerase chain reaction TILs Tumor-infiltrating Leukocytes IHC Immunohystochemistry mAB Monoclonal Antibody TETs Thymic Epithelial Tumors SNPs Single Nucleotide Polymorphisms NPC Nasopharyngeal Carcinoma IPI Ipilimumab H&E Hematoxylin Eosin	('H&E', 'Chemical', '-', (456, 459))	('Carcinoma', 'Disease', (431, 440))	('IPI', 'Chemical', 'MESH:D000074324', (441, 444))	('Carcinoma', 'Disease', 'MESH:D002277', (431, 440))	('Hematoxylin Eosin', 'Chemical', '-', (460, 477))	('OS', 'Chemical', '-', (40, 42))	('PMA', 'Chemical', 'MESH:D013755', (168, 171))	('NPC', 'Disease', 'MESH:D052556', (412, 415))	('Single Nucleotide Polymorphisms', 'Var', (380, 411))	('Tumor', 'Phenotype', 'HP:0002664', (368, 373))	('NPC', 'Phenotype', 'HP:0100630', (412, 415))	('Myasthenia', 'Phenotype', 'HP:0003473', (63, 73))	('Tumor', 'Phenotype', 'HP:0002664', (266, 271))	('Tumors', 'Phenotype', 'HP:0002664', (368, 374))	('Epithelial Tumors', 'Disease', (357, 374))	('Phorbol 12-Myristate 13-acetate', 'Chemical', 'MESH:D013755', (172, 203))	('Cytotoxic', 'Disease', (7, 16))	('Carcinoma', 'Phenotype', 'HP:0030731', (431, 440))	('NPC', 'Disease', (412, 415))	('Myasthenia Gravis', 'Disease', (63, 80))	('Ipilimumab', 'Chemical', 'MESH:D000074324', (445, 455))	('Cytotoxic', 'Disease', 'MESH:D064420', (7, 16))	('Nasopharyngeal Carcinoma', 'Phenotype', 'HP:0100630', (416, 440))	('Epithelial Tumors', 'Disease', 'MESH:D002277', (357, 374))	('Myasthenia Gravis', 'Disease', 'MESH:D009157', (63, 80))
24662	27832160	Detection was performed using 2 step Mach 3 Mouse HRP Polymer Detection (Biocare M3M530L, Biocare, Concord, CA, USA) 20/20 minutes.	('Biocare', 'Var', (73, 80))	('M3M530L', 'Var', (81, 88))	('Mouse', 'Species', '10090', (44, 49))
24674	27832160	The collagens CO1A1, CO1A2, CO3A1, CO5A1, CO6A1, CO6A2 and CO6A3 were distinguished by 17, 18, 7, 2, 20, 24 and 97 unique peptides respectively.	('CO6A1', 'Var', (42, 47))	('CO6A3', 'Var', (59, 64))	('CO6A2', 'Var', (49, 54))	('peptides', 'Chemical', 'MESH:D010455', (122, 130))
24735	27832160	The loss of CD3E leads to absence of mature double and single positive thymocytes implicating its role in pre-TCR development.	('absence', 'NegReg', (26, 33))	('CD3E', 'Gene', (12, 16))	('CD3E', 'Gene', '916', (12, 16))	('loss', 'Var', (4, 8))
24744	27832160	High levels of stathmin have been associated with poor prognosis in multiple cancer types and resistance to drugs stabilizing microtubules, such as taxane.	('resistance', 'MPA', (94, 104))	('associated', 'Reg', (34, 44))	('cancer', 'Disease', (77, 83))	('taxane', 'Chemical', 'MESH:C080625', (148, 154))	('High levels', 'Var', (0, 11))	('cancer', 'Disease', 'MESH:D009369', (77, 83))	('stathmin', 'Gene', (15, 23))	('stathmin', 'Gene', '3925', (15, 23))	('cancer', 'Phenotype', 'HP:0002664', (77, 83))
24745	27832160	Furthermore, depletion of stathmin leads to cell cycle arrest in the G2 phase and apoptosis.	('apoptosis', 'CPA', (82, 91))	('cell cycle arrest in the G2 phase', 'CPA', (44, 77))	('depletion', 'Var', (13, 22))	('cell cycle arrest', 'Phenotype', 'HP:0011018', (44, 61))	('stathmin', 'Gene', '3925', (26, 34))	('stathmin', 'Gene', (26, 34))
24812	25364773	Screening of serum for classic paraneoplastic autoantibodies by Western blot (Euroimmun, Lubeck, Germany) and autoimmune encephalitis autoantibodies by cell-based assays (Euroimmun) showed positivity for anti-Hu, anti-CV2, and anti-GABAB receptor but negativity for anti-Ri, anti-Yo, anti-Ma2/Ta, anti-amphiphysin, anti-LGI1, anti-CASPR2, anti-NMDAR, anti-GAD, anti-glycine receptor, anti-AQP4, anti-AChR (tested with the most sensitive radioimunnoassay), and anti-MuSK.	('anti-glycine', 'Var', (361, 373))	('CASPR2', 'Gene', '26047', (331, 337))	('AQP4', 'Gene', (389, 393))	('CV2', 'Gene', (218, 221))	('GAD', 'Gene', (356, 359))	('paraneoplastic', 'Disease', 'MESH:D010257', (31, 45))	('CV2', 'Gene', '168667', (218, 221))	('LGI1', 'Gene', (320, 324))	('AQP4', 'Gene', '361', (389, 393))	('autoimmune encephalitis', 'Disease', 'MESH:C535841', (110, 133))	('autoimmune encephalitis', 'Disease', (110, 133))	('Ma2', 'Gene', (289, 292))	('GAD', 'Gene', '2571', (356, 359))	('man', 'Species', '9606', (100, 103))	('LGI1', 'Gene', '9211', (320, 324))	('paraneoplastic', 'Disease', (31, 45))	('anti-NMDAR', 'Var', (339, 349))	('anti-AChR', 'Var', (395, 404))	('Ma2', 'Gene', '10687', (289, 292))	('CASPR2', 'Gene', (331, 337))	('GABAB', 'Chemical', '-', (232, 237))	('encephalitis', 'Phenotype', 'HP:0002383', (121, 133))
24826	25364773	It is also the first case associated with thymoma and co-occurrence with 2 other paraneoplastic antibodies, namely anti-Hu and anti-CV2.	('paraneoplastic', 'Disease', 'MESH:D010257', (81, 95))	('CV2', 'Gene', '168667', (132, 135))	('CV2', 'Gene', (132, 135))	('paraneoplastic', 'Disease', (81, 95))	('thymoma', 'Disease', 'MESH:D013945', (42, 49))	('thymoma', 'Disease', (42, 49))	('thymoma', 'Phenotype', 'HP:0100522', (42, 49))	('anti-Hu', 'Var', (115, 122))	('associated', 'Reg', (26, 36))
24829	25364773	In our case, the rapid response to plasmapheresis after symptom reoccurrence strongly suggests (although does not prove) that the main causative factor was humoral immunity associated with GABAB antibodies rather than T-cell immunity implicated in CV2 and Hu paraneoplastic syndromes.	('CV2', 'Gene', (248, 251))	('GABAB', 'Chemical', '-', (189, 194))	('antibodies', 'Var', (195, 205))	('Hu paraneoplastic syndromes', 'Disease', (256, 283))	('Hu paraneoplastic syndromes', 'Disease', 'MESH:D010257', (256, 283))	('CV2', 'Gene', '168667', (248, 251))
24862	19946549	Autoantibody-mediated destruction of nicotinic acetylcholine receptors at the neuromuscular junction causes sporadic skeletal muscle weakness.	('causes', 'Reg', (101, 107))	('muscle weakness', 'Disease', (126, 141))	('nicotinic acetylcholine receptors', 'Protein', (37, 70))	('muscle weakness', 'Phenotype', 'HP:0001324', (126, 141))	('muscle weakness', 'Disease', 'MESH:D018908', (126, 141))	('destruction', 'Var', (22, 33))
24922	19946549	In some patients with this condition, the presence of voltage-gated potassium channel antibodies is also associated with other symptoms of autonomic dysfunction including somnolence, sweating, hypersalivation and appetite alteration.	('sweating', 'Disease', (183, 191))	('hypersalivation', 'Disease', (193, 208))	('appetite alteration', 'Disease', (213, 232))	('somnolence', 'Disease', (171, 181))	('somnolence', 'Disease', 'MESH:D006970', (171, 181))	('hypersalivation', 'Disease', 'MESH:D012798', (193, 208))	('autonomic dysfunction', 'Disease', 'MESH:D001342', (139, 160))	('autonomic dysfunction', 'Disease', (139, 160))	('hypersalivation', 'Phenotype', 'HP:0003781', (193, 208))	('sweating', 'Phenotype', 'HP:0000975', (183, 191))	('autonomic dysfunction', 'Phenotype', 'HP:0012332', (139, 160))	('antibodies', 'Var', (86, 96))	('associated', 'Reg', (105, 115))	('voltage-gated potassium channel', 'Protein', (54, 85))	('presence', 'Var', (42, 50))	('patients', 'Species', '9606', (8, 16))
24977	28392652	The pathogenesis of oral lesions in PNP remains unclear, but the presence of autoantibodies against Dsg3 and/or cell-mediated immune responses may play a role in damaging mucosal epithelia.	('Dsg3', 'Gene', (100, 104))	('presence', 'Var', (65, 73))	('oral lesions', 'Phenotype', 'HP:0100649', (20, 32))	('autoantibodies', 'Var', (77, 91))	('damaging mucosal epithelia', 'Disease', 'MESH:D009059', (162, 188))	('PNP', 'Disease', (36, 39))	('Dsg3', 'Gene', '1830', (100, 104))	('damaging mucosal epithelia', 'Disease', (162, 188))
24998	25382196	According to the histological and immunohistochemical results, from WHO pathological classification perspective there were 11 (5.1%) patients of type A, 47 (21.8%) of type AB, 38 (17.6%) of type B1, 43 (19.9%) of type B2, 21 (9.7%) of type B3, and 56 (25.9%) of thymic carcinoma (Supplementary Table 2).	('thymic carcinoma', 'Disease', 'MESH:D013945', (262, 278))	('B2, 21', 'Gene', '28907;9267', (218, 224))	('B1, 43', 'Gene', '28905', (195, 201))	('carcinoma', 'Phenotype', 'HP:0030731', (269, 278))	('patients', 'Species', '9606', (133, 141))	('type AB', 'Var', (167, 174))	('thymic carcinoma', 'Disease', (262, 278))
25110	26543766	Hereditary HNPGLs are mostly caused by mutations of the SDHD gene, but SDHB and SDHC mutations are not uncommon in such patients.	('SDHD', 'Gene', (56, 60))	('SDHD', 'Gene', '6392', (56, 60))	('caused by', 'Reg', (29, 38))	('PGLs', 'Phenotype', 'HP:0002668', (13, 17))	('SDHB', 'Gene', '6390', (71, 75))	('mutations', 'Var', (39, 48))	('SDHB', 'Gene', (71, 75))	('SDHC', 'Gene', (80, 84))	('patients', 'Species', '9606', (120, 128))	('HNPGLs', 'Phenotype', 'HP:0002864', (11, 17))	('SDHC', 'Gene', '6391', (80, 84))	('Hereditary HNPGLs', 'Disease', (0, 17))
25111	26543766	Multiple head and neck paragangliomas are common in patients with SDHD mutations, while malignant head and neck paraganglioma is mostly seen in patients with SDHB mutations (Burnichon et al.	('SDHB', 'Gene', '6390', (158, 162))	('head and neck paraganglioma', 'Phenotype', 'HP:0002864', (98, 125))	('paragangliomas', 'Phenotype', 'HP:0002668', (23, 37))	('SDHD', 'Gene', (66, 70))	('paraganglioma', 'Phenotype', 'HP:0002668', (23, 36))	('head and neck paraganglioma', 'Phenotype', 'HP:0002864', (9, 36))	('mutations', 'Var', (71, 80))	('neck paragangliomas', 'Disease', (18, 37))	('SDHB', 'Gene', (158, 162))	('common', 'Reg', (42, 48))	('patients', 'Species', '9606', (52, 60))	('neck paraganglioma', 'Disease', 'MESH:D010235', (18, 36))	('neck paraganglioma', 'Disease', (107, 125))	('neck paraganglioma', 'Disease', 'MESH:D010235', (107, 125))	('head and neck paragangliomas', 'Phenotype', 'HP:0002864', (9, 37))	('neck paragangliomas', 'Disease', 'MESH:D010235', (18, 37))	('patients', 'Species', '9606', (144, 152))	('neck paragangliomas', 'Phenotype', 'HP:0002864', (18, 37))	('SDHD', 'Gene', '6392', (66, 70))	('paraganglioma', 'Phenotype', 'HP:0002668', (112, 125))
25174	26543766	Recurrent genetic alterations have so far been reported for thymomas as well as for thymic squamous cell carcinoma.	('genetic alterations', 'Var', (10, 29))	('thymoma', 'Phenotype', 'HP:0100522', (60, 67))	('squamous cell carcinoma', 'Phenotype', 'HP:0002860', (91, 114))	('carcinoma', 'Phenotype', 'HP:0030731', (105, 114))	('squamous cell carcinoma', 'Disease', (91, 114))	('thymomas', 'Disease', 'MESH:D013945', (60, 68))	('thymomas', 'Disease', (60, 68))	('squamous cell carcinoma', 'Disease', 'MESH:D002294', (91, 114))	('reported', 'Reg', (47, 55))
25175	26543766	Deletions of chromosome 6p are reported with type A thymoma and gains of chromosome 1q and losses of chromosomes 6 and 13q are reported with type B3 thymomas (Zettl et al.).	('thymoma', 'Phenotype', 'HP:0100522', (149, 156))	('thymoma', 'Phenotype', 'HP:0100522', (52, 59))	('type B3 thymomas', 'Disease', 'MESH:D013945', (141, 157))	('type A thymoma', 'Disease', (45, 59))	('losses', 'NegReg', (91, 97))	('type A thymoma', 'Disease', 'MESH:D013945', (45, 59))	('gains', 'PosReg', (64, 69))	('type B3 thymomas', 'Disease', (141, 157))	('Deletions', 'Var', (0, 9))
25179	26543766	Only 2 % of PGLs are found in the mediastinum and are associated with germ line mutations in either SDHB or SDHD.	('PGLs', 'Phenotype', 'HP:0002668', (12, 16))	('mutations', 'Var', (80, 89))	('SDHD', 'Gene', (108, 112))	('SDHB', 'Gene', '6390', (100, 104))	('SDHB', 'Gene', (100, 104))	('associated', 'Reg', (54, 64))	('SDHD', 'Gene', '6392', (108, 112))
25183	26543766	Mutations in the genes encoding succinate dehydrogenase (SDH) subunits B, C, and D cause extra-adrenal PGLs.	('SDH', 'Gene', (57, 60))	('extra-adrenal PGLs', 'Disease', (89, 107))	('Mutations', 'Var', (0, 9))	('cause', 'Reg', (83, 88))	('PGLs', 'Phenotype', 'HP:0002668', (103, 107))	('succinate dehydrogenase', 'Gene', '6390', (32, 55))	('SDH', 'Gene', '6390', (57, 60))	('succinate dehydrogenase', 'Gene', (32, 55))
25203	25000259	ASXL1 and DNMT3A mutation in a cytogenetically normal B3 thymoma The molecular drivers of thymoma are poorly understood.	('thymoma', 'Disease', 'MESH:D013945', (57, 64))	('thymoma', 'Disease', (57, 64))	('ASXL1', 'Gene', '171023', (0, 5))	('mutation', 'Var', (17, 25))	('thymoma', 'Phenotype', 'HP:0100522', (57, 64))	('thymoma', 'Disease', 'MESH:D013945', (90, 97))	('thymoma', 'Disease', (90, 97))	('ASXL1', 'Gene', (0, 5))	('DNMT3A', 'Gene', (10, 16))	('DNMT3A', 'Gene', '1788', (10, 16))	('thymoma', 'Phenotype', 'HP:0100522', (90, 97))
25204	25000259	Outside of the identification of rarely occurring epidermal growth factor receptor and v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog mutations via candidate gene sequencing, mutations in common cancer genes have yet to be observed.	('mutations', 'Var', (149, 158))	('epidermal growth factor receptor', 'Gene', '1956', (50, 82))	('cancer', 'Phenotype', 'HP:0002664', (210, 216))	('sarcoma', 'Phenotype', 'HP:0100242', (118, 125))	('sarcoma viral', 'Disease', 'MESH:D001102', (118, 131))	('cancer', 'Disease', 'MESH:D009369', (210, 216))	('epidermal growth factor receptor', 'Gene', (50, 82))	('sarcoma viral', 'Disease', (118, 131))	('cancer', 'Disease', (210, 216))
25206	25000259	Thus, we attempted to identify somatic driver mutations in a cytogenetically normal thymoma.	('thymoma', 'Disease', 'MESH:D013945', (84, 91))	('thymoma', 'Phenotype', 'HP:0100522', (84, 91))	('mutations', 'Var', (46, 55))	('thymoma', 'Disease', (84, 91))
25208	25000259	Mutations in known tumor suppressors DNMT3A (p.G728D) and ASXL1 (p.E657fs), consistent with mutations of known consequence in acute myeloid leukemia, were identified.	('acute myeloid leukemia', 'Phenotype', 'HP:0004808', (126, 148))	('DNMT3A', 'Gene', (37, 43))	('DNMT3A', 'Gene', '1788', (37, 43))	('p.G728D', 'Mutation', 'p.G728D', (45, 52))	('tumor', 'Disease', 'MESH:D009369', (19, 24))	('leukemia', 'Phenotype', 'HP:0001909', (140, 148))	('p.E657fs', 'Mutation', 'p.E657fsX', (65, 73))	('tumor', 'Phenotype', 'HP:0002664', (19, 24))	('ASXL1', 'Gene', '171023', (58, 63))	('acute myeloid leukemia', 'Disease', (126, 148))	('tumor', 'Disease', (19, 24))	('p.E657fs', 'Var', (65, 73))	('myeloid leukemia', 'Phenotype', 'HP:0012324', (132, 148))	('p.G728D', 'Var', (45, 52))	('ASXL1', 'Gene', (58, 63))	('acute myeloid leukemia', 'Disease', 'MESH:D015470', (126, 148))
25219	25000259	Amplifications and rare activating mutations of EGFR and overexpression of HER2, KIT, BCL2 and TP53, as well as loss of CDKN2A have been previously described.	('overexpression', 'PosReg', (57, 71))	('EGFR', 'Gene', '1956', (48, 52))	('activating', 'PosReg', (24, 34))	('CDKN2A', 'Gene', (120, 126))	('BCL2', 'Gene', '596', (86, 90))	('HER2', 'Gene', (75, 79))	('EGFR', 'Gene', (48, 52))	('KIT', 'Gene', (81, 84))	('CDKN2A', 'Gene', '1029', (120, 126))	('loss', 'NegReg', (112, 116))	('Amplifications', 'Var', (0, 14))	('HER2', 'Gene', '2064', (75, 79))	('BCL2', 'Gene', (86, 90))	('TP53', 'Gene', '7157', (95, 99))	('TP53', 'Gene', (95, 99))
25225	25000259	In this article, we report the identification of DNMT3A and ASXL1 mutations in a cytogenetically normal stage IVB type B3 thymoma.	('mutations', 'Var', (66, 75))	('ASXL1', 'Gene', '171023', (60, 65))	('thymoma', 'Disease', 'MESH:D013945', (122, 129))	('thymoma', 'Disease', (122, 129))	('ASXL1', 'Gene', (60, 65))	('thymoma', 'Phenotype', 'HP:0100522', (122, 129))	('DNMT3A', 'Gene', (49, 55))	('DNMT3A', 'Gene', '1788', (49, 55))
25226	25000259	This is the first identification of driver point mutations in B3 thymoma and suggests that further genomic profiling of cytogenetically normal B3 thymomas may reveal the specific molecular drivers of this tumor type.	('thymoma', 'Phenotype', 'HP:0100522', (146, 153))	('point mutations', 'Var', (43, 58))	('tumor', 'Disease', 'MESH:D009369', (205, 210))	('thymoma', 'Disease', 'MESH:D013945', (65, 72))	('thymomas', 'Disease', (146, 154))	('thymomas', 'Disease', 'MESH:D013945', (146, 154))	('thymoma', 'Disease', 'MESH:D013945', (146, 153))	('tumor', 'Phenotype', 'HP:0002664', (205, 210))	('tumor', 'Disease', (205, 210))	('thymoma', 'Disease', (65, 72))	('thymoma', 'Phenotype', 'HP:0100522', (65, 72))	('thymoma', 'Disease', (146, 153))
25242	25000259	Sixteen copy number gains, 1 copy number loss (Table 2) and 6 structural variants (Table 3) were also observed.	('copy number loss', 'Disease', (29, 45))	('copy number loss', 'Disease', 'MESH:D016388', (29, 45))	('copy number', 'Var', (8, 19))	('gains', 'PosReg', (20, 25))
25246	25000259	Fourteen nonsynonymous, 1 nonsense and 2 frameshift somatic mutations were observed in the tumor (Table 1).	('tumor', 'Disease', 'MESH:D009369', (91, 96))	('nonsynonymous', 'Var', (9, 22))	('tumor', 'Phenotype', 'HP:0002664', (91, 96))	('nonsense', 'Var', (26, 34))	('frameshift somatic mutations', 'Var', (41, 69))	('tumor', 'Disease', (91, 96))
25247	25000259	Of these mutations, four stood out with clear functional relevance:frameshift mutations in FAM193A and ASXL1, a nonsense mutation in GRM5, and a nonsynonymous mutation in DNMT3A.	('ASXL1', 'Gene', (103, 108))	('GRM5', 'Gene', (133, 137))	('DNMT3A', 'Gene', (171, 177))	('DNMT3A', 'Gene', '1788', (171, 177))	('FAM193A', 'Gene', (91, 98))	('frameshift mutations', 'Var', (67, 87))	('FAM193A', 'Gene', '8603', (91, 98))	('ASXL1', 'Gene', '171023', (103, 108))	('GRM5', 'Gene', '2915', (133, 137))
25248	25000259	Although the mutations in FAM193A and GRM5 clearly impact protein function, the relevance of these mutations to tumorigenesis is not immediately apparent.	('GRM5', 'Gene', '2915', (38, 42))	('tumor', 'Disease', 'MESH:D009369', (112, 117))	('GRM5', 'Gene', (38, 42))	('tumor', 'Phenotype', 'HP:0002664', (112, 117))	('FAM193A', 'Gene', (26, 33))	('FAM193A', 'Gene', '8603', (26, 33))	('protein function', 'MPA', (58, 74))	('tumor', 'Disease', (112, 117))	('mutations', 'Var', (13, 22))	('impact', 'Reg', (51, 57))
25249	25000259	On the other hand, the somatic mutations in DNMT3A and ASXL1 are of the type previously observed in other tumor types and expected to contribute to tumorigenesis.	('mutations', 'Var', (31, 40))	('tumor', 'Phenotype', 'HP:0002664', (148, 153))	('DNMT3A', 'Gene', (44, 50))	('ASXL1', 'Gene', (55, 60))	('DNMT3A', 'Gene', '1788', (44, 50))	('tumor', 'Disease', (148, 153))	('contribute', 'Reg', (134, 144))	('tumor', 'Disease', 'MESH:D009369', (106, 111))	('tumor', 'Phenotype', 'HP:0002664', (106, 111))	('ASXL1', 'Gene', '171023', (55, 60))	('tumor', 'Disease', 'MESH:D009369', (148, 153))	('tumor', 'Disease', (106, 111))
25252	25000259	The nonsynonymous mutation observed in this thymoma sample leads to a nonconservative substitution of aspartate for glycine at amino-acid 728 (p.G728D) within the DNA methylase domain of DNMT3A.	('DNMT3A', 'Gene', (187, 193))	('p.G728D', 'Mutation', 'p.G728D', (143, 150))	('thymoma', 'Disease', (44, 51))	('DNMT3A', 'Gene', '1788', (187, 193))	('glycine', 'Chemical', 'MESH:D005998', (116, 123))	('leads to', 'Reg', (59, 67))	('thymoma', 'Phenotype', 'HP:0100522', (44, 51))	('aspartate', 'Chemical', 'MESH:D001224', (102, 111))	('p.G728D', 'Var', (143, 150))	('thymoma', 'Disease', 'MESH:D013945', (44, 51))
25253	25000259	This region is known to be responsible for the hydrophobic interaction between DNMT3A and its regulatory subunit DNMT3L, an interaction that is required for activation of DNMT3A methyltransferase activity and previously shown to be disrupted by mutations in this region.	('DNMT3L', 'Gene', (113, 119))	('DNMT3L', 'Gene', '29947', (113, 119))	('mutations', 'Var', (245, 254))	('DNMT3A', 'Gene', (171, 177))	('DNMT3A', 'Gene', '1788', (171, 177))	('hydrophobic interaction', 'MPA', (47, 70))	('responsible', 'Reg', (27, 38))	('DNMT3A', 'Gene', (79, 85))	('DNMT3A', 'Gene', '1788', (79, 85))	('activity', 'MPA', (196, 204))
25255	25000259	Strikingly and unusually, this somatic mutation was observed in homozygous state in the tumor: 61 of 62 (98.4%) exome sequencing reads from the tumor supported the mutation, 0 of 41 (0%) of exome sequencing reads from the normal sample supported the mutation, the homozygous state was confirmed via Sanger sequencing (Figure 2, inset), and no evidence for loss of heterozygosity was observed in the exome or low-pass whole-genome sequencing data.	('tumor', 'Disease', (144, 149))	('tumor', 'Disease', 'MESH:D009369', (88, 93))	('mutation', 'Var', (164, 172))	('tumor', 'Phenotype', 'HP:0002664', (88, 93))	('tumor', 'Disease', 'MESH:D009369', (144, 149))	('tumor', 'Phenotype', 'HP:0002664', (144, 149))	('tumor', 'Disease', (88, 93))
25257	25000259	Finally, a previously sequenced AML, reported by Hou et al., carried a mutation at this position (p.G728R) and at a nearby position (p.F731L), supporting the notion that homozygous or compound heterozygous mutations at the DNMT3A:DNMT3L interface are required to effectively disrupt methyltransferase activity.	('p.F731L', 'Var', (133, 140))	('AML', 'Disease', 'MESH:D015470', (32, 35))	('disrupt', 'NegReg', (275, 282))	('p.G728R', 'Mutation', 'p.G728R', (98, 105))	('DNMT3L', 'Gene', (230, 236))	('p.F731L', 'Mutation', 'rs143019657', (133, 140))	('methyltransferase', 'Enzyme', (283, 300))	('AML', 'Phenotype', 'HP:0004808', (32, 35))	('AML', 'Disease', (32, 35))	('DNMT3L', 'Gene', '29947', (230, 236))	('DNMT3A', 'Gene', (223, 229))	('DNMT3A', 'Gene', '1788', (223, 229))	('p.G728R', 'Var', (98, 105))	('activity', 'MPA', (301, 309))
25258	25000259	Thus, the type, location and unusual zygosity of this somatic mutation strongly suggest mutations in DNMT3A have a causal role in the etiology of thymoma.	('causal role', 'Reg', (115, 126))	('thymoma', 'Phenotype', 'HP:0100522', (146, 153))	('DNMT3A', 'Gene', (101, 107))	('DNMT3A', 'Gene', '1788', (101, 107))	('mutations', 'Var', (88, 97))	('thymoma', 'Disease', 'MESH:D013945', (146, 153))	('thymoma', 'Disease', (146, 153))
25261	25000259	The heterozygous deletion of a single guanine nucleotide within exon 12 of ASXL1 leads to out-of-frame translation beginning at codon 657 and premature truncation of the protein, removing >50% of the protein including the PHD domain responsible from histone interactions.	('removing', 'NegReg', (179, 187))	('ASXL1', 'Gene', '171023', (75, 80))	('ASXL1', 'Gene', (75, 80))	('guanine nucleotide', 'Chemical', 'MESH:D006150', (38, 56))	('out-of-frame translation', 'MPA', (90, 114))	('protein', 'Protein', (200, 207))	('deletion', 'Var', (17, 25))	('truncation', 'MPA', (152, 162))
25262	25000259	Similar heterozygous C-terminal truncations are sufficient to induce myelodysplastic syndrome.	('myelodysplastic syndrome', 'Phenotype', 'HP:0002863', (69, 93))	('induce', 'Reg', (62, 68))	('C-terminal', 'Var', (21, 31))	('myelodysplastic syndrome', 'Disease', (69, 93))	('myelodysplastic syndrome', 'Disease', 'MESH:D009190', (69, 93))
25263	25000259	Previously observed frameshift or nonsense mutations in ASXL1 across numerous tumor types catalogued in The Cancer Genome Atlas (TCGA) have been observed both upstream and downstream of amino-acid 657, with the highest concentration centered at position 657 (Figure 3).	('ASXL1', 'Gene', (56, 61))	('numerous tumor', 'Disease', 'MESH:D009369', (69, 83))	('tumor', 'Phenotype', 'HP:0002664', (78, 83))	('amino-acid', 'Var', (186, 196))	('numerous tumor', 'Disease', (69, 83))	('frameshift', 'Var', (20, 30))	('Cancer Genome Atlas', 'Disease', 'MESH:D009369', (108, 127))	('Cancer Genome Atlas', 'Disease', (108, 127))	('ASXL1', 'Gene', '171023', (56, 61))	('nonsense mutations', 'Var', (34, 52))	('Cancer', 'Phenotype', 'HP:0002664', (108, 114))
25264	25000259	In fact, the majority of previously observed ASXL1 mutations occur in the same exon as this mutation, exon 12.	('ASXL1', 'Gene', '171023', (45, 50))	('ASXL1', 'Gene', (45, 50))	('mutations', 'Var', (51, 60))
25265	25000259	Thus, both the type and location of this somatic mutation strongly suggests mutations in ASXL1 have a causal role in the etiology of thymomas.	('mutations', 'Var', (76, 85))	('thymoma', 'Phenotype', 'HP:0100522', (133, 140))	('ASXL1', 'Gene', '171023', (89, 94))	('ASXL1', 'Gene', (89, 94))	('thymomas', 'Disease', (133, 141))	('thymomas', 'Disease', 'MESH:D013945', (133, 141))
25266	25000259	A number of focal copy number gains were observed in this tumor, the most interesting being an amplification of the HOXA cluster (see Discussion section).	('tumor', 'Phenotype', 'HP:0002664', (58, 63))	('tumor', 'Disease', (58, 63))	('HOXA', 'Gene', (116, 120))	('HOXA', 'Gene', '3197', (116, 120))	('tumor', 'Disease', 'MESH:D009369', (58, 63))	('gains', 'PosReg', (30, 35))	('copy number', 'Var', (18, 29))
25268	25000259	Our results show that mutations in DNMT3A and ASXL1 have a role in the development of thymoma.	('ASXL1', 'Gene', (46, 51))	('DNMT3A', 'Gene', '1788', (35, 41))	('thymoma', 'Disease', 'MESH:D013945', (86, 93))	('thymoma', 'Disease', (86, 93))	('mutations', 'Var', (22, 31))	('ASXL1', 'Gene', '171023', (46, 51))	('thymoma', 'Phenotype', 'HP:0100522', (86, 93))	('DNMT3A', 'Gene', (35, 41))	('role', 'Reg', (59, 63))
25271	25000259	These results are reminiscent of the preferential occurrence of driver point mutations in cytogenetically normal AML and suggests further sequencing of cytogenetically normal thymomas are fertile ground for the identification of the molecular drivers of thymic cancer.	('thymic cancer', 'Disease', 'MESH:D013953', (254, 267))	('AML', 'Disease', 'MESH:D015470', (113, 116))	('cancer', 'Phenotype', 'HP:0002664', (261, 267))	('AML', 'Phenotype', 'HP:0004808', (113, 116))	('AML', 'Disease', (113, 116))	('thymomas', 'Disease', (175, 183))	('thymoma', 'Phenotype', 'HP:0100522', (175, 182))	('thymic cancer', 'Disease', (254, 267))	('thymomas', 'Disease', 'MESH:D013945', (175, 183))	('point mutations', 'Var', (71, 86))
25277	25000259	The most common DNMT3A mutations in AML occur at p.R882.	('AML', 'Disease', 'MESH:D015470', (36, 39))	('DNMT3A', 'Gene', '1788', (16, 22))	('DNMT3A', 'Gene', (16, 22))	('AML', 'Disease', (36, 39))	('AML', 'Phenotype', 'HP:0004808', (36, 39))	('mutations', 'Var', (23, 32))	('p.R882', 'Var', (49, 55))
25278	25000259	Mutations at this position disrupt binding at the DNMT3A:DNMT3A interface, and impact activity in dominant-negative manner, or at least reduce the odds of proper tetramer assembly by ~75% as a single mutated DNMT3A protein is sufficient to disrupt tetramer assembly.	('DNMT3A', 'Gene', (50, 56))	('DNMT3A', 'Gene', '1788', (208, 214))	('DNMT3A', 'Gene', '1788', (50, 56))	('DNMT3A', 'Gene', (57, 63))	('DNMT3A', 'Gene', '1788', (57, 63))	('binding', 'Interaction', (35, 42))	('tetramer assembly', 'MPA', (248, 265))	('activity', 'MPA', (86, 94))	('reduce', 'NegReg', (136, 142))	('Mutations', 'Var', (0, 9))	('impact', 'Reg', (79, 85))	('disrupt', 'Reg', (27, 34))	('proper tetramer assembly', 'MPA', (155, 179))	('DNMT3A', 'Gene', (208, 214))
25279	25000259	Alternatively, the DNMT3L:DNMT3A interface is disrupted by somatic mutations within the mutational hotspot region centered on the p.G728D mutation observed in this thymoma.	('disrupted', 'NegReg', (46, 55))	('thymoma', 'Disease', 'MESH:D013945', (164, 171))	('DNMT3A', 'Gene', (26, 32))	('DNMT3L', 'Gene', '29947', (19, 25))	('DNMT3A', 'Gene', '1788', (26, 32))	('p.G728D', 'Var', (130, 137))	('thymoma', 'Disease', (164, 171))	('thymoma', 'Phenotype', 'HP:0100522', (164, 171))	('p.G728D', 'Mutation', 'p.G728D', (130, 137))	('DNMT3L', 'Gene', (19, 25))
25280	25000259	Heterozygous mutations at this site may not be expected to influence activity as markedly as mutations at p.R882 as they likely allow for the formation of partially complete complexes, for example, DNMT3A:DNMT3A:DNMT3L complexes could form 50% of the time.	('DNMT3A', 'Gene', (198, 204))	('DNMT3L', 'Gene', (212, 218))	('mutations', 'Var', (93, 102))	('activity', 'MPA', (69, 77))	('DNMT3A', 'Gene', (205, 211))	('DNMT3A', 'Gene', '1788', (198, 204))	('DNMT3A', 'Gene', '1788', (205, 211))	('influence', 'Reg', (59, 68))	('DNMT3L', 'Gene', '29947', (212, 218))	('allow', 'Reg', (128, 133))
25281	25000259	Thus, it is notable that the p.G728D mutation was observed in homozygous state in this tumor.	('tumor', 'Phenotype', 'HP:0002664', (87, 92))	('p.G728D', 'Var', (29, 36))	('tumor', 'Disease', (87, 92))	('p.G728D', 'Mutation', 'p.G728D', (29, 36))	('tumor', 'Disease', 'MESH:D009369', (87, 92))
25282	25000259	The second confidently identified driver mutation was a frameshift mutation in exon 12 of ASXL1.	('frameshift mutation in', 'Var', (56, 78))	('ASXL1', 'Gene', '171023', (90, 95))	('ASXL1', 'Gene', (90, 95))
25283	25000259	ASXL1 is a known tumor suppressor in hematological malignancies, where the majority of frameshift and nonsense mutations are also observed in exon 12.	('frameshift', 'Var', (87, 97))	('tumor', 'Disease', (17, 22))	('hematological malignancies', 'Disease', 'MESH:D019337', (37, 63))	('ASXL1', 'Gene', '171023', (0, 5))	('hematological malignancies', 'Phenotype', 'HP:0004377', (37, 63))	('nonsense mutations', 'Var', (102, 120))	('ASXL1', 'Gene', (0, 5))	('tumor', 'Disease', 'MESH:D009369', (17, 22))	('hematological malignancies', 'Disease', (37, 63))	('tumor', 'Phenotype', 'HP:0002664', (17, 22))
25289	25000259	Although co-occurrence of DNMT3A and ASXL1 mutations are quite rare in epithelial and hematological malignancies, sequencing of a larger number of thymomas will be required to determine whether this co-occurrence is a happenstance of our subject selection or whether it points to a specific requirement of marked epigenetic reprogramming in the neoplastic transformation of thymic cells.	('hematological malignancies', 'Phenotype', 'HP:0004377', (86, 112))	('DNMT3A', 'Gene', (26, 32))	('neoplastic transformation of thymic cells', 'Phenotype', 'HP:0100521', (345, 386))	('thymomas', 'Disease', 'MESH:D013945', (147, 155))	('DNMT3A', 'Gene', '1788', (26, 32))	('ASXL1', 'Gene', '171023', (37, 42))	('ASXL1', 'Gene', (37, 42))	('thymoma', 'Phenotype', 'HP:0100522', (147, 154))	('mutations', 'Var', (43, 52))	('hematological malignancies', 'Disease', (86, 112))	('hematological malignancies', 'Disease', 'MESH:D019337', (86, 112))	('thymomas', 'Disease', (147, 155))
25290	25000259	The extent of DNMT3A and ASXL1 mutations in thymoma should be explored, and treatments targeting epigenetic reprogramming should be considered in the future.	('ASXL1', 'Gene', (25, 30))	('mutations', 'Var', (31, 40))	('thymoma', 'Disease', (44, 51))	('thymoma', 'Disease', 'MESH:D013945', (44, 51))	('thymoma', 'Phenotype', 'HP:0100522', (44, 51))	('ASXL1', 'Gene', '171023', (25, 30))	('DNMT3A', 'Gene', (14, 20))	('DNMT3A', 'Gene', '1788', (14, 20))
25298	25000259	Nonsynonymous, in-frame, frameshift, nonsense or canonical splice-site donor/acceptor site variants were retained for further analysis.	('donor', 'Species', '9606', (71, 76))	('frameshift', 'Var', (25, 35))	('nonsense', 'Var', (37, 45))
25301	25000259	Significant windows (P-value threshold=1E-8) were stringently filtered to retain called copy number variations only where the ratio of tumor to normal reads, adjusted for the difference in total number of reads, was at least 1.5X greater for copy number gains or 0.5X lower for copy number losses.	('tumor', 'Phenotype', 'HP:0002664', (135, 140))	('tumor', 'Disease', (135, 140))	('lower', 'NegReg', (268, 273))	('copy number loss', 'Disease', (278, 294))	('gains', 'PosReg', (254, 259))	('copy number loss', 'Disease', 'MESH:D016388', (278, 294))	('copy number', 'Var', (242, 253))	('tumor', 'Disease', 'MESH:D009369', (135, 140))
25302	25000259	For structural variants, an initial set of raw candidate structural variants was called using SVDetect with at least seven reads supporting structural variant calls in the tumor sample and three reads supporting calls in the normal sample.	('tumor', 'Phenotype', 'HP:0002664', (172, 177))	('calls', 'Reg', (159, 164))	('structural variant', 'Var', (140, 158))	('tumor', 'Disease', (172, 177))	('tumor', 'Disease', 'MESH:D009369', (172, 177))
25314	17986328	Congenital myasthenic syndromes stem from genetic mutations that result in abnormal neuromuscular transmission.	('mutations', 'Var', (50, 59))	('Congenital myasthenic syndromes', 'Disease', (0, 31))	('Congenital myasthenic syndromes', 'Disease', 'MESH:D020294', (0, 31))	('abnormal neuromuscular transmission', 'Phenotype', 'HP:0003398', (75, 110))
25364	17986328	In most cases, antibodies bind to the main immunogenic region of the alpha-subunit of the AChR, though MG patients with antibodies to MuSK exhibit clinical weakness and electrophysiologic findings that are quite similar to MG patients with AChR antibodies.	('antibodies', 'Var', (120, 130))	('antibodies to MuSK', 'Phenotype', 'HP:0030210', (120, 138))	('MuSK', 'Gene', '4593', (134, 138))	('weakness', 'Disease', (156, 164))	('MuSK', 'Gene', (134, 138))	('AChR', 'Gene', (90, 94))	('bind', 'Interaction', (26, 30))	('patients', 'Species', '9606', (226, 234))	('patients', 'Species', '9606', (106, 114))	('weakness', 'Disease', 'MESH:D018908', (156, 164))
25376	17986328	Edrophonium chloride temporarily improves the safety factor of neuromuscular transmission and may elicit improved strength in patients with abnormal neuromuscular transmission.	('Edrophonium', 'Var', (0, 11))	('improves', 'PosReg', (33, 41))	('elicit', 'Reg', (98, 104))	('patients', 'Species', '9606', (126, 134))	('strength', 'MPA', (114, 122))	('Edrophonium chloride', 'Chemical', 'MESH:D004491', (0, 20))	('improved', 'PosReg', (105, 113))	('abnormal neuromuscular transmission', 'Phenotype', 'HP:0003398', (140, 175))	('safety factor of neuromuscular transmission', 'MPA', (46, 89))
25411	17986328	AChR blocking antibodies compete for the acetylcholine binding site or allosterically inhibit binding of radiolabelled alpha-bungarotoxin to the AChR.	('AChR', 'Gene', (0, 4))	('binding', 'Interaction', (94, 101))	('acetylcholine binding site', 'MPA', (41, 67))	('inhibit', 'NegReg', (86, 93))	('antibodies', 'Var', (14, 24))	('acetylcholine', 'Chemical', 'MESH:D000109', (41, 54))
25412	17986328	Approximately 4% of patients with negative AChR binding antibodies have an elevated AChR modulating antibody assay, and approximately 1% of patients with negative AChR binding antibodies demonstrate increased AChR blocking antibodies.	('elevated', 'PosReg', (75, 83))	('antibodies', 'Var', (56, 66))	('patients', 'Species', '9606', (20, 28))	('patients', 'Species', '9606', (140, 148))	('AChR modulating antibody assay', 'MPA', (84, 114))	('AChR', 'Gene', (43, 47))
25419	17986328	Antibodies to MuSK have been demonstrated recently in about one third of patients with generalized SN MG.	('SN MG', 'Disease', 'MESH:D000080343', (99, 104))	('Antibodies', 'Var', (0, 10))	('MuSK', 'Gene', (14, 18))	('MuSK', 'Gene', '4593', (14, 18))	('SN MG', 'Disease', (99, 104))	('patients', 'Species', '9606', (73, 81))	('Antibodies to MuSK', 'Phenotype', 'HP:0030210', (0, 18))
25424	17986328	Patients with ryanodine antibodies may exhibit severe, treatment-resistant MG associated with malignant thymomas.	('ryanodine antibodies', 'Var', (14, 34))	('malignant thymomas', 'Disease', 'MESH:D013945', (94, 112))	('ryanodine', 'Chemical', 'MESH:D012433', (14, 23))	('Patients', 'Species', '9606', (0, 8))	('men', 'Species', '9606', (60, 63))	('malignant thymomas', 'Phenotype', 'HP:0100697', (94, 112))	('malignant thymomas', 'Disease', (94, 112))	('thymoma', 'Phenotype', 'HP:0100522', (104, 111))
25466	17986328	Occasional patients are unable to tolerate an alternating-day regimen due to mood instability, variation in MG, or difficult glycemic control in occasional diabetic patients.	('diabetic', 'Disease', (156, 164))	('men', 'Species', '9606', (66, 69))	('variation', 'Var', (95, 104))	('patients', 'Species', '9606', (165, 173))	('diabetic', 'Disease', 'MESH:D003920', (156, 164))	('patients', 'Species', '9606', (11, 19))
25513	17986328	The most common cyclosporine interactions and potential complications include non-steroidal anti-inflammatory agents with impaired renal function, angiotensin converting enzyme inhibitors eliciting hyperkalemia, and HMG CoA reductase inhibitors precipitating cholesterol-lowering agent myopathy.	('HMG CoA reductase', 'Gene', (216, 233))	('cholesterol', 'Chemical', 'MESH:D002784', (259, 270))	('eliciting', 'Reg', (188, 197))	('steroid', 'Chemical', 'MESH:D013256', (82, 89))	('impaired renal function', 'Disease', 'MESH:D007674', (122, 145))	('myopathy', 'Disease', 'MESH:D009135', (286, 294))	('HMG CoA reductase', 'Gene', '3156', (216, 233))	('hyperkalemia', 'Disease', (198, 210))	('cyclosporine', 'Chemical', 'MESH:D016572', (16, 28))	('impaired renal function', 'Disease', (122, 145))	('myopathy', 'Phenotype', 'HP:0003198', (286, 294))	('myopathy', 'Disease', (286, 294))	('precipitating', 'Reg', (245, 258))	('hyperkalemia', 'Disease', 'MESH:D006947', (198, 210))	('interactions', 'Var', (29, 41))	('hyperkalemia', 'Phenotype', 'HP:0002153', (198, 210))
25541	17986328	High infusion rates may be associated with thrombosis and stroke.	('High', 'Var', (0, 4))	('stroke', 'Phenotype', 'HP:0001297', (58, 64))	('associated', 'Reg', (27, 37))	('stroke', 'Disease', (58, 64))	('thrombosis', 'Disease', (43, 53))	('stroke', 'Disease', 'MESH:D020521', (58, 64))	('thrombosis', 'Disease', 'MESH:D013927', (43, 53))
25617	31409307	Based on the results of mass spectrometry, COL17A1 was only up-regulated in type AB, but not in type B2/B3, and had the greatest fold-change (~920X).	('up-regulated', 'PosReg', (60, 72))	('COL17A1', 'Gene', '1308', (43, 50))	('COL17A1', 'Gene', (43, 50))	('type AB', 'Var', (76, 83))
25619	31409307	The amount and the percentage of thymoma containing COL17A1 was significantly (P < 0.01) higher in type AB as compared to type B2/B3 (Fig.	('COL17A1', 'Gene', (52, 59))	('thymoma', 'Phenotype', 'HP:0100522', (33, 40))	('type AB', 'Var', (99, 106))	('higher', 'PosReg', (89, 95))	('thymoma', 'Gene', '7063', (33, 40))	('COL17A1', 'Gene', '1308', (52, 59))	('thymoma', 'Gene', (33, 40))
25692	26962777	Now, extended transsternal thymectomy (ETT) is believed as the standard surgical technique, and several retrospective studies have shown that ETT contributed to the amelioration of myasthenic symptoms and may inhibit the progression of OMG to GMG.	('ETT', 'Var', (142, 145))	('MG', 'Disease', 'MESH:D000080343', (237, 239))	('inhibit', 'NegReg', (209, 216))	('myasthenic symptoms', 'Disease', (181, 200))	('myasthenic symptoms', 'Phenotype', 'HP:0003473', (181, 200))	('myasthenic symptoms', 'Disease', 'MESH:D051271', (181, 200))	('MG', 'Disease', 'MESH:D000080343', (244, 246))	('amelioration', 'PosReg', (165, 177))
25716	26962777	A comparison of groups that did and did not experience POA indicated that the only statistically significant differences were that patients with POA were more likely to have a thymoma (P < 0.001) and an ectopic thymus (P = 0.005).	('patients', 'Species', '9606', (131, 139))	('ectopic thymus', 'Phenotype', 'HP:0010517', (203, 217))	('thymoma', 'Disease', 'MESH:D013945', (176, 183))	('thymoma', 'Disease', (176, 183))	('POA', 'Var', (145, 148))	('thymoma', 'Phenotype', 'HP:0100522', (176, 183))
25753	25860215	All patients showed a predominance of CD3+ T cells over CD20+ B cells, and CD4+ Th cells over CD8+ cytotoxic T cells.	('CD4', 'Gene', (75, 78))	('CD3+', 'Var', (38, 42))	('CD8', 'Gene', (94, 97))	('CD20', 'Gene', (56, 60))	('CD20', 'Gene', '54474', (56, 60))	('CD8', 'Gene', '925', (94, 97))	('patients', 'Species', '9606', (4, 12))	('CD4', 'Gene', '920', (75, 78))
25763	25860215	Good syndrome (GS) is characterized as thymoma complicated with hypogammaglobulinemia and involves various immunodeficient conditions including depleted B cells, reduced T cells, and inversion of the CD4/CD8 ratio.	('reduced', 'NegReg', (162, 169))	('Good syndrome', 'Disease', (0, 13))	('hypogammaglobulinemia', 'Disease', 'MESH:D000361', (64, 85))	('inversion', 'Var', (183, 192))	('CD8', 'Gene', '925', (204, 207))	('hypogammaglobulinemia', 'Phenotype', 'HP:0004313', (64, 85))	('GS', 'Disease', 'MESH:D011125', (15, 17))	('immunodeficient', 'Disease', 'MESH:D007153', (107, 122))	('immunodeficient', 'Disease', (107, 122))	('CD4', 'Gene', '920', (200, 203))	('reduced T cells', 'Phenotype', 'HP:0005403', (162, 177))	('T cells', 'CPA', (170, 177))	('thymoma', 'Phenotype', 'HP:0100522', (39, 46))	('Good syndrome', 'Disease', 'MESH:D013577', (0, 13))	('CD4', 'Gene', (200, 203))	('thymoma', 'Gene', '7063', (39, 46))	('hypogammaglobulinemia', 'Disease', (64, 85))	('thymoma', 'Gene', (39, 46))	('CD8', 'Gene', (204, 207))
25787	25860215	The mouse monoclonal antibodies used to analyze lymphocyte subsets were anti-CD3, anti-CD20, anti-CD4 and anti-CD8 (Leu4, Leu12, Leu3a + 3b, and Leu2a, respectively; BD Bioscience, San Jose, CA).	('mouse', 'Species', '10090', (4, 9))	('Leu4', 'Var', (116, 120))	('CD4', 'Gene', '920', (98, 101))	('Leu2a', 'Var', (145, 150))	('Leu3a + 3b', 'Var', (129, 139))	('CD20', 'Gene', '54474', (87, 91))	('CD20', 'Gene', (87, 91))	('Leu12', 'Var', (122, 127))	('CD4', 'Gene', (98, 101))	('CD8', 'Gene', (111, 114))	('CD8', 'Gene', '925', (111, 114))
25795	25860215	The GS patient showed diffuse infiltration of CD3+ T cells in the lamina propria, whereas CD20+ B cells were rarely seen.	('CD3+ T', 'Var', (46, 52))	('patient', 'Species', '9606', (7, 14))	('CD20', 'Gene', '54474', (90, 94))	('CD20', 'Gene', (90, 94))	('GS', 'Disease', 'MESH:D011125', (4, 6))
25803	25860215	GS presents with thymoma complicated with hypogammaglobulinemia, few or absent B cells, abnormal CD4/CD8 ratio, CD4 T cell lymphopenia, and impaired T cell mitogenic response as first described by Good et al.	('impaired T', 'Disease', (140, 150))	('T cell lymphopenia', 'Disease', (116, 134))	('T cell lymphopenia', 'Disease', 'MESH:D008231', (116, 134))	('hypogammaglobulinemia', 'Disease', 'MESH:D000361', (42, 63))	('thymoma', 'Phenotype', 'HP:0100522', (17, 24))	('hypogammaglobulinemia', 'Phenotype', 'HP:0004313', (42, 63))	('GS', 'Disease', 'MESH:D011125', (0, 2))	('thymoma', 'Gene', '7063', (17, 24))	('lymphopenia', 'Phenotype', 'HP:0001888', (123, 134))	('thymoma', 'Gene', (17, 24))	('CD8', 'Gene', '925', (101, 104))	('absent B cells', 'Phenotype', 'HP:0005365', (72, 86))	('CD4 T cell lymphopenia', 'Phenotype', 'HP:0005407', (112, 134))	('CD4', 'Gene', '920', (97, 100))	('hypogammaglobulinemia', 'Disease', (42, 63))	('CD4', 'Gene', '920', (112, 115))	('CD4', 'Gene', (97, 100))	('impaired T', 'Disease', 'MESH:D009422', (140, 150))	('abnormal', 'Var', (88, 96))	('CD4', 'Gene', (112, 115))	('CD8', 'Gene', (101, 104))
25811	25860215	In this study, CD3+ and CD4+ T cells were mainly distributed throughout both the connective tissue papillae and the lamina propria from both GS and OLP patients.	('CD3+', 'Var', (15, 19))	('CD4', 'Gene', (24, 27))	('CD4', 'Gene', '920', (24, 27))	('patients', 'Species', '9606', (152, 160))	('GS', 'Disease', 'MESH:D011125', (141, 143))
25822	15974803	The Ews-ERG Fusion Protein Can Initiate Neoplasia from Lineage-Committed Haematopoietic Cells The EWS-ERG fusion protein is found in human sarcomas with the chromosomal translocation t(21;22)(q22;q12), where the translocation is considered to be an initiating event in sarcoma formation within uncommitted mesenchymal cells, probably long-lived progenitors capable of self renewal.	('ERG', 'Gene', (102, 105))	('sarcoma', 'Disease', (269, 276))	('Ews', 'Gene', (4, 7))	('sarcoma', 'Phenotype', 'HP:0100242', (269, 276))	('Neoplasia', 'Disease', 'MESH:D009369', (40, 49))	('human', 'Species', '9606', (133, 138))	('ERG', 'Gene', '13876', (8, 11))	('sarcoma', 'Disease', 'MESH:D012509', (139, 146))	('sarcomas', 'Disease', 'MESH:D012509', (139, 147))	('sarcomas', 'Phenotype', 'HP:0100242', (139, 147))	('ERG', 'Gene', (8, 11))	('sarcoma', 'Disease', (139, 146))	('sarcomas', 'Disease', (139, 147))	('t(21;22)(q22;q12', 'Var', (183, 199))	('t(21;22)(q22;q12)', 'STRUCTURAL_ABNORMALITY', 'None', (183, 200))	('Neoplasia', 'Phenotype', 'HP:0002664', (40, 49))	('Neoplasia', 'Disease', (40, 49))	('ERG', 'Gene', '13876', (102, 105))	('Ews', 'Gene', '14030', (4, 7))	('sarcoma', 'Phenotype', 'HP:0100242', (139, 146))	('sarcoma', 'Disease', 'MESH:D012509', (269, 276))
25826	15974803	This conditional Ews gene fusion model of tumourigenesis shows that Ews-ERG can cause haematopoietic tumours and the precursor cells are committed cells.	('tumour', 'Phenotype', 'HP:0002664', (42, 48))	('tumour', 'Disease', (101, 107))	('tumour', 'Disease', 'MESH:D009369', (42, 48))	('haematopoietic tumours', 'Disease', (86, 108))	('tumour', 'Disease', (42, 48))	('Ews-ERG', 'Var', (68, 75))	('tumours', 'Phenotype', 'HP:0002664', (101, 108))	('haematopoietic tumours', 'Disease', 'MESH:D009369', (86, 108))	('cause', 'Reg', (80, 85))	('tumour', 'Phenotype', 'HP:0002664', (101, 107))	('tumour', 'Disease', 'MESH:D009369', (101, 107))
25827	15974803	Using a mouse model, these authors study the potential of a known cancer-related gene to cause tumors in cells committed to different lineages.	('tumors', 'Disease', 'MESH:D009369', (95, 101))	('gene', 'Var', (81, 85))	('cause', 'Reg', (89, 94))	('cancer', 'Phenotype', 'HP:0002664', (66, 72))	('tumors', 'Phenotype', 'HP:0002664', (95, 101))	('mouse', 'Species', '10090', (8, 13))	('cancer', 'Disease', 'MESH:D009369', (66, 72))	('tumors', 'Disease', (95, 101))	('cancer', 'Disease', (66, 72))
25828	15974803	Chromosomal translocations are characteristic of many human cancers, and are especially well studied in leukaemias, lymphomas, and sarcomas.	('lymphomas', 'Phenotype', 'HP:0002665', (116, 125))	('cancers', 'Phenotype', 'HP:0002664', (60, 67))	('cancers', 'Disease', (60, 67))	('lymphoma', 'Phenotype', 'HP:0002665', (116, 124))	('Chromosomal translocations', 'Var', (0, 26))	('cancers', 'Disease', 'MESH:D009369', (60, 67))	('sarcomas', 'Disease', 'MESH:D012509', (131, 139))	('leukaemias', 'Disease', (104, 114))	('sarcomas', 'Phenotype', 'HP:0100242', (131, 139))	('lymphomas', 'Disease', (116, 125))	('sarcoma', 'Phenotype', 'HP:0100242', (131, 138))	('sarcomas', 'Disease', (131, 139))	('leukaemias', 'Disease', 'MESH:D007938', (104, 114))	('lymphomas', 'Disease', 'MESH:D008223', (116, 125))	('cancer', 'Phenotype', 'HP:0002664', (60, 66))	('human', 'Species', '9606', (54, 59))
25830	15974803	The main outcomes of the reciprocal translocations are either forced oncogene expression, as found in lymphoid malignancies, or gene fusion, found in both leukaemias and sarcomas.	('expression', 'MPA', (78, 88))	('sarcomas', 'Phenotype', 'HP:0100242', (170, 178))	('leukaemias and sarcomas', 'Disease', 'MESH:D007938', (155, 178))	('gene fusion', 'Var', (128, 139))	('lymphoid malignancies', 'Disease', 'MESH:D008223', (102, 123))	('lymphoid malignancies', 'Disease', (102, 123))	('sarcoma', 'Phenotype', 'HP:0100242', (170, 177))	('lymphoid malignancies', 'Phenotype', 'HP:0002665', (102, 123))	('oncogene', 'Protein', (69, 77))	('forced', 'PosReg', (62, 68))
25839	15974803	Finally, the EWS gene can also be involved with the CHOP gene by chromosomal translocation in malignant myxoid liposarcoma, analogous to FUS-CHOP.	('CHOP', 'Gene', (52, 56))	('liposarcoma', 'Phenotype', 'HP:0012034', (111, 122))	('malignant myxoid liposarcoma', 'Disease', (94, 122))	('chromosomal translocation', 'Var', (65, 90))	('sarcoma', 'Phenotype', 'HP:0100242', (115, 122))	('CHOP', 'Gene', '13198', (52, 56))	('malignant myxoid liposarcoma', 'Disease', 'MESH:D018208', (94, 122))	('CHOP', 'Gene', '13198', (141, 145))	('EWS', 'Gene', (13, 16))	('myxoid liposarcoma', 'Phenotype', 'HP:0012268', (104, 122))	('CHOP', 'Gene', (141, 145))
25840	15974803	The chromosomal translocations in Ewing's and other sarcomas are considered as primary initiating events.	('sarcomas', 'Disease', 'MESH:D012509', (52, 60))	('sarcomas', 'Phenotype', 'HP:0100242', (52, 60))	('sarcoma', 'Phenotype', 'HP:0100242', (52, 59))	("Ewing's", 'Disease', 'MESH:C563168', (34, 41))	('sarcomas', 'Disease', (52, 60))	('Ewing', 'Disease', (34, 39))	('chromosomal translocations', 'Var', (4, 30))
25842	15974803	The fusion protein may therefore be instructive by imparting a phenotype on the cell by affecting a specific differentiation programme, which must be part of the genetic make-up of the cancer stem cell, since the chromosomal translocation is an initiating and persistent feature.	('affecting', 'Reg', (88, 97))	('cancer', 'Phenotype', 'HP:0002664', (185, 191))	('fusion', 'Var', (4, 10))	('cancer', 'Disease', 'MESH:D009369', (185, 191))	('cancer', 'Disease', (185, 191))
25843	15974803	The pre-existing chromosomal translocation creates a cellular environment allowing secondary mutations to arise in progeny cells, resulting in overt cancer.	('cancer', 'Disease', (149, 155))	('chromosomal translocation', 'Var', (17, 42))	('resulting in', 'Reg', (130, 142))	('mutations', 'Var', (93, 102))	('overt', 'Disease', (143, 148))	('cancer', 'Phenotype', 'HP:0002664', (149, 155))	('cancer', 'Disease', 'MESH:D009369', (149, 155))
25845	15974803	We have analysed whether EWS fusions function only in the domain of mesenchymal progenitors and whether they function in other cell lineages, specifically within committed cells, as has been demonstrated for MLL fusions.	('MLL', 'Gene', (208, 211))	('fusions', 'Var', (29, 36))	('MLL', 'Gene', '214162', (208, 211))	('EWS', 'Gene', (25, 28))
25847	15974803	These methods were either the knock-in model, which involved fusing the MLL gene partner AF9 into the mouse Mll gene, resulting in acute myeloid leukaemias in mice, or the translocator model to give de novo chromosomal translocations, resulting in cell-specific leukaemias.	('leukaemias', 'Disease', (262, 272))	('MLL', 'Gene', '214162', (72, 75))	('AF9', 'Gene', (89, 92))	('mice', 'Species', '10090', (159, 163))	('acute myeloid leukaemias', 'Phenotype', 'HP:0004808', (131, 155))	('myeloid leukaemias', 'Phenotype', 'HP:0012324', (137, 155))	('leukaemias', 'Disease', (145, 155))	('leukaemias', 'Disease', 'MESH:D007938', (262, 272))	('Mll', 'Gene', '214162', (108, 111))	('MLL', 'Gene', (72, 75))	('acute myeloid leukaemias', 'Disease', 'MESH:D007938', (131, 155))	('fusing', 'Var', (61, 67))	('acute myeloid leukaemias', 'Disease', (131, 155))	('mouse', 'Species', '10090', (102, 107))	('leukaemias', 'Disease', 'MESH:D007938', (145, 155))	('Mll', 'Gene', (108, 111))
25850	15974803	We have sought to determine whether an Ews-ERG fusion can be oncogenic in a cell type not generally associated with human tumours (specifically in lymphoid cells) and also to determine whether Ews-ERG fusion can initiate leukaemia from committed cells.	('fusion', 'Var', (47, 53))	('tumours', 'Phenotype', 'HP:0002664', (122, 129))	('leukaemia', 'Disease', (221, 230))	('Ews-ERG', 'Gene', (39, 46))	('tumours', 'Disease', 'MESH:D009369', (122, 129))	('tumours', 'Disease', (122, 129))	('leukaemia', 'Disease', 'MESH:D007938', (221, 230))	('tumour', 'Phenotype', 'HP:0002664', (122, 128))	('human', 'Species', '9606', (116, 121))
25852	15974803	Our results show that Ews-ERG can function as an oncogene in committed cells of mice and suggest that EWS-ERG is able to contribute to neoplasia in a variety of cellular contexts in vivo.	('neoplasia', 'Disease', (135, 144))	('neoplasia', 'Phenotype', 'HP:0002664', (135, 144))	('contribute', 'Reg', (121, 131))	('neoplasia', 'Disease', 'MESH:D009369', (135, 144))	('mice', 'Species', '10090', (80, 84))	('EWS-ERG', 'Var', (102, 109))
25861	15974803	We investigated the ability of Ews-ERG fusion protein to contribute to leukaemogenesis by causing the inversion of the ERG-containing cassette in lymphoid cells using Rag1-Cre knock-in mice.	('Rag1', 'Gene', (167, 171))	('inversion', 'Var', (102, 111))	('contribute', 'Reg', (57, 67))	('causing', 'Reg', (90, 97))	('mice', 'Species', '10090', (185, 189))	('ERG-containing cassette', 'Gene', (119, 142))	('leukaemogenesis', 'Disease', (71, 86))	('Rag1', 'Gene', '19373', (167, 171))
25872	15974803	The Rag1-Cre knock-in allele was previously shown to be specific for lymphoid cells using a reporter assay dependent on Cre-mediated deletion of a loxP-flanked (floxed) segment of the Lmo2 gene.	('Rag1', 'Gene', (4, 8))	('deletion', 'Var', (133, 141))	('Rag1', 'Gene', '19373', (4, 8))	('Lmo2', 'Gene', (184, 188))	('Lmo2', 'Gene', '16909', (184, 188))
25873	15974803	We have sustained these observations using an additional reporter assay, namely the ROSA-loxSTOP-lacZ (ROSA26-R) allele where beta-galactosidase (betagal) expression is activated by deletion of a loxP-pA site.	('activated', 'PosReg', (169, 178))	('loxP-pA', 'Chemical', '-', (196, 203))	('ROSA-loxSTOP-lacZ', 'Chemical', '-', (84, 101))	('expression', 'MPA', (155, 165))	('beta-galactosidase', 'Gene', (126, 144))	('betagal', 'Gene', (146, 153))	('deletion', 'Var', (182, 190))	('beta-galactosidase', 'Gene', '12091', (126, 144))	('ROSA26', 'Gene', '14910', (103, 109))	('ROSA26', 'Gene', (103, 109))
25886	15974803	The situation with the thymomas of invertor mice varied from mainly CD4+CD8+ DP cells (e.g., M2 in Figure 5) to mainly CD8+ single positive (SP) cells (e.g., M3 in Figure 5) to mainly double negative cells (e.g., M4 in Figure 5).	('CD4', 'Gene', '12504', (68, 71))	('SP', 'Chemical', '-', (141, 143))	('thymoma', 'Phenotype', 'HP:0100522', (23, 30))	('CD8+', 'Var', (119, 123))	('DP', 'Chemical', '-', (77, 79))	('CD4', 'Gene', (68, 71))	('thymomas', 'Disease', (23, 31))	('mice', 'Species', '10090', (44, 48))	('thymomas', 'Disease', 'MESH:D013945', (23, 31))
25888	15974803	While we found either CD8+ SP or CD4+CD8+ DP thymomas, none showed a CD4+ SP phenotype.	('CD8+ SP', 'Var', (22, 29))	('CD4', 'Gene', (69, 72))	('thymomas', 'Disease', (45, 53))	('DP', 'Chemical', '-', (42, 44))	('thymomas', 'Disease', 'MESH:D013945', (45, 53))	('SP', 'Chemical', '-', (27, 29))	('thymoma', 'Phenotype', 'HP:0100522', (45, 52))	('CD4', 'Gene', '12504', (69, 72))	('CD8+ SP', 'Chemical', '-', (22, 29))	('CD4', 'Gene', (33, 36))	('SP', 'Chemical', '-', (74, 76))	('CD4', 'Gene', '12504', (33, 36))
25891	15974803	The probe detects a 5-kb band in non-lymphoid DNA corresponding to the intact Tcrb gene; if V-D-J or D-J joins have occurred, new restriction fragments are created, giving rise to "rearranged" bands on the hybridisation autoradiograph.	('Tcrb', 'Gene', '21577', (78, 82))	('Tcrb', 'Gene', (78, 82))	('V-D-J', 'Var', (92, 97))	('D-J joins', 'Var', (101, 110))
25896	15974803	Confirmation that the Tcrb rearrangements observed by hybridisations were due to productive V-D-J joins was made by sequence analysis of the Tcrb genes in four of the cases.	('Tcrb', 'Gene', (141, 145))	('Tcrb', 'Gene', '21577', (141, 145))	('rearrangements', 'Var', (27, 41))	('Tcrb', 'Gene', (22, 26))	('Tcrb', 'Gene', '21577', (22, 26))
25902	15974803	Our results show that lymphomas arise when Ews-ERG is aberrantly expressed in the committed cells of the lymphoid lineage.	('arise', 'Reg', (32, 37))	('lymphoma', 'Phenotype', 'HP:0002665', (22, 30))	('aberrantly', 'Var', (54, 64))	('lymphomas', 'Disease', (22, 31))	('lymphomas', 'Disease', 'MESH:D008223', (22, 31))	('Ews-ERG', 'Gene', (43, 50))	('lymphomas', 'Phenotype', 'HP:0002665', (22, 31))
25918	15974803	Leukaemogenesis in Ews-ERG invertor mice thus concurs with the hypothesis that EWS fusions can cause neoplasia arising in various cell types.	('EWS', 'Gene', (79, 82))	('neoplasia', 'Disease', (101, 110))	('Leukaemogenesis', 'Disease', (0, 15))	('cause', 'Reg', (95, 100))	('neoplasia', 'Disease', 'MESH:D009369', (101, 110))	('neoplasia', 'Phenotype', 'HP:0002664', (101, 110))	('mice', 'Species', '10090', (36, 40))	('fusions', 'Var', (83, 90))
26065	29850538	Currently, immunotherapy based on the blockage of programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) is satisfactory in a variety of aggressive tumor species.	('programmed death 1', 'Gene', (50, 68))	('aggressive tumor', 'Disease', 'MESH:D001523', (142, 158))	('tumor', 'Phenotype', 'HP:0002664', (153, 158))	('aggressive tumor', 'Disease', (142, 158))	('PD-1', 'Gene', (70, 74))	('programmed death 1', 'Gene', '5133', (50, 68))	('PD-1', 'Gene', '5133', (70, 74))	('blockage', 'Var', (38, 46))
26102	29850538	Considering that the biological behaviors of type B3 thymoma were similar to that of thymic carcinoma, it was classified as thymus carcinoma for analysis.	('type B3', 'Var', (45, 52))	('carcinoma', 'Phenotype', 'HP:0030731', (131, 140))	('thymoma', 'Phenotype', 'HP:0100522', (53, 60))	('carcinoma', 'Phenotype', 'HP:0030731', (92, 101))	('thymic carcinoma', 'Disease', (85, 101))	('thymus carcinoma', 'Disease', (124, 140))	('thymic carcinoma', 'Disease', 'MESH:D013945', (85, 101))	('thymus carcinoma', 'Disease', 'MESH:D013953', (124, 140))	('thymoma', 'Disease', 'MESH:D013945', (53, 60))	('thymoma', 'Disease', (53, 60))
26122	29850538	The high expression of PD-L1 in thymoma can be an independent risk factor for tumor recurrence and predict a poor overall survival.	('PD-L1', 'Gene', (23, 28))	('thymoma', 'Phenotype', 'HP:0100522', (32, 39))	('tumor', 'Disease', 'MESH:D009369', (78, 83))	('tumor', 'Phenotype', 'HP:0002664', (78, 83))	('high', 'Var', (4, 8))	('tumor', 'Disease', (78, 83))	('thymoma', 'Disease', 'MESH:D013945', (32, 39))	('thymoma', 'Disease', (32, 39))
26138	29850538	Overall, the current findings indicated that the expressions of PD-L1 protein and mRNA differed in thymoma and thymic carcinomas, and PD-L1 may serve as a potential marker of invasiveness and prognosis.	('thymoma', 'Disease', 'MESH:D013945', (99, 106))	('thymic carcinomas', 'Disease', (111, 128))	('protein', 'Protein', (70, 77))	('thymoma', 'Disease', (99, 106))	('carcinoma', 'Phenotype', 'HP:0030731', (118, 127))	('expressions', 'MPA', (49, 60))	('mRNA', 'MPA', (82, 86))	('PD-L1', 'Gene', (64, 69))	('thymic carcinomas', 'Disease', 'MESH:D013945', (111, 128))	('differed', 'Reg', (87, 95))	('PD-L1', 'Var', (134, 139))	('thymoma', 'Phenotype', 'HP:0100522', (99, 106))	('carcinomas', 'Phenotype', 'HP:0030731', (118, 128))
26165	28101136	The lymphoid population showed intense positivity for CD3, CD5, CD8, and CD99 (Figures 4A to 4D) and weak positivity for CD4 and CD43.	('CD8', 'Gene', (64, 67))	('CD99', 'Gene', '4267', (73, 77))	('CD43', 'Gene', '6693', (129, 133))	('CD5', 'Gene', (59, 62))	('CD4', 'Gene', (121, 124))	('CD43', 'Gene', (129, 133))	('CD8', 'Gene', '925', (64, 67))	('CD5', 'Gene', '921', (59, 62))	('CD4', 'Gene', '920', (121, 124))	('CD99', 'Gene', (73, 77))	('CD3', 'Var', (54, 57))	('CD4', 'Gene', (129, 132))	('CD4', 'Gene', '920', (129, 132))
26166	28101136	The cytokeratin cocktail showed positivity in the tumour's epithelial component (Figures 4E and 4F).	('positivity', 'Var', (32, 42))	("tumour's epithelial component", 'Disease', (50, 79))	('tumour', 'Phenotype', 'HP:0002664', (50, 56))	("tumour's epithelial component", 'Disease', 'MESH:D000077216', (50, 79))
26267	31195997	Autoimmune encephalitis (AE), which is characterized by the subacute (days to weeks) development of seizures, recent memory loss, mental confusion and psychiatric symptoms due to antibodies against neuronal cell surface and synaptic proteins, is newly recognized autoimmune disorders involved in synaptic transmission and neuronal excitability.	('memory loss', 'Disease', (117, 128))	('psychiatric symptoms', 'Phenotype', 'HP:0000708', (151, 171))	('memory loss', 'Disease', 'MESH:D008569', (117, 128))	('memory loss', 'Phenotype', 'HP:0002354', (117, 128))	('autoimmune disorders', 'Phenotype', 'HP:0002960', (263, 283))	('mental confusion', 'Disease', (130, 146))	('confusion', 'Phenotype', 'HP:0001289', (137, 146))	('autoimmune disorders', 'Disease', 'MESH:D001327', (263, 283))	('psychiatric', 'Disease', 'MESH:D001523', (151, 162))	('mental confusion', 'Disease', 'MESH:D003221', (130, 146))	('due', 'Reg', (172, 175))	('Autoimmune encephalitis', 'Disease', (0, 23))	('seizures', 'Disease', (100, 108))	('Autoimmune encephalitis', 'Disease', 'MESH:C535841', (0, 23))	('psychiatric', 'Disease', (151, 162))	('seizures', 'Disease', 'MESH:D012640', (100, 108))	('antibodies', 'Var', (179, 189))	('seizures', 'Phenotype', 'HP:0001250', (100, 108))	('encephalitis', 'Phenotype', 'HP:0002383', (11, 23))	('autoimmune disorders', 'Disease', (263, 283))
26276	31195997	Histological examination showed WHO type B2: Kpan(+++), CK19(+++), CD30(+++), CD20(-), CD3(-), CD5(+), TdT(+), and Ki67(+, 90%).	('CK19', 'Gene', (56, 60))	('CD20(-', 'Var', (78, 84))	('TdT', 'Gene', (103, 106))	('CD30(+++', 'Var', (67, 75))	('CK19', 'Gene', '3880', (56, 60))	('CD5', 'Gene', (95, 98))	('CD3(-', 'Var', (87, 92))	('TdT', 'Gene', '1791', (103, 106))	('CD5', 'Gene', '921', (95, 98))
26329	29221139	'Dangerous' autoantigen presentation in the context of autoimmune regulator (AIRE) deficiency, abnormal T cell selection, and failure in regulatory T cell (Treg) generation are postulated intra-tumorous mechanisms, not mutually exclusive, driving the autoimmune response in thymoma-associated MG.	('intra-tumorous', 'Disease', (188, 202))	('abnormal T', 'Disease', (95, 105))	('rat', 'Species', '10116', (166, 169))	('thymoma', 'Disease', (274, 281))	('autoimmune response', 'Phenotype', 'HP:0002960', (251, 270))	('thymoma', 'Disease', 'MESH:D013945', (274, 281))	('abnormal T cell', 'Phenotype', 'HP:0002843', (95, 110))	('tumor', 'Phenotype', 'HP:0002664', (194, 199))	("'Dangerous'", 'PosReg', (0, 11))	('thymoma', 'Phenotype', 'HP:0100522', (274, 281))	('autoimmune regulator', 'Gene', '326', (55, 75))	('intra-tumorous', 'Disease', 'MESH:D009369', (188, 202))	('abnormal T', 'Disease', 'MESH:D000014', (95, 105))	('deficiency', 'Var', (83, 93))	('autoimmune regulator', 'Gene', (55, 75))
26386	29221139	CK/LMP1 double positive TECs were never detected in MG and non-MG thymomas (Figure 5), whereas CK/LMP2A double positive cells were only occasionally found in MG-associated thymomas (Figure 5A), whereas rare CK/LMP2A double positive TECs were found in one of the three non-MG thymomas, found positive for EBV DNA and EBER1 [MG (-) T14] (Table 2) (Figure 5B).	('LMP2A', 'Gene', (98, 103))	('thymomas', 'Disease', 'MESH:D013945', (275, 283))	('thymoma', 'Phenotype', 'HP:0100522', (66, 73))	('non-MG thymomas', 'Disease', 'MESH:D013945', (268, 283))	('LMP2A', 'Gene', (210, 215))	('TEC', 'Gene', '7006', (24, 27))	('TEC', 'Gene', (232, 235))	('thymomas', 'Disease', (275, 283))	('LMP2A', 'Gene', '17494231', (98, 103))	('thymomas', 'Disease', 'MESH:D013945', (172, 180))	('non-MG thymomas', 'Disease', 'MESH:D013945', (59, 74))	('non-MG thymomas', 'Disease', (268, 283))	('LMP2A', 'Gene', '17494231', (210, 215))	('thymomas', 'Disease', (172, 180))	('non-MG thymomas', 'Disease', (59, 74))	('TEC', 'Gene', (24, 27))	('EBV', 'Species', '10376', (304, 307))	('thymomas', 'Disease', 'MESH:D013945', (66, 74))	('EBER1 [MG (-) T14]', 'Var', (316, 334))	('TEC', 'Gene', '7006', (232, 235))	('thymomas', 'Disease', (66, 74))	('thymoma', 'Phenotype', 'HP:0100522', (275, 282))	('thymoma', 'Phenotype', 'HP:0100522', (172, 179))
26412	29221139	Since the 80's several studies attempted to identify EBV nucleic acids in MG and non-MG thymomas producing contrasting results, likely because of the different approaches employed and the use of virus detection techniques that would not be considered sufficiently sensitive today.	('EBV', 'Gene', (53, 56))	('nucleic acids', 'Var', (57, 70))	('non-MG thymomas', 'Disease', 'MESH:D013945', (81, 96))	('EBV', 'Species', '10376', (53, 56))	('thymoma', 'Phenotype', 'HP:0100522', (88, 95))	('non-MG thymomas', 'Disease', (81, 96))
26428	29221139	This sample was from a MG patient [MG (+) T24, Table 1] positive for anti-AChR, -titin and -ryanodine receptor antibodies, having concomitant stiff-person syndrome associated with glutamic acid decarboxylase (GAD) antibodies, and transient myositis.	('anti-AChR', 'Protein', (69, 78))	('titin', 'Gene', (81, 86))	('patient', 'Species', '9606', (26, 33))	('GAD', 'Gene', '2571', (209, 212))	('stiff-person syndrome', 'Disease', (142, 163))	('person', 'Species', '9606', (148, 154))	('glutamic acid decarboxylase', 'Gene', '2571', (180, 207))	('myositis', 'Disease', 'MESH:D009220', (240, 248))	('myositis', 'Disease', (240, 248))	('glutamic acid decarboxylase', 'Gene', (180, 207))	('titin', 'Gene', '7273', (81, 86))	('positive', 'Reg', (56, 64))	('GAD', 'Gene', (209, 212))	('transient', 'Disease', (230, 239))	('antibodies', 'Var', (111, 121))	('myositis', 'Phenotype', 'HP:0100614', (240, 248))
26444	29221139	EBV dysregulation of the host B cell system can lead to abnormal B cell survival and breakdown of B cell tolerance through mechanisms that involve: a) LMP1 and LMP2A expression, which are able to mimic activated CD40 and B cell receptor signaling; b) induction of the anti-apoptotic protein Bcl-2, known to be overexpressed in MG-associated thymomas; c) synthesis of the B cell growth factor BAFF, known to be increased in serum and thymus of MG patients; and d) hypersensitivity to TLR stimulation.	('thymoma', 'Phenotype', 'HP:0100522', (341, 348))	('LMP2A', 'Gene', (160, 165))	('hypersensitivity', 'Disease', 'MESH:D004342', (463, 479))	('dysregulation', 'Var', (4, 17))	('LMP2A', 'Gene', '17494231', (160, 165))	('BAFF', 'Gene', '10673', (392, 396))	('thymomas', 'Disease', (341, 349))	('synthesis', 'MPA', (354, 363))	('thymomas', 'Disease', 'MESH:D013945', (341, 349))	('BAFF', 'Gene', (392, 396))	('abnormal B cell', 'Phenotype', 'HP:0002846', (56, 71))	('overexpressed', 'PosReg', (310, 323))	('patients', 'Species', '9606', (446, 454))	('Bcl-2', 'Gene', (291, 296))	('hypersensitivity', 'Disease', (463, 479))	('EBV', 'Species', '10376', (0, 3))
26470	29221139	Briefly, amplification was performed in a total volume of 25 mul containing 0.5 mug of DNA, 1X Taqman Universal PCR Master Mix (Thermo Fisher Scientific), 0.18 muM forward and reverse Pol primers, 0.1 muM FAM-labeled Pol probe, 0.09 muM forward and reverse beta2m primers, and 0.08 muM VIC-labeled beta2m probe.	('0.18', 'Var', (155, 159))	('beta2m', 'Gene', '567', (298, 304))	('beta2m', 'Gene', (298, 304))	('beta2m', 'Gene', '567', (257, 263))	('Mix', 'Gene', (123, 126))	('beta2m', 'Gene', (257, 263))	('Mix', 'Gene', '83881', (123, 126))
26477	29221139	For EBNA2 and gp350/220, real-time PCR reactions were performed in duplicate in a final volume of 20 mul containing 1X SYBR Green mix (Thermo Fisher Scientific) and 1 muM of each primer, whose sequence was as previously described.	('mix', 'Gene', '83881', (130, 133))	('EBNA2', 'Gene', (4, 9))	('EBNA2', 'Gene', '17494192', (4, 9))	('mix', 'Gene', (130, 133))	('SYBR Green', 'Chemical', '-', (119, 129))	('gp350/220', 'Var', (14, 23))
26493	29221139	Secondary antibodies were: Cy2-conjugated goat anti-mouse IgG, Cy3-conjugated goat anti-rabbit IgG and Cy3-conjugated goat anti-rat IgG (Jackson Immunoresearch Laboratories).	('Cy3-conjugated', 'Var', (63, 77))	('goat', 'Species', '9925', (118, 122))	('Cy2-conjugated', 'Var', (27, 41))	('goat', 'Species', '9925', (78, 82))	('mouse', 'Species', '10090', (52, 57))	('rabbit', 'Species', '9986', (88, 94))	('Cy3', 'Chemical', '-', (103, 106))	('goat', 'Species', '9925', (42, 46))	('rat', 'Species', '10116', (164, 167))	('Cy2', 'Chemical', '-', (27, 30))	('Cy3', 'Chemical', '-', (63, 66))	('rat', 'Species', '10116', (128, 131))	('Cy3-conjugated', 'Var', (103, 117))
26549	28514756	Conversely, median FFR was significantly worse in patients who received adjuvant therapy (128.5 months; 95% CI 40.7-216.3 months) compared to median FFR of 160.7 months (95% CI 30.6-290.8 months) in patients who did not receive adjuvant therapy (p = 0.001).	('FFR', 'MPA', (19, 22))	('patients', 'Species', '9606', (50, 58))	('worse', 'NegReg', (41, 46))	('adjuvant', 'Var', (72, 80))	('patients', 'Species', '9606', (199, 207))
26629	27789964	Three gene mutations were identified, including two with PIK3CA mutation and one with EGFR mutation.	('PIK3CA', 'Gene', '5290', (57, 63))	('mutation', 'Var', (64, 72))	('EGFR', 'Gene', '1956', (86, 90))	('EGFR', 'Gene', (86, 90))	('PIK3CA', 'Gene', (57, 63))
26630	27789964	The three patients with mutant genes included two cases of thymoma (one with EGFR and the other with PIK3CA mutation) in addition to a case of thymic carcinoma (PIK3CA mutation).	('PIK3CA', 'Gene', '5290', (101, 107))	('thymoma', 'Disease', 'MESH:D013945', (59, 66))	('PIK3CA', 'Gene', (161, 167))	('carcinoma', 'Phenotype', 'HP:0030731', (150, 159))	('thymic carcinoma', 'Disease', (143, 159))	('PIK3CA', 'Gene', '5290', (161, 167))	('thymoma', 'Disease', (59, 66))	('mutant genes', 'Var', (24, 36))	('thymic carcinoma', 'Disease', 'MESH:D013945', (143, 159))	('EGFR', 'Gene', '1956', (77, 81))	('patients', 'Species', '9606', (10, 18))	('thymoma', 'Phenotype', 'HP:0100522', (59, 66))	('EGFR', 'Gene', (77, 81))	('PIK3CA', 'Gene', (101, 107))
26633	27789964	PIK3CA and EGFR mutations represent candidate driver genes and treatment targets in TET.	('EGFR', 'Gene', '1956', (11, 15))	('EGFR', 'Gene', (11, 15))	('mutations', 'Var', (16, 25))	('PIK3CA', 'Gene', (0, 6))	('PIK3CA', 'Gene', '5290', (0, 6))
26639	27789964	In the present study, we identified mutations associated with tumorigenesis using next-generation sequencing (NGS) of 22 hotspot genes in a series of 52 TET patients.	('tumor', 'Phenotype', 'HP:0002664', (62, 67))	('tumor', 'Disease', (62, 67))	('mutations', 'Var', (36, 45))	('patients', 'Species', '9606', (157, 165))	('associated', 'Reg', (46, 56))	('tumor', 'Disease', 'MESH:D009369', (62, 67))
26653	27789964	Histologically, there were five patients with type A thymoma (9.6%) (Figure 1A), eight with type AB (15.4%) (Figure 1B), six with type B1 (11.5%) (Figure 1C), nine with type B2 (17.3%) (Figure 1D), nine with type B3 thymoma (17.3%) (Figure 1E), and 15 with thymic carcinoma (28.8%) (Figure 1F).	('patients', 'Species', '9606', (32, 40))	('thymoma', 'Disease', 'MESH:D013945', (53, 60))	('thymoma', 'Phenotype', 'HP:0100522', (53, 60))	('thymoma', 'Disease', 'MESH:D013945', (216, 223))	('thymoma', 'Disease', (216, 223))	('type AB', 'Var', (92, 99))	('thymoma', 'Phenotype', 'HP:0100522', (216, 223))	('thymic carcinoma', 'Disease', (257, 273))	('type A thymoma', 'Disease', (46, 60))	('thymic carcinoma', 'Disease', 'MESH:D013945', (257, 273))	('carcinoma', 'Phenotype', 'HP:0030731', (264, 273))	('type A thymoma', 'Disease', 'MESH:D013945', (46, 60))	('thymoma', 'Disease', (53, 60))
26658	27789964	One patient carried an EGFR mutation (E746_750de), and two cases harbored PIK3CA mutation (both E545Q) (Table 2).	('E746_750de', 'Var', (38, 48))	('PIK3CA', 'Gene', '5290', (74, 80))	('E545Q', 'Var', (96, 101))	('patient', 'Species', '9606', (4, 11))	('EGFR', 'Gene', '1956', (23, 27))	('E545Q', 'Mutation', 'rs104886003', (96, 101))	('EGFR', 'Gene', (23, 27))	('PIK3CA', 'Gene', (74, 80))
26670	27789964	Two cases of PIK3CA mutation and one with EGFR mutation were identified.	('EGFR', 'Gene', '1956', (42, 46))	('PIK3CA', 'Gene', (13, 19))	('EGFR', 'Gene', (42, 46))	('mutation', 'Var', (20, 28))	('PIK3CA', 'Gene', '5290', (13, 19))
26674	27789964	From a histological point of view, some gene variations commonly seen in epithelial origin tumors may be found in TET.	('tumors', 'Disease', 'MESH:D009369', (91, 97))	('tumors', 'Disease', (91, 97))	('tumors', 'Phenotype', 'HP:0002664', (91, 97))	('variations', 'Var', (45, 55))	('tumor', 'Phenotype', 'HP:0002664', (91, 96))
26676	27789964	The frequency of PIK3CA mutations is ~2%-5% in other solid carcinomas.	('carcinomas', 'Phenotype', 'HP:0030731', (59, 69))	('PIK3CA', 'Gene', (17, 23))	('PIK3CA', 'Gene', '5290', (17, 23))	('solid carcinomas', 'Disease', 'MESH:D018250', (53, 69))	('carcinoma', 'Phenotype', 'HP:0030731', (59, 68))	('mutations', 'Var', (24, 33))	('solid carcinomas', 'Disease', (53, 69))
26677	27789964	Data pertaining to PIK3CA mutations in thymoma and thymic carcinoma have not been widely reported.	('PIK3CA', 'Gene', (19, 25))	('PIK3CA', 'Gene', '5290', (19, 25))	('thymoma', 'Phenotype', 'HP:0100522', (39, 46))	('thymoma and thymic carcinoma', 'Disease', 'MESH:D013945', (39, 67))	('mutations', 'Var', (26, 35))	('carcinoma', 'Phenotype', 'HP:0030731', (58, 67))
26678	27789964	Until now, only one study by Wheler et al reported a PIK3CA mutation in one of the 12 TET patients.	('mutation', 'Var', (60, 68))	('patients', 'Species', '9606', (90, 98))	('PIK3CA', 'Gene', (53, 59))	('PIK3CA', 'Gene', '5290', (53, 59))
26679	27789964	In the present cohort, two PIK3CA mutations were detected in thymoma with a frequency of 3.8%.	('thymoma', 'Disease', 'MESH:D013945', (61, 68))	('detected', 'Reg', (49, 57))	('thymoma', 'Disease', (61, 68))	('PIK3CA', 'Gene', (27, 33))	('thymoma', 'Phenotype', 'HP:0100522', (61, 68))	('PIK3CA', 'Gene', '5290', (27, 33))	('mutations', 'Var', (34, 43))
26680	27789964	Epidermal growth factor receptor (EGFR) mutations have been identified as driver genes in non-small-cell lung cancer (NSCLC) at a frequency of 40%-50% in the East Asian population.	('lung cancer', 'Phenotype', 'HP:0100526', (105, 116))	('NSCLC', 'Phenotype', 'HP:0030358', (118, 123))	('EGFR', 'Gene', (34, 38))	('Epidermal growth factor receptor', 'Gene', (0, 32))	('cancer', 'Phenotype', 'HP:0002664', (110, 116))	('lung cancer', 'Disease', 'MESH:D008175', (105, 116))	('mutations', 'Var', (40, 49))	('NSCLC', 'Disease', (118, 123))	('non-small-cell lung cancer', 'Phenotype', 'HP:0030358', (90, 116))	('small-cell lung cancer', 'Phenotype', 'HP:0030357', (94, 116))	('Epidermal growth factor receptor', 'Gene', '1956', (0, 32))	('NSCLC', 'Disease', 'MESH:D002289', (118, 123))	('EGFR', 'Gene', '1956', (34, 38))	('lung cancer', 'Disease', (105, 116))
26681	27789964	The EGFR mutations in TET have been identified in previous studies.	('EGFR', 'Gene', (4, 8))	('mutations', 'Var', (9, 18))	('TET', 'Gene', (22, 25))	('EGFR', 'Gene', '1956', (4, 8))
26682	27789964	No representative clinical characteristics associated with EGFR mutations were found, although most patients were diagnosed with thymoma but not thymic carcinoma.	('thymic carcinoma', 'Disease', (145, 161))	('thymoma', 'Disease', 'MESH:D013945', (129, 136))	('carcinoma', 'Phenotype', 'HP:0030731', (152, 161))	('EGFR', 'Gene', (59, 63))	('thymoma', 'Disease', (129, 136))	('thymic carcinoma', 'Disease', 'MESH:D013945', (145, 161))	('thymoma', 'Phenotype', 'HP:0100522', (129, 136))	('patients', 'Species', '9606', (100, 108))	('mutations', 'Var', (64, 73))	('EGFR', 'Gene', '1956', (59, 63))	('diagnosed', 'Reg', (114, 123))
26683	27789964	In the current study, our patient who carried the EGFR mutation represented type B3.	('EGFR', 'Gene', (50, 54))	('EGFR', 'Gene', '1956', (50, 54))	('patient', 'Species', '9606', (26, 33))	('mutation', 'Var', (55, 63))
26689	27789964	EGFR-tyrosine kinase inhibitors (TKIs) displayed adequate efficacy in NSCLC patients who carried EGFR mutations.	('patients', 'Species', '9606', (76, 84))	('EGFR', 'Gene', (0, 4))	('EGFR', 'Gene', '1956', (97, 101))	('NSCLC', 'Disease', (70, 75))	('NSCLC', 'Disease', 'MESH:D002289', (70, 75))	('EGFR', 'Gene', (97, 101))	('mutations', 'Var', (102, 111))	('EGFR', 'Gene', '1956', (0, 4))	('NSCLC', 'Phenotype', 'HP:0030358', (70, 75))
26691	27789964	However, no association was found between EGFR mutations and gefitinib efficacy.	('gefitinib', 'Chemical', 'MESH:D000077156', (61, 70))	('EGFR', 'Gene', '1956', (42, 46))	('EGFR', 'Gene', (42, 46))	('mutations', 'Var', (47, 56))
26692	27789964	The role of EGFR mutations in carcinomas may be different in thymoma compared with NSCLC.	('thymoma', 'Disease', 'MESH:D013945', (61, 68))	('NSCLC', 'Disease', (83, 88))	('thymoma', 'Disease', (61, 68))	('NSCLC', 'Disease', 'MESH:D002289', (83, 88))	('EGFR', 'Gene', '1956', (12, 16))	('thymoma', 'Phenotype', 'HP:0100522', (61, 68))	('carcinomas', 'Disease', (30, 40))	('NSCLC', 'Phenotype', 'HP:0030358', (83, 88))	('carcinoma', 'Phenotype', 'HP:0030731', (30, 39))	('carcinomas', 'Phenotype', 'HP:0030731', (30, 40))	('EGFR', 'Gene', (12, 16))	('carcinomas', 'Disease', 'MESH:D002277', (30, 40))	('mutations', 'Var', (17, 26))
26693	27789964	In our cohort, only one patient with thymoma carried the EGFR mutation.	('thymoma', 'Disease', 'MESH:D013945', (37, 44))	('thymoma', 'Disease', (37, 44))	('thymoma', 'Phenotype', 'HP:0100522', (37, 44))	('patient', 'Species', '9606', (24, 31))	('EGFR', 'Gene', '1956', (57, 61))	('mutation', 'Var', (62, 70))	('EGFR', 'Gene', (57, 61))
26702	27789964	Furthermore, functional analyses of the mutations are needed to determine the molecular mechanisms of tumorigenesis.	('mutations', 'Var', (40, 49))	('tumor', 'Phenotype', 'HP:0002664', (102, 107))	('tumor', 'Disease', (102, 107))	('tumor', 'Disease', 'MESH:D009369', (102, 107))
26703	27789964	In conclusion, this study reports the incidence of PIK3CA and EGFR mutations in some TET patients.	('EGFR', 'Gene', '1956', (62, 66))	('EGFR', 'Gene', (62, 66))	('mutations', 'Var', (67, 76))	('PIK3CA', 'Gene', (51, 57))	('patients', 'Species', '9606', (89, 97))	('PIK3CA', 'Gene', '5290', (51, 57))
26757	26509934	Alterations in these processes can cause severe autoimmunity such as autoimmune polyendocrine syndrome type 1 (APS-1) and immune dysregulation, polyendocrinopathy, enteropathy X-linked (IPEX) syndrome.	('immune dysregulation', 'Phenotype', 'HP:0002958', (122, 142))	('Alterations', 'Var', (0, 11))	('autoimmunity', 'Phenotype', 'HP:0002960', (48, 60))	('enteropathy', 'Phenotype', 'HP:0002242', (164, 175))	('enteropathy X-linked (IPEX) syndrome', 'Disease', 'MESH:C580192', (164, 200))	('autoimmune polyendocrine syndrome', 'Disease', (69, 102))	('polyendocrinopathy', 'Disease', (144, 162))	('APS-1', 'Gene', '326', (111, 116))	('cause', 'Reg', (35, 40))	('APS-1', 'Gene', (111, 116))	('autoimmune polyendocrine syndrome', 'Disease', 'MESH:C538275', (69, 102))	('immune dysregulation', 'Disease', (122, 142))
26813	23487479	Accumulation of Tc-99m MIBI in benign and malignant thymomas is previously described.	('malignant thymomas', 'Disease', 'MESH:D013945', (42, 60))	('benign', 'Disease', (31, 37))	('thymoma', 'Phenotype', 'HP:0100522', (52, 59))	('Tc-99m', 'Var', (16, 22))	('Tc-99', 'Chemical', '-', (16, 21))	('malignant thymomas', 'Phenotype', 'HP:0100697', (42, 60))	('malignant thymomas', 'Disease', (42, 60))	('MIBI', 'Chemical', 'MESH:C055887', (23, 27))
26851	23091703	Moreover, DQ5, the serologic equivalent of DQB1*05:02, has been shown to be strongly associated with anti-MuSK MG in a Dutch cohort.	('DQB1', 'Gene', '3119', (43, 47))	('MuSK', 'Gene', (106, 110))	('MuSK', 'Gene', '4593', (106, 110))	('DQ5', 'Var', (10, 13))	('DQB1', 'Gene', (43, 47))	('associated', 'Reg', (85, 95))
26884	31304461	The impact of WT1 mutations on the activity of peptide vaccine-based immunotherapy also appears unclear.	('WT1', 'Gene', '7490', (14, 17))	('WT1', 'Gene', (14, 17))	('mutations', 'Var', (18, 27))
26885	31304461	Although not common, 3% of advanced and pretreated TETs harbor recurrent WT1 mutations (4% among recurrent thymic carcinomas).	('thymic carcinomas', 'Disease', (107, 124))	('carcinoma', 'Phenotype', 'HP:0030731', (114, 123))	('carcinomas', 'Phenotype', 'HP:0030731', (114, 124))	('WT1', 'Gene', '7490', (73, 76))	('thymic carcinomas', 'Disease', 'MESH:D013945', (107, 124))	('mutations', 'Var', (77, 86))	('WT1', 'Gene', (73, 76))
26886	31304461	This raises another question: does the presence of WT1 mutations predict for response to WT1-based immunotherapy?	('WT1', 'Gene', (89, 92))	('predict', 'Reg', (65, 72))	('mutations', 'Var', (55, 64))	('WT1', 'Gene', '7490', (51, 54))	('WT1', 'Gene', (51, 54))	('WT1', 'Gene', '7490', (89, 92))
26917	30918333	Cytometric cell-based assays for anti-striational antibodies in myasthenia gravis with myositis and/or myocarditis The purposes of the present study were to identify anti-striational antibodies in myasthenia gravis (MG) patients with myositis and/or myocarditis using a combination of cell-based assays and flow cytometry (cytometric cell-based assays) and to describe the main clinical implications.	('myositis', 'Phenotype', 'HP:0100614', (87, 95))	('MG', 'Disease', 'MESH:D000080343', (216, 218))	('myositis', 'Disease', 'MESH:D009220', (87, 95))	('myasthenia gravis', 'Disease', (64, 81))	('patients', 'Species', '9606', (220, 228))	('myocarditis', 'Disease', (250, 261))	('myasthenia gravis', 'Disease', 'MESH:D009157', (197, 214))	('myocarditis', 'Disease', 'MESH:D009205', (103, 114))	('myositis', 'Disease', (87, 95))	('myositis', 'Phenotype', 'HP:0100614', (234, 242))	('anti-striational antibodies', 'Var', (166, 193))	('myositis', 'Disease', 'MESH:D009220', (234, 242))	('myasthenia', 'Phenotype', 'HP:0003473', (64, 74))	('myocarditis', 'Disease', 'MESH:D009205', (250, 261))	('myasthenia gravis', 'Disease', (197, 214))	('myocarditis', 'Phenotype', 'HP:0012819', (103, 114))	('myasthenia gravis', 'Disease', 'MESH:D009157', (64, 81))	('clinical', 'Species', '191496', (378, 386))	('myasthenia', 'Phenotype', 'HP:0003473', (197, 207))	('myositis', 'Disease', (234, 242))	('myocarditis', 'Disease', (103, 114))	('myocarditis', 'Phenotype', 'HP:0012819', (250, 261))
26921	30918333	MG patients with myositis and/or myocarditis as well as late-onset and thymoma-associated MG had anti-titin, anti-ryanodine receptor, and anti-Kv1.4 antibodies.	('myocarditis', 'Phenotype', 'HP:0012819', (33, 44))	('anti-ryanodine', 'Var', (109, 123))	('thymoma', 'Disease', (71, 78))	('myositis', 'Phenotype', 'HP:0100614', (17, 25))	('myositis', 'Disease', 'MESH:D009220', (17, 25))	('thymoma', 'Phenotype', 'HP:0100522', (71, 78))	('MG', 'Disease', 'MESH:D000080343', (0, 2))	('myositis', 'Disease', (17, 25))	('Kv1.4', 'Gene', (143, 148))	('myocarditis', 'Disease', 'MESH:D009205', (33, 44))	('patients', 'Species', '9606', (3, 11))	('MG', 'Disease', 'MESH:D000080343', (90, 92))	('titin', 'Gene', '7273', (102, 107))	('Kv1.4', 'Gene', '3739', (143, 148))	('thymoma', 'Disease', 'MESH:D013945', (71, 78))	('myocarditis', 'Disease', (33, 44))	('titin', 'Gene', (102, 107))
26939	30918333	In addition, we randomly selected 30 patients with anti-signal recognition particle myopathy, 30 with inclusion body myositis, and 30 with Duchenne muscular dystrophy as disease controls.	('myositis', 'Phenotype', 'HP:0100614', (117, 125))	('patients', 'Species', '9606', (37, 45))	('Duchenne muscular dystrophy', 'Disease', (139, 166))	('myopathy', 'Disease', 'MESH:D009135', (84, 92))	('myositis', 'Disease', 'MESH:D009220', (117, 125))	('Duchenne muscular dystrophy', 'Disease', 'MESH:D020388', (139, 166))	('muscular dystrophy', 'Phenotype', 'HP:0003560', (148, 166))	('myopathy', 'Phenotype', 'HP:0003198', (84, 92))	('myositis', 'Disease', (117, 125))	('anti-signal', 'Var', (51, 62))	('myopathy', 'Disease', (84, 92))
26971	30918333	Unexpectedly, 61% (55/90) of the disease control patients and 23% (7/30) of healthy controls showed positivity for anti-ryanodine receptor antibodies.	('anti-ryanodine receptor antibodies', 'Protein', (115, 149))	('patients', 'Species', '9606', (49, 57))	('positivity', 'Var', (100, 110))
27013	30918333	On the other hand, our results suggest that the production of anti-ryanodine receptor antibodies may be a secondary phenomenon related to the muscle necrosis observed in immune-mediated necrotizing myopathy or muscular dystrophy.	('muscle necrosis', 'Disease', (142, 157))	('men', 'Species', '9606', (121, 124))	('necrotizing myopathy', 'Phenotype', 'HP:0008978', (186, 206))	('anti-ryanodine', 'Var', (62, 76))	('muscle necrosis', 'Disease', 'MESH:D009336', (142, 157))	('necrotizing myopathy', 'Disease', 'MESH:D009135', (186, 206))	('muscular dystrophy', 'Disease', (210, 228))	('muscular dystrophy', 'Phenotype', 'HP:0003560', (210, 228))	('muscular dystrophy', 'Disease', 'MESH:D009136', (210, 228))	('myopathy', 'Phenotype', 'HP:0003198', (198, 206))	('necrotizing myopathy', 'Disease', (186, 206))
27043	30918333	The diagnosis of MG was made based on the patient exhibiting the typical history and signs of fluctuating weakness in the voluntary muscles, the presence of serum anti-acetylcholine receptor or anti-muscle-specific kinase antibody, and abnormal findings of neuromuscular junction transmission.	('weakness', 'Disease', (106, 114))	('weakness', 'Disease', 'MESH:D018908', (106, 114))	('MG', 'Disease', 'MESH:D000080343', (17, 19))	('patient', 'Species', '9606', (42, 49))	('anti-muscle-specific', 'Var', (194, 214))	('fluctuating', 'MPA', (94, 105))
27122	28147469	Chromosome 12p abnormalities, which are specific genetic alterations found in testicular seminomas, are also present in mediastinal seminomas.	('testicular seminomas', 'Disease', (78, 98))	('testicular seminomas', 'Phenotype', 'HP:0100617', (78, 98))	('seminomas', 'Disease', 'MESH:D018239', (132, 141))	('seminomas', 'Disease', (132, 141))	('Chromosome', 'Var', (0, 10))	('testicular seminoma', 'Phenotype', 'HP:0100617', (78, 97))	('seminomas', 'Disease', 'MESH:D018239', (89, 98))	('seminomas', 'Disease', (89, 98))	('testicular seminomas', 'Disease', 'MESH:D018239', (78, 98))
27124	28147469	reported a unique pattern of a KIT exon 17 mutations in mediastinal seminomas, which are rare in testicular seminomas.	('testicular seminomas', 'Disease', (97, 117))	('seminomas', 'Disease', 'MESH:D018239', (108, 117))	('testicular seminoma', 'Phenotype', 'HP:0100617', (97, 116))	('KIT exon 17', 'Gene', (31, 42))	('testicular seminomas', 'Phenotype', 'HP:0100617', (97, 117))	('seminomas', 'Disease', (108, 117))	('testicular seminomas', 'Disease', 'MESH:D018239', (97, 117))	('mutations', 'Var', (43, 52))	('seminomas', 'Disease', 'MESH:D018239', (68, 77))	('seminomas', 'Disease', (68, 77))
27131	28147469	They obtain chromosomal and molecular abnormalities such as chromosome 12p abnormalities and KIT mutations and transform from thymic epithelial tumors into GCTs (seminoma) or from seminomas into thymic epithelial tumors.	('mutations', 'Var', (97, 106))	('chromosome 12p abnormalities', 'Disease', 'MESH:C538301', (60, 88))	('KIT', 'Gene', (93, 96))	('tumors', 'Phenotype', 'HP:0002664', (213, 219))	('epithelial tumors', 'Disease', (133, 150))	('GCTs', 'Disease', (156, 160))	('epithelial tumor', 'Phenotype', 'HP:0031492', (202, 218))	('epithelial tumors', 'Disease', 'MESH:D002277', (133, 150))	('tumor', 'Phenotype', 'HP:0002664', (213, 218))	('transform', 'Reg', (111, 120))	('seminoma', 'Disease', (180, 188))	('seminomas', 'Disease', 'MESH:D018239', (180, 189))	('seminomas', 'Disease', (180, 189))	('seminoma', 'Disease', 'MESH:D018239', (180, 188))	('seminoma', 'Disease', (162, 170))	('chromosome 12p abnormalities', 'Disease', (60, 88))	('GCTs', 'Phenotype', 'HP:0100728', (156, 160))	('molecular abnormalities', 'Disease', (28, 51))	('seminoma', 'Disease', 'MESH:D018239', (162, 170))	('epithelial tumors', 'Disease', (202, 219))	('tumors', 'Phenotype', 'HP:0002664', (144, 150))	('epithelial tumors', 'Disease', 'MESH:D002277', (202, 219))	('epithelial tumor', 'Phenotype', 'HP:0031492', (133, 149))	('molecular abnormalities', 'Disease', 'MESH:C567116', (28, 51))	('tumor', 'Phenotype', 'HP:0002664', (144, 149))
27190	33835748	The proportion of patients displaying abnormal decreases in responses in the trapezius, abductor digiti minimi, or flexor carpi ulnaris muscles on the RNS test was higher in the GOMG group (p<0.001, p=0.002, and p<0.001, respectively).	('GOMG', 'Var', (178, 182))	('RNS', 'Chemical', '-', (151, 154))	('patients', 'Species', '9606', (18, 26))	('decreases', 'NegReg', (47, 56))	('responses', 'MPA', (60, 69))	('GOMG', 'Chemical', '-', (178, 182))
27191	33835748	The Cox proportional-hazards model revealed that an abnormal result on the RNS test was significantly associated with conversion to generalized MG [hazard ratio (HR)=3.13, 95% confidence interval (CI)=1.18-8.32].	('associated with', 'Reg', (102, 117))	('RNS test', 'Gene', (75, 83))	('abnormal', 'Var', (52, 60))	('generalized MG', 'Disease', (132, 146))	('RNS', 'Chemical', '-', (75, 78))	('conversion', 'Disease', (118, 128))
27193	33835748	An abnormal result on the RNS test, especially in the limb muscles, is an independent predictor of the conversion from ocular to generalized MG.	('abnormal', 'Var', (3, 11))	('RNS', 'Gene', (26, 29))	('ocular', 'Disease', (119, 125))	('generalized MG', 'Disease', (129, 143))	('RNS', 'Chemical', '-', (26, 29))
27211	33835748	Inclusion criteria were 1) diagnosed as ocular MG, 2) positivity in the neostigmine challenge test and/or in the serological test for autoantibodies, including AChR antibody and MuSK antibody, and 3) the RNS test conducted at five muscles [OO, nasalis (NA), abductor digiti minimi (ADM), flexor carpi ulnaris (FCU), and trapezius (TR)] during the diagnostic workup.	('neostigmine', 'Chemical', 'MESH:D009388', (72, 83))	('OO', 'Chemical', '-', (240, 242))	('TR', 'Gene', '2149', (331, 333))	('MuSK', 'Gene', '4593', (178, 182))	('FCU', 'Chemical', '-', (310, 313))	('MuSK antibody', 'Phenotype', 'HP:0030210', (178, 191))	('MuSK', 'Gene', (178, 182))	('RNS', 'Chemical', '-', (204, 207))	('positivity', 'Var', (54, 64))
27239	33835748	The AChR antibody titer was also higher in the GOMG group (9.1 nmol/L) than in the ROMG group (5.0 nmol/L, p<0.001), as was the proportion of patients who used oral prednisolone (58.0% vs. 33.3%, p=0.039).	('ROMG', 'Chemical', '-', (83, 87))	('higher', 'PosReg', (33, 39))	('AChR antibody', 'Protein', (4, 17))	('GOMG', 'Chemical', '-', (47, 51))	('GOMG', 'Var', (47, 51))	('patients', 'Species', '9606', (142, 150))	('prednisolone', 'Chemical', 'MESH:D011239', (165, 177))
27248	33835748	In contrast, the proportions of patients showing decreased responses in the TR, ADM, and FCU muscles were significantly higher in the GOMG group (37.5%, 16.7%, and 37.5%, respectively) than in the ROMG group (8.0%, 0%, and 8.0%; p<0.001, p=0.002, and p<0.001, respectively).	('patients', 'Species', '9606', (32, 40))	('TR', 'Gene', '2149', (76, 78))	('decreased', 'NegReg', (49, 58))	('ROMG', 'Chemical', '-', (197, 201))	('GOMG', 'Var', (134, 138))	('GOMG', 'Chemical', '-', (134, 138))	('responses', 'MPA', (59, 68))	('FCU', 'Chemical', '-', (89, 92))
27249	33835748	The proportion of subjects showing a decreased response in at least one of the five muscles was also significantly higher in the GOMG group (75.0%) than in the ROMG group (38.6%, p=0.002).	('higher', 'PosReg', (115, 121))	('GOMG', 'Var', (129, 133))	('ROMG', 'Chemical', '-', (160, 164))	('GOMG', 'Chemical', '-', (129, 133))
27251	33835748	Similar to the comparison of the proportion of abnormal responses based on a threshold of 10%, the decreases in ADM, FCU, and TR muscles were significantly larger in the GOMG group than in the ROMG group (p=0.011, p=0.009, and p=0.044, respectively).	('decreases', 'NegReg', (99, 108))	('FCU', 'CPA', (117, 120))	('GOMG', 'Chemical', '-', (170, 174))	('GOMG', 'Var', (170, 174))	('FCU', 'Chemical', '-', (117, 120))	('ROMG', 'Chemical', '-', (193, 197))	('ADM', 'CPA', (112, 115))	('TR', 'Gene', '2149', (126, 128))
27254	33835748	The incidence of symptom conversion to generalized MG was significantly higher in the RNS-test-positive group than in the RNS-test-negative group (log-rank test, p=0.001).	('RNS', 'Chemical', '-', (122, 125))	('RNS', 'Chemical', '-', (86, 89))	('generalized MG', 'Disease', (39, 53))	('higher', 'PosReg', (72, 78))	('RNS-test-positive', 'Var', (86, 103))
27302	33835748	The proportions of AChR-antibody positivity and presence of thymoma were also higher in the GOMG group than in the ROMG group, but the differences did not reach statistical significance.	('thymoma', 'Disease', 'MESH:D013945', (60, 67))	('thymoma', 'Disease', (60, 67))	('thymoma', 'Phenotype', 'HP:0100522', (60, 67))	('higher', 'PosReg', (78, 84))	('ROMG', 'Chemical', '-', (115, 119))	('GOMG', 'Chemical', '-', (92, 96))	('GOMG', 'Var', (92, 96))	('AChR-antibody', 'Protein', (19, 32))
27375	31764848	Concerning the variants of GBS, AIDP was identified in 12 cases, AMAN in 5 cases, AMSAN in 3 cases, and MFS in 5 cases.	('AMSAN', 'Chemical', 'None', (82, 87))	('GBS', 'Disease', 'MESH:D020275', (27, 30))	('GBS', 'Disease', (27, 30))	('MFS', 'Disease', (104, 107))	('AMAN', 'Chemical', 'None', (65, 69))	('variants', 'Var', (15, 23))	('MFS', 'Disease', 'MESH:D008382', (104, 107))	('AIDP', 'Disease', (32, 36))	('AIDP', 'Chemical', 'None', (32, 36))
27402	31764848	Any infections or other incentives could make the body more likely to produce antibodies to peripheral nerves causing GBS.	('infections', 'Disease', (4, 14))	('GBS', 'Disease', (118, 121))	('antibodies', 'Var', (78, 88))	('infections', 'Disease', 'MESH:D007239', (4, 14))	('peripheral nerves', 'Protein', (92, 109))	('GBS', 'Disease', 'MESH:D020275', (118, 121))
27433	26303293	The MRI demonstrated that the lesion involving the left cingulate gyrus increased in size, and an abnormal signal intensity lesion in the left corona radiata, which was presumably the cause of his right hemiparesis, and edematous swelling of the bilateral medial temporal regions appeared (Fig.	('increased', 'PosReg', (72, 81))	('edematous swelling', 'Disease', (220, 238))	('edematous swelling', 'Disease', 'MESH:D004487', (220, 238))	('edematous swelling', 'Phenotype', 'HP:0000969', (220, 238))	('right hemiparesis', 'Disease', 'MESH:D010291', (197, 214))	('right hemiparesis', 'Phenotype', 'HP:0040293', (197, 214))	('lesion', 'Var', (124, 130))	('right hemiparesis', 'Disease', (197, 214))	('hemiparesis', 'Phenotype', 'HP:0001269', (203, 214))	('edema', 'Phenotype', 'HP:0000969', (220, 225))
27476	33329350	This led to the identification of more patients with antibodies to the classical antigens AChR and MuSK and to the third MG autoantigen, the low-density lipoprotein receptor-related protein 4 (LRP4), while antibodies against other extracellular or intracellular targets, such as agrin, Kv1.4 potassium channels, collagen Q, titin, the ryanodine receptor and cortactin have been found in some MG patients.	('patients', 'Species', '9606', (39, 47))	('titin', 'Gene', '7273', (324, 329))	('low-density lipoprotein receptor-related protein 4', 'Gene', '4038', (141, 191))	('ACh', 'Chemical', 'MESH:D000109', (90, 93))	('titin', 'Gene', (324, 329))	('patients', 'Species', '9606', (395, 403))	('LRP4', 'Gene', '4038', (193, 197))	('cortactin', 'Gene', (358, 367))	('collagen Q', 'Gene', '8292', (312, 322))	('MuSK', 'Gene', (99, 103))	('LRP4', 'Gene', (193, 197))	('Kv1.4', 'Gene', (286, 291))	('agrin', 'Gene', '375790', (279, 284))	('agrin', 'Gene', (279, 284))	('cortactin', 'Gene', '2017', (358, 367))	('Kv1.4', 'Gene', '3739', (286, 291))	('antibodies', 'Var', (53, 63))	('low-density lipoprotein receptor-related protein 4', 'Gene', (141, 191))	('collagen Q', 'Gene', (312, 322))	('ryanodine receptor', 'Gene', '6261', (335, 353))	('MuSK', 'Gene', '4593', (99, 103))	('ryanodine receptor', 'Gene', (335, 353))
27498	33329350	They are composed of five homologous subunits with a stoichiometry of alpha2betadeltaepsilon in adult and alpha2betagammadelta in fetal or adult denervated muscles.	('epsilon', 'Disease', (85, 92))	('epsilon', 'Disease', 'MESH:D001321', (85, 92))	('alpha2betagammadelta', 'Var', (106, 126))
27506	33329350	Lastly, antibodies that bind close to the AChR ligand binding site are thought to directly block acetylcholine binding and receptor activation.	('acetylcholine binding', 'MPA', (97, 118))	('activation', 'PosReg', (132, 142))	('receptor', 'MPA', (123, 131))	('ACh', 'Chemical', 'MESH:D000109', (42, 45))	('acetylcholine', 'Chemical', 'MESH:D000109', (97, 110))	('block', 'NegReg', (91, 96))	('antibodies', 'Var', (8, 18))
27528	33329350	Interestingly, LRP4 antibodies have also been reported in 10-23% of amyotrophic lateral sclerosis (ALS) patients and in 3.6% patients with other neurological diseases but not in healthy controls.	('LRP4', 'Gene', '4038', (15, 19))	('ALS', 'Disease', (99, 102))	('amyotrophic lateral sclerosis', 'Disease', 'MESH:D000690', (68, 97))	('amyotrophic lateral sclerosis', 'Phenotype', 'HP:0007354', (68, 97))	('antibodies', 'Var', (20, 30))	('LRP4', 'Gene', (15, 19))	('neurological diseases', 'Disease', (145, 166))	('reported', 'Reg', (46, 54))	('neurological diseases', 'Disease', 'MESH:D020271', (145, 166))	('ALS', 'Phenotype', 'HP:0007354', (99, 102))	('ALS', 'Disease', 'MESH:D008113', (99, 102))	('patients', 'Species', '9606', (104, 112))	('amyotrophic lateral sclerosis', 'Disease', (68, 97))	('patients', 'Species', '9606', (125, 133))
27538	33329350	In a Caucasian patient cohort Kv1.4 antibodies were associated with LOMG patients and mild disease, often remaining purely ocular, while in Japanese patients they correlated with increased disease severity, myasthenic crises and the presence of thymoma.	('patient', 'Species', '9606', (15, 22))	('patients', 'Species', '9606', (149, 157))	('antibodies', 'Var', (36, 46))	('thymoma', 'Disease', (245, 252))	('Kv1.4', 'Gene', (30, 35))	('myasthenic crises', 'Phenotype', 'HP:0003473', (207, 224))	('thymoma', 'Phenotype', 'HP:0100522', (245, 252))	('associated', 'Reg', (52, 62))	('myasthenic crises', 'Disease', (207, 224))	('patients', 'Species', '9606', (73, 81))	('Kv1.4', 'Gene', '3739', (30, 35))	('patient', 'Species', '9606', (73, 80))	('patient', 'Species', '9606', (149, 156))	('LOMG patients', 'Disease', (68, 81))	('increased', 'PosReg', (179, 188))	('thymoma', 'Disease', 'MESH:D013945', (245, 252))	('mild disease', 'Disease', (86, 98))
27560	33329350	Antibodies against rapsyn have been found in about 15% of MG patients, including among SNMG.	('Antibodies', 'Var', (0, 10))	('rapsyn', 'Gene', '5913', (19, 25))	('SNMG', 'Disease', (87, 91))	('patients', 'Species', '9606', (61, 69))	('found', 'Reg', (36, 41))	('rapsyn', 'Gene', (19, 25))
27618	33329350	Indeed, antibodies against clustered AChRs belong to the complement-activating subclasses and cause complement depositions on the cell surface.	('AChRs', 'Gene', (37, 42))	('men', 'Species', '9606', (63, 66))	('complement depositions on', 'MPA', (100, 125))	('ACh', 'Chemical', 'MESH:D000109', (37, 40))	('cause', 'Reg', (94, 99))	('clustered AChRs', 'Gene', (27, 42))	('antibodies', 'Var', (8, 18))	('men', 'Species', '9606', (106, 109))
27658	33329350	The identification of peptides derived from the human AChR alpha subunit as T cell dominant epitopes, lead to the construction of altered peptides with single amino acid substitutions (termed altered peptide ligands, APL), some of which were found to inhibit T cell proliferative responses in vitro.	('human', 'Species', '9606', (48, 53))	('substitutions', 'Var', (170, 183))	('rat', 'Species', '10116', (273, 276))	('inhibit', 'NegReg', (251, 258))	('ACh', 'Chemical', 'MESH:D000109', (54, 57))	('T cell proliferative responses', 'CPA', (259, 289))	('APL', 'Gene', (217, 220))	('APL', 'Gene', '18010', (217, 220))
27719	33246468	In our study, only AMC distinguished from type B1 and B2 thymomas was enrolled to research, because most of type B3 thymic carcinomas can easily be distinguished from cysts preoperatively by CT manifestations.	('thymic carcinomas', 'Disease', (116, 133))	('thymoma', 'Phenotype', 'HP:0100522', (57, 64))	('thymic carcinomas', 'Disease', 'MESH:D013953', (116, 133))	('thymomas', 'Disease', 'MESH:D013945', (57, 65))	('AMC', 'Chemical', '-', (19, 22))	('carcinomas', 'Phenotype', 'HP:0030731', (123, 133))	('thymomas', 'Disease', (57, 65))	('type B3', 'Var', (108, 115))
27765	29664052	The presence of MG gives thymomas some special pathological and clinical characteristics and may influence its prognosis.	('thymomas', 'Disease', 'MESH:D013945', (25, 33))	('thymoma', 'Phenotype', 'HP:0100522', (25, 32))	('presence', 'Var', (4, 12))	('influence', 'Reg', (97, 106))	('thymomas', 'Disease', (25, 33))
27864	25426445	It is clear that anti-cytokine autoantibodies are an important and emerging mechanisms of adult-onset immunodeficiency and can be responsible for severe opportunistic infection in previously healthy adults.	('opportunistic infection', 'Disease', 'MESH:D009894', (153, 176))	('responsible', 'Reg', (130, 141))	('opportunistic infection', 'Phenotype', 'HP:0031690', (153, 176))	('immunodeficiency', 'Phenotype', 'HP:0002721', (102, 118))	('opportunistic infection', 'Disease', (153, 176))	('anti-cytokine autoantibodies', 'Var', (17, 45))	('immunodeficiency', 'Disease', 'MESH:D007153', (102, 118))	('immunodeficiency', 'Disease', (102, 118))
27973	25059994	In our understanding these pathophysiological alterations resulted in a reduction of the arterial blood pressure and the tissue perfusion, followed by a considerable rise of catecholamine levels in this trial.	('reduction', 'NegReg', (72, 81))	('arterial blood pressure', 'MPA', (89, 112))	('catecholamine', 'Chemical', 'MESH:D002395', (174, 187))	('tissue perfusion', 'CPA', (121, 137))	('rise', 'PosReg', (166, 170))	('alterations', 'Var', (46, 57))	('rise of catecholamine levels', 'Phenotype', 'HP:0003334', (166, 194))	('reduction of the arterial blood pressure', 'Phenotype', 'HP:0002615', (72, 112))	('catecholamine levels', 'MPA', (174, 194))
28171	31167928	Lymphocyte-driven regional immunopathology in pneumonitis caused by impaired central immune tolerance Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a monogenic disorder caused by AIRE mutations, presents with several autoimmune diseases.	('APECED', 'Gene', '326', (166, 172))	('autoimmune disease', 'Phenotype', 'HP:0002960', (244, 262))	('autoimmune diseases', 'Disease', 'MESH:D001327', (244, 263))	('pneumonitis', 'Disease', (46, 57))	('AIRE', 'Gene', (206, 210))	('APECED', 'Gene', (166, 172))	('mutations', 'Var', (211, 220))	('ectodermal dystrophy', 'Phenotype', 'HP:0000968', (144, 164))	('autoimmune diseases', 'Disease', (244, 263))	('AIRE', 'Gene', '326', (206, 210))	('Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy', 'Disease', 'MESH:C538275', (102, 164))	('pneumonitis', 'Disease', 'MESH:D011014', (46, 57))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (244, 263))
28175	31167928	Autoantibodies against BPIFB1 and KCNRG and the homozygous c.967_979del13 AIRE mutation are associated with pneumonitis development.	('associated with', 'Reg', (92, 107))	('KCNRG', 'Gene', (34, 39))	('AIRE', 'Gene', (74, 78))	('AIRE', 'Gene', '326', (74, 78))	('pneumonitis', 'Disease', (108, 119))	('c.967_979del13', 'Var', (59, 73))	('BPIFB1', 'Gene', '92747', (23, 29))	('pneumonitis', 'Disease', 'MESH:D011014', (108, 119))	('BPIFB1', 'Gene', (23, 29))	('KCNRG', 'Gene', '283518', (34, 39))	('c.967_979del13', 'Mutation', 'c.967_979del13', (59, 73))
28181	31167928	Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) or autoimmune polyglandular syndrome type 1 is a monogenic disorder most often caused by biallelic mutations in the thymus-enriched autoimmune regulator (AIRE) gene.	('AIRE', 'Gene', (226, 230))	('autoimmune regulator', 'Gene', (204, 224))	('autoimmune polyglandular syndrome', 'Disease', (75, 108))	('autoimmune regulator', 'Gene', '326', (204, 224))	('APECED', 'Gene', '326', (64, 70))	('AIRE', 'Gene', '326', (226, 230))	('autoimmune polyglandular syndrome', 'Disease', 'MESH:D016884', (75, 108))	('ectodermal dystrophy', 'Phenotype', 'HP:0000968', (42, 62))	('Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy', 'Disease', 'MESH:C538275', (0, 62))	('APECED', 'Gene', (64, 70))	('biallelic mutations', 'Var', (161, 180))	('caused by', 'Reg', (151, 160))
28183	31167928	Aire deficiency also features breakdown in B lymphocyte tolerance; Aire-/- B lymphocytes have been implicated in contributing to organ-specific autoimmune damage via direct priming of T lymphocytes.	('autoimmune damage', 'Disease', (144, 161))	('Aire-/- B', 'Var', (67, 76))	('Aire deficiency', 'Disease', 'MESH:D009041', (0, 15))	('B lymphocyte tolerance', 'CPA', (43, 65))	('autoimmune damage', 'Disease', 'MESH:D020274', (144, 161))	('contributing', 'Reg', (113, 125))	('Aire deficiency', 'Disease', (0, 15))
28186	31167928	Although autoantibodies against the lung-specific bactericidal/permeability-increasing fold-containing B1 (BPIFB1) and the potassium channel regulator KCNRG have been associated with the development of APECED pneumonitis, the immunopathogenesis of APECED pneumonitis in humans remains elusive, and no effective treatment is known.	('KCNRG', 'Gene', '283518', (151, 156))	('BPIFB1', 'Gene', (107, 113))	('associated with', 'Reg', (167, 182))	('KCNRG', 'Gene', (151, 156))	('APECED pneumonitis', 'Disease', 'MESH:C538275', (248, 266))	('autoantibodies', 'Var', (9, 23))	('humans', 'Species', '9606', (270, 276))	('potassium', 'Chemical', 'MESH:D011188', (123, 132))	('APECED pneumonitis', 'Disease', (202, 220))	('BPIFB1', 'Gene', '92747', (107, 113))	('APECED pneumonitis', 'Disease', 'MESH:C538275', (202, 220))	('APECED pneumonitis', 'Disease', (248, 266))
28205	31167928	Bronchiectasis was the most common radiographic finding (81%) followed by GGO or mosaicism (76.2%), a tree-in-bud pattern, nodular opacities, or mucus plugging, each of which was seen in more than half of the patients (Fig.	('mosaicism', 'Var', (81, 90))	('nodular opacities', 'Disease', (123, 140))	('Bronchiectasis', 'Phenotype', 'HP:0002110', (0, 14))	('Bronchiectasis', 'Disease', (0, 14))	('nodular opacities', 'Disease', 'MESH:D003318', (123, 140))	('patients', 'Species', '9606', (209, 217))	('GGO', 'Disease', (74, 77))	('Bronchiectasis', 'Disease', 'MESH:D001987', (0, 14))	('tree-in-bud pattern', 'Phenotype', 'HP:0032174', (102, 121))
28215	31167928	Progressively worsening bronchiectasis-associated lung disease occurred later in untreated pneumonitis, associated with Gram-negative or Gram-positive bacteria (n = 4) or NTM (n = 2).	('bronchiectasis', 'Phenotype', 'HP:0002110', (24, 38))	('bronchiectasis-associated lung disease', 'Disease', 'MESH:D001987', (24, 62))	('bronchiectasis-associated lung disease', 'Disease', (24, 62))	('lung disease', 'Phenotype', 'HP:0002088', (50, 62))	('pneumonitis', 'Disease', (91, 102))	('Gram-negative', 'Var', (120, 133))	('pneumonitis', 'Disease', 'MESH:D011014', (91, 102))
28223	31167928	Autoantibodies against BPIFB1 and KCNRG have been associated with APECED pneumonitis in previous studies.	('KCNRG', 'Gene', (34, 39))	('BPIFB1', 'Gene', '92747', (23, 29))	('BPIFB1', 'Gene', (23, 29))	('APECED pneumonitis', 'Disease', (66, 84))	('KCNRG', 'Gene', '283518', (34, 39))	('associated', 'Reg', (50, 60))	('Autoantibodies', 'Var', (0, 14))	('APECED pneumonitis', 'Disease', 'MESH:C538275', (66, 84))
28230	31167928	We found an association between carrying the AIRE c.967_979del13 mutation in homozygosity and the time to development of pneumonitis (Fig.	('pneumonitis', 'Disease', 'MESH:D011014', (121, 132))	('AIRE', 'Gene', (45, 49))	('c.967_979del13', 'Mutation', 'c.967_979del13', (50, 64))	('AIRE', 'Gene', '326', (45, 49))	('c.967_979del13', 'Var', (50, 64))	('pneumonitis', 'Disease', (121, 132))
28231	31167928	2C); no other genotype-phenotype correlations were observed, nor did we identify specific human leukocyte antigen (HLA) haplotype associations with the time to development of pneumonitis.	('HLA', 'Gene', (115, 118))	('pneumonitis', 'Disease', 'MESH:D011014', (175, 186))	('haplotype', 'Var', (120, 129))	('human', 'Species', '9606', (90, 95))	('pneumonitis', 'Disease', (175, 186))
28254	31167928	All six available deep lung tissue samples showed lymphocytic or lymphoplasmacytic bronchiolitis and/or peribronchiolar inflammation dominated by CD4+ and CD8+ T lymphocytes, with the latter prominent within intraepithelial areas.	('lymphoplasmacytic bronchiolitis', 'Disease', (65, 96))	('lymphoplasmacytic bronchiolitis', 'Disease', 'MESH:D001988', (65, 96))	('CD8', 'Gene', (155, 158))	('CD4+', 'Var', (146, 150))	('inflammation', 'Disease', 'MESH:D007249', (120, 132))	('CD8', 'Gene', '925', (155, 158))	('bronchiolitis', 'Phenotype', 'HP:0011950', (83, 96))	('lymphocytic', 'Disease', (50, 61))	('inflammation', 'Disease', (120, 132))
28266	31167928	Besides thymoma, thymic AIRE is decreased in patients with biallelic hypomorphic RAG mutations who manifest immune deficiency, dysregulation, and autoimmunity.	('autoimmunity', 'Phenotype', 'HP:0002960', (146, 158))	('autoimmunity', 'Disease', (146, 158))	('immune deficiency', 'Disease', 'MESH:D007153', (108, 125))	('thymoma', 'Phenotype', 'HP:0100522', (8, 15))	('immune deficiency', 'Disease', (108, 125))	('man', 'Species', '9606', (99, 102))	('biallelic hypomorphic', 'Var', (59, 80))	('autoimmunity', 'Disease', 'MESH:D001327', (146, 158))	('AIRE', 'Gene', (24, 28))	('AIRE', 'Gene', '326', (24, 28))	('patients', 'Species', '9606', (45, 53))	('thymoma', 'Disease', 'MESH:D013945', (8, 15))	('decreased', 'NegReg', (32, 41))	('immune deficiency', 'Phenotype', 'HP:0002721', (108, 125))	('thymoma', 'Disease', (8, 15))
28273	31167928	We next examined histological features of lung disease in Aire-/- mice and found that Aire-/- mouse lung tissue exhibited histological abnormalities similar to those seen in patients with APECED pneumonitis.	('lung disease', 'Phenotype', 'HP:0002088', (42, 54))	('lung disease', 'Disease', 'MESH:D008171', (42, 54))	('APECED pneumonitis', 'Disease', (188, 206))	('mice', 'Species', '10090', (66, 70))	('patients', 'Species', '9606', (174, 182))	('mouse', 'Species', '10090', (94, 99))	('histological abnormalities', 'Phenotype', 'HP:0002664', (122, 148))	('APECED pneumonitis', 'Disease', 'MESH:C538275', (188, 206))	('Aire-/-', 'Var', (86, 93))	('lung disease', 'Disease', (42, 54))
28279	31167928	CD4+ T lymphocytes are critical to promote pneumonitis, so as could be predicted, Aire-/-Ighn-/- mice manifested only partial amelioration of lung tissue injury relative to Aire-/- mice (Fig.	('mice', 'Species', '10090', (181, 185))	('Aire-/-Ighn-/-', 'Var', (82, 96))	('man', 'Species', '9606', (102, 105))	('lung tissue injury', 'Disease', (142, 160))	('lung tissue injury', 'Disease', 'MESH:D055370', (142, 160))	('mice', 'Species', '10090', (97, 101))	('pneumonitis', 'Disease', (43, 54))	('pneumonitis', 'Disease', 'MESH:D011014', (43, 54))
28280	31167928	Together, these data indicate that although both Aire-/- alphabeta T and B lymphocytes drive airway neutrophilia, Aire-/- alphabeta T lymphocytes predominate over Aire-/- B lymphocytes in promoting autoimmune lung tissue injury.	('airway neutrophilia', 'Disease', (93, 112))	('airway neutrophilia', 'Disease', 'MESH:C563010', (93, 112))	('autoimmune lung tissue injury', 'Disease', 'MESH:D055370', (198, 227))	('promoting', 'PosReg', (188, 197))	('autoimmune lung tissue injury', 'Disease', (198, 227))	('Aire-/- alphabeta T', 'Var', (114, 133))	('neutrophilia', 'Phenotype', 'HP:0011897', (100, 112))
28310	31167928	Beyond chest CT, measurement of autoantibodies against BPIFB1 and KCNRG is a valuable, albeit less sensitive, screen for APECED pneumonitis.	('BPIFB1', 'Gene', '92747', (55, 61))	('KCNRG', 'Gene', (66, 71))	('BPIFB1', 'Gene', (55, 61))	('autoantibodies', 'Var', (32, 46))	('APECED pneumonitis', 'Disease', (121, 139))	('KCNRG', 'Gene', '283518', (66, 71))	('APECED pneumonitis', 'Disease', 'MESH:C538275', (121, 139))
28316	31167928	We found an association between the homozygous c.967_979del13 AIRE mutation and development of pneumonitis.	('pneumonitis', 'Disease', (95, 106))	('c.967_979del13', 'Mutation', 'c.967_979del13', (47, 61))	('AIRE', 'Gene', '326', (62, 66))	('AIRE', 'Gene', (62, 66))	('pneumonitis', 'Disease', 'MESH:D011014', (95, 106))	('c.967_979del13', 'Var', (47, 61))
28319	31167928	Enrollment in our study and uniform pulmonary evaluation of European patients with APECED with c.967_979del13 homozygosity will help address this possibility.	('APECED', 'Gene', (83, 89))	('c.967_979del13', 'Mutation', 'c.967_979del13', (95, 109))	('patients', 'Species', '9606', (69, 77))	('c.967_979del13', 'Var', (95, 109))	('APECED', 'Gene', '326', (83, 89))
28330	31167928	Within the lung parenchyma, CD4 and CD8 lymphocyte peribronchial and bronchiolar infiltration with associated follicular bronchiolitis and large B lymphocyte aggregates deeper in the lung parenchyma was also consistently observed, whereas CD4 and CD8 interstitial tissue lymphocytosis was seen less often.	('lymphocytosis', 'Disease', (271, 284))	('CD4', 'Var', (28, 31))	('CD8', 'Gene', (247, 250))	('follicular bronchiolitis', 'Disease', 'MESH:D001988', (110, 134))	('CD8', 'Gene', '925', (247, 250))	('lymphocytosis', 'Disease', 'MESH:D008218', (271, 284))	('lymphocytosis', 'Phenotype', 'HP:0100827', (271, 284))	('bronchiolitis', 'Phenotype', 'HP:0011950', (121, 134))	('CD8', 'Gene', (36, 39))	('follicular bronchiolitis', 'Disease', (110, 134))	('bronchiolar infiltration', 'CPA', (69, 93))	('CD8', 'Gene', '925', (36, 39))	('large B lymphocyte aggregates', 'CPA', (139, 168))
28361	31167928	Inclusion criteria consisted of either a clinical APECED diagnosis based on developing any two manifestations within the classic triad of CMC, hypoparathyroidism, and adrenal insufficiency (n = 46) or a genetic diagnosis (i.e., biallelic AIRE mutations and/or deletions) without a classic diagnostic dyad (n = 4).	('AIRE', 'Gene', (238, 242))	('AIRE', 'Gene', '326', (238, 242))	('CMC', 'Phenotype', 'HP:0002728', (138, 141))	('APECED', 'Gene', '326', (50, 56))	('deletions', 'Var', (260, 269))	('hypoparathyroidism', 'Disease', (143, 161))	('adrenal insufficiency', 'Phenotype', 'HP:0000846', (167, 188))	('adrenal insufficiency', 'Disease', 'MESH:D000309', (167, 188))	('hypoparathyroidism', 'Disease', 'MESH:D007011', (143, 161))	('APECED', 'Gene', (50, 56))	('hypoparathyroidism', 'Phenotype', 'HP:0000829', (143, 161))	('mutations', 'Var', (243, 252))	('CMC', 'Disease', (138, 141))	('adrenal insufficiency', 'Disease', (167, 188))	('man', 'Species', '9606', (95, 98))
28384	29438696	We further observe enrichment of mutations in HRAS, NRAS, and TP53.	('NRAS', 'Gene', (52, 56))	('TP53', 'Gene', '7157', (62, 66))	('NRAS', 'Gene', '4893', (52, 56))	('HRAS', 'Gene', '3265', (46, 50))	('TP53', 'Gene', (62, 66))	('mutations', 'Var', (33, 42))	('HRAS', 'Gene', (46, 50))
28387	29438696	They identify high prevalence of GTF2I mutations and enrichment of mutations in HRAS, NRAS, and TP53 and link over-expression of muscle auto-antigens and increased aneuploidy in thymoma and patients' risk of having myasthenia gravis.	('NRAS', 'Gene', (86, 90))	('myasthenia', 'Phenotype', 'HP:0003473', (215, 225))	('HRAS', 'Gene', '3265', (80, 84))	('GTF2I', 'Gene', (33, 38))	('myasthenia gravis', 'Disease', (215, 232))	('TP53', 'Gene', (96, 100))	('NRAS', 'Gene', '4893', (86, 90))	('over-expression', 'PosReg', (110, 125))	('patients', 'Species', '9606', (190, 198))	('aneuploidy in thymoma', 'Disease', (164, 185))	('GTF2I', 'Gene', '2969', (33, 38))	('mutations', 'Var', (39, 48))	('mutations', 'Var', (67, 76))	('aneuploidy in thymoma', 'Disease', 'MESH:D000782', (164, 185))	('thymoma', 'Phenotype', 'HP:0100522', (178, 185))	('myasthenia gravis', 'Disease', 'MESH:D009157', (215, 232))	('HRAS', 'Gene', (80, 84))	('TP53', 'Gene', '7157', (96, 100))
28394	29438696	However, mutations in EGFR and KIT are uncommon.	('mutations', 'Var', (9, 18))	('KIT', 'Gene', (31, 34))	('EGFR', 'Gene', '1956', (22, 26))	('EGFR', 'Gene', (22, 26))
28395	29438696	documented that histological subtypes of thymoma exhibited differential molecular profiles with thymic carcinomas displaying more chromosomal gains and losses and occasionally harboring somatic mutations in KIT.	('thymic carcinomas', 'Disease', (96, 113))	('carcinomas', 'Phenotype', 'HP:0030731', (103, 113))	('KIT', 'Gene', (207, 210))	('thymoma', 'Gene', (41, 48))	('losses', 'NegReg', (152, 158))	('thymic carcinomas', 'Disease', 'MESH:D013945', (96, 113))	('thymoma', 'Phenotype', 'HP:0100522', (41, 48))	('carcinoma', 'Phenotype', 'HP:0030731', (103, 112))	('chromosomal gains', 'Var', (130, 147))	('thymoma', 'Gene', '7063', (41, 48))
28397	29438696	Exome sequencing has revealed a high frequency of recurrent mutations in the GTF2I gene in type A and AB thymomas.	('AB thymomas', 'Disease', (102, 113))	('thymoma', 'Phenotype', 'HP:0100522', (105, 112))	('GTF2I', 'Gene', (77, 82))	('GTF2I', 'Gene', '2969', (77, 82))	('mutations', 'Var', (60, 69))	('type A', 'Disease', (91, 97))	('AB thymomas', 'Disease', 'MESH:D013945', (102, 113))
28399	29438696	Nevertheless, these efforts have helped identify unique molecular changes in TETs such as an anti-apoptotic gene signature and mutations in genes involved in histone modification, DNA methylation and chromatin remodeling in thymic carcinomas.	('thymic carcinomas', 'Disease', 'MESH:D013945', (224, 241))	('carcinoma', 'Phenotype', 'HP:0030731', (231, 240))	('carcinomas', 'Phenotype', 'HP:0030731', (231, 241))	('thymic carcinomas', 'Disease', (224, 241))	('mutations', 'Var', (127, 136))	('anti-apoptotic gene', 'Gene', (93, 112))
28412	29438696	The vast majority of mutations in HRAS and NRAS occurred at known gain-of-function codons (HRAS: codon 12, 13, 117; NRAS: codon 61).	('HRAS', 'Gene', (91, 95))	('HRAS', 'Gene', (34, 38))	('NRAS', 'Gene', (43, 47))	('HRAS', 'Gene', '3265', (91, 95))	('NRAS', 'Gene', (116, 120))	('gain-of-function', 'PosReg', (66, 82))	('NRAS', 'Gene', '4893', (43, 47))	('NRAS', 'Gene', '4893', (116, 120))	('HRAS', 'Gene', '3265', (34, 38))	('mutations', 'Var', (21, 30))
28413	29438696	In TP53, all mutations were known pathogenic loss of function mutations.	('mutations', 'Var', (13, 22))	('TP53', 'Gene', '7157', (3, 7))	('TP53', 'Gene', (3, 7))	('loss of function', 'NegReg', (45, 61))
28414	29438696	This suggests that mutations in GTF2I, HRAS, NRAS, and TP53 are most likely founder mutations occurring at the onset or very early in tumor development.	('GTF2I', 'Gene', (32, 37))	('NRAS', 'Gene', '4893', (45, 49))	('TP53', 'Gene', '7157', (55, 59))	('TP53', 'Gene', (55, 59))	('GTF2I', 'Gene', '2969', (32, 37))	('mutations', 'Var', (19, 28))	('tumor', 'Disease', 'MESH:D009369', (134, 139))	('HRAS', 'Gene', '3265', (39, 43))	('NRAS', 'Gene', (45, 49))	('tumor', 'Phenotype', 'HP:0002664', (134, 139))	('HRAS', 'Gene', (39, 43))	('tumor', 'Disease', (134, 139))
28423	29438696	We observed that cases in subtypes 1 and 3 are associated with higher lymphocyte content (p < 0.01), GTF2I mutation is predominantly seen in subtypes 3 and 4, and HRAS mutation is predominantly observed in subtype 4.	('GTF2I', 'Gene', '2969', (101, 106))	('HRAS', 'Gene', '3265', (163, 167))	('mutation', 'Var', (107, 115))	('lymphocyte content', 'MPA', (70, 88))	('HRAS', 'Gene', (163, 167))	('higher', 'PosReg', (63, 69))	('GTF2I', 'Gene', (101, 106))
28428	29438696	The opposite is seen in the AB-, B-, and C-like clusters where tumor suppression is down-regulated (p53, and TAp73a), and oncogenes are up-regulated (MYC/Max, MYB, FOXM1, and E2F1) (Figure 3D).	('tumor', 'Disease', (63, 68))	('tumor', 'Phenotype', 'HP:0002664', (63, 68))	('up-regulated', 'PosReg', (136, 148))	('MYB', 'Gene', (159, 162))	('TAp73a', 'Var', (109, 115))	('MYC', 'Gene', '4609', (150, 153))	('FOXM1', 'Gene', '2305', (164, 169))	('p53', 'Gene', '7157', (100, 103))	('tumor', 'Disease', 'MESH:D009369', (63, 68))	('MYB', 'Gene', '4602', (159, 162))	('FOXM1', 'Gene', (164, 169))	('down-regulated', 'NegReg', (84, 98))	('E2F1', 'Gene', (175, 179))	('oncogenes', 'CPA', (122, 131))	('MYC', 'Gene', (150, 153))	('E2F1', 'Gene', '1869', (175, 179))	('p53', 'Gene', (100, 103))
28430	29438696	Given the predominance of GTF2I mutations in type A & AB thymomas, we utilized our multi-platform data to further characterize GTF2I-mutated tumors.	('AB thymomas', 'Disease', (54, 65))	('tumor', 'Phenotype', 'HP:0002664', (141, 146))	('GTF2I', 'Gene', (26, 31))	('tumors', 'Disease', (141, 147))	('tumors', 'Disease', 'MESH:D009369', (141, 147))	('thymoma', 'Phenotype', 'HP:0100522', (57, 64))	('tumors', 'Phenotype', 'HP:0002664', (141, 147))	('mutations', 'Var', (32, 41))	('GTF2I', 'Gene', (127, 132))	('GTF2I', 'Gene', '2969', (26, 31))	('GTF2I', 'Gene', '2969', (127, 132))	('AB thymomas', 'Disease', 'MESH:D013945', (54, 65))
28432	29438696	GTF2I mutations are very rare in cancer with no observed L424H mutations in any other of the ~10,000 tumor samples profiled by the TCGA (Figure 4B).	('cancer', 'Disease', (33, 39))	('000 tumor', 'Disease', (97, 106))	('cancer', 'Disease', 'MESH:D009369', (33, 39))	('tumor', 'Phenotype', 'HP:0002664', (101, 106))	('GTF2I', 'Gene', (0, 5))	('000 tumor', 'Disease', 'MESH:D009369', (97, 106))	('cancer', 'Phenotype', 'HP:0002664', (33, 39))	('GTF2I', 'Gene', '2969', (0, 5))	('L424H', 'Mutation', 'p.L424H', (57, 62))	('mutations', 'Var', (6, 15))	('L424H', 'Var', (57, 62))
28433	29438696	There are occasional (<1%) GTF2I mutations in other cancers and these are exclusively at sites other than L424H.	('L424H', 'Mutation', 'p.L424H', (106, 111))	('GTF2I', 'Gene', '2969', (27, 32))	('cancer', 'Phenotype', 'HP:0002664', (52, 58))	('cancers', 'Disease', (52, 59))	('mutations', 'Var', (33, 42))	('cancers', 'Phenotype', 'HP:0002664', (52, 59))	('GTF2I', 'Gene', (27, 32))	('cancers', 'Disease', 'MESH:D009369', (52, 59))
28434	29438696	We examined the transcriptional response associated with GTF2I mutations using RNA-seq data analysis (Figure 4C).	('mutations', 'Var', (63, 72))	('GTF2I', 'Gene', (57, 62))	('GTF2I', 'Gene', '2969', (57, 62))
28435	29438696	Ten GTF2I mutant samples were misclassified by our predictor as wild type and all had a low variant allele frequency, concordant low tumor purity, and high lymphocyte grade (Figure S2B).	('mutant', 'Var', (10, 16))	('tumor', 'Phenotype', 'HP:0002664', (133, 138))	('low tumor', 'Disease', 'MESH:D009800', (129, 138))	('GTF2I', 'Gene', (4, 9))	('low tumor', 'Disease', (129, 138))	('high lymphocyte', 'Phenotype', 'HP:0100827', (151, 166))	('GTF2I', 'Gene', '2969', (4, 9))
28436	29438696	The GTF2I mutants had higher expression of genes involved in cell morphogenesis, receptor tyrosine kinase signaling, retinoic acid receptors, neuronal processes, as well as the WNT and SHH signaling pathways.	('higher', 'PosReg', (22, 28))	('mutants', 'Var', (10, 17))	('GTF2I', 'Gene', '2969', (4, 9))	('GTF2I', 'Gene', (4, 9))	('receptor tyrosine kinase signaling', 'MPA', (81, 115))	('expression', 'MPA', (29, 39))	('WNT and', 'Pathway', (177, 184))
28437	29438696	DNA methylation changes that associated with GTF2I mutations were indistinguishable from changes associated with histological type and lymphocyte grade (Figure 4D).	('GTF2I', 'Gene', (45, 50))	('mutations', 'Var', (51, 60))	('GTF2I', 'Gene', '2969', (45, 50))
28438	29438696	RPPA data was available for 42 thymoma samples of types A or AB, of which 32 exhibited GTF2I mutations.	('thymoma', 'Gene', '7063', (31, 38))	('mutations', 'Var', (93, 102))	('thymoma', 'Gene', (31, 38))	('exhibited', 'Reg', (77, 86))	('GTF2I', 'Gene', (87, 92))	('thymoma', 'Phenotype', 'HP:0100522', (31, 38))	('GTF2I', 'Gene', '2969', (87, 92))
28439	29438696	After correcting for multiple hypothesis testing, we found 91 proteins to be significantly downregulated in the GTF2I mutant tumors.	('downregulated', 'NegReg', (91, 104))	('proteins', 'Protein', (62, 70))	('tumor', 'Phenotype', 'HP:0002664', (125, 130))	('GTF2I', 'Gene', (112, 117))	('tumors', 'Disease', (125, 131))	('tumors', 'Disease', 'MESH:D009369', (125, 131))	('tumors', 'Phenotype', 'HP:0002664', (125, 131))	('mutant', 'Var', (118, 124))	('GTF2I', 'Gene', '2969', (112, 117))
28440	29438696	Pathway analysis demonstrated lower expression of the apoptosis, cell cycle, DNA damage response, hormone receptor signaling, breast hormone signaling, RAS/MAPK, RTK and TSC/mTOR pathways in GTF2I mutant tumors (Figure 4E).	('RAS/MAPK', 'Pathway', (152, 160))	('apoptosis', 'CPA', (54, 63))	('lower', 'NegReg', (30, 35))	('tumors', 'Disease', 'MESH:D009369', (204, 210))	('GTF2I', 'Gene', (191, 196))	('RTK', 'Pathway', (162, 165))	('hormone receptor', 'MPA', (98, 114))	('tumor', 'Phenotype', 'HP:0002664', (204, 209))	('cell cycle', 'CPA', (65, 75))	('DNA damage', 'MPA', (77, 87))	('GTF2I', 'Gene', '2969', (191, 196))	('mutant', 'Var', (197, 203))	('tumors', 'Disease', (204, 210))	('breast hormone signaling', 'MPA', (126, 150))	('mTOR', 'Gene', (174, 178))	('mTOR', 'Gene', '2475', (174, 178))	('expression', 'MPA', (36, 46))	('tumors', 'Phenotype', 'HP:0002664', (204, 210))
28446	29438696	Furthermore, MG status was neither associated with mutations in any single gene (including GTF2I) nor with any methylation signature or microRNA profile (data not shown).	('GTF2I', 'Gene', (91, 96))	('mutations', 'Var', (51, 60))	('GTF2I', 'Gene', '2969', (91, 96))
28453	29438696	Expression levels of the medium size neurofilament, NEFM, that exhibits immunogenic similarities with the AChR a-subunit and titin were 23.8-fold higher in MG+ compared to MG- thymomas and even higher (30-fold) in MG+ type A/AB subset (FDR=0) (Figure 5D).	('higher', 'PosReg', (146, 152))	('higher', 'PosReg', (194, 200))	('titin', 'Gene', '7273', (125, 130))	('Expression levels', 'MPA', (0, 17))	('thymomas', 'Disease', (176, 184))	('thymomas', 'Disease', 'MESH:D013945', (176, 184))	('titin', 'Gene', (125, 130))	('MG+', 'Var', (156, 159))	('NEFM', 'Gene', '4741', (52, 56))	('NEFM', 'Gene', (52, 56))	('thymoma', 'Phenotype', 'HP:0100522', (176, 183))
28460	29438696	Of distinct interest, a single TC sample exhibited an exceptionally high TMB (21.29 mutations per megabase), and was excluded from the analysis in Figure 6B to avoid skewing the results.	('mutations', 'Var', (84, 93))	('TMB', 'Chemical', '-', (73, 76))	('TMB', 'MPA', (73, 76))
28461	29438696	However, a further analysis of this sample revealed a characteristic mutation pattern of SNVs most similar to COSMIC signature 6 (cosine similarity = 0.91, http://cancer.sanger.ac.uk/cosmic/signatures) and a significant enrichment of 1-base indels (19% vs 5% in remaining samples), which is associated with microsatellite unstable tumors with defective DNA mismatch repair (Figure 6C).	('SNVs', 'Gene', (89, 93))	('1-base indels', 'Var', (234, 247))	('microsatellite unstable tumors', 'Disease', (307, 337))	('tumor', 'Phenotype', 'HP:0002664', (331, 336))	('microsatellite unstable tumors', 'Disease', 'MESH:D053842', (307, 337))	('cancer', 'Phenotype', 'HP:0002664', (163, 169))	('tumors', 'Phenotype', 'HP:0002664', (331, 337))	('cancer', 'Disease', (163, 169))	('cancer', 'Disease', 'MESH:D009369', (163, 169))
28462	29438696	Interestingly, this sample has a pathogenic nonsense mutation (E37*) in MLH1 (https://www.ncbi.nlm.nih.gov/clinvar/variation/89641/) with a concomitant loss of MLH1 mRNA expression (2.6-fold down-regulation against the median).	('MLH1', 'Gene', (160, 164))	('E37*', 'Var', (63, 67))	('loss', 'NegReg', (152, 156))	('down-regulation', 'NegReg', (191, 206))	('pathogenic', 'Reg', (33, 43))	('mRNA expression', 'MPA', (165, 180))	('E37*', 'SUBSTITUTION', 'None', (63, 67))	('MLH1', 'Gene', '4292', (72, 76))	('MLH1', 'Gene', (72, 76))	('MLH1', 'Gene', '4292', (160, 164))
28463	29438696	To our knowledge, this is the first report of a microsatellite unstable Thymic Carcinoma.	('microsatellite unstable', 'Var', (48, 71))	('Carcinoma', 'Disease', (79, 88))	('Carcinoma', 'Phenotype', 'HP:0030731', (79, 88))	('Carcinoma', 'Disease', 'MESH:D002277', (79, 88))
28466	29438696	using the publically available TCGA TET dataset also demonstrated separation of TETs into four clusters defined by: GTF2I mutations, T-cell signaling, chromosomal stability, and chromosomal instability.	('chromosomal instability', 'Phenotype', 'HP:0040012', (178, 201))	('GTF2I', 'Gene', (116, 121))	('T-cell', 'MPA', (133, 139))	('mutations', 'Var', (122, 131))	('GTF2I', 'Gene', '2969', (116, 121))
28467	29438696	GTF2I L424H mutations are unique to TETs and is the most common mutation in this tumor type.	('L424H', 'Mutation', 'p.L424H', (6, 11))	('L424H', 'Var', (6, 11))	('GTF2I', 'Gene', (0, 5))	('tumor', 'Disease', 'MESH:D009369', (81, 86))	('tumor', 'Phenotype', 'HP:0002664', (81, 86))	('GTF2I', 'Gene', '2969', (0, 5))	('tumor', 'Disease', (81, 86))
28469	29438696	Mutations in GTF2I have been described rarely in other tumor types and are present at different codons.	('tumor', 'Disease', 'MESH:D009369', (55, 60))	('tumor', 'Phenotype', 'HP:0002664', (55, 60))	('tumor', 'Disease', (55, 60))	('Mutations', 'Var', (0, 9))	('GTF2I', 'Gene', (13, 18))	('GTF2I', 'Gene', '2969', (13, 18))
28470	29438696	RNA-seq identified higher expression of genes involved in cell morphogenesis, receptor tyrosine kinases, retinoic acid receptors, neuronal processes, as well as the WNT and SHH signaling pathways in the GTF2I mutant tumors.	('expression', 'MPA', (26, 36))	('higher', 'PosReg', (19, 25))	('tumors', 'Disease', (216, 222))	('tumors', 'Disease', 'MESH:D009369', (216, 222))	('tumors', 'Phenotype', 'HP:0002664', (216, 222))	('GTF2I', 'Gene', (203, 208))	('tumor', 'Phenotype', 'HP:0002664', (216, 221))	('mutant', 'Var', (209, 215))	('GTF2I', 'Gene', '2969', (203, 208))
28472	29438696	GTF2IRD1 is a GTF2I family member, located near GTF2I, which was also upregulated in our dataset in GTF2I mutants.	('GTF2I', 'Gene', '2969', (100, 105))	('GTF2I', 'Gene', '2969', (0, 5))	('GTF2I', 'Gene', (0, 5))	('GTF2IRD1', 'Gene', (0, 8))	('GTF2IRD1', 'Gene', '9569', (0, 8))	('GTF2I', 'Gene', (14, 19))	('GTF2I', 'Gene', (48, 53))	('upregulated', 'PosReg', (70, 81))	('GTF2I', 'Gene', (100, 105))	('mutants', 'Var', (106, 113))	('GTF2I', 'Gene', '2969', (14, 19))	('GTF2I', 'Gene', '2969', (48, 53))
28486	29438696	An exception is the finding of a microsatellite unstable thymic carcinoma, which may suggest the use of immune checkpoint therapy for these very rare cases.	('thymic carcinoma', 'Disease', (57, 73))	('microsatellite unstable', 'Var', (33, 56))	('carcinoma', 'Phenotype', 'HP:0030731', (64, 73))	('thymic carcinoma', 'Disease', 'MESH:D013945', (57, 73))
28490	29438696	Incorporation of molecularly defined subtypes for histological diagnosis, as well as drug development based on these genomic data, particularly targeting mutant GTF2I, may have significant clinical implications for patients with TETs.	('patients', 'Species', '9606', (215, 223))	('GTF2I', 'Gene', '2969', (161, 166))	('GTF2I', 'Gene', (161, 166))	('mutant', 'Var', (154, 160))
28520	29438696	After passing quality control, bisulfite-converted DNA samples were whole genome amplified followed by enzymatic fragmentation and hybridized overnight to BeadChips followed by a locus-specific base extension with labeled nucleotides (cy3 and cy5).	('cy3', 'Var', (235, 238))	('bisulfite', 'Chemical', 'MESH:C042345', (31, 40))	('cy5', 'Var', (243, 246))
28553	29438696	For each filter, we then calculated a reads-per-million (RPM) abundance metric as: To detect genomic integration of specific viruses we performed de novo assembly of RNA-seq and DNA-seq sequence data with ABySS v1.3.4, using for each library the reads classified by BBT as human, the virus, multi-match and no match.	('BBT', 'Chemical', '-', (266, 269))	('v1.3', 'Gene', (211, 215))	('RPM', 'Chemical', '-', (57, 60))	('multi-match', 'Var', (291, 302))	('human', 'Species', '9606', (273, 278))	('v1.3', 'Gene', '28816', (211, 215))
28585	29438696	A Fisher's exact test p value <= 0.15 was returned when comparing the number of reads with gapped alignments versus reads without in the normal to the tumor.	('tumor', 'Disease', (151, 156))	('gapped alignments', 'Var', (91, 108))	('tumor', 'Disease', 'MESH:D009369', (151, 156))	('tumor', 'Phenotype', 'HP:0002664', (151, 156))
28589	29438696	Functional annotation of mutations was performed with Oncotator (http://www.broadinstitute.org/cancer/cga/oncotator) using Gencode V18.	('cga', 'Gene', (102, 105))	('mutations', 'Var', (25, 34))	('cancer', 'Disease', 'MESH:D009369', (95, 101))	('cancer', 'Disease', (95, 101))	('cga', 'Gene', '1113', (102, 105))	('cancer', 'Phenotype', 'HP:0002664', (95, 101))
28590	29438696	At BCM, mutations in BAM files were detected as follows: Atlas-SNP of the Atlas2 Suite was run to list all variants found in multiple reads at a single locus; and variants were annotated with dbSNP by ANNOVAR and COSMIC (Catalogue Of Somatic Mutations In Cancer).	('Cancer', 'Phenotype', 'HP:0002664', (255, 261))	('variants', 'Var', (163, 171))	('Cancer', 'Disease', (255, 261))	('Cancer', 'Disease', 'MESH:D009369', (255, 261))
28606	29438696	Multi-omics definition of four robust molecular TET subtypes associated with survival Thymomas have the lowest mutational burden among adult cancers Enrichment of HRAS, NRAS, TP53, and recurrent GTF2I mutations are observed Expression of autoimmune targets and aneuploidy links thymoma to myasthenia gravis	('adult cancers', 'Disease', 'MESH:C535836', (135, 148))	('aneuploidy links thymoma to myasthenia gravis', 'Disease', 'MESH:D009157', (261, 306))	('GTF2I', 'Gene', (195, 200))	('Thymoma', 'Phenotype', 'HP:0100522', (86, 93))	('TP53', 'Gene', '7157', (175, 179))	('myasthenia', 'Phenotype', 'HP:0003473', (289, 299))	('NRAS', 'Gene', (169, 173))	('HRAS', 'Gene', '3265', (163, 167))	('HRAS', 'Gene', (163, 167))	('aneuploidy links thymoma to myasthenia gravis', 'Disease', (261, 306))	('cancers', 'Phenotype', 'HP:0002664', (141, 148))	('cancer', 'Phenotype', 'HP:0002664', (141, 147))	('thymoma', 'Phenotype', 'HP:0100522', (278, 285))	('adult cancers', 'Disease', (135, 148))	('Thymoma', 'Gene', (86, 93))	('mutations', 'Var', (201, 210))	('TP53', 'Gene', (175, 179))	('Thymoma', 'Gene', '7063', (86, 93))	('NRAS', 'Gene', '4893', (169, 173))	('GTF2I', 'Gene', '2969', (195, 200))
28658	26273398	WHO classification was type A/B in three (11.5%) patients, type B1 in three (11.5%), type B1/B2 in one (3.8%), type B2 in three (11.5%), and type B3 in seven (26.9%) patients.	('B1/B2', 'Gene', '28905;3383', (90, 95))	('type B2', 'Var', (111, 118))	('B1/B2', 'Gene', (90, 95))	('patients', 'Species', '9606', (49, 57))	('patients', 'Species', '9606', (166, 174))
28683	26273398	In Kaplan-Meier analysis, a MTV and a TLG higher than 83.5 cm3 and 371.3, respectively, was associated with a poor prognosis (Fig 3).	('371.3', 'Var', (67, 72))	('MTV', 'Chemical', '-', (28, 31))	('MTV', 'Var', (28, 31))	('TLG', 'Chemical', '-', (38, 41))
28720	23580814	No carcinoma cells were observed, favoring T1N0M0.	('carcinoma', 'Disease', 'MESH:D002277', (3, 12))	('carcinoma', 'Phenotype', 'HP:0030731', (3, 12))	('carcinoma', 'Disease', (3, 12))	('T1N0M0', 'Var', (43, 49))
28744	19513285	Myasthenia gravis (MG) is an autoimmune disease in which muscular weakness and fatigability of skeletal muscles are caused by an antibody against the acetylcholine receptor (AChR) at the neuromuscular junction.	('AChR', 'Gene', (174, 178))	('autoimmune disease', 'Disease', 'MESH:D001327', (29, 47))	('autoimmune disease', 'Phenotype', 'HP:0002960', (29, 47))	('muscular weakness', 'Phenotype', 'HP:0001324', (57, 74))	('antibody', 'Var', (129, 137))	('caused by', 'Reg', (116, 125))	('Myasthenia gravis', 'Disease', (0, 17))	('muscular weakness', 'Disease', 'MESH:D018908', (57, 74))	('Myasthenia gravis', 'Disease', 'MESH:D009157', (0, 17))	('muscular weakness', 'Disease', (57, 74))	('Myasthenia', 'Phenotype', 'HP:0003473', (0, 10))	('fatigability', 'CPA', (79, 91))	('autoimmune disease', 'Disease', (29, 47))	('fatigability of skeletal muscles', 'Phenotype', 'HP:0030197', (79, 111))
28787	20197733	Given the small number of patients treated in this study, selection based on presence of c-KIT mutations might be warranted.	('c-KIT', 'Gene', (89, 94))	('c-KIT', 'Gene', '3815', (89, 94))	('mutations', 'Var', (95, 104))	('patients', 'Species', '9606', (26, 34))
28791	20197733	c-KIT positivity by immunohistochemistry (IHC) has been observed in 73 to 86% of TC.	('c-KIT', 'Gene', (0, 5))	('positivity', 'Var', (6, 16))	('c-KIT', 'Gene', '3815', (0, 5))
28797	20197733	Other inclusion criteria were age more than 18 years, presence of measurable and/or evaluable disease (by WHO Response Criteria), performance status 0 to 2 (Eastern Cooperative Oncology Group), adequate end organ function (total bilirubin <1.5 x upper limit of normal [ULN], serum glutamic oxaloacetic transaminase and serum glutamic pyruvic transaminase <2.5 x ULN, creatinine <1.5 x ULN, absolute neutrophil count >1.5 x 109/L, platelets >100 x 109/L, and leukocytes >3 x 109/L), and life expectancy more than 3 months.	('creatinine', 'Chemical', 'MESH:D003404', (367, 377))	('>100 x 109/L', 'Var', (440, 452))	('Oncology', 'Phenotype', 'HP:0002664', (177, 185))	('platelets', 'CPA', (430, 439))	('absolute neutrophil count', 'CPA', (390, 415))	('serum glutamic pyruvic transaminase', 'MPA', (319, 354))	('serum glutamic oxaloacetic transaminase', 'Phenotype', 'HP:0031956', (275, 314))	('serum glutamic oxaloacetic transaminase', 'MPA', (275, 314))	('creatinine', 'MPA', (367, 377))	('life expectancy', 'CPA', (486, 501))
28808	20197733	The PCR products were purified (Qiaquick PCR purification KIT, Qiagen, The Netherlands) and screened for mutations by bidirectional sequence analysis, using the forward and reverse PCR primers.	('KIT', 'Gene', '3815', (58, 61))	('KIT', 'Gene', (58, 61))	('mutations', 'Var', (105, 114))
28834	20197733	have described a case of epidermoid carcinoma of the thymus with strong expression of KIT, an activating mutation in exon 11 of the KIT gene (V560del) and a response to imatinib that lasted 6 months.	('KIT', 'Gene', (86, 89))	('epidermoid carcinoma of the thymus', 'Disease', 'MESH:D002294', (25, 59))	('KIT', 'Gene', '3815', (132, 135))	('V560del', 'Var', (142, 149))	('KIT', 'Gene', (132, 135))	('imatinib', 'Chemical', 'MESH:D000068877', (169, 177))	('carcinoma', 'Phenotype', 'HP:0030731', (36, 45))	('activating', 'PosReg', (94, 104))	('V560del', 'Mutation', 'p.560delV', (142, 149))	('KIT', 'Gene', '3815', (86, 89))	('epidermoid carcinoma of the thymus', 'Disease', (25, 59))
28836	20197733	They also found no c-KIT mutations in exons 9, 11, 13, and 17 of the KIT gene in 21 of 22 cases of TC by direct DNA sequencing.	('KIT', 'Gene', (69, 72))	('mutations', 'Var', (25, 34))	('KIT', 'Gene', '3815', (21, 24))	('c-KIT', 'Gene', (19, 24))	('KIT', 'Gene', '3815', (69, 72))	('KIT', 'Gene', (21, 24))	('c-KIT', 'Gene', '3815', (19, 24))
28841	20197733	In 22 cases of thymoma and 11 cases of TC analyzed for mutations of exons 9, 11,13, and 17 of the KIT gene, only one case of TC harbored a missense mutation in exon 11 (L576P).	('thymoma', 'Disease', (15, 22))	('mutations', 'Var', (55, 64))	('thymoma', 'Phenotype', 'HP:0100522', (15, 22))	('KIT', 'Gene', '3815', (98, 101))	('L576P', 'Mutation', 'rs121913513', (169, 174))	('KIT', 'Gene', (98, 101))	('thymoma', 'Disease', 'MESH:D013945', (15, 22))
28842	20197733	The presence of mutations in the c-KIT gene determines response to imatinib therapy.	('mutations', 'Var', (16, 25))	('c-KIT', 'Gene', (33, 38))	('imatinib', 'Chemical', 'MESH:D000068877', (67, 75))	('response', 'MPA', (55, 63))	('c-KIT', 'Gene', '3815', (33, 38))
28848	20197733	A recent report (W. Pao, personal communication) identified two KIT mutations in six resected TC analyzed, one of which is a novel mutation.	('mutations', 'Var', (68, 77))	('KIT', 'Gene', '3815', (64, 67))	('KIT', 'Gene', (64, 67))
28851	20197733	The rarity of KIT mutations in this disease may be the reason for this negative result.	('KIT', 'Gene', '3815', (14, 17))	('KIT', 'Gene', (14, 17))	('mutations', 'Var', (18, 27))
28852	20197733	Selection of patients with TC harboring KIT mutations may be of interest for further studies.	('KIT', 'Gene', '3815', (40, 43))	('KIT', 'Gene', (40, 43))	('patients', 'Species', '9606', (13, 21))	('mutations', 'Var', (44, 53))
2065	30714278	Neuromyotonia was diagnosed according to the presence of typical electromyography abnormalities and/or autoantibodies against LGI1/CASPR2.	('Neuromyotonia', 'Disease', (0, 13))	('Neuromyotonia', 'Disease', 'MESH:D020386', (0, 13))	('CASPR2', 'Gene', '26047', (131, 137))	('LGI1', 'Gene', '9211', (126, 130))	('LGI1', 'Gene', (126, 130))	('electromyography abnormalities', 'Phenotype', 'HP:0003457', (65, 95))	('autoantibodies', 'Var', (103, 117))	('CASPR2', 'Gene', (131, 137))
28859	30714278	Three patients had Netrin-1 receptor antibodies, two with neuromyotonia and concomitant CASPR2+LGI1 antibodies and one with spontaneous muscle overactivity without electromyography evidence of neuromyotonia.	('antibodies', 'Var', (37, 47))	('neuromyotonia', 'Disease', 'MESH:D020386', (58, 71))	('LGI1', 'Gene', '9211', (95, 99))	('LGI1', 'Gene', (95, 99))	('Netrin-1', 'Gene', (19, 27))	('CASPR2', 'Gene', (88, 94))	('neuromyotonia', 'Disease', (193, 206))	('neuromyotonia', 'Disease', 'MESH:D020386', (193, 206))	('CASPR2', 'Gene', '26047', (88, 94))	('patients', 'Species', '9606', (6, 14))	('Netrin-1', 'Gene', '9423', (19, 27))	('muscle overactivity', 'Phenotype', 'HP:0000752', (136, 155))	('neuromyotonia', 'Disease', (58, 71))
28866	30714278	NMT can be associated with myasthenia gravis (MG) with unknown frequency 6.	('associated', 'Reg', (11, 21))	('myasthenia gravis', 'Disease', 'MESH:D009157', (27, 44))	('myasthenia', 'Phenotype', 'HP:0003473', (27, 37))	('NMT', 'Var', (0, 3))	('myasthenia gravis', 'Disease', (27, 44))
28879	30714278	Patients were defined as having NMT if the following criteria were fulfilled: (i) the presence of cramps and/or muscle twitching (myokymia and/or fasciculations) affecting at least two skeletal regions; (ii) no pyridostigmine treatment, or symptom persistence after the drug suspension 18; (iii) electromyography (EMG) compatible with NMT (myokymic/neuromyotonic discharges) 4 or, in patients without EMG available, seropositivity for CASPR2 and/or LGI1 antibodies, which can typically be associated with NMT 19.	('LGI1', 'Gene', (449, 453))	('fasciculations', 'Phenotype', 'HP:0002380', (146, 160))	('NMT 1', 'Gene', '4836', (505, 510))	('fasciculations', 'Disease', (146, 160))	('seropositivity', 'Var', (416, 430))	('neuromyotonic', 'Disease', 'None', (349, 362))	('muscle twitching', 'Phenotype', 'HP:0002380', (112, 128))	('LGI1', 'Gene', '9211', (449, 453))	('twitching', 'Phenotype', 'HP:0010546', (119, 128))	('Patients', 'Species', '9606', (0, 8))	('myokymia', 'Disease', 'MESH:D020385', (130, 138))	('NMT', 'Disease', (335, 338))	('CASPR2', 'Gene', (435, 441))	('patients', 'Species', '9606', (384, 392))	('fasciculation', 'Phenotype', 'HP:0002380', (146, 159))	('neuromyotonic', 'Disease', (349, 362))	('fasciculations', 'Disease', 'MESH:D005207', (146, 160))	('NMT 1', 'Gene', (505, 510))	('CASPR2', 'Gene', '26047', (435, 441))	('myokymia', 'Disease', (130, 138))	('myokymia', 'Phenotype', 'HP:0002411', (130, 138))
28903	30714278	As a whole, 6/23 patients had autoantibodies against neuronal cell-surface proteins.	('patients', 'Species', '9606', (17, 25))	('neuronal cell-surface proteins', 'Protein', (53, 83))	('autoantibodies', 'Var', (30, 44))
28907	30714278	One patient with periocular myokymia and fasciculations in the four limbs had isolated antibodies to the Netrin-1 receptor DCC.	('Netrin-1', 'Gene', (105, 113))	('myokymia', 'Phenotype', 'HP:0002411', (28, 36))	('fasciculation', 'Phenotype', 'HP:0002380', (41, 54))	('myokymia and fasciculations', 'Disease', 'MESH:D005207', (28, 55))	('patient', 'Species', '9606', (4, 11))	('DCC', 'Gene', (123, 126))	('Netrin-1', 'Gene', '9423', (105, 113))	('DCC', 'Gene', '1630', (123, 126))	('antibodies', 'Var', (87, 97))	('fasciculations', 'Phenotype', 'HP:0002380', (41, 55))
28927	30714278	Previous studies compared patients with peripheral nerve hyperexcitability with or without typical EMG features of NMT, concluding that the frequency of VGKC antibodies (including CASPR2 and LGI1 antibodies) is increased in both groups, thus probably implicated in the pathogenesis, and that the EMG features reflect quantitative rather than qualitative differences 18.	('antibodies', 'Var', (158, 168))	('CASPR2', 'Gene', '26047', (180, 186))	('patients', 'Species', '9606', (26, 34))	('increased', 'PosReg', (211, 220))	('LGI1', 'Gene', '9211', (191, 195))	('CASPR2', 'Gene', (180, 186))	('rat', 'Species', '10116', (330, 333))	('LGI1', 'Gene', (191, 195))	('VGKC', 'Gene', (153, 157))
28940	30714278	In our series, the autoantibodies tended to associate with recurrent thymoma.	('thymoma', 'Gene', '7063', (69, 76))	('autoantibodies', 'Var', (19, 33))	('thymoma', 'Gene', (69, 76))	('thymoma', 'Phenotype', 'HP:0100522', (69, 76))	('associate with', 'Reg', (44, 58))
28950	30242309	This cohort study combined with a patient-led survey found that antibodies to the extracellular aspects of leucine-rich glioma inactivated protein, contactin-associated protein 2, and contactin 2 were variably present in 45% of patients with neuromyotonia.	('contactin 2', 'Gene', '6900', (184, 195))	('glioma', 'Phenotype', 'HP:0009733', (120, 126))	('contactin-associated protein 2', 'Gene', '26047', (148, 178))	('neuromyotonia', 'Disease', (242, 255))	('present', 'Reg', (210, 217))	('antibodies', 'Var', (64, 74))	('patients', 'Species', '9606', (228, 236))	('patient', 'Species', '9606', (34, 41))	('neuromyotonia', 'Disease', 'MESH:D020386', (242, 255))	('glioma', 'Disease', (120, 126))	('contactin 2', 'Gene', (184, 195))	('contactin-associated protein 2', 'Gene', (148, 178))	('patient', 'Species', '9606', (228, 235))	('glioma', 'Disease', 'MESH:D005910', (120, 126))
28969	30242309	Antibodies to LGI1 were strongly associated with limbic encephalitis, whereas antibodies to CASPR2 were found more often in patients with Morvan syndrome or NMT, sometimes with LGI1.	('LGI1', 'Gene', '9211', (177, 181))	('Morvan syndrome', 'Disease', 'OMIM:201300', (138, 153))	('LGI1', 'Gene', (177, 181))	('Antibodies', 'Var', (0, 10))	('NMT', 'Disease', (157, 160))	('LGI1', 'Gene', '9211', (14, 18))	('Morvan syndrome', 'Disease', (138, 153))	('CASPR2', 'Gene', (92, 98))	('encephalitis', 'Disease', (56, 68))	('encephalitis', 'Disease', 'MESH:D004660', (56, 68))	('LGI1', 'Gene', (14, 18))	('encephalitis', 'Phenotype', 'HP:0002383', (56, 68))	('patients', 'Species', '9606', (124, 132))	('associated with', 'Reg', (33, 48))
28970	30242309	Contactin-associated protein 2 antibodies were associated with underlying thymomas, but contactin 2 antibodies were uncommon.	('contactin 2', 'Gene', '6900', (88, 99))	('Contactin-associated protein 2', 'Gene', (0, 30))	('thymoma', 'Phenotype', 'HP:0100522', (74, 81))	('thymomas', 'Disease', (74, 82))	('thymomas', 'Disease', 'MESH:D013945', (74, 82))	('antibodies', 'Var', (31, 41))	('associated', 'Reg', (47, 57))	('contactin 2', 'Gene', (88, 99))	('Contactin-associated protein 2', 'Gene', '26047', (0, 30))
29019	30242309	However, results of the live cell-based assays were positive in 17 of the 38 patients (45%), including CASPR2 antibodies in 11 (29%), LGI1 antibodies in 8 (21%), and contactin 2 antibodies in 5 (13%) (Figure 2A).	('contactin 2', 'Gene', '6900', (166, 177))	('LGI1', 'Gene', '9211', (134, 138))	('LGI1', 'Gene', (134, 138))	('positive', 'Reg', (52, 60))	('patients', 'Species', '9606', (77, 85))	('contactin 2', 'Gene', (166, 177))	('CASPR2', 'Gene', (103, 109))	('antibodies', 'Var', (110, 120))
29022	30242309	However, of the 6 patients with both CASPR2 and LGI1 antibodies, 3 (50%) had thymoma and 1 had developed prostate cancer; 1 had mild disease that responded to carbamazepine alone.	('thymoma', 'Disease', (77, 84))	('CASPR2', 'Gene', (37, 43))	('prostate cancer', 'Disease', (105, 120))	('thymoma', 'Phenotype', 'HP:0100522', (77, 84))	('carbamazepine', 'Chemical', 'MESH:D002220', (159, 172))	('LGI1', 'Gene', '9211', (48, 52))	('cancer', 'Phenotype', 'HP:0002664', (114, 120))	('LGI1', 'Gene', (48, 52))	('prostate cancer', 'Disease', 'MESH:D011471', (105, 120))	('patients', 'Species', '9606', (18, 26))	('prostate cancer', 'Phenotype', 'HP:0012125', (105, 120))	('thymoma', 'Disease', 'MESH:D013945', (77, 84))	('antibodies', 'Var', (53, 63))
29066	30242309	Nevertheless, 3 of the 6 patients (50%) with both CASPR2 and LGI1 antibodies had many features of Morvan syndrome, including thymoma; however, none had developed encephalopathy, and the diagnosis remained NMT.	('LGI1', 'Gene', '9211', (61, 65))	('LGI1', 'Gene', (61, 65))	('thymoma', 'Phenotype', 'HP:0100522', (125, 132))	('encephalopathy', 'Phenotype', 'HP:0001298', (162, 176))	('CASPR2', 'Gene', (50, 56))	('encephalopathy', 'Disease', (162, 176))	('Morvan syndrome', 'Disease', 'OMIM:201300', (98, 113))	('encephalopathy', 'Disease', 'MESH:D001927', (162, 176))	('patients', 'Species', '9606', (25, 33))	('thymoma', 'Disease', 'MESH:D013945', (125, 132))	('antibodies', 'Var', (66, 76))	('Morvan syndrome', 'Disease', (98, 113))	('thymoma', 'Disease', (125, 132))
29071	30242309	By contrast, LGI1 antibodies modulate VGKC function on brain slices and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid currents in hippocampal neurons and internalize the LGI1-disintegrin and metalloproteinase 22 receptor complex in transfected human embryonic kidney cells.	('function', 'MPA', (43, 51))	('LGI1', 'Gene', '9211', (13, 17))	('LGI1', 'Gene', (13, 17))	('modulate', 'Reg', (29, 37))	('VGKC', 'Protein', (38, 42))	('LGI1', 'Gene', (181, 185))	('LGI1', 'Gene', '9211', (181, 185))	('human', 'Species', '9606', (255, 260))	('internalize', 'MPA', (165, 176))	('antibodies', 'Var', (18, 28))	('alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid', 'Chemical', 'MESH:D018350', (72, 128))
29073	30242309	These findings are typical of neuropathic pain models and consistent with a contribution of CASPR2 antibodies to producing pain via an effect at the levels of the dorsal root in NMT.	('neuropathic pain', 'Disease', (30, 46))	('pain', 'Disease', 'MESH:D010146', (42, 46))	('pain', 'Disease', (42, 46))	('antibodies', 'Var', (99, 109))	('effect', 'Reg', (135, 141))	('CASPR2', 'Gene', (92, 98))	('producing', 'Disease', (113, 122))	('neuropathic pain', 'Disease', 'MESH:D009437', (30, 46))	('pain', 'Phenotype', 'HP:0012531', (123, 127))	('pain', 'Disease', 'MESH:D010146', (123, 127))	('pain', 'Disease', (123, 127))	('pain', 'Phenotype', 'HP:0012531', (42, 46))
29091	30242309	Moreover, although heterogeneity of clinical features and related antibodies may limit interpretation of significant correlations, the coexistence of LGI1 and CASPR2 antibodies may suggest the presence of thymoma, often accompanied by autonomic and central nervous system involvement.	('antibodies', 'Var', (166, 176))	('thymoma', 'Phenotype', 'HP:0100522', (205, 212))	('men', 'Species', '9606', (279, 282))	('LGI1', 'Gene', '9211', (150, 154))	('LGI1', 'Gene', (150, 154))	('thymoma', 'Disease', 'MESH:D013945', (205, 212))	('thymoma', 'Disease', (205, 212))	('CASPR2', 'Gene', (159, 165))
29266	28174490	With the lesion size increased, the detection rate of necrosis in lesions increased by CEUS (Table 2).	('CEUS', 'Var', (87, 91))	('CEUS', 'Chemical', '-', (87, 91))	('necrosis', 'Disease', (54, 62))	('necrosis', 'Disease', 'MESH:D009336', (54, 62))
29296	28174490	performed biopsy of peripheral lung masses and revealed that CEUS improved necrosis detection rate and success rate of biopsy as the lesion size increased compared with conventional ultrasound.	('success', 'CPA', (103, 110))	('CEUS', 'Var', (61, 65))	('CEUS', 'Chemical', '-', (61, 65))	('necrosis', 'Disease', 'MESH:D009336', (75, 83))	('improved', 'PosReg', (66, 74))	('biopsy', 'CPA', (119, 125))	('necrosis', 'Disease', (75, 83))
29316	28174490	Last, although CEUS improved the accuracy rate of biopsy compared to conventional ultrasound, there was high risk for biopsy in lesions close to heart or large vessels.	('improved', 'PosReg', (20, 28))	('accuracy', 'MPA', (33, 41))	('biopsy', 'CPA', (50, 56))	('CEUS', 'Var', (15, 19))	('CEUS', 'Chemical', '-', (15, 19))
29318	28174490	CEUS prior to biopsy could improve the accuracy rate of biopsy, reduce the risk of complications, and thus become clinically important for mediastinal biopsy.	('biopsy', 'CPA', (56, 62))	('accuracy', 'MPA', (39, 47))	('reduce', 'NegReg', (64, 70))	('CEUS', 'Var', (0, 4))	('CEUS', 'Chemical', '-', (0, 4))	('improve', 'PosReg', (27, 34))
29327	27999265	Almost all thymoma-associated MG (TAMG) patients have antibodies to the AChR; very rare exceptions have been seen in anti-MuSK+ or in double seronegative patients, while anti-LRP4 autoantibodies have not been reported.	('TAMG', 'Chemical', '-', (34, 38))	('antibodies', 'Var', (54, 64))	('thymoma', 'Disease', 'MESH:D013945', (11, 18))	('AChR', 'Protein', (72, 76))	('thymoma', 'Disease', (11, 18))	('thymoma', 'Phenotype', 'HP:0100522', (11, 18))
29328	27999265	The molecular events that characterize thymic neoplasms, including point mutations, chromosomal aberrations, and epigenetic modifications, such as changes in DNA methylation, have been described in the last few years.	('chromosomal aberrations', 'Phenotype', 'HP:0040012', (84, 107))	('neoplasms', 'Phenotype', 'HP:0002664', (46, 55))	('DNA', 'MPA', (158, 161))	('thymic neoplasms', 'Disease', 'MESH:D013953', (39, 55))	('changes', 'Reg', (147, 154))	('thymic neoplasms', 'Disease', (39, 55))	('neoplasm', 'Phenotype', 'HP:0002664', (46, 54))	('thymic neoplasm', 'Phenotype', 'HP:0100521', (39, 54))	('point mutations', 'Var', (67, 82))	('thymic neoplasms', 'Phenotype', 'HP:0100521', (39, 55))
29329	27999265	Aberrant DNA methylation is the most widespread epigenetic alteration in carcinogenesis, and consists of the addition of a methyl group to cytosines, mainly in a CpG dinucleotide context, leading to gene silencing when occurring in the promoter region of a gene.	('carcinogenesis', 'Disease', (73, 87))	('Aberrant', 'Var', (0, 8))	('methylation', 'Var', (13, 24))	('cytosines', 'Chemical', 'MESH:D003596', (139, 148))	('carcinogenesis', 'Disease', 'MESH:D063646', (73, 87))	('gene', 'MPA', (199, 203))
29331	27999265	Interestingly, promoter methylation of the CDKN2A gene was reported in up to 11% of thymomas and 25% of thymic carcinoma, while aberrant MGMT methylation and loss of its protein expression was more frequent in thymic carcinoma than in thymoma.	('thymoma', 'Disease', (235, 242))	('reported', 'Reg', (59, 67))	('CDKN2A', 'Gene', (43, 49))	('carcinoma', 'Phenotype', 'HP:0030731', (217, 226))	('thymoma', 'Phenotype', 'HP:0100522', (84, 91))	('aberrant', 'Var', (128, 136))	('thymoma', 'Phenotype', 'HP:0100522', (235, 242))	('promoter', 'MPA', (15, 23))	('protein expression', 'MPA', (170, 188))	('thymic carcinoma', 'Disease', 'MESH:D013953', (210, 226))	('thymomas', 'Disease', 'MESH:D013945', (84, 92))	('carcinoma', 'Phenotype', 'HP:0030731', (111, 120))	('thymomas', 'Disease', (84, 92))	('thymic carcinoma', 'Disease', 'MESH:D013953', (104, 120))	('thymic carcinoma', 'Disease', (210, 226))	('thymoma', 'Disease', 'MESH:D013945', (84, 91))	('thymoma', 'Disease', 'MESH:D013945', (235, 242))	('thymic carcinoma', 'Disease', (104, 120))	('loss', 'NegReg', (158, 162))	('thymoma', 'Disease', (84, 91))
29337	27999265	DNMT3B and DNMT1 studied regions were largely hypomethylated both in blood and tumor tissue DNA.	('tumor', 'Disease', 'MESH:D009369', (79, 84))	('hypomethylated', 'Var', (46, 60))	('tumor', 'Phenotype', 'HP:0002664', (79, 84))	('tumor', 'Disease', (79, 84))
29348	27999265	MTHFR is one of the major enzymes in folate metabolism since it catalyzes the irreversible conversion of 5,10-methylene THF (the methyl donor in the conversion of dUMP to dTMP) into 5-methyl THF, which remethylates homocysteine to methionine, necessary for the formation of S-adenosylmethionine, the universal donor of methyl groups; therefore, this key protein controls whether folate is partitioned towards DNA precursor synthesis or DNA methylation, and an alteration of this enzyme can interfere with the provision of methyl groups necessary for DNA methylation reactions.	('S-adenosylmethionine', 'Chemical', 'MESH:D012436', (274, 294))	('5,10-methylene THF', 'Chemical', '-', (105, 123))	('methionine', 'Chemical', 'MESH:D008715', (231, 241))	('methionine', 'Chemical', 'MESH:D008715', (284, 294))	('homocysteine', 'Chemical', 'MESH:D006710', (215, 227))	('interfere', 'NegReg', (490, 499))	('folate', 'Chemical', 'MESH:D005492', (379, 385))	('alteration', 'Var', (460, 470))	('folate', 'Chemical', 'MESH:D005492', (37, 43))
29350	27999265	Moreover, it is also emerging that MTHFR hypermethylation could be involved in cancer formation; in fact, a correlation between MTHFR hypermethylation and lung cancer or cervical cancer lesions was observed.	('MTHFR', 'Gene', (128, 133))	('cancer', 'Disease', 'MESH:D009369', (160, 166))	('cancer', 'Phenotype', 'HP:0002664', (79, 85))	('cancer', 'Phenotype', 'HP:0002664', (179, 185))	('cancer', 'Disease', (160, 166))	('cancer', 'Disease', 'MESH:D009369', (79, 85))	('lung cancer', 'Disease', (155, 166))	('correlation', 'Interaction', (108, 119))	('lung cancer', 'Phenotype', 'HP:0100526', (155, 166))	('cancer', 'Disease', 'MESH:D009369', (179, 185))	('cancer', 'Phenotype', 'HP:0002664', (160, 166))	('cancer', 'Disease', (79, 85))	('lung cancer', 'Disease', 'MESH:D008175', (155, 166))	('hypermethylation', 'Var', (134, 150))	('cancer', 'Disease', (179, 185))
29353	27999265	The silencing of MTHFR could cause a significant decrease in the global 5-methylcytosine content, leading to the activation of proto-oncogenes, as well as to global hypomethylation, as demonstrated in lung cancer by Vaissiere and coworkers.	('global 5-methylcytosine content', 'MPA', (65, 96))	('cancer', 'Phenotype', 'HP:0002664', (206, 212))	('lung cancer', 'Disease', 'MESH:D008175', (201, 212))	('5-methylcytosine', 'Chemical', 'MESH:D044503', (72, 88))	('decrease', 'NegReg', (49, 57))	('activation', 'PosReg', (113, 123))	('global hypomethylation', 'MPA', (158, 180))	('MTHFR', 'Gene', (17, 22))	('proto-oncogenes', 'MPA', (127, 142))	('lung cancer', 'Phenotype', 'HP:0100526', (201, 212))	('lung cancer', 'Disease', (201, 212))	('silencing', 'Var', (4, 13))
29355	27999265	In this regard, it was suggested that MTHFR hypermethylation might confer a growth advantage to cancer cells and contribute to the cancer phenotype in tumors of the upper aero-digestive tract.	('cancer', 'Disease', (131, 137))	('tumor', 'Phenotype', 'HP:0002664', (151, 156))	('growth advantage', 'CPA', (76, 92))	('cancer', 'Phenotype', 'HP:0002664', (96, 102))	('contribute', 'Reg', (113, 123))	('tumors', 'Disease', (151, 157))	('tumors', 'Disease', 'MESH:D009369', (151, 157))	('tumors', 'Phenotype', 'HP:0002664', (151, 157))	('cancer', 'Phenotype', 'HP:0002664', (131, 137))	('MTHFR', 'Gene', (38, 43))	('hypermethylation', 'Var', (44, 60))	('cancer', 'Disease', 'MESH:D009369', (96, 102))	('cancer', 'Disease', 'MESH:D009369', (131, 137))	('cancer', 'Disease', (96, 102))
29357	27999265	This study revealed a clear involvement of MTHFR promoter methylation in TAMG, particularly the higher methylation levels in tumor tissue with respect to other tissues.	('involvement', 'Reg', (28, 39))	('tumor', 'Disease', 'MESH:D009369', (125, 130))	('MTHFR', 'Gene', (43, 48))	('TAMG', 'Chemical', '-', (73, 77))	('tumor', 'Phenotype', 'HP:0002664', (125, 130))	('methylation levels', 'MPA', (103, 121))	('tumor', 'Disease', (125, 130))	('methylation', 'Var', (58, 69))	('higher', 'PosReg', (96, 102))
29359	27999265	Obviously other studies need to further explore the significance of MTHFR methylation in TAMG, in order to better understand its pathogenic role in the onset of thymomas.	('methylation', 'Var', (74, 85))	('MTHFR', 'Gene', (68, 73))	('thymoma', 'Phenotype', 'HP:0100522', (161, 168))	('thymomas', 'Disease', (161, 169))	('thymomas', 'Disease', 'MESH:D013945', (161, 169))	('TAMG', 'Chemical', '-', (89, 93))
29360	27999265	The MTHFR protein is also required for the synthesis of DNA precursors, and impairments of this protein could contribute to cancer development by increasing the rate of point mutations and chromosome instability in rapidly dividing cells.	('increasing', 'PosReg', (146, 156))	('cancer', 'Disease', (124, 130))	('chromosome instability', 'Phenotype', 'HP:0040012', (189, 211))	('impairments', 'Var', (76, 87))	('cancer', 'Phenotype', 'HP:0002664', (124, 130))	('chromosome instability', 'CPA', (189, 211))	('point mutations', 'Var', (169, 184))	('contribute', 'Reg', (110, 120))	('cancer', 'Disease', 'MESH:D009369', (124, 130))
29362	27999265	In this regard, it was observed that females with increased BRCA1 blood methylation have a 3.5-fold increased risk for early-onset breast cancer with histological features commonly seen in tumors arising in women with germline BRCA1 mutations.	('BRCA1', 'Gene', (60, 65))	('tumor', 'Phenotype', 'HP:0002664', (189, 194))	('increased', 'PosReg', (50, 59))	('BRCA1', 'Gene', (227, 232))	('tumors', 'Disease', (189, 195))	('tumors', 'Disease', 'MESH:D009369', (189, 195))	('tumors', 'Phenotype', 'HP:0002664', (189, 195))	('cancer', 'Phenotype', 'HP:0002664', (138, 144))	('breast cancer', 'Disease', 'MESH:D001943', (131, 144))	('breast cancer', 'Disease', (131, 144))	('mutations', 'Var', (233, 242))	('breast cancer', 'Phenotype', 'HP:0003002', (131, 144))
29363	27999265	Similarly, glutathione S-transferase 1 (GSTP1) promoter methylation in peripheral DNA is regarded as a potential prognostic marker of prostate cancer.	('GSTP1', 'Gene', (40, 45))	('cancer', 'Phenotype', 'HP:0002664', (143, 149))	('prostate cancer', 'Disease', (134, 149))	('glutathione', 'Chemical', 'MESH:D005978', (11, 22))	('prostate cancer', 'Disease', 'MESH:D011471', (134, 149))	('methylation', 'Var', (56, 67))	('prostate cancer', 'Phenotype', 'HP:0012125', (134, 149))
29372	27999265	In early tumor stages, DNMTs seem to lead to methylation-associated repression of tumor suppressor genes and to promote tumor initiation, while in advanced tumor stages the downregulation of de novo DNMTs seems to be associated with promoter DNA hypomethylation of specific oncogenes and, consequently, would promote tumorigenesis.	('tumor', 'Phenotype', 'HP:0002664', (317, 322))	('tumor', 'Disease', (156, 161))	('tumor', 'Disease', (82, 87))	('downregulation', 'NegReg', (173, 187))	('promoter DNA hypomethylation', 'Var', (233, 261))	('promote', 'PosReg', (112, 119))	('tumor', 'Disease', 'MESH:D009369', (156, 161))	('tumor', 'Disease', 'MESH:D009369', (82, 87))	('repression', 'NegReg', (68, 78))	('tumor', 'Disease', (9, 14))	('methylation-associated', 'MPA', (45, 67))	('promote', 'PosReg', (309, 316))	('tumor', 'Disease', (120, 125))	('tumor', 'Disease', 'MESH:D009369', (9, 14))	('tumor', 'Disease', (317, 322))	('tumor', 'Phenotype', 'HP:0002664', (156, 161))	('tumor', 'Disease', 'MESH:D009369', (120, 125))	('tumor', 'Phenotype', 'HP:0002664', (82, 87))	('tumor initiation', 'Disease', 'MESH:D009369', (120, 136))	('tumor', 'Disease', 'MESH:D009369', (317, 322))	('tumor initiation', 'Disease', (120, 136))	('tumor', 'Phenotype', 'HP:0002664', (9, 14))	('tumor', 'Phenotype', 'HP:0002664', (120, 125))
29375	27999265	Aberrant DNMT3A methylation was also observed in other cancers, such as in acute myeloid leukemia and in breast cancer, where DNMT3A expression is associated with advanced stages.	('cancers', 'Disease', 'MESH:D009369', (55, 62))	('leukemia', 'Phenotype', 'HP:0001909', (89, 97))	('acute myeloid leukemia', 'Disease', (75, 97))	('myeloid leukemia', 'Phenotype', 'HP:0012324', (81, 97))	('cancer', 'Phenotype', 'HP:0002664', (55, 61))	('observed', 'Reg', (37, 45))	('acute myeloid leukemia', 'Disease', 'MESH:D015470', (75, 97))	('acute myeloid leukemia', 'Phenotype', 'HP:0004808', (75, 97))	('DNMT3A', 'Gene', (9, 15))	('breast cancer', 'Disease', 'MESH:D001943', (105, 118))	('cancers', 'Phenotype', 'HP:0002664', (55, 62))	('cancer', 'Phenotype', 'HP:0002664', (112, 118))	('breast cancer', 'Disease', (105, 118))	('methylation', 'Var', (16, 27))	('cancers', 'Disease', (55, 62))	('breast cancer', 'Phenotype', 'HP:0003002', (105, 118))
29376	27999265	Studies performed in mice with conditional knockout of Dnmt3a revealed a role for DNA methylation in mediating the self-renewal and differentiation of normal hematopoietic stem cells and leukemia stem cells.	('Dnmt3a', 'Gene', (55, 61))	('methylation', 'Var', (86, 97))	('differentiation', 'CPA', (132, 147))	('leukemia', 'Disease', (187, 195))	('leukemia', 'Phenotype', 'HP:0001909', (187, 195))	('leukemia', 'Disease', 'MESH:D007938', (187, 195))	('self-renewal', 'CPA', (115, 127))
29377	27999265	A functional role of this gene in thymic epithelial tumors emerged from studies that focused on mutation analysis, revealing that DNMT3A is one the most frequently mutated genes in thymic carcinoma, and that the mutation p.G728D is associated with B3 thymomas.	('thymomas', 'Disease', (251, 259))	('thymomas', 'Disease', 'MESH:D013945', (251, 259))	('tumor', 'Phenotype', 'HP:0002664', (52, 57))	('DNMT3A', 'Gene', (130, 136))	('tumors', 'Phenotype', 'HP:0002664', (52, 58))	('p.G728D', 'Var', (221, 228))	('p.G728D', 'Mutation', 'p.G728D', (221, 228))	('thymic epithelial tumors', 'Disease', (34, 58))	('thymic epithelial tumors', 'Disease', 'MESH:C536905', (34, 58))	('thymoma', 'Phenotype', 'HP:0100522', (251, 258))	('thymic carcinoma', 'Disease', (181, 197))	('thymic carcinoma', 'Disease', 'MESH:D013953', (181, 197))	('associated', 'Reg', (232, 242))	('carcinoma', 'Phenotype', 'HP:0030731', (188, 197))
29379	27999265	From the DNA promoter methylation analyses performed in this study, the involvement of MTHFR and DNMT3A methylation in thymoma-associated myasthenia gravis has been proven, even if other studies are needed to assess a potential pathogenic role of these genes in TAMG.	('DNMT3A', 'Gene', (97, 103))	('TAMG', 'Chemical', '-', (262, 266))	('thymoma-associated myasthenia gravis', 'Disease', (119, 155))	('thymoma-associated myasthenia gravis', 'Disease', 'MESH:D009157', (119, 155))	('thymoma', 'Phenotype', 'HP:0100522', (119, 126))	('methylation', 'Var', (104, 115))	('MTHFR', 'Gene', (87, 92))	('myasthenia', 'Phenotype', 'HP:0003473', (138, 148))	('involvement', 'Reg', (72, 83))
29438	25230752	Clinical and serologic parallels to APS-I in patients with thymomas, and autoantigen transcripts in their tumors1 Patients with the autoimmune polyendocrine syndrome type I (APS-I), caused by mutations in the autoimmune regulator (AIRE) gene, and myasthenia gravis (MG) with thymoma, show intriguing but unexplained parallels.	('APS-I', 'Gene', (174, 179))	('autoimmune regulator', 'Gene', (209, 229))	('thymoma', 'Disease', (59, 66))	('patients', 'Species', '9606', (45, 53))	('thymoma', 'Phenotype', 'HP:0100522', (59, 66))	('mutations', 'Var', (192, 201))	('APS-I', 'Gene', '326', (36, 41))	('myasthenia gravis', 'Disease', (247, 264))	('AIRE', 'Gene', (231, 235))	('thymomas', 'Disease', 'MESH:D013945', (59, 67))	('myasthenia', 'Phenotype', 'HP:0003473', (247, 257))	('APS-I', 'Gene', (36, 41))	('thymomas', 'Disease', (59, 67))	('thymoma', 'Disease', 'MESH:D013945', (275, 282))	('autoimmune polyendocrine syndrome type I', 'Gene', '326', (132, 172))	('tumors', 'Phenotype', 'HP:0002664', (106, 112))	('APS-I', 'Gene', '326', (174, 179))	('thymoma', 'Disease', 'MESH:D013945', (59, 66))	('myasthenia gravis', 'Disease', 'MESH:D009157', (247, 264))	('autoimmune polyendocrine syndrome type I', 'Gene', (132, 172))	('thymoma', 'Disease', (275, 282))	('thymoma', 'Phenotype', 'HP:0100522', (275, 282))	('autoimmune regulator', 'Gene', '326', (209, 229))	('Patients', 'Species', '9606', (114, 122))
29439	25230752	They include uncommon manifestations like autoimmune adrenal insufficiency (AI), hypoparathyroidism (HP), and chronic mucocutaneous candidiasis (CMC) plus autoantibodies neutralizing IL-17, IL-22 and type I interferons.	('neutralizing', 'Var', (170, 182))	('IL-22', 'Gene', (190, 195))	('hypoparathyroidism', 'Disease', (81, 99))	('adrenal insufficiency', 'Phenotype', 'HP:0000846', (53, 74))	('hypoparathyroidism', 'Phenotype', 'HP:0000829', (81, 99))	('IL-17', 'Gene', '3605', (183, 188))	('hypoparathyroidism', 'Disease', 'MESH:D007011', (81, 99))	('IL-17', 'Gene', (183, 188))	('candidiasis', 'Disease', 'MESH:D002177', (132, 143))	('autoimmune adrenal insufficiency', 'Disease', (42, 74))	('autoimmune adrenal insufficiency', 'Disease', 'MESH:D000309', (42, 74))	('IL-22', 'Gene', '50616', (190, 195))	('chronic mucocutaneous candidiasis', 'Phenotype', 'HP:0002728', (110, 143))	('candidiasis', 'Disease', (132, 143))
29456	25230752	Remarkably, at diagnosis almost 100% of these patients have autoAbs neutralizing type I interferons (IFNs), especially IFN-alpha2, IFN-alpha8 and the related IFN-omega.	('patients', 'Species', '9606', (46, 54))	('neutralizing', 'Var', (68, 80))	('autoAbs', 'Var', (60, 67))	('IFN-alpha8', 'Gene', (131, 141))	('IFN-alpha8', 'Gene', '3445', (131, 141))	('IFN-alpha2', 'Gene', (119, 129))	('IFN-alpha2', 'Gene', '3440', (119, 129))
29461	25230752	Occasional thymoma patients have been reported with autoimmune endocrine or ectodermal manifestations, or even CMC plus autoAbs neutralizing IL-17 and IL-22/ deficiencies in Th17 and Th22 cells, very similar to those observed in APS-I.	('patients', 'Species', '9606', (19, 27))	('deficiencies', 'Var', (158, 170))	('IL-17', 'Gene', (141, 146))	('thymoma', 'Disease', 'MESH:D013945', (11, 18))	('IL-17', 'Gene', '3605', (141, 146))	('CMC plus autoAbs', 'Disease', 'MESH:C535816', (111, 127))	('thymoma', 'Disease', (11, 18))	('IL-22', 'Gene', '50616', (151, 156))	('ectodermal manifestations', 'CPA', (76, 101))	('thymoma', 'Phenotype', 'HP:0100522', (11, 18))	('IL-22', 'Gene', (151, 156))	('CMC plus autoAbs', 'Disease', (111, 127))	('neutralizing', 'NegReg', (128, 140))
29489	25230752	Both are unusual in autoimmune patients like these who had no genomic AIRE mutations (asterisked in Table II and Supplemental Table III).	('AIRE', 'Gene', (70, 74))	('patients', 'Species', '9606', (31, 39))	('mutations', 'Var', (75, 84))
29492	25230752	Of the 121 MG patients without thymomas at diagnosis, only one with LOMG (P11) showed clear APS-I-typical features, while another (P12) had pernicious anemia and thyroid disease, and a strong family history of thyroid autoimmunity (Table II).	('thymomas', 'Disease', (31, 39))	('thyroid disease', 'Phenotype', 'HP:0000820', (162, 177))	('thyroid autoimmunity', 'Disease', 'MESH:D013967', (210, 230))	('anemia', 'Phenotype', 'HP:0001903', (151, 157))	('thymomas', 'Disease', 'MESH:D013945', (31, 39))	('autoimmunity', 'Phenotype', 'HP:0002960', (218, 230))	('thymoma', 'Phenotype', 'HP:0100522', (31, 38))	('thyroid disease', 'Disease', (162, 177))	('thyroid autoimmunity', 'Disease', (210, 230))	('anemia', 'Disease', (151, 157))	('LOMG (P11', 'Var', (68, 77))	('anemia', 'Disease', 'MESH:D000740', (151, 157))	('patients', 'Species', '9606', (14, 22))	('thyroid disease', 'Disease', 'MESH:D013959', (162, 177))
29505	25230752	Among 4 such patients, P5 had high-index autoAbs against 21OH and 17OH (Table II), but, unfortunately, we did not have access to his thymoma.	('17OH', 'Protein', (66, 70))	('thymoma', 'Disease', 'MESH:D013945', (133, 140))	('21OH', 'Chemical', '-', (57, 61))	('thymoma', 'Disease', (133, 140))	('patients', 'Species', '9606', (13, 21))	('21OH', 'Protein', (57, 61))	('thymoma', 'Phenotype', 'HP:0100522', (133, 140))	('autoAbs', 'Var', (41, 48))	('17OH', 'Chemical', '-', (66, 70))
29525	25230752	In 3 of the 4 patients with autoimmune thyroid disease (P1, P13 and P14), it presented later than their MG and their thymomas.	('autoimmune thyroid disease', 'Disease', 'MESH:D013967', (28, 54))	('P13', 'Var', (60, 63))	('P1', 'Var', (56, 58))	('thymomas', 'Disease', (117, 125))	('thymomas', 'Disease', 'MESH:D013945', (117, 125))	('thyroid disease', 'Phenotype', 'HP:0000820', (39, 54))	('autoimmune thyroid disease', 'Disease', (28, 54))	('P14', 'Var', (68, 71))	('patients', 'Species', '9606', (14, 22))	('thymoma', 'Phenotype', 'HP:0100522', (117, 124))
29531	25230752	Conversely, AIRE was very low in P21, but she had adrenal autoAbs despite z-scores >2.5 for 17OH and 21OH.	('adrenal autoAbs', 'Disease', 'MESH:D000310', (50, 65))	('17OH', 'Chemical', '-', (92, 96))	('z-scores', 'Var', (74, 82))	('21OH', 'Chemical', '-', (101, 105))	('adrenal autoAbs', 'Disease', (50, 65))
29532	25230752	Overall, these findings provide no clear support for general TSAg under-expression in thymomas as the main cause of the associated autoimmunity.	('under-expression', 'Var', (66, 82))	('thymomas', 'Disease', (86, 94))	('thymomas', 'Disease', 'MESH:D013945', (86, 94))	('thymoma', 'Phenotype', 'HP:0100522', (86, 93))	('autoimmunity', 'Phenotype', 'HP:0002960', (131, 143))	('TSAg', 'Chemical', '-', (61, 65))
29545	25230752	Interestingly too, MG has been reported in rare patients with hypomorphic RAG1 mutations who also have disorganized AIRE-deficient thymi, and/ or IFN-alpha autoAbs, which again implicates aberrant AIRE-deficient thymopoiesis in autoimmunization in these disparate syndromes.	('hypomorphic RAG1', 'Disease', (62, 78))	('AIRE-deficient', 'Disease', (197, 211))	('AIRE-deficient', 'Disease', 'MESH:D016884', (197, 211))	('hypomorphic RAG1', 'Disease', 'None', (62, 78))	('IFN-alpha', 'Gene', '3440', (146, 155))	('AIRE-deficient', 'Disease', (116, 130))	('AIRE-deficient', 'Disease', 'MESH:D016884', (116, 130))	('AIRE-deficient thymopoiesis', 'Disease', 'MESH:D016884', (197, 224))	('AIRE-deficient thymopoiesis', 'Disease', (197, 224))	('IFN-alpha', 'Gene', (146, 155))	('patients', 'Species', '9606', (48, 56))	('mutations', 'Var', (79, 88))
29548	25230752	Similarly, further manifestations appeared >=15 years after initial presentation in several thymoma patients (eg, P1-P3, P8 and P9; Tables II and Supplemental Table SIII), but they might have been missed in many others where pre-thymomectomy follow-up was much shorter, as possibly in a previous study (where only 28 patients were tested for autoAbs).	('P1-P3', 'Var', (114, 119))	('thymoma', 'Disease', 'MESH:D013945', (92, 99))	('thymoma', 'Disease', (92, 99))	('thymoma', 'Phenotype', 'HP:0100522', (92, 99))	('patients', 'Species', '9606', (100, 108))	('patients', 'Species', '9606', (317, 325))
29553	25230752	Whereas APS-I patients have genomic AIRE mutations from conception, the AIRE-deficiency arises only in the tumors and decades later in life in thymoma patients.	('mutations', 'Var', (41, 50))	('AIRE-deficiency', 'Disease', (72, 87))	('thymoma', 'Disease', 'MESH:D013945', (143, 150))	('tumors', 'Disease', (107, 113))	('AIRE-deficiency', 'Disease', 'MESH:D016884', (72, 87))	('tumors', 'Phenotype', 'HP:0002664', (107, 113))	('thymoma', 'Disease', (143, 150))	('patients', 'Species', '9606', (151, 159))	('tumors', 'Disease', 'MESH:D009369', (107, 113))	('thymoma', 'Phenotype', 'HP:0100522', (143, 150))	('patients', 'Species', '9606', (14, 22))	('AIRE', 'Gene', (36, 40))
29627	24444077	Immunohistochemically, the epidermoid cells of the tumor were positive to pan-CK (AE1/AE3), CK5/6, CK7 and p63, but negative to CD5.	('pan-CK', 'Var', (74, 80))	('tumor', 'Phenotype', 'HP:0002664', (51, 56))	('CD5', 'Gene', (128, 131))	('AE1/AE3', 'Gene', (82, 89))	('positive', 'Reg', (62, 70))	('CK7', 'Gene', (99, 102))	('p63', 'Gene', (107, 110))	('tumor', 'Disease', (51, 56))	('CD5', 'Gene', '921', (128, 131))	('CK5/6', 'Gene', '3852', (92, 97))	('CK5/6', 'Gene', (92, 97))	('AE1/AE3', 'Gene', '6521;6508', (82, 89))	('p63', 'Gene', '8626', (107, 110))	('CK7', 'Gene', '3855', (99, 102))	('tumor', 'Disease', 'MESH:D009369', (51, 56))
29633	24444077	By immunohistochemical staining, the neoplastic cells revealed the positivity for pan-CK (AE1/AE3), CK5/6, CK19 and p63, as well as negativity for CD5 and CD117 (Figure 4).	('CK19', 'Gene', (107, 111))	('CD117', 'Var', (155, 160))	('CD5', 'Gene', '921', (147, 150))	('p63', 'Gene', (116, 119))	('CK5/6', 'Gene', (100, 105))	('CK5/6', 'Gene', '3852', (100, 105))	('CK19', 'Gene', '3880', (107, 111))	('p63', 'Gene', '8626', (116, 119))	('AE1/AE3', 'Gene', (90, 97))	('AE1/AE3', 'Gene', '6521;6508', (90, 97))	('pan-CK', 'Protein', (82, 88))	('CD5', 'Gene', (147, 150))
29660	24444077	It is necessary for the further study to clarify if MAML2 rearrangement presents in the rare MEC component of combined thymic epithelial tumors.	('tumors', 'Phenotype', 'HP:0002664', (137, 143))	('rearrangement', 'Var', (58, 71))	('epithelial tumors', 'Disease', (126, 143))	('MAML2', 'Gene', (52, 57))	('MAML2', 'Gene', '84441', (52, 57))	('epithelial tumors', 'Disease', 'MESH:D002277', (126, 143))	('epithelial tumor', 'Phenotype', 'HP:0031492', (126, 142))	('presents', 'Reg', (72, 80))	('tumor', 'Phenotype', 'HP:0002664', (137, 142))
29722	19809436	Each patient was required to fulfil the following criteria: age, 15-70 years; Eastern Cooperative Oncology Group (ECOG) performance status (PS), 0-2; adequate organ function, that is, leukocyte count >=4000 mul-1, platelet count >=105 mul-1, hemoglobin >=10.0 g dl-1, serum creatinine <1.5 mg dl-1, creatinine clearance >=60 ml min-1, serum bilirubin <1.5 mg dl-1, serum alanine transaminase and aspartate transaminase levels less than double the upper limit of the institutional normal range; and PaO2 >=70 mm Hg.	('mul-1', 'Gene', '79594', (207, 212))	('mul-1', 'Gene', (235, 240))	('min-1', 'Gene', '966', (328, 333))	('min-1', 'Gene', (328, 333))	('patient', 'Species', '9606', (5, 12))	('serum creatinine', 'MPA', (268, 284))	('mul-1', 'Gene', '79594', (235, 240))	('mul-1', 'Gene', (207, 212))	('>=10.0 g dl-1', 'Var', (253, 266))	('Oncology', 'Phenotype', 'HP:0002664', (98, 106))	('creatinine clearance', 'MPA', (299, 319))	('serum bilirubin', 'MPA', (335, 350))	('less than', 'NegReg', (426, 435))
29881	32457832	Moreover, both interventions can decrease glucose, glutamine, and growth factor availability, depriving cancer cells of their major fuels and creating an unfavorable physiological environment for unchecked growth and proliferation.	('depriving', 'NegReg', (94, 103))	('glutamine', 'Chemical', 'MESH:D005973', (51, 60))	('decrease', 'NegReg', (33, 41))	('cancer', 'Phenotype', 'HP:0002664', (104, 110))	('interventions', 'Var', (15, 28))	('creating', 'Reg', (142, 150))	('glutamine', 'MPA', (51, 60))	('major fuels', 'MPA', (126, 137))	('glucose', 'MPA', (42, 49))	('cancer', 'Disease', (104, 110))	('cancer', 'Disease', 'MESH:D009369', (104, 110))	('glucose', 'Chemical', 'MESH:D005947', (42, 49))
29921	32457832	Calorie restriction reduces tumor incidence by 75% in rodents and by 50% in rhesus monkeys.	('tumor', 'Disease', (28, 33))	('reduces', 'NegReg', (20, 27))	('Calorie restriction', 'Var', (0, 19))	('tumor', 'Disease', 'MESH:D009369', (28, 33))	('rhesus monkeys', 'Species', '9544', (76, 90))	('tumor', 'Phenotype', 'HP:0002664', (28, 33))
29989	32143154	Thus, it was diagnosed as clinically T1aN0M0 stage I (Masaoka stage I) thymoma and thymectomy through a median sternotomy was performed.	('thymoma', 'Phenotype', 'HP:0100522', (71, 78))	('T1aN0M0 stage', 'Var', (37, 50))	('thymoma', 'Disease', (71, 78))	('thymoma', 'Disease', 'MESH:D013945', (71, 78))
30174	28787670	About one third are associated with myasthenia gravis and their resection significantly improves the symptoms of myasthenia gravis.	('associated', 'Reg', (20, 30))	('myasthenia', 'Phenotype', 'HP:0003473', (36, 46))	('improves', 'PosReg', (88, 96))	('myasthenia', 'Phenotype', 'HP:0003473', (113, 123))	('myasthenia gravis', 'Disease', (113, 130))	('myasthenia gravis', 'Disease', (36, 53))	('symptoms', 'MPA', (101, 109))	('resection', 'Var', (64, 73))	('myasthenia gravis', 'Disease', 'MESH:D009157', (113, 130))	('myasthenia gravis', 'Disease', 'MESH:D009157', (36, 53))
30208	24885581	As to histological type, five patients had type A, 33 type AB, 19 type B1, 39 type B2, and 15 type B3 thymomas, whereas 68 patients had thymic carcinoma, including 11 with neuroendocrine carcinomas according to the 2004 WHO classification.	('type B1', 'Var', (66, 73))	('neuroendocrine carcinomas', 'Phenotype', 'HP:0100634', (172, 197))	('thymomas', 'Disease', 'MESH:D013945', (102, 110))	('neuroendocrine carcinomas', 'Disease', (172, 197))	('carcinoma', 'Phenotype', 'HP:0030731', (187, 196))	('thymic carcinoma', 'Disease', (136, 152))	('type AB', 'Var', (54, 61))	('patients', 'Species', '9606', (123, 131))	('carcinomas', 'Phenotype', 'HP:0030731', (187, 197))	('neuroendocrine carcinoma', 'Phenotype', 'HP:0100634', (172, 196))	('patients', 'Species', '9606', (30, 38))	('thymoma', 'Phenotype', 'HP:0100522', (102, 109))	('thymic carcinoma', 'Disease', 'MESH:D013945', (136, 152))	('carcinoma', 'Phenotype', 'HP:0030731', (143, 152))	('thymomas', 'Disease', (102, 110))	('neuroendocrine carcinomas', 'Disease', 'MESH:D018278', (172, 197))
30242	24885581	As to histology, according to the 2004 WHO classification five patients had type A, 19 type B1, 39 type B2, 15 type B3, and 33 type AB thymomas.	('type B3', 'Var', (111, 118))	('thymoma', 'Phenotype', 'HP:0100522', (135, 142))	('type AB thymomas', 'Disease', 'MESH:D013945', (127, 143))	('type B2', 'Var', (99, 106))	('patients', 'Species', '9606', (63, 71))	('type AB thymomas', 'Disease', (127, 143))
30277	24885581	Although our results did not demonstrate a significant association between abnormalities or secondary malignancies and survival, some studies have reported that types A and AB thymoma have a low association with myasthenia gravis, whereas types B1 and B2 are more likely to be associated with myasthenia gravis.	('myasthenia', 'Phenotype', 'HP:0003473', (293, 303))	('association', 'Interaction', (195, 206))	('malignancies', 'Disease', 'MESH:D009369', (102, 114))	('myasthenia gravis', 'Disease', 'MESH:D009157', (212, 229))	('myasthenia gravis', 'Disease', (293, 310))	('AB thymoma', 'Disease', 'MESH:D013945', (173, 183))	('malignancies', 'Disease', (102, 114))	('AB thymoma', 'Disease', (173, 183))	('myasthenia', 'Phenotype', 'HP:0003473', (212, 222))	('types A', 'Var', (161, 168))	('myasthenia gravis', 'Disease', 'MESH:D009157', (293, 310))	('myasthenia gravis', 'Disease', (212, 229))	('thymoma', 'Phenotype', 'HP:0100522', (176, 183))
30323	23446204	Higher focal FDG uptake was seen in patients with type B3 thymoma than in those with type A, AB, B1, or B2 thymoma (p<0.006).	('thymoma', 'Phenotype', 'HP:0100522', (107, 114))	('thymoma', 'Gene', (58, 65))	('patients', 'Species', '9606', (36, 44))	('thymoma', 'Gene', '7063', (107, 114))	('type B3', 'Var', (50, 57))	('thymoma', 'Phenotype', 'HP:0100522', (58, 65))	('Higher', 'PosReg', (0, 6))	('thymoma', 'Gene', (107, 114))	('thymoma', 'Gene', '7063', (58, 65))	('FDG', 'Chemical', 'MESH:D019788', (13, 16))	('focal FDG uptake', 'CPA', (7, 23))
30530	25667444	Aberrant WNT signaling has been reported in several tumor types.	('tumor', 'Phenotype', 'HP:0002664', (52, 57))	('Aberrant', 'Var', (0, 8))	('tumor', 'Disease', (52, 57))	('WNT signaling', 'Pathway', (9, 22))	('reported', 'Reg', (32, 40))	('tumor', 'Disease', 'MESH:D009369', (52, 57))
30531	25667444	In particular, stabilizing mutations of beta-catenin in the mouse thymic epithelium blocks thymus development and function.	('mutations', 'Var', (27, 36))	('beta-catenin', 'Protein', (40, 52))	('function', 'CPA', (114, 122))	('blocks', 'NegReg', (84, 90))	('mouse', 'Species', '10090', (60, 65))	('thymus development', 'CPA', (91, 109))
30546	25667444	For CTNNB1, slides were washed with TBST wash buffer (Dako) and then incubated at room temperature for 60 minutes with Signal Stain protein block (Cell Signaling) containing a 1:200 dilution of rabbit monoclonal antibody to CD45, clone EP322Y (Epitomics, Burlingame, CA, USA).	('Dako', 'Chemical', '-', (54, 58))	('rabbit', 'Species', '9986', (194, 200))	('CTNNB1', 'Gene', '1499', (4, 10))	('CD45', 'Gene', '5788', (224, 228))	('rat', 'Species', '10116', (92, 95))	('CTNNB1', 'Gene', (4, 10))	('EP322Y', 'Var', (236, 242))	('CD45', 'Gene', (224, 228))	('TBST wash', 'Chemical', '-', (36, 45))
30559	25667444	Lees-Miller (University of Calgary, Canada); H226 (ATCC), human epithelial lung squamous cell carcinoma; and H522 (ATCC), human epithelial lung adenocarcinoma.	('human', 'Species', '9606', (122, 127))	('carcinoma', 'Phenotype', 'HP:0030731', (94, 103))	('human', 'Species', '9606', (58, 63))	('squamous cell carcinoma', 'Phenotype', 'HP:0002860', (80, 103))	('carcinoma', 'Phenotype', 'HP:0030731', (149, 158))	('epithelial lung squamous cell carcinoma', 'Disease', 'MESH:D002294', (64, 103))	('epithelial lung squamous cell carcinoma', 'Disease', (64, 103))	('H522', 'Var', (109, 113))	('lung adenocarcinoma', 'Phenotype', 'HP:0030078', (139, 158))	('epithelial lung adenocarcinoma', 'Disease', (128, 158))	('lung squamous cell carcinoma', 'Phenotype', 'HP:0030359', (75, 103))	('epithelial lung adenocarcinoma', 'Disease', 'MESH:D000077192', (128, 158))
30564	25667444	A tumor nuclear mask was generated by inverting the cytoplasmic mask within the tumor mask.	('tumor', 'Disease', 'MESH:D009369', (80, 85))	('inverting', 'Var', (38, 47))	('cytoplasmic mask', 'MPA', (52, 68))	('tumor', 'Disease', 'MESH:D009369', (2, 7))	('tumor', 'Phenotype', 'HP:0002664', (80, 85))	('rat', 'Species', '10116', (29, 32))	('tumor', 'Phenotype', 'HP:0002664', (2, 7))	('tumor', 'Disease', (80, 85))	('tumor', 'Disease', (2, 7))
30580	25667444	NOTCH1 mutations and overexpression have been noted in squamous lung and head and neck cancer.	('squamous lung', 'Disease', (55, 68))	('squamous lung', 'Disease', 'MESH:D002294', (55, 68))	('neck cancer', 'Disease', (82, 93))	('head and neck cancer', 'Phenotype', 'HP:0012288', (73, 93))	('cancer', 'Phenotype', 'HP:0002664', (87, 93))	('overexpression', 'PosReg', (21, 35))	('neck cancer', 'Disease', 'MESH:D006258', (82, 93))	('NOTCH1', 'Gene', '4851', (0, 6))	('NOTCH1', 'Gene', (0, 6))	('mutations', 'Var', (7, 16))
30583	25667444	In thymoma microarrays, high gene expression of NOTCH signaling proteins was associated with metastatic disease.	('NOTCH', 'Protein', (48, 53))	('thymoma', 'Disease', 'MESH:D013945', (3, 10))	('thymoma', 'Disease', (3, 10))	('high gene', 'Var', (24, 33))	('thymoma', 'Phenotype', 'HP:0100522', (3, 10))	('metastatic disease', 'Disease', (93, 111))	('associated', 'Reg', (77, 87))
30600	33572388	Thymoma types A and AB are generally considered benign tumors; type B1 is a low-grade malignant tumor (10-year survival rate of 90%); type B2 shows a higher degree of malignancy; and type B3 shows the advanced stage and a poor prognosis, similar to that of thymic carcinoma.	('malignant tumor', 'Disease', (86, 101))	('type B3', 'Var', (183, 190))	('tumor', 'Phenotype', 'HP:0002664', (96, 101))	('benign tumors', 'Disease', (48, 61))	('tumor', 'Phenotype', 'HP:0002664', (55, 60))	('Thymoma', 'Phenotype', 'HP:0100522', (0, 7))	('carcinoma', 'Phenotype', 'HP:0030731', (264, 273))	('thymic carcinoma', 'Disease', 'MESH:D013953', (257, 273))	('tumors', 'Phenotype', 'HP:0002664', (55, 61))	('malignant tumor', 'Disease', 'MESH:D009369', (86, 101))	('Thymoma', 'Disease', (0, 7))	('type B2', 'Var', (134, 141))	('benign tumors', 'Disease', 'MESH:D009369', (48, 61))	('thymic carcinoma', 'Disease', (257, 273))	('malignancy', 'Disease', 'MESH:D009369', (167, 177))	('malignancy', 'Disease', (167, 177))
30701	33402862	On the other hand, the deletion of Meis1 downregulates p21, p15, p16, and p19arf expression in cardiomyocytes and improves the cell cycle (Muralidhar and Sadek, 2016).	('p15', 'Gene', (60, 63))	('p16', 'Gene', '1029', (65, 68))	('cell cycle', 'CPA', (127, 137))	('p15', 'Gene', '1030', (60, 63))	('deletion', 'Var', (23, 31))	('p21', 'Gene', (55, 58))	('Meis1', 'Gene', (35, 40))	('downregulates', 'NegReg', (41, 54))	('p21', 'Gene', '644914', (55, 58))	('p19arf', 'Gene', (74, 80))	('p19arf', 'Gene', '1029', (74, 80))	('p16', 'Gene', (65, 68))	('improves', 'PosReg', (114, 122))	('expression', 'MPA', (81, 91))
30714	33402862	Meis1 is essential for normal hematopoiesis, as was indicated by Meis1 mutant mice having an internal hemorrhage, liver hypoplasia, and anemia (Azcoitia et al., 2005).	('Meis1', 'Gene', (65, 70))	('anemia', 'Phenotype', 'HP:0001903', (136, 142))	('liver hypoplasia', 'Disease', 'MESH:D017093', (114, 130))	('hemorrhage', 'Disease', 'MESH:D006470', (102, 112))	('liver hypoplasia', 'Disease', (114, 130))	('anemia', 'Disease', (136, 142))	('hematopoiesis', 'Disease', 'MESH:C536227', (30, 43))	('anemia', 'Disease', 'MESH:D000740', (136, 142))	('mutant', 'Var', (71, 77))	('Azcoitia', 'Disease', (144, 152))	('hemorrhage', 'Disease', (102, 112))	('hematopoiesis', 'Disease', (30, 43))	('mice', 'Species', '10090', (78, 82))	('Azcoitia', 'Disease', 'None', (144, 152))	('internal hemorrhage', 'Phenotype', 'HP:0011029', (93, 112))
30727	33402862	Under normal circumstances, 11 Hox paralogs in locus C are involved in healthy urogenital development; however, in the case of bladder cancer, these gene family variants are upregulated (Cantile et al., 2003).	('variants', 'Var', (161, 169))	('upregulated', 'PosReg', (174, 185))	('bladder cancer', 'Phenotype', 'HP:0009725', (127, 141))	('men', 'Species', '9606', (97, 100))	('cancer', 'Phenotype', 'HP:0002664', (135, 141))	('bladder cancer', 'Disease', 'MESH:D001749', (127, 141))	('bladder cancer', 'Disease', (127, 141))
30728	33402862	Genetic and epigenetic modifications have an important function in carcinoma formation.	('carcinoma', 'Disease', 'MESH:D009369', (67, 76))	('Genetic', 'Var', (0, 7))	('carcinoma', 'Phenotype', 'HP:0030731', (67, 76))	('epigenetic modifications', 'Var', (12, 36))	('carcinoma', 'Disease', (67, 76))
30729	33402862	DNA hypermethylation is among the most common and characterized epigenetic modification in human malignancies.	('malignancies', 'Disease', 'MESH:D009369', (97, 109))	('human', 'Species', '9606', (91, 96))	('malignancies', 'Disease', (97, 109))	('hypermethylation', 'Var', (4, 20))
30736	33402862	Alternative splicing has a significant function in the posttranscriptional regulation of genes, as well as cancer development or progression.	('posttranscriptional regulation of genes', 'MPA', (55, 94))	('men', 'Species', '9606', (121, 124))	('cancer', 'Phenotype', 'HP:0002664', (107, 113))	('progression', 'CPA', (129, 140))	('function', 'Reg', (39, 47))	('cancer', 'Disease', 'MESH:D009369', (107, 113))	('Alternative splicing', 'Var', (0, 20))	('cancer', 'Disease', (107, 113))
30739	33402862	Moreover, Meis2 knockdown significantly inhibits the migration and invasion capacities of bladder cancer cells (Xie et al., 2019).	('bladder cancer', 'Disease', (90, 104))	('cancer', 'Phenotype', 'HP:0002664', (98, 104))	('knockdown', 'Var', (16, 25))	('invasion capacities', 'CPA', (67, 86))	('bladder cancer', 'Phenotype', 'HP:0009725', (90, 104))	('inhibits', 'NegReg', (40, 48))	('Meis2', 'Gene', (10, 15))	('bladder cancer', 'Disease', 'MESH:D001749', (90, 104))
30748	33402862	Mutations that affect HOX/PBX/MEIS interactions may also contribute to breast cancer (Dard et al., 2018).	('breast cancer', 'Disease', (71, 84))	('breast cancer', 'Phenotype', 'HP:0003002', (71, 84))	('contribute', 'Reg', (57, 67))	('interactions', 'Interaction', (35, 47))	('Mutations', 'Var', (0, 9))	('cancer', 'Phenotype', 'HP:0002664', (78, 84))	('breast cancer', 'Disease', 'MESH:D001943', (71, 84))
30752	33402862	Distant metastasis and associated mortality are closely related to Meis2 expression in colorectal cancer (Wan et al., 2019).	('cancer', 'Phenotype', 'HP:0002664', (98, 104))	('expression', 'Var', (73, 83))	('Meis2', 'Gene', (67, 72))	('colorectal cancer', 'Phenotype', 'HP:0003003', (87, 104))	('mortality', 'Disease', 'MESH:D003643', (34, 43))	('colorectal cancer', 'Disease', (87, 104))	('Distant metastasis', 'CPA', (0, 18))	('mortality', 'Disease', (34, 43))	('colorectal cancer', 'Disease', 'MESH:D015179', (87, 104))
30754	33402862	Moreover, high Meis2 expression may reduce the overall survival period of patients with colorectal cancer (Wan et al., 2019).	('colorectal cancer', 'Disease', (88, 105))	('reduce', 'NegReg', (36, 42))	('patients', 'Species', '9606', (74, 82))	('colorectal cancer', 'Disease', 'MESH:D015179', (88, 105))	('expression', 'MPA', (21, 31))	('cancer', 'Phenotype', 'HP:0002664', (99, 105))	('high', 'Var', (10, 14))	('colorectal cancer', 'Phenotype', 'HP:0003003', (88, 105))	('overall survival period', 'CPA', (47, 70))	('Meis2', 'Protein', (15, 20))
30760	33402862	In addition, the knockdown of Hoxa9 and Hoxa4 in HT29 cells leads to a significant decrease in cell proliferation, and their overexpression causes an increase in the self-renewal ability of colorectal CSCs (Bhatlekar et al., 2018).	('cell proliferation', 'CPA', (95, 113))	('Hoxa4', 'Gene', (40, 45))	('HT29 cells', 'CellLine', 'CVCL:0320', (49, 59))	('Hoxa4', 'Gene', '3201', (40, 45))	('colorectal CSCs', 'Disease', (190, 205))	('colorectal CSCs', 'Disease', 'MESH:D015179', (190, 205))	('decrease', 'NegReg', (83, 91))	('increase', 'PosReg', (150, 158))	('knockdown', 'Var', (17, 26))	('Hoxa9', 'Gene', (30, 35))	('overexpression', 'PosReg', (125, 139))
30769	33402862	(2016) showed that the expression of Meis1 has a reverse association with lymph node involvement, metastasis, and tumor staging in ESCC (Rad et al., 2016).	('tumor', 'Disease', 'MESH:D009369', (114, 119))	('tumor', 'Phenotype', 'HP:0002664', (114, 119))	('lymph node involvement', 'CPA', (74, 96))	('metastasis', 'CPA', (98, 108))	('Meis1', 'Gene', (37, 42))	('tumor', 'Disease', (114, 119))	('expression', 'Var', (23, 33))	('Rad', 'Gene', '6236', (137, 140))	('men', 'Species', '9606', (92, 95))	('Rad', 'Gene', (137, 140))	('ESCC', 'Disease', (131, 135))
30791	33402862	Nuclear receptor SET domain-containing protein-1 (NSD1) silencing by epigenetic modification leads to Sotos syndrome, as well as nonhereditary neuroblastoma and glioma development (Berdasco et al., 2009).	('Nuclear receptor SET domain-containing protein-1', 'Gene', (0, 48))	('NSD1', 'Gene', '64324', (50, 54))	('glioma', 'Disease', 'MESH:D005910', (161, 167))	('Sotos syndrome', 'Disease', 'MESH:D058495', (102, 116))	('neuroblastoma', 'Disease', 'MESH:D009447', (143, 156))	('leads', 'Reg', (93, 98))	('Nuclear receptor SET domain-containing protein-1', 'Gene', '64324', (0, 48))	('glioma', 'Phenotype', 'HP:0009733', (161, 167))	('Sotos syndrome', 'Disease', (102, 116))	('neuroblastoma', 'Disease', (143, 156))	('epigenetic modification', 'Var', (69, 92))	('NSD1', 'Gene', (50, 54))	('glioma', 'Disease', (161, 167))	('neuroblastoma', 'Phenotype', 'HP:0003006', (143, 156))	('silencing', 'NegReg', (56, 65))	('men', 'Species', '9606', (175, 178))
30792	33402862	Hypermethylation of Nsd1 causes the upregulation of Meis1 transcript and protein due to the absence of NSD1 binding to the Meis1 promoter in neuroblastoma cells (Berdasco et al., 2009).	('neuroblastoma', 'Disease', 'MESH:D009447', (141, 154))	('absence', 'NegReg', (92, 99))	('Meis1', 'Gene', (52, 57))	('Nsd1', 'Gene', (20, 24))	('neuroblastoma', 'Disease', (141, 154))	('NSD1', 'Gene', (103, 107))	('Hypermethylation', 'Var', (0, 16))	('binding', 'Interaction', (108, 115))	('protein', 'Protein', (73, 80))	('upregulation', 'PosReg', (36, 48))	('neuroblastoma', 'Phenotype', 'HP:0003006', (141, 154))	('transcript', 'MPA', (58, 68))	('Nsd1', 'Gene', '64324', (20, 24))	('NSD1', 'Gene', '64324', (103, 107))
30814	33402862	Intriguingly, stable transfection of the dominant-negative variant of MEIS1 has generated clones with altered cell proliferation, increased differentiated phenotype, and elevated contact inhibition and cell death.	('elevated', 'PosReg', (170, 178))	('death', 'Disease', 'MESH:D003643', (207, 212))	('death', 'Disease', (207, 212))	('differentiated phenotype', 'CPA', (140, 164))	('contact inhibition', 'CPA', (179, 197))	('MEIS1', 'Gene', (70, 75))	('cell proliferation', 'CPA', (110, 128))	('variant', 'Var', (59, 66))	('increased', 'PosReg', (130, 139))	('altered', 'Reg', (102, 109))
30832	33402862	Mutations in the MEIS-HOX signaling pathway and its downstream proteins have been found to cause MLL (Zhou et al., 2014).	('cause', 'Reg', (91, 96))	('MEIS-HOX signaling pathway', 'Pathway', (17, 43))	('Mutations', 'Var', (0, 9))	('MLL', 'Gene', (97, 100))	('MLL', 'Gene', '4297', (97, 100))
30834	33402862	In vivo studies have shown that PU.1 mutation contributes to MLL development by modulating MEIS-HOX downstream genes (Zhou et al., 2014).	('MLL', 'Gene', '4297', (61, 64))	('mutation', 'Var', (37, 45))	('MLL', 'Gene', (61, 64))	('men', 'Species', '9606', (72, 75))	('modulating', 'Reg', (80, 90))	('MEIS-HOX downstream genes', 'Gene', (91, 116))	('PU.1', 'Gene', '6688', (32, 36))	('contributes', 'Reg', (46, 57))	('PU.1', 'Gene', (32, 36))
30839	33402862	In cases with an inactivation mutation of Meis1 in fetal liver cells, myeloid transformation loses its capability for the differentiation and self-renewal of leukemia stem cells (Wong et al., 2007).	('Meis1', 'Gene', (42, 47))	('loses', 'NegReg', (93, 98))	('leukemia', 'Disease', (158, 166))	('leukemia', 'Phenotype', 'HP:0001909', (158, 166))	('leukemia', 'Disease', 'MESH:D007938', (158, 166))	('myeloid transformation', 'CPA', (70, 92))	('inactivation mutation', 'Var', (17, 38))
30849	33402862	Moreover, pre-B-cell ALL patients were observed to have E2A-PBX1 chimeric oncoprotein resulting from chromosomal translocation t(1;19), and translocation results in mutant oncoprotein (Carroll et al., 1984).	('t(1;19', 'Var', (127, 133))	('translocation', 'Var', (140, 153))	('PBX1', 'Gene', (60, 64))	('mutant', 'Var', (165, 171))	('E2A', 'Gene', '6929', (56, 59))	('oncoprotein', 'Protein', (74, 85))	('E2A', 'Gene', (56, 59))	('results in', 'Reg', (154, 164))	('pre-B', 'Gene', (10, 15))	('patients', 'Species', '9606', (25, 33))	('oncoprotein', 'Protein', (172, 183))	('PBX1', 'Gene', '5087', (60, 64))	('chimeric', 'Var', (65, 73))	('pre-B', 'Gene', '10113', (10, 15))
30851	33402862	MEIS1 and MEIS2 interact with HOX and PBX variants in leukemia (Garcia-Cuellar et al., 2015).	('leukemia', 'Disease', (54, 62))	('Garcia-Cuellar', 'Disease', (64, 78))	('leukemia', 'Phenotype', 'HP:0001909', (54, 62))	('variants', 'Var', (42, 50))	('Garcia-Cuellar', 'Disease', 'MESH:C536767', (64, 78))	('PBX', 'Gene', (38, 41))	('leukemia', 'Disease', 'MESH:D007938', (54, 62))
30852	33402862	The presence of PBX3 and MEIS1 increases HOXA9-induced leukemia (Garcia-Cuellar et al., 2015).	('PBX3', 'Gene', '5090', (16, 20))	('Garcia-Cuellar', 'Disease', 'MESH:C536767', (65, 79))	('leukemia', 'Phenotype', 'HP:0001909', (55, 63))	('increases', 'PosReg', (31, 40))	('leukemia', 'Disease', 'MESH:D007938', (55, 63))	('HOXA9', 'Gene', '3205', (41, 46))	('Garcia-Cuellar', 'Disease', (65, 79))	('leukemia', 'Disease', (55, 63))	('MEIS1', 'Gene', (25, 30))	('HOXA9', 'Gene', (41, 46))	('presence', 'Var', (4, 12))	('PBX3', 'Gene', (16, 20))
30858	33402862	The deletion of Meis2 differentially modulates TAL1, and thereby impairs endothelial specification and endothelial to hematopoietic transition (Wang et al., 2018b).	('Meis2', 'Gene', (16, 21))	('TAL1', 'Gene', '6886', (47, 51))	('impairs', 'NegReg', (65, 72))	('endothelial to hematopoietic transition', 'CPA', (103, 142))	('TAL1', 'Gene', (47, 51))	('endothelial specification', 'CPA', (73, 98))	('modulates', 'Reg', (37, 46))	('deletion', 'Var', (4, 12))
30859	33402862	Aberrant expression of Tlx1/Hox11 also results in T-cell leukemogenesis via Meis1 and Meis2 (Milech et al., 2010).	('Aberrant expression', 'Var', (0, 19))	('results in', 'Reg', (39, 49))	('Hox11', 'Gene', (28, 33))	('T-cell leukemogenesis', 'Phenotype', 'HP:0005517', (50, 71))	('T-cell leukemogenesis', 'Disease', (50, 71))	('Hox11', 'Gene', '15404', (28, 33))
30860	33402862	It has been found that Meis1/Hoxa9 deregulation has an important function in the progression of leukemia (Collins and Hess, 2016).	('deregulation', 'Var', (35, 47))	('leukemia', 'Disease', (96, 104))	('leukemia', 'Phenotype', 'HP:0001909', (96, 104))	('leukemia', 'Disease', 'MESH:D007938', (96, 104))	('Meis1/Hoxa9', 'Gene', (23, 34))
30861	33402862	Meis1 mutations lead blood cells to develop the symptoms of leukemia, as well as gain the chemoresistance and proliferation of leukemia cells by triggering other MEIS-cofactors (summarized in Table 1).	('gain', 'PosReg', (81, 85))	('leukemia', 'Phenotype', 'HP:0001909', (60, 68))	('leukemia', 'Disease', (127, 135))	('leukemia', 'Phenotype', 'HP:0001909', (127, 135))	('leukemia', 'Disease', 'MESH:D007938', (127, 135))	('leukemia', 'Disease', 'MESH:D007938', (60, 68))	('proliferation', 'CPA', (110, 123))	('develop', 'PosReg', (36, 43))	('chemoresistance', 'CPA', (90, 105))	('Meis1', 'Gene', (0, 5))	('leukemia', 'Disease', (60, 68))	('mutations', 'Var', (6, 15))
30862	33402862	The ectopic expression of Meis1 has been shown to inhibit cell proliferation in nonsmall-cell lung cancer (NSCLC) (Li et al., 2014).	('nonsmall-cell lung cancer', 'Disease', 'MESH:D002289', (80, 105))	('NSCLC', 'Disease', (107, 112))	('inhibit', 'NegReg', (50, 57))	('cell proliferation', 'CPA', (58, 76))	('NSCLC', 'Disease', 'MESH:D002289', (107, 112))	('nonsmall-cell lung cancer', 'Disease', (80, 105))	('lung cancer', 'Phenotype', 'HP:0100526', (94, 105))	('Meis1', 'Gene', (26, 31))	('ectopic expression', 'Var', (4, 22))	('cancer', 'Phenotype', 'HP:0002664', (99, 105))
30875	33402862	Blocking of HIF-1alpha complexes has been shown to cause increased metastasis and angiogenesis and an increase in cancer cell proliferation (Lin et al., 2017; Yang et al., 2017).	('cancer', 'Disease', 'MESH:D009369', (114, 120))	('Blocking', 'Var', (0, 8))	('angiogenesis', 'CPA', (82, 94))	('metastasis', 'CPA', (67, 77))	('HIF-1alpha', 'Gene', (12, 22))	('cancer', 'Phenotype', 'HP:0002664', (114, 120))	('increase', 'PosReg', (102, 110))	('increased', 'PosReg', (57, 66))	('HIF-1alpha', 'Gene', '3091', (12, 22))	('cancer', 'Disease', (114, 120))
30877	33402862	Surprisingly, however, cells that have a high expression of HIF-2alpha are more aggressive against radiotherapy and FDG uptake (Sun et al., 2015; Higashi et al., 2016).	('more', 'PosReg', (75, 79))	('high expression', 'Var', (41, 56))	('HIF-2alpha', 'Gene', (60, 70))	('HIF-2alpha', 'Gene', '2034', (60, 70))	('FDG', 'Chemical', 'MESH:D019788', (116, 119))
30888	33402862	Moreover, it has been shown that miRNA-196a modulates the expression of target genes (cadherin-11, calponin-1, and osteopontin) by regulating Hoxc8 in melanocyte and melanoma cells (Mueller and Bosserhoff, 2011).	('melanoma', 'Phenotype', 'HP:0002861', (166, 174))	('melanoma', 'Disease', (166, 174))	('modulates', 'Reg', (44, 53))	('calponin-1', 'Gene', '1264', (99, 109))	('Hoxc8', 'Gene', (142, 147))	('miRNA-196a', 'Var', (33, 43))	('expression', 'MPA', (58, 68))	('osteopontin', 'Gene', '6696', (115, 126))	('melanoma', 'Disease', 'MESH:D008545', (166, 174))	('cadherin-11', 'Gene', '1009', (86, 97))	('Hoxc8', 'Gene', '3224', (142, 147))	('osteopontin', 'Gene', (115, 126))	('cadherin-11', 'Gene', (86, 97))	('regulating', 'Reg', (131, 141))	('calponin-1', 'Gene', (99, 109))
30890	33402862	Furthermore, the knockdown of Pbx1 by short interfering RNAs (siRNA) leads to the suppression of cell growth (Shiraishi et al., 2007).	('Pbx1', 'Gene', (30, 34))	('cell growth', 'CPA', (97, 108))	('knockdown', 'Var', (17, 26))	('Pbx1', 'Gene', '5087', (30, 34))	('suppression', 'NegReg', (82, 93))
30895	33402862	Moreover, a detailed DNA methylation analysis of all stages of human melanoma revealed that Hoxa9 DNA hypermethylation had a function in tumor development when compared to benign samples (Wouters et al., 2017).	('melanoma', 'Disease', 'MESH:D008545', (69, 77))	('tumor', 'Disease', (137, 142))	('tumor', 'Disease', 'MESH:D009369', (137, 142))	('human', 'Species', '9606', (63, 68))	('Hoxa9', 'Var', (92, 97))	('men', 'Species', '9606', (150, 153))	('hypermethylation', 'Var', (102, 118))	('melanoma', 'Phenotype', 'HP:0002861', (69, 77))	('tumor', 'Phenotype', 'HP:0002664', (137, 142))	('melanoma', 'Disease', (69, 77))
30899	33402862	Following the disruption of HOX-PBX interaction with double active peptide, c-Fos expression increases and apoptosis takes place (Platais et al., 2018).	('expression', 'MPA', (82, 92))	('c-Fos', 'Gene', '2353', (76, 81))	('increases', 'PosReg', (93, 102))	('interaction', 'Interaction', (36, 47))	('disruption', 'Var', (14, 24))	('apoptosis', 'CPA', (107, 116))	('c-Fos', 'Gene', (76, 81))
30901	33402862	The misregulated expression of Hoxc6 and Hoxa10 cluster proteins are involved in the proliferation, survival and migration of oral cell carcinoma.	('oral cell carcinoma', 'Disease', (126, 145))	('Hoxc6', 'Gene', '3223', (31, 36))	('Hoxa10', 'Gene', (41, 47))	('misregulated', 'Var', (4, 16))	('expression', 'MPA', (17, 27))	('involved', 'Reg', (69, 77))	('Hoxa10', 'Gene', '3206', (41, 47))	('survival', 'CPA', (100, 108))	('Hoxc6', 'Gene', (31, 36))	('migration', 'CPA', (113, 122))	('carcinoma', 'Phenotype', 'HP:0030731', (136, 145))	('oral cell carcinoma', 'Disease', 'MESH:C538614', (126, 145))
30902	33402862	Disruption of Hoxc6 and Hoxa10 gene expression could enhance tumor progression (Carrera et al., 2015; Tang et al., 2019).	('Hoxa10', 'Gene', (24, 30))	('Hoxa10', 'Gene', '3206', (24, 30))	('tumor', 'Disease', 'MESH:D009369', (61, 66))	('Hoxc6', 'Gene', (14, 19))	('enhance', 'PosReg', (53, 60))	('tumor', 'Phenotype', 'HP:0002664', (61, 66))	('Hoxc6', 'Gene', '3223', (14, 19))	('tumor', 'Disease', (61, 66))	('Disruption', 'Var', (0, 10))
30906	33402862	The hypermethylation of Meis1 has been identified in adenoid cystic carcinoma samples using the methylated CpG island amplification and microarray methods, but further validation studies are needed (Bell et al., 2011).	('adenoid cystic carcinoma', 'Disease', (53, 77))	('carcinoma', 'Phenotype', 'HP:0030731', (68, 77))	('adenoid cystic carcinoma', 'Disease', 'MESH:D003528', (53, 77))	('Meis1', 'Gene', (24, 29))	('hypermethylation', 'Var', (4, 20))
30907	33402862	Hoxa9 hypermethylation was also reported in the promoter methylation analysis of OSCC patient tissues (Guerrero-Preston et al., 2011) and salivary rinses (Schussel et al., 2013), which leads to the growth advantage of the tumor, and an increase in metastasis (Uchida et al., 2014).	('hypermethylation', 'Var', (6, 22))	('metastasis', 'CPA', (248, 258))	('tumor', 'Disease', 'MESH:D009369', (222, 227))	('growth advantage', 'CPA', (198, 214))	('OS', 'Phenotype', 'HP:0002669', (81, 83))	('patient', 'Species', '9606', (86, 93))	('tumor', 'Phenotype', 'HP:0002664', (222, 227))	('tumor', 'Disease', (222, 227))	('increase', 'PosReg', (236, 244))
30908	33402862	Moreover, miR-139-5p inhibits cell proliferation, invasion, and migration by directly targeting Hoxa9 expression (Wang et al., 2017b).	('invasion', 'CPA', (50, 58))	('inhibits', 'NegReg', (21, 29))	('cell proliferation', 'CPA', (30, 48))	('expression', 'MPA', (102, 112))	('Hoxa9', 'Protein', (96, 101))	('targeting', 'Reg', (86, 95))	('migration', 'CPA', (64, 73))	('miR-139-5p', 'Var', (10, 20))	('miR-139-5p', 'Chemical', '-', (10, 20))
30910	33402862	Pbx2 and hypermethylation of Meis1 and HoxA9, however, may be considered prognostic markers of oral cancer.	('Pbx2', 'Gene', '5089', (0, 4))	('cancer', 'Phenotype', 'HP:0002664', (100, 106))	('HoxA9', 'Gene', (39, 44))	('Meis1', 'Gene', (29, 34))	('hypermethylation', 'Var', (9, 25))	('HoxA9', 'Gene', '3205', (39, 44))	('Pbx2', 'Gene', (0, 4))	('cancer', 'Disease', (100, 106))	('cancer', 'Disease', 'MESH:D009369', (100, 106))
30920	33402862	Similarly, lncRNA HOTAIR transcribed from the Hoxc locus of DNA in uterine cancers leads to cellular proliferation, metastasis, and radiotherapy resistance via the MAPK signaling pathway (Li et al., 2018).	('Hoxc', 'Gene', (46, 50))	('HOTAIR', 'Gene', (18, 24))	('cancers', 'Disease', 'MESH:D009369', (75, 82))	('cellular proliferation', 'CPA', (92, 114))	('cancers', 'Phenotype', 'HP:0002664', (75, 82))	('radiotherapy resistance', 'CPA', (132, 155))	('HOTAIR', 'Gene', '100124700', (18, 24))	('cancers', 'Disease', (75, 82))	('leads to', 'Reg', (83, 91))	('Hoxc', 'Gene', '3220', (46, 50))	('uterine cancer', 'Phenotype', 'HP:0010784', (67, 81))	('uterine cancers', 'Phenotype', 'HP:0010784', (67, 82))	('metastasis', 'CPA', (116, 126))	('cancer', 'Phenotype', 'HP:0002664', (75, 81))	('DNA', 'Gene', (60, 63))	('lncRNA', 'Var', (11, 17))
30932	33402862	In a case with retroperitoneal leiomyoma, it was reported that tumor cells had a t(9;22)(q33;q12) translocation, which resulted in a fusion of Ewsr1 and Pbx3 genes (Panagopoulos et al., 2015).	('tumor', 'Disease', (63, 68))	('tumor', 'Phenotype', 'HP:0002664', (63, 68))	('Pbx3', 'Gene', '5090', (153, 157))	('fusion', 'Var', (133, 139))	('Ewsr1', 'Gene', (143, 148))	('resulted in', 'Reg', (119, 130))	('t(9;22)(q33;q12)', 'STRUCTURAL_ABNORMALITY', 'None', (81, 97))	('retroperitoneal leiomyoma', 'Disease', (15, 40))	('tumor', 'Disease', 'MESH:D009369', (63, 68))	('Pbx3', 'Gene', (153, 157))	('Ewsr1', 'Gene', '2130', (143, 148))	('retroperitoneal leiomyoma', 'Disease', 'MESH:D007889', (15, 40))
30937	33402862	The aberrantly expressed Hoxa9 in patients with epithelial ovarian cancer has no significant predictive value during first-line platinum-taxane chemotherapy (Pontikakis et al., 2017).	('epithelial ovarian cancer', 'Disease', 'MESH:D000077216', (48, 73))	('ovarian cancer', 'Phenotype', 'HP:0100615', (59, 73))	('platinum-taxane', 'Chemical', '-', (128, 143))	('cancer', 'Phenotype', 'HP:0002664', (67, 73))	('patients', 'Species', '9606', (34, 42))	('epithelial ovarian cancer', 'Phenotype', 'HP:0025318', (48, 73))	('aberrantly expressed', 'Var', (4, 24))	('Hoxa9', 'Gene', (25, 30))	('epithelial ovarian cancer', 'Disease', (48, 73))
30939	33402862	Although, the methylation analyses of Hoxa9 with large cohorts has shown that Hoxa9 is hypermethylated in both high-grade serous ovarian cancer (Montavon et al., 2012) and primary ovarian cancer patients, (Wu et al., 2007) the association of hypermethylation with the stage, histological types, grade, and ascites could not be established (Xing et al., 2015).	('ovarian cancer', 'Phenotype', 'HP:0100615', (129, 143))	('serous ovarian cancer', 'Disease', 'MESH:D018284', (122, 143))	('cancer', 'Phenotype', 'HP:0002664', (188, 194))	('primary ovarian cancer', 'Disease', 'MESH:D016649', (172, 194))	('primary ovarian cancer', 'Disease', (172, 194))	('cancer', 'Phenotype', 'HP:0002664', (137, 143))	('ascites', 'Phenotype', 'HP:0001541', (306, 313))	('ovarian cancer', 'Phenotype', 'HP:0100615', (180, 194))	('Hoxa9', 'Gene', (78, 83))	('patients', 'Species', '9606', (195, 203))	('ascites', 'Disease', (306, 313))	('serous ovarian cancer', 'Disease', (122, 143))	('hypermethylated', 'Var', (87, 102))	('ascites', 'Disease', 'MESH:D001201', (306, 313))
30940	33402862	Interestingly, a study on ovarian cancer cell line and normal tissue showed that DNA methylation of some of the analyzed genes, including Hoxa9, Hoxa10, MiR-34b, Prom1, Cables1, Sparc, and Rsk4, had an inverse correlation with their expression level (Niskakoski et al., 2014).	('cancer', 'Phenotype', 'HP:0002664', (34, 40))	('Sparc', 'Gene', (178, 183))	('Cables1', 'Gene', '91768', (169, 176))	('Rsk4', 'Gene', (189, 193))	('Rsk4', 'Gene', '27330', (189, 193))	('methylation', 'Var', (85, 96))	('Prom1', 'Gene', (162, 167))	('ovarian cancer', 'Disease', 'MESH:D010051', (26, 40))	('MiR-34b', 'Gene', (153, 160))	('MiR-34b', 'Gene', '407041', (153, 160))	('Hoxa10', 'Gene', (145, 151))	('ovarian cancer', 'Disease', (26, 40))	('Hoxa10', 'Gene', '3206', (145, 151))	('Sparc', 'Gene', '6678', (178, 183))	('ovarian cancer', 'Phenotype', 'HP:0100615', (26, 40))	('expression level', 'MPA', (233, 249))	('Prom1', 'Gene', '8842', (162, 167))	('Cables1', 'Gene', (169, 176))	('Hoxa9', 'Gene', (138, 143))
30954	33402862	T3M4, a cellosaurus cell line, is known to have stimulated cell proliferation through the formation of HOXB2-A10-PBX HD heterodimers and associated pancreatic carcinogenesis (Aulisa et al., 2009).	('T3M4', 'Var', (0, 4))	('pancreatic carcinogenesis', 'Disease', (148, 173))	('cell proliferation', 'CPA', (59, 77))	('HOXB2', 'Gene', '3212', (103, 108))	('HOXB2', 'Gene', (103, 108))	('pancreatic carcinogenesis', 'Disease', 'MESH:D063646', (148, 173))	('stimulated', 'PosReg', (48, 58))	('HD', 'Disease', 'MESH:D006816', (117, 119))
30957	33402862	Studies have shown that the expression of mitochondrial genes could be downregulated when Meis1 specific siRNA was transfected into PaC cells (Tomoeda et al., 2011).	('downregulated', 'NegReg', (71, 84))	('PaC', 'Phenotype', 'HP:0006699', (132, 135))	('PaC', 'CellLine', 'CVCL:E280', (132, 135))	('expression', 'MPA', (28, 38))	('PaC', 'Phenotype', 'HP:0002894', (132, 135))	('transfected', 'Var', (115, 126))	('mitochondrial genes', 'Gene', (42, 61))
30958	33402862	In addition, MEIS proteins could contribute to the Warburg effect to facilitate the abnormal growth of cells in the hypoxic tumor microenvironment via transactivation of HIFs and cooperation with HOX proteins.	('men', 'Species', '9606', (142, 145))	('tumor', 'Phenotype', 'HP:0002664', (124, 129))	('facilitate', 'PosReg', (69, 79))	('transactivation', 'Var', (151, 166))	('hypoxic tumor', 'Disease', (116, 129))	('abnormal growth', 'Phenotype', 'HP:0001507', (84, 99))	('HIFs', 'Disease', (170, 174))	('hypoxic tumor', 'Disease', 'MESH:D009369', (116, 129))	('HIFs', 'Disease', 'None', (170, 174))
30968	33402862	Binding of the HOTTIP to WDR5 induces Hoxa9 expression, which is also a significant factor for PCSCs maintenance (Cheng et al., 2015; Fu et al., 2017).	('PC', 'Phenotype', 'HP:0012125', (95, 97))	('Hoxa9', 'Protein', (38, 43))	('WDR5', 'Gene', '11091', (25, 29))	('HOTTIP', 'Gene', '100316868', (15, 21))	('Binding', 'Var', (0, 7))	('WDR5', 'Gene', (25, 29))	('HOTTIP', 'Gene', (15, 21))	('induces', 'Reg', (30, 37))
30973	33402862	Mutations in Hoxb13 generate a critical risk of developing prostate cancer (PC) (Johng et al., 2019).	('risk', 'Reg', (40, 44))	('cancer', 'Phenotype', 'HP:0002664', (68, 74))	('prostate cancer', 'Disease', 'MESH:D011471', (59, 74))	('prostate cancer', 'Phenotype', 'HP:0012125', (59, 74))	('Hoxb13', 'Gene', (13, 19))	('Hoxb13', 'Gene', '10481', (13, 19))	('PC', 'Phenotype', 'HP:0012125', (76, 78))	('Mutations', 'Var', (0, 9))	('prostate cancer', 'Disease', (59, 74))
30976	33402862	Depletion of Meis1 and Meis2 in vivo may cause tumor growth and an increase in the expression of protumorigenic genes c-Myc and CD142 (Bhanvadia et al., 2018).	('tumor', 'Phenotype', 'HP:0002664', (100, 105))	('Meis2', 'Gene', (23, 28))	('tumor', 'Disease', (100, 105))	('CD142', 'Gene', '2152', (128, 133))	('c-Myc', 'Gene', '4609', (118, 123))	('Depletion', 'Var', (0, 9))	('tumor', 'Disease', 'MESH:D009369', (47, 52))	('increase', 'PosReg', (67, 75))	('cause', 'Reg', (41, 46))	('c-Myc', 'Gene', (118, 123))	('expression', 'MPA', (83, 93))	('tumor', 'Phenotype', 'HP:0002664', (47, 52))	('CD142', 'Gene', (128, 133))	('tumor', 'Disease', 'MESH:D009369', (100, 105))	('tumor', 'Disease', (47, 52))	('Meis1', 'Gene', (13, 18))
31005	33402862	In addition, the expression of Meis1/2 is associated with antimetastasis in PC (Bhanvadia et al., 2018).	('associated', 'Reg', (42, 52))	('PC', 'Phenotype', 'HP:0012125', (76, 78))	('Meis1/2', 'Gene', (31, 38))	('antimetastasis', 'Disease', (58, 72))	('expression', 'Var', (17, 27))	('Meis1/2', 'Gene', '150365', (31, 38))
31010	33402862	Sarcoma is genetically complicated as well, such that an increase in mutational burden, complex karyotype, translocation, and amplification could be the genetic basis of the disease (Dancsok et al., 2017).	('amplification', 'MPA', (126, 139))	('translocation', 'Var', (107, 120))	('Sarcoma', 'Disease', (0, 7))	('Sarcoma', 'Disease', 'MESH:D012509', (0, 7))	('mutational burden', 'MPA', (69, 86))	('increase', 'PosReg', (57, 65))	('Sarcoma', 'Phenotype', 'HP:0100242', (0, 7))
31013	33402862	In addition, in vivo silencing of Meis1 remarkably suppresses xenograft tumor growth (Lin et al., 2019).	('tumor', 'Phenotype', 'HP:0002664', (72, 77))	('Meis1', 'Gene', (34, 39))	('tumor', 'Disease', (72, 77))	('suppresses', 'NegReg', (51, 61))	('tumor', 'Disease', 'MESH:D009369', (72, 77))	('silencing', 'Var', (21, 30))
31018	33402862	The vascular invasion, cellular necrosis, and perinephric fat invasion seen in both cases indicated that the Meis1-Ncoa2 fusion gene could be malignant (Argani et al., 2018).	('Ncoa2', 'Gene', (115, 120))	('necrosis', 'Disease', (32, 40))	('necrosis', 'Disease', 'MESH:D009336', (32, 40))	('vascular invasion', 'CPA', (4, 21))	('Ncoa2', 'Gene', '10499', (115, 120))	('fusion gene', 'Var', (121, 132))
31024	33402862	On the other hand, Hoxa9 expression is upregulated in OS tissues, and the silencing of Hoxa9 recovers the miR-873 downregulation effects.	('miR-873', 'Gene', (106, 113))	('upregulated', 'PosReg', (39, 50))	('expression', 'MPA', (25, 35))	('Hoxa9', 'Gene', (19, 24))	('OS', 'Phenotype', 'HP:0002669', (54, 56))	('recovers', 'NegReg', (93, 101))	('silencing', 'Var', (74, 83))	('miR-873', 'Gene', '100126316', (106, 113))	('downregulation', 'NegReg', (114, 128))	('Hoxa9', 'Gene', (87, 92))
31027	33402862	The silencing of Meis1 in the xenograft model was found to suppress tumor size in sarcoma (Lin et al., 2019).	('tumor', 'Disease', (68, 73))	('Meis1', 'Gene', (17, 22))	('sarcoma', 'Disease', 'MESH:D012509', (82, 89))	('tumor', 'Disease', 'MESH:D009369', (68, 73))	('tumor', 'Phenotype', 'HP:0002664', (68, 73))	('sarcoma', 'Disease', (82, 89))	('suppress', 'NegReg', (59, 67))	('sarcoma', 'Phenotype', 'HP:0100242', (82, 89))	('silencing', 'Var', (4, 13))
31084	33402862	MEIS1 could trigger cell proliferation in colorectal cancer, while MEIS2 determines the relationship between colorectal cancer growth and death (Wan et al., 2019).	('colorectal cancer', 'Disease', (109, 126))	('cancer', 'Phenotype', 'HP:0002664', (120, 126))	('colorectal cancer', 'Phenotype', 'HP:0003003', (42, 59))	('cell proliferation', 'CPA', (20, 38))	('MEIS1', 'Var', (0, 5))	('colorectal cancer', 'Disease', (42, 59))	('colorectal cancer', 'Disease', 'MESH:D015179', (109, 126))	('death', 'Disease', 'MESH:D003643', (138, 143))	('death', 'Disease', (138, 143))	('cancer', 'Phenotype', 'HP:0002664', (53, 59))	('colorectal cancer', 'Phenotype', 'HP:0003003', (109, 126))	('colorectal cancer', 'Disease', 'MESH:D015179', (42, 59))	('trigger', 'Reg', (12, 19))
31085	33402862	MEIS2 could increase colorectal dependent cell death (Wang et al., 2019b).	('colorectal dependent cell death', 'Disease', (21, 52))	('MEIS2', 'Var', (0, 5))	('colorectal dependent cell death', 'Disease', 'MESH:D015179', (21, 52))	('increase', 'PosReg', (12, 20))
31091	33402862	The expression of noncoding RNAs has often been found to impair cancer (Di Leva et al., 2014; Hayes et al., 2014; Sanchez Calle et al., 2018).	('noncoding RNAs', 'Protein', (18, 32))	('cancer', 'Disease', (64, 70))	('RNAs', 'Protein', (28, 32))	('cancer', 'Disease', 'MESH:D009369', (64, 70))	('expression', 'Var', (4, 14))	('impair', 'NegReg', (57, 63))	('cancer', 'Phenotype', 'HP:0002664', (64, 70))
31106	33402862	lncRNA CASC11, TUG1, PCAT6, LOC730100, and LINK-A have important functions in the proliferation and metastasis of the bladder cancer, laryngocarcinoma, cervical, glioblastoma, and ovarian carcinoma (Li et al., 2019c; Luo et al., 2019; Lv et al., 2019; Zhang et al., 2019; Zhuang et al., 2019).	('laryngocarcinoma', 'Disease', (134, 150))	('ovarian carcinoma', 'Phenotype', 'HP:0025318', (180, 197))	('CASC11', 'Gene', (7, 13))	('LOC730100', 'Var', (28, 37))	('glioblastoma', 'Disease', 'MESH:D005909', (162, 174))	('metastasis of the bladder cancer', 'Disease', (100, 132))	('TUG1', 'Gene', '55000', (15, 19))	('CASC11', 'Gene', '100270680', (7, 13))	('cervical', 'Disease', (152, 160))	('glioblastoma', 'Disease', (162, 174))	('glioblastoma', 'Phenotype', 'HP:0012174', (162, 174))	('carcinoma', 'Phenotype', 'HP:0030731', (141, 150))	('laryngocarcinoma', 'Disease', 'None', (134, 150))	('cancer', 'Phenotype', 'HP:0002664', (126, 132))	('bladder cancer', 'Phenotype', 'HP:0009725', (118, 132))	('proliferation', 'CPA', (82, 95))	('metastasis of the bladder cancer', 'Disease', 'MESH:D001749', (100, 132))	('ovarian carcinoma', 'Disease', 'MESH:D010051', (180, 197))	('carcinoma', 'Phenotype', 'HP:0030731', (188, 197))	('PCAT6', 'Gene', (21, 26))	('ovarian carcinoma', 'Disease', (180, 197))	('PC', 'Phenotype', 'HP:0012125', (21, 23))	('PCAT6', 'Gene', '100506696', (21, 26))	('TUG1', 'Gene', (15, 19))
31123	33402862	Two small peptides, HXR9 and CXR9, were shown to induce apoptosis in NSCLC cells, breast, ovarian, prostate, and meningioma cells by disrupting the interaction of HOX and PBX (Plowright et al., 2009; Morgan et al., 2010; Morgan et al., 2012; Ando et al., 2014).	('HXR9', 'Var', (20, 24))	('ovarian', 'Disease', 'MESH:D010049', (90, 97))	('meningioma', 'Disease', (113, 123))	('HOX', 'Protein', (163, 166))	('NSCLC', 'Disease', (69, 74))	('disrupting', 'NegReg', (133, 143))	('ovarian', 'Disease', (90, 97))	('NSCLC', 'Disease', 'MESH:D002289', (69, 74))	('interaction', 'Interaction', (148, 159))	('meningioma', 'Phenotype', 'HP:0002858', (113, 123))	('PBX', 'Gene', (171, 174))	('induce', 'PosReg', (49, 55))	('meningioma', 'Disease', 'MESH:D008577', (113, 123))	('apoptosis', 'CPA', (56, 65))	('CXR9', 'Var', (29, 33))
31125	33402862	PHOX2B expression was reported as reduced in neuroblastoma cells as a result of small molecule combination, which included curcumin, SAHA, and trichostatin (Di Zanni et al., 2015).	('reduced', 'NegReg', (34, 41))	('neuroblastoma', 'Phenotype', 'HP:0003006', (45, 58))	('PHOX2B', 'Gene', (0, 6))	('curcumin', 'Chemical', 'MESH:D003474', (123, 131))	('small', 'Var', (80, 85))	('combination', 'Interaction', (95, 106))	('expression', 'MPA', (7, 17))	('PHOX2B', 'Gene', '8929', (0, 6))	('neuroblastoma', 'Disease', 'MESH:D009447', (45, 58))	('trichostatin', 'Chemical', 'MESH:C012589', (143, 155))	('neuroblastoma', 'Disease', (45, 58))
31130	33402862	CCI-006 also impairs mitochondria in the case of CCI-007 and increases apoptosis.	('apoptosis', 'CPA', (71, 80))	('CCI-007', 'Chemical', '-', (49, 56))	('impairs', 'NegReg', (13, 20))	('mitochondria', 'MPA', (21, 33))	('CCI-006', 'Chemical', '-', (0, 7))	('increases', 'PosReg', (61, 70))	('CCI-006', 'Var', (0, 7))	('CCI-007', 'Var', (49, 56))
31149	33402862	Disruption of the MEIS-PBX interaction could also cause caspase-dependent apoptosis in a cell-dependent manner.	('cause', 'Reg', (50, 55))	('interaction', 'Interaction', (27, 38))	('caspase', 'Gene', '841', (56, 63))	('caspase', 'Gene', (56, 63))	('Disruption', 'Var', (0, 10))
31159	33402862	In a number of in vitro studies where MEIS and MEIS partner proteins were targeted indirectly by small molecules or noncoding RNAs, cancer proliferation, spread, metastasis, and invasion could have been suppressed.	('metastasis', 'CPA', (162, 172))	('spread', 'CPA', (154, 160))	('cancer', 'Disease', (132, 138))	('cancer', 'Phenotype', 'HP:0002664', (132, 138))	('suppressed', 'NegReg', (203, 213))	('invasion', 'CPA', (178, 186))	('small molecules', 'Var', (97, 112))	('cancer', 'Disease', 'MESH:D009369', (132, 138))
31209	30915134	Injury to this nerve results in hemi-diaphragm paralysis and paradoxical movement of the diaphragm and causes respiratory problems.	('Injury', 'Var', (0, 6))	('paralysis', 'Disease', (47, 56))	('paralysis', 'Phenotype', 'HP:0003470', (47, 56))	('respiratory problems', 'Phenotype', 'HP:0002795', (110, 130))	('paralysis', 'Disease', 'MESH:D010243', (47, 56))	('causes', 'Reg', (103, 109))	('results in', 'Reg', (21, 31))	('paradoxical movement of the diaphragm', 'CPA', (61, 98))	('diaphragm paralysis', 'Phenotype', 'HP:0006597', (37, 56))	('respiratory problems', 'Disease', (110, 130))
31373	29147359	The success of sunitinib also was unrelated to mutations in EGFT, c-KIT, KRAS, and BRAF.	('KRAS', 'Gene', (73, 77))	('KRAS', 'Gene', '3845', (73, 77))	('c-KIT', 'Gene', (66, 71))	('mutations', 'Var', (47, 56))	('c-KIT', 'Gene', '3815', (66, 71))	('sunitinib', 'Chemical', 'MESH:D000077210', (15, 24))	('BRAF', 'Gene', '673', (83, 87))	('EGFT', 'Gene', (60, 64))	('BRAF', 'Gene', (83, 87))
31477	25119822	The Association of PTPN22 R620W Polymorphism Is Stronger with Late-Onset AChR-Myasthenia Gravis in Turkey A functional single nucleotide polymorphism (SNP) of the PTPN22 gene encoding a protein tyrosine phosphatase has been associated with autoimmune disorders including myasthenia gravis (MG).	('protein tyrosine phosphatase', 'Gene', '26191', (186, 214))	('PTPN22', 'Gene', '100539686', (19, 25))	('R620W', 'Var', (26, 31))	('protein tyrosine phosphatase', 'Gene', (186, 214))	('autoimmune disorders', 'Disease', (240, 260))	('R620W', 'Mutation', 'rs2476601', (26, 31))	('myasthenia gravis', 'Disease', 'MESH:D009157', (271, 288))	('Myasthenia', 'Phenotype', 'HP:0003473', (78, 88))	('autoimmune disorders', 'Phenotype', 'HP:0002960', (240, 260))	('PTPN22', 'Gene', (163, 169))	('associated', 'Reg', (224, 234))	('autoimmune disorders', 'Disease', 'MESH:D001327', (240, 260))	('myasthenia', 'Phenotype', 'HP:0003473', (271, 281))	('Myasthenia Gravis', 'Disease', 'MESH:D009157', (78, 95))	('PTPN22', 'Gene', (19, 25))	('PTPN22', 'Gene', '100539686', (163, 169))	('Myasthenia Gravis', 'Disease', (78, 95))	('myasthenia gravis', 'Disease', (271, 288))
31478	25119822	As the PTPN22 R620W polymorphism has a wide variation of allele frequencies among different populations, this polymorphism was investigated in MG in Turkey.	('R620W', 'Var', (14, 19))	('R620W', 'Mutation', 'rs2476601', (14, 19))	('Turkey', 'Species', '9103', (149, 155))	('PTPN22', 'Gene', (7, 13))
31480	25119822	DNA samples from 416 patients with clinically diagnosed generalized MG (231 with Abs to acetylcholine receptor, AChR-MG), 53 with Abs to muscle-specific kinase (MuSK-MG), 55 patients with no detectable Abs (SN-MG), 77 patients with thymoma (TAMG) and 293 healthy controls (HC) were genotyped for the SNP (PTPN22 R620W, C1858T, rs2476601).	('thymoma', 'Disease', (232, 239))	('rs2476601', 'Mutation', 'rs2476601', (327, 336))	('R620W', 'Mutation', 'rs2476601', (312, 317))	('thymoma', 'Phenotype', 'HP:0100522', (232, 239))	('generalized MG', 'Disease', (56, 70))	('TAMG', 'Chemical', '-', (241, 245))	('patients', 'Species', '9606', (218, 226))	('rs2476601', 'Var', (327, 336))	('patients', 'Species', '9606', (174, 182))	('C1858T', 'Mutation', 'rs2476601', (319, 325))	('MuSK-MG', 'CellLine', 'CVCL:1698', (161, 168))	('patients', 'Species', '9606', (21, 29))	('thymoma', 'Disease', 'MESH:D013945', (232, 239))	('C1858T', 'Var', (319, 325))	('muscle-specific kinase', 'Gene', '4593', (137, 159))	('muscle-specific kinase', 'Gene', (137, 159))	('SN-MG', 'Chemical', '-', (207, 212))
31484	25119822	In contrast to findings in other autoimmune diseases, the distribution of the PTPN22 polymorphism in this population provides a susceptibility marker for AChR-MG.	('autoimmune diseases', 'Phenotype', 'HP:0002960', (33, 52))	('autoimmune disease', 'Phenotype', 'HP:0002960', (33, 51))	('autoimmune diseases', 'Disease', 'MESH:D001327', (33, 52))	('AChR-MG', 'Disease', (154, 161))	('PTPN22', 'Gene', (78, 84))	('susceptibility', 'Reg', (128, 142))	('polymorphism', 'Var', (85, 97))	('autoimmune diseases', 'Disease', (33, 52))
31494	25119822	Altered T cell receptor (TCR) signaling has been recognized as a risk factor for other autoimmune diseases.	('autoimmune disease', 'Phenotype', 'HP:0002960', (87, 105))	('autoimmune diseases', 'Disease', 'MESH:D001327', (87, 106))	('Altered', 'Var', (0, 7))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (87, 106))	('autoimmune diseases', 'Disease', (87, 106))
31496	25119822	A single nucleotide polymorphism (SNP) of PTPN22 causing an amino acid change (R620W, C1858T, dbSNP reference: rs2476601) has been shown to affect the interaction of this protein phosphatase with Src family kinases in T cell activation.	('rs2476601', 'Mutation', 'rs2476601', (111, 120))	('T cell', 'CPA', (218, 224))	('interaction', 'Interaction', (151, 162))	('protein phosphatase', 'Enzyme', (171, 190))	('C1858T', 'Var', (86, 92))	('PTPN22', 'Gene', (42, 48))	('R620W', 'Var', (79, 84))	('R620W', 'Mutation', 'rs2476601', (79, 84))	('affect', 'Reg', (140, 146))	('C1858T', 'Mutation', 'rs2476601', (86, 92))	('amino acid change', 'MPA', (60, 77))	('Src', 'Enzyme', (196, 199))
31497	25119822	Individuals carrying the variant allele of PTPN22 (T allele encoding W620) may have changes in the threshold for thymic selection and be prone to autoimmunity.	('autoimmunity', 'Phenotype', 'HP:0002960', (146, 158))	('autoimmunity', 'Disease', (146, 158))	('changes', 'Reg', (84, 91))	('threshold for thymic selection', 'MPA', (99, 129))	('autoimmunity', 'Disease', 'MESH:D001327', (146, 158))	('PTPN22', 'Gene', (43, 49))	('prone', 'Reg', (137, 142))	('W620', 'Var', (69, 73))
31498	25119822	MG was shown to be associated with PTPN22 R620W polymorphism similar to several other autoimmune diseases.	('associated', 'Reg', (19, 29))	('PTPN22', 'Gene', (35, 41))	('autoimmune diseases', 'Disease', 'MESH:D001327', (86, 105))	('R620W', 'Var', (42, 47))	('R620W', 'Mutation', 'rs2476601', (42, 47))	('autoimmune diseases', 'Disease', (86, 105))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (86, 105))	('autoimmune disease', 'Phenotype', 'HP:0002960', (86, 104))
31499	25119822	The polymorphic allele was increased in the non-thymoma MG patients without anti-titin antibodies (ATA) (odds ratio [OR]: 1.97).	('titin', 'Gene', (81, 86))	('thymoma', 'Phenotype', 'HP:0100522', (48, 55))	('non-thymoma', 'Disease', (44, 55))	('thymoma MG', 'Disease', (48, 58))	('polymorphic', 'Var', (4, 15))	('thymoma MG', 'Disease', 'MESH:D013945', (48, 58))	('titin', 'Gene', '7273', (81, 86))	('patients', 'Species', '9606', (59, 67))	('non-thymoma', 'Disease', 'MESH:D013945', (44, 55))
31500	25119822	In subsequent studies on Swedish, German and Hungarian MG patients, this PTPN22 variant was associated with AChR-MG and with thymoma-associated MG (TAMG) in one study.	('thymoma', 'Phenotype', 'HP:0100522', (125, 132))	('AChR-MG', 'Disease', (108, 115))	('TAMG', 'Chemical', '-', (148, 152))	('variant', 'Var', (80, 87))	('PTPN22', 'Gene', (73, 79))	('thymoma', 'Disease', 'MESH:D013945', (125, 132))	('patients', 'Species', '9606', (58, 66))	('associated', 'Reg', (92, 102))	('thymoma', 'Disease', (125, 132))	('Hungarian MG', 'CellLine', 'CVCL:J029', (45, 57))
31501	25119822	The first genome-wide association study published in MG recently revealed the expected association with PTPN22 (rs2476601; OR: 1.71) in a larger sample of EOMG cases from European populations.	('EOMG', 'Chemical', '-', (155, 159))	('rs2476601;', 'Var', (112, 122))	('PTPN22', 'Gene', (104, 110))	('rs2476601', 'Mutation', 'rs2476601', (112, 121))	('association', 'Interaction', (87, 98))
31503	25119822	Because the PTPN22 R620W polymorphism demonstrates a wide variation among different populations, with the highest polymorphic allele presence being in Scandinavia (15%) yet absent in Asian and African populations, this polymorphism is being investigated in this study as a susceptibility marker in MG patients and within heterogeneous disease subgroups from Turkey.	('R620W', 'Var', (19, 24))	('patients', 'Species', '9606', (301, 309))	('Turkey', 'Species', '9103', (358, 364))	('PTPN22', 'Gene', (12, 18))	('R620W', 'Mutation', 'rs2476601', (19, 24))
31512	25119822	DNA samples from patients and HC were genotyped by polymerase chain reaction (PCR) based on restriction fragment length polymorphism (RFLP) analysis for the SNP (rs2476601, R620W, C1858T, C T) of PTPN22 gene.	('PTPN22', 'Gene', (196, 202))	('rs2476601', 'Mutation', 'rs2476601', (162, 171))	('C1858T', 'Var', (180, 186))	('men', 'Species', '9606', (108, 111))	('R620W', 'Mutation', 'rs2476601', (173, 178))	('rs2476601', 'Var', (162, 171))	('C1858T', 'Mutation', 'rs2476601', (180, 186))	('patients', 'Species', '9606', (17, 25))	('R620W', 'Var', (173, 178))
31517	25119822	The distribution of the PTPN22 C1858T polymorphism (C T) revealed that the genotype frequencies were in Hardy-Weinberg equilibrium in the HC.	('C1858T', 'Var', (31, 37))	('PTPN22', 'Gene', (24, 30))	('C1858T', 'Mutation', 'rs2476601', (31, 37))
31518	25119822	The PTPN22 C1858T genotypes implicated significant differences between groups (Table 2).	('C1858T', 'Mutation', 'rs2476601', (11, 17))	('PTPN22', 'Gene', (4, 10))	('C1858T', 'Var', (11, 17))
31525	25119822	When the AChR-MG patients were subgrouped according to 50 years of age as the cut-off for disease onset, the PTPN22 T allele was more strongly associated with LOMG.	('associated with', 'Reg', (143, 158))	('T allele', 'Var', (116, 124))	('LOMG', 'Disease', (159, 163))	('patients', 'Species', '9606', (17, 25))	('LOMG', 'Chemical', '-', (159, 163))	('PTPN22', 'Gene', (109, 115))
31531	25119822	The associations of PTPN22 polymorphism with EOMG (p = 0.10, OR: 1.95) and being women (p = 0.10, OR: 1.95) in AChR-MG patients were not statistically significant with this analysis.	('polymorphism', 'Var', (27, 39))	('women', 'Species', '9606', (81, 86))	('patients', 'Species', '9606', (119, 127))	('AChR-MG', 'Disease', (111, 118))	('EOMG', 'Disease', (45, 49))	('EOMG', 'Chemical', '-', (45, 49))	('associations', 'Interaction', (4, 16))	('PTPN22', 'Gene', (20, 26))
31532	25119822	The PTPN22 R620W polymorphism is accepted as a general risk factor for autoimmune diseases with prominent production of auto-antibodies.	('autoimmune diseases', 'Phenotype', 'HP:0002960', (71, 90))	('PTPN22', 'Gene', (4, 10))	('autoimmune disease', 'Phenotype', 'HP:0002960', (71, 89))	('R620W', 'Var', (11, 16))	('R620W', 'Mutation', 'rs2476601', (11, 16))	('autoimmune diseases', 'Disease', 'MESH:D001327', (71, 90))	('autoimmune diseases', 'Disease', (71, 90))
31533	25119822	MG, being a prototypic auto-antibody mediated disease, has also been one of the diseases showing association with the PTPN22 R620W polymorphism.	('R620W', 'Mutation', 'rs2476601', (125, 130))	('PTPN22', 'Gene', (118, 124))	('R620W', 'Var', (125, 130))
31534	25119822	A relatively strong association of the polymorphic PTPN22 1858 T allele was demonstrated with AChR-MG also in this population from Turkey, where the MAF of the polymorphic allele was as low as 2%.	('polymorphic', 'Var', (39, 50))	('Turkey', 'Species', '9103', (131, 137))	('AChR-MG', 'Disease', (94, 101))	('PTPN22', 'Gene', (51, 57))
31539	25119822	In another study from Germany, EOMG but also TAMG subgroups had increased frequencies of the PTPN22 polymorphic allele compared with ethnically matched controls (OR: 2.4 and 2.5).	('TAMG', 'Chemical', '-', (45, 49))	('EOMG', 'Chemical', '-', (31, 35))	('PTPN22', 'Gene', (93, 99))	('polymorphic', 'Var', (100, 111))
31540	25119822	Based on the recently performed meta-analyses and genome-wide results, the most robust conclusion is that the minor allele (T) of PTPN22 polymorphism is associated with the presence of anti-AChR Abs and with the absence of thymoma in MG.	('anti-AChR Abs', 'Disease', (185, 198))	('thymoma', 'Disease', 'MESH:D013945', (223, 230))	('associated', 'Reg', (153, 163))	('PTPN22', 'Gene', (130, 136))	('absence of thymoma', 'Phenotype', 'HP:0005359', (212, 230))	('thymoma', 'Disease', (223, 230))	('polymorphism', 'Var', (137, 149))	('thymoma', 'Phenotype', 'HP:0100522', (223, 230))
31546	25119822	However, we have also observed an inbalance of the sex distribution in this relatively smaller subgroup of AChR-MG and the association with the PTPN22 R620W polymorphism was even stronger in women of LOMG group compared with healthy women.	('association', 'Interaction', (123, 134))	('women', 'Species', '9606', (191, 196))	('LOMG', 'Chemical', '-', (200, 204))	('AChR-MG', 'Gene', (107, 114))	('stronger', 'PosReg', (179, 187))	('R620W', 'Var', (151, 156))	('R620W', 'Mutation', 'rs2476601', (151, 156))	('women', 'Species', '9606', (233, 238))	('PTPN22', 'Gene', (144, 150))
31548	25119822	This difference of PTPN22 in women and men was not observed previously in the genome-wide association study, but similar findings have been proposed previously in rheumatoid arthritis (RA) for PTPN22 .	('arthritis', 'Phenotype', 'HP:0001369', (174, 183))	('women', 'Species', '9606', (29, 34))	('men', 'Species', '9606', (31, 34))	('rheumatoid arthritis', 'Disease', (163, 183))	('rheumatoid arthritis', 'Disease', 'MESH:D001172', (163, 183))	('RA', 'Phenotype', 'HP:0001370', (185, 187))	('PTPN22', 'Var', (193, 199))	('men', 'Species', '9606', (39, 42))	('RA', 'Disease', 'MESH:D001172', (185, 187))	('rheumatoid arthritis', 'Phenotype', 'HP:0001370', (163, 183))
31554	25119822	Among the non-HLA genetic associations with autoimmune diseases, the PTPN22 R620W gene polymorphism was shown to be a major risk factor in association studies of several diseases in Caucasian populations including North American, Spanish, British, Dutch, French-Canadian and Swedish patients.	('autoimmune diseases', 'Phenotype', 'HP:0002960', (44, 63))	('risk factor', 'Reg', (124, 135))	('R620W', 'Mutation', 'rs2476601', (76, 81))	('PTPN22', 'Gene', (69, 75))	('patients', 'Species', '9606', (283, 291))	('British', 'Disease', (239, 246))	('autoimmune disease', 'Phenotype', 'HP:0002960', (44, 62))	('HLA', 'Gene', '3123', (14, 17))	('autoimmune diseases', 'Disease', 'MESH:D001327', (44, 63))	('R620W', 'Var', (76, 81))	('HLA', 'Gene', (14, 17))	('autoimmune diseases', 'Disease', (44, 63))
31555	25119822	However, there were considerable ethnical differences in the polymorphic allele frequencies of PTPN22 R620W polymorphism in different populations with a North-South gradient ranging between 15.5% and 2.1% in Europe.	('R620W', 'Var', (102, 107))	('R620W', 'Mutation', 'rs2476601', (102, 107))	('PTPN22', 'Gene', (95, 101))
31556	25119822	The frequency of the PTPN22 polymorphism was also relatively low in the healthy population from Turkey in the present data as well as in another sample from Turkey.	('Turkey', 'Species', '9103', (157, 163))	('PTPN22', 'Gene', (21, 27))	('polymorphism', 'Var', (28, 40))	('Turkey', 'Species', '9103', (96, 102))	('low', 'NegReg', (61, 64))
31557	25119822	Our previous results on the absence of the association with this PTPN22 polymorphism in other autoimmune diseases such as RA and Takayasu's arthritis in this population underlines the specificity of the current finding in AChR-MG, also supporting the relationship with specific humoral autoimmunity.	('RA', 'Phenotype', 'HP:0001370', (122, 124))	('arthritis', 'Phenotype', 'HP:0001369', (140, 149))	('autoimmunity', 'Disease', (286, 298))	('autoimmune disease', 'Phenotype', 'HP:0002960', (94, 112))	('PTPN22', 'Gene', (65, 71))	('autoimmune diseases', 'Disease', 'MESH:D001327', (94, 113))	("Takayasu's arthritis", 'Disease', (129, 149))	('humoral autoimmunity', 'Phenotype', 'HP:0005363', (278, 298))	('autoimmunity', 'Disease', 'MESH:D001327', (286, 298))	('polymorphism', 'Var', (72, 84))	('autoimmunity', 'Phenotype', 'HP:0002960', (286, 298))	('RA', 'Disease', 'MESH:D001172', (122, 124))	('autoimmune diseases', 'Disease', (94, 113))	('AChR-MG', 'Disease', (222, 229))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (94, 113))	("Takayasu's arthritis", 'Disease', 'MESH:D001015', (129, 149))
31559	25119822	Moreover, the findings identify PTPN22 R620W polymorphism as the strongest susceptibility marker for LOMG among all other MG subgroups and provide a hint for a sex related difference in susceptibility for AChR-MG.	('R620W', 'Mutation', 'rs2476601', (39, 44))	('AChR-MG', 'Disease', (205, 212))	('LOMG', 'Disease', (101, 105))	('PTPN22', 'Gene', (32, 38))	('LOMG', 'Chemical', '-', (101, 105))	('R620W', 'Var', (39, 44))	('susceptibility', 'Reg', (75, 89))
31579	17277895	These cells, the precursors of conventional TCRalphabeta T lymphocytes, go on to rearrange their TCRalpha genes and undergo positive and negative selection for self/non-self discrimination through the engagement of TCR with peptide present in a major histocompatibility complex on antigen-presenting cells.	('TCRalpha', 'Gene', (97, 105))	('TCRalpha', 'Gene', '28695', (97, 105))	('rearrange', 'Var', (81, 90))	('TCR', 'Protein', (215, 218))	('TCRalphabeta T', 'Disease', 'MESH:D001260', (44, 58))	('men', 'Species', '9606', (207, 210))	('TCRalpha', 'Gene', (44, 52))	('TCRalpha', 'Gene', '28695', (44, 52))	('TCRalphabeta T', 'Disease', (44, 58))	('engagement', 'Interaction', (201, 211))	('Th', 'Gene', '21823', (0, 2))
31621	17277895	For all the examined patients the mean spirometric values were in the normal range (FEV1 73.2+-22.33%, VC 86.0+-22.0%, FEV1/VC 0.87+-0.18, FEF25 76.8+-38.93%, FEF50 68.3+-35.78%, FEF75 68.2+-34.78%).	('spirometric', 'MPA', (39, 50))	('FEF50', 'Var', (159, 164))	('patients', 'Species', '9606', (21, 29))	('FEV1/VC', 'Var', (119, 126))	('FEF25', 'Var', (139, 144))	('FEV1', 'Var', (84, 88))
31812	18510682	Occasionally, clonally expanded lymphocytes with a characteristic CD3+, CD57+ phenotype may not have LGL morphology on a peripheral smear but may represent in vivo antigen-activated cytotoxic effector T cells.	('CD3+', 'Var', (66, 70))	('CD57', 'Gene', '27087', (72, 76))	('CD57', 'Gene', (72, 76))
31839	18510682	Thus, combined CsA therapy can sustain a longer duration of initial remission than CS, however, discontinuation of maintenance therapy was strongly correlated with relapse (P < 0 001) and caused relapses with a median of 3 months with a range of 1 5-40 months.	('relapse', 'Disease', (164, 171))	('CsA', 'Gene', '1442', (15, 18))	('rat', 'Species', '10116', (50, 53))	('discontinuation', 'Var', (96, 111))	('CsA', 'Gene', (15, 18))	('caused', 'Reg', (188, 194))
31892	18510682	Alemtuzumab causes prolonged, severe CD4 and CD8 lymphopenia and PRCA due to parvovirus B19 infection in a patient with cutaneous T-cell lymphoma treated with alemtuzumab has been reported.	('CD8 lymphopenia', 'Phenotype', 'HP:0005415', (45, 60))	('PRCA', 'Phenotype', 'HP:0012410', (65, 69))	('lymphopenia', 'Disease', 'MESH:D008231', (49, 60))	('lymphoma', 'Phenotype', 'HP:0002665', (137, 145))	('parvovirus B19 infection', 'Disease', (77, 101))	('alemtuzumab', 'Chemical', 'MESH:D000074323', (159, 170))	('cutaneous T-cell lymphoma', 'Phenotype', 'HP:0012192', (120, 145))	('CD4', 'Gene', '920', (37, 40))	('Alemtuzumab', 'Chemical', 'MESH:D000074323', (0, 11))	('cell lymphoma', 'Phenotype', 'HP:0012191', (132, 145))	('PRCA', 'Disease', (65, 69))	('CD8', 'Gene', '925', (45, 48))	('CD4', 'Gene', (37, 40))	('cutaneous T-cell lymphoma', 'Disease', (120, 145))	('cutaneous T-cell lymphoma', 'Disease', 'MESH:D016410', (120, 145))	('Alemtuzumab', 'Var', (0, 11))	('lymphopenia', 'Disease', (49, 60))	('parvovirus B19 infection', 'Disease', 'MESH:D016731', (77, 101))	('lymphopenia', 'Phenotype', 'HP:0001888', (49, 60))	('T-cell lymphoma', 'Phenotype', 'HP:0012190', (130, 145))	('CD8', 'Gene', (45, 48))	('patient', 'Species', '9606', (107, 114))
31893	18510682	Tacrolimus (FK506) is often associated with chronic B19 infection-associated anaemia in organ transplant recipients and cessation of tacrolimus or replacement with other immunosuppressants results in an improvement of anaemia.	('anaemia', 'Disease', (77, 84))	('anaemia', 'Disease', (218, 225))	('anaemia', 'Disease', 'MESH:D000740', (218, 225))	('FK506', 'Chemical', 'MESH:D016559', (12, 17))	('Tacrolimus', 'Chemical', 'MESH:D016559', (0, 10))	('anaemia', 'Phenotype', 'HP:0001903', (77, 84))	('tacrolimus', 'Chemical', 'MESH:D016559', (133, 143))	('anaemia', 'Phenotype', 'HP:0001903', (218, 225))	('associated with', 'Reg', (28, 43))	('infection-associated anaemia in organ transplant recipients', 'Phenotype', 'HP:0410256', (56, 115))	('cessation', 'Var', (120, 129))	('B19', 'Gene', (52, 55))	('anaemia', 'Disease', 'MESH:D000740', (77, 84))	('B19', 'Gene', '59271', (52, 55))
31905	18510682	The two most important initial steps in the management of anti-EPO antibody-mediated PRCA are transfusions for symptomatic anaemia and stopping the administration of rhEPO.	('anti-EPO', 'Var', (58, 66))	('rat', 'Species', '10116', (156, 159))	('anaemia', 'Disease', 'MESH:D000740', (123, 130))	('PRCA', 'Phenotype', 'HP:0012410', (85, 89))	('anaemia', 'Disease', (123, 130))	('anaemia', 'Phenotype', 'HP:0001903', (123, 130))
31910	18510682	Thus, a recent animal study suggested that a possible alternative strategy might be to administer Hematide to patients with PRCA due to anti-rhEPO antibodies, which should enable ongoing stimulation of erythropoiesis.	('Hematide', 'Chemical', 'MESH:C514771', (98, 106))	('PRCA', 'Disease', (124, 128))	('rat', 'Species', '10116', (68, 71))	('anti-rhEPO antibodies', 'Var', (136, 157))	('PRCA', 'Phenotype', 'HP:0012410', (124, 128))	('patients', 'Species', '9606', (110, 118))
32061	33228633	Patients affected by mucosal-dominant PV only have detectable anti-DSG3 IgG AA, whereas those with mucocutaneous form of PV have both anti-DSG3 and DSG1 IgG AA.	('anti-DSG3', 'Var', (62, 71))	('Patients', 'Species', '9606', (0, 8))	('IgG', 'Gene', '668542', (72, 75))	('IgG', 'Gene', (72, 75))	('IgG', 'Gene', '668542', (153, 156))	('IgG', 'Gene', (153, 156))
32298	33228633	Direct immunofluorescence revealed intercellular epidermal IgG in one dog (unpublished data); two follow-up studies using sera from this dog supported the involvement of anti-DSG3 IgG in the dissociation of keratinocytes in canine PNP.	('dog', 'Species', '9615', (70, 73))	('IgG', 'Gene', '668542', (59, 62))	('IgG', 'Gene', (59, 62))	('IgG', 'Gene', '668542', (180, 183))	('dog', 'Species', '9615', (137, 140))	('anti-DSG3', 'Var', (170, 179))	('IgG', 'Gene', (180, 183))	('dissociation of keratinocytes', 'MPA', (191, 220))	('canine', 'Species', '9615', (224, 230))	('involvement', 'Reg', (155, 166))
32459	31610957	When patients were stratified by R status, those with R2 resection had worse overall survival (median survival, 11.8 [R0/R1] vs 5.5 [R2] years; P = .005) and progression-free survival (median progression-free survival, 2.8 [R0/R1] vs. 1.7 [R2] years; P = .005).	('progression-free survival', 'CPA', (158, 183))	('patients', 'Species', '9606', (5, 13))	('overall survival', 'CPA', (77, 93))	('worse', 'NegReg', (71, 76))	('R2 resection', 'Var', (54, 66))
32490	31610957	In line with the data that suggest resection of all gross disease or even debulking may improve outcomes, all patients with thymic carcinoma underwent resection with curative intent:in cases of R2 resections, disease was left only on critical structures that were unresectable.	('R2 resections', 'Var', (194, 207))	('carcinoma', 'Phenotype', 'HP:0030731', (131, 140))	('thymic carcinoma', 'Disease', (124, 140))	('thymic carcinoma', 'Disease', 'MESH:D013953', (124, 140))	('patients', 'Species', '9606', (110, 118))
32675	33629204	Additionally, giant cell myositis can also be induced with anti-PD-1 antibodies, suggesting that T cell hyperactivation may be a common critical factor in driving these phenotypes.	('induced', 'Reg', (46, 53))	('myositis', 'Phenotype', 'HP:0100614', (25, 33))	('giant cell myositis', 'Disease', 'MESH:D009220', (14, 33))	('giant cell myositis', 'Disease', (14, 33))	('antibodies', 'Var', (69, 79))	('anti-PD-1 antibodies', 'Var', (59, 79))
32690	29269707	A Case of Paraneoplastic Limbic Encephalitis in a Patient with Invasive Thymoma with Anti-Glutamate Receptor Antibody-Positive Cerebrospinal Fluid: A Case Report Background: Thymoma is known to cause autoimmune neuromuscular disease.	('Paraneoplastic Limbic Encephalitis', 'Disease', (10, 44))	('autoimmune neuromuscular disease', 'Disease', (200, 232))	('Thymoma', 'Phenotype', 'HP:0100522', (174, 181))	('Paraneoplastic Limbic Encephalitis', 'Disease', 'MESH:D020363', (10, 44))	('autoimmune neuromuscular disease', 'Disease', 'MESH:D001327', (200, 232))	('Thymoma', 'Phenotype', 'HP:0100522', (72, 79))	('Patient', 'Species', '9606', (50, 57))	('Encephalitis', 'Phenotype', 'HP:0002383', (32, 44))	('cause', 'Reg', (194, 199))	('Thymoma', 'Var', (174, 181))
32729	29269707	For example, patients with anti-Hu antibody usually have small-cell lung cancer (SCLC), and patients with anti-Yo antibody usually have breast, ovarian, or uterine cancer.	('small-cell lung cancer', 'Disease', 'MESH:D055752', (57, 79))	('cancer', 'Disease', (73, 79))	('cancer', 'Disease', 'MESH:D009369', (73, 79))	('ovarian', 'Disease', (144, 151))	('lung cancer', 'Phenotype', 'HP:0100526', (68, 79))	('cancer', 'Phenotype', 'HP:0002664', (164, 170))	('small-cell lung cancer', 'Disease', (57, 79))	('patients', 'Species', '9606', (13, 21))	('patients', 'Species', '9606', (92, 100))	('cancer', 'Phenotype', 'HP:0002664', (73, 79))	('uterine cancer', 'Phenotype', 'HP:0010784', (156, 170))	('SCLC', 'Disease', (81, 85))	('cancer', 'Disease', (164, 170))	('cancer', 'Disease', 'MESH:D009369', (164, 170))	('SCLC', 'Disease', 'MESH:D018288', (81, 85))	('anti-Hu antibody', 'Var', (27, 43))	('breast', 'Disease', (136, 142))
32747	29269707	Symptoms caused by anti-NMDA receptor encephalitis can be improved by adding anti-tumor therapy and immunotherapy early in the disease course.	('encephalitis', 'Disease', 'MESH:D004660', (38, 50))	('encephalitis', 'Disease', (38, 50))	('NMDA', 'Chemical', '-', (24, 28))	('tumor', 'Disease', 'MESH:D009369', (82, 87))	('encephalitis', 'Phenotype', 'HP:0002383', (38, 50))	('tumor', 'Phenotype', 'HP:0002664', (82, 87))	('tumor', 'Disease', (82, 87))	('anti-NMDA', 'Var', (19, 28))
32849	26232146	The aim was provide insights in how HRQOL in MG stands across borders and time, compare the scores to general population controls and other chronic disorders and assess the impact of potential predictors for quality of life such as a) clinical characteristics b) antibodies c) thymoma and d) treatment in a population-based cohort.	('thymoma', 'Disease', 'MESH:D013945', (277, 284))	('thymoma', 'Disease', (277, 284))	('thymoma', 'Phenotype', 'HP:0100522', (277, 284))	('chronic disorders', 'Disease', (140, 157))	('antibodies c', 'Var', (263, 275))	('chronic disorders', 'Disease', 'MESH:D002908', (140, 157))
32936	23978943	Those patients with antibodies that target the VGKC-associated protein Caspr2 have been particularly associated with acquired neuromyotonia in the setting of MG and/or thymoma.	('Caspr2', 'Gene', (71, 77))	('Caspr2', 'Gene', '26047', (71, 77))	('antibodies', 'Var', (20, 30))	('thymoma', 'Disease', 'MESH:D013945', (168, 175))	('thymoma', 'Disease', (168, 175))	('neuromyotonia', 'Disease', (126, 139))	('patients', 'Species', '9606', (6, 14))	('thymoma', 'Phenotype', 'HP:0100522', (168, 175))	('associated with', 'Reg', (101, 116))	('neuromyotonia', 'Disease', 'MESH:D020386', (126, 139))
32984	23978943	Some patients with acquired neuromyotonia or Morvan syndrome have antibodies to the VGKC complex.	('VGKC complex', 'Protein', (84, 96))	('patients', 'Species', '9606', (5, 13))	('neuromyotonia or Morvan syndrome', 'Disease', 'MESH:D020386', (28, 60))	('neuromyotonia or Morvan syndrome', 'Disease', (28, 60))	('antibodies', 'Var', (66, 76))
32986	23978943	Although there is growing recognition that LGI1 IgG and Caspr2 IgG are associated with diverse neurologic presentations, even at low titers, LGI1 antibodies are often associated with seizures and cognitive impairment, consistent with their localization at central nervous system synapses.	('antibodies', 'Var', (146, 156))	('LGI1', 'Gene', (43, 47))	('cognitive impairment', 'Phenotype', 'HP:0100543', (196, 216))	('seizures', 'Phenotype', 'HP:0001250', (183, 191))	('cognitive impairment', 'Disease', (196, 216))	('associated with', 'Reg', (167, 182))	('cognitive impairment', 'Disease', 'MESH:D003072', (196, 216))	('seizures', 'Disease', 'MESH:D012640', (183, 191))	('Caspr2', 'Gene', (56, 62))	('LGI1', 'Gene', (141, 145))	('LGI1', 'Gene', '9211', (141, 145))	('Caspr2', 'Gene', '26047', (56, 62))	('seizures', 'Disease', (183, 191))	('associated', 'Reg', (71, 81))	('LGI1', 'Gene', '9211', (43, 47))
32987	23978943	Caspr2 organizes VGKCs on both central nervous system and peripheral nervous system axons, and patients with Caspr2 antibodies may have encephalitis and/or acquired neuromyotonia.	('Caspr2', 'Gene', (109, 115))	('patients', 'Species', '9606', (95, 103))	('antibodies', 'Var', (116, 126))	('encephalitis', 'Phenotype', 'HP:0002383', (136, 148))	('Caspr2', 'Gene', '26047', (109, 115))	('neuromyotonia', 'Disease', (165, 178))	('Caspr2', 'Gene', (0, 6))	('neuromyotonia', 'Disease', 'MESH:D020386', (165, 178))	('Caspr2', 'Gene', '26047', (0, 6))	('encephalitis', 'Disease', 'MESH:D004660', (136, 148))	('encephalitis', 'Disease', (136, 148))
32988	23978943	It is likely that Caspr2 antibodies cause disease by disrupting the VGKC complex on central nervous system and/or peripheral nervous system axons, but the pathogenic mechanisms have not been proven.	('VGKC complex', 'Protein', (68, 80))	('cause', 'Reg', (36, 41))	('Caspr2', 'Gene', '26047', (18, 24))	('disease', 'Disease', (42, 49))	('antibodies', 'Var', (25, 35))	('Caspr2', 'Gene', (18, 24))	('disrupting', 'NegReg', (53, 63))
32989	23978943	Caspr2 antibodies may also be associated with MG and/or thymoma, and have recently been shown to be associated with diverse pain syndromes.	('associated', 'Reg', (30, 40))	('pain', 'Phenotype', 'HP:0012531', (124, 128))	('pain', 'Disease', 'MESH:D010146', (124, 128))	('pain', 'Disease', (124, 128))	('associated', 'Reg', (100, 110))	('antibodies', 'Var', (7, 17))	('Caspr2', 'Gene', (0, 6))	('thymoma', 'Disease', 'MESH:D013945', (56, 63))	('thymoma', 'Disease', (56, 63))	('Caspr2', 'Gene', '26047', (0, 6))	('thymoma', 'Phenotype', 'HP:0100522', (56, 63))
33001	30734484	It is well understood that antibodies against the acetylcholinereceptor (AchR) are essential for the development of MG, and that anti-AchR can block the post-synaptic membrane, AchR, as well as reduce the quantity of AchR at the neuromuscular junction, leading to a decrease in the responses to neurotransmitter Ach at muscular contractions.	('Ach', 'Chemical', 'MESH:D000109', (134, 137))	('quantity', 'MPA', (205, 213))	('block', 'NegReg', (143, 148))	('Ach', 'Chemical', 'MESH:D000109', (217, 220))	('AchR', 'Protein', (177, 181))	('men', 'Species', '9606', (108, 111))	('Ach', 'Chemical', 'MESH:D000109', (312, 315))	('Ach', 'Chemical', 'MESH:D000109', (73, 76))	('Ach', 'Chemical', 'MESH:D000109', (177, 180))	('post-synaptic membrane', 'MPA', (153, 175))	('anti-AchR', 'Var', (129, 138))	('decrease', 'NegReg', (266, 274))	('reduce', 'NegReg', (194, 200))
33045	30734484	Among them, AIRE and IL-7R, acting as immune regulators, as well as CHRNA3 (subunit of AchR), were significantly downregulated in thymoma-related MG and repressed by an epigenetics mechanism.8  Nevertheless, the precise mechanisms underlying the deficiency of AIRE in thymoma-related MG have not been clarified.	('AIRE', 'Gene', (12, 16))	('AIRE', 'Gene', '326', (12, 16))	('thymoma', 'Disease', 'MESH:D013945', (130, 137))	('thymoma', 'Disease', (130, 137))	('thymoma', 'Phenotype', 'HP:0100522', (268, 275))	('AIRE', 'Gene', (260, 264))	('thymoma', 'Phenotype', 'HP:0100522', (130, 137))	('IL-7R', 'Gene', '3575', (21, 26))	('CHRNA3', 'Gene', (68, 74))	('AIRE', 'Gene', '326', (260, 264))	('thymoma', 'Disease', 'MESH:D013945', (268, 275))	('Ach', 'Chemical', 'MESH:D000109', (87, 90))	('CHRNA3', 'Gene', '1136', (68, 74))	('thymoma', 'Disease', (268, 275))	('deficiency', 'Var', (246, 256))	('IL-7R', 'Gene', (21, 26))
33053	30734484	In conclusion, we successfully identified novel genetic alterations for molecular understanding of the occurrence and development of thymoma-related MG.	('thymoma', 'Disease', 'MESH:D013945', (133, 140))	('thymoma', 'Disease', (133, 140))	('men', 'Species', '9606', (125, 128))	('thymoma', 'Phenotype', 'HP:0100522', (133, 140))	('genetic alterations', 'Var', (48, 67))
33071	33458590	MG is mostly caused by antibodies against the acetylcholine receptor (AChR) and rarely by antibodies against muscle specific kinase (MuSK).	('muscle specific kinase', 'Gene', '4593', (109, 131))	('MuSK', 'Gene', (133, 137))	('antibodies', 'Var', (23, 33))	('acetylcholine receptor', 'Protein', (46, 68))	('MuSK', 'Gene', '4593', (133, 137))	('acetylcholine', 'Chemical', 'MESH:D000109', (46, 59))	('muscle specific kinase', 'Gene', (109, 131))	('caused by', 'Reg', (13, 22))
33076	33458590	Among those without a thymoma, the largest subgroup consists of young women (age < 50 years) with anti-AChR antibodies.	('thymoma', 'Disease', (22, 29))	('anti-AChR antibodies', 'Var', (98, 118))	('thymoma', 'Phenotype', 'HP:0100522', (22, 29))	('thymoma', 'Disease', 'MESH:D013945', (22, 29))	('women', 'Species', '9606', (70, 75))
33128	33458590	Absence of definite fluctuations, absence of response to anticholinesterases, and difficulty in finding decrement in classically-examined muscles in repetitive nerve stimulation in some patients with MuSK MG may suggest ALS in the face of bulbar symptoms/head drop without ocular symptoms.	('ALS', 'Phenotype', 'HP:0007354', (220, 223))	('bulbar symptoms', 'Phenotype', 'HP:0002483', (239, 254))	('MuSK MG', 'Var', (200, 207))	('suggest', 'Reg', (212, 219))	('ALS', 'Disease', (220, 223))	('MuSK MG', 'CellLine', 'CVCL:1698', (200, 207))	('bulbar symptoms/head', 'Disease', (239, 259))	('men', 'Species', '9606', (109, 112))	('symptoms/head drop', 'Disease', (246, 264))	('patients', 'Species', '9606', (186, 194))
33380	24847446	Milciclib, an inhibitor of cyclin-dependent kinase 2/cyclin A complex and tropomyosin receptor kinase A (TrkA) is being evaluated in two phase II studies in patients with recurrent B3 thymoma and thymic carcinoma (NCT01011439 and NCT 01301391).	('cyclin A', 'Gene', (53, 61))	('thymoma', 'Phenotype', 'HP:0100522', (184, 191))	('TrkA', 'Gene', (105, 109))	('NCT 01301391', 'Var', (230, 242))	('cyclin A', 'Gene', '890', (53, 61))	('tropomyosin receptor kinase A', 'Gene', '4914', (74, 103))	('TrkA', 'Gene', '4914', (105, 109))	('carcinoma', 'Phenotype', 'HP:0030731', (203, 212))	('patients', 'Species', '9606', (157, 165))	('thymic carcinoma', 'Disease', (196, 212))	('cyclin-dependent kinase 2', 'Gene', (27, 52))	('Milciclib', 'Chemical', '-', (0, 9))	('cyclin-dependent kinase 2', 'Gene', '1017', (27, 52))	('thymic carcinoma', 'Disease', 'MESH:D013945', (196, 212))	('NCT01011439', 'Var', (214, 225))	('thymoma', 'Disease', 'MESH:D013945', (184, 191))	('tropomyosin receptor kinase A', 'Gene', (74, 103))	('thymoma', 'Disease', (184, 191))
33472	33704915	Among these circRNAs, hsa_circ_0001173, hsa_circ_0007291, hsa_circ_0003550, and hsa_circ_0001947 were significantly upregulated in thymoma tissues compared with normal thymic tissues.	('thymoma', 'Phenotype', 'HP:0100522', (131, 138))	('hsa_circ_0001173', 'Var', (22, 38))	('hsa_circ_0001947', 'Var', (80, 96))	('upregulated', 'PosReg', (116, 127))	('hsa_circ_0007291', 'Var', (40, 56))	('hsa_circ_0003550', 'Var', (58, 74))	('thymoma', 'Disease', 'MESH:D013945', (131, 138))	('thymoma', 'Disease', (131, 138))
33474	33704915	Finally, we also found that SCAP (hsa_circ_0007291 parental gene) and AFF2 (hsa_circ_0001947 parental gene) were all significantly related with progression-free survival (PFS) of thymoma patients in a Kaplan-Meier plot (p-value <0.05).	('related with', 'Reg', (131, 143))	('patients', 'Species', '9606', (187, 195))	('progression-free survival', 'CPA', (144, 169))	('hsa_circ_0001947', 'Var', (76, 92))	('thymoma', 'Disease', 'MESH:D013945', (179, 186))	('thymoma', 'Disease', (179, 186))	('thymoma', 'Phenotype', 'HP:0100522', (179, 186))
33475	33704915	The expression levels of hsa_circ_0001173, hsa_circ_0007291, hsa_circ_0003550, and hsa_circ_0001947 were significantly upregulated and positively correlated with immune imbalance in thymoma patients.	('expression levels', 'MPA', (4, 21))	('hsa_circ_0003550', 'Var', (61, 77))	('correlated', 'Reg', (146, 156))	('upregulated', 'PosReg', (119, 130))	('immune imbalance', 'Disease', (162, 178))	('patients', 'Species', '9606', (190, 198))	('imbalance', 'Phenotype', 'HP:0002172', (169, 178))	('thymoma', 'Disease', 'MESH:D013945', (182, 189))	('hsa_circ_0007291', 'Var', (43, 59))	('thymoma', 'Disease', (182, 189))	('thymoma', 'Phenotype', 'HP:0100522', (182, 189))	('immune imbalance', 'Phenotype', 'HP:0002958', (162, 178))	('hsa_circ_0001947', 'Var', (83, 99))	('hsa_circ_0001173', 'Var', (25, 41))
33484	33704915	A number of investigations have demonstrated that circRNAs are associated with several types of cancer, such as gastric cancer, papillary thyroid cancer, hepatocellular carcinoma, and malignant melanoma.	('cancer', 'Disease', (146, 152))	('circRNAs', 'Var', (50, 58))	('gastric cancer', 'Disease', 'MESH:D013274', (112, 126))	('carcinoma', 'Phenotype', 'HP:0030731', (169, 178))	('cancer', 'Disease', (120, 126))	('malignant melanoma', 'Phenotype', 'HP:0002861', (184, 202))	('hepatocellular carcinoma', 'Phenotype', 'HP:0001402', (154, 178))	('malignant melanoma', 'Disease', 'MESH:D008545', (184, 202))	('cancer', 'Phenotype', 'HP:0002664', (146, 152))	('papillary thyroid cancer', 'Disease', (128, 152))	('cancer', 'Disease', (96, 102))	('cancer', 'Phenotype', 'HP:0002664', (120, 126))	('cancer', 'Phenotype', 'HP:0002664', (96, 102))	('associated', 'Reg', (63, 73))	('hepatocellular carcinoma', 'Disease', 'MESH:D006528', (154, 178))	('gastric cancer', 'Phenotype', 'HP:0012126', (112, 126))	('papillary thyroid cancer', 'Phenotype', 'HP:0002895', (128, 152))	('cancer', 'Disease', 'MESH:D009369', (146, 152))	('cancer', 'Disease', 'MESH:D009369', (120, 126))	('hepatocellular carcinoma', 'Disease', (154, 178))	('malignant melanoma', 'Disease', (184, 202))	('cancer', 'Disease', 'MESH:D009369', (96, 102))	('papillary thyroid cancer', 'Disease', 'MESH:D000077273', (128, 152))	('thyroid cancer', 'Phenotype', 'HP:0002890', (138, 152))	('gastric cancer', 'Disease', (112, 126))
33498	33704915	15 ,  16  As shown in Figure 2, the expression levels of hsa_circ_0001173, hsa_circ_0007291, hsa_circ_0003550, and hsa_circ_0001947 were significantly upregulated in thymoma tissue compared with control tissues (p-values were all less than 0.01).	('thymoma', 'Phenotype', 'HP:0100522', (166, 173))	('hsa_circ_0001947', 'Var', (115, 131))	('upregulated', 'PosReg', (151, 162))	('thymoma', 'Disease', 'MESH:D013945', (166, 173))	('hsa_circ_0001173', 'Var', (57, 73))	('hsa_circ_0003550', 'Var', (93, 109))	('hsa_circ_0007291', 'Var', (75, 91))	('thymoma', 'Disease', (166, 173))	('expression levels', 'MPA', (36, 53))
33499	33704915	Some mRNAs were associated with more than one miRNA, such as NM_001455 was targeted by hsa-miR-1-5p, hsa-miR-182-5p, hsa-miR-21-3p and hsa-miR-5006-5p.	('hsa-miR-21-3p', 'Gene', '406995', (117, 130))	('hsa-miR-5006', 'Gene', (135, 147))	('hsa-miR-21-3p', 'Gene', (117, 130))	('hsa-miR-5006', 'Gene', '100847026', (135, 147))	('NM_001455', 'Gene', (61, 70))	('hsa-miR-182', 'Gene', (101, 112))	('associated', 'Reg', (16, 26))	('hsa-miR-1-5p', 'Var', (87, 99))	('hsa-miR-182', 'Gene', '406958', (101, 112))
33504	33704915	Patients with high expression of SCAP and AFF2 showed better overall survival.	('SCAP', 'Gene', (33, 37))	('Patients', 'Species', '9606', (0, 8))	('high expression', 'Var', (14, 29))	('AFF2', 'Gene', (42, 46))	('better', 'PosReg', (54, 60))
33506	33704915	The present study demonstrated that hsa_circ_0001173, hsa_circ_0007291, hsa_circ_0003550, and hsa_circ_0001947 were expressed at high levels and associated with important pathological pathways in thymoma patients.	('patients', 'Species', '9606', (204, 212))	('thymoma', 'Disease', 'MESH:D013945', (196, 203))	('hsa_circ_0001947', 'Var', (94, 110))	('hsa_circ_0001173', 'Var', (36, 52))	('thymoma', 'Disease', (196, 203))	('associated with', 'Reg', (145, 160))	('thymoma', 'Phenotype', 'HP:0100522', (196, 203))	('hsa_circ_0003550', 'Var', (72, 88))
33507	33704915	Furthermore, the expression of the parental gene of hsa_circ_0007291 and hsa_circ_0001947 was associated with survival rate of thymoma patients.	('hsa_circ_0001947', 'Var', (73, 89))	('hsa_circ_0007291', 'Var', (52, 68))	('patients', 'Species', '9606', (135, 143))	('thymoma', 'Disease', 'MESH:D013945', (127, 134))	('thymoma', 'Disease', (127, 134))	('expression', 'MPA', (17, 27))	('thymoma', 'Phenotype', 'HP:0100522', (127, 134))	('survival rate', 'CPA', (110, 123))	('associated', 'Reg', (94, 104))
33512	33704915	At the same time, we found that SCAP (hsa_circ_0007291 parental gene) and AFF2 (hsa_circ_0001947 parental gene) were all significantly related with progression-free survival (PFS) of thymoma patients in the Kaplan-Meier plot.	('related with', 'Reg', (135, 147))	('patients', 'Species', '9606', (191, 199))	('thymoma', 'Phenotype', 'HP:0100522', (183, 190))	('hsa_circ_0001947', 'Var', (80, 96))	('progression-free survival', 'CPA', (148, 173))	('thymoma', 'Disease', 'MESH:D013945', (183, 190))	('thymoma', 'Disease', (183, 190))
33515	33704915	30  Therefore, hsa_circ_0007291 and hsa_circ_0001947 may also participate in immune disorders by affecting the instability of the parental gene SCAP and AFF2.	('instability', 'MPA', (111, 122))	('hsa_circ_0001947', 'Var', (36, 52))	('hsa_circ_0007291', 'Var', (15, 31))	('participate', 'Reg', (62, 73))	('affecting', 'Reg', (97, 106))	('immune disorders', 'Disease', 'MESH:D007154', (77, 93))	('immune disorders', 'Disease', (77, 93))
33516	33704915	In the preliminary exploration of this study, hsa_circ_0001173, hsa_circ_0007291, hsa_circ_0003550, and hsa_circ_0001947 in thymoma tissues showed some potential as biomarkers of disease, such as high specific expression, sensitive detection, and correlated with patient survival rates.	('patient', 'Species', '9606', (263, 270))	('hsa_circ_0001947', 'Var', (104, 120))	('hsa_circ_0003550', 'Var', (82, 98))	('hsa_circ_0001173', 'Var', (46, 62))	('hsa_circ_0007291', 'Var', (64, 80))	('thymoma', 'Disease', 'MESH:D013945', (124, 131))	('thymoma', 'Disease', (124, 131))	('thymoma', 'Phenotype', 'HP:0100522', (124, 131))
33523	32194681	The area under the curve in receiver-operating characteristic curve analysis for predicting malignancy was significantly greater for SUVmax than for volume-based metabolic parameters using all classification methods.	('malignancy', 'Disease', 'MESH:D009369', (92, 102))	('SUVmax', 'Var', (133, 139))	('malignancy', 'Disease', (92, 102))
33562	32194681	SUVmax vs. MTV P<0.0001) or p-malignant lesions (0.8562, 0.6616, and 0.4691, respectively, SUVmax vs. TLG P=0.0002.	('TLG', 'Disease', 'MESH:C564972', (102, 105))	('0.4691', 'Var', (69, 75))	('TLG', 'Disease', (102, 105))	('p-malignant lesions', 'CPA', (28, 47))	('0.8562', 'Var', (49, 55))	('MTV', 'Chemical', '-', (11, 14))
33619	30832724	Bioinformatic analysis of TCGA 450 K methylation array data, transcriptome sequencing data, WHO histologic classification and Masaoka staging system was performed to identify differentially expressed methylation sites between thymoma and thymic carcinoma as well as the different DNA methylation sites associated with the overall survival in patients with TETs.	('thymic carcinoma', 'Disease', 'MESH:D013945', (238, 254))	('associated', 'Reg', (302, 312))	('thymoma', 'Disease', 'MESH:D013945', (226, 233))	('thymoma', 'Disease', (226, 233))	('patients', 'Species', '9606', (342, 350))	('carcinoma', 'Phenotype', 'HP:0030731', (245, 254))	('thymoma', 'Phenotype', 'HP:0100522', (226, 233))	('methylation', 'Var', (200, 211))	('thymic carcinoma', 'Disease', (238, 254))
33620	30832724	Using pyrosequencing, 4 different methylation sites (cg05784862, cg07154254, cg02543462, and cg06288355) were sequenced from tumor tissues of 100 Chinese patients with TETs.	('cg02543462', 'Var', (77, 87))	('tumor', 'Disease', 'MESH:D009369', (125, 130))	('cg07154254', 'Chemical', '-', (65, 75))	('tumor', 'Phenotype', 'HP:0002664', (125, 130))	('cg06288355', 'Chemical', '-', (93, 103))	('cg05784862', 'Var', (53, 63))	('cg05784862', 'Chemical', '-', (53, 63))	('cg06288355', 'Var', (93, 103))	('patients', 'Species', '9606', (154, 162))	('tumor', 'Disease', (125, 130))	('cg02543462', 'Chemical', '-', (77, 87))	('cg07154254', 'Var', (65, 75))
33622	30832724	cg05784862(KSR1), cg07154254(ELF3), cg02543462(ILRN), and cg06288355(RAG1) were identified as independent prognostic factors for overall survival in patients with TETs after adjusting for Masaoka staging in 100 Chinese patients.	('cg06288355', 'Var', (58, 68))	('patients', 'Species', '9606', (219, 227))	('cg02543462', 'Var', (36, 46))	('patients', 'Species', '9606', (149, 157))	('cg07154254', 'Chemical', '-', (18, 28))	('RAG1', 'Gene', (69, 73))	('KSR1', 'Gene', '8844', (11, 15))	('ELF3', 'Gene', (29, 33))	('ELF3', 'Gene', '1999', (29, 33))	('KSR1', 'Gene', (11, 15))	('RAG1', 'Gene', '5896', (69, 73))	('cg02543462', 'Chemical', '-', (36, 46))	('cg07154254', 'Var', (18, 28))	('cg05784862', 'Var', (0, 10))	('cg05784862', 'Chemical', '-', (0, 10))	('cg06288355', 'Chemical', '-', (58, 68))
33624	30832724	The methylation levels of cg05784862(KSR1), cg07154254(ELF3), cg02543462(ILRN), and cg06288355(RAG1) sites are associated with the progression of TETs and may serve as new biomarkers for predicting the overall survival in patients with TETs.	('KSR1', 'Gene', (37, 41))	('RAG1', 'Gene', (95, 99))	('ELF3', 'Gene', (55, 59))	('cg02543462', 'Chemical', '-', (62, 72))	('RAG1', 'Gene', '5896', (95, 99))	('cg07154254', 'Var', (44, 54))	('cg06288355', 'Var', (84, 94))	('methylation levels', 'MPA', (4, 22))	('patients', 'Species', '9606', (222, 230))	('TETs', 'Disease', (146, 150))	('cg06288355', 'Chemical', '-', (84, 94))	('cg02543462', 'Var', (62, 72))	('cg05784862', 'Var', (26, 36))	('cg05784862', 'Chemical', '-', (26, 36))	('cg07154254', 'Chemical', '-', (44, 54))	('associated with', 'Reg', (111, 126))	('KSR1', 'Gene', '8844', (37, 41))	('ELF3', 'Gene', '1999', (55, 59))
33629	30832724	Epigenetic alterations such as DNA methylation, histone modification, and loss of genome imprinting play crucial roles in the formation and progression of cancer.	('DNA methylation', 'Var', (31, 46))	('cancer', 'Phenotype', 'HP:0002664', (155, 161))	('loss', 'NegReg', (74, 78))	('histone modification', 'Var', (48, 68))	('cancer', 'Disease', (155, 161))	('cancer', 'Disease', 'MESH:D009369', (155, 161))
33630	30832724	Over the past decade, many researchers have demonstrated the presence of aberrant DNA methylation in various types of tumor.	('tumor', 'Disease', 'MESH:D009369', (118, 123))	('tumor', 'Phenotype', 'HP:0002664', (118, 123))	('aberrant', 'Var', (73, 81))	('tumor', 'Disease', (118, 123))	('DNA', 'Protein', (82, 85))
33634	30832724	On the other hand, the genes regulated by hypermethylation sites manifested more diverse functions and were predominately involved in neuroactive ligand-receptor interactions (hsa04080, adjusted P = 4.53 x 10-24), calcium signaling pathways (hsa04020, adjusted P = 4.72 x 10-13), and cAMP signaling pathways (hsa04024, adjusted P = 8.33 x 10-8).	('hsa04024', 'Var', (309, 317))	('involved', 'Reg', (122, 130))	('calcium signaling pathways', 'Pathway', (214, 240))	('cAMP', 'Chemical', '-', (284, 288))	('calcium', 'Chemical', 'MESH:D002118', (214, 221))	('hypermethylation sites', 'Var', (42, 64))	('interactions', 'Interaction', (162, 174))	('neuroactive', 'MPA', (134, 145))	('sites', 'Var', (59, 64))	('hsa04080', 'Var', (176, 184))	('cAMP signaling pathways', 'Pathway', (284, 307))	('hsa04020', 'Var', (242, 250))
33642	30832724	Among these CpG sites, methylation status in four genes, KSR1, ELF3, ILRN, RAG1, had shown strong association with overall survival and corresponding mRNA expression (Additional file 6: Figure S2 and Additional file 7: Figure S3).	('association', 'Interaction', (98, 109))	('KSR1', 'Gene', (57, 61))	('RAG1', 'Gene', (75, 79))	('ELF3', 'Gene', (63, 67))	('RAG1', 'Gene', '5896', (75, 79))	('mRNA expression', 'MPA', (150, 165))	('methylation status', 'Var', (23, 41))	('overall', 'MPA', (115, 122))	('ELF3', 'Gene', '1999', (63, 67))	('KSR1', 'Gene', '8844', (57, 61))	('ILRN', 'Gene', (69, 73))
33643	30832724	Median beta values for the probes of cg05784862(KSR1), cg07154254(ELF3), cg02543462(ILRN), and cg06288355(RAG1) were chosen as cut-off values to categorize patients into low and high methylation subgroups.	('patients', 'Species', '9606', (156, 164))	('ELF3', 'Gene', (66, 70))	('RAG1', 'Gene', (106, 110))	('ELF3', 'Gene', '1999', (66, 70))	('cg07154254', 'Chemical', '-', (55, 65))	('RAG1', 'Gene', '5896', (106, 110))	('cg05784862', 'Var', (37, 47))	('cg05784862', 'Chemical', '-', (37, 47))	('KSR1', 'Gene', '8844', (48, 52))	('cg02543462', 'Chemical', '-', (73, 83))	('cg06288355', 'Var', (95, 105))	('KSR1', 'Gene', (48, 52))	('cg06288355', 'Chemical', '-', (95, 105))	('cg02543462', 'Var', (73, 83))	('cg07154254', 'Var', (55, 65))
33644	30832724	3, patients with high methylation in the first three methylation sites exhibited excellent prognosis, whereas those with low methylation in the last methylation site were associated with significantly longer overall survival.	('longer', 'PosReg', (201, 207))	('patients', 'Species', '9606', (3, 11))	('overall survival', 'MPA', (208, 224))	('high methylation', 'Var', (17, 33))
33645	30832724	Moreover, after adjustment for age, gender, WHO histological type, Masaoka stage, presence of myasthenia gravis, tumor site, and radiotherapy, cg07154254(ELF3) (HR = 1.091 x 10-6 95% CI 0.000-0.098, P = 0.018) and cg02543462(ILRN) (HR = 9.744 x 10-4 95% CI 0.000-0.669, P = 0.037) remained significantly associated with overall survival.	('cg07154254', 'Chemical', '-', (143, 153))	('tumor', 'Disease', (113, 118))	('associated with', 'Reg', (304, 319))	('overall', 'MPA', (320, 327))	('myasthenia gravis', 'Disease', (94, 111))	('myasthenia gravis', 'Disease', 'MESH:D009157', (94, 111))	('tumor', 'Disease', 'MESH:D009369', (113, 118))	('cg07154254', 'Var', (143, 153))	('cg02543462', 'Chemical', '-', (214, 224))	('tumor', 'Phenotype', 'HP:0002664', (113, 118))	('ELF3', 'Gene', (154, 158))	('cg02543462', 'Var', (214, 224))	('myasthenia', 'Phenotype', 'HP:0003473', (94, 104))	('ELF3', 'Gene', '1999', (154, 158))
33646	30832724	Cg05784862(KSR1) (HR = 0.014 95% CI 0.000-1.297, P = 0.065) and cg06288355(RAG1) (HR = 62.037 95% CI 0.934-4122.5, P = 0.054) had borderline significance for overall survival after adjustment mainly because of extremely low number of deaths.	('RAG1', 'Gene', (75, 79))	('RAG1', 'Gene', '5896', (75, 79))	('KSR1', 'Gene', '8844', (11, 15))	('death', 'Disease', 'MESH:D003643', (234, 239))	('death', 'Disease', (234, 239))	('KSR1', 'Gene', (11, 15))	('cg06288355', 'Var', (64, 74))	('overall', 'MPA', (158, 165))	('cg06288355', 'Chemical', '-', (64, 74))	('Cg05784862', 'Var', (0, 10))
33650	30832724	Beta values for cg05784862(KSR1), cg07154254(ELF3), and cg02543462(ILRN) were significantly lower in patients with WHO histological type C compared with those with type A-B3.	('ELF3', 'Gene', (45, 49))	('patients', 'Species', '9606', (101, 109))	('KSR1', 'Gene', '8844', (27, 31))	('cg02543462', 'Chemical', '-', (56, 66))	('KSR1', 'Gene', (27, 31))	('cg07154254', 'Var', (34, 44))	('cg05784862', 'Var', (16, 26))	('cg05784862', 'Chemical', '-', (16, 26))	('cg02543462', 'Var', (56, 66))	('cg07154254', 'Chemical', '-', (34, 44))	('ELF3', 'Gene', '1999', (45, 49))	('lower', 'NegReg', (92, 97))
33651	30832724	Cg06288355(RAG1) exhibited opposite pattern (Fig.	('RAG1', 'Gene', (11, 15))	('Cg06288355', 'Chemical', '-', (0, 10))	('Cg06288355', 'Var', (0, 10))	('RAG1', 'Gene', '5896', (11, 15))
33658	30832724	In the current field of TETs, tumor size, gene mutation, protein expression, and miRNA had been reported to affect the prognosis of patients with TETs and potentially be used as prognostic biomarkers for TETs.	('affect', 'Reg', (108, 114))	('tumor', 'Disease', 'MESH:D009369', (30, 35))	('TETs', 'Disease', (146, 150))	('tumor', 'Phenotype', 'HP:0002664', (30, 35))	('miRNA', 'MPA', (81, 86))	('prognosis', 'CPA', (119, 128))	('gene mutation', 'Var', (42, 55))	('tumor', 'Disease', (30, 35))	('patients', 'Species', '9606', (132, 140))	('protein', 'Protein', (57, 64))
33662	30832724	Four DNA methylation sites (cg05784862, cg07154254, cg02543462, and cg06288355) that predict the overall survival in patients with TETs were selected, and a prognostic model was constructed which has a higher accuracy compared to the commonly used Masaoka staging (AUC 1.000 vs 0.742, P = 2.7 x 10-6).	('cg07154254', 'Var', (40, 50))	('cg02543462', 'Chemical', '-', (52, 62))	('cg02543462', 'Var', (52, 62))	('cg07154254', 'Chemical', '-', (40, 50))	('cg05784862', 'Var', (28, 38))	('patients', 'Species', '9606', (117, 125))	('cg06288355', 'Var', (68, 78))	('cg06288355', 'Chemical', '-', (68, 78))	('cg05784862', 'Chemical', '-', (28, 38))
33665	30832724	The four DNA methylation sites (cg05784862, cg07154254, cg02543462, and cg06288355) were selected by comparing WHO's type A-B3 and type C DNA methylation levels; therefore, they can be used to differentially diagnose for type C TETs.	('cg06288355', 'Var', (72, 82))	('cg02543462', 'Chemical', '-', (56, 66))	('cg06288355', 'Chemical', '-', (72, 82))	('cg07154254', 'Var', (44, 54))	('cg05784862', 'Var', (32, 42))	('cg05784862', 'Chemical', '-', (32, 42))	('cg02543462', 'Var', (56, 66))	('cg07154254', 'Chemical', '-', (44, 54))	('type C TETs', 'Disease', (221, 232))
33666	30832724	KSR1 gene is an oncogene regulated by the cg05784862 site.	('cg05784862', 'Chemical', '-', (42, 52))	('KSR1', 'Gene', (0, 4))	('KSR1', 'Gene', '8844', (0, 4))	('cg05784862', 'Var', (42, 52))
33667	30832724	In this study, patients with poor prognosis showed lower levels of cg05784862 site methylation in the tissue, resulting in higher expression of KSR1 gene.	('expression', 'MPA', (130, 140))	('patients', 'Species', '9606', (15, 23))	('KSR1', 'Gene', '8844', (144, 148))	('KSR1', 'Gene', (144, 148))	('higher', 'PosReg', (123, 129))	('cg05784862', 'Var', (67, 77))	('cg05784862', 'Chemical', '-', (67, 77))	('lower', 'NegReg', (51, 56))
33672	30832724	ELF3, a transcription factor, is regulated by the cg07154254 site.	('ELF3', 'Gene', '1999', (0, 4))	('cg07154254 site', 'Var', (50, 65))	('cg07154254', 'Chemical', '-', (50, 60))	('ELF3', 'Gene', (0, 4))
33673	30832724	Our results showed that patients with poor prognosis had lower levels of cg07154254 site methylation in the tissue, which results in higher expression of ELF3 gene.	('expression', 'MPA', (140, 150))	('cg07154254', 'Chemical', '-', (73, 83))	('higher', 'PosReg', (133, 139))	('ELF3', 'Gene', '1999', (154, 158))	('patients', 'Species', '9606', (24, 32))	('ELF3', 'Gene', (154, 158))	('cg07154254 site methylation', 'Var', (73, 100))	('lower', 'NegReg', (57, 62))
33678	30832724	ILRN gene is mainly involved in immune response and is regulated by the cg02543462 site.	('ILRN', 'Gene', (0, 4))	('cg02543462', 'Chemical', '-', (72, 82))	('cg02543462 site', 'Var', (72, 87))
33680	30832724	The RAG1 is mainly involved in immune regulation and is regulated by the cg06288355 site.	('RAG1', 'Gene', (4, 8))	('cg06288355', 'Chemical', '-', (73, 83))	('cg06288355', 'Var', (73, 83))	('RAG1', 'Gene', '5896', (4, 8))	('regulated', 'Reg', (56, 65))
33682	30832724	KSR1, ELF3, ILRN, and RAG1 regulated by the DNA methylation sites cg05784862, cg07154254, cg02543462, and cg06288355, respectively, are known to be involved in tumorigenesis, progression, and death, which is one of the reasons for using them as prognostic biomarkers in patients with TETs.	('ILRN', 'Gene', (12, 16))	('KSR1', 'Gene', (0, 4))	('death', 'Disease', (192, 197))	('tumor', 'Phenotype', 'HP:0002664', (160, 165))	('cg07154254', 'Chemical', '-', (78, 88))	('cg05784862', 'Chemical', '-', (66, 76))	('progression', 'CPA', (175, 186))	('ELF3', 'Gene', '1999', (6, 10))	('cg06288355', 'Chemical', '-', (106, 116))	('death', 'Disease', 'MESH:D003643', (192, 197))	('involved', 'Reg', (148, 156))	('cg02543462', 'Var', (90, 100))	('tumor', 'Disease', (160, 165))	('RAG1', 'Gene', (22, 26))	('ELF3', 'Gene', (6, 10))	('cg05784862', 'Var', (66, 76))	('patients', 'Species', '9606', (270, 278))	('KSR1', 'Gene', '8844', (0, 4))	('RAG1', 'Gene', '5896', (22, 26))	('tumor', 'Disease', 'MESH:D009369', (160, 165))	('cg02543462', 'Chemical', '-', (90, 100))	('cg07154254', 'Var', (78, 88))	('cg06288355', 'Var', (106, 116))
33693	30832724	Taken together, ELF3, KSR1, ILRN, and RAG1 methylation sites can be used to determine the prognosis of patients with TETs and can also differentially diagnose subtypes of TETs.	('diagnose', 'Reg', (150, 158))	('TETs', 'Disease', (171, 175))	('KSR1', 'Gene', (22, 26))	('RAG1', 'Gene', (38, 42))	('methylation', 'Var', (43, 54))	('TETs', 'Disease', (117, 121))	('RAG1', 'Gene', '5896', (38, 42))	('ELF3', 'Gene', '1999', (16, 20))	('ELF3', 'Gene', (16, 20))	('patients', 'Species', '9606', (103, 111))	('KSR1', 'Gene', '8844', (22, 26))
33719	30832724	The total sum of products with coefficient of four candidate methylation sites in univariate Cox regression and corresponding beta values were calculated as risk scores for each patient in the validation set.	('Cox', 'Gene', (93, 96))	('patient', 'Species', '9606', (178, 185))	('methylation', 'Var', (61, 72))	('Cox', 'Gene', '1351', (93, 96))
33721	30832724	ELF3 E74 like ETS transcription factor 3 ILRN Interleukin 1 receptor type 1 KEGG Kyoto Encyclopedia of Genes and Genomes KSR Kinase suppressor of ras 1 RAG1 Recombination activating 1 ROC Receiver operating characteristic curve TETs Thymic epithelial tumors GW, SL, CC, and JH contributed to the conception and design.	('tumors', 'Phenotype', 'HP:0002664', (251, 257))	('RAG1', 'Gene', '5896', (152, 156))	('SL', 'Disease', 'MESH:C564794', (262, 264))	('epithelial tumors', 'Disease', (240, 257))	('RAG1', 'Gene', (152, 156))	('E74', 'Var', (5, 8))	('ELF3', 'Gene', '1999', (0, 4))	('epithelial tumors', 'Disease', 'MESH:D002277', (240, 257))	('tumor', 'Phenotype', 'HP:0002664', (251, 256))	('ELF3', 'Gene', (0, 4))
33732	30168897	The median OS was 29.5 months patients with high TGF-beta expression versus 62.9 in patients with low TGF-beta (P = 0.052).	('high', 'Var', (44, 48))	('TGF-beta', 'Gene', (49, 57))	('OS', 'Gene', '17451', (11, 13))	('patients', 'Species', '9606', (84, 92))	('TGF-beta', 'Gene', '7040', (102, 110))	('patients', 'Species', '9606', (30, 38))	('TGF-beta', 'Gene', '7040', (49, 57))	('TGF-beta', 'Gene', (102, 110))
33781	30168897	Among all patients, the median OS (mOS) in patients with high PD-L1 expression was shorter than in patients with low PD-L1 expression (mOS: 29.5 months, [95% confidence interval, CI 20.0-39.0] vs. 42.6 months [95% CI 0-98.3]; P = 0.186) (Fig 5a).	('OS', 'Gene', '17451', (31, 33))	('mOS', 'Gene', (35, 38))	('high', 'Var', (57, 61))	('patients', 'Species', '9606', (43, 51))	('shorter', 'NegReg', (83, 90))	('OS', 'Gene', '17451', (36, 38))	('expression', 'Var', (68, 78))	('patients', 'Species', '9606', (99, 107))	('mOS', 'Gene', (135, 138))	('mOS', 'Gene', '17451', (35, 38))	('OS', 'Gene', '17451', (136, 138))	('mOS', 'Gene', '17451', (135, 138))	('patients', 'Species', '9606', (10, 18))	('PD-L1', 'Gene', (62, 67))
33782	30168897	The mOS in patients with high TGF-beta expression was also shorter than in patients with low TGF-beta expression (29.5 months [95% CI 18.6-40.4] vs. 62.9 months [95% CI 15.6-110.1]; P = 0.052) (Fig 5b).	('TGF-beta', 'Gene', '7040', (93, 101))	('TGF-beta', 'Gene', (93, 101))	('mOS', 'Gene', '17451', (4, 7))	('shorter', 'NegReg', (59, 66))	('patients', 'Species', '9606', (75, 83))	('high', 'Var', (25, 29))	('TGF-beta', 'Gene', '7040', (30, 38))	('TGF-beta', 'Gene', (30, 38))	('patients', 'Species', '9606', (11, 19))	('mOS', 'Gene', (4, 7))
33786	30168897	In contrast, high CD8 expression correlated with better OS in advanced thymic carcinoma compared to low CD8 expression (50.7 months [95% CI 18.2-83.2] vs. 15.1 months [95% CI 0.0-36.4], respectively; P = 0.154) (Fig 6).	('OS', 'Gene', '17451', (56, 58))	('high', 'Var', (13, 17))	('thymic carcinoma', 'Disease', (71, 87))	('carcinoma', 'Phenotype', 'HP:0030731', (78, 87))	('thymic carcinoma', 'Disease', 'MESH:D013945', (71, 87))	('CD8', 'Gene', (104, 107))	('CD8', 'Gene', (18, 21))	('CD8', 'Gene', '925', (18, 21))	('CD8', 'Gene', '925', (104, 107))
33790	30168897	The median PFS (mPFS) was significantly shorter in thymic carcinoma patients with high PD-L1 expression compared to patients with low PD-L1 expression (mPFS: 10.6 months [95% CI 0-24.9] vs. NE [95% CI 0-NE]; P = 0.043) (Fig 7b).	('PD-L1', 'Gene', (87, 92))	('high', 'Var', (82, 86))	('PFS', 'MPA', (11, 14))	('patients', 'Species', '9606', (116, 124))	('patients', 'Species', '9606', (68, 76))	('thymic carcinoma', 'Disease', (51, 67))	('shorter', 'NegReg', (40, 47))	('thymic carcinoma', 'Disease', 'MESH:D013945', (51, 67))	('carcinoma', 'Phenotype', 'HP:0030731', (58, 67))
33807	30168897	Our results demonstrate that high TGF-beta expression is numerically associated with poor OS in thymic carcinoma.	('high', 'Var', (29, 33))	('TGF-beta', 'Gene', (34, 42))	('OS', 'Gene', '17451', (90, 92))	('associated', 'Reg', (69, 79))	('thymic carcinoma', 'Disease', (96, 112))	('TGF-beta', 'Gene', '7040', (34, 42))	('expression', 'MPA', (43, 53))	('thymic carcinoma', 'Disease', 'MESH:D013945', (96, 112))	('carcinoma', 'Phenotype', 'HP:0030731', (103, 112))
33808	30168897	This observation is consistent with previous reports of the immunosuppressive role of TGF-beta in the tumor microenviroment.37, 38 We further found that high PD-L1 expression may be associated with poor PFS, which is consistent with the results of several previously published papers.	('TGF-beta', 'Gene', '7040', (86, 94))	('PFS', 'Disease', (203, 206))	('expression', 'MPA', (164, 174))	('TGF-beta', 'Gene', (86, 94))	('tumor', 'Disease', 'MESH:D009369', (102, 107))	('poor PFS', 'Disease', (198, 206))	('PD-L1', 'Protein', (158, 163))	('tumor', 'Phenotype', 'HP:0002664', (102, 107))	('tumor', 'Disease', (102, 107))	('high', 'Var', (153, 157))
33810	30168897	concluded that high PD-L1 expression was associated with poorer OS in patients with advanced TETs,31 consistent with our findings.	('high', 'Var', (15, 19))	('expression', 'MPA', (26, 36))	('poorer', 'Disease', (57, 63))	('patients', 'Species', '9606', (70, 78))	('OS', 'Gene', '17451', (64, 66))	('PD-L1', 'Protein', (20, 25))
33860	25378848	Pleural fluid analysis revealed lymphocyte predominant (95%), exudative red colored fluid with raised values of lactate dehydogenase (LDH - 1654 IU/L) and ADA (271.9 IU/L).	('ADA', 'Gene', '100', (155, 158))	('lactate', 'Chemical', 'MESH:D019344', (112, 119))	('raised', 'PosReg', (95, 101))	('ADA', 'Gene', (155, 158))	('Pleural fluid', 'Phenotype', 'HP:0002202', (0, 13))	('raised values of lactate', 'Phenotype', 'HP:0002151', (95, 119))	('exudative red colored fluid', 'MPA', (62, 89))	('raised values of lactate dehydogenase', 'Phenotype', 'HP:0025435', (95, 132))	('lactate dehydogenase', 'MPA', (112, 132))	('LDH', 'Var', (134, 137))	('271.9', 'Var', (160, 165))
33918	31829410	The following codes were used for patient identification: (i) registered site on cancer, thymus (C37) and (ii) ICD-O-3 histology codes 8020, 8023, 8033, 8070, 8082, 8123, 8140, 8200, 8260, 8310, 8430, 8480, 8560, 8576, 8580-8585 and 8586 with a behavior code of 3 (i.e.	('8576', 'Var', (213, 217))	('8020', 'Var', (135, 139))	('cancer', 'Disease', 'MESH:D009369', (81, 87))	('8200', 'Var', (177, 181))	('8082', 'Var', (159, 163))	('cancer', 'Disease', (81, 87))	('8140', 'Var', (171, 175))	('8123', 'Var', (165, 169))	('8023', 'Var', (141, 145))	('8260', 'Var', (183, 187))	('8033', 'Var', (147, 151))	('patient', 'Species', '9606', (34, 41))	('8586', 'Var', (233, 237))	('cancer', 'Phenotype', 'HP:0002664', (81, 87))	('8310', 'Var', (189, 193))	('8070', 'Var', (153, 157))	('8480', 'Var', (201, 205))
34138	31736571	These are more likely to occur in the elderly and those with severe MG. Antibodies against striated muscles (anti-titin, anti-ryanodine, and anti-Kv 1.4 antibodies) have been implicated.	('titin', 'Gene', '7273', (114, 119))	('ryanodine', 'Chemical', 'MESH:D012433', (126, 135))	('Kv 1.4', 'Gene', (146, 152))	('MG', 'Disease', 'MESH:D009157', (68, 70))	('anti-ryanodine', 'Var', (121, 135))	('titin', 'Gene', (114, 119))	('Kv 1.4', 'Gene', '3739', (146, 152))
34144	31736571	It is important to note that IVIG and plasma exchange could worsen stress cardiomyopathy due to fluid overload and hemodynamic instability, respectively.	('stress cardiomyopathy', 'Disease', 'MESH:D054549', (67, 88))	('stress cardiomyopathy', 'Disease', (67, 88))	('worsen', 'NegReg', (60, 66))	('cardiomyopathy', 'Phenotype', 'HP:0001638', (74, 88))	('fluid overload', 'Phenotype', 'HP:0011105', (96, 110))	('plasma exchange', 'Var', (38, 53))
34285	31331197	On both CT and MRI, the most frequent qualitative parameters of thymoma were at lateral position, in mass shape, absence of SI loss on the opposed-phase image relative to the in-phase image, high SI in T2-weighted with fat suppression, and having attenuated soft or mixed tissue.	('thymoma', 'Disease', 'MESH:D013945', (64, 71))	('thymoma', 'Disease', (64, 71))	('absence of SI loss', 'Disease', 'MESH:D004832', (113, 131))	('thymoma', 'Phenotype', 'HP:0100522', (64, 71))	('high SI', 'Var', (191, 198))	('absence of SI loss', 'Disease', (113, 131))
34353	29163772	This and the known potential of senescence to eliminate pre-cancerous cells make us hypothesize, that genetic and epigenetic alterations that interfere with thymic involution could contribute to the development of thymomas and TSCCs.	('epigenetic alterations', 'Var', (114, 136))	('thymomas', 'Disease', 'MESH:D013945', (214, 222))	('TSCCs', 'Disease', (227, 232))	('cancer', 'Disease', 'MESH:D009369', (60, 66))	('thymoma', 'Phenotype', 'HP:0100522', (214, 221))	('contribute', 'Reg', (181, 191))	('cancer', 'Disease', (60, 66))	('thymomas', 'Disease', (214, 222))	('cancer', 'Phenotype', 'HP:0002664', (60, 66))
34357	29163772	cFLIP is expressed in various splice variants (mainly cFLIPL (cFLIPlong) and cFLIPS (cFLIPshort)) in normal tissues and many tumors and is regulated by various factors, including NF-kappaB.	('cFLIPS', 'Var', (77, 83))	('tumor', 'Phenotype', 'HP:0002664', (125, 130))	('tumors', 'Disease', 'MESH:D009369', (125, 131))	('tumors', 'Disease', (125, 131))	('tumors', 'Phenotype', 'HP:0002664', (125, 131))
34370	29163772	Subsequently, cFLIP expression decreased more rapidly in pTECs from NTs (n=4) than in 3 of 4 investigated neoplastic pTECs (Figure 2).	('pTECs', 'Chemical', '-', (117, 122))	('NTs', 'Var', (68, 71))	('est', 'Gene', '6783', (96, 99))	('decreased', 'NegReg', (31, 40))	('est', 'Gene', (96, 99))	('pTECs', 'Chemical', '-', (57, 62))	('cFLIP', 'Protein', (14, 19))
34379	29163772	To test this hypothesis, cFLIP RNA and protein levels were downregulated in 2 to 4 day-old pTECs by cFLIP shRNA (Figure 4A).	('est', 'Gene', (4, 7))	('est', 'Gene', '6783', (4, 7))	('downregulated', 'NegReg', (59, 72))	('cFLIP shRNA', 'Var', (100, 111))	('pTECs', 'Chemical', '-', (91, 96))
34381	29163772	The thymic carcinoma cell line, 1889c, and HaCaT keratinocytes showed a similar reduction of cell survival upon cFLIP knockdown (Supplementary Figure 4A-4B).	('knockdown', 'Var', (118, 127))	('reduction', 'NegReg', (80, 89))	('cFLIP', 'Protein', (112, 117))	('HaCaT', 'CellLine', 'CVCL:0038', (43, 48))	('cell survival', 'CPA', (93, 106))	('thymic carcinoma', 'Disease', (4, 20))	('thymic carcinoma', 'Disease', 'MESH:D013945', (4, 20))	('carcinoma', 'Phenotype', 'HP:0030731', (11, 20))
34382	29163772	However, following cFLIP knockdown, only 1889c cells and HaCaT cells but not pTECs could be rescued from TNFalpha-induced cell death through the pan-caspase inhibitor Z-VAD-FMK or the necroptosis inhibitor, Necrostatin-1 (Nec1) (Figure 4C-4D und Supplementary Figure 4B-4D).	('Necrostatin-1', 'Chemical', 'MESH:C507699', (207, 220))	('TNFalpha-induced', 'Gene', (105, 121))	('HaCaT cells', 'CellLine', 'CVCL:0038', (57, 68))	('Nec1', 'Gene', (222, 226))	('(Nec1', 'Gene', '5122', (221, 226))	('pTECs', 'Chemical', '-', (77, 82))	('knockdown', 'Var', (25, 34))	('Z-VAD-FMK', 'Chemical', 'MESH:C096713', (167, 176))
34384	29163772	Taken together, cFLIP counteracts senescence in neoplastic pTECs and prevents their death by a mechanism that is independent of caspases and the necroptosis inducer, RIPK1.	('pTECs', 'Chemical', '-', (59, 64))	('cFLIP', 'Var', (16, 21))	('senescence', 'MPA', (34, 44))	('death', 'CPA', (84, 89))	('prevents', 'NegReg', (69, 77))
34385	29163772	Since cFLIP expression is driven by activated NF-kappaB (p65) in some non-thymic tumors, we treated neoplastic pTECs and control cell lines with the NF-kappaB inhibitor, EF24 (Figure 5).	('Since cFLIP', 'Gene', (0, 11))	('thymic tumors', 'Disease', (74, 87))	('activated', 'PosReg', (36, 45))	('NF-kappaB', 'Protein', (46, 55))	('pTECs', 'Chemical', '-', (111, 116))	('driven', 'Reg', (26, 32))	('thymic tumor', 'Phenotype', 'HP:0100521', (74, 86))	('Since cFLIP', 'Gene', '8837', (0, 11))	('thymic tumors', 'Disease', 'MESH:D013953', (74, 87))	('tumor', 'Phenotype', 'HP:0002664', (81, 86))	('tumors', 'Phenotype', 'HP:0002664', (81, 87))	('p65', 'Var', (57, 60))
34387	29163772	Furthermore, EF24 treatment induced premature senescence in terms of X-Gal staining and accelerated p16 overexpression (data not shown).	('accelerated', 'PosReg', (88, 99))	('p16', 'Protein', (100, 103))	('premature senescence', 'MPA', (36, 56))	('X-Gal', 'Chemical', 'MESH:C044888', (69, 74))	('treatment', 'Var', (18, 27))	('EF24 treatment', 'Var', (13, 27))
34390	29163772	Therefore, like cFLIP knockdown, NF-kappaB inhibition can facilitate TNFalpha-induced cell death of pTECs by a caspase and RIPK1 independent mechanism.	('facilitate', 'PosReg', (58, 68))	('inhibition', 'Var', (43, 53))	('pTECs', 'Chemical', '-', (100, 105))	('NF-kappaB', 'Protein', (33, 42))	('TNFalpha-induced', 'Gene', (69, 85))
34392	29163772	Autophagic vacuoles were detected already 24 hours after shRNA-mediated cFLIP knockdown in all cultured pTECs of thymomas (n=3) (Figure 6A) but only after 48 hours in a minority of 1889c TC cells (Figure 6B).	('knockdown', 'Var', (78, 87))	('Autophagic vacuoles', 'Phenotype', 'HP:0003736', (0, 19))	('1889c TC', 'CellLine', 'CVCL:D024', (181, 189))	('Autophagic vacuoles', 'CPA', (0, 19))	('thymoma', 'Phenotype', 'HP:0100522', (113, 120))	('pTECs', 'Chemical', '-', (104, 109))	('thymomas', 'Disease', (113, 121))	('cFLIP', 'Gene', (72, 77))	('thymomas', 'Disease', 'MESH:D013945', (113, 121))
34400	29163772	The main new findings here are i) higher expression of cFLIP in thymomas and TSCCs compared to NT in vivo; ii) delayed decline of cFLIP levels and delayed senescence in cultured neoplastic pTECs compared to normal pTECs; iii) regulation of cFLIP expression through NF-kappaB signaling in neoplastic pTECs; and iv) cell death induction through autophagy and apoptosis by cFLIP knockdown and NF-kappaB inhibition in pTECs.	('pTECs', 'Chemical', '-', (189, 194))	('cFLIP', 'MPA', (130, 135))	('expression', 'MPA', (41, 51))	('inhibition', 'NegReg', (400, 410))	('cell death induction', 'CPA', (314, 334))	('NF-kappaB', 'Protein', (390, 399))	('pTECs', 'Chemical', '-', (299, 304))	('thymoma', 'Phenotype', 'HP:0100522', (64, 71))	('thymomas', 'Disease', 'MESH:D013945', (64, 72))	('apoptosis', 'CPA', (357, 366))	('cFLIP', 'Protein', (370, 375))	('pTECs', 'Chemical', '-', (214, 219))	('pTECs', 'Chemical', '-', (414, 419))	('thymomas', 'Disease', (64, 72))	('autophagy', 'CPA', (343, 352))	('knockdown', 'Var', (376, 385))
34402	29163772	Genetic gains of BCL-2 family genes belong to the commonest genetic abnormalities in TETs, and BCL-2 and BIRC3 overexpression are almost consistent features of TCs.	('TCs', 'Disease', (160, 163))	('TETs', 'Disease', (85, 89))	('mos', 'Gene', (132, 135))	('genetic abnormalities', 'Disease', (60, 81))	('BCL-2 family genes', 'Gene', (17, 35))	('gains', 'PosReg', (8, 13))	('TCs', 'Chemical', 'MESH:D013667', (160, 163))	('Genetic', 'Var', (0, 7))	('BIRC3', 'Gene', (105, 110))	('est', 'Gene', (56, 59))	('L-', 'Chemical', '-', (97, 99))	('mos', 'Gene', '4342', (132, 135))	('TETs', 'Chemical', 'MESH:C010349', (85, 89))	('BIRC3', 'Gene', '330', (105, 110))	('est', 'Gene', '6783', (56, 59))	('L-', 'Chemical', '-', (19, 21))	('genetic abnormalities', 'Disease', 'MESH:D030342', (60, 81))
34404	29163772	Since survival of primary cell cultures established from thymomas was significantly attenuated by TNFalpha treatment only after cFLIP knockdown, increased cFLIP expression appears to be functionally relevant.	('survival', 'CPA', (6, 14))	('thymoma', 'Phenotype', 'HP:0100522', (57, 64))	('attenuated', 'NegReg', (84, 94))	('thymomas', 'Disease', 'MESH:D013945', (57, 65))	('thymomas', 'Disease', (57, 65))	('est', 'Gene', (40, 43))	('TNFalpha', 'Gene', (98, 106))	('treatment', 'Var', (107, 116))	('est', 'Gene', '6783', (40, 43))
34408	29163772	Since cFLIP expression levels are decreased in CSQCC compared to normal tissues, TRAIL therapy has been considered effective and safe for patients with cFLIPlow CSQSC.	('Since cFLIP', 'Gene', (0, 11))	('TRAIL', 'Gene', (81, 86))	('decreased', 'NegReg', (34, 43))	('CSQCC', 'Disease', (47, 52))	('Since cFLIP', 'Gene', '8837', (0, 11))	('TRAIL', 'Gene', '8743', (81, 86))	('cFLIPlow', 'Var', (152, 160))	('patients', 'Species', '9606', (138, 146))
34410	29163772	Increased expression of the large variant of cFLIP cFLIPL and additionally increases expression of the small cFLIP variant cFLIPS in B2 thymoma subtype (Figure 1) occurred across the spectrum of indolent to aggressive thymoma subtypes and highly malignant TSCC suggesting that cFLIP is an important regulator of TEC homoeostasis rather than driver of aggressiveness.	('variant', 'Var', (115, 122))	('est', 'Gene', (265, 268))	('aggressiveness', 'Disease', (351, 365))	('thymoma subtype', 'Disease', (136, 151))	('aggressiveness', 'Phenotype', 'HP:0000718', (351, 365))	('aggressive thymoma subtypes', 'Disease', 'MESH:D013945', (207, 234))	('increases', 'PosReg', (75, 84))	('TEC homoeostasis', 'Disease', (312, 328))	('aggressiveness', 'Disease', 'MESH:D001523', (351, 365))	('thymoma', 'Phenotype', 'HP:0100522', (136, 143))	('thymoma', 'Phenotype', 'HP:0100522', (218, 225))	('expression', 'MPA', (10, 20))	('thymoma subtype', 'Disease', 'MESH:D013945', (136, 151))	('thymoma subtype', 'Disease', 'MESH:D013945', (218, 233))	('est', 'Gene', '6783', (265, 268))	('aggressive thymoma subtypes', 'Disease', (207, 234))	('expression', 'MPA', (85, 95))	('TEC homoeostasis', 'Disease', 'MESH:C536980', (312, 328))	('cFLIP', 'Gene', (45, 50))
34416	29163772	Since blockade of the extrinsic apoptotic pathway delays thymic involution in mice, conditional cFLIP overexpression and knockout in murine TECs in vivo may give hints to the role of cFLIP in thymoma development and thymic involution, respectively.	('thymoma', 'Disease', 'MESH:D013945', (192, 199))	('extrinsic apoptotic pathway', 'Pathway', (22, 49))	('thymoma', 'Disease', (192, 199))	('TEC', 'Gene', (140, 143))	('TEC', 'Gene', '7006', (140, 143))	('blockade', 'Var', (6, 14))	('murine', 'Species', '10090', (133, 139))	('thymoma', 'Phenotype', 'HP:0100522', (192, 199))	('delays', 'NegReg', (50, 56))	('thymic involution', 'CPA', (57, 74))	('mice', 'Species', '10090', (78, 82))
34417	29163772	cFLIPS overexpression in B2 thymoma (Figure 1) suggests that the small cFLIP variant could play a role in the development of the B2 thymomen, how far cFLIPS in involved in blocking the thymic senescence and involution muss be investigated further in TECs isolated from these neoplastic tissues of B2 thymoma.	('thymoma', 'Phenotype', 'HP:0100522', (28, 35))	('variant', 'Var', (77, 84))	('TEC', 'Gene', '7006', (250, 253))	('est', 'Gene', (51, 54))	('thymic senescence', 'CPA', (185, 202))	('thymoma', 'Disease', 'MESH:D013945', (300, 307))	('thymoma', 'Disease', 'MESH:D013945', (28, 35))	('role', 'Reg', (98, 102))	('play', 'Reg', (91, 95))	('thymoma', 'Disease', (28, 35))	('est', 'Gene', '6783', (51, 54))	('thymoma', 'Disease', (300, 307))	('est', 'Gene', (229, 232))	('thymoma', 'Phenotype', 'HP:0100522', (300, 307))	('est', 'Gene', '6783', (229, 232))	('TEC', 'Gene', (250, 253))
34420	29163772	Rarely, p16 deficiency in TETs results from homozygous loss of the CDKN2A locus at 9p21.3.	('loss', 'NegReg', (55, 59))	('CDKN2A', 'Gene', (67, 73))	('p16', 'Gene', (8, 11))	('TETs', 'Chemical', 'MESH:C010349', (26, 30))	('deficiency', 'Var', (12, 22))
34424	29163772	c-FLIPL but not cFLIPS attenuates autophagy by directly acting on the autophagy machinery by inhibiting Atg3 binding to LC3, thereby decreasing LC3 processing.	('acting', 'Reg', (56, 62))	('autophagy', 'CPA', (34, 43))	('LC3', 'Gene', '84557', (120, 123))	('autophagy machinery', 'CPA', (70, 89))	('LC3', 'Gene', (120, 123))	('LC3', 'Gene', '84557', (144, 147))	('attenuates', 'NegReg', (23, 33))	('LC3', 'Gene', (144, 147))	('decreasing', 'NegReg', (133, 143))	('Atg3', 'Protein', (104, 108))	('c-FLIPL', 'Var', (0, 7))	('inhibiting', 'NegReg', (93, 103))	('binding', 'Interaction', (109, 116))
34425	29163772	Unexpectedly, in all four primary thymoma epithelial cell cultures tested, cFLIP knockdown induced autophagosome formation and rendered pTECs sensitive to TNFalpha-induced cell death that could not be prevented by single agent pan-caspase and necroptosis inhibition.	('est', 'Gene', (68, 71))	('cFLIP', 'Gene', (75, 80))	('thymoma epithelial', 'Disease', (34, 52))	('est', 'Gene', '6783', (68, 71))	('induced', 'Reg', (91, 98))	('knockdown', 'Var', (81, 90))	('autophagosome formation', 'CPA', (99, 122))	('thymoma epithelial', 'Disease', 'MESH:D013945', (34, 52))	('pTECs', 'Chemical', '-', (136, 141))	('thymoma', 'Phenotype', 'HP:0100522', (34, 41))	('sensitive', 'MPA', (142, 151))
34426	29163772	This suggests that cFLIP in thymomas prevents epithelial cell death mainly through blockade of both apoptosis and autophagy.	('cFLIP', 'Var', (19, 24))	('thymomas', 'Disease', (28, 36))	('prevents', 'NegReg', (37, 45))	('thymoma', 'Phenotype', 'HP:0100522', (28, 35))	('autophagy', 'CPA', (114, 123))	('thymomas', 'Disease', 'MESH:D013945', (28, 36))	('est', 'Gene', '6783', (9, 12))	('est', 'Gene', (9, 12))	('epithelial cell death', 'CPA', (46, 67))	('apoptosis', 'CPA', (100, 109))
34429	29163772	Since TNFalpha treatment reduced survival of cFLIP-depleted, thymoma-derived pTECs by cFLIPshRNA or EF24 compared to untreated controls (Figure 5C and 7C), cell death control by intrinsic pathways is strongly operative in TETs and may need attention in future therapeutic trials for thymoma patients (see below).	('cFLIPshRNA', 'Var', (86, 96))	('TNFalpha', 'Gene', (6, 14))	('survival', 'CPA', (33, 41))	('reduced', 'NegReg', (25, 32))	('thymoma', 'Disease', (283, 290))	('thymoma', 'Disease', 'MESH:D013945', (61, 68))	('thymoma', 'Phenotype', 'HP:0100522', (283, 290))	('thymoma', 'Disease', (61, 68))	('patients', 'Species', '9606', (291, 299))	('thymoma', 'Phenotype', 'HP:0100522', (61, 68))	('pTECs', 'Chemical', '-', (77, 82))	('thymoma', 'Disease', 'MESH:D013945', (283, 290))	('TETs', 'Chemical', 'MESH:C010349', (222, 226))
34430	29163772	cFLIP expression is regulated by a broad spectrum of mechanisms, including histone acetylation DNA damage and ubiquitination miR-375 sonic hedgehog and myc signalling; and Hsp90.	('miR-375', 'Var', (125, 132))	('Hsp90', 'Gene', (172, 177))	('cFLIP', 'Gene', (0, 5))	('histone acetylation', 'MPA', (75, 94))	('Hsp90', 'Gene', '3320', (172, 177))	('ubiquitination', 'MPA', (110, 124))	('myc signalling', 'CPA', (152, 166))
34431	29163772	Here we focussed on NF-kappaB-driven cFLIP expression because it is common in many cancers Indeed, the NF-kappaB inhibitor, EF24 elicited cFLIP downregulation in primary thymoma TECs and 1889 thymic carcinoma cells (Figure 4A and Supplementary Figure 6A) and sensitized them to TNFalpha induced cell death (Figure 4B and 4C and Supplementary Figure 6B and 6C).	('cancers', 'Disease', 'MESH:D009369', (83, 90))	('cancers', 'Phenotype', 'HP:0002664', (83, 90))	('cell death', 'CPA', (295, 305))	('thymoma', 'Phenotype', 'HP:0100522', (170, 177))	('cFLIP', 'MPA', (138, 143))	('thymoma TECs', 'Disease', (170, 182))	('cancer', 'Phenotype', 'HP:0002664', (83, 89))	('thymic carcinoma', 'Disease', (192, 208))	('downregulation', 'NegReg', (144, 158))	('thymoma TECs', 'Disease', 'MESH:D013945', (170, 182))	('EF24', 'Var', (124, 128))	('thymic carcinoma', 'Disease', 'MESH:D013945', (192, 208))	('carcinoma', 'Phenotype', 'HP:0030731', (199, 208))	('cancers', 'Disease', (83, 90))
34432	29163772	Like cFLIP knockdown, NF-kappaB blockade induced both apoptosis and autophagy in 1889c TC cells (Supplementary Figure 7 and Figure 7) and in primary thymoma-derived TECs (Figure 4; Figure 5 and Figure 7).	('apoptosis', 'CPA', (54, 63))	('thymoma', 'Phenotype', 'HP:0100522', (149, 156))	('1889c TC', 'CellLine', 'CVCL:D024', (81, 89))	('TEC', 'Gene', (165, 168))	('thymoma', 'Disease', 'MESH:D013945', (149, 156))	('NF-kappaB', 'Protein', (22, 31))	('induced', 'Reg', (41, 48))	('autophagy', 'CPA', (68, 77))	('TEC', 'Gene', '7006', (165, 168))	('blockade', 'Var', (32, 40))	('thymoma', 'Disease', (149, 156))
34481	28278141	MG with thymoma is particularly associated with autoantibodies against postsynaptic nicotinic acetylcholine receptors (AchR-Abs).	('thymoma', 'Phenotype', 'HP:0100522', (8, 15))	('postsynaptic nicotinic acetylcholine receptors', 'Protein', (71, 117))	('acetylcholine', 'Chemical', 'MESH:D000109', (94, 107))	('thymoma', 'Disease', 'MESH:D013945', (8, 15))	('associated', 'Reg', (32, 42))	('thymoma', 'Disease', (8, 15))	('autoantibodies', 'Var', (48, 62))
34754	20859116	Given the contribution of genetic variation in development of other cancers, it would indeed be surprising if genetic risk factors were not present for thymoma.	('thymoma', 'Phenotype', 'HP:0100522', (152, 159))	('cancer', 'Phenotype', 'HP:0002664', (68, 74))	('thymoma', 'Gene', '7063', (152, 159))	('cancers', 'Phenotype', 'HP:0002664', (68, 75))	('thymoma', 'Gene', (152, 159))	('cancers', 'Disease', (68, 75))	('cancers', 'Disease', 'MESH:D009369', (68, 75))	('genetic variation', 'Var', (26, 43))
34797	32384230	Patients with TNM stage IV or R2 resection were suggested for postoperative chemotherapy.	('TNM', 'Gene', '10178', (14, 17))	('Patients', 'Species', '9606', (0, 8))	('R2 resection', 'Var', (30, 42))	('TNM', 'Gene', (14, 17))
34822	32384230	Incomplete resection was a risk factor for tumor recurrence (HR 4.784, 95% CI: 1.067-21.450, P = 0.041), while older age was a protective factor (HR 0.930, 95% CI: 0.880-0.984, P = 0.012)(Table 4).	('tumor', 'Phenotype', 'HP:0002664', (43, 48))	('tumor', 'Disease', (43, 48))	('tumor', 'Disease', 'MESH:D009369', (43, 48))	('Incomplete resection', 'Var', (0, 20))
34841	32384230	Complete resection is quite an important factor in thymoma prognosis and tumor recurrence.9, 13 This study demonstrated that resection status did not significantly influence the survival, but incomplete resection increased the possibility of tumor recurrence.	('thymoma', 'Gene', '7063', (51, 58))	('tumor', 'Disease', 'MESH:D009369', (73, 78))	('thymoma', 'Gene', (51, 58))	('tumor', 'Disease', 'MESH:D009369', (242, 247))	('tumor', 'Phenotype', 'HP:0002664', (73, 78))	('incomplete resection', 'Var', (192, 212))	('tumor', 'Phenotype', 'HP:0002664', (242, 247))	('tumor', 'Disease', (73, 78))	('tumor', 'Disease', (242, 247))	('thymoma', 'Phenotype', 'HP:0100522', (51, 58))
34886	31375453	The registry was queried to identify patients who were at least 20 years old when diagnosed with a first primary invasive tumor of the thymus (International Classification of Diseases for Oncology, 3rd edition [ICD-O-3] site codes C37.9 and histology codes 8580-8586) in California between 1988 and 2015.	('patients', 'Species', '9606', (37, 45))	('C37.9', 'Var', (231, 236))	('Oncology', 'Phenotype', 'HP:0002664', (188, 196))	('invasive tumor', 'Disease', 'MESH:D009361', (113, 127))	('tumor of the thymus', 'Phenotype', 'HP:0100521', (122, 141))	('tumor', 'Phenotype', 'HP:0002664', (122, 127))	('invasive tumor', 'Disease', (113, 127))
34892	31375453	Both thymoma (ICD-O-3 codes 8580-8585) and thymic carcinoma (code 8586) were included.	('thymoma', 'Disease', 'MESH:D013945', (5, 12))	('thymoma', 'Disease', (5, 12))	('thymic carcinoma', 'Disease', (43, 59))	('thymic carcinoma', 'Disease', 'MESH:D013953', (43, 59))	('thymoma', 'Phenotype', 'HP:0100522', (5, 12))	('carcinoma', 'Phenotype', 'HP:0030731', (50, 59))	('code 8586', 'Var', (61, 70))
34930	31375453	Similar to prior studies, we found that rates of thymic malignancies were higher among APIs than other races/ethnicities.	('APIs', 'Var', (87, 91))	('malignancies', 'Disease', (56, 68))	('higher', 'Reg', (74, 80))	('malignancies', 'Disease', 'MESH:D009369', (56, 68))
34958	28771603	PD-L1 positivity (>= 25% of tumor membrane expression) was frequent in TETs (15/23, 65%), more common in thymomas compared to thymic carcinomas (p<0.01), and was associated with longer overall survival (p = 0.02).	('thymic carcinomas', 'Disease', 'MESH:D013945', (126, 143))	('thymomas', 'Disease', 'MESH:D013945', (105, 113))	('overall', 'MPA', (185, 192))	('tumor', 'Disease', (28, 33))	('thymoma', 'Phenotype', 'HP:0100522', (105, 112))	('positivity', 'Var', (6, 16))	('longer', 'PosReg', (178, 184))	('carcinomas', 'Phenotype', 'HP:0030731', (133, 143))	('carcinoma', 'Phenotype', 'HP:0030731', (133, 142))	('PD-L1', 'Gene', (0, 5))	('thymic carcinomas', 'Disease', (126, 143))	('common', 'Reg', (95, 101))	('tumor', 'Disease', 'MESH:D009369', (28, 33))	('thymomas', 'Disease', (105, 113))	('PD-L1', 'Gene', '29126', (0, 5))	('tumor', 'Phenotype', 'HP:0002664', (28, 33))
34977	28771603	Based on reported clinical trials of patients treated with durvalumab in which PD-L1 expression >= 25% has been associated with improved outcomes,, we pre-specified the definition of patients as PD-L1 "positive" as those with M-score >= 25%.	('>= 25%', 'Var', (96, 102))	('patients', 'Species', '9606', (37, 45))	('improved', 'PosReg', (128, 136))	('PD-L1', 'Gene', (195, 200))	('PD-L1', 'Gene', (79, 84))	('durvalumab', 'Chemical', 'MESH:C000613593', (59, 69))	('PD-L1', 'Gene', '29126', (195, 200))	('PD-L1', 'Gene', '29126', (79, 84))	('patients', 'Species', '9606', (183, 191))
34986	28771603	PD-L1 positivity was more common in thymomas compared with thymic carcinomas (11/12 vs. 4/11, p<0.01) as summarized in Table 2.	('carcinoma', 'Phenotype', 'HP:0030731', (66, 75))	('carcinomas', 'Phenotype', 'HP:0030731', (66, 76))	('thymic carcinomas', 'Disease', 'MESH:D013945', (59, 76))	('positivity', 'Var', (6, 16))	('thymoma', 'Phenotype', 'HP:0100522', (36, 43))	('PD-L1', 'Gene', (0, 5))	('common', 'Reg', (26, 32))	('thymomas', 'Disease', (36, 44))	('thymomas', 'Disease', 'MESH:D013945', (36, 44))	('thymic carcinomas', 'Disease', (59, 76))	('PD-L1', 'Gene', '29126', (0, 5))
34992	28771603	High/moderate CD137 expression co-associated with several markers, including CD8 (p = 0.01), CTLA-4 (p = 0.008), and ICOS (p = 0.03).	('CD8', 'Gene', (77, 80))	('ICOS', 'Gene', '29851', (117, 121))	('CD137', 'Gene', '3604', (14, 19))	('co-associated', 'Reg', (31, 44))	('CTLA-4', 'Gene', '1493', (93, 99))	('expression', 'MPA', (20, 30))	('CD8', 'Gene', '925', (77, 80))	('CTLA-4', 'Gene', (93, 99))	('High/moderate', 'Var', (0, 13))	('CD137', 'Gene', (14, 19))	('ICOS', 'Gene', (117, 121))
34993	28771603	High/moderate GITR expression co-associated with PD-1 (p = 0.043).	('PD-1', 'Gene', (49, 53))	('GITR', 'Gene', '8784', (14, 18))	('PD-1', 'Gene', '5133', (49, 53))	('GITR', 'Gene', (14, 18))	('High/moderate', 'Var', (0, 13))
34999	28771603	The presence of moderate and high levels of CD3+ TILs (IHC 2 or 3 vs IHC 1) was also associated with an improved OS (mOS 80 months [95% CI:34-80] versus 43 months [95% CI 23-79], p = 0.04, Fig 3B).	('mOS', 'Gene', (117, 120))	('improved', 'PosReg', (104, 112))	('CD3+', 'Var', (44, 48))	('OS', 'Gene', '17451', (118, 120))	('CD3+ TILs', 'Chemical', '-', (44, 53))	('mOS', 'Gene', '17451', (117, 120))	('OS', 'Gene', '17451', (113, 115))
35006	28771603	The finding that PD-L1 expression is associated with improved survival has been noted in other tumor types as well.	('survival', 'MPA', (62, 70))	('PD-L1', 'Gene', '29126', (17, 22))	('expression', 'Var', (23, 33))	('tumor', 'Disease', 'MESH:D009369', (95, 100))	('tumor', 'Phenotype', 'HP:0002664', (95, 100))	('PD-L1', 'Gene', (17, 22))	('improved', 'PosReg', (53, 61))	('tumor', 'Disease', (95, 100))
35007	28771603	For example, in patients with non-small cell lung cancers (NSCLCs), PD-L1 expression was associated with improved overall survival independent of age and stage of disease and also associated with improved overall survival in early stage patients.	('non-small cell lung cancers', 'Phenotype', 'HP:0030358', (30, 57))	('overall survival', 'MPA', (114, 130))	('cancers', 'Phenotype', 'HP:0002664', (50, 57))	('expression', 'Var', (74, 84))	('patients', 'Species', '9606', (16, 24))	('small cell lung cancers', 'Phenotype', 'HP:0030357', (34, 57))	('non-small cell lung cancers', 'Disease', (30, 57))	('overall', 'MPA', (205, 212))	('PD-L1', 'Gene', (68, 73))	('lung cancers', 'Phenotype', 'HP:0100526', (45, 57))	('cancer', 'Phenotype', 'HP:0002664', (50, 56))	('improved', 'PosReg', (105, 113))	('non-small cell lung cancers', 'Disease', 'MESH:D002289', (30, 57))	('patients', 'Species', '9606', (237, 245))	('improved', 'PosReg', (196, 204))	('PD-L1', 'Gene', '29126', (68, 73))
35009	28771603	This association between high PD-L1 expression and improved benefit from PD-1/PD-L1 blockade in other tumor types raises the possibility that anti-PD-1/PD-L1 drugs may be effective therapy for patients with TETs.	('patients', 'Species', '9606', (193, 201))	('PD-L1', 'Gene', '29126', (152, 157))	('PD-1', 'Gene', (147, 151))	('PD-1/PD-L1 blockade', 'Disease', 'MESH:D010300', (73, 92))	('PD-L1', 'Gene', (78, 83))	('PD-1', 'Gene', '5133', (147, 151))	('tumor', 'Disease', 'MESH:D009369', (102, 107))	('PD-L1', 'Gene', (152, 157))	('PD-1', 'Gene', (73, 77))	('PD-L1', 'Gene', (30, 35))	('high', 'Var', (25, 29))	('PD-1', 'Gene', '5133', (73, 77))	('PD-L1', 'Gene', '29126', (30, 35))	('PD-L1', 'Gene', '29126', (78, 83))	('PD-1/PD-L1 blockade', 'Disease', (73, 92))	('tumor', 'Disease', (102, 107))	('expression', 'MPA', (36, 46))	('tumor', 'Phenotype', 'HP:0002664', (102, 107))
35026	28771603	Abcam EPR1161) which have no known cutpoint or predictive appreciation with response to anti-PD(L1) therapy and therefore may have limited clinical implications.	('Abcam', 'Gene', (0, 5))	('PD(L1', 'Gene', '29126', (93, 98))	('EPR1161', 'Var', (6, 13))
35028	28771603	Padda et al concluded that high PD-L1 expression associated with poorer overall survival while Katsuya et al.	('PD-L1', 'Gene', (32, 37))	('overall', 'MPA', (72, 79))	('expression', 'MPA', (38, 48))	('poorer', 'NegReg', (65, 71))	('high', 'Var', (27, 31))	('PD-L1', 'Gene', '29126', (32, 37))
35032	28771603	Yokoyama and colleagues similarly described improved overall survival in high PD-L1 expression, however this series was limited to only thymic carcinoma histology.	('carcinoma', 'Phenotype', 'HP:0030731', (143, 152))	('PD-L1', 'Gene', (78, 83))	('thymic carcinoma', 'Disease', (136, 152))	('overall survival', 'MPA', (53, 69))	('PD-L1', 'Gene', '29126', (78, 83))	('improved', 'PosReg', (44, 52))	('high', 'Var', (73, 77))	('thymic carcinoma', 'Disease', 'MESH:D013945', (136, 152))
35049	22973113	Alterations affecting chromosome 6p21.3 (MHC locus) and 6q25.2-25.3 are the most frequently observed genetic alterations in thymomas and thymic squamous cell carcinomas.	('MHC', 'Gene', '3107', (41, 44))	('thymomas', 'Disease', (124, 132))	('thymomas', 'Disease', 'MESH:D013945', (124, 132))	('Alterations', 'Var', (0, 11))	('squamous cell carcinomas', 'Disease', (144, 168))	('squamous cell carcinomas', 'Disease', 'MESH:D002294', (144, 168))	('carcinoma', 'Phenotype', 'HP:0030731', (158, 167))	('squamous cell carcinomas', 'Phenotype', 'HP:0002860', (144, 168))	('MHC', 'Gene', (41, 44))	('thymoma', 'Phenotype', 'HP:0100522', (124, 131))	('carcinomas', 'Phenotype', 'HP:0030731', (158, 168))
35052	22973113	While epidermal growth factor receptor (EGFR) overexpression is common in thymomas (70%) and about half (53%) of thymic carcinomas, EGFR mutations are exceedingly rare, with only three EGFR mutations noted in a total of 158 tumors analyzed.	('overexpression', 'PosReg', (46, 60))	('tumor', 'Phenotype', 'HP:0002664', (224, 229))	('tumors', 'Disease', (224, 230))	('carcinoma', 'Phenotype', 'HP:0030731', (120, 129))	('carcinomas', 'Phenotype', 'HP:0030731', (120, 130))	('EGFR', 'Gene', '1956', (132, 136))	('epidermal growth factor receptor', 'Gene', (6, 38))	('EGFR', 'Gene', (185, 189))	('tumors', 'Disease', 'MESH:D009369', (224, 230))	('thymoma', 'Phenotype', 'HP:0100522', (74, 81))	('EGFR', 'Gene', (40, 44))	('epidermal growth factor receptor', 'Gene', '1956', (6, 38))	('thymomas', 'Disease', 'MESH:D013945', (74, 82))	('thymic carcinomas', 'Disease', 'MESH:D013945', (113, 130))	('thymic carcinomas', 'Disease', (113, 130))	('thymomas', 'Disease', (74, 82))	('EGFR', 'Gene', '1956', (185, 189))	('tumors', 'Phenotype', 'HP:0002664', (224, 230))	('EGFR', 'Gene', (132, 136))	('mutations', 'Var', (137, 146))	('EGFR', 'Gene', '1956', (40, 44))
35053	22973113	RAS mutations are also rare, with a series at Memorial Sloan-Kettering Cancer Center showing only three (two thymomas and one thymic carcinoma) out of 45 (7%) TETs displaying RAS mutations.	('Cancer', 'Disease', (71, 77))	('Cancer', 'Disease', 'MESH:D009369', (71, 77))	('thymoma', 'Phenotype', 'HP:0100522', (109, 116))	('carcinoma', 'Phenotype', 'HP:0030731', (133, 142))	('thymomas', 'Disease', (109, 117))	('thymic carcinoma', 'Disease', (126, 142))	('mutations', 'Var', (4, 13))	('thymomas', 'Disease', 'MESH:D013945', (109, 117))	('thymic carcinoma', 'Disease', 'MESH:D013945', (126, 142))	('Cancer', 'Phenotype', 'HP:0002664', (71, 77))
35132	22973113	The potential use of imatinib for thymic carcinoma generated a great deal of excitement following the publication of a case report of imatinib leading to an impressive response in a patient with metastatic epidermoid carcinoma of the thymus.	('epidermoid carcinoma of the thymus', 'Disease', 'MESH:D002294', (206, 240))	('carcinoma', 'Phenotype', 'HP:0030731', (41, 50))	('carcinoma of the thymus', 'Phenotype', 'HP:0100521', (217, 240))	('thymic carcinoma', 'Disease', 'MESH:D013945', (34, 50))	('patient', 'Species', '9606', (182, 189))	('thymic carcinoma', 'Disease', (34, 50))	('imatinib', 'Chemical', 'MESH:D000068877', (21, 29))	('epidermoid carcinoma of the thymus', 'Disease', (206, 240))	('imatinib', 'Var', (134, 142))	('imatinib', 'Chemical', 'MESH:D000068877', (134, 142))	('carcinoma', 'Phenotype', 'HP:0030731', (217, 226))
35140	22973113	It was discovered that three tumors analyzed had no c-KIT or PDGFR mutations, and only one of four tumors analyzed demonstrated c-KIT expression by immunohistochemistry.	('c-KIT', 'Gene', '3815', (128, 133))	('tumors', 'Disease', 'MESH:D009369', (99, 105))	('c-KIT', 'Gene', (52, 57))	('PDGFR', 'Gene', (61, 66))	('tumor', 'Phenotype', 'HP:0002664', (29, 34))	('mutations', 'Var', (67, 76))	('PDGFR', 'Gene', '5159', (61, 66))	('c-KIT', 'Gene', '3815', (52, 57))	('tumors', 'Phenotype', 'HP:0002664', (29, 35))	('c-KIT', 'Gene', (128, 133))	('tumors', 'Disease', 'MESH:D009369', (29, 35))	('tumor', 'Phenotype', 'HP:0002664', (99, 104))	('tumors', 'Disease', (29, 35))	('tumors', 'Phenotype', 'HP:0002664', (99, 105))	('tumors', 'Disease', (99, 105))
35148	22973113	It turns out that c-KIT mutations, which may well be required in order for patients to respond to imatinib, are actually rather rare in thymic carcinomas.	('carcinomas', 'Phenotype', 'HP:0030731', (143, 153))	('c-KIT', 'Gene', (18, 23))	('thymic carcinomas', 'Disease', 'MESH:D013945', (136, 153))	('carcinoma', 'Phenotype', 'HP:0030731', (143, 152))	('patients', 'Species', '9606', (75, 83))	('thymic carcinomas', 'Disease', (136, 153))	('c-KIT', 'Gene', '3815', (18, 23))	('imatinib', 'Chemical', 'MESH:D000068877', (98, 106))	('mutations', 'Var', (24, 33))
35150	22973113	All c-KIT mutations occurred in tumors expressing c-KIT by immunohistochemistry and all occurred in poorly differentiated squamous cell carcinomas with a particularly solid growth pattern.	('c-KIT', 'Gene', (4, 9))	('c-KIT', 'Gene', (50, 55))	('squamous cell carcinomas', 'Disease', 'MESH:D002294', (122, 146))	('squamous cell carcinomas', 'Disease', (122, 146))	('c-KIT', 'Gene', '3815', (50, 55))	('c-KIT', 'Gene', '3815', (4, 9))	('occurred', 'Reg', (88, 96))	('squamous cell carcinomas', 'Phenotype', 'HP:0002860', (122, 146))	('tumors', 'Phenotype', 'HP:0002664', (32, 38))	('carcinomas', 'Phenotype', 'HP:0030731', (136, 146))	('tumor', 'Phenotype', 'HP:0002664', (32, 37))	('carcinoma', 'Phenotype', 'HP:0030731', (136, 145))	('tumors', 'Disease', (32, 38))	('mutations', 'Var', (10, 19))	('occurred', 'Reg', (20, 28))	('tumors', 'Disease', 'MESH:D009369', (32, 38))
35151	22973113	There were a total of twelve such cases in the series, meaning c-KIT mutations were seen in half of them.	('mutations', 'Var', (69, 78))	('c-KIT', 'Gene', '3815', (63, 68))	('c-KIT', 'Gene', (63, 68))
35153	22973113	Positive tumors should be evaluated for c-KIT mutations, and imatinib therapy could be considered for those tumors with likely sensitive mutations in exons 9 or 11.	('mutations', 'Var', (46, 55))	('tumor', 'Phenotype', 'HP:0002664', (108, 113))	('c-KIT', 'Gene', '3815', (40, 45))	('tumor', 'Phenotype', 'HP:0002664', (9, 14))	('mutations', 'Var', (137, 146))	('tumors', 'Phenotype', 'HP:0002664', (9, 15))	('imatinib', 'Chemical', 'MESH:D000068877', (61, 69))	('tumors', 'Disease', (108, 114))	('tumors', 'Disease', 'MESH:D009369', (108, 114))	('tumors', 'Phenotype', 'HP:0002664', (108, 114))	('tumors', 'Disease', (9, 15))	('tumors', 'Disease', 'MESH:D009369', (9, 15))	('c-KIT', 'Gene', (40, 45))
35156	22973113	There are two case reports of pretreated patients thymic carcinoma with c-KIT mutations (one in exon 11, the other in exon 17) experiencing impressive responses to sorafenib.	('thymic carcinoma', 'Disease', (50, 66))	('thymic carcinoma', 'Disease', 'MESH:D013945', (50, 66))	('c-KIT', 'Gene', (72, 77))	('carcinoma', 'Phenotype', 'HP:0030731', (57, 66))	('mutations', 'Var', (78, 87))	('patients', 'Species', '9606', (41, 49))	('c-KIT', 'Gene', '3815', (72, 77))	('sorafenib', 'Chemical', 'MESH:D000077157', (164, 173))
35164	22973113	SU014813 is an oral multitargeted TKI that targets the VEGF receptors, PDGFRs, KIT, and FMS-like tyrosine kinase 3.	('VEGF', 'Gene', (55, 59))	('SU014813', 'Chemical', '-', (0, 8))	('FMS-like tyrosine kinase 3', 'Gene', '2322', (88, 114))	('SU014813', 'Var', (0, 8))	('VEGF', 'Gene', '7422', (55, 59))	('PDGFR', 'Gene', (71, 76))	('PDGFR', 'Gene', '5159', (71, 76))	('FMS-like tyrosine kinase 3', 'Gene', (88, 114))
35172	22973113	None of five patients analyzed, including the patient with the PR, were found to have EGFR-activating or KRAS mutations by DNA sequencing.	('patient', 'Species', '9606', (46, 53))	('mutations', 'Var', (110, 119))	('patient', 'Species', '9606', (13, 20))	('EGFR', 'Gene', '1956', (86, 90))	('patients', 'Species', '9606', (13, 21))	('KRAS', 'Gene', (105, 109))	('EGFR', 'Gene', (86, 90))	('KRAS', 'Gene', '3845', (105, 109))
35173	22973113	EGFR-activating mutations have been found to be a predictor for response among patients with non-small cell lung cancer.	('small cell lung cancer', 'Phenotype', 'HP:0030357', (97, 119))	('EGFR', 'Gene', (0, 4))	('cancer', 'Phenotype', 'HP:0002664', (113, 119))	('non-small cell lung cancer', 'Phenotype', 'HP:0030358', (93, 119))	('mutations', 'Var', (16, 25))	('lung cancer', 'Phenotype', 'HP:0100526', (108, 119))	('patients', 'Species', '9606', (79, 87))	('non-small cell lung cancer', 'Disease', 'MESH:D002289', (93, 119))	('EGFR', 'Gene', '1956', (0, 4))	('non-small cell lung cancer', 'Disease', (93, 119))
35179	22973113	Therefore, inhibitors of HDAC enzymes alter the patterns of gene expression and can lead to cellular differentiation, growth arrest, and/or apoptosis of cancer cells.	('cancer', 'Disease', 'MESH:D009369', (153, 159))	('cellular differentiation', 'CPA', (92, 116))	('lead to', 'Reg', (84, 91))	('patterns of gene expression', 'MPA', (48, 75))	('cancer', 'Disease', (153, 159))	('apoptosis', 'CPA', (140, 149))	('growth arrest', 'Phenotype', 'HP:0001510', (118, 131))	('growth arrest', 'CPA', (118, 131))	('cancer', 'Phenotype', 'HP:0002664', (153, 159))	('inhibitors', 'Var', (11, 21))	('alter', 'Reg', (38, 43))	('HDAC', 'Gene', (25, 29))	('HDAC', 'Gene', '9734', (25, 29))
35201	22973113	Positivity for IGF-1R was observed more frequently in recurrent disease, in more aggressive histologic subtypes, and in cases of advanced disease.	('recurrent disease', 'Disease', (54, 71))	('advanced disease', 'Disease', 'MESH:D020178', (129, 145))	('IGF-1R', 'Gene', (15, 21))	('IGF-1R', 'Gene', '3480', (15, 21))	('observed', 'Reg', (26, 34))	('Positivity', 'Var', (0, 10))	('advanced disease', 'Disease', (129, 145))
35207	22973113	PHA-848125AC is an orally administered inhibitor of cyclindependent kinase 2/cyclin A complex and TrkA.	('cyclin A', 'Gene', (77, 85))	('cyclin A', 'Gene', '890', (77, 85))	('TrkA', 'Gene', '4914', (98, 102))	('TrkA', 'Gene', (98, 102))	('PHA-848125AC', 'Var', (0, 12))	('848125AC', 'Chemical', '-', (4, 12))
35277	31033234	Indeed, prior studies including a small number of thymic cysts reported that three-fourths or more of thymic cysts had CT attenuation equal to that of the chest wall muscle, which was attributed to high calcium or protein contents, hemorrhage, or streak artifacts.11, 12 Focal necrosis existed in 33.3% of thymomas in our results, consistent with the results of other studies, where focal necrosis was found in 28-42% of thymomas.	('calcium', 'Chemical', 'MESH:D002118', (203, 210))	('necrosis', 'Disease', (389, 397))	('thymoma', 'Phenotype', 'HP:0100522', (306, 313))	('necrosis', 'Disease', 'MESH:D009336', (277, 285))	('thymoma', 'Phenotype', 'HP:0100522', (421, 428))	('thymomas', 'Disease', (306, 314))	('artifacts.11', 'Var', (254, 266))	('thymomas', 'Disease', 'MESH:D013945', (306, 314))	('hemorrhage', 'Disease', (232, 242))	('thymomas', 'Disease', (421, 429))	('thymomas', 'Disease', 'MESH:D013945', (421, 429))	('necrosis', 'Disease', 'MESH:D009336', (389, 397))	('hemorrhage', 'Disease', 'MESH:D006470', (232, 242))	('necrosis', 'Disease', (277, 285))
35392	27227948	The thymus plays a primary role in early-onset MG mediated by anti-AChR antibodies.	('MG', 'Disease', 'MESH:D000080343', (47, 49))	('anti-AChR antibodies', 'Var', (62, 82))	('mediated', 'Reg', (50, 58))	('antibodies', 'Var', (72, 82))
35484	26904321	Additional oncogenic events, such as inactivation of tumor suppression genes and/or activation of protooncogenes, may also be required before clones become malignant and are capable of widespread dissemination and growth.	('tumor', 'Disease', 'MESH:D009369', (53, 58))	('inactivation', 'Var', (37, 49))	('tumor', 'Phenotype', 'HP:0002664', (53, 58))	('tumor', 'Disease', (53, 58))
35515	22882218	In approximately 85% of MG patients, circulating antibodies against the acetylcholine receptor (AChR) bungarotoxin-binding site are not only the pathogenic effector immune molecules but also provide a sensitive and specific diagnostic test.	('ACh', 'Chemical', 'MESH:D000109', (96, 99))	('AChR', 'Gene', (96, 100))	('acetylcholine', 'Chemical', 'MESH:D000109', (72, 85))	('patients', 'Species', '9606', (27, 35))	('antibodies', 'Var', (49, 59))
35523	22882218	Evidence from classical experiments indicates that anti-AChR antibodies are pathogenic (the main cause of weakness in MG), leading to end-plate AChR loss, simplification of the postsynaptic membrane and derangement of neuromuscular transmission.	('weakness', 'Disease', (106, 114))	('weakness', 'Disease', 'MESH:D018908', (106, 114))	('derangement', 'Reg', (203, 214))	('antibodies', 'Var', (61, 71))	('anti-AChR', 'Protein', (51, 60))	('ACh', 'Chemical', 'MESH:D000109', (144, 147))	('loss', 'NegReg', (149, 153))	('derangement of neuromuscular transmission', 'Phenotype', 'HP:0003398', (203, 244))	('end-plate AChR', 'MPA', (134, 148))	('ACh', 'Chemical', 'MESH:D000109', (56, 59))	('neuromuscular transmission', 'MPA', (218, 244))	('simplification of the postsynaptic membrane', 'MPA', (155, 198))
35526	22882218	Antibody binding reduces the number and/or function of muscle AChRs by three main mechanisms: complement activation resulting in destruction and focal lysis of the postsynaptic folds at the NMJ leading to the destruction of AChR and AChR-related proteins at the end-plate (i.e., rapsyn and voltage-gated sodium channels); cross-linking of adjacent AChRs resulting in their accelerated internalization and degradation; and blocking of the acetylcholine (ACh)-binding site.	('ACh', 'Chemical', 'MESH:D000109', (233, 236))	('function', 'MPA', (43, 51))	('reduces', 'NegReg', (17, 24))	('ACh', 'Chemical', 'MESH:D000109', (62, 65))	('rapsyn', 'Gene', (279, 285))	('sodium', 'Chemical', 'MESH:D012964', (304, 310))	('cross-linking', 'Var', (322, 335))	('internalization', 'MPA', (385, 400))	('ACh', 'Chemical', 'MESH:D000109', (224, 227))	('ACh', 'Chemical', 'MESH:D000109', (453, 456))	('ACh', 'Chemical', 'MESH:D000109', (348, 351))	('accelerated', 'PosReg', (373, 384))	('acetylcholine', 'MPA', (438, 451))	('acetylcholine', 'Chemical', 'MESH:D000109', (438, 451))	('rapsyn', 'Gene', '5913', (279, 285))	('blocking', 'NegReg', (422, 430))	('degradation', 'MPA', (405, 416))	('AChR', 'Protein', (224, 228))
35528	22882218	The thymus gland plays an incompletely understood but critical role in the pathogenesis of MG with AChR autoantibodies.	('ACh', 'Chemical', 'MESH:D000109', (99, 102))	('AChR', 'Gene', (99, 103))	('autoantibodies', 'Var', (104, 118))
35540	22882218	As a primary site for the establishment of immune regulation, derangements in the thymus gland may lead to a defect in the immune system's suppression of autoreactive lymphocytes, allowing for the development of anti-AChR immune responses.	('derangements', 'Var', (62, 74))	('lead to', 'Reg', (99, 106))	('allowing for', 'Reg', (180, 192))	('ACh', 'Chemical', 'MESH:D000109', (217, 220))	('defect in the immune system', 'Phenotype', 'HP:0002715', (109, 136))	('derangements in the thymus', 'Phenotype', 'HP:0000777', (62, 88))	('suppression', 'CPA', (139, 150))	('anti-AChR immune responses', 'CPA', (212, 238))
35545	22882218	AChR-related antibodies in MG can be classified into three types (based on the effects of the antibodies on AChRs and AChR turnover): binding, blocking and modulating.	('ACh', 'Chemical', 'MESH:D000109', (0, 3))	('modulating', 'Var', (156, 166))	('ACh', 'Chemical', 'MESH:D000109', (108, 111))	('ACh', 'Chemical', 'MESH:D000109', (118, 121))	('binding', 'Interaction', (134, 141))
35547	22882218	As noted, autoantibodies against AChRs can be detected in approximately 80-85% of patients with generalized MG and 50-75% of patients with ocular MG.	('autoantibodies', 'Var', (10, 24))	('AChRs', 'Gene', (33, 38))	('patients', 'Species', '9606', (82, 90))	('generalized MG', 'Disease', (96, 110))	('detected', 'Reg', (46, 54))	('ACh', 'Chemical', 'MESH:D000109', (33, 36))	('patients', 'Species', '9606', (125, 133))
35557	22882218	Modulating AChR antibodies accelerate the rate of AChR internalization by cross-linking adjacent receptors and are detected by measuring the amount of internalized, processed 125I-alpha-bungarotoxin-labeled AChR released from cultured cells.	('Modulating', 'Var', (0, 10))	('cross-linking', 'Interaction', (74, 87))	('ACh', 'Chemical', 'MESH:D000109', (11, 14))	('accelerate', 'PosReg', (27, 37))	('AChR', 'Gene', (11, 15))	('internalization', 'MPA', (55, 70))	('ACh', 'Chemical', 'MESH:D000109', (207, 210))	('125I-alpha-bungarotoxin', 'Chemical', '-', (175, 198))	('ACh', 'Chemical', 'MESH:D000109', (50, 53))
35579	22882218	The role of MuSK in mature adult muscle is less clear, but inhibition of MuSK synthesis has been found to cause AChR dispersion and end-plate disruption.	('cause', 'Reg', (106, 111))	('end-plate disruption', 'CPA', (132, 152))	('MuSK synthesis', 'Gene', (73, 87))	('inhibition', 'Var', (59, 69))	('AChR dispersion', 'CPA', (112, 127))	('ACh', 'Chemical', 'MESH:D000109', (112, 115))
35588	22882218	Recent studies, however, demonstrate that complement activation may not be necessary for the onset of MuSK MG in mice and that both divalent and monovalent antibodies may induce MuSK dysfunction without the activation of complement.	('MuSK dysfunction', 'Disease', (178, 194))	('MuSK dysfunction', 'Disease', 'MESH:D009157', (178, 194))	('MuSK dysfunction', 'Phenotype', 'HP:0030210', (178, 194))	('monovalent antibodies', 'Var', (145, 166))	('mice', 'Species', '10090', (113, 117))	('induce', 'Reg', (171, 177))
35593	22882218	While MG patients with anti-MuSK antibodies may have presentations similar to anti-AChR-positive MG, they frequently have atypical clinical features, such as selective facial, bulbar, neck and respiratory muscle weakness and marked muscle atrophy, occasionally with relative sparing of ocular muscles.	('patients', 'Species', '9606', (9, 17))	('muscle atrophy', 'Disease', 'MESH:D009133', (232, 246))	('respiratory muscle weakness', 'Phenotype', 'HP:0002747', (193, 220))	('selective facial', 'Disease', (158, 174))	('bulbar', 'Disease', (176, 182))	('respiratory muscle weakness', 'Disease', (193, 220))	('anti-MuSK antibodies', 'Var', (23, 43))	('respiratory muscle weakness', 'Disease', 'MESH:D012131', (193, 220))	('ACh', 'Chemical', 'MESH:D000109', (83, 86))	('anti-MuSK antibodies', 'Phenotype', 'HP:0030210', (23, 43))	('muscle weakness', 'Phenotype', 'HP:0001324', (205, 220))	('MuSK antibodies', 'Phenotype', 'HP:0030210', (28, 43))	('muscle atrophy', 'Disease', (232, 246))	('muscle atrophy', 'Phenotype', 'HP:0003202', (232, 246))	('antibodies', 'Var', (33, 43))	('neck', 'Disease', (184, 188))
35618	22882218	In general, anti-titin antibodies correlate with disease severity and may identify patients more likely to be refractory to therapy, including thymectomy.	('antibodies', 'Var', (23, 33))	('titin', 'Gene', (17, 22))	('thymectomy', 'Disease', (143, 153))	('patients', 'Species', '9606', (83, 91))	('titin', 'Gene', '7273', (17, 22))
35637	22882218	The combination of titin and RyR antibody positivity is approximately 95% sensitive and 70% specific for thymoma in MG. RyR antibodies are positively associated with invasive/malignant thymoma, so that their presence in an MG patient undergoing thymectomy should alert the surgeon to choose a technique that assures complete exploration and removal.	('RyR', 'Gene', (120, 123))	('RyR', 'Gene', '6261', (120, 123))	('thymoma', 'Disease', (105, 112))	('thymoma', 'Disease', 'MESH:D013945', (105, 112))	('titin', 'Gene', '7273', (19, 24))	('thymoma', 'Phenotype', 'HP:0100522', (105, 112))	('patient', 'Species', '9606', (226, 233))	('thymoma', 'Disease', 'MESH:D013945', (185, 192))	('thymoma', 'Phenotype', 'HP:0100522', (185, 192))	('thymoma', 'Disease', (185, 192))	('RyR', 'Gene', (29, 32))	('RyR', 'Gene', '6261', (29, 32))	('titin', 'Gene', (19, 24))	('antibodies', 'Var', (124, 134))	('associated with', 'Reg', (150, 165))
35665	22882218	Autoantibodies to other end-plate proteins may play a role in patients with anti-AChR- and anti-MuSK negative MG.	('anti-AChR-', 'Protein', (76, 86))	('play', 'Reg', (47, 51))	('anti-MuSK', 'Var', (91, 100))	('ACh', 'Chemical', 'MESH:D000109', (81, 84))	('negative', 'NegReg', (101, 109))	('patients', 'Species', '9606', (62, 70))	('anti-MuSK negative', 'Phenotype', 'HP:0030210', (91, 109))
35666	22882218	Recent studies have identified anti-lipoprotein receptor-related protein 4 antibodies in approximately 9% of double-seronegative generalized MG patients.	('antibodies', 'Var', (75, 85))	('lipoprotein receptor-related protein 4', 'Gene', (36, 74))	('patients', 'Species', '9606', (144, 152))	('lipoprotein receptor-related protein 4', 'Gene', '4038', (36, 74))	('generalized MG', 'Disease', (129, 143))
35693	33362698	On the opposite of the scale, MuSK MG has a more dangerous prognosis with prominent bulbar, neck and respiratory muscle involvement and frequent respiratory crisis.	('respiratory muscle involvement', 'Disease', 'MESH:D012131', (101, 131))	('frequent respiratory crisis', 'Phenotype', 'HP:0002205', (136, 163))	('bulbar', 'Disease', (84, 90))	('MuSK MG', 'Var', (30, 37))	('respiratory crisis', 'CPA', (145, 163))	('MuSK MG', 'CellLine', 'CVCL:1698', (30, 37))	('respiratory muscle involvement', 'Disease', (101, 131))
35695	33362698	The thymus does not appear to be involved (no LFH, no thymoma) in patients with MuSK MG. Interestingly, MuSK MG has a marked female dominance with a female to male ratio of 9:1.	('thymoma', 'Disease', (54, 61))	('MuSK MG', 'Var', (104, 111))	('thymoma', 'Phenotype', 'HP:0100522', (54, 61))	('MuSK MG', 'CellLine', 'CVCL:1698', (104, 111))	('MuSK MG', 'CellLine', 'CVCL:1698', (80, 87))	('patients', 'Species', '9606', (66, 74))	('thymoma', 'Disease', 'MESH:D013945', (54, 61))
35700	33362698	The combination of antibodies to agrin and LRP4 produces more severe symptoms than LRP4 alone.	('LRP4', 'Gene', '4038', (43, 47))	('LRP4', 'Gene', (83, 87))	('antibodies', 'Var', (19, 29))	('LRP4', 'Gene', '4038', (83, 87))	('agrin', 'Gene', '375790', (33, 38))	('combination', 'Interaction', (4, 15))	('LRP4', 'Gene', (43, 47))	('agrin', 'Gene', (33, 38))
35708	33362698	The immunopathologic mechanisms by which these Abs can affect the signal transmission are: cross-linking of AChR leading to increased endocytosis; activation of complement cascade causing AChR loss and destruction of the postjunctional membrane; and also by directly blocking the acetylcholine binding to AChR site (Figure 1A).	('AChR', 'MPA', (188, 192))	('affect', 'Reg', (55, 61))	('loss', 'NegReg', (193, 197))	('increased', 'PosReg', (124, 133))	('cross-linking', 'Var', (91, 104))	('endocytosis', 'MPA', (134, 145))	('signal transmission', 'MPA', (66, 85))	('AChR', 'Gene', (108, 112))	('destruction', 'NegReg', (202, 213))	('acetylcholine', 'Chemical', 'MESH:D000109', (280, 293))	('blocking', 'NegReg', (267, 275))	('acetylcholine', 'MPA', (280, 293))	('binding', 'Interaction', (294, 301))
35743	33362698	In contrast, MuSK cell-based assay (MuSK-CBAs; HEK293 cells transfected with MuSK recombinant antigen) has been reported to have increased sensitivity (6-10%) due to additional detection of conformation-dependent MuSK Abs.	('MuSK', 'Gene', (36, 40))	('MuSK', 'Gene', (77, 81))	('HEK293', 'CellLine', 'CVCL:0045', (47, 53))	('MuSK', 'Gene', '4593', (77, 81))	('MuSK', 'Gene', '4593', (13, 17))	('MuSK', 'Gene', (13, 17))	('MuSK', 'Gene', '4593', (213, 217))	('MuSK', 'Gene', (213, 217))	('conformation-dependent', 'Var', (190, 212))	('MuSK Abs', 'Phenotype', 'HP:0030210', (213, 221))	('MuSK', 'Gene', '4593', (36, 40))
35774	33362698	In Japanese patients the presence of Kv1.4Abs has been associated with mild to severe disease, myasthenia crisis, and thymic abnormalities.	('patients', 'Species', '9606', (12, 20))	('thymic abnormalities', 'Phenotype', 'HP:0000777', (118, 138))	('myasthenia', 'Phenotype', 'HP:0003473', (95, 105))	('Kv1.4', 'Gene', '3739', (37, 42))	('presence', 'Var', (25, 33))	('associated', 'Reg', (55, 65))	('thymic abnormalities', 'Disease', 'MESH:D013953', (118, 138))	('mild to severe disease', 'Disease', (71, 93))	('thymic abnormalities', 'Disease', (118, 138))	('myasthenia crisis', 'Disease', 'MESH:D020294', (95, 112))	('Kv1.4', 'Gene', (37, 42))	('myasthenia crisis', 'Disease', (95, 112))
35797	33362698	In contrast, LRP-4 Abs positive patients generally have milder phenotype and they respond well to pyridostigmine, prednisone as well as IVIG treatments similar to AChR Abs positive patients.	('positive', 'Var', (23, 31))	('AChR Abs', 'Chemical', '-', (163, 171))	('patients', 'Species', '9606', (32, 40))	('LRP-4', 'Gene', (13, 18))	('pyridostigmine', 'Chemical', 'MESH:D011729', (98, 112))	('prednisone', 'Chemical', 'MESH:D011241', (114, 124))	('Abs positive', 'Var', (19, 31))	('patients', 'Species', '9606', (181, 189))	('LRP-4', 'Gene', '4038', (13, 18))
35897	31967407	Alterations of its controlled activity have been shown to result in a wide spectrum of clinical behaviors including many autoimmune disorders (Bernard et al., 2016; Josefowicz et al., 2012; Sakaguchi et al., 2008; Savage et al., 2014) and thymic epithelial tumors (TETs).	('thymic epithelial tumors', 'Disease', (239, 263))	('thymic epithelial tumors', 'Disease', 'MESH:C536905', (239, 263))	('clinical', 'Species', '191496', (87, 95))	('Alterations', 'Var', (0, 11))	('tumors', 'Phenotype', 'HP:0002664', (257, 263))	('autoimmune disorders', 'Disease', (121, 141))	('autoimmune disorders', 'Phenotype', 'HP:0002960', (121, 141))	('controlled activity', 'MPA', (19, 38))	('result in', 'Reg', (58, 67))	('autoimmune disorders', 'Disease', 'MESH:D001327', (121, 141))	('tumor', 'Phenotype', 'HP:0002664', (257, 262))
36074	31967407	Furthermore, knockdown of CNOT on mice was shown to result in significant increase in pulmonary metastasis (Faraji et al., 2014).	('mice', 'Species', '10090', (34, 38))	('pulmonary metastasis', 'Disease', (86, 106))	('increase', 'PosReg', (74, 82))	('CNOT', 'Gene', (26, 30))	('pulmonary metastasis', 'Disease', 'MESH:D009362', (86, 106))	('knockdown', 'Var', (13, 22))
36079	31967407	SHMT1 polymorphism was also shown to be correlated with clinical outcomes (Bahari et al., 2016; Wang et al., 2014).	('correlated', 'Reg', (40, 50))	('polymorphism', 'Var', (6, 18))	('clinical', 'Species', '191496', (56, 64))	('SHMT1', 'Gene', (0, 5))
36084	31967407	The abnormally developed T cell might impair immunosurveillance of cancer and could also cause autoimmune diseases.	('cancer', 'Disease', 'MESH:D009369', (67, 73))	('autoimmune diseases', 'Disease', (95, 114))	('abnormally', 'Var', (4, 14))	('cancer', 'Disease', (67, 73))	('cause', 'Reg', (89, 94))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (95, 114))	('impair', 'NegReg', (38, 44))	('cancer', 'Phenotype', 'HP:0002664', (67, 73))	('immunosurveillance', 'CPA', (45, 63))	('autoimmune diseases', 'Disease', 'MESH:D001327', (95, 114))
36150	31737381	Other studies of patients with thymic neoplasia also detect autoantibodies against cytokines and a decrease in in vitro cytokine production in response to T-cell simulation.	('neoplasia', 'Phenotype', 'HP:0002664', (38, 47))	('in in vitro cytokine production', 'MPA', (108, 139))	('decrease', 'NegReg', (99, 107))	('autoantibodies', 'Var', (60, 74))	('patients', 'Species', '9606', (17, 25))	('thymic neoplasia', 'Disease', 'MESH:C564767', (31, 47))	('thymic neoplasia', 'Phenotype', 'HP:0100521', (31, 47))	('thymic neoplasia', 'Disease', (31, 47))
36263	30758142	The mechanisms of the beneficial effect of macrolide antibiotics in DPB are thought to be the result of immunomodulation rather than antibiotics.25, 26, 27 The reduced effect of macrolide antibiotics on the proinflammatory response may be beneficial to the abnormal immune status of the small airway wall in patients with thymic neoplasm.	('neoplasm', 'Phenotype', 'HP:0002664', (329, 337))	('thymic neoplasm', 'Disease', 'MESH:D013953', (322, 337))	('patients', 'Species', '9606', (308, 316))	('macrolide antibiotics', 'Chemical', '-', (43, 64))	('proinflammatory response', 'MPA', (207, 231))	('antibiotics.25', 'Var', (133, 147))	('reduced', 'NegReg', (160, 167))	('thymic neoplasm', 'Disease', (322, 337))	('macrolide antibiotics', 'Chemical', '-', (178, 199))	('thymic neoplasm', 'Phenotype', 'HP:0100521', (322, 337))
36292	25105128	Few lymphocytes of both mature (CD5+/CD1a-/Tdt-) and immature (CD1a+, Tdt+) T cell phenotypes were seen scattered among the EC or in the perivascular spaces (PVS).	('Tdt', 'Gene', '1791', (70, 73))	('Tdt', 'Gene', (70, 73))	('CD1a+', 'Var', (63, 68))	('Tdt', 'Gene', '1791', (43, 46))	('perivascular spaces', 'Phenotype', 'HP:0012520', (137, 156))	('Tdt', 'Gene', (43, 46))	('PVS', 'Phenotype', 'HP:0012520', (158, 161))
36335	23193443	Thymoma-associated MG may also have additional paraneoplasia-associated antibodies (e.g., antivoltage-gated K+ and Ca++ channels, anti-Hu, antidihydropyrimidinase-related protein 5, and antiglutamic acid decarboxylase antibodies).	('paraneoplasia', 'Disease', 'None', (47, 60))	('Thymoma', 'Gene', '7063', (0, 7))	('antidihydropyrimidinase-related', 'Protein', (139, 170))	('Thymoma', 'Phenotype', 'HP:0100522', (0, 7))	('antiglutamic acid decarboxylase', 'Protein', (186, 217))	('paraneoplasia', 'Disease', (47, 60))	('anti-Hu', 'Var', (130, 137))	('Thymoma', 'Gene', (0, 7))	('antiglutamic acid decarboxylase antibodies', 'Phenotype', 'HP:0025329', (186, 228))
36349	23193443	Since the presence of striational autoantibodies is associated with a more severe disease in all MG subgroups, these antibodies can therefore be used as prognostic determinants in MG patients.	('associated with', 'Reg', (52, 67))	('presence', 'Var', (10, 18))	('striational autoantibodies', 'Protein', (22, 48))	('patients', 'Species', '9606', (183, 191))
36363	23193443	When the nerve action potential reaches the synaptic bouton, depolarization opens voltage gated Calcium channels on the presynaptic membrane, triggering release of ACh into the synaptic cleft.	('ACh', 'Chemical', 'MESH:D000109', (164, 167))	('ACh', 'Protein', (164, 167))	('triggering', 'Reg', (142, 152))	('depolarization', 'Var', (61, 75))	('release', 'MPA', (153, 160))
36392	23193443	IL-18-deficient mice are resistant to EAMG, and pharmacologic block of IL-18 suppresses EAMG.	('EAMG', 'Chemical', '-', (88, 92))	('suppresses', 'NegReg', (77, 87))	('pharmacologic', 'Var', (48, 61))	('EAMG', 'Chemical', '-', (38, 42))	('EAMG', 'MPA', (88, 92))	('IL-18', 'Gene', (71, 76))	('mice', 'Species', '10090', (16, 20))
36396	23193443	MG patients with anti-MuSK antibodies do not have anti-AChR Abs, except as reported in a group of Japanese patients.	('MuSK antibodies', 'Phenotype', 'HP:0030210', (22, 37))	('ACh', 'Chemical', 'MESH:D000109', (55, 58))	('anti-MuSK antibodies', 'Var', (17, 37))	('antibodies', 'Var', (27, 37))	('anti-MuSK antibodies', 'Phenotype', 'HP:0030210', (17, 37))	('patients', 'Species', '9606', (3, 11))	('patients', 'Species', '9606', (107, 115))
36613	29702286	The search for additional treatment options for patients with TET has led to several studies evaluating the expression of PD-L1 in TET, as high expression of PD-L1 has been found to be predictive of benefit in patients with NSCLC treated with checkpoint inhibitors in the first-line setting.	('PD-L1', 'Gene', '29126', (158, 163))	('high expression', 'Var', (139, 154))	('benefit', 'PosReg', (199, 206))	('NSCLC', 'Disease', (224, 229))	('PD-L1', 'Gene', (122, 127))	('NSCLC', 'Disease', 'MESH:D002289', (224, 229))	('PD-L1', 'Gene', (158, 163))	('patients', 'Species', '9606', (210, 218))	('PD-L1', 'Gene', '29126', (122, 127))	('patients', 'Species', '9606', (48, 56))
36618	29702286	finding that high PD-L1 expression was associated with a worse prognosis and Yokoyama et al.	('high', 'Var', (13, 17))	('PD-L1', 'Gene', (18, 23))	('PD-L1', 'Gene', '29126', (18, 23))	('expression', 'MPA', (24, 34))
36619	29702286	finding that high PD-L1 was associated with a better prognosis.	('high', 'Var', (13, 17))	('PD-L1', 'Gene', (18, 23))	('PD-L1', 'Gene', '29126', (18, 23))
36630	29702286	Demographic and clinical factors were summarized separately by PD-L1 (positive versus negative, high/moderate versus low) and PD-1 (positive versus negative, high/moderate versus low) status separately.	('PD-1', 'Gene', (126, 130))	('PD-1', 'Gene', '5133', (126, 130))	('positive', 'Var', (70, 78))	('PD-L1', 'Gene', (63, 68))	('positive', 'Var', (132, 140))	('PD-L1', 'Gene', '29126', (63, 68))
36638	29702286	When only high/moderate levels of PD-L1 and PD-1 were assessed (>= 3+ by IHC), 57% of patients had high/moderate PD-L1 expression whereas only 31% of all patients had high/moderate PD-1 expression.	('PD-1', 'Gene', (44, 48))	('expression', 'MPA', (119, 129))	('PD-1', 'Gene', '5133', (44, 48))	('PD-1', 'Gene', (181, 185))	('PD-1', 'Gene', '5133', (181, 185))	('PD-L1', 'Gene', (113, 118))	('patients', 'Species', '9606', (154, 162))	('PD-L1', 'Gene', (34, 39))	('high/moderate', 'Var', (99, 112))	('PD-L1', 'Gene', '29126', (113, 118))	('PD-L1', 'Gene', '29126', (34, 39))	('patients', 'Species', '9606', (86, 94))
36641	29702286	PD-1 positivity was not associated with WHO grade (p = 0.12) or stage (p = 0.18) however, high/moderate expression of PD-1 (compared to low or no expression) was associated with lower WHO grade (p = 0.03).	('PD-1', 'Gene', '5133', (118, 122))	('PD-1', 'Gene', (0, 4))	('lower', 'NegReg', (178, 183))	('PD-1', 'Gene', '5133', (0, 4))	('high/moderate expression', 'Var', (90, 114))	('WHO grade', 'CPA', (184, 193))	('PD-1', 'Gene', (118, 122))
36645	29702286	Survival was not significantly different for patients with PD-1 expression, high PD-L1 (compared to low PD-L1), and high PD-1 expression.	('PD-1', 'Gene', (59, 63))	('PD-L1', 'Gene', (81, 86))	('PD-1', 'Gene', '5133', (59, 63))	('PD-L1', 'Gene', '29126', (104, 109))	('PD-1', 'Gene', (121, 125))	('PD-1', 'Gene', '5133', (121, 125))	('patients', 'Species', '9606', (45, 53))	('PD-L1', 'Gene', '29126', (81, 86))	('high', 'Var', (76, 80))	('PD-L1', 'Gene', (104, 109))
36668	29702286	reported that high PD-L1 expression was associated with a better prognosis, including longer OS and progression-free survival.	('PD-L1', 'Gene', (19, 24))	('progression-free survival', 'CPA', (100, 125))	('expression', 'MPA', (25, 35))	('longer OS', 'CPA', (86, 95))	('PD-L1', 'Gene', '29126', (19, 24))	('high', 'Var', (14, 18))
36671	29702286	Marchevsky and Walts reported expression of PD-L1 in 92% of thymomas and 50% of thymic carcinomas and found higher PD-L1 expression in B2/3 thymoma compared to AB and B1 thymoma.	('thymic carcinomas', 'Disease', (80, 97))	('thymoma', 'Disease', (60, 67))	('thymoma', 'Phenotype', 'HP:0100522', (60, 67))	('expression', 'MPA', (121, 131))	('thymoma', 'Disease', (140, 147))	('thymoma', 'Phenotype', 'HP:0100522', (140, 147))	('thymomas', 'Disease', 'MESH:D013945', (60, 68))	('thymoma', 'Disease', (170, 177))	('carcinoma', 'Phenotype', 'HP:0030731', (87, 96))	('thymic carcinomas', 'Disease', 'MESH:D013953', (80, 97))	('thymoma', 'Phenotype', 'HP:0100522', (170, 177))	('thymomas', 'Disease', (60, 68))	('B2/3', 'Var', (135, 139))	('higher', 'PosReg', (108, 114))	('carcinomas', 'Phenotype', 'HP:0030731', (87, 97))	('PD-L1', 'Gene', (115, 120))	('thymoma', 'Disease', 'MESH:D013945', (60, 67))	('PD-L1', 'Gene', '29126', (115, 120))	('thymoma', 'Disease', 'MESH:D013945', (140, 147))	('PD-L1', 'Gene', (44, 49))	('PD-L1', 'Gene', '29126', (44, 49))	('thymoma', 'Disease', 'MESH:D013945', (170, 177))
36679	29702286	of an association between high PD-L1 expression and worse clinical outcomes (p = 0.10, log-rank test; p = 0.12 after three thymic carcinoma patients were excluded).	('high', 'Var', (26, 30))	('PD-L1', 'Gene', '29126', (31, 36))	('thymic carcinoma', 'Disease', (123, 139))	('thymic carcinoma', 'Disease', 'MESH:D013953', (123, 139))	('patients', 'Species', '9606', (140, 148))	('carcinoma', 'Phenotype', 'HP:0030731', (130, 139))	('expression', 'MPA', (37, 47))	('PD-L1', 'Gene', (31, 36))
36697	29702286	Our study also showed no statistically significant differences in survival in patients with high PD-L1 or PD-1 expression.	('PD-1', 'Gene', '5133', (106, 110))	('high', 'Var', (92, 96))	('PD-L1', 'Gene', '29126', (97, 102))	('PD-1', 'Gene', (106, 110))	('patients', 'Species', '9606', (78, 86))	('PD-L1', 'Gene', (97, 102))
36698	29702286	We found that high PD-1 expression was associated with lower histologic grade but found no relationship between either PD-L1 or PD-1 and stage or diagnosis of MG.	('expression', 'MPA', (24, 34))	('PD-L1', 'Gene', '29126', (119, 124))	('PD-L1', 'Gene', (119, 124))	('high', 'Var', (14, 18))	('lower', 'NegReg', (55, 60))	('histologic grade', 'CPA', (61, 77))	('PD-1', 'Gene', (128, 132))	('PD-1', 'Gene', '5133', (128, 132))	('MG', 'Disease', 'MESH:D000080343', (159, 161))	('PD-1', 'Gene', (19, 23))	('PD-1', 'Gene', '5133', (19, 23))
36780	29348988	Dysregulation of the immune function in autoimmune diseases like MG can potentially lead to cancer development and can help explain the linking of autoimmune mechanisms with cancer.	('autoimmune diseases', 'Disease', (40, 59))	('lead to', 'Reg', (84, 91))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (40, 59))	('cancer', 'Disease', (92, 98))	('cancer', 'Disease', 'MESH:D009369', (92, 98))	('Dysregulation', 'Var', (0, 13))	('autoimmune disease', 'Phenotype', 'HP:0002960', (40, 58))	('cancer', 'Disease', (174, 180))	('cancer', 'Disease', 'MESH:D009369', (174, 180))	('autoimmune diseases', 'Disease', 'MESH:D001327', (40, 59))	('cancer', 'Phenotype', 'HP:0002664', (92, 98))	('cancer', 'Phenotype', 'HP:0002664', (174, 180))
36828	28095872	The sections were incubated overnight at 4  C with the following primary antibodies: CD1alpha (1:100, DAKO), CD3 (1:100, DAKO), CD5 (1:200, DAKO), CD20 (1:100, DAKO), CD99 (1:200, DAKO), CK (Pan) (1:200, DAKO), CK19 (1:200, DAKO), CK20 (1:100, DAKO), Ki-67 (1:200, DAKO), p63 (1:100, DAKO) and TdT (1:100, DAKO).	('1:100', 'Var', (114, 119))	('p63', 'Gene', (272, 275))	('CD20', 'Gene', (147, 151))	('CD1alpha', 'Gene', (85, 93))	('CK20', 'Gene', (231, 235))	('p63', 'Gene', '8626', (272, 275))	('TdT', 'Gene', (294, 297))	('1:200', 'Var', (197, 202))	('CD99', 'Gene', (167, 171))	('CD20', 'Gene', '54474', (147, 151))	('CK19', 'Gene', (211, 215))	('1:100', 'Var', (277, 282))	('1:200', 'Var', (258, 263))	('1:100', 'Var', (95, 100))	('CK20', 'Gene', '54474', (231, 235))	('1:100', 'Var', (237, 242))	('CK19', 'Gene', '3880', (211, 215))	('1:100', 'Var', (299, 304))	('CD99', 'Gene', '4267', (167, 171))	('CD5', 'Gene', (128, 131))	('1:200, DAKO', 'Var', (217, 228))	('CD1alpha', 'Gene', '909', (85, 93))	('CD3', 'Gene', (109, 112))	('TdT', 'Gene', '1791', (294, 297))	('CD5', 'Gene', '921', (128, 131))
36963	27591911	Pathological examination revealed squamous cell carcinoma invading into the pericardium and lung (Masaoka stage III), pT3N0M0 WHO stage III.	('squamous cell carcinoma', 'Disease', (34, 57))	('pT3N0M0', 'Var', (118, 125))	('squamous cell carcinoma', 'Phenotype', 'HP:0002860', (34, 57))	('squamous cell carcinoma', 'Disease', 'MESH:D002294', (34, 57))	('carcinoma', 'Phenotype', 'HP:0030731', (48, 57))
37036	23709420	In cases of R1 resection, higher WHO histological type (B2, B3), advanced Masaoka stage, larger thymoma size (>=8 cm) and no adjuvant therapy, a higher risk of recurrence was observed.	('thymoma', 'Gene', (96, 103))	('R1 resection', 'Var', (12, 24))	('Masaoka', 'Disease', (74, 81))	('thymoma', 'Phenotype', 'HP:0100522', (96, 103))	('thymoma', 'Gene', '7063', (96, 103))
37113	17592498	The frequency of the invasive tumours and the rate of incomplete resection were higher in type B3 and C than other histologic subtypes (P<0.01).	('type B3', 'Var', (90, 97))	('tumours', 'Phenotype', 'HP:0002664', (30, 37))	('invasive tumours', 'Disease', (21, 37))	('invasive tumours', 'Disease', 'MESH:D009361', (21, 37))	('higher', 'PosReg', (80, 86))	('tumour', 'Phenotype', 'HP:0002664', (30, 36))
37129	17592498	It has been also reported that most of type A, AB, B1 and B2 TETs behave in a benign fashion but type B3 and C have to be considered malignant tumours with a potential to metastasize (Truong et al, 1990; Hsu et al, 1994).	('type B3', 'Var', (97, 104))	('tumour', 'Phenotype', 'HP:0002664', (143, 149))	('malignant tumours', 'Disease', 'MESH:D009369', (133, 150))	('malignant tumours', 'Disease', (133, 150))	('tumours', 'Phenotype', 'HP:0002664', (143, 150))	('TETs', 'Chemical', '-', (61, 65))	('metastasize', 'CPA', (171, 182))
37224	30800305	The administration of both octreotide and diphenhydramine were temporally associated with their own incremental improvements in blood pressure.	('diphenhydramine', 'Var', (42, 57))	('diphenhydramine', 'Chemical', 'MESH:D004155', (42, 57))	('improvements', 'PosReg', (112, 124))	('octreotide', 'Chemical', 'MESH:D015282', (27, 37))	('blood pressure', 'MPA', (128, 142))
37285	29249764	Several lines of evidence from animal studies have indicated that only neonatal fully functioning thymus resection negatively affected the immunological tolerance and that the removal of the normal functioning thymus can generate de novo autoimmune disease even in normal young mice.	('generate', 'Reg', (221, 229))	('autoimmune disease', 'Disease', 'MESH:D001327', (238, 256))	('negatively', 'NegReg', (115, 125))	('autoimmune disease', 'Phenotype', 'HP:0002960', (238, 256))	('affected', 'Reg', (126, 134))	('mice', 'Species', '10090', (278, 282))	('removal', 'Var', (176, 183))	('immunological tolerance', 'CPA', (139, 162))	('autoimmune disease', 'Disease', (238, 256))
37467	24765147	Notably, immunohistochemistry revealed that the tissue sections contained a number of CD68+, MUM-1+, CK+ and CD1a+ cells, but there was no detectable anti-S-100 or anti-CD21 staining.	('CK+', 'Var', (101, 104))	('CD1a', 'Gene', (109, 113))	('CD68', 'Gene', (86, 90))	('MUM-1', 'Gene', '84939', (93, 98))	('CD68', 'Gene', '968', (86, 90))	('MUM-1', 'Gene', (93, 98))	('CD21', 'Gene', (169, 173))	('CD21', 'Gene', '1380', (169, 173))	('CD1a', 'Gene', '909', (109, 113))
37484	32513923	Deletion of Bax and Bak1 prevented rapid apoptosis, but treatment with dexamethasone for greater 6 days still led to cell death that was characterized by release of cytochrome c into the cytosol, activation of caspases, and loss of cell membrane integrity.	('Bak1', 'Gene', (20, 24))	('Bax', 'Gene', (12, 15))	('cytochrome c', 'Gene', '172582', (165, 177))	('cell membrane integrity', 'CPA', (232, 255))	('dexamethasone', 'Chemical', 'MESH:D003907', (71, 84))	('caspases', 'Gene', (210, 218))	('caspases', 'Gene', '12371', (210, 218))	('cell death', 'CPA', (117, 127))	('activation', 'PosReg', (196, 206))	('loss', 'NegReg', (224, 228))	('cytochrome c', 'Gene', (165, 177))	('Deletion', 'Var', (0, 8))
37485	32513923	In WEHI7 thymoma cells, this did not occur when Bcl2l11 (Bim) was deleted in addition to Bax and Bak1.	('deleted', 'Var', (66, 73))	('Bcl2l11', 'Gene', (48, 55))	('Bcl2l11', 'Gene', '12125', (48, 55))	('thymoma', 'Phenotype', 'HP:0100522', (9, 16))
37491	32513923	In sensitive lymphoid cells such as WEHI7 cells, the glucocorticoid Dex induces apoptosis within 24-48 h. When Dex-sensitive cell lines are transfected to over-express Bcl2, or both Bax and Bak1 are mutated in lymphoid cells, they are much more resistant, indicating that the major way Dex induces rapid lymphocyte apoptosis is via activation of BAX and/or BAK1.	('mutated', 'Var', (199, 206))	('Dex', 'Chemical', 'MESH:D003907', (286, 289))	('BAK1', 'Gene', (357, 361))	('Bcl2', 'Gene', (168, 172))	('BAX', 'Gene', (346, 349))	('Dex', 'Chemical', 'MESH:D003907', (111, 114))	('Bcl2', 'Gene', '12043', (168, 172))	('rapid lymphocyte apoptosis', 'CPA', (298, 324))	('activation', 'PosReg', (332, 342))	('Dex', 'Chemical', 'MESH:D003907', (68, 71))
37494	32513923	In thymocytes, it is clear that BIM plays a major role in triggering Dex-induced apoptosis, because thymocytes from Bim deleted mice are much more resistant to Dex than thymocytes from wild-type mice.	('mice', 'Species', '10090', (195, 199))	('Dex', 'Chemical', 'MESH:D003907', (69, 72))	('deleted', 'Var', (120, 127))	('resistant', 'MPA', (147, 156))	('Bim', 'Gene', (116, 119))	('Dex', 'Chemical', 'MESH:D003907', (160, 163))	('mice', 'Species', '10090', (128, 132))	('more', 'PosReg', (142, 146))
37495	32513923	In order to determine the requirements for pro- and anti-apoptotic BCL2 family members in Dex-induced apoptosis of cells of the murine WEHI7 thymoma line, we determined the effect of mutating genes using CrispR/Cas9.	('murine', 'Species', '10090', (128, 134))	('BCL2', 'Gene', '12043', (67, 71))	('Dex', 'Chemical', 'MESH:D003907', (90, 93))	('mutating', 'Var', (183, 191))	('thymoma', 'Phenotype', 'HP:0100522', (141, 148))	('BCL2', 'Gene', (67, 71))
37496	32513923	We were surprised to find that although rapid Dex-induced apoptosis required BAX or BAK1, when Bax-/-Bak1-/- WEHI7 cells were maintained in Dex for longer periods, they were still able to release cytochrome c from the mitochondria, activate the apoptosome, and undergo apoptosis.	('activate', 'PosReg', (232, 240))	('Dex', 'Chemical', 'MESH:D003907', (140, 143))	('cytochrome c', 'Gene', '172582', (196, 208))	('Bax-/-Bak1-/-', 'Var', (95, 108))	('apoptosome', 'Pathway', (245, 255))	('undergo', 'Reg', (261, 268))	('Dex', 'Chemical', 'MESH:D003907', (46, 49))	('cytochrome c', 'Gene', (196, 208))	('apoptosis', 'CPA', (269, 278))
37512	32513923	To determine whether APAF1 was required for Dex-induced death of the Bax-/-Bak1-/- WEHI7 cells, we mutated the genes for APAF1 to generate multiple, independent, Bax-/-Bak1-/-Apaf1-/- WEHI7 clones, treated them with Dex, and assessed their viability by measuring PI uptake.	('Dex', 'Chemical', 'MESH:D003907', (216, 219))	('APAF1', 'Gene', (121, 126))	('Apaf1', 'Gene', (175, 180))	('APAF1', 'Gene', '11783', (21, 26))	('Dex', 'Chemical', 'MESH:D003907', (44, 47))	('APAF1', 'Gene', '11783', (121, 126))	('PI uptake', 'CPA', (263, 272))	('mutated', 'Var', (99, 106))	('Apaf1', 'Gene', '11783', (175, 180))	('APAF1', 'Gene', (21, 26))
37513	32513923	In these clones, and in Bax-/-Bak1-/-Casp9-/- WEHI7 clones, Dex caused much less PI uptake than in the Bax-/-Bak1-/- WEHI7 cells (Fig.	('less', 'NegReg', (76, 80))	('Casp9', 'Gene', (37, 42))	('Dex', 'Var', (60, 63))	('Dex', 'Chemical', 'MESH:D003907', (60, 63))	('PI uptake', 'CPA', (81, 90))	('Casp9', 'Gene', '12371', (37, 42))
37519	32513923	Although release of Cytc from the mitochondria (and death of the cells) was much slower than in the wild-type WEHI7 cells, Dex was still able to cause the release of Cytc, in the absence of BAX and BAK1.	('Dex', 'Var', (123, 126))	('Dex', 'Chemical', 'MESH:D003907', (123, 126))	('release', 'MPA', (155, 162))	('release', 'MPA', (9, 16))
37526	32513923	As with the WEHI7 lines, mutation of BIM in addition to BAX and BAK1 in the p53-/- T lymphoma cells also reduced the percentage of cells that took up PI following Dex treatment, although some Bax-/-Bak1-/-Bim-/- cells did take up PI, and this was reduced by treating the cells with QVD (Figs.	('- T lymphoma', 'Phenotype', 'HP:0012190', (81, 93))	('p53', 'Gene', (76, 79))	('BAK1', 'Gene', (64, 68))	('lymphoma', 'Disease', (85, 93))	('mutation', 'Var', (25, 33))	('Dex', 'Chemical', 'MESH:D003907', (163, 166))	('lymphoma', 'Disease', 'MESH:D008223', (85, 93))	('BIM', 'Gene', (37, 40))	('lymphoma', 'Phenotype', 'HP:0002665', (85, 93))	('T lymphoma', 'Phenotype', 'HP:0012190', (83, 93))	('reduced', 'NegReg', (105, 112))	('p53', 'Gene', '22060', (76, 79))
37529	32513923	Cleavage of both caspase 9 and caspase 3 in Dex-treated Bax-/-Bak1-/-Bim-/- p53-/- T lymphoma cells was much less than in the parental Bax-/-Bak1-/- p53-/- T lymphoma cells (Fig.	('p53', 'Gene', (76, 79))	('lymphoma', 'Disease', (158, 166))	('- T lymphoma', 'Phenotype', 'HP:0012190', (154, 166))	('caspase 3', 'Gene', '12367', (31, 40))	('lymphoma', 'Disease', 'MESH:D008223', (158, 166))	('p53', 'Gene', '22060', (76, 79))	('- T lymphoma', 'Phenotype', 'HP:0012190', (81, 93))	('lymphoma', 'Disease', (85, 93))	('caspase 9', 'Gene', (17, 26))	('lymphoma', 'Disease', 'MESH:D008223', (85, 93))	('Dex', 'Chemical', 'MESH:D003907', (44, 47))	('Bax-/-Bak1-/-Bim-/-', 'Var', (56, 75))	('T lymphoma', 'Phenotype', 'HP:0012190', (156, 166))	('p53', 'Gene', (149, 152))	('caspase 3', 'Gene', (31, 40))	('less', 'NegReg', (109, 113))	('T lymphoma', 'Phenotype', 'HP:0012190', (83, 93))	('p53', 'Gene', '22060', (149, 152))	('lymphoma', 'Phenotype', 'HP:0002665', (158, 166))	('Cleavage', 'MPA', (0, 8))	('caspase 9', 'Gene', '12371', (17, 26))	('lymphoma', 'Phenotype', 'HP:0002665', (85, 93))
37532	32513923	Consistent with the partial protection of the Bax-/-Bak1-/-p53-/- T lymphoma cells afforded by additionally mutating Bim, in the Bax-/-Bak1-/-Bim-/- p53-/- T lymphoma cells release of Cytc into the cytosol was reduced, but not eliminated (Fig.	('p53', 'Gene', (59, 62))	('p53', 'Gene', (149, 152))	('lymphoma', 'Disease', (68, 76))	('mutating', 'Var', (108, 116))	('reduced', 'NegReg', (210, 217))	('lymphoma', 'Disease', 'MESH:D008223', (68, 76))	('lymphoma', 'Disease', (158, 166))	('- T lymphoma', 'Phenotype', 'HP:0012190', (154, 166))	('p53', 'Gene', '22060', (59, 62))	('lymphoma', 'Phenotype', 'HP:0002665', (68, 76))	('p53', 'Gene', '22060', (149, 152))	('T lymphoma', 'Phenotype', 'HP:0012190', (66, 76))	('Bim', 'Gene', (117, 120))	('lymphoma', 'Disease', 'MESH:D008223', (158, 166))	('lymphoma', 'Phenotype', 'HP:0002665', (158, 166))	('T lymphoma', 'Phenotype', 'HP:0012190', (156, 166))	('release of Cytc into the cytosol', 'MPA', (173, 205))	('- T lymphoma', 'Phenotype', 'HP:0012190', (64, 76))
37544	32513923	Altogether, these experiments show that in Dex-treated cells that lack BAX and BAK1, BIM is necessary and sufficient to cause Cytc release and apoptosis.	('cause', 'Reg', (120, 125))	('BIM', 'Var', (85, 88))	('lack', 'NegReg', (66, 70))	('Cytc release', 'MPA', (126, 138))	('apoptosis', 'CPA', (143, 152))	('Dex', 'Chemical', 'MESH:D003907', (43, 46))	('BAK1', 'Gene', (79, 83))	('BAX', 'Gene', (71, 74))
37546	32513923	While activation on the apoptosome is necessary for processing of caspase 9, caspase 3, and rapid cell death as indicated by uptake of PI, the point of no return leading to cell death:as indicated by loss of clonagenic capacity:occurs upstream of the apoptosome, prior to, or at the point of, mitochondrial outer membrane permeability and release of cytochrome c. To determine the point at which cells were committed to die, we exposed wild type and mutant cells to dexamethasone, then washed the cells, and cultured them in soft agar to determine their clonagenic potential.	('cytochrome c', 'Gene', '172582', (350, 362))	('caspase 3', 'Gene', '12367', (77, 86))	('caspase 9', 'Gene', '12371', (66, 75))	('mutant', 'Var', (450, 456))	('caspase 9', 'Gene', (66, 75))	('caspase 3', 'Gene', (77, 86))	('cytochrome c', 'Gene', (350, 362))	('dexamethasone', 'Chemical', 'MESH:D003907', (466, 479))
37552	32513923	These experiments suggest that in some Dex-treated cells, BIM can act in the absence of BAX and BAK1 to cause cell death, but requires the presence of one or more other Dex-induced proteins.	('Dex', 'Chemical', 'MESH:D003907', (39, 42))	('Dex', 'Chemical', 'MESH:D003907', (169, 172))	('cell death', 'CPA', (110, 120))	('BIM', 'Var', (58, 61))
37555	32513923	To further exclude the possibility that the BAX-like BH3-only protein BID may play a role in Dex-induced killing in the absence of BAX and BAK1, we mutated BID in the Bax-/-Bak1-/- WEHI7 cells.	('BH3', 'Chemical', 'MESH:C006008', (53, 56))	('Dex', 'Chemical', 'MESH:D003907', (93, 96))	('BID', 'Gene', (70, 73))	('mutated', 'Var', (148, 155))	('BID', 'Gene', '12122', (70, 73))	('BID', 'Gene', (156, 159))	('BID', 'Gene', '12122', (156, 159))
37561	32513923	In addition, addition of the BCL2-specific inhibitor ABT199 or the BCL2/BCLXL dual inhibitor ABT737 had no influence on the Dex-induced killing of Bax-/-Bak1-/- WEHI7 cells (Supplementary Fig.	('BCL2', 'Gene', '12043', (29, 33))	('Dex-induced killing', 'CPA', (124, 143))	('BCL2', 'Gene', '12043', (67, 71))	('Dex', 'Chemical', 'MESH:D003907', (124, 127))	('ABT737', 'Var', (93, 99))	('ABT737', 'Chemical', 'MESH:C501332', (93, 99))	('BCLXL', 'Gene', (72, 77))	('BCLXL', 'Gene', '12048', (72, 77))	('ABT199', 'Var', (53, 59))	('ABT199', 'Chemical', 'MESH:C579720', (53, 59))	('BCL2', 'Gene', (29, 33))	('BCL2', 'Gene', (67, 71))
37564	32513923	We therefore mutated VDAC2 in the Bax-/-Bak1-/- WEHI7 cells.	('mutated', 'Var', (13, 20))	('VDAC2', 'Gene', '22334', (21, 26))	('VDAC2', 'Gene', (21, 26))
37565	32513923	S7, the absence of VDAC2 had no impact on Dex-induced killing of Bax-/-Bak1-/- WEHI7 cells.	('absence', 'Var', (8, 15))	('Dex', 'Chemical', 'MESH:D003907', (42, 45))	('VDAC2', 'Gene', '22334', (19, 24))	('VDAC2', 'Gene', (19, 24))
37569	32513923	However, we were not able to identify any of these genes, and were surprized to find that cells with mutations to both BAX and BAK1 could still be induced to undergo apoptosis if exposed to Dex for more than a few days.	('BAX', 'Gene', (119, 122))	('mutations', 'Var', (101, 110))	('BAK1', 'Gene', (127, 131))	('induced', 'Reg', (147, 154))	('Dex', 'Chemical', 'MESH:D003907', (190, 193))	('apoptosis', 'CPA', (166, 175))
37571	32513923	One possibility is that there is some residual BAX or BAK1, that is able to accumulate over several days until it reaches a level sufficient to allow release of cytochrome c. Reasons for discounting this possibility are firstly, that neither BAX nor BAK1 could be detected by western blot in the double-mutant cells at any stage, even after 6 days treatment with Dex; secondly, the monoclonal antibodies against BAX and BAK1 were directed at amino-terminal regions, so any remaining protein would have its antibody binding epitopes preserved; thirdly, if residual BAX or BAK1 were present, deleting BCL2, BCLXL and MCL-1 would have greatly increased the sensitivity of the cells to Dex, but we did not see this; and fourthly, mutation of Bax and Bak1 had similar effects in an independent lymphoid line.	('mutation', 'Var', (726, 734))	('cytochrome c', 'Gene', (161, 173))	('MCL-1', 'Gene', (615, 620))	('Bak1', 'Gene', (746, 750))	('Bax', 'Gene', (738, 741))	('MCL-1', 'Gene', '17210', (615, 620))	('BCLXL', 'Gene', (605, 610))	('sensitivity', 'MPA', (654, 665))	('increased', 'PosReg', (640, 649))	('BCLXL', 'Gene', '12048', (605, 610))	('Dex', 'Chemical', 'MESH:D003907', (363, 366))	('Dex', 'Chemical', 'MESH:D003907', (682, 685))	('BCL2', 'Gene', (599, 603))	('BCL2', 'Gene', '12043', (599, 603))	('cytochrome c', 'Gene', '172582', (161, 173))
37574	32513923	Furthermore, mutation of BID had no impact on Dex-induced killing in Bax-/-Bak1-/- WEHI7 cells.	('BID', 'Gene', '12122', (25, 28))	('BID', 'Gene', (25, 28))	('mutation', 'Var', (13, 21))	('Dex', 'Chemical', 'MESH:D003907', (46, 49))	('Dex-induced killing', 'MPA', (46, 65))
37576	32513923	reported that treatment of Bax/Bak1 double KO mouse embryonic fibroblasts with a diterpenoid compound-induced BIM, which migrated to the mitochondria, altered the conformation of BCL2, and together they permeabilized the outer mitochondial membrane to cause release of cytochrome c. However, we do not believe this is happening in our lymphoid cells, as mutation of genes for BCL2, BCLXL or MCL-1, alone or in combination, did not prevent Dex induced, BIM-dependent release of cytochrome c or their death.	('MCL-1', 'Gene', '17210', (391, 396))	('cytochrome c', 'Gene', (269, 281))	('BCL2', 'Gene', (179, 183))	('cytochrome c', 'Gene', (477, 489))	('cytochrome c', 'Gene', '172582', (269, 281))	('mutation', 'Var', (354, 362))	('BCL2', 'Gene', '12043', (179, 183))	('cytochrome c', 'Gene', '172582', (477, 489))	('mouse', 'Species', '10090', (46, 51))	('BCLXL', 'Gene', (382, 387))	('BCLXL', 'Gene', '12048', (382, 387))	('Dex', 'Chemical', 'MESH:D003907', (439, 442))	('BCL2', 'Gene', (376, 380))	('BCL2', 'Gene', '12043', (376, 380))	('MCL-1', 'Gene', (391, 396))
37587	32513923	Antibodies used were to ACTIN (AC-15, Sigma #A1978), MCL-1 (Rockland #600-401-394S), BAX (N-20 Santa Cruz Biotechnology #sc-493), BAK1 (aa23-38, #B5897 Sigma), BCL-2 (#610539, BD Biosciences), Cytochrome c (#556433, BD Biosciences), VDAC2 (M.T.	('#556433', 'Var', (207, 214))	('BCL-2', 'Gene', (160, 165))	('VDAC2', 'Gene', (233, 238))	('MCL-1', 'Gene', '17210', (53, 58))	('#610539', 'Var', (167, 174))	('MCL-1', 'Gene', (53, 58))	('Cytochrome c', 'Gene', '172582', (193, 205))	('Cytochrome c', 'Gene', (193, 205))	('BCL-2', 'Gene', '12043', (160, 165))	('VDAC2', 'Gene', '22334', (233, 238))
37588	32513923	Ryan, Monash University), Cleaved CASP3 (#9661, Cell Signaling Technology), Cleaved CASP-9 (#9509, Cell Signaling Technology), PUMA (#ab9645, Abcam), VDAC1(Abcam, ab15895), Rabbit polyclonal antibodies raised against amino acids 19-32 of mBOK (gift from Francine Ke, WEHI), BID (BD Biosciences, #559681), BCLXL (#2764, Cell Signaling Technology), BIM, APAF1, BMF, and CASP9 are from in house (L. O'Reilly, WEHI).	('CASP3', 'Gene', (34, 39))	('BMF', 'Gene', '171543', (359, 362))	('VDAC1', 'Gene', (150, 155))	('PUMA', 'Gene', '170770', (127, 131))	('BMF', 'Gene', (359, 362))	('CASP9', 'Gene', (368, 373))	('CASP9', 'Gene', '12371', (368, 373))	('PUMA', 'Gene', (127, 131))	('CASP-9', 'Gene', (84, 90))	('APAF1', 'Gene', '11783', (352, 357))	('BOK', 'Gene', '51800', (239, 242))	('VDAC1', 'Gene', '22333', (150, 155))	('BCLXL', 'Gene', '12048', (305, 310))	('CASP-9', 'Gene', '12371', (84, 90))	('BID', 'Gene', (274, 277))	('CASP3', 'Gene', '12367', (34, 39))	('APAF1', 'Gene', (352, 357))	('BOK', 'Gene', (239, 242))	('BID', 'Gene', '12122', (274, 277))	('#2764', 'Var', (312, 317))	('BCLXL', 'Gene', (305, 310))
37662	28002319	The cells were labeled with anti-CD4, CD8, CD3, propidium iodide, or CFDA-SE, cell cycle, proliferation kinetics, and mutation frequency of T cell receptor, respectively.	('CD3', 'Gene', (43, 46))	('propidium iodide', 'Chemical', 'MESH:D011419', (48, 64))	('CD3', 'Gene', '12503', (43, 46))	('CFDA-SE', 'Chemical', 'MESH:C087165', (69, 76))	('T cell receptor', 'Protein', (140, 155))	('mutation', 'Var', (118, 126))	('CD4', 'Gene', (33, 36))	('CD4', 'Gene', '12504', (33, 36))
37695	28002319	The cells were collected by centrifugation and labeled with anti-CD4-PE-CF594 and anti-CD8-PE antibodies (eBioscience).	('CD4', 'Gene', (65, 68))	('anti-CD8-PE', 'Var', (82, 93))	('CD4', 'Gene', '12504', (65, 68))
37698	28002319	Mf of T cell receptor was calculated as follows:  where CD3-/CD4+ cells were T cell receptor mutants and CD3+/CD4+ cells were normal cells.	('T cell receptor', 'Gene', (77, 92))	('CD4', 'Gene', '12504', (61, 64))	('CD4', 'Gene', (110, 113))	('mutants', 'Var', (93, 100))	('CD3', 'Gene', (56, 59))	('CD3', 'Gene', '12503', (56, 59))	('CD4', 'Gene', '12504', (110, 113))	('CD3', 'Gene', (105, 108))	('CD3', 'Gene', '12503', (105, 108))	('CD4', 'Gene', (61, 64))
37702	28002319	Cytometry analysis showed that there were similar proportions of G1 cells in MSCs transfusion and control mice (64.24% vs 69.98%; Table 2), whereas irradiated mice had significantly more G1 cells than the other 2 groups (90.53% vs 64.24% and 69.98%).	('mice', 'Species', '10090', (106, 110))	('G1 cells', 'CPA', (65, 73))	('MSCs transfusion', 'Var', (77, 93))	('mice', 'Species', '10090', (159, 163))
37743	27957331	Notably, serum levels of the IL-6 and IL-17A cytokines were higher in anti-IL-6 seropositive than:negative APECED patients or healthy controls.	('serum levels of', 'MPA', (9, 24))	('seropositive', 'Var', (80, 92))	('higher', 'PosReg', (60, 66))	('IL-6', 'Gene', (29, 33))	('APECED', 'Gene', '326', (107, 113))	('IL-6', 'Gene', '3569', (29, 33))	('IL-17A', 'Gene', '3605', (38, 44))	('IL-6', 'Gene', (75, 79))	('IL-6', 'Gene', '3569', (75, 79))	('patients', 'Species', '9606', (114, 122))	('IL-17A', 'Gene', (38, 44))	('APECED', 'Gene', (107, 113))
37746	27957331	For instance, neutralizing antibodies against IFN-gamma lead to disseminated mycobacterial infections 1, 2, high-avidity antibodies against IL-6 cause serious staphylococcal infections 3, anti-granulocyte macrophage colony-stimulating factor autoantibodies have been linked to cryptococcal meningitis 4, and anti-IL-12p70 autoantibodies to recurrent Burkholderia gladioli suppurative lymphadenitis 5.	('IFN-gamma', 'Gene', '3458', (46, 55))	('IFN-gamma', 'Gene', (46, 55))	('antibodies', 'Var', (121, 131))	('neutralizing', 'Var', (14, 26))	('IL-6', 'Gene', '3569', (140, 144))	('staphylococcal infections', 'Disease', 'MESH:D013203', (159, 184))	('IL-6', 'Gene', (140, 144))	('lymphadenitis', 'Phenotype', 'HP:0002840', (384, 397))	('cryptococcal meningitis', 'Phenotype', 'HP:0032160', (277, 300))	('cryptococcal meningitis', 'Disease', (277, 300))	('cryptococcal meningitis', 'Disease', 'MESH:D016919', (277, 300))	('staphylococcal infections', 'Disease', (159, 184))	('meningitis', 'Phenotype', 'HP:0001287', (290, 300))	('linked', 'Reg', (267, 273))	('lymphadenitis', 'Disease', 'MESH:D008199', (384, 397))	('anti-IL-12p70', 'Var', (308, 321))	('staphylococcal infections', 'Phenotype', 'HP:0007499', (159, 184))	('disseminated mycobacterial infections 1', 'Disease', (64, 103))	('mycobacterial infections', 'Phenotype', 'HP:0011274', (77, 101))	('recurrent Burkholderia gladioli', 'Phenotype', 'HP:0002842', (340, 371))	('Burkholderia gladioli', 'Species', '28095', (350, 371))	('lymphadenitis', 'Disease', (384, 397))
37747	27957331	Moreover, autoantibodies neutralizing the T helper (Th)17 cytokines interleukin (IL)-22, IL-17F, and IL-17A are associated with chronic mucocutaneous candidiasis (CMC) in most patients with the rare monogenic disease autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) and also in a few patients with thymic epithelial cell neoplasia 6, 7.	('neoplasia', 'Disease', (344, 353))	('APECED', 'Gene', (281, 287))	('autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy', 'Disease', 'MESH:D016884', (217, 279))	('patients', 'Species', '9606', (307, 315))	('IL-17A', 'Gene', '3605', (101, 107))	('epithelial cell neoplasia', 'Phenotype', 'HP:0031492', (328, 353))	('APECED', 'Gene', '326', (281, 287))	('neoplasia', 'Phenotype', 'HP:0002664', (344, 353))	('IL-17F', 'Gene', (89, 95))	('interleukin (IL)-22', 'Gene', (68, 87))	('chronic mucocutaneous candidiasis', 'Disease', (128, 161))	('chronic mucocutaneous candidiasis', 'Disease', 'MESH:D002178', (128, 161))	('associated with', 'Reg', (112, 127))	('CMC', 'Phenotype', 'HP:0002728', (163, 166))	('IL-17F', 'Gene', '112744', (89, 95))	('IL-17A', 'Gene', (101, 107))	('neutralizing', 'Var', (25, 37))	('chronic mucocutaneous candidiasis', 'Phenotype', 'HP:0002728', (128, 161))	('patients', 'Species', '9606', (176, 184))	('neoplasia', 'Disease', 'MESH:D009369', (344, 353))	('interleukin (IL)-22', 'Gene', '50616', (68, 87))	('ectodermal dystrophy', 'Phenotype', 'HP:0000968', (259, 279))
37748	27957331	The obvious connections between these syndromes are aberrations in thymic epithelium 6, 8, 9, the major cell type to express the AIRE gene that is mutated in APECED 10, 11 and often under-expressed in the thymoma epithelial cells 12.	('AIRE', 'Gene', (129, 133))	('thymoma', 'Phenotype', 'HP:0100522', (205, 212))	('AIRE', 'Gene', '326', (129, 133))	('under-expressed', 'NegReg', (182, 197))	('thymoma', 'Disease', (205, 212))	('APECED', 'Gene', '326', (158, 164))	('APECED', 'Gene', (158, 164))	('thymoma', 'Disease', 'MESH:D013945', (205, 212))	('mutated', 'Var', (147, 154))
37754	27957331	The APECED diagnosis was confirmed by mutation analysis of AIRE genes and by the presence of autoantibodies to IFN-omega and IFN-alpha2.	('presence', 'Reg', (81, 89))	('IFN-alpha2', 'Gene', (125, 135))	('IFN-alpha2', 'Gene', '3440', (125, 135))	('AIRE', 'Gene', (59, 63))	('mutation analysis', 'Var', (38, 55))	('AIRE', 'Gene', '326', (59, 63))	('APECED', 'Gene', '326', (4, 10))	('APECED', 'Gene', (4, 10))
37775	27957331	But we found autoantibodies to IL-6 in 8 of the 41 APECED (A1, A9, A18, A22, A27, A32, A34, A36) patients' sera (19.5%, Fig.	('IL-6', 'Gene', (31, 35))	('A34', 'Var', (87, 90))	('A18', 'Var', (67, 70))	('A27', 'Var', (77, 80))	('APECED', 'Gene', (51, 57))	('A36', 'Var', (92, 95))	('A32', 'Var', (82, 85))	('IL-6', 'Gene', '3569', (31, 35))	('A22', 'Var', (72, 75))	('APECED', 'Gene', '326', (51, 57))	('autoantibodies', 'Var', (13, 27))	('patients', 'Species', '9606', (97, 105))
37776	27957331	1D; Supporting information Table S1); also in 13 (12.5%) of 104 thymoma patients (T1, T14, T23, T24, T31, T32, T34, T37, T43, T48, T50, T53, T56), though mostly at moderate levels (Fig.	('T56', 'CellLine', 'CVCL:J280', (141, 144))	('T24', 'Var', (96, 99))	('T34', 'Var', (111, 114))	('T32', 'Var', (106, 109))	('T14', 'Gene', (86, 89))	('T43', 'Var', (121, 124))	('T53', 'Var', (136, 139))	('thymoma', 'Disease', 'MESH:D013945', (64, 71))	('T31', 'Var', (101, 104))	('T37', 'Var', (116, 119))	('T50', 'Var', (131, 134))	('thymoma', 'Disease', (64, 71))	('T23', 'Var', (91, 94))	('thymoma', 'Phenotype', 'HP:0100522', (64, 71))	('T14', 'Gene', '939', (86, 89))	('T56', 'Var', (141, 144))	('T1', 'Var', (82, 84))	('T48', 'Var', (126, 129))	('patients', 'Species', '9606', (72, 80))
37777	27957331	Three of the anti-IL-6 positive thymoma patients also had autoantibodies against IFN-alpha2a, IL-17s, and/ or IL-22.	('IL-6', 'Gene', '3569', (18, 22))	('IL-22', 'Gene', '50616', (110, 115))	('IL-17s', 'Protein', (94, 100))	('thymoma', 'Phenotype', 'HP:0100522', (32, 39))	('patients', 'Species', '9606', (40, 48))	('IFN-alpha2', 'Gene', (81, 91))	('IFN-alpha2', 'Gene', '3440', (81, 91))	('thymoma', 'Disease', 'MESH:D013945', (32, 39))	('thymoma', 'Disease', (32, 39))	('IL-6', 'Gene', (18, 22))	('autoantibodies', 'Var', (58, 72))	('IL-22', 'Gene', (110, 115))
37779	27957331	Similarly, T37 had severe acne at age 25, but we found high-level IL-6 antibodies only >10 years later.	('IL-6', 'Gene', '3569', (66, 70))	('acne', 'Phenotype', 'HP:0001061', (26, 30))	('acne', 'Disease', (26, 30))	('T37', 'Var', (11, 14))	('IL-6', 'Gene', (66, 70))
37790	27957331	Further supporting the p40-specific cross-reactivity between IL-12 and IL-23 noted above, these cytokines both strongly blocked binding by the anti-IL-23 antibodies (p < 0.0001 for each), with almost equal potency (p > 0.05) (Fig.	('IL-23', 'Gene', '51561', (71, 76))	('IL-23', 'Gene', (71, 76))	('antibodies', 'Var', (154, 164))	('p40', 'Gene', '3578', (23, 26))	('blocked', 'NegReg', (120, 127))	('IL-23', 'Gene', '51561', (148, 153))	('binding', 'Interaction', (128, 135))	('IL-23', 'Gene', (148, 153))	('p40', 'Gene', (23, 26))
37801	27957331	To help to understand the biological significance of these autoantibodies against IL-6, we next tested their capacity to inhibit signaling from its receptor via phosphorylation of STAT3, which acts downstream in this pathway.	('inhibit', 'NegReg', (121, 128))	('STAT3', 'Gene', (180, 185))	('autoantibodies', 'Var', (59, 73))	('phosphorylation', 'MPA', (161, 176))	('IL-6', 'Gene', (82, 86))	('IL-6', 'Gene', '3569', (82, 86))	('tested', 'Reg', (96, 102))	('STAT3', 'Gene', '6774', (180, 185))	('signaling', 'MPA', (129, 138))
37806	27957331	This finding suggests that IL-6-specific autoantibodies could prolong the half-life of IL-6 in vivo and so indirectly enhance IL-17A production by Th17 cells.	('autoantibodies', 'Var', (41, 55))	('IL-17A', 'Gene', '3605', (126, 132))	('enhance', 'PosReg', (118, 125))	('IL-6', 'Gene', (27, 31))	('half-life', 'MPA', (74, 83))	('IL-17A', 'Gene', (126, 132))	('IL-6', 'Gene', (87, 91))	('IL-6', 'Gene', '3569', (27, 31))	('prolong', 'PosReg', (62, 69))	('IL-6', 'Gene', '3569', (87, 91))
37814	27957331	Indeed, an autosomal dominant form of hyper-IgE syndrome that is caused by STAT3 mutations is characterized by susceptibility to staphylococcal abscesses and CMC 27.	('abscesses', 'Phenotype', 'HP:0025615', (144, 153))	('CMC 27', 'Disease', (158, 164))	('caused', 'Reg', (65, 71))	('staphylococcal abscesses', 'Disease', (129, 153))	('STAT3', 'Gene', '6774', (75, 80))	('hyper-IgE syndrome', 'Disease', 'MESH:D007589', (38, 56))	('STAT3', 'Gene', (75, 80))	('hyper-IgE syndrome', 'Disease', (38, 56))	('mutations', 'Var', (81, 90))	('CMC', 'Phenotype', 'HP:0002728', (158, 161))
37815	27957331	In addition, high titer neutralizing autoantibodies to IL-6 have previously been associated with chronic staphylococcal cellulitis and subcutaneous abscesses in one patient 3.	('staphylococcal cellulitis', 'Disease', 'MESH:D002481', (105, 130))	('IL-6', 'Gene', '3569', (55, 59))	('cellulitis', 'Phenotype', 'HP:0100658', (120, 130))	('high titer neutralizing autoantibodies', 'Var', (13, 51))	('patient', 'Species', '9606', (165, 172))	('abscesses', 'Phenotype', 'HP:0025615', (148, 157))	('staphylococcal cellulitis', 'Disease', (105, 130))	('IL-6', 'Gene', (55, 59))	('subcutaneous abscesses', 'Disease', (135, 157))	('associated', 'Reg', (81, 91))
37840	24959269	Expression and polymorphisms of T cell immunoglobulin domain and mucin domain protein-1 in thymoma with or without myasthenia gravis The present study aimed to investigate the expression and association of the single-nucleotide polymorphism (SNP) -1637A/G in the promoter region of the T cell immunoglobulin domain and mucin domain protein-1 (Tim-1) gene in patients diagnosed with thymoma with or without myasthenia gravis (MG).	('thymoma', 'Disease', (91, 98))	('thymoma', 'Phenotype', 'HP:0100522', (91, 98))	('myasthenia gravis', 'Disease', (406, 423))	('mucin', 'Gene', (65, 70))	('thymoma', 'Disease', 'MESH:D013945', (382, 389))	('single-nucleotide', 'Var', (210, 227))	('mucin', 'Gene', '100508689', (65, 70))	('mucin', 'Gene', (319, 324))	('-1637A/G', 'Mutation', 'rs7702919', (247, 255))	('myasthenia gravis', 'Disease', 'MESH:D009157', (115, 132))	('thymoma', 'Disease', (382, 389))	('mucin', 'Gene', '100508689', (319, 324))	('thymoma', 'Phenotype', 'HP:0100522', (382, 389))	('Tim-1', 'Gene', '26762', (343, 348))	('myasthenia', 'Phenotype', 'HP:0003473', (406, 416))	('myasthenia gravis', 'Disease', 'MESH:D009157', (406, 423))	('thymoma', 'Disease', 'MESH:D013945', (91, 98))	('patients', 'Species', '9606', (358, 366))	('myasthenia gravis', 'Disease', (115, 132))	('association', 'Interaction', (191, 202))	('myasthenia', 'Phenotype', 'HP:0003473', (115, 125))	('Tim-1', 'Gene', (343, 348))
37842	24959269	The Tim-1 gene -1637A/G polymorphism was detected using the single allele-specific primer polymerase chain reaction.	('Tim-1', 'Gene', (4, 9))	('-1637A/G', 'Mutation', 'rs7702919', (15, 23))	('Tim-1', 'Gene', '26762', (4, 9))	('polymorphism', 'Var', (24, 36))
37854	24959269	An increasing number of muscle autoantibodies, such as muscle-specific tyrosine kinase, titin and ryanodine receptor (RyR) antibodies, have been found in patients with MG. MG is paraneoplastic in association with thymoma, which is detected in 10-15% of MG patients.	('found', 'Reg', (145, 150))	('paraneoplastic', 'Disease', 'MESH:D010257', (178, 192))	('thymoma', 'Disease', 'MESH:D013945', (213, 220))	('ryanodine receptor', 'Gene', (98, 116))	('patients', 'Species', '9606', (256, 264))	('patients', 'Species', '9606', (154, 162))	('thymoma', 'Disease', (213, 220))	('RyR', 'Gene', (118, 121))	('RyR', 'Gene', '6261', (118, 121))	('titin', 'Gene', '7273', (88, 93))	('paraneoplastic', 'Disease', (178, 192))	('tyrosine', 'Chemical', 'MESH:D014443', (71, 79))	('titin', 'Gene', (88, 93))	('thymoma', 'Phenotype', 'HP:0100522', (213, 220))	('ryanodine receptor', 'Gene', '6261', (98, 116))	('MG. MG', 'Var', (168, 174))
37863	24959269	It has been reported that Tim-1 polymorphisms are associated with various immune-related diseases, including rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, diabetes, tumors and asthma.	('Tim-1', 'Gene', (26, 31))	('diabetes', 'Disease', 'MESH:D003920', (181, 189))	('rheumatoid arthritis', 'Disease', 'MESH:D001172', (109, 129))	('systemic lupus erythematosus', 'Phenotype', 'HP:0002725', (131, 159))	('tumor', 'Phenotype', 'HP:0002664', (191, 196))	('tumors', 'Disease', (191, 197))	('multiple sclerosis', 'Disease', 'MESH:D009103', (161, 179))	('asthma', 'Disease', 'MESH:D001249', (202, 208))	('systemic lupus erythematosus', 'Disease', 'MESH:D008180', (131, 159))	('asthma', 'Phenotype', 'HP:0002099', (202, 208))	('tumors', 'Disease', 'MESH:D009369', (191, 197))	('Tim-1', 'Gene', '26762', (26, 31))	('diabetes', 'Disease', (181, 189))	('polymorphisms', 'Var', (32, 45))	('asthma', 'Disease', (202, 208))	('rheumatoid arthritis', 'Phenotype', 'HP:0001370', (109, 129))	('arthritis', 'Phenotype', 'HP:0001369', (120, 129))	('systemic lupus erythematosus', 'Disease', (131, 159))	('rheumatoid arthritis', 'Disease', (109, 129))	('multiple sclerosis', 'Disease', (161, 179))	('tumors', 'Phenotype', 'HP:0002664', (191, 197))	('associated', 'Reg', (50, 60))
37865	24959269	The present study aimed to investigate the expression of Tim-1 in thymoma patients with and without MG and to examine whether the single-nucleotide polymorphism (SNP) -1637A/G in the promoter region of the Tim-1 gene contributes to the susceptibility of thymoma with MG.	('Tim-1', 'Gene', '26762', (206, 211))	('Tim-1', 'Gene', (206, 211))	('patients', 'Species', '9606', (74, 82))	('-1637A/G', 'Mutation', 'rs7702919', (167, 175))	('thymoma', 'Disease', 'MESH:D013945', (66, 73))	('thymoma', 'Disease', (66, 73))	('thymoma', 'Disease', 'MESH:D013945', (254, 261))	('thymoma', 'Disease', (254, 261))	('single-nucleotide polymorphism', 'Var', (130, 160))	('Tim-1', 'Gene', '26762', (57, 62))	('thymoma', 'Phenotype', 'HP:0100522', (66, 73))	('thymoma', 'Phenotype', 'HP:0100522', (254, 261))	('Tim-1', 'Gene', (57, 62))	('susceptibility', 'Reg', (236, 250))
37882	24959269	Single allele-specific primer polymerase chain reaction was performed on 1637A/G in the promoter region of the TIM-1 gene.	('TIM-1', 'Gene', '26762', (111, 116))	('1637A/G', 'SUBSTITUTION', 'None', (73, 80))	('TIM-1', 'Gene', (111, 116))	('1637A/G', 'Var', (73, 80))
37907	24959269	The signaling pathways triggered downstream of Tim-1 cross-linking have been investigated using either Tim-1 antibodies or Tim-4 as ligands.	('Tim-1', 'Gene', '26762', (103, 108))	('cross-linking', 'Var', (53, 66))	('Tim-1', 'Gene', (103, 108))	('Tim-4', 'Gene', (123, 128))	('Tim-1', 'Gene', '26762', (47, 52))	('Tim-1', 'Gene', (47, 52))	('Tim-4', 'Gene', '91937', (123, 128))
37908	24959269	Reporter assays have shown that the overexpression of Tim-1 resulted in increased transcription from the interleukin (IL)-4 promoter and nuclear factor of activated T-cells/activator protein-1 transcriptional activation, dependent on Y276 in the Tim-1 cytoplasmic tail.	('transcription', 'MPA', (82, 95))	('activator protein-1', 'Gene', (173, 192))	('increased', 'PosReg', (72, 81))	('overexpression', 'PosReg', (36, 50))	('activator protein-1', 'Gene', '2353', (173, 192))	('Tim-1', 'Gene', (54, 59))	('Y276', 'Var', (234, 238))	('activation', 'PosReg', (209, 219))	('Tim-1', 'Gene', '26762', (246, 251))	('Tim-1', 'Gene', (246, 251))	('Tim-1', 'Gene', '26762', (54, 59))
37915	24959269	Previous studies have aimed to determine whether Tim-1 gene polymorphisms were associated with the incidence of asthma, rheumatoid arthritis and hepatitis A virus infection.	('polymorphisms', 'Var', (60, 73))	('associated', 'Reg', (79, 89))	('asthma', 'Phenotype', 'HP:0002099', (112, 118))	('Tim-1', 'Gene', '26762', (49, 54))	('hepatitis', 'Phenotype', 'HP:0012115', (145, 154))	('arthritis', 'Phenotype', 'HP:0001369', (131, 140))	('rheumatoid arthritis and hepatitis A virus infection', 'Disease', 'MESH:D001172', (120, 172))	('Tim-1', 'Gene', (49, 54))	('asthma', 'Disease', (112, 118))	('rheumatoid arthritis', 'Phenotype', 'HP:0001370', (120, 140))	('asthma', 'Disease', 'MESH:D001249', (112, 118))
37917	24959269	To the best of our knowledge, this study is the first to investigate the expression of Tim-1 in thymoma patients with and without MG, and to examine whether the -1637A/G SNP in the promoter region of Tim-1 contributes to the susceptibility of thymoma with MG.	('thymoma', 'Disease', 'MESH:D013945', (243, 250))	('thymoma', 'Disease', (243, 250))	('Tim-1', 'Gene', '26762', (87, 92))	('Tim-1', 'Gene', (87, 92))	('thymoma', 'Disease', 'MESH:D013945', (96, 103))	('thymoma', 'Disease', (96, 103))	('Tim-1', 'Gene', (200, 205))	('thymoma', 'Phenotype', 'HP:0100522', (243, 250))	('-1637A/G', 'Mutation', 'rs7702919', (161, 169))	('Tim-1', 'Gene', '26762', (200, 205))	('the -1637A/G', 'Var', (157, 169))	('thymoma', 'Phenotype', 'HP:0100522', (96, 103))	('patients', 'Species', '9606', (104, 112))	('susceptibility', 'Reg', (225, 239))
37922	24959269	The effects of Tim-1 polymorphism on transcription and translation, and whether Tim-1 is involved in thymoma with MG via the TCR signaling pathway, requires further investigation.	('thymoma', 'Disease', (101, 108))	('effects', 'Reg', (4, 11))	('thymoma', 'Phenotype', 'HP:0100522', (101, 108))	('involved', 'Reg', (89, 97))	('Tim-1', 'Gene', (80, 85))	('Tim-1', 'Gene', '26762', (80, 85))	('Tim-1', 'Gene', (15, 20))	('Tim-1', 'Gene', '26762', (15, 20))	('thymoma', 'Disease', 'MESH:D013945', (101, 108))	('transcription', 'MPA', (37, 50))	('translation', 'MPA', (55, 66))	('polymorphism', 'Var', (21, 33))
37931	32884767	Tc 99 m sestamibi showed a main pathologic increased uptake on immediate imaging and a decreased signal on delayed imaging in the anterior mediastinum and a slight uptake at the lower third of left thyroid lobe (Figures 1, 2).	('uptake', 'MPA', (53, 59))	('left thyroid lobe', 'Disease', (193, 210))	('decreased', 'NegReg', (87, 96))	('left thyroid lobe', 'Disease', 'MESH:D013959', (193, 210))	('Tc 99 m sestamibi', 'Chemical', 'MESH:D017256', (0, 17))	('Tc 99 m', 'Var', (0, 7))	('increased', 'PosReg', (43, 52))	('uptake', 'MPA', (164, 170))	('signal', 'MPA', (97, 103))
38020	30949298	Both of them show limited coverage, being higher in DCE-MR compared to PWI.	('higher', 'PosReg', (42, 48))	('mi', 'Chemical', 'MESH:C011506', (20, 22))	('DCE', 'Chemical', 'MESH:C024565', (52, 55))	('DCE-MR', 'Var', (52, 58))
38108	30949298	As well as thymic NETs, low ADC values suggest aggressiveness and poor differentiation, and DCE-MRI with a TTP > 2 min indicates a high-grade tumor (Figure 3).	('tumor', 'Phenotype', 'HP:0002664', (142, 147))	('ADC values', 'MPA', (28, 38))	('mi', 'Chemical', 'MESH:C011506', (14, 16))	('tumor', 'Disease', (142, 147))	('DCE', 'Chemical', 'MESH:C024565', (92, 95))	('aggressiveness', 'Phenotype', 'HP:0000718', (47, 61))	('mi', 'Chemical', 'MESH:C011506', (115, 117))	('NETs', 'Phenotype', 'HP:0100634', (18, 22))	('low', 'Var', (24, 27))	('aggressiveness', 'Disease', 'MESH:D001523', (47, 61))	('tumor', 'Disease', 'MESH:D009369', (142, 147))	('aggressiveness', 'Disease', (47, 61))
38122	30949298	RECIL criteria are aligned with response evaluation criteria in solid tumors, in as much as it suggests a uni-dimensional measurement method, but introduce tumor metabolic evaluation with 18FDG-PET/CT.	('solid tumors', 'Disease', (64, 76))	('tumor', 'Phenotype', 'HP:0002664', (70, 75))	('tumor', 'Disease', 'MESH:D009369', (156, 161))	('tumor', 'Disease', (70, 75))	('18FDG-PET/CT', 'Var', (188, 200))	('tumor', 'Phenotype', 'HP:0002664', (156, 161))	('solid tumors', 'Disease', 'MESH:D009369', (64, 76))	('18FDG', 'Chemical', 'MESH:D019788', (188, 193))	('tumors', 'Phenotype', 'HP:0002664', (70, 76))	('men', 'Species', '9606', (129, 132))	('tumor', 'Disease', (156, 161))	('men', 'Species', '9606', (112, 115))	('tumor', 'Disease', 'MESH:D009369', (70, 75))
38127	30949298	The study by Mosavi et al showed a difference in ADC values between indolent NHL, aggressive NHL and HL using whole-body DWI, with ADC values being lower in indolent NHL (597 +- 115 mm2/s) rather than aggressive NHL (822 +- 266 mm2/s) and HL (1020 +- 547 mm2/s) (Figure 5).	('NHL', 'Phenotype', 'HP:0012539', (93, 96))	('HL', 'Phenotype', 'HP:0012189', (167, 169))	('mm2', 'Gene', '10687', (255, 258))	('mm2', 'Gene', '10687', (182, 185))	('indolent', 'Var', (157, 165))	('HL', 'Phenotype', 'HP:0012189', (213, 215))	('mm2', 'Gene', (255, 258))	('HL', 'Phenotype', 'HP:0012189', (94, 96))	('mm2', 'Gene', '10687', (228, 231))	('HL', 'Phenotype', 'HP:0012189', (78, 80))	('NHL', 'Phenotype', 'HP:0012539', (166, 169))	('ADC', 'MPA', (131, 134))	('mm2', 'Gene', (182, 185))	('NHL', 'Phenotype', 'HP:0012539', (77, 80))	('lower', 'NegReg', (148, 153))	('HL', 'Phenotype', 'HP:0012189', (101, 103))	('mm2', 'Gene', (228, 231))	('NHL', 'Phenotype', 'HP:0012539', (212, 215))	('ADC', 'MPA', (49, 52))
38166	30949298	In addition, DWI has a potential impact on lung cancer differentiation.	('lung cancer', 'Disease', (43, 54))	('lung cancer', 'Phenotype', 'HP:0100526', (43, 54))	('cancer', 'Phenotype', 'HP:0002664', (48, 54))	('DWI', 'Var', (13, 16))	('lung cancer', 'Disease', 'MESH:D008175', (43, 54))	('impact', 'Reg', (33, 39))
38242	28072694	Patients who received HITHOC had significantly longer median survival length compared to the patients without HITHOC (Hedges g = 0.763, P < 0.001).	('Patients', 'Species', '9606', (0, 8))	('longer', 'PosReg', (47, 53))	('patients', 'Species', '9606', (93, 101))	('HITHOC', 'Var', (22, 28))
38243	28072694	In addition, HITHOC therapy was favored (Hedges g = 0.848, P < 0.001) in terms of median survival length, tumor-free survival rate, with tumor survival rate or Karnofsky performance status (KPS) scale.	('HITHOC', 'Var', (13, 19))	('tumor', 'Disease', (137, 142))	('tumor', 'Disease', 'MESH:D009369', (106, 111))	('median survival length', 'CPA', (82, 104))	('tumor', 'Phenotype', 'HP:0002664', (106, 111))	('tumor', 'Disease', 'MESH:D009369', (137, 142))	('tumor', 'Phenotype', 'HP:0002664', (137, 142))	('tumor', 'Disease', (106, 111))
38261	28072694	Results of the quantitative meta-analysis of the 5 RCT articles showed that average of the median survival length was significantly longer in the patients treated with HITHOC compared to the patients without HITHOC therapy (Hedges g = 0.763, P < 0.001, Fig.	('patients', 'Species', '9606', (191, 199))	('HITHOC', 'Var', (168, 174))	('survival length', 'CPA', (98, 113))	('longer', 'PosReg', (132, 138))	('patients', 'Species', '9606', (146, 154))
38263	28072694	Of the 22 noncontrolled clinical studies, while 1 study reported that HITHOC did not have advantage compared to non-HITHOC therapy, the rest 21 studies indicated that HITHOC seemed to be able extend patients' life.	('extend', 'PosReg', (192, 198))	('patients', 'Species', '9606', (199, 207))	('HITHOC', 'Var', (167, 173))
38283	28072694	After searching online databases, extracting relevant statistical data and performing meta-analysis, and systematic review, we found that HITHOC has dramatic effect on extending patient's median survival length and 1 to 5 year survival rate, especially in the patients with thymoma.	('patient', 'Species', '9606', (260, 267))	('thymoma', 'Disease', (274, 281))	('extending', 'PosReg', (168, 177))	('patient', 'Species', '9606', (178, 185))	('HITHOC', 'Var', (138, 144))	('patients', 'Species', '9606', (260, 268))	('thymoma', 'Phenotype', 'HP:0100522', (274, 281))	('median survival length', 'CPA', (188, 210))	('thymoma', 'Disease', 'MESH:D013945', (274, 281))
38291	28072694	Thus, the ability of penetration of cytotoxic drugs (such as cisplatin) into the lung tissues may improve the local therapy of residual microscopic tumor cells on the lung surface with the use of HITHOC in patients with malignant pleural tumors after lung-sparing radical tumor resections Kerscher et al reported their experiences of the anesthesia and intensive care management in patients undergoing HITHOC, and they indicated that anesthesia during the procedure of CRS + HITHOC may lead to unexpected side effects including high pressure of intrathoracic and central venous system, and potential risk of systemic hyperthermia.	('tumor', 'Phenotype', 'HP:0002664', (238, 243))	('malignant pleural tumors', 'Disease', (220, 244))	('CRS +', 'Var', (469, 474))	('systemic hyperthermia', 'Disease', 'MESH:D005334', (608, 629))	('tumor', 'Phenotype', 'HP:0002664', (148, 153))	('tumor', 'Disease', (272, 277))	('tumor', 'Disease', 'MESH:D009369', (272, 277))	('malignant pleural tumors', 'Disease', 'MESH:D016066', (220, 244))	('cisplatin', 'Chemical', 'MESH:D002945', (61, 70))	('tumor', 'Disease', (238, 243))	('hyperthermia', 'Phenotype', 'HP:0001945', (617, 629))	('high pressure', 'MPA', (528, 541))	('tumor', 'Phenotype', 'HP:0002664', (272, 277))	('patients', 'Species', '9606', (382, 390))	('tumor', 'Disease', 'MESH:D009369', (238, 243))	('tumor', 'Disease', (148, 153))	('tumors', 'Phenotype', 'HP:0002664', (238, 244))	('systemic hyperthermia', 'Disease', (608, 629))	('patients', 'Species', '9606', (206, 214))	('tumor', 'Disease', 'MESH:D009369', (148, 153))
38298	28072694	In this regard, evidence from experimental and clinical studies indicated that malignant cells are selectively killed by hyperthermia in the range of 41 to 42  C. Heat not only inhibits RNA synthesis and mitosis arrest, but also increases the number of unstable lysosomes with increased destructive capacity.	('hyperthermia', 'Disease', 'MESH:D005334', (121, 133))	('RNA synthesis', 'MPA', (186, 199))	('hyperthermia', 'Phenotype', 'HP:0001945', (121, 133))	('destructive capacity', 'CPA', (287, 307))	('hyperthermia', 'Disease', (121, 133))	('42  C', 'Gene', '6281', (156, 161))	('mitosis arrest', 'Disease', 'MESH:D006323', (204, 218))	('Heat', 'Var', (163, 167))	('increases', 'PosReg', (229, 238))	('42  C', 'Gene', (156, 161))	('mitosis arrest', 'Disease', (204, 218))	('inhibits', 'NegReg', (177, 185))	('increased', 'PosReg', (277, 286))	('number of unstable lysosomes', 'MPA', (243, 271))
38431	31413632	Sunitinib (oral tyrosine kinase inhibitor of VEGFRs, KIT, and PDGFRs) showed some activity in the treatment of TETs irrespective of histological subtype and presence of KIT mutations with median progression-free survival at 3.7 months and overall survival at 15.4 months.	('mutations', 'Var', (173, 182))	('Sunitinib', 'Chemical', 'MESH:D000077210', (0, 9))	('VEGFRs', 'Gene', (45, 51))	('activity', 'MPA', (82, 90))	('VEGFRs', 'Gene', '2321;2324;3791', (45, 51))
38648	27781146	In Japanese study, other autoimmune disorders occurred more often in seropositive MG patients (24.1%), than in MuSK-Ab-positive patients (8.4%) among which ATDs were predominant (Nakata et al., 2013).	('autoimmune disorders', 'Disease', (25, 45))	('autoimmune disorders', 'Phenotype', 'HP:0002960', (25, 45))	('ATDs', 'Disease', 'None', (156, 160))	('autoimmune disorders', 'Disease', 'MESH:D001327', (25, 45))	('seropositive', 'Var', (69, 81))	('ATDs', 'Disease', (156, 160))
38738	15150553	Specifically, HTLV-I sequences were amplified using SG231/SG238 for pol (239 bp product, nucleotide position 2802-3038) (Ehrlich et al, 1990) and SK43/SK44 for tax (161 bp product, nucleotide position 7359-7517) (Saito and Ichijo, 1992; Manca et al, 2002).	('HTLV-I', 'Gene', (14, 20))	('HTLV-I', 'Species', '11908', (14, 20))	('SG231/SG238', 'Var', (52, 63))	('SK43/SK44', 'Var', (146, 155))
38745	15150553	For HTLV-I, Western blot reactivity was defined as the presence of bands (2+ intensity) for recombinant gp46I and gp21 (env proteins) and p19 and p24 (gag proteins).	('HTLV-I', 'Gene', (4, 10))	('p19', 'Gene', (138, 141))	('gp46I', 'Var', (104, 109))	('p19', 'Gene', '51561', (138, 141))	('p21', 'Gene', (115, 118))	('p24', 'Gene', '10959', (146, 149))	('p21', 'Gene', '644914', (115, 118))	('p24', 'Gene', (146, 149))	('HTLV-I', 'Species', '11908', (4, 10))	('gag', 'Gene', (151, 154))	('gag', 'Gene', '1491934', (151, 154))
38746	15150553	For HTLV-II, bands of 2+ intensity for recombinant gp46II (env) and p24 (gag) were considered diagnostic.	('p24', 'Gene', '10959', (68, 71))	('gag', 'Gene', '1491934', (73, 76))	('p24', 'Gene', (68, 71))	('gp46II', 'Var', (51, 57))	('gag', 'Gene', (73, 76))	('HTLV-II', 'Species', '11909', (4, 11))	('HTLV-II', 'Gene', (4, 11))
38789	15150553	On sequencing, part of the HFV bel1 gene was deleted, suggesting the presence of a replication-incompetent variant of the virus.	('HFV', 'Species', '11641', (27, 30))	('presence', 'Reg', (69, 77))	('HFV bel1', 'Gene', (27, 35))	('deleted', 'Var', (45, 52))
38833	33889334	PWCA has been commonly associated with mixed type AB thymoma, though our patient's final histological type was B2 thymoma.	('PWCA', 'Var', (0, 4))	('thymoma', 'Phenotype', 'HP:0100522', (114, 121))	('thymoma', 'Phenotype', 'HP:0100522', (53, 60))	('patient', 'Species', '9606', (73, 80))	('AB thymoma', 'Disease', 'MESH:D013945', (50, 60))	('thymoma', 'Disease', 'MESH:D013945', (114, 121))	('AB thymoma', 'Disease', (50, 60))	('thymoma', 'Disease', (114, 121))	('associated', 'Reg', (23, 33))	('thymoma', 'Disease', 'MESH:D013945', (53, 60))	('thymoma', 'Disease', (53, 60))
38863	29263700	In terms of the grade of malignancy of thymoma, most studies on 18F-FDG PET for TETs were conducted based on a simplified World Health Organization (WHO) classification: low-risk group (type A, AB, and B1) and high-risk group (type B2 and B3),3,4,8,10,12,13,15,16 or low-risk group (type A, AB, and B1) and high-risk group (type B2, B3, and TC), because patients with type B2 or B3 thymoma or TC have a worse prognosis than those with type A, AB, or B1.	('thymoma', 'Disease', (39, 46))	('18F-FDG', 'Chemical', 'MESH:D019788', (64, 71))	('type B2', 'Var', (368, 375))	('malignancy of thymoma', 'Disease', 'MESH:D013945', (25, 46))	('thymoma', 'Phenotype', 'HP:0100522', (39, 46))	('thymoma', 'Disease', 'MESH:D013945', (382, 389))	('thymoma', 'Disease', (382, 389))	('patients', 'Species', '9606', (354, 362))	('thymoma', 'Disease', 'MESH:D013945', (39, 46))	('malignancy of thymoma', 'Disease', (25, 46))	('thymoma', 'Phenotype', 'HP:0100522', (382, 389))
38941	29263700	A recent study demonstrated that type B3 thymoma had worse disease-free and overall survival than the other histological subtypes, and Benveniste et al demonstrated a significant difference in SUVmax between type B3 and the other subtypes.	('disease-free', 'CPA', (59, 71))	('overall survival', 'CPA', (76, 92))	('thymoma', 'Disease', 'MESH:D013945', (41, 48))	('thymoma', 'Disease', (41, 48))	('type B3', 'Var', (33, 40))	('SUVmax', 'MPA', (193, 199))	('worse', 'NegReg', (53, 58))	('thymoma', 'Phenotype', 'HP:0100522', (41, 48))
38987	25003519	 CTLA4 Variants and Haplotype Contribute Genetic Susceptibility to Myasthenia Gravis in Northern Chinese Population Cytotoxic T lymphocyte-associated antigen-4 (CTLA4), a critical negative regulator of the T-cell response, has been considered a candidate for many autoimmune diseases.	('CTLA4', 'Gene', '1493', (161, 166))	('Susceptibility', 'Reg', (49, 63))	('CTLA4', 'Gene', (161, 166))	('autoimmune diseases', 'Disease', 'MESH:D001327', (264, 283))	('Cytotoxic', 'Disease', 'MESH:D064420', (116, 125))	('Variants', 'Var', (7, 15))	('Myasthenia Gravis', 'Disease', 'MESH:D009157', (67, 84))	('CTLA4', 'Gene', '1493', (1, 6))	('autoimmune diseases', 'Disease', (264, 283))	('Cytotoxic', 'Disease', (116, 125))	('CTLA4', 'Gene', (1, 6))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (264, 283))	('Myasthenia Gravis', 'Disease', (67, 84))	('autoimmune disease', 'Phenotype', 'HP:0002960', (264, 282))	('Myasthenia', 'Phenotype', 'HP:0003473', (67, 77))
38989	25003519	To investigate the role of CTLA4 variants in the susceptibility to MG and the contribution to subtypes of MG. Six autoimmune disease-related risk alleles of CTLA4 (rs1863800, rs733618, rs4553808, rs5742909, rs231775, and rs3087243) were investigated for MG in northern Chinese.	('rs231775', 'Var', (207, 215))	('rs231775', 'DBSNP_MENTION', 'None', (207, 215))	('rs733618', 'DBSNP_MENTION', 'None', (175, 183))	('CTLA4', 'Gene', (157, 162))	('autoimmune disease', 'Phenotype', 'HP:0002960', (114, 132))	('rs1863800', 'DBSNP_MENTION', 'None', (164, 173))	('autoimmune disease', 'Disease', 'MESH:D001327', (114, 132))	('rs5742909', 'DBSNP_MENTION', 'None', (196, 205))	('rs4553808', 'DBSNP_MENTION', 'None', (185, 194))	('rs733618', 'Var', (175, 183))	('rs3087243', 'Var', (221, 230))	('rs5742909', 'Var', (196, 205))	('rs3087243', 'DBSNP_MENTION', 'None', (221, 230))	('rs1863800', 'Var', (164, 173))	('autoimmune disease', 'Disease', (114, 132))	('rs4553808', 'Var', (185, 194))
38991	25003519	rs1863800*C, rs733618*C, and rs231775*G were significantly associated with the whole cohort of patients with MG after permutation correction for multiple-testing adjustment (P = 0.027, 0.001, and 0.032, respectively).	('rs231775*G', 'Var', (29, 39))	('patients', 'Species', '9606', (95, 103))	('rs733618*C', 'Var', (13, 23))	('associated', 'Reg', (59, 69))	('rs1863800*C', 'Var', (0, 11))	('men', 'Species', '9606', (168, 171))
38994	25003519	A predisposing effect of rs1863800*C, rs733618*C, and rs231775*G of CTLA4 gene to general risk of MG in Chinese was demonstrated for the first time, which was likely derived from EOMG, SPMG, MG without thymoma and the female patients.	('patients', 'Species', '9606', (225, 233))	('rs733618*C', 'Var', (38, 48))	('CTLA4', 'Gene', (68, 73))	('thymoma', 'Disease', 'MESH:D013945', (202, 209))	('thymoma', 'Disease', (202, 209))	('rs231775*G', 'Var', (54, 64))	('rs1863800*C', 'Var', (25, 36))	('EOMG', 'Chemical', '-', (179, 183))	('thymoma', 'Phenotype', 'HP:0100522', (202, 209))
39002	25003519	In addition, 80-85% of cases of MG are caused by autoantibodies against muscle acetylcholine receptor (AChR).	('autoantibodies', 'Var', (49, 63))	('caused by', 'Reg', (39, 48))	('acetylcholine', 'Chemical', 'MESH:D000109', (79, 92))	('AChR', 'Gene', (103, 107))
39010	25003519	Although CTLA4 expressed similarly between MG and control peripheral blood mononuclear cells, rs733618, and rs4553808 could influence the CTLA4 mRNA level.	('rs733618', 'Var', (94, 102))	('rs4553808', 'Var', (108, 117))	('CTLA4', 'Gene', (9, 14))	('CTLA4 mRNA level', 'MPA', (138, 154))	('rs733618', 'DBSNP_MENTION', 'None', (94, 102))	('influence', 'Reg', (124, 133))	('rs4553808', 'DBSNP_MENTION', 'None', (108, 117))
39011	25003519	In addition, rs733618, and rs4553808 were reported to be associated with MG by influencing the alternative splicing and expression of CTLA4 in Swedish-Caucasians; rs231775 was associated with thymoma manifestations of MG in Swedish-Caucasians and German-Caucasians.	('CTLA4', 'Gene', (134, 139))	('rs231775', 'Var', (163, 171))	('thymoma', 'Disease', 'MESH:D013945', (192, 199))	('rs733618', 'Var', (13, 21))	('rs4553808', 'Var', (27, 36))	('expression', 'MPA', (120, 130))	('influencing', 'Reg', (79, 90))	('rs231775', 'DBSNP_MENTION', 'None', (163, 171))	('thymoma', 'Disease', (192, 199))	('alternative splicing', 'MPA', (95, 115))	('thymoma', 'Phenotype', 'HP:0100522', (192, 199))	('associated with', 'Reg', (176, 191))	('rs4553808', 'DBSNP_MENTION', 'None', (27, 36))	('rs733618', 'DBSNP_MENTION', 'None', (13, 21))
39013	25003519	Accordingly, a comprehensive genotyping of six previously identified autoimmune-related candidate variants in CTLA4 (rs1863800, rs733618, rs4553808, rs5742909, rs231775, and rs3087243) was carried out as the largest study in Chinese patients with MG by far.	('rs3087243', 'Var', (174, 183))	('rs4553808', 'Var', (138, 147))	('rs5742909', 'DBSNP_MENTION', 'None', (149, 158))	('rs231775', 'Var', (160, 168))	('rs231775', 'DBSNP_MENTION', 'None', (160, 168))	('rs733618', 'DBSNP_MENTION', 'None', (128, 136))	('rs3087243', 'DBSNP_MENTION', 'None', (174, 183))	('rs1863800', 'DBSNP_MENTION', 'None', (117, 126))	('rs4553808', 'DBSNP_MENTION', 'None', (138, 147))	('rs733618', 'Var', (128, 136))	('patients', 'Species', '9606', (233, 241))	('CTLA4', 'Gene', (110, 115))	('rs5742909', 'Var', (149, 158))	('rs1863800', 'Var', (117, 126))
39019	25003519	The six variants in CTLA4 (rs1863800, rs733618, rs4553808, rs5742909, rs231775, rs3087243) were identified following polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP).	('rs231775', 'Var', (70, 78))	('men', 'Species', '9606', (165, 168))	('rs231775', 'DBSNP_MENTION', 'None', (70, 78))	('rs4553808', 'Var', (48, 57))	('rs1863800', 'Var', (27, 36))	('rs733618', 'DBSNP_MENTION', 'None', (38, 46))	('CTLA4', 'Gene', (20, 25))	('rs5742909', 'Var', (59, 68))	('rs5742909', 'DBSNP_MENTION', 'None', (59, 68))	('rs1863800', 'DBSNP_MENTION', 'None', (27, 36))	('rs3087243', 'Var', (80, 89))	('rs733618', 'Var', (38, 46))	('rs4553808', 'DBSNP_MENTION', 'None', (48, 57))	('rs3087243', 'DBSNP_MENTION', 'None', (80, 89))
39024	25003519	Compared to those in HapMap CEU, the minor allele frequencies (MAFs) of rs1863800, rs231775, and rs3087243 were much lower, and the MAFs of rs733618 and rs5742909 were much higher (Table 2).	('rs733618', 'Var', (140, 148))	('rs231775', 'DBSNP_MENTION', 'None', (83, 91))	('rs1863800', 'DBSNP_MENTION', 'None', (72, 81))	('MAF', 'Gene', '4094', (63, 66))	('lower', 'NegReg', (117, 122))	('MAF', 'Gene', (63, 66))	('rs3087243', 'Var', (97, 106))	('MAF', 'Gene', '4094', (132, 135))	('rs5742909', 'DBSNP_MENTION', 'None', (153, 162))	('minor', 'MPA', (37, 42))	('rs3087243', 'DBSNP_MENTION', 'None', (97, 106))	('rs231775', 'Var', (83, 91))	('rs1863800', 'Var', (72, 81))	('MAF', 'Gene', (132, 135))	('rs5742909', 'Var', (153, 162))	('higher', 'PosReg', (173, 179))	('rs733618', 'DBSNP_MENTION', 'None', (140, 148))
39025	25003519	The power analysis showed that 94.9% (additive) and 89.3% (allelic) power were required to detect a genotype relative risk of 2.5 at an alpha level of 0.05 for variants with an MAF of 30%, assuming a prevalence of 0.01% of MG in Chinese.	('variants', 'Var', (160, 168))	('MAF', 'Gene', (177, 180))	('MAF', 'Gene', '4094', (177, 180))
39027	25003519	The additive, log-additive and allele contrast model all indicated that the minor alleles of rs1863800, rs733618, rs231775, and rs3087243 distributed differently between MG and controls.	('rs1863800', 'Var', (93, 102))	('rs733618', 'DBSNP_MENTION', 'None', (104, 112))	('rs1863800', 'DBSNP_MENTION', 'None', (93, 102))	('rs3087243', 'Var', (128, 137))	('rs231775', 'DBSNP_MENTION', 'None', (114, 122))	('rs733618', 'Var', (104, 112))	('rs3087243', 'DBSNP_MENTION', 'None', (128, 137))	('rs231775', 'Var', (114, 122))
39028	25003519	After a further permutation correction (n = 1000) for multiple-testing adjustment, only rs1863800, rs733618, and rs231775 reached significance (P = 0.027, 0.001 and 0.032, respectively).	('rs733618', 'DBSNP_MENTION', 'None', (99, 107))	('rs231775', 'Var', (113, 121))	('rs231775', 'DBSNP_MENTION', 'None', (113, 121))	('rs733618', 'Var', (99, 107))	('men', 'Species', '9606', (77, 80))	('rs1863800', 'Var', (88, 97))	('rs1863800', 'DBSNP_MENTION', 'None', (88, 97))
39029	25003519	On the whole, the contribution of rs1863800*C, rs733618*C, and rs231775*G for MG existed more significantly in EOMG, seropositive MG (SPMG), female patients, and MG without thymoma than the respective opposite subgroups.	('rs733618*C', 'Var', (47, 57))	('patients', 'Species', '9606', (148, 156))	('rs1863800*C', 'Var', (34, 45))	('thymoma', 'Phenotype', 'HP:0100522', (173, 180))	('thymoma', 'Disease', 'MESH:D013945', (173, 180))	('thymoma', 'Disease', (173, 180))	('EOMG', 'Disease', (111, 115))	('rs231775*G', 'Var', (63, 73))	('EOMG', 'Chemical', '-', (111, 115))
39031	25003519	Moreover, the distribution of above three risk alleles among subgroups were compared only within the patients with MG according to the age at onset of MG, AChR/MuSK antibody status, thymus status, muscles involved, Osserman type and gender, where an increased 733618*C in EOMG than in LOMG (0.506 vs 0.317) and an increased rs231775*A in patients with thymoma than those without thymoma (0.357 vs 0.214, OR = 2.037, range = 1.099-3.774) were observed (Table S3).	('thymoma', 'Disease', 'MESH:D013945', (352, 359))	('patients', 'Species', '9606', (101, 109))	('thymoma', 'Phenotype', 'HP:0100522', (352, 359))	('MuSK', 'Gene', '4593', (160, 164))	('733618*C', 'Var', (260, 268))	('patients', 'Species', '9606', (338, 346))	('thymoma', 'Disease', 'MESH:D013945', (379, 386))	('EOMG', 'Chemical', '-', (272, 276))	('MuSK antibody', 'Phenotype', 'HP:0030210', (160, 173))	('thymoma', 'Disease', (379, 386))	('thymoma', 'Disease', (352, 359))	('rs231775*A', 'Var', (324, 334))	('MuSK', 'Gene', (160, 164))	('thymoma', 'Phenotype', 'HP:0100522', (379, 386))
39032	25003519	Overall, rs1863800*C, rs733618*C, and rs231775*G could confer the general risk of MG, even after the permutation correction and adjustment for covariance.	('rs1863800*C', 'Var', (9, 20))	('rs733618*C', 'Var', (22, 32))	('risk', 'Reg', (74, 78))	('rs231775*G', 'Var', (38, 48))	('men', 'Species', '9606', (134, 137))
39033	25003519	A haplotype CCACG, containing rs1863800*C, rs733618*C, and rs231775*G was identified to increase the general risk of MG by 1.535-fold (P = 0.021, after permutation adjustment).	('rs1863800*C', 'Var', (30, 41))	('increase', 'PosReg', (88, 96))	('men', 'Species', '9606', (170, 173))	('rs231775*G', 'Var', (59, 69))	('rs733618*C', 'Var', (43, 53))
39035	25003519	In addition, the case-only analysis indicated that rs733618*C and rs231775*A were also associated with EOMG and presence of thymoma, respectively.	('EOMG', 'Chemical', '-', (103, 107))	('associated', 'Reg', (87, 97))	('thymoma', 'Disease', 'MESH:D013945', (124, 131))	('thymoma', 'Disease', (124, 131))	('EOMG', 'Disease', (103, 107))	('rs733618*C', 'Var', (51, 61))	('rs231775*A', 'Var', (66, 76))	('thymoma', 'Phenotype', 'HP:0100522', (124, 131))
39036	25003519	There are accumulating evidences to suggest the role of CTLA4 variants to autoimmune diseases including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Graves' disease, Hashimoto's thyroiditis, postpartum thyroiditis, Addison's disease, insulin-dependent diabetes mellitus, vitiligo and multiple sclerosis.	('autoimmune diseases', 'Disease', (74, 93))	('RA', 'Disease', 'MESH:D001172', (162, 164))	('arthritis', 'Phenotype', 'HP:0001369', (151, 160))	('vitiligo', 'Phenotype', 'HP:0001045', (289, 297))	("Hashimoto's thyroiditis", 'Phenotype', 'HP:0000872', (184, 207))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (74, 93))	("Graves' disease", 'Phenotype', 'HP:0100647', (167, 182))	('CTLA4', 'Gene', (56, 61))	('autoimmune disease', 'Phenotype', 'HP:0002960', (74, 92))	('insulin-dependent diabetes mellitus', 'Disease', 'MESH:D003922', (252, 287))	('vitiligo', 'Disease', (289, 297))	('rheumatoid arthritis', 'Disease', (140, 160))	('multiple sclerosis', 'Disease', 'MESH:D009103', (302, 320))	('thyroiditis', 'Disease', (196, 207))	('thyroiditis', 'Disease', (220, 231))	('systemic lupus erythematosus', 'Phenotype', 'HP:0002725', (104, 132))	('systemic lupus erythematosus', 'Disease', 'MESH:D008180', (104, 132))	('rheumatoid arthritis', 'Disease', 'MESH:D001172', (140, 160))	('vitiligo', 'Disease', 'MESH:D014820', (289, 297))	('insulin-dependent diabetes mellitus', 'Phenotype', 'HP:0100651', (252, 287))	("Addison's disease", 'Phenotype', 'HP:0008207', (233, 250))	('thyroiditis', 'Disease', 'MESH:D013959', (196, 207))	("Graves' disease", 'Disease', 'MESH:D006111', (167, 182))	('thyroiditis', 'Disease', 'MESH:D013959', (220, 231))	("Addison's disease", 'Disease', (233, 250))	('insulin-dependent diabetes mellitus', 'Disease', (252, 287))	('SLE', 'Disease', 'MESH:D008180', (134, 137))	('SLE', 'Disease', (134, 137))	("Hashimoto's thyroiditis", 'Disease', (184, 207))	('variants', 'Var', (62, 70))	("Addison's disease", 'Disease', 'MESH:D000224', (233, 250))	("Hashimoto's thyroiditis", 'Disease', 'MESH:D050031', (184, 207))	('diabetes mellitus', 'Phenotype', 'HP:0000819', (270, 287))	("Graves' disease", 'Disease', (167, 182))	('thyroiditis', 'Phenotype', 'HP:0100646', (196, 207))	('multiple sclerosis', 'Disease', (302, 320))	('rheumatoid arthritis', 'Phenotype', 'HP:0001370', (140, 160))	('thyroiditis', 'Phenotype', 'HP:0100646', (220, 231))	('autoimmune diseases', 'Disease', 'MESH:D001327', (74, 93))	('systemic lupus erythematosus', 'Disease', (104, 132))
39037	25003519	With regard to MG, the most significant association was reported for two promoter variants (rs733618 and rs4553808) in Swedish-Caucasians.	('rs4553808', 'DBSNP_MENTION', 'None', (105, 114))	('rs733618', 'Var', (92, 100))	('rs4553808', 'Var', (105, 114))	('significant association', 'Reg', (28, 51))	('rs733618', 'DBSNP_MENTION', 'None', (92, 100))
39038	25003519	Besides, rs231775*A, which was protective against several autoimmune diseases, was reported to exert a predisposing effect to paraneoplastic MG in thymoma German-Caucasian patients.	('autoimmune diseases', 'Disease', 'MESH:D001327', (58, 77))	('thymoma', 'Disease', 'MESH:D013945', (147, 154))	('thymoma', 'Disease', (147, 154))	('autoimmune diseases', 'Disease', (58, 77))	('paraneoplastic MG', 'Disease', (126, 143))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (58, 77))	('thymoma', 'Phenotype', 'HP:0100522', (147, 154))	('effect', 'Reg', (116, 122))	('patients', 'Species', '9606', (172, 180))	('rs231775*A', 'Var', (9, 19))	('paraneoplastic MG', 'Disease', 'MESH:D000080343', (126, 143))	('autoimmune disease', 'Phenotype', 'HP:0002960', (58, 76))
39042	25003519	The subtype analysis also indicated that CTLA4 risk alleles mainly confer the risk of EOMG.	('CTLA4', 'Gene', (41, 46))	('EOMG', 'Disease', (86, 90))	('alleles', 'Var', (52, 59))	('EOMG', 'Chemical', '-', (86, 90))
39044	25003519	Interestingly, a recently study in German-Caucasians suggested rs231775*G was associated with LOMG, where EOMG was not discussed.	('associated', 'Reg', (78, 88))	('LOMG', 'Disease', (94, 98))	('EOMG', 'Chemical', '-', (106, 110))	('rs231775*G', 'Var', (63, 73))
39045	25003519	Complementarily, it was found that the rs231775*G was associated with EOMG rather than JMG and LOMG.	('EOMG', 'Chemical', '-', (70, 74))	('rs231775*G', 'Var', (39, 49))	('JMG', 'Disease', (87, 90))	('EOMG', 'Disease', (70, 74))	('associated', 'Reg', (54, 64))	('men', 'Species', '9606', (6, 9))
39048	25003519	The case-only analysis in the present study indicated that rs231775*A was also associated with MG coupled with thymoma (OR = 2.037, range = 1.099-3.774), which is opposite to its protective role reported in other autoimmune diseases.	('associated', 'Reg', (79, 89))	('thymoma', 'Phenotype', 'HP:0100522', (111, 118))	('autoimmune diseases', 'Disease', (213, 232))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (213, 232))	('MG coupled', 'Disease', (95, 105))	('rs231775*A', 'Var', (59, 69))	('thymoma', 'Disease', 'MESH:D013945', (111, 118))	('autoimmune disease', 'Phenotype', 'HP:0002960', (213, 231))	('thymoma', 'Disease', (111, 118))	('autoimmune diseases', 'Disease', 'MESH:D001327', (213, 232))
39049	25003519	The paradox that the gain-of-function rs231775*A in predisposing to paraneoplastic MG could be explained by the nontolerogenic selection of CD4+ T-cells in MG-associated thymomas.	('CD4', 'Gene', (140, 143))	('thymoma', 'Phenotype', 'HP:0100522', (170, 177))	('paraneoplastic MG', 'Disease', (68, 85))	('CD4', 'Gene', '920', (140, 143))	('gain-of-function', 'PosReg', (21, 37))	('rs231775*A', 'Var', (38, 48))	('thymomas', 'Disease', (170, 178))	('thymomas', 'Disease', 'MESH:D013945', (170, 178))	('paraneoplastic MG', 'Disease', 'MESH:D000080343', (68, 85))
39050	25003519	Promoter analysis indicated that rs733618*C might disturb the binding with transcript factor, NF-1, which was validated by chromatin immunoprecipitation assay and gel shift assay.	('rs733618*C', 'Var', (33, 43))	('disturb', 'NegReg', (50, 57))	('binding', 'Interaction', (62, 69))	('NF-1', 'Gene', '4763', (94, 98))	('NF-1', 'Gene', (94, 98))
39051	25003519	rs231775*A (aliases: +49, T17A) is a gain-of-function missense mutation associated with altered expression and activation of T-cell.	('T17A', 'Var', (26, 30))	('activation', 'PosReg', (111, 121))	('T17A', 'SUBSTITUTION', 'None', (26, 30))	('gain-of-function', 'PosReg', (37, 53))	('expression', 'MPA', (96, 106))	('rs231775*A', 'Var', (0, 10))	('T-cell', 'CPA', (125, 131))
39052	25003519	Considering the tight linkage of three risk alleles, rs1863800*C-rs733618*C-rs231775*G might be corresponding to a lower surface expression of CTLA4 and reduced inhibitory function of CTLA4, predisposing to MG without thymoma.	('surface expression', 'MPA', (121, 139))	('thymoma', 'Disease', (218, 225))	('reduced', 'NegReg', (153, 160))	('CTLA4', 'Gene', (143, 148))	('thymoma', 'Phenotype', 'HP:0100522', (218, 225))	('inhibitory function', 'MPA', (161, 180))	('lower', 'NegReg', (115, 120))	('rs1863800*C-rs733618*C-rs231775*G', 'Var', (53, 86))	('CTLA4', 'Gene', (184, 189))	('thymoma', 'Disease', 'MESH:D013945', (218, 225))
39056	25003519	Third, the gene-specific hypomethylation and noncoding RNAs are also potential mechanisms in many autoimmune diseases such as SLE and RA, suggesting that the epigenetics of CTLA4 might be addressed as well.	('SLE', 'Disease', (126, 129))	('hypomethylation', 'Var', (25, 40))	('autoimmune diseases', 'Disease', (98, 117))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (98, 117))	('noncoding RNAs', 'Var', (45, 59))	('autoimmune disease', 'Phenotype', 'HP:0002960', (98, 116))	('RA', 'Disease', 'MESH:D001172', (134, 136))	('mechanisms', 'Reg', (79, 89))	('autoimmune diseases', 'Disease', 'MESH:D001327', (98, 117))	('SLE', 'Disease', 'MESH:D008180', (126, 129))
39062	23691442	The overall hospitalization and chest tube duration were shorter in the VATS lobectomy group (n=949) than in the open thoracotomy (OT) lobectomy group (n=753).	('VATS', 'Var', (72, 76))	('chest tube duration', 'CPA', (32, 51))	('hospitalization', 'MPA', (12, 27))	('OT', 'Chemical', '-', (131, 133))	('shorter', 'NegReg', (57, 64))
39064	23691442	In the thymoma patients, there was no significant difference in the chest tube duration, morbidity rate, mortality rate, and hospital length of stay between the VATS thymectomy group (n=41) and open thymectomy group (n=41).	('patients', 'Species', '9606', (15, 23))	('thymoma', 'Disease', 'MESH:D013945', (7, 14))	('thymoma', 'Disease', (7, 14))	('thymoma', 'Phenotype', 'HP:0100522', (7, 14))	('VATS', 'Var', (161, 165))
39102	23691442	The postoperative LOS and chest tube duration were shorter in the VATS lobectomy group than in the OT lobectomy group, comparable with previous reports.	('VATS', 'Var', (66, 70))	('OT', 'Chemical', '-', (99, 101))	('shorter', 'NegReg', (51, 58))
39165	25187234	Primary mutations for Leber's hereditary optic neuropathy of 11778/ND4, 3460/ND1, 14484/ND6 and 4171/ND1 were absent.	('neuropathy', 'Phenotype', 'HP:0009830', (47, 57))	("Leber's hereditary optic neuropathy", 'Disease', (22, 57))	('4171/ND1', 'Var', (96, 104))	('11778/ND4', 'Var', (61, 70))	('14484/ND6', 'Var', (82, 91))	('optic neuropathy', 'Phenotype', 'HP:0001138', (41, 57))	("Leber's hereditary optic neuropathy", 'Disease', 'MESH:D029242', (22, 57))	('3460/ND1', 'Var', (72, 80))
39176	25187234	Although rare, thymoma associated with visual symptoms has been reported in association with paraneoplastic autoantibodies, such as cancer-associated retinopathy (CAR) with anti-retinal antibodies, paraneoplastic optic neuropathy (PON) with anti-CRMP5 antibody, or NMO with AQP4-IgG.	('paraneoplastic optic neuropathy', 'Disease', (198, 229))	('anti-retinal antibodies', 'Var', (173, 196))	('retinopathy', 'Disease', 'MESH:D012164', (150, 161))	('visual symptoms', 'Disease', (39, 54))	('paraneoplastic autoantibodies', 'Disease', (93, 122))	('CRMP5', 'Gene', (246, 251))	('retinopathy', 'Phenotype', 'HP:0000488', (150, 161))	('cancer', 'Disease', 'MESH:D009369', (132, 138))	('retinopathy', 'Disease', (150, 161))	('AQP4', 'Gene', (274, 278))	('thymoma', 'Disease', 'MESH:D013945', (15, 22))	('neuropathy', 'Phenotype', 'HP:0009830', (219, 229))	('paraneoplastic autoantibodies', 'Disease', 'MESH:D050031', (93, 122))	('CRMP5', 'Gene', '56896', (246, 251))	('thymoma', 'Disease', (15, 22))	('cancer', 'Disease', (132, 138))	('paraneoplastic optic neuropathy', 'Disease', 'MESH:D020364', (198, 229))	('AQP4', 'Gene', '361', (274, 278))	('thymoma', 'Phenotype', 'HP:0100522', (15, 22))	('cancer', 'Phenotype', 'HP:0002664', (132, 138))	('visual symptoms', 'Disease', 'MESH:D014786', (39, 54))	('optic neuropathy', 'Phenotype', 'HP:0001138', (213, 229))
39188	25187234	The clinical significance of APQ4-IgG associated with cancer is unclear.	('associated', 'Reg', (38, 48))	('cancer', 'Disease', 'MESH:D009369', (54, 60))	('cancer', 'Disease', (54, 60))	('APQ4-IgG', 'Var', (29, 37))	('cancer', 'Phenotype', 'HP:0002664', (54, 60))
39189	25187234	APQ4-IgG was found to be associated with cancer in 0.004% of cases, including 1 thymoma patient screened for paraneoplastic autoantibodies.	('APQ4-IgG', 'Var', (0, 8))	('patient', 'Species', '9606', (88, 95))	('paraneoplastic autoantibodies', 'Disease', (109, 138))	('thymoma', 'Phenotype', 'HP:0100522', (80, 87))	('cancer', 'Phenotype', 'HP:0002664', (41, 47))	('associated', 'Reg', (25, 35))	('paraneoplastic autoantibodies', 'Disease', 'MESH:D050031', (109, 138))	('cancer', 'Disease', (41, 47))	('cancer', 'Disease', 'MESH:D009369', (41, 47))	('thymoma', 'Disease', 'MESH:D013945', (80, 87))	('thymoma', 'Disease', (80, 87))
39303	22346015	When the histopathology and clinical outcome was correlated, it was observed that 10 patients (33.3%) with hyperplastic glands achieved complete remission when compared with 2 patients (8.7%) with thymoma, 4 (33.3%) with normal gland, 1 (50%) with involuted thymus, and 2 (66.7%) with thymic cyst (P=0.11).	('patients', 'Species', '9606', (176, 184))	('thymoma', 'Phenotype', 'HP:0100522', (197, 204))	('hyperplastic glands', 'Var', (107, 126))	('patients', 'Species', '9606', (85, 93))	('thymoma', 'Disease', 'MESH:D013945', (197, 204))	('thymoma', 'Disease', (197, 204))
39330	22346015	In our study, 33.3% of patients with hyperplastic thymus glands achieved complete remission in comparison to 8.7% with thymoma, but the difference was not significant.	('thymoma', 'Disease', 'MESH:D013945', (119, 126))	('patients', 'Species', '9606', (23, 31))	('thymoma', 'Disease', (119, 126))	('hyperplastic thymus', 'Phenotype', 'HP:0010516', (37, 56))	('hyperplastic', 'Var', (37, 49))	('thymoma', 'Phenotype', 'HP:0100522', (119, 126))
39402	33786130	Improper handling causes blood loss, obscures the field of vision, and may thus elongate the surgical procedure.	('field of vision', 'MPA', (50, 65))	('blood loss', 'Disease', (25, 35))	('elongate', 'Reg', (80, 88))	('obscures', 'NegReg', (37, 45))	('surgical procedure', 'CPA', (93, 111))	('causes', 'Reg', (18, 24))	('blood loss', 'Disease', 'MESH:D006473', (25, 35))	('Improper', 'Var', (0, 8))
39431	32923112	Higher pHSP27 serum concentrations were observed in seropositive MG and those not treated with steroids.	('serum concentrations', 'MPA', (14, 34))	('HSP27', 'Gene', (8, 13))	('Higher', 'PosReg', (0, 6))	('seropositive MG', 'Var', (52, 67))	('HSP27', 'Gene', '3315', (8, 13))	('steroids', 'Chemical', 'MESH:D013256', (95, 103))
39447	32923112	Dysregulated HSPs have already been associated with several autoimmune diseases, such as Rheumatoid Arthritis, Systemic Lupus Erythematosus or Multiple Sclerosis.	('Arthritis', 'Phenotype', 'HP:0001369', (100, 109))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (60, 79))	('Rheumatoid Arthritis', 'Phenotype', 'HP:0001370', (89, 109))	('Systemic Lupus Erythematosus', 'Disease', (111, 139))	('Rheumatoid Arthritis', 'Disease', 'MESH:D001172', (89, 109))	('Systemic Lupus Erythematosus', 'Disease', 'MESH:D008180', (111, 139))	('Rheumatoid Arthritis', 'Disease', (89, 109))	('Multiple Sclerosis', 'Disease', 'MESH:D009103', (143, 161))	('Multiple Sclerosis', 'Disease', (143, 161))	('Systemic Lupus Erythematosus', 'Phenotype', 'HP:0002725', (111, 139))	('Dysregulated', 'Var', (0, 12))	('HSP', 'Gene', (13, 16))	('autoimmune disease', 'Phenotype', 'HP:0002960', (60, 78))	('autoimmune diseases', 'Disease', 'MESH:D001327', (60, 79))	('associated', 'Reg', (36, 46))	('autoimmune diseases', 'Disease', (60, 79))	('HSP', 'Gene', '7190', (13, 16))
39491	32923112	Patients with TETs had significantly higher HSP90alpha serum concentrations compared to healthy volunteers (HSP90alpha[ng/ml] TETs 13.8 +- 1.0 vs. healthy volunteers 6.2 +- 0.4; p < .001; Figure 2a) and regTs (HSP90alpha[ng/ml] TETs vs. regT 6.2 +- 0.9; p < .001; Figure 2a), respectively.	('HSP90alpha', 'Gene', '3320', (210, 220))	('HSP90alpha', 'Gene', (44, 54))	('higher', 'PosReg', (37, 43))	('regTs', 'Chemical', '-', (203, 208))	('HSP90alpha', 'Gene', '3320', (108, 118))	('HSP90alpha', 'Gene', (210, 220))	('regT', 'Chemical', '-', (203, 207))	('HSP90alpha', 'Gene', (108, 118))	('Patients', 'Species', '9606', (0, 8))	('TETs', 'Var', (14, 18))	('regT', 'Chemical', '-', (237, 241))	('HSP90alpha', 'Gene', '3320', (44, 54))
39512	32923112	High HSP90alpha serum concentrations in patients with thymomas (n = 84); cutoff: 24.9 ng/ml) were associated with significantly worse FFR (p = .008, Figure 2g).	('HSP90alpha', 'Gene', (5, 15))	('HSP90alpha', 'Gene', '3320', (5, 15))	('High', 'Var', (0, 4))	('thymoma', 'Phenotype', 'HP:0100522', (54, 61))	('patients', 'Species', '9606', (40, 48))	('worse', 'NegReg', (128, 133))	('serum concentrations', 'MPA', (16, 36))	('thymomas', 'Disease', (54, 62))	('thymomas', 'Disease', 'MESH:D013945', (54, 62))	('FFR', 'Disease', (134, 137))
39539	32923112	Also, patients with high HSP90 tumor expression in colon cancer had better OS.	('colon cancer', 'Disease', (51, 63))	('tumor', 'Phenotype', 'HP:0002664', (31, 36))	('tumor', 'Disease', (31, 36))	('high', 'Var', (20, 24))	('HSP90', 'Gene', (25, 30))	('patients', 'Species', '9606', (6, 14))	('HSP90', 'Gene', '3320', (25, 30))	('colon cancer', 'Disease', 'MESH:D015179', (51, 63))	('colon cancer', 'Phenotype', 'HP:0003003', (51, 63))	('cancer', 'Phenotype', 'HP:0002664', (57, 63))	('tumor', 'Disease', 'MESH:D009369', (31, 36))
39566	32923112	Secretion of HSP90alpha was dependent upon its up-stream regulator ADAM10 (affecting HSP90 content in exosomes) and plasma HSP90alpha detection by ELISA was particularly effective in patients with high ADAM10 expression.	('HSP90alpha', 'Gene', (13, 23))	('ADAM10', 'Gene', '102', (67, 73))	('HSP90', 'Gene', (85, 90))	('HSP90alpha', 'Gene', (123, 133))	('ADAM10', 'Gene', (67, 73))	('HSP90', 'Gene', (123, 128))	('HSP90alpha', 'Gene', '3320', (13, 23))	('high', 'Var', (197, 201))	('HSP90', 'Gene', (13, 18))	('ADAM10', 'Gene', '102', (202, 208))	('HSP90', 'Gene', '3320', (85, 90))	('HSP90', 'Gene', '3320', (13, 18))	('ADAM10', 'Gene', (202, 208))	('HSP90', 'Gene', '3320', (123, 128))	('HSP90alpha', 'Gene', '3320', (123, 133))	('Secretion', 'MPA', (0, 9))	('plasma', 'MPA', (116, 122))	('patients', 'Species', '9606', (183, 191))
39567	32923112	Western blotting and proteomics may identify ELISA false negative results for HSP90alpha, particularly in patients with low ADAM10 expression and those with hyperphosphorylated HSP90alpha.	('HSP90alpha', 'Gene', (78, 88))	('HSP90alpha', 'Gene', '3320', (177, 187))	('expression', 'MPA', (131, 141))	('low', 'NegReg', (120, 123))	('patients', 'Species', '9606', (106, 114))	('ADAM10', 'Gene', '102', (124, 130))	('HSP90alpha', 'Gene', '3320', (78, 88))	('hyperphosphorylated', 'Var', (157, 176))	('ADAM10', 'Gene', (124, 130))	('HSP90alpha', 'Gene', (177, 187))	('negative', 'NegReg', (57, 65))
39757	31895819	Mean surgery time was longer in patients underwent PMC than those without PMC (SMD = 0.41 95%CI: 0.23-0.60, P < .001, Fig.	('PMC', 'Var', (51, 54))	('patients', 'Species', '9606', (32, 40))	('longer', 'PosReg', (22, 28))
39758	31895819	Patients underwent PMC suffered from more blood loss during thymectomy than non-PMC patients (SMD = 0.35 95%CI: 0.16-0.54 P < .001, Fig.	('PMC', 'Var', (19, 22))	('blood loss', 'Disease', (42, 52))	('patients', 'Species', '9606', (84, 92))	('Patients', 'Species', '9606', (0, 8))	('blood loss', 'Disease', 'MESH:D006473', (42, 52))
39790	31895819	In our opinion, the large-dose anti-cholinesterase medication was used in MG patients with worse MG situations and higher clinical stages, so large-dose pyridostigmine represents a higher risk of PMC.	('MG', 'Disease', 'MESH:D009157', (97, 99))	('pyridostigmine', 'Chemical', 'MESH:D011729', (153, 167))	('MG', 'Disease', 'MESH:D009157', (74, 76))	('large-dose', 'Var', (142, 152))	('patients', 'Species', '9606', (77, 85))	('PMC', 'Disease', (196, 199))
39895	24646138	This retrospective study was conducted in order to investigate whether the rate of recurrence is significantly different following thymoma resection relative to the extent of Resection.	('thymoma', 'Gene', (131, 138))	('resection', 'Var', (139, 148))	('thymoma', 'Phenotype', 'HP:0100522', (131, 138))	('thymoma', 'Gene', '7063', (131, 138))
39982	33847622	The thymic adenocarcinoma and type A thymoma both had the mutation of KMT2A, but the mutation sites were different.	('thymic adenocarcinoma', 'Disease', (4, 25))	('thymoma', 'Phenotype', 'HP:0100522', (37, 44))	('carcinoma', 'Phenotype', 'HP:0030731', (16, 25))	('mutation', 'Var', (58, 66))	('thymic adenocarcinoma', 'Disease', 'MESH:D000230', (4, 25))	('KMT2A', 'Gene', (70, 75))	('type A thymoma', 'Disease', (30, 44))	('KMT2A', 'Gene', '4297', (70, 75))	('type A thymoma', 'Disease', 'MESH:D013945', (30, 44))
39983	33847622	KMT2A mutation may be a common genetic change in thymic tumorigenesis.	('tumor', 'Phenotype', 'HP:0002664', (56, 61))	('tumor', 'Disease', (56, 61))	('mutation', 'Var', (6, 14))	('KMT2A', 'Gene', (0, 5))	('KMT2A', 'Gene', '4297', (0, 5))	('tumor', 'Disease', 'MESH:D009369', (56, 61))
40015	33847622	The thymic adenocarcinoma harbored many mutations, including ARID1A c.421del(p.A141Pfs*91) (Fig.	('ARID1A', 'Gene', (61, 67))	('carcinoma', 'Phenotype', 'HP:0030731', (16, 25))	('ARID1A', 'Gene', '8289', (61, 67))	('thymic adenocarcinoma', 'Disease', 'MESH:D000230', (4, 25))	('thymic adenocarcinoma', 'Disease', (4, 25))	('p.A141Pfs*91', 'Mutation', 'p.A141PfsX91', (77, 89))	('c.421del', 'Mutation', 'c.421del', (68, 76))	('c.421del', 'Var', (68, 76))
40016	33847622	3A), CTCF c.517G>T(p.G173*) (Fig.	('CTCF', 'Gene', '10664', (5, 9))	('c.517G>T', 'Mutation', 'c.517G>T', (10, 18))	('p.G173*', 'Mutation', 'p.G173fsX', (19, 26))	('CTCF', 'Gene', (5, 9))	('c.517G>T', 'Var', (10, 18))
40017	33847622	3B), KMT2A c.2155A>C(p.S719R) (Fig.	('KMT2A', 'Gene', (5, 10))	('p.S719R', 'Mutation', 'p.S719R', (21, 28))	('KMT2A', 'Gene', '4297', (5, 10))	('c.2155A>C', 'Var', (11, 20))	('c.2155A>C', 'Mutation', 'c.2155A>C', (11, 20))
40018	33847622	3C), BAP1 c.673G>A(p.D225N), ERBIN c.2900C>G(p.S967C), LZTR1 c.2216C>T(p.S739L), POLE c.52G>C(p.E18Q), and SRC c.1334A>C(p.K445T) (Supplemental Figure 1).	('c.2216C>T', 'Var', (61, 70))	('c.673G>A', 'Mutation', 'rs1409798282', (10, 18))	('c.2900C>G', 'Var', (35, 44))	('p.K445T', 'Mutation', 'p.K445T', (121, 128))	('c.52G>C', 'Mutation', 'c.52G>C', (86, 93))	('ERBIN', 'Gene', (29, 34))	('BAP1', 'Gene', '8314', (5, 9))	('p.S967C', 'Mutation', 'p.S967C', (45, 52))	('ERBIN', 'Gene', '55914', (29, 34))	('p.S739L', 'Mutation', 'rs762991620', (71, 78))	('c.1334A>C', 'Mutation', 'c.1334A>C', (111, 120))	('LZTR1', 'Gene', (55, 60))	('c.2900C>G', 'Mutation', 'c.2900C>G', (35, 44))	('BAP1', 'Gene', (5, 9))	('SRC', 'Gene', '6714', (107, 110))	('p.E18Q', 'Mutation', 'p.E18Q', (94, 100))	('LZTR1', 'Gene', '8216', (55, 60))	('p.D225N', 'Mutation', 'rs1409798282', (19, 26))	('c.2216C>T', 'Mutation', 'rs762991620', (61, 70))	('c.673G>A', 'Var', (10, 18))	('SRC', 'Gene', (107, 110))
40019	33847622	The type A thymoma showed KMT2A c.5343del(p.V1782Yfs*38) and NRAS c.182A>G(p.Q61R) mutations (Fig.	('p.Q61R', 'Mutation', 'rs11554290', (75, 81))	('type A thymoma', 'Disease', (4, 18))	('KMT2A', 'Gene', (26, 31))	('type A thymoma', 'Disease', 'MESH:D013945', (4, 18))	('c.5343del', 'Mutation', 'c.5343del', (32, 41))	('p.V1782Yfs*38', 'Mutation', 'p.V1782YfsX38', (42, 55))	('c.182A>G', 'Mutation', 'rs11554290', (66, 74))	('KMT2A', 'Gene', '4297', (26, 31))	('NRAS', 'Gene', (61, 65))	('thymoma', 'Phenotype', 'HP:0100522', (11, 18))	('c.5343del', 'Var', (32, 41))	('NRAS', 'Gene', '4893', (61, 65))
40020	33847622	The MIA revealed a BRAF c.1405G>A(p.G469R) mutation (Fig.	('p.G469R', 'Mutation', 'rs121913357', (34, 41))	('BRAF', 'Gene', '673', (19, 23))	('c.1405G>A', 'Var', (24, 33))	('c.1405G>A', 'Mutation', 'rs121913357', (24, 33))	('BRAF', 'Gene', (19, 23))
40034	33847622	Although the thymic adenocarcinoma and type A thymoma both had the mutation of KMT2A, the mutation sites were different.	('mutation', 'Var', (67, 75))	('thymoma', 'Phenotype', 'HP:0100522', (46, 53))	('thymic adenocarcinoma', 'Disease', 'MESH:D000230', (13, 34))	('type A thymoma', 'Disease', (39, 53))	('KMT2A', 'Gene', (79, 84))	('thymic adenocarcinoma', 'Disease', (13, 34))	('KMT2A', 'Gene', '4297', (79, 84))	('type A thymoma', 'Disease', 'MESH:D013945', (39, 53))	('carcinoma', 'Phenotype', 'HP:0030731', (25, 34))
40036	33847622	Previous studies identified many genetic aberrations in thymic adenocarcinoma, including a homozygous deletion at the HLA locus and KRAS mutation.	('KRAS', 'Gene', (132, 136))	('HLA', 'Gene', (118, 121))	('KRAS', 'Gene', '3845', (132, 136))	('deletion', 'Var', (102, 110))	('carcinoma', 'Phenotype', 'HP:0030731', (68, 77))	('thymic adenocarcinoma', 'Disease', 'MESH:D000230', (56, 77))	('thymic adenocarcinoma', 'Disease', (56, 77))
40039	33847622	Here, we showed the mutation of KMT2A can occur in thymic adenocarcinoma and type A thymoma, suggesting that KMT2A mutation may not specific to type B2 and B3 thymomas, but a common genetic change in thymic tumorigenesis.	('thymomas', 'Disease', (159, 167))	('KMT2A', 'Gene', (32, 37))	('occur', 'Reg', (42, 47))	('KMT2A', 'Gene', (109, 114))	('mutation', 'Var', (20, 28))	('KMT2A', 'Gene', '4297', (32, 37))	('thymomas', 'Disease', 'MESH:D013945', (159, 167))	('tumor', 'Disease', 'MESH:D009369', (207, 212))	('thymoma', 'Phenotype', 'HP:0100522', (84, 91))	('KMT2A', 'Gene', '4297', (109, 114))	('tumor', 'Phenotype', 'HP:0002664', (207, 212))	('thymic adenocarcinoma', 'Disease', 'MESH:D000230', (51, 72))	('thymic adenocarcinoma', 'Disease', (51, 72))	('tumor', 'Disease', (207, 212))	('type A thymoma', 'Disease', (77, 91))	('carcinoma', 'Phenotype', 'HP:0030731', (63, 72))	('type A thymoma', 'Disease', 'MESH:D013945', (77, 91))	('thymoma', 'Phenotype', 'HP:0100522', (159, 166))
40040	33847622	ARID1A mutation was found in a B2 thymoma previously.	('ARID1A', 'Gene', '8289', (0, 6))	('thymoma', 'Disease', 'MESH:D013945', (34, 41))	('ARID1A', 'Gene', (0, 6))	('thymoma', 'Disease', (34, 41))	('mutation', 'Var', (7, 15))	('found', 'Reg', (20, 25))	('thymoma', 'Phenotype', 'HP:0100522', (34, 41))
40069	31608320	TMB, which reflects the number of non-synonymous single nucleotide variants (nsSNVs) in a tumor affects the odds of generating antigens that can trigger an anti-tumor immune response and thereby influence the ability of ICIs to generate clinical responses in patients.	('single nucleotide variants', 'Var', (49, 75))	('patients', 'Species', '9606', (259, 267))	('tumor', 'Phenotype', 'HP:0002664', (90, 95))	('tumor', 'Disease', (90, 95))	('clinical responses', 'CPA', (237, 255))	('tumor', 'Disease', 'MESH:D009369', (161, 166))	('influence', 'Reg', (195, 204))	('ICI', 'Chemical', 'MESH:C481040', (220, 223))	('tumor', 'Phenotype', 'HP:0002664', (161, 166))	('antigens', 'MPA', (127, 135))	('trigger', 'Reg', (145, 152))	('ICIs', 'CPA', (220, 224))	('tumor', 'Disease', (161, 166))	('tumor', 'Disease', 'MESH:D009369', (90, 95))
40098	31608320	High PD-L1 expression was associated with longer survival (median PFS 24 vs. 2.9 months; median OS not reached vs. 15.5 months).	('High', 'Var', (0, 4))	('PD-L1', 'Gene', (5, 10))	('expression', 'MPA', (11, 21))	('longer', 'PosReg', (42, 48))	('PD-L1', 'Gene', '29126', (5, 10))
40102	31608320	Tumors with high PD-L1 expression were more likely to respond to treatment.	('PD-L1', 'Gene', '29126', (17, 22))	('Tumor', 'Phenotype', 'HP:0002664', (0, 5))	('respond to treatment', 'MPA', (54, 74))	('high', 'Var', (12, 16))	('Tumors', 'Disease', (0, 6))	('Tumors', 'Disease', 'MESH:D009369', (0, 6))	('Tumors', 'Phenotype', 'HP:0002664', (0, 6))	('PD-L1', 'Gene', (17, 22))	('expression', 'MPA', (23, 33))
40109	31608320	High PD-L1 expression appears to be associated with a greater likelihood of response and a subset of patients achieve durable responses.	('PD-L1', 'Gene', (5, 10))	('patients', 'Species', '9606', (101, 109))	('PD-L1', 'Gene', '29126', (5, 10))	('High', 'Var', (0, 4))
40114	31608320	Evaluation of peripheral blood mononuclear cells showed a strong immunologic response to the epitope of mutated CDC73 protein.	('CDC73', 'Gene', '79577', (112, 117))	('protein', 'Protein', (118, 125))	('mutated', 'Var', (104, 111))	('CDC73', 'Gene', (112, 117))
40139	31608320	The risk of irAEs affecting most other organ systems, such as the lungs, gastrointestinal tract, skin and endocrine organs, does not appear to be substantially higher in TET patients when compared with patients with other cancers.	('TET', 'Var', (170, 173))	('irAEs', 'Disease', (12, 17))	('cancers', 'Phenotype', 'HP:0002664', (222, 229))	('patients', 'Species', '9606', (202, 210))	('cancers', 'Disease', (222, 229))	('patients', 'Species', '9606', (174, 182))	('cancers', 'Disease', 'MESH:D009369', (222, 229))	('gastrointestinal tract', 'Disease', 'MESH:D005770', (73, 95))	('cancer', 'Phenotype', 'HP:0002664', (222, 228))	('gastrointestinal tract', 'Disease', (73, 95))
40150	31608320	These observations merit further investigation and should prompt consideration of avoiding immunotherapy in thymoma patients with anti-AchR autoantibodies and severe B-cell lymphopenia even in the absence of a clinical history of paraneoplastic autoimmune disease.	('autoimmune disease', 'Phenotype', 'HP:0002960', (245, 263))	('B-cell lymphopenia', 'Disease', (166, 184))	('anti-AchR autoantibodies', 'Var', (130, 154))	('patients', 'Species', '9606', (116, 124))	('thymoma', 'Disease', 'MESH:D013945', (108, 115))	('paraneoplastic autoimmune disease', 'Disease', 'MESH:D001327', (230, 263))	('lymphopenia', 'Phenotype', 'HP:0001888', (173, 184))	('B-cell lymphopenia', 'Phenotype', 'HP:0010976', (166, 184))	('thymoma', 'Disease', (108, 115))	('autoantibodies', 'Var', (140, 154))	('paraneoplastic autoimmune disease', 'Disease', (230, 263))	('thymoma', 'Phenotype', 'HP:0100522', (108, 115))	('B-cell lymphopenia', 'Disease', 'MESH:D008231', (166, 184))
40406	32341644	MM-or-better status was defined as the goal treatment for TMG patients.	('men', 'Species', '9606', (49, 52))	('MM-or-better', 'Var', (0, 12))	('patients', 'Species', '9606', (62, 70))	('TMG', 'Disease', (58, 61))
40412	32341644	Myasthenia gravis (MG) is an autoimmune neuromuscular disorder predominantly mediated by antibodies against the acetylcholine receptor (AChR).	('AChR', 'Gene', (136, 140))	('antibodies', 'Var', (89, 99))	('Myasthenia gravis', 'Disease', (0, 17))	('Myasthenia gravis', 'Disease', 'MESH:D009157', (0, 17))	('autoimmune neuromuscular disorder', 'Disease', (29, 62))	('mediated by', 'Reg', (77, 88))	('Myasthenia', 'Phenotype', 'HP:0003473', (0, 10))	('autoimmune neuromuscular disorder', 'Phenotype', 'HP:0002960', (29, 62))	('autoimmune neuromuscular disorder', 'Disease', 'MESH:D001327', (29, 62))	('acetylcholine', 'Chemical', 'MESH:D000109', (112, 125))
40435	32341644	The myasthenia gravis foundation of America (MGFA) classified post-intervention status (PIS) as complete stable remission (CSR), pharmacologic remission (PR), minimal manifestation (MM), improved (I), unchanged (U), worse (W), exacerbation (E) and died of MG (D of MG).	('exacerbation', 'PosReg', (227, 239))	('myasthenia gravis', 'Disease', 'MESH:D009157', (4, 21))	('minimal', 'Var', (159, 166))	('improved', 'PosReg', (187, 195))	('myasthenia', 'Phenotype', 'HP:0003473', (4, 14))	('worse', 'Reg', (216, 221))	('myasthenia gravis', 'Disease', (4, 21))
40484	32341644	A Norwegian study showed that patients with high anti-titin Ab levels had a more severe course of MG, but a study on Japanese patients showed the opposite result when controlled for onset age.	('high', 'Var', (44, 48))	('patients', 'Species', '9606', (30, 38))	('titin', 'Gene', '7273', (54, 59))	('patients', 'Species', '9606', (126, 134))	('titin', 'Gene', (54, 59))
40486	32341644	The incidence of thymoma in our MG patients was B2 > B1 > AB > B3 > A.	('B2 > B1 > AB > B3 > A', 'Var', (48, 69))	('thymoma', 'Disease', 'MESH:D013945', (17, 24))	('thymoma', 'Disease', (17, 24))	('thymoma', 'Phenotype', 'HP:0100522', (17, 24))	('patients', 'Species', '9606', (35, 43))
40593	29416500	A literature review of published reports describing anti-Hu positivity in thymic neoplasms highlighted that a definite autonomic disease due to anti-Hu antibodies is extremely rare in patients with thymoma but without myasthenia gravis, with only one case published so far.	('myasthenia', 'Phenotype', 'HP:0003473', (218, 228))	('thymic neoplasms', 'Disease', 'MESH:D013953', (74, 90))	('autonomic disease', 'Disease', (119, 136))	('autonomic disease', 'Disease', 'MESH:D001342', (119, 136))	('thymic neoplasms', 'Disease', (74, 90))	('anti-Hu', 'Var', (144, 151))	('thymic neoplasm', 'Phenotype', 'HP:0100521', (74, 89))	('myasthenia gravis', 'Disease', 'MESH:D009157', (218, 235))	('thymic neoplasms', 'Phenotype', 'HP:0100521', (74, 90))	('neoplasms', 'Phenotype', 'HP:0002664', (81, 90))	('autonomic disease', 'Phenotype', 'HP:0012332', (119, 136))	('Hu positivity', 'Phenotype', 'HP:0030873', (57, 70))	('neoplasm', 'Phenotype', 'HP:0002664', (81, 89))	('patients', 'Species', '9606', (184, 192))	('thymoma', 'Phenotype', 'HP:0100522', (198, 205))	('myasthenia gravis', 'Disease', (218, 235))	('due', 'Reg', (137, 140))	('thymoma', 'Gene', '7063', (198, 205))	('thymoma', 'Gene', (198, 205))
40624	29416500	Histological examination of the mass confirmed a pT2N0 thymoma (modified Masaoka clinical staging 2b; Koga et al.,).	('pT2N0', 'Var', (49, 54))	('thymoma', 'Gene', (55, 62))	('thymoma', 'Gene', '7063', (55, 62))	('thymoma', 'Phenotype', 'HP:0100522', (55, 62))
40633	29416500	Indeed, ANNA-1 are known to produce definite PNS syndrome with chronic gastrointestinal pseudo-obstruction or, less frequently, acute pandysautonomia (Antoine and Camdessanche,).	('dysautonomia', 'Phenotype', 'HP:0012332', (137, 149))	('chronic gastrointestinal pseudo-obstruction', 'Disease', (63, 106))	('PNS syndrome', 'Disease', 'MESH:D010523', (45, 57))	('acute pandysautonomia', 'Disease', 'MESH:D059787', (128, 149))	('intestinal pseudo-obstruction', 'Phenotype', 'HP:0004389', (77, 106))	('acute pandysautonomia', 'Disease', (128, 149))	('chronic gastrointestinal pseudo-obstruction', 'Disease', 'MESH:D007418', (63, 106))	('ANNA-1', 'Var', (8, 14))	('PNS syndrome', 'Disease', (45, 57))
40642	29416500	Furthermore, retrospective screening of ANNA-1 positivity in 172 individuals with thymoma calculated an overall frequency of 3%, corresponding to 5 patients (Vernino et al.,), whose data are also reported in a more recent survey (Vernino and Lennon,).	('patients', 'Species', '9606', (148, 156))	('ANNA-1', 'Gene', (40, 46))	('thymoma', 'Phenotype', 'HP:0100522', (82, 89))	('thymoma', 'Gene', '7063', (82, 89))	('thymoma', 'Gene', (82, 89))	('positivity', 'Var', (47, 57))
40643	29416500	Another case of thymoma with anti-Hu antibodies and PNS was described in a young male patient with myasthenia gravis (Simonelli et al.,).	('anti-Hu', 'Var', (29, 36))	('myasthenia gravis', 'Disease', 'MESH:D009157', (99, 116))	('thymoma', 'Phenotype', 'HP:0100522', (16, 23))	('myasthenia', 'Phenotype', 'HP:0003473', (99, 109))	('thymoma', 'Gene', '7063', (16, 23))	('thymoma', 'Gene', (16, 23))	('patient', 'Species', '9606', (86, 93))	('myasthenia gravis', 'Disease', (99, 116))
40843	27347224	Each condition involves a mutation in the dystrophin gene which codes for a large protein that is part of the dystrophin-glycoprotein complex.	('mutation', 'Var', (26, 34))	('dystrophin', 'Gene', '1756', (110, 120))	('dystrophin', 'Gene', (42, 52))	('dystrophin', 'Gene', (110, 120))	('codes', 'Reg', (64, 69))	('dystrophin', 'Gene', '1756', (42, 52))
40846	27347224	DMD is an X-linked recessive disorder whereby mutations in the dystrophin gene disrupt the reading frame and result in absent dystrophin protein, which links cytoplasmic actin to the dystrophin-glycoprotein complex at the cell membrane.	('dystrophin', 'Gene', (183, 193))	('mutations', 'Var', (46, 55))	('DMD', 'Disease', 'MESH:D020388', (0, 3))	('disrupt', 'NegReg', (79, 86))	('dystrophin', 'Gene', '1756', (63, 73))	('dystrophin', 'Gene', (126, 136))	('DMD', 'Disease', (0, 3))	('absent dystrophin protein', 'Phenotype', 'HP:0030097', (119, 144))	('dystrophin', 'Gene', '1756', (183, 193))	('reading frame', 'MPA', (91, 104))	('X-linked recessive disorder', 'Disease', (10, 37))	('X-linked recessive disorder', 'Disease', 'MESH:D040181', (10, 37))	('dystrophin', 'Gene', (63, 73))	('absent', 'NegReg', (119, 125))	('dystrophin', 'Gene', '1756', (126, 136))
40869	27347224	Mutations in the 5' end of the dystrophin gene lead to absence of the M-isoform in the heart and skeletal muscle (though skeletal is protected due to intact exon skipping).	('dystrophin', 'Gene', '1756', (31, 41))	('Mutations', 'Var', (0, 9))	('absence', 'NegReg', (55, 62))	('dystrophin', 'Gene', (31, 41))	('M-isoform', 'MPA', (70, 79))
40876	27347224	In X-linked EDMD, mutations are seen in the emerin gene, which produces a protein component of the inner nuclear membrane.	('emerin', 'Gene', (44, 50))	('X-linked EDMD', 'Disease', 'MESH:C564052', (3, 16))	('emerin', 'Gene', '2010', (44, 50))	('X-linked EDMD', 'Disease', (3, 16))	('mutations', 'Var', (18, 27))
40881	27347224	Autosomal Dominant Emery-Dreifuss muscular dystrophy (EDMD2) is caused by a mutation in lamin A/C gene.	('Emery-Dreifuss muscular dystrophy', 'Disease', (19, 52))	('EDMD2', 'Disease', 'MESH:D020389', (54, 59))	('muscular dystrophy', 'Phenotype', 'HP:0003560', (34, 52))	('lamin A/C', 'Gene', (88, 97))	('caused by', 'Reg', (64, 73))	('lamin A/C', 'Gene', '4000', (88, 97))	('EDMD2', 'Disease', (54, 59))	('mutation', 'Var', (76, 84))	('Emery-Dreifuss muscular dystrophy', 'Disease', 'MESH:D020389', (19, 52))
40886	27347224	Cardiac abnormalities vary among the subtypes and LGMD1B has clinically significant cardiac findings.	('LGMD', 'Phenotype', 'HP:0006785', (50, 54))	('LGMD1B', 'Var', (50, 56))	('Cardiac abnormalities', 'Disease', 'MESH:D006331', (0, 21))	('cardiac', 'MPA', (84, 91))	('Cardiac abnormalities', 'Phenotype', 'HP:0001627', (0, 21))	('Cardiac abnormalities', 'Disease', (0, 21))
40892	27347224	These result in mutations in proteins of the sarcoglycan complex, part of the dystrophin-glycoprotein complex.	('dystrophin', 'Gene', (78, 88))	('mutations', 'Var', (16, 25))	('proteins', 'Protein', (29, 37))	('result in', 'Reg', (6, 15))	('dystrophin', 'Gene', '1756', (78, 88))
40903	27347224	DM1 results from an expansion of the trinucleotide CTG in the 3' untranslated region of the myotonic dystrophy protein kinase (DMPK) gene.	('trinucleotide CTG', 'Chemical', '-', (37, 54))	('DM1', 'Gene', (0, 3))	('results from', 'Reg', (4, 16))	('myotonic dystrophy protein kinase', 'Gene', (92, 125))	('DMPK', 'Gene', '1760', (127, 131))	('expansion', 'Var', (20, 29))	('DMPK', 'Gene', (127, 131))	('DM1', 'Gene', '1760', (0, 3))	('myotonic dystrophy protein kinase', 'Gene', '1760', (92, 125))
40911	27347224	Holter monitoring should be performed in patients with EKG abnormalities as a means for detecting asymptomatic arrhythmias or conduction block.	('conduction block', 'Disease', 'MESH:D054537', (126, 142))	('arrhythmias', 'Disease', (111, 122))	('arrhythmias', 'Phenotype', 'HP:0011675', (111, 122))	('EKG abnormalities', 'Phenotype', 'HP:0003115', (55, 72))	('patients', 'Species', '9606', (41, 49))	('arrhythmia', 'Phenotype', 'HP:0011675', (111, 121))	('conduction block', 'Disease', (126, 142))	('abnormalities', 'Var', (59, 72))	('arrhythmias', 'Disease', 'MESH:D001145', (111, 122))
40921	27347224	Studies have showed that only 5% of patients treated with deflazacort for >3 years had a significantly decreased EF, compared with 58% of untreated patients.	('patients', 'Species', '9606', (148, 156))	('patients', 'Species', '9606', (36, 44))	('decreased', 'NegReg', (103, 112))	('deflazacort', 'Var', (58, 69))	('deflazacort', 'Chemical', 'MESH:C021988', (58, 69))
40942	27347224	Based on these, P188 could become an important acute therapy in DMD during times of increased cardiac stress.	('DMD', 'Disease', (64, 67))	('P188', 'Var', (16, 20))	('DMD', 'Disease', 'MESH:D020388', (64, 67))
40945	27347224	Gene therapy offers the promise of a cure by replacing the mutated dystrophin gene in all muscle tissues.	('dystrophin', 'Gene', '1756', (67, 77))	('dystrophin', 'Gene', (67, 77))	('mutated', 'Var', (59, 66))
40947	27347224	The basis of exon-skipping therapy is to use splice-switching oligonucleotides to bypass the mutated exam with a stop codon and continue to translate a smaller, truncated dystrophin protein.	('dystrophin', 'Gene', (171, 181))	('mutated', 'Var', (93, 100))	('smaller', 'NegReg', (152, 159))	('oligonucleotides', 'Chemical', 'MESH:D009841', (62, 78))	('dystrophin', 'Gene', '1756', (171, 181))
40952	27347224	Ataluren is an investigational orally administered drug being developed for the treatment of genetic defects caused by nonsense (stop) mutations.	('nonsense', 'Var', (119, 127))	('genetic defects', 'Disease', 'MESH:D030342', (93, 108))	('genetic defects', 'Disease', (93, 108))
40962	27347224	In addition, Ach receptor antibodies react with portions of the autonomic nervous system leading to cardiac arrhythmias or other disturbances of hemodynamics.	('arrhythmias', 'Phenotype', 'HP:0011675', (108, 119))	('antibodies', 'Var', (26, 36))	('cardiac arrhythmias', 'Disease', 'MESH:D001145', (100, 119))	('cardiac arrhythmias', 'Disease', (100, 119))	('Ach receptor', 'Gene', (13, 25))	('leading to', 'Reg', (89, 99))	('cardiac arrhythmia', 'Phenotype', 'HP:0011675', (100, 118))	('arrhythmia', 'Phenotype', 'HP:0011675', (108, 118))	('react', 'Reg', (37, 42))	('cardiac arrhythmias', 'Phenotype', 'HP:0011675', (100, 119))	('disturbances of hemodynamics', 'MPA', (129, 157))
40973	27347224	Another series of 650 myasthenic patients reported that myocarditis was clinically suspected in about 12% of those with antibodies to Kv 1.4 but in none of those without.	('patients', 'Species', '9606', (33, 41))	('antibodies', 'Var', (120, 130))	('myasthenic', 'Disease', (22, 32))	('myocarditis', 'Disease', 'MESH:D009205', (56, 67))	('Kv 1.4', 'Gene', (134, 140))	('myasthenic', 'Disease', 'MESH:D020294', (22, 32))	('myocarditis', 'Phenotype', 'HP:0012819', (56, 67))	('myocarditis', 'Disease', (56, 67))
40983	27347224	Patients with these ganglionic Ach receptor antibodies can present with cardiac arrhythmia as part of a pan-dysautonomia with abnormalities of gastric motility, othostatic hypotension and sudomotor activity.	('present with', 'Reg', (59, 71))	('othostatic hypotension', 'Disease', (161, 183))	('hypotension', 'Phenotype', 'HP:0002615', (172, 183))	('cardiac arrhythmia', 'Disease', (72, 90))	('othostatic hypotension', 'Disease', 'MESH:D007022', (161, 183))	('dysautonomia with abnormalities of gastric motility', 'Disease', 'MESH:D054969', (108, 159))	('antibodies', 'Var', (44, 54))	('abnormalities of gastric motility', 'Phenotype', 'HP:0030895', (126, 159))	('dysautonomia', 'Phenotype', 'HP:0012332', (108, 120))	('Patients', 'Species', '9606', (0, 8))	('ganglionic', 'Protein', (20, 30))	('cardiac arrhythmia', 'Disease', 'MESH:D001145', (72, 90))	('-dysautonomia', 'Phenotype', 'HP:0012332', (107, 120))	('sudomotor activity', 'Phenotype', 'HP:0000970', (188, 206))	('cardiac arrhythmia', 'Phenotype', 'HP:0011675', (72, 90))	('othostatic hypotension', 'Phenotype', 'HP:0001278', (161, 183))	('arrhythmia', 'Phenotype', 'HP:0011675', (80, 90))
40989	27347224	Arrhythmia related to dysautonomia from antiganglionic Ach receptor antibodies will often improve with anticholinesterase or immunomodulatory treatment.	('dysautonomia', 'Phenotype', 'HP:0012332', (22, 34))	('Arrhythmia', 'Disease', (0, 10))	('cholinesterase', 'Gene', (107, 121))	('cholinesterase', 'Gene', '590', (107, 121))	('Arrhythmia', 'Phenotype', 'HP:0011675', (0, 10))	('antibodies', 'Var', (68, 78))	('improve', 'PosReg', (90, 97))	('dysautonomia', 'Disease', (22, 34))	('Arrhythmia', 'Disease', 'MESH:D001145', (0, 10))	('antiganglionic', 'Var', (40, 54))	('Ach receptor', 'Gene', (55, 67))	('dysautonomia', 'Disease', 'MESH:D054969', (22, 34))
41005	26365387	Important examples include autoimmune polyendocrine syndrome type I (APS-1) associated with antibodies against type I interferons and TH17-related cytokines, pulmonary alveolar proteinosis (PAP) caused by antibodies against GM-CSF, and acquired susceptibility to mycobacterial infection associated with antibodies to IFN-gamma.	('IFN-gamma', 'Gene', '3458', (317, 326))	('IFN-gamma', 'Gene', (317, 326))	('mycobacterial infection', 'Phenotype', 'HP:0011274', (263, 286))	('susceptibility to mycobacterial infection', 'Phenotype', 'HP:0011274', (245, 286))	('TH1', 'Gene', (134, 137))	('APS-1', 'Gene', '326', (69, 74))	('associated', 'Reg', (76, 86))	('antibodies', 'Var', (205, 215))	('mycobacterial infection', 'Disease', 'MESH:D009165', (263, 286))	('antibodies', 'Var', (92, 102))	('alveolar proteinosis', 'Phenotype', 'HP:0006517', (168, 188))	('TH1', 'Gene', '51497', (134, 137))	('autoimmune polyendocrine syndrome type I', 'Disease', (27, 67))	('autoimmune polyendocrine syndrome type I', 'Disease', 'MESH:C538275', (27, 67))	('pulmonary alveolar proteinosis', 'Disease', 'MESH:D011649', (158, 188))	('mycobacterial infection', 'Disease', (263, 286))	('GM-CSF', 'Gene', (224, 230))	('pulmonary alveolar proteinosis', 'Disease', (158, 188))	('APS-1', 'Gene', (69, 74))
41051	26365387	We observed that all 5 patients with APS-1 in the cohort (101B, 096B, 094T, 561T, and 098T) fell within this assignment.	('APS-1', 'Gene', (37, 42))	('561T', 'CellLine', 'CVCL:N758', (76, 80))	('patients', 'Species', '9606', (23, 31))	('561T', 'Var', (76, 80))	('101B', 'Var', (58, 62))	('094T', 'Var', (70, 74))	('APS-1', 'Gene', '326', (37, 42))
41052	26365387	The other 4 patients with high type I interferon reactivity all had chronic candidiasis, a key clinical feature of APS-1, which in patients with APS-1 has been proposed to be caused by neutralizing ACAAs to the TH17 cytokines IL-17A, IL-17F, and IL-22.	('patients', 'Species', '9606', (131, 139))	('IL-22', 'Gene', '50616', (246, 251))	('patients', 'Species', '9606', (12, 20))	('IL-22', 'Gene', (246, 251))	('TH1', 'Gene', (211, 214))	('chronic candidiasis', 'Disease', 'MESH:D002177', (68, 87))	('chronic candidiasis', 'Disease', (68, 87))	('IL-17F', 'Gene', '112744', (234, 240))	('ACAAs', 'Chemical', '-', (198, 203))	('IL-17A', 'Gene', '3605', (226, 232))	('neutralizing', 'Var', (185, 197))	('TH1', 'Gene', '51497', (211, 214))	('APS-1', 'Gene', '326', (145, 150))	('IL-17A', 'Gene', (226, 232))	('APS-1', 'Gene', '326', (115, 120))	('APS-1', 'Gene', (145, 150))	('APS-1', 'Gene', (115, 120))	('IL-17F', 'Gene', (234, 240))
41053	26365387	Two of these 4 patients (092B and 512B) had coincident thymoma, for which antibodies against type I interferons and TH1 and TH17 cytokines have been described.	('patients', 'Species', '9606', (15, 23))	('TH1', 'Gene', '51497', (116, 119))	('092B', 'Var', (25, 29))	('TH1', 'Gene', '51497', (124, 127))	('TH1', 'Gene', (116, 119))	('thymoma', 'Disease', 'MESH:D013945', (55, 62))	('thymoma', 'Disease', (55, 62))	('TH1', 'Gene', (124, 127))	('thymoma', 'Phenotype', 'HP:0100522', (55, 62))
41055	26365387	Given the specificity of type I interferon ACAAs for APS-1 and the clinical similarity of these patients with those with APS-1, we speculate that these patients might harbor an undescribed mutation in AIRE or a mutation in a gene that might phenocopy APS-1.	('AIRE', 'Gene', '326', (201, 205))	('APS-1', 'Gene', '326', (53, 58))	('APS-1', 'Gene', (53, 58))	('APS-1', 'Gene', '326', (121, 126))	('harbor', 'Reg', (167, 173))	('APS-1', 'Gene', '326', (251, 256))	('mutation', 'Var', (189, 197))	('APS-1', 'Gene', (251, 256))	('patients', 'Species', '9606', (152, 160))	('patients', 'Species', '9606', (96, 104))	('AIRE', 'Gene', (201, 205))	('APS-1', 'Gene', (121, 126))	('ACAAs', 'Chemical', '-', (43, 48))
41077	26365387	In the presence of sera containing IFN-alphaACAAs but not the presence of sera from healthy control subjects, this synergistic increase in TNF-alpha levels was blocked (Fig 5, B).	('ACAAs', 'Chemical', '-', (44, 49))	('IFN-alphaACAAs', 'Var', (35, 49))	('TNF-alpha', 'Gene', (139, 148))	('TNF-alpha', 'Gene', '7124', (139, 148))
41096	26365387	Indeed, on both our protein microarrays and bead-based assay, serum samples 092B and 562B were reactive against IL-12 in addition to IL-23.	('IL-23', 'Gene', '51561', (133, 138))	('562B', 'Var', (85, 89))	('IL-12', 'Protein', (112, 117))	('092B', 'Var', (76, 80))	('IL-23', 'Gene', (133, 138))
41098	26365387	Using both protein microarrays and our bead-based assay, we successfully detected ACAAs in samples 562B and 092B against the shared IL-12p40 subunit (Fig 2).	('p40', 'Gene', (137, 140))	('detected', 'Reg', (73, 81))	('562B', 'Var', (99, 103))	('p40', 'Gene', '3578', (137, 140))	('092B', 'Var', (108, 112))	('ACAAs', 'Disease', (82, 87))	('ACAAs', 'Chemical', '-', (82, 87))
41102	26365387	After unblinding, we found that sample 514B was derived from a healthy control subject; however, this sample also demonstrated autoantibodies against the autoantigens PM/Scl-60, PM/Scl-100, and GRP-78, suggesting possible undiagnosed or not yet clinically apparent autoimmunity.	('PM/Scl-100', 'Gene', (178, 188))	('autoimmunity', 'Disease', 'MESH:D001327', (265, 277))	('GRP-78', 'Gene', (194, 200))	('PM/Scl-60', 'Var', (167, 176))	('GRP-78', 'Gene', '3309', (194, 200))	('autoimmunity', 'Phenotype', 'HP:0002960', (265, 277))	('autoimmunity', 'Disease', (265, 277))	('PM/Scl-100', 'Gene', '5394', (178, 188))
41104	26365387	The other MIP-1alpha-reactive sample (098B) was obtained from a patient with PAP and contained autoantibodies against GM-CSF and the autoantigens PM/Scl-60 and PM/Scl-100.	('patient', 'Species', '9606', (64, 71))	('PM/Scl-100', 'Gene', '5394', (160, 170))	('GM-CSF', 'Gene', (118, 124))	('PM/Scl-100', 'Gene', (160, 170))	('PM/Scl-60', 'Var', (146, 155))	('MIP-1alpha', 'Gene', (10, 20))	('MIP-1alpha', 'Gene', '6348', (10, 20))
41147	25663933	Association between polymorphisms in the promoter region of T cell immunoglobulin and mucin domain-3 and myasthenia gravis-associated thymoma Thymoma is a type of benign or low-grade malignant tumor, occurring on the thymic epithelium.	('myasthenia', 'Phenotype', 'HP:0003473', (105, 115))	('myasthenia', 'Disease', (105, 115))	('thymoma', 'Disease', (134, 141))	('Thymoma', 'Disease', 'MESH:D013945', (142, 149))	('malignant tumor', 'Disease', 'MESH:D018198', (183, 198))	('T cell immunoglobulin and mucin domain-3', 'Gene', '84868', (60, 100))	('polymorphisms', 'Var', (20, 33))	('malignant tumor', 'Disease', (183, 198))	('thymoma', 'Phenotype', 'HP:0100522', (134, 141))	('tumor', 'Phenotype', 'HP:0002664', (193, 198))	('thymoma', 'Disease', 'MESH:D013945', (134, 141))	('Thymoma', 'Phenotype', 'HP:0100522', (142, 149))	('myasthenia', 'Disease', 'MESH:D020294', (105, 115))	('Association', 'Interaction', (0, 11))	('Thymoma', 'Disease', (142, 149))
41150	25663933	In order to understand the etiology and pathogenesis of MG-associated thymoma in the Han population of North China, the present study investigated the association between a polymorphism on the -574 locus in the promoter of Tim-3 and the risk of MG-associated thymoma in the Han Chinese population.	('Tim-3', 'Gene', (223, 228))	('thymoma', 'Disease', (259, 266))	('association', 'Interaction', (151, 162))	('thymoma', 'Disease', 'MESH:D013945', (70, 77))	('thymoma', 'Phenotype', 'HP:0100522', (259, 266))	('thymoma', 'Disease', (70, 77))	('polymorphism on the -574', 'Var', (173, 197))	('thymoma', 'Phenotype', 'HP:0100522', (70, 77))	('thymoma', 'Disease', 'MESH:D013945', (259, 266))
41154	25663933	In conclusion, the present study indicated that an association may exist between the polymorphism of the -574 locus in the Tim-3 promoter and MG-associated thymoma.	('thymoma', 'Phenotype', 'HP:0100522', (156, 163))	('thymoma', 'Disease', (156, 163))	('thymoma', 'Disease', 'MESH:D013945', (156, 163))	('Tim-3', 'Gene', (123, 128))	('polymorphism', 'Var', (85, 97))
41174	25663933	Tim-3 polymorphism has been demonstrated to alter the interaction between Tim-3 and its ligand, thereby affecting the process that results in certain immune diseases and being actively involved in the pathogenesis of tumors.	('tumor', 'Phenotype', 'HP:0002664', (217, 222))	('polymorphism', 'Var', (6, 18))	('results in', 'Reg', (131, 141))	('tumors', 'Disease', (217, 223))	('alter', 'Reg', (44, 49))	('tumors', 'Disease', 'MESH:D009369', (217, 223))	('involved', 'Reg', (185, 193))	('tumors', 'Phenotype', 'HP:0002664', (217, 223))	('immune diseases', 'Disease', (150, 165))	('Tim-3', 'Gene', (74, 79))	('interaction', 'Interaction', (54, 65))	('affecting', 'Reg', (104, 113))	('Tim-3', 'Gene', (0, 5))
41205	25663933	Therefore, the present study hypothesized that Tim-3 may be a protective factor of autoimmune diseases (it may protect patients from suffering from autoimmune diseases or decrease the possibility of suffering from autoimmune diseases), while Tim-3 polymorphisms may be closely associated with autoimmune diseases.	('autoimmune diseases', 'Disease', 'MESH:D001327', (214, 233))	('polymorphisms', 'Var', (248, 261))	('Tim-3', 'Gene', (47, 52))	('autoimmune diseases', 'Disease', (214, 233))	('associated', 'Reg', (277, 287))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (214, 233))	('decrease', 'NegReg', (171, 179))	('autoimmune diseases', 'Disease', 'MESH:D001327', (293, 312))	('autoimmune disease', 'Phenotype', 'HP:0002960', (214, 232))	('autoimmune diseases', 'Disease', (293, 312))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (293, 312))	('autoimmune disease', 'Phenotype', 'HP:0002960', (293, 311))	('autoimmune diseases', 'Disease', 'MESH:D001327', (148, 167))	('Tim-3', 'Gene', (242, 247))	('autoimmune diseases', 'Disease', (148, 167))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (148, 167))	('autoimmune disease', 'Phenotype', 'HP:0002960', (83, 101))	('autoimmune disease', 'Phenotype', 'HP:0002960', (148, 166))	('autoimmune diseases', 'Disease', 'MESH:D001327', (83, 102))	('patients', 'Species', '9606', (119, 127))	('autoimmune diseases', 'Disease', (83, 102))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (83, 102))
41210	25663933	A recent study also demonstrated that, following tumor-associated expression of the receptor Tim-3 by dendritic cells, Tim-3 inhibited the antitumor efficacy of DNA vaccines and chemotherapy.	('tumor', 'Disease', 'MESH:D009369', (49, 54))	('tumor', 'Disease', (143, 148))	('Tim-3', 'Gene', (93, 98))	('tumor', 'Phenotype', 'HP:0002664', (49, 54))	('tumor', 'Disease', (49, 54))	('chemotherapy', 'CPA', (178, 190))	('Tim-3', 'Var', (119, 124))	('inhibited', 'NegReg', (125, 134))	('tumor', 'Disease', 'MESH:D009369', (143, 148))	('tumor', 'Phenotype', 'HP:0002664', (143, 148))
41211	25663933	Therefore, Tim-3 may be a risk factor of tumorigenesis, while Tim-3 polymorphisms may be associated with cancer.	('tumor', 'Phenotype', 'HP:0002664', (41, 46))	('associated', 'Reg', (89, 99))	('Tim-3', 'Gene', (11, 16))	('Tim-3', 'Gene', (62, 67))	('tumor', 'Disease', (41, 46))	('cancer', 'Disease', (105, 111))	('cancer', 'Disease', 'MESH:D009369', (105, 111))	('polymorphisms', 'Var', (68, 81))	('risk factor', 'Reg', (26, 37))	('cancer', 'Phenotype', 'HP:0002664', (105, 111))	('tumor', 'Disease', 'MESH:D009369', (41, 46))
41213	25663933	These findings indicated an association between the -574 locus polymorphism and MG-associated thymoma in the Han population of North China.	('thymoma', 'Disease', 'MESH:D013945', (94, 101))	('thymoma', 'Phenotype', 'HP:0100522', (94, 101))	('thymoma', 'Disease', (94, 101))	('the -574 locus polymorphism', 'Var', (48, 75))
41237	19587811	Active immunization of mice and rabbits with the extracellular domain of MuSK protein led to EAMG and associated changes in neuromuscular junctions.	('rabbits', 'Species', '9986', (32, 39))	('EAMG', 'Disease', (93, 97))	('changes', 'Reg', (113, 120))	('extracellular domain', 'Var', (49, 69))	('neuromuscular junctions', 'MPA', (124, 147))	('mice', 'Species', '10090', (23, 27))
41238	19587811	Passive immunization of mice with IgG from MuSK MG patients induced EAMG and further demonstrated marked reduction of postsynaptic AChR staining by fluorescent-alpha-bungarotoxin.	('induced', 'Reg', (60, 67))	('mice', 'Species', '10090', (24, 28))	('EAMG', 'Disease', (68, 72))	('reduction', 'NegReg', (105, 114))	('patients', 'Species', '9606', (51, 59))	('MuSK MG', 'Var', (43, 50))	('postsynaptic AChR staining', 'MPA', (118, 144))
41249	19587811	In the present study, thymoma was not seen in any cases of MuSK-MG in contrast to three patients with double seronegative (DSN)-MG and 13 cases of AChR-MG.	('MuSK-MG', 'Var', (59, 66))	('thymoma', 'Disease', (22, 29))	('DSN', 'Chemical', '-', (123, 126))	('patients', 'Species', '9606', (88, 96))	('thymoma', 'Phenotype', 'HP:0100522', (22, 29))	('MuSK-MG', 'CellLine', 'CVCL:1698', (59, 66))	('thymoma', 'Disease', 'MESH:D013945', (22, 29))
41253	19587811	Both studies emphasized the lack of a germinal center or lymphocytic infiltrates in MuSK-MG, in contrast to the changes typically seen in the majority of AChR-MG patients, and about half the DSN-MG patients had histological changes similar to those in AChR-MG patients.	('patients', 'Species', '9606', (162, 170))	('MuSK-MG', 'CellLine', 'CVCL:1698', (84, 91))	('patients', 'Species', '9606', (198, 206))	('patients', 'Species', '9606', (260, 268))	('lymphocytic infiltrates', 'CPA', (57, 80))	('MuSK-MG', 'Var', (84, 91))	('DSN', 'Chemical', '-', (191, 194))
41258	19587811	found significant muscle atrophy and fatty replacement in facial and bulbar muscles in MuSK-MG which were not found in AChR-MG patients.	('MuSK-MG', 'Var', (87, 94))	('muscle atrophy', 'Phenotype', 'HP:0003202', (18, 32))	('muscle atrophy', 'Disease', (18, 32))	('patients', 'Species', '9606', (127, 135))	('MuSK-MG', 'CellLine', 'CVCL:1698', (87, 94))	('muscle atrophy', 'Disease', 'MESH:D009133', (18, 32))	('fatty replacement', 'CPA', (37, 54))
41261	19587811	Similarly, biceps muscle biopsies from eight patients from Japan with MuSK-MG failed to show a significant reduction in AChR or alterations to postsynaptic morphology.	('postsynaptic morphology', 'MPA', (143, 166))	('MuSK-MG', 'Var', (70, 77))	('alterations', 'Reg', (128, 139))	('patients', 'Species', '9606', (45, 53))	('MuSK-MG', 'CellLine', 'CVCL:1698', (70, 77))	('AChR', 'Protein', (120, 124))	('reduction', 'NegReg', (107, 116))
41262	19587811	These findings suggest that the pathogenic mechanism of neuromuscular transmission defect in MuSK-MG is different from that in AChR-MG and is not through complement-mediated AChR defect.	('MuSK-MG', 'Var', (93, 100))	('defect', 'NegReg', (83, 89))	('neuromuscular transmission', 'MPA', (56, 82))	('MuSK-MG', 'CellLine', 'CVCL:1698', (93, 100))
41273	19587811	Myasthenic weakness in MuSK-MG tends to be more severe and refractory to treatment than that observed in patients with other forms of generalized MG. An Italian series observed more MuSK-MG patients than DSN-MG patients who were classified as severe by the MG Foundation of America (MGFA) clinical classifications.	('DSN', 'Chemical', '-', (204, 207))	('MGFA', 'Chemical', '-', (283, 287))	('patients', 'Species', '9606', (105, 113))	('patients', 'Species', '9606', (211, 219))	('MuSK-MG', 'CellLine', 'CVCL:1698', (23, 30))	('patients', 'Species', '9606', (190, 198))	('Myasthenic weakness', 'Disease', (0, 19))	('Myasthenic weakness', 'Phenotype', 'HP:0003473', (0, 19))	('MuSK-MG', 'CellLine', 'CVCL:1698', (182, 189))	('MuSK-MG', 'Var', (182, 189))	('Myasthenic weakness', 'Disease', 'MESH:D018908', (0, 19))
41280	19587811	There is some evidence that myasthenic crisis is also more common (35-80%) in patients with MuSK-MG (Table 1 and 3).	('myasthenic', 'Disease', 'MESH:D020294', (28, 38))	('myasthenic crisis', 'Phenotype', 'HP:0003473', (28, 45))	('MuSK-MG', 'CellLine', 'CVCL:1698', (92, 99))	('patients', 'Species', '9606', (78, 86))	('MuSK-MG', 'Var', (92, 99))	('myasthenic', 'Disease', (28, 38))
41285	19587811	Three main patterns of generalized disease have been observed in MuSK-MG, two of which may be helpful in distinguishing these patients from AChR-MG patients.	('patients', 'Species', '9606', (148, 156))	('MuSK-MG', 'Var', (65, 72))	('generalized disease', 'Disease', (23, 42))	('patients', 'Species', '9606', (126, 134))	('MuSK-MG', 'CellLine', 'CVCL:1698', (65, 72))
41311	19587811	reported that positive edrophonium testing is significantly less common in the MuSK-MG group than in either the AChR-MG or DSN-MG group.	('DSN', 'Chemical', '-', (123, 126))	('less', 'NegReg', (60, 64))	('edrophonium testing', 'MPA', (23, 42))	('MuSK-MG', 'Var', (79, 86))	('edrophonium', 'Chemical', 'MESH:D004491', (23, 34))	('MuSK-MG', 'CellLine', 'CVCL:1698', (79, 86))
41312	19587811	The most striking finding with edrophonium testing in MuSK-MG is that it may worsen patients' myasthenic symptoms (hypersensitivity) or precipitate nicotinic (intolerance) and muscarinic side effects, such as increased weakness, widespread fasciculation, severe stomach cramping, or diarrhea.	('increased weakness', 'Disease', 'MESH:D018908', (209, 227))	('worsen', 'PosReg', (77, 83))	('MuSK-MG', 'Var', (54, 61))	('diarrhea', 'Disease', (283, 291))	('increased weakness', 'Disease', (209, 227))	('patients', 'Species', '9606', (84, 92))	('MuSK-MG', 'CellLine', 'CVCL:1698', (54, 61))	('testing', 'Var', (43, 50))	('diarrhea', 'Disease', 'MESH:D003967', (283, 291))	('edrophonium', 'Gene', (31, 42))	('edrophonium', 'Chemical', 'MESH:D004491', (31, 42))	('myasthenic symptoms', 'Phenotype', 'HP:0003473', (94, 113))	('myasthenic symptoms', 'Disease', 'MESH:D051271', (94, 113))	('precipitate', 'Reg', (136, 147))	('hypersensitivity)', 'Disease', 'MESH:D004342', (115, 132))	('severe stomach cramping', 'Disease', (255, 278))	('fasciculation', 'Disease', (240, 253))	('fasciculation', 'Phenotype', 'HP:0002380', (240, 253))	('fasciculation', 'Disease', 'MESH:D005207', (240, 253))	('myasthenic symptoms', 'Disease', (94, 113))	('diarrhea', 'Phenotype', 'HP:0002014', (283, 291))
41316	19587811	The low percentage of positive edrophonium testing may reflect the poor responsiveness to anticholinesterase treatment which has been reported in MuSK-MG. More than 70% of MuSK-MG patients were nonresponsive to anticholinesterase therapy, a significantly higher proportion than for other MG populations.	('MuSK-MG', 'CellLine', 'CVCL:1698', (146, 153))	('nonresponsive to anticholinesterase therapy', 'MPA', (194, 237))	('MuSK-MG', 'CellLine', 'CVCL:1698', (172, 179))	('edrophonium', 'Chemical', 'MESH:D004491', (31, 42))	('patients', 'Species', '9606', (180, 188))	('MuSK-MG', 'Var', (172, 179))
41322	19587811	For instance, RNS of limb muscles was abnormal in 57% of patients with MuSK-MG versus 78% of DSN-MG patients.	('RNS of limb muscles', 'CPA', (14, 33))	('MuSK-MG', 'CellLine', 'CVCL:1698', (71, 78))	('patients', 'Species', '9606', (57, 65))	('abnormal', 'Reg', (38, 46))	('MuSK-MG', 'Var', (71, 78))	('patients', 'Species', '9606', (100, 108))	('DSN', 'Chemical', '-', (93, 96))
41334	19587811	In several studies, the percentage of MuSK-MG patients with abnormal jitter on EDC recording was significantly lower than for either AChR-MG or DSN-MG patients.	('patients', 'Species', '9606', (46, 54))	('MuSK-MG', 'Var', (38, 45))	('jitter', 'MPA', (69, 75))	('patients', 'Species', '9606', (151, 159))	('DSN', 'Chemical', '-', (144, 147))	('lower', 'NegReg', (111, 116))	('EDC', 'MPA', (79, 82))	('MuSK-MG', 'CellLine', 'CVCL:1698', (38, 45))
41388	19587811	However, the maintenance dose of corticosteroids in one series was significantly higher in MuSK-MG patients (30 mg/48 hours) than in AChR-MG (18 mg for 2 days) or DSN-MG patients (10 mg for 2 days).	('patients', 'Species', '9606', (170, 178))	('MuSK-MG', 'CellLine', 'CVCL:1698', (91, 98))	('higher', 'PosReg', (81, 87))	('patients', 'Species', '9606', (99, 107))	('MuSK-MG', 'Var', (91, 98))	('DSN', 'Chemical', '-', (163, 166))	('steroids', 'Chemical', 'MESH:D013256', (40, 48))
41390	19587811	In patients with MuSK-MG, the percentage of remission ranged from 10 to 35% (mean, 22%) and was significantly lower than that reported in AChR-MG (24-58%, mean, 38%)(p=0.005).	('lower', 'NegReg', (110, 115))	('patients', 'Species', '9606', (3, 11))	('MuSK-MG', 'CellLine', 'CVCL:1698', (17, 24))	('MuSK-MG', 'Var', (17, 24))
41568	10992731	His HLA typing was A11, A31, B51, B13, Cw4, Cw6, DR09 and DR12.	('A31', 'Var', (24, 27))	('Cw6', 'Var', (44, 47))	('DR09', 'Var', (49, 53))	('B13', 'Gene', '4698', (34, 37))	('B51', 'Var', (29, 32))	('A11', 'Var', (19, 22))	('B13', 'Gene', (34, 37))
41657	23956858	Our study revealed the probability of the modified PR in the programmed high-dose steroid treatment group was significantly higher than that in the no preoperative steroid treatment group, and this finding was independent of the previously mentioned prognostic factors in the multivariate analysis.	('programmed', 'Var', (61, 71))	('steroid', 'Chemical', 'MESH:D013256', (82, 89))	('steroid', 'Chemical', 'MESH:D013256', (164, 171))	('modified', 'Var', (42, 50))	('higher', 'PosReg', (124, 130))
41666	23956858	We suggest that one of the reasons for the clinical effects of preoperative high-dose steroid treatment is the blockage of pathways by which immunoactivation causes cellular damage and undesirable clinical outcomes at a stretch.	('steroid', 'Chemical', 'MESH:D013256', (86, 93))	('cellular damage', 'CPA', (165, 180))	('immunoactivation', 'Var', (141, 157))
41692	21072172	In contrast, knockdown of MS4a4B accelerated T cell proliferation.	('MS4a4B', 'Gene', '60361', (26, 32))	('accelerated', 'PosReg', (33, 44))	('MS4a4B', 'Gene', (26, 32))	('T cell proliferation', 'CPA', (45, 65))	('accelerated T cell', 'Phenotype', 'HP:0100828', (33, 51))	('knockdown', 'Var', (13, 22))
41703	21072172	Moreover, CD20 has been used as the target of anti-CD20 treatment for B cell lymphoma and autoimmune diseases, which to date has been considered as the most successful antibody-based therapeutics.	('anti-CD20', 'Gene', (46, 55))	('autoimmune diseases', 'Disease', 'MESH:D001327', (90, 109))	('anti-CD20', 'Var', (46, 55))	('lymphoma', 'Phenotype', 'HP:0002665', (77, 85))	('B cell lymphoma', 'Disease', 'MESH:D016393', (70, 85))	('autoimmune diseases', 'Disease', (90, 109))	('B cell lymphoma', 'Disease', (70, 85))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (90, 109))	('B cell lymphoma', 'Phenotype', 'HP:0012191', (70, 85))
41707	21072172	In contrast, overexpression of HTm4 in U937 cells inhibits the G1-S transition of cell cycle through interaction with cyclin-dependent kinase-associated (CDK-associated) phosphatase-CDK2 (KAP-CDK2) complexes.	('cyclin', 'Gene', '18538', (118, 124))	('cyclin', 'Gene', (118, 124))	('G1-S transition of cell cycle', 'CPA', (63, 92))	('HTm4', 'Var', (31, 35))	('interaction', 'Interaction', (101, 112))	('inhibits', 'NegReg', (50, 58))	('U937', 'CellLine', 'CVCL:0007', (39, 43))
41712	21072172	We found that MS4a4B negatively regulates T cell proliferation by interfering with cell cycle progression from G0/G1 phase into S-G2/M phases through inhibition of the Cdk2-Rb pathway, and that silence of MS4a4B in thymoma is, at least partially, responsible for the uncontrollable propagation of tumor T cells.	('MS4a4B', 'Gene', (14, 20))	('negatively', 'NegReg', (21, 31))	('inhibition', 'NegReg', (150, 160))	('T cell proliferation', 'CPA', (42, 62))	('tumor', 'Disease', (297, 302))	('thymoma', 'Disease', 'MESH:D013945', (215, 222))	('cell cycle progression', 'CPA', (83, 105))	('tumor', 'Disease', 'MESH:D009369', (297, 302))	('silence', 'Var', (194, 201))	('Cdk2', 'Gene', '12566', (168, 172))	('interfering', 'NegReg', (66, 77))	('thymoma', 'Disease', (215, 222))	('thymoma', 'Phenotype', 'HP:0100522', (215, 222))	('tumor', 'Phenotype', 'HP:0002664', (297, 302))	('MS4a4B', 'Gene', '60361', (205, 211))	('regulates', 'Reg', (32, 41))	('Cdk2', 'Gene', (168, 172))	('MS4a4B', 'Gene', (205, 211))	('MS4a4B', 'Gene', '60361', (14, 20))
41719	21072172	Lack of MS4a4B protein in thymoma cells led us to postulate that MS4a4B may be required for appropriate functioning of mature T cells and the absence of this protein may be, at least in part, responsible for the uncontrollable growth of thymoma.	('thymoma', 'Disease', (26, 33))	('absence', 'Var', (142, 149))	('MS4a4B', 'Gene', (65, 71))	('MS4a4B', 'Gene', (8, 14))	('thymoma', 'Phenotype', 'HP:0100522', (26, 33))	('thymoma', 'Disease', 'MESH:D013945', (237, 244))	('thymoma', 'Disease', (237, 244))	('thymoma', 'Phenotype', 'HP:0100522', (237, 244))	('MS4a4B', 'Gene', '60361', (65, 71))	('MS4a4B', 'Gene', '60361', (8, 14))	('thymoma', 'Disease', 'MESH:D013945', (26, 33))
41745	21072172	Consistent with the findings from over-expression studies, knockdown of MS4a4B accelerated proliferation of T32 cells (Fig.	('T32', 'CellLine', 'CVCL:E445', (108, 111))	('MS4a4B', 'Gene', '60361', (72, 78))	('proliferation', 'CPA', (91, 104))	('knockdown', 'Var', (59, 68))	('accelerated', 'PosReg', (79, 90))	('MS4a4B', 'Gene', (72, 78))
41751	21072172	The results showed that knockdown of MS4a4B accelerated IL-2-induced proliferation of T32 cells (Fig.	('T32', 'CellLine', 'CVCL:E445', (86, 89))	('MS4a4B', 'Gene', (37, 43))	('accelerated', 'PosReg', (44, 55))	('IL-2', 'Gene', '16183', (56, 60))	('IL-2', 'Gene', (56, 60))	('knockdown', 'Var', (24, 33))	('MS4a4B', 'Gene', '60361', (37, 43))
41760	21072172	HTm4 was found to prevent cell cycle progression from G0/G1 phase into S-G2/M phase in hematopoeotic cells.	('hematopoeotic', 'Disease', 'None', (87, 100))	('hematopoeotic', 'Disease', (87, 100))	('HTm4', 'Var', (0, 4))	('prevent', 'NegReg', (18, 25))	('cell cycle progression', 'CPA', (26, 48))
41771	21072172	Consistent with the observation from over-expression experiments, knockdown of MS4a4B protein promoted cell cycle progression from G0/G1 phase into S-G2/M phase (Fig.	('MS4a4B', 'Gene', (79, 85))	('cell cycle progression', 'CPA', (103, 125))	('protein', 'Protein', (86, 93))	('MS4a4B', 'Gene', '60361', (79, 85))	('knockdown', 'Var', (66, 75))	('promoted', 'PosReg', (94, 102))
41782	21072172	Notably, MS4a4B expression enhanced the production of the calcium/calmodulin-dependent protein kinase (CaM kinase) IIalpha, also known as Camk2a, whose kinase activity is dependent upon its activation by calmodulin (CaM).	('MS4a4B', 'Gene', (9, 15))	('production', 'MPA', (40, 50))	('expression', 'Var', (16, 26))	('enhanced', 'PosReg', (27, 35))	('Camk2a', 'Gene', '12322', (138, 144))	('CaM', 'Gene', '12314', (216, 219))	('CaM', 'Gene', (216, 219))	('MS4a4B', 'Gene', '60361', (9, 15))	('calcium', 'Chemical', 'MESH:D002118', (58, 65))	('calmodulin', 'Gene', '12314', (66, 76))	('calmodulin', 'Gene', '12314', (204, 214))	('Camk2a', 'Gene', (138, 144))	('calmodulin', 'Gene', (66, 76))	('CaM', 'Gene', (103, 106))	('CaM', 'Gene', '12314', (103, 106))	('calmodulin', 'Gene', (204, 214))
41788	21072172	We further examined whether inhibition of Cdk2 activity subsequently resulted in higher levels of hypophosphorylated retinoblastoma protein (Rb), a crucial suppressor protein for gene transcription, and cell cycle progression.	('hypophosphorylated retinoblastoma', 'Disease', 'MESH:D012175', (98, 131))	('Cdk2', 'Gene', (42, 46))	('hypophosphorylated retinoblastoma', 'Disease', (98, 131))	('higher', 'PosReg', (81, 87))	('inhibition', 'Var', (28, 38))	('retinoblastoma', 'Phenotype', 'HP:0009919', (117, 131))	('activity', 'MPA', (47, 55))	('cell cycle progression', 'CPA', (203, 225))	('Cdk2', 'Gene', '12566', (42, 46))
41800	21072172	HTm4 has been found to bind to cyclin-dependent kinase-associated (CDK-associated) phosphatase-CDK2 (KAP-CDK2) complexes by its C-terminal region and to stimulate the phosphatase activity of KAP, which subsequently causes cell cycle arrest at the G0/G1 phase.	('stimulate', 'PosReg', (153, 162))	('causes', 'Reg', (215, 221))	('phosphatase activity', 'MPA', (167, 187))	('cell cycle arrest at the G0/G1 phase', 'CPA', (222, 258))	('cell cycle arrest', 'Phenotype', 'HP:0011018', (222, 239))	('bind', 'Interaction', (23, 27))	('cyclin', 'Gene', '18538', (31, 37))	('HTm4', 'Var', (0, 4))	('cyclin', 'Gene', (31, 37))	('KAP', 'Enzyme', (191, 194))
41806	21072172	In contrast, the inhibitory role of MS4a4B on cell cycle and cell proliferation is similar to that of HTm4 in hematopoietic cells, in which overexpression of HTm4 causes cell cycle arrest at the G0/G1 phase.	('MS4a4B', 'Gene', '60361', (36, 42))	('cell cycle arrest', 'Phenotype', 'HP:0011018', (170, 187))	('MS4a4B', 'Gene', (36, 42))	('overexpression', 'PosReg', (140, 154))	('HTm4', 'Var', (158, 162))	('cell cycle arrest at the G0/G1 phase', 'CPA', (170, 206))
41875	30792779	An analysis of lymphocyte subsets was as follows: cells with CD45 surface antigen 83% (N: 90-100), CD3 49% (N: 29-59), CD8 31% (N: 19-48), CD19 2% (N: 11-16) and NK 30% (N: 4-33.5).	('CD19', 'Gene', (139, 143))	('CD45', 'Gene', '5788', (61, 65))	('CD8', 'Gene', (119, 122))	('CD19', 'Gene', '930', (139, 143))	('CD8', 'Gene', '925', (119, 122))	('CD3', 'Var', (99, 102))	('CD45', 'Gene', (61, 65))
41955	17764580	Genomic DNA from the paraffin embedded 39 thymoma tissues (A 6, AB 11, B1 7, B2 7, B3 8) labeled with Cy-3 was co-hybridized with the reference placenta gDNA labeled with Cy-5.	('paraffin', 'Chemical', 'MESH:D010232', (21, 29))	('Cy-5', 'Chemical', 'MESH:C085321', (171, 175))	('Cy-3', 'Var', (102, 106))	('thymoma tissues', 'Disease', 'MESH:D013945', (42, 57))	('thymoma tissues', 'Disease', (42, 57))	('thymoma', 'Phenotype', 'HP:0100522', (42, 49))	('A 6, AB 11, B1 7, B2 7, B3 8', 'Gene', '28873;4712;56246', (59, 87))	('Cy-3', 'Chemical', '-', (102, 106))
41956	17764580	Using the CAMVS software, we investigated the deletions on chromosomes 1, 2, 3, 4, 5, 6, 8, 12, 13 and 18 throughout the thymoma.	('thymoma', 'Gene', '7063', (121, 128))	('thymoma', 'Phenotype', 'HP:0100522', (121, 128))	('deletions', 'Var', (46, 55))	('thymoma', 'Gene', (121, 128))
41973	17764580	Chromosome 9q gain was identified only in type B1 thymoma, while chromosome 1q gain was present only in type B3 thymoma.	('thymoma', 'Gene', (112, 119))	('gain', 'PosReg', (14, 18))	('thymoma', 'Gene', '7063', (50, 57))	('thymoma', 'Phenotype', 'HP:0100522', (112, 119))	('thymoma', 'Phenotype', 'HP:0100522', (50, 57))	('Chromosome', 'Var', (0, 10))	('thymoma', 'Gene', '7063', (112, 119))	('thymoma', 'Gene', (50, 57))
41983	17764580	In type B3, frequent deletions were observed in chromosome 6 open reading frame 10 (C6orf10, 6p21.3), butyrophilin subfamily 3, member A2 (BTN3A2, 6p22.1), and thiopurine s-methyltransferase (TPMT, 6p22.3), with a frequency of 75% (6/8), 87.5% (7/8), 75% (6/8), respectively.	('thiopurine s-methyltransferase', 'Gene', (160, 190))	('TPMT', 'Gene', '7172', (192, 196))	('C6orf10', 'Gene', '10665', (84, 91))	('thiopurine s-methyltransferase', 'Gene', '7172', (160, 190))	('C6orf10', 'Gene', (84, 91))	('deletions', 'Var', (21, 30))	('chromosome 6 open reading frame 10', 'Gene', '10665', (48, 82))	('chromosome 6 open reading frame 10', 'Gene', (48, 82))	('BTN3A2', 'Gene', (139, 145))	('BTN3A2', 'Gene', '11118', (139, 145))	('TPMT', 'Gene', (192, 196))	('butyrophilin subfamily 3, member A2', 'Gene', '11118', (102, 137))
41993	17764580	demonstrated for the first time recurrent chromosomal imbalances in type B3 thymoma with CGH and FISH methods.	('imbalances', 'Phenotype', 'HP:0002172', (54, 64))	('chromosomal imbalances', 'Var', (42, 64))	('thymoma', 'Gene', '7063', (76, 83))	('thymoma', 'Phenotype', 'HP:0100522', (76, 83))	('CGH', 'Gene', (89, 92))	('thymoma', 'Gene', (76, 83))	('CGH', 'Gene', '3342', (89, 92))
41994	17764580	They identified 16 cases of type B3 that showed chromosomal gains (1q, Xq, and 8p12) and losses (6 and 13q), while 12 cases of type A did not reveal any chromosomal abnormalities, with the exception of one case with a partial loss of 6p.	('chromosomal abnormalities', 'Disease', 'MESH:D002869', (153, 178))	('gains', 'PosReg', (60, 65))	('losses', 'NegReg', (89, 95))	('8p12', 'Var', (79, 83))	('chromosomal abnormalities', 'Disease', (153, 178))
41995	17764580	Subsequently, the same group, using CGH and microsatellite analyses, inferred two pathways of thymoma tumorigenesis by demonstrating that type A (3/8 cases) presented with consistent LOH in the region 6p23.3-25.5 only, while type B3 revealed various aberrations such as APC on chromosome 5q21 (3/14 cases), RB on 13q14 (5/14 cases), and p53 gene on 17p13.1 (4/14 cases) loci, as well as LOH in the region 6p23.3-25.5 (5/14 cases).	('thymoma', 'Gene', '7063', (94, 101))	('CGH', 'Gene', (36, 39))	('APC', 'Disease', (270, 273))	('p53', 'Gene', (337, 340))	('LOH', 'Var', (387, 390))	('p53', 'Gene', '7157', (337, 340))	('type', 'Var', (138, 142))	('thymoma', 'Gene', (94, 101))	('CGH', 'Gene', '3342', (36, 39))	('tumor', 'Disease', 'MESH:D009369', (102, 107))	('thymoma', 'Phenotype', 'HP:0100522', (94, 101))	('RB', 'Disease', 'MESH:D012175', (307, 309))	('tumor', 'Phenotype', 'HP:0002664', (102, 107))	('tumor', 'Disease', (102, 107))	('APC', 'Disease', 'MESH:D011125', (270, 273))
42030	17764580	NEDD9 (T61428, neural precursor cell expressed developmentally down regulating 9) and CTNNB (AA442092, cadherin-associated protein beta 1), which are known to be the adhesion-related genes, were deleted in type B3, suggesting increased cell motility for metastasis.	('deleted', 'Var', (195, 202))	('CTNNB', 'Gene', '1499', (86, 91))	('CTNNB', 'Gene', (86, 91))	('down regulating', 'NegReg', (63, 78))	('NEDD9', 'Gene', (0, 5))	('cell motility for metastasis', 'CPA', (236, 264))	('NEDD9', 'Gene', '4739', (0, 5))	('increased', 'PosReg', (226, 235))
42051	17764580	Briefly, four mug of placenta and thymoma tissue DNA were fluorescently labeled with Cy3 or Cy5-dUTP (Dupont NEN Life Sciences, Boston, MA, USA), respectively, using BioPrime DNA Labeling System (Invitrogen, Carlsbad, CA, USA).	('thymoma', 'Gene', '7063', (34, 41))	('thymoma', 'Gene', (34, 41))	('Cy3', 'Chemical', '-', (85, 88))	('Cy3', 'Var', (85, 88))	('thymoma', 'Phenotype', 'HP:0100522', (34, 41))	('Cy5-dUTP', 'Var', (92, 100))	('Cy5-dUTP', 'Chemical', 'MESH:C088942', (92, 100))
42085	33413522	The five-year survival rate among the patients who underwent incomplete resection (71%) was significantly lower than that among those who underwent complete resection (100%), indicating a poorer prognosis in the latter group (p < 0.001) (Fig.	('survival', 'CPA', (14, 22))	('lower', 'NegReg', (106, 111))	('incomplete', 'Var', (61, 71))	('patients', 'Species', '9606', (38, 46))
42132	20651610	Mutations in the kit gene have been related to response to imatinib in gastrointestinal stromal tumor and one case report of thymic carcinoma.	('thymic carcinoma', 'Disease', (125, 141))	('thymic carcinoma', 'Disease', 'MESH:D013953', (125, 141))	('related', 'Reg', (36, 43))	('gastrointestinal stromal tumor', 'Phenotype', 'HP:0100723', (71, 101))	('tumor', 'Phenotype', 'HP:0002664', (96, 101))	('carcinoma', 'Phenotype', 'HP:0030731', (132, 141))	('response to imatinib', 'MPA', (47, 67))	('gastrointestinal stromal tumor', 'Disease', (71, 101))	('Mutations', 'Var', (0, 9))	('gastrointestinal stromal tumor', 'Disease', 'MESH:D046152', (71, 101))	('imatinib', 'Chemical', 'MESH:D000068877', (59, 67))	('kit', 'Gene', (17, 20))
42148	20651610	c-kit mutations have also been described in several of these tumors.	('tumors', 'Disease', (61, 67))	('tumors', 'Disease', 'MESH:D009369', (61, 67))	('described', 'Reg', (31, 40))	('tumor', 'Phenotype', 'HP:0002664', (61, 66))	('tumors', 'Phenotype', 'HP:0002664', (61, 67))	('mutations', 'Var', (6, 15))	('c-kit', 'Gene', (0, 5))
42149	20651610	Responsiveness of GISTs to treatment with the kinase inhibitor imatinib depends largely on the exonic location of the c-kit mutation.	('mutation', 'Var', (124, 132))	('c-kit', 'Gene', (118, 123))	('imatinib', 'Chemical', 'MESH:D000068877', (63, 71))	('GISTs', 'Phenotype', 'HP:0100723', (18, 23))
42150	20651610	Higher objective response rates to imatinib have been described in patients with mutations of exon 11 compared with patients with wild-type receptor or with mutations of exon 9.	('objective response rates', 'MPA', (7, 31))	('patients', 'Species', '9606', (67, 75))	('patients', 'Species', '9606', (116, 124))	('mutations of exon', 'Var', (81, 98))	('Higher', 'PosReg', (0, 6))	('imatinib', 'Chemical', 'MESH:D000068877', (35, 43))
42151	20651610	Mutations have been also described in patients with negative c-kit expression, evaluated by immunohistochemistry (IHC).	('c-kit', 'Protein', (61, 66))	('Mutations', 'Var', (0, 9))	('patients', 'Species', '9606', (38, 46))
42155	20651610	reported two c-kit mutations, of seven thymic carcinomas analyzed.	('c-kit', 'Gene', (13, 18))	('thymic carcinomas', 'Disease', 'MESH:D013953', (39, 56))	('carcinoma', 'Phenotype', 'HP:0030731', (46, 55))	('thymic carcinomas', 'Disease', (39, 56))	('mutations', 'Var', (19, 28))	('carcinomas', 'Phenotype', 'HP:0030731', (46, 56))
42157	20651610	reported a case of poorly differentiated epidermoid carcinoma with V560del kit mutation who responded to imatinib.	('epidermoid carcinoma', 'Disease', 'MESH:D002294', (41, 61))	('carcinoma', 'Phenotype', 'HP:0030731', (52, 61))	('V560del', 'DELETION', 'None', (67, 74))	('imatinib', 'Chemical', 'MESH:D000068877', (105, 113))	('epidermoid carcinoma', 'Disease', (41, 61))	('V560del', 'Var', (67, 74))	('responded to imatinib', 'MPA', (92, 113))
42158	20651610	In 2009, another case of thymic carcinoma with D820E kit mutation was reported that responded to sorafenib, a multitargeted tyrosine kinase inhibitor, with weak c-kit inhibitory activity.	('D820E', 'Var', (47, 52))	('sorafenib', 'Chemical', 'MESH:D000077157', (97, 106))	('carcinoma', 'Phenotype', 'HP:0030731', (32, 41))	('D820E', 'Mutation', 'rs1057519711', (47, 52))	('responded', 'MPA', (84, 93))	('thymic carcinoma', 'Disease', (25, 41))	('thymic carcinoma', 'Disease', 'MESH:D013953', (25, 41))	('kit', 'Gene', (53, 56))
42206	20651610	We observed the previously reported single-nucleotide polymorphism corresponding to M541L in one type A thymoma and in one thymic carcinoma.	('A thymoma', 'Disease', 'MESH:D013945', (102, 111))	('M541L', 'Mutation', 'rs3822214', (84, 89))	('thymic carcinoma', 'Disease', (123, 139))	('thymic carcinoma', 'Disease', 'MESH:D013953', (123, 139))	('A thymoma', 'Disease', (102, 111))	('M541L', 'Var', (84, 89))	('carcinoma', 'Phenotype', 'HP:0030731', (130, 139))	('thymoma', 'Phenotype', 'HP:0100522', (104, 111))
42230	20651610	Only a few c-kit mutations have been reported in the literature in TEM and exclusively in thymic carcinomas.	('thymic carcinomas', 'Disease', 'MESH:D013953', (90, 107))	('carcinoma', 'Phenotype', 'HP:0030731', (97, 106))	('c-kit', 'Gene', (11, 16))	('carcinomas', 'Phenotype', 'HP:0030731', (97, 107))	('TEM', 'Disease', (67, 70))	('reported', 'Reg', (37, 45))	('mutations', 'Var', (17, 26))	('thymic carcinomas', 'Disease', (90, 107))
42231	20651610	No kit mutations were reported in thymomas among 88 cases sequenced.	('thymomas', 'Disease', (34, 42))	('thymoma', 'Phenotype', 'HP:0100522', (34, 41))	('thymomas', 'Disease', 'MESH:D013945', (34, 42))	('mutations', 'Var', (7, 16))
42234	20651610	reported a V560del mutation of kit in a case of metastatic poorly differentiated epidermoid carcinoma.	('V560del', 'Var', (11, 18))	('kit', 'Gene', (31, 34))	('epidermoid carcinoma', 'Disease', (81, 101))	('carcinoma', 'Phenotype', 'HP:0030731', (92, 101))	('V560del', 'Mutation', 'p.560delV', (11, 18))	('epidermoid carcinoma', 'Disease', 'MESH:D002294', (81, 101))
42236	20651610	reported a case of an undifferentiated thymic carcinoma carrying mutation D820E encoded by kit exon 17.	('D820E', 'Var', (74, 79))	('D820E', 'Mutation', 'rs1057519711', (74, 79))	('carcinoma', 'Phenotype', 'HP:0030731', (46, 55))	('undifferentiated thymic carcinoma', 'Disease', 'MESH:D002277', (22, 55))	('undifferentiated thymic carcinoma', 'Disease', (22, 55))
42238	20651610	The mutation D820E of c-kit activation loop has been previously reported as an acquired resistant mutation to imatinib and sunitinib treatment in GISTs.	('sunitinib', 'Chemical', 'MESH:D000077210', (123, 132))	('imatinib', 'Chemical', 'MESH:D000068877', (110, 118))	('GISTs', 'Phenotype', 'HP:0100723', (146, 151))	('D820E', 'Var', (13, 18))	('D820E', 'Mutation', 'rs1057519711', (13, 18))	('c-kit activation loop', 'Gene', (22, 43))
42241	20651610	H697Y showed higher sensitivity to sunitinib than imatinib in vitro when transfected in Ba/F3 cells.	('H697Y', 'Var', (0, 5))	('Ba/F3', 'CellLine', 'CVCL:0161', (88, 93))	('sensitivity', 'MPA', (20, 31))	('sunitinib', 'Chemical', 'MESH:D000077210', (35, 44))	('imatinib', 'Chemical', 'MESH:D000068877', (50, 58))	('higher', 'PosReg', (13, 19))	('H697Y', 'Mutation', 'rs763308199', (0, 5))
42242	20651610	These results underline the importance to extend the analysis to regions of kit in thymic carcinomas beyond the most frequent sites of mutations in GISTs: exon 9, 11, 13, and 17.	('carcinoma', 'Phenotype', 'HP:0030731', (90, 99))	('carcinomas', 'Phenotype', 'HP:0030731', (90, 100))	('GISTs', 'Phenotype', 'HP:0100723', (148, 153))	('thymic carcinomas', 'Disease', 'MESH:D013953', (83, 100))	('thymic carcinomas', 'Disease', (83, 100))	('exon 9', 'Var', (155, 161))
42245	20651610	in 2008 identified the L576P kit mutation in exon 17 of a thymic carcinoma.	('carcinoma', 'Phenotype', 'HP:0030731', (65, 74))	('L576P kit', 'Var', (23, 32))	('L576P', 'Mutation', 'rs121913513', (23, 28))	('thymic carcinoma', 'Disease', (58, 74))	('thymic carcinoma', 'Disease', 'MESH:D013953', (58, 74))
42247	20651610	In GISTs, kit mutations have been described both in c-kit positive tumors (the majority) and in c-kit negative tumors.	('mutations', 'Var', (14, 23))	('tumor', 'Phenotype', 'HP:0002664', (111, 116))	('GISTs', 'Phenotype', 'HP:0100723', (3, 8))	('tumors', 'Disease', (111, 117))	('tumors', 'Disease', 'MESH:D009369', (111, 117))	('tumors', 'Phenotype', 'HP:0002664', (111, 117))	('tumor', 'Phenotype', 'HP:0002664', (67, 72))	('tumors', 'Phenotype', 'HP:0002664', (67, 73))	('tumors', 'Disease', (67, 73))	('tumors', 'Disease', 'MESH:D009369', (67, 73))
42248	20651610	Durable responses to imatinib were also observed in patients with exon 11 mutation and a very low expression of c-kit.	('exon 11 mutation', 'Var', (66, 82))	('c-kit', 'Protein', (112, 117))	('patients', 'Species', '9606', (52, 60))	('imatinib', 'Chemical', 'MESH:D000068877', (21, 29))
42255	20651610	Because of the rarity of thymic carcinomas and that responses have only been described in case reports, and the frequency of reported mutations is probably less than 10% in thymic carcinomas, this represents only approximately five cases potentially diagnosed in the United States every year.	('thymic carcinomas', 'Disease', (173, 190))	('thymic carcinomas', 'Disease', 'MESH:D013953', (173, 190))	('carcinoma', 'Phenotype', 'HP:0030731', (180, 189))	('carcinomas', 'Phenotype', 'HP:0030731', (180, 190))	('carcinoma', 'Phenotype', 'HP:0030731', (32, 41))	('carcinomas', 'Phenotype', 'HP:0030731', (32, 42))	('thymic carcinomas', 'Disease', (25, 42))	('mutations', 'Var', (134, 143))	('thymic carcinomas', 'Disease', 'MESH:D013953', (25, 42))
42256	20651610	This would make a phase II study in thymic carcinomas with c-kit mutations very difficult to accrue.	('c-kit', 'Gene', (59, 64))	('thymic carcinomas', 'Disease', 'MESH:D013953', (36, 53))	('carcinoma', 'Phenotype', 'HP:0030731', (43, 52))	('thymic carcinomas', 'Disease', (36, 53))	('carcinomas', 'Phenotype', 'HP:0030731', (43, 53))	('mutations', 'Var', (65, 74))
42326	32194741	However, it was membranous throughout the neoplastic tissue in type B3 thymomas, and in the invasive front at the periphery of type B2 thymomas (Fig.	('type B3', 'Var', (63, 70))	('thymomas', 'Disease', 'MESH:D013945', (71, 79))	('thymoma', 'Phenotype', 'HP:0100522', (135, 142))	('thymoma', 'Phenotype', 'HP:0100522', (71, 78))	('thymomas', 'Disease', (135, 143))	('type B2 thymomas', 'Disease', 'MESH:D013945', (127, 143))	('type B2 thymomas', 'Disease', (127, 143))	('thymomas', 'Disease', 'MESH:D013945', (135, 143))	('neoplastic tissue', 'Phenotype', 'HP:0002664', (42, 59))	('thymomas', 'Disease', (71, 79))
42349	32194741	Inactivation of APC as well as Wnt signaling activation blocks the degradation of beta-catenin, and thus increases its concentration in cytoplasm allowing translocation of beta-catenin to nucleus.	('concentration in cytoplasm', 'MPA', (119, 145))	('APC', 'Gene', '324', (16, 19))	('degradation', 'MPA', (67, 78))	('blocks', 'NegReg', (56, 62))	('beta-catenin', 'Protein', (82, 94))	('APC', 'Gene', (16, 19))	('translocation', 'MPA', (155, 168))	('increases', 'PosReg', (105, 114))	('Inactivation', 'Var', (0, 12))
42386	31779680	Thymoma complicated with myasthenia gravis and Good syndrome - a therapeutic conundrum: a case report Thymomas are known to be associated with myasthenia gravis and Good syndrome.	('myasthenia gravis', 'Disease', (25, 42))	('myasthenia gravis', 'Disease', 'MESH:D009157', (143, 160))	('associated', 'Reg', (127, 137))	('Thymoma', 'Phenotype', 'HP:0100522', (102, 109))	('Thymoma', 'Phenotype', 'HP:0100522', (0, 7))	('myasthenia gravis', 'Disease', 'MESH:D009157', (25, 42))	('myasthenia', 'Phenotype', 'HP:0003473', (143, 153))	('myasthenia', 'Phenotype', 'HP:0003473', (25, 35))	('Thymomas', 'Var', (102, 110))	('myasthenia gravis', 'Disease', (143, 160))	('Good syndrome', 'Disease', (165, 178))
42593	28744421	Despite two cycles of doxorubicin, cyclophosphamide, and cisplatin, the patient's scans showed progressive disease and she also had worsening symptoms; therefore, we felt surgical intervention was necessary, and waiting for concurrent radiation therapy would have resulted in an unacceptable surgical treatment delay.	('cyclophosphamide', 'Chemical', 'MESH:D003520', (35, 51))	('doxorubicin', 'Chemical', 'MESH:D004317', (22, 33))	('cyclophosphamide', 'Var', (35, 51))	('cisplatin', 'Var', (57, 66))	('patient', 'Species', '9606', (72, 79))	('cisplatin', 'Chemical', 'MESH:D002945', (57, 66))
42596	28744421	Depolarizing neuromuscular blockade anesthetic agents cause unpredictable respiratory failure and post extubation in myasthenia gravis patients, as the available amount of AChR is not consistent because of the presence of the anti-AChR antibodies .	('myasthenia gravis', 'Disease', (117, 134))	('patients', 'Species', '9606', (135, 143))	('respiratory failure', 'Phenotype', 'HP:0002878', (74, 93))	('presence', 'Reg', (210, 218))	('myasthenia gravis', 'Disease', 'MESH:D009157', (117, 134))	('myasthenia', 'Phenotype', 'HP:0003473', (117, 127))	('respiratory failure', 'Disease', 'MESH:D012131', (74, 93))	('respiratory failure', 'Disease', (74, 93))	('anti-AChR', 'Var', (226, 235))
42627	33108502	In negative selection, antigen presentation induces apoptosis of thymocytes expressing TCRs with high affinity for autoantigens.	('antigen presentation', 'Var', (23, 43))	('TCR', 'Gene', (87, 90))	('apoptosis', 'CPA', (52, 61))	('TCR', 'Gene', '6962', (87, 90))
42644	33108502	Congenital loss-of-function AIRE mutations lead to the severe dysimmune manifestations observed in autoimmune polyendocrine syndrome type 1 (APS-1): hypoparathyroidism, adrenal insufficiency and chronic mucocutaneous candidiasis.	('candidiasis', 'Disease', 'MESH:D002177', (217, 228))	('adrenal insufficiency', 'Phenotype', 'HP:0000846', (169, 190))	('adrenal insufficiency', 'Disease', 'MESH:D000309', (169, 190))	('autoimmune polyendocrine syndrome type 1', 'Gene', '326', (99, 139))	('hypoparathyroidism', 'Phenotype', 'HP:0000829', (149, 167))	('adrenal insufficiency', 'Disease', (169, 190))	('mutations', 'Var', (33, 42))	('AIRE', 'Gene', (28, 32))	('loss-of-function', 'NegReg', (11, 27))	('candidiasis', 'Disease', (217, 228))	('chronic mucocutaneous candidiasis', 'Phenotype', 'HP:0002728', (195, 228))	('autoimmune polyendocrine syndrome type 1', 'Gene', (99, 139))	('hypoparathyroidism', 'Disease', (149, 167))	('AIRE', 'Gene', '326', (28, 32))	('APS-1', 'Gene', '326', (141, 146))	('hypoparathyroidism', 'Disease', 'MESH:D007011', (149, 167))	('APS-1', 'Gene', (141, 146))
42647	33108502	Despite the aberrant T cell selection observed in APS-1, it is rare for autoimmune manifestations to affect the CNS beyond the pituitary gland.	('APS-1', 'Gene', '326', (50, 55))	('aberrant', 'Var', (12, 20))	('APS-1', 'Gene', (50, 55))	('aberrant T cell', 'Phenotype', 'HP:0002843', (12, 27))	('T cell selection', 'CPA', (21, 37))	('autoimmune manifestations', 'Phenotype', 'HP:0002960', (72, 97))
42654	33108502	Evidence that T cells can result in CNS immune-mediated damage is provided by either CNS-reactive T cells in patient CNS tissue and/or cerebrospinal fluid (CSF) samples or association between HLA haplotypes and susceptibility to CNS autoimmune disease.	('HLA', 'Gene', '3119', (192, 195))	('patient', 'Species', '9606', (109, 116))	('CNS autoimmune disease', 'Disease', (229, 251))	('HLA', 'Gene', (192, 195))	('CNS autoimmune disease', 'Disease', 'MESH:D001327', (229, 251))	('association', 'Reg', (172, 183))	('haplotypes', 'Var', (196, 206))	('autoimmune disease', 'Phenotype', 'HP:0002960', (233, 251))
42658	33108502	In Rasmussen encephalitis, there is demonstrable infiltration of CNS parenchyma by IFNgamma-producing CD8+, CD4+ and gammadelta-T cells, although as of yet without an identifiable autoantigenic target.	('CD8', 'Gene', (102, 105))	('gammadelta-T cells', 'Var', (117, 135))	('CD8', 'Gene', '925', (102, 105))	('encephalitis', 'Phenotype', 'HP:0002383', (13, 25))	('CD4+', 'Var', (108, 112))	('IFNgamma', 'Gene', '3458', (83, 91))	('IFNgamma', 'Gene', (83, 91))	('encephalitis', 'Disease', 'MESH:D004660', (13, 25))	('encephalitis', 'Disease', (13, 25))
42664	33108502	The correlation between levels of circulating anti-PIT 1 antibody and aberrant PIT-1 expression in thymomas supports the role of dysfunctional thymic selection in anti-PIT-1 antibody syndrome.	('expression', 'MPA', (85, 95))	('thymomas', 'Disease', (99, 107))	('PIT 1', 'Gene', (51, 56))	('thymomas', 'Disease', 'MESH:D013945', (99, 107))	('PIT-1 antibody syndrome', 'Disease', (168, 191))	('PIT-1', 'Gene', (168, 173))	('PIT-1', 'Gene', (79, 84))	('aberrant', 'Var', (70, 78))	('PIT 1', 'Gene', '5449', (51, 56))	('thymoma', 'Phenotype', 'HP:0100522', (99, 106))	('PIT-1', 'Gene', '5449', (168, 173))	('PIT-1', 'Gene', '5449', (79, 84))	('PIT-1 antibody syndrome', 'Disease', 'MESH:D000069281', (168, 191))
42665	33108502	Association of HLA haplotypes with increased risk of CNS autoimmune disease also implicates T cell effects as key drivers of CNS inflammation.	('CNS inflammation', 'Disease', 'MESH:D007249', (125, 141))	('CNS autoimmune disease', 'Disease', (53, 75))	('HLA', 'Gene', (15, 18))	('haplotypes', 'Var', (19, 29))	('autoimmune disease', 'Phenotype', 'HP:0002960', (57, 75))	('CNS autoimmune disease', 'Disease', 'MESH:D001327', (53, 75))	('CNS inflammation', 'Disease', (125, 141))	('HLA', 'Gene', '3119', (15, 18))
42685	33108502	Systemic loss of Treg cell function due to mutations in the Treg master regulator, FOXP3, leads to immune dysregulation, polyendocrinopathy, enteropathy, and X-linked (IPEX) syndrome, characterised by severe multi-organ autoimmunity.	('polyendocrinopathy', 'Disease', (121, 139))	('X-linked (IPEX) syndrome', 'Disease', 'MESH:C580192', (158, 182))	('Treg', 'Chemical', '-', (60, 64))	('FOXP3', 'Gene', (83, 88))	('enteropathy', 'Phenotype', 'HP:0002242', (141, 152))	('enteropathy', 'Disease', (141, 152))	('loss', 'NegReg', (9, 13))	('Treg', 'Chemical', '-', (17, 21))	('enteropathy', 'Disease', 'MESH:C538273', (141, 152))	('leads to', 'Reg', (90, 98))	('autoimmunity', 'Phenotype', 'HP:0002960', (220, 232))	('mutations', 'Var', (43, 52))	('immune dysregulation', 'Disease', (99, 119))	('FOXP3', 'Gene', '50943', (83, 88))	('polyendocrinopathy', 'Disease', 'MESH:D016884', (121, 139))	('immune dysregulation', 'Phenotype', 'HP:0002958', (99, 119))
42690	33108502	Conditional Foxn1 ablation in mice, which accelerates thymic involution, reduces Aire expression and disrupts negative selection, also induces autoimmune infiltration of pro-inflammatory cells in the CNS.	('mice', 'Species', '10090', (30, 34))	('Aire', 'Protein', (81, 85))	('reduces', 'NegReg', (73, 80))	('negative selection', 'MPA', (110, 128))	('Foxn1', 'Gene', (12, 17))	('accelerates', 'PosReg', (42, 53))	('thymic involution', 'CPA', (54, 71))	('disrupts', 'NegReg', (101, 109))	('autoimmune infiltration', 'Phenotype', 'HP:0002960', (143, 166))	('ablation', 'Var', (18, 26))	('induces', 'Reg', (135, 142))
42691	33108502	TEC-specific knockout of Map3k14 in mice leads to drastic decrease in thymic development and IL-17 secretion of dendritic epidermal gammadelta T cells, as a result of downstream loss of expression of Rorc and Il23r, genes required for IL-17 synthesis in gammadelta T cells.	('Map3k14', 'Gene', '53859', (25, 32))	('Il23r', 'Gene', (209, 214))	('loss', 'NegReg', (178, 182))	('Rorc', 'Gene', (200, 204))	('knockout', 'Var', (13, 21))	('Il23r', 'Gene', '209590', (209, 214))	('decrease', 'NegReg', (58, 66))	('Map3k14', 'Gene', (25, 32))	('IL-17 secretion', 'MPA', (93, 108))	('mice', 'Species', '10090', (36, 40))	('Rorc', 'Gene', '19885', (200, 204))	('thymic development', 'CPA', (70, 88))
42693	33108502	Finally, Irf8 is part of a transcriptional program that facilitates Aire expression in TECs; thus, Irf8 dysfunction may alter representation of AIRE-regulated CNS autoantigens in the thymus.	('Aire', 'Protein', (68, 72))	('Irf8', 'Gene', '3394', (9, 13))	('AIRE', 'Gene', (144, 148))	('alter', 'Reg', (120, 125))	('dysfunction', 'Var', (104, 115))	('AIRE', 'Gene', '326', (144, 148))	('facilitates', 'PosReg', (56, 67))	('Irf8', 'Gene', '3394', (99, 103))	('Irf8', 'Gene', (9, 13))	('representation of', 'MPA', (126, 143))	('TECs', 'Chemical', '-', (87, 91))	('Irf8', 'Gene', (99, 103))
42694	33108502	CLEC16A, variants of which are associated with susceptibility to MS, is involved in the control of TEC autophagy, a process that regulates MHC-associated thymic presentation of lysosomal, nuclear and mitochondrial peptide antigens.	('CLEC16A', 'Gene', '23274', (0, 7))	('MHC', 'Gene', (139, 142))	('CLEC16A', 'Gene', (0, 7))	('involved', 'Reg', (72, 80))	('MHC', 'Gene', '3107', (139, 142))	('variants', 'Var', (9, 17))
42695	33108502	Silencing of Clec16a protects against autoimmunity by inducing CD4+ T cell hyporeactivity, and CLEC16A expression is upregulated in peripheral APCs of MS patients.	('Clec16a', 'Gene', '23274', (13, 20))	('expression', 'MPA', (103, 113))	('CLEC16A', 'Gene', (95, 102))	('patients', 'Species', '9606', (154, 162))	('upregulated', 'PosReg', (117, 128))	('peripheral APCs', 'Disease', (132, 147))	('CD4+ T cell hyporeactivity', 'MPA', (63, 89))	('autoimmunity', 'Phenotype', 'HP:0002960', (38, 50))	('CLEC16A', 'Gene', '23274', (95, 102))	('inducing', 'Reg', (54, 62))	('Silencing', 'Var', (0, 9))	('Clec16a', 'Gene', (13, 20))
42696	33108502	EAE severity in mice is exacerbated by dysfunction in PRSS16, which encodes a serine protease controlling peptide presentation to developing thymocytes.	('serine', 'Chemical', 'MESH:D012694', (78, 84))	('EAE', 'Disease', (0, 3))	('PRSS16', 'Gene', (54, 60))	('PRSS16', 'Gene', '54373', (54, 60))	('mice', 'Species', '10090', (16, 20))	('dysfunction', 'Var', (39, 50))	('exacerbated', 'PosReg', (24, 35))
42697	33108502	Like many putative autoimmune diseases, major genetic variants associated with MS occur in the MHC class II subgroup of the HLA complex: HLA-DRB1*15:01-containing haplotypes carry the strongest association with MS risk.	('HLA', 'Gene', '3119', (137, 140))	('haplotypes', 'Var', (163, 173))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (19, 38))	('HLA-DRB1', 'Gene', (137, 145))	('HLA', 'Gene', '3119', (124, 127))	('HLA-DRB1', 'Gene', '3123', (137, 145))	('autoimmune disease', 'Phenotype', 'HP:0002960', (19, 37))	('HLA', 'Gene', (137, 140))	('MHC', 'Gene', (95, 98))	('autoimmune diseases', 'Disease', 'MESH:D001327', (19, 38))	('MHC', 'Gene', '3107', (95, 98))	('autoimmune diseases', 'Disease', (19, 38))	('variants', 'Var', (54, 62))	('association', 'Interaction', (194, 205))	('HLA', 'Gene', (124, 127))
42698	33108502	Autoimmunity-associated MHC polymorphisms are typically thought to alter TCR-pMHC complex binding dynamics and may cause extensive TCR-pMHC microcluster formation leading to escape of autoreactive T cells.	('MHC', 'Gene', (24, 27))	('MHC', 'Gene', '3107', (136, 139))	('alter', 'Reg', (67, 72))	('escape', 'CPA', (174, 180))	('MHC', 'Gene', '3107', (24, 27))	('binding', 'Interaction', (90, 97))	('polymorphisms', 'Var', (28, 41))	('cause', 'Reg', (115, 120))	('MHC', 'Gene', (78, 81))	('Autoimmunity', 'Phenotype', 'HP:0002960', (0, 12))	('MHC', 'Gene', (136, 139))	('MHC', 'Gene', '3107', (78, 81))
42699	33108502	Variants in other genes associated with susceptibility to MS or other CNS autoimmune diseases might hence affect central thymic tolerance processes in addition to their presently understood roles in peripheral immunity.	('Variants', 'Var', (0, 8))	('autoimmune diseases', 'Disease', (74, 93))	('autoimmune diseases', 'Disease', 'MESH:D001327', (74, 93))	('CNS autoimmune disease', 'Disease', 'MESH:D001327', (70, 92))	('central thymic tolerance processes', 'CPA', (113, 147))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (74, 93))	('autoimmune disease', 'Phenotype', 'HP:0002960', (74, 92))	('affect', 'Reg', (106, 112))	('CNS autoimmune disease', 'Disease', (70, 92))
42701	33108502	The pathological effects of manipulating thymic expression of CNS antigens in murine EAE provide insight into the roles of thymic selection in CNS inflammation.	('CNS inflammation', 'Disease', 'MESH:D007249', (143, 159))	('CNS inflammation', 'Disease', (143, 159))	('murine', 'Species', '10090', (78, 84))	('manipulating', 'Var', (28, 40))
42704	33108502	Similar protective effects of Mbp and Aqp thymic expression are seen in EAE models induced by MBP and AQP4 respectively, with peripheral expansion of CNS-reactive T cells not seen in wild-type mice.	('Mbp', 'Gene', '17196', (30, 33))	('AQP4', 'Var', (102, 106))	('MBP', 'Var', (94, 97))	('EAE', 'Disease', (72, 75))	('mice', 'Species', '10090', (193, 197))	('Mbp', 'Gene', (30, 33))	('induced', 'Reg', (83, 90))
42714	33108502	An additional explanation for the rarity of CNS inflammation in the context of thymic dysfunction is that antibodies against pro-inflammatory cytokines may preferentially block peripheral pathogenic processes leading to CNS autoimmunity.	('thymic dysfunction', 'Disease', 'MESH:D013953', (79, 97))	('thymic dysfunction', 'Disease', (79, 97))	('preferentially', 'PosReg', (156, 170))	('antibodies', 'Var', (106, 116))	('CNS inflammation', 'Disease', 'MESH:D007249', (44, 60))	('autoimmunity', 'Phenotype', 'HP:0002960', (224, 236))	('CNS inflammation', 'Disease', (44, 60))	('block', 'NegReg', (171, 176))
42722	33108502	Molecular mimicry between AQP4 and Clostridium perfringens has been implicated as an environmental factor in NMOSD.	('NMOSD', 'Disease', (109, 114))	('AQP4', 'Gene', (26, 30))	('Clostridium perfringens', 'Species', '1502', (35, 58))	('Molecular', 'Var', (0, 9))
42723	33108502	NMO patients can harbour AQP4-specific TH17-polarised cells cross-reactive against C. perfringens antigens, and C. perfringens is overrepresented in their gut microbiome.	('TH1', 'Gene', '51497', (39, 42))	('C. perfringens', 'Species', '1502', (83, 97))	('C. perfringens', 'Var', (112, 126))	('gut microbiome', 'Species', '749906', (155, 169))	('TH1', 'Gene', (39, 42))	('NMO', 'Disease', (0, 3))	('C. perfringens', 'Species', '1502', (112, 126))	('patients', 'Species', '9606', (4, 12))
42730	33108502	Nonetheless, several lines of indirect evidence from patient studies point to potentially important roles of dysfunctions in thymic tolerance in human CNS autoimmune disease.	('autoimmune disease', 'Phenotype', 'HP:0002960', (155, 173))	('dysfunctions', 'Var', (109, 121))	('human', 'Species', '9606', (145, 150))	('CNS autoimmune disease', 'Disease', (151, 173))	('patient', 'Species', '9606', (53, 60))	('CNS autoimmune disease', 'Disease', 'MESH:D001327', (151, 173))
42731	33108502	TRECs are circular non-replicating DNA fragments, produced as a result of V(D)J recombination of TCR chain loci during thymocyte development, which can be detected in peripheral blood T cells.	('V(D)J recombination', 'Var', (74, 93))	('TCR', 'Gene', '6962', (97, 100))	('TCR', 'Gene', (97, 100))
42738	33108502	In addition, MS-associated genetic variants of IL7RA, which promotes early thymocyte survival, were associated with an increased frequency of RTEs.	('promotes', 'PosReg', (60, 68))	('RTEs', 'Disease', (142, 146))	('variants', 'Var', (35, 43))	('IL7RA', 'Gene', (47, 52))	('associated', 'Reg', (100, 110))	('early thymocyte survival', 'CPA', (69, 93))	('MS-associated', 'Disease', (13, 26))	('IL7RA', 'Gene', '3575', (47, 52))
42770	33108502	As most patients harbour anti-AQP4 antibodies years before thymectomy and disease onset, this risk appears to be independent of CNS-reactive antibody production and may instead reflect direct precipitation of CNS autoimmunity by the abrupt loss of thymopoiesis, possibly due to loss of thymic tTreg cell output.	('Treg', 'Chemical', '-', (294, 298))	('abrupt loss of thymopoiesis', 'Disease', 'MESH:D000033', (233, 260))	('autoimmunity', 'Phenotype', 'HP:0002960', (213, 225))	('abrupt loss of thymopoiesis', 'Disease', (233, 260))	('antibodies', 'Var', (35, 45))	('anti-AQP4 antibodies', 'Var', (25, 45))	('patients', 'Species', '9606', (8, 16))
42776	33108502	Just as alterations in thymic function can lead to pathophysiological features of CNS autoimmunity, successful therapeutic amelioration of CNS autoimmune disease can be associated with measurable changes in thymic T cell tolerance.	('CNS autoimmune disease', 'Disease', (139, 161))	('alterations', 'Var', (8, 19))	('lead to', 'Reg', (43, 50))	('CNS autoimmune disease', 'Disease', 'MESH:D001327', (139, 161))	('changes', 'Reg', (196, 203))	('CNS', 'Disease', (82, 85))	('autoimmune disease', 'Phenotype', 'HP:0002960', (143, 161))	('autoimmunity', 'Phenotype', 'HP:0002960', (86, 98))
42785	33108502	The modulation of thymopoiesis has unique potential as a source of novel therapies for CNS autoimmune diseases.	('autoimmune diseases', 'Phenotype', 'HP:0002960', (91, 110))	('CNS autoimmune disease', 'Disease', 'MESH:D001327', (87, 109))	('modulation', 'Var', (4, 14))	('autoimmune disease', 'Phenotype', 'HP:0002960', (91, 109))	('autoimmune diseases', 'Disease', 'MESH:D001327', (91, 110))	('CNS autoimmune disease', 'Disease', (87, 109))	('autoimmune diseases', 'Disease', (91, 110))
42791	33108502	Nutritional factors may play a role: both zinc and vitamin D supplementation has been shown to modulate thymopoiesis in mice.	('mice', 'Species', '10090', (120, 124))	('vitamin D', 'Chemical', 'MESH:D014807', (51, 60))	('supplementation', 'Var', (61, 76))	('modulate', 'Reg', (95, 103))	('thymopoiesis', 'CPA', (104, 116))
42798	33108502	Moreover, findings in athymic nude mice suggest ATO transplantation can effectively promote central T cell tolerance (i.e.	('ATO', 'Var', (48, 51))	('ATO', 'Chemical', '-', (48, 51))	('promote', 'PosReg', (84, 91))	('central T cell tolerance', 'CPA', (92, 116))	('nude mice', 'Species', '10090', (30, 39))
42800	33108502	The potential efficacy of this strategy for CNS autoimmune diseases is supported by a proof-of-concept study in a preclinical model, in which transplantation of embryonic stem cell-derived TEPs engineered to express MOG rendered mice resistant to later EAE induction through deletion of MOG-autoreactive T cells and generation of MOG-specific Treg cells.	('autoimmune diseases', 'Disease', 'MESH:D001327', (48, 67))	('Treg', 'Chemical', '-', (343, 347))	('CNS autoimmune disease', 'Disease', (44, 66))	('autoimmune diseases', 'Disease', (48, 67))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (48, 67))	('MOG-autoreactive', 'Gene', (287, 303))	('MOG', 'Gene', (216, 219))	('CNS autoimmune disease', 'Disease', 'MESH:D001327', (44, 66))	('deletion', 'Var', (275, 283))	('mice', 'Species', '10090', (229, 233))	('autoimmune disease', 'Phenotype', 'HP:0002960', (48, 66))
42808	33108502	Population-level transcriptomic analysis of peripheral T cell pools allows to identify overrepresentation of specific TCRbeta chain locus rearrangements, which gives an indication of overall clonal diversity in peripheral T cells and allows to detect disease-relevant, clonally expanded T cell populations (e.g.	('TCRbeta', 'Gene', (118, 125))	('TCRbeta', 'Gene', '6955', (118, 125))	('rearrangements', 'Var', (138, 152))
42829	32117321	Furthermore, antibodies against other extracellular or intracellular targets, such as titin, the ryanodine receptor, agrin, collagen Q, Kv1.4 potassium channels and cortactin have been found in some MG patients, which can be useful biomarkers.	('titin', 'Gene', '7273', (86, 91))	('Kv1.4', 'Gene', (136, 141))	('agrin', 'Protein', (117, 122))	('ryanodine receptor', 'Gene', (97, 115))	('antibodies', 'Var', (13, 23))	('titin', 'Gene', (86, 91))	('MG', 'Disease', 'MESH:D009157', (199, 201))	('patients', 'Species', '9606', (202, 210))	('Kv1.4', 'Gene', '3739', (136, 141))	('collagen Q', 'Gene', (124, 134))	('cortactin', 'Gene', (165, 174))	('ryanodine receptor', 'Gene', '6261', (97, 115))	('collagen Q', 'Gene', '8292', (124, 134))	('found', 'Reg', (185, 190))	('cortactin', 'Gene', '2017', (165, 174))
42835	32117321	MG is antibody-mediated, caused by autoantibodies targeting components of the neuromuscular junction (NMJ).	('autoantibodies', 'Var', (35, 49))	('MG', 'Disease', 'MESH:D009157', (0, 2))	('caused', 'Reg', (25, 31))
42844	32117321	Furthermore, antibodies against MuSK are found in approximately 6% of the patients, while relatively recently antibodies against LRP4 have been found in about 2% of MG patients.	('antibodies', 'Var', (13, 23))	('patients', 'Species', '9606', (74, 82))	('MG', 'Disease', 'MESH:D009157', (165, 167))	('patients', 'Species', '9606', (168, 176))	('LRP4', 'Gene', (129, 133))	('LRP4', 'Gene', '4038', (129, 133))
42866	32117321	Finally, an approach based on labeling of the recombinant AChR alpha subunit with Renilla luciferase and measuring the precipitated fluorescence by serum autoantibodies was able to detect AChR antibodies in 32% of MG patients.	('antibodies', 'Var', (193, 203))	('detect', 'Reg', (181, 187))	('Renilla luciferase', 'Disease', 'None', (82, 100))	('MG', 'Disease', 'MESH:D009157', (214, 216))	('Renilla luciferase', 'Disease', (82, 100))	('patients', 'Species', '9606', (217, 225))	('AChR', 'Gene', (188, 192))
42898	32117321	However, LRP4 antibodies belong mostly to the IgG1 subclass, and they have been shown to cause in vitro complement-mediated cell lysis of C2C12 myotubes, so complement activation could also play a role in MG patients.	('MG', 'Disease', 'MESH:D009157', (205, 207))	('patients', 'Species', '9606', (208, 216))	('cause', 'Reg', (89, 94))	('LRP4', 'Gene', (9, 13))	('antibodies', 'Var', (14, 24))	('complement-mediated cell lysis', 'CPA', (104, 134))	('LRP4', 'Gene', '4038', (9, 13))
42902	32117321	We found that 19% had LRP4 antibodies, corresponding to 2% of all MG patients, with considerable variability among the various countries (from 7% for Norway and Turkey to 33% for Poland).	('LRP4', 'Gene', '4038', (22, 26))	('Turkey', 'Species', '9103', (161, 167))	('antibodies', 'Var', (27, 37))	('MG', 'Disease', 'MESH:D009157', (66, 68))	('patients', 'Species', '9606', (69, 77))	('LRP4', 'Gene', (22, 26))
42905	32117321	Interestingly, LRP4 antibodies have also been detected in 10-23% of amyotrophic lateral sclerosis (ALS) patients and are thus not exclusively specific for MG.	('LRP4', 'Gene', '4038', (15, 19))	('ALS', 'Disease', (99, 102))	('amyotrophic lateral sclerosis', 'Disease', 'MESH:D000690', (68, 97))	('amyotrophic lateral sclerosis', 'Phenotype', 'HP:0007354', (68, 97))	('antibodies', 'Var', (20, 30))	('detected', 'Reg', (46, 54))	('ALS', 'Disease', 'MESH:D000690', (99, 102))	('LRP4', 'Gene', (15, 19))	('MG', 'Disease', 'MESH:D009157', (155, 157))	('ALS', 'Phenotype', 'HP:0007354', (99, 102))	('patients', 'Species', '9606', (104, 112))	('amyotrophic lateral sclerosis', 'Disease', (68, 97))
42917	32117321	On the other hand, the presence of titin antibodies in all age groups appears to be related with more severe symptom manifestation, although this relation has not been confirmed by all relevant studies.	('titin', 'Gene', (35, 40))	('titin', 'Gene', '7273', (35, 40))	('presence', 'Var', (23, 31))	('related', 'Reg', (84, 91))
42938	32117321	Importantly, patients with agrin antibodies presented with mild to severe symptoms and moderate response to treatment, thus their early detection could aid in disease management.	('patients', 'Species', '9606', (13, 21))	('antibodies', 'Var', (33, 43))	('agrin', 'Protein', (27, 32))	('aid', 'Reg', (152, 155))
42939	32117321	Agrin antibodies appear to be pathogenic, since in in vitro studies they were capable of inhibiting MuSK activation by agrin and AChR clustering, while immunization of mice with neural, but not muscle, agrin induced MG-like symptoms.	('agrin', 'Protein', (119, 124))	('inhibiting', 'NegReg', (89, 99))	('mice', 'Species', '10090', (168, 172))	('antibodies', 'Var', (6, 16))	('AChR', 'Gene', (129, 133))	('MG', 'Disease', 'MESH:D009157', (216, 218))	('MuSK', 'CPA', (100, 104))
42944	32117321	It appears therefore, that only in Japanese populations, the Kv1.4 antibodies are an important biomarker indicating increased risk of myocarditis or cardiac dysfunction among MG patients.	('myocarditis', 'Phenotype', 'HP:0012819', (134, 145))	('myocarditis', 'Disease', (134, 145))	('cardiac dysfunction', 'Disease', (149, 168))	('Kv1.4', 'Gene', (61, 66))	('Kv1.4', 'Gene', '3739', (61, 66))	('patients', 'Species', '9606', (178, 186))	('cardiac dysfunction', 'Disease', 'MESH:D006331', (149, 168))	('myocarditis', 'Disease', 'MESH:D009205', (134, 145))	('MG', 'Disease', 'MESH:D009157', (175, 177))	('antibodies', 'Var', (67, 77))
42953	32117321	However, cortactin antibodies have also been found in up to 12.5% of patients with other autoimmune diseases and 5.2% of healthy controls, while they have been described as myositis-associated, since they are found in 7.6-26% of patients with polymyositis, dermatomyositis and immune-mediated necrotizing myopathy.	('polymyositis', 'Disease', (243, 255))	('patients', 'Species', '9606', (229, 237))	('autoimmune diseases', 'Disease', (89, 108))	('cortactin', 'Gene', (9, 18))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (89, 108))	('myositis', 'Disease', (247, 255))	('dermatomyositis', 'Disease', 'MESH:D003882', (257, 272))	('found', 'Reg', (209, 214))	('patients', 'Species', '9606', (69, 77))	('myositis', 'Disease', (264, 272))	('autoimmune disease', 'Phenotype', 'HP:0002960', (89, 107))	('autoimmune diseases', 'Disease', 'MESH:D001327', (89, 108))	('necrotizing myopathy', 'Phenotype', 'HP:0008978', (293, 313))	('antibodies', 'Var', (19, 29))	('myositis', 'Phenotype', 'HP:0100614', (173, 181))	('cortactin', 'Gene', '2017', (9, 18))	('myopathy', 'Disease', 'MESH:D009135', (305, 313))	('myositis', 'Disease', 'MESH:D009220', (173, 181))	('polymyositis', 'Disease', 'MESH:D017285', (243, 255))	('myositis', 'Phenotype', 'HP:0100614', (247, 255))	('myositis', 'Disease', (173, 181))	('myopathy', 'Disease', (305, 313))	('dermatomyositis', 'Disease', (257, 272))	('myopathy', 'Phenotype', 'HP:0003198', (305, 313))	('myositis', 'Phenotype', 'HP:0100614', (264, 272))	('myositis', 'Disease', 'MESH:D009220', (247, 255))	('myositis', 'Disease', 'MESH:D009220', (264, 272))	('found', 'Reg', (45, 50))
42956	32117321	Antibodies against AChE have been reported in 5-50% of MG patients.	('Antibodies', 'Var', (0, 10))	('AChE', 'Gene', (19, 23))	('AChE', 'Gene', '43', (19, 23))	('patients', 'Species', '9606', (58, 66))	('MG', 'Disease', 'MESH:D009157', (55, 57))
42959	32117321	Recently, antibodies against ColQ were found in a fraction of MG patients (3%) using CBA, including some SNMG patients, although they were also present in a similar fraction of the control cohort used in the study.	('found', 'Reg', (39, 44))	('CBA', 'Chemical', '-', (85, 88))	('ColQ', 'Gene', (29, 33))	('MG', 'Disease', 'MESH:D009157', (62, 64))	('patients', 'Species', '9606', (65, 73))	('antibodies', 'Var', (10, 20))	('ColQ', 'Gene', '8292', (29, 33))	('MG', 'Disease', 'MESH:D009157', (107, 109))	('patients', 'Species', '9606', (110, 118))
42963	32117321	Moreover, these antibodies are not MG specific and have been also associated with Grave's ophthalmopathy.	("Grave's ophthalmopathy", 'Disease', (82, 104))	('antibodies', 'Var', (16, 26))	('associated', 'Reg', (66, 76))	("Grave's ophthalmopathy", 'Disease', 'MESH:D049970', (82, 104))	('MG', 'Disease', 'MESH:D009157', (35, 37))
42968	32117321	Patients with MuSK antibodies tend to have more severe symptoms and generalized weakness, whereas treatment withdrawal in these patients can often lead to disease exacerbation.	('antibodies', 'Var', (19, 29))	('MuSK', 'Gene', (14, 18))	('generalized weakness', 'Phenotype', 'HP:0003324', (68, 88))	('Patients', 'Species', '9606', (0, 8))	('generalized weakness', 'Disease', (68, 88))	('MuSK antibodies', 'Phenotype', 'HP:0030210', (14, 29))	('patients', 'Species', '9606', (128, 136))
42973	32117321	Especially in the case of Japanese patients, the presence of Kv1.4 antibodies has been associated with cardiac dysfunction and severe complications, so they should be monitored accordingly.	('presence', 'Var', (49, 57))	('Kv1.4', 'Gene', (61, 66))	('cardiac dysfunction', 'Disease', (103, 122))	('cardiac dysfunction', 'Disease', 'MESH:D006331', (103, 122))	('Kv1.4', 'Gene', '3739', (61, 66))	('associated', 'Reg', (87, 97))	('antibodies', 'Protein', (67, 77))	('patients', 'Species', '9606', (35, 43))
43047	29021446	The pathogenesis linking thymoma and MCD has yet to be delineated, but disturbances in the T-lymphocyte function resulting from a remote effect of thymectomy may induce nephrotic syndrome through the accelerated production of biological mediators, thereby increasing the glomerular permeability.	('increasing', 'PosReg', (256, 266))	('thymoma', 'Gene', (25, 32))	('nephrotic syndrome', 'Disease', 'MESH:D009404', (169, 187))	('disturbances', 'Var', (71, 83))	('glomerular permeability', 'MPA', (271, 294))	('nephrotic syndrome', 'Disease', (169, 187))	('MCD', 'Phenotype', 'HP:0012579', (37, 40))	('MCD', 'Gene', (37, 40))	('induce', 'Reg', (162, 168))	('nephrotic syndrome', 'Phenotype', 'HP:0000100', (169, 187))	('thymoma', 'Phenotype', 'HP:0100522', (25, 32))	('production of biological mediators', 'MPA', (212, 246))	('accelerated', 'PosReg', (200, 211))	('MCD', 'Gene', '4582', (37, 40))	('thymoma', 'Gene', '7063', (25, 32))
43127	27524908	Previous studies demonstrated that negative or low level TS expression benefited more from pemetrexed-based chemotherapy than positive or high levels of TS in NSCLC patients.	('pemetrexed', 'Chemical', 'MESH:D000068437', (91, 101))	('negative', 'Var', (35, 43))	('TS', 'Gene', '7298', (57, 59))	('benefited', 'PosReg', (71, 80))	('NSCLC', 'Disease', (159, 164))	('NSCLC', 'Disease', 'MESH:D002289', (159, 164))	('patients', 'Species', '9606', (165, 173))	('TS', 'Gene', '7298', (153, 155))
43176	33236521	Furthermore, multivariate analyses were performed to identify whether the presence of FBs was associated with higher Masaoka stage and poor prognosis in patients with thymoma.	('a', 'Gene', '351', (120, 121))	('higher', 'PosReg', (110, 116))	('FBs', 'Gene', (86, 89))	('thymoma', 'Disease', 'MESH:D013945', (167, 174))	('a', 'Gene', '351', (127, 128))	('a', 'Gene', '351', (118, 119))	('a', 'Gene', '351', (94, 95))	('a', 'Gene', '351', (173, 174))	('a', 'Gene', '351', (22, 23))	('a', 'Gene', '351', (28, 29))	('thymoma', 'Disease', (167, 174))	('a', 'Gene', '351', (100, 101))	('a', 'Gene', '351', (131, 132))	('thymoma', 'Phenotype', 'HP:0100522', (167, 174))	('a', 'Gene', '351', (19, 20))	('a', 'Gene', '351', (91, 92))	('a', 'Gene', '351', (154, 155))	('a', 'Gene', '351', (123, 124))	('patients', 'Species', '9606', (153, 161))	('presence', 'Var', (74, 82))	('a', 'Gene', '351', (26, 27))
43217	33236521	Finally, multivariate analyses were compared to identify whether the presence of FBs was associated with higher Masaoka stage and with poor prognosis in patients with thymoma.	('a', 'Gene', '351', (89, 90))	('a', 'Gene', '351', (24, 25))	('a', 'Gene', '351', (15, 16))	('a', 'Gene', '351', (95, 96))	('a', 'Gene', '351', (40, 41))	('a', 'Gene', '351', (126, 127))	('thymoma', 'Disease', 'MESH:D013945', (167, 174))	('a', 'Gene', '351', (86, 87))	('a', 'Gene', '351', (118, 119))	('a', 'Gene', '351', (173, 174))	('a', 'Gene', '351', (22, 23))	('presence', 'Var', (69, 77))	('thymoma', 'Disease', (167, 174))	('a', 'Gene', '351', (115, 116))	('thymoma', 'Phenotype', 'HP:0100522', (167, 174))	('a', 'Gene', '351', (154, 155))	('a', 'Gene', '351', (122, 123))	('a', 'Gene', '351', (3, 4))	('a', 'Gene', '351', (18, 19))	('patients', 'Species', '9606', (153, 161))	('FBs', 'Gene', (81, 84))	('higher', 'PosReg', (105, 111))	('a', 'Gene', '351', (113, 114))
43250	33236521	Although age, sex, tumor diameter, and histology were not significantly associated with higher Masaoka stage, the presence of FBs was significantly associated with higher Masaoka stage (Table 2, odds ratio, 31.32; 95% confidence interval [CI]: 6.308-155.5; P < 0.0001).	('a', 'Gene', '351', (142, 143))	('a', 'Gene', '351', (96, 97))	('FBs', 'Disease', (126, 129))	('a', 'Gene', '351', (72, 73))	('tumor', 'Disease', (19, 24))	('a', 'Gene', '351', (78, 79))	('a', 'Gene', '351', (181, 182))	('a', 'Gene', '351', (174, 175))	('tumor', 'Disease', 'MESH:D009369', (19, 24))	('a', 'Gene', '351', (101, 102))	('a', 'Gene', '351', (105, 106))	('A', 'Gene', '351', (0, 1))	('a', 'Gene', '351', (172, 173))	('a', 'Gene', '351', (131, 132))	('tumor', 'Phenotype', 'HP:0002664', (19, 24))	('a', 'Gene', '351', (187, 188))	('a', 'Gene', '351', (148, 149))	('a', 'Gene', '351', (154, 155))	('a', 'Gene', '351', (98, 99))	('a', 'Gene', '351', (235, 236))	('presence', 'Var', (114, 122))	('a', 'Gene', '351', (27, 28))	('a', 'Gene', '351', (35, 36))	('a', 'Gene', '351', (66, 67))	('a', 'Gene', '351', (9, 10))	('a', 'Gene', '351', (201, 202))	('a', 'Gene', '351', (177, 178))
43266	33236521	18 ,  19 ,  20 ,  21 ,  22 ,  23 ,  24  For example, the presence of FBs has been reportedly associated with poor prognosis in patients with lung squamous cell carcinoma.	('a', 'Gene', '351', (168, 169))	('carcinoma', 'Phenotype', 'HP:0030731', (160, 169))	('a', 'Gene', '351', (93, 94))	('lung squamous cell carcinoma', 'Disease', 'MESH:D002294', (141, 169))	('squamous cell carcinoma', 'Phenotype', 'HP:0002860', (146, 169))	('a', 'Gene', '351', (149, 150))	('patients', 'Species', '9606', (127, 135))	('lung squamous cell carcinoma', 'Disease', (141, 169))	('presence', 'Var', (57, 65))	('a', 'Gene', '351', (128, 129))	('a', 'Gene', '351', (46, 47))	('a', 'Gene', '351', (74, 75))	('FBs', 'Gene', (69, 72))	('a', 'Gene', '351', (99, 100))	('a', 'Gene', '351', (161, 162))
43301	33236521	In conclusion, our results indicated that the presence of FBs in patients with thymoma was associated with higher Masaoka stage, higher recurrence rate, and poorer RFS.	('a', 'Gene', '351', (120, 121))	('a', 'Gene', '351', (39, 40))	('a', 'Gene', '351', (32, 33))	('a', 'Gene', '351', (117, 118))	('presence', 'Var', (46, 54))	('thymoma', 'Disease', 'MESH:D013945', (79, 86))	('higher', 'PosReg', (107, 113))	('a', 'Gene', '351', (85, 86))	('a', 'Gene', '351', (115, 116))	('a', 'Gene', '351', (124, 125))	('FBs', 'Gene', (58, 61))	('thymoma', 'Disease', (79, 86))	('patients', 'Species', '9606', (65, 73))	('a', 'Gene', '351', (148, 149))	('a', 'Gene', '351', (91, 92))	('thymoma', 'Phenotype', 'HP:0100522', (79, 86))	('a', 'Gene', '351', (66, 67))	('higher', 'PosReg', (129, 135))	('a', 'Gene', '351', (97, 98))	('a', 'Gene', '351', (153, 154))	('a', 'Gene', '351', (88, 89))	('RFS', 'CPA', (164, 167))
43362	30328513	The top 5 listed KEGG signaling pathways were as follows: hsa03320 (PPAR signaling pathway); Hsa04923 (regulation of lipolysis in adipocytes); Hsa04152 (AMPK signaling pathway); Hsa00360 (phenylalanine metabolism) and Hsa00980 (metabolism of xenobiotics by cytochrome P450).	('PPAR', 'Gene', '5465', (68, 72))	('PPAR', 'Gene', (68, 72))	('Hsa04152', 'Var', (143, 151))	('hsa03320', 'Var', (58, 66))	('phenylalanine', 'Chemical', 'MESH:D010649', (188, 201))	('Hsa00360', 'Var', (178, 186))	('Hsa04923', 'Var', (93, 101))	('Hsa00980', 'Var', (218, 226))
43406	30328513	In malignant ovarian cancer, changes in SELENBP1 expression are useful indicators of abnormal selenium/androgen pathways, and such changes may reveal prognostic information relating to ovarian cancer (Huang et al.).	('ovarian cancer', 'Phenotype', 'HP:0100615', (185, 199))	('reveal', 'Reg', (143, 149))	('cancer', 'Phenotype', 'HP:0002664', (21, 27))	('malignant ovarian cancer', 'Disease', (3, 27))	('changes', 'Var', (29, 36))	('selenium', 'Chemical', 'MESH:D012643', (94, 102))	('ovarian cancer', 'Phenotype', 'HP:0100615', (13, 27))	('abnormal selenium', 'Phenotype', 'HP:0031903', (85, 102))	('ovarian cancer', 'Disease', 'MESH:D010051', (185, 199))	('ovarian cancer', 'Disease', 'MESH:D010051', (13, 27))	('expression', 'MPA', (49, 59))	('malignant ovarian cancer', 'Disease', 'MESH:D010051', (3, 27))	('ovarian cancer', 'Disease', (185, 199))	('cancer', 'Phenotype', 'HP:0002664', (193, 199))	('selenium/androgen', 'MPA', (94, 111))	('SELENBP1', 'Gene', (40, 48))	('SELENBP1', 'Gene', '8991', (40, 48))
43491	29364837	During the follow-up period, an improvement or normalization of neurological status was observed in all dogs in the RT and RT + TMZ arms and in 7/30 of the patients included in the palliation arm.	('patients', 'Species', '9606', (156, 164))	('neurological status', 'MPA', (64, 83))	('normalization', 'MPA', (47, 60))	('dogs', 'Species', '9615', (104, 108))	('RT + TMZ', 'Var', (123, 131))	('improvement', 'PosReg', (32, 43))	('RT + TMZ', 'Chemical', '-', (123, 131))	('normalization of neurological status', 'Phenotype', 'HP:0002344', (47, 83))
43492	29364837	A reduction in the frequency and/or intensity of seizures was observed in all dogs in the RT and RT + TMZ arms and in 11/30 of the dogs treated under the palliation protocol.	('RT + TMZ', 'Chemical', '-', (97, 105))	('seizures', 'Disease', 'MESH:D012640', (49, 57))	('reduction', 'NegReg', (2, 11))	('dogs', 'Species', '9615', (131, 135))	('seizures', 'Disease', (49, 57))	('seizures', 'Phenotype', 'HP:0001250', (49, 57))	('dogs', 'Species', '9615', (78, 82))	('RT + TMZ', 'Var', (97, 105))	('seizure', 'Phenotype', 'HP:0001250', (49, 56))
43528	29364837	The localization was C6 on the left side in one dog, C6-T1 (3 left, 1 right) in four dogs, C7-T1 in three dogs (2 right, 1 left) and T1-T2 in two dogs (1 right, 1 left).	('dogs', 'Species', '9615', (106, 110))	('T1-T2', 'Var', (133, 138))	('dogs', 'Species', '9615', (85, 89))	('dog', 'Species', '9615', (146, 149))	('dog', 'Species', '9615', (85, 88))	('dogs', 'Species', '9615', (146, 150))	('dog', 'Species', '9615', (106, 109))	('C7-T1', 'Var', (91, 96))	('C6-T1', 'Var', (53, 58))	('dog', 'Species', '9615', (48, 51))
43572	29364837	The anemia remained stable during the follow-up period (35.5% hematocrit or HCT) in one case.	('anemia', 'Disease', 'MESH:D000740', (4, 10))	('anemia', 'Phenotype', 'HP:0001903', (4, 10))	('anemia', 'Disease', (4, 10))	('35.5', 'Var', (56, 60))
43598	29364837	Although one year and two year progression-free survivals were similar in the RT and RT + TMZ groups, median progression-free survival in the RT + TMZ arm (345 days) was significantly longer (p = 0.027) than in the RT arm (255 days).	('RT + TMZ', 'Chemical', '-', (85, 93))	('RT + TMZ', 'Chemical', '-', (142, 150))	('RT + TMZ', 'Var', (142, 150))	('longer', 'PosReg', (184, 190))	('progression-free survival', 'CPA', (109, 134))
43599	29364837	This result showed that TMZ can delay disease progression, despite the lack of a change in effective survival time.	('TMZ', 'Chemical', 'MESH:D000077204', (24, 27))	('disease progression', 'CPA', (38, 57))	('TMZ', 'Var', (24, 27))
43673	29364837	The PTV coverage is considered acceptable for the V95% and the V107% levels (respectively, PTV volume receiving less than 95% and more than 107% of the prescribed dose) of 5% and 7%.	('V95%', 'Var', (50, 54))	('PTV', 'Chemical', '-', (4, 7))	('V107%', 'Var', (63, 68))	('less', 'NegReg', (112, 116))	('PTV', 'Chemical', '-', (91, 94))
43780	27576953	Thymoma has been most classically associated with MG where antibodies directed toward the acetyl choline receptor (AchR) result in post synaptic membrane destruction at the neuromuscular junction.	('associated', 'Reg', (34, 44))	('Thymoma', 'Gene', '7063', (0, 7))	('Thymoma', 'Phenotype', 'HP:0100522', (0, 7))	('synaptic membrane destruction at the neuromuscular junction', 'Phenotype', 'HP:0003398', (136, 195))	('antibodies directed', 'Var', (59, 78))	('result in', 'Reg', (121, 130))	('Thymoma', 'Gene', (0, 7))	('AchR', 'Gene', (115, 119))
43796	27576953	A subsequent MRI confirmed the solitary solid/cystic rim-enhancing lesion in the left posterior frontal lobe with moderate vasogenic odema resulting in a 3.5 cm midline shift (Fig.	('lesion', 'Var', (67, 73))	('vasogenic odema', 'Phenotype', 'HP:0100665', (123, 138))	('vasogenic odema', 'Disease', (123, 138))	('vasogenic odema', 'Disease', 'MESH:D001929', (123, 138))
44039	25002944	Rarely, pre-operative imaging including 99mTc/ 99mTc-MIBI scintiscan will pick up a concomitant thymoma during evaluation of primary hyperparathyroidism.	('primary hyperparathyroidism', 'Phenotype', 'HP:0008200', (125, 152))	('99mTc/ 99mTc-MIBI', 'Var', (40, 57))	('primary hyperparathyroidism', 'Disease', (125, 152))	('hyperparathyroidism', 'Phenotype', 'HP:0000843', (133, 152))	('thymoma', 'Disease', 'MESH:D013945', (96, 103))	('thymoma', 'Disease', (96, 103))	('thymoma', 'Phenotype', 'HP:0100522', (96, 103))	('pick up', 'Reg', (74, 81))	('99mTc-MIBI', 'Chemical', '-', (47, 57))	('primary hyperparathyroidism', 'Disease', 'MESH:D049950', (125, 152))
44087	19375665	The precise origin of the autoimmune response in MG is not known, but abnormalities of the thymus gland (hyperplasia and neoplasia) almost certainly play a part in patients with anti-AChR antibodies, and genetic predisposition is also likely to influence which patients develop the disorder.	('anti-AChR', 'Var', (178, 187))	('influence', 'Reg', (245, 254))	('neoplasia', 'Phenotype', 'HP:0002664', (121, 130))	('abnormalities of the thymus', 'Phenotype', 'HP:0000777', (70, 97))	('patients', 'Species', '9606', (261, 269))	('patients', 'Species', '9606', (164, 172))	('autoimmune response', 'Phenotype', 'HP:0002960', (26, 45))	('abnormalities of the thymus gland (hyperplasia and neoplasia) almost', 'Disease', 'MESH:D013952', (70, 138))
44116	19375665	The presence of these anti-muscle antibodies, particularly anti-ryanodine receptor antibodies, has been associated with more severe, generalised, or predominantly oropharyngeal weakness, and frequent myasthenic crises.	('generalised', 'Disease', (133, 144))	('myasthenic crises', 'Phenotype', 'HP:0003473', (200, 217))	('anti-ryanodine', 'Var', (59, 73))	('associated', 'Reg', (104, 114))	('myasthenic crises', 'Disease', (200, 217))	('weakness', 'Disease', (177, 185))	('weakness', 'Disease', 'MESH:D018908', (177, 185))	('presence', 'Var', (4, 12))	('anti-muscle', 'Protein', (22, 33))
44121	19375665	Additional paraneoplasia-associated antibodies (and their related syndromes) might occur in thymomatous MG, including anti-voltage-gated K+ and Ca2+ channel, anti-Hu (antineuronal nuclear autoantibody 1), anti-dihydropyrimidinase-related protein 5 (formerly anti-collapsin response mediator protein 5), and anti-glutamic acid decarboxylase antibodies.	('thymomatous MG', 'Disease', (92, 106))	('anti-Hu', 'Var', (158, 165))	('collapsin response mediator protein 5', 'Gene', '56896', (263, 300))	('Ca2+', 'Chemical', 'MESH:D000069285', (144, 148))	('anti-glutamic acid decarboxylase antibodies', 'Phenotype', 'HP:0025329', (307, 350))	('collapsin response mediator protein 5', 'Gene', (263, 300))	('thymoma', 'Phenotype', 'HP:0100522', (92, 99))	('Additional paraneoplasia', 'Disease', 'MESH:D006938', (0, 24))	('anti-glutamic acid decarboxylase', 'Protein', (307, 339))	('neoplasia', 'Phenotype', 'HP:0002664', (15, 24))	('thymomatous MG', 'Disease', 'MESH:D000080343', (92, 106))	('antineuronal nuclear autoantibody', 'Phenotype', 'HP:0025353', (167, 200))	('dihydropyrimidinase-related protein 5', 'Gene', '56896', (210, 247))	('dihydropyrimidinase-related protein 5', 'Gene', (210, 247))	('Additional paraneoplasia', 'Disease', (0, 24))
44126	19375665	Whereas patients with anti-MUSK antibodies can have presentations similar to anti-AChR-positive MG, they commonly have atypical clinical features, such as selective facial, bulbar, neck, and respiratory muscle weakness and marked muscle atrophy, occasionally with relative sparing of ocular muscles.	('antibodies', 'Var', (32, 42))	('respiratory muscle weakness', 'Phenotype', 'HP:0002747', (191, 218))	('MUSK', 'Gene', '4593', (27, 31))	('selective facial', 'Disease', (155, 171))	('neck', 'Disease', (181, 185))	('muscle atrophy', 'Disease', 'MESH:D009133', (230, 244))	('anti-MUSK antibodies', 'Phenotype', 'HP:0030210', (22, 42))	('respiratory muscle weakness', 'Disease', (191, 218))	('respiratory muscle weakness', 'Disease', 'MESH:D012131', (191, 218))	('bulbar', 'Disease', (173, 179))	('MUSK antibodies', 'Phenotype', 'HP:0030210', (27, 42))	('muscle weakness', 'Phenotype', 'HP:0001324', (203, 218))	('muscle atrophy', 'Phenotype', 'HP:0003202', (230, 244))	('MUSK', 'Gene', (27, 31))	('muscle atrophy', 'Disease', (230, 244))	('patients', 'Species', '9606', (8, 16))
44144	19375665	Although antibodies to the AChR directly result in the destruction of the muscle endplate, the high-affinity, highly mutated nature of the anti-AChR IgGs indicates that the autoantibody response is T-cell dependent, with CD4 T cells helping the B cells to produce the pathogenic antibodies.	('antibodies', 'Var', (9, 19))	('result in', 'Reg', (41, 50))	('CD4', 'Gene', (221, 224))	('CD4', 'Gene', '920', (221, 224))
44161	19375665	Recent evidence indicates that anti-MUSK antibodies adversely affect the maintenance of AChR clustering at the muscle endplate, leading to reduced numbers of functional AChRs.	('affect', 'Reg', (62, 68))	('anti-MUSK antibodies', 'Phenotype', 'HP:0030210', (31, 51))	('MUSK', 'Gene', (36, 40))	('MUSK antibodies', 'Phenotype', 'HP:0030210', (36, 51))	('antibodies', 'Var', (41, 51))	('AChR', 'Protein', (88, 92))	('reduced', 'NegReg', (139, 146))	('MUSK', 'Gene', '4593', (36, 40))
44186	19375665	In disorders of the NMJ, low rates of nerve stimulation (2-5 Hz) produce a progressive decrease or decrement in the amplitude of the compound muscle action potential.	('men', 'Species', '9606', (104, 107))	('NMJ', 'Gene', (20, 23))	('amplitude of the compound muscle action potential', 'MPA', (116, 165))	('decrease', 'NegReg', (87, 95))	('decrement', 'NegReg', (99, 108))	('disorders', 'Var', (3, 12))
44213	19375665	Plasma exchange can also reduce coagulation factors, particularly with repeated treatments, leading to bleeding tendencies.	('leading to', 'Reg', (92, 102))	('bleeding tendencies', 'Disease', 'MESH:C536965', (103, 122))	('coagulation factors', 'MPA', (32, 51))	('reduce', 'NegReg', (25, 31))	('men', 'Species', '9606', (85, 88))	('Plasma', 'Var', (0, 6))	('bleeding tendencies', 'Disease', (103, 122))	('bleeding tendencies', 'Phenotype', 'HP:0001892', (103, 122))
44251	19375665	Sustained benefit has been reported in anti-ryanodine-receptor-positive patients, which has been hypothesised to be due to enhancement of ryanodine-receptor-related sarcoplasmic calcium release.	('anti-ryanodine-receptor-positive', 'Var', (39, 71))	('calcium', 'Chemical', 'MESH:D002118', (178, 185))	('enhancement', 'PosReg', (123, 134))	('men', 'Species', '9606', (130, 133))	('patients', 'Species', '9606', (72, 80))
44309	9151708	The effect of glucocorticoids (GCs)1 is selective; the immature CD4+CD8+ thymocyte fraction is rapidly killed by GC treatment, whereas both the precursor population (TCR-CD4-CD8-) and mature thymocytes (CD4+ or CD8+) are relatively resistant.	('CD4', 'Gene', '12504', (64, 67))	('CD4', 'Gene', (203, 206))	('treatment', 'Var', (116, 125))	('CD4', 'Gene', '12504', (203, 206))	('CD4', 'Gene', (170, 173))	('CD4', 'Gene', (64, 67))	('CD4', 'Gene', '12504', (170, 173))
44311	9151708	In addition, antibodies against SWI3 interfere with the ability of rat GR to activate transcription in Drosophila melanogaster nuclear extracts.	('rat', 'Species', '10116', (67, 70))	('antibodies', 'Var', (13, 23))	('interfere', 'NegReg', (37, 46))	('activate transcription', 'MPA', (77, 99))	('Drosophila melanogaster', 'Species', '7227', (103, 126))	('SWI3', 'Gene', (32, 36))
44312	9151708	The other subunits of the SWI-SNF complex so far identified include the SWI1 (ADR6), SWI2 (SNF2), SNF5, SNF6, SNF11, and SWP73.	('SNF11', 'Gene', (110, 115))	('SNF6', 'Gene', (104, 108))	('SWI1', 'Gene', (72, 76))	('SWP73', 'Gene', '855757', (121, 126))	('SWI2', 'Var', (85, 89))	('ADR6', 'Gene', (78, 82))	('SWI1', 'Gene', '856091', (72, 76))	('SNF6', 'Gene', '856360', (104, 108))	('ADR6', 'Gene', '856091', (78, 82))	('SWP73', 'Gene', (121, 126))	('SNF11', 'Gene', '851645', (110, 115))	('SNF2', 'Gene', (91, 95))	('SNF2', 'Gene', '854465', (91, 95))
44388	9151708	The level of expression of lacZ gene in the SRG3 transformant was only ~22% of the mutant cells transformed with the yeast SWI3 (a positive control), whereas the LacZ expression level in mutant cells transformed only with a vector plasmid was ~20% of the SWI3 transformed cells.	('expression', 'MPA', (13, 23))	('lacZ', 'Gene', (27, 31))	('yeast', 'Species', '4932', (117, 122))	('mutant', 'Var', (83, 89))
44416	9151708	When the level of SRG3 protein was reduced to ~50-30% of normal level of thymoma cells by expressing anti-sense RNA to the gene, apoptosis induced by GC on these cells was significantly reduced (Fig.	('thymoma', 'Phenotype', 'HP:0100522', (73, 80))	('anti-sense RNA', 'Var', (101, 115))	('apoptosis', 'CPA', (129, 138))	('reduced', 'NegReg', (35, 42))	('reduced', 'NegReg', (186, 193))	('thymoma', 'Disease', 'MESH:D013945', (73, 80))	('thymoma', 'Disease', (73, 80))
44421	9151708	In yeast, transcriptional activation by GR is blocked by disrupting any one of SWI1, SWI2, and SWI3 genes, suggesting the possibility that the SWI-SNF complex is required for the GC sensitivity of thymocytes.	('SWI1', 'Gene', '856091', (79, 83))	('SWI1', 'Gene', (79, 83))	('SWI3 genes', 'Gene', (95, 105))	('SWI2', 'Gene', (85, 89))	('yeast', 'Species', '4932', (3, 8))	('disrupting', 'Var', (57, 67))
44485	31639039	These results demonstrate anti-tumor activity of PD-L1 inhibition in patients with relapsed thymoma accompanied by a high frequency of immune-related adverse events.	('thymoma', 'Disease', 'MESH:D013945', (92, 99))	('tumor', 'Phenotype', 'HP:0002664', (31, 36))	('thymoma', 'Disease', (92, 99))	('PD-L1', 'Gene', '29126', (49, 54))	('tumor', 'Disease', (31, 36))	('thymoma', 'Phenotype', 'HP:0100522', (92, 99))	('patients', 'Species', '9606', (69, 77))	('inhibition', 'Var', (55, 65))	('PD-L1', 'Gene', (49, 54))	('tumor', 'Disease', 'MESH:D009369', (31, 36))
44508	31639039	Targets used for identification included: CD3, CD4, CD8 and CD45RO for T cells (helper, cytotoxic and memory T cells); CD3, CD4, and FoxP3 for regulatory T cells (Tregs); CD3, CD20 and CD79 for B and plasma cells; CD3 (negativity) and CD16 for NK cells; and CD68 and CD163 for myeloid cells/macrophages.	('CD4', 'Gene', '920', (47, 50))	('CD4', 'Gene', '920', (124, 127))	('CD3', 'Var', (171, 174))	('CD8', 'Gene', (52, 55))	('CD4', 'Gene', '920', (60, 63))	('CD16', 'Gene', '2214', (235, 239))	('CD4', 'Gene', (47, 50))	('CD16', 'Gene', '2214', (267, 271))	('CD4', 'Gene', (124, 127))	('CD20', 'Gene', (176, 180))	('CD4', 'Gene', (60, 63))	('FoxP3', 'Gene', (133, 138))	('memory T', 'Disease', 'MESH:D008569', (102, 110))	('CD3', 'Var', (42, 45))	('CD68', 'Gene', '968', (258, 262))	('CD16', 'Gene', (235, 239))	('CD16', 'Gene', (267, 271))	('CD20', 'Gene', '54474', (176, 180))	('CD3', 'Var', (119, 122))	('FoxP3', 'Gene', '50943', (133, 138))	('CD8', 'Gene', '925', (52, 55))	('CD68', 'Gene', (258, 262))	('memory T', 'Disease', (102, 110))	('N', 'Chemical', 'MESH:D009584', (244, 245))
44567	31639039	This observation suggests that tumor response was related to avelumab rather than steroids used to treat irAEs.	('tumor', 'Phenotype', 'HP:0002664', (31, 36))	('tumor', 'Disease', (31, 36))	('avelumab', 'Var', (61, 69))	('steroids', 'Chemical', 'MESH:D013256', (82, 90))	('tumor', 'Disease', 'MESH:D009369', (31, 36))
44609	31639039	The anti-tumor effect seen in our patients could be related to the known mechanism of action of anti-PD-L1 MAbs, i.e., blockade of the binding of PD-L1 to PD-1 activates antigen-specific T cells that destroy tumor cells bearing target antigens.	('activates', 'PosReg', (160, 169))	('PD-L1', 'Gene', '29126', (146, 151))	('tumor', 'Disease', 'MESH:D009369', (9, 14))	('tumor', 'Disease', 'MESH:D009369', (208, 213))	('blockade', 'Var', (119, 127))	('PD-L1', 'Gene', '29126', (101, 106))	('tumor', 'Phenotype', 'HP:0002664', (9, 14))	('tumor', 'Phenotype', 'HP:0002664', (208, 213))	('antigen-specific T cells', 'CPA', (170, 194))	('PD-1', 'Gene', (155, 159))	('tumor', 'Disease', (9, 14))	('patients', 'Species', '9606', (34, 42))	('tumor', 'Disease', (208, 213))	('binding', 'Interaction', (135, 142))	('PD-1', 'Gene', '5133', (155, 159))	('PD-L1', 'Gene', (146, 151))	('PD-L1', 'Gene', (101, 106))
44615	31639039	We hypothesize that under these conditions blockade of the PD-1/PD-L1 pathway results in the disinhibition of effector T cells that are capable of inducing thymic epithelial cell death and overcoming immunological tolerance against normal tissue antigens expressed on thymic epithelium.	('disinhibition', 'NegReg', (93, 106))	('blockade', 'Var', (43, 51))	('overcoming', 'PosReg', (189, 199))	('PD-1', 'Gene', (59, 63))	('PD-1', 'Gene', '5133', (59, 63))	('PD-L1', 'Gene', (64, 69))	('inducing', 'PosReg', (147, 155))	('immunological tolerance', 'CPA', (200, 223))	('PD-L1', 'Gene', '29126', (64, 69))	('disinhibition', 'Phenotype', 'HP:0000734', (93, 106))	('thymic epithelial cell death', 'CPA', (156, 184))
44656	24637658	MiR15b, miR122, miR-140-3p, miR185, miR192, miR20b and miR-885-5p were in lower levels in MG patients than in controls.	('miR122', 'Gene', '406906', (8, 14))	('miR20b', 'Gene', '574032', (44, 50))	('miR192', 'Gene', '406967', (36, 42))	('miR-140', 'Gene', '406932', (16, 23))	('miR-885', 'Gene', '100126334', (55, 62))	('miR192', 'Gene', (36, 42))	('MiR15b', 'Gene', '406949', (0, 6))	('miR20b', 'Gene', (44, 50))	('MiR15b', 'Gene', (0, 6))	('miR-140', 'Gene', (16, 23))	('miR-885', 'Gene', (55, 62))	('miR185', 'Var', (28, 34))	('patients', 'Species', '9606', (93, 101))	('miR122', 'Gene', (8, 14))
44759	24637658	However, other cells should be contributing to the altered circulating profile of MG, because miR122, miR140-3p, miR192 and miR885-5p were not differentially expressed in PBMCs.	('miR122', 'Gene', '406906', (94, 100))	('miR192', 'Gene', '406967', (113, 119))	('miR885', 'Gene', '100126334', (124, 130))	('miR140-3p', 'Var', (102, 111))	('miR192', 'Gene', (113, 119))	('miR122', 'Gene', (94, 100))	('miR140-3p', 'Chemical', '-', (102, 111))	('miR885', 'Gene', (124, 130))
44760	24637658	MiRNA-15b and miR20b are two of the miRNAs found at lower levels in MG patients.	('patients', 'Species', '9606', (71, 79))	('MiRNA-15b', 'Var', (0, 9))	('miR20b', 'Gene', '574032', (14, 20))	('miR', 'Gene', '220972', (14, 17))	('miR', 'Gene', (14, 17))	('miR', 'Gene', '220972', (36, 39))	('miR20b', 'Gene', (14, 20))	('miR', 'Gene', (36, 39))
44767	24637658	When B cells have low levels of miR185, cells produce high titers of autoreactive antibodies and lead to autoimmune features in mice.	('autoreactive', 'Protein', (69, 81))	('mice', 'Species', '10090', (128, 132))	('miR185', 'Var', (32, 38))	('titers', 'MPA', (59, 65))	('autoimmune features', 'Phenotype', 'HP:0002960', (105, 124))	('autoimmune features', 'CPA', (105, 124))	('lead to', 'Reg', (97, 104))
44913	31360225	Small-scale clinical studies have shown significant improvements in respiratory function and muscle strength in thymectomized patients after PLEX.	('improvements', 'PosReg', (52, 64))	('muscle strength', 'CPA', (93, 108))	('PLEX', 'Var', (141, 145))	('men', 'Species', '9606', (59, 62))	('patients', 'Species', '9606', (126, 134))	('respiratory function', 'CPA', (68, 88))
44929	31360225	Thymectomy was indicated in generalized forms of anti-AChR-positive MG, in patients under 55-years old, and in all patients with thymoma, regardless of age.	('patients', 'Species', '9606', (115, 123))	('thymoma', 'Disease', (129, 136))	('patients', 'Species', '9606', (75, 83))	('thymoma', 'Phenotype', 'HP:0100522', (129, 136))	('anti-AChR-positive', 'Var', (49, 67))	('thymoma', 'Disease', 'MESH:D013945', (129, 136))
45040	27816689	The final histopathology confirmed the diagnosis of stage IIA poorly differentiated squamous cell carcinoma p-G3, p-T2, p-N0, p-R0.	('p-N0', 'Var', (120, 124))	('p-T2', 'Var', (114, 118))	('p-G3', 'Var', (108, 112))	('carcinoma', 'Phenotype', 'HP:0030731', (98, 107))	('squamous cell carcinoma', 'Phenotype', 'HP:0002860', (84, 107))	('squamous cell carcinoma', 'Disease', (84, 107))	('squamous cell carcinoma', 'Disease', 'MESH:D002294', (84, 107))
45131	25346762	Specific immunohistochemical markers and chromosomal gains and losses might be necessary in some cases to distinguish these tumors from other lung carcinomas.	('tumor', 'Phenotype', 'HP:0002664', (124, 129))	('lung carcinomas', 'Disease', (142, 157))	('tumors', 'Disease', 'MESH:D009369', (124, 130))	('tumors', 'Disease', (124, 130))	('tumors', 'Phenotype', 'HP:0002664', (124, 130))	('chromosomal gains', 'Var', (41, 58))	('lung carcinomas', 'Disease', 'MESH:D008175', (142, 157))	('carcinoma', 'Phenotype', 'HP:0030731', (147, 156))	('carcinomas', 'Phenotype', 'HP:0030731', (147, 157))	('losses', 'NegReg', (63, 69))
45305	25592632	Overexpression of KIT has been reported in about 80% of thymic carcinomas, and mutations in the gene encoding this receptor are noted in about 10% of these cancers.	('cancers', 'Phenotype', 'HP:0002664', (156, 163))	('carcinomas', 'Phenotype', 'HP:0030731', (63, 73))	('KIT', 'Gene', (18, 21))	('cancers', 'Disease', (156, 163))	('reported', 'Reg', (31, 39))	('cancers', 'Disease', 'MESH:D009369', (156, 163))	('thymic carcinomas', 'Disease', 'MESH:D013945', (56, 73))	('cancer', 'Phenotype', 'HP:0002664', (156, 162))	('carcinoma', 'Phenotype', 'HP:0030731', (63, 72))	('thymic carcinomas', 'Disease', (56, 73))	('mutations', 'Var', (79, 88))
45436	25592632	At the same time, findings of clinical trials have validated that blockade of PD-L1/PD-1 signalling and CTLA4 is a meaningful therapeutic regimen in selected cancers.	('PD-L1', 'Gene', (78, 83))	('cancers', 'Phenotype', 'HP:0002664', (158, 165))	('cancers', 'Disease', (158, 165))	('cancers', 'Disease', 'MESH:D009369', (158, 165))	('blockade', 'Var', (66, 74))	('PD-L1', 'Gene', '29126', (78, 83))	('CTLA4', 'Gene', (104, 109))	('cancer', 'Phenotype', 'HP:0002664', (158, 164))
45449	25592632	Analyses of existing scientific literature suggest that alterations in KIT, although frequent, might not be a determinant response to sunitinib in thymic carcinoma.	('alterations', 'Var', (56, 67))	('KIT', 'Gene', (71, 74))	('carcinoma', 'Phenotype', 'HP:0030731', (154, 163))	('thymic carcinoma', 'Disease', (147, 163))	('thymic carcinoma', 'Disease', 'MESH:D013945', (147, 163))	('sunitinib', 'Chemical', 'MESH:D000077210', (134, 143))
45461	23444221	Copy number aberrations of genes regulating normal thymus development in thymic epithelial tumors To determine if the deregulation of genes relevant for normal thymus development can contribute to the biology of thymic epithelial tumors.	('tumors', 'Phenotype', 'HP:0002664', (91, 97))	('thymic epithelial tumors', 'Disease', (212, 236))	('thymic epithelial tumors', 'Disease', 'MESH:C536905', (212, 236))	('tumors', 'Phenotype', 'HP:0002664', (230, 236))	('tumor', 'Phenotype', 'HP:0002664', (91, 96))	('thymic epithelial tumors', 'Disease', 'MESH:C536905', (73, 97))	('thymic epithelial tumors', 'Disease', (73, 97))	('tumor', 'Phenotype', 'HP:0002664', (230, 235))	('Copy number aberrations', 'Var', (0, 23))
45466	23444221	Immunohistochemistry on a series of 132 thymic epithelial tumors including those evaluated by comparative genomic hybridization, revealed a correlation between protein expression and copy number status only for FOXC1 but not for PBX1.	('PBX1', 'Gene', (229, 233))	('tumor', 'Phenotype', 'HP:0002664', (58, 63))	('correlation', 'Interaction', (140, 151))	('copy number status', 'Var', (183, 201))	('tumors', 'Phenotype', 'HP:0002664', (58, 64))	('PBX1', 'Gene', '5087', (229, 233))	('thymic epithelial tumors', 'Disease', 'MESH:C536905', (40, 64))	('FOXC1', 'Gene', (211, 216))	('protein expression', 'MPA', (160, 178))	('thymic epithelial tumors', 'Disease', (40, 64))
45477	23444221	Several cell lineage-specific transcription factors, implicated in organogenesis, have been found to be ectopically reactivated by copy number (CN) aberrations in cancers, including NKX2-1 (TITF) in lung cancer, ESR1 in breast cancer, GATA6 in pancreatic cancer and MITF in melanoma.	('ESR1', 'Gene', (212, 216))	('copy number', 'Var', (131, 142))	('pancreatic cancer', 'Disease', 'MESH:D010190', (244, 261))	('melanoma', 'Disease', 'MESH:D008545', (274, 282))	('breast cancer', 'Phenotype', 'HP:0003002', (220, 233))	('lung cancer', 'Disease', (199, 210))	('cancers', 'Disease', 'MESH:D009369', (163, 170))	('cancer', 'Phenotype', 'HP:0002664', (255, 261))	('GATA6', 'Gene', '2627', (235, 240))	('breast cancer', 'Disease', 'MESH:D001943', (220, 233))	('pancreatic cancer', 'Disease', (244, 261))	('breast cancer', 'Disease', (220, 233))	('lung cancer', 'Disease', 'MESH:D008175', (199, 210))	('MITF', 'Gene', '4286', (266, 270))	('aberrations', 'Var', (148, 159))	('melanoma', 'Phenotype', 'HP:0002861', (274, 282))	('NKX2-1', 'Gene', '7080', (182, 188))	('melanoma', 'Disease', (274, 282))	('cancer', 'Phenotype', 'HP:0002664', (204, 210))	('lung cancer', 'Phenotype', 'HP:0100526', (199, 210))	('pancreatic cancer', 'Phenotype', 'HP:0002894', (244, 261))	('NKX2-1', 'Gene', (182, 188))	('MITF', 'Gene', (266, 270))	('cancers', 'Phenotype', 'HP:0002664', (163, 170))	('GATA6', 'Gene', (235, 240))	('cancers', 'Disease', (163, 170))	('cancer', 'Phenotype', 'HP:0002664', (227, 233))	('cancer', 'Phenotype', 'HP:0002664', (163, 169))	('ESR1', 'Gene', '2099', (212, 216))
45498	23444221	Positive controls were stained with anti-FOXC1 and anti-PBX1 antibodies and negative controls using respective isogenic serum instead of the primary antibodies.	('PBX1', 'Gene', '5087', (56, 60))	('PBX1', 'Gene', (56, 60))	('anti-FOXC1', 'Var', (36, 46))
45501	23444221	TY82 thymic carcinoma cell line was purchased from Japan Health Science Foundation (Tokyo), whereas, NIH-H82, NIH-H69, NIH-H23, NIH-H460, NIH-H1355, HEK-293, NIH-3T3 and U2OS were obtained from ATCC (Manassas, VA).	('HEK-293', 'CellLine', 'CVCL:0045', (149, 156))	('thymic carcinoma', 'Disease', (5, 21))	('NIH-H23', 'Var', (119, 126))	('NIH-3T3', 'CellLine', 'CVCL:0594', (158, 165))	('NIH-H1355', 'CellLine', 'CVCL:1464', (138, 147))	('thymic carcinoma', 'Disease', 'MESH:D013945', (5, 21))	('carcinoma', 'Phenotype', 'HP:0030731', (12, 21))	('NIH-H69', 'CellLine', 'CVCL:0601', (110, 117))	('NIH-H460', 'Var', (128, 136))	('NIH-H23', 'CellLine', 'CVCL:0601', (119, 126))	('NIH-H82', 'CellLine', 'CVCL:0601', (101, 108))	('U2OS', 'CellLine', 'CVCL:0042', (170, 174))	('NIH-H82', 'Var', (101, 108))	('NIH-H460', 'CellLine', 'CVCL:0459', (128, 136))
45504	23444221	Protein extraction and western blot were performed as previously described using anti-N-terminal-FOXC1 (1:200, overnight 4 C incubation, Santa Cruz biotecgnology, Inc., Santa Cruz CA), anti-PBX1 (1:1000, overnight 4 C incubation, Cell Signaling Technology, Danvers, MA) anti-TBX1 (1:1000, overnight 4 C incubation, Epitomics, Burlingame, CA) and anti-alpha-Tubulin (1:2000, 1-hour room temperature incubation, Cell Signaling) antibodies, respectively.	('PBX1', 'Gene', (190, 194))	('alpha-Tubulin', 'Gene', (351, 364))	('PBX1', 'Gene', '5087', (190, 194))	('alpha-Tubulin', 'Gene', '10376', (351, 364))	('1:1000', 'Var', (281, 287))
45511	23444221	The CN loss of chromosome 6p has also been described in another case of A thymoma by Zetel et al..	('CN loss', 'Var', (4, 11))	('thymoma', 'Phenotype', 'HP:0100522', (74, 81))	('A thymoma', 'Disease', 'MESH:D013945', (72, 81))	('A thymoma', 'Disease', (72, 81))
45516	23444221	PBX1 CN gain was a more frequent event in aggressive histotypes (B2+B2/B3, B3 and TC) than in A and AB (Fisher exact test p<0.001; Figure 2D), and in relapsed tumors than in primary tumors (chi2 test p=0.027).	('primary tumors', 'Disease', (174, 188))	('tumors', 'Phenotype', 'HP:0002664', (182, 188))	('tumor', 'Phenotype', 'HP:0002664', (159, 164))	('primary tumors', 'Disease', 'MESH:D009369', (174, 188))	('PBX1', 'Gene', (0, 4))	('tumors', 'Disease', (182, 188))	('tumors', 'Disease', 'MESH:D009369', (182, 188))	('tumors', 'Disease', (159, 165))	('relapsed', 'Disease', (150, 158))	('tumors', 'Phenotype', 'HP:0002664', (159, 165))	('B2+B2/B3', 'Var', (65, 73))	('tumors', 'Disease', 'MESH:D009369', (159, 165))	('gain', 'PosReg', (8, 12))	('tumor', 'Phenotype', 'HP:0002664', (182, 187))	('PBX1', 'Gene', '5087', (0, 4))
45521	23444221	Chromosome 6p23.5 (FOXC1) deletion was evaluated in 6 tumors with and 5 without CN loss, according to CGH results.	('tumors', 'Disease', 'MESH:D009369', (54, 60))	('deletion', 'Var', (26, 34))	('tumor', 'Phenotype', 'HP:0002664', (54, 59))	('FOXC1', 'Gene', (19, 24))	('tumors', 'Disease', (54, 60))	('tumors', 'Phenotype', 'HP:0002664', (54, 60))
45533	23444221	No correlation was observed between copy number gain of the PBX1 locus and PBX1 protein expression by immunohistochemistry (p=0.575).	('PBX1', 'Gene', (60, 64))	('copy number', 'Var', (36, 47))	('PBX1', 'Gene', (75, 79))	('protein', 'Protein', (80, 87))	('PBX1', 'Gene', '5087', (60, 64))	('PBX1', 'Gene', '5087', (75, 79))	('expression', 'MPA', (88, 98))
45537	23444221	More aggressive histotypes (B1/B2, B2, B2/B3, B3 and TC) exhibited higher frequency of PBX1 expression (42.9%; 24/56) than less aggressive ones (A, AB, B1) (13.6%; 8/59; Fisher exact test p=0.001).	('higher', 'PosReg', (67, 73))	('B2/B3', 'Var', (39, 44))	('PBX1', 'Gene', '5087', (87, 91))	('PBX1', 'Gene', (87, 91))	('expression', 'MPA', (92, 102))
45539	23444221	Since FOXC1 gene mutations have been shown in endometrial and ovarian cancers, we sequenced the entire FOXC1 coding region in the 59 FFPE TET samples analyzed by CGH and in the three TET cell lines.	('cancer', 'Phenotype', 'HP:0002664', (70, 76))	('FOXC1', 'Gene', (103, 108))	('endometrial and ovarian cancers', 'Disease', 'MESH:D016889', (46, 77))	('shown', 'Reg', (37, 42))	('ovarian cancers', 'Phenotype', 'HP:0100615', (62, 77))	('cancers', 'Phenotype', 'HP:0002664', (70, 77))	('FOXC1', 'Gene', (6, 11))	('mutations', 'Var', (17, 26))
45542	23444221	One AB thymoma carried a glycine insertion in another poly-glycine region between amino acid 375 and 380.	('glycine', 'Chemical', 'MESH:D005998', (25, 32))	('glycine', 'Chemical', 'MESH:D005998', (59, 66))	('AB thymoma', 'Disease', (4, 14))	('poly-glycine', 'Chemical', 'MESH:C011080', (54, 66))	('glycine insertion', 'Var', (25, 42))	('thymoma', 'Phenotype', 'HP:0100522', (7, 14))	('AB thymoma', 'Disease', 'MESH:D013945', (4, 14))
45552	23444221	If FOXC1 is a genuine tumor suppressor gene, reconstitution of FOXC1 into these cells should impede cell growth.	('cell growth', 'CPA', (100, 111))	('FOXC1', 'Gene', (3, 8))	('impede', 'NegReg', (93, 99))	('tumor', 'Disease', 'MESH:D009369', (22, 27))	('tumor', 'Phenotype', 'HP:0002664', (22, 27))	('tumor', 'Disease', (22, 27))	('FOXC1', 'Gene', (63, 68))	('reconstitution', 'Var', (45, 59))
45553	23444221	Soft agar assay showed that constitutive expression of FOXC1 in U2OS cells significantly reduced the number of colony outgrowth in comparison to the vector-transfected clones and U2OS parental cells (Figure 4D-E).	('U2OS', 'CellLine', 'CVCL:0042', (179, 183))	('FOXC1', 'Gene', (55, 60))	('reduced', 'NegReg', (89, 96))	('expression', 'Var', (41, 51))	('U2OS', 'CellLine', 'CVCL:0042', (64, 68))	('agar', 'Chemical', 'MESH:D000362', (5, 9))
45558	23444221	Lineage-specific transcription factors, implicated in organogenesis, have been found deregulated by CN aberrations and they have been demonstrated to be able to drive the cancer phenotype.	('aberrations', 'Var', (103, 114))	('cancer', 'Disease', 'MESH:D009369', (171, 177))	('drive', 'PosReg', (161, 166))	('deregulated', 'NegReg', (85, 96))	('cancer', 'Disease', (171, 177))	('cancer', 'Phenotype', 'HP:0002664', (171, 177))
45560	23444221	Subjects carrying the 22q11.2 deletion syndrome present variable pathologic phenotypes at birth including cardiac defects, abnormal faces, thymic hypoplasia, cleft palate and hypocalcaemia.	('thymic hypoplasia', 'Phenotype', 'HP:0000777', (139, 156))	('cardiac defects', 'Disease', 'MESH:D006331', (106, 121))	('cleft palate', 'Disease', 'MESH:D002972', (158, 170))	('abnormal faces', 'Phenotype', 'HP:0000271', (123, 137))	('cleft palate', 'Phenotype', 'HP:0000175', (158, 170))	('cardiac defects', 'Disease', (106, 121))	('hypocalcaemia', 'Phenotype', 'HP:0002901', (175, 188))	('hypocalcaemia', 'Disease', (175, 188))	('hypocalcaemia', 'Disease', 'None', (175, 188))	('deletion syndrome', 'Var', (30, 47))	('thymic hypoplasia', 'Disease', 'MESH:D013953', (139, 156))	('abnormal faces', 'Disease', (123, 137))	('thymic hypoplasia', 'Disease', (139, 156))	('cleft palate', 'Disease', (158, 170))
45567	23444221	In vitro, TBX1 expression restores contact inhibition and reduces anchorage-independent cell growth in soft agar.	('anchorage-independent cell growth in soft agar', 'CPA', (66, 112))	('TBX1', 'Gene', (10, 14))	('reduces', 'NegReg', (58, 65))	('expression', 'Var', (15, 25))	('restores', 'PosReg', (26, 34))	('agar', 'Chemical', 'MESH:D000362', (108, 112))	('contact inhibition', 'MPA', (35, 53))
45568	23444221	In vivo, the ectopic expression of TBX1 suppresses the growth of skin carcinoma cells.	('carcinoma', 'Phenotype', 'HP:0030731', (70, 79))	('skin carcinoma', 'Disease', (65, 79))	('skin carcinoma', 'Disease', 'MESH:D012878', (65, 79))	('suppresses', 'NegReg', (40, 50))	('TBX1', 'Gene', (35, 39))	('ectopic expression', 'Var', (13, 31))
45573	23444221	In contrast, CN gain of PBX1 is involved in a large region of CN gain of the whole chromosome 1q, being 1q CN gain a frequent event in TETs.	('PBX1', 'Gene', '5087', (24, 28))	('gain', 'PosReg', (65, 69))	('CN gain', 'Var', (13, 20))	('PBX1', 'Gene', (24, 28))
45576	23444221	FOXC1 expression was reduced in TETs with the CN loss, but PBX1 expression was not increased in tumors with CN gain.	('reduced', 'NegReg', (21, 28))	('PBX1', 'Gene', '5087', (59, 63))	('tumor', 'Phenotype', 'HP:0002664', (96, 101))	('CN loss', 'Var', (46, 53))	('tumors', 'Disease', (96, 102))	('PBX1', 'Gene', (59, 63))	('expression', 'MPA', (6, 16))	('tumors', 'Phenotype', 'HP:0002664', (96, 102))	('tumors', 'Disease', 'MESH:D009369', (96, 102))	('FOXC1', 'Gene', (0, 5))
45582	23444221	The extra-glycine insertions in polyglycine regions (of 6 and 10-glycine) were observed in three tumors and have been previously described as polymorphisms, thus unlikely affecting the protein function.	('glycine', 'Chemical', 'MESH:D005998', (65, 72))	('glycine', 'Chemical', 'MESH:D005998', (10, 17))	('tumor', 'Phenotype', 'HP:0002664', (97, 102))	('6 and 10-glycine', 'Chemical', '-', (56, 72))	('polyglycine', 'Chemical', 'MESH:C011080', (32, 43))	('tumors', 'Disease', (97, 103))	('tumors', 'Phenotype', 'HP:0002664', (97, 103))	('glycine', 'Chemical', 'MESH:D005998', (36, 43))	('observed', 'Reg', (79, 87))	('extra-glycine insertions', 'Var', (4, 28))	('tumors', 'Disease', 'MESH:D009369', (97, 103))
45583	23444221	Methylation of FOXC1 promoter is a candidate mechanism for repression of FOXC1 expression in tumors without FOXC1 CN loss, since FOXC1 promoter methylation has been described in other cancer types and correlated with FOXC1 silencing.	('cancer', 'Disease', (184, 190))	('tumor', 'Phenotype', 'HP:0002664', (93, 98))	('Methylation', 'Var', (0, 11))	('methylation', 'Var', (144, 155))	('tumors', 'Disease', 'MESH:D009369', (93, 99))	('cancer', 'Phenotype', 'HP:0002664', (184, 190))	('FOXC1', 'Gene', (129, 134))	('FOXC1', 'Gene', (73, 78))	('tumors', 'Phenotype', 'HP:0002664', (93, 99))	('FOXC1 CN loss', 'Disease', 'MESH:D015431', (108, 121))	('FOXC1 CN loss', 'Disease', (108, 121))	('repression', 'NegReg', (59, 69))	('tumors', 'Disease', (93, 99))	('cancer', 'Disease', 'MESH:D009369', (184, 190))	('silencing', 'NegReg', (223, 232))
45587	23444221	To evaluate the functional significance of FOXC1 deletion in TETs, we reconstituted FOXC1-negative U2OS cells, and demonstrated that ectopic FOXC1 attenuated anchorage-independent growth and motility of U2OS cells in vitro, suggesting that FOXC1 may act as a tumor growth suppressor gene.	('attenuated', 'NegReg', (147, 157))	('tumor', 'Disease', (259, 264))	('U2OS', 'CellLine', 'CVCL:0042', (203, 207))	('anchorage-independent growth', 'CPA', (158, 186))	('tumor', 'Disease', 'MESH:D009369', (259, 264))	('ectopic', 'Var', (133, 140))	('FOXC1', 'Gene', (141, 146))	('tumor', 'Phenotype', 'HP:0002664', (259, 264))	('deletion', 'Var', (49, 57))	('FOXC1', 'Gene', (43, 48))	('U2OS', 'CellLine', 'CVCL:0042', (99, 103))
45592	23444221	Ectopic FOXC1 overexpression in breast cancer cell lines increases cell proliferation, invasion and migration.	('breast cancer', 'Disease', (32, 45))	('breast cancer', 'Phenotype', 'HP:0003002', (32, 45))	('migration', 'CPA', (100, 109))	('cancer', 'Phenotype', 'HP:0002664', (39, 45))	('FOXC1', 'Gene', (8, 13))	('Ectopic', 'Var', (0, 7))	('increases', 'PosReg', (57, 66))	('invasion', 'CPA', (87, 95))	('breast cancer', 'Disease', 'MESH:D001943', (32, 45))	('cell proliferation', 'CPA', (67, 85))	('overexpression', 'PosReg', (14, 28))
45599	23444221	We evaluated the copy number (CN) aberrations of genes involved in normal thymus development in thymic epithelial tumors, following the intriguing idea that the ectopic deregulation of genes relevant for proliferation and differentiation of embryonic cells, can contribute to tumor growth.	('tumor', 'Disease', 'MESH:D009369', (114, 119))	('tumor', 'Disease', 'MESH:D009369', (276, 281))	('tumor', 'Phenotype', 'HP:0002664', (114, 119))	('tumor', 'Phenotype', 'HP:0002664', (276, 281))	('copy number', 'Var', (17, 28))	('tumor', 'Disease', (114, 119))	('thymic epithelial tumors', 'Disease', (96, 120))	('tumor', 'Disease', (276, 281))	('contribute', 'Reg', (262, 272))	('thymic epithelial tumors', 'Disease', 'MESH:C536905', (96, 120))	('tumors', 'Phenotype', 'HP:0002664', (114, 120))
45698	19604398	B1 to B2, or B2 to B3) may lead to different categorisation, especially in highly biological active tumors such as B3 thymomas.	('tumor', 'Phenotype', 'HP:0002664', (100, 105))	('B2 to B3', 'Var', (13, 21))	('thymoma', 'Phenotype', 'HP:0100522', (118, 125))	('highly biological active', 'MPA', (75, 99))	('tumors', 'Disease', (100, 106))	('thymomas', 'Disease', (118, 126))	('thymomas', 'Disease', 'MESH:D013945', (118, 126))	('tumors', 'Disease', 'MESH:D009369', (100, 106))	('tumors', 'Phenotype', 'HP:0002664', (100, 106))	('lead to', 'Reg', (27, 34))
45701	19604398	There is a significant difference between cancer-related survival for patients according to WHO classification A-B2 and B3-C. Prognosis is good in patients with type A to B2 thymomas with no tumor related death.	('patients', 'Species', '9606', (70, 78))	('tumor', 'Disease', 'MESH:D009369', (191, 196))	('cancer', 'Phenotype', 'HP:0002664', (42, 48))	('thymomas', 'Disease', 'MESH:D013945', (174, 182))	('type A', 'Disease', (161, 167))	('thymoma', 'Phenotype', 'HP:0100522', (174, 181))	('thymomas', 'Disease', (174, 182))	('patients', 'Species', '9606', (147, 155))	('cancer', 'Disease', (42, 48))	('tumor', 'Disease', (191, 196))	('cancer', 'Disease', 'MESH:D009369', (42, 48))	('tumor', 'Phenotype', 'HP:0002664', (191, 196))	('B3-C.', 'Var', (120, 125))	('death', 'Disease', 'MESH:D003643', (205, 210))	('death', 'Disease', (205, 210))
46009	27684107	An ELISA assay (Kansas City Analytical Services) was used to measure the following vaccination induced and natural protective antibodies in serum: anti-tetanus toxoid IgG, anti-diphtheria toxoid IgG, anti-varicella zoster virus IgG and anti-Epstein Barr virus viral capsid antigen IgG.	('tetanus', 'Disease', 'MESH:D013746', (152, 159))	('Epstein Barr virus', 'Species', '10376', (241, 259))	('anti-varicella', 'Var', (200, 214))	('tetanus', 'Disease', (152, 159))	('varicella zoster', 'Phenotype', 'HP:0032170', (205, 221))
46037	27684107	Some investigators have suggested that the potential for an overshoot makes TPE a suboptimal acute therapy in autoimmune diseases compared with IVIg due to the potential for worsening of disease related to the overshoot.	('TPE', 'Var', (76, 79))	('autoimmune diseases', 'Disease', (110, 129))	('autoimmune disease', 'Phenotype', 'HP:0002960', (110, 128))	('autoimmune diseases', 'Disease', 'MESH:D001327', (110, 129))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (110, 129))
46058	27684107	In this study of patients with AChR MG, we show that TPE rapidly lowers all Igs, including AChR-Ab and protective Abs.	('Igs', 'Disease', (76, 79))	('AChR-Ab', 'Disease', (91, 98))	('lowers', 'NegReg', (65, 71))	('TPE', 'Var', (53, 56))	('protective Abs', 'Disease', (103, 117))	('patients', 'Species', '9606', (17, 25))
46152	28491357	Although not well characterised in cats for this purpose, CD4 and CD8 antibodies are available for use in cats and a study in dogs demonstrated that histologically confirmed cases of thymoma contained at least 10% of cells co-expressing CD4 and CD8, while in almost all cases of mediastinal lymphoma, CD4/CD8 co-expression was limited to <2% of lymphocytes.	('mediastinal lymphoma', 'Disease', (279, 299))	('CD4', 'Var', (237, 240))	('thymoma', 'Gene', '7063', (183, 190))	('mediastinal lymphoma', 'Disease', 'MESH:D008480', (279, 299))	('thymoma', 'Phenotype', 'HP:0100522', (183, 190))	('dogs', 'Species', '9615', (126, 130))	('cats', 'Species', '9685', (106, 110))	('lymphoma', 'Phenotype', 'HP:0002665', (291, 299))	('thymoma', 'Gene', (183, 190))	('CD8', 'Var', (245, 248))	('cats', 'Species', '9685', (35, 39))
46192	26358060	Immunohistochemical stains will show positivity for smooth muscle actin and desmin in the majority of cases.	('positivity', 'Var', (37, 47))	('smooth muscle actin', 'Protein', (52, 71))	('desmin', 'Gene', '1674', (76, 82))	('desmin', 'Gene', (76, 82))
46262	26358060	A recurrent genetic aberration in EHE, including mediastinal cases, is translocation of the CAMTA1 gene on chromosome 1p and fusion with the WWTR1 gene on chromosome 3q.	('WWTR1', 'Gene', (141, 146))	('CAMTA1', 'Gene', (92, 98))	('EHE', 'Disease', (34, 37))	('WWTR1', 'Gene', '25937', (141, 146))	('EHE', 'Phenotype', 'HP:0032060', (34, 37))	('fusion', 'Var', (125, 131))	('CAMTA1', 'Gene', '23261', (92, 98))	('translocation', 'Var', (71, 84))
46300	26358060	The differential diagnosis is broad and includes eES/PNET with variant translocations and eES-like tumours unrelated to EWS (small blue round cell tumours), as well as synovial sarcomas and undifferentiated pleomorphic sarcomas with a small cell morphology.	('tumours', 'Phenotype', 'HP:0002664', (99, 106))	('tumours', 'Phenotype', 'HP:0002664', (147, 154))	('tumours', 'Disease', 'MESH:D009369', (99, 106))	('variant translocations', 'Var', (63, 85))	('tumours', 'Disease', 'MESH:D009369', (147, 154))	('ES', 'Phenotype', 'HP:0012254', (50, 52))	('eES/PNET', 'Disease', (49, 57))	('tumour', 'Phenotype', 'HP:0002664', (99, 105))	('tumour', 'Phenotype', 'HP:0002664', (147, 153))	('synovial sarcomas', 'Phenotype', 'HP:0012570', (168, 185))	('synovial sarcomas', 'Disease', (168, 185))	('cell tumours', 'Disease', 'MESH:C538614', (142, 154))	('cell tumours', 'Disease', (142, 154))	('sarcomas', 'Phenotype', 'HP:0100242', (219, 227))	('sarcoma', 'Phenotype', 'HP:0100242', (219, 226))	('undifferentiated pleomorphic sarcomas', 'Disease', 'MESH:D002277', (190, 227))	('undifferentiated pleomorphic sarcomas', 'Disease', (190, 227))	('synovial sarcomas', 'Disease', 'MESH:D013584', (168, 185))	('synovial sarcoma', 'Phenotype', 'HP:0012570', (168, 184))	('sarcoma', 'Phenotype', 'HP:0100242', (177, 184))	('ES', 'Phenotype', 'HP:0012254', (91, 93))	('tumours', 'Disease', (99, 106))	('tumours', 'Disease', (147, 154))	('sarcomas', 'Phenotype', 'HP:0100242', (177, 185))
46329	26358060	Variants of MPNST, which have also been reported in the mediastinum, may show divergent mesenchymal differentiation with components of skeletal muscle (rhabdomyosarcoma, the so-called Triton tumour), osteosarcoma and chondrosarcoma.	('MPNST', 'Phenotype', 'HP:0100697', (12, 17))	('rhabdomyosarcoma', 'Disease', (152, 168))	('Variants', 'Var', (0, 8))	('chondrosarcoma', 'Disease', (217, 231))	('sarcoma', 'Phenotype', 'HP:0100242', (161, 168))	('Triton tumour', 'Disease', (184, 197))	('rhabdomyosarcoma', 'Disease', 'MESH:D012208', (152, 168))	('sarcoma', 'Phenotype', 'HP:0100242', (224, 231))	('Triton tumour', 'Disease', 'MESH:D009369', (184, 197))	('chondrosarcoma', 'Phenotype', 'HP:0006765', (217, 231))	('sarcoma', 'Phenotype', 'HP:0100242', (205, 212))	('osteosarcoma', 'Disease', (200, 212))	('rhabdomyosarcoma', 'Phenotype', 'HP:0002859', (152, 168))	('tumour', 'Phenotype', 'HP:0002664', (191, 197))	('osteosarcoma', 'Phenotype', 'HP:0002669', (200, 212))	('MPNST', 'Gene', (12, 17))	('osteosarcoma', 'Disease', 'MESH:D012516', (200, 212))	('chondrosarcoma', 'Disease', 'MESH:D002813', (217, 231))
46353	26358060	It is conceivable that a number of these tumours may not actually have a normal tissue counterpart but instead reflect the consequence of genetic aberrations in which translocations and other genetic errors culminate in histological patterns, which are not encountered in normal tissue.	('tumour', 'Phenotype', 'HP:0002664', (41, 47))	('tumours', 'Phenotype', 'HP:0002664', (41, 48))	('translocations', 'Var', (167, 181))	('culminate in', 'Reg', (207, 219))	('tumours', 'Disease', 'MESH:D009369', (41, 48))	('tumours', 'Disease', (41, 48))
46396	26358060	The diagnosis was supported by demonstration of a translocation involving the EWSR1 gene by FISH analysis; the partner gene was not identified.	('EWSR1', 'Gene', '2130', (78, 83))	('EWSR1', 'Gene', (78, 83))	('translocation', 'Var', (50, 63))
46460	30932350	revealed alterations of PI3K caused by mutations in a subgroup of thymomas, leading to an effective strategy to treat these tumors by targeting PI3K.6 Enkner et al.	('tumor', 'Phenotype', 'HP:0002664', (124, 129))	('thymomas', 'Disease', (66, 74))	('mutations', 'Var', (39, 48))	('alterations', 'Reg', (9, 20))	('thymomas', 'Disease', 'MESH:D013945', (66, 74))	('tumors', 'Disease', (124, 130))	('tumors', 'Disease', 'MESH:D009369', (124, 130))	('PI3K', 'Gene', (24, 28))	('tumors', 'Phenotype', 'HP:0002664', (124, 130))	('thymoma', 'Phenotype', 'HP:0100522', (66, 73))
46462	30932350	reported mutations in five tyrosine kinase genes (KIT, DDR2, PDGFRA, ROS1, IGF1R).7 However, there is still limited knowledge of the pathogenesis of thymoma.	('thymoma', 'Gene', '7063', (149, 156))	('thymoma', 'Phenotype', 'HP:0100522', (149, 156))	('IGF1R', 'Gene', (75, 80))	('mutations', 'Var', (9, 18))	('ROS1', 'Gene', (69, 73))	('thymoma', 'Gene', (149, 156))	('ROS1', 'Gene', '6098', (69, 73))	('DDR2', 'Gene', '4921', (55, 59))	('IGF1R', 'Gene', '3480', (75, 80))	('PDGFRA', 'Gene', (61, 67))	('PDGFRA', 'Gene', '5156', (61, 67))	('DDR2', 'Gene', (55, 59))
46501	30932350	In conclusion, we successfully identified novel genetic alterations and provide novel molecular profiles for thymoma.	('thymoma', 'Gene', (109, 116))	('thymoma', 'Gene', '7063', (109, 116))	('thymoma', 'Phenotype', 'HP:0100522', (109, 116))	('genetic alterations', 'Var', (48, 67))
46505	26649279	Thymic carcinomas have been found to frequently harbor mutations in epigenetic regulatory genes.	('epigenetic regulatory genes', 'Gene', (68, 95))	('carcinomas', 'Phenotype', 'HP:0030731', (7, 17))	('carcinomas', 'Disease', (7, 17))	('carcinomas', 'Disease', 'MESH:D002277', (7, 17))	('mutations', 'Var', (55, 64))	('harbor', 'Reg', (48, 54))	('carcinoma', 'Phenotype', 'HP:0030731', (7, 16))
46506	26649279	A specific mutation in GTF2I on chromosome 7 is present at a high frequency in World Health Organization (WHO) subtype A and AB thymomas.	('GTF2I', 'Gene', (23, 28))	('GTF2I', 'Gene', '2969', (23, 28))	('AB thymomas', 'Disease', 'MESH:D013945', (125, 136))	('AB thymomas', 'Disease', (125, 136))	('mutation', 'Var', (11, 19))	('thymoma', 'Phenotype', 'HP:0100522', (128, 135))
46617	16784312	In autoimmune polyendocrinopathy syndrome type 1 (APS1; OMIM 240300), recessive AIRE mutations lead to autoimmunity targetting endocrine and other epithelial tissues, although chronic candidiasis usually appears first.	('candidiasis', 'Disease', (184, 195))	('lead to', 'Reg', (95, 102))	('APS1', 'Gene', '326', (50, 54))	('autoimmune polyendocrinopathy syndrome type 1', 'Gene', '326', (3, 48))	('mutations', 'Var', (85, 94))	('autoimmune polyendocrinopathy syndrome type 1', 'Gene', (3, 48))	('candidiasis', 'Disease', 'MESH:D002177', (184, 195))	('AIRE', 'Gene', (80, 84))	('autoimmunity', 'Phenotype', 'HP:0002960', (103, 115))	('APS1', 'Gene', (50, 54))
46621	16784312	Unexpectedly, in 60/60 Finnish and 16/16 Norwegian APS1 patients with both AIRE alleles mutated, we found high titre neutralising immunoglobulin G autoantibodies to most IFN-alpha subtypes and especially IFN-omega (60% homologous to IFN-alpha):mostly in the earliest samples.	('patients', 'Species', '9606', (56, 64))	('IFN-alpha', 'Gene', '3439', (170, 179))	('IFN-alpha', 'Gene', (170, 179))	('neutralising', 'NegReg', (117, 129))	('IFN', 'Gene', (170, 173))	('IFN', 'Gene', (204, 207))	('APS1', 'Gene', '326', (51, 55))	('immunoglobulin G', 'Protein', (130, 146))	('IFN', 'Gene', '3439', (233, 236))	('high titre', 'Phenotype', 'HP:0010702', (106, 116))	('IFN', 'Gene', (233, 236))	('APS1', 'Gene', (51, 55))	('mutated', 'Var', (88, 95))	('IFN-alpha', 'Gene', (233, 242))	('IFN', 'Gene', '3439', (204, 207))	('IFN-alpha', 'Gene', '3439', (233, 242))	('IFN', 'Gene', '3439', (170, 173))
46625	16784312	Anti-type I IFN autoantibodies preceded overt candidiasis (and several of the autoimmune disorders) in the informative patients, and persisted for decades thereafter.	('IFN', 'Gene', (12, 15))	('candidiasis', 'Disease', 'MESH:D002177', (46, 57))	('candidiasis', 'Disease', (46, 57))	('autoimmune disorders', 'Disease', 'MESH:D001327', (78, 98))	('IFN', 'Gene', '3439', (12, 15))	('patients', 'Species', '9606', (119, 127))	('overt candidiasis', 'Phenotype', 'HP:0005411', (40, 57))	('Anti-type', 'Var', (0, 9))	('autoimmune disorders', 'Phenotype', 'HP:0002960', (78, 98))	('autoimmune disorders', 'Disease', (78, 98))
46637	16784312	Patients with this rare disease characteristically have defects (or mutations) in both copies of a gene called AIRE (for autoimmune regulator).	('autoimmune regulator', 'Gene', (121, 141))	('autoimmune regulator', 'Gene', '326', (121, 141))	('defects', 'Var', (56, 63))	('Patients', 'Species', '9606', (0, 8))	('AIRE', 'Gene', (111, 115))	('mutations', 'Var', (68, 77))
46639	16784312	People carrying AIRE mutations make an autoimmune response against some of their own tissues, typically the endocrine (hormone-producing) tissues that control body metabolism.	('autoimmune response', 'Phenotype', 'HP:0002960', (39, 58))	('AIRE', 'Gene', (16, 20))	('People', 'Species', '9606', (0, 6))	('mutations', 'Var', (21, 30))
46688	16784312	As healthy and disease controls, we tested sera from ten AIRE-heterozygous unaffected first-degree relatives (six from Finland with R257X allele and four from Norway:two with R257X, one with 12421243insA, and one with 967/979del13 alleles) and from patients with APS2 (n = 9) or sporadic AD (n = 11), HP (n = 2), or CMC (n = 3):all without APS1.	('HP', 'Phenotype', 'HP:0000829', (301, 303))	('CMC', 'Phenotype', 'HP:0002728', (316, 319))	('tested', 'Reg', (36, 42))	('patients', 'Species', '9606', (249, 257))	('AD', 'Disease', 'MESH:D000544', (288, 290))	('AD', 'Disease', (288, 290))	('R257X', 'Mutation', 'rs121434254', (132, 137))	('APS2', 'Gene', (263, 267))	('APS1', 'Gene', (340, 344))	('967/979del13', 'Mutation', 'c.967/979del13', (218, 230))	('R257X', 'Mutation', 'rs121434254', (175, 180))	('AD', 'Phenotype', 'HP:0008207', (288, 290))	('R257X', 'Var', (175, 180))	('APS2', 'Gene', '170685', (263, 267))	('APS1', 'Gene', '326', (340, 344))	('12421243insA', 'Mutation', 'c.12421243insA', (191, 203))
46689	16784312	Six patients with sporadic AD and eight patients with APS2 were found negative for the two most common APS1 AIRE mutations, R257X and 967/979del13.	('967/979del13', 'Var', (134, 146))	('AD', 'Phenotype', 'HP:0008207', (27, 29))	('R257X', 'Mutation', 'rs121434254', (124, 129))	('patients', 'Species', '9606', (40, 48))	('APS1', 'Gene', '326', (103, 107))	('R257X', 'Var', (124, 129))	('AD', 'Disease', 'MESH:D000544', (27, 29))	('APS2', 'Gene', (54, 58))	('APS2', 'Gene', '170685', (54, 58))	('patients', 'Species', '9606', (4, 12))	('APS1', 'Gene', (103, 107))	('967/979del13', 'Mutation', 'c.967/979del13', (134, 146))	('AD', 'Disease', (27, 29))
46701	16784312	Buffy coats were collected from an APS1 patient with an R257X mutation in one AIRE allele and 967/979del13 in the other, and from two healthy blood donors; the buffy coats were washed and then cryopreserved in liquid nitrogen.	('patient', 'Species', '9606', (40, 47))	('R257X mutation', 'Var', (56, 70))	('967/979del13', 'Mutation', 'c.967/979del13', (94, 106))	('APS1', 'Gene', '326', (35, 39))	('nitrogen', 'Chemical', 'MESH:D009584', (217, 225))	('APS1', 'Gene', (35, 39))	('R257X', 'Mutation', 'rs121434254', (56, 61))
46709	16784312	We first screened for anti-IFN autoantibodies in 60 typical Finnish APS1 patients with both AIRE alleles mutated, and then in 16 such patients from Norway (Table 2).	('IFN', 'Gene', '3439', (27, 30))	('APS1', 'Gene', (68, 72))	('patients', 'Species', '9606', (134, 142))	('mutated', 'Var', (105, 112))	('IFN', 'Gene', (27, 30))	('APS1', 'Gene', '326', (68, 72))	('patients', 'Species', '9606', (73, 81))
46727	16784312	All 60 genotyped APS1 Finnish patients with mutations in both AIRE alleles had at least one R257X allele:which is the predominant Finnish mutation :whereas 12 of the 16 patients from Norway had at least one 967/979del13 mutation (Table 1).	('patients', 'Species', '9606', (169, 177))	('967/979del13', 'Mutation', 'c.967/979del13', (207, 219))	('APS1', 'Gene', (17, 21))	('R257X', 'Mutation', 'rs121434254', (92, 97))	('patients', 'Species', '9606', (30, 38))	('mutations', 'Var', (44, 53))	('APS1', 'Gene', '326', (17, 21))
46730	16784312	Titres were high in the one patient with only one identified AIRE mutation (Table 1; "x" in Figure 1B) and even in two of the four individuals with no detected AIRE mutations ("y" and "z" in Figure 1B); the other two were completely negative against all IFNs tested, but neither had the full APS1 triad by age 39 (patients E and F; see footnote of Table 3) and one (patient F) is the only affected member of a sibship of 14.	('patient', 'Species', '9606', (366, 373))	('patients', 'Species', '9606', (314, 322))	('APS1', 'Gene', '326', (292, 296))	('AIRE', 'Gene', (61, 65))	('patient', 'Species', '9606', (28, 35))	('IFN', 'Gene', '3439', (254, 257))	('mutation', 'Var', (66, 74))	('APS1', 'Gene', (292, 296))	('IFN', 'Gene', (254, 257))	('patient', 'Species', '9606', (314, 321))
46755	16784312	Against IL-12, we also found moderate levels of binding autoantibodies in early sera from only five R257X homozygous patients.	('IL-12', 'Gene', (8, 13))	('patients', 'Species', '9606', (117, 125))	('R257X', 'Mutation', 'rs121434254', (100, 105))	('R257X', 'Var', (100, 105))
46756	16784312	Only in one of patient did the anti-IL-12 antibodies precede the anti-IFN antibodies (patient A; Table 3), and only in one other did they persist (for ~6 y).	('IFN', 'Gene', (70, 73))	('anti-IL-12', 'Var', (31, 41))	('patient', 'Species', '9606', (15, 22))	('patient', 'Species', '9606', (86, 93))	('IFN', 'Gene', '3439', (70, 73))
46770	16784312	Normally, these highly specialised APCs play a key role in antibody diversification by retaining and displaying native antigens that select and stimulate germinal centre B cells as their antibodies mutate.	('germinal centre B cells', 'CPA', (154, 177))	('stimulate', 'PosReg', (144, 153))	('APC', 'Disease', 'MESH:D011125', (35, 38))	('APC', 'Disease', (35, 38))	('mutate', 'Var', (198, 204))
46782	16784312	It now appears that APS1 is even more variable than previously realised; one or more of the characteristic "APS1 triad" (CMC, HP, and AD) may be missing (e.g., Tables 1 and 2):even in patients with both AIRE alleles mutated.	('CMC', 'Phenotype', 'HP:0002728', (121, 124))	('HP', 'Phenotype', 'HP:0000829', (126, 128))	('APS1', 'Gene', '326', (20, 24))	('patients', 'Species', '9606', (184, 192))	('AD', 'Disease', 'MESH:D000544', (134, 136))	('APS1', 'Gene', '326', (108, 112))	('AD', 'Disease', (134, 136))	('APS1', 'Gene', (20, 24))	('AD', 'Phenotype', 'HP:0008207', (134, 136))	('APS1', 'Gene', (108, 112))	('mutated', 'Var', (216, 223))
46785	16784312	In addition, they were clearly negative in two further clinically doubtful cases with no AIRE mutations detected (patients E and F see footnote of Table 3), and in unaffected parents or siblings.	('patients', 'Species', '9606', (114, 122))	('negative', 'NegReg', (31, 39))	('AIRE', 'Gene', (89, 93))	('mutations', 'Var', (94, 103))
46788	16784312	In theory, the anti-type I IFN antibodies might predispose to candidiasis.	('candidiasis', 'Disease', 'MESH:D002177', (62, 73))	('IFN', 'Gene', '3439', (27, 30))	('anti-type', 'Var', (15, 24))	('candidiasis', 'Disease', (62, 73))	('IFN', 'Gene', (27, 30))	('antibodies', 'Var', (31, 41))	('predispose', 'Reg', (48, 58))
46791	16784312	If these mutations predispose via parallel pathways to CMC and anti-IFN responses, the latter might hold clues to some even more crucial common defect upstream.	('IFN', 'Gene', '3439', (68, 71))	('mutations', 'Var', (9, 18))	('IFN', 'Gene', (68, 71))	('CMC', 'Disease', (55, 58))	('predispose', 'Reg', (19, 29))	('CMC', 'Phenotype', 'HP:0002728', (55, 58))
46807	16784312	In marked contrast, anti-IL-12 antibodies were much more common in MG/thymoma patients than in patients with APS1, where their very early transient appearance in a few patients suggests that they might be more prevalent before the onset of APS1.	('APS1', 'Gene', '326', (240, 244))	('APS1', 'Gene', (109, 113))	('patients', 'Species', '9606', (95, 103))	('MG/thymoma', 'Disease', 'MESH:D013945', (67, 77))	('patients', 'Species', '9606', (78, 86))	('MG/thymoma', 'Disease', (67, 77))	('common', 'Reg', (57, 63))	('APS1', 'Gene', '326', (109, 113))	('APS1', 'Gene', (240, 244))	('patients', 'Species', '9606', (168, 176))	('thymoma', 'Phenotype', 'HP:0100522', (70, 77))	('anti-IL-12', 'Var', (20, 30))
46825	16784312	If so, the abnormalities in this process in AIRE-mutant patients:or excessive cell death:might somehow lead to autoimmunisation against autoantigens such as type I IFNs that might be even more abundant in the APS1 than the normal thymus; the above hierarchy might be a valuable clue to help to identify the cell types responsible.	('patients', 'Species', '9606', (56, 64))	('IFN', 'Gene', '3439', (164, 167))	('AIRE-mutant', 'Var', (44, 55))	('autoimmunisation', 'MPA', (111, 127))	('IFN', 'Gene', (164, 167))	('APS1', 'Gene', (209, 213))	('lead to', 'Reg', (103, 110))	('APS1', 'Gene', '326', (209, 213))
46830	16784312	Because they are so APS1-specific and so consistent in this very variable condition, the autoantibodies against IFN-alpha and especially IFN-omega should be valuable diagnostically, e.g., to identify atypical or prodromal APS1 in patients with isolated candidiasis, AD, or HP, and perhaps also for prognosis, if they subsequently prove to predict onset time of the disease.	('IFN', 'Gene', '3439', (137, 140))	('atypical', 'Var', (200, 208))	('IFN', 'Gene', '3439', (112, 115))	('APS1', 'Gene', '326', (20, 24))	('IFN-alpha', 'Gene', (112, 121))	('prodromal', 'Reg', (212, 221))	('IFN', 'Gene', (137, 140))	('AD', 'Phenotype', 'HP:0008207', (266, 268))	('HP', 'Phenotype', 'HP:0000829', (273, 275))	('isolated candidiasis', 'Disease', 'MESH:D002177', (244, 264))	('APS1', 'Gene', (222, 226))	('IFN', 'Gene', (112, 115))	('AD', 'Disease', (266, 268))	('AD', 'Disease', 'MESH:D000544', (266, 268))	('IFN-alpha', 'Gene', '3439', (112, 121))	('patients', 'Species', '9606', (230, 238))	('APS1', 'Gene', (20, 24))	('isolated candidiasis', 'Disease', (244, 264))	('APS1', 'Gene', '326', (222, 226))
46940	29455227	Among 15 cases, an elevated CSF protein level without pleocytosis was found in 10 cases (66.7%); reduced nerve conduction was found in 13 cases (86.6%); a positive repetitive nerve stimulation test occurred in 11 cases (73.3%); anti-AChR antibodies were found in 13 cases (86.6%); anti-GQ1b antibodies were found in 6 cases (40%); a positive edrophonium chloride test was present in 10 cases (66.7%); and a co-occurring thymoma or thymectomy occurred in 4 cases (26.6%).	('elevated CSF protein level without pleocytosis', 'Phenotype', 'HP:0012229', (19, 65))	('anti-GQ1b', 'Var', (281, 290))	('edrophonium chloride', 'Chemical', 'MESH:D004491', (342, 362))	('CSF', 'Gene', '1437', (28, 31))	('reduced nerve conduction', 'Phenotype', 'HP:0000762', (97, 121))	('thymectomy', 'Disease', (431, 441))	('thymoma', 'Phenotype', 'HP:0100522', (420, 427))	('elevated CSF protein', 'Phenotype', 'HP:0002922', (19, 39))	('elevated', 'PosReg', (19, 27))	('edrophonium chloride test', 'MPA', (342, 367))	('CSF', 'Gene', (28, 31))	('thymoma', 'Disease', 'MESH:D013945', (420, 427))	('thymoma', 'Disease', (420, 427))
46946	29455227	Myasthenia gravis (MG) is an autoimmune disorder caused by antibodies against acetylcholine receptors (AchR) targeting the neuromuscular junction, resulting in muscle weakness and fluctuating fatiguability.	('caused by', 'Reg', (49, 58))	('autoimmune disorder caused by antibodies against acetylcholine receptors', 'Phenotype', 'HP:0030208', (29, 101))	('MG', 'Disease', 'MESH:D000080343', (19, 21))	('muscle weakness', 'Phenotype', 'HP:0001324', (160, 175))	('Myasthenia gravis', 'Disease', (0, 17))	('autoimmune disorder', 'Disease', (29, 48))	('fatiguability', 'Disease', 'MESH:D005221', (192, 205))	('antibodies', 'Var', (59, 69))	('Myasthenia gravis', 'Disease', 'MESH:D009157', (0, 17))	('acetylcholine', 'Chemical', 'MESH:D000109', (78, 91))	('autoimmune disorder', 'Disease', 'MESH:D001327', (29, 48))	('AchR', 'Gene', (103, 107))	('muscle weakness', 'Disease', 'MESH:D018908', (160, 175))	('Myasthenia', 'Phenotype', 'HP:0003473', (0, 10))	('fatiguability', 'Disease', (192, 205))	('muscle weakness', 'Disease', (160, 175))	('autoimmune disorder', 'Phenotype', 'HP:0002960', (29, 48))
46953	29455227	One of the most common subtype of GBS, MFS is an immune-mediated neuropathy that involves the triad symptoms of acute ophthalmoplegia, ataxia and areflexia in the presence of anti-GQ1b antibodies.	('ophthalmoplegia', 'Phenotype', 'HP:0000602', (118, 133))	('areflexia', 'Phenotype', 'HP:0001284', (146, 155))	('anti-GQ1b', 'Var', (175, 184))	('MFS', 'Disease', (39, 42))	('neuropathy', 'Disease', 'MESH:D009422', (65, 75))	('neuropathy', 'Phenotype', 'HP:0009830', (65, 75))	('ataxia and areflexia', 'Disease', 'MESH:D019846', (135, 155))	('ataxia', 'Phenotype', 'HP:0001251', (135, 141))	('acute ophthalmoplegia', 'Disease', 'MESH:D009886', (112, 133))	('acute ophthalmoplegia', 'Disease', (112, 133))	('neuropathy', 'Disease', (65, 75))
46960	29455227	Patients with combined GBS and MG were identified and their clinical data (such as gender, age, nationality, past history, precipitating factors, clinical presentations, laboratory examinations, CSF findings, variants of GBS, anti-AChR antibody presence, anti-GQ1b antibody presence, thymoma, treatment and outcome) were all comprehensively evaluated.	('anti-AChR antibody presence', 'Phenotype', 'HP:0032264', (226, 253))	('variants', 'Var', (209, 217))	('thymoma', 'Disease', (284, 291))	('thymoma', 'Phenotype', 'HP:0100522', (284, 291))	('GBS', 'Gene', (221, 224))	('Patients', 'Species', '9606', (0, 8))	('MG', 'Disease', 'MESH:D000080343', (31, 33))	('CSF', 'Gene', (195, 198))	('thymoma', 'Disease', 'MESH:D013945', (284, 291))	('CSF', 'Gene', '1437', (195, 198))
46981	29455227	In accessory examinations, the clinical features, from most to least common, were the presence of anti-AchR antibodies (86.6%), a positive nerve conduction test (86.6%), a positive repetitive nerve stimulation test (73.3%), an elevated CSF protein level in the absence of pleocytosis (66.7%), a positive edrophonium chloride test (66.7%), and the presence of anti-GQ1b antibodies (40%).	('CSF', 'Gene', (236, 239))	('anti-AchR', 'Gene', (98, 107))	('positive', 'Reg', (130, 138))	('positive nerve conduction test', 'Phenotype', 'HP:0040129', (130, 160))	('CSF', 'Gene', '1437', (236, 239))	('edrophonium chloride test', 'MPA', (304, 329))	('nerve conduction test', 'CPA', (139, 160))	('antibodies', 'Var', (108, 118))	('elevated', 'PosReg', (227, 235))	('elevated CSF protein', 'Phenotype', 'HP:0002922', (227, 247))	('anti-GQ1b', 'Protein', (359, 368))	('edrophonium chloride', 'Chemical', 'MESH:D004491', (304, 324))
46995	30871151	Multiomics Analysis Reveals that GLS and GLS2 Differentially Modulate the Clinical Outcomes of Cancer Kidney-type glutaminase (GLS) and liver-type glutaminase (GLS2) are dysregulated in many cancers, making them appealing targets for cancer therapy.	('cancer', 'Phenotype', 'HP:0002664', (234, 240))	('GLS', 'Gene', (160, 163))	('Cancer', 'Disease', 'MESH:D009369', (95, 101))	('GLS', 'Gene', (33, 36))	('GLS', 'Gene', (127, 130))	('cancer', 'Disease', (191, 197))	('cancers', 'Phenotype', 'HP:0002664', (191, 198))	('cancers', 'Disease', (191, 198))	('dysregulated', 'Var', (170, 182))	('cancer', 'Disease', 'MESH:D009369', (234, 240))	('cancer', 'Phenotype', 'HP:0002664', (191, 197))	('GLS2', 'Gene', '27165', (41, 45))	('glutaminase', 'Gene', '2744', (147, 158))	('Cancer', 'Phenotype', 'HP:0002664', (95, 101))	('glutaminase', 'Gene', '2744', (114, 125))	('GLS2', 'Gene', '27165', (160, 164))	('GLS', 'Gene', '2744', (41, 44))	('GLS2', 'Gene', (41, 45))	('GLS2', 'Gene', (160, 164))	('GLS', 'Gene', '2744', (160, 163))	('Cancer', 'Disease', (95, 101))	('cancer', 'Disease', 'MESH:D009369', (191, 197))	('GLS', 'Gene', '2744', (33, 36))	('cancers', 'Disease', 'MESH:D009369', (191, 198))	('Cancer Kidney', 'Phenotype', 'HP:0009726', (95, 108))	('Modulate', 'Reg', (61, 69))	('glutaminase', 'Gene', (147, 158))	('GLS', 'Gene', '2744', (127, 130))	('GLS', 'Gene', (41, 44))	('cancer', 'Disease', (234, 240))	('glutaminase', 'Gene', (114, 125))
46999	30871151	The cross-cancer relationship of glutaminases with mutations and copy number alterations was also investigated.	('glutaminase', 'Gene', (33, 44))	('mutations', 'Var', (51, 60))	('cross-cancer', 'Disease', 'MESH:C537866', (4, 16))	('cancer', 'Phenotype', 'HP:0002664', (10, 16))	('cross-cancer', 'Disease', (4, 16))	('copy number alterations', 'Var', (65, 88))	('glutaminase', 'Gene', '2744', (33, 44))
47012	30871151	Underlying mechanisms aside, modifications in basal enzymatic activity result in potential susceptibilities that could be targeted in cancer treatment.	('basal enzymatic activity', 'MPA', (46, 70))	('cancer', 'Disease', (134, 140))	('cancer', 'Disease', 'MESH:D009369', (134, 140))	('modifications', 'Var', (29, 42))	('susceptibilities', 'MPA', (91, 107))	('cancer', 'Phenotype', 'HP:0002664', (134, 140))
47015	30871151	It is now recognized that the dysregulation of glutamine metabolism is a prominent phenomenon that results in the proliferation of cancer cells.	('cancer', 'Disease', (131, 137))	('dysregulation', 'Var', (30, 43))	('cancer', 'Phenotype', 'HP:0002664', (131, 137))	('glutamine', 'Chemical', 'MESH:D005973', (47, 56))	('proliferation', 'CPA', (114, 127))	('results in', 'Reg', (99, 109))	('glutamine metabolism', 'MPA', (47, 67))	('cancer', 'Disease', 'MESH:D009369', (131, 137))
47042	30871151	In addition, the OncoPrint sub-tool of CBioPortal was used to analyze the integrated status of mutations and CNAs for glutaminases and their functional protein partners.	('glutaminase', 'Gene', '2744', (118, 129))	('mutations', 'Var', (95, 104))	('glutaminase', 'Gene', (118, 129))
47083	30871151	The results showed that the promoter of the GLS gene is significantly hypomethylated in BLCA, BRCA, COAD, ESCA, HNSC, KIRC, KIRP, PRAD, READ, THCA, and UCEC, but it is not statistically significantly hypermethylated in any cancer tissue (Figure 4a).	('hypomethylated', 'Var', (70, 84))	('READ', 'Disease', 'None', (136, 140))	('GLS', 'Gene', '2744', (44, 47))	('cancer', 'Phenotype', 'HP:0002664', (223, 229))	('COAD', 'Disease', (100, 104))	('GLS', 'Gene', (44, 47))	('BRCA', 'Gene', '672', (94, 98))	('BRCA', 'Gene', (94, 98))	('cancer', 'Disease', 'MESH:D009369', (223, 229))	('READ', 'Disease', (136, 140))	('cancer', 'Disease', (223, 229))	('COAD', 'Disease', 'MESH:D029424', (100, 104))
47088	30871151	The N-termini of the GLS variants start with a 16-residue sequence, predicted to confine the proteins to the mitochondria.	('GLS', 'Gene', '2744', (21, 24))	('variants', 'Var', (25, 33))	('GLS', 'Gene', (21, 24))
47103	30871151	In this study, although we selected the STRING to investigate the mutations and CNAs, we have provided the PPI networks obtained by FunRich analysis to show the indirect connections of the proteins found in STRING (and GeneMANIA) to GLS/GLS2 (Supplementary Figure S1).	('mutations', 'Var', (66, 75))	('GLS2', 'Gene', '27165', (237, 241))	('proteins', 'Protein', (189, 197))	('GLS', 'Gene', '2744', (233, 236))	('GLS', 'Gene', '2744', (237, 240))	('GLS', 'Gene', (233, 236))	('GLS', 'Gene', (237, 240))	('GLS2', 'Gene', (237, 241))
47104	30871151	One can further note that it is intuitive that functional protein partners of glutaminases would experience various genetic alterations including mutations and CNAs, irrespective of the database.	('mutations', 'Var', (146, 155))	('experience', 'Reg', (97, 107))	('glutaminase', 'Gene', (78, 89))	('glutaminase', 'Gene', '2744', (78, 89))	('CNAs', 'Disease', (160, 164))
47105	30871151	We individually examined the genetic alterations of GLS and GLS2 in various types of cancer using cBioPortal and subsequently provided a comparative report with respect to the functional protein partners of glutaminases obtained from the PPI network analysis.	('GLS', 'Gene', (52, 55))	('GLS2', 'Gene', (60, 64))	('GLS', 'Gene', '2744', (60, 63))	('cancer', 'Disease', 'MESH:D009369', (85, 91))	('GLS', 'Gene', (60, 63))	('cancer', 'Disease', (85, 91))	('glutaminase', 'Gene', '2744', (207, 218))	('GLS2', 'Gene', '27165', (60, 64))	('GLS', 'Gene', '2744', (52, 55))	('cancer', 'Phenotype', 'HP:0002664', (85, 91))	('genetic', 'Var', (29, 36))	('glutaminase', 'Gene', (207, 218))
47108	30871151	We also observed that GLS mutation mainly occurred in uterine, lung, and stomach cancer and spans over the glutaminase (located between amino acids 244 and 530) and ankyrin repeat (located between amino acids 557 and 643) domains, with a hotspot in G597=/X597_splice/G597G, where 5 mutations were reported.	('occurred', 'Reg', (42, 50))	('stomach cancer', 'Disease', 'MESH:D013274', (73, 87))	('mutation', 'Var', (26, 34))	('lung', 'Disease', (63, 67))	('stomach cancer', 'Phenotype', 'HP:0012126', (73, 87))	('GLS', 'Gene', (22, 25))	('uterine', 'Disease', (54, 61))	('glutaminase', 'Gene', '2744', (107, 118))	('stomach cancer', 'Disease', (73, 87))	('GLS', 'Gene', '2744', (22, 25))	('cancer', 'Phenotype', 'HP:0002664', (81, 87))	('G597=/X597_splice/G597G', 'Var', (249, 272))	('glutaminase', 'Gene', (107, 118))
47112	30871151	In GLS2, there were 226 mutations in total, including 175 missense, 46 truncating, and 5 in-frame mutations.	('GLS2', 'Gene', '27165', (3, 7))	('GLS2', 'Gene', (3, 7))	('truncating', 'MPA', (71, 81))	('missense', 'Var', (58, 66))
47115	30871151	Like GLS, GLS2 mutations also mainly occurred in uterine, lung, and stomach cancer, spanning over the glutaminase (located between amino acids 177 and 463) and Ankyrin repeats (located between amino acids 490 and 575) domains, with a hotspot at E533K (Figure 5b(ii)).	('glutaminase', 'Gene', '2744', (102, 113))	('GLS', 'Gene', '2744', (5, 8))	('lung', 'Disease', (58, 62))	('mutations', 'Var', (15, 24))	('glutaminase', 'Gene', (102, 113))	('cancer', 'Phenotype', 'HP:0002664', (76, 82))	('occurred', 'Reg', (37, 45))	('GLS', 'Gene', '2744', (10, 13))	('GLS2', 'Gene', (10, 14))	('GLS', 'Gene', (5, 8))	('E533K', 'Mutation', 'rs1298789195', (245, 250))	('stomach cancer', 'Disease', 'MESH:D013274', (68, 82))	('uterine', 'Disease', (49, 56))	('stomach cancer', 'Phenotype', 'HP:0012126', (68, 82))	('GLS', 'Gene', (10, 13))	('E533K', 'Var', (245, 250))	('stomach cancer', 'Disease', (68, 82))	('GLS2', 'Gene', '27165', (10, 14))
47120	30871151	The alterations in the GLS-centered-signature-gene occur most dominantly in neuroendocrine prostate cancer (NEPC).	('neuroendocrine prostate cancer', 'Disease', 'MESH:D011471', (76, 106))	('alterations', 'Var', (4, 15))	('GLS', 'Gene', '2744', (23, 26))	('cancer', 'Phenotype', 'HP:0002664', (100, 106))	('GLS', 'Gene', (23, 26))	('prostate cancer', 'Phenotype', 'HP:0012125', (91, 106))	('neuroendocrine prostate cancer', 'Disease', (76, 106))
47121	30871151	Similarly, the analysis of the integrated status of mutations and CNAs for the GLS2 gene and its functional protein partners (Figure 5c(ii)) resulted in alteration frequency ranges of 20.2% to 44.9%, with a threshold of 60% as a minimum percentage of altered cases.	('mutations', 'Var', (52, 61))	('alteration', 'Reg', (153, 163))	('GLS2', 'Gene', '27165', (79, 83))	('GLS2', 'Gene', (79, 83))
47123	30871151	Unlike GLS, the alterations in the GLS2-centered-signature-gene occur mainly in lung cancer.	('lung cancer', 'Disease', 'MESH:D008175', (80, 91))	('alterations', 'Var', (16, 27))	('GLS2', 'Gene', '27165', (35, 39))	('GLS', 'Gene', '2744', (7, 10))	('lung cancer', 'Disease', (80, 91))	('lung cancer', 'Phenotype', 'HP:0100526', (80, 91))	('GLS', 'Gene', (7, 10))	('cancer', 'Phenotype', 'HP:0002664', (85, 91))	('GLS', 'Gene', '2744', (35, 38))	('GLS', 'Gene', (35, 38))	('GLS2', 'Gene', (35, 39))
47126	30871151	Compared to GLS2-centered gene set, the fluctuation range of genetic alterations is significantly larger in the GLS-centered gene set (Figure 5d(i,ii)).	('GLS2', 'Gene', (12, 16))	('GLS', 'Gene', '2744', (12, 15))	('GLS', 'Gene', (12, 15))	('GLS', 'Gene', '2744', (112, 115))	('genetic alterations', 'Var', (61, 80))	('GLS2', 'Gene', '27165', (12, 16))	('GLS', 'Gene', (112, 115))	('larger', 'PosReg', (98, 104))	('fluctuation', 'MPA', (40, 51))
47129	30871151	It is worth noting that whereas the alteration in GLUL solely occurred due to amplification, the alteration in TP53 largely takes place due to mutations.	('TP53', 'Gene', '7157', (111, 115))	('TP53', 'Gene', (111, 115))	('due', 'Reg', (136, 139))	('GLUL', 'Gene', '2752', (50, 54))	('GLUL', 'Gene', (50, 54))	('mutations', 'Var', (143, 152))
47130	30871151	This result is consistent with the overall integrated status of mutations and CNAs for glutaminases and their functional protein partners, as explained in the preceding paragraph.	('glutaminase', 'Gene', '2744', (87, 98))	('mutations', 'Var', (64, 73))	('glutaminase', 'Gene', (87, 98))
47135	30871151	Also, patients with low GLS expression exhibited a positive correlation with poor OS in bladder, kidney, and lung cancer (Figure 6a(i,viii,xi)).	('lung cancer', 'Disease', (109, 120))	('lung cancer', 'Phenotype', 'HP:0100526', (109, 120))	('bladder', 'Disease', (88, 95))	('cancer', 'Phenotype', 'HP:0002664', (114, 120))	('lung cancer', 'Disease', 'MESH:D008175', (109, 120))	('patients', 'Species', '9606', (6, 14))	('poor OS', 'Disease', (77, 84))	('low', 'Var', (20, 23))	('GLS', 'Gene', '2744', (24, 27))	('kidney', 'Disease', (97, 103))	('GLS', 'Gene', (24, 27))
47142	30871151	The underexpression of GLS2 in these types of cancer was, however, positively correlated with high survival.	('cancer', 'Disease', 'MESH:D009369', (46, 52))	('cancer', 'Disease', (46, 52))	('GLS2', 'Gene', (23, 27))	('GLS2', 'Gene', '27165', (23, 27))	('underexpression', 'Var', (4, 19))	('high survival', 'CPA', (94, 107))	('cancer', 'Phenotype', 'HP:0002664', (46, 52))	('correlated', 'Reg', (78, 88))
47145	30871151	Moreover, any deviation in GLS2 expression, compared to the expression mark observed in normal tissues, was associated with poor prognosis in bladder and pancreatic cancer in general (Figure 6b(i,ix).	('GLS2', 'Gene', '27165', (27, 31))	('bladder', 'Disease', (142, 149))	('expression', 'MPA', (32, 42))	('pancreatic cancer', 'Disease', 'MESH:D010190', (154, 171))	('cancer', 'Phenotype', 'HP:0002664', (165, 171))	('pancreatic cancer', 'Phenotype', 'HP:0002894', (154, 171))	('GLS2', 'Gene', (27, 31))	('deviation', 'Var', (14, 23))	('pancreatic cancer', 'Disease', (154, 171))
47159	30871151	In the case of other cancers of interest, such as breast, brain, and colon cancer, the non-co-occurrence of GLS/GLS2 (low/low) is associated with a poor prognosis compared to that of co-occurrence (Figure 7a(i-iv,vi-viii)).	('cancer', 'Phenotype', 'HP:0002664', (21, 27))	('colon cancer', 'Disease', (69, 81))	('GLS2', 'Gene', (112, 116))	('non-co-occurrence', 'Var', (87, 104))	('GLS', 'Gene', '2744', (112, 115))	('cancer', 'Phenotype', 'HP:0002664', (75, 81))	('cancers', 'Disease', 'MESH:D009369', (21, 28))	('cancers', 'Phenotype', 'HP:0002664', (21, 28))	('GLS', 'Gene', (112, 115))	('brain', 'Disease', (58, 63))	('breast', 'Disease', (50, 56))	('cancers', 'Disease', (21, 28))	('GLS2', 'Gene', '27165', (112, 116))	('GLS', 'Gene', '2744', (108, 111))	('colon cancer', 'Disease', 'MESH:D015179', (69, 81))	('colon cancer', 'Phenotype', 'HP:0003003', (69, 81))	('GLS', 'Gene', (108, 111))
47199	30871151	In this agreement, previous studies demonstrated that DNA methylation is associated with cancer progression and prognosis by regulating gene stability and transcript.	('gene stability', 'MPA', (136, 150))	('cancer', 'Disease', 'MESH:D009369', (89, 95))	('associated', 'Reg', (73, 83))	('methylation', 'Var', (58, 69))	('regulating', 'Reg', (125, 135))	('cancer', 'Disease', (89, 95))	('transcript', 'MPA', (155, 165))	('cancer', 'Phenotype', 'HP:0002664', (89, 95))
47204	30871151	Previous studies commonly reported that mutations in oncogenes such as KRAS, PIK3CA, BRAF were associated with clinical outcomes in various cancers.	('PIK3CA', 'Gene', (77, 83))	('PIK3CA', 'Gene', '5290', (77, 83))	('BRAF', 'Gene', (85, 89))	('BRAF', 'Gene', '673', (85, 89))	('cancers', 'Phenotype', 'HP:0002664', (140, 147))	('KRAS', 'Gene', (71, 75))	('mutations', 'Var', (40, 49))	('cancers', 'Disease', (140, 147))	('KRAS', 'Gene', '3845', (71, 75))	('cancers', 'Disease', 'MESH:D009369', (140, 147))	('cancer', 'Phenotype', 'HP:0002664', (140, 146))	('associated', 'Reg', (95, 105))
47208	30871151	GLS mutations mainly occurred in uterine, lung, and stomach cancer, whereas GLS2 mutations were mainly found in uterine, lung, and stomach cancer.	('lung', 'Disease', (42, 46))	('stomach cancer', 'Disease', (52, 66))	('stomach cancer', 'Disease', (131, 145))	('GLS', 'Gene', (0, 3))	('GLS2', 'Gene', '27165', (76, 80))	('GLS', 'Gene', '2744', (76, 79))	('stomach cancer', 'Disease', 'MESH:D013274', (52, 66))	('found', 'Reg', (103, 108))	('GLS2', 'Gene', (76, 80))	('stomach cancer', 'Phenotype', 'HP:0012126', (52, 66))	('stomach cancer', 'Disease', 'MESH:D013274', (131, 145))	('stomach cancer', 'Phenotype', 'HP:0012126', (131, 145))	('occurred', 'Reg', (21, 29))	('mutations', 'Var', (4, 13))	('GLS', 'Gene', (76, 79))	('uterine', 'Disease', (33, 40))	('cancer', 'Phenotype', 'HP:0002664', (139, 145))	('GLS', 'Gene', '2744', (0, 3))	('cancer', 'Phenotype', 'HP:0002664', (60, 66))
47209	30871151	We also examined the combined status of mutations and CNAs of each glutaminase member and their respective functional protein partners, identified using STRING-based PPI network analysis.	('mutations', 'Var', (40, 49))	('glutaminase', 'Gene', (67, 78))	('glutaminase', 'Gene', '2744', (67, 78))
47212	30871151	Alterations in NEPC and lung cancer were found to occur largely due to amplifications and mutations, respectively.	('amplifications', 'Var', (71, 85))	('NEPC', 'Disease', (15, 19))	('mutations', 'Var', (90, 99))	('cancer', 'Phenotype', 'HP:0002664', (29, 35))	('lung cancer', 'Disease', (24, 35))	('lung cancer', 'Phenotype', 'HP:0100526', (24, 35))	('lung cancer', 'Disease', 'MESH:D008175', (24, 35))
47213	30871151	Moreover, the expression of combined GLS- and GLS2-centered- signature-gene set regulated clinical prognosis in certain cancers which further predict that the functional partners of GLS and GLS2 contribute to significant CNAs and mutations and subsequently regulate the clinical outcomes in cancers.	('GLS', 'Gene', '2744', (190, 193))	('GLS2', 'Gene', (190, 194))	('GLS', 'Gene', '2744', (46, 49))	('mutations', 'Var', (230, 239))	('GLS', 'Gene', (182, 185))	('cancer', 'Phenotype', 'HP:0002664', (120, 126))	('GLS', 'Gene', (46, 49))	('GLS', 'Gene', '2744', (37, 40))	('GLS', 'Gene', (190, 193))	('cancers', 'Phenotype', 'HP:0002664', (120, 127))	('cancers', 'Disease', 'MESH:D009369', (291, 298))	('regulate', 'Reg', (257, 265))	('cancers', 'Disease', (120, 127))	('GLS', 'Gene', (37, 40))	('cancer', 'Phenotype', 'HP:0002664', (291, 297))	('GLS2', 'Gene', '27165', (190, 194))	('cancers', 'Phenotype', 'HP:0002664', (291, 298))	('GLS2', 'Gene', '27165', (46, 50))	('cancers', 'Disease', (291, 298))	('GLS', 'Gene', '2744', (182, 185))	('CNAs', 'MPA', (221, 225))	('cancers', 'Disease', 'MESH:D009369', (120, 127))	('GLS2', 'Gene', (46, 50))
47223	30871151	In general, high GLS expression resulted in poor survival in patients with breast, esophagus, head-and-neck, and blood cancer, and high survival in patients with bladder, kidney, and lung cancer.	('blood cancer', 'Disease', 'MESH:D009369', (113, 125))	('poor', 'NegReg', (44, 48))	('patients', 'Species', '9606', (148, 156))	('lung cancer', 'Disease', 'MESH:D008175', (183, 194))	('patients', 'Species', '9606', (61, 69))	('lung cancer', 'Phenotype', 'HP:0100526', (183, 194))	('blood cancer', 'Disease', (113, 125))	('breast', 'Disease', (75, 81))	('cancer', 'Phenotype', 'HP:0002664', (119, 125))	('kidney', 'Disease', (171, 177))	('bladder', 'Disease', (162, 169))	('GLS', 'Gene', '2744', (17, 20))	('blood cancer', 'Phenotype', 'HP:0001909', (113, 125))	('cancer', 'Phenotype', 'HP:0002664', (188, 194))	('esophagus', 'Disease', (83, 92))	('high', 'Var', (12, 16))	('head-and-neck', 'Disease', (94, 107))	('lung cancer', 'Disease', (183, 194))	('GLS', 'Gene', (17, 20))
47235	30871151	In addition, the partial-occurrence (low/high) of glutaminases was associated with poor clinical outcomes in lung and gastric cancer.	('cancer', 'Phenotype', 'HP:0002664', (126, 132))	('glutaminase', 'Gene', (50, 61))	('gastric cancer', 'Disease', (118, 132))	('gastric cancer', 'Disease', 'MESH:D013274', (118, 132))	('glutaminase', 'Gene', '2744', (50, 61))	('partial-occurrence', 'Var', (17, 35))	('gastric cancer', 'Phenotype', 'HP:0012126', (118, 132))	('lung', 'Disease', (109, 113))
47236	30871151	These results suggest that the co-expression of GLS and GLS2 could also be utilized as a prognostic marker for patients with certain types of cancer.	('GLS', 'Gene', (48, 51))	('cancer', 'Disease', 'MESH:D009369', (142, 148))	('GLS', 'Gene', (56, 59))	('GLS2', 'Gene', '27165', (56, 60))	('cancer', 'Phenotype', 'HP:0002664', (142, 148))	('co-expression', 'Var', (31, 44))	('patients', 'Species', '9606', (111, 119))	('GLS', 'Gene', '2744', (48, 51))	('GLS', 'Gene', '2744', (56, 59))	('GLS2', 'Gene', (56, 60))	('cancer', 'Disease', (142, 148))
47239	30871151	The biological basis of the biomarker significance possibly comes in part from the accumulated mutations and CNAs of the glutaminases along with their functional protein partners.	('glutaminase', 'Gene', (121, 132))	('glutaminase', 'Gene', '2744', (121, 132))	('mutations', 'Var', (95, 104))	('CNAs', 'Var', (109, 113))
47242	30871151	Our analysis shows that the upregulation of GLS with hypomethylation is positively correlated with poor prognosis in patients with breast, colon, and head-and-neck cancers.	('GLS', 'Gene', '2744', (44, 47))	('cancer', 'Phenotype', 'HP:0002664', (164, 170))	('head-and-neck cancers', 'Disease', (150, 171))	('GLS', 'Gene', (44, 47))	('cancers', 'Phenotype', 'HP:0002664', (164, 171))	('breast', 'Disease', (131, 137))	('hypomethylation', 'Var', (53, 68))	('patients', 'Species', '9606', (117, 125))	('head-and-neck cancers', 'Disease', 'MESH:D006258', (150, 171))	('colon', 'Disease', (139, 144))	('upregulation', 'PosReg', (28, 40))	('head-and-neck cancer', 'Phenotype', 'HP:0012288', (150, 170))
47265	30072739	Emerging biomarkers for anti-PD-1 response include the expression level of its ligand PD-L1 , mutation burden or mismatch-repair deficiency , and tumor-infiltrating lymphocytes .	('PD-1', 'Gene', '5133', (29, 33))	('deficiency', 'Disease', 'MESH:D007153', (129, 139))	('expression level', 'MPA', (55, 71))	('tumor', 'Phenotype', 'HP:0002664', (146, 151))	('PD-L1', 'Gene', '29126', (86, 91))	('tumor', 'Disease', (146, 151))	('mismatch-repair', 'MPA', (113, 128))	('mutation burden', 'Var', (94, 109))	('deficiency', 'Disease', (129, 139))	('PD-L1', 'Gene', (86, 91))	('PD-1', 'Gene', (29, 33))	('tumor', 'Disease', 'MESH:D009369', (146, 151))
47267	30072739	Somatic mutations in oncogenes and tumor suppressors represent the most classic biomarkers as they are the main direct drivers of cancer progression .	('tumor', 'Disease', 'MESH:D009369', (35, 40))	('cancer', 'Disease', 'MESH:D009369', (130, 136))	('tumor', 'Phenotype', 'HP:0002664', (35, 40))	('cancer', 'Disease', (130, 136))	('tumor', 'Disease', (35, 40))	('oncogenes', 'Gene', (21, 30))	('cancer', 'Phenotype', 'HP:0002664', (130, 136))	('Somatic mutations', 'Var', (0, 17))
47270	30072739	Several other types of non-coding RNAs, such as long-noncoding RNAs (lncRNAs) , enhancer RNAs  and circular RNAs  have also been implicated in various cancer types .	('circular RNAs', 'Var', (99, 112))	('cancer', 'Phenotype', 'HP:0002664', (151, 157))	('enhancer', 'PosReg', (80, 88))	('implicated', 'Reg', (129, 139))	('long-noncoding', 'Var', (48, 62))	('cancer', 'Disease', (151, 157))	('cancer', 'Disease', 'MESH:D009369', (151, 157))
47280	30072739	Here we performed a pan-cancer analysis of ~22 nt size-selected small RNA-seq (smRNA-seq) datasets from TCGA, exploring the expression of small RNAs mapping to annotated human snoRNAs in 10,262 patient samples across 32 cancer types.	('patient', 'Species', '9606', (194, 201))	('small', 'Var', (138, 143))	('cancer', 'Phenotype', 'HP:0002664', (24, 30))	('snoRNA', 'Gene', '85390', (176, 182))	('cancer', 'Phenotype', 'HP:0002664', (220, 226))	('cancer', 'Disease', (24, 30))	('cancer', 'Disease', 'MESH:D009369', (24, 30))	('cancer', 'Disease', 'MESH:D009369', (220, 226))	('human', 'Species', '9606', (170, 175))	('cancer', 'Disease', (220, 226))	('snoRNA', 'Gene', (176, 182))
47294	30072739	This pan-cancer sdRNA transcriptome is derived from several subtypes of snoRNAs with distinct structures and motifs, such as canonical C/D box snoRNAs, H/ACA box snoRNAs, C/D box small Cajal body RNAs (scaRNAs), H/ACA box scaRNAs, hybrid snoRNAs, and several other subtypes (Figure 1b, Table S1, Table S2).	('snoRNA', 'Gene', '85390', (143, 149))	('cancer', 'Disease', (9, 15))	('snoRNA', 'Gene', (162, 168))	('snoRNA', 'Gene', '85390', (72, 78))	('snoRNA', 'Gene', '85390', (162, 168))	('snoRNA', 'Gene', '85390', (238, 244))	('cancer', 'Phenotype', 'HP:0002664', (9, 15))	('snoRNA', 'Gene', (143, 149))	('C/D box', 'Var', (171, 178))	('snoRNA', 'Gene', (72, 78))	('cancer', 'Disease', 'MESH:D009369', (9, 15))	('snoRNA', 'Gene', (238, 244))
47299	30072739	In the case of C/D snoRNAs, these analyses revealed three classes of read distributions, corresponding to 5' sdRNAs, 3' sdRNAs, or mixed sdRNAs (Figure 1c).	('D snoRNAs', 'Phenotype', 'HP:0025267', (17, 26))	('C/D', 'Var', (15, 18))	('snoRNA', 'Gene', (19, 25))	('mixed', 'Disease', (131, 136))	('snoRNA', 'Gene', '85390', (19, 25))	('D snoRNA', 'Phenotype', 'HP:0025267', (17, 25))
47309	30072739	The sdRNA transcriptome exhibited a wide dynamic range of expression across all cancers (Figure S5a), such that 300.13 +- 4.21 (mean +- s.e.m.)	('300.13 +- 4.21', 'Var', (112, 126))	('cancers', 'Disease', 'MESH:D009369', (80, 87))	('cancer', 'Phenotype', 'HP:0002664', (80, 86))	('cancers', 'Disease', (80, 87))	('sdRNA', 'Gene', (4, 9))	('cancers', 'Phenotype', 'HP:0002664', (80, 87))
47391	30072739	For instance, high expression of sdRNAs derived from SNORA116, an H/ACA snoRNA, was connected to poorer survival in three independent cohorts: lower grade gliomas (LGG), liver hepatocellular carcinoma (LIHC), and uterine corpus endometrial carcinoma (UCEC) (Figure 7b).	('endometrial carcinoma', 'Phenotype', 'HP:0012114', (228, 249))	('gliomas', 'Phenotype', 'HP:0009733', (155, 162))	('expression', 'MPA', (19, 29))	('snoRNA', 'Gene', '85390', (72, 78))	('corpus endometrial carcinoma', 'Disease', (221, 249))	('corpus endometrial carcinoma', 'Disease', 'MESH:D016889', (221, 249))	('hepatocellular carcinoma', 'Phenotype', 'HP:0001402', (176, 200))	('ACA snoRNA', 'Phenotype', 'HP:0025267', (68, 78))	('carcinoma', 'Phenotype', 'HP:0030731', (191, 200))	('liver hepatocellular carcinoma', 'Disease', 'MESH:D006528', (170, 200))	('liver hepatocellular carcinoma', 'Disease', (170, 200))	('glioma', 'Phenotype', 'HP:0009733', (155, 161))	('SNORA116', 'Var', (53, 61))	('poorer', 'NegReg', (97, 103))	('carcinoma', 'Phenotype', 'HP:0030731', (240, 249))	('snoRNA', 'Gene', (72, 78))	('gliomas', 'Disease', (155, 162))	('gliomas', 'Disease', 'MESH:D005910', (155, 162))
47392	30072739	As another example, high levels of sdRNAs from SNORD145, a CD snoRNA, were associated with shorter survival times in kidney clear cell carcinoma (KIRC), sarcoma (SARC), and uterine corpus endometrial carcinoma (UCEC) (Figure 7c).	('sarcoma', 'Disease', 'MESH:D012509', (153, 160))	('corpus endometrial carcinoma', 'Disease', 'MESH:D016889', (181, 209))	('endometrial carcinoma', 'Phenotype', 'HP:0012114', (188, 209))	('carcinoma', 'Phenotype', 'HP:0030731', (135, 144))	('sarcoma', 'Disease', (153, 160))	('SARC', 'Phenotype', 'HP:0100242', (162, 166))	('carcinoma', 'Phenotype', 'HP:0030731', (200, 209))	('kidney clear cell carcinoma', 'Disease', 'MESH:C538614', (117, 144))	('SNORD145', 'Var', (47, 55))	('shorter', 'NegReg', (91, 98))	('sarcoma', 'Phenotype', 'HP:0100242', (153, 160))	('D snoRNA', 'Phenotype', 'HP:0025267', (60, 68))	('snoRNA', 'Gene', (62, 68))	('survival times', 'CPA', (99, 113))	('corpus endometrial carcinoma', 'Disease', (181, 209))	('sdRNAs', 'MPA', (35, 41))	('snoRNA', 'Gene', '85390', (62, 68))	('kidney clear cell carcinoma', 'Disease', (117, 144))
47393	30072739	SdRNAs from SNORA116 and SNORD145 thus appear to be indicators of cancers with a more aggressive course.	('cancer', 'Phenotype', 'HP:0002664', (66, 72))	('SNORA116', 'Var', (12, 20))	('cancers', 'Phenotype', 'HP:0002664', (66, 73))	('SNORD145', 'Var', (25, 33))	('cancers', 'Disease', (66, 73))	('cancers', 'Disease', 'MESH:D009369', (66, 73))
47411	30072739	Because the ImmuneSurv score analyses were conducted in a cancer type-specific manner, we then sought a global assessment of sdRNAs and their relationships to cancer immunity regardless of cancer type (PANCAN32), by compiling all sdRNAs that were found to be significant in any of the 5 categories: PD-L1, CD8+ T cell abundance, GZMA, survival, or copy number variation (supplemental results, Figure S9) in any cancer type.	('cancer', 'Phenotype', 'HP:0002664', (58, 64))	('cancer', 'Disease', 'MESH:D009369', (411, 417))	('cancer immunity regardless of cancer', 'Disease', 'MESH:D009369', (159, 195))	('cancer', 'Disease', 'MESH:D009369', (189, 195))	('CD8', 'Gene', (306, 309))	('GZMA', 'Gene', '3001', (329, 333))	('cancer', 'Disease', (159, 165))	('cancer', 'Phenotype', 'HP:0002664', (159, 165))	('cancer', 'Disease', 'MESH:D009369', (58, 64))	('GZMA', 'Gene', (329, 333))	('PD-L1', 'Gene', (299, 304))	('PD-L1', 'Gene', '29126', (299, 304))	('cancer', 'Disease', (411, 417))	('cancer', 'Disease', 'MESH:D009369', (159, 165))	('CD8', 'Gene', '925', (306, 309))	('copy number variation', 'Var', (348, 369))	('cancer', 'Disease', (189, 195))	('cancer', 'Phenotype', 'HP:0002664', (411, 417))	('cancer', 'Phenotype', 'HP:0002664', (189, 195))	('cancer immunity regardless of cancer', 'Disease', (159, 195))	('cancer', 'Disease', (58, 64))
47422	30072739	Of note, SNORD115 has been demonstrated to act as a regulator of alternative splicing , and its deletion is sufficient to cause Prader-Willi syndrome.	('SNORD115', 'Gene', '692218', (9, 17))	('cause', 'Reg', (122, 127))	('deletion', 'Var', (96, 104))	('Prader-Willi syndrome', 'Disease', 'MESH:D011218', (128, 149))	('Prader-Willi syndrome', 'Disease', (128, 149))	('alternative splicing', 'MPA', (65, 85))	('SNORD115', 'Gene', (9, 17))
47449	30072739	GISTIC 2.0 copy number variation calls were obtained from the GDAC Firehose (http://gdac.broadinstitute.org/) on September 2017.	('copy number variation', 'Var', (11, 32))	('DAC', 'Gene', (63, 66))	('DAC', 'Gene', '6468', (63, 66))
47451	30072739	Raw fastq files for independent smRNA-seq datasets (GSE33858, GSE46622, E-MTAB-3494) were accessed by NCBI GEO (https://www.ncbi.nlm.nih.gov/geo/) or EBI (https://www.ebi.ac.uk/).	('EBI', 'Gene', (150, 153))	('GSE46622', 'Var', (62, 70))	('EBI', 'Gene', '6907', (150, 153))	('GSE33858', 'Var', (52, 60))	('ebi', 'Gene', '6907', (167, 170))	('ebi', 'Gene', (167, 170))
47477	30072739	As these tables report the precise genomic coordinates in which the amplification or deletion was identified, we utilized a q < 0.05 threshold and subsequently intersected the coordinates with the snoRNA annotations .	('deletion', 'Var', (85, 93))	('snoRNA', 'Gene', (197, 203))	('snoRNA', 'Gene', '85390', (197, 203))
47478	30072739	Amplification and deletion calls for individual snoRNAs were then compiled into separate tables.	('deletion', 'Var', (18, 26))	('snoRNA', 'Gene', (48, 54))	('snoRNA', 'Gene', '85390', (48, 54))
47481	30072739	For pan-cancer analysis, we considered all sdRNAs that were found to be significant in at least one cancer type across the following 5 analyses: CD274 correlation, GMZA correlation, CD8+ T cell abundance, copy number variation, and survival.	('cancer', 'Disease', (8, 14))	('CD8', 'Gene', (182, 185))	('cancer', 'Phenotype', 'HP:0002664', (100, 106))	('CD8', 'Gene', '925', (182, 185))	('CD274', 'Gene', '29126', (145, 150))	('cancer', 'Phenotype', 'HP:0002664', (8, 14))	('cancer', 'Disease', (100, 106))	('cancer', 'Disease', 'MESH:D009369', (100, 106))	('copy number variation', 'Var', (205, 226))	('cancer', 'Disease', 'MESH:D009369', (8, 14))	('CD274', 'Gene', (145, 150))
47487	30072739	Thus, for the example above (NNSNSN), sdRNAs from snoRNA X were found to be significantly associated with survival and significant for CNV in cancer type Y.	('cancer', 'Disease', 'MESH:D009369', (142, 148))	('snoRNA', 'Gene', (50, 56))	('cancer', 'Phenotype', 'HP:0002664', (142, 148))	('associated with', 'Reg', (90, 105))	('sdRNAs', 'Var', (38, 44))	('snoRNA', 'Gene', '85390', (50, 56))	('cancer', 'Disease', (142, 148))
47603	32463597	Both datasets showed that high expression of KITLG was significantly associated with type A and AB thymoma.	('type A', 'Disease', (85, 91))	('high', 'Var', (26, 30))	('AB thymoma', 'Disease', (96, 106))	('associated', 'Reg', (69, 79))	('thymoma', 'Phenotype', 'HP:0100522', (99, 106))	('AB thymoma', 'Disease', 'MESH:D013945', (96, 106))	('KITLG', 'Gene', (45, 50))
47650	32463597	The development of thymoma is a multistep process involving epigenetic alterations.	('epigenetic alterations', 'Var', (60, 82))	('thymoma', 'Disease', 'MESH:D013945', (19, 26))	('thymoma', 'Disease', (19, 26))	('thymoma', 'Phenotype', 'HP:0100522', (19, 26))
47652	32463597	The level of DNMT1, DNMT3A, and DNMT3L appeared lower in the KITLGhigh group (P < 0.001), which was different from other tumors (Fig 5a).	('DNMT3L', 'Gene', '29947', (32, 38))	('tumor', 'Phenotype', 'HP:0002664', (121, 126))	('lower', 'NegReg', (48, 53))	('tumors', 'Disease', (121, 127))	('tumors', 'Phenotype', 'HP:0002664', (121, 127))	('DNMT1', 'Gene', '1786', (13, 18))	('DNMT3A', 'Gene', (20, 26))	('DNMT3A', 'Gene', '1788', (20, 26))	('DNMT1', 'Gene', (13, 18))	('tumors', 'Disease', 'MESH:D009369', (121, 127))	('DNMT3L', 'Gene', (32, 38))	('KITLGhigh', 'Var', (61, 70))
47662	32463597	In addition, there were no changes in the mRNA levels of BRAF, MEK1/2, and ERK1/2 (P > 0.05) (Fig 7a), while the protein expression of p-BRAF, p-MEK1/2, and p-ERK1/2 was notably upregulated by pcDNA3.1(+)-KITLG plasmid (P < 0.001) (Fig 7b).	('protein expression', 'MPA', (113, 131))	('mRNA levels', 'MPA', (42, 53))	('ERK1/2', 'Gene', (159, 165))	('MEK1/2', 'Gene', '5604;5605', (63, 69))	('BRAF', 'Gene', '673', (57, 61))	('MEK1/2', 'Gene', '5604;5605', (145, 151))	('MEK1/2', 'Gene', (63, 69))	('BRAF', 'Gene', (137, 141))	('BRAF', 'Gene', (57, 61))	('MEK1/2', 'Gene', (145, 151))	('upregulated', 'PosReg', (178, 189))	('BRAF', 'Gene', '673', (137, 141))	('ERK1/2', 'Gene', '5595;5594', (159, 165))	('ERK1/2', 'Gene', '5595;5594', (75, 81))	('ERK1/2', 'Gene', (75, 81))	('pcDNA3.1(+)-KITLG plasmid', 'Var', (193, 218))
47665	32463597	Fortunately, the TCGA network provides valuable information regarding the genetic changes in critical genes involved in the cancer pathways in different subtypes of thymoma patients.	('cancer', 'Disease', (124, 130))	('genetic', 'Var', (74, 81))	('patients', 'Species', '9606', (173, 181))	('thymoma', 'Disease', 'MESH:D013945', (165, 172))	('cancer', 'Phenotype', 'HP:0002664', (124, 130))	('thymoma', 'Disease', (165, 172))	('thymoma', 'Phenotype', 'HP:0100522', (165, 172))	('cancer', 'Disease', 'MESH:D009369', (124, 130))
47669	32463597	The KITLGhigh group contained significantly more patients with the A and AB subtypes, suggesting KITLG might be another independent biomarker of type A and AB thymoma.	('AB thymoma', 'Disease', 'MESH:D013945', (156, 166))	('KITLG', 'Var', (97, 102))	('patients', 'Species', '9606', (49, 57))	('AB thymoma', 'Disease', (156, 166))	('thymoma', 'Phenotype', 'HP:0100522', (159, 166))
47672	32463597	Finally, we realized that differentially methylated genes related to KITLGhigh could contribute to the pathogenesis of type A and AB thymoma.	('type A', 'Disease', (119, 125))	('contribute', 'Reg', (85, 95))	('thymoma', 'Phenotype', 'HP:0100522', (133, 140))	('AB thymoma', 'Disease', 'MESH:D013945', (130, 140))	('KITLGhigh', 'Gene', (69, 78))	('differentially methylated', 'Var', (26, 51))	('AB thymoma', 'Disease', (130, 140))
47676	32463597	As previous studies reported, KITLG can result in the activation of several downstream signaling pathways, such as STAT and PI3K/AKT.	('downstream signaling pathways', 'Pathway', (76, 105))	('AKT', 'Gene', '207', (129, 132))	('KITLG', 'Var', (30, 35))	('activation', 'PosReg', (54, 64))	('STAT', 'Pathway', (115, 119))	('AKT', 'Gene', (129, 132))
47686	32463597	Fortunately, several molecules have been found to be closely related to thymoma, and PI3K pathway inhibitors as a novel therapy for relapsed or refractory thymoma have been in phase II clinical trials.11 Our results support that high expression of KITLG is an important biomarker for type A and AB thymoma.	('type A', 'Disease', (284, 290))	('thymoma', 'Disease', 'MESH:D013945', (298, 305))	('thymoma', 'Disease', (298, 305))	('thymoma', 'Disease', 'MESH:D013945', (155, 162))	('thymoma', 'Disease', 'MESH:D013945', (72, 79))	('thymoma', 'Phenotype', 'HP:0100522', (155, 162))	('thymoma', 'Disease', (72, 79))	('thymoma', 'Phenotype', 'HP:0100522', (298, 305))	('AB thymoma', 'Disease', 'MESH:D013945', (295, 305))	('thymoma', 'Disease', (155, 162))	('AB thymoma', 'Disease', (295, 305))	('high', 'Var', (229, 233))	('thymoma', 'Phenotype', 'HP:0100522', (72, 79))	('KITLG', 'Gene', (248, 253))
47690	31394971	The incidence of thymomas in F344/N rats was slightly higher in males than in females, while the incidences in SD and WH rats were higher in females than in males.	('thymomas', 'Disease', (17, 25))	('thymomas', 'Disease', 'MESH:D013945', (17, 25))	('higher', 'PosReg', (54, 60))	('F344/N', 'Var', (29, 35))	('F344/N', 'Mutation', 'p.F344N', (29, 35))	('rats', 'Species', '10116', (121, 125))	('thymoma', 'Phenotype', 'HP:0100522', (17, 24))	('rats', 'Species', '10116', (36, 40))
47749	31394971	Of the remaining 28 malignant thymomas that exhibited no metastases, 17 were diagnosed due to unequivocal tissue invasion, and 11 were diagnosed based upon cytological features, such as pleomorphism, cellular atypia, karyomegaly, anisokaryosis, prominent nucleoli, and increased mitoses.	('malignant thymomas', 'Phenotype', 'HP:0100697', (20, 38))	('increased', 'PosReg', (269, 278))	('metastases', 'Disease', (57, 67))	('cellular atypia', 'CPA', (200, 215))	('malignant thymomas', 'Disease', (20, 38))	('thymoma', 'Phenotype', 'HP:0100522', (30, 37))	('metastases', 'Disease', 'MESH:D009362', (57, 67))	('anisokaryosis', 'CPA', (230, 243))	('malignant thymomas', 'Disease', 'MESH:D013945', (20, 38))	('mitoses', 'CPA', (279, 286))	('karyomegaly', 'CPA', (217, 228))	('pleomorphism', 'Var', (186, 198))
47812	31394971	The thymomas in F344/N, SD, WH, and WO rats in this review were variable in microscopic appearance and were divided into 6, 3, 4, and 2 categories, respectively, based upon morphological patterns (see Table 2).	('rats', 'Species', '10116', (39, 43))	('thymomas', 'Disease', (4, 12))	('thymomas', 'Disease', 'MESH:D013945', (4, 12))	('F344/N', 'Var', (16, 22))	('F344/N', 'Mutation', 'p.F344N', (16, 22))	('thymoma', 'Phenotype', 'HP:0100522', (4, 11))
47853	30855492	Immunohistochemical analysis showed a Ki-67 level of 40% to 50%, and was positive for cytokeratin (CK)19, CK5/6, and CK7 in the neoplastic epithelial cells and for leucocyte common antigen, CD3, CD5, CD20, CD99, CD1a, and terminal deoxynucleotidyl transferase in the lymphocytes.	('CD1a', 'Gene', '909', (212, 216))	('CD99', 'Gene', '4267', (206, 210))	('CK7', 'Gene', (117, 120))	('CD5', 'Gene', (195, 198))	('terminal deoxynucleotidyl transferase', 'Enzyme', (222, 259))	('Ki-67', 'Var', (38, 43))	('CK7', 'Gene', '3855', (117, 120))	('CD99', 'Gene', (206, 210))	('CD5', 'Gene', '921', (195, 198))	('CK5/6', 'Gene', '3852', (106, 111))	('CD1a', 'Gene', (212, 216))	('positive', 'Reg', (73, 81))	('CD20', 'Gene', '54474', (200, 204))	('CD20', 'Gene', (200, 204))	('CK5/6', 'Gene', (106, 111))
47987	27247812	Lgi1 antibodies, mainly found in patients with LE or idiopathic epilepsy, are generally not associated with tumors.	('idiopathic epilepsy', 'Disease', (53, 72))	('Lgi1', 'Gene', (0, 4))	('patients', 'Species', '9606', (33, 41))	('tumor', 'Phenotype', 'HP:0002664', (108, 113))	('antibodies', 'Var', (5, 15))	('Lgi1', 'Gene', '9211', (0, 4))	('tumors', 'Disease', (108, 114))	('tumors', 'Disease', 'MESH:D009369', (108, 114))	('idiopathic epilepsy', 'Disease', 'MESH:C562694', (53, 72))	('tumors', 'Phenotype', 'HP:0002664', (108, 114))	('epilepsy', 'Phenotype', 'HP:0001250', (64, 72))	('found', 'Reg', (24, 29))
47988	27247812	Lgi1 antibodies are also associated with hyponatremia secondary to SIADH due to their binding to hypothalamic paraventricular nucleus neurons.	('hyponatremia', 'Disease', (41, 53))	('Lgi1', 'Gene', (0, 4))	('SIADH', 'Disease', (67, 72))	('associated', 'Reg', (25, 35))	('antibodies', 'Var', (5, 15))	('Lgi1', 'Gene', '9211', (0, 4))	('binding', 'Interaction', (86, 93))	('SIADH', 'Disease', 'MESH:D007177', (67, 72))	('hyponatremia', 'Phenotype', 'HP:0002902', (41, 53))	('hyponatremia', 'Disease', 'MESH:D007010', (41, 53))
47989	27247812	Caspr2 antibodies, found in MoS and NMT, are often associated with thymoma and less often with paraneoplastic LE.	('thymoma', 'Phenotype', 'HP:0100522', (67, 74))	('paraneoplastic LE', 'Disease', 'MESH:D010257', (95, 112))	('antibodies', 'Var', (7, 17))	('paraneoplastic LE', 'Disease', (95, 112))	('associated', 'Reg', (51, 61))	('Caspr2', 'Gene', (0, 6))	('Caspr2', 'Gene', '26047', (0, 6))	('thymoma', 'Disease', 'MESH:D013945', (67, 74))	('thymoma', 'Disease', (67, 74))
47990	27247812	Although our patient technically fulfills the criteria for MoS diagnosis, her central nervous system symptoms were initially attributed to SLE and electrolyte disturbance whereas her mild nerve hyperexcitability and autonomic findings were due to Caspr2 antibody.	('antibody', 'Var', (254, 262))	('patient', 'Species', '9606', (13, 20))	('Caspr2', 'Gene', (247, 253))	('nerve hyperexcitability', 'Disease', 'MESH:D009437', (188, 211))	('central nervous system symptoms', 'Disease', (78, 109))	('due to', 'Reg', (240, 246))	('SLE', 'Disease', 'MESH:D008180', (139, 142))	('SLE', 'Disease', (139, 142))	('Caspr2', 'Gene', '26047', (247, 253))	('SLE', 'Phenotype', 'HP:0002725', (139, 142))	('attributed', 'Reg', (125, 135))	('electrolyte disturbance', 'Phenotype', 'HP:0003111', (147, 170))	('nerve hyperexcitability', 'Disease', (188, 211))
48012	25780436	Decreased expression of CD4+, CD8+, or CD3+ was present in 71% of the patients.	('CD8', 'Gene', (30, 33))	('patients', 'Species', '9606', (70, 78))	('CD8', 'Gene', '925', (30, 33))	('CD', 'Chemical', 'MESH:D002104', (39, 41))	('CD3+', 'Var', (39, 43))	('CD4', 'Gene', (24, 27))	('Decreased', 'NegReg', (0, 9))	('CD4', 'Gene', '920', (24, 27))	('CD', 'Chemical', 'MESH:D002104', (30, 32))	('expression', 'MPA', (10, 20))	('CD', 'Chemical', 'MESH:D002104', (24, 26))
48072	25780436	Patients who were administered pyridinium bromide neostigmine combined with steroid therapy exhibited no early exacerbation of weakness.	('pyridinium', 'Var', (31, 41))	('Patients', 'Species', '9606', (0, 8))	('steroid', 'Chemical', 'MESH:D013256', (76, 83))	('pyridinium bromide neostigmine', 'Chemical', '-', (31, 61))	('weakness', 'Disease', (127, 135))	('weakness', 'Disease', 'MESH:D018908', (127, 135))
48097	25780436	However, follow-up of the Titin-Ab-positive patients was necessary, particularly for diagnosis by enhanced CT. Foreign studies have reported that positive RyR-Ab is associated with GMG, particularly with severe oropharyngeal muscle weakness that often occurs during myasthenic crises; however, no such correlation was found in the 3 positive patients who were followed up.	('RyR', 'Gene', (155, 158))	('patients', 'Species', '9606', (44, 52))	('Titin', 'Gene', '7273', (26, 31))	('associated', 'Reg', (165, 175))	('patients', 'Species', '9606', (342, 350))	('Titin', 'Gene', (26, 31))	('GMG', 'Chemical', 'MESH:C118417', (181, 184))	('RyR', 'Gene', '6261', (155, 158))	('GMG', 'Disease', (181, 184))	('muscle weakness', 'Disease', 'MESH:D018908', (225, 240))	('muscle weakness', 'Phenotype', 'HP:0001324', (225, 240))	('positive', 'Var', (146, 154))	('myasthenic crises', 'Phenotype', 'HP:0003473', (266, 283))	('muscle weakness', 'Disease', (225, 240))
48098	25780436	In this group, 71% of patients had abnormal CD series, with the majority displaying decreased CD4+ and CD8+, indicating that immune cells also play a role in the pathogenesis of MG. MG is usually mitigated in the morning and worsens in the evening and patients may experience incomplete paralysis in the later stages.	('CD', 'Chemical', 'MESH:D002104', (94, 96))	('mitigated', 'NegReg', (196, 205))	('MG. MG', 'Var', (178, 184))	('CD series', 'MPA', (44, 53))	('paralysis', 'Disease', (287, 296))	('patients', 'Species', '9606', (252, 260))	('CD4', 'Gene', (94, 97))	('patients', 'Species', '9606', (22, 30))	('CD4', 'Gene', '920', (94, 97))	('CD', 'Chemical', 'MESH:D002104', (44, 46))	('paralysis', 'Phenotype', 'HP:0003470', (287, 296))	('paralysis', 'Disease', 'MESH:D010243', (287, 296))	('CD8', 'Gene', (103, 106))	('CD8', 'Gene', '925', (103, 106))	('decreased', 'NegReg', (84, 93))	('CD', 'Chemical', 'MESH:D002104', (103, 105))
48159	24459636	Although some studies report enhanced survival after R0 resection relative to patients who do not undergo resection, these reports are small, mainly retrospective, and subject to selection bias.	('enhanced', 'PosReg', (29, 37))	('R0 resection', 'Var', (53, 65))	('patients', 'Species', '9606', (78, 86))	('survival', 'MPA', (38, 46))
48408	29088744	By combining this cut-off point with that of B10, we used the MGFA classification of MG to evaluate the significance of B10 in MG. We found that in 75 patients with MG, percentage of B10 > 0.55% was mainly about the patients of type II and type III, percentage of B10 < 0.55% was mainly about the patients of type IV and type V (Table 4, Figure 5).	('B10', 'Gene', '5169', (264, 267))	('B10', 'Gene', (45, 48))	('B10', 'Gene', (264, 267))	('B10', 'Gene', '5169', (183, 186))	('patients', 'Species', '9606', (297, 305))	('B10', 'Gene', (183, 186))	('> 0.55%', 'Var', (187, 194))	('patients', 'Species', '9606', (151, 159))	('patients', 'Species', '9606', (216, 224))	('MGFA', 'Chemical', '-', (62, 66))	('B10', 'Gene', '5169', (120, 123))	('B10', 'Gene', (120, 123))	('B10', 'Gene', '5169', (45, 48))
48428	29088744	Basic research has currently recognized the following Breg phenotypes: CD19+CD24+CD38+, CD19+CD5+CD1d+, CD19+CD24+CD27+, CD19+CD38+CD1d+IgM+CD147+, CD25hiCD71hiCD73lo and CD27intCD38hi.	('CD38', 'Gene', (178, 182))	('CD24', 'Gene', (109, 113))	('CD1d', 'Gene', (131, 135))	('CD25hiCD71hiCD73lo', 'Var', (148, 166))	('CD38', 'Gene', '952', (126, 130))	('CD19', 'Gene', (104, 108))	('CD19', 'Gene', (121, 125))	('CD38', 'Gene', (81, 85))	('CD1d', 'Gene', (97, 101))	('CD19', 'Gene', (88, 92))	('CD19', 'Gene', '930', (121, 125))	('CD1d', 'Gene', '912', (131, 135))	('CD24', 'Gene', (76, 80))	('CD38', 'Gene', (126, 130))	('CD19', 'Gene', '930', (104, 108))	('CD19', 'Gene', (71, 75))	('CD24', 'Gene', '100133941', (109, 113))	('CD19', 'Gene', '930', (88, 92))	('CD38', 'Gene', '952', (178, 182))	('CD1d', 'Gene', '912', (97, 101))	('CD38', 'Gene', '952', (81, 85))	('CD19', 'Gene', '930', (71, 75))	('CD24', 'Gene', '100133941', (76, 80))
48488	29088744	The sequences of primers were sense 5'-TCTTCCTCACCCCCATGGAA-3' and antisense 5'- ACTGCAGCACAGCGTTATCT-3' for CD19; sense 5'- TTCCAGTGTCTCGGAGGGAT-3' and antisense 5'- GCTGGCCACAGCTTTCAAGA-3' for IL-10; sense 5'-GAAGGTGAAGGTCGGAGTC-3' and antisense 5'-GGGTGGAATCATATTGGAAC-3' for GAPDH.	('CD19', 'Gene', (109, 113))	('antisense', 'Var', (238, 247))	('IL-10', 'Gene', '3586', (195, 200))	('GAPDH', 'Gene', '2597', (279, 284))	('CD19', 'Gene', '930', (109, 113))	('GAPDH', 'Gene', (279, 284))	('IL-10', 'Gene', (195, 200))
48496	27823582	Domain-swapped T cell receptors improve the safety of TCR gene therapy T cells engineered to express a tumor-specific alphabeta T cell receptor (TCR) mediate anti-tumor immunity.	('TCR', 'Gene', (145, 148))	('tumor', 'Phenotype', 'HP:0002664', (103, 108))	('TCR', 'Gene', '328483', (145, 148))	('alphabeta T', 'Disease', (118, 129))	('tumor', 'Disease', (163, 168))	('safety', 'MPA', (44, 50))	('T cell receptor', 'Gene', '328483', (15, 30))	('tumor', 'Disease', 'MESH:D009369', (163, 168))	('improve', 'PosReg', (32, 39))	('tumor', 'Disease', (103, 108))	('tumor', 'Phenotype', 'HP:0002664', (163, 168))	('TCR', 'Gene', (54, 57))	('T cell receptor', 'Gene', (128, 143))	('TCR', 'Gene', '328483', (54, 57))	('tumor', 'Disease', 'MESH:D009369', (103, 108))	('Domain-swapped', 'Var', (0, 14))	('T cell receptor', 'Gene', '328483', (128, 143))	('T cell receptor', 'Gene', (15, 30))	('alphabeta T', 'Disease', 'MESH:D001260', (118, 129))
48509	27823582	More importantly, mispaired T cell receptors may cause the immune cells to attack healthy cells in the body, leading to autoimmune disease.	('mispaired', 'Var', (18, 27))	('autoimmune disease', 'Disease', (120, 138))	('leading to', 'Reg', (109, 119))	('T cell receptor', 'Gene', (28, 43))	('T cell receptor', 'Gene', '328483', (28, 43))	('autoimmune disease', 'Phenotype', 'HP:0002960', (120, 138))	('autoimmune disease', 'Disease', 'MESH:D001327', (120, 138))	('cause', 'Reg', (49, 54))
48513	27823582	Like normal T cell receptors, the dsTCRs were exported to the T cell surface and were able to interact with other proteins involved in immune responses.	('T cell receptor', 'Gene', '328483', (12, 27))	('dsTCRs', 'Var', (34, 40))	('interact', 'Interaction', (94, 102))	('T cell receptor', 'Gene', (12, 27))
48515	27823582	Unlike other cancer-specific receptors, dsTCRs did not mispair with the resident T cell receptors in mouse or human cells, and did not cause autoimmune disease in mice.	('autoimmune disease', 'Disease', 'MESH:D001327', (141, 159))	('T cell receptor', 'Gene', (81, 96))	('autoimmune disease', 'Phenotype', 'HP:0002960', (141, 159))	('cancer', 'Phenotype', 'HP:0002664', (13, 19))	('mouse', 'Species', '10090', (101, 106))	('cancer', 'Disease', (13, 19))	('cancer', 'Disease', 'MESH:D009369', (13, 19))	('human', 'Species', '9606', (110, 115))	('autoimmune disease', 'Disease', (141, 159))	('mice', 'Species', '10090', (163, 167))	('cause', 'Reg', (135, 140))	('T cell receptor', 'Gene', '328483', (81, 96))	('dsTCRs', 'Var', (40, 46))
48519	27823582	Accordingly, transfer of the alpha and beta genes encoding a tumor-reactive alphabeta TCR can impart anti-tumor reactivity to a cancer patient's T cells.	('cancer', 'Disease', 'MESH:D009369', (128, 134))	('patient', 'Species', '9606', (135, 142))	('alphabeta T', 'Disease', (76, 87))	('transfer', 'Var', (13, 21))	('tumor', 'Disease', 'MESH:D009369', (61, 66))	('tumor', 'Disease', 'MESH:D009369', (106, 111))	('cancer', 'Phenotype', 'HP:0002664', (128, 134))	('tumor', 'Phenotype', 'HP:0002664', (61, 66))	('tumor', 'Phenotype', 'HP:0002664', (106, 111))	('alphabeta T', 'Disease', 'MESH:D001260', (76, 87))	('tumor', 'Disease', (61, 66))	('tumor', 'Disease', (106, 111))	('cancer', 'Disease', (128, 134))
48522	27823582	Among these is that TCR-transduced alphabeta T cells express two alpha and two beta chains, a non-physiological situation in which the introduced TCR alpha and beta chains can mispair with the endogenous TCR beta and alpha chains, respectively.	('TCR beta', 'Gene', (204, 212))	('alphabeta T', 'Disease', (35, 46))	('mispair', 'Var', (176, 183))	('TCR beta', 'Gene', '21577', (204, 212))	('TCR alpha', 'Gene', '21473', (146, 155))	('alphabeta T', 'Disease', 'MESH:D001260', (35, 46))	('TCR alpha', 'Gene', (146, 155))
48523	27823582	TCR chain mispairing reduces the level of correctly-paired, tumor-reactive TCR heterodimers expressed on the T cell surface, possibly reducing therapeutic efficacy.	('therapeutic', 'MPA', (143, 154))	('TCR heterodimers', 'Protein', (75, 91))	('reducing', 'NegReg', (134, 142))	('mispairing', 'Var', (10, 20))	('tumor', 'Disease', 'MESH:D009369', (60, 65))	('reducing therapeutic efficacy', 'Phenotype', 'HP:0020173', (134, 163))	('tumor', 'Phenotype', 'HP:0002664', (60, 65))	('level of', 'MPA', (33, 41))	('tumor', 'Disease', (60, 65))	('reduces', 'NegReg', (21, 28))
48536	27823582	We transfected CD3+ 293T cells with each F5 TCR variant and evaluated A2/MART1 tetramer binding by flow cytometry.	('CD3', 'Gene', '12501', (15, 18))	('293T', 'CellLine', 'CVCL:0063', (20, 24))	('F5 TCR', 'Gene', (41, 47))	('variant', 'Var', (48, 55))	('A2/MART1', 'Protein', (70, 78))	('TCR', 'Gene', (44, 47))	('CD3', 'Gene', (15, 18))	('binding', 'Interaction', (88, 95))
48538	27823582	To determine whether dsTCR chains properly assemble CD3 when mispaired with a wtTCR chain, we prepared hybrid constructs in which only the alpha or beta chain of F5 TCR was domain-swapped at the C-cp junction, and tested for expression on the surface of CD3+ 293T (Figure 2C).	('tested', 'Reg', (214, 220))	('CD3', 'Gene', (254, 257))	('F5 TCR', 'Gene', (162, 168))	('CD3', 'Gene', (52, 55))	('CD3', 'Gene', '12501', (254, 257))	('293T', 'CellLine', 'CVCL:0063', (259, 263))	('CD3', 'Gene', '12501', (52, 55))	('domain-swapped', 'Var', (173, 187))
48542	27823582	We constructed dsTCRC and hybrid wt/ds variants of two additional clinically relevant human TCRs - HLA-A2/MART1-specific M1 TCR and HLA-A2/NY-ESO-1-specific 1 G4 TCR -as well as the H-2Kb/ovalbumin-specific OTI murine TCR.	('H-2Kb', 'Gene', (182, 187))	('murine', 'Species', '10090', (211, 217))	('human', 'Species', '9606', (86, 91))	('H-2Kb', 'Gene', '14972', (182, 187))	('ovalbumin', 'Gene', '282665', (188, 197))	('NY-ESO-1', 'Gene', '246100', (139, 147))	('NY-ESO-1', 'Gene', (139, 147))	('variants', 'Var', (39, 47))	('ovalbumin', 'Gene', (188, 197))
48544	27823582	Altering the spatial relationship between constant TCR domains could potentially alter the orientation of CD3 chains in the TCR/CD3 complex, impairing its function.	('orientation', 'MPA', (91, 102))	('CD3', 'Gene', (106, 109))	('impairing', 'NegReg', (141, 150))	('Altering', 'Var', (0, 8))	('alter', 'Reg', (81, 86))	('CD3', 'Gene', '12501', (106, 109))	('function', 'MPA', (155, 163))	('CD3', 'Gene', (128, 131))	('CD3', 'Gene', '12501', (128, 131))
48561	27823582	Consistent with multimer staining results, dsTCRs mediated antigen-specific release of IL-2, whereas hybrid wt/dsTCRs simulating mispairing did not (Figure 3G).	('dsTCRs', 'Var', (43, 49))	('antigen-specific release', 'MPA', (59, 83))	('IL-2', 'Gene', (87, 91))	('IL-2', 'Gene', '16183', (87, 91))
48566	27823582	Nonetheless, T cells transduced with either wtTCR or dsTCRs were functional, secreting IFN-gamma and upregulating cell surface CD25 in an antigen-specific manner when coincubated with target cells (Figure 3I,J).	('IFN-gamma', 'Gene', (87, 96))	('cell surface CD25', 'MPA', (114, 131))	('IFN-gamma', 'Gene', '15978', (87, 96))	('upregulating', 'PosReg', (101, 113))	('dsTCRs', 'Var', (53, 59))
48574	27823582	Mice that develop TI-GvHD due to TCR chain mispairing exhibit destruction of the hematopoietic compartment and rapid weight loss, generally necessitating sacrifice within 1-2 days of onset of cachexia.	('weight loss', 'Disease', 'MESH:D015431', (117, 128))	('cachexia', 'Phenotype', 'HP:0004326', (192, 200))	('weight loss', 'Disease', (117, 128))	('weight loss', 'Phenotype', 'HP:0001824', (117, 128))	('TCR chain', 'Protein', (33, 42))	('cachexia', 'Disease', (192, 200))	('mispairing', 'Var', (43, 53))	('cachexia', 'Disease', 'MESH:D002100', (192, 200))	('Mice', 'Species', '10090', (0, 4))	('TI-GvHD', 'Chemical', '-', (18, 25))	('TI-GvHD', 'Disease', (18, 25))
48582	27823582	Thus, dsTCRs prevent mispairing and thereby prevent mispairing-related autoimmune complications in a model of TCR gene therapy.	('prevent', 'NegReg', (44, 51))	('autoimmune complications', 'Disease', 'MESH:D001327', (71, 95))	('mispairing', 'MPA', (21, 31))	('dsTCRs', 'Var', (6, 12))	('autoimmune complications', 'Phenotype', 'HP:0002960', (71, 95))	('autoimmune complications', 'Disease', (71, 95))	('mispairing-related', 'Disease', (52, 70))
48590	27823582	Both wtTCR- and dsTCR-transduced T cells slowed tumor growth when mice were injected with 1 T cell per 500 tumor cells, and prevented tumor growth entirely at higher tested ratios (Figure 4:figure supplement 4).	('dsTCR-transduced', 'Var', (16, 32))	('tumor', 'Disease', (48, 53))	('tumor', 'Disease', (107, 112))	('tumor', 'Phenotype', 'HP:0002664', (107, 112))	('mice', 'Species', '10090', (66, 70))	('slowed', 'NegReg', (41, 47))	('tumor', 'Disease', 'MESH:D009369', (134, 139))	('prevented', 'NegReg', (124, 133))	('tumor', 'Disease', 'MESH:D009369', (48, 53))	('tumor', 'Disease', 'MESH:D009369', (107, 112))	('tumor', 'Phenotype', 'HP:0002664', (134, 139))	('tumor', 'Phenotype', 'HP:0002664', (48, 53))	('tumor', 'Disease', (134, 139))
48593	27823582	We hypothesized that combining dsTCRs with endogenous TCR knockdown would improve cell surface expression of dsTCRs while also eliminating TI-GvHD entirely.	('TI-GvHD', 'Chemical', '-', (139, 146))	('improve', 'PosReg', (74, 81))	('TCR', 'Gene', (54, 57))	('cell surface expression', 'MPA', (82, 105))	('eliminating', 'NegReg', (127, 138))	('TI-GvHD', 'MPA', (139, 146))	('knockdown', 'Var', (58, 67))
48597	27823582	However, knockdown greatly improved surface expression and tetramer binding of the P14 dsTCR by reducing competition for assembly with CD3 chains (Figure 5B).	('P14', 'Gene', '20202', (83, 86))	('improved', 'PosReg', (27, 35))	('knockdown', 'Var', (9, 18))	('tetramer binding', 'Interaction', (59, 75))	('reducing', 'NegReg', (96, 104))	('surface expression', 'MPA', (36, 54))	('P14', 'Gene', (83, 86))	('competition', 'Interaction', (105, 116))	('CD3', 'Gene', (135, 138))	('CD3', 'Gene', '12501', (135, 138))
48602	27823582	In fact, knockdown of both endogenous chains increased mispairing of P14 wtalpha, suggesting the reduction of competing endogenous alpha enabled more mispairing of the weak P14 wtalpha with the remaining endogenous beta chain.	('reduction', 'NegReg', (97, 106))	('P14', 'Gene', '20202', (69, 72))	('P14', 'Gene', '20202', (173, 176))	('knockdown', 'Var', (9, 18))	('P14', 'Gene', (69, 72))	('mispairing', 'MPA', (55, 65))	('P14', 'Gene', (173, 176))	('mispairing', 'MPA', (150, 160))
48603	27823582	As allelic exclusion in TCR-transduced HSCs is incomplete, however, there remains a risk that TCR mispairing can precipitate autoimmunity.	('precipitate', 'Reg', (113, 124))	('autoimmunity', 'Disease', (125, 137))	('TCR', 'Gene', (94, 97))	('autoimmunity', 'Disease', 'MESH:D001327', (125, 137))	('mispairing', 'Var', (98, 108))	('autoimmunity', 'Phenotype', 'HP:0002960', (125, 137))
48604	27823582	HSCs transduced with dsTCRs would retain the advantages of wtTCR-engineered HSCs while eliminating the risk of autoimmunity.	('autoimmunity', 'Phenotype', 'HP:0002960', (111, 123))	('autoimmunity', 'Disease', 'MESH:D001327', (111, 123))	('autoimmunity', 'Disease', (111, 123))	('dsTCRs', 'Var', (21, 27))
48617	27823582	T cells expressing chimeric dsTCRs were activated and secreted IFN-gamma in response to coincubation with cognate antigen-expressing target cells (Figure 7G,H).	('IFN-gamma', 'Gene', (63, 72))	('chimeric dsTCRs', 'Var', (19, 34))	('dsTCRs', 'Var', (28, 34))	('secreted', 'MPA', (54, 62))	('IFN-gamma', 'Gene', '15978', (63, 72))
48619	27823582	As observed in Jurkats, chimeric dsalphadelta, dsalphagamma, and dsbetadelta chains did not mispair productively with wild-type alphabeta TCR chains (Figure 7F-H).	('dsalpha', 'Chemical', '-', (33, 40))	('alphabeta T', 'Disease', (128, 139))	('Jurkats', 'CellLine', 'CVCL:0065', (15, 22))	('dsalpha', 'Chemical', '-', (47, 54))	('dsbeta', 'Chemical', '-', (65, 71))	('chimeric', 'Var', (24, 32))	('alphabeta T', 'Disease', 'MESH:D001260', (128, 139))
48621	27823582	Thus, substitution of constant domains of tumor-specific alphabeta TCRs with corresponding gammadelta TCR domains produces a chimeric receptor that mediates functional, antigen-specific T cell immunity with minimized mispairing risk.	('tumor', 'Disease', (42, 47))	('alphabeta TCRs', 'Disease', (57, 71))	('mediates', 'Reg', (148, 156))	('substitution', 'Var', (6, 18))	('tumor', 'Disease', 'MESH:D009369', (42, 47))	('alphabeta TCRs', 'Disease', 'None', (57, 71))	('tumor', 'Phenotype', 'HP:0002664', (42, 47))
48623	27823582	However, mispairing between introduced and endogenous TCR chains produces autoreactive human T cells in vitro and causes graft-vs-host disease in mice, indicating that TCR gene transfer poses a non-theoretical risk of autoimmunity.	('autoreactive human T cells', 'CPA', (74, 100))	('graft-vs-host disease', 'CPA', (121, 142))	('human', 'Species', '9606', (87, 92))	('autoimmunity', 'Phenotype', 'HP:0002960', (218, 230))	('mispairing', 'Var', (9, 19))	('autoimmunity', 'Disease', (218, 230))	('mice', 'Species', '10090', (146, 150))	('autoimmunity', 'Disease', 'MESH:D001327', (218, 230))	('causes', 'Reg', (114, 120))
48624	27823582	By swapping constant domains between alpha and beta chains of a clinically-relevant alphabeta TCR, we generated a receptor that retains antigenic specificity and function but does not mispair with endogenous TCRs.	('alphabeta T', 'Disease', 'MESH:D001260', (84, 95))	('alphabeta T', 'Disease', (84, 95))	('swapping', 'Var', (3, 11))	('function', 'MPA', (162, 170))	('antigenic specificity', 'MPA', (136, 157))
48625	27823582	neither alpha nor beta self-associate); (2) mispairing between wt and ds chains results in a receptor that incompletely assembles with CD3 chains and is degraded; (3) mispaired wt/dsTCRs that escape degradation and express on the surface with an incomplete complement of CD3 chains will have impaired signaling capacity.	('signaling capacity', 'MPA', (301, 319))	('CD3', 'Gene', (271, 274))	('CD3', 'Gene', '12501', (135, 138))	('CD3', 'Gene', '12501', (271, 274))	('mispairing', 'Var', (44, 54))	('CD3', 'Gene', (135, 138))	('impaired', 'NegReg', (292, 300))	('mispaired', 'Var', (167, 176))
48634	27823582	Third, swapping domains closer to the V-C junction would avoid reorienting constant domains with respect to each other, thereby preserving all contacts with CD3.	('CD3', 'Gene', (157, 160))	('CD3', 'Gene', '12501', (157, 160))	('swapping', 'Var', (7, 15))	('contacts', 'MPA', (143, 151))	('preserving', 'Reg', (128, 138))	('reorienting constant domains', 'MPA', (63, 91))
48654	27823582	HLA-A2 and beta2-microglobulin were expressed in E. coli, refolded in the presence of MART126-35(A27L) (ELAGIGILTV) or NY-ESO-1157-165(C165V) (SLLMWITQV) heteroclitic peptides, purified, and biotinylated as previously described.	('MART126-35', 'Var', (86, 96))	('A27L', 'Mutation', 'p.A27L', (97, 101))	('NY-ESO-1', 'Gene', '246100', (119, 127))	('NY-ESO-1', 'Gene', (119, 127))	('E. coli', 'Species', '562', (49, 56))	('C165V', 'Mutation', 'p.C165V', (135, 140))
48698	27823582	Surface expression was assessed by flow cytometry with the following antibodies: anti-CD3epsilon-PE-Cy7 (clone 2 C11), anti-Valpha2-PE (clone B20.1), anti-Vbeta5-FITC (clone MR9-4), and HLA-A2/MART1(ELAGIGILTV) and H-2Kb/ovalbumin(SIINFEKL) dextramers.	('SIINFEKL', 'Disease', 'None', (231, 239))	('ovalbumin', 'Gene', '282665', (221, 230))	('ovalbumin', 'Gene', (221, 230))	('C11', 'Gene', '108083', (113, 116))	('SIINFEKL', 'Disease', (231, 239))	('C11', 'Gene', (113, 116))	('H-2Kb', 'Gene', (215, 220))	('H-2Kb', 'Gene', '14972', (215, 220))	('anti-CD3epsilon-PE-Cy7', 'Var', (81, 103))
48707	27823582	Flow cytometry analysis was performed on 1 x 106 cells per sample, and stained with anti-mouse CD45, HLA-A2/MART1(ELAGIGILTV) multimer, and the following anti-human antibodies: CD45, CD19, CD3, CD4, and CD8.	('CD3', 'Gene', (189, 192))	('CD8', 'Gene', (203, 206))	('CD19', 'Var', (183, 187))	('CD4', 'Gene', (177, 180))	('CD8', 'Gene', '925', (203, 206))	('human', 'Species', '9606', (159, 164))	('CD4', 'Gene', (95, 98))	('CD3', 'Gene', '12501', (189, 192))	('CD4', 'Gene', '12504', (177, 180))	('CD4', 'Gene', (194, 197))	('CD4', 'Gene', '12504', (194, 197))	('CD4', 'Gene', '12504', (95, 98))	('mouse', 'Species', '10090', (89, 94))
48719	27823582	Mouse splenocytes (2 x 106 cells/well) were activated in 1 mL C10 containing 2 mug/mL concanavalin A and 1 ng/mL IL-7 for 48 hr, then transduced with retroviral supernatant encoding OTI wtTCR, OTI dsTCR, or no TCR as described.	('OTI wtTCR', 'Var', (182, 191))	('OTI dsTCR', 'Var', (193, 202))	('IL-7', 'Gene', (113, 117))	('IL-7', 'Gene', '16196', (113, 117))	('Mouse', 'Species', '10090', (0, 5))
48734	27823582	After 72 hr incubation, the supernatant was tested with a commercial ELISA kit for secreted mouse interferon-gamma (BD) and the T cells were tested by flow cytometry for surface expression of Valpha2 TCRalpha, Vbeta5 TCRbeta, H-2Kb/Ova257-264 tetramer-specific TCR, and activation markers (anti-CD25 (clone PC61), anti-CD44 (clone IM7), and CD62L [clone MEL-14]).	('TCRalpha', 'Gene', '21473', (200, 208))	('TCRalpha', 'Gene', (200, 208))	('TCRbeta', 'Gene', (217, 224))	('IM7', 'Gene', '100035768', (331, 334))	('CD62L', 'Gene', '20343', (341, 346))	('anti-CD25', 'Var', (290, 299))	('CD62L', 'Gene', (341, 346))	('mouse', 'Species', '10090', (92, 97))	('TCRbeta', 'Gene', '21577', (217, 224))	('CD44', 'Gene', '12505', (319, 323))	('IM7', 'Gene', (331, 334))	('CD44', 'Gene', (319, 323))	('H-2Kb', 'Gene', (226, 231))	('H-2Kb', 'Gene', '14972', (226, 231))
48761	27823582	Thank you for submitting your article "Domain-swapped T cell receptors improve the safety of TCR gene therapy" for consideration by eLife.	('T cell receptor', 'Gene', '328483', (54, 69))	('TCR', 'Gene', (93, 96))	('safety', 'MPA', (83, 89))	('Domain-swapped', 'Var', (39, 53))	('T cell receptor', 'Gene', (54, 69))	('improve', 'PosReg', (71, 78))
48762	27823582	Summary: This interesting manuscript builds and tests domain-swapped chains of the T cell receptor heterodimer to demonstrate that a number of domain-swapped combinations permit reasonable maintenance of assembly and function upon heterologous expression, yet substantially prevent assembly with 'wild-type' endogenous chains and the functional consequences thereof.	('prevent', 'NegReg', (274, 281))	('domain-swapped combinations', 'Var', (143, 170))	('combinations', 'Var', (158, 170))	('T cell receptor', 'Gene', '328483', (83, 98))	('function', 'MPA', (217, 225))	('T cell receptor', 'Gene', (83, 98))	('assembly', 'MPA', (282, 290))	('assembly', 'MPA', (204, 212))
48764	27823582	Essential revisions: This is an exciting manuscript, but there are a few concerns we'd like you to address: 1) One concern relates to the somewhat sketchy quantification of the comparative efficiency of the domain-swapped T cell receptors.	('T cell receptor', 'Gene', '328483', (222, 237))	('domain-swapped', 'Var', (207, 221))	('T cell receptor', 'Gene', (222, 237))
48767	27823582	3) A major question in the manuscript is how the successful swapping strategies impact TCR/CD3 architecture on T cells, and what the authors perceive to be the 'loss of stabilizing contacts in the extracellular domains.	('swapping', 'Var', (60, 68))	('CD3', 'Gene', '12501', (91, 94))	('stabilizing contacts', 'MPA', (169, 189))	('impact', 'Reg', (80, 86))	('CD3', 'Gene', (91, 94))
48768	27823582	Figure 1 outlines the oft-discussed charges in the TM helices and how they are believed to interact and help align the CD3 chains, but it is not necessarily the case (albeit possible) that swapping these around would lead to a loss of stabilizing contacts in the extracellular parts, given what we know (and don't know) about the structural relationships and the constraints on TCR/CD3 overall architecture.	('loss', 'NegReg', (227, 231))	('CD3', 'Gene', (119, 122))	('CD3', 'Gene', '12501', (119, 122))	('stabilizing contacts', 'MPA', (235, 255))	('swapping', 'Var', (189, 197))	('CD3', 'Gene', (382, 385))	('CD3', 'Gene', '12501', (382, 385))
48769	27823582	10.7554/eLife.19095.020 [...] Essential revisions:  This is an exciting manuscript, but there are a few concerns we'd like you to address:  1) One concern relates to the somewhat sketchy quantification of the comparative efficiency of the domain-swapped T cell receptors.	('T cell receptor', 'Gene', (254, 269))	('domain-swapped', 'Var', (239, 253))	('T cell receptor', 'Gene', '328483', (254, 269))
48770	27823582	Specifically, there are two distinct ultimate functional outcomes in vivo being measured, and are correlatable with two distinct consequences of domain-swapped TCRs (dsTCRs); reduction of pairing with endogenous TCR chains correlatable with loss of GVH induction activity, and reduction of cell-surface dsTCR levels potentially correlatable with possible quantitative reduction of anti-tumor activity.	('loss', 'NegReg', (241, 245))	('tumor', 'Disease', (386, 391))	('pairing', 'MPA', (188, 195))	('cell-surface dsTCR levels', 'MPA', (290, 315))	('GVH', 'Gene', '110063', (249, 252))	('tumor', 'Disease', 'MESH:D009369', (386, 391))	('reduction', 'NegReg', (277, 286))	('reduction', 'NegReg', (175, 184))	('tumor', 'Phenotype', 'HP:0002664', (386, 391))	('activity', 'MPA', (263, 271))	('domain-swapped', 'Var', (145, 159))	('GVH', 'Gene', (249, 252))	('reduction', 'NegReg', (368, 377))
48841	26308738	AChR acetylcholine receptor CI confidence interval MG myasthenia gravis Acquired myasthenia gravis (MG) is an antibody-mediated autoimmune disease in which skeletal muscle weakness occurs as a result of impaired neuromuscular transmission because of loss of nicotinic acetylcholine receptors (AChRs) at the neuromuscular junction and disruption of postsynaptic membrane morphology.1 Acquired MG is a relatively common neuromuscular disease in dogs,2 but is less frequent in cats.3 The most common clinical signs of MG in cats include generalized weakness without megaesophagus and generalized weakness associated with a cranial mediastinal mass.2  Autoantibodies to AChRs are found in most human patients with acquired MG and rarely seen in healthy humans or patients with other diseases.4 A similar specificity of AChR antibodies is also present in dogs and cats with acquired MG.5 The presence of pathogenic AChR antibodies proves an autoimmune response against AChRs, which is not detected with other causes of muscle weakness.	('AChR', 'Gene', (0, 4))	('AChR', 'Gene', (666, 670))	('autoimmune disease', 'Disease', 'MESH:D001327', (128, 146))	('generalized weakness', 'Phenotype', 'HP:0003324', (534, 554))	('loss of nicotinic acetylcholine receptors', 'Phenotype', 'HP:0030208', (250, 291))	('AChR', 'Gene', (293, 297))	('myasthenia gravis', 'Disease', (81, 98))	('human', 'Species', '9606', (749, 754))	('cats', 'Species', '9685', (474, 478))	('dogs', 'Species', '9615', (850, 854))	('patients', 'Species', '9606', (759, 767))	('antibodies', 'Var', (915, 925))	('AChR', 'Gene', '751106', (0, 4))	('AChR', 'Gene', '751106', (666, 670))	('generalized weakness', 'Phenotype', 'HP:0003324', (581, 601))	('autoimmune disease', 'Phenotype', 'HP:0002960', (128, 146))	('AChR', 'Gene', (910, 914))	('muscle weakness', 'Phenotype', 'HP:0001324', (1014, 1029))	('myasthenia', 'Phenotype', 'HP:0003473', (81, 91))	('acetylcholine', 'Chemical', 'MESH:D000109', (268, 281))	('AChR', 'Gene', '751106', (293, 297))	('neuromuscular disease', 'Disease', (418, 439))	('patients', 'Species', '9606', (696, 704))	('cats', 'Species', '9685', (521, 525))	('myasthenia gravis', 'Disease', (54, 71))	('acetylcholine', 'Chemical', 'MESH:D000109', (5, 18))	('neuromuscular disease', 'Disease', 'MESH:D009468', (418, 439))	('AChR', 'Gene', (815, 819))	('AChR', 'Gene', (964, 968))	('AChR', 'Gene', '751106', (910, 914))	('muscle weakness', 'Phenotype', 'HP:0001324', (165, 180))	('dogs', 'Species', '9615', (443, 447))	('muscle weakness', 'Disease', (1014, 1029))	('human', 'Species', '9606', (690, 695))	('pathogenic', 'Reg', (899, 909))	('AChR', 'Gene', '751106', (815, 819))	('AChR', 'Gene', '751106', (964, 968))	('cats', 'Species', '9685', (859, 863))	('autoimmune response', 'Phenotype', 'HP:0002960', (936, 955))	('muscle weakness', 'Disease', 'MESH:D018908', (1014, 1029))	('myasthenia gravis', 'Disease', 'MESH:D009157', (81, 98))	('humans', 'Species', '9606', (749, 755))	('muscle weakness', 'Disease', (165, 180))	('myasthenia', 'Phenotype', 'HP:0003473', (54, 64))	('myasthenia gravis', 'Disease', 'MESH:D009157', (54, 71))	('muscle weakness', 'Disease', 'MESH:D018908', (165, 180))	('autoimmune disease', 'Disease', (128, 146))
49071	30607194	The white blood cells count found normochromic normocytic anaemia with Hb at 10.3 g/dl, WBC count 12 G/L without peripheral blasts, platelet count was at 35 G/L.	('anaemia', 'Disease', 'MESH:D000740', (58, 65))	('35 G/L', 'SUBSTITUTION', 'None', (154, 160))	('anaemia', 'Disease', (58, 65))	('35 G/L', 'Var', (154, 160))	('12 G/L', 'SUBSTITUTION', 'None', (98, 104))	('normocytic anaemia', 'Phenotype', 'HP:0001897', (47, 65))	('12 G/L', 'Var', (98, 104))	('normochromic normocytic anaemia', 'Phenotype', 'HP:0001895', (34, 65))	('anaemia', 'Phenotype', 'HP:0001903', (58, 65))
49093	30607194	NOTCH1 is the best-characterised member and was discovered from cases of human T-lymphoblastic lymphoma/leukaemia harbouring t(7; 9)(q34; q34.4), which juxtaposes B enhancer/promoter elements on chromosome 7.	('T-lymphoblastic lymphoma/leukaemia', 'Disease', (79, 113))	('lymphoma', 'Phenotype', 'HP:0002665', (95, 103))	('T-lymphoblastic lymphoma/leukaemia', 'Phenotype', 'HP:0005517', (79, 113))	('human', 'Species', '9606', (73, 78))	('NOTCH1', 'Gene', '4851', (0, 6))	('NOTCH1', 'Gene', (0, 6))	('T-lymphoblastic lymphoma/leukaemia', 'Disease', 'MESH:D054218', (79, 113))	('t(7; 9)(q34; q34.4', 'Var', (125, 143))
49172	28872098	Some papers have shown that patients with incomplete resection can achieve an overall survival comparable to those with complete resection, while others have shown that incomplete resection is associated with increased recurrence and worsening survival.	('worsening', 'NegReg', (234, 243))	('incomplete', 'Var', (169, 179))	('recurrence', 'CPA', (219, 229))	('patients', 'Species', '9606', (28, 36))	('survival', 'MPA', (244, 252))
49243	24872711	All rheumatologic tests were normal (urinalysis, collected 24-hour urine for calculation of creatinine, quantities of proteinuria and protein/creatinine ratios, antinuclear antibodies, anti-double stranded DNA, antiphospholide antibody, anti-Smith antibodies, and C3 and C4).	('protein/creatinine ratios', 'MPA', (134, 159))	('antinuclear antibodies', 'Phenotype', 'HP:0003493', (161, 183))	('proteinuria', 'Disease', (118, 129))	('proteinuria', 'Phenotype', 'HP:0000093', (118, 129))	('creatinine', 'MPA', (92, 102))	('proteinuria', 'Disease', 'MESH:D011507', (118, 129))	('anti-double', 'Var', (185, 196))	('antinuclear', 'Protein', (161, 172))	('creatinine', 'Chemical', 'MESH:D003404', (142, 152))	('creatinine', 'Chemical', 'MESH:D003404', (92, 102))	('antiphospholide', 'Protein', (211, 226))
49288	22824515	Graves disease (GD) is an autoimmune disease caused by self-reactive plasma cells which produce antibodies to the thyrotropin receptor that stimulate thyroid-stimulating hormone receptors and increase the production of thyroid hormone.	('Graves disease', 'Phenotype', 'HP:0100647', (0, 14))	('autoimmune disease', 'Disease', (26, 44))	('Graves disease', 'Disease', (0, 14))	('GD', 'Disease', 'MESH:D005776', (16, 18))	('thyrotropin receptor', 'Gene', (114, 134))	('autoimmune disease', 'Disease', 'MESH:D001327', (26, 44))	('autoimmune disease', 'Phenotype', 'HP:0002960', (26, 44))	('stimulate', 'PosReg', (140, 149))	('Graves disease', 'Disease', 'MESH:D006111', (0, 14))	('thyroid-stimulating hormone receptors', 'MPA', (150, 187))	('antibodies', 'Var', (96, 106))	('thyrotropin receptor', 'Gene', '7253', (114, 134))	('increase', 'PosReg', (192, 200))	('production of thyroid hormone', 'MPA', (205, 234))	('GD', 'Phenotype', 'HP:0100647', (16, 18))
49295	22824515	The immunophenotyping by flow cytometry revealed a predominance of T lymphoblasts (CD1a+, CD2+, CD4+, CD8+, sCD3-, TdT+) consistent with T-lymphoblastic leukemia/lymphoma (T-LBL/L).	('lymphoma', 'Phenotype', 'HP:0002665', (162, 170))	('T lymphoblasts', 'CPA', (67, 81))	('T-LBL', 'Chemical', '-', (172, 177))	('lymphoblastic leukemia', 'Phenotype', 'HP:0005526', (139, 161))	('CD4+', 'Var', (96, 100))	('CD1a', 'Gene', '909', (83, 87))	('T-lymphoblastic leukemia/lymphoma', 'Disease', (137, 170))	('TdT', 'Gene', (115, 118))	('CD8+', 'Var', (102, 106))	('T-lymphoblastic leukemia/lymphoma', 'Disease', 'MESH:D054218', (137, 170))	('TdT', 'Gene', '1791', (115, 118))	('-lymphoblastic leukemia/lymphoma', 'Phenotype', 'HP:0005531', (138, 170))	('CD1a', 'Gene', (83, 87))	('leukemia', 'Phenotype', 'HP:0001909', (153, 161))
49391	29387212	Subsequent to transfection, thymoma Wnt4 and JNK mRNA and protein expression were significantly decreased in shRNA-treated groups, with the strongest inhibition being 52.37%.	('JNK', 'Gene', '5599', (45, 48))	('decreased', 'NegReg', (96, 105))	('Wnt4', 'Gene', (36, 40))	('transfection', 'Var', (14, 26))	('thymoma', 'Disease', 'MESH:D013945', (28, 35))	('thymoma', 'Disease', (28, 35))	('Wnt4', 'Gene', '54361', (36, 40))	('thymoma', 'Phenotype', 'HP:0100522', (28, 35))	('JNK', 'Gene', (45, 48))
49475	29387212	Notably, shRNA transfection produced a large number of apoptotic (Hoechst 33342++/PI+) and necrotic (Hoechst 33342+/PI++) cells (Fig.	('Hoechst 33342+/PI++', 'Var', (101, 120))	('Hoechst 33342++/PI+', 'Var', (66, 85))	('necrotic', 'Disease', (91, 99))	('Hoechst 33342', 'Chemical', 'MESH:C017807', (66, 79))	('apoptotic', 'CPA', (55, 64))	('Hoechst 33342', 'Chemical', 'MESH:C017807', (101, 114))	('necrotic', 'Disease', 'MESH:D009336', (91, 99))	('transfection', 'Var', (15, 27))
49477	29387212	The apoptosis rate following shRNA transfection was 14.70+-0.62%, which was significant compared with controls (Fig.	('shRNA', 'Gene', (29, 34))	('transfection', 'Var', (35, 47))	('apoptosis', 'CPA', (4, 13))	('rat', 'Species', '10116', (14, 17))
49484	29387212	In addition, Wnt4 and JNK expression and apoptosis changes were observed in thymoma cells subsequent to Wnt4 gene silencing.	('thymoma', 'Disease', (76, 83))	('Wnt4', 'Gene', (104, 108))	('JNK', 'Gene', (22, 25))	('Wnt4', 'Gene', '54361', (104, 108))	('thymoma', 'Phenotype', 'HP:0100522', (76, 83))	('observed', 'Reg', (64, 72))	('gene silencing', 'Var', (109, 123))	('JNK', 'Gene', '5599', (22, 25))	('apoptosis changes', 'CPA', (41, 58))	('thymoma', 'Disease', 'MESH:D013945', (76, 83))	('Wnt4', 'Gene', (13, 17))	('Wnt4', 'Gene', '54361', (13, 17))
49492	29387212	Studies have shown that inhibition of Wnt signaling induces apoptosis and suppresses cell proliferation.	('rat', 'Species', '10116', (97, 100))	('cell proliferation', 'CPA', (85, 103))	('apoptosis', 'CPA', (60, 69))	('suppresses', 'NegReg', (74, 84))	('Wnt', 'Protein', (38, 41))	('inhibition', 'Var', (24, 34))
49508	27603335	In current clinical practice, daily fever and arthromyalgias are almost mandatory and in vast majority of the patients these symptoms are accompanied by elevated acute phase reactants, included hyperferritinemia (>5000 mug/L) on absence of specific markers of disease.	('myalgias', 'Phenotype', 'HP:0003326', (52, 60))	('arthromyalgias', 'Disease', (46, 60))	('acute phase reactants', 'MPA', (162, 183))	('arthromyalgias', 'Disease', 'None', (46, 60))	('fever', 'Disease', 'MESH:D005334', (36, 41))	('elevated', 'PosReg', (153, 161))	('fever', 'Disease', (36, 41))	('fever', 'Phenotype', 'HP:0001945', (36, 41))	('hyperferritinemia', 'Disease', 'MESH:C538137', (194, 211))	('hyperferritinemia', 'Disease', (194, 211))	('man', 'Species', '9606', (72, 75))	('hyperferritinemia', 'Phenotype', 'HP:0003281', (194, 211))	('>5000 mug/L', 'Var', (213, 224))	('patients', 'Species', '9606', (110, 118))	('daily fever', 'Phenotype', 'HP:0001954', (30, 41))
49521	27603335	resulted in a gradual subside of the symptoms; 1 month later, in the subsequent rheumatological control, CRP was 0.07 mg/dL, ferritin 487 ng/mL, and ESR 20 mm/h.	('CRP', 'Gene', (105, 108))	('0.07 mg/dL', 'Var', (113, 123))	('ferritin', 'Protein', (125, 133))	('CRP', 'Gene', '1401', (105, 108))
49648	30216434	They have recently been linked to mutations in the thymoma-specific transcription factor regulating growth factor signalling GTF2I and, to a lesser extent, HRAS, NRAS and TP53  1, 2.	('TP53', 'Gene', (171, 175))	('thymoma', 'Gene', '7063', (51, 58))	('GTF2I', 'Gene', '2969', (125, 130))	('thymoma', 'Phenotype', 'HP:0100522', (51, 58))	('thymoma', 'Gene', (51, 58))	('HRAS', 'Gene', '3265', (156, 160))	('NRAS', 'Gene', '4893', (162, 166))	('HRAS', 'Gene', (156, 160))	('GTF2I', 'Gene', (125, 130))	('linked', 'Reg', (24, 30))	('NRAS', 'Gene', (162, 166))	('mutations', 'Var', (34, 43))	('TP53', 'Gene', '7157', (171, 175))
49652	30216434	anti-acetylcholine receptor antibodies in myasthenia gravis (occurring in 17-40% of patients with thymoma); anti-glutamic acid decarboxylase (GAD65) and anti-glycine receptor antibodies in Stiff-person syndrome; anti-Kv1 Voltage-Gated K+ Channels (VGKC) or anti-Contactin-associated protein-like 2 (Caspr2) antibodies in acquired neuromyotonia and autoimmune encephalitis; and anti-P/Q-type Voltage-Gated Calcium Channels (VGCC) antibodies in Lambert-Eaton syndrome and autoimmune encephalitis 6.	('encephalitis', 'Phenotype', 'HP:0002383', (359, 371))	('myasthenia gravis', 'Disease', (42, 59))	('Lambert-Eaton syndrome', 'Disease', 'MESH:D015624', (443, 465))	('neuromyotonia', 'Disease', 'MESH:D020386', (330, 343))	('myasthenia', 'Phenotype', 'HP:0003473', (42, 52))	('Stiff-person syndrome', 'Disease', (189, 210))	('autoimmune encephalitis', 'Disease', 'MESH:C535841', (470, 493))	('neuromyotonia', 'Disease', (330, 343))	('autoimmune encephalitis', 'Disease', (470, 493))	('patients', 'Species', '9606', (84, 92))	('thymoma', 'Phenotype', 'HP:0100522', (98, 105))	('VGCC', 'Gene', (423, 427))	('acetylcholine receptor antibodies', 'Phenotype', 'HP:0030208', (5, 38))	('thymoma', 'Gene', '7063', (98, 105))	('Caspr2', 'Gene', (299, 305))	('thymoma', 'Gene', (98, 105))	('autoimmune encephalitis', 'Disease', 'MESH:C535841', (348, 371))	('myasthenia gravis', 'Disease', 'MESH:D009157', (42, 59))	('autoimmune encephalitis', 'Disease', (348, 371))	('person', 'Species', '9606', (195, 201))	('Caspr2', 'Gene', '26047', (299, 305))	('encephalitis', 'Phenotype', 'HP:0002383', (481, 493))	('GAD65', 'Gene', (142, 147))	('GAD65', 'Gene', '2572', (142, 147))	('Lambert-Eaton syndrome', 'Disease', (443, 465))	('anti-P/Q-type', 'Var', (377, 390))
49802	34011098	Dysfunction in the baroreflex mechanism may leads to dizziness, syncope, atrioventricular block, and even lethal atrial fibrillation.	('Dysfunction', 'Var', (0, 11))	('atrioventricular block', 'Disease', (73, 95))	('syncope', 'Disease', (64, 71))	('dizziness', 'Disease', 'MESH:D004244', (53, 62))	('atrioventricular block', 'Phenotype', 'HP:0001678', (73, 95))	('atrial fibrillation', 'Disease', (113, 132))	('atrial fibrillation', 'Disease', 'MESH:D001281', (113, 132))	('atrial fibrillation', 'Phenotype', 'HP:0005110', (113, 132))	('syncope', 'Disease', 'MESH:D013575', (64, 71))	('dizziness', 'Disease', (53, 62))	('atrioventricular block', 'Disease', 'MESH:D054537', (73, 95))	('dizziness', 'Phenotype', 'HP:0002321', (53, 62))	('syncope', 'Phenotype', 'HP:0001279', (64, 71))	('leads to', 'Reg', (44, 52))	('lethal atrial fibrillation', 'Phenotype', 'HP:0004754', (106, 132))
49842	34011098	Anti-Kv1.4 antibodies were found to be associated with myocarditis in MG patients.	('associated with', 'Reg', (39, 54))	('myocarditis', 'Disease', 'MESH:D009205', (55, 66))	('Kv1.4', 'Gene', '3739', (5, 10))	('antibodies', 'Var', (11, 21))	('myocarditis', 'Phenotype', 'HP:0012819', (55, 66))	('myocarditis', 'Disease', (55, 66))	('patients', 'Species', '9606', (73, 81))	('Kv1.4', 'Gene', (5, 10))
49843	34011098	Suzuki et al found that 10% of 650 MG patients were seropositive for anti-Kv1.4 antibodies, and eight patients who were clinically diagnosed with myocarditis were all anti-Kv1.4 antibody positive.	('myocarditis', 'Disease', 'MESH:D009205', (146, 157))	('Kv1.4', 'Gene', '3739', (74, 79))	('patients', 'Species', '9606', (102, 110))	('Kv1.4', 'Gene', (172, 177))	('myocarditis', 'Disease', (146, 157))	('myocarditis', 'Phenotype', 'HP:0012819', (146, 157))	('patients', 'Species', '9606', (38, 46))	('Kv1.4', 'Gene', (74, 79))	('antibodies', 'Var', (80, 90))	('Kv1.4', 'Gene', '3739', (172, 177))
50122	29670572	Moreover, an animal-model experiment has shown that acetylcholine mediates the conduction of information between gustatory bud recipient cells and increases the activities of gustatory afferent neurofibers.	('increases', 'PosReg', (147, 156))	('acetylcholine', 'Var', (52, 65))	('conduction of information between gustatory', 'MPA', (79, 122))	('acetylcholine', 'Chemical', 'MESH:D000109', (52, 65))	('gustatory', 'Protein', (175, 184))	('activities', 'MPA', (161, 171))
50156	29670572	For example, azathioprine, methotrexate, and nifedipine can induce dysgeusia, the drug-induced gustatory function disorder.	('nifedipine', 'Chemical', 'MESH:D009543', (45, 55))	('dysgeusia', 'Disease', (67, 76))	('gustatory function disorder', 'Disease', (95, 122))	('azathioprine', 'Chemical', 'MESH:D001379', (13, 25))	('dysgeusia', 'Phenotype', 'HP:0031249', (67, 76))	('dysgeusia', 'Disease', 'MESH:D004408', (67, 76))	('azathioprine', 'Var', (13, 25))	('gustatory function disorder', 'Disease', 'MESH:D012640', (95, 122))	('induce', 'Reg', (60, 66))	('methotrexate', 'Chemical', 'MESH:D008727', (27, 39))
50399	27794397	Tissue samples from patients with histologically confirmed, unresectable advanced (Masaoka stage III or stage IV) TETs enrolled in clinical trials at the National Cancer Institute (NCI) between December 2007 and December 2012 (ClinicalTrials.gov Identifier: NCT 00965250, NCT00589290, NCT01100944, NCT01621568) were included in this analysis.	('NCT00589290', 'Var', (272, 283))	('NCT01621568', 'Var', (298, 309))	('NCT01100944', 'Var', (285, 296))	('Cancer', 'Phenotype', 'HP:0002664', (163, 169))	('patients', 'Species', '9606', (20, 28))	('Cancer', 'Disease', 'MESH:D009369', (163, 169))	('Cancer', 'Disease', (163, 169))
50440	27794397	Among patients with thymic carcinoma (n=34), those with high mesothelin expression, defined as mesothelin expression in > 50% cells (n=19), had a significantly improved overall survival over patients with either no or low mesothelin expression (n=15) [median not reached vs. 1.60 years (95% CI: 1.24-4.94 years); HR=4.46, 95% CI: 1.55-12.80; P=0.0026] (Figure 3B).	('overall survival', 'MPA', (169, 185))	('carcinoma', 'Phenotype', 'HP:0030731', (27, 36))	('patients', 'Species', '9606', (191, 199))	('mesothelin', 'Gene', (222, 232))	('mesothelin', 'Gene', (61, 71))	('mesothelin', 'Gene', (95, 105))	('patients', 'Species', '9606', (6, 14))	('thymic carcinoma', 'Disease', (20, 36))	('thymic carcinoma', 'Disease', 'MESH:D013953', (20, 36))	('improved', 'PosReg', (160, 168))	('mesothelin', 'Gene', '10232', (222, 232))	('mesothelin', 'Gene', '10232', (61, 71))	('mesothelin', 'Gene', '10232', (95, 105))	('high', 'Var', (56, 60))
50463	27794397	Partial responses to DMOT4039A, an antibody-drug conjugate targeting mesothelin have also been observed in advanced pancreatic cancer and platinum-resistant ovarian cancer.	('DMOT4039A', 'Var', (21, 30))	('DMOT4039A', 'Chemical', '-', (21, 30))	('cancer', 'Phenotype', 'HP:0002664', (127, 133))	('platinum-resistant ovarian cancer', 'Disease', 'MESH:D010051', (138, 171))	('cancer', 'Phenotype', 'HP:0002664', (165, 171))	('ovarian cancer', 'Phenotype', 'HP:0100615', (157, 171))	('mesothelin', 'Gene', '10232', (69, 79))	('platinum-resistant ovarian cancer', 'Disease', (138, 171))	('pancreatic cancer', 'Phenotype', 'HP:0002894', (116, 133))	('pancreatic cancer', 'Disease', (116, 133))	('mesothelin', 'Gene', (69, 79))	('pancreatic cancer', 'Disease', 'MESH:D010190', (116, 133))
50472	27794397	Mesothelin expression was prognostic in thymic carcinoma with high mesothelin expression being associated with significantly prolonged survival.	('Mesothelin', 'Gene', '10232', (0, 10))	('thymic carcinoma', 'Disease', (40, 56))	('mesothelin', 'Gene', (67, 77))	('Mesothelin', 'Gene', (0, 10))	('thymic carcinoma', 'Disease', 'MESH:D013953', (40, 56))	('carcinoma', 'Phenotype', 'HP:0030731', (47, 56))	('prolonged', 'PosReg', (125, 134))	('mesothelin', 'Gene', '10232', (67, 77))	('high', 'Var', (62, 66))
50477	27794397	High mesothelin expression in thymic carcinoma is associated with longer survival.	('mesothelin', 'Gene', '10232', (5, 15))	('High', 'Var', (0, 4))	('carcinoma', 'Phenotype', 'HP:0030731', (37, 46))	('mesothelin', 'Gene', (5, 15))	('thymic carcinoma', 'Disease', (30, 46))	('thymic carcinoma', 'Disease', 'MESH:D013953', (30, 46))	('expression', 'MPA', (16, 26))
50525	32506527	As some therapeutic decisions are based on groupings of thymoma subtypes, we performed a subclassification of thymomas according to the ESMO clinical practice guidelines for diagnosis, treatment and follow-up into groups including (B2, B3) versus (A, AB, B1) and (B3) versus (A, AB, B1, B2).	('thymoma', 'Gene', '7063', (110, 117))	('B3', 'Var', (264, 266))	('thymoma', 'Gene', '7063', (56, 63))	('thymomas', 'Disease', (110, 118))	('thymomas', 'Disease', 'MESH:D013945', (110, 118))	('thymoma', 'Gene', (56, 63))	('thymoma', 'Gene', (110, 117))	('B2', 'Var', (232, 234))	('thymoma', 'Phenotype', 'HP:0100522', (110, 117))	('thymoma', 'Phenotype', 'HP:0100522', (56, 63))
50532	32506527	In this respect, alterations of GTF2I, which has a high mutation frequency in type A and AB thymomas when compared to other thymoma subtypes and thymic carcinomas, is a good example.	('carcinoma', 'Phenotype', 'HP:0030731', (152, 161))	('thymoma', 'Gene', '7063', (124, 131))	('thymic carcinomas', 'Disease', (145, 162))	('GTF2I', 'Gene', (32, 37))	('AB thymomas', 'Disease', (89, 100))	('AB thymomas', 'Disease', 'MESH:D013945', (89, 100))	('type A', 'Disease', (78, 84))	('thymic carcinomas', 'Disease', 'MESH:D013953', (145, 162))	('thymoma', 'Phenotype', 'HP:0100522', (92, 99))	('GTF2I', 'Gene', '2969', (32, 37))	('thymoma', 'Gene', (124, 131))	('carcinomas', 'Phenotype', 'HP:0030731', (152, 162))	('thymoma', 'Gene', '7063', (92, 99))	('alterations', 'Var', (17, 28))	('thymoma', 'Phenotype', 'HP:0100522', (124, 131))	('thymoma', 'Gene', (92, 99))
50533	32506527	18 ,  19  Other examples are mutations in KIT or TP53 in thymic carcinomas.	('KIT', 'Gene', (42, 45))	('TP53', 'Gene', '7157', (49, 53))	('TP53', 'Gene', (49, 53))	('thymic carcinomas', 'Disease', 'MESH:D013953', (57, 74))	('mutations', 'Var', (29, 38))	('thymic carcinomas', 'Disease', (57, 74))	('carcinoma', 'Phenotype', 'HP:0030731', (64, 73))	('KIT', 'Gene', '3815', (42, 45))	('carcinomas', 'Phenotype', 'HP:0030731', (64, 74))
50567	29983810	The biopsy response consulted by a group anatomopathologists was: lobular neoplasia consisting of solid neoplasms of polygonal epithelial elements (CK19+, CD117-, CD20-, CD5-) mixed with immature T elements (TdT +).	('neoplasms', 'Phenotype', 'HP:0002664', (104, 113))	('CD117-', 'Var', (155, 161))	('neoplasm', 'Phenotype', 'HP:0002664', (104, 112))	('neoplasms', 'Disease', 'MESH:D009369', (104, 113))	('neoplasms', 'Disease', (104, 113))	('CD5', 'Gene', (170, 173))	('CK19+', 'Var', (148, 153))	('CD20', 'Gene', '54474', (163, 167))	('CD20', 'Gene', (163, 167))	('neoplasia', 'Phenotype', 'HP:0002664', (74, 83))	('TdT', 'Gene', (208, 211))	('CD5', 'Gene', '921', (170, 173))	('lobular neoplasia', 'Disease', (66, 83))	('lobular neoplasia', 'Phenotype', 'HP:0030076', (66, 83))	('TdT', 'Gene', '1791', (208, 211))	('lobular neoplasia', 'Disease', 'MESH:D009369', (66, 83))
50604	29403543	Although patients with autoantibodies to muscle-specific tyrosine kinase (anti-MuSK positive) are more likely to become treatment refractory than those with autoantibodies to the acetylcholine receptor (anti-AChR positive), each of these serotypes is substantially represented in the refractory MG population.	('patients', 'Species', '9606', (9, 17))	('AChR', 'Chemical', '-', (208, 212))	('anti-MuSK positive', 'Phenotype', 'HP:0030210', (74, 92))	('men', 'Species', '9606', (125, 128))	('autoantibodies', 'Var', (23, 37))	('treatment', 'Disease', (120, 129))	('MuSK', 'Gene', (79, 83))	('MuSK', 'Gene', '4593', (79, 83))
50613	29403543	However, recent work has demonstrated heterogeneity in disease course and treatment response based on patient antibody profile: patients with antibodies to muscle-specific tyrosine kinase (anti-MuSK positive) appear to be less responsive to conventional treatment than those with antibodies to the acetylcholine receptor (anti-AChR positive) or those without anti-MuSK or anti-AChR antibodies.	('men', 'Species', '9606', (79, 82))	('MuSK', 'Gene', '4593', (194, 198))	('responsive to conventional treatment', 'MPA', (227, 263))	('patient', 'Species', '9606', (102, 109))	('MuSK', 'Gene', (364, 368))	('MuSK', 'Gene', '4593', (364, 368))	('less', 'NegReg', (222, 226))	('men', 'Species', '9606', (259, 262))	('AChR', 'Chemical', '-', (377, 381))	('anti-MuSK positive', 'Phenotype', 'HP:0030210', (189, 207))	('patient', 'Species', '9606', (128, 135))	('patients', 'Species', '9606', (128, 136))	('AChR', 'Chemical', '-', (327, 331))	('antibodies', 'Var', (142, 152))	('MuSK', 'Gene', (194, 198))
50646	29403543	Patients who were anti-MuSK positive also had more severe disease at onset, with 60.1% exhibiting bulbar dysfunction compared with 35.2% of patients who were anti-AChR positive and 23.8% of those who were DN (p < 0.001).	('MuSK', 'Gene', (23, 27))	('MuSK', 'Gene', '4593', (23, 27))	('Patients', 'Species', '9606', (0, 8))	('positive', 'Var', (28, 36))	('anti-MuSK positive', 'Phenotype', 'HP:0030210', (18, 36))	('patients', 'Species', '9606', (140, 148))	('DN', 'Chemical', '-', (205, 207))	('bulbar dysfunction', 'Disease', (98, 116))	('AChR', 'Chemical', '-', (163, 167))
50647	29403543	These differences continued to be pronounced at maximal worsening, with 83.6% of patients who were anti-MuSK positive exhibiting bulbar symptoms compared with 58.6% and 43.8% in the anti-AChR-positive and DN groups, respectively.	('positive', 'Var', (109, 117))	('anti-MuSK positive', 'Phenotype', 'HP:0030210', (99, 117))	('bulbar symptoms', 'Disease', (129, 144))	('bulbar symptoms', 'Phenotype', 'HP:0002483', (129, 144))	('patients', 'Species', '9606', (81, 89))	('MuSK', 'Gene', (104, 108))	('MuSK', 'Gene', '4593', (104, 108))	('DN', 'Chemical', '-', (205, 207))	('AChR', 'Chemical', '-', (187, 191))
50654	29403543	Taken together, the Suh and Baggi studies show that MG associated with anti-MuSK antibodies tends toward a more severe form of MG that is more resistant to treatment with more severe symptomatology (e.g.	('antibodies', 'Var', (81, 91))	('anti-MuSK antibodies', 'Phenotype', 'HP:0030210', (71, 91))	('MuSK', 'Gene', (76, 80))	('MuSK', 'Gene', '4593', (76, 80))	('men', 'Species', '9606', (161, 164))
50656	29403543	Although the reasons for the severity of anti-MuSK-positive MG remain unclear, evidence exists that anti-MuSK antibodies do not bind complement and may disrupt multiple components of the NMJ, including those that help to anchor and stabilize the AChR molecular scaffold of the postsynaptic membrane.	('MuSK', 'Gene', '4593', (46, 50))	('MuSK', 'Gene', '4593', (105, 109))	('anti-MuSK antibodies', 'Phenotype', 'HP:0030210', (100, 120))	('anti-MuSK-positive', 'Phenotype', 'HP:0030210', (41, 59))	('AChR', 'Chemical', '-', (246, 250))	('men', 'Species', '9606', (139, 142))	('disrupt', 'NegReg', (152, 159))	('antibodies', 'Var', (110, 120))	('MuSK', 'Gene', (46, 50))	('MuSK', 'Gene', (105, 109))
50660	29403543	In the case series analyzed by Baggi and colleagues, approximately 70%, 46%, and 50% of patients with anti-AChR-positive, anti-MuSK-positive, and DN MG, respectively, had undergone thymic surgery.	('MuSK', 'Gene', (127, 131))	('thymic surgery', 'Disease', (181, 195))	('MuSK', 'Gene', '4593', (127, 131))	('patients', 'Species', '9606', (88, 96))	('DN', 'Chemical', '-', (146, 148))	('anti-AChR-positive', 'Protein', (102, 120))	('anti-MuSK-positive', 'Phenotype', 'HP:0030210', (122, 140))	('DN MG', 'Var', (146, 151))	('AChR', 'Chemical', '-', (107, 111))
50661	29403543	Although most patients who underwent thymic surgery demonstrated some degree of thymic abnormality (involuted thymus histology or thymic hyperplasia), progression to frank thymoma was much more common in the anti-AChR-positive group (~30%) than in the anti-MuSK-positive and DN groups (0 and 2%, respectively).	('thymic hyperplasia', 'Disease', 'MESH:D013952', (130, 148))	('DN', 'Chemical', '-', (275, 277))	('MuSK', 'Gene', '4593', (257, 261))	('frank thymoma', 'Disease', (166, 179))	('MuSK', 'Gene', (257, 261))	('AChR', 'Chemical', '-', (213, 217))	('anti-MuSK-positive', 'Phenotype', 'HP:0030210', (252, 270))	('thymoma', 'Phenotype', 'HP:0100522', (172, 179))	('thymic hyperplasia', 'Disease', (130, 148))	('thymic hyperplasia', 'Phenotype', 'HP:0010516', (130, 148))	('frank thymoma', 'Disease', 'MESH:D013945', (166, 179))	('patients', 'Species', '9606', (14, 22))	('anti-AChR-positive', 'Var', (208, 226))	('thymic abnormality', 'Phenotype', 'HP:0000777', (80, 98))
50719	29403543	The primary endpoint did not differ significantly between patients treated with eculizumab versus placebo; however, eculizumab treatment significantly improved the assessed secondary efficacy outcomes compared with placebo.	('improved', 'PosReg', (151, 159))	('eculizumab', 'Var', (116, 126))	('eculizumab', 'Chemical', 'MESH:C481642', (80, 90))	('men', 'Species', '9606', (132, 135))	('eculizumab', 'Chemical', 'MESH:C481642', (116, 126))	('patients', 'Species', '9606', (58, 66))
50779	22937421	Vimentin positivity and smooth muscle actin, desmin, epithelial membrane antigen, CD 45, CD 30, and CD 3 negativity as in our case made the final diagnosis.	('Vimentin', 'Gene', '7431', (0, 8))	('desmin', 'Gene', (45, 51))	('CD 30', 'Gene', (89, 94))	('negativity', 'NegReg', (105, 115))	('positivity', 'Var', (9, 19))	('desmin', 'Gene', '1674', (45, 51))	('smooth muscle actin', 'Protein', (24, 43))	('epithelial membrane antigen, CD 45', 'Gene', '5788', (53, 87))	('CD 30', 'Gene', '943', (89, 94))	('Vimentin', 'Gene', (0, 8))
50808	30568129	After irradiation and chemotherapy, the thymoma was successfully resected, and additional immunoabsorption therapy alleviated the symptoms of MG. MG was subsequently controlled well with 10 mg of prednisolone.	('prednisolone', 'Chemical', 'MESH:D011239', (196, 208))	('thymoma', 'Disease', (40, 47))	('alleviated', 'NegReg', (115, 125))	('thymoma', 'Phenotype', 'HP:0100522', (40, 47))	('MG. MG', 'Var', (142, 148))	('thymoma', 'Disease', 'MESH:D013945', (40, 47))
50820	30568129	In addition to antibodies to the neuromuscular junction, anti-neuronal antibodies may also provoke depression, anxiety, dementia, and autonomic failure.	('anxiety', 'Disease', 'MESH:D001007', (111, 118))	('depression', 'Phenotype', 'HP:0000716', (99, 109))	('depression', 'Disease', (99, 109))	('dementia', 'Phenotype', 'HP:0000726', (120, 128))	('anxiety', 'Disease', (111, 118))	('dementia', 'Disease', (120, 128))	('anxiety', 'Phenotype', 'HP:0000739', (111, 118))	('autonomic failure', 'Disease', 'MESH:D006333', (134, 151))	('provoke', 'Reg', (91, 98))	('autonomic failure', 'Phenotype', 'HP:0012332', (134, 151))	('dementia', 'Disease', 'MESH:D003704', (120, 128))	('autonomic failure', 'Disease', (134, 151))	('anti-neuronal antibodies', 'Var', (57, 81))	('depression', 'Disease', 'MESH:D000275', (99, 109))
50824	30568129	Anti-striational antibodies, such as anti-titin, anti-ryanodine receptor, and anti-Kv1.4, are often detected in some MG patients.	('titin', 'Gene', '7273', (42, 47))	('titin', 'Gene', (42, 47))	('Anti-striational', 'Protein', (0, 16))	('anti-ryanodine', 'Var', (49, 63))	('Kv1.4', 'Gene', (83, 88))	('patients', 'Species', '9606', (120, 128))	('Kv1.4', 'Gene', '3739', (83, 88))	('detected', 'Reg', (100, 108))
50842	30568129	In particular, the subtype thymoma-associated MG can generate various immunological disturbances, including effects on non-motor systems due to T cell malfunctions, which are highly influenced by thymoma.	('immunological disturbances', 'Phenotype', 'HP:0002715', (70, 96))	('thymoma', 'Disease', 'MESH:D013945', (196, 203))	('subtype', 'Var', (19, 26))	('effects', 'Reg', (108, 115))	('generate', 'Reg', (53, 61))	('immunological disturbances', 'MPA', (70, 96))	('thymoma', 'Disease', (196, 203))	('thymoma', 'Disease', 'MESH:D013945', (27, 34))	('thymoma', 'Disease', (27, 34))	('thymoma', 'Phenotype', 'HP:0100522', (196, 203))	('thymoma', 'Phenotype', 'HP:0100522', (27, 34))	('non-motor systems', 'MPA', (119, 136))
50904	28632791	For patients with thymomas, incomplete resection (including R1 or R2 resection) was the predisposing factor for thymoma recurrence.	('thymoma', 'Phenotype', 'HP:0100522', (18, 25))	('thymoma', 'Disease', 'MESH:D013945', (112, 119))	('thymoma', 'Disease', (112, 119))	('thymomas', 'Disease', (18, 26))	('thymomas', 'Disease', 'MESH:D013945', (18, 26))	('thymoma', 'Phenotype', 'HP:0100522', (112, 119))	('thymoma', 'Disease', 'MESH:D013945', (18, 25))	('R2 resection', 'Var', (66, 78))	('patients', 'Species', '9606', (4, 12))	('thymoma', 'Disease', (18, 25))
50905	28632791	In our study, we also found that patients with R1 or R2 resection of thymoma had worse prognosis and higher recurrence rates than patients with R0 resection.	('thymoma', 'Phenotype', 'HP:0100522', (69, 76))	('patients', 'Species', '9606', (33, 41))	('thymoma', 'Disease', (69, 76))	('patients', 'Species', '9606', (130, 138))	('thymoma', 'Disease', 'MESH:D013945', (69, 76))	('recurrence rates', 'CPA', (108, 124))	('R2 resection', 'Var', (53, 65))
50971	12709261	Six of the peptides generated specific CTL responses after immunization, but only two of these peptides (RAD23-31 and RAD24-31) were capable of generating a weak vaccination-induced protection against adoptive tumor growth.	('tumor', 'Phenotype', 'HP:0002664', (210, 215))	('RAD24-31', 'Var', (118, 126))	('tumor', 'Disease', (210, 215))	('RAD23-31', 'Var', (105, 113))	('CTL', 'MPA', (39, 42))	('tumor', 'Disease', 'MESH:D009369', (210, 215))
50973	12709261	However, prophylactic vaccination with RAD23-31 and RAD24-31 peptides combined with anti-CTLA4 Ab treatment and did not improve tumor resistance.	('tumor', 'Disease', 'MESH:D009369', (128, 133))	('CTLA4', 'Gene', (89, 94))	('RAD24-31', 'Var', (52, 60))	('tumor', 'Phenotype', 'HP:0002664', (128, 133))	('RAD23-31', 'Var', (39, 47))	('CTLA4', 'Gene', '12477', (89, 94))	('tumor', 'Disease', (128, 133))
50990	12709261	Only two of the RAD50 peptides, RAD23-31 and RAD24-31, with KD values of 280 and 70 NM respectively, induced a CTL response (Fig.	('RAD24-31', 'Var', (45, 53))	('RAD23-31', 'Var', (32, 40))	('RAD50', 'Gene', '19360', (16, 21))	('RAD50', 'Gene', (16, 21))	('CTL response', 'MPA', (111, 123))	('induced', 'Reg', (101, 108))
51000	12709261	Groups of 7-8 mice were vaccinationated three times with a pool of the six RAD50 peptides or a mixture of the two immunogenic RAD23-31 and RAD24-31 peptides.	('RAD50', 'Gene', (75, 80))	('mice', 'Species', '10090', (14, 18))	('RAD50', 'Gene', '19360', (75, 80))	('RAD24-31', 'Var', (139, 147))
51003	12709261	A significant protection against tumor take was obtained in mice vaccinated with a mixture of RAD23-31 and RAD24-31 peptides (p < 0.03).	('tumor', 'Disease', 'MESH:D009369', (33, 38))	('RAD24-31 peptides', 'Var', (107, 124))	('RAD23-31', 'Var', (94, 102))	('tumor', 'Phenotype', 'HP:0002664', (33, 38))	('tumor', 'Disease', (33, 38))	('mice', 'Species', '10090', (60, 64))
51015	12709261	However, neither RAD23-31 and RAD24-31 peptide vaccination alone nor combined with anti-CTLA4 Ab treatment did delay tumor take in this experiment.	('tumor', 'Phenotype', 'HP:0002664', (117, 122))	('delay tumor', 'Disease', 'MESH:D009369', (111, 122))	('CTLA4', 'Gene', '12477', (88, 93))	('delay tumor', 'Disease', (111, 122))	('RAD24-31', 'Var', (30, 38))	('CTLA4', 'Gene', (88, 93))
51016	12709261	Vaccination with a mixture of two immunogenic RAD50-peptides, RAD23-31 and RAD24-31, detected among six H-2b binding ones, had some protective capacity in mice against tumor take following a subcutaneous inoculation of 106 SM7 thymoma cells.	('RAD23-31', 'Var', (62, 70))	('tumor', 'Disease', (168, 173))	('RAD50', 'Gene', '19360', (46, 51))	('RAD50', 'Gene', (46, 51))	('SM7', 'CellLine', 'CVCL:D159', (223, 226))	('thymoma', 'Disease', 'MESH:D013945', (227, 234))	('mice', 'Species', '10090', (155, 159))	('thymoma', 'Disease', (227, 234))	('tumor', 'Disease', 'MESH:D009369', (168, 173))	('thymoma', 'Phenotype', 'HP:0100522', (227, 234))	('RAD24-31', 'Var', (75, 83))	('tumor', 'Phenotype', 'HP:0002664', (168, 173))
51029	12709261	Thirdly, CTLA4 blockade, which suppresses inhibitory costimulatory signals in responder T cells, tended to delay the rejection of inoculated SM7 tumor cells in naive mice (Fig.	('blockade', 'Var', (15, 23))	('tumor', 'Disease', 'MESH:D009369', (145, 150))	('rejection', 'CPA', (117, 126))	('CTLA4', 'Gene', '12477', (9, 14))	('tumor', 'Phenotype', 'HP:0002664', (145, 150))	('delay', 'NegReg', (107, 112))	('tumor', 'Disease', (145, 150))	('mice', 'Species', '10090', (166, 170))	('CTLA4', 'Gene', (9, 14))	('SM7', 'CellLine', 'CVCL:D159', (141, 144))	('suppresses', 'NegReg', (31, 41))	('inhibitory costimulatory signals', 'MPA', (42, 74))
51030	12709261	However, CTLA4 blockage failed to improve survival in RAD23-31 and RAD24-31 vaccinated mice, although a protective collaboration between vaccination and CTLA4 blocking has been demonstrated previously.	('CTLA4', 'Gene', '12477', (9, 14))	('blockage', 'Var', (15, 23))	('CTLA4', 'Gene', '12477', (153, 158))	('mice', 'Species', '10090', (87, 91))	('CTLA4', 'Gene', (9, 14))	('CTLA4', 'Gene', (153, 158))
51033	12709261	Finally, the observation that only three of five vaccinated and protected mice developed memory for tumor rejection after a second tumor challenge, suggests that the RAD23-31 and RAD24-31 peptides are at best weak rejection epitopes which would be assumed to result in generation of weak memory.	('weak memory', 'Phenotype', 'HP:0002354', (283, 294))	('tumor', 'Phenotype', 'HP:0002664', (100, 105))	('tumor', 'Disease', 'MESH:D009369', (131, 136))	('tumor', 'Disease', (100, 105))	('RAD23-31', 'Var', (166, 174))	('tumor', 'Phenotype', 'HP:0002664', (131, 136))	('tumor', 'Disease', (131, 136))	('mice', 'Species', '10090', (74, 78))	('tumor', 'Disease', 'MESH:D009369', (100, 105))	('RAD24-31', 'Var', (179, 187))
51034	12709261	It is unclear why vaccination with the two immunogenic peptides (RAD23-31, RAD24-31) alone showed protection, but lacked protection in the present study when mixed with the four non-immunogenic peptides in the RAD50 peptide mixture.	('RAD50', 'Gene', (210, 215))	('RAD24-31', 'Var', (75, 83))	('lacked', 'NegReg', (114, 120))	('RAD50', 'Gene', '19360', (210, 215))
51074	12709261	The percentage of specific lysis (SL) was calculated from the following formula: Groups of 7-10 C57BL/6J mice were vaccinated three times s.c. at weekly intervals with a mixture of six RAD50, a mixture of RAD23-31 and RAD24-31 peptides and a mixture of four immunogenic peptides derived from other potentially upregulated SM7 proteins (see Table 1).	('RAD50', 'Gene', (185, 190))	('SM7', 'CellLine', 'CVCL:D159', (322, 325))	('RAD23-31', 'Var', (205, 213))	('RAD24-31', 'Var', (218, 226))	('mice', 'Species', '10090', (105, 109))	('RAD50', 'Gene', '19360', (185, 190))
51087	31817988	Additionally, knockdown of RASSF10 or ASPP2 induced constitutive phosphorylation of SMAD2 (Smad family member 2).	('ASPP2', 'Gene', (38, 43))	('RASSF10', 'Gene', (27, 34))	('constitutive phosphorylation', 'MPA', (52, 80))	('SMAD2', 'Gene', (84, 89))	('knockdown', 'Var', (14, 23))	('phospho', 'Chemical', 'MESH:C033601', (65, 72))
51088	31817988	Moreover, we found that epigenetic reduction of RASSF10 levels correlates with tumor progression and poor survival in human cancers.	('tumor', 'Phenotype', 'HP:0002664', (79, 84))	('tumor', 'Disease', (79, 84))	('epigenetic reduction', 'Var', (24, 44))	('cancer', 'Phenotype', 'HP:0002664', (124, 130))	('RASSF10', 'Gene', (48, 55))	('cancers', 'Phenotype', 'HP:0002664', (124, 131))	('human', 'Species', '9606', (118, 123))	('tumor', 'Disease', 'MESH:D009369', (79, 84))	('cancers', 'Disease', (124, 131))	('cancers', 'Disease', 'MESH:D009369', (124, 131))
51089	31817988	This data suggests that epigenetic loss of RASSF10 contributes to tumorigenesis by promoting EMT induced by TGFbeta.	('tumor', 'Phenotype', 'HP:0002664', (66, 71))	('promoting', 'PosReg', (83, 92))	('RASSF10', 'Gene', (43, 50))	('tumor', 'Disease', (66, 71))	('contributes', 'Reg', (51, 62))	('EMT', 'Gene', (93, 96))	('EMT', 'Gene', '3702', (93, 96))	('epigenetic loss', 'Var', (24, 39))	('tumor', 'Disease', 'MESH:D009369', (66, 71))
51090	31817988	Cancer is caused by a multistep genetic and epigenetic transformation of normal cells into highly invasive and immortal tumor cells.	('Cancer', 'Phenotype', 'HP:0002664', (0, 6))	('Cancer', 'Disease', (0, 6))	('epigenetic', 'Var', (44, 54))	('tumor', 'Disease', 'MESH:D009369', (120, 125))	('Cancer', 'Disease', 'MESH:D009369', (0, 6))	('tumor', 'Phenotype', 'HP:0002664', (120, 125))	('tumor', 'Disease', (120, 125))
51093	31817988	Different genetic and epigenetic alterations have been identified that are associated with EMT.	('rat', 'Species', '10116', (37, 40))	('EMT', 'Gene', '3702', (91, 94))	('epigenetic alterations', 'Var', (22, 44))	('EMT', 'Gene', (91, 94))	('associated', 'Reg', (75, 85))
51094	31817988	Epithelial cadherin (CDH1) is a master mediator of cell-cell adherens junctions and loss of CDH1 expression is associated with disruption of apical-basal polarity and integrity of epithelial cells.	('apical-basal polarity', 'CPA', (141, 162))	('CDH1', 'Gene', '999', (21, 25))	('associated', 'Reg', (111, 121))	('CDH1', 'Gene', (92, 96))	('expression', 'Species', '29278', (97, 107))	('loss', 'Var', (84, 88))	('CDH1', 'Gene', (21, 25))	('CDH1', 'Gene', '999', (92, 96))	('integrity of epithelial', 'CPA', (167, 190))
51103	31817988	Epigenetic inactivation of RASSF10 through promoter hypermethylation has been reported in various tumor entities including lung cancer, thyroid cancer, melanoma and several others.	('thyroid cancer', 'Disease', 'MESH:D013964', (136, 150))	('melanoma', 'Phenotype', 'HP:0002861', (152, 160))	('melanoma', 'Disease', (152, 160))	('cancer', 'Phenotype', 'HP:0002664', (144, 150))	('melanoma', 'Disease', 'MESH:D008545', (152, 160))	('lung cancer', 'Disease', (123, 134))	('lung cancer', 'Phenotype', 'HP:0100526', (123, 134))	('tumor entities', 'Disease', (98, 112))	('RASSF10', 'Gene', (27, 34))	('thyroid cancer', 'Disease', (136, 150))	('tumor', 'Phenotype', 'HP:0002664', (98, 103))	('tumor entities', 'Disease', 'MESH:D009369', (98, 112))	('lung cancer', 'Disease', 'MESH:D008175', (123, 134))	('cancer', 'Phenotype', 'HP:0002664', (128, 134))	('thyroid cancer', 'Phenotype', 'HP:0002890', (136, 150))	('promoter', 'MPA', (43, 51))	('Epigenetic inactivation', 'Var', (0, 23))	('reported', 'Reg', (78, 86))
51108	31817988	Furthermore, we found that RASSF10, but not ASPP2, is frequently hypermethylated in human cancers and the loss of RASSF10 is associated with advanced tumor stages and impaired survival of cancer patients.	('cancers', 'Disease', (90, 97))	('cancer', 'Phenotype', 'HP:0002664', (90, 96))	('RASSF10', 'Gene', (27, 34))	('cancer', 'Disease', 'MESH:D009369', (188, 194))	('tumor', 'Phenotype', 'HP:0002664', (150, 155))	('RASSF10', 'Gene', (114, 121))	('associated', 'Reg', (125, 135))	('patients', 'Species', '9606', (195, 203))	('cancer', 'Disease', 'MESH:D009369', (90, 96))	('cancers', 'Disease', 'MESH:D009369', (90, 97))	('impaired', 'NegReg', (167, 175))	('human', 'Species', '9606', (84, 89))	('cancer', 'Disease', (188, 194))	('tumor', 'Disease', (150, 155))	('loss', 'Var', (106, 110))	('cancer', 'Phenotype', 'HP:0002664', (188, 194))	('tumor', 'Disease', 'MESH:D009369', (150, 155))	('cancers', 'Phenotype', 'HP:0002664', (90, 97))	('survival', 'CPA', (176, 184))	('cancer', 'Disease', (90, 96))
51109	31817988	We studied human cancer cell lines (CCLE, cancer cell line encyclopedia, Broad Institute, n = 917,) and found that expression of RASSF10 (238755_at) significantly correlated with the expression of genes associated with the GO (gene ontology) terms cell periphery, plasma membrane (apical), epidermal/epithelial cell differentiation and cell-cell junction (Table 1).	('238755_at', 'Var', (138, 147))	('cancer', 'Phenotype', 'HP:0002664', (42, 48))	('correlated', 'Reg', (163, 173))	('human', 'Species', '9606', (11, 16))	('cancer', 'Disease', 'MESH:D009369', (17, 23))	('expression', 'Species', '29278', (115, 125))	('expression', 'Species', '29278', (183, 193))	('cancer', 'Disease', (17, 23))	('cancer', 'Disease', (42, 48))	('expression', 'MPA', (183, 193))	('cancer', 'Disease', 'MESH:D009369', (42, 48))	('RASSF10', 'Gene', (129, 136))	('cancer', 'Phenotype', 'HP:0002664', (17, 23))
51113	31817988	Therefore, we generated a RASSF10 knockout in the prototypic epithelial cell line A549 by CRISPR/Cas9 (Figure 1c; frameshift deletion mutation).	('rat', 'Species', '10116', (18, 21))	('A549', 'CellLine', 'CVCL:0023', (82, 86))	('frameshift deletion mutation', 'Var', (114, 142))	('RASSF10', 'Gene', (26, 33))
51116	31817988	In contrast, RASSF10 re-expression in HeLa cells with epigenetically inactivated endogenous RASSF10 halted cell proliferation (G1/G0 induction) measured by flow cytometry (Figure 1h).	('expression', 'Species', '29278', (24, 34))	('RASSF10', 'Gene', (92, 99))	('rat', 'Species', '10116', (119, 122))	('cell proliferation', 'CPA', (107, 125))	('halted', 'NegReg', (100, 106))	('HeLa', 'CellLine', 'CVCL:0030', (38, 42))	('epigenetically inactivated', 'Var', (54, 80))
51121	31817988	We assumed that loss of the tumor-suppressor RASSF10 in cancer contributes to the transition of epithelial to mesenchymal cell phenotypes.	('tumor', 'Disease', (28, 33))	('RASSF10', 'Gene', (45, 52))	('cancer', 'Phenotype', 'HP:0002664', (56, 62))	('loss', 'Var', (16, 20))	('tumor', 'Disease', 'MESH:D009369', (28, 33))	('cancer', 'Disease', (56, 62))	('cancer', 'Disease', 'MESH:D009369', (56, 62))	('tumor', 'Phenotype', 'HP:0002664', (28, 33))
51123	31817988	However, this induction was not significant (p-value >= 0.14) in the wtRASSF10 cells suggesting that depletion of RASSF10 enhances significantly the ability of A549 cells to invade an ECM.	('depletion', 'Var', (101, 110))	('A549', 'CellLine', 'CVCL:0023', (160, 164))	('RASSF10', 'Gene', (114, 121))	('enhances', 'PosReg', (122, 130))
51124	31817988	RASSF10 knockdown revealed that RASSF10 inhibits induced TGFbeta-target gene expression associated with extracellular matrix (COL5A1) and matrix metallopeptidase 2 (MMP2) or direct induction of EMT (SNAI2 and SPOCK1) (Figure 3a).	('SNAI2', 'Gene', '6591', (199, 204))	('SNAI2', 'Gene', (199, 204))	('TGFbeta-target gene', 'Gene', (57, 76))	('CO', 'Chemical', 'MESH:D002245', (126, 128))	('EMT', 'Gene', '3702', (194, 197))	('inhibits', 'NegReg', (40, 48))	('EMT', 'Gene', (194, 197))	('RASSF10', 'Var', (32, 39))	('expression', 'Species', '29278', (77, 87))
51126	31817988	Interestingly, we observed that CDH1 levels are reduced by RASSF10 knockdown (Figure 3b,c) and CDH1 expression is significantly positively correlated with RASSF10 expression (CCLE correlation analysis; Figure 3g).	('CDH1', 'Gene', '999', (95, 99))	('knockdown', 'Var', (67, 76))	('reduced', 'NegReg', (48, 55))	('RASSF10', 'Gene', (59, 66))	('expression', 'Species', '29278', (100, 110))	('CDH1', 'Gene', (32, 36))	('expression', 'Species', '29278', (163, 173))	('expression', 'MPA', (100, 110))	('expression', 'MPA', (163, 173))	('correlated', 'Interaction', (139, 149))	('CDH1', 'Gene', (95, 99))	('CDH1', 'Gene', '999', (32, 36))
51127	31817988	RASSF10 deletion by CRISPR/Cas9 further reduced TGFbeta driven CDH1 repression (Figure 3d).	('CDH1', 'Gene', (63, 67))	('RASSF10', 'Gene', (0, 7))	('CDH1', 'Gene', '999', (63, 67))	('reduced', 'NegReg', (40, 47))	('TGFbeta', 'Gene', (48, 55))	('deletion', 'Var', (8, 16))
51134	31817988	RASSF10 co-localized with ASPP1 and ASPP2, whereas the latter was altered in its localization by RASSF10 (Figure S2).	('altered', 'Reg', (66, 73))	('RASSF10', 'Gene', (0, 7))	('ASPP1', 'Gene', '21981', (26, 31))	('RASSF10', 'Var', (97, 104))	('ASPP1', 'Gene', (26, 31))
51139	31817988	We used CRISPR/Cas9 to generate three RASSF10 negative clones in A549 ( RX-A,B,C), which we controlled by PCR and sequencing the deletion within the coding region of RASSF10 (Figure 1).	('RX-A,B,C', 'Chemical', 'MESH:C096849', (72, 80))	('A549', 'CellLine', 'CVCL:0023', (65, 69))	('RASSF10', 'Gene', (38, 45))	('deletion', 'Var', (129, 137))	('RASSF10', 'Gene', (166, 173))	('rat', 'Species', '10116', (27, 30))
51140	31817988	Using three A549 RASSF10-negative clones and three RASSF10-positive wt clones (wt-A,B,C), we could show that knockout of endogenous RASSF10 abolishes its co-precipitation with ASPP2 (Figure 4f).	('co-precipitation', 'MPA', (154, 170))	('knockout', 'Var', (109, 117))	('abolishes', 'NegReg', (140, 149))	('RASSF10', 'Gene', (132, 139))	('A549', 'CellLine', 'CVCL:0023', (12, 16))
51148	31817988	Induction of RASSF10 strongly increased endogenous ASPP2 protein levels (Figure 5b), which was not due to increased ASPP2 RNA expression (Figure 5c).	('expression', 'Species', '29278', (126, 136))	('RASSF10', 'Gene', (13, 20))	('N', 'Chemical', 'MESH:D009584', (123, 124))	('endogenous ASPP2 protein levels', 'MPA', (40, 71))	('increased', 'PosReg', (30, 39))	('Induction', 'Var', (0, 9))
51152	31817988	We only found minimal genomic alterations of RASSF10 (2.4%) and ASPP2 (4.7%) compared to 62% of TP53 mutations in cancer cell lines (n = 881; Broad CCLE/Cancer Cell Line Encyclopedia; analyzed using).	('cancer', 'Disease', 'MESH:D009369', (114, 120))	('Cancer', 'Disease', 'MESH:D009369', (153, 159))	('mutations', 'Var', (101, 110))	('TP53', 'Gene', (96, 100))	('RASSF10', 'Var', (45, 52))	('cancer', 'Phenotype', 'HP:0002664', (114, 120))	('rat', 'Species', '10116', (34, 37))	('Cancer', 'Phenotype', 'HP:0002664', (153, 159))	('Cancer', 'Disease', (153, 159))	('cancer', 'Disease', (114, 120))
51157	31817988	In summary, we are not convinced that mutations of RASSF10 and ASPP2 are likely to contribute to tumorigenesis, whereas occurrence of TP53 mutations in cancer is consistent with literature.	('tumor', 'Disease', 'MESH:D009369', (97, 102))	('cancer', 'Disease', (152, 158))	('cancer', 'Disease', 'MESH:D009369', (152, 158))	('ASPP2', 'Gene', (63, 68))	('tumor', 'Phenotype', 'HP:0002664', (97, 102))	('RASSF10', 'Gene', (51, 58))	('tumor', 'Disease', (97, 102))	('rat', 'Species', '10116', (182, 185))	('cancer', 'Phenotype', 'HP:0002664', (152, 158))	('mutations', 'Var', (38, 47))	('contribute', 'Reg', (83, 93))
51172	31817988	In breast cancer we can show that high RASSF10 methylation is associated with reduced RASSF10 expression, we observed that loss of RASSF10 expression correlates with progressed breast cancer grade and reduced overall survival of breast cancer patients (Figure 8e-g, Table S2).	('breast cancer', 'Disease', (177, 190))	('cancer', 'Phenotype', 'HP:0002664', (184, 190))	('expression', 'Species', '29278', (94, 104))	('reduced', 'NegReg', (201, 208))	('loss', 'NegReg', (123, 127))	('breast cancer', 'Disease', 'MESH:D001943', (229, 242))	('RASSF10', 'Gene', (131, 138))	('breast cancer', 'Disease', (229, 242))	('patients', 'Species', '9606', (243, 251))	('cancer', 'Phenotype', 'HP:0002664', (10, 16))	('methylation', 'Var', (47, 58))	('expression', 'Species', '29278', (139, 149))	('RASSF10', 'Gene', (86, 93))	('breast cancer', 'Phenotype', 'HP:0003002', (229, 242))	('breast cancer', 'Phenotype', 'HP:0003002', (3, 16))	('reduced', 'NegReg', (78, 85))	('expression', 'MPA', (94, 104))	('cancer', 'Phenotype', 'HP:0002664', (236, 242))	('RASSF10', 'Gene', (39, 46))	('overall survival', 'CPA', (209, 225))	('breast cancer', 'Phenotype', 'HP:0003002', (177, 190))	('progressed', 'PosReg', (166, 176))	('breast cancer', 'Disease', 'MESH:D001943', (3, 16))	('breast cancer', 'Disease', (3, 16))	('breast cancer', 'Disease', 'MESH:D001943', (177, 190))
51175	31817988	Supplementary Table S2 summarizes that low RASSF10 expression is associated with reduced 5 year survival rates of cancers: kidney cancer, 24% (papillary, significant) and 12% (clear cell, significant); head and neck cancer, 18% (significant); lymphoma, 22% (mantle cell, significant) and 5% (B-cell); thymoma, 8%; liver cancer, 34% (significant); lung cancer, 18% (significant); gastric cancer, 7%; and breast cancer, 21% (significant).	('cancers', 'Phenotype', 'HP:0002664', (114, 121))	('cancers', 'Disease', (114, 121))	('cancer', 'Phenotype', 'HP:0002664', (320, 326))	('lung cancer', 'Disease', (347, 358))	('cancer', 'Phenotype', 'HP:0002664', (114, 120))	('liver cancer', 'Disease', 'MESH:D006528', (314, 326))	('cancer', 'Phenotype', 'HP:0002664', (352, 358))	('reduced', 'NegReg', (81, 88))	('lymphoma', 'Disease', (243, 251))	('thymoma', 'Disease', 'MESH:D013945', (301, 308))	('breast cancer', 'Phenotype', 'HP:0003002', (403, 416))	('gastric cancer', 'Disease', (379, 393))	('lymphoma', 'Disease', 'MESH:D008223', (243, 251))	('RASSF10', 'Gene', (43, 50))	('head and neck cancer', 'Phenotype', 'HP:0012288', (202, 222))	('kidney cancer', 'Phenotype', 'HP:0009726', (123, 136))	('cancer', 'Phenotype', 'HP:0002664', (216, 222))	('kidney cancer', 'Disease', (123, 136))	('liver cancer', 'Phenotype', 'HP:0002896', (314, 326))	('breast cancer', 'Disease', 'MESH:D001943', (403, 416))	('liver cancer', 'Disease', (314, 326))	('breast cancer', 'Disease', (403, 416))	('lung cancer', 'Disease', 'MESH:D008175', (347, 358))	('thymoma', 'Disease', (301, 308))	('cancers', 'Disease', 'MESH:D009369', (114, 121))	('thymoma', 'Phenotype', 'HP:0100522', (301, 308))	('gastric cancer', 'Disease', 'MESH:D013274', (379, 393))	('lung cancer', 'Phenotype', 'HP:0100526', (347, 358))	('expression', 'Species', '29278', (51, 61))	('head and neck cancer', 'Disease', 'MESH:D006258', (202, 222))	('rat', 'Species', '10116', (105, 108))	('lymphoma', 'Phenotype', 'HP:0002665', (243, 251))	('low', 'Var', (39, 42))	('gastric cancer', 'Phenotype', 'HP:0012126', (379, 393))	('cancer', 'Phenotype', 'HP:0002664', (130, 136))	('kidney cancer', 'Disease', 'MESH:D007680', (123, 136))
51179	31817988	Interestingly, we found an enhanced phosphorylation of SMAD2 after TGFbeta treatment and knockdown of ASPP2.	('TGFbeta', 'Gene', (67, 74))	('ASPP2', 'Gene', (102, 107))	('phospho', 'Chemical', 'MESH:C033601', (36, 43))	('enhanced', 'PosReg', (27, 35))	('SMAD2', 'Protein', (55, 60))	('knockdown', 'Var', (89, 98))	('phosphorylation', 'MPA', (36, 51))
51181	31817988	However, YAP1 levels were rather unaffected after RASSF10 or ASPP2 knockdown.	('knockdown', 'Var', (67, 76))	('rat', 'Species', '10116', (26, 29))	('YAP1 levels', 'MPA', (9, 20))	('ASPP2', 'Gene', (61, 66))	('RASSF10', 'Gene', (50, 57))
51184	31817988	These data indicated that loss of RASSF10 or ASPP2 induced constitutive activation of TGFbeta signaling and EMT.	('activation', 'PosReg', (72, 82))	('ASPP2', 'Gene', (45, 50))	('RASSF10', 'Gene', (34, 41))	('EMT', 'Gene', (108, 111))	('EMT', 'Gene', '3702', (108, 111))	('TGFbeta signaling', 'Pathway', (86, 103))	('loss', 'Var', (26, 30))
51191	31817988	Loss of RASSF10 altered the TGFbeta gene expression profile and induced expression of COL5A1, MMP2, SNAI2 and SPOCK1 (Figure 3a) and constitutive SMAD2 phosphorylation (Figure 9a), suggesting that RASSF10 plays a suppressive role in TGFbeta signaling and EMT.	('phospho', 'Chemical', 'MESH:C033601', (152, 159))	('altered', 'Reg', (16, 23))	('COL5A1', 'Gene', (86, 92))	('phosphorylation', 'MPA', (152, 167))	('EMT', 'Gene', (255, 258))	('EMT', 'Gene', '3702', (255, 258))	('induced', 'Reg', (64, 71))	('expression', 'MPA', (72, 82))	('RASSF10', 'Gene', (8, 15))	('SPOCK1', 'Gene', (110, 116))	('SNAI2', 'Gene', (100, 105))	('Loss', 'Var', (0, 4))	('expression', 'Species', '29278', (41, 51))	('expression', 'Species', '29278', (72, 82))	('SNAI2', 'Gene', '6591', (100, 105))	('MMP2', 'Gene', (94, 98))	('TGFbeta gene', 'Gene', (28, 40))	('expression profile', 'MPA', (41, 59))	('CO', 'Chemical', 'MESH:D002245', (86, 88))
51193	31817988	Additionally, we observed that depletion of RASSF10 significantly promotes TGFbeta induced invasion of A549 cells in an extracellular matrix (Table 2).	('invasion of A549 cells in an extracellular matrix', 'CPA', (91, 140))	('A549', 'CellLine', 'CVCL:0023', (103, 107))	('promotes', 'PosReg', (66, 74))	('depletion', 'Var', (31, 40))	('RASSF10', 'Gene', (44, 51))	('TGFbeta', 'Gene', (75, 82))
51195	31817988	Interestingly, we observed that RASSF10 induced E-cadherin (CDH1) levels and loss of RASSF10 expression reduced CDH1 levels (Figure 3).	('RASSF10', 'Gene', (85, 92))	('induced', 'Reg', (40, 47))	('reduced', 'NegReg', (104, 111))	('CDH1', 'Gene', '999', (60, 64))	('expression', 'Species', '29278', (93, 103))	('expression', 'MPA', (93, 103))	('CDH1', 'Gene', (112, 116))	('CDH1', 'Gene', (60, 64))	('RASSF10', 'Gene', (32, 39))	('loss', 'Var', (77, 81))	('CDH1', 'Gene', '999', (112, 116))
51202	31817988	Our data indicate that knockdown of ASPP2 induces beta-Catenin levels and phospho-SMAD2 under TGFbeta treatment (Figure 9a).	('phospho-SMAD2', 'MPA', (74, 87))	('induces', 'PosReg', (42, 49))	('phospho', 'Chemical', 'MESH:C033601', (74, 81))	('knockdown', 'Var', (23, 32))	('beta-Catenin levels', 'MPA', (50, 69))	('ASPP2', 'Gene', (36, 41))
51208	31817988	We found that knockdown and knockout of RASSF10 increased mitosis and increased cell proliferation (Figure 1) and significantly promotes TGFbeta induced ECM invasion (Table 2), as well as RASSF10 re-expression halted proliferation (Figure 1).	('increased', 'PosReg', (48, 57))	('expression', 'Species', '29278', (199, 209))	('increased', 'PosReg', (70, 79))	('TGFbeta', 'Gene', (137, 144))	('rat', 'Species', '10116', (92, 95))	('cell proliferation', 'CPA', (80, 98))	('halted', 'NegReg', (210, 216))	('mitosis', 'CPA', (58, 65))	('knockout', 'Var', (28, 36))	('promotes', 'PosReg', (128, 136))	('rat', 'Species', '10116', (224, 227))	('RASSF10', 'Gene', (40, 47))
51209	31817988	As RASSF10 and ASPP2 are both linked to the cell polarity network, their presence would negatively regulate the mitotic/proliferative potential.	('presence', 'Var', (73, 81))	('RASSF10', 'Gene', (3, 10))	('regulate', 'Reg', (99, 107))	('negatively', 'NegReg', (88, 98))	('ASPP2', 'Gene', (15, 20))	('mitotic/proliferative potential', 'CPA', (112, 143))	('rat', 'Species', '10116', (127, 130))
51210	31817988	Loss of the RASSF10-ASPP2 complex would lead to disturbance of cell polarity and thereby would interfere with the coordination of mitosis, as it is known that the positioning of the spindle apparatus is coordinated with polarity signals at the cell cortex.	('coordination of mitosis', 'Disease', (114, 137))	('cell polarity', 'CPA', (63, 76))	('disturbance', 'MPA', (48, 59))	('lead to', 'Reg', (40, 47))	('rat', 'Species', '10116', (194, 197))	('interfere', 'NegReg', (95, 104))	('RASSF10-ASPP2', 'Gene', (12, 25))	('Loss', 'Var', (0, 4))	('coordination of mitosis', 'Disease', 'MESH:D001259', (114, 137))
51212	31817988	In our study we found a significant epigenetic silencing of RASSF10, but not ASPP2 in different tumor entities (Figure 6 and Figure 7).	('RASSF10', 'Gene', (60, 67))	('tumor', 'Phenotype', 'HP:0002664', (96, 101))	('tumor entities', 'Disease', 'MESH:D009369', (96, 110))	('epigenetic silencing', 'Var', (36, 56))	('tumor entities', 'Disease', (96, 110))
51213	31817988	Promoter hypermethylation of tumor suppressor genes is an established mechanism of their silencing in carcinogenesis.	('carcinogenesis', 'Disease', 'MESH:D063646', (102, 116))	('tumor', 'Disease', 'MESH:D009369', (29, 34))	('carcinogenesis', 'Disease', (102, 116))	('tumor', 'Phenotype', 'HP:0002664', (29, 34))	('tumor', 'Disease', (29, 34))	('silencing', 'NegReg', (89, 98))	('Promoter hypermethylation', 'Var', (0, 25))
51217	31817988	Our clinical data set revealed that hypermethylation of the CpG island of RASSF10 is a common and general event in human tumorigenesis (Figure 7 and Figure 8).	('RASSF10', 'Gene', (74, 81))	('tumor', 'Phenotype', 'HP:0002664', (121, 126))	('tumor', 'Disease', (121, 126))	('hypermethylation', 'Var', (36, 52))	('human', 'Species', '9606', (115, 120))	('tumor', 'Disease', 'MESH:D009369', (121, 126))
51218	31817988	We could broadly show that in independent data sets loss of RASSF10 correlated not only with reduced patient survival rates in various tumor types (kidney cancer, thymoma, lymphoma, breast cancer, colon carcinoma, head and neck cancer, liver cancer, lung cancer and gastric cancer), but also with tumor stage/grade (thymoma, breast cancer) and tumor types (kidney cancer, melanoma and colon carcinoma) (Figure 8 and Table S2).	('RASSF10', 'Gene', (60, 67))	('liver cancer', 'Disease', 'MESH:D006528', (236, 248))	('lung cancer', 'Phenotype', 'HP:0100526', (250, 261))	('thymoma', 'Phenotype', 'HP:0100522', (163, 170))	('breast cancer', 'Phenotype', 'HP:0003002', (325, 338))	('tumor', 'Phenotype', 'HP:0002664', (135, 140))	('colon carcinoma', 'Disease', 'MESH:D015179', (385, 400))	('breast cancer', 'Phenotype', 'HP:0003002', (182, 195))	('tumor', 'Disease', (297, 302))	('breast cancer', 'Disease', 'MESH:D001943', (325, 338))	('gastric cancer', 'Phenotype', 'HP:0012126', (266, 280))	('liver cancer', 'Phenotype', 'HP:0002896', (236, 248))	('patient survival rates', 'CPA', (101, 123))	('breast cancer', 'Disease', (325, 338))	('melanoma', 'Phenotype', 'HP:0002861', (372, 380))	('cancer', 'Phenotype', 'HP:0002664', (255, 261))	('liver cancer', 'Disease', (236, 248))	('rat', 'Species', '10116', (118, 121))	('breast cancer', 'Disease', 'MESH:D001943', (182, 195))	('head and neck cancer', 'Disease', 'MESH:D006258', (214, 234))	('tumor', 'Disease', (344, 349))	('breast cancer', 'Disease', (182, 195))	('tumor', 'Disease', 'MESH:D009369', (297, 302))	('thymoma, lymphoma', 'Disease', 'MESH:D013945', (163, 180))	('thymoma', 'Disease', 'MESH:D013945', (316, 323))	('colon carcinoma', 'Disease', (197, 212))	('lung cancer', 'Disease', (250, 261))	('tumor', 'Disease', 'MESH:D009369', (344, 349))	('kidney cancer', 'Disease', 'MESH:D007680', (357, 370))	('loss', 'Var', (52, 56))	('kidney cancer', 'Disease', 'MESH:D007680', (148, 161))	('tumor', 'Disease', (135, 140))	('gastric cancer', 'Disease', (266, 280))	('cancer', 'Phenotype', 'HP:0002664', (228, 234))	('thymoma', 'Disease', 'MESH:D013945', (163, 170))	('tumor', 'Phenotype', 'HP:0002664', (297, 302))	('thymoma', 'Disease', (316, 323))	('melanoma and colon carcinoma', 'Disease', 'MESH:D015179', (372, 400))	('patient', 'Species', '9606', (101, 108))	('colon carcinoma', 'Disease', 'MESH:D015179', (197, 212))	('thymoma', 'Phenotype', 'HP:0100522', (316, 323))	('carcinoma', 'Phenotype', 'HP:0030731', (203, 212))	('tumor', 'Disease', 'MESH:D009369', (135, 140))	('kidney cancer', 'Phenotype', 'HP:0009726', (357, 370))	('cancer', 'Phenotype', 'HP:0002664', (155, 161))	('gastric cancer', 'Disease', 'MESH:D013274', (266, 280))	('lung cancer', 'Disease', 'MESH:D008175', (250, 261))	('colon carcinoma', 'Disease', (385, 400))	('kidney cancer', 'Disease', (357, 370))	('reduced', 'NegReg', (93, 100))	('cancer', 'Phenotype', 'HP:0002664', (189, 195))	('tumor', 'Phenotype', 'HP:0002664', (344, 349))	('kidney cancer', 'Phenotype', 'HP:0009726', (148, 161))	('kidney cancer', 'Disease', (148, 161))	('carcinoma', 'Phenotype', 'HP:0030731', (391, 400))	('head and neck cancer', 'Phenotype', 'HP:0012288', (214, 234))	('lymphoma', 'Phenotype', 'HP:0002665', (172, 180))	('cancer', 'Phenotype', 'HP:0002664', (242, 248))	('thymoma', 'Disease', (163, 170))
51220	31817988	Our present comprehensive work is the finalization of our previous research in smaller data sets in which we have shown that the promoter of RASSF10 is methylated in patient tumors samples of the adrenal gland, head and neck, sarcoma, pancreas carcinoma and Merkel cell carcinoma.	('sarcoma', 'Phenotype', 'HP:0100242', (226, 233))	('tumors', 'Disease', (174, 180))	('tumors', 'Disease', 'MESH:D009369', (174, 180))	('pancreas carcinoma', 'Disease', 'MESH:D010190', (235, 253))	('RASSF10', 'Gene', (141, 148))	('Merkel cell carcinoma', 'Disease', 'MESH:D015266', (258, 279))	('pancreas carcinoma', 'Disease', (235, 253))	('sarcoma', 'Disease', 'MESH:D012509', (226, 233))	('carcinoma', 'Phenotype', 'HP:0030731', (270, 279))	('tumor', 'Phenotype', 'HP:0002664', (174, 179))	('Merkel cell carcinoma', 'Disease', (258, 279))	('methylated', 'Var', (152, 162))	('patient', 'Species', '9606', (166, 173))	('sarcoma', 'Disease', (226, 233))	('carcinoma', 'Phenotype', 'HP:0030731', (244, 253))	('tumors', 'Phenotype', 'HP:0002664', (174, 180))
51221	31817988	We showed the epigenetic inactivation of RASSF10 in thyroid cancer, lung cancer, skin cancer, breast cancer and showed that RASSF10 inhibited growth of breast cancer, pancreas carcinoma and sarcoma cell lines.	('thyroid cancer', 'Disease', (52, 66))	('sarcoma', 'Disease', 'MESH:D012509', (190, 197))	('lung cancer', 'Phenotype', 'HP:0100526', (68, 79))	('sarcoma', 'Disease', (190, 197))	('epigenetic inactivation', 'Var', (14, 37))	('breast cancer', 'Phenotype', 'HP:0003002', (94, 107))	('skin cancer', 'Disease', (81, 92))	('inhibited', 'NegReg', (132, 141))	('pancreas carcinoma', 'Disease', 'MESH:D010190', (167, 185))	('pancreas carcinoma', 'Disease', (167, 185))	('thyroid cancer', 'Disease', 'MESH:D013964', (52, 66))	('RASSF10', 'Gene', (41, 48))	('cancer', 'Phenotype', 'HP:0002664', (73, 79))	('cancer', 'Phenotype', 'HP:0002664', (159, 165))	('sarcoma', 'Phenotype', 'HP:0100242', (190, 197))	('breast cancer', 'Disease', 'MESH:D001943', (94, 107))	('breast cancer', 'Disease', (94, 107))	('skin cancer', 'Phenotype', 'HP:0008069', (81, 92))	('thyroid cancer', 'Phenotype', 'HP:0002890', (52, 66))	('lung cancer', 'Disease', (68, 79))	('cancer', 'Phenotype', 'HP:0002664', (86, 92))	('growth', 'CPA', (142, 148))	('breast cancer', 'Phenotype', 'HP:0003002', (152, 165))	('skin cancer', 'Disease', 'MESH:D012878', (81, 92))	('breast cancer', 'Disease', 'MESH:D001943', (152, 165))	('RASSF10', 'Gene', (124, 131))	('cancer', 'Phenotype', 'HP:0002664', (101, 107))	('breast cancer', 'Disease', (152, 165))	('lung cancer', 'Disease', 'MESH:D008175', (68, 79))	('cancer', 'Phenotype', 'HP:0002664', (60, 66))	('carcinoma', 'Phenotype', 'HP:0030731', (176, 185))
51224	31817988	It is obvious to measure methylated tumor DNA instead of RNA due to its superior stability in cells and body fluids (circulating DNA).	('N', 'Chemical', 'MESH:D009584', (43, 44))	('N', 'Chemical', 'MESH:D009584', (130, 131))	('methylated', 'Var', (25, 35))	('tumor', 'Disease', 'MESH:D009369', (36, 41))	('N', 'Chemical', 'MESH:D009584', (58, 59))	('tumor', 'Phenotype', 'HP:0002664', (36, 41))	('tumor', 'Disease', (36, 41))
51226	31817988	However, in DNA, we observed that already low levels of methylation inactivated RASSF10 and therefore a common threshold level could abrogate RASSF10 expression irrespective of the tissue.	('expression', 'MPA', (150, 160))	('abrogate', 'NegReg', (133, 141))	('N', 'Chemical', 'MESH:D009584', (13, 14))	('RASSF10', 'Gene', (142, 149))	('methylation', 'Var', (56, 67))	('RASSF10', 'Gene', (80, 87))	('expression', 'Species', '29278', (150, 160))	('inactivated', 'NegReg', (68, 79))
51229	31817988	Liquid biopsies are FDA approved for lung cancer EGFR mutation tests as companion diagnostic.	('lung cancer', 'Disease', (37, 48))	('lung cancer', 'Phenotype', 'HP:0100526', (37, 48))	('cancer', 'Phenotype', 'HP:0002664', (42, 48))	('EGFR', 'Gene', (49, 53))	('mutation tests', 'Var', (54, 68))	('lung cancer', 'Disease', 'MESH:D008175', (37, 48))
51247	31817988	The following antibodies were used: a-GAPDH (FL335, sc-25778 from Santa Cruz), a-GFP from Rainer Renkawitz (Giessen, Germany), a-RASSF10 (AP12444c-ev2020, Abgent, San Diego, United States), a-p65 (610868, BD Biosciences, Heidelberg, Germany), a-ASPP1 (sc50890, Santa Cruz, Santa Cruz, United States), a-ASPP2 (sc53861, Santa Cruz), a-YAP1 (sc15407, Santa Cruz), a-ss-Catenin (9562S, Cell Signaling), a-phospho-SMAD2 ser465/467 (3101, Cell signaling), a-Flag (M2, Sigma), a-GST (B-14 sc138, Santa Cruz), a-V5 Tag (ab9116, Abcam, Cambridge, United Kingdom), HRP-coupled secondary antibodies anti-rabbit (sc2004, sc2357, Santa Cruz), anti-mouse (sc2005, sc516102, Santa Cruz) and anti-goat (sc2021, Santa Cruz), alexafluor568 (Thermo Fisher Scientific).	('GAPDH', 'Gene', (38, 43))	('sc-25778', 'Chemical', 'MESH:D012538', (52, 60))	('sc2004', 'Var', (602, 608))	('BD Biosciences', 'Disease', 'MESH:D001528', (205, 219))	('sc2021', 'Var', (688, 694))	('ASPP1', 'Gene', '21981', (245, 250))	('p65', 'Gene', '19697', (192, 195))	('sc2005', 'Var', (643, 649))	('p65', 'Gene', (192, 195))	('alexafluor568', 'Chemical', 'MESH:C107873', (709, 722))	('9562S', 'CellLine', 'CVCL:Z231', (376, 381))	('ASPP1', 'Gene', (245, 250))	('phospho', 'Chemical', 'MESH:C033601', (402, 409))	('mouse', 'Species', '10090', (636, 641))	('BD Biosciences', 'Disease', (205, 219))	('GAPDH', 'Gene', '14433', (38, 43))
51257	31817988	RASSF10's coding sequence was amplified from genomic DNA, ASPP1 (IRAVp968F02130D) and ASPP2 (IRATp970A06136D) were obtained from the former Deutschen Ressourcenzentrum fur Genomforschung (RZPD) now THE I.M.A.G.E.	('IRATp970A06136D', 'Var', (93, 108))	('ASPP1', 'Gene', (58, 63))	('N', 'Chemical', 'MESH:D009584', (54, 55))	('ASPP1', 'Gene', '21981', (58, 63))	('IRAVp968F02130D', 'Var', (65, 80))	('IRAVp968F02130D', 'Chemical', 'MESH:C000900', (65, 80))
51260	31817988	Susanne Maaz cloned p53 (IRALp962F088Q) into pCDNA3.1/nV5-DEST (Thermo Fisher Scientific) and YAP1 (IRAKp961L0779) was cloned into EYFP (Clontech) by Desiree Block and A.J.	('IRALp962F088Q', 'Var', (25, 38))	('N', 'Chemical', 'MESH:D009584', (48, 49))	('p53', 'Gene', '2768677', (20, 23))	('p53', 'Gene', (20, 23))
51262	31817988	Deletion mutants and domain mutants of RASSF10 were generated by site directed mutations as above.	('rat', 'Species', '10116', (56, 59))	('RASSF10', 'Gene', (39, 46))	('Deletion', 'Var', (0, 8))
51266	31817988	For the evaluation of the invasion capacity of A549 wildtype and RASSF10 deletion clones transwell extracellular matrix (ECM) invasion assays were performed.	('deletion', 'Var', (73, 81))	('RASSF10', 'Gene', (65, 72))	('A549', 'CellLine', 'CVCL:0023', (47, 51))
51271	31817988	We are now showing that RASSF10 expression inhibits signs of EMT in cancer cell lines, but we are also reporting its mode of action as a tumor suppressor.	('EMT', 'Gene', '3702', (61, 64))	('cancer', 'Phenotype', 'HP:0002664', (68, 74))	('tumor', 'Disease', (137, 142))	('expression', 'Var', (32, 42))	('RASSF10', 'Gene', (24, 31))	('cancer', 'Disease', 'MESH:D009369', (68, 74))	('expression', 'Species', '29278', (32, 42))	('cancer', 'Disease', (68, 74))	('tumor', 'Disease', 'MESH:D009369', (137, 142))	('inhibits', 'NegReg', (43, 51))	('tumor', 'Phenotype', 'HP:0002664', (137, 142))	('EMT', 'Gene', (61, 64))
51274	31817988	We show that RASSF10 induces the protein levels of ASPP2 that is also an inhibitor of EMT.	('EMT', 'Gene', (86, 89))	('RASSF10', 'Var', (13, 20))	('induces', 'Reg', (21, 28))	('EMT', 'Gene', '3702', (86, 89))	('protein levels', 'MPA', (33, 47))	('ASPP2', 'Protein', (51, 56))
51275	31817988	In human cancers, RASSF10, but not ASPP2, is epigenetically inactivated by promoter hypermethylation.	('cancers', 'Disease', 'MESH:D009369', (9, 16))	('cancers', 'Phenotype', 'HP:0002664', (9, 16))	('cancers', 'Disease', (9, 16))	('human', 'Species', '9606', (3, 8))	('cancer', 'Phenotype', 'HP:0002664', (9, 15))	('promoter hypermethylation', 'Var', (75, 100))	('RASSF10', 'Gene', (18, 25))
51278	31817988	The following are available online at , Figure S1: Structure of RASSF10., Figure S2: RASSF10 (RX) localizes with overexpressed ASPP1/2 (A1/A2) and induces endogenous ASPP2, Figure S3: Characterization of RASSF10 binding to ASPP1/2 and competition; Figure S4: ASPP2 is not epigenetically regulated in human cancers; Figure S5: No SMAD2 and SMAD3 binding at the RASSF10 promoter.	('cancers', 'Phenotype', 'HP:0002664', (306, 313))	('RASSF10', 'Var', (85, 92))	('SMAD3', 'Gene', '4088', (339, 344))	('cancers', 'Disease', (306, 313))	('binding', 'Interaction', (212, 219))	('N', 'Chemical', 'MESH:D009584', (326, 327))	('cancers', 'Disease', 'MESH:D009369', (306, 313))	('RASSF10', 'Gene', (360, 367))	('SMAD3', 'Gene', (339, 344))	('human', 'Species', '9606', (300, 305))	('cancer', 'Phenotype', 'HP:0002664', (306, 312))	('binding', 'Interaction', (345, 352))
51282	31817988	Figure 8: Methylation Expression Correlation: RASSF10, Dataset Project: TCGA, Data Type: 450k Methylation Array 450k Infinium chip, Select: cg05817758, beta value and log2 (normalized rsem+1) of RASSF10, Correlation method: Spearman, Fit linear regression, for Breast invasive carcinoma.	('Breast invasive carcinoma', 'Disease', 'MESH:D001943', (261, 286))	('carcinoma', 'Phenotype', 'HP:0030731', (277, 286))	('cg05817758', 'Var', (140, 150))	('Breast invasive carcinoma', 'Disease', (261, 286))	('Expression', 'Species', '29278', (22, 32))
51455	22974165	It has been reported that different subtypes of thymoma have different genetic characteristics, recent studies indicated that chromosomal 1 gain plays an important role in molecular genetic mechanism of thymic epithelium tumors.	('thymoma', 'Phenotype', 'HP:0100522', (48, 55))	('tumors', 'Phenotype', 'HP:0002664', (221, 227))	('tumor', 'Phenotype', 'HP:0002664', (221, 226))	('thymic epithelium tumors', 'Disease', 'MESH:D013953', (203, 227))	('thymoma', 'Disease', (48, 55))	('thymoma', 'Disease', 'MESH:D013945', (48, 55))	('chromosomal', 'Var', (126, 137))	('thymic epithelium tumors', 'Disease', (203, 227))
51470	22974165	Mutational ras protein can affect cell proliferation, cell cycle regulation and anti-apoptotic signal by decreasing the activity of endogenous GTPase, or transcriptional decreasing the expression of Fas receptor and regulating the last time of the p38 activity of Jun N-terminal protein kinase (JNK) by Ral-GEF (Ras related GTPase-guanine exchange factor) pathway Meanwhile, N-ras has different function to the generation of cancer in different individuals.	('expression', 'MPA', (185, 195))	('cell proliferation', 'CPA', (34, 52))	('Mutational', 'Var', (0, 10))	('cancer', 'Disease', 'MESH:D009369', (425, 431))	('JNK', 'Gene', (295, 298))	('activity', 'MPA', (120, 128))	('JNK', 'Gene', '5599', (295, 298))	('Ral-GEF', 'Gene', (303, 310))	('N-ras', 'Gene', '4893', (375, 380))	('N-ras', 'Gene', (375, 380))	('affect', 'Reg', (27, 33))	('p38', 'Gene', (248, 251))	('Ras related GTPase-guanine exchange factor', 'Gene', '5900', (312, 354))	('decreasing', 'NegReg', (105, 115))	('Ral-GEF', 'Gene', '5900', (303, 310))	('decreasing', 'NegReg', (170, 180))	('cancer', 'Disease', (425, 431))	('activity', 'MPA', (252, 260))	('Fas', 'Protein', (199, 202))	('cell cycle', 'CPA', (54, 64))	('cancer', 'Phenotype', 'HP:0002664', (425, 431))	('Ras related GTPase-guanine exchange factor', 'Gene', (312, 354))	('regulating', 'Reg', (216, 226))	('p38', 'Gene', '1432', (248, 251))
51494	22974165	It was also revealed that the molecular change of type B2, B3 thymoma might be similar with thymic carcinoma, and differ from other types of thymoma.	('thymic carcinoma', 'Disease', (92, 108))	('thymoma', 'Disease', 'MESH:D013945', (62, 69))	('thymoma', 'Disease', 'MESH:D013945', (141, 148))	('thymic carcinoma', 'Disease', 'MESH:D013945', (92, 108))	('type B2', 'Var', (50, 57))	('thymoma', 'Disease', (62, 69))	('thymoma', 'Disease', (141, 148))	('carcinoma', 'Phenotype', 'HP:0030731', (99, 108))	('thymoma', 'Phenotype', 'HP:0100522', (62, 69))	('thymoma', 'Phenotype', 'HP:0100522', (141, 148))
51495	22974165	Considering previous research results of our group that p53 protein positive expression increased in type B3 thymoma, it can be inferred that p73 and p53 protein mutants might embrace a synergistic effect in thymoma.	('thymoma', 'Disease', 'MESH:D013945', (208, 215))	('thymoma', 'Disease', (208, 215))	('p73', 'Gene', '7161', (142, 145))	('thymoma', 'Disease', (109, 116))	('p53', 'Gene', (56, 59))	('p73', 'Gene', (142, 145))	('thymoma', 'Phenotype', 'HP:0100522', (208, 215))	('mutants', 'Var', (162, 169))	('thymoma', 'Phenotype', 'HP:0100522', (109, 116))	('p53', 'Gene', '7157', (56, 59))	('increased', 'PosReg', (88, 97))	('p53', 'Gene', (150, 153))	('p53', 'Gene', '7157', (150, 153))	('thymoma', 'Disease', 'MESH:D013945', (109, 116))
51769	30787364	Most studies tried to address the tumorigenesis by characterizing genetic alteration on a single gene level, and only a few systematic researches have been demonstrated.	('genetic alteration', 'Var', (66, 84))	('tumor', 'Phenotype', 'HP:0002664', (34, 39))	('tumor', 'Disease', (34, 39))	('tumor', 'Disease', 'MESH:D009369', (34, 39))
51793	30787364	Earlier researches show that changes in certain genes appear to be involved in thymic tumorigenesis.	('tumor', 'Phenotype', 'HP:0002664', (86, 91))	('involved', 'Reg', (67, 75))	('changes', 'Var', (29, 36))	('tumor', 'Disease', (86, 91))	('genes', 'Gene', (48, 53))	('thymic', 'Disease', (79, 85))	('tumor', 'Disease', 'MESH:D009369', (86, 91))
51794	30787364	Our data demonstrate that some gene mutations might play an important role in the pathogenesis of thymomas.	('thymomas', 'Disease', 'MESH:D013945', (98, 106))	('thymoma', 'Phenotype', 'HP:0100522', (98, 105))	('mutations', 'Var', (36, 45))	('thymomas', 'Disease', (98, 106))	('play', 'Reg', (52, 56))
51837	25738169	Antibodies to LGI1 are associated with limbic encephalitis previously attributed to voltage-gated potassium channels (VGKC).	('Antibodies', 'Var', (0, 10))	('encephalitis', 'Disease', 'MESH:D004660', (46, 58))	('encephalitis', 'Disease', (46, 58))	('LGI1', 'Gene', (14, 18))	('associated', 'Reg', (23, 33))	('encephalitis', 'Phenotype', 'HP:0002383', (46, 58))
51862	25738169	These 2 patients had been previously reported as having limbic encephalitis associated with VGKC antibodies and shared similarities with our patient, including subacute onset of cognitive and memory deficits associated with thymoma recurrence or residual thymoma, coexistence of LGI1 or Caspr2 antibodies with GABAA receptor antibody, and remarkable brain MRI abnormalities, which are strikingly similar to those reported in other patients with GABAA receptor encephalitis.	('encephalitis', 'Disease', 'MESH:D004660', (63, 75))	('patient', 'Species', '9606', (431, 438))	('Caspr2', 'Gene', '26047', (287, 293))	('thymoma', 'Disease', 'MESH:D013945', (224, 231))	('thymoma', 'Disease', 'MESH:D013945', (255, 262))	('encephalitis', 'Phenotype', 'HP:0002383', (460, 472))	('encephalitis', 'Phenotype', 'HP:0002383', (63, 75))	('patient', 'Species', '9606', (8, 15))	('brain MRI abnormalities', 'Disease', (350, 373))	('patient', 'Species', '9606', (141, 148))	('thymoma', 'Disease', (255, 262))	('memory deficits', 'Phenotype', 'HP:0002354', (192, 207))	('LGI1', 'Gene', (279, 283))	('brain MRI abnormalities', 'Disease', 'MESH:D025063', (350, 373))	('thymoma', 'Disease', (224, 231))	('thymoma', 'Phenotype', 'HP:0100522', (255, 262))	('thymoma', 'Phenotype', 'HP:0100522', (224, 231))	('antibodies', 'Var', (97, 107))	('cognitive and memory deficits', 'Disease', 'MESH:D003072', (178, 207))	('patients', 'Species', '9606', (431, 439))	('associated', 'Reg', (76, 86))	('patients', 'Species', '9606', (8, 16))	('encephalitis', 'Disease', (460, 472))	('Caspr2', 'Gene', (287, 293))	('encephalitis', 'Disease', (63, 75))	('VGKC', 'Gene', (92, 96))	('encephalitis', 'Disease', 'MESH:D004660', (460, 472))
51874	33188420	Six years prior, he had received curative treatment for a 8x9 cm pT1N0M0 type AB thymoma by radical surgical resection (Figure 1A-B).	('thymoma', 'Phenotype', 'HP:0100522', (81, 88))	('pT1N0M0 type', 'Var', (65, 77))	('AB thymoma', 'Disease', 'MESH:D013945', (78, 88))	('AB thymoma', 'Disease', (78, 88))
51964	29720797	Acetylcholinesterase inhibitors produce improvement in autonomic functions, just as in motor weakness, i.e., in pupillary dysfunction, all changes were seen to reverse with the administration of acetylcholine inhibitors; Shukla et al.	('acetylcholine', 'Chemical', 'MESH:D000109', (195, 208))	('pupillary dysfunction', 'Disease', (112, 133))	('autonomic functions', 'MPA', (55, 74))	('weakness', 'Disease', (93, 101))	('pupillary dysfunction', 'Disease', 'MESH:D011681', (112, 133))	('inhibitors', 'Var', (21, 31))	('weakness', 'Disease', 'MESH:D018908', (93, 101))	('improvement', 'PosReg', (40, 51))	('Acetylcholinesterase', 'Gene', (0, 20))	('Acetylcholinesterase', 'Gene', '43', (0, 20))
52003	29720797	The analyzed parameters included female sex (odds ratio [OR] 1.11 [0.13-9.41], P = 0.92), AChR antibody positivity (OR 2.77 [0.44-17.62], P = 0.29), invasive thymoma (OR 1.39 [0.40-4.71], P = 0.57), and young age of onset (OR 1.11 [0.67-1.82], P = 0.64).	('invasive thymoma', 'Disease', 'MESH:D013945', (149, 165))	('invasive thymoma', 'Disease', (149, 165))	('thymoma', 'Phenotype', 'HP:0100522', (158, 165))	('positivity', 'Var', (104, 114))	('AChR antibody', 'Gene', (90, 103))
52007	29720797	Myasthenia Gravis is an antibody-mediated autoimmune disease where pathogenic antibodies to alpha-3 ganglionic acetylcholine receptor subunits cause autonomic dysfunction.	('Myasthenia Gravis', 'Disease', (0, 17))	('antibodies', 'Var', (78, 88))	('acetylcholine', 'Chemical', 'MESH:D000109', (111, 124))	('autonomic dysfunction', 'Disease', 'MESH:D001342', (149, 170))	('autonomic dysfunction', 'Disease', (149, 170))	('autoimmune disease', 'Disease', (42, 60))	('cause', 'Reg', (143, 148))	('autonomic dysfunction', 'Phenotype', 'HP:0012332', (149, 170))	('Myasthenia', 'Phenotype', 'HP:0003473', (0, 10))	('alpha-3 ganglionic', 'Protein', (92, 110))	('autoimmune disease', 'Phenotype', 'HP:0002960', (42, 60))	('Myasthenia Gravis', 'Disease', 'MESH:D009157', (0, 17))	('autoimmune disease', 'Disease', 'MESH:D001327', (42, 60))
52018	29720797	Cardiac dysfunction in myasthenic crises has also been reported in association with antivoltage-gated potassium channel Kv 1.4 antibodies.	('Cardiac dysfunction', 'Disease', (0, 19))	('Cardiac dysfunction', 'Disease', 'MESH:D006331', (0, 19))	('myasthenic crises', 'Phenotype', 'HP:0003473', (23, 40))	('antibodies', 'Var', (127, 137))	('myasthenic crises', 'Disease', (23, 40))
52026	29720797	Sluggish bowel motility resulting in bacterial overgrowth and deconjugation of bile acids can produce diarrhea and malabsorption.	('malabsorption', 'Phenotype', 'HP:0002024', (115, 128))	('produce', 'Reg', (94, 101))	('diarrhea', 'Disease', (102, 110))	('overgrowth', 'Phenotype', 'HP:0001548', (47, 57))	('bile acids', 'Chemical', 'MESH:D001647', (79, 89))	('diarrhea', 'Disease', 'MESH:D003967', (102, 110))	('malabsorption', 'Disease', (115, 128))	('malabsorption', 'Disease', 'MESH:D008286', (115, 128))	('bacterial', 'CPA', (37, 46))	('deconjugation', 'Var', (62, 75))	('bowel motility', 'Disease', (9, 23))	('overgrowth', 'PosReg', (47, 57))	('bowel motility', 'Disease', 'MESH:D015835', (9, 23))	('diarrhea', 'Phenotype', 'HP:0002014', (102, 110))
52083	28454444	However, the 24-h urine protein, KAP, LAM and beta2-microglobulin levels were 3.54 g/24 h, 27.94 mg/h, 2948 mg/h and 33.40 mg/l, respectively, indicating no significant change compared with the levels prior to treatment.	('KAP', 'MPA', (33, 36))	('beta2-microglobulin', 'Gene', '567', (46, 65))	('LAM', 'Chemical', '-', (38, 41))	('beta2-microglobulin', 'Gene', (46, 65))	('urine protein', 'MPA', (18, 31))	('2948 mg/h', 'Var', (103, 112))	('urine protein', 'Phenotype', 'HP:0000093', (18, 31))
52087	28454444	In the 24-h urine analysis, the KAP and LAM levels were 40.30 mg/h and 748.80 mg/h, respectively, indicating a 68% decrease in comparison to the values prior to treatment.	('decrease', 'NegReg', (115, 123))	('LAM', 'Chemical', '-', (40, 43))	('748.80', 'Var', (71, 77))
52124	28331834	ECT resulted in improved local control and should be considered among the available adjuvant treatments in pets carrying visceral tumors.	('local control', 'CPA', (25, 38))	('ECT', 'Var', (0, 3))	('tumor', 'Phenotype', 'HP:0002664', (130, 135))	('visceral tumors', 'Disease', 'MESH:D059265', (121, 136))	('improved', 'PosReg', (16, 24))	('tumors', 'Phenotype', 'HP:0002664', (130, 136))	('visceral tumors', 'Disease', (121, 136))
52172	22309880	After the evacuation of pericardial hemorrhagic fluid (550 cc), the collapse disappeared, and the patient's symptoms were relieved entirely.	('disappeared', 'NegReg', (77, 88))	('550 cc', 'Var', (55, 61))	('patient', 'Species', '9606', (98, 105))	('collapse', 'MPA', (68, 76))	('pericardial hemorrhagic', 'Disease', (24, 47))	('pericardial hemorrhagic fluid', 'Phenotype', 'HP:0001698', (24, 53))	('pericardial hemorrhagic', 'Disease', 'MESH:D006470', (24, 47))
52312	31293579	PF skin lesions showed more CD4+GATA-3+ Th2 cells than CD3+T-Bet+ compared to the Th1-dominated GVHD-like skin lesions which inversely showed a stronger presence of CD3+T-Bet+ Th1 cells than CD4+GATA-3+ Th2 cells (Figures 3A,B).	('Th1', 'Gene', '51497', (176, 179))	('GVHD-like skin lesions', 'Disease', 'MESH:D012871', (96, 118))	('Th1', 'Gene', (176, 179))	('Th1', 'Gene', '51497', (82, 85))	('GVHD-like skin lesions', 'Disease', (96, 118))	('CD3+T-Bet+', 'Var', (165, 175))	('GATA-3', 'Gene', '2625', (32, 38))	('GATA-3', 'Gene', (32, 38))	('GATA-3', 'Gene', '2625', (195, 201))	('Th1', 'Gene', (82, 85))	('GATA-3', 'Gene', (195, 201))
52329	31293579	Anti-laminin 332 antibodies are pathogenic autoantibodies in anti-laminin 332 mucous membrane pemphigoid, a distinct subepidermal autoimmune bullous disorder showing predominant mucosal lesions.	('autoimmune bullous disorder', 'Disease', (130, 157))	('pathogenic', 'Reg', (32, 42))	('mucosal lesions', 'Disease', 'MESH:D009059', (178, 193))	('autoimmune bullous disorder', 'Disease', 'MESH:D001327', (130, 157))	('mucosal lesions', 'Disease', (178, 193))	('anti-laminin', 'Var', (61, 73))	('Anti-laminin', 'Protein', (0, 12))
52349	31293579	reported on a patient with thymoma and associated proteinuria due to minimal change glomerulonephritis, in which antitumoral therapy with belinostat, cisplatin, doxorubicin, and cyclophosphamide resulted in a complete resolution of the tumor, reduction of proteinuria and increase in the Th1/Th2 ratio.	('minimal change glomerulonephritis', 'Phenotype', 'HP:0012579', (69, 102))	('glomerulonephritis', 'Phenotype', 'HP:0000099', (84, 102))	('proteinuria', 'Disease', (256, 267))	('proteinuria', 'Disease', (50, 61))	('reduction', 'NegReg', (243, 252))	('thymoma', 'Disease', (27, 34))	('doxorubicin', 'Chemical', 'MESH:D004317', (161, 172))	('tumor', 'Disease', 'MESH:D009369', (236, 241))	('thymoma', 'Phenotype', 'HP:0100522', (27, 34))	('proteinuria', 'Disease', 'MESH:D011507', (256, 267))	('proteinuria', 'Disease', 'MESH:D011507', (50, 61))	('tumor', 'Phenotype', 'HP:0002664', (117, 122))	('cisplatin', 'Var', (150, 159))	('tumor', 'Phenotype', 'HP:0002664', (236, 241))	('cyclophosphamide', 'Chemical', 'MESH:D003520', (178, 194))	('proteinuria', 'Phenotype', 'HP:0000093', (50, 61))	('proteinuria', 'Phenotype', 'HP:0000093', (256, 267))	('cisplatin', 'Chemical', 'MESH:D002945', (150, 159))	('glomerulonephritis', 'Disease', 'MESH:D005921', (84, 102))	('tumor', 'Disease', (236, 241))	('patient', 'Species', '9606', (14, 21))	('Th1', 'Gene', (288, 291))	('rat', 'Species', '10116', (296, 299))	('increase', 'PosReg', (272, 280))	('belinostat', 'Chemical', 'MESH:C487081', (138, 148))	('minimal', 'Disease', (69, 76))	('Th1', 'Gene', '51497', (288, 291))	('tumor', 'Disease', (117, 122))	('thymoma', 'Disease', 'MESH:D013945', (27, 34))	('glomerulonephritis', 'Disease', (84, 102))	('tumor', 'Disease', 'MESH:D009369', (117, 122))
52365	29479559	Additionally, serum studies revealed presence of systemic antibodies to thyroperoxidase (37.8 kIU/L, reference range 0-5.5 kIU/L), thyroglobulin (372.2 kIU/L, reference range 0-5 kIU/L), Ro/SSA (6.8 AI, reference range < 1 AI), and an ANA titer of 80 (reference range 0-40) with a nucleolar pattern.	('372.2 kIU/L', 'Var', (146, 157))	('thyroperoxidase', 'Enzyme', (72, 87))	('Ro/SSA', 'Gene', (187, 193))	('Ro/SSA', 'Gene', '6737', (187, 193))
52380	29479559	It has been proven that the antibodies to VGKC actually target the associated proteins LGI1 and Caspr2, and not the channel itself, therefore rendering the term, "antibodies to VGKC" obsolete.	('LGI1', 'Gene', '9211', (87, 91))	('VGKC', 'Gene', (42, 46))	('antibodies', 'Var', (28, 38))	('LGI1', 'Gene', (87, 91))	('Caspr2', 'Gene', (96, 102))	('target', 'Reg', (56, 62))	('Caspr2', 'Gene', '26047', (96, 102))
52422	24824976	In three patients with chest MRI, the signal intensity on T1- and T2-weighted images of the intrathymic cyst was evaluated in reference to the skeletal muscle (hyperintense, isointense, or hypointense) in consensus.	('patients', 'Species', '9606', (9, 17))	('hypointense', 'Var', (189, 200))	('hyperintense', 'Var', (160, 172))	('isointense', 'Var', (174, 184))
52478	24824976	The small number of cases with MRI or PET/CT is another limitation, which is also likely due to the skewed population with high suspicion of neoplasm therefore undergoing surgical resection.	('neoplasm', 'Disease', (141, 149))	('neoplasm', 'Disease', 'MESH:D009369', (141, 149))	('MRI', 'Var', (31, 34))	('neoplasm', 'Phenotype', 'HP:0002664', (141, 149))
52515	24321421	Patients with severe MG status, including MGFA IIB or more were likely to have ph-PSL therapy after obtaining the patients' consent.	('ph-PSL therapy', 'Disease', (79, 93))	('PSL', 'Chemical', 'MESH:D011239', (82, 85))	('Patients', 'Species', '9606', (0, 8))	('MGFA', 'Chemical', '-', (42, 46))	('MGFA IIB', 'Var', (42, 50))	('patients', 'Species', '9606', (114, 122))
52531	24321421	At study entry, MG disease severity was significantly greater in the ph-PSL group compared to the control group (MGFA Class >= IIB, 42 [60.0%] versus 7 [11.3%], respectively; P < 0.001).	('greater', 'PosReg', (54, 61))	('ph-PSL', 'Var', (69, 75))	('PSL', 'Chemical', 'MESH:D011239', (72, 75))	('MGFA', 'Chemical', '-', (113, 117))
52541	24321421	Overall, anticholinesterase therapy was withdrawn significantly more frequently in the ph-PSL group than in the control group during both the preoperative phase (P < 0.001) and the postoperative phase (P = 0.002).	('withdrawn', 'MPA', (40, 49))	('ph-PSL', 'Var', (87, 93))	('PSL', 'Chemical', 'MESH:D011239', (90, 93))	('cholinesterase', 'Gene', (13, 27))	('cholinesterase', 'Gene', '590', (13, 27))
52548	24321421	The rates of patients improved at three and five years were 92% and 96%, respectively, in the ph-PSL group compared to 57% and 76%, respectively, in the control group (P < 0.001) (Figure 4a).	('ph-PSL', 'Var', (94, 100))	('patients', 'Species', '9606', (13, 21))	('improved', 'PosReg', (22, 30))	('PSL', 'Chemical', 'MESH:D011239', (97, 100))
52549	24321421	MG status among patients in the ph-PSL group improved more rapidly compared to the control group.	('improved', 'PosReg', (45, 53))	('patients', 'Species', '9606', (16, 24))	('MG status', 'MPA', (0, 9))	('PSL', 'Chemical', 'MESH:D011239', (35, 38))	('ph-PSL', 'Var', (32, 38))
52565	24321421	In turn, discontinuation of anti-cholinesterase revives and stabilizes the function of AchR.	('revives', 'PosReg', (48, 55))	('function', 'MPA', (75, 83))	('discontinuation', 'Var', (9, 24))	('cholinesterase', 'Gene', (33, 47))	('stabilizes', 'NegReg', (60, 70))	('AchR', 'Gene', (87, 91))	('cholinesterase', 'Gene', '590', (33, 47))
52646	31379720	Repeated antibody tests in the follow-up 2 weeks showed reduced titers of AChR-Ab, titin-Ab anti-M7, SMA-Ab, and CAE-Ab.	('AChR-Ab', 'Gene', (74, 81))	('CAE', 'Chemical', '-', (113, 116))	('reduced', 'NegReg', (56, 63))	('titin', 'Gene', (83, 88))	('titers', 'MPA', (64, 70))	('titin', 'Gene', '7273', (83, 88))	('anti-M7', 'Var', (92, 99))
52652	31379720	The thymus is a central immune organ and its dysfunction leads to many autoimmune diseases.	('autoimmune diseases', 'Phenotype', 'HP:0002960', (71, 90))	('dysfunction', 'Var', (45, 56))	('man', 'Species', '9606', (66, 69))	('autoimmune diseases', 'Disease', 'MESH:D001327', (71, 90))	('autoimmune diseases', 'Disease', (71, 90))	('leads to', 'Reg', (57, 65))
52662	31379720	However, the presence of anti-M7 in patients with MG and myocarditis, as well as its relationship with thymoma has not yet been reported.	('patients', 'Species', '9606', (36, 44))	('anti-M7', 'Var', (25, 32))	('myocarditis', 'Disease', 'MESH:D009205', (57, 68))	('thymoma', 'Disease', 'MESH:D013945', (103, 110))	('myocarditis', 'Phenotype', 'HP:0012819', (57, 68))	('thymoma', 'Disease', (103, 110))	('myocarditis', 'Disease', (57, 68))	('MG', 'Disease', 'MESH:D000080343', (50, 52))	('thymoma', 'Phenotype', 'HP:0100522', (103, 110))
52665	31379720	In conclusion, we predict that the thymoma-associated autoantibodies (titin-Ab, SMA-Ab, and CAE-Ab) and anti-M7 may play an important role in concurrent of MG and myositis and myocarditis.	('CAE', 'Chemical', '-', (92, 95))	('titin', 'Gene', '7273', (70, 75))	('myositis', 'Phenotype', 'HP:0100614', (163, 171))	('anti-M7', 'Var', (104, 111))	('titin', 'Gene', (70, 75))	('thymoma', 'Disease', 'MESH:D013945', (35, 42))	('myositis and myocarditis', 'Disease', 'MESH:D009205', (163, 187))	('myocarditis', 'Phenotype', 'HP:0012819', (176, 187))	('thymoma', 'Disease', (35, 42))	('thymoma', 'Phenotype', 'HP:0100522', (35, 42))	('MG', 'Disease', 'MESH:D000080343', (156, 158))
52678	30519470	Change in hydrostatic pressure gradient across the diaphragm by thoracentesis triggered a sudden onset of dyspnoea caused by the influx of a large volume of ascites into the pleural cavity through a hole in the diaphragm.	('pleural', 'Disease', (174, 181))	('hydrostatic pressure gradient', 'MPA', (10, 39))	('ascites', 'Disease', (157, 164))	('ascites', 'Phenotype', 'HP:0001541', (157, 164))	('dyspnoea', 'Disease', (106, 114))	('dyspnoea', 'Disease', 'MESH:D004417', (106, 114))	('ascites', 'Disease', 'MESH:D001201', (157, 164))	('Change', 'Var', (0, 6))	('influx of', 'MPA', (129, 138))	('pleural', 'Disease', 'MESH:D010995', (174, 181))
52711	30442178	The rationale behind such molecular reclassifications is that genetic alterations underlying cancer pathology predict response to therapy and may therefore offer a more precise view on cancer than histology.	('cancer', 'Disease', (93, 99))	('cancer', 'Disease', 'MESH:D009369', (93, 99))	('predict', 'Reg', (110, 117))	('cancer', 'Phenotype', 'HP:0002664', (185, 191))	('cancer', 'Phenotype', 'HP:0002664', (93, 99))	('genetic alterations', 'Var', (62, 81))	('cancer', 'Disease', 'MESH:D009369', (185, 191))	('cancer', 'Disease', (185, 191))	('response to therapy', 'MPA', (118, 137))
52712	30442178	The use of individual actionable mutations to select cancers for treatment across histotypes is already being tested in the so-called basket trials with variable success rates.	('cancers', 'Phenotype', 'HP:0002664', (53, 60))	('cancers', 'Disease', (53, 60))	('cancers', 'Disease', 'MESH:D009369', (53, 60))	('mutations', 'Var', (33, 42))	('cancer', 'Phenotype', 'HP:0002664', (53, 59))
52714	30442178	To determine effects of oncogenic mutations on protein profiles, we used the energy distance, which compares the Euclidean distances of protein profiles in tumors with an oncogenic mutation (inner distance) to that in tumors without the mutation (outer distance) and performed Monte Carlo simulations for the significance analysis.	('tumors', 'Disease', (156, 162))	('tumor', 'Phenotype', 'HP:0002664', (156, 161))	('tumor', 'Phenotype', 'HP:0002664', (218, 223))	('mutation', 'Var', (181, 189))	('tumors', 'Phenotype', 'HP:0002664', (156, 162))	('tumors', 'Phenotype', 'HP:0002664', (218, 224))	('tumors', 'Disease', 'MESH:D009369', (156, 162))	('tumors', 'Disease', (218, 224))	('tumors', 'Disease', 'MESH:D009369', (218, 224))
52720	30442178	Next-generation sequencing has facilitated comprehensive mutational profiling of all major cancers and has led to the discovery of oncogenic driver mutations, many of which can be targeted therapeutically.	('mutations', 'Var', (148, 157))	('cancers', 'Phenotype', 'HP:0002664', (91, 98))	('cancers', 'Disease', 'MESH:D009369', (91, 98))	('cancers', 'Disease', (91, 98))	('cancer', 'Phenotype', 'HP:0002664', (91, 97))
52722	30442178	However, sequencing data has shown that actionable mutations, albeit with different frequencies, occur across cancers, which has raised the question about histotype-independent therapies and novel ways of tumor classifications no longer relying on histology but on genetic profiles.	('cancers', 'Disease', (110, 117))	('mutations', 'Var', (51, 60))	('tumor', 'Disease', 'MESH:D009369', (205, 210))	('cancer', 'Phenotype', 'HP:0002664', (110, 116))	('tumor', 'Phenotype', 'HP:0002664', (205, 210))	('tumor', 'Disease', (205, 210))	('cancers', 'Phenotype', 'HP:0002664', (110, 117))	('cancers', 'Disease', 'MESH:D009369', (110, 117))
52725	30442178	That targeted therapies against the same single molecular alteration can be effective across cancers, as shown, for instance, by the efficacy of anti-Her2 therapy in both gastric and breast cancers or the clinical benefit from inhibition of mutated cKIT in gastrointestinal stromal tumors (GIST) and melanoma or mastocytosis.	('gastric and breast cancers', 'Disease', 'MESH:D013274', (171, 197))	('melanoma or mastocytosis', 'Disease', (300, 324))	('cancers', 'Disease', 'MESH:D009369', (190, 197))	('Her2', 'Gene', '2064', (150, 154))	('cancers', 'Disease', 'MESH:D009369', (93, 100))	('gastrointestinal stromal tumors', 'Disease', (257, 288))	('GIST', 'Phenotype', 'HP:0100723', (290, 294))	('tumors', 'Phenotype', 'HP:0002664', (282, 288))	('Her2', 'Gene', (150, 154))	('cancer', 'Phenotype', 'HP:0002664', (190, 196))	('mutated', 'Var', (241, 248))	('melanoma', 'Phenotype', 'HP:0002861', (300, 308))	('cancers', 'Phenotype', 'HP:0002664', (190, 197))	('cKIT', 'Gene', '3815', (249, 253))	('tumor', 'Phenotype', 'HP:0002664', (282, 287))	('cancers', 'Disease', (190, 197))	('cancers', 'Phenotype', 'HP:0002664', (93, 100))	('cancers', 'Disease', (93, 100))	('melanoma or mastocytosis', 'Disease', 'MESH:D008415', (300, 324))	('gastrointestinal stromal tumors', 'Phenotype', 'HP:0100723', (257, 288))	('gastrointestinal stromal tumors', 'Disease', 'MESH:D046152', (257, 288))	('cancer', 'Phenotype', 'HP:0002664', (93, 99))	('breast cancers', 'Phenotype', 'HP:0003002', (183, 197))	('inhibition', 'Var', (227, 237))	('mastocytosis', 'Phenotype', 'HP:0100495', (312, 324))	('cKIT', 'Gene', (249, 253))	('breast cancer', 'Phenotype', 'HP:0003002', (183, 196))
52726	30442178	However, the fact that inhibition of BRAF mutated at V600 is effective in melanoma but not in colorectal cancer is a prominent example against the general transferability of knowledge on a single actionable mutation from one histological tumor type to another.	('tumor', 'Disease', 'MESH:D009369', (238, 243))	('colorectal cancer', 'Disease', 'MESH:D015179', (94, 111))	('BRAF', 'Gene', '673', (37, 41))	('tumor', 'Phenotype', 'HP:0002664', (238, 243))	('rectal cancer', 'Phenotype', 'HP:0100743', (98, 111))	('BRAF', 'Gene', (37, 41))	('mutated at V600', 'Var', (42, 57))	('melanoma', 'Disease', 'MESH:D008545', (74, 82))	('melanoma', 'Disease', (74, 82))	('melanoma', 'Phenotype', 'HP:0002861', (74, 82))	('colorectal cancer', 'Phenotype', 'HP:0003003', (94, 111))	('tumor', 'Disease', (238, 243))	('cancer', 'Phenotype', 'HP:0002664', (105, 111))	('colorectal cancer', 'Disease', (94, 111))	('ran', 'Gene', (156, 159))	('ran', 'Gene', '5901', (156, 159))
52728	30442178	Using mutational profiles or just single genetic aberrations, as is the case in the current basket trials, is unlikely to cover the full scope of (tissue-specific) molecular effects including epigenetic mechanisms and downstream regulation such as post-translational modifications.	('mutational', 'Var', (6, 16))	('ran', 'Gene', (254, 257))	('ran', 'Gene', '5901', (254, 257))
52743	30442178	To address the question of how mutational differences between two classes affect protein expressions in more than one histotype in the same way, we performed a cross-cancer effect analysis.	('mutational', 'Var', (31, 41))	('affect', 'Reg', (74, 80))	('protein expressions', 'MPA', (81, 100))	('cross-cancer', 'Disease', (160, 172))	('cancer', 'Phenotype', 'HP:0002664', (166, 172))	('cross-cancer', 'Disease', 'MESH:C537866', (160, 172))
52758	30442178	At this point, it is unclear whether the reason for this inconsistency between genetic and protein profiles is the differential translation of genetic profiles into protein levels in different cancer types, or organ- and tissue-specific protein base levels that are modulated by mutations:or a combination of both.	('ran', 'Gene', (129, 132))	('cancer', 'Disease', 'MESH:D009369', (193, 199))	('mutations', 'Var', (279, 288))	('ran', 'Gene', '5901', (129, 132))	('cancer', 'Disease', (193, 199))	('modulated', 'Reg', (266, 275))	('cancer', 'Phenotype', 'HP:0002664', (193, 199))
52772	30442178	In the proposal by Ciriello et al., tumors are classified by the presence of somatic mutations and copy number alterations in cancer-related pathways.	('cancer', 'Phenotype', 'HP:0002664', (126, 132))	('tumors', 'Disease', 'MESH:D009369', (36, 42))	('cancer', 'Disease', (126, 132))	('cancer', 'Disease', 'MESH:D009369', (126, 132))	('copy number alterations', 'Var', (99, 122))	('tumor', 'Phenotype', 'HP:0002664', (36, 41))	('tumors', 'Disease', (36, 42))	('tumors', 'Phenotype', 'HP:0002664', (36, 42))
52784	30442178	The least pronounced but still significant class discriminability is achieved for classes C12 and C5 in breast cancer (sdis = - 0.31, p = 4.4e-3; srand = - 8.0e-5).	('ran', 'Gene', (147, 150))	('sdis', 'Chemical', '-', (119, 123))	('ran', 'Gene', '5901', (147, 150))	('C12', 'Var', (90, 93))	('cancer', 'Phenotype', 'HP:0002664', (111, 117))	('breast cancer', 'Disease', 'MESH:D001943', (104, 117))	('breast cancer', 'Disease', (104, 117))	('breast cancer', 'Phenotype', 'HP:0003002', (104, 117))
52803	30442178	With CES = 2%, the overall classification effectivity score of this classification is the lowest among all tested classifications indicating that global comparisons based on somatic mutations only are not effective in classifying tumors in a meaningful way if the available protein profiles are considered relevant.	('CES', 'Chemical', '-', (5, 8))	('tumors', 'Disease', 'MESH:D009369', (230, 236))	('tumors', 'Disease', (230, 236))	('tumors', 'Phenotype', 'HP:0002664', (230, 236))	('CES', 'Var', (5, 8))	('lowest', 'NegReg', (90, 96))	('tumor', 'Phenotype', 'HP:0002664', (230, 235))
52806	30442178	For this classification, class discriminability sdis is highest between class toLGG (cases that are most similar to low-grade glioma cases by their mutation profile) and class toPRAD for low-grade glioma (LGG) (sdis = - 3.26; p = 0.0; srand = - 6.1e-5; characteristic protein profiles increased in toLGG: p70S6K_pT389; increased in ToPRAD: YAP_pS127, HER2_pY1248, HER2, EGFR_pY1068, EGFR_pY1173, Src_pY416, and Cyclin_D1).	('glioma', 'Phenotype', 'HP:0009733', (126, 132))	('EGFR', 'Gene', (370, 374))	('HER2', 'Gene', '2064', (351, 355))	('increased', 'PosReg', (285, 294))	('sdis', 'Chemical', '-', (48, 52))	('glioma', 'Phenotype', 'HP:0009733', (197, 203))	('p70S6K', 'Gene', '6198', (305, 311))	('Cyclin_D1', 'Gene', (411, 420))	('EGFR', 'Gene', (383, 387))	('sdis', 'Chemical', '-', (211, 215))	('EGFR', 'Gene', '1956', (370, 374))	('HER2', 'Gene', '2064', (364, 368))	('HER2', 'Gene', (351, 355))	('ran', 'Gene', (236, 239))	('glioma', 'Disease', (126, 132))	('ran', 'Gene', '5901', (236, 239))	('increased', 'PosReg', (319, 328))	('glioma', 'Disease', 'MESH:D005910', (126, 132))	('p70S6K', 'Gene', (305, 311))	('EGFR', 'Gene', '1956', (383, 387))	('glioma', 'Disease', (197, 203))	('Src_pY416', 'Var', (396, 405))	('HER2', 'Gene', (364, 368))	('Cyclin_D1', 'Gene', '595', (411, 420))	('glioma', 'Disease', 'MESH:D005910', (197, 203))
52829	30442178	Using the same approach as above, we are systematically evaluating all major actionable somatic mutations and copy number alterations against which drugs are approved for clinical use or which are currently tested in clinical trials with respect to their effects on proteins across cancers.	('cancers', 'Disease', (282, 289))	('cancer', 'Phenotype', 'HP:0002664', (282, 288))	('cancers', 'Disease', 'MESH:D009369', (282, 289))	('copy number alterations', 'Var', (110, 133))	('cancers', 'Phenotype', 'HP:0002664', (282, 289))	('mutations', 'Var', (96, 105))
52834	30442178	Overall, our analysis showed for all analyzed 12 actionable genes (OncoKB evidence levels 1-3) that the mutational status is associated with significant differences in protein profiles in histotypes for which the respective targeted drugs are approved or currently being clinically tested and showed additional mutation-associated protein profiles in 9 histological tumor types.	('tumor', 'Disease', (366, 371))	('mutational', 'Var', (104, 114))	('associated', 'Reg', (125, 135))	('protein profiles', 'MPA', (168, 184))	('tumor', 'Phenotype', 'HP:0002664', (366, 371))	('tumor', 'Disease', 'MESH:D009369', (366, 371))	('differences', 'Reg', (153, 164))
52836	30442178	Only KRAS/NRAS mutations in colorectal cancer do not result in discriminable protein profiles comparing wild-type and mutated cases, whereas an effect can be observed for thyroid cancer and melanoma.	('result', 'Reg', (53, 59))	('NRAS', 'Gene', '4893', (10, 14))	('colorectal cancer', 'Phenotype', 'HP:0003003', (28, 45))	('melanoma', 'Phenotype', 'HP:0002861', (190, 198))	('melanoma', 'Disease', (190, 198))	('rectal cancer', 'Phenotype', 'HP:0100743', (32, 45))	('cancer', 'Phenotype', 'HP:0002664', (179, 185))	('mutations', 'Var', (15, 24))	('colorectal cancer', 'Disease', (28, 45))	('KRAS', 'Gene', (5, 9))	('melanoma', 'Disease', 'MESH:D008545', (190, 198))	('KRAS', 'Gene', '3845', (5, 9))	('cancer', 'Phenotype', 'HP:0002664', (39, 45))	('thyroid cancer', 'Disease', (171, 185))	('thyroid cancer', 'Phenotype', 'HP:0002890', (171, 185))	('NRAS', 'Gene', (10, 14))	('colorectal cancer', 'Disease', 'MESH:D015179', (28, 45))	('thyroid cancer', 'Disease', 'MESH:D013964', (171, 185))
52839	30442178	Our results demonstrate that in addition to confirming known druggable genes in the available cell line data, protein profile discriminability in between presence or absence of oncogenic mutations is predictive of drug response in cell line data across cancers (p = 0.048, Table 2).	('cancers', 'Phenotype', 'HP:0002664', (253, 260))	('cancers', 'Disease', (253, 260))	('cancers', 'Disease', 'MESH:D009369', (253, 260))	('mutations', 'Var', (187, 196))	('protein', 'MPA', (110, 117))	('cancer', 'Phenotype', 'HP:0002664', (253, 259))
52840	30442178	BRAF mutations are actionable in melanomas (OncoKB level 1).	('melanomas', 'Disease', 'MESH:D008545', (33, 42))	('melanoma', 'Phenotype', 'HP:0002861', (33, 41))	('melanomas', 'Phenotype', 'HP:0002861', (33, 42))	('mutations', 'Var', (5, 14))	('BRAF', 'Gene', '673', (0, 4))	('BRAF', 'Gene', (0, 4))	('melanomas', 'Disease', (33, 42))
52841	30442178	Mutations of BRAF are frequent enough in our data for melanoma (46% cases with mutation) and thyroid carcinoma (not yet reported by OncoKB, 56% cases with mutation) for further analysis.	('thyroid carcinoma', 'Phenotype', 'HP:0002890', (93, 110))	('thyroid carcinoma', 'Disease', (93, 110))	('carcinoma', 'Phenotype', 'HP:0030731', (101, 110))	('BRAF', 'Gene', '673', (13, 17))	('melanoma', 'Disease', 'MESH:D008545', (54, 62))	('melanoma', 'Phenotype', 'HP:0002861', (54, 62))	('BRAF', 'Gene', (13, 17))	('melanoma', 'Disease', (54, 62))	('Mutations', 'Var', (0, 9))	('mutation', 'Var', (79, 87))	('thyroid carcinoma', 'Disease', 'MESH:D013964', (93, 110))
52842	30442178	The actionable mutations create discriminable groups of cases for thyroid carcinoma (sdis = - 2.07; p = 0.0; srand = - 1.0e-4) and melanoma (sdis = - 0.10; p = 4.7e-3; srand = - 1.1e-4).	('melanoma', 'Phenotype', 'HP:0002861', (131, 139))	('thyroid carcinoma', 'Phenotype', 'HP:0002890', (66, 83))	('melanoma', 'Disease', (131, 139))	('thyroid carcinoma', 'Disease', (66, 83))	('sdis', 'Chemical', '-', (85, 89))	('melanoma', 'Disease', 'MESH:D008545', (131, 139))	('mutations', 'Var', (15, 24))	('carcinoma', 'Phenotype', 'HP:0030731', (74, 83))	('ran', 'Gene', (110, 113))	('ran', 'Gene', '5901', (110, 113))	('sdis', 'Chemical', '-', (141, 145))	('ran', 'Gene', (169, 172))	('thyroid carcinoma', 'Disease', 'MESH:D013964', (66, 83))	('ran', 'Gene', '5901', (169, 172))
52846	30442178	CDK4 amplification is actionable for differentiated sarcomas (OncoKB level 2).	('sarcomas', 'Disease', 'MESH:D012509', (52, 60))	('amplification', 'Var', (5, 18))	('sarcomas', 'Phenotype', 'HP:0100242', (52, 60))	('sarcoma', 'Phenotype', 'HP:0100242', (52, 59))	('sarcomas', 'Disease', (52, 60))	('CDK4', 'Gene', (0, 4))	('CDK4', 'Gene', '1019', (0, 4))
52848	30442178	For sarcoma, 36% of the cases show CDK4 amplification and protein profiles are discriminable (sdis = - 0.34; p = 0.0; srand = - 6.0e-5) with E-Cadherin, Caveolin-1, Akt_pS473, Cyclin_B1, ER-alpha, Akt_pT308, YAP_pS127, S6_pS240_S244, and Cyclin_E1 decreased and HSP70, Syk, Lck, Src_pY416, and Src_pY527 increased in CDK4 amplified cases.	('CDK4', 'Gene', '1019', (317, 321))	('Cyclin_B1', 'Gene', (176, 185))	('decreased', 'NegReg', (248, 257))	('Lck', 'Gene', (274, 277))	('ER-alpha', 'Gene', (187, 195))	('E-Cadherin', 'Gene', '999', (141, 151))	('ER-alpha', 'Gene', '2099', (187, 195))	('increased', 'PosReg', (304, 313))	('sdis', 'Chemical', '-', (94, 98))	('sarcoma', 'Disease', 'MESH:D012509', (4, 11))	('Syk', 'Gene', '6850', (269, 272))	('Cyclin_B1', 'Gene', '891', (176, 185))	('CDK4', 'Gene', (35, 39))	('HSP70', 'Gene', (262, 267))	('ran', 'Gene', (119, 122))	('sarcoma', 'Disease', (4, 11))	('ran', 'Gene', '5901', (119, 122))	('Syk', 'Gene', (269, 272))	('Cyclin_E1', 'Gene', '898', (238, 247))	('E-Cadherin', 'Gene', (141, 151))	('Caveolin-1', 'Gene', (153, 163))	('CDK4', 'Gene', (317, 321))	('CDK4', 'Gene', '1019', (35, 39))	('sarcoma', 'Phenotype', 'HP:0100242', (4, 11))	('Src_pY416', 'Var', (279, 288))	('Caveolin-1', 'Gene', '857', (153, 163))	('Src_pY527', 'Var', (294, 303))	('Cyclin_E1', 'Gene', (238, 247))	('HSP70', 'Gene', '3308', (262, 267))	('Lck', 'Gene', '3932', (274, 277))
52850	30442178	EGFR mutations are actionable in non-small cell lung cancer (OncoKB level 1).	('EGFR', 'Gene', (0, 4))	('non-small cell lung cancer', 'Disease', (33, 59))	('small cell lung cancer', 'Phenotype', 'HP:0030357', (37, 59))	('mutations', 'Var', (5, 14))	('cancer', 'Phenotype', 'HP:0002664', (53, 59))	('lung cancer', 'Phenotype', 'HP:0100526', (48, 59))	('non-small cell lung cancer', 'Phenotype', 'HP:0030358', (33, 59))	('EGFR', 'Gene', '1956', (0, 4))	('non-small cell lung cancer', 'Disease', 'MESH:D002289', (33, 59))
52852	30442178	Lung adenocarcinoma (LUAD) cases with actionable mutation of EGFR are discriminable from those without by protein profile (sdis = - 0.44; p = 5.9e-4; srand = 3.1e-5).	('sdis', 'Chemical', '-', (123, 127))	('LUAD', 'Phenotype', 'HP:0030078', (21, 25))	('ran', 'Gene', (151, 154))	('ran', 'Gene', '5901', (151, 154))	('mutation', 'Var', (49, 57))	('carcinoma', 'Phenotype', 'HP:0030731', (10, 19))	('Lung adenocarcinoma', 'Phenotype', 'HP:0030078', (0, 19))	('Lung adenocarcinoma', 'Disease', (0, 19))	('Lung adenocarcinoma', 'Disease', 'MESH:D000077192', (0, 19))	('EGFR', 'Gene', '1956', (61, 65))	('EGFR', 'Gene', (61, 65))
52853	30442178	EGFR_pY1068 levels are increased for cases with the respective mutations, and Claudin-7 levels are decreased among those cases.	('mutations', 'Var', (63, 72))	('decreased', 'NegReg', (99, 108))	('EGFR', 'Gene', (0, 4))	('Claudin-7', 'Gene', '1366', (78, 87))	('increased', 'PosReg', (23, 32))	('EGFR', 'Gene', '1956', (0, 4))	('Claudin-7', 'Gene', (78, 87))
52854	30442178	ERBB2/HER2 amplification is actionable in breast cancer and gastric cancer (level 1 evidence, FDA-approved).	('cancer', 'Phenotype', 'HP:0002664', (68, 74))	('ERBB2', 'Gene', '2064', (0, 5))	('cancer', 'Phenotype', 'HP:0002664', (49, 55))	('ERBB2', 'Gene', (0, 5))	('gastric cancer', 'Disease', (60, 74))	('breast cancer', 'Disease', 'MESH:D001943', (42, 55))	('breast cancer', 'Phenotype', 'HP:0003002', (42, 55))	('gastric cancer', 'Disease', 'MESH:D013274', (60, 74))	('breast cancer', 'Disease', (42, 55))	('HER2', 'Gene', (6, 10))	('HER2', 'Gene', '2064', (6, 10))	('gastric cancer', 'Phenotype', 'HP:0012126', (60, 74))	('amplification', 'Var', (11, 24))
52864	30442178	Two histological tumor types in which ERBB2 amplification has a similar impact on proteins are breast (BRCA) and gastric (STAD) cancers (p = 2.3e-3).	('cancers', 'Phenotype', 'HP:0002664', (128, 135))	('tumor', 'Disease', (17, 22))	('BRCA', 'Gene', '672', (103, 107))	('BRCA', 'Gene', (103, 107))	('gastric (STAD) cancers', 'Disease', 'MESH:D013274', (113, 135))	('amplification', 'Var', (44, 57))	('ERBB2', 'Gene', (38, 43))	('proteins', 'MPA', (82, 90))	('ERBB2', 'Gene', '2064', (38, 43))	('cancer', 'Phenotype', 'HP:0002664', (128, 134))	('tumor', 'Disease', 'MESH:D009369', (17, 22))	('impact', 'Reg', (72, 78))	('tumor', 'Phenotype', 'HP:0002664', (17, 22))
52869	30442178	For FGFR1 amplification, clinical evidence (OncoKB level 3) exists on its actionability in lung squamous cell carcinomas.	('carcinoma', 'Phenotype', 'HP:0030731', (110, 119))	('FGFR1', 'Gene', (4, 9))	('carcinomas', 'Phenotype', 'HP:0030731', (110, 120))	('lung squamous cell carcinomas', 'Disease', (91, 120))	('FGFR1', 'Gene', '2260', (4, 9))	('amplification', 'Var', (10, 23))	('squamous cell carcinomas', 'Phenotype', 'HP:0002860', (96, 120))	('lung squamous cell carcinomas', 'Disease', 'MESH:D002294', (91, 120))	('squamous cell carcinoma', 'Phenotype', 'HP:0002860', (96, 119))
52870	30442178	Our analysis shows that besides lung squamous cell carcinoma, protein expression of amplified cases is discriminable from non-amplified cases in renal clear cell carcinoma, testicular germ cell tumors, lung adenocarcinoma, endometrial carcinoma, breast cancer, and thymoma (all currently not reported by OncoKB).	('endometrial carcinoma', 'Disease', 'MESH:D016889', (223, 244))	('breast cancer', 'Phenotype', 'HP:0003002', (246, 259))	('renal clear cell carcinoma', 'Disease', 'MESH:C538614', (145, 171))	('renal clear cell carcinoma', 'Disease', (145, 171))	('thymoma', 'Disease', (265, 272))	('thymoma', 'Phenotype', 'HP:0100522', (265, 272))	('breast cancer', 'Disease', 'MESH:D001943', (246, 259))	('breast cancer', 'Disease', (246, 259))	('lung adenocarcinoma', 'Disease', (202, 221))	('squamous cell carcinoma', 'Phenotype', 'HP:0002860', (37, 60))	('carcinoma', 'Phenotype', 'HP:0030731', (212, 221))	('tumors', 'Phenotype', 'HP:0002664', (194, 200))	('lung squamous cell carcinoma', 'Disease', 'MESH:D002294', (32, 60))	('lung squamous cell carcinoma', 'Disease', (32, 60))	('lung adenocarcinoma', 'Disease', 'MESH:D000077192', (202, 221))	('endometrial carcinoma', 'Disease', (223, 244))	('carcinoma', 'Phenotype', 'HP:0030731', (235, 244))	('tumor', 'Phenotype', 'HP:0002664', (194, 199))	('lung adenocarcinoma', 'Phenotype', 'HP:0030078', (202, 221))	('tumors', 'Disease', (194, 200))	('cancer', 'Phenotype', 'HP:0002664', (253, 259))	('carcinoma', 'Phenotype', 'HP:0030731', (162, 171))	('protein expression', 'MPA', (62, 80))	('thymoma', 'Disease', 'MESH:D013945', (265, 272))	('testicular', 'Disease', (173, 183))	('amplified', 'Var', (84, 93))	('endometrial carcinoma', 'Phenotype', 'HP:0012114', (223, 244))	('tumors', 'Disease', 'MESH:D009369', (194, 200))	('carcinoma', 'Phenotype', 'HP:0030731', (51, 60))
52873	30442178	A cross-cancer effect is found between breast cancer and lung adenocarcinoma with HER2, HER2_pY1248, and EGFR_pY1068 levels decrease and 4E-BP1 levels increase associated with FGFR1 amplification for both histological tumor types.	('breast cancer', 'Phenotype', 'HP:0003002', (39, 52))	('A cross-cancer', 'Disease', 'MESH:C537866', (0, 14))	('increase', 'PosReg', (151, 159))	('HER2', 'Gene', '2064', (88, 92))	('4E-BP1', 'Gene', (137, 143))	('decrease', 'NegReg', (124, 132))	('EGFR', 'Gene', (105, 109))	('breast cancer', 'Disease', 'MESH:D001943', (39, 52))	('tumor', 'Disease', (218, 223))	('breast cancer', 'Disease', (39, 52))	('A cross-cancer', 'Disease', (0, 14))	('tumor', 'Disease', 'MESH:D009369', (218, 223))	('lung adenocarcinoma', 'Disease', (57, 76))	('HER2', 'Gene', (82, 86))	('cancer', 'Phenotype', 'HP:0002664', (8, 14))	('FGFR1', 'Gene', '2260', (176, 181))	('HER2', 'Gene', (88, 92))	('EGFR', 'Gene', '1956', (105, 109))	('tumor', 'Phenotype', 'HP:0002664', (218, 223))	('cancer', 'Phenotype', 'HP:0002664', (46, 52))	('lung adenocarcinoma', 'Disease', 'MESH:D000077192', (57, 76))	('4E-BP1', 'Gene', '1978', (137, 143))	('lung adenocarcinoma', 'Phenotype', 'HP:0030078', (57, 76))	('carcinoma', 'Phenotype', 'HP:0030731', (67, 76))	('FGFR1', 'Gene', (176, 181))	('HER2', 'Gene', '2064', (82, 86))	('levels', 'MPA', (144, 150))	('amplification', 'Var', (182, 195))
52874	30442178	Certain FGFR3 mutations are actionable in bladder cancer (OncoKB level 3).	('bladder cancer', 'Phenotype', 'HP:0009725', (42, 56))	('FGFR3', 'Gene', '2261', (8, 13))	('cancer', 'Phenotype', 'HP:0002664', (50, 56))	('actionable', 'Reg', (28, 38))	('bladder cancer', 'Disease', 'MESH:D001749', (42, 56))	('bladder cancer', 'Disease', (42, 56))	('mutations', 'Var', (14, 23))	('FGFR3', 'Gene', (8, 13))
52875	30442178	Targetable FGFR3 mutations are only frequent enough in urothelial and bladder carcinoma for our analysis.	('frequent', 'Reg', (36, 44))	('bladder carcinoma', 'Phenotype', 'HP:0002862', (70, 87))	('FGFR3', 'Gene', '2261', (11, 16))	('carcinoma', 'Phenotype', 'HP:0030731', (78, 87))	('bladder carcinoma', 'Disease', 'MESH:D001749', (70, 87))	('FGFR3', 'Gene', (11, 16))	('bladder carcinoma', 'Disease', (70, 87))	('urothelial', 'Disease', (55, 65))	('mutations', 'Var', (17, 26))
52876	30442178	The protein profiles of cases with at least one of these mutations are discriminable from the profiles of those without (sdis = - 0.76; p = 2.7e-3; srand = - 1.3e-5).	('ran', 'Gene', '5901', (149, 152))	('mutations', 'Var', (57, 66))	('sdis', 'Chemical', '-', (121, 125))	('ran', 'Gene', (149, 152))
52877	30442178	E-Cadherin, beta-Catenin, HER2, Ku80, PTEN, IRS1, and 53BP1 are increased among cases having one or more specific FGF3 mutation.	('53BP1', 'Gene', (54, 59))	('53BP1', 'Gene', '7158', (54, 59))	('FGF3', 'Gene', (114, 118))	('mutation', 'Var', (119, 127))	('Ku80', 'Gene', '7520', (32, 36))	('beta-Catenin', 'Gene', '1499', (12, 24))	('PTEN', 'Gene', '5728', (38, 42))	('Ku80', 'Gene', (32, 36))	('HER2', 'Gene', (26, 30))	('E-Cadherin', 'Gene', (0, 10))	('FGF3', 'Gene', '2248', (114, 118))	('IRS1', 'Gene', '3667', (44, 48))	('IRS1', 'Gene', (44, 48))	('HER2', 'Gene', '2064', (26, 30))	('increased', 'PosReg', (64, 73))	('E-Cadherin', 'Gene', '999', (0, 10))	('PTEN', 'Gene', (38, 42))	('beta-Catenin', 'Gene', (12, 24))
52878	30442178	IDH1 mutations are actionable in acute myeloid leukemia, cholangiocarcinoma, and glioma (OncoKB level 3).	('leukemia', 'Phenotype', 'HP:0001909', (47, 55))	('cholangiocarcinoma', 'Disease', 'MESH:D018281', (57, 75))	('carcinoma', 'Phenotype', 'HP:0030731', (66, 75))	('glioma', 'Phenotype', 'HP:0009733', (81, 87))	('cholangiocarcinoma', 'Phenotype', 'HP:0030153', (57, 75))	('acute myeloid leukemia', 'Disease', (33, 55))	('myeloid leukemia', 'Phenotype', 'HP:0012324', (39, 55))	('mutations', 'Var', (5, 14))	('glioma', 'Disease', (81, 87))	('acute myeloid leukemia', 'Disease', 'MESH:D015470', (33, 55))	('glioma', 'Disease', 'MESH:D005910', (81, 87))	('acute myeloid leukemia', 'Phenotype', 'HP:0004808', (33, 55))	('IDH1', 'Gene', (0, 4))	('cholangiocarcinoma', 'Disease', (57, 75))	('IDH1', 'Gene', '3417', (0, 4))
52879	30442178	Specific IDH1 mutations lead to discriminable protein profiles for low-grade glioma (sdis = - 0.47; p = 0.0; srand = - 3.1e-6) and glioblastoma (sdis = - 1.59; p = 5.0e-4; srand = - 1.0e-5).	('glioma', 'Disease', 'MESH:D005910', (77, 83))	('IDH1', 'Gene', (9, 13))	('glioblastoma', 'Phenotype', 'HP:0012174', (131, 143))	('sdis', 'Chemical', '-', (85, 89))	('IDH1', 'Gene', '3417', (9, 13))	('ran', 'Gene', (110, 113))	('ran', 'Gene', '5901', (110, 113))	('glioma', 'Disease', (77, 83))	('ran', 'Gene', (173, 176))	('protein profiles', 'MPA', (46, 62))	('ran', 'Gene', '5901', (173, 176))	('sdis', 'Chemical', '-', (145, 149))	('mutations', 'Var', (14, 23))	('glioblastoma', 'Disease', (131, 143))	('glioma', 'Phenotype', 'HP:0009733', (77, 83))	('glioblastoma', 'Disease', 'MESH:D005909', (131, 143))
52881	30442178	For glioblastoma IGFBP2, EGFR_pY1068, HER2_pY1248, Caveolin-1, Akt_pT308, Fibronectin, Collagen_VI, and EGFR_pY1173 are decreased in the group of mutated cases.	('decreased', 'NegReg', (120, 129))	('Fibronectin', 'Gene', (74, 85))	('HER2', 'Gene', (38, 42))	('EGFR', 'Gene', (25, 29))	('mutated', 'Var', (146, 153))	('EGFR', 'Gene', (104, 108))	('Caveolin-1', 'Gene', '857', (51, 61))	('glioblastoma', 'Disease', (4, 16))	('glioblastoma', 'Disease', 'MESH:D005909', (4, 16))	('Caveolin-1', 'Gene', (51, 61))	('Fibronectin', 'Gene', '2335', (74, 85))	('glioblastoma', 'Phenotype', 'HP:0012174', (4, 16))	('IGFBP2', 'Gene', '3485', (17, 23))	('IGFBP2', 'Gene', (17, 23))	('EGFR', 'Gene', '1956', (25, 29))	('HER2', 'Gene', '2064', (38, 42))	('EGFR', 'Gene', '1956', (104, 108))
52882	30442178	Therefore, IGFBP2, EGFR_pY1068, HER2_pY1248, and EGFR_pY1173 are affected in the same way by IDH1 mutations in low-grade glioma and glioblastoma, and we report a cross-cancer effect for those groups.	('HER2', 'Gene', '2064', (32, 36))	('EGFR', 'Gene', (19, 23))	('glioblastoma', 'Disease', (132, 144))	('glioma', 'Disease', (121, 127))	('cancer', 'Phenotype', 'HP:0002664', (168, 174))	('glioblastoma', 'Phenotype', 'HP:0012174', (132, 144))	('EGFR', 'Gene', (49, 53))	('glioma', 'Disease', 'MESH:D005910', (121, 127))	('cross-cancer', 'Disease', 'MESH:C537866', (162, 174))	('IDH1', 'Gene', (93, 97))	('HER2', 'Gene', (32, 36))	('EGFR', 'Gene', '1956', (19, 23))	('glioma', 'Phenotype', 'HP:0009733', (121, 127))	('cross-cancer', 'Disease', (162, 174))	('IGFBP2', 'Gene', '3485', (11, 17))	('EGFR', 'Gene', '1956', (49, 53))	('IDH1', 'Gene', '3417', (93, 97))	('mutations', 'Var', (98, 107))	('affected', 'Reg', (65, 73))	('glioblastoma', 'Disease', 'MESH:D005909', (132, 144))	('IGFBP2', 'Gene', (11, 17))
52883	30442178	KIT mutations are actionable in gastrointestinal stromal tumors (OncoKB level 1).	('gastrointestinal stromal tumors', 'Disease', (32, 63))	('tumor', 'Phenotype', 'HP:0002664', (57, 62))	('tumors', 'Phenotype', 'HP:0002664', (57, 63))	('mutations', 'Var', (4, 13))	('gastrointestinal stromal tumors', 'Disease', 'MESH:D046152', (32, 63))	('KIT', 'Gene', (0, 3))	('gastrointestinal stromal tumors', 'Phenotype', 'HP:0100723', (32, 63))
52884	30442178	For the tested KIT mutations, only testicular germ cell tumors (TGCT) had enough mutated cases sufficient for our analysis.	('tumor', 'Phenotype', 'HP:0002664', (56, 61))	('KIT', 'Gene', (15, 18))	('mutations', 'Var', (19, 28))	('tumors', 'Disease', (56, 62))	('tumors', 'Disease', 'MESH:D009369', (56, 62))	('tumors', 'Phenotype', 'HP:0002664', (56, 62))
52885	30442178	The protein profiles of the mutated and wild-type cases are discriminable (sdis = - 0.90; p = 4.5e-3; srand = - 2.6e-4) with decreased E-Cadherin and Fibronectin expression in wildtype cases and increased c-Kit, STAT5-alpha, and Syk expression levels.	('Fibronectin', 'Gene', '2335', (150, 161))	('mutated', 'Var', (28, 35))	('c-Kit', 'Gene', (205, 210))	('Fibronectin', 'Gene', (150, 161))	('E-Cadherin', 'Gene', '999', (135, 145))	('expression levels', 'MPA', (233, 250))	('sdis', 'Chemical', '-', (75, 79))	('c-Kit', 'Gene', '3815', (205, 210))	('decreased', 'NegReg', (125, 134))	('Syk', 'Gene', '6850', (229, 232))	('STAT5-alpha', 'Gene', '6776', (212, 223))	('expression', 'MPA', (162, 172))	('ran', 'Gene', (103, 106))	('ran', 'Gene', '5901', (103, 106))	('Syk', 'Gene', (229, 232))	('STAT5-alpha', 'Gene', (212, 223))	('increased', 'PosReg', (195, 204))	('E-Cadherin', 'Gene', (135, 145))
52887	30442178	KRAS/NRAS mutations are therapeutically relevant for melanomas, colorectal cancer, and thyroid cancer (OncoKB level 3).	('melanomas', 'Disease', (53, 62))	('KRAS', 'Gene', '3845', (0, 4))	('colorectal cancer', 'Disease', (64, 81))	('NRAS', 'Gene', (5, 9))	('cancer', 'Phenotype', 'HP:0002664', (95, 101))	('thyroid cancer', 'Disease', 'MESH:D013964', (87, 101))	('melanoma', 'Phenotype', 'HP:0002861', (53, 61))	('melanomas', 'Phenotype', 'HP:0002861', (53, 62))	('NRAS', 'Gene', '4893', (5, 9))	('colorectal cancer', 'Disease', 'MESH:D015179', (64, 81))	('melanomas', 'Disease', 'MESH:D008545', (53, 62))	('rectal cancer', 'Phenotype', 'HP:0100743', (68, 81))	('cancer', 'Phenotype', 'HP:0002664', (75, 81))	('mutations', 'Var', (10, 19))	('KRAS', 'Gene', (0, 4))	('colorectal cancer', 'Phenotype', 'HP:0003003', (64, 81))	('thyroid cancer', 'Phenotype', 'HP:0002890', (87, 101))	('thyroid cancer', 'Disease', (87, 101))
52888	30442178	Specific KRAS/NRAS mutations are correlated with differences in protein profiles for melanomas and thyroid cancer and also for testicular germ cell tumors, endometrial carcinoma, and lung adenocarcinoma (in conformity with OncoKB level 4 data).	('melanomas', 'Disease', (85, 94))	('carcinoma', 'Phenotype', 'HP:0030731', (193, 202))	('thyroid cancer', 'Disease', (99, 113))	('differences', 'Reg', (49, 60))	('endometrial carcinoma', 'Phenotype', 'HP:0012114', (156, 177))	('carcinoma', 'Phenotype', 'HP:0030731', (168, 177))	('NRAS', 'Gene', '4893', (14, 18))	('tumor', 'Phenotype', 'HP:0002664', (148, 153))	('endometrial carcinoma', 'Disease', 'MESH:D016889', (156, 177))	('KRAS', 'Gene', '3845', (9, 13))	('melanomas', 'Phenotype', 'HP:0002861', (85, 94))	('tumors', 'Phenotype', 'HP:0002664', (148, 154))	('thyroid cancer', 'Disease', 'MESH:D013964', (99, 113))	('protein profiles', 'MPA', (64, 80))	('lung adenocarcinoma', 'Disease', (183, 202))	('KRAS', 'Gene', (9, 13))	('thyroid cancer', 'Phenotype', 'HP:0002890', (99, 113))	('melanoma', 'Phenotype', 'HP:0002861', (85, 93))	('tumors', 'Disease', (148, 154))	('NRAS', 'Gene', (14, 18))	('cancer', 'Phenotype', 'HP:0002664', (107, 113))	('lung adenocarcinoma', 'Disease', 'MESH:D000077192', (183, 202))	('mutations', 'Var', (19, 28))	('melanomas', 'Disease', 'MESH:D008545', (85, 94))	('tumors', 'Disease', 'MESH:D009369', (148, 154))	('endometrial carcinoma', 'Disease', (156, 177))	('lung adenocarcinoma', 'Phenotype', 'HP:0030078', (183, 202))
52891	30442178	For melanoma (sdis = - 0.16; p = 1.0e-3; and = 5.2e-6) E-Cadherin, Caveolin-1, and c-Kit expression levels are decreased for mutated cases, and MAPK_pT202_Y204 is increased.	('E-Cadherin', 'Gene', '999', (55, 65))	('mutated', 'Var', (125, 132))	('MAPK_pT202_Y204', 'Var', (144, 159))	('decreased', 'NegReg', (111, 120))	('sdis', 'Chemical', '-', (14, 18))	('expression levels', 'MPA', (89, 106))	('Caveolin-1', 'Gene', '857', (67, 77))	('c-Kit', 'Gene', (83, 88))	('c-Kit', 'Gene', '3815', (83, 88))	('E-Cadherin', 'Gene', (55, 65))	('melanoma', 'Phenotype', 'HP:0002861', (4, 12))	('melanoma', 'Disease', (4, 12))	('Caveolin-1', 'Gene', (67, 77))	('melanoma', 'Disease', 'MESH:D008545', (4, 12))
52892	30442178	For thyroid carcinoma (sdis = - 1.53; p = 0.0; srand = - 3.0e-4), the level of Fibronectin is decreased in mutated cases.	('sdis', 'Chemical', '-', (23, 27))	('carcinoma', 'Phenotype', 'HP:0030731', (12, 21))	('mutated', 'Var', (107, 114))	('ran', 'Gene', (48, 51))	('ran', 'Gene', '5901', (48, 51))	('thyroid carcinoma', 'Disease', 'MESH:D013964', (4, 21))	('decreased', 'NegReg', (94, 103))	('Fibronectin', 'Gene', '2335', (79, 90))	('Fibronectin', 'Gene', (79, 90))	('thyroid carcinoma', 'Phenotype', 'HP:0002890', (4, 21))	('thyroid carcinoma', 'Disease', (4, 21))
52893	30442178	For lung adenocarcinoma and endometrial carcinoma, we observed a cross-cancer effect for KRAS/NRAS-mutated cases as ATM levels are decreased, and MAPK_pT202_Y204, Claudin-7, S6_pS235_S236, and MEK1_pS217_S221 are increased in both histological tumor types consistently.	('S6_pS235_S236', 'Var', (174, 187))	('endometrial carcinoma', 'Disease', (28, 49))	('Claudin-7', 'Gene', '1366', (163, 172))	('lung adenocarcinoma', 'Disease', (4, 23))	('tumor', 'Phenotype', 'HP:0002664', (244, 249))	('endometrial carcinoma', 'Phenotype', 'HP:0012114', (28, 49))	('NRAS', 'Gene', '4893', (94, 98))	('carcinoma', 'Phenotype', 'HP:0030731', (40, 49))	('cancer', 'Phenotype', 'HP:0002664', (71, 77))	('MEK', 'Gene', '5609', (193, 196))	('ATM', 'Gene', '472', (116, 119))	('carcinoma', 'Phenotype', 'HP:0030731', (14, 23))	('KRAS', 'Gene', '3845', (89, 93))	('endometrial carcinoma', 'Disease', 'MESH:D016889', (28, 49))	('lung adenocarcinoma', 'Disease', 'MESH:D000077192', (4, 23))	('cross-cancer', 'Disease', 'MESH:C537866', (65, 77))	('MEK', 'Gene', (193, 196))	('lung adenocarcinoma', 'Phenotype', 'HP:0030078', (4, 23))	('MAPK_pT202_Y204', 'Var', (146, 161))	('KRAS', 'Gene', (89, 93))	('NRAS', 'Gene', (94, 98))	('tumor', 'Disease', (244, 249))	('cross-cancer', 'Disease', (65, 77))	('decreased', 'NegReg', (131, 140))	('ATM', 'Gene', (116, 119))	('Claudin-7', 'Gene', (163, 172))	('tumor', 'Disease', 'MESH:D009369', (244, 249))	('increased', 'PosReg', (213, 222))
52894	30442178	MDM2 amplification is actionable in liposarcoma (OncoKB level 3).	('liposarcoma', 'Disease', (36, 47))	('amplification', 'Var', (5, 18))	('liposarcoma', 'Phenotype', 'HP:0012034', (36, 47))	('liposarcoma', 'Disease', 'MESH:D008080', (36, 47))	('MDM2', 'Gene', '4193', (0, 4))	('MDM2', 'Gene', (0, 4))	('sarcoma', 'Phenotype', 'HP:0100242', (40, 47))
52895	30442178	Besides sarcoma, the protein profiles of cases with MDM2 amplification are discriminable from those with normal copy numbers for renal clear cell carcinoma, lung adenocarcinoma, thyroid carcinoma, breast cancer, ovarian carcinoma, and low-grade glioma (all currently not reported by OncoKB).	('carcinoma', 'Phenotype', 'HP:0030731', (167, 176))	('sarcoma', 'Phenotype', 'HP:0100242', (8, 15))	('MDM2', 'Gene', (52, 56))	('renal clear cell carcinoma', 'Disease', 'MESH:C538614', (129, 155))	('glioma', 'Phenotype', 'HP:0009733', (245, 251))	('lung adenocarcinoma', 'Disease', 'MESH:D000077192', (157, 176))	('renal clear cell carcinoma', 'Disease', (129, 155))	('breast cancer', 'Phenotype', 'HP:0003002', (197, 210))	('lung adenocarcinoma', 'Phenotype', 'HP:0030078', (157, 176))	('thyroid carcinoma', 'Disease', 'MESH:D013964', (178, 195))	('MDM2', 'Gene', '4193', (52, 56))	('carcinoma', 'Phenotype', 'HP:0030731', (220, 229))	('breast cancer', 'Disease', 'MESH:D001943', (197, 210))	('thyroid carcinoma', 'Disease', (178, 195))	('breast cancer', 'Disease', (197, 210))	('amplification', 'Var', (57, 70))	('cancer', 'Phenotype', 'HP:0002664', (204, 210))	('ovarian carcinoma', 'Disease', 'MESH:D010051', (212, 229))	('ovarian carcinoma', 'Disease', (212, 229))	('thyroid carcinoma', 'Phenotype', 'HP:0002890', (178, 195))	('carcinoma', 'Phenotype', 'HP:0030731', (146, 155))	('sarcoma', 'Disease', 'MESH:D012509', (8, 15))	('carcinoma', 'Phenotype', 'HP:0030731', (186, 195))	('sarcoma', 'Disease', (8, 15))	('glioma', 'Disease', (245, 251))	('ovarian carcinoma', 'Phenotype', 'HP:0025318', (212, 229))	('lung adenocarcinoma', 'Disease', (157, 176))	('glioma', 'Disease', 'MESH:D005910', (245, 251))
52896	30442178	Protein levels of sarcoma cases with MDM2 amplifications are discriminable from those without, with a dissimilarity score of sdis = - 0.41 (p = 0.0; srand = - 8.9e-5).	('sarcoma', 'Disease', 'MESH:D012509', (18, 25))	('ran', 'Gene', '5901', (150, 153))	('sarcoma', 'Disease', (18, 25))	('MDM2', 'Gene', '4193', (37, 41))	('sarcoma', 'Phenotype', 'HP:0100242', (18, 25))	('MDM2', 'Gene', (37, 41))	('amplifications', 'Var', (42, 56))	('sdis', 'Chemical', '-', (125, 129))	('ran', 'Gene', (150, 153))	('Protein levels', 'MPA', (0, 14))
52897	30442178	Amplified cases show decreased levels of E-Cadherin, Akt_pS473, Akt_pT308, ER-alpha, Caveolin-1, S6_pS240_S244, S6_pS235_S236, and Cyclin_B1 and increased levels of HSP70, Syk, and Lck.	('Lck', 'Gene', (181, 184))	('Akt_pT308', 'Gene', (64, 73))	('HSP70', 'Gene', '3308', (165, 170))	('Cyclin_B1', 'Gene', '891', (131, 140))	('Caveolin-1', 'Gene', (85, 95))	('E-Cadherin', 'Gene', (41, 51))	('Caveolin-1', 'Gene', '857', (85, 95))	('S6_pS240_S244', 'Var', (97, 110))	('levels', 'MPA', (155, 161))	('ER-alpha', 'Gene', (75, 83))	('increased', 'PosReg', (145, 154))	('ER-alpha', 'Gene', '2099', (75, 83))	('Syk', 'Gene', '6850', (172, 175))	('HSP70', 'Gene', (165, 170))	('S6_pS235_S236', 'Var', (112, 125))	('Syk', 'Gene', (172, 175))	('decreased', 'NegReg', (21, 30))	('Cyclin_B1', 'Gene', (131, 140))	('Lck', 'Gene', '3932', (181, 184))	('Akt_pS473', 'Protein', (53, 62))	('E-Cadherin', 'Gene', '999', (41, 51))
52900	30442178	In addition to these histotypes, we found 11 other histological tumor types (renal clear cell carcinoma, low-grade glioma, renal papillary cell carcinoma, colon carcinoma, thyroid carcinoma, thymoma, sarcoma, lung adenocarcinoma, testicular germ cell tumors, prostate adenocarcinoma, glioblastoma, breast and ovarian carcinoma) where MET amplification is associated with a significant change in protein expression.	('glioma', 'Disease', (115, 121))	('tumor', 'Disease', (251, 256))	('breast and ovarian carcinoma', 'Disease', 'MESH:D001943', (298, 326))	('glioblastoma', 'Phenotype', 'HP:0012174', (284, 296))	('protein expression', 'MPA', (395, 413))	('sarcoma', 'Phenotype', 'HP:0100242', (200, 207))	('MET amplification', 'Var', (334, 351))	('glioma', 'Disease', 'MESH:D005910', (115, 121))	('carcinoma', 'Phenotype', 'HP:0030731', (144, 153))	('tumor', 'Disease', 'MESH:D009369', (251, 256))	('lung adenocarcinoma', 'Disease', (209, 228))	('thyroid carcinoma', 'Disease', 'MESH:D013964', (172, 189))	('thymoma', 'Disease', 'MESH:D013945', (191, 198))	('tumor', 'Phenotype', 'HP:0002664', (64, 69))	('thyroid carcinoma', 'Disease', (172, 189))	('renal papillary cell carcinoma', 'Disease', (123, 153))	('tumors', 'Phenotype', 'HP:0002664', (251, 257))	('glioma', 'Phenotype', 'HP:0009733', (115, 121))	('lung adenocarcinoma', 'Disease', 'MESH:D000077192', (209, 228))	('thymoma', 'Disease', (191, 198))	('tumor', 'Phenotype', 'HP:0002664', (251, 256))	('thyroid carcinoma', 'Phenotype', 'HP:0002890', (172, 189))	('thymoma', 'Phenotype', 'HP:0100522', (191, 198))	('carcinoma', 'Phenotype', 'HP:0030731', (94, 103))	('lung adenocarcinoma', 'Phenotype', 'HP:0030078', (209, 228))	('carcinoma', 'Phenotype', 'HP:0030731', (180, 189))	('prostate adenocarcinoma', 'Disease', (259, 282))	('tumors', 'Disease', (251, 257))	('colon carcinoma', 'Disease', (155, 170))	('change', 'Reg', (385, 391))	('renal clear cell carcinoma', 'Disease', 'MESH:C538614', (77, 103))	('ovarian carcinoma', 'Phenotype', 'HP:0025318', (309, 326))	('renal clear cell carcinoma', 'Disease', (77, 103))	('renal papillary cell carcinoma', 'Disease', 'MESH:C538614', (123, 153))	('carcinoma', 'Phenotype', 'HP:0030731', (219, 228))	('tumor', 'Disease', (64, 69))	('glioblastoma', 'Disease', 'MESH:D005909', (284, 296))	('sarcoma', 'Disease', 'MESH:D012509', (200, 207))	('tumors', 'Disease', 'MESH:D009369', (251, 257))	('colon carcinoma', 'Disease', 'MESH:D015179', (155, 170))	('sarcoma', 'Disease', (200, 207))	('prostate adenocarcinoma', 'Disease', 'MESH:D011471', (259, 282))	('tumor', 'Disease', 'MESH:D009369', (64, 69))	('carcinoma', 'Phenotype', 'HP:0030731', (161, 170))	('glioblastoma', 'Disease', (284, 296))
52903	30442178	MET amplification is present in renal clear cell carcinoma cases, and protein profiles of amplified and non-amplified cases can be discriminated (sdis = - 0.18; p = 0.0; srand = - 2.0e-5; Src_pY527, Bcl-2, beta-Catenin, PTEN, MAPK_pT202_Y204 are decreased in amplified cases and ACC1, Cyclin_B1, ASNS, ACC_pS79, and Transglutaminase are increased).	('Cyclin_B1', 'Gene', '891', (285, 294))	('ran', 'Gene', (171, 174))	('ran', 'Gene', '5901', (171, 174))	('beta-Catenin', 'Gene', '1499', (206, 218))	('ASNS', 'Gene', (296, 300))	('Src_pY527', 'Var', (188, 197))	('PTEN', 'Gene', '5728', (220, 224))	('carcinoma', 'Phenotype', 'HP:0030731', (49, 58))	('increased', 'PosReg', (337, 346))	('ACC_pS79', 'MPA', (302, 310))	('ACC1', 'Gene', (279, 283))	('renal clear cell carcinoma', 'Disease', 'MESH:C538614', (32, 58))	('beta-Catenin', 'Gene', (206, 218))	('MAPK_pT202_Y204', 'Gene', (226, 241))	('renal clear cell carcinoma', 'Disease', (32, 58))	('decreased', 'NegReg', (246, 255))	('ACC1', 'Gene', '597', (279, 283))	('Cyclin_B1', 'Gene', (285, 294))	('ran', 'Gene', (317, 320))	('ran', 'Gene', '5901', (317, 320))	('sdis', 'Chemical', '-', (146, 150))	('Bcl-2', 'Gene', (199, 204))	('ASNS', 'Gene', '440', (296, 300))	('PTEN', 'Gene', (220, 224))	('Bcl-2', 'Gene', '596', (199, 204))
52905	30442178	PIK3CA activating mutations are actionable for breast cancer (OncoKB evidence level 3).	('breast cancer', 'Disease', (47, 60))	('activating', 'PosReg', (7, 17))	('breast cancer', 'Phenotype', 'HP:0003002', (47, 60))	('PIK3CA', 'Gene', (0, 6))	('PIK3CA', 'Gene', '5290', (0, 6))	('cancer', 'Phenotype', 'HP:0002664', (54, 60))	('breast cancer', 'Disease', 'MESH:D001943', (47, 60))	('mutations', 'Var', (18, 27))
52907	30442178	OncoKB level 4 data lists all available histological tumor types as possibly actionable for PIK3CA activating mutations.	('mutations', 'Var', (110, 119))	('PIK3CA', 'Gene', '5290', (92, 98))	('tumor', 'Disease', 'MESH:D009369', (53, 58))	('tumor', 'Phenotype', 'HP:0002664', (53, 58))	('tumor', 'Disease', (53, 58))	('PIK3CA', 'Gene', (92, 98))
52909	30442178	Breast cancer cases with PIK3CA-activating mutations are discriminable from those without (sdis = - 0.52; p = 0.0; srand = 6.2e-6) with specific proteins (increased levels) PR, ER-alpha, MAPK_pT202_Y204, Fibronectin, AR, and GATA3 in mutated cases and Cyclin_B1, Cyclin_E1, ASNS, and HER2 being decreased.	('ran', 'Gene', (116, 119))	('ran', 'Gene', '5901', (116, 119))	('Breast cancer', 'Phenotype', 'HP:0003002', (0, 13))	('Cyclin_B1', 'Gene', '891', (252, 261))	('PIK3CA', 'Gene', '5290', (25, 31))	('increased', 'PosReg', (155, 164))	('HER2', 'Gene', '2064', (284, 288))	('Cyclin_E1', 'Gene', '898', (263, 272))	('ASNS', 'Gene', '440', (274, 278))	('cancer', 'Phenotype', 'HP:0002664', (7, 13))	('mutated', 'Var', (234, 241))	('GATA3', 'Gene', '2625', (225, 230))	('PIK3CA', 'Gene', (25, 31))	('Cyclin_E1', 'Gene', (263, 272))	('Fibronectin', 'Gene', '2335', (204, 215))	('Cyclin_B1', 'Gene', (252, 261))	('sdis', 'Chemical', '-', (91, 95))	('ASNS', 'Gene', (274, 278))	('ER-alpha', 'Gene', (177, 185))	('GATA3', 'Gene', (225, 230))	('HER2', 'Gene', (284, 288))	('Breast cancer', 'Disease', 'MESH:D001943', (0, 13))	('mutations', 'Var', (43, 52))	('ER-alpha', 'Gene', '2099', (177, 185))	('Breast cancer', 'Disease', (0, 13))	('Fibronectin', 'Gene', (204, 215))
52913	30442178	However, many open questions remain because apart from mutations with unknown functional effects, it is often not possible even for oncogenic mutations with established clinical relevance in one cancer type to transfer knowledge of actionability to another cancer type.	('mutations', 'Var', (142, 151))	('cancer', 'Phenotype', 'HP:0002664', (257, 263))	('cancer', 'Disease', (195, 201))	('cancer', 'Disease', 'MESH:D009369', (195, 201))	('cancer', 'Disease', 'MESH:D009369', (257, 263))	('ran', 'Gene', (211, 214))	('ran', 'Gene', '5901', (211, 214))	('cancer', 'Disease', (257, 263))	('cancer', 'Phenotype', 'HP:0002664', (195, 201))
52919	30442178	This indicates that identical genetic alterations are not translated into protein profiles in the same way in different histotypes.	('ran', 'Gene', '5901', (59, 62))	('ran', 'Gene', (59, 62))	('genetic alterations', 'Var', (30, 49))
52923	30442178	In addition to showing that our analysis identifies protein-level effects for known actionable genes and corresponding cancer types, our approach also identified protein-level alterations indicative of potential novel actionable gene:cancer combinations that are so far unknown according to OncoKB including level 4 evidence (biological information).	('cancer', 'Phenotype', 'HP:0002664', (234, 240))	('cancer', 'Disease', 'MESH:D009369', (119, 125))	('cancer', 'Disease', (119, 125))	('combinations', 'Var', (241, 253))	('cancer', 'Disease', 'MESH:D009369', (234, 240))	('cancer', 'Disease', (234, 240))	('cancer', 'Phenotype', 'HP:0002664', (119, 125))
52924	30442178	This includes ERBB2/HER2 amplification in endometrial carcinoma, renal papillary carcinoma, testicular germ cell tumors, urothelial carcinoma, renal clear cell carcinoma, colon carcinoma, ovarian carcinoma, thymoma, thyroid carcinoma, cervical carcinoma, and head and neck squamous cell carcinoma.	('colon carcinoma', 'Disease', 'MESH:D015179', (171, 186))	('tumors', 'Disease', (113, 119))	('carcinoma', 'Phenotype', 'HP:0030731', (160, 169))	('carcinoma', 'Phenotype', 'HP:0030731', (177, 186))	('carcinoma', 'Phenotype', 'HP:0030731', (81, 90))	('HER2', 'Gene', (20, 24))	('thymoma', 'Disease', 'MESH:D013945', (207, 214))	('renal papillary carcinoma', 'Disease', (65, 90))	('cervical carcinoma', 'Disease', (235, 253))	('tumors', 'Disease', 'MESH:D009369', (113, 119))	('carcinoma', 'Phenotype', 'HP:0030731', (54, 63))	('endometrial carcinoma', 'Disease', (42, 63))	('thyroid carcinoma', 'Disease', 'MESH:D013964', (216, 233))	('ERBB2', 'Gene', (14, 19))	('urothelial carcinoma', 'Disease', 'MESH:D014526', (121, 141))	('thyroid carcinoma', 'Disease', (216, 233))	('thymoma', 'Disease', (207, 214))	('renal clear cell carcinoma', 'Disease', 'MESH:C538614', (143, 169))	('cervical carcinoma', 'Disease', 'MESH:D002575', (235, 253))	('renal clear cell carcinoma', 'Disease', (143, 169))	('thymoma', 'Phenotype', 'HP:0100522', (207, 214))	('neck squamous cell carcinoma', 'Disease', (268, 296))	('ovarian carcinoma', 'Disease', 'MESH:D010051', (188, 205))	('ERBB2', 'Gene', '2064', (14, 19))	('ovarian carcinoma', 'Disease', (188, 205))	('endometrial carcinoma', 'Phenotype', 'HP:0012114', (42, 63))	('neck squamous cell carcinoma', 'Disease', 'MESH:D000077195', (268, 296))	('thyroid carcinoma', 'Phenotype', 'HP:0002890', (216, 233))	('HER2', 'Gene', '2064', (20, 24))	('amplification', 'Var', (25, 38))	('tumors', 'Phenotype', 'HP:0002664', (113, 119))	('renal papillary carcinoma', 'Disease', 'MESH:D007681', (65, 90))	('endometrial carcinoma', 'Disease', 'MESH:D016889', (42, 63))	('colon carcinoma', 'Disease', (171, 186))	('carcinoma', 'Phenotype', 'HP:0030731', (132, 141))	('ovarian carcinoma', 'Phenotype', 'HP:0025318', (188, 205))	('squamous cell carcinoma', 'Phenotype', 'HP:0002860', (273, 296))	('tumor', 'Phenotype', 'HP:0002664', (113, 118))	('urothelial carcinoma', 'Disease', (121, 141))
52928	30442178	Interestingly, actionable genes with copy number alterations showed effects on protein expression for more histotypes than those with simple somatic mutations (10.2 affected tumor types on average for amplifications vs. 2.14 for simple somatic mutations).	('tumor', 'Disease', (174, 179))	('protein expression', 'MPA', (79, 97))	('tumor', 'Disease', 'MESH:D009369', (174, 179))	('effects', 'Reg', (68, 75))	('tumor', 'Phenotype', 'HP:0002664', (174, 179))	('copy number alterations', 'Var', (37, 60))
52932	30442178	With respect to the actionable gene analysis, our approach may underestimate the number of potentially druggable genes, but the fact that it readily identifies many well-established actionable gene, cancer combinations, such as, for instance, HER2 amplification in breast and gastric cancer, indicates its validity.	('cancer', 'Phenotype', 'HP:0002664', (199, 205))	('cancer', 'Disease', 'MESH:D009369', (284, 290))	('cancer', 'Disease', (284, 290))	('HER2', 'Gene', (243, 247))	('cancer', 'Disease', 'MESH:D009369', (199, 205))	('cancer', 'Phenotype', 'HP:0002664', (284, 290))	('HER2', 'Gene', '2064', (243, 247))	('cancer', 'Disease', (199, 205))	('gastric cancer', 'Phenotype', 'HP:0012126', (276, 290))	('breast and gastric cancer', 'Disease', 'MESH:D013274', (265, 290))	('amplification', 'Var', (248, 261))
52939	30442178	By evaluating protein-level effects of genetic aberrations, our approach facilitates the identification of functionally relevant mutations and may therefore contribute to predicting actionable mutations across cancers and to guide basket trial design.	('cancer', 'Phenotype', 'HP:0002664', (210, 216))	('mutations', 'Var', (129, 138))	('facilitates', 'PosReg', (73, 84))	('cancers', 'Disease', 'MESH:D009369', (210, 217))	('cancers', 'Phenotype', 'HP:0002664', (210, 217))	('cancers', 'Disease', (210, 217))
53083	20814442	Aortic body tumors have been described rarely in horses and have differentiating neuroendocrine, histologic, and immunohistochemical features including negativity for cytokeratin, a marker for which the neoplastic cells in this case were strongly positive.	('horses', 'Species', '9796', (49, 55))	('body tumors', 'Disease', (7, 18))	('tumor', 'Phenotype', 'HP:0002664', (12, 17))	('body tumors', 'Disease', 'MESH:D002345', (7, 18))	('tumors', 'Phenotype', 'HP:0002664', (12, 18))	('negativity', 'Var', (152, 162))
53127	33467055	An additional patient showed a monoclonal rearrangement of B-cell receptor genes but no morphological features of lymphoma.	('men', 'Species', '9606', (51, 54))	('B-cell receptor', 'Protein', (59, 74))	('patient', 'Species', '9606', (14, 21))	('lymphoma', 'Disease', (114, 122))	('lymphoma', 'Disease', 'MESH:D008223', (114, 122))	('lymphoma', 'Phenotype', 'HP:0002665', (114, 122))	('monoclonal rearrangement', 'Var', (31, 55))
53140	33467055	A third patient presented with non-myasthenic neurological deficits and showed anti-muscle-specific kinase (MuSK) antibodies.	('anti-muscle-specific', 'Var', (79, 99))	('non-myasthenic neurological deficits', 'Disease', 'MESH:D009461', (31, 67))	('myasthenic neurological deficits', 'Phenotype', 'HP:0003473', (35, 67))	('non-myasthenic neurological deficits', 'Disease', (31, 67))	('patient', 'Species', '9606', (8, 15))	('MuSK', 'Gene', '4593', (108, 112))	('neurological deficits', 'Phenotype', 'HP:0000707', (46, 67))	('MuSK', 'Gene', (108, 112))	('antibodies', 'Var', (114, 124))
53151	33467055	Since the age of the lymphoma-free patients with LESA-like TH in the current series averaged 52 years, while the average age of patients with thymic MALT lymphoma was slightly higher (58 and 56 years, in our and other studies, respectively), we hypothesize that LESA-like TH could be a precursor lesion in at least a subset of thymic MALT lymphomas.	('TH', 'Phenotype', 'HP:0010516', (59, 61))	('thymic MALT lymphomas', 'Disease', 'MESH:D018442', (327, 348))	('LESA-like', 'Var', (49, 58))	('lymphoma-free', 'Disease', (21, 34))	('thymic MALT lymphoma', 'Disease', 'MESH:D018442', (327, 347))	('lymphomas', 'Phenotype', 'HP:0002665', (339, 348))	('thymic MALT lymphoma', 'Disease', (142, 162))	('lymphoma', 'Phenotype', 'HP:0002665', (154, 162))	('lymphoma', 'Phenotype', 'HP:0002665', (21, 29))	('thymic MALT lymphoma', 'Disease', 'MESH:D018442', (142, 162))	('lymphoma', 'Phenotype', 'HP:0002665', (339, 347))	('lymphoma-free', 'Disease', 'MESH:D008569', (21, 34))	('patients', 'Species', '9606', (35, 43))	('thymic MALT lymphomas', 'Disease', (327, 348))	('patients', 'Species', '9606', (128, 136))	('TH', 'Phenotype', 'HP:0010516', (272, 274))
53172	33467055	Apart from these two patients, LOMG and anti-MuSK-MG typically do not emerge in the context of thymic pathology but have been thought to reflect a loss of peripheral tolerance.	('peripheral tolerance', 'CPA', (155, 175))	('LOMG', 'Disease', (31, 35))	('MG', 'Chemical', 'MESH:D008274', (33, 35))	('anti-MuSK-MG', 'Var', (40, 52))	('MG', 'Chemical', 'MESH:D008274', (50, 52))	('patients', 'Species', '9606', (21, 29))	('MuSK-MG', 'CellLine', 'CVCL:1698', (45, 52))
53202	30894954	The affected patients are most commonly between 40 and 70 years of age and have a thymoma, fewer or no B cells in the peripheral blood, hypogammaglobulinemia, inversion of the CD4-to-CD8 ratio, and defects in cell-mediated immunity.	('hypogammaglobulinemia', 'Disease', (136, 157))	('hypogammaglobulinemia', 'Disease', 'MESH:D000361', (136, 157))	('thymoma', 'Disease', (82, 89))	('patients', 'Species', '9606', (13, 21))	('CD4', 'Gene', (176, 179))	('thymoma', 'Phenotype', 'HP:0100522', (82, 89))	('cell-mediated immunity', 'CPA', (209, 231))	('defects', 'Reg', (198, 205))	('hypogammaglobulinemia', 'Phenotype', 'HP:0004313', (136, 157))	('inversion', 'Var', (159, 168))	('CD4', 'Gene', '920', (176, 179))	('CD8', 'Gene', (183, 186))	('CD8', 'Gene', '925', (183, 186))	('thymoma', 'Disease', 'MESH:D013945', (82, 89))
53208	30894954	A primary HSV-1 infection in oral and perioral sites usually manifests as gingivostomatitis, whereas reactivation of the virus in the trigeminal sensory ganglion gives rise to mild cutaneous and mucocutaneous disease, which is often termed as recurrent herpes labialis.	('gingivostomatitis', 'Phenotype', 'HP:0010280', (74, 91))	('HSV-1 infection', 'Disease', 'MESH:C536395', (10, 25))	('trigeminal sensory ganglion', 'Phenotype', 'HP:0100661', (134, 161))	('mucocutaneous disease', 'Disease', (195, 216))	('reactivation', 'Var', (101, 113))	('gingivostomatitis', 'Disease', 'MESH:D013283', (74, 91))	('recurrent herpes labialis', 'Phenotype', 'HP:0410028', (243, 268))	('man', 'Species', '9606', (61, 64))	('herpes labialis', 'Phenotype', 'HP:0410028', (253, 268))	('recurrent herpes', 'Phenotype', 'HP:0005353', (243, 259))	('gives rise to', 'Reg', (162, 175))	('mucocutaneous disease', 'Disease', 'MESH:D007897', (195, 216))	('HSV-1 infection', 'Disease', (10, 25))	('gingivostomatitis', 'Disease', (74, 91))	('infection in oral', 'Phenotype', 'HP:0100649', (16, 33))
53261	29774108	High pretreatment Fibrinogen serum concentration (>=452.5 mg/dL) was significantly associated with worse cause specific survival (CSS; p = 0.001) and freedom from recurrence (FFR; p = 0.043), high NLR (>=4.0) with worse FFR (p = 0.008), and high PLR (>=136.5) with worse CSS (p = 0.032).	('high', 'Var', (192, 196))	('Fibrinogen', 'Gene', (18, 28))	('cause specific survival', 'CPA', (105, 128))	('freedom', 'CPA', (150, 157))	('FFR', 'Gene', (175, 178))	('FFR', 'Gene', (220, 223))	('CSS', 'Chemical', '-', (130, 133))	('CSS', 'Chemical', '-', (271, 274))	('Fibrinogen', 'Gene', '2244', (18, 28))	('FFR', 'Gene', '738', (175, 178))	('FFR', 'Gene', '738', (220, 223))	('worse', 'NegReg', (99, 104))
53279	29774108	To date, only one study has investigated the roles of pretreatment NLR and PLR in patients with TCs, demonstrating that high pretreatment NLR was associated with larger tumor size and worse outcome.	('tumor', 'Disease', 'MESH:D009369', (169, 174))	('patients', 'Species', '9606', (82, 90))	('high', 'Var', (120, 124))	('tumor', 'Phenotype', 'HP:0002664', (169, 174))	('NLR', 'Gene', (138, 141))	('tumor', 'Disease', (169, 174))
53295	29774108	Fibrinogen serum concentrations were significantly higher in patients with TETs (390.2 +- 11.4 mg/dL) compared to healthy volunteers (314.8 +- 10.7 mg/dL; p < 0.001).	('Fibrinogen', 'Gene', (0, 10))	('TETs', 'Var', (75, 79))	('patients', 'Species', '9606', (61, 69))	('Fibrinogen', 'Gene', '2244', (0, 10))	('higher', 'PosReg', (51, 57))
53297	29774108	We also detected significantly elevated NLR and PLR in patients with TETs (3.4 +- 0.3 and 179.8 +- 12.1, respectively) compared to controls (1.8 +- 0.1 and 133.4 +- 7.1; p < 0.001 and p = 0.001, respectively).	('NLR', 'MPA', (40, 43))	('patients', 'Species', '9606', (55, 63))	('TETs', 'Var', (69, 73))	('elevated', 'PosReg', (31, 39))	('PLR', 'MPA', (48, 51))
53317	29774108	By calculating the Youden Index, we identified 452.5 mg/dL as an optimal cut-off value for discriminating between low and high Fibrinogen.	('Fibrinogen', 'Gene', (127, 137))	('high Fibrinogen', 'Phenotype', 'HP:0011899', (122, 137))	('low', 'MPA', (114, 117))	('Fibrinogen', 'Gene', '2244', (127, 137))	('452.5 mg/dL', 'Var', (47, 58))
53363	29774108	Moreover, associations between high PLR and NLR and worse prognosis are reported in several malignancies, including paranasal sinus carcinomas, laryngeal SCC, esophageal carcinoma, colorectal cancer, and lymphomas.	('colorectal cancer', 'Phenotype', 'HP:0003003', (181, 198))	('lymphomas', 'Disease', 'MESH:D008223', (204, 213))	('lymphomas', 'Phenotype', 'HP:0002665', (204, 213))	('esophageal carcinoma', 'Phenotype', 'HP:0011459', (159, 179))	('paranasal sinus carcinomas', 'Disease', 'MESH:D010255', (116, 142))	('paranasal sinus carcinomas', 'Disease', (116, 142))	('cancer', 'Phenotype', 'HP:0002664', (192, 198))	('associations', 'Interaction', (10, 22))	('high', 'Var', (31, 35))	('colorectal cancer', 'Disease', 'MESH:D015179', (181, 198))	('laryngeal SCC', 'Disease', (144, 157))	('paranasal sinus carcinomas', 'Phenotype', 'HP:0030072', (116, 142))	('lymphomas', 'Disease', (204, 213))	('colorectal cancer', 'Disease', (181, 198))	('esophageal carcinoma', 'Disease', 'MESH:D004938', (159, 179))	('malignancies', 'Disease', 'MESH:D009369', (92, 104))	('carcinoma', 'Phenotype', 'HP:0030731', (170, 179))	('malignancies', 'Disease', (92, 104))	('carcinoma', 'Phenotype', 'HP:0030731', (132, 141))	('esophageal carcinoma', 'Disease', (159, 179))	('carcinomas', 'Phenotype', 'HP:0030731', (132, 142))
53380	29774108	Notably, after exclusion of TCs, Fibrinogen serum concentrations did not significantly differ in MG-positive compared to MG-negative thymomas (p = 0.051).	('thymomas', 'Disease', 'MESH:D013945', (133, 141))	('MG-positive', 'Var', (97, 108))	('Fibrinogen', 'Gene', (33, 43))	('thymoma', 'Phenotype', 'HP:0100522', (133, 140))	('thymomas', 'Disease', (133, 141))	('Fibrinogen', 'Gene', '2244', (33, 43))
53563	26809342	Over 95 %, of HIV-negative patients who developed CMVR were found, ultimately, to have one or more factors contributing to a relative decline in immune function, such as advanced age, an underlying malignancy, an autoimmune disease or organ/bone transplantation requiring systemic immunosuppression, administration of periocular or intraocular corticosteroids, diabetes mellitus, or, less commonly, an inherited or acquired immune disorder, such as Good syndrome.	('CMVR', 'Var', (50, 54))	('diabetes mellitus', 'Phenotype', 'HP:0000819', (361, 378))	('HIV', 'Species', '12721', (14, 17))	('Good syndrome', 'Disease', 'MESH:D013577', (449, 462))	('diabetes mellitus', 'Disease', (361, 378))	('autoimmune disease', 'Disease', (213, 231))	('immune disorder', 'Disease', 'MESH:D007154', (424, 439))	('patients', 'Species', '9606', (27, 35))	('diabetes mellitus', 'Disease', 'MESH:D003920', (361, 378))	('malignancy', 'Disease', 'MESH:D009369', (198, 208))	('decline in immune function', 'Phenotype', 'HP:0002721', (134, 160))	('autoimmune disease', 'Phenotype', 'HP:0002960', (213, 231))	('immune function', 'MPA', (145, 160))	('malignancy', 'Disease', (198, 208))	('Good syndrome', 'Disease', (449, 462))	('decline', 'NegReg', (134, 141))	('autoimmune disease', 'Disease', 'MESH:D001327', (213, 231))	('immune disorder', 'Disease', (424, 439))
53567	26101855	Here, we generated K5-DeltaN64Ctnnb1/ERT2 transgenic mice, which express an N-terminal deletion mutant of beta-catenin fused to a mutated ligand-binding domain of estrogen receptor (ERT2) under the control of the bovine cytokeratin 5 (K5) promoter.	('cytokeratin 5', 'Gene', '281268', (220, 233))	('K5-DeltaN64Ctnnb1/ERT2', 'Var', (19, 41))	('ERT2', 'Gene', (182, 186))	('bovine', 'Species', '9913', (213, 219))	('cytokeratin 5', 'Gene', (220, 233))	('transgenic mice', 'Species', '10090', (42, 57))
53569	26101855	Forced expression of DeltaN64Ctnnb1/ERT2 in the Tg1 and Tg4 mice developed small thymoma lesions in response to tamoxifen treatment.	('small thymoma lesions', 'Disease', 'MESH:D013945', (75, 96))	('tamoxifen', 'Chemical', 'MESH:D013629', (112, 121))	('Tg1', 'Gene', '493101', (48, 51))	('thymoma', 'Phenotype', 'HP:0100522', (81, 88))	('small thymoma lesions', 'Disease', (75, 96))	('Tg', 'Chemical', '-', (56, 58))	('DeltaN64Ctnnb1/ERT2', 'Var', (21, 40))	('mice', 'Species', '10090', (60, 64))	('Tg', 'Chemical', '-', (48, 50))	('Tg1', 'Gene', (48, 51))
53579	26101855	In addition, mTECs express p63, AIRE and UEA-1, whereas cTECs express beta5t and Ly51; these additional markers can be used to further sub-classify EpCAM+ TEC populations in the physiological or pathological thymus.	('EpCAM', 'Gene', (148, 153))	('Ly51', 'Gene', '13809', (81, 85))	('EpCAM', 'Gene', '17075', (148, 153))	('Ly51', 'Gene', (81, 85))	('p63', 'Var', (27, 30))	('cTECs', 'Chemical', '-', (56, 61))
53587	26101855	The type B1 thymoma is a lymphocyte-rich tumor, and the type B2 thymoma exhibits an increased number of clustered or scattered neoplastic epithelial cells among a large population of infiltrated lymphocytes.	('tumor', 'Phenotype', 'HP:0002664', (41, 46))	('thymoma', 'Gene', '7063', (12, 19))	('tumor', 'Disease', (41, 46))	('type B2', 'Var', (56, 63))	('thymoma', 'Phenotype', 'HP:0100522', (12, 19))	('thymoma', 'Phenotype', 'HP:0100522', (64, 71))	('thymoma', 'Gene', '7063', (64, 71))	('thymoma', 'Gene', (12, 19))	('tumor', 'Disease', 'MESH:D009369', (41, 46))	('thymoma', 'Gene', (64, 71))
53594	26101855	Previous molecular genetic studies have identified loss of heterozygosity (LOH) at the adenomatous polyposis coli (APC) locus was associated with the type B thymomas.	('thymomas', 'Disease', (157, 165))	('thymomas', 'Disease', 'MESH:D013945', (157, 165))	('adenomatous polyposis coli', 'Phenotype', 'HP:0005227', (87, 113))	('adenomatous polyposis coli', 'Disease', 'MESH:D011125', (87, 113))	('adenomatous polyposis coli', 'Disease', (87, 113))	('loss of heterozygosity', 'Var', (51, 73))	('thymoma', 'Phenotype', 'HP:0100522', (157, 164))	('APC', 'Phenotype', 'HP:0005227', (115, 118))
53595	26101855	The critical role of APC-mediated signaling in thymic epithelial differentiation and carcinogenesis was further explored in mice by conditional ablation of the Apc gene using K14-Cre.	('conditional ablation', 'Var', (132, 152))	('carcinogenesis', 'Disease', 'MESH:D063646', (85, 99))	('APC', 'Phenotype', 'HP:0005227', (21, 24))	('Apc', 'Gene', (160, 163))	('mice', 'Species', '10090', (124, 128))	('Apc', 'Gene', '11789', (160, 163))	('carcinogenesis', 'Disease', (85, 99))	('K14', 'Gene', '16664', (175, 178))	('K14', 'Gene', (175, 178))
53596	26101855	Interestingly, loss of Apc in K14-expressing TECs caused thymic atrophy and squamous metaplasia, suggesting that Apc is required for thymic epithelial differentiation and development.	('thymic atrophy', 'Disease', (57, 71))	('K14', 'Gene', '16664', (30, 33))	('Apc', 'Gene', (23, 26))	('thymic atrophy', 'Disease', 'MESH:D013953', (57, 71))	('Apc', 'Gene', (113, 116))	('loss', 'Var', (15, 19))	('K14', 'Gene', (30, 33))	('Apc', 'Gene', '11789', (23, 26))	('Apc', 'Gene', '11789', (113, 116))	('squamous metaplasia', 'Disease', (76, 95))	('squamous metaplasia', 'Phenotype', 'HP:0002860', (76, 95))	('squamous metaplasia', 'Disease', 'MESH:D008679', (76, 95))
53607	26101855	These mice harbor an N-terminal, 64-amino-acid truncation of beta-catenin fused to the tamoxifen (Tam)-inducible ligand-binding domain of estrogen receptor (ERT2) driven by a bovine K5 promoter (Figure 1A).	('bovine', 'Species', '9913', (175, 181))	('mice', 'Species', '10090', (6, 10))	('truncation', 'Var', (47, 57))	('Tam', 'Chemical', 'MESH:D013629', (98, 101))	('beta-catenin', 'Protein', (61, 73))	('tamoxifen', 'Chemical', 'MESH:D013629', (87, 96))	('ERT2', 'Gene', (157, 161))
53608	26101855	The expression of DeltaN64Ctnnb1/ERT2 in various organs of transgenic mouse lines 1, 4, and 10 (hereafter referred to Tg1, Tg4, and Tg10) were detected using an anti-beta-Catenin antibody for western blot analysis.	('beta-Catenin', 'Gene', (166, 178))	('transgenic', 'Species', '10090', (59, 69))	('Tg1', 'Gene', '493101', (132, 135))	('Tg1', 'Gene', '493101', (118, 121))	('Tg', 'Chemical', '-', (132, 134))	('Tg', 'Chemical', '-', (118, 120))	('mouse', 'Species', '10090', (70, 75))	('Tg', 'Chemical', '-', (123, 125))	('beta-Catenin', 'Gene', '12387', (166, 178))	('Tg1', 'Gene', (118, 121))	('Tg1', 'Gene', (132, 135))	('DeltaN64Ctnnb1/ERT2', 'Var', (18, 37))
53609	26101855	We found that Tg1 and Tg4 exhibited comparable amounts of the DeltaN64Ctnnb1/ERT2 fusion protein in the skin, whereas skin from Tg10 expressed lower levels of DeltaN64Ctnnb1/ERT2 fusion protein (Figure 1B).	('Tg', 'Chemical', '-', (14, 16))	('Tg', 'Chemical', '-', (128, 130))	('Tg', 'Chemical', '-', (22, 24))	('DeltaN64Ctnnb1/ERT2', 'Var', (62, 81))	('Tg1', 'Gene', '493101', (128, 131))	('Tg1', 'Gene', '493101', (14, 17))	('Tg1', 'Gene', (128, 131))	('Tg1', 'Gene', (14, 17))
53610	26101855	In the thymus and the esophagus, we observed higher DeltaN64Ctnnb1/ERT2 protein levels in the Tg1 mice than in Tg4 or Tg10 mice (Figure 1B).	('Tg1', 'Gene', '493101', (118, 121))	('Tg', 'Chemical', '-', (111, 113))	('Tg', 'Chemical', '-', (118, 120))	('Tg', 'Chemical', '-', (94, 96))	('Tg1', 'Gene', '493101', (94, 97))	('DeltaN64Ctnnb1/ERT2', 'Var', (52, 71))	('higher', 'PosReg', (45, 51))	('Tg1', 'Gene', (94, 97))	('Tg1', 'Gene', (118, 121))	('mice', 'Species', '10090', (98, 102))	('mice', 'Species', '10090', (123, 127))
53611	26101855	In general, DeltaN64Ctnnb1/ERT2 expression of Tg10 was lowest among three transgenic lines (Figure 1B).	('Tg1', 'Gene', '493101', (46, 49))	('DeltaN64Ctnnb1/ERT2', 'Var', (12, 31))	('Tg1', 'Gene', (46, 49))	('transgenic', 'Species', '10090', (74, 84))	('lowest', 'NegReg', (55, 61))	('expression', 'MPA', (32, 42))
53615	26101855	Furthermore, we characterized DeltaN64Ctnnb1/ERT2 expression and activation in the TECs of the Tg1 mice at 8 weeks of age.	('mice', 'Species', '10090', (99, 103))	('Tg1', 'Gene', '493101', (95, 98))	('Tg1', 'Gene', (95, 98))	('DeltaN64Ctnnb1/ERT2', 'Var', (30, 49))	('activation', 'MPA', (65, 75))
53619	26101855	Using RT-qPCR, we found that DeltaN64Ctnnb1/ERT2 expression detected by the transgene-specific primers (Myc-NLS or ERT2) was significantly enriched in CD45-EpCAM+UEA1+ mTECs (Figure 1C).	('DeltaN64Ctnnb1/ERT2', 'Var', (29, 48))	('Myc', 'Gene', (104, 107))	('Myc', 'Gene', '17869', (104, 107))	('EpCAM', 'Gene', '17075', (156, 161))	('EpCAM', 'Gene', (156, 161))
53622	26101855	These data suggest that the DeltaN64Ctnnb1/ERT2 transgene, driven by K5 promoter, is restricted and can be induced by Tam to activate its target genes in mTECs.	('Tam', 'Chemical', 'MESH:D013629', (118, 121))	('DeltaN64Ctnnb1/ERT2', 'Var', (28, 47))	('activate', 'PosReg', (125, 133))
53627	26101855	We performed K5/K8 co-immunostaining on the thymic sections of non-Tg control, Tg1, and Tg4 mice after vehicle or Tam treatment for 3 or 28 days.	('Tg4', 'Var', (88, 91))	('Tg', 'Chemical', '-', (79, 81))	('Tg', 'Chemical', '-', (67, 69))	('Tg', 'Chemical', '-', (88, 90))	('Tg1', 'Gene', '493101', (79, 82))	('Tg1', 'Gene', (79, 82))	('Tam', 'Chemical', 'MESH:D013629', (114, 117))	('mice', 'Species', '10090', (92, 96))
53628	26101855	In the non-Tg control, we observed K5- and K8-expressing cells predominately in the medulla and cortex, respectively (Figure 1E).	('Tg', 'Chemical', '-', (11, 13))	('K8-expressing', 'Var', (43, 56))	('K5-', 'Var', (35, 38))
53633	26101855	In agreement with these reports, we observed that hair follicles had grown into deeper layers of the dermis, with marked expansion of outer root sheet (ORS) cells, in Tg1 and Tg4 mice that received Tam compared to those that received vehicle (EtOH) only (Supplementary Figure 3A).	('expansion', 'PosReg', (121, 130))	('mice', 'Species', '10090', (179, 183))	('Tam', 'Chemical', 'MESH:D013629', (198, 201))	('Tg4', 'Var', (175, 178))	('Tg', 'Chemical', '-', (167, 169))	('Tg1', 'Gene', '493101', (167, 170))	('Tg1', 'Gene', (167, 170))	('hair follicles', 'CPA', (50, 64))	('EtOH', 'Chemical', 'MESH:D000431', (243, 247))	('Tg', 'Chemical', '-', (175, 177))
53634	26101855	We also examined potential leakage activation of DeltaN64Ctnnb1/ERT2 fusion protein in the absence of Tam.	('DeltaN64Ctnnb1/ERT2', 'Var', (49, 68))	('Tam', 'Chemical', 'MESH:D013629', (102, 105))	('leakage activation', 'MPA', (27, 45))
53635	26101855	We observed darker skin, indicating hair follicles in growing state, on the back skin of shaved Tg1 and Tg4 mice compared to non-Tg controls without Tam treatment for 16-20 days (Supplemental Figure 3B), suggesting possible leaky expression and activity of beta-catenin.	('Tg', 'Chemical', '-', (104, 106))	('Tg', 'Chemical', '-', (129, 131))	('mice', 'Species', '10090', (108, 112))	('activity', 'MPA', (245, 253))	('Tg4', 'Var', (104, 107))	('Tg1', 'Gene', '493101', (96, 99))	('Tg1', 'Gene', (96, 99))	('darker skin', 'Phenotype', 'HP:0000953', (12, 23))	('Tg', 'Chemical', '-', (96, 98))	('Tam', 'Chemical', 'MESH:D013629', (149, 152))
53636	26101855	Taken together, our data suggest that DeltaN64Ctnnb1/ERT2 can be induced by Tam treatment in both TECs and hair follicles in Tg mice, although leaky expression of active DeltaN64Ctnnb1/ERT2 may be present.	('Tam', 'Chemical', 'MESH:D013629', (76, 79))	('mice', 'Species', '10090', (128, 132))	('DeltaN64Ctnnb1/ERT2', 'Var', (38, 57))	('induced', 'Reg', (65, 72))	('Tg', 'Chemical', '-', (125, 127))
53638	26101855	We found manifest thymic tumors specifically in Tg1 and Tg4 mice but not in the non-Tg littermates (Figure 2A and 2B).	('tumor', 'Phenotype', 'HP:0002664', (25, 30))	('Tg', 'Chemical', '-', (84, 86))	('tumors', 'Disease', (25, 31))	('Tg1', 'Gene', '493101', (48, 51))	('tumors', 'Phenotype', 'HP:0002664', (25, 31))	('tumors', 'Disease', 'MESH:D009369', (25, 31))	('Tg', 'Chemical', '-', (56, 58))	('Tg4', 'Var', (56, 59))	('mice', 'Species', '10090', (60, 64))	('Tg', 'Chemical', '-', (48, 50))	('Tg1', 'Gene', (48, 51))
53640	26101855	Also, one of five Tg4 mice developed manifest thymomas at late onset (18 months) (Figure 2B).	('Tg', 'Chemical', '-', (18, 20))	('thymoma', 'Phenotype', 'HP:0100522', (46, 53))	('thymomas', 'Disease', (46, 54))	('Tg4', 'Var', (18, 21))	('thymomas', 'Disease', 'MESH:D013945', (46, 54))	('mice', 'Species', '10090', (22, 26))
53641	26101855	The low incidence of thymoma development in Tg4 mice might reflect the lower expression of DeltaN64Ctnnb1/ERT2 in the Tg4 thymus overall (Figure 1B).	('thymoma', 'Gene', (21, 28))	('expression', 'MPA', (77, 87))	('Tg', 'Chemical', '-', (118, 120))	('mice', 'Species', '10090', (48, 52))	('DeltaN64Ctnnb1/ERT2', 'Var', (91, 110))	('Tg', 'Chemical', '-', (44, 46))	('thymoma', 'Phenotype', 'HP:0100522', (21, 28))	('thymoma', 'Gene', '7063', (21, 28))	('lower', 'NegReg', (71, 76))
53642	26101855	These data suggest that a leaky expression of activated beta-catenin cause thymoma development in the Tg1 and Tg4 mice without Tam treatment.	('Tg', 'Chemical', '-', (110, 112))	('Tg1', 'Gene', '493101', (102, 105))	('thymoma', 'Gene', '7063', (75, 82))	('Tg1', 'Gene', (102, 105))	('thymoma', 'Phenotype', 'HP:0100522', (75, 82))	('leaky', 'Var', (26, 31))	('Tam', 'Chemical', 'MESH:D013629', (127, 130))	('cause', 'Reg', (69, 74))	('mice', 'Species', '10090', (114, 118))	('Tg', 'Chemical', '-', (102, 104))	('thymoma', 'Gene', (75, 82))	('activated beta-catenin', 'Protein', (46, 68))
53648	26101855	The K5-expressing lesions accumulated and formed a sheet-like pattern at 6 months that seemed to correspond to the pre-lesions of Tg1 thymomas at 10 and 12 months (Figure 2D).	('thymomas', 'Disease', (134, 142))	('thymomas', 'Disease', 'MESH:D013945', (134, 142))	('thymoma', 'Phenotype', 'HP:0100522', (134, 141))	('Tg1', 'Gene', '493101', (130, 133))	('Tg1', 'Gene', (130, 133))	('K5-expressing', 'Var', (4, 17))
53657	26101855	Therefore, it is possible that the sustained K5+ and UEA1+Ly51- subsets in Tg1 thymomas arising from the mTECs, where the DeltaN64Ctnnb1/ERT2 transgene was expressed, maintained the differentiation characteristics of mTECs during thymoma progression.	('thymoma', 'Gene', '7063', (79, 86))	('thymoma', 'Gene', (230, 237))	('Ly51', 'Gene', '13809', (58, 62))	('Tg1', 'Gene', '493101', (75, 78))	('Tg1', 'Gene', (75, 78))	('thymomas', 'Disease', (79, 87))	('thymomas', 'Disease', 'MESH:D013945', (79, 87))	('thymoma', 'Gene', (79, 86))	('Ly51', 'Gene', (58, 62))	('DeltaN64Ctnnb1/ERT2', 'Var', (122, 141))	('thymoma', 'Phenotype', 'HP:0100522', (230, 237))	('differentiation characteristics', 'CPA', (182, 213))	('thymoma', 'Phenotype', 'HP:0100522', (79, 86))	('thymoma', 'Gene', '7063', (230, 237))
53658	26101855	To examine whether the Wnt/beta-catenin canonical pathway is activated in DeltaN64Ctnnb1/ERT2 thymomas in the absence of Tam, we introduced the TOP-Gal transgene to allow the measurement of Wnt/beta-catenin activation.	('Gal', 'Gene', (148, 151))	('Gal', 'Gene', '14419', (148, 151))	('DeltaN64Ctnnb1/ERT2', 'Var', (74, 93))	('activated', 'PosReg', (61, 70))	('thymomas', 'Disease', (94, 102))	('thymomas', 'Disease', 'MESH:D013945', (94, 102))	('Tam', 'Chemical', 'MESH:D013629', (121, 124))	('thymoma', 'Phenotype', 'HP:0100522', (94, 101))	('Wnt/beta-catenin canonical pathway', 'Pathway', (23, 57))
53661	26101855	We next examined several targeted genes of Wnt/beta-catenin canonical pathway, which should be activated if the DeltaN64Ctnnb1/ERT2 transgene is functional during thymoma progression.	('Wnt/beta-catenin canonical pathway', 'Pathway', (43, 77))	('thymoma', 'Phenotype', 'HP:0100522', (163, 170))	('thymoma', 'Gene', '7063', (163, 170))	('DeltaN64Ctnnb1/ERT2', 'Var', (112, 131))	('thymoma', 'Gene', (163, 170))
53670	26101855	Furthermore, the Ctnnb1K5-fx/fx thymic phenotype, including the decreased frequency of proliferating thymocytes (total, CD4-CD8-DN and CD4+CD8+DP; Figure 4D) and the increased percentage of annexin V-labeled apoptotic cells (total and CD4+CD8+DP; Figure 4E), was significantly reversed by the transgenic expression of stabilized beta-catenin in K5-expressing cells.	('CD4', 'Gene', (120, 123))	('CD8-DN', 'Chemical', '-', (124, 130))	('DP', 'Chemical', '-', (243, 245))	('DP', 'Chemical', '-', (143, 145))	('transgenic', 'Var', (293, 303))	('transgenic', 'Species', '10090', (293, 303))	('proliferating thymocytes', 'CPA', (87, 111))	('Ctnnb1K5-fx/fx', 'Var', (17, 31))	('annexin V', 'Gene', (190, 199))	('CD4', 'Gene', '12504', (120, 123))	('annexin V', 'Gene', '11747', (190, 199))	('CD4', 'Gene', (135, 138))	('CD4', 'Gene', '12504', (235, 238))	('CD4', 'Gene', (235, 238))	('CD4', 'Gene', '12504', (135, 138))	('decreased', 'NegReg', (64, 73))
53681	26101855	Furthermore, one potential target gene of p53/p63 is p21WAF1/cip1, which can be suppressed by increasing levels of DeltaNp63 isoforms.	('p21WAF1/cip1', 'Gene', (53, 65))	('p53/p63', 'Var', (42, 49))	('p21WAF1/cip1', 'Gene', '12575', (53, 65))
53686	26101855	In 2-month-old Tg1 thymi, beta5t was expressed in the cortical area similarly to non-Tg thymi and was weakly detected in focal microscopic lesions in medullary area (Figure 6A).	('beta5t', 'Var', (26, 32))	('Tg1', 'Gene', '493101', (15, 18))	('Tg1', 'Gene', (15, 18))	('Tg', 'Chemical', '-', (15, 17))	('Tg', 'Chemical', '-', (85, 87))
53697	26101855	In this study, the transgenic mice expressing DeltaN64Ctnnb1/ERT2 under the control of K5 promoter enable us to monitor thymoma progression from early lesions to manifest thymomas.	('thymoma', 'Gene', (171, 178))	('thymomas', 'Disease', (171, 179))	('thymomas', 'Disease', 'MESH:D013945', (171, 179))	('DeltaN64Ctnnb1/ERT2', 'Var', (46, 65))	('transgenic mice', 'Species', '10090', (19, 34))	('thymoma', 'Phenotype', 'HP:0100522', (120, 127))	('thymoma', 'Gene', '7063', (171, 178))	('thymoma', 'Phenotype', 'HP:0100522', (171, 178))	('thymoma', 'Gene', '7063', (120, 127))	('thymoma', 'Gene', (120, 127))
53702	26101855	Both K10 and loricrin were focally expressed in some neoplastic cells in Tg1 thymomas, suggesting that over-expression of the DeltaN64Ctnnb1/ERT2 fusion protein in TECs may adopt squamous cell-fate differentiation.	('loricrin', 'Gene', (13, 21))	('squamous cell-fate differentiation', 'CPA', (179, 213))	('thymomas', 'Disease', (77, 85))	('adopt', 'Reg', (173, 178))	('thymoma', 'Phenotype', 'HP:0100522', (77, 84))	('over-expression', 'PosReg', (103, 118))	('K10', 'Gene', (5, 8))	('K10', 'Gene', '16661', (5, 8))	('DeltaN64Ctnnb1/ERT2', 'Var', (126, 145))	('loricrin', 'Gene', '16939', (13, 21))	('Tg1', 'Gene', '493101', (73, 76))	('Tg1', 'Gene', (73, 76))	('thymomas', 'Disease', 'MESH:D013945', (77, 85))
53703	26101855	Although the molecular genetics of human thymomas are largely unclear, the presence of APC mutations has been linked to pathogenesis of type B3 thymomas.	('thymomas', 'Disease', (41, 49))	('thymomas', 'Disease', (144, 152))	('thymomas', 'Disease', 'MESH:D013945', (144, 152))	('thymomas', 'Disease', 'MESH:D013945', (41, 49))	('human', 'Species', '9606', (35, 40))	('linked', 'Reg', (110, 116))	('APC', 'Gene', (87, 90))	('APC', 'Phenotype', 'HP:0005227', (87, 90))	('mutations', 'Var', (91, 100))	('thymoma', 'Phenotype', 'HP:0100522', (41, 48))	('thymoma', 'Phenotype', 'HP:0100522', (144, 151))
53708	26101855	In our study, the transgenic mice expressing the DeltaN64Ctnnb1/ERT2 fusion protein exhibited leaky beta-catenin activation in K5-expressing cells, but this phenotype did not lead to early lethality, thus enabling us to monitor thymoma development as the transgenic animals aged.	('transgenic mice', 'Species', '10090', (18, 33))	('transgenic', 'Species', '10090', (18, 28))	('thymoma', 'Phenotype', 'HP:0100522', (228, 235))	('thymoma', 'Gene', '7063', (228, 235))	('leaky beta-catenin activation', 'MPA', (94, 123))	('thymoma', 'Gene', (228, 235))	('DeltaN64Ctnnb1/ERT2', 'Var', (49, 68))	('transgenic', 'Species', '10090', (255, 265))
53710	26101855	The thymomas that developed in the Tg1 and Tg4 mice reflect the expression levels of the DeltaN64Ctnnb1/ERT2 transgene and share histological appearance (e.g.	('thymomas', 'Disease', (4, 12))	('thymomas', 'Disease', 'MESH:D013945', (4, 12))	('Tg', 'Chemical', '-', (43, 45))	('DeltaN64Ctnnb1/ERT2', 'Var', (89, 108))	('Tg1', 'Gene', '493101', (35, 38))	('expression levels', 'MPA', (64, 81))	('Tg1', 'Gene', (35, 38))	('thymoma', 'Phenotype', 'HP:0100522', (4, 11))	('mice', 'Species', '10090', (47, 51))	('Tg', 'Chemical', '-', (35, 37))
53715	26101855	Previously, SV40 T-antigen, driven by its own viral early region elements, which include an enhancer and a promoter, caused thymic epithelial carcinomas in transgenic mice.	('epithelial carcinomas', 'Disease', 'MESH:D002277', (131, 152))	('caused', 'Reg', (117, 123))	('transgenic mice', 'Species', '10090', (156, 171))	('carcinomas', 'Phenotype', 'HP:0030731', (142, 152))	('epithelial carcinomas', 'Disease', (131, 152))	('SV40 T-antigen', 'Var', (12, 26))	('carcinoma', 'Phenotype', 'HP:0030731', (142, 151))
53719	26101855	These transgenic mouse models suggest that dysregulated cell cycle control can be the critical determinant for thymoma development.	('dysregulated cell cycle', 'Phenotype', 'HP:0011018', (43, 66))	('mouse', 'Species', '10090', (17, 22))	('thymoma', 'Phenotype', 'HP:0100522', (111, 118))	('thymoma', 'Gene', '7063', (111, 118))	('cell cycle control', 'CPA', (56, 74))	('thymoma', 'Gene', (111, 118))	('dysregulated', 'Var', (43, 55))	('transgenic', 'Species', '10090', (6, 16))
53720	26101855	Consistently, the levels of cell cycle regulators p21, p27, and p53 have been examined in encapsulated thymomas in a clinical study.	('thymomas', 'Disease', (103, 111))	('p53', 'Var', (64, 67))	('thymomas', 'Disease', 'MESH:D013945', (103, 111))	('p27', 'Var', (55, 58))	('thymoma', 'Phenotype', 'HP:0100522', (103, 110))
53721	26101855	Increased p53 and decreased p21 and p27 in thymoma tissue correlated with poor prognosis for shorter disease-free survival, suggesting that aberrant regulation of cell-cycle progression contributes to the clinical outcomes of the patients with thymomas.	('thymoma', 'Gene', (43, 50))	('aberrant', 'Var', (140, 148))	('thymoma', 'Gene', '7063', (244, 251))	('p21', 'Protein', (28, 31))	('thymoma', 'Gene', (244, 251))	('thymomas', 'Disease', (244, 252))	('decreased', 'NegReg', (18, 27))	('thymomas', 'Disease', 'MESH:D013945', (244, 252))	('thymoma', 'Phenotype', 'HP:0100522', (43, 50))	('patients', 'Species', '9606', (230, 238))	('Increased', 'PosReg', (0, 9))	('p27', 'Protein', (36, 39))	('thymoma', 'Gene', '7063', (43, 50))	('p53', 'Protein', (10, 13))	('contributes', 'Reg', (186, 197))	('thymoma', 'Phenotype', 'HP:0100522', (244, 251))
53745	26101855	Expression of DeltaN64Ctnnb1/ERT2 was detected by the transgene-specific Myc-NLS primers (5'-GAG CAA AAG CTC ATT TCT GAA-3'and 5'-TAC TTG CTC TTG CGT GAA GG-3') or ERT2 primers (5'-CTT GCT CTT GGA CAG GAA CC-3' and 5'-CGA GAT GAT GTA GCC AGC AG-3').	('Myc', 'Gene', (73, 76))	('GCC', 'Gene', (234, 237))	('GAA', 'Gene', '14387', (201, 204))	('GAA', 'Gene', (150, 153))	('GCC', 'Gene', '14917', (234, 237))	('TTG', 'Gene', (134, 137))	('GAA', 'Gene', '14387', (150, 153))	('TTG', 'Gene', '21817', (134, 137))	('GAA', 'Gene', '14387', (117, 120))	('TTG', 'Gene', '21817', (142, 145))	('TTG', 'Gene', (142, 145))	('Myc', 'Gene', '17869', (73, 76))	('DeltaN64Ctnnb1/ERT2', 'Var', (14, 33))	('GAA', 'Gene', (117, 120))	('GAA', 'Gene', (201, 204))
53817	25722666	Immunohistochemical analysis revealed positivity for pan-cytokeratin AE1/AE3 in the tumor cells, and positivity for TdT and CD99 in the immature T lymphocytes.	('AE3', 'Gene', '6508', (73, 76))	('tumor', 'Disease', 'MESH:D009369', (84, 89))	('TdT', 'Gene', '1791', (116, 119))	('CD99', 'Gene', '4267', (124, 128))	('positivity', 'Var', (38, 48))	('AE1', 'Gene', '6521', (69, 72))	('AE3', 'Gene', (73, 76))	('tumor', 'Phenotype', 'HP:0002664', (84, 89))	('AE1', 'Gene', (69, 72))	('tumor', 'Disease', (84, 89))	('CD99', 'Gene', (124, 128))	('positivity', 'Var', (101, 111))	('TdT', 'Gene', (116, 119))
53830	25722666	Thymic epithelial cells are an essential component of the thymic stromal microenvironment, and dysfunction of the thymic stromal microenvironment can cause autoimmune diseases.	('autoimmune diseases', 'Phenotype', 'HP:0002960', (156, 175))	('cause', 'Reg', (150, 155))	('autoimmune diseases', 'Disease', 'MESH:D001327', (156, 175))	('autoimmune diseases', 'Disease', (156, 175))	('dysfunction', 'Var', (95, 106))
53850	24348669	To define the cause of thrombogenic states, laboratory tests including antinuclear antibody, anticardiolipin antibody, lupus coagulant, protein C and protein S activities, antithrombin III, factor V Leiden mutation, human leukocyte antigen-B51 and skin pathergy test were performed, but all results were normal.	('protein C', 'MPA', (136, 145))	('human', 'Species', '9606', (216, 221))	('antithrombin III', 'Phenotype', 'HP:0001976', (172, 188))	('factor V Leiden', 'Gene', (190, 205))	('mutation', 'Var', (206, 214))	('antithrombin III', 'Gene', (172, 188))	('antinuclear antibody', 'Phenotype', 'HP:0003493', (71, 91))	('factor V Leiden', 'Gene', '2153', (190, 205))	('antithrombin III', 'Gene', '462', (172, 188))	('lupus coagulant', 'Phenotype', 'HP:0025343', (119, 134))	('protein', 'Protein', (150, 157))	('lupus coagulant', 'Disease', (119, 134))	('lupus coagulant', 'Disease', 'MESH:D025861', (119, 134))
54009	31462247	The final staging diagnosis of the tumor was pT1aN0M0 pStage I.	('tumor', 'Disease', 'MESH:D009369', (35, 40))	('pT1aN0M0 pStage I', 'Var', (45, 62))	('tumor', 'Phenotype', 'HP:0002664', (35, 40))	('tumor', 'Disease', (35, 40))
54078	30697185	(2) An edrophonium test involves injections of edrophonium chloride to briefly relieve weakness in people with MG. Edrophonium chloride blocks the breakdown of acetylcholine and temporarily increases the levels of acetylcholine at neuromuscular junctions.	('blocks', 'NegReg', (136, 142))	('edrophonium chloride', 'Chemical', 'MESH:D004491', (47, 67))	('Edrophonium chloride', 'Chemical', 'MESH:D004491', (115, 135))	('weakness', 'Disease', (87, 95))	('levels of acetylcholine at neuromuscular junctions', 'MPA', (204, 254))	('breakdown of acetylcholine', 'MPA', (147, 173))	('edrophonium', 'Chemical', 'MESH:D004491', (47, 58))	('increases', 'PosReg', (190, 199))	('weakness', 'Disease', 'MESH:D018908', (87, 95))	('acetylcholine', 'Chemical', 'MESH:D000109', (160, 173))	('Edrophonium chloride', 'Var', (115, 135))	('acetylcholine', 'Chemical', 'MESH:D000109', (214, 227))	('edrophonium', 'Chemical', 'MESH:D004491', (7, 18))	('people', 'Species', '9606', (99, 105))
54245	25482724	Mutations of epigenetic regulatory genes are common in thymic carcinomas Genetic alterations and etiology of thymic epithelial tumors (TETs) are largely unknown, hampering the development of effective targeted therapies for patients with TETs.	('tumor', 'Phenotype', 'HP:0002664', (127, 132))	('thymic carcinomas', 'Disease', (55, 72))	('thymic epithelial tumors', 'Disease', (109, 133))	('hampering', 'NegReg', (162, 171))	('thymic epithelial tumors', 'Disease', 'MESH:C536905', (109, 133))	('carcinomas', 'Phenotype', 'HP:0030731', (62, 72))	('tumors', 'Phenotype', 'HP:0002664', (127, 133))	('epithelial tumor', 'Phenotype', 'HP:0031492', (116, 132))	('thymic carcinomas', 'Disease', 'MESH:D013945', (55, 72))	('Mutations', 'Var', (0, 9))	('patients', 'Species', '9606', (224, 232))	('carcinoma', 'Phenotype', 'HP:0030731', (62, 71))
54247	25482724	Comparative sequence analysis of 78 TET/blood paired samples obtained from 47 thymic carcinoma (TC) and 31 thymoma patients revealed a total of 86 somatic non-synonymous sequence variations across 39 different genes in 33 (42%) TETs.	('thymoma', 'Phenotype', 'HP:0100522', (107, 114))	('non-synonymous sequence variations', 'Var', (155, 189))	('patients', 'Species', '9606', (115, 123))	('thymic carcinoma', 'Disease', (78, 94))	('thymic carcinoma', 'Disease', 'MESH:D013945', (78, 94))	('carcinoma', 'Phenotype', 'HP:0030731', (85, 94))	('thymoma', 'Disease', 'MESH:D013945', (107, 114))	('thymoma', 'Disease', (107, 114))
54258	25482724	Although the next generation sequencing (NGS) approach has shed light on the cancer genome of several common cancer types, efforts on mapping the genetic makeup of rare tumors such as TETs has lagged behind, and the knowledge of TETs at the genomic level is limited to the sporadic reports of TP53 and KIT mutations.	('KIT', 'Gene', (302, 305))	('cancer', 'Disease', 'MESH:D009369', (109, 115))	('mutations', 'Var', (306, 315))	('cancer', 'Disease', (77, 83))	('cancer', 'Disease', 'MESH:D009369', (77, 83))	('TP53', 'Gene', (293, 297))	('cancer', 'Disease', (109, 115))	('TP53', 'Gene', '7157', (293, 297))	('tumors', 'Disease', 'MESH:D009369', (169, 175))	('tumor', 'Phenotype', 'HP:0002664', (169, 174))	('TETs', 'Disease', (184, 188))	('tumors', 'Phenotype', 'HP:0002664', (169, 175))	('cancer', 'Phenotype', 'HP:0002664', (77, 83))	('cancer', 'Phenotype', 'HP:0002664', (109, 115))	('tumors', 'Disease', (169, 175))
54261	25482724	By whole genome and transcriptome sequencing, we previously demonstrated that common cancer-associated gene mutations were rare in an aggressive B3 thymoma.	('mutations', 'Var', (108, 117))	('cancer', 'Disease', 'MESH:D009369', (85, 91))	('cancer', 'Disease', (85, 91))	('thymoma', 'Disease', 'MESH:D013945', (148, 155))	('thymoma', 'Disease', (148, 155))	('cancer', 'Phenotype', 'HP:0002664', (85, 91))	('thymoma', 'Phenotype', 'HP:0100522', (148, 155))
54262	25482724	Very recently, we identified a unique somatic missense mutation in the GTF2I gene that is prevalent in indolent early stage TETs and associated with good prognosis.	('prevalent', 'Reg', (90, 99))	('GTF2I', 'Gene', (71, 76))	('missense mutation', 'Var', (46, 63))	('GTF2I', 'Gene', '2969', (71, 76))	('associated', 'Reg', (133, 143))
54271	25482724	As the 197 cancer-gene panel was selected independently of the mutations found in our recent exome sequencing study of TETs, the results are in line with our previous data and further confirm that somatic mutations are more prevalent in TCs than thymomas.	('cancer', 'Phenotype', 'HP:0002664', (11, 17))	('thymoma', 'Phenotype', 'HP:0100522', (246, 253))	('mutations', 'Var', (205, 214))	('TCs', 'Disease', (237, 240))	('cancer', 'Disease', 'MESH:D009369', (11, 17))	('cancer', 'Disease', (11, 17))	('thymomas', 'Disease', (246, 254))	('prevalent', 'Reg', (224, 233))	('thymomas', 'Disease', 'MESH:D013945', (246, 254))
54273	25482724	Thirty-seven (43%) of those somatic variations were previously reported in COSMIC and 12 in dbSNP137 and ESP6500 polymorphism databases (Table S2).	('ESP6500', 'Gene', (105, 112))	('dbSNP137', 'Chemical', '-', (92, 100))	('variations', 'Var', (36, 46))	('dbSNP137', 'Gene', (92, 100))
54275	25482724	The tumor that carried the highest number of mutations was a TC with 13 mutations affecting 12 genes (Table S2), which was probably due to the presence of mutations of the DNA repair genes MLH1 and XRCC1.	('tumor', 'Disease', (4, 9))	('mutations', 'Var', (72, 81))	('mutations', 'Var', (45, 54))	('XRCC1', 'Gene', (198, 203))	('mutations', 'Var', (155, 164))	('tumor', 'Disease', 'MESH:D009369', (4, 9))	('MLH1', 'Gene', '4292', (189, 193))	('XRCC1', 'Gene', '7515', (198, 203))	('MLH1', 'Gene', (189, 193))	('tumor', 'Phenotype', 'HP:0002664', (4, 9))
54278	25482724	Similarly, recurrent mutations of BAP1, CDKN2A, CYLD and TP53 were also found in TCs of our recent study.	('found', 'Reg', (72, 77))	('TCs', 'Disease', (81, 84))	('BAP1', 'Gene', (34, 38))	('CDKN2A', 'Gene', (40, 46))	('CYLD', 'Gene', (48, 52))	('CDKN2A', 'Gene', '1029', (40, 46))	('CYLD', 'Gene', '1540', (48, 52))	('TP53', 'Gene', '7157', (57, 61))	('TP53', 'Gene', (57, 61))	('BAP1', 'Gene', '8314', (34, 38))	('mutations', 'Var', (21, 30))
54279	25482724	To examine the potential impact of the mutations on gene function, we employed SIFT and Polyphen2 algorithms and found that 51 of 58 SIFT- and Polyphen2-predictable somatic variations (88%) are likely to affect the gene functions based on at least one of the two prediction models (Table S2).	('SIFT', 'Disease', 'None', (133, 137))	('gene functions', 'MPA', (215, 229))	('affect', 'Reg', (204, 210))	('Polyphen2 algorithms', 'Disease', 'None', (88, 108))	('SIFT', 'Disease', 'None', (79, 83))	('Polyphen2 algorithms', 'Disease', (88, 108))	('SIFT', 'Disease', (133, 137))	('variations', 'Var', (173, 183))	('SIFT', 'Disease', (79, 83))
54280	25482724	Consistent with previous reports, TP53 mutations were found in 17% (13/78) of TETs, 26% (12/47) being in TCs and 3% (1/31) in thymomas (Chi square test, p = 0.0097), and KIT mutations in 9% (4/47) TCs and none in thymomas (p = 0.1471) (Figure 1B and 1C).	('thymomas', 'Disease', (126, 134))	('thymomas', 'Disease', (213, 221))	('TCs', 'Disease', (197, 200))	('thymomas', 'Disease', 'MESH:D013945', (126, 134))	('TP53', 'Gene', (34, 38))	('thymomas', 'Disease', 'MESH:D013945', (213, 221))	('mutations', 'Var', (39, 48))	('found', 'Reg', (54, 59))	('thymoma', 'Phenotype', 'HP:0100522', (126, 133))	('thymoma', 'Phenotype', 'HP:0100522', (213, 220))	('mutations', 'Var', (174, 183))	('TP53', 'Gene', '7157', (34, 38))
54281	25482724	A KIT L576P mutation identified in a TC (Table S2) was previously reported in melanomas that responded to imatinib treatment.	('melanomas', 'Disease', (78, 87))	('L576P', 'Mutation', 'rs121913513', (6, 11))	('L576P', 'Var', (6, 11))	('melanomas', 'Phenotype', 'HP:0002861', (78, 87))	('KIT', 'Gene', (2, 5))	('reported', 'Reg', (66, 74))	('melanomas', 'Disease', 'MESH:D008545', (78, 87))	('imatinib', 'Chemical', 'MESH:D000068877', (106, 114))
54285	25482724	Combined together, a total of 9 CYLD mutations (3 frameshift, 1 nonsense, 1 splice-site error and 4 missenses) were found in 11% (7 of 63) TCs and none in 69 thymomas (Fisher's exact test, p < 0.001).	('TCs', 'Disease', (139, 142))	('thymomas', 'Disease', (158, 166))	('thymomas', 'Disease', 'MESH:D013945', (158, 166))	('frameshift', 'Var', (50, 60))	('thymoma', 'Phenotype', 'HP:0100522', (158, 165))	('found', 'Reg', (116, 121))	('CYLD', 'Gene', (32, 36))	('CYLD', 'Gene', '1540', (32, 36))
54289	25482724	Intriguingly, 9 out of the 39 mutated genes identified in this study encode epigenetic regulatory proteins (chromatin remodeling, histone modification and DNA methylation) and were found mutated with significantly higher incidence in TCs (18/47, 38%) than thymomas (3/31, 10%) (p = 0.0081, Fisher's exact test; Figure 2C), within which 7 were recurrently mutated in TCs (16/47) but not in thymomas (0/31) (Fisher's exact tests; p = 0.0001; Figure 2D).	('encode', 'Reg', (69, 75))	('thymomas', 'Disease', (389, 397))	('mutated', 'Var', (187, 194))	('thymomas', 'Disease', 'MESH:D013945', (389, 397))	('TCs', 'Disease', (366, 369))	('thymoma', 'Phenotype', 'HP:0100522', (256, 263))	('TCs', 'Disease', (234, 237))	('thymomas', 'Disease', 'MESH:D013945', (256, 264))	('thymoma', 'Phenotype', 'HP:0100522', (389, 396))	('thymomas', 'Disease', (256, 264))
54291	25482724	Six TCs (13%) showed BAP1 mutations (Table S2) of which three were frameshift indels (A378fs, G560fs, G132fs), one nonsense (E200*), one exon 2 splice site error and one inframe insertion (M231IWins).	('G560fs', 'Mutation', 'p.G560fsX', (94, 100))	('A378fs', 'Var', (86, 92))	('BAP1', 'Gene', (21, 25))	('G132fs', 'Var', (102, 108))	('E200*', 'Var', (125, 130))	('G132fs', 'Mutation', 'p.G132fsX', (102, 108))	('E200*', 'SUBSTITUTION', 'None', (125, 130))	('G560fs', 'Var', (94, 100))	('A378fs', 'Mutation', 'p.A378fsX', (86, 92))	('BAP1', 'Gene', '8314', (21, 25))
54292	25482724	Similar loss-of-function mutations of BAP1 have been documented in renal clear cell carcinoma.	('mutations', 'Var', (25, 34))	('BAP1', 'Gene', (38, 42))	('carcinoma', 'Phenotype', 'HP:0030731', (84, 93))	('loss-of-function', 'NegReg', (8, 24))	('renal clear cell carcinoma', 'Disease', 'MESH:C538614', (67, 93))	('renal clear cell carcinoma', 'Disease', (67, 93))	('BAP1', 'Gene', '8314', (38, 42))
54293	25482724	Loss-of-function germline mutations of BAP1 also predispose to uveal and cutaneous melanomas, mesothelioma, clear cell renal cancer and atpical cutaneous melanocytic proliferation.	('renal cancer', 'Phenotype', 'HP:0009726', (119, 131))	('Loss-of-function', 'NegReg', (0, 16))	('mesothelioma', 'Disease', 'MESH:D008654', (94, 106))	('clear cell renal cancer', 'Phenotype', 'HP:0006770', (108, 131))	('cutaneous melanomas', 'Phenotype', 'HP:0012056', (73, 92))	('cutaneous melanocytic proliferation', 'Phenotype', 'HP:0100814', (144, 179))	('cancer', 'Phenotype', 'HP:0002664', (125, 131))	('cutaneous melanomas', 'Disease', 'MESH:C562393', (73, 92))	('germline mutations', 'Var', (17, 35))	('clear cell renal cancer', 'Disease', 'MESH:C538614', (108, 131))	('cutaneous melanomas', 'Disease', (73, 92))	('atpical cutaneous melanocytic proliferation', 'Disease', 'MESH:D059545', (136, 179))	('BAP1', 'Gene', '8314', (39, 43))	('mesothelioma', 'Disease', (94, 106))	('clear cell renal cancer', 'Disease', (108, 131))	('atpical cutaneous melanocytic proliferation', 'Disease', (136, 179))	('melanomas', 'Phenotype', 'HP:0002861', (83, 92))	('BAP1', 'Gene', (39, 43))
54294	25482724	Two ASXL1 nonsense mutations (C594* and Y700*) were identified in two TCs and one missense (D756A) in a B2 thymoma (Figure 3A and Tables S2).	('thymoma', 'Phenotype', 'HP:0100522', (107, 114))	('Y700*', 'SUBSTITUTION', 'None', (40, 45))	('thymoma', 'Disease', 'MESH:D013945', (107, 114))	('ASXL1', 'Gene', '171023', (4, 9))	('C594*', 'Var', (30, 35))	('Y700*', 'Var', (40, 45))	('D756A', 'Mutation', 'rs768821774', (92, 97))	('ASXL1', 'Gene', (4, 9))	('C594*', 'SUBSTITUTION', 'None', (30, 35))	('thymoma', 'Disease', (107, 114))
54295	25482724	A nonsense mutation of ASXL1 has been recently reported in a cytogenetically normal B3 thymoma.	('thymoma', 'Phenotype', 'HP:0100522', (87, 94))	('ASXL1', 'Gene', '171023', (23, 28))	('nonsense mutation', 'Var', (2, 19))	('ASXL1', 'Gene', (23, 28))	('thymoma', 'Disease', 'MESH:D013945', (87, 94))	('thymoma', 'Disease', (87, 94))
54296	25482724	Recurrent somatic ASXL1 mutations also occur in myelodysplastic syndrome, myeloproliferative neoplasms, and acute myeloid leukemia, and are associated with adverse outcome.	('acute myeloid leukemia', 'Disease', (108, 130))	('associated', 'Reg', (140, 150))	('leukemia', 'Phenotype', 'HP:0001909', (122, 130))	('myelodysplastic syndrome', 'Phenotype', 'HP:0002863', (48, 72))	('myelodysplastic syndrome', 'Disease', (48, 72))	('acute myeloid leukemia', 'Disease', 'MESH:D015470', (108, 130))	('myelodysplastic syndrome', 'Disease', 'MESH:D009190', (48, 72))	('myeloid leukemia', 'Phenotype', 'HP:0012324', (114, 130))	('acute myeloid leukemia', 'Phenotype', 'HP:0004808', (108, 130))	('myeloproliferative neoplasms', 'Disease', (74, 102))	('ASXL1', 'Gene', '171023', (18, 23))	('myeloproliferative neoplasms', 'Phenotype', 'HP:0005547', (74, 102))	('mutations', 'Var', (24, 33))	('neoplasms', 'Phenotype', 'HP:0002664', (93, 102))	('occur', 'Reg', (39, 44))	('myeloproliferative neoplasms', 'Disease', 'MESH:D009196', (74, 102))	('ASXL1', 'Gene', (18, 23))
54298	25482724	Six SEDT2 missense mutations (G1672E, M1526I, E464Q, D1351N, K2028E and L1776R) and one frameshift deletion (H143 fs) were found in four TCs and one B2 thymoma (Figure 3A and Table S2).	('K2028E', 'Mutation', 'rs267601017', (61, 67))	('thymoma', 'Phenotype', 'HP:0100522', (152, 159))	('E464Q', 'Var', (46, 51))	('L1776R', 'Var', (72, 78))	('K2028E', 'Var', (61, 67))	('D1351N', 'Var', (53, 59))	('E464Q', 'Mutation', 'rs1460453950', (46, 51))	('M1526I', 'Var', (38, 44))	('G1672E', 'Mutation', 'p.G1672E', (30, 36))	('thymoma', 'Disease', 'MESH:D013945', (152, 159))	('H143 fs', 'Mutation', 'p.H143fsX', (109, 116))	('G1672E', 'Var', (30, 36))	('SEDT2', 'Gene', (4, 9))	('M1526I', 'Mutation', 'p.M1526I', (38, 44))	('D1351N', 'Mutation', 'rs1318154109', (53, 59))	('L1776R', 'Mutation', 'p.L1776R', (72, 78))	('thymoma', 'Disease', (152, 159))
54299	25482724	In clear cell renal carcinoma and pediatric glioma, SETD2 loss-of-function mutations have been observed.	('pediatric glioma', 'Disease', 'MESH:D005910', (34, 50))	('pediatric glioma', 'Disease', (34, 50))	('loss-of-function', 'NegReg', (58, 74))	('clear cell renal carcinoma', 'Disease', (3, 29))	('clear cell renal carcinoma', 'Phenotype', 'HP:0006770', (3, 29))	('mutations', 'Var', (75, 84))	('SETD2', 'Gene', '29072', (52, 57))	('glioma', 'Phenotype', 'HP:0009733', (44, 50))	('carcinoma', 'Phenotype', 'HP:0030731', (20, 29))	('SETD2', 'Gene', (52, 57))	('clear cell renal carcinoma', 'Disease', 'MESH:C538614', (3, 29))	('renal carcinoma', 'Phenotype', 'HP:0005584', (14, 29))
54300	25482724	Whether the SETD2 mutations, the majority of which (6/7) are missense in TETs, may disrupt its tumor suppressor function remains to be investigated.	('SETD2', 'Gene', '29072', (12, 17))	('missense', 'Var', (61, 69))	('SETD2', 'Gene', (12, 17))	('disrupt', 'NegReg', (83, 90))	('tumor', 'Disease', 'MESH:D009369', (95, 100))	('tumor', 'Phenotype', 'HP:0002664', (95, 100))	('tumor', 'Disease', (95, 100))	('mutations', 'Var', (18, 27))
54302	25482724	Four potential loss-of-function mutations of TET2 (E452 del, L1816fs, F662fs and exon 8 splice donor site error) were found in two TCs and one AB thymoma (Figure 3A and Table S2).	('L1816fs', 'Var', (61, 68))	('TET2', 'Gene', (45, 49))	('thymoma', 'Phenotype', 'HP:0100522', (146, 153))	('F662fs', 'Var', (70, 76))	('F662fs', 'Mutation', 'p.F662fsX', (70, 76))	('AB thymoma', 'Disease', (143, 153))	('donor', 'Species', '9606', (95, 100))	('E452 del', 'Var', (51, 59))	('TET2', 'Gene', '54790', (45, 49))	('L1816fs', 'Mutation', 'p.L1816fsX', (61, 68))	('E452 del', 'Mutation', 'p.452delE', (51, 59))	('loss-of-function', 'NegReg', (15, 31))	('AB thymoma', 'Disease', 'MESH:D013945', (143, 153))
54303	25482724	TET2 inactivation mutations have been associated with lymphoid and myeloid malignancies.	('TET2', 'Gene', (0, 4))	('associated', 'Reg', (38, 48))	('lymphoid and myeloid malignancies', 'Disease', 'MESH:D008223', (54, 87))	('TET2', 'Gene', '54790', (0, 4))	('inactivation mutations', 'Var', (5, 27))
54304	25482724	Three TCs showed four DNMT3A mutations including one TC with S827fs and Y683D mutations, two other TCs with L723F and exon 23 splice acceptor site mutations respectively (Figure 3A and Table S2).	('Y683D', 'Mutation', 'p.Y683D', (72, 77))	('DNMT3A', 'Gene', (22, 28))	('DNMT3A', 'Gene', '1788', (22, 28))	('S827fs', 'Var', (61, 67))	('Y683D mutations', 'Var', (72, 87))	('S827fs', 'Mutation', 'p.S827fsX', (61, 67))	('L723F', 'Mutation', 'p.L723F', (108, 113))
54305	25482724	All DNMT3A mutations occurred in the catalytic domain (Figure 3A), which may result in impairment of enzymatic activity.	('mutations', 'Var', (11, 20))	('enzymatic activity', 'MPA', (101, 119))	('occurred', 'Reg', (21, 29))	('DNMT3A', 'Gene', (4, 10))	('DNMT3A', 'Gene', '1788', (4, 10))
54306	25482724	Similar DNMT3A mutations with high frequency spreading around the catalytic domain were also found in T-cell lymphomas, acute myeloid leukemia and recently a B2 thymoma.	('DNMT3A', 'Gene', (8, 14))	('acute myeloid leukemia', 'Phenotype', 'HP:0004808', (120, 142))	('DNMT3A', 'Gene', '1788', (8, 14))	('lymphomas', 'Phenotype', 'HP:0002665', (109, 118))	('leukemia', 'Phenotype', 'HP:0001909', (134, 142))	('thymoma', 'Disease', 'MESH:D013945', (161, 168))	('T-cell lymphomas', 'Disease', 'MESH:D016399', (102, 118))	('T-cell lymphomas', 'Disease', (102, 118))	('mutations', 'Var', (15, 24))	('acute myeloid leukemia', 'Disease', (120, 142))	('myeloid leukemia', 'Phenotype', 'HP:0012324', (126, 142))	('thymoma', 'Disease', (161, 168))	('T-cell lymphomas', 'Phenotype', 'HP:0012190', (102, 118))	('thymoma', 'Phenotype', 'HP:0100522', (161, 168))	('acute myeloid leukemia', 'Disease', 'MESH:D015470', (120, 142))	('found', 'Reg', (93, 98))
54307	25482724	Although all patients with thymoma enrolled in this study had advanced-stage disease (stage IVA/IVB) (Table 2), the mutation frequency among thymomas was significantly lower than that observed in TCs.	('mutation', 'Var', (116, 124))	('IVA', 'Disease', 'MESH:C538167', (92, 95))	('lower', 'NegReg', (168, 173))	('patients', 'Species', '9606', (13, 21))	('thymoma', 'Disease', 'MESH:D013945', (141, 148))	('thymoma', 'Disease', 'MESH:D013945', (27, 34))	('thymomas', 'Disease', (141, 149))	('thymoma', 'Disease', (27, 34))	('thymomas', 'Disease', 'MESH:D013945', (141, 149))	('thymoma', 'Disease', (141, 148))	('thymoma', 'Phenotype', 'HP:0100522', (27, 34))	('thymoma', 'Phenotype', 'HP:0100522', (141, 148))	('IVA', 'Disease', (92, 95))
54309	25482724	Interestingly patients with tumors harboring mutant TP53 displayed poorer overall survival than those with wild-type TP53 (median survival 19 months vs. 106 months; Log-rank Mantel-Cox Test, p = 0.0003; 95% CI of ratio 2.234-22.39; Figure 4B).	('mutant', 'Var', (45, 51))	('TP53', 'Gene', '7157', (52, 56))	('TP53', 'Gene', '7157', (117, 121))	('tumors', 'Disease', (28, 34))	('TP53', 'Gene', (117, 121))	('tumors', 'Disease', 'MESH:D009369', (28, 34))	('Cox', 'Gene', '1351', (181, 184))	('overall survival', 'MPA', (74, 90))	('tumors', 'Phenotype', 'HP:0002664', (28, 34))	('TP53', 'Gene', (52, 56))	('Cox', 'Gene', (181, 184))	('poorer', 'NegReg', (67, 73))	('patients', 'Species', '9606', (14, 22))	('tumor', 'Phenotype', 'HP:0002664', (28, 33))
54312	25482724	Six TET patients with epigenetic gene mutations received PACB treatment and all patients showed stable disease except a patient with a SETD2 (G1672E)-mutant B2 thymoma who achieved a partial response (Table 2).	('thymoma', 'Disease', (160, 167))	('SETD2', 'Gene', (135, 140))	('G1672E', 'Mutation', 'p.G1672E', (142, 148))	('patients', 'Species', '9606', (8, 16))	('patients', 'Species', '9606', (80, 88))	('PACB', 'Chemical', '-', (57, 61))	('thymoma', 'Phenotype', 'HP:0100522', (160, 167))	('patient', 'Species', '9606', (120, 127))	('G1672E)-mutant', 'Var', (142, 156))	('stable disease', 'Disease', (96, 110))	('patient', 'Species', '9606', (8, 15))	('thymoma', 'Disease', 'MESH:D013945', (160, 167))	('SETD2', 'Gene', '29072', (135, 140))	('patient', 'Species', '9606', (80, 87))	('stable disease', 'Disease', 'MESH:D060050', (96, 110))	('epigenetic gene mutations', 'Var', (22, 47))
54318	25482724	In addition to the previously reported TP53 and KIT mutations, here we showed that chromatin remodeling, histone modification, and DNA methylation genes are frequently mutated in advanced-stage TCs.	('mutated', 'Var', (168, 175))	('TCs', 'Disease', (194, 197))	('chromatin remodeling', 'Gene', (83, 103))	('TP53', 'Gene', '7157', (39, 43))	('histone', 'MPA', (105, 112))	('TP53', 'Gene', (39, 43))
54319	25482724	Recent NGS projects revealed high frequency of clusters of epigenetic regulatory gene mutations in kidney carcinoma, metastasizing uveal melanomas and pediatric high grade glioma, medulloblastoma, and T-lineage acute lymphoblastic leukaemia.	('glioma', 'Disease', 'MESH:D005910', (172, 178))	('T-lineage acute lymphoblastic leukaemia', 'Disease', (201, 240))	('acute lymphoblastic leukaemia', 'Phenotype', 'HP:0006721', (211, 240))	('epigenetic regulatory gene mutations', 'Var', (59, 95))	('glioma', 'Phenotype', 'HP:0009733', (172, 178))	('uveal melanomas', 'Disease', (131, 146))	('medulloblastoma', 'Disease', 'MESH:D008527', (180, 195))	('uveal melanomas', 'Phenotype', 'HP:0007716', (131, 146))	('medulloblastoma', 'Phenotype', 'HP:0002885', (180, 195))	('medulloblastoma', 'Disease', (180, 195))	('melanomas', 'Phenotype', 'HP:0002861', (137, 146))	('T-lineage acute lymphoblastic leukaemia', 'Phenotype', 'HP:0006727', (201, 240))	('kidney carcinoma', 'Disease', (99, 115))	('kidney carcinoma', 'Disease', 'MESH:C538614', (99, 115))	('T-lineage acute lymphoblastic leukaemia', 'Disease', 'MESH:D015456', (201, 240))	('carcinoma', 'Phenotype', 'HP:0030731', (106, 115))	('kidney carcinoma', 'Phenotype', 'HP:0005584', (99, 115))	('glioma', 'Disease', (172, 178))	('uveal melanomas', 'Disease', 'MESH:C536494', (131, 146))
54321	25482724	Whole exome sequencing of more patient samples will be required to clarify the frequency of the epigenetic regulatory gene mutations in TETs, especially in TCs.	('patient', 'Species', '9606', (31, 38))	('mutations', 'Var', (123, 132))	('TCs', 'Disease', (156, 159))
54322	25482724	The seven epigenetic regulatory genes (BAP1, ASXL1, SETD2, SMARCA4, DNMT3A, TET2, and WT1) have been previously categorized as drivers when mutated in other cancers and were found recurrently mutated only in TCs but not thymomas.	('TCs', 'Disease', (208, 211))	('thymomas', 'Disease', 'MESH:D013945', (220, 228))	('cancers', 'Disease', 'MESH:D009369', (157, 164))	('BAP1', 'Gene', '8314', (39, 43))	('SETD2', 'Gene', '29072', (52, 57))	('ASXL1', 'Gene', '171023', (45, 50))	('thymomas', 'Disease', (220, 228))	('TET2', 'Gene', (76, 80))	('DNMT3A', 'Gene', (68, 74))	('SMARCA4', 'Gene', '6597', (59, 66))	('mutated', 'Var', (140, 147))	('BAP1', 'Gene', (39, 43))	('ASXL1', 'Gene', (45, 50))	('WT1', 'Gene', (86, 89))	('cancers', 'Phenotype', 'HP:0002664', (157, 164))	('cancers', 'Disease', (157, 164))	('TET2', 'Gene', '54790', (76, 80))	('cancer', 'Phenotype', 'HP:0002664', (157, 163))	('SMARCA4', 'Gene', (59, 66))	('WT1', 'Gene', '7490', (86, 89))	('DNMT3A', 'Gene', '1788', (68, 74))	('thymoma', 'Phenotype', 'HP:0100522', (220, 227))	('SETD2', 'Gene', (52, 57))
54323	25482724	SIFT and Polyphen2 algorithms predicted the damaging nature of most of the mutations in these seven genes (Table S2), implicating the potential importance of these mutations in TCs.	('Polyphen2 algorithms', 'Disease', 'None', (9, 29))	('SIFT', 'Disease', 'None', (0, 4))	('Polyphen2 algorithms', 'Disease', (9, 29))	('mutations', 'Var', (75, 84))	('SIFT', 'Disease', (0, 4))
54324	25482724	The most prevalent epigenetic gene mutation was in the BAP1 tumor suppressor gene, that has histone deubiquitinase activity.	('prevalent', 'Reg', (9, 18))	('BAP1', 'Gene', (55, 59))	('tumor', 'Disease', 'MESH:D009369', (60, 65))	('tumor', 'Phenotype', 'HP:0002664', (60, 65))	('tumor', 'Disease', (60, 65))	('epigenetic gene mutation', 'Var', (19, 43))	('BAP1', 'Gene', '8314', (55, 59))
54325	25482724	BAP1 mutation in clear cell renal carcinoma correlated with high tumor grade and worse prognosis.	('BAP1', 'Gene', (0, 4))	('clear cell renal carcinoma', 'Disease', 'MESH:C538614', (17, 43))	('tumor', 'Phenotype', 'HP:0002664', (65, 70))	('clear cell renal carcinoma', 'Disease', (17, 43))	('high tumor', 'Disease', (60, 70))	('clear cell renal carcinoma', 'Phenotype', 'HP:0006770', (17, 43))	('carcinoma', 'Phenotype', 'HP:0030731', (34, 43))	('BAP1', 'Gene', '8314', (0, 4))	('renal carcinoma', 'Phenotype', 'HP:0005584', (28, 43))	('mutation', 'Var', (5, 13))	('high tumor', 'Disease', 'MESH:D009369', (60, 70))
54326	25482724	All BAP1 mutations affected stage IVB TCs.	('affected', 'Reg', (19, 27))	('BAP1', 'Gene', (4, 8))	('mutations', 'Var', (9, 18))	('stage IVB TCs', 'Disease', (28, 41))	('BAP1', 'Gene', '8314', (4, 8))
54327	25482724	However, given the relatively small sample size and variability of therapies, we have not been able to establish the prognostic values of BAP1 mutations in TCs.	('BAP1', 'Gene', '8314', (138, 142))	('TCs', 'Disease', (156, 159))	('mutations', 'Var', (143, 152))	('BAP1', 'Gene', (138, 142))
54330	25482724	ASXL1 and BAP1 mutations were mutually exclusive and together accounted for 17% of TCs.	('BAP1', 'Gene', (10, 14))	('ASXL1', 'Gene', '171023', (0, 5))	('mutations', 'Var', (15, 24))	('ASXL1', 'Gene', (0, 5))	('TCs', 'Disease', (83, 86))	('accounted for', 'Reg', (62, 75))	('BAP1', 'Gene', '8314', (10, 14))
54331	25482724	Mutations of de-novo cytosine methyltransferase DNMT3A have been reported in T-cell lymphomas which are often accompanied with mutations of TET2 cytosine dioxymethyltransferase, an enzyme acting at an intermediate step toward methylcytosine demethylation.	('reported', 'Reg', (65, 73))	('accompanied', 'Reg', (110, 121))	('T-cell lymphomas', 'Disease', 'MESH:D016399', (77, 93))	('T-cell lymphomas', 'Disease', (77, 93))	('DNMT3A', 'Gene', (48, 54))	('DNMT3A', 'Gene', '1788', (48, 54))	('Mutations', 'Var', (0, 9))	('TET2', 'Gene', '54790', (140, 144))	('T-cell lymphomas', 'Phenotype', 'HP:0012190', (77, 93))	('lymphomas', 'Phenotype', 'HP:0002665', (84, 93))	('mutations', 'Var', (127, 136))	('TET2', 'Gene', (140, 144))
54333	25482724	As the mutated epigenetic regulatory genes identified in this study function at different levels of epigenetic regulations (chromatin remodeling, histone modification and DNA methylation), it is not surprising that patients with epigenetic regulatory gene mutations may not respond to chemotherapy and HDAC inhibitor combination therapy (Table 2).	('patients', 'Species', '9606', (215, 223))	('HDAC', 'Gene', (302, 306))	('epigenetic regulatory gene', 'Gene', (229, 255))	('HDAC', 'Gene', '9734', (302, 306))	('mutations', 'Var', (256, 265))
54334	25482724	Understanding how and whether the mutated epigenetic regulatory genes may play a role in thymic epithelial cell transformation will help to tailor specific drugs to tumors with specific epigenetic alterations, as piloted in non-small cell lung cancer and leukemia studies.	('leukemia', 'Phenotype', 'HP:0001909', (255, 263))	('leukemia', 'Disease', 'MESH:D007938', (255, 263))	('lung cancer', 'Phenotype', 'HP:0100526', (239, 250))	('cancer', 'Phenotype', 'HP:0002664', (244, 250))	('tumors', 'Disease', (165, 171))	('leukemia', 'Disease', (255, 263))	('play', 'Reg', (74, 78))	('tumors', 'Disease', 'MESH:D009369', (165, 171))	('tumors', 'Phenotype', 'HP:0002664', (165, 171))	('non-small cell lung cancer', 'Phenotype', 'HP:0030358', (224, 250))	('small cell lung cancer', 'Phenotype', 'HP:0030357', (228, 250))	('non-small cell lung cancer', 'Disease', 'MESH:D002289', (224, 250))	('tumor', 'Phenotype', 'HP:0002664', (165, 170))	('non-small cell lung cancer', 'Disease', (224, 250))	('mutated', 'Var', (34, 41))
54335	25482724	Future work requires the determination of the mutation impact on the functions of the encoded proteins and the epigenetic landscape of the tumor cells.	('tumor', 'Disease', 'MESH:D009369', (139, 144))	('functions', 'MPA', (69, 78))	('tumor', 'Phenotype', 'HP:0002664', (139, 144))	('tumor', 'Disease', (139, 144))	('impact', 'Reg', (55, 61))	('mutation', 'Var', (46, 54))
54336	25482724	TP53 mutations correlated with poorer patient survival, reflecting the high mutation frequency in stage IVB TCs.	('stage IVB TCs', 'Disease', (98, 111))	('TP53', 'Gene', '7157', (0, 4))	('TP53', 'Gene', (0, 4))	('poorer', 'NegReg', (31, 37))	('mutations', 'Var', (5, 14))	('patient', 'Species', '9606', (38, 45))
54338	25482724	However the prognostic role of mutant P53 remains controversial, probably mainly because most studies are based only on immunohistochemistry analysis.	('P53', 'Gene', '7157', (38, 41))	('mutant', 'Var', (31, 37))	('P53', 'Gene', (38, 41))
54339	25482724	CYLD activates NFKB signaling through deubiquitination of NFKB upstream regulators ubiquitylated by cIAP ubiquitin E3 ligase, and inhibition of cIAP by cIAP antagonist blocks NFKB activation.	('NFKB signaling', 'Pathway', (15, 29))	('inhibition', 'Var', (130, 140))	('CYLD', 'Gene', (0, 4))	('NFKB', 'Gene', (175, 179))	('activates', 'PosReg', (5, 14))	('CYLD', 'Gene', '1540', (0, 4))	('ubiquitylated', 'MPA', (83, 96))	('NFKB', 'Gene', (58, 62))	('deubiquitination', 'MPA', (38, 54))
54340	25482724	Five of the 9 mutations in TETs were framshift, nonsense and splice-site error (Figure 3B), which are probably non-functional, in line with the tumor suppressor role of CYLD.	('tumor', 'Disease', (144, 149))	('tumor', 'Phenotype', 'HP:0002664', (144, 149))	('TETs', 'Gene', (27, 31))	('tumor', 'Disease', 'MESH:D009369', (144, 149))	('splice-site error', 'Var', (61, 78))	('framshift', 'Var', (37, 46))	('CYLD', 'Gene', (169, 173))	('nonsense', 'Var', (48, 56))	('mutations', 'Var', (14, 23))	('CYLD', 'Gene', '1540', (169, 173))
54341	25482724	Anti-inflammation drugs aspirin and prostaglandin A1 were used in a phase I trial to block NFKB signaling in cylindromatosis patients with CYLD mutations.	('patients', 'Species', '9606', (125, 133))	('CYLD', 'Gene', '1540', (139, 143))	('cylindromatosis', 'Disease', 'MESH:C536611', (109, 124))	('cylindromatosis', 'Disease', (109, 124))	('aspirin', 'Chemical', 'MESH:D001241', (24, 31))	('NFKB', 'Protein', (91, 95))	('mutations', 'Var', (144, 153))	('CYLD', 'Gene', (139, 143))	('prostaglandin A1', 'Chemical', 'MESH:C100573', (36, 52))	('block', 'NegReg', (85, 90))
54342	25482724	In conclusion, our study shows that chromatin remodeling, histone modification and DNA methylation regulatory genes are frequently mutated in TCs, and that the genetic architecture of thymoma is different from that of TCs.	('chromatin remodeling', 'Gene', (36, 56))	('thymoma', 'Phenotype', 'HP:0100522', (184, 191))	('mutated', 'Var', (131, 138))	('DNA methylation regulatory genes', 'Gene', (83, 115))	('TCs', 'Disease', (142, 145))	('histone modification', 'Gene', (58, 78))	('thymoma', 'Disease', 'MESH:D013945', (184, 191))	('thymoma', 'Disease', (184, 191))
54352	25482724	A panel of 197 cancer-associated genes (Table S1) were selected for targeted exome capture based on their known frequency of mutations in most common tumor types, in particular: (1) variations were reported in the Catalogue of Somatic Mutations in Cancer (COSMIC) Cancer Gene Census or (2) were known or drivers of solid tumors not yet listed in the COSMIC census at the time this reagent was designed or (3) were in pathways under investigation within NCI for other projects.	('cancer', 'Disease', 'MESH:D009369', (15, 21))	('tumor', 'Phenotype', 'HP:0002664', (150, 155))	('tumor', 'Disease', (321, 326))	('solid tumors', 'Disease', (315, 327))	('tumor', 'Disease', 'MESH:D009369', (321, 326))	('Cancer', 'Phenotype', 'HP:0002664', (248, 254))	('Cancer', 'Phenotype', 'HP:0002664', (264, 270))	('tumors', 'Phenotype', 'HP:0002664', (321, 327))	('variations', 'Var', (182, 192))	('cancer', 'Disease', (15, 21))	('tumor', 'Phenotype', 'HP:0002664', (321, 326))	('Cancer', 'Disease', (264, 270))	('solid tumors', 'Disease', 'MESH:D009369', (315, 327))	('Cancer', 'Disease', (248, 254))	('cancer', 'Phenotype', 'HP:0002664', (15, 21))	('tumor', 'Disease', (150, 155))	('Mutations', 'Var', (235, 244))	('tumor', 'Disease', 'MESH:D009369', (150, 155))	('Cancer', 'Disease', 'MESH:D009369', (264, 270))	('Cancer', 'Disease', 'MESH:D009369', (248, 254))
54356	25482724	SIFT scores range from 0 to 1, and scores < 0.05 suggest that the amino acid change is damaging (sift.jcvi.org/www/SIFT_help.html).	('amino acid change', 'Var', (66, 83))	('SIFT', 'Disease', 'None', (0, 4))	('SIFT', 'Disease', (115, 119))	('SIFT', 'Disease', 'None', (115, 119))	('SIFT', 'Disease', (0, 4))
54455	23937886	In the present study, the total recurrence rates had no significant decrease in patients with S + R compared with S alone, though adjuvant RT had a trend of reducing local recurrence (P = 0.09).	('local recurrence', 'CPA', (166, 182))	('S + R', 'Var', (94, 99))	('patients', 'Species', '9606', (80, 88))
54486	22554706	Thorough analyses of cohorts of patients with unusual susceptibility to chronic mucocutaneous candidiasis (CMC) resulting from Th17 deficiency has confirmed the role of Th17 cells and Th17 cytokines in human host defense against Candida and has provided valuable insight into the complex process of Th17 cell development.	('mucocutaneous candidiasis', 'Disease', (80, 105))	('patients', 'Species', '9606', (32, 40))	('CMC', 'Phenotype', 'HP:0002728', (107, 110))	('human', 'Species', '9606', (202, 207))	('resulting', 'Reg', (112, 121))	('mucocutaneous candidiasis', 'Disease', 'MESH:D002178', (80, 105))	('Th17', 'Gene', (127, 131))	('Candida', 'Species', '5476', (229, 236))	('deficiency', 'Var', (132, 142))	('chronic mucocutaneous candidiasis', 'Phenotype', 'HP:0002728', (72, 105))
54494	22554706	Identification of novel mutations in genes that impair T cell differentiation and function in immune deficient patients will expand our knowledge of the role of specific T cell subsets in host defense against pathogens.	('genes', 'Gene', (37, 42))	('T cell differentiation', 'CPA', (55, 77))	('impair', 'NegReg', (48, 54))	('immune deficient', 'Phenotype', 'HP:0002721', (94, 110))	('mutations', 'Var', (24, 33))	('patients', 'Species', '9606', (111, 119))
54496	22554706	The recent descriptions of infectious susceptibility to CMC in patients with defects in Th17 development and function resulting from single gene mutations or as part of a syndrome have served to clearly define the role of Th17 T cells in human host defense.	('CMC', 'Phenotype', 'HP:0002728', (56, 59))	('defects', 'NegReg', (77, 84))	('mutations', 'Var', (145, 154))	('Th17', 'Gene', (88, 92))	('patients', 'Species', '9606', (63, 71))	('CMC', 'Disease', (56, 59))	('human', 'Species', '9606', (238, 243))	('function', 'MPA', (109, 117))
54499	22554706	This review will summarize the clinical aspects of patients with genetic defects that result in Th17 deficiency.	('result', 'Reg', (86, 92))	('patients', 'Species', '9606', (51, 59))	('genetic defects', 'Disease', 'MESH:D030342', (65, 80))	('genetic defects', 'Disease', (65, 80))	('deficiency', 'Var', (101, 111))	('Th17', 'Gene', (96, 100))
54523	22554706	In contrast, IL12p40 and IL12Rbeta1-deficient patients, both of whom have impaired IL-23 signaling, have reduced populations of Th17 cells.	('patients', 'Species', '9606', (46, 54))	('impaired', 'NegReg', (74, 82))	('IL-23', 'Gene', '51561', (83, 88))	('IL12Rbeta1-deficient', 'Disease', 'MESH:D007153', (25, 45))	('IL-23', 'Gene', (83, 88))	('IL12p40', 'Var', (13, 20))	('reduced', 'NegReg', (105, 112))	('IL12Rbeta1-deficient', 'Disease', (25, 45))
54524	22554706	IL12p40 and IL23p19 form heterodimers to make active IL-23, while IL12Rbeta1 and IL23R heterodimerize to form the active IL-23 receptor.	('IL-23', 'Gene', (53, 58))	('23R', 'Species', '1040604', (83, 86))	('IL23R', 'Var', (81, 86))	('IL-23', 'Gene', '51561', (121, 126))	('IL12p40', 'Var', (0, 7))	('IL12Rbeta1', 'Gene', (66, 76))	('IL-23', 'Gene', (121, 126))	('IL23p19', 'Var', (12, 19))	('IL12Rbeta1', 'Gene', '3594', (66, 76))	('23p', 'Species', '1040607', (14, 17))	('heterodimers', 'MPA', (25, 37))	('IL-23', 'Gene', '51561', (53, 58))
54525	22554706	The reduction in Th17 populations in IL12p40 and IL12Rbeta1-deficient patients is not as severe as in STAT3 deficient patients, suggesting that IL-23 is important for Th17 development and/or maintenance, but some redundancy may exist to allow reduced Th17 development.	('patients', 'Species', '9606', (70, 78))	('IL12Rbeta1-deficient', 'Disease', (49, 69))	('IL-23', 'Gene', '51561', (144, 149))	('IL12p40', 'Var', (37, 44))	('IL-23', 'Gene', (144, 149))	('STAT3', 'Gene', '6774', (102, 107))	('IL12Rbeta1-deficient', 'Disease', 'MESH:D007153', (49, 69))	('STAT3', 'Gene', (102, 107))	('patients', 'Species', '9606', (118, 126))	('Th17 development', 'CPA', (251, 267))
54526	22554706	Since candidal infections in IL12p40 and IL12Rbeta1-deficient patients are not common, it is likely that the majority of these patients retain adequate Th17 function to prevent susceptibility to CMC.	('IL12p40', 'Var', (29, 36))	('candidal infections', 'Disease', (6, 25))	('CMC', 'Disease', (195, 198))	('IL12Rbeta1-deficient', 'Disease', 'MESH:D007153', (41, 61))	('patients', 'Species', '9606', (127, 135))	('patients', 'Species', '9606', (62, 70))	('candidal infections', 'Disease', 'MESH:D007239', (6, 25))	('IL12Rbeta1-deficient', 'Disease', (41, 61))	('CMC', 'Phenotype', 'HP:0002728', (195, 198))
54528	22554706	Since the IL12p40 and IL12Rbeta1-deficient patients are obviously deficient in IL-12 responses, which accounts for their susceptibility to mycobacterial infections, identification of IL-23R or IL23p19 deficient patients would likely provide more specific insight into the importance of IL-23 in human Th17 differentiation and host defense against Candida.	('mycobacterial infections', 'Disease', (139, 163))	('IL-1', 'Gene', (79, 83))	('IL-1', 'Gene', '3553', (79, 83))	('IL12p40', 'Var', (10, 17))	('susceptibility to mycobacterial infections', 'Phenotype', 'HP:0011274', (121, 163))	('human', 'Species', '9606', (295, 300))	('IL-23R', 'Gene', (183, 189))	('patients', 'Species', '9606', (211, 219))	('deficient', 'NegReg', (66, 75))	('IL-23R', 'Gene', '149233', (183, 189))	('IL23p19', 'Gene', (193, 200))	('patients', 'Species', '9606', (43, 51))	('IL12Rbeta1-deficient', 'Disease', (22, 42))	('23p', 'Species', '1040607', (195, 198))	('IL-23', 'Gene', (286, 291))	('IL-23', 'Gene', '51561', (286, 291))	('IL-23', 'Gene', (183, 188))	('IL-23', 'Gene', '51561', (183, 188))	('bacterial infections', 'Phenotype', 'HP:0002718', (143, 163))	('Candida', 'Species', '5476', (347, 354))	('IL12Rbeta1-deficient', 'Disease', 'MESH:D007153', (22, 42))	('mycobacterial infections', 'Disease', 'MESH:D009165', (139, 163))
54530	22554706	In immunocompromised individuals, however, C albicans can cause chronic mucocutaneous and sometimes fatal invasive infections.	('C albicans', 'Var', (43, 53))	('invasive infections', 'Disease', (106, 125))	('cause', 'Reg', (58, 63))	('invasive infections', 'Disease', 'MESH:D009362', (106, 125))	('mucocutaneous', 'Disease', (72, 85))
54531	22554706	Neutrophil defects are associated with systemic candidiasis and susceptibility to a wide variety of bacteria.	('Neutrophil defects', 'Var', (0, 18))	('systemic candidiasis', 'Disease', (39, 59))	('systemic candidiasis', 'Disease', 'MESH:C536777', (39, 59))	('associated', 'Reg', (23, 33))
54532	22554706	CMC disease and invasive candidiasis has also been described in a large Iranian family with a homozygous nonsense mutation in CARD9, a signaling protein that along with Syk tyrosine kinase is downstream of the anti-fungal receptors Dectin-1, Dectin-2, and Mincle (Fig.	('Dectin-1', 'Gene', (232, 240))	('Syk', 'Gene', '6850', (169, 172))	('CMC disease', 'Disease', 'MESH:C535816', (0, 11))	('described', 'Reg', (51, 60))	('CARD9', 'Gene', (126, 131))	('invasive candidiasis', 'Disease', 'MESH:D058365', (16, 36))	('CARD9', 'Gene', '64170', (126, 131))	('Mincle', 'Gene', '26253', (256, 262))	('Dectin-1', 'Gene', '64581', (232, 240))	('invasive candidiasis', 'Disease', (16, 36))	('Mincle', 'Gene', (256, 262))	('large Iranian', 'Phenotype', 'HP:0000256', (66, 79))	('Syk', 'Gene', (169, 172))	('CMC disease', 'Disease', (0, 11))	('CMC', 'Phenotype', 'HP:0002728', (0, 3))	('Dectin-2', 'Gene', (242, 250))	('Dectin-2', 'Gene', '93978', (242, 250))	('nonsense mutation', 'Var', (105, 122))
54536	22554706	These include autosomal dominant hyper IgE syndrome (AD-HIES) with mutations in signal transducer and activator of transcription-3 (STAT3) and autosomal recessive (AR)-HIES with mutations in dedicator of cytokinesis gene-8 (DOCK8).	('AD-HIES', 'Disease', (53, 60))	('autosomal dominant hyper IgE syndrome', 'Disease', 'MESH:D007589', (14, 51))	('STAT3', 'Gene', '6774', (132, 137))	('DOCK8', 'Gene', '81704', (224, 229))	('AD-HIES', 'Disease', 'MESH:D000544', (53, 60))	('signal transducer and activator of transcription-3', 'Gene', '6774', (80, 130))	('STAT3', 'Gene', (132, 137))	('mutations', 'Var', (67, 76))	('mutations', 'Var', (178, 187))	('DOCK8', 'Gene', (224, 229))	('autosomal dominant hyper IgE syndrome', 'Disease', (14, 51))
54539	22554706	AD-HIES due to mutations in STAT3 is a multisystem immune deficiency characterized by highly elevated serum levels of IgE, local and invasive infections with S. aureus that result in cold abscesses and recurrent pneumonia with pneumatocele formation, skeletal abnormalities, and coarse facial features.	('result in', 'Reg', (173, 182))	('skeletal abnormalities', 'Disease', (251, 273))	('AD-HIES', 'Disease', (0, 7))	('skeletal abnormalities', 'Disease', 'MESH:C538496', (251, 273))	('cold abscesses', 'Disease', (183, 197))	('serum levels', 'MPA', (102, 114))	('coarse facial features', 'Phenotype', 'HP:0000280', (279, 301))	('IgE', 'Gene', (118, 121))	('immune deficiency', 'Phenotype', 'HP:0002721', (51, 68))	('abscesses', 'Phenotype', 'HP:0025615', (188, 197))	('multisystem immune deficiency', 'Disease', (39, 68))	('mutations', 'Var', (15, 24))	('invasive infections', 'Disease', 'MESH:D009362', (133, 152))	('recurrent pneumonia', 'Phenotype', 'HP:0006532', (202, 221))	('STAT3', 'Gene', (28, 33))	('pneumatocele formation', 'CPA', (227, 249))	('AD-HIES', 'Disease', 'MESH:D000544', (0, 7))	('IgE', 'Gene', '3497', (118, 121))	('pneumonia with pneumatocele', 'Phenotype', 'HP:0025419', (212, 239))	('pneumonia', 'Phenotype', 'HP:0002090', (212, 221))	('multisystem immune deficiency', 'Disease', 'MESH:D007154', (39, 68))	('pneumonia', 'Disease', 'MESH:D011014', (212, 221))	('STAT3', 'Gene', '6774', (28, 33))	('invasive infections', 'Disease', (133, 152))	('skeletal abnormalities', 'Phenotype', 'HP:0000924', (251, 273))	('pneumonia', 'Disease', (212, 221))	('S. aureus', 'Species', '1280', (158, 167))	('elevated', 'PosReg', (93, 101))
54543	22554706	Since patients with AD-HIES due to STAT3 mutations are susceptible to CMC disease and STAT3 is essential for Th17 cell development and Th17 cells play an important role in mucosal immunity against Candida, Ma et al evaluated these patients for potential defects in Th17 development.	('mutations', 'Var', (41, 50))	('AD-HIES', 'Disease', 'MESH:D000544', (20, 27))	('STAT3', 'Gene', (35, 40))	('STAT3', 'Gene', '6774', (35, 40))	('STAT3', 'Gene', (86, 91))	('patients', 'Species', '9606', (231, 239))	('CMC', 'Phenotype', 'HP:0002728', (70, 73))	('CMC disease', 'Disease', 'MESH:C535816', (70, 81))	('STAT3', 'Gene', '6774', (86, 91))	('AD-HIES', 'Disease', (20, 27))	('Candida', 'Species', '5476', (197, 204))	('patients', 'Species', '9606', (6, 14))	('CMC disease', 'Disease', (70, 81))	('susceptible', 'Reg', (55, 66))
54547	22554706	Furthermore, sorted naive CD4+ T cells from AD-HIES patients failed to differentiate into Th17 T cells when stimulated with anti-CD2 and anti-CD3 plus anti-CD28 in the presence of IL-1beta plus IL-6 or IL-23, confirming the requirement for STAT3 in Th17 differentiation.	('CD28', 'Gene', (156, 160))	('STAT3', 'Gene', (240, 245))	('AD-HIES', 'Disease', (44, 51))	('CD28', 'Gene', '940', (156, 160))	('IL-6', 'Gene', (194, 198))	('CD4', 'Gene', '920', (26, 29))	('STAT3', 'Gene', '6774', (240, 245))	('IL-23', 'Gene', '51561', (202, 207))	('IL-6', 'Gene', '3569', (194, 198))	('IL-23', 'Gene', (202, 207))	('CD2', 'Gene', (156, 159))	('AD-HIES', 'Disease', 'MESH:D000544', (44, 51))	('CD4', 'Gene', (26, 29))	('CD2', 'Gene', '914', (156, 159))	('CD2', 'Gene', (129, 132))	('anti-CD3', 'Var', (137, 145))	('patients', 'Species', '9606', (52, 60))	('CD2', 'Gene', '914', (129, 132))
54549	22554706	Thus, analysis of T cells from patients with STAT3 mutations has clearly demonstrated an essential role for STAT3 in Th17 differentiation and mucosal and epithelial immunity against Candida and S aureus (Fig.	('STAT3', 'Gene', '6774', (108, 113))	('mutations', 'Var', (51, 60))	('S aureus', 'Species', '1280', (194, 202))	('STAT3', 'Gene', (45, 50))	('STAT3', 'Gene', (108, 113))	('Th17 differentiation', 'CPA', (117, 137))	('epithelia', 'Disease', 'None', (154, 163))	('epithelia', 'Disease', (154, 163))	('patients', 'Species', '9606', (31, 39))	('Candida', 'Species', '5476', (182, 189))	('STAT3', 'Gene', '6774', (45, 50))
54552	22554706	AR-HIES due to mutations in DOCK8 is characterized by highly elevated serum IgE levels, hypereosinophilia, recurrent sinopulmonary infections, unusual susceptibility to herpesvirus infections, candidal dermatitis, and atopy.	('hypereosinophilia', 'Disease', (88, 105))	('herpesvirus infections', 'Disease', 'MESH:D006566', (169, 191))	('dermatitis', 'Phenotype', 'HP:0011123', (202, 212))	('elevated', 'PosReg', (61, 69))	('DOCK8', 'Gene', (28, 33))	('sinopulmonary infections', 'Disease', (117, 141))	('candidal dermatitis', 'Phenotype', 'HP:0005411', (193, 212))	('mutations', 'Var', (15, 24))	('sinopulmonary infections', 'Disease', 'MESH:C536718', (117, 141))	('hypereosinophilia', 'Disease', 'MESH:D004802', (88, 105))	('DOCK8', 'Gene', '81704', (28, 33))	('elevated serum IgE', 'Phenotype', 'HP:0003212', (61, 79))	('hypereosinophilia', 'Phenotype', 'HP:0032061', (88, 105))	('IgE', 'Gene', (76, 79))	('dermatitis', 'Disease', 'MESH:D003872', (202, 212))	('dermatitis', 'Disease', (202, 212))	('herpesvirus infections', 'Disease', (169, 191))	('susceptibility', 'Reg', (151, 165))	('susceptibility to herpesvirus', 'Phenotype', 'HP:0005353', (151, 180))	('atopy', 'Disease', (218, 223))	('recurrent', 'Disease', (107, 116))	('recurrent sinopulmonary infections', 'Phenotype', 'HP:0005425', (107, 141))	('IgE', 'Gene', '3497', (76, 79))
54553	22554706	In addition, DOCK8 deficient patients tend to be T cell lymphopenic with poor T cell proliferation after activation with anti-CD3 and anti-CD28.	('T cell lymphopenic', 'Disease', (49, 67))	('DOCK8', 'Gene', '81704', (13, 18))	('patients', 'Species', '9606', (29, 37))	('anti-CD3', 'Protein', (121, 129))	('T cell proliferation', 'CPA', (78, 98))	('CD28', 'Gene', '940', (139, 143))	('anti-CD3', 'Var', (121, 129))	('DOCK8', 'Gene', (13, 18))	('T cell lymphopenic', 'Disease', 'MESH:C565427', (49, 67))	('CD28', 'Gene', (139, 143))	('poor', 'NegReg', (73, 77))	('deficient', 'Var', (19, 28))
54555	22554706	Previous analysis of a cohort of AR-HIES patient, some of whom were later confirmed to have DOCK8 deficiency, revealed that these patients have defects in Th17 differentiation.	('deficiency', 'Var', (98, 108))	('patient', 'Species', '9606', (130, 137))	('DOCK8', 'Gene', (92, 97))	('Th17 differentiation', 'CPA', (155, 175))	('patient', 'Species', '9606', (41, 48))	('patients', 'Species', '9606', (130, 138))	('DOCK8', 'Gene', '81704', (92, 97))	('defects', 'NegReg', (144, 151))
54556	22554706	RORgammat expression, which is critical for Th17 differentiation, was markedly reduced in peripheral T cells from patients with AD-HIES due to STAT3 mutations, as well as in AR-HIES patients.	('STAT3', 'Gene', (143, 148))	('mutations', 'Var', (149, 158))	('reduced', 'NegReg', (79, 86))	('AD-HIES', 'Disease', 'MESH:D000544', (128, 135))	('STAT3', 'Gene', '6774', (143, 148))	('patients', 'Species', '9606', (182, 190))	('RORgammat expression', 'Protein', (0, 20))	('patients', 'Species', '9606', (114, 122))	('AD-HIES', 'Disease', (128, 135))
54559	22554706	IL-17 production was impaired in both groups of HIES patients, although the impairment was more severe in the patients with STAT3 mutations.	('STAT3', 'Gene', '6774', (124, 129))	('patients', 'Species', '9606', (53, 61))	('STAT3', 'Gene', (124, 129))	('mutations', 'Var', (130, 139))	('impaired', 'NegReg', (21, 29))	('IL-17', 'Gene', '3605', (0, 5))	('patients', 'Species', '9606', (110, 118))	('IL-17', 'Gene', (0, 5))
54560	22554706	Thus, defective Th17 differentiation occurs by a different mechanism in AR-HIES versus AD-HIES due to STAT3 mutations.	('AR-HIES versus AD-HIES', 'Disease', 'MESH:D007589', (72, 94))	('AR-HIES versus AD-HIES', 'Disease', (72, 94))	('mutations', 'Var', (108, 117))	('STAT3', 'Gene', '6774', (102, 107))	('Th17 differentiation', 'CPA', (16, 36))	('STAT3', 'Gene', (102, 107))
54561	22554706	It is likely that impaired Th17 differentiation and IL-17 production contributes to the susceptibility of AR-HIES patients with DOCK8 mutations to candidal dermatitis.	('IL-17', 'Gene', '3605', (52, 57))	('Th17 differentiation', 'CPA', (27, 47))	('dermatitis', 'Disease', 'MESH:D003872', (156, 166))	('IL-17', 'Gene', (52, 57))	('candidal dermatitis', 'Phenotype', 'HP:0005411', (147, 166))	('dermatitis', 'Disease', (156, 166))	('dermatitis', 'Phenotype', 'HP:0011123', (156, 166))	('mutations', 'Var', (134, 143))	('DOCK8', 'Gene', '81704', (128, 133))	('patients', 'Species', '9606', (114, 122))	('impaired', 'NegReg', (18, 26))	('DOCK8', 'Gene', (128, 133))
54564	22554706	In a search for genetic causes of AD-CMC disease, two groups of investigators independently identified heterozygous mutations in STAT1 as a novel cause of deficiency of Th17 differentiation and AD-CMC.	('AD-CMC disease', 'Disease', 'MESH:C535816', (34, 48))	('heterozygous mutations', 'Var', (103, 125))	('AD-CMC disease', 'Disease', (34, 48))	('CMC', 'Phenotype', 'HP:0002728', (197, 200))	('Th17 differentiation', 'CPA', (169, 189))	('CMC', 'Phenotype', 'HP:0002728', (37, 40))	('STAT1', 'Gene', (129, 134))	('cause', 'Reg', (146, 151))	('AD-CMC', 'Disease', (194, 200))	('deficiency', 'NegReg', (155, 165))	('STAT1', 'Gene', '6772', (129, 134))
54571	22554706	This analysis identified heterozygous mutations within highly conserved residues in exon 10 of STAT1, which lies within coiled-coil domain.	('mutations', 'Var', (38, 47))	('STAT1', 'Gene', (95, 100))	('STAT1', 'Gene', '6772', (95, 100))
54578	22554706	Thus, STAT1 mutations within the coiled-coil domain appeared to be gain of function mutations.	('STAT1', 'Gene', (6, 11))	('gain of function', 'PosReg', (67, 83))	('mutations', 'Var', (12, 21))	('STAT1', 'Gene', '6772', (6, 11))
54579	22554706	Stimulation of EBV-immortalized B cells and fibroblasts from patients with gain of function mutations in STAT1 resulted in augmented responses to IFNalpha, IFNgamma, and IL-27, cytokines known to be antagonistic to Th17 development.	('augmented', 'PosReg', (123, 132))	('IL-27', 'Gene', (170, 175))	('STAT1', 'Gene', '6772', (105, 110))	('patients', 'Species', '9606', (61, 69))	('gain of function', 'PosReg', (75, 91))	('IL-27', 'Gene', '246778', (170, 175))	('mutations', 'Var', (92, 101))	('STAT1', 'Gene', (105, 110))	('IFNalpha', 'Gene', (146, 154))	('IFNalpha', 'Gene', '3439', (146, 154))
54580	22554706	Interestingly, cellular responses to predominantly STAT3 activating cytokines that promote Th17 differentiation, like IL-6 and IL-21, also resulted in increased STAT1 phosphorylation in EBV B cells from patients with gain of function STAT1 mutations compared to healthy controls.	('STAT3', 'Gene', '6774', (51, 56))	('increased', 'PosReg', (151, 160))	('STAT1', 'Gene', '6772', (161, 166))	('IL-21', 'Gene', (127, 132))	('STAT3', 'Gene', (51, 56))	('IL-6', 'Gene', (118, 122))	('STAT1', 'Gene', '6772', (234, 239))	('IL-6', 'Gene', '3569', (118, 122))	('patients', 'Species', '9606', (203, 211))	('gain of function', 'PosReg', (217, 233))	('IL-21', 'Gene', '59067', (127, 132))	('Th17 differentiation', 'CPA', (91, 111))	('mutations', 'Var', (240, 249))	('STAT1', 'Gene', (161, 166))	('STAT1', 'Gene', (234, 239))
54582	22554706	Finally, percentages of IL17A+, IL17F+, and IL-22+ T cells, as well as production of IL-17A and IL-22 in patients with gain of function STAT1 mutations were significantly lower than healthy controls and patients with loss of function STAT1 mutations, providing the molecular basis for CMC disease in these patients.	('IL-17A', 'Gene', '3605', (85, 91))	('STAT1', 'Gene', '6772', (234, 239))	('CMC disease', 'Disease', 'MESH:C535816', (285, 296))	('IL-22', 'Gene', '50616', (96, 101))	('IL-22', 'Gene', (96, 101))	('STAT1', 'Gene', (136, 141))	('CMC', 'Phenotype', 'HP:0002728', (285, 288))	('mutations', 'Var', (142, 151))	('production', 'MPA', (71, 81))	('IL17A', 'Gene', '3605', (24, 29))	('patients', 'Species', '9606', (203, 211))	('IL-17A', 'Gene', (85, 91))	('STAT1', 'Gene', '6772', (136, 141))	('patients', 'Species', '9606', (306, 314))	('patients', 'Species', '9606', (105, 113))	('IL17A', 'Gene', (24, 29))	('gain of function', 'PosReg', (119, 135))	('IL17F', 'Gene', (32, 37))	('STAT1', 'Gene', (234, 239))	('IL-22', 'Gene', '50616', (44, 49))	('IL-22', 'Gene', (44, 49))	('CMC disease', 'Disease', (285, 296))	('IL17F', 'Gene', '112744', (32, 37))	('lower', 'NegReg', (171, 176))
54584	22554706	A fascinating aspect of the role of STAT1 in human immune deficiencies is that mutations in one gene can lead to three very different phenotypes: CMC disease, mycobacterial disease, or susceptibility to viral disease.	('STAT1', 'Gene', '6772', (36, 41))	('mycobacterial disease', 'Disease', 'MESH:C567070', (159, 180))	('mycobacterial disease', 'Disease', (159, 180))	('lead to', 'Reg', (105, 112))	('viral disease', 'Disease', 'MESH:D001102', (203, 216))	('CMC', 'Phenotype', 'HP:0002728', (146, 149))	('CMC disease', 'Disease', 'MESH:C535816', (146, 157))	('viral disease', 'Disease', (203, 216))	('human', 'Species', '9606', (45, 50))	('immune deficiencies', 'Disease', (51, 70))	('immune deficiencies', 'Disease', 'MESH:D007153', (51, 70))	('STAT1', 'Gene', (36, 41))	('immune deficiencies', 'Phenotype', 'HP:0002721', (51, 70))	('CMC disease', 'Disease', (146, 157))	('mutations', 'Var', (79, 88))
54590	22554706	Neutralizing antibodies against cytokines, in particular type 1 interferons and Th17 cytokines, are the most prevalent autoantibodies in APECED patients (reviewed in).	('patients', 'Species', '9606', (144, 152))	('APECED', 'Gene', '326', (137, 143))	('Neutralizing', 'Var', (0, 12))	('APECED', 'Gene', (137, 143))
54592	22554706	Autoantibodies against IL-17A, IL-17F, and IL-22 appear to be more prevalent in APECED patients with CMC than those without CMC, suggesting a causal role in CMC (Fig.	('APECED', 'Gene', (80, 86))	('IL-22', 'Gene', '50616', (43, 48))	('CMC', 'Phenotype', 'HP:0002728', (124, 127))	('IL-17A', 'Gene', '3605', (23, 29))	('CMC', 'Phenotype', 'HP:0002728', (101, 104))	('IL-17F', 'Gene', '112744', (31, 37))	('CMC', 'Disease', (157, 160))	('IL-22', 'Gene', (43, 48))	('prevalent', 'Reg', (67, 76))	('CMC', 'Disease', (101, 104))	('IL-17A', 'Gene', (23, 29))	('CMC', 'Phenotype', 'HP:0002728', (157, 160))	('patients', 'Species', '9606', (87, 95))	('Autoantibodies', 'Var', (0, 14))	('APECED', 'Gene', '326', (80, 86))	('IL-17F', 'Gene', (31, 37))
54595	22554706	These observations suggest that AIRE mutations in APECED may contribute to impaired innate responses to Candida, which could subsequently impair IL-17 and IL-22 production, although this remains to be formally evaluated.	('Candida', 'Species', '5476', (104, 111))	('AIRE', 'Gene', '326', (32, 36))	('APECED', 'Gene', '326', (50, 56))	('IL-17', 'Gene', '3605', (145, 150))	('innate responses to Candida', 'MPA', (84, 111))	('IL-17', 'Gene', (145, 150))	('APECED', 'Gene', (50, 56))	('impaired', 'NegReg', (75, 83))	('mutations', 'Var', (37, 46))	('impair', 'NegReg', (138, 144))	('IL-22', 'Gene', '50616', (155, 160))	('IL-22', 'Gene', (155, 160))	('AIRE', 'Gene', (32, 36))
54598	22554706	Thymomas are associated with autoimmune manifestations, most notably with antibodies against muscle acetylcholine receptors that cause myasthenia gravis.	('cause', 'Reg', (129, 134))	('Thymomas', 'Disease', 'MESH:D013945', (0, 8))	('antibodies', 'Var', (74, 84))	('myasthenia gravis', 'Disease', (135, 152))	('muscle acetylcholine receptors', 'Protein', (93, 123))	('Thymomas', 'Disease', (0, 8))	('myasthenia gravis', 'Disease', 'MESH:D009157', (135, 152))	('myasthenia', 'Phenotype', 'HP:0003473', (135, 145))	('autoimmune manifestations', 'Phenotype', 'HP:0002960', (29, 54))
54607	22554706	Evaluation of an infant who was the product of a consanguineous union that presented with candidal dermatitis and subsequent Staphylococcus aureus dermatitis resulted in the first description of autosomal recessive CMC disease due to a homozygous nonsense mutation in the IL-17RA gene (Q248X/Q248X).	('Staphylococcus aureus dermatitis', 'Phenotype', 'HP:0002726', (125, 157))	('dermatitis', 'Phenotype', 'HP:0011123', (147, 157))	('Q248X', 'Var', (292, 297))	('CMC', 'Phenotype', 'HP:0002728', (215, 218))	('candidal dermatitis', 'Phenotype', 'HP:0005411', (90, 109))	('Q248X', 'SUBSTITUTION', 'None', (292, 297))	('IL-17RA', 'Gene', '23765', (272, 279))	('autosomal recessive CMC disease', 'Disease', (195, 226))	('Q248X', 'Mutation', 'p.Q248X', (286, 291))	('autosomal recessive CMC disease', 'Disease', 'MESH:C535816', (195, 226))	('due to', 'Reg', (227, 233))	('dermatitis', 'Disease', 'MESH:D003872', (99, 109))	('dermatitis', 'Disease', 'MESH:D003872', (147, 157))	('dermatitis', 'Disease', (99, 109))	('Q248X', 'Mutation', 'p.Q248X', (292, 297))	('dermatitis', 'Disease', (147, 157))	('infant', 'Species', '9606', (17, 23))	('IL-17RA', 'Gene', (272, 279))	('Q248X', 'Var', (286, 291))	('Staphylococcus aureus', 'Species', '1280', (125, 146))	('Q248X', 'SUBSTITUTION', 'None', (286, 291))	('dermatitis', 'Phenotype', 'HP:0011123', (99, 109))
54608	22554706	The Q248X/Q248X mutation resulted in absent expression of IL-17RA on the patient's blood cells and fibroblasts and a complete absence of responsiveness to IL-17A/F.	('IL-17A', 'Gene', (155, 161))	('IL-17RA', 'Gene', (58, 65))	('Q248X', 'Var', (4, 9))	('expression', 'MPA', (44, 54))	('Q248X', 'Var', (10, 15))	('absence', 'NegReg', (126, 133))	('IL-17RA', 'Gene', '23765', (58, 65))	('patient', 'Species', '9606', (73, 80))	('IL-17A', 'Gene', '3605', (155, 161))	('absent', 'NegReg', (37, 43))	('Q248X', 'SUBSTITUTION', 'None', (4, 9))	('Q248X', 'Mutation', 'p.Q248X', (4, 9))	('Q248X', 'Mutation', 'p.Q248X', (10, 15))	('Q248X', 'SUBSTITUTION', 'None', (10, 15))
54609	22554706	Responsiveness to IL-17 cytokines was restored to the patient's fibroblasts by transfection with wild type IL-17RA, confirming the lack of IL-17RA expression as the cause the patient's CMC disease.	('patient', 'Species', '9606', (54, 61))	('IL-17', 'Gene', (18, 23))	('IL-17', 'Gene', '3605', (107, 112))	('IL-17RA', 'Gene', '23765', (107, 114))	('CMC disease', 'Disease', 'MESH:C535816', (185, 196))	('IL-17', 'Gene', '3605', (18, 23))	('IL-17', 'Gene', (107, 112))	('cause', 'Reg', (165, 170))	('patient', 'Species', '9606', (175, 182))	('IL-17', 'Gene', '3605', (139, 144))	('IL-17RA', 'Gene', '23765', (139, 146))	('lack', 'Var', (131, 135))	('IL-17', 'Gene', (139, 144))	('IL-17RA', 'Gene', (107, 114))	('CMC disease', 'Disease', (185, 196))	('Responsiveness', 'MPA', (0, 14))	('CMC', 'Phenotype', 'HP:0002728', (185, 188))	('IL-17RA', 'Gene', (139, 146))
54610	22554706	Additionally, Puel et al evaluated a multiplex family with autosomal dominant inheritance of CMC disease, identifying a heterozygous missense mutation in the IL-17F gene.	('IL-17F', 'Gene', '112744', (158, 164))	('CMC', 'Phenotype', 'HP:0002728', (93, 96))	('IL-17F', 'Gene', (158, 164))	('CMC disease', 'Disease', 'MESH:C535816', (93, 104))	('missense mutation', 'Var', (133, 150))	('CMC disease', 'Disease', (93, 104))
54611	22554706	The mutation resulted in the substitution of the serine residue at position 65 of the protein with a leucine residue (S65L).	('substitution', 'Var', (29, 41))	('resulted in', 'Reg', (13, 24))	('serine', 'Chemical', 'MESH:D012694', (49, 55))	('leucine', 'Chemical', 'MESH:D007930', (101, 108))	('S65L', 'Mutation', 'rs748486078', (118, 122))
54612	22554706	The S65 residue is conserved across all mammalian species and is believed to be involved in ligand-receptor interaction.	('involved', 'Reg', (80, 88))	('mammalian', 'Species', '9606', (40, 49))	('interaction', 'Interaction', (108, 119))	('S65', 'Var', (4, 7))
54613	22554706	The production of inflammatory cytokines by normal fibroblasts and blood cells elicited by mutant IL-17F(S65L) homodimers was severely impaired.	('IL-17F', 'Gene', '112744', (98, 104))	('impaired', 'NegReg', (135, 143))	('IL-17F', 'Gene', (98, 104))	('production of inflammatory cytokines', 'MPA', (4, 40))	('homodimers', 'Protein', (111, 121))	('mutant', 'Var', (91, 97))	('S65L', 'Mutation', 'rs748486078', (105, 109))
54619	22554706	In the cases of STAT1, STAT3, IL12Rbeta1, DOCK8, IL-17RA, and IL-17F mutations, thorough analyses of the molecular mechanisms that underlie these disorders has revealed defective Th17 cell development or effector function that results in susceptibility to CMC disease.	('STAT3', 'Gene', (23, 28))	('defective', 'NegReg', (169, 178))	('effector function', 'CPA', (204, 221))	('IL-17RA', 'Gene', '23765', (49, 56))	('STAT3', 'Gene', '6774', (23, 28))	('IL12Rbeta1', 'Gene', (30, 40))	('DOCK8', 'Gene', (42, 47))	('STAT1', 'Gene', (16, 21))	('mutations', 'Var', (69, 78))	('CMC disease', 'Disease', (256, 267))	('IL12Rbeta1', 'Gene', '3594', (30, 40))	('CMC disease', 'Disease', 'MESH:C535816', (256, 267))	('IL-17F', 'Gene', (62, 68))	('STAT1', 'Gene', '6772', (16, 21))	('susceptibility', 'Reg', (238, 252))	('DOCK8', 'Gene', '81704', (42, 47))	('IL-17RA', 'Gene', (49, 56))	('IL-17F', 'Gene', '112744', (62, 68))	('CMC', 'Phenotype', 'HP:0002728', (256, 259))	('Th17 cell development', 'CPA', (179, 200))
54623	22554706	Analysis of Th17 cell populations in MyD88 and IRAK-4 deficient patients was worthwhile because although they do not suffer CMC disease, the finding of normal Th17 cell populations in these patients demonstrated that IL-1beta is not absolutely required for Th17 cell development in humans.	('CMC', 'Phenotype', 'HP:0002728', (124, 127))	('patients', 'Species', '9606', (64, 72))	('patients', 'Species', '9606', (190, 198))	('IRAK-4', 'Gene', (47, 53))	('CMC disease', 'Disease', 'MESH:C535816', (124, 135))	('MyD88', 'Gene', (37, 42))	('MyD88', 'Gene', '4615', (37, 42))	('IRAK-4', 'Gene', '51135', (47, 53))	('humans', 'Species', '9606', (282, 288))	('deficient', 'Var', (54, 63))	('CMC disease', 'Disease', (124, 135))
54624	22554706	In rare cases, oral candidiasis has been observed in patients with mutations in NEMO/IKKgamma, who have reduced NFkappaB activation.	('NFkappaB', 'Protein', (112, 120))	('reduced', 'NegReg', (104, 111))	('patients', 'Species', '9606', (53, 61))	('oral candidiasis', 'Disease', (15, 31))	('IKKgamma', 'Gene', (85, 93))	('activation', 'MPA', (121, 131))	('IKKgamma', 'Gene', '8517', (85, 93))	('mutations', 'Var', (67, 76))	('oral candidiasis', 'Disease', 'MESH:D002180', (15, 31))	('NEMO', 'Gene', (80, 84))	('NEMO', 'Gene', '8517', (80, 84))
54629	22554706	Analysis of STAT1 mutations reveals great phenotypic variation: CMC disease, mycobacterial disease, or viral disease.	('CMC disease', 'Disease', (64, 75))	('viral disease', 'Disease', 'MESH:D001102', (103, 116))	('mycobacterial disease', 'Disease', 'MESH:C567070', (77, 98))	('mycobacterial disease', 'Disease', (77, 98))	('CMC', 'Phenotype', 'HP:0002728', (64, 67))	('STAT1', 'Gene', (12, 17))	('viral disease', 'Disease', (103, 116))	('CMC disease', 'Disease', 'MESH:C535816', (64, 75))	('STAT1', 'Gene', '6772', (12, 17))	('mutations', 'Var', (18, 27))
54673	18699992	By immunoprecipitation, target antigens (in decreasing order of incidence) include desmoglein 3, desmoglein 1, envoplakin (210 kd), periplakin (190 kd), desmoplakin I (250 kd), desmoplakin II (210 kd) and bullous pemphigoid antigen I (230 kd).	('desmoplakin I', 'Disease', (153, 166))	('envoplakin', 'Gene', (111, 121))	('desmoglein 3', 'Gene', (83, 95))	('desmoplakin I', 'Disease', 'MESH:D020754', (177, 190))	('desmoplakin II', 'Disease', 'MESH:C537730', (177, 191))	('desmoplakin I', 'Disease', 'MESH:D020754', (153, 166))	('envoplakin', 'Gene', '2125', (111, 121))	('bullous pemphigoid antigen', 'Disease', (205, 231))	('desmoplakin II', 'Disease', (177, 191))	('desmoglein 3', 'Gene', '1830', (83, 95))	('desmoglein 1', 'Gene', (97, 109))	('210 kd', 'Var', (123, 129))	('desmoglein 1', 'Gene', '1828', (97, 109))
54739	31644609	Lesions may also affect the nasopharynx, oropharynx, and larynx, leading to odynophagia, dysphagia, and hoarseness that require assessment by an ear, nose, and throat specialist.	('dysphagia', 'Phenotype', 'HP:0002015', (89, 98))	('hoarseness', 'Disease', (104, 114))	('odynophagia, dysphagia', 'Disease', 'MESH:D003680', (76, 98))	('hoarseness', 'Phenotype', 'HP:0001609', (104, 114))	('affect', 'Reg', (17, 23))	('odynophagia', 'Phenotype', 'HP:0032043', (76, 87))	('leading to', 'Reg', (65, 75))	('Lesions', 'Var', (0, 7))
54786	31644609	Autoantibodies against these intercellular and intracellular adhesion glycoproteins trigger bronchial epithelial desquamation and sloughing into the airway lumen, resulting in epithelial inflammation and subsequent fibrosis.	('inflammation', 'Disease', 'MESH:D007249', (187, 199))	('trigger', 'Reg', (84, 91))	('inflammation', 'Disease', (187, 199))	('sloughing into the', 'CPA', (130, 148))	('bronchial epithelial desquamation', 'Disease', (92, 125))	('desquamation', 'Phenotype', 'HP:0040189', (113, 125))	('Autoantibodies', 'Var', (0, 14))	('fibrosis', 'Disease', 'MESH:D005355', (215, 223))	('fibrosis', 'Disease', (215, 223))
54791	31644609	Anti-epiplakin antibodies injected into mice induce a disruption of bronchial epithelium integrity and mononuclear cell inflammation, providing evidence of its pathogenic role in bronchiolitis obliterans.	('bronchiolitis obliterans', 'Disease', (179, 203))	('bronchiolitis', 'Phenotype', 'HP:0011950', (179, 192))	('disruption', 'NegReg', (54, 64))	('Anti-epiplakin', 'Protein', (0, 14))	('bronchiolitis obliterans', 'Disease', 'MESH:D001989', (179, 203))	('inflammation', 'Disease', 'MESH:D007249', (120, 132))	('bronchiolitis obliterans', 'Phenotype', 'HP:0011946', (179, 203))	('mice', 'Species', '10090', (40, 44))	('antibodies', 'Var', (15, 25))	('inflammation', 'Disease', (120, 132))
54877	31757999	Within the past years, a deregulation or mutation of the activin signaling axis was found in numerous malignancies.	('deregulation', 'Var', (25, 37))	('malignancies', 'Disease', 'MESH:D009369', (102, 114))	('found', 'Reg', (84, 89))	('mutation', 'Var', (41, 49))	('malignancies', 'Disease', (102, 114))	('activin', 'Gene', (57, 64))	('activin', 'Gene', '83729', (57, 64))
54928	31757999	In particular, low number of immature tumor vessels showed a 35-fold higher risk for tumor recurrence compared to TETs with high number of immature tumor vessels (HR 35.3; p = 0.021).	('tumor', 'Phenotype', 'HP:0002664', (38, 43))	('tumor', 'Disease', (38, 43))	('tumor', 'Disease', (85, 90))	('low', 'Var', (15, 18))	('tumor', 'Phenotype', 'HP:0002664', (148, 153))	('tumor', 'Disease', 'MESH:D009369', (148, 153))	('immature tumor', 'Disease', (139, 153))	('TETs', 'Disease', 'MESH:C536905', (114, 118))	('immature tumor', 'Disease', (29, 43))	('tumor', 'Disease', (148, 153))	('TETs', 'Disease', (114, 118))	('tumor', 'Disease', 'MESH:D009369', (85, 90))	('tumor', 'Disease', 'MESH:D009369', (38, 43))	('immature tumor', 'Disease', 'MESH:D013724', (29, 43))	('tumor', 'Phenotype', 'HP:0002664', (85, 90))	('immature tumor', 'Disease', 'MESH:D013724', (139, 153))
54935	31757999	In particular, high Follistatin serum levels were associated with shorter overall survival (OS) and poor prognosis in hepatocellular carcinoma, emergence of bone metastases in prostate cancer or tumor proliferation of lung adenocarcinoma cells.	('high', 'Var', (15, 19))	('lung adenocarcinoma', 'Phenotype', 'HP:0030078', (218, 237))	('shorter', 'NegReg', (66, 73))	('bone metastases in prostate cancer', 'Disease', 'MESH:D011471', (157, 191))	('serum levels', 'MPA', (32, 44))	('cancer', 'Phenotype', 'HP:0002664', (185, 191))	('hepatocellular carcinoma', 'Disease', 'MESH:D006528', (118, 142))	('hepatocellular carcinoma', 'Phenotype', 'HP:0001402', (118, 142))	('overall survival', 'MPA', (74, 90))	('tumor proliferation of lung adenocarcinoma', 'Disease', 'MESH:C538231', (195, 237))	('carcinoma', 'Phenotype', 'HP:0030731', (133, 142))	('carcinoma', 'Phenotype', 'HP:0030731', (228, 237))	('hepatocellular carcinoma', 'Disease', (118, 142))	('Follistatin', 'MPA', (20, 31))	('tumor proliferation of lung adenocarcinoma', 'Disease', (195, 237))	('bone metastases in prostate cancer', 'Disease', (157, 191))	('prostate cancer', 'Phenotype', 'HP:0012125', (176, 191))	('tumor', 'Phenotype', 'HP:0002664', (195, 200))
54939	31757999	demonstrated that cultured lung adenocarcinoma cells secreted Follistatin, and that inhibition of Follistatin led to significantly augmented Activin A induced apoptosis.	('Activin', 'Gene', (141, 148))	('augmented', 'PosReg', (131, 140))	('carcinoma', 'Phenotype', 'HP:0030731', (37, 46))	('lung adenocarcinoma', 'Disease', 'MESH:C538231', (27, 46))	('lung adenocarcinoma', 'Phenotype', 'HP:0030078', (27, 46))	('Activin', 'Gene', '83729', (141, 148))	('inhibition', 'Var', (84, 94))	('lung adenocarcinoma', 'Disease', (27, 46))	('Follistatin', 'Gene', (98, 109))	('apoptosis', 'CPA', (159, 168))
54941	31757999	In accordance to that, inhibition of p21 increased endothelial cell proliferation and resistance to Activin A mediated growth inhibition.	('endothelial cell proliferation', 'CPA', (51, 81))	('increased', 'PosReg', (41, 50))	('inhibition', 'Var', (23, 33))	('Activin', 'Gene', (100, 107))	('resistance to', 'CPA', (86, 99))	('p21', 'Gene', (37, 40))	('Activin', 'Gene', '83729', (100, 107))	('p21', 'Gene', '644914', (37, 40))
54963	31757999	Similar, in HeLa cells, nuclear expression of Follistatin delayed glucose deprivation-induced apoptosis by attenuating RNA synthesis, which represents a key process of cellular energy homeostasis and cell survival.	('attenuating', 'NegReg', (107, 118))	('HeLa', 'CellLine', 'CVCL:0030', (12, 16))	('nuclear expression', 'Var', (24, 42))	('Follistatin', 'Gene', (46, 57))	('glucose deprivation-induced', 'Disease', (66, 93))	('RNA synthesis', 'MPA', (119, 132))	('glucose', 'Chemical', 'MESH:D005947', (66, 73))
55313	32985506	Thymic abnormalities often affect T-cell homeostasis and function, and have been thought to be a main cause of autoimmune diseases such as MG in patients.	('patients', 'Species', '9606', (145, 153))	('function', 'MPA', (57, 65))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (111, 130))	('cause', 'Reg', (102, 107))	('autoimmune diseases', 'Disease', 'MESH:D001327', (111, 130))	('T-cell homeostasis', 'MPA', (34, 52))	('Thymic abnormalities', 'Var', (0, 20))	('Thymic abnormalities', 'Phenotype', 'HP:0000777', (0, 20))	('autoimmune diseases', 'Disease', (111, 130))	('affect', 'Reg', (27, 33))
55319	32985506	Consistently, we observed more CD31+ naive CD4+ T cells in thymoma patients compared to patients with other thymic tumors including thymic cysts, thymic carcinomas, teratomas, and lymphomas (Supplementary Fig.	('teratomas', 'Phenotype', 'HP:0009792', (165, 174))	('carcinoma', 'Phenotype', 'HP:0030731', (153, 162))	('carcinomas', 'Phenotype', 'HP:0030731', (153, 163))	('lymphomas', 'Disease', 'MESH:D008223', (180, 189))	('thymoma', 'Disease', (59, 66))	('lymphomas', 'Phenotype', 'HP:0002665', (180, 189))	('thymoma', 'Phenotype', 'HP:0100522', (59, 66))	('teratoma', 'Phenotype', 'HP:0009792', (165, 173))	('more', 'PosReg', (26, 30))	('teratomas', 'Disease', 'MESH:D013724', (165, 174))	('CD31+', 'Var', (31, 36))	('tumors', 'Phenotype', 'HP:0002664', (115, 121))	('CD4', 'Gene', '920', (43, 46))	('thymic carcinomas', 'Disease', (146, 163))	('tumor', 'Phenotype', 'HP:0002664', (115, 120))	('lymphomas', 'Disease', (180, 189))	('patients', 'Species', '9606', (67, 75))	('teratomas', 'Disease', (165, 174))	('thymic carcinomas', 'Disease', 'MESH:D013953', (146, 163))	('CD4', 'Gene', (43, 46))	('lymphoma', 'Phenotype', 'HP:0002665', (180, 188))	('thymic tumors', 'Disease', (108, 121))	('thymoma', 'Disease', 'MESH:D013945', (59, 66))	('patients', 'Species', '9606', (88, 96))	('thymic tumors', 'Disease', 'MESH:D013953', (108, 121))	('thymic tumor', 'Phenotype', 'HP:0100521', (108, 120))
55329	32985506	In-line with findings in the discovery set, CD31+ naive T cells were increased in patients with thymomas (Supplementary Fig.	('thymomas', 'Disease', (96, 104))	('CD31+', 'Var', (44, 49))	('increased', 'PosReg', (69, 78))	('patients', 'Species', '9606', (82, 90))	('thymomas', 'Disease', 'MESH:D013945', (96, 104))	('thymoma', 'Phenotype', 'HP:0100522', (96, 103))
55397	32985506	Our study shows more borderline cases in IL-8 assay in patients aged 40 years and younger, compared to patients aged over 40 years.	('assay', 'Var', (46, 51))	('IL-8', 'Gene', '3576', (41, 45))	('IL-8', 'Gene', (41, 45))	('patients', 'Species', '9606', (55, 63))	('patients', 'Species', '9606', (103, 111))
55503	19381821	EGFR mutation analysis was performed on five tumor blocks.	('tumor', 'Phenotype', 'HP:0002664', (45, 50))	('EGFR', 'Gene', (0, 4))	('tumor', 'Disease', (45, 50))	('EGFR', 'Gene', '1956', (0, 4))	('mutation', 'Var', (5, 13))	('tumor', 'Disease', 'MESH:D009369', (45, 50))
55504	19381821	None of the tumor blocks subjected to genomic analyses demonstrated presence of EGFR or KRAS mutations.	('mutations', 'Var', (93, 102))	('tumor', 'Disease', 'MESH:D009369', (12, 17))	('EGFR', 'Gene', '1956', (80, 84))	('EGFR', 'Gene', (80, 84))	('tumor', 'Phenotype', 'HP:0002664', (12, 17))	('KRAS', 'Gene', (88, 92))	('KRAS', 'Gene', '3845', (88, 92))	('tumor', 'Disease', (12, 17))
55571	31116133	Several recent case reports of unusual presentations of patients with neutralizing autoantibodies to IFN-gamma and granulocyt macrophage colony-stimulating factor and expand the spectrum of clinical manifestations and suggest that anticytokine-mediated acquired immunodeficiency causing susceptibility to infection may be underdiagnosed.	('infection', 'Disease', (305, 314))	('acquired immunodeficiency', 'Disease', (253, 278))	('patients', 'Species', '9606', (56, 64))	('infection', 'Disease', 'MESH:D007239', (305, 314))	('immunodeficiency', 'Phenotype', 'HP:0002721', (262, 278))	('granulocyt macrophage colony-stimulating factor', 'Gene', '1437', (115, 162))	('IFN-gamma', 'Gene', '3458', (101, 110))	('IFN-gamma', 'Gene', (101, 110))	('man', 'Species', '9606', (199, 202))	('acquired immunodeficiency', 'Disease', 'MESH:D000163', (253, 278))	('granulocyt macrophage colony-stimulating factor', 'Gene', (115, 162))	('neutralizing', 'Var', (70, 82))	('susceptibility to infection', 'Phenotype', 'HP:0002719', (287, 314))
55573	31116133	The spectrum of identified infections in patients with neutralizing antibodies to IFN-gamma has a strong endemic component.	('infection', 'Disease', (27, 36))	('patients', 'Species', '9606', (41, 49))	('IFN-gamma', 'Gene', (82, 91))	('IFN-gamma', 'Gene', '3458', (82, 91))	('infection', 'Disease', 'MESH:D007239', (27, 36))	('neutralizing antibodies', 'Var', (55, 78))
55586	31116133	Autoantibodies to cytokines have been identified as an emerging alternative pathological mechanism leading to a compromised immune response and susceptibility to infection and may be considered as autoimmune phenocopies of primary immunodeficiencies.	('susceptibility to infection', 'Phenotype', 'HP:0002719', (144, 171))	('autoimmune phenocopies of primary immunodeficiencies', 'Disease', 'MESH:C580174', (197, 249))	('immunodeficiencies', 'Phenotype', 'HP:0002721', (231, 249))	('infection', 'Disease', (162, 171))	('Autoantibodies', 'Var', (0, 14))	('infection', 'Disease', 'MESH:D007239', (162, 171))	('compromised immune response', 'Phenotype', 'HP:0002721', (112, 139))	('immune response', 'CPA', (124, 139))
55595	31116133	Neutralizing autoantibodies to IFN-gamma (AIGA) are the autoimmune correlate to primary Mendelian defects in the IFN-gamma signalling pathway.	('IFN-gamma', 'Gene', '3458', (31, 40))	('IFN-gamma', 'Gene', (31, 40))	('Mendelian defects', 'Disease', (88, 105))	('Neutralizing', 'Var', (0, 12))	('Mendelian defects', 'Disease', 'MESH:D005128', (88, 105))	('IFN-gamma', 'Gene', '3458', (113, 122))	('IFN-gamma', 'Gene', (113, 122))
55622	31116133	Auto-antibodies to GM-CSF are the autoimmune correlate of the much rarer primary GM-CSF-Receptor deficiency causing pulmonary alveolar proteinosis (PAP) by impairing the alveolar macrophage mediated surfactant lipid and protein metabolism and leading to accumulation and respiratory insufficiency.	('pulmonary alveolar proteinosis', 'Disease', 'MESH:D011649', (116, 146))	('respiratory insufficiency', 'Phenotype', 'HP:0002093', (271, 296))	('GM-CSF', 'Gene', '1437', (19, 25))	('alveolar proteinosis', 'Phenotype', 'HP:0006517', (126, 146))	('GM-CSF', 'Gene', '1437', (81, 87))	('pulmonary alveolar proteinosis', 'Disease', (116, 146))	('accumulation', 'MPA', (254, 266))	('causing', 'Reg', (108, 115))	('alveolar', 'Disease', (170, 178))	('lipid', 'Chemical', 'MESH:D008055', (210, 215))	('alveolar', 'Disease', 'MESH:D002282', (126, 134))	('respiratory insufficiency', 'Disease', (271, 296))	('impairing', 'NegReg', (156, 165))	('alveolar', 'Disease', 'MESH:D002282', (170, 178))	('GM-CSF', 'Gene', (19, 25))	('GM-CSF', 'Gene', (81, 87))	('leading to', 'Reg', (243, 253))	('respiratory insufficiency', 'Disease', 'MESH:D012131', (271, 296))	('alveolar', 'Disease', (126, 134))	('deficiency', 'Var', (97, 107))
55647	31116133	Auto immune regulator (AIRE) deficiency causes autoimmune polyglandular syndrome type I (APS1), which is a complex autoimmune syndrome with CMC as its only infectious manifestation.	('AIRE', 'Gene', (23, 27))	('causes', 'Reg', (40, 46))	('APS1', 'Gene', '326', (89, 93))	('AIRE', 'Gene', '326', (23, 27))	('autoimmune syndrome', 'Disease', (115, 134))	('man', 'Species', '9606', (167, 170))	('autoimmune polyglandular syndrome type I', 'Disease', 'MESH:D016884', (47, 87))	('autoimmune polyglandular syndrome type I', 'Disease', (47, 87))	('APS1', 'Gene', (89, 93))	('autoimmune syndrome', 'Phenotype', 'HP:0002960', (115, 134))	('CMC', 'Phenotype', 'HP:0002728', (140, 143))	('deficiency', 'Var', (29, 39))	('autoimmune syndrome', 'Disease', 'MESH:D001327', (115, 134))
55651	31116133	presented a patient with chronic variable immunodeficiency caused by a heterozygous NFKB2 mutation.	('NFKB2', 'Gene', (84, 89))	('immunodeficiency', 'Phenotype', 'HP:0002721', (42, 58))	('immunodeficiency', 'Disease', (42, 58))	('immunodeficiency', 'Disease', 'MESH:D007153', (42, 58))	('NFKB2', 'Gene', '4791', (84, 89))	('caused by', 'Reg', (59, 68))	('patient', 'Species', '9606', (12, 19))	('mutation', 'Var', (90, 98))
55656	31116133	In line with this are findings in hypomorphic recombination activation gene deficient patients and Thymoma patients where the incidence and complexity of the patients anticytokine patterns where positively correlated with increased susceptibilities to infections.	('infection', 'Disease', (252, 261))	('patients', 'Species', '9606', (107, 115))	('infection', 'Disease', 'MESH:D007239', (252, 261))	('anticytokine', 'MPA', (167, 179))	('Thymoma', 'Disease', (99, 106))	('Thymoma', 'Phenotype', 'HP:0100522', (99, 106))	('susceptibilities', 'MPA', (232, 248))	('susceptibilities to infections', 'Phenotype', 'HP:0002719', (232, 262))	('Thymoma', 'Disease', 'MESH:D013945', (99, 106))	('patients', 'Species', '9606', (158, 166))	('deficient', 'Var', (76, 85))	('correlated', 'Reg', (206, 216))	('patients', 'Species', '9606', (86, 94))
55661	31116133	One patient with complete gp130 deficiency presented early onset severe recurrent bacterial infections including Staphylococcus aureus, Streptococcus milleri and GrpA Streptococci, but not fungal infections and an impaired acute phase response.	('gp130', 'Gene', '3572', (26, 31))	('Staphylococcus aureus', 'Species', '1280', (113, 134))	('Streptococcus milleri', 'Species', '33040', (136, 157))	('bacterial infections', 'Disease', 'MESH:D001424', (82, 102))	('Staphylococcus aureus', 'Disease', (113, 134))	('patient', 'Species', '9606', (4, 11))	('impaired acute phase response', 'Phenotype', 'HP:0031404', (214, 243))	('recurrent bacterial infections', 'Phenotype', 'HP:0002718', (72, 102))	('bacterial infections', 'Phenotype', 'HP:0002718', (82, 102))	('gp130', 'Gene', (26, 31))	('bacterial infections', 'Disease', (82, 102))	('fungal infections', 'Disease', (189, 206))	('fungal infections', 'Phenotype', 'HP:0002841', (189, 206))	('deficiency', 'Var', (32, 42))	('fungal infections', 'Disease', 'MESH:D009181', (189, 206))
55672	31116133	Autoantibodies to cytokines may cause acquired susceptibility to infection.	('susceptibility to infection', 'Phenotype', 'HP:0002719', (47, 74))	('infection', 'Disease', (65, 74))	('Autoantibodies', 'Var', (0, 14))	('infection', 'Disease', 'MESH:D007239', (65, 74))	('acquired susceptibility', 'MPA', (38, 61))	('cause', 'Reg', (32, 37))
55690	20859134	None of 5 samples evaluated by DNA sequencing showed evidence of EGFR or KRAS mutations.	('KRAS', 'Gene', (73, 77))	('EGFR', 'Gene', '1956', (65, 69))	('KRAS', 'Gene', '3845', (73, 77))	('EGFR', 'Gene', (65, 69))	('mutations', 'Var', (78, 87))
55706	20859134	This patient harbored an activating mutation in exon 11 of the KIT gene (V5660del).	('patient', 'Species', '9606', (5, 12))	('V5660del', 'Var', (73, 81))	('activating', 'PosReg', (25, 35))	('V5660del', 'Mutation', 'p.5660delV', (73, 81))	('KIT', 'Gene', (63, 66))
55719	20859134	HDAC inhibition can alter gene expression and induce apoptosis.	('HDAC', 'Gene', (0, 4))	('apoptosis', 'CPA', (53, 62))	('HDAC', 'Gene', '9734', (0, 4))	('gene expression', 'MPA', (26, 41))	('inhibition', 'Var', (5, 15))	('alter', 'Reg', (20, 25))	('induce', 'Reg', (46, 52))
55734	20859134	In one case a patient was found to have a missense mutation in exon 17 (D820E) of the c-KIT gene that was detected by direct sequencing.	('D820E', 'Mutation', 'rs1057519711', (72, 77))	('c-KIT', 'Gene', (86, 91))	('missense mutation in', 'Var', (42, 62))	('patient', 'Species', '9606', (14, 21))	('c-KIT', 'Gene', '3815', (86, 91))	('D820E', 'Var', (72, 77))
55770	20859134	SU014813 is an orally administered multi-kinase inhibitor that targets VEGFRs, PDGFRs, KIT and FLT-3.	('SU014813', 'Chemical', '-', (0, 8))	('VEGFRs', 'Gene', (71, 77))	('KIT', 'Gene', (87, 90))	('FLT-3', 'Gene', '2322', (95, 100))	('SU014813', 'Var', (0, 8))	('PDGFR', 'Gene', (79, 84))	('VEGFRs', 'Gene', '2321;3791', (71, 77))	('PDGFR', 'Gene', '5159', (79, 84))	('FLT-3', 'Gene', (95, 100))
55780	20859134	PHA-848125 is an orally administered potent inhibitor of the CDK2/Cyclin A complex and TRKA.	('Cyclin A', 'Gene', (66, 74))	('PHA-848125', 'Var', (0, 10))	('CDK2', 'Gene', (61, 65))	('TRKA', 'Gene', (87, 91))	('CDK2', 'Gene', '1017', (61, 65))	('Cyclin A', 'Gene', '890', (66, 74))	('TRKA', 'Gene', '4914', (87, 91))
55782	20859134	Based on these results an ongoing multicenter phase II study is evaluating PHA-848125-AC in patients with thymic carcinoma (ClinicalTrials.gov Identifier: NCT01011439).	('PHA-848125-AC', 'Var', (75, 88))	('patients', 'Species', '9606', (92, 100))	('thymic carcinoma', 'Disease', (106, 122))	('thymic carcinoma', 'Disease', 'MESH:D013945', (106, 122))	('carcinoma', 'Phenotype', 'HP:0030731', (113, 122))
55802	17498299	Strong CD57 positivity in thymomas may suggest a concomitant neuromuscular disorder, notably myasthenia gravis.	('neuromuscular disorder', 'Disease', (61, 83))	('thymomas', 'Disease', (26, 34))	('myasthenia gravis', 'Disease', (93, 110))	('thymomas', 'Disease', 'MESH:D013945', (26, 34))	('neuromuscular disorder', 'Disease', 'MESH:D009468', (61, 83))	('thymoma', 'Phenotype', 'HP:0100522', (26, 33))	('CD57', 'Gene', (7, 11))	('myasthenia gravis', 'Disease', 'MESH:D009157', (93, 110))	('CD57', 'Gene', '27087', (7, 11))	('positivity', 'Var', (12, 22))	('myasthenia', 'Phenotype', 'HP:0003473', (93, 103))
55831	17498299	The majority of non-neoplastic lymphocytes showed an immunophenotype characteristic of immature T cells (CD3+, CD5+, CD1a+, CD99+; Ki67 proliferation index > 80%).	('CD1a', 'Gene', (117, 121))	('CD99', 'Gene', '4267', (124, 128))	('CD3+', 'Var', (105, 109))	('CD1a', 'Gene', '909', (117, 121))	('CD5', 'Gene', (111, 114))	('CD99', 'Gene', (124, 128))	('CD5', 'Gene', '921', (111, 114))
55833	17498299	The lymphocytes in foci of medullary differentiation showed a mature T cell phenotype (CD3+, CD5+, CD1a-, CD99-; Ki67 proliferation index <10%) and contained a large number of CD20+ B lymphocytes.	('CD1a', 'Gene', '909', (99, 103))	('CD99', 'Gene', (106, 110))	('CD5', 'Gene', (93, 96))	('CD1a', 'Gene', (99, 103))	('CD20', 'Gene', '54474', (176, 180))	('CD20', 'Gene', (176, 180))	('CD5', 'Gene', '921', (93, 96))	('CD3+', 'Var', (87, 91))	('CD99', 'Gene', '4267', (106, 110))
55836	17498299	Admixed T lymphocytes were CD3+, CD5+, CD1a+, CD99+, with high Ki67 proliferation index (>80%), whereas lymphocytes in the medullary islands were mature T cells (CD3+, CD5+, CD1a-, CD99-; Ki67 proliferation index <10%) and CD20+ B cells.	('CD5', 'Gene', (168, 171))	('CD1a', 'Gene', '909', (174, 178))	('CD5', 'Gene', '921', (168, 171))	('CD99', 'Gene', (181, 185))	('CD20', 'Gene', '54474', (223, 227))	('CD20', 'Gene', (223, 227))	('CD1a', 'Gene', (39, 43))	('CD99', 'Gene', '4267', (46, 50))	('CD1a', 'Gene', (174, 178))	('CD5', 'Gene', (33, 36))	('CD1a', 'Gene', '909', (39, 43))	('CD99', 'Gene', '4267', (181, 185))	('CD99', 'Gene', (46, 50))	('CD3+', 'Var', (162, 166))	('CD5', 'Gene', '921', (33, 36))
55838	17498299	Type B2 and B3 thymomas showed a similar immunophenotype with a variable CK7 expression, and immature intratumoral non-neoplastic T lymphocytes (CD3+, CD5+, CD1a+, CD99+; Ki67 proliferation index >80%).	('CD99', 'Gene', '4267', (164, 168))	('CD5', 'Gene', (151, 154))	('expression', 'MPA', (77, 87))	('CD3+', 'Var', (145, 149))	('CD1a', 'Gene', '909', (157, 161))	('tumor', 'Phenotype', 'HP:0002664', (107, 112))	('tumor', 'Disease', (107, 112))	('CD5', 'Gene', '921', (151, 154))	('thymoma', 'Phenotype', 'HP:0100522', (15, 22))	('CD99', 'Gene', (164, 168))	('CK7', 'Gene', '3855', (73, 76))	('CD1a', 'Gene', (157, 161))	('thymomas', 'Disease', (15, 23))	('thymomas', 'Disease', 'MESH:D013945', (15, 23))	('tumor', 'Disease', 'MESH:D009369', (107, 112))	('CK7', 'Gene', (73, 76))
55840	17498299	Small stromal lymphoid aggregates containing mature T lymphocytes (CD3+, CD5+, CD1a-, CD99-, Ki67 proliferation index <10%) and CD20+ B lymphocytes were observed in all B2 and B3 thymomas.	('thymomas', 'Disease', (179, 187))	('thymomas', 'Disease', 'MESH:D013945', (179, 187))	('CD3+', 'Var', (67, 71))	('CD1a', 'Gene', '909', (79, 83))	('CD99', 'Gene', '4267', (86, 90))	('CD5', 'Gene', (73, 76))	('CD20', 'Gene', '54474', (128, 132))	('CD20', 'Gene', (128, 132))	('CD5', 'Gene', '921', (73, 76))	('thymoma', 'Phenotype', 'HP:0100522', (179, 186))	('CD99', 'Gene', (86, 90))	('CD1a', 'Gene', (79, 83))
55848	17498299	The stroma contained large lymphocytic aggregates containing a predominant cell population of CD20 B lymphocytes and mature T cells (CD3+, CD5+, CD1a-, CD99-, Ki67 proliferation index <10%).	('CD1a', 'Gene', (145, 149))	('CD99', 'Gene', '4267', (152, 156))	('CD3+', 'Var', (133, 137))	('CD1a', 'Gene', '909', (145, 149))	('CD20', 'Gene', '54474', (94, 98))	('CD20', 'Gene', (94, 98))	('CD5', 'Gene', (139, 142))	('CD99', 'Gene', (152, 156))	('CD5', 'Gene', '921', (139, 142))
55862	17498299	Only few studies have addressed the prevalence of neuroendocrine differentiation in human thymic neoplasms and demonstrated reactivity for synaptophysin, neuron-specific enolase, and/or chromogranin in 58% thymic carcinomas and atypical thymomas.	('neuroendocrine differentiation', 'CPA', (50, 80))	('synaptophysin', 'Gene', '6855', (139, 152))	('thymic carcinomas', 'Disease', 'MESH:D013945', (206, 223))	('neoplasms', 'Disease', (97, 106))	('thymomas', 'Disease', 'MESH:D013945', (237, 245))	('thymic carcinomas', 'Disease', (206, 223))	('thymomas', 'Disease', (237, 245))	('thymic neoplasms', 'Phenotype', 'HP:0100521', (90, 106))	('carcinoma', 'Phenotype', 'HP:0030731', (213, 222))	('carcinomas', 'Phenotype', 'HP:0030731', (213, 223))	('neoplasms', 'Phenotype', 'HP:0002664', (97, 106))	('neoplasm', 'Phenotype', 'HP:0002664', (97, 105))	('thymoma', 'Phenotype', 'HP:0100522', (237, 244))	('reactivity', 'Var', (124, 134))	('human', 'Species', '9606', (84, 89))	('neuron-specific enolase', 'Gene', (154, 177))	('synaptophysin', 'Gene', (139, 152))	('neoplasms', 'Disease', 'MESH:D009369', (97, 106))	('neuron-specific enolase', 'Gene', '2026', (154, 177))
55865	17498299	In their excellent study, Pan et al reported CD57 positivity in 76% short-spindled and 80% long-spindled variants.	('CD57', 'Gene', (45, 49))	('short-spindled', 'Disease', (68, 82))	('positivity', 'Var', (50, 60))	('CD57', 'Gene', '27087', (45, 49))
55881	17498299	In agreement with previous reports, in this study, the stromal lymphoid cell population in the MNT contained numerous CD20+ B cells and mature T cells, whereas intratumoral lymphocytes showed an immature T cell phenotype (CD3+, CD1a+, CD99+, Ki67 proliferation index >80%).	('CD99', 'Gene', (235, 239))	('CD1a', 'Gene', (228, 232))	('CD3+', 'Var', (222, 226))	('CD99', 'Gene', '4267', (235, 239))	('tumor', 'Disease', 'MESH:D009369', (165, 170))	('tumor', 'Phenotype', 'HP:0002664', (165, 170))	('CD1a', 'Gene', '909', (228, 232))	('Ki67 proliferation index', 'CPA', (242, 266))	('CD20', 'Gene', '54474', (118, 122))	('CD20', 'Gene', (118, 122))	('tumor', 'Disease', (165, 170))
55893	17498299	Strong CD57 positivity in neoplastic epithelial cells in thymomas may suggest a concomitant neuromuscular disorder, notably myasthenia gravis.	('neuromuscular disorder', 'Disease', 'MESH:D009468', (92, 114))	('myasthenia', 'Phenotype', 'HP:0003473', (124, 134))	('myasthenia gravis', 'Disease', (124, 141))	('myasthenia gravis', 'Disease', 'MESH:D009157', (124, 141))	('CD57', 'Gene', (7, 11))	('thymoma', 'Phenotype', 'HP:0100522', (57, 64))	('thymomas', 'Disease', 'MESH:D013945', (57, 65))	('CD57', 'Gene', '27087', (7, 11))	('positivity', 'Var', (12, 22))	('neuromuscular disorder', 'Disease', (92, 114))	('thymomas', 'Disease', (57, 65))
55919	33923771	Detection of modulating and blocking AChR-Ab through RIPA is commercially available but adds little diagnostic value, although others recently emphasized their significance.	('modulating', 'Var', (13, 23))	('AChR-Ab', 'Gene', (37, 44))	('blocking', 'NegReg', (28, 36))	('ACh', 'Chemical', 'MESH:D000109', (37, 40))
55924	33923771	The technique detects autoantibodies to clustered AChR in about 15% of RIPA-seronegative MG patients.	('clustered AChR', 'Protein', (40, 54))	('patients', 'Species', '9606', (92, 100))	('autoantibodies', 'Var', (22, 36))	('ACh', 'Chemical', 'MESH:D000109', (50, 53))	('RIPA-seronegative MG', 'Disease', (71, 91))	('detects', 'Reg', (14, 21))
56018	32337145	We found out that rates of remission were better in post thymectomy patients than patients on various medical treatment options including corticosteroids, immunosuppressants, intravenous immunoglobulins and acetylcholinesterase inhibitors alone.	('patients', 'Species', '9606', (82, 90))	('better', 'PosReg', (42, 48))	('men', 'Species', '9606', (115, 118))	('acetylcholinesterase', 'Gene', (207, 227))	('post thymectomy', 'Var', (52, 67))	('patients', 'Species', '9606', (68, 76))	('steroids', 'Chemical', 'MESH:D013256', (145, 153))	('acetylcholinesterase', 'Gene', '43', (207, 227))
56031	32337145	It is proposed that anti-acetylcholine receptor antibodies cause damage to the postsynaptic membrane.	('acetylcholine', 'Chemical', 'MESH:D000109', (25, 38))	('antibodies', 'Var', (48, 58))	('damage', 'MPA', (65, 71))	('anti-acetylcholine receptor', 'Protein', (20, 47))	('acetylcholine receptor antibodies', 'Phenotype', 'HP:0030208', (25, 58))
56033	32337145	Depletion of AchR hinders myofiber's response to acetylcholine.	('hinders', 'NegReg', (18, 25))	('acetylcholine', 'Chemical', 'MESH:D000109', (49, 62))	('response to acetylcholine', 'MPA', (37, 62))	('Depletion', 'Var', (0, 9))	('AchR', 'Protein', (13, 17))	('myofiber', 'CPA', (26, 34))
56051	32337145	In about half of patients with seronegative myasthenia gravis, antibody to muscle-specific kinase is positive.	('myasthenia', 'Phenotype', 'HP:0003473', (44, 54))	('patients', 'Species', '9606', (17, 25))	('positive', 'Reg', (101, 109))	('myasthenia gravis', 'Disease', (44, 61))	('antibody', 'Var', (63, 71))	('myasthenia gravis', 'Disease', 'MESH:D009157', (44, 61))
56075	32337145	And he found out that before landmark analysis, the thymectomy group had a higher cumulative incidence of pharmacologic remission (p = 0.009) and complete stable remission (p = 0.022) than the medical treatment group.	('thymectomy', 'Var', (52, 62))	('higher', 'PosReg', (75, 81))	('pharmacologic remission', 'MPA', (106, 129))	('men', 'Species', '9606', (206, 209))
56120	31193429	Thoracoscopic thymectomy in comparison with thymectomy from open surgical approach contributes to a significant decrease in the length of patients' stay in the intensive care unit and hospital, and the duration of analgesia with narcotic analgesics in the postoperative period.	('decrease', 'NegReg', (112, 120))	('Thoracoscopic', 'Var', (0, 13))	('analgesia', 'Disease', (214, 223))	('analgesia', 'Disease', 'MESH:D000699', (214, 223))	('patients', 'Species', '9606', (138, 146))
56294	28506287	Kaplan-Meier analysis and log-rank tests showed that DFS rates were higher in patients with WHO type A + AB and type B1 thymoma than in those with type B2 thymoma (P < 0.001 and P = 0.014, respectively) and type B3 thymoma (P < 0.001 and P = 0.011, respectively) (Fig.	('DFS', 'MPA', (53, 56))	('thymoma', 'Disease', (215, 222))	('thymoma', 'Disease', 'MESH:D013945', (120, 127))	('thymoma', 'Disease', (120, 127))	('higher', 'PosReg', (68, 74))	('thymoma', 'Disease', 'MESH:D013945', (155, 162))	('patients', 'Species', '9606', (78, 86))	('thymoma', 'Phenotype', 'HP:0100522', (215, 222))	('thymoma', 'Phenotype', 'HP:0100522', (155, 162))	('thymoma', 'Phenotype', 'HP:0100522', (120, 127))	('type B2 thymoma', 'Disease', (147, 162))	('type B3 thymoma', 'Disease', (207, 222))	('thymoma', 'Disease', (155, 162))	('type B1', 'Var', (112, 119))	('thymoma', 'Disease', 'MESH:D013945', (215, 222))	('type B2 thymoma', 'Disease', 'MESH:D013945', (147, 162))	('type B3 thymoma', 'Disease', 'MESH:D013945', (207, 222))
56298	28506287	Subsequent analysis using the Cox multivariate model revealed the following independent predictors of OS: Masaoka stage (stage IVa vs. stage I, P = 0.048) and WHO histological classification (type B1 and type B3 vs. type A + B, P = 0.016 and P = 0.004, respectively) (Table 3).	('Cox', 'Gene', '1351', (30, 33))	('Cox', 'Gene', (30, 33))	('type B1', 'Var', (192, 199))	('Masaoka stage', 'Disease', (106, 119))
21452	22312479	The presence of striational antibodies is associated with more severe disease in all MG subgroups.	('severe disease', 'Disease', (63, 77))	('associated with', 'Reg', (42, 57))	('presence', 'Var', (4, 12))	('severe disease', 'Disease', 'MESH:D056729', (63, 77))	('striational antibodies', 'Protein', (16, 38))
56374	22312479	Some disease mechanisms which may occur in MG, such as the presence of matrix metalloproteinase-3 (MMP-3), may also have a specific pathogenetic effect.	('matrix metalloproteinase-3', 'Gene', '4314', (71, 97))	('matrix metalloproteinase-3', 'Gene', (71, 97))	('MMP-3', 'Gene', '4314', (99, 104))	('MMP-3', 'Gene', (99, 104))	('presence', 'Var', (59, 67))
56390	22312479	Logistic regression analyses revealed that female gender and mild ocular symptoms were independently predictive of headache associated with MG. MG is characterized by reduced muscle endurance and is often accompanied by respiratory complications.	('headache', 'Disease', 'MESH:D006261', (115, 123))	('respiratory complications', 'Phenotype', 'HP:0011947', (220, 245))	('mild ocular symptoms', 'Phenotype', 'HP:0032037', (61, 81))	('MG. MG', 'Var', (140, 146))	('headache', 'Disease', (115, 123))	('headache', 'Phenotype', 'HP:0002315', (115, 123))	('reduced', 'NegReg', (167, 174))	('muscle endurance', 'CPA', (175, 191))
56452	21861913	Irregularities are usually the signs of local invasion and aggressive carcinomas.	('Irregularities', 'Var', (0, 14))	('local invasion', 'CPA', (40, 54))	('carcinoma', 'Phenotype', 'HP:0030731', (70, 79))	('carcinomas', 'Phenotype', 'HP:0030731', (70, 80))	('aggressive carcinomas', 'Disease', 'MESH:D001523', (59, 80))	('aggressive carcinomas', 'Disease', (59, 80))
56551	32489444	In this study, one of the four patients with combination B2-B3 showed gross infiltration of mediastinal structures at recurrence and died.	('combination B2-B3', 'Var', (45, 62))	('B2-B3', 'Var', (57, 62))	('died', 'Disease', (133, 137))	('patients', 'Species', '9606', (31, 39))	('died', 'Disease', 'MESH:D003643', (133, 137))
56571	32373124	The subgroup that is associated with thymoma and almost consistently with anti-acetylcholine receptor (AChR) antibodies, is termed thymoma-associated MG (TAMG).	('TAMG', 'Chemical', '-', (154, 158))	('acetylcholine', 'Chemical', 'MESH:D000109', (79, 92))	('thymoma', 'Disease', 'MESH:D013945', (37, 44))	('thymoma', 'Phenotype', 'HP:0100522', (131, 138))	('thymoma', 'Disease', (37, 44))	('associated', 'Reg', (21, 31))	('thymoma', 'Phenotype', 'HP:0100522', (37, 44))	('AChR', 'Gene', (103, 107))	('anti-acetylcholine', 'Var', (74, 92))	('thymoma', 'Disease', 'MESH:D013945', (131, 138))	('thymoma', 'Disease', (131, 138))
56574	32373124	Besides, the polymorphism of the non-MHC gene, CTLA4 that affects T cell receptor signaling appears to correlate with TAMG.	('polymorphism', 'Var', (13, 25))	('CTLA4', 'Gene', (47, 52))	('TAMG', 'Chemical', '-', (118, 122))	('affects', 'Reg', (58, 65))	('T cell receptor signaling', 'MPA', (66, 91))	('correlate', 'Reg', (103, 112))	('TAMG', 'Disease', (118, 122))	('CTLA4', 'Gene', '1493', (47, 52))
56597	32373124	When focusing on functional pathways derived from the KEGG database (N = 310), 19 functional pathways (6%) showed an MG association in AB thymomas: ten pathways, such as those related to Oxidative phosphorylation, Parkinson disease, and Alzheimer disease, were significantly upregulated, while nine pathways, such as those related to Adherens junction, AGE-RAGE signaling, and TGF-beta signaling, were significantly downregulated in MG+ compared to MG- type AB thymomas.	('TGF-beta', 'Gene', '7039', (377, 385))	('downregulated', 'NegReg', (416, 429))	('Parkinson disease', 'Disease', (214, 231))	('upregulated', 'PosReg', (275, 286))	('AB thymomas', 'Disease', (135, 146))	('thymoma', 'Phenotype', 'HP:0100522', (138, 145))	('TGF-beta', 'Gene', (377, 385))	('AB thymomas', 'Disease', 'MESH:D013945', (458, 469))	('AB thymomas', 'Disease', 'MESH:D013945', (135, 146))	('type AB thymomas', 'Disease', (453, 469))	('RAGE', 'Gene', (357, 361))	('Alzheimer disease', 'Phenotype', 'HP:0002511', (237, 254))	('Parkinson disease', 'Disease', 'MESH:D010300', (214, 231))	('RAGE', 'Gene', '177', (357, 361))	('thymoma', 'Phenotype', 'HP:0100522', (461, 468))	('Oxidative', 'MPA', (187, 196))	('Alzheimer disease', 'Disease', 'MESH:D000544', (237, 254))	('Alzheimer disease', 'Disease', (237, 254))	('type AB thymomas', 'Disease', 'MESH:D013945', (453, 469))	('MG+', 'Var', (433, 436))
56598	32373124	In type B2 thymoma, only eight functional pathways showed an MG association: the pathway related to Olfactory transduction was significantly upregulated in MG+ cases, while seven pathways, such as Protein processing, Metabolism, and DNA replication, were downregulated in MG+ B2 thymomas (Table 1).	('thymomas', 'Disease', (279, 287))	('thymomas', 'Disease', 'MESH:D013945', (279, 287))	('thymoma', 'Disease', 'MESH:D013945', (11, 18))	('thymoma', 'Disease', 'MESH:D013945', (279, 286))	('pathway', 'Pathway', (81, 88))	('downregulated', 'NegReg', (255, 268))	('thymoma', 'Disease', (11, 18))	('thymoma', 'Disease', (279, 286))	('upregulated', 'PosReg', (141, 152))	('thymoma', 'Phenotype', 'HP:0100522', (11, 18))	('MG+', 'Var', (156, 159))	('thymoma', 'Phenotype', 'HP:0100522', (279, 286))
56603	32373124	In contrast, five pathways, such as those related to T cell cluster, MacTh1 cluster, and LCK median, were significantly upregulated in MG+ type B2 thymoma (Table 2).	('LCK', 'Gene', '3932', (89, 92))	('thymoma', 'Disease', 'MESH:D013945', (147, 154))	('upregulated', 'PosReg', (120, 131))	('thymoma', 'Disease', (147, 154))	('thymoma', 'Phenotype', 'HP:0100522', (147, 154))	('MG+ type B2', 'Var', (135, 146))	('LCK', 'Gene', (89, 92))
56605	32373124	Vice versa, the Olfactory transduction pathway that was significantly upregulated in MG+ type B2 thymomas, was downregulated in MG+ type AB thymomas, although the difference was significant only in the TdT-low subset (and with a minor trend in the TdT-high subset) (Figure 2 and Table S1).	('thymomas', 'Disease', (140, 148))	('thymomas', 'Disease', 'MESH:D013945', (140, 148))	('Olfactory transduction pathway', 'Pathway', (16, 46))	('TdT', 'Gene', (202, 205))	('thymoma', 'Phenotype', 'HP:0100522', (97, 104))	('TdT', 'Gene', (248, 251))	('TdT', 'Gene', '1791', (202, 205))	('thymomas', 'Disease', (97, 105))	('TdT', 'Gene', '1791', (248, 251))	('type AB thymomas', 'Disease', (132, 148))	('downregulated', 'NegReg', (111, 124))	('thymomas', 'Disease', 'MESH:D013945', (97, 105))	('thymoma', 'Phenotype', 'HP:0100522', (140, 147))	('type AB thymomas', 'Disease', 'MESH:D013945', (132, 148))	('upregulated', 'PosReg', (70, 81))	('MG+ type B2', 'Var', (85, 96))
56692	31681579	The numbers of thymomas according to each WHO type were as follows: 16 (10.1%) type A; 47 (29.5%) type AB; 16 (10.1%) type B1; 45 (28.3%) type B2; 35 (22.0%) type B3.	('thymoma', 'Phenotype', 'HP:0100522', (15, 22))	('type B1', 'Var', (118, 125))	('type A', 'Var', (79, 85))	('type AB', 'Var', (98, 105))	('thymomas', 'Disease', 'MESH:D013945', (15, 23))	('thymomas', 'Disease', (15, 23))
56699	31681579	The numbers of thymomas according to each WHO type were as follows: 11 (12.4%) type A; 28 (31.5%) type AB; 14 (15.7%) type B1; 20 (22.4%) type B2; 16 (18.0%) type B3.	('thymoma', 'Phenotype', 'HP:0100522', (15, 22))	('B1; 20', 'Gene', '8289', (123, 129))	('B1; 20', 'Gene', (123, 129))	('type AB', 'Var', (98, 105))	('thymomas', 'Disease', 'MESH:D013945', (15, 23))	('thymomas', 'Disease', (15, 23))
56716	31681579	Contour (OR = 3.711, P = 0.005), abutment >=50% (OR = 4.277, P = 0.02), and adjacent lung abnormalities (OR = 3.916, P = 0.031) were risk factors for postoperative recurrence or metastasis.	('lung abnormalities', 'Disease', (85, 103))	('>=50', 'Var', (42, 46))	('lung abnormalities', 'Disease', 'MESH:C567034', (85, 103))	('lung abnormalities', 'Phenotype', 'HP:0002088', (85, 103))	('men', 'Species', '9606', (37, 40))	('metastasis', 'CPA', (178, 188))	('postoperative recurrence', 'CPA', (150, 174))
56773	29940999	The origin of autoimmune dysfunction in patients with MG is unknown, but thymic abnormalities and defects in immune regulation play important roles in patients with anti-AChR antibodies.	('thymic abnormalities and defects', 'Disease', 'MESH:D000014', (73, 105))	('autoimmune dysfunction', 'Disease', 'MESH:D001327', (14, 36))	('thymic abnormalities', 'Phenotype', 'HP:0000777', (73, 93))	('anti-AChR antibodies', 'Var', (165, 185))	('patients', 'Species', '9606', (40, 48))	('patients', 'Species', '9606', (151, 159))	('autoimmune dysfunction', 'Disease', (14, 36))	('autoimmune dysfunction', 'Phenotype', 'HP:0002960', (14, 36))
56799	29940999	The average dose of prednisone required was also lower in the surgical group as compared to the non-surgical group (44 mg vs. 60 mg, p < 0.001).	('prednisone', 'Chemical', 'MESH:D011241', (20, 30))	('lower', 'NegReg', (49, 54))	('surgical', 'Var', (62, 70))	('dose of prednisone', 'MPA', (12, 30))
56880	28514294	TNFAIP3 gene rs7749323 polymorphism is associated with late onset myasthenia gravis In this study, we intended to genotype 2 single nucleotide polymorphisms (SNPs) of tumor necrosis factor alpha-induced protein 3 (TNFAIP3) genes and explore an association of TNFAIP3 genetic polymorphism with the patients of myasthenia gravis (MG) at clinical level.	('rs7749323 polymorphism', 'Var', (13, 35))	('myasthenia gravis', 'Disease', (66, 83))	('associated', 'Reg', (39, 49))	('myasthenia', 'Phenotype', 'HP:0003473', (66, 76))	('tumor necrosis factor alpha-induced protein 3', 'Gene', '7128', (167, 212))	('myasthenia gravis', 'Disease', (309, 326))	('rs7749323', 'Mutation', 'rs7749323', (13, 22))	('myasthenia', 'Phenotype', 'HP:0003473', (309, 319))	('TNFAIP3', 'Gene', '7128', (0, 7))	('TNFAIP3', 'Gene', (0, 7))	('TNFAIP3', 'Gene', '7128', (214, 221))	('patients', 'Species', '9606', (297, 305))	('myasthenia gravis', 'Disease', 'MESH:D009157', (66, 83))	('TNFAIP3', 'Gene', (214, 221))	('myasthenia gravis', 'Disease', 'MESH:D009157', (309, 326))	('TNFAIP3', 'Gene', '7128', (259, 266))	('tumor necrosis factor alpha-induced protein 3', 'Gene', (167, 212))	('TNFAIP3', 'Gene', (259, 266))	('tumor', 'Phenotype', 'HP:0002664', (167, 172))	('polymorphism', 'Var', (23, 35))
56883	28514294	The distribution of TNFAIP3 gene rs7749323*A allele of late onset MG (LOMG, with positive acetylcholine receptor antibody and without thymoma) subgrouped patients was also significantly higher than that of gender- and age-matched healthy controls (7.4% vs 2.4%, odds ratio [OR] = 3.27, 95% confidence interval [CI] 1.01-10.6, P = .04).	('TNFAIP3', 'Gene', (20, 27))	('thymoma', 'Disease', (134, 141))	('positive acetylcholine receptor antibody', 'Phenotype', 'HP:0030208', (81, 121))	('thymoma', 'Phenotype', 'HP:0100522', (134, 141))	('patients', 'Species', '9606', (154, 162))	('late onset MG', 'Disease', (55, 68))	('acetylcholine', 'Chemical', 'MESH:D000109', (90, 103))	('rs7749323*A', 'Var', (33, 44))	('TNFAIP3', 'Gene', '7128', (20, 27))	('rs7749323', 'Mutation', 'rs7749323', (33, 42))	('higher', 'PosReg', (186, 192))	('thymoma', 'Disease', 'MESH:D013945', (134, 141))
56886	28514294	Therefore, it is suggested that the SNPs in the 3' flanking region (rs7749323) of TNFAIP3 gene and the genetic variations of TNFAIP3 gene may take an important role in the susceptibility of LOMG.	('TNFAIP3', 'Gene', '7128', (125, 132))	('rs7749323', 'Var', (68, 77))	('rs7749323', 'Mutation', 'rs7749323', (68, 77))	('TNFAIP3', 'Gene', '7128', (82, 89))	('TNFAIP3', 'Gene', (125, 132))	('LOMG', 'Disease', (190, 194))	('TNFAIP3', 'Gene', (82, 89))
56893	28514294	From the human genetic studies, it is known that the polymorphisms in the TNFAIP3 gene may associate with the susceptibility of multiple autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), psoriasis, Crohn disease, as well as other autoimmune diseases.	('Crohn disease', 'Phenotype', 'HP:0100280', (242, 255))	('Crohn disease', 'Disease', 'MESH:D003424', (242, 255))	('autoimmune diseases', 'Disease', (137, 156))	('psoriasis', 'Phenotype', 'HP:0003765', (231, 240))	('TNFAIP3', 'Gene', '7128', (74, 81))	('human', 'Species', '9606', (9, 14))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (137, 156))	('rheumatoid arthritis', 'Disease', (204, 224))	('TNFAIP3', 'Gene', (74, 81))	('psoriasis', 'Disease', 'MESH:D011565', (231, 240))	('systemic lupus erythematosus', 'Phenotype', 'HP:0002725', (168, 196))	('Crohn disease', 'Disease', (242, 255))	('psoriasis', 'Disease', (231, 240))	('RA', 'Phenotype', 'HP:0001370', (226, 228))	('systemic lupus erythematosus', 'Disease', 'MESH:D008180', (168, 196))	('rheumatoid arthritis', 'Disease', 'MESH:D001172', (204, 224))	('SLE', 'Disease', 'MESH:D008180', (198, 201))	('SLE', 'Disease', (198, 201))	('autoimmune diseases', 'Disease', 'MESH:D001327', (274, 293))	('SLE', 'Phenotype', 'HP:0002725', (198, 201))	('polymorphisms', 'Var', (53, 66))	('RA', 'Disease', 'MESH:D001172', (226, 228))	('autoimmune diseases', 'Disease', (274, 293))	('rheumatoid arthritis', 'Phenotype', 'HP:0001370', (204, 224))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (274, 293))	('associate with', 'Reg', (91, 105))	('systemic lupus erythematosus', 'Disease', (168, 196))	('arthritis', 'Phenotype', 'HP:0001369', (215, 224))	('autoimmune diseases', 'Disease', 'MESH:D001327', (137, 156))
56895	28514294	We hypothesized that the generic variants in the TNFAIP3 gene may have an association with the MG, and in the current report, we performed a research to explore the association of polymorphisms in the TNFAIP3 gene with MG, and furthermore examine the relationship between the generic variations of TNFAIP3 gene and clinical manifestations for this disease.	('TNFAIP3', 'Gene', '7128', (201, 208))	('TNFAIP3', 'Gene', (49, 56))	('association', 'Interaction', (165, 176))	('association', 'Reg', (74, 85))	('TNFAIP3', 'Gene', (201, 208))	('TNFAIP3', 'Gene', '7128', (298, 305))	('polymorphisms', 'Var', (180, 193))	('TNFAIP3', 'Gene', '7128', (49, 56))	('TNFAIP3', 'Gene', (298, 305))	('variants', 'Var', (33, 41))
56905	28514294	According to previous publication on genome-wide association studies (GWAS), 2 types of single nucleotide polymorphisms (SNPs) (rs5029939 and rs7749323) are believed to have positive associations with the immune-mediated disease.	('rs5029939', 'Mutation', 'rs5029939', (128, 137))	('positive', 'PosReg', (174, 182))	('rs7749323', 'Var', (142, 151))	('associations', 'Reg', (183, 195))	('rs7749323', 'Mutation', 'rs7749323', (142, 151))	('rs5029939', 'Var', (128, 137))	('immune-mediated disease', 'Disease', (205, 228))
56906	28514294	In this case, both the rs5029939 and rs7749323 were selected to perform the experiments and the results were listed in Table 2.	('rs7749323', 'Mutation', 'rs7749323', (37, 46))	('rs5029939', 'Var', (23, 32))	('rs5029939', 'Mutation', 'rs5029939', (23, 32))	('rs7749323', 'Var', (37, 46))
56925	28514294	The distributions of 2 SNPs in the MG subjects and healthy controls are listed in Table 3, showing that there is no significant statistical difference in the rs5029939 and rs7749323 frequency of allele and genotype between the MG subjects and healthy controls (Table 3).	('rs7749323', 'Mutation', 'rs7749323', (172, 181))	('rs7749323', 'Var', (172, 181))	('rs5029939', 'Var', (158, 167))	('rs5029939', 'Mutation', 'rs5029939', (158, 167))
56928	28514294	It is noticed from Table 3 that the distribution of TNFAIP3 gene rs7749323*A allele was significantly higher in the LOMG group in comparison with that of age-matched healthy control group (age >= 50 years old) (7.4% vs 2.4%, odds ratio [OR] = 3.27, 95% confidence interval [CI] 1.01-10.6, P = .04).	('TNFAIP3', 'Gene', '7128', (52, 59))	('rs7749323*A', 'Var', (65, 76))	('TNFAIP3', 'Gene', (52, 59))	('higher', 'PosReg', (102, 108))	('rs7749323', 'Mutation', 'rs7749323', (65, 74))
56929	28514294	Further analysis to the genotype frequencies indicates a close association of the rs7749323 with the LOMG group.	('association', 'Interaction', (63, 74))	('LOMG group', 'Disease', (101, 111))	('rs7749323', 'Mutation', 'rs7749323', (82, 91))	('rs7749323', 'Var', (82, 91))
56930	28514294	Carriers of rs7749323*A allele are found to be more frequent in the LOMG group than that in the age-matched healthy control group (14.9% vs 4.8%, OR = 3.47, 95% CI 1.04-11.6, dominant model: P = .03).	('rs7749323*A', 'Var', (12, 23))	('rs7749323', 'Mutation', 'rs7749323', (12, 21))	('LOMG', 'Disease', (68, 72))
56934	28514294	2 indicating that the Rs5029939 and rs7749323 were linked closely each other (D' = 1, r2 = 0.81) resulting in a haplotype block.	('Rs5029939', 'Mutation', 'Rs5029939', (22, 31))	('Rs5029939', 'Var', (22, 31))	('rs7749323', 'Mutation', 'rs7749323', (36, 45))	('rs7749323', 'Var', (36, 45))
56936	28514294	In this study, the rs7749323 (locates in 3' flanking region) of TNFAIP3 gene is found to have an associate with the LOMG (with positive AChR Ab and without thymoma) in the northern Han Chinese population.	('AChR Ab', 'Chemical', '-', (136, 143))	('thymoma', 'Phenotype', 'HP:0100522', (156, 163))	('associate', 'Reg', (97, 106))	('rs7749323', 'Mutation', 'rs7749323', (19, 28))	('thymoma', 'Disease', 'MESH:D013945', (156, 163))	('TNFAIP3', 'Gene', '7128', (64, 71))	('rs7749323', 'Var', (19, 28))	('TNFAIP3', 'Gene', (64, 71))	('LOMG', 'Disease', (116, 120))	('thymoma', 'Disease', (156, 163))
56937	28514294	On the other hand, there is still lack of evidence supporting the presence of an association of the MG subjects with the TNFAIP3 gene polymorphism.	('association', 'Interaction', (81, 92))	('TNFAIP3', 'Gene', (121, 128))	('polymorphism', 'Var', (134, 146))	('TNFAIP3', 'Gene', '7128', (121, 128))
56938	28514294	In fact, the autoantibodies against AChR in an MG subject might impair a neuromuscular transmission and furthermore bring up a muscle weakness.	('muscle weakness', 'Disease', (127, 142))	('neuromuscular transmission', 'MPA', (73, 99))	('AChR', 'Gene', (36, 40))	('muscle weakness', 'Disease', 'MESH:D018908', (127, 142))	('bring up', 'Reg', (116, 124))	('autoantibodies', 'Var', (13, 27))	('muscle weakness', 'Phenotype', 'HP:0001324', (127, 142))	('impair', 'NegReg', (64, 70))
56940	28514294	In this study, the rs7749323 is found to closely associate with the LOMG subjects that have positive AChR Ab expression.	('associate', 'Reg', (49, 58))	('AChR Ab', 'Gene', (101, 108))	('LOMG', 'Disease', (68, 72))	('AChR Ab', 'Chemical', '-', (101, 108))	('rs7749323', 'Var', (19, 28))	('rs7749323', 'Mutation', 'rs7749323', (19, 28))
56941	28514294	On the other hand, although the rs5029939 is reported to associate with SLE in the GWAS, there is no significant difference for the allele or genotype frequency of rs5029939 in the TNFAIP3 susceptibility genes between the positive AChR Ab group and healthy control.	('TNFAIP3', 'Gene', (181, 188))	('rs5029939', 'Var', (164, 173))	('rs5029939', 'Mutation', 'rs5029939', (32, 41))	('SLE', 'Disease', 'MESH:D008180', (72, 75))	('SLE', 'Disease', (72, 75))	('rs5029939', 'Mutation', 'rs5029939', (164, 173))	('associate', 'Reg', (57, 66))	('SLE', 'Phenotype', 'HP:0002725', (72, 75))	('TNFAIP3', 'Gene', '7128', (181, 188))	('AChR Ab', 'Chemical', '-', (231, 238))	('rs5029939', 'Var', (32, 41))
56942	28514294	This viewpoint may be supported by the observations on the cytotoxic T-lymphocyte antigen 4 (CTLA-4) and human lymphocyte antigen (HLA)-DQA1 polymorphism which are regarded as independent risk factors in the susceptibility of MG disease.	('cytotoxic T-lymphocyte antigen 4', 'Gene', '1493', (59, 91))	('MG disease', 'Disease', (226, 236))	('cytotoxic T-lymphocyte antigen 4', 'Gene', (59, 91))	('MG disease', 'Disease', 'MESH:D000080343', (226, 236))	('polymorphism', 'Var', (141, 153))	('CTLA-4', 'Gene', (93, 99))	('lymphocyte antigen (HLA)-DQA1', 'Gene', (111, 140))	('lymphocyte antigen (HLA)-DQA1', 'Gene', '3117', (111, 140))	('human', 'Species', '9606', (105, 110))
56943	28514294	So far, there are reports supporting the strong associations of LOMG with the tumor necrosis factor Receptor Superfamily Member 11a (TNFRSF11A) rs4574025 (OR = 1.42 [1.24-1.63], P = 3.91 x 10-7), zinc figer- and BTB domin containing 10 (ZBTB10) rs6998967 (OR = 0.53 [0.42-0.65], P = 8.86 x 10-10), and HLA region rs111945767 (OR = 0.52 [0.44-0.61], P = 3.13 x 10-17) in the European population, as well as with the protein tyrosine phosphatase nonreceptor 22 gene (PTPN22) R62W (OR = 3.1 [1.2-8.2], P = .03) and the HLA region rs111256513 (OR = 2.22 [1.2-8.2], P = 2.48 x 10-6) in the Turkey population.	('PTPN22', 'Gene', '100539686', (465, 471))	('tumor', 'Phenotype', 'HP:0002664', (78, 83))	('R62W', 'Var', (473, 477))	('rs111256513', 'Mutation', 'rs111256513', (527, 538))	('tumor necrosis', 'Disease', 'MESH:D009336', (78, 92))	('rs6998967', 'Mutation', 'rs6998967', (245, 254))	('R62W', 'Mutation', 'p.R62W', (473, 477))	('tumor necrosis', 'Disease', (78, 92))	('HLA', 'Gene', (516, 519))	('HLA', 'Gene', (302, 305))	('rs111945767', 'Mutation', 'rs111945767', (313, 324))	('rs111256513', 'Var', (527, 538))	('associations', 'Interaction', (48, 60))	('Turkey', 'Species', '9103', (585, 591))	('PTPN22', 'Gene', (465, 471))	('rs4574025', 'Mutation', 'rs4574025', (144, 153))	('HLA', 'Gene', '3123', (516, 519))	('HLA', 'Gene', '3123', (302, 305))	('rs111945767', 'Var', (313, 324))	('rs4574025', 'Var', (144, 153))	('ZBTB10', 'Gene', '100549819', (237, 243))	('ZBTB10', 'Gene', (237, 243))	('TNFRSF11A', 'Gene', (133, 142))	('TNFRSF11A', 'Gene', '100545473', (133, 142))
56944	28514294	There are also reports on a significant association of EOMG with the HLA region rs113519545 (OR = 5.71 [3.77-8.88], P = 2.24 x 10-16) in the Turkey population and the CTLA-4 gene in the Han population of northern China.	('rs113519545', 'Mutation', 'rs113519545', (80, 91))	('Turkey', 'Species', '9103', (141, 147))	('rs113519545', 'Var', (80, 91))	('CTLA-4', 'Gene', (167, 173))	('HLA', 'Gene', '3123', (69, 72))	('EOMG', 'Disease', (55, 59))	('HLA', 'Gene', (69, 72))	('association', 'Interaction', (40, 51))	('EOMG', 'Chemical', '-', (55, 59))
56950	28514294	Particularly, there is no significant evidence to support an association of rs7749323 with the TAMG, although the AChR Abs were found to express in 94% of TAMG subjects.	('TAMG', 'Disease', (95, 99))	('TAMG', 'Chemical', '-', (155, 159))	('AChR Ab', 'Chemical', '-', (114, 121))	('rs7749323', 'Var', (76, 85))	('rs7749323', 'Mutation', 'rs7749323', (76, 85))	('TAMG', 'Chemical', '-', (95, 99))
56951	28514294	The results indicate that the rs7749323 gene may play an important role only in the susceptibility of LOMG.	('LOMG', 'Disease', (102, 106))	('rs7749323', 'Var', (30, 39))	('rs7749323', 'Mutation', 'rs7749323', (30, 39))
56953	28514294	Thus, to better evaluate the results from the present study and clarify the substantial role of TNFAIP3 gene polymorphism with the susceptibility of MG, a further study is suggested to perform with a larger number of cohort and more candidates of SNP.	('TNFAIP3', 'Gene', '7128', (96, 103))	('TNFAIP3', 'Gene', (96, 103))	('polymorphism', 'Var', (109, 121))
56957	28514294	On the other hand, although patients' cells show increased expression of NF-kappaB-mediated proinflammatory cytokines, the TNFAIP3 mutant truncated proteins are likely to act by haplosufficiency since they do not exert a dominant-negative effect in overexpression experiment.	('mutant', 'Var', (131, 137))	('increased', 'PosReg', (49, 58))	('proteins', 'Protein', (148, 156))	('NF-kappaB', 'Gene', '4790', (73, 82))	('TNFAIP3', 'Gene', '7128', (123, 130))	('patients', 'Species', '9606', (28, 36))	('expression', 'MPA', (59, 69))	('NF-kappaB', 'Gene', (73, 82))	('TNFAIP3', 'Gene', (123, 130))
56958	28514294	In summary, this study demonstrates that the rs7749323 in the TNFAIP3 gene is strongly associated with the LOMG (with positive AChR Ab but without thymoma).	('TNFAIP3', 'Gene', (62, 69))	('AChR Ab', 'Chemical', '-', (127, 134))	('LOMG', 'Disease', (107, 111))	('thymoma', 'Disease', 'MESH:D013945', (147, 154))	('thymoma', 'Disease', (147, 154))	('rs7749323', 'Var', (45, 54))	('associated', 'Reg', (87, 97))	('thymoma', 'Phenotype', 'HP:0100522', (147, 154))	('rs7749323', 'Mutation', 'rs7749323', (45, 54))	('TNFAIP3', 'Gene', '7128', (62, 69))
56960	28514294	It is also suggested to perform a furthermore study with a large number of cohort as well as more candidates of SNP to elucidate the effect of variation in the genes of TNFAIP3 pathway on the susceptibility of MG.	('TNFAIP3', 'Gene', '7128', (169, 176))	('TNFAIP3', 'Gene', (169, 176))	('variation', 'Var', (143, 152))
56961	27770408	A case of atypical type A thymoma variant An atypical type A thymoma variant was newly added to the WHO classification of type A thymoma family in 2015.	('thymoma', 'Disease', (26, 33))	('thymoma', 'Disease', 'MESH:D013945', (61, 68))	('type A thymoma', 'Disease', 'MESH:D013945', (54, 68))	('type A thymoma', 'Disease', 'MESH:D013945', (122, 136))	('thymoma', 'Disease', (129, 136))	('thymoma', 'Phenotype', 'HP:0100522', (26, 33))	('thymoma', 'Disease', (61, 68))	('atypical type A thymoma', 'Disease', (45, 68))	('atypical type A thymoma', 'Disease', 'MESH:D013945', (45, 68))	('atypical type A thymoma', 'Disease', (10, 33))	('atypical type A thymoma', 'Disease', 'MESH:D013945', (10, 33))	('thymoma', 'Phenotype', 'HP:0100522', (129, 136))	('thymoma', 'Phenotype', 'HP:0100522', (61, 68))	('variant', 'Var', (34, 41))	('type A thymoma', 'Disease', 'MESH:D013945', (19, 33))	('type A thymoma', 'Disease', (122, 136))	('thymoma', 'Disease', 'MESH:D013945', (129, 136))	('thymoma', 'Disease', 'MESH:D013945', (26, 33))
57003	27770408	In that report, Ki-67 LI in type A thymoma was 0.3-11.0 % (median 3.0) and in thymic carcinoma was 12.2-43.3 % (median 23.2 %).	('type A thymoma', 'Disease', (28, 42))	('type A thymoma', 'Disease', 'MESH:D013945', (28, 42))	('thymic carcinoma', 'Disease', (78, 94))	('thymic carcinoma', 'Disease', 'MESH:D013945', (78, 94))	('carcinoma', 'Phenotype', 'HP:0030731', (85, 94))	('Ki-67', 'Var', (16, 21))	('thymoma', 'Phenotype', 'HP:0100522', (35, 42))
57025	22174595	However, a repeat CD55/59 flow cytometry confirmed a new diagnosis of paroxysmal nocturnal hemoglobinuria (PNH), with over 80% CD55/59-deficient red cells and granulocytes (Fig.	('paroxysmal nocturnal hemoglobinuria', 'Phenotype', 'HP:0004818', (70, 105))	('paroxysmal nocturnal hemoglobinuria', 'Disease', 'MESH:D006457', (70, 105))	('paroxysmal nocturnal hemoglobinuria', 'Disease', (70, 105))	('CD55/59-deficient', 'Var', (127, 144))	('hemoglobinuria', 'Phenotype', 'HP:0003641', (91, 105))	('PNH', 'Phenotype', 'HP:0004818', (107, 110))
57031	22174595	The pathogenesis of this disorder involves a somatic mutation in the PIG-A gene with consequent deficiency in glycosylphosphatidylinositol(GPI)-anchored membrane proteins, such as surface complement deactivators CD55 (decay-accelerating factor) and CD59 (protectin).	('CD55', 'Gene', (212, 216))	('mutation', 'Var', (53, 61))	('CD59', 'Gene', (249, 253))	('deficiency in glycosylphosphatidylinositol(GPI)-anchored', 'Disease', 'MESH:C537277', (96, 152))	('PIG-A', 'Gene', (69, 74))	('PIG-A', 'Gene', '100156880', (69, 74))	('CD59', 'Gene', '397347', (249, 253))
57051	22174595	In the majority of patients with a detectable mutant population, the proportion of PNH cells ultimately decreased after immunosuppressive therapy.	('patients', 'Species', '9606', (19, 27))	('decreased', 'NegReg', (104, 113))	('mutant', 'Var', (46, 52))	('PNH', 'Disease', (83, 86))	('PNH', 'Phenotype', 'HP:0004818', (83, 86))
57054	22174595	It is hypothesized that while PIG-A mutations occur sporadically in healthy population, impaired immune surveillance or autoattack against normal progenitors is critical for expansion and hematopoietic dominance of the PNH clone.	('PNH', 'Phenotype', 'HP:0004818', (219, 222))	('PIG-A', 'Gene', '100156880', (30, 35))	('mutations', 'Var', (36, 45))	('PIG-A', 'Gene', (30, 35))
57055	22174595	The mutant population has the ability to restore hematopoiesis:in our patient ironically leading to remission from severe aplastic anemia unresponsive to standard treatment.	('hematopoiesis', 'Disease', 'MESH:C536227', (49, 62))	('aplastic anemia', 'Phenotype', 'HP:0001915', (122, 137))	('mutant', 'Var', (4, 10))	('aplastic anemia', 'Disease', 'MESH:D000741', (122, 137))	('anemia', 'Phenotype', 'HP:0001903', (131, 137))	('patient', 'Species', '9606', (70, 77))	('hematopoiesis', 'Disease', (49, 62))	('aplastic anemia', 'Disease', (122, 137))
57111	31591867	After multivariate analysis, high dose remained independently associated with improved OS (hazard ratio [HR] = 0.32; 95% confidence interval [CI], 0.10-0.98; p = 0.046), while type C thymoma remained independently associated with poor OS (HR = 6.70; 95% CI, 2.05-21.8; p = 0.002).	('improved', 'PosReg', (78, 86))	('thymoma', 'Phenotype', 'HP:0100522', (183, 190))	('type C thymoma', 'Disease', (176, 190))	('type C thymoma', 'Disease', 'MESH:D013945', (176, 190))	('high dose', 'Var', (29, 38))
57112	31591867	High dose also remained independently associated with improved PFS (HR = 0.35; 95% CI, 0.16-0.75; p = 0.007), and type C thymoma remained independently associated with poor PFS (HR = 3.82; 95% CI, 1.76-8.26; p = 0.001) (Table 5).	('type C thymoma', 'Disease', 'MESH:D013945', (114, 128))	('thymoma', 'Phenotype', 'HP:0100522', (121, 128))	('High dose', 'Var', (0, 9))	('PFS', 'MPA', (63, 66))	('type C thymoma', 'Disease', (114, 128))	('improved', 'PosReg', (54, 62))	('PFS', 'MPA', (173, 176))	('poor', 'NegReg', (168, 172))
57224	26273355	Thy0517 cells were seeded into a six-well plate, at 2 x 105 cells per well, in an antibiotic-free normal-growth medium supplemented with 10% FBS, and incubated until 70% confluency was achieved.	('FBS', 'Disease', 'MESH:D005198', (141, 144))	('FBS', 'Disease', (141, 144))	('Thy0517', 'Var', (0, 7))
57236	26273355	Immunoblot analysis was conducted on untreated total cell lysates or lysates from Thy0517 cells treated with FOXN1 siRNA, BCA1 siRNA or control siRNA.	('FOXN1', 'Gene', '8456', (109, 114))	('FOXN1', 'Gene', (109, 114))	('BCA1', 'Var', (122, 126))
57244	26273355	To assess the effect of FOXN1 and BCA1 on thymoma cell growth and viability, Thy0517 cells were treated with FOXN1 siRNA, BCA1 siRNA and control siRNA, and their proliferation was measured using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay.	('FOXN1', 'Gene', '8456', (109, 114))	('3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide', 'Chemical', 'MESH:C022616', (204, 264))	('BCA1', 'Var', (122, 126))	('thymoma', 'Disease', 'MESH:D013945', (42, 49))	('FOXN1', 'Gene', '8456', (24, 29))	('thymoma', 'Disease', (42, 49))	('FOXN1', 'Gene', (109, 114))	('thymoma', 'Phenotype', 'HP:0100522', (42, 49))	('FOXN1', 'Gene', (24, 29))	('MTT', 'Chemical', '-', (199, 202))
57255	26273355	Western blot results also showed that the expression of both FOXN1 and BCA1 were significantly higher in Thy0517 cells than in CRL7660 cells (P = 0.000; Fig 4).	('FOXN1', 'Gene', '8456', (61, 66))	('CRL', 'Gene', (127, 130))	('higher', 'PosReg', (95, 101))	('BCA1', 'Gene', (71, 75))	('expression', 'MPA', (42, 52))	('FOXN1', 'Gene', (61, 66))	('CRL', 'Gene', '133396', (127, 130))	('Thy0517', 'Var', (105, 112))
57257	26273355	Following transfection of Thy0517 cells with FOXN1 siRNA, the expression of FOXN1 mRNA and BCA1 mRNA was 0.230 +- 0.028 and 0.418 +- 0.015, respectively, and was reduced compared with the expression in cells transfected with control siRNA and control cells without siRNA (Table 4).	('FOXN1', 'Gene', (45, 50))	('FOXN1', 'Gene', (76, 81))	('reduced', 'NegReg', (162, 169))	('0.230 +- 0.028', 'Var', (105, 119))	('expression', 'MPA', (62, 72))	('BCA1', 'Gene', (91, 95))	('0.418 +- 0.015', 'Var', (124, 138))	('FOXN1', 'Gene', '8456', (45, 50))	('FOXN1', 'Gene', '8456', (76, 81))
57259	26273355	After transfection of Thy0517 cells with FOXN1 siRNA, the expression of FOXN1 and BCA1 was 0.096 +- 0.001 and 0.117 +- 0.007, respectively, and was significantly reduced compared with the expression in cells transfected with control siRNA and control cells without siRNA (P = 0.000).	('FOXN1', 'Gene', (41, 46))	('FOXN1', 'Gene', (72, 77))	('FOXN1', 'Gene', '8456', (41, 46))	('expression', 'MPA', (58, 68))	('reduced', 'NegReg', (162, 169))	('BCA1', 'Gene', (82, 86))	('0.096 +- 0.001', 'Var', (91, 105))	('FOXN1', 'Gene', '8456', (72, 77))	('0.117 +- 0.007', 'Var', (110, 124))
57260	26273355	However, BCA1 siRNA could not reduce the expression of FOXN1 (0.583 +- 0.030, P > 0.05), but did reduce that of BCA1 (0.112 +- 0.002, P = 0.000) compared with the expression in cells transfected with control siRNA and control cells without siRNA.	('FOXN1', 'Gene', (55, 60))	('BCA1', 'Gene', (9, 13))	('siRNA', 'Var', (14, 19))	('FOXN1', 'Gene', '8456', (55, 60))	('reduce', 'NegReg', (97, 103))
57261	26273355	To determine the biological significance of FOXN1 and BCA1 in the Thy0517 cell line, MTT cell proliferation assays were performed with and without FOXN1/BCA1 silencing.	('FOXN1', 'Gene', '8456', (44, 49))	('FOXN1', 'Gene', '8456', (147, 152))	('MTT', 'Chemical', '-', (85, 88))	('FOXN1', 'Gene', (44, 49))	('silencing', 'Var', (158, 167))	('FOXN1', 'Gene', (147, 152))
57270	26273355	This causes an alymphoid thymus, severe primary T cell immunodeficiency in nude mice and humans, congenital alopecia, and defective immunity, which all lead to death in early childhood from severe infection.	('immunodeficiency', 'Phenotype', 'HP:0002721', (55, 71))	('causes', 'Reg', (5, 11))	('severe primary T cell immunodeficiency', 'Phenotype', 'HP:0005352', (33, 71))	('alymphoid thymus', 'Disease', 'MESH:C536288', (15, 31))	('alopecia', 'Phenotype', 'HP:0001596', (108, 116))	('congenital alopecia', 'Disease', (97, 116))	('nude mice', 'Species', '10090', (75, 84))	('primary T cell immunodeficiency', 'Disease', (40, 71))	('humans', 'Species', '9606', (89, 95))	('severe infection', 'Phenotype', 'HP:0032169', (190, 206))	('infection', 'Disease', 'MESH:D007239', (197, 206))	('congenital alopecia', 'Phenotype', 'HP:0005597', (97, 116))	('congenital alopecia', 'Disease', 'MESH:C535981', (97, 116))	('alymphoid thymus', 'Disease', (15, 31))	('infection', 'Disease', (197, 206))	('primary T cell immunodeficiency', 'Disease', 'MESH:C536780', (40, 71))	('defective', 'Var', (122, 131))
57280	26273355	Molecular therapy using siRNA has shown great potential for diseases caused by abnormal gene over-expression or mutation, such as various cancers, viral infections, and genetic disorders.	('abnormal', 'Var', (79, 87))	('mutation', 'Var', (112, 120))	('genetic disorders', 'Disease', (169, 186))	('viral infections', 'Disease', (147, 163))	('viral infections', 'Disease', 'MESH:D001102', (147, 163))	('over-expression', 'PosReg', (93, 108))	('genetic disorders', 'Disease', 'MESH:D030342', (169, 186))	('cancers', 'Phenotype', 'HP:0002664', (138, 145))	('cancers', 'Disease', (138, 145))	('cancers', 'Disease', 'MESH:D009369', (138, 145))
57284	26273355	The RT-PCR and Western blot results showed that the expression of both FOXN1 and BCA1 was higher in Thy0517 cells than in CRL7660 cells.	('FOXN1', 'Gene', '8456', (71, 76))	('Thy0517', 'Var', (100, 107))	('CRL', 'Gene', (122, 125))	('expression', 'MPA', (52, 62))	('BCA1', 'Gene', (81, 85))	('FOXN1', 'Gene', (71, 76))	('CRL', 'Gene', '133396', (122, 125))	('higher', 'PosReg', (90, 96))
57285	26273355	Following transfection of Thy0517 cells with FOXN1 siRNA and BCA1 siRNA, RT-PCR and Western blot showed that the inhibition of FOXN1 expression downregulated the expression of BCA1, while the inhibition of BCA1 did not induce the same effect on FOXN1.	('expression', 'MPA', (133, 143))	('FOXN1', 'Gene', (45, 50))	('BCA1', 'Gene', (176, 180))	('FOXN1', 'Gene', (245, 250))	('downregulated', 'NegReg', (144, 157))	('inhibition', 'Var', (113, 123))	('FOXN1', 'Gene', '8456', (127, 132))	('expression', 'MPA', (162, 172))	('FOXN1', 'Gene', '8456', (45, 50))	('FOXN1', 'Gene', (127, 132))	('FOXN1', 'Gene', '8456', (245, 250))
57289	26273355	In this study, MTT assays showed that in the Thy0517 cell line, the inhibition of FOXN1 and BCA1 suppressed the proliferation of thymoma cells.	('FOXN1', 'Gene', '8456', (82, 87))	('thymoma', 'Disease', (129, 136))	('BCA1', 'Gene', (92, 96))	('inhibition', 'Var', (68, 78))	('thymoma', 'Phenotype', 'HP:0100522', (129, 136))	('FOXN1', 'Gene', (82, 87))	('MTT', 'Chemical', '-', (15, 18))	('suppressed', 'NegReg', (97, 107))	('thymoma', 'Disease', 'MESH:D013945', (129, 136))
57336	23554796	Postoperative morbidity was 26.7% and 33.3%, respectively, for the VATS and T3b group and respiratory complications (mainly including prolonged intubation, pneumonia and pleural effusion) were common, but they were no significant differences between the two groups.	('pneumonia', 'Phenotype', 'HP:0002090', (156, 165))	('T3b', 'Var', (76, 79))	('pneumonia', 'Disease', (156, 165))	('pneumonia', 'Disease', 'MESH:D011014', (156, 165))	('respiratory complications', 'Phenotype', 'HP:0011947', (90, 115))	('pleural effusion', 'Disease', 'MESH:D010996', (170, 186))	('prolonged intubation', 'Disease', (134, 154))	('pleural effusion', 'Disease', (170, 186))	('pleural effusion', 'Phenotype', 'HP:0002202', (170, 186))
57340	23554796	Only 1 patient was lost to follow-up and 1 patient died from myasthenic crisis 1 year postoperatively in the T3b group.	('myasthenic crisis', 'Phenotype', 'HP:0003473', (61, 78))	('patient', 'Species', '9606', (7, 14))	('patient', 'Species', '9606', (43, 50))	('myasthenic', 'Disease', (61, 71))	('T3b', 'Var', (109, 112))	('myasthenic', 'Disease', 'MESH:D020294', (61, 71))
57403	32051728	Additionally, anti-GQ1b antibodies lead to impaired neuromuscular transmission in a mouse diaphragm model.	('anti-GQ1b antibodies', 'Var', (14, 34))	('impaired', 'NegReg', (43, 51))	('neuromuscular transmission', 'MPA', (52, 78))	('antibodies', 'Var', (24, 34))	('mouse', 'Species', '10090', (84, 89))
57405	32051728	Furthermore, some clinical evidence also supports the presence of molecular mimicry between gangliosides and antecedent infectious agents in patients with GBS.	('gangliosides', 'Protein', (92, 104))	('molecular mimicry', 'Var', (66, 83))	('GBS', 'Disease', 'MESH:D020275', (155, 158))	('patients', 'Species', '9606', (141, 149))	('GBS', 'Disease', (155, 158))
57418	30863491	The down-regulation of CA9 transcription in TC cell lines by small interfering RNAs significantly inhibited CA9 expression, which inhibited proliferation and increased sensitivity to irradiation.	('small interfering', 'Var', (61, 78))	('proliferation', 'CPA', (140, 153))	('increased sensitivity to irradiation', 'Phenotype', 'HP:0011133', (158, 194))	('sensitivity to', 'MPA', (168, 182))	('inhibited', 'NegReg', (98, 107))	('CA9', 'Gene', '768', (23, 26))	('inhibited', 'NegReg', (130, 139))	('CA9', 'Gene', (108, 111))	('RNAs', 'Protein', (79, 83))	('transcription', 'MPA', (27, 40))	('CA9', 'Gene', '768', (108, 111))	('down-regulation', 'NegReg', (4, 19))	('CA9', 'Gene', (23, 26))	('increased', 'PosReg', (158, 167))	('expression', 'MPA', (112, 122))
57427	30863491	Several molecularly-targeted therapies developed using gene expression studies and analysis of mutations include a KIT inhibitor, epidermal growth factor receptor tyrosine kinase inhibitors, a histone deacetylase inhibitor, and an anti-insulin like growth factor 1 receptor antibody.	('insulin like growth factor 1 receptor', 'Gene', (236, 273))	('epidermal growth factor receptor', 'Gene', '1956', (130, 162))	('KIT inhibitor', 'Gene', (115, 128))	('mutations', 'Var', (95, 104))	('epidermal growth factor receptor', 'Gene', (130, 162))	('insulin like growth factor 1 receptor', 'Gene', '3480', (236, 273))
57453	30863491	Interestingly, cell proliferation, specifically under hypoxia, was significantly suppressed by the knockdown of CA9 expression by Ty-82 cells.	('CA9', 'Gene', '768', (112, 115))	('hypoxia', 'Disease', (54, 61))	('suppressed', 'NegReg', (81, 91))	('Ty-82', 'Chemical', '-', (130, 135))	('hypoxia', 'Disease', 'MESH:D000860', (54, 61))	('knockdown', 'Var', (99, 108))	('cell proliferation', 'CPA', (15, 33))	('CA9', 'Gene', (112, 115))
57477	30863491	Moreover, CA9 expression was significantly associated with shorter RFS.	('expression', 'Var', (14, 24))	('CA9', 'Gene', (10, 13))	('shorter', 'NegReg', (59, 66))	('CA9', 'Gene', '768', (10, 13))	('RFS', 'Disease', (67, 70))
57484	30863491	Here we show that inhibition of CA9 expression reduced the proliferation of TC cells, suggesting that inhibition of CA9 exerts an antitumor effect on TC.	('proliferation', 'CPA', (59, 72))	('CA9', 'Gene', '768', (116, 119))	('inhibition', 'Var', (102, 112))	('tumor', 'Disease', 'MESH:D009369', (134, 139))	('CA9', 'Gene', (32, 35))	('tumor', 'Phenotype', 'HP:0002664', (134, 139))	('inhibition', 'Var', (18, 28))	('reduced', 'NegReg', (47, 54))	('CA9', 'Gene', '768', (32, 35))	('tumor', 'Disease', (134, 139))	('CA9', 'Gene', (116, 119))
57485	30863491	Moreover, inhibition of CA9 expression enhanced the radiosensitivity of a TC cell line, suggesting that the combination of radiation and a CA9 inhibitor may synergize to more potently inhibit the growth of TC cells.	('inhibit', 'NegReg', (184, 191))	('radiosensitivity', 'MPA', (52, 68))	('CA9', 'Gene', (24, 27))	('growth', 'MPA', (196, 202))	('CA9', 'Gene', '768', (24, 27))	('a TC', 'CellLine', 'CVCL:B035', (72, 76))	('inhibition', 'Var', (10, 20))	('CA9', 'Gene', '768', (139, 142))	('CA9', 'Gene', (139, 142))	('enhanced', 'PosReg', (39, 47))
57487	30863491	Although we have to confirm the effect using other TC cell lines in detail, inhibition of CA9 expression might have other synergic effect to improve radiosensitivity of TC cells even in normoxic condition.	('CA9', 'Gene', (90, 93))	('CA9', 'Gene', '768', (90, 93))	('improve', 'PosReg', (141, 148))	('radiosensitivity', 'CPA', (149, 165))	('inhibition', 'Var', (76, 86))
57507	30863491	Physiologic thymic specimens were collected simultaneously from the surgically resected thymic tissue corresponding to TETs (TH25N, TH37N, TH41N, and TH42N were collected with TH25, TH37, TH41, and TH42, respectively).	('TH37N', 'Var', (132, 137))	('TH42N', 'Chemical', '-', (150, 155))	('TH25N', 'Chemical', '-', (125, 130))	('TH41N', 'Var', (139, 144))	('TH41N', 'Chemical', '-', (139, 144))	('TH37N', 'Chemical', '-', (132, 137))
57522	30863491	Total proteins were extracted from Ty-82 cells using PRO-PREP (iNtRON Biotechnology, Kyungki-Do, Korea) and from MP57 cells using lysis buffer [10% Glycerol, 10mM Tris-HCl (pH7.5), 1mM EDTA, 400 mM NaCl, 0.5% NP40, 4 mg/mL aprotonin, PMSF, proteasome inhibitor MG-132 and 1mM DTT], separated using SDS-PAGE (12.5% gels), electrophoretically transferred to membranes that were then incubated overnight at 4  C with the antibodies against CA9 (ab15086, 1:2000) (Abcam, Tokyo, Japan), HIF1a (CST #3716, 1:1000) (Cell Signaling Technology, MA, USA), beta-actin (CST #3700, 1:1000) (Cell Signaling Technology, MA, USA), and Hsc70 (1:4000) (Sigma, St. Louis, MO, USA).	('CA9', 'Gene', '768', (437, 440))	('Hsc70', 'Gene', '3312', (619, 624))	('HIF1a', 'Gene', (482, 487))	('CA9', 'Gene', (437, 440))	('beta-actin', 'Gene', '728378', (546, 556))	('HIF1a', 'Gene', '3091', (482, 487))	('Ty-82', 'Chemical', '-', (35, 40))	('CST #3716', 'Var', (489, 498))	('Hsc70', 'Gene', (619, 624))	('beta-actin', 'Gene', (546, 556))	('CST #3700', 'Var', (558, 567))
57524	30863491	CA9-specific small interfering RNAs (siRNA) (ON-TARGET plus Human CA9 siRNAs J-005244-05 [siRNA1] and J-005244-06 [siRNA2]) were purchased from Dharmacon (GE Healthcare, Japan).	('J-005244-05', 'Var', (77, 88))	('CA9', 'Gene', (66, 69))	('CA9', 'Gene', '768', (0, 3))	('CA9', 'Gene', (0, 3))	('CA9', 'Gene', '768', (66, 69))	('J-005244-06', 'Var', (102, 113))	('Human', 'Species', '9606', (60, 65))
57533	30863491	Proliferation rates were calculated using the absorbance at each time compared with those of the plates at 0 h. Ty-82 cells (4.0 x 103 cells/well), MP57 cells (2.0 x 103 cells/well) were plated in 96-well plates in 10% FBS-RPMI-1640 for 24 h (Ty-82) or 72 h (MP57) after siRNA transfection, cultured under hypoxia or normoxia for 6 h (Ty-82) or 24 h (MP57) and then irradiated.	('hypoxia', 'Disease', (306, 313))	('Ty-82', 'Chemical', '-', (112, 117))	('hypoxia', 'Disease', 'MESH:D000860', (306, 313))	('transfection', 'Var', (277, 289))	('Ty-82', 'Chemical', '-', (335, 340))	('Ty-82', 'Chemical', '-', (243, 248))	('siRNA', 'Gene', (271, 276))	('RPMI-1640', 'Chemical', '-', (223, 232))
57551	29631544	Progressive multifocal leukoencephalopathy (PML) is a rare and potentially fatal demyelinating disease of the central nervous system caused by reactivation of the JC virus (JCV).	('Progressive multifocal leukoencephalopathy', 'Disease', 'MESH:D007968', (0, 42))	('demyelinating disease of the central nervous system', 'Disease', 'MESH:D020278', (81, 132))	('demyelinating disease of the central nervous system', 'Phenotype', 'HP:0007305', (81, 132))	('caused by', 'Reg', (133, 142))	('reactivation', 'Var', (143, 155))	('leukoencephalopathy', 'Phenotype', 'HP:0002352', (23, 42))	('Progressive multifocal leukoencephalopathy', 'Disease', (0, 42))
57574	29631544	Lymphocyte subgroups were as follows: CD4, 14.9% (normal range 25.0%-54.0%); CD8, 25.0% (normal range 2.0%-56.0%); CD4/CD8 ratio, 0.6; CD19, 0.4% (normal range 5.0%-24.0%); and CD20, 1.1% (normal range 3.0%-20.0%).	('CD8', 'Gene', (77, 80))	('CD4', 'Gene', (38, 41))	('CD8', 'Gene', '925', (77, 80))	('CD8', 'Gene', (119, 122))	('CD8', 'Gene', '925', (119, 122))	('CD4', 'Gene', '920', (38, 41))	('CD4', 'Gene', (115, 118))	('CD20', 'Var', (177, 181))	('CD19', 'Var', (135, 139))	('CD4', 'Gene', '920', (115, 118))
57581	29631544	Brain MRI showed hyperintense lesions in the left frontal white matter on T2-weighted images and fluid-attenuated inversion recovery images (Fig.	('age', 'Gene', '5973', (135, 138))	('age', 'Gene', '5973', (88, 91))	('hyperintense lesions', 'Var', (17, 37))	('age', 'Gene', (135, 138))	('age', 'Gene', (88, 91))
57597	29631544	Our patient had CD4+, CD8+, and CD19+ lymphopenia, and hypogammaglobulinemia, which are characteristics of GS.	('hypogammaglobulinemia', 'Disease', (55, 76))	('patient', 'Species', '9606', (4, 11))	('lymphopenia', 'Disease', (38, 49))	('CD4', 'Gene', (16, 19))	('hypogammaglobulinemia', 'Disease', 'MESH:D000361', (55, 76))	('lymphopenia', 'Phenotype', 'HP:0001888', (38, 49))	('CD19+', 'Var', (32, 37))	('CD4', 'Gene', '920', (16, 19))	('CD8', 'Gene', (22, 25))	('GS', 'Disease', 'MESH:D011125', (107, 109))	('hypogammaglobulinemia', 'Phenotype', 'HP:0004313', (55, 76))	('CD8', 'Gene', '925', (22, 25))	('lymphopenia', 'Disease', 'MESH:D008231', (38, 49))
57601	29631544	Chemotherapeutic agents, such as cyclophosphamide, doxorubicin, vincristine, and methotrexate, can cause lymphopenia, including decreases in CD19+ B cells, CD4+ and CD8+ T cells, and decreased IgM levels with normal IgG levels.	('doxorubicin', 'Var', (51, 62))	('vincristine', 'Chemical', 'MESH:D014750', (64, 75))	('CD4', 'Gene', '920', (156, 159))	('decreased IgM', 'Phenotype', 'HP:0002850', (183, 196))	('doxorubicin', 'Chemical', 'MESH:D004317', (51, 62))	('decreased', 'NegReg', (183, 192))	('CD4', 'Gene', (156, 159))	('IgG levels', 'MPA', (216, 226))	('CD8', 'Gene', '925', (165, 168))	('vincristine', 'Var', (64, 75))	('age', 'Gene', (17, 20))	('lymphopenia', 'Disease', (105, 116))	('lymphopenia', 'Phenotype', 'HP:0001888', (105, 116))	('cyclophosphamide', 'Var', (33, 49))	('CD19+', 'MPA', (141, 146))	('cyclophosphamide', 'Chemical', 'MESH:D003520', (33, 49))	('decreases', 'NegReg', (128, 137))	('CD8', 'Gene', (165, 168))	('methotrexate', 'Var', (81, 93))	('age', 'Gene', '5973', (17, 20))	('IgM levels', 'MPA', (193, 203))	('lymphopenia', 'Disease', 'MESH:D008231', (105, 116))	('methotrexate', 'Chemical', 'MESH:D008727', (81, 93))
57693	29087033	We observed better survival in the TMM group (98.7 vs. 88.4%; P = 0.022); however, there was no significant difference in DFS between the groups (97.3 vs. 93.0%; P = 0.250).	('survival', 'CPA', (19, 27))	('TMM', 'Chemical', '-', (35, 38))	('TMM', 'Var', (35, 38))	('better', 'PosReg', (12, 18))
57812	24439931	The test reagents (antibodies pairs) for both IGF-1 and IGF-1R (DY291 and DYC305-2 respectively) were obtained from R&D Systems.	('IGF-1', 'Gene', (46, 51))	('IGF-1R', 'Gene', '3480', (56, 62))	('IGF-1', 'Gene', '3479', (46, 51))	('DYC305-2', 'Var', (74, 82))	('IGF-1', 'Gene', '3479', (56, 61))	('IGF-1R', 'Gene', (56, 62))	('IGF-1', 'Gene', (56, 61))
57870	24439931	The most frequently detected pre-treatment antibody was anti-IFNalpha (54%) followed by anti-IL12, anti-IL17A, and anti-IL22 in 39%, 4%, and 2% samples respectively.	('IFNalpha', 'Gene', '3439', (61, 69))	('IL17A', 'Gene', (104, 109))	('IFNalpha', 'Gene', (61, 69))	('anti-IL12', 'Var', (88, 97))	('IL17A', 'Gene', '3605', (104, 109))	('IL22', 'Gene', (120, 124))	('IL22', 'Gene', '50616', (120, 124))
57897	24439931	In our study anti-IFNalpha and anti-IL12 autoantibodies were identified most frequently and this is consistent with previous reports.	('anti-IL12', 'Var', (31, 40))	('IFNalpha', 'Gene', (18, 26))	('IFNalpha', 'Gene', '3439', (18, 26))
57903	24439931	This suggests that cixutumumab may be modulating the immune system in the milieu of a disease like thymoma that is already prone to development of autoimmunity.	('autoimmunity', 'Disease', 'MESH:D001327', (147, 159))	('modulating', 'Reg', (38, 48))	('cixutumumab', 'Var', (19, 30))	('cixutumumab', 'Chemical', 'MESH:C557414', (19, 30))	('autoimmunity', 'Phenotype', 'HP:0002960', (147, 159))	('thymoma', 'Gene', '7063', (99, 106))	('thymoma', 'Phenotype', 'HP:0100522', (99, 106))	('autoimmunity', 'Disease', (147, 159))	('thymoma', 'Gene', (99, 106))
57926	23577124	The lack of common cancer-associated mutations in this patient suggests that thymomas may evolve through mechanisms distinctive from other tumor types, and supports the rationale for additional high-throughput sequencing screens to better understand the somatic genetic architecture of thymoma.	('tumor', 'Disease', 'MESH:D009369', (139, 144))	('thymoma', 'Disease', (77, 84))	('thymomas', 'Disease', (77, 85))	('cancer', 'Disease', 'MESH:D009369', (19, 25))	('thymoma', 'Phenotype', 'HP:0100522', (286, 293))	('thymoma', 'Phenotype', 'HP:0100522', (77, 84))	('cancer', 'Disease', (19, 25))	('tumor', 'Phenotype', 'HP:0002664', (139, 144))	('tumor', 'Disease', (139, 144))	('mutations', 'Var', (37, 46))	('thymoma', 'Disease', 'MESH:D013945', (286, 293))	('patient', 'Species', '9606', (55, 62))	('cancer', 'Phenotype', 'HP:0002664', (19, 25))	('thymoma', 'Disease', 'MESH:D013945', (77, 84))	('thymoma', 'Disease', (286, 293))	('thymomas', 'Disease', 'MESH:D013945', (77, 85))
57942	23577124	Here we describe the characterization of thymoma specific mutations from the complete genome and transcriptome sequencing of a case of B3 thymoma.	('mutations', 'Var', (58, 67))	('thymoma', 'Disease', 'MESH:D013945', (41, 48))	('thymoma', 'Disease', (41, 48))	('thymoma', 'Disease', 'MESH:D013945', (138, 145))	('thymoma', 'Disease', (138, 145))	('thymoma', 'Phenotype', 'HP:0100522', (41, 48))	('thymoma', 'Phenotype', 'HP:0100522', (138, 145))
57958	23577124	Candidate mutations were evaluated in the sequence of tumor and normal DNA using Macvector (MacVector, Cary, NC).	('mutations', 'Var', (10, 19))	('tumor', 'Disease', 'MESH:D009369', (54, 59))	('tumor', 'Disease', (54, 59))	('tumor', 'Phenotype', 'HP:0002664', (54, 59))
57986	23577124	On the contrary, chromosomes affected by CN loss presented 24% more SNPs in normal than in tumor DNA (standard deviation 11%).	('tumor', 'Disease', 'MESH:D009369', (91, 96))	('tumor', 'Phenotype', 'HP:0002664', (91, 96))	('more', 'PosReg', (63, 67))	('tumor', 'Disease', (91, 96))	('CN loss', 'Var', (41, 48))	('SNPs', 'MPA', (68, 72))
57990	23577124	Mutations affecting UTRs, ncRNA (different from miRNA) and highly conserved regions defined according to the non-repeat masked regions available in UCSC genome browser website (n = 52).	('ncRNA', 'Gene', (26, 31))	('Mutations', 'Var', (0, 9))	('ncRNA', 'Gene', '54719', (26, 31))	('UTRs', 'Gene', (20, 24))
57996	23577124	RT-PCR demonstrated the presence of the junction transcript in this t(11:X) B3 thymoma but absence in another thymoma without the t(11;X) translocation (Figure 2B).	('t(11:X) B3', 'Var', (68, 78))	('thymoma', 'Disease', 'MESH:D013945', (79, 86))	('thymoma', 'Disease', 'MESH:D013945', (110, 117))	('thymoma', 'Disease', (79, 86))	('thymoma', 'Disease', (110, 117))	('thymoma', 'Phenotype', 'HP:0100522', (79, 86))	('thymoma', 'Phenotype', 'HP:0100522', (110, 117))
58000	23577124	Our data showed the mutations (single nucleotide variation and insertion/deletion), copy number aberrations and the translocation of a case of B3 thymoma.	('thymoma', 'Phenotype', 'HP:0100522', (146, 153))	('single nucleotide variation', 'Var', (31, 58))	('translocation', 'CPA', (116, 129))	('copy number aberrations', 'Var', (84, 107))	('thymoma', 'Disease', 'MESH:D013945', (146, 153))	('insertion/deletion', 'Var', (63, 81))	('thymoma', 'Disease', (146, 153))
58004	23577124	Although, some reports described mutations in thymic carcinomas such as KIT and TP53 mutations, for example, only sporadic mutations have been described in thymomas.	('thymoma', 'Phenotype', 'HP:0100522', (156, 163))	('KIT', 'Gene', (72, 75))	('TP53', 'Gene', '7157', (80, 84))	('TP53', 'Gene', (80, 84))	('mutations', 'Var', (85, 94))	('thymomas', 'Disease', (156, 164))	('thymomas', 'Disease', 'MESH:D013945', (156, 164))	('thymic carcinomas', 'Disease', 'MESH:D013945', (46, 63))	('carcinomas', 'Phenotype', 'HP:0030731', (53, 63))	('thymic carcinomas', 'Disease', (46, 63))
58005	23577124	Despite the less aggressive behavior of thymomas, compared to carcinomas and leukemias, our high-throughput screening revealed a similar mutation rate 0.72/Mb (single nucleotide variations and insertion/deletions) of that observed in neoplasms such as breast cancer (1/Mb) and myelogenous leukemias (0.56/Mb).	('leukemias', 'Disease', (289, 298))	('carcinomas', 'Disease', (62, 72))	('neoplasms', 'Phenotype', 'HP:0002664', (234, 243))	('leukemias', 'Disease', 'MESH:D007938', (77, 86))	('breast cancer', 'Phenotype', 'HP:0003002', (252, 265))	('leukemias', 'Phenotype', 'HP:0001909', (77, 86))	('breast cancer', 'Disease', 'MESH:D001943', (252, 265))	('neoplasms', 'Disease', 'MESH:D009369', (234, 243))	('breast cancer', 'Disease', (252, 265))	('carcinomas', 'Phenotype', 'HP:0030731', (62, 72))	('carcinomas', 'Disease', 'MESH:D002277', (62, 72))	('leukemia', 'Phenotype', 'HP:0001909', (77, 85))	('thymoma', 'Phenotype', 'HP:0100522', (40, 47))	('leukemia', 'Phenotype', 'HP:0001909', (289, 297))	('leukemias', 'Disease', (77, 86))	('leukemias', 'Disease', 'MESH:D007938', (289, 298))	('thymomas', 'Disease', 'MESH:D013945', (40, 48))	('aggressive behavior', 'Phenotype', 'HP:0000718', (17, 36))	('cancer', 'Phenotype', 'HP:0002664', (259, 265))	('neoplasms', 'Disease', (234, 243))	('myelogenous leukemias', 'Disease', 'MESH:D007951', (277, 298))	('leukemias', 'Phenotype', 'HP:0001909', (289, 298))	('0.72/Mb', 'Var', (151, 158))	('myelogenous leukemias', 'Disease', (277, 298))	('myelogenous leukemias', 'Phenotype', 'HP:0012324', (277, 298))	('thymomas', 'Disease', (40, 48))
58006	23577124	However, a higher average number of mutations was reported for lung cancer (8/Mb) and melanoma (up to 111/Mb).	('melanoma', 'Disease', 'MESH:D008545', (86, 94))	('lung cancer', 'Disease', 'MESH:D008175', (63, 74))	('melanoma', 'Phenotype', 'HP:0002861', (86, 94))	('melanoma', 'Disease', (86, 94))	('cancer', 'Phenotype', 'HP:0002664', (68, 74))	('mutations', 'Var', (36, 45))	('lung cancer', 'Disease', (63, 74))	('lung cancer', 'Phenotype', 'HP:0100526', (63, 74))
58015	23577124	Indeed, chromosomes with CN loss had fewer SNPs in tumor than in normal DNA (average difference 24%).	('tumor', 'Phenotype', 'HP:0002664', (51, 56))	('tumor', 'Disease', (51, 56))	('fewer', 'NegReg', (37, 42))	('SNPs in', 'MPA', (43, 50))	('CN loss', 'Var', (25, 32))	('tumor', 'Disease', 'MESH:D009369', (51, 56))
58016	23577124	On the contrary, in chromosomes without CN loss, the number of SNPs in tumor and normal was similar (average 2% more SNPs in normal with a standard deviation of 2%).	('tumor', 'Disease', (71, 76))	('tumor', 'Phenotype', 'HP:0002664', (71, 76))	('tumor', 'Disease', 'MESH:D009369', (71, 76))	('CN loss', 'Var', (40, 47))
58022	23577124	However, the CN loss of chromosome 13 is intriguing because this affects the loci of well-characterized tumor suppressor genes such as RB1 and BRCA2.	('BRCA2', 'Gene', '675', (143, 148))	('tumor', 'Phenotype', 'HP:0002664', (104, 109))	('RB1', 'Gene', (135, 138))	('tumor', 'Disease', (104, 109))	('affects', 'Reg', (65, 72))	('loci', 'MPA', (77, 81))	('CN loss', 'Var', (13, 20))	('RB1', 'Gene', '5925', (135, 138))	('BRCA2', 'Gene', (143, 148))	('tumor', 'Disease', 'MESH:D009369', (104, 109))
58028	23577124	This result was expected, because the poly-A tail capture strategy, adopted for mRNA enrichment, was not expected to capture the C11orf73-ODZ1 fusion transcript, since the nature of their tail-to-tail (3'-3') fusion was doomed to lose the poly-A tails of both genes.	('ODZ1', 'Gene', (138, 142))	('C11orf73', 'Gene', (129, 137))	('poly-A tails', 'MPA', (239, 251))	('tail-to-tail', 'Var', (188, 200))	('C11orf73', 'Gene', '51501', (129, 137))	('lose', 'NegReg', (230, 234))	('poly-A', 'Chemical', 'MESH:D011061', (239, 245))	('ODZ1', 'Gene', '10178', (138, 142))	('poly-A', 'Chemical', 'MESH:D011061', (38, 44))
58037	23577124	LDB3 mutation was localized in a splicing site but RNA sequencing data did not show any mis-spliced transcripts.	('mutation', 'Var', (5, 13))	('LDB3', 'Gene', '11155', (0, 4))	('LDB3', 'Gene', (0, 4))
58042	23577124	According to the literature, PHF15 and BCOR mutations can be related to the neoplastic phenotype.	('PHF15', 'Gene', (29, 34))	('PHF15', 'Gene', '23338', (29, 34))	('related', 'Reg', (61, 68))	('BCOR', 'Gene', (39, 43))	('mutations', 'Var', (44, 53))	('BCOR', 'Gene', '54880', (39, 43))
58052	23577124	Interestingly, BCOR mutated allele was preferentially expressed, accounting for 90% of the RNA sequencing reads (Table 3).	('BCOR', 'Gene', '54880', (15, 19))	('BCOR', 'Gene', (15, 19))	('mutated', 'Var', (20, 27))
58054	23577124	Germline BCOR mutations cause Oculofaciocardiodental syndrome, an inherited X-linked syndrome characterized by cardiac defects and dysmorphic appearance.	('Oculofaciocardiodental syndrome', 'Disease', (30, 61))	('BCOR', 'Gene', (9, 13))	('cause', 'Reg', (24, 29))	('X-linked syndrome', 'Disease', (76, 93))	('cardiac defects', 'Disease', 'MESH:D006331', (111, 126))	('BCOR', 'Gene', '54880', (9, 13))	('Oculofaciocardiodental syndrome', 'Disease', 'MESH:C537465', (30, 61))	('X-linked syndrome', 'Disease', 'MESH:C564486', (76, 93))	('dysmorphic', 'Disease', (131, 141))	('dysmorphic', 'Disease', 'None', (131, 141))	('dysmorphic appearance', 'Phenotype', 'HP:0001999', (131, 152))	('mutations', 'Var', (14, 23))	('cardiac defects', 'Disease', (111, 126))
58055	23577124	Similar genetic inherited malformations are also observed in the presence of the 22q11.2 deletion that is responsible for a group of syndromes such as the Di George or the velo-cardio-facial syndrome frequently associated with thymic aplasia or hypoplasia.	('inherited malformations', 'Disease', (16, 39))	('cardio-facial syndrome', 'Disease', 'MESH:D059347', (177, 199))	('thymic aplasia or hypoplasia', 'Disease', 'MESH:C536288', (227, 255))	('thymic aplasia or hypoplasia', 'Disease', (227, 255))	('inherited malformations', 'Disease', 'MESH:D000014', (16, 39))	('cardio-facial syndrome', 'Disease', (177, 199))	('deletion', 'Var', (89, 97))	('22q11.2', 'Gene', (81, 88))	('associated', 'Reg', (211, 221))	('Di George', 'Disease', (155, 164))	('thymic aplasia or hypoplasia', 'Phenotype', 'HP:0010515', (227, 255))
58056	23577124	The 22q11.2 deletion syndromes are linked to the loss of TBX1, a gene necessary for normal thymus development.	('loss', 'NegReg', (49, 53))	('deletion syndromes', 'Var', (12, 30))	('TBX1', 'Gene', '6899', (57, 61))	('TBX1', 'Gene', (57, 61))	('22q11.2', 'Gene', (4, 11))
58058	23577124	Recently, BCOR has been described as mutated in a subset of acute myeloid leukemia patients; about 50% of which present with both BCOR and DNMT3A mutations suggesting a potential cooperation of the two genes, possibly through an epigenetic mechanisms.	('acute myeloid leukemia', 'Phenotype', 'HP:0004808', (60, 82))	('mutations', 'Var', (146, 155))	('BCOR', 'Gene', '54880', (10, 14))	('acute myeloid leukemia', 'Disease', (60, 82))	('cooperation', 'Interaction', (179, 190))	('BCOR', 'Gene', (10, 14))	('BCOR', 'Gene', (130, 134))	('acute myeloid leukemia', 'Disease', 'MESH:D015470', (60, 82))	('myeloid leukemia', 'Phenotype', 'HP:0012324', (66, 82))	('patients', 'Species', '9606', (83, 91))	('BCOR', 'Gene', '54880', (130, 134))	('DNMT3A', 'Gene', (139, 145))	('DNMT3A', 'Gene', '1788', (139, 145))	('leukemia', 'Phenotype', 'HP:0001909', (74, 82))
58059	23577124	BCOR was significantly mutated in medulloblastoma such as other nuclear co-repressor (N-CoR) complex genes.	('medulloblastoma', 'Disease', 'MESH:D008527', (34, 49))	('BCOR', 'Gene', '54880', (0, 4))	('medulloblastoma', 'Phenotype', 'HP:0002885', (34, 49))	('medulloblastoma', 'Disease', (34, 49))	('mutated', 'Var', (23, 30))	('BCOR', 'Gene', (0, 4))
58063	23577124	Perhaps whole exome sequencing is a more cost effective strategy to address this question than a targeted re-sequencing of all the exons of tier 1 genes, allowing the identification of other recurrent non-synonymous mutations in thymic epithelial tumors besides these 12 genes.	('tumor', 'Phenotype', 'HP:0002664', (247, 252))	('thymic epithelial tumors', 'Disease', 'MESH:C536905', (229, 253))	('thymic epithelial tumors', 'Disease', (229, 253))	('tumors', 'Phenotype', 'HP:0002664', (247, 253))	('epithelial tumor', 'Phenotype', 'HP:0031492', (236, 252))	('non-synonymous mutations', 'Var', (201, 225))
58065	23577124	It is also conceivable that genetic alterations other than mutations are of importance in the causation and progression of thymomas, such as epigenetic changes, or miRNA alterations, as described in other tumor types.	('miRNA alterations', 'Var', (164, 181))	('tumor', 'Disease', 'MESH:D009369', (205, 210))	('thymoma', 'Phenotype', 'HP:0100522', (123, 130))	('tumor', 'Disease', (205, 210))	('tumor', 'Phenotype', 'HP:0002664', (205, 210))	('epigenetic changes', 'Var', (141, 159))	('thymomas', 'Disease', (123, 131))	('thymomas', 'Disease', 'MESH:D013945', (123, 131))
58068	23577124	Whole genome sequencing and accompanying transcriptome sequencing describe for the first time the mutations of a thymoma on a genome wide scale and offer an unprecedented view of those events responsible for the growth of these tumors.	('thymoma', 'Disease', 'MESH:D013945', (113, 120))	('thymoma', 'Disease', (113, 120))	('tumor', 'Phenotype', 'HP:0002664', (228, 233))	('thymoma', 'Phenotype', 'HP:0100522', (113, 120))	('mutations', 'Var', (98, 107))	('tumors', 'Disease', (228, 234))	('tumors', 'Phenotype', 'HP:0002664', (228, 234))	('tumors', 'Disease', 'MESH:D009369', (228, 234))
58069	23577124	The absence of mutations affecting the most common cancer genes suggests a possible thymoma specific pattern of mutations indicating the necessity of additional genome wide screenings rather than to determine the mutation frequency of a panel of common cancer genes.	('cancer', 'Disease', 'MESH:D009369', (253, 259))	('thymoma', 'Phenotype', 'HP:0100522', (84, 91))	('cancer', 'Phenotype', 'HP:0002664', (51, 57))	('mutations', 'Var', (112, 121))	('cancer', 'Disease', (253, 259))	('cancer', 'Disease', (51, 57))	('cancer', 'Disease', 'MESH:D009369', (51, 57))	('thymoma', 'Disease', 'MESH:D013945', (84, 91))	('cancer', 'Phenotype', 'HP:0002664', (253, 259))	('thymoma', 'Disease', (84, 91))
58077	22481857	Immunohistochemical staining was performed on sections from the thymus using antibodies against cytokeratin (34betaE12; Dako, Denmark, dilution 1:50), CD3 (1F4; Serotec, UK, dilution 1:20), CD79alpha (HM57; Dako, Denmark, dilution 1:50) and Ki-67 (MIB-5; Dako, Denmark, dilution 1:100).	('Ki-67', 'Gene', (241, 246))	('CD79alpha', 'Gene', '100913063', (190, 199))	('CD3', 'Var', (151, 154))	('CD79alpha', 'Gene', (190, 199))	('cytokeratin', 'Protein', (96, 107))
58158	20740204	However, it is well known that irradiation therapy can cause transient lymphocytopenia due to raised lymphocyte turnover.	('raised', 'PosReg', (94, 100))	('transient lymphocytopenia', 'Phenotype', 'HP:0005510', (61, 86))	('lymphocytopenia', 'Phenotype', 'HP:0001888', (71, 86))	('irradiation therapy', 'Var', (31, 50))	('raised lymphocyte', 'Phenotype', 'HP:0100827', (94, 111))	('lymphocytopenia', 'Disease', 'MESH:D008231', (71, 86))	('lymphocytopenia', 'Disease', (71, 86))	('lymphocyte', 'MPA', (101, 111))
58190	32926538	We also identified that PD-L1 expression could be an independent prognostic factor for OS in thymoma patients through multivariate analysis (HR 1.89, 95% CI: 1.09-3.28, P = 0.023).	('thymoma', 'Phenotype', 'HP:0100522', (93, 100))	('patients', 'Species', '9606', (101, 109))	('expression', 'Var', (30, 40))	('thymoma', 'Disease', 'MESH:D013945', (93, 100))	('PD-L1', 'Gene', (24, 29))	('thymoma', 'Disease', (93, 100))	('PD-L1', 'Gene', '29126', (24, 29))
58202	32926538	11  Thus, blocking PD-L1 makes effective immunotherapy possible.	('blocking', 'Var', (10, 18))	('PD-L1', 'Gene', (19, 24))	('PD-L1', 'Gene', '29126', (19, 24))
58216	32722121	Primary Driver Mutations in GTF2I Specific to the Development of Thymomas Thymomas are rare mediastinal tumors that are difficult to treat and pose a major public health concern.	('tumor', 'Phenotype', 'HP:0002664', (104, 109))	('Mutations', 'Var', (15, 24))	('Thymomas Thymomas', 'Phenotype', 'HP:0100522', (65, 82))	('Thymoma', 'Phenotype', 'HP:0100522', (65, 72))	('tumors', 'Phenotype', 'HP:0002664', (104, 110))	('tumors', 'Disease', (104, 110))	('tumors', 'Disease', 'MESH:D009369', (104, 110))	('GTF2I', 'Gene', (28, 33))	('Thymomas', 'Disease', (65, 73))	('GTF2I', 'Gene', '2969', (28, 33))	('Thymoma', 'Phenotype', 'HP:0100522', (74, 81))
58217	32722121	Type A thymomas possess a missense mutation in GTF2I (chromosome 7 c.74146970T>A) with high frequency.	('A thymomas', 'Disease', (5, 15))	('GTF2I', 'Gene', (47, 52))	('c.74146970T>A', 'Mutation', 'c.74146970T>A', (67, 80))	('GTF2I', 'Gene', '2969', (47, 52))	('A thymomas', 'Disease', 'MESH:D013945', (5, 15))	('A thymomas', 'Phenotype', 'HP:0100522', (5, 15))	('thymoma', 'Phenotype', 'HP:0100522', (7, 14))	('c.74146970T>A', 'Var', (67, 80))	('missense', 'Var', (26, 34))
58219	32722121	We aimed to detect this missense mutation in GTF2I in other thymoma subtypes (types B).	('thymoma', 'Disease', 'MESH:D013945', (60, 67))	('thymoma', 'Disease', (60, 67))	('missense mutation', 'Var', (24, 41))	('GTF2I', 'Gene', '2969', (45, 50))	('thymoma', 'Phenotype', 'HP:0100522', (60, 67))	('GTF2I', 'Gene', (45, 50))
58222	32722121	Subsequently, we performed targeted sequencing to detect mutant GTF2I coupled with molecular barcoding.	('mutant', 'Var', (57, 63))	('GTF2I', 'Gene', (64, 69))	('GTF2I', 'Gene', '2969', (64, 69))
58223	32722121	We used PyClone analysis to determine the fraction of tumor cells harboring mutant GTF2I.	('C', 'Chemical', 'MESH:D003596', (10, 11))	('tumor', 'Disease', 'MESH:D009369', (54, 59))	('mutant', 'Var', (76, 82))	('tumor', 'Phenotype', 'HP:0002664', (54, 59))	('tumor', 'Disease', (54, 59))	('GTF2I', 'Gene', (83, 88))	('GTF2I', 'Gene', '2969', (83, 88))
58224	32722121	We detected the missense mutation (chromosome 7 c.74146970T>A) in GTF2I in 14 thymomas among the 22 samples (64%).	('thymomas', 'Disease', 'MESH:D013945', (78, 86))	('GTF2I', 'Gene', '2969', (66, 71))	('thymomas', 'Disease', (78, 86))	('thymoma', 'Phenotype', 'HP:0100522', (78, 85))	('c.74146970T>A', 'Var', (48, 61))	('GTF2I', 'Gene', (66, 71))	('missense', 'Var', (16, 24))	('c.74146970T>A', 'Mutation', 'c.74146970T>A', (48, 61))
58226	32722121	The allele fraction for the tumors containing the mutations was variable, primarily owing to the coexistence of normal lymphocytes in the tumors, especially in type B thymomas.	('mutations', 'Var', (50, 59))	('tumors', 'Disease', (28, 34))	('tumors', 'Disease', 'MESH:D009369', (28, 34))	('tumors', 'Phenotype', 'HP:0002664', (28, 34))	('thymoma', 'Phenotype', 'HP:0100522', (167, 174))	('tumors', 'Disease', (138, 144))	('type B thymomas', 'Disease', (160, 175))	('tumors', 'Disease', 'MESH:D009369', (138, 144))	('tumors', 'Phenotype', 'HP:0002664', (138, 144))	('type B thymomas', 'Disease', 'MESH:D013945', (160, 175))	('tumor', 'Phenotype', 'HP:0002664', (28, 33))	('tumor', 'Phenotype', 'HP:0002664', (138, 143))
58227	32722121	PyClone analysis revealed a high cellular prevalence of mutant GTF2I in tumor cells.	('tumor', 'Phenotype', 'HP:0002664', (72, 77))	('tumor', 'Disease', (72, 77))	('mutant', 'Var', (56, 62))	('GTF2I', 'Gene', (63, 68))	('tumor', 'Disease', 'MESH:D009369', (72, 77))	('C', 'Chemical', 'MESH:D003596', (2, 3))	('GTF2I', 'Gene', '2969', (63, 68))
58228	32722121	Mutant GTF2I was not detected in other carcinomas (lung, gastric, colorectal, or hepatocellular carcinoma) or lymphomas.	('carcinoma', 'Phenotype', 'HP:0030731', (96, 105))	('GTF2I', 'Gene', '2969', (7, 12))	('GTF2I', 'Gene', (7, 12))	('lymphomas', 'Disease', (110, 119))	('lymphomas', 'Disease', 'MESH:D008223', (110, 119))	('carcinomas', 'Disease', 'MESH:D009369', (39, 49))	('hepatocellular carcinoma', 'Phenotype', 'HP:0001402', (81, 105))	('carcinoma', 'Phenotype', 'HP:0030731', (39, 48))	('lymphomas', 'Phenotype', 'HP:0002665', (110, 119))	('colorectal', 'Disease', 'MESH:D015179', (66, 76))	('hepatocellular carcinoma', 'Disease', (81, 105))	('carcinomas', 'Disease', (39, 49))	('hepatocellular carcinoma', 'Disease', 'MESH:D006528', (81, 105))	('Mutant', 'Var', (0, 6))	('carcinomas', 'Phenotype', 'HP:0030731', (39, 49))	('colorectal', 'Disease', (66, 76))	('lymphoma', 'Phenotype', 'HP:0002665', (110, 118))	('gastric', 'Disease', (57, 64))
58229	32722121	In conclusion, the majority of thymomas harbor mutations in GTF2I that can be potentially used as a novel therapeutic target in patients with thymomas.	('thymomas', 'Disease', (31, 39))	('thymomas', 'Disease', 'MESH:D013945', (31, 39))	('GTF2I', 'Gene', (60, 65))	('thymomas', 'Disease', (142, 150))	('thymomas', 'Disease', 'MESH:D013945', (142, 150))	('mutations', 'Var', (47, 56))	('thymoma', 'Phenotype', 'HP:0100522', (31, 38))	('GTF2I', 'Gene', '2969', (60, 65))	('patients', 'Species', '9606', (128, 136))	('thymoma', 'Phenotype', 'HP:0100522', (142, 149))
58235	32722121	Recent studies showed a missense mutation (chromosome 7 c.74146970T>A) in GTF2I (GTF: general transcription factor) present with high frequency in type A thymomas.	('c.74146970T>A', 'Mutation', 'c.74146970T>A', (56, 69))	('GTF2I', 'Gene', (74, 79))	('type A thymomas', 'Disease', 'MESH:D013945', (147, 162))	('type A thymomas', 'Disease', (147, 162))	('c.74146970T>A', 'Var', (56, 69))	('GTF2I', 'Gene', '2969', (74, 79))	('thymoma', 'Phenotype', 'HP:0100522', (154, 161))	('A thymomas', 'Phenotype', 'HP:0100522', (152, 162))
58238	32722121	Thus, it seemed unreasonable to hypothesize that mutations in GTF2I account for the development of the type A component, with other mechanisms responsible for the development of the type B component.	('mutations', 'Var', (49, 58))	('account', 'Reg', (68, 75))	('GTF2I', 'Gene', (62, 67))	('type A component', 'MPA', (103, 119))	('GTF2I', 'Gene', '2969', (62, 67))
58239	32722121	Thus, we focused on the importance of mutations in GTF2I in the development of type B thymomas using targeted sequencing coupled with techniques in molecular barcoding: more sensitive and specific assays than the whole-exome sequencing approach used in previous studies.	('type B thymomas', 'Disease', (79, 94))	('GTF2I', 'Gene', '2969', (51, 56))	('type B thymomas', 'Disease', 'MESH:D013945', (79, 94))	('thymoma', 'Phenotype', 'HP:0100522', (86, 93))	('mutations', 'Var', (38, 47))	('GTF2I', 'Gene', (51, 56))
58251	32722121	We detected point mutations in GTF2I in all the type A and AB thymomas; several type B thymomas were also positive for these GTF2I mutations.	('thymoma', 'Phenotype', 'HP:0100522', (87, 94))	('GTF2I', 'Gene', '2969', (125, 130))	('GTF2I', 'Gene', '2969', (31, 36))	('positive', 'Reg', (106, 114))	('type B thymomas', 'Disease', (80, 95))	('AB thymomas', 'Disease', 'MESH:D013945', (59, 70))	('AB thymomas', 'Disease', (59, 70))	('type B thymomas', 'Disease', 'MESH:D013945', (80, 95))	('thymoma', 'Phenotype', 'HP:0100522', (62, 69))	('GTF2I', 'Gene', (125, 130))	('type', 'Disease', (48, 52))	('GTF2I', 'Gene', (31, 36))	('point mutations', 'Var', (12, 27))	('detected', 'Reg', (3, 11))
58252	32722121	The type A and B portions of the type AB thymomas harbored mutant GTF2I.	('GTF2I', 'Gene', '2969', (66, 71))	('type AB thymomas', 'Disease', 'MESH:D013945', (33, 49))	('mutant', 'Var', (59, 65))	('thymoma', 'Phenotype', 'HP:0100522', (41, 48))	('type AB thymomas', 'Disease', (33, 49))	('GTF2I', 'Gene', (66, 71))	('harbored', 'Reg', (50, 58))
58253	32722121	The allele fraction with the mutant GTF2I was lower in type B thymomas compared to in type A thymomas; this could be attributed to the presence of normal cells in the tumor specimens.	('type B thymomas', 'Disease', (55, 70))	('thymoma', 'Phenotype', 'HP:0100522', (93, 100))	('GTF2I', 'Gene', (36, 41))	('mutant', 'Var', (29, 35))	('type B thymomas', 'Disease', 'MESH:D013945', (55, 70))	('tumor', 'Disease', 'MESH:D009369', (167, 172))	('GTF2I', 'Gene', '2969', (36, 41))	('type A thymomas', 'Disease', (86, 101))	('lower', 'NegReg', (46, 51))	('type A thymomas', 'Disease', 'MESH:D013945', (86, 101))	('tumor', 'Phenotype', 'HP:0002664', (167, 172))	('A thymomas', 'Phenotype', 'HP:0100522', (91, 101))	('thymoma', 'Phenotype', 'HP:0100522', (62, 69))	('tumor', 'Disease', (167, 172))
58254	32722121	Mutations in GTF2I were detected in 14 out of 22 patients with thymomas (64%).	('thymomas', 'Disease', (63, 71))	('detected', 'Reg', (24, 32))	('thymomas', 'Disease', 'MESH:D013945', (63, 71))	('Mutations', 'Var', (0, 9))	('GTF2I', 'Gene', (13, 18))	('patients', 'Species', '9606', (49, 57))	('GTF2I', 'Gene', '2969', (13, 18))	('thymoma', 'Phenotype', 'HP:0100522', (63, 70))
58255	32722121	Mutant GTF2I was detected in at least one sample from all the subtypes of thymomas (A, AB, B1, B2, and B3).	('GTF2I', 'Gene', '2969', (7, 12))	('AB, B1, B2, and B3', 'Gene', '28905;2925;680', (87, 105))	('thymoma', 'Phenotype', 'HP:0100522', (74, 81))	('Mutant', 'Var', (0, 6))	('thymomas', 'Disease', (74, 82))	('thymomas', 'Disease', 'MESH:D013945', (74, 82))	('GTF2I', 'Gene', (7, 12))	('detected', 'Reg', (17, 25))
58256	32722121	Thus, the GTF2I mutation may well be called a prevalent mutation in thymomas in general.	('mutation', 'Var', (16, 24))	('thymoma', 'Phenotype', 'HP:0100522', (68, 75))	('GTF2I', 'Gene', (10, 15))	('thymomas', 'Disease', (68, 76))	('GTF2I', 'Gene', '2969', (10, 15))	('thymomas', 'Disease', 'MESH:D013945', (68, 76))
58259	32722121	Mutant GTF2I was harbored in ~20%-90% of the tumor cells among all the thymomas (Figure 1), suggesting a high cellular prevalence of mutant GTF2I.	('GTF2I', 'Gene', '2969', (7, 12))	('tumor', 'Phenotype', 'HP:0002664', (45, 50))	('GTF2I', 'Gene', (7, 12))	('thymomas', 'Disease', 'MESH:D013945', (71, 79))	('thymoma', 'Phenotype', 'HP:0100522', (71, 78))	('tumor', 'Disease', (45, 50))	('GTF2I', 'Gene', (140, 145))	('Mutant', 'Var', (0, 6))	('GTF2I', 'Gene', '2969', (140, 145))	('mutant', 'Var', (133, 139))	('thymomas', 'Disease', (71, 79))	('tumor', 'Disease', 'MESH:D009369', (45, 50))
58260	32722121	This GTF2I mutation appeared to trigger clonal expansion and is retained ubiquitously within the tumors of the same clone.	('GTF2I', 'Gene', (5, 10))	('tumor', 'Phenotype', 'HP:0002664', (97, 102))	('GTF2I', 'Gene', '2969', (5, 10))	('tumors', 'Disease', (97, 103))	('tumors', 'Phenotype', 'HP:0002664', (97, 103))	('mutation', 'Var', (11, 19))	('tumors', 'Disease', 'MESH:D009369', (97, 103))
58261	32722121	PD-L1 expression was evaluated immunohistochemically in thymomas with the GTF2I mutation (GTF2I+) and without (GTF2I-; Figure 2A,B).	('GTF2I', 'Gene', '2969', (111, 116))	('GTF2I', 'Gene', (74, 79))	('GTF2I', 'Gene', '2969', (90, 95))	('mutation', 'Var', (80, 88))	('thymomas', 'Disease', (56, 64))	('GTF2I', 'Gene', '2969', (74, 79))	('thymomas', 'Disease', 'MESH:D013945', (56, 64))	('PD-L1', 'Gene', (0, 5))	('GTF2I', 'Gene', (111, 116))	('PD-L1', 'Gene', '29126', (0, 5))	('GTF2I', 'Gene', (90, 95))	('thymoma', 'Phenotype', 'HP:0100522', (56, 63))
58264	32722121	The staining intensity of PD-L1 was significantly higher in the GTF2I+ group compared to in the GTF2I- group (Figure 2C), which suggests the mutually exclusive presence of PD-L1 expression and the GTF2I mutation in tumor cells.	('GTF2I', 'Gene', '2969', (96, 101))	('PD-L1', 'Gene', '29126', (172, 177))	('GTF2I', 'Gene', '2969', (64, 69))	('higher', 'PosReg', (50, 56))	('GTF2I', 'Gene', (197, 202))	('PD-L1', 'Gene', '29126', (26, 31))	('tumor', 'Disease', 'MESH:D009369', (215, 220))	('PD-L1', 'Gene', (26, 31))	('GTF2I', 'Gene', (64, 69))	('GTF2I', 'Gene', '2969', (197, 202))	('tumor', 'Phenotype', 'HP:0002664', (215, 220))	('mutation', 'Var', (203, 211))	('C', 'Chemical', 'MESH:D003596', (118, 119))	('GTF2I', 'Gene', (96, 101))	('tumor', 'Disease', (215, 220))	('staining intensity', 'MPA', (4, 22))	('PD-L1', 'Gene', (172, 177))
58265	32722121	The age, sex, smoking habits, tumor size, histological type, Masaoka stage, and PD-L1 expression were assessed using multivariate analysis to identify factors affecting the mutation status of GTF2I.	('PD-L1', 'Gene', (80, 85))	('age', 'Gene', (4, 7))	('PD-L1', 'Gene', '29126', (80, 85))	('tumor', 'Disease', 'MESH:D009369', (30, 35))	('mutation', 'Var', (173, 181))	('age', 'Gene', '5973', (71, 74))	('GTF2I', 'Gene', (192, 197))	('tumor', 'Phenotype', 'HP:0002664', (30, 35))	('age', 'Gene', '5973', (4, 7))	('tumor', 'Disease', (30, 35))	('GTF2I', 'Gene', '2969', (192, 197))	('age', 'Gene', (71, 74))
58266	32722121	Based on a Cox proportional hazards model, the histology and PD-L1 expression were factors that determined the presence of mutations in GTF2I; sex (p = 0.41), age (p = 0.43), smoking habit (p = 0.68), tumor size (p = 0.97), and tumor stage (p = 0.46) did not correlate with the mutation status of GTF2I.	('C', 'Chemical', 'MESH:D003596', (11, 12))	('GTF2I', 'Gene', (297, 302))	('tumor', 'Disease', 'MESH:D009369', (228, 233))	('PD-L1', 'Gene', (61, 66))	('age', 'Gene', '5973', (236, 239))	('tumor', 'Disease', 'MESH:D009369', (201, 206))	('GTF2I', 'Gene', (136, 141))	('age', 'Gene', '5973', (159, 162))	('age', 'Gene', (159, 162))	('GTF2I', 'Gene', '2969', (297, 302))	('tumor', 'Phenotype', 'HP:0002664', (228, 233))	('tumor', 'Phenotype', 'HP:0002664', (201, 206))	('PD-L1', 'Gene', '29126', (61, 66))	('tumor', 'Disease', (228, 233))	('GTF2I', 'Gene', '2969', (136, 141))	('tumor', 'Disease', (201, 206))	('age', 'Gene', (236, 239))	('mutations', 'Var', (123, 132))
58267	32722121	In essence, mutant GTF2I was detected at a higher extent in type A and AB thymomas compared to in types B1-B3.	('type A', 'Disease', (60, 66))	('GTF2I', 'Gene', (19, 24))	('detected', 'Reg', (29, 37))	('thymoma', 'Phenotype', 'HP:0100522', (74, 81))	('GTF2I', 'Gene', '2969', (19, 24))	('mutant', 'Var', (12, 18))	('AB thymomas', 'Disease', 'MESH:D013945', (71, 82))	('AB thymomas', 'Disease', (71, 82))
58268	32722121	PD-L1-negative thymomas harbored mutant GTF2I significantly more frequently when compared to PD-L1-positive thymomas (HR: 12.60, 95% CI: 1.19-133.89).	('thymoma', 'Phenotype', 'HP:0100522', (15, 22))	('GTF2I', 'Gene', (40, 45))	('PD-L1-negative thymomas harbored', 'Disease', (0, 32))	('PD-L1-positive thymomas', 'Disease', 'MESH:D010300', (93, 116))	('GTF2I', 'Gene', '2969', (40, 45))	('mutant', 'Var', (33, 39))	('PD-L1-positive thymomas', 'Disease', (93, 116))	('C', 'Chemical', 'MESH:D003596', (133, 134))	('thymoma', 'Phenotype', 'HP:0100522', (108, 115))	('PD-L1-negative thymomas harbored', 'Disease', 'MESH:D010300', (0, 32))
58270	32722121	The pre-surgery blood exam data were analyzed, which revealed that serum LDH levels were significantly higher in thymomas with mutant GTF2I than those with wildtype GTF2I (thymomas with mutant GTF2I, 224.3 +- 13.3; thymomas with wildtype GTF2I, 183.7 +- 12.1; p < 0.05).	('higher', 'PosReg', (103, 109))	('thymomas', 'Disease', 'MESH:D013945', (172, 180))	('GTF2I', 'Gene', '2969', (193, 198))	('thymoma', 'Phenotype', 'HP:0100522', (113, 120))	('thymomas', 'Disease', 'MESH:D013945', (113, 121))	('serum LDH levels', 'MPA', (67, 83))	('mutant', 'Var', (127, 133))	('GTF2I', 'Gene', (193, 198))	('thymomas', 'Disease', (172, 180))	('GTF2I', 'Gene', '2969', (238, 243))	('thymoma', 'Phenotype', 'HP:0100522', (215, 222))	('GTF2I', 'Gene', '2969', (134, 139))	('thymomas', 'Disease', 'MESH:D013945', (215, 223))	('GTF2I', 'Gene', '2969', (165, 170))	('thymomas', 'Disease', (113, 121))	('GTF2I', 'Gene', (238, 243))	('GTF2I', 'Gene', (134, 139))	('GTF2I', 'Gene', (165, 170))	('thymomas', 'Disease', (215, 223))	('thymoma', 'Phenotype', 'HP:0100522', (172, 179))
58271	32722121	In addition, the PLR was significantly higher in thymomas with mutant GTF2I than those with wildtype GTF2I (thymomas with mutant GTF2I, 137.2 +- 13.1; thymomas with wildtype GTF2I, 97.0 +- 15.7; p < 0.05).	('thymomas', 'Disease', (151, 159))	('higher', 'PosReg', (39, 45))	('thymomas', 'Disease', 'MESH:D013945', (108, 116))	('GTF2I', 'Gene', '2969', (129, 134))	('GTF2I', 'Gene', (129, 134))	('thymomas', 'Disease', (108, 116))	('GTF2I', 'Gene', (101, 106))	('thymoma', 'Phenotype', 'HP:0100522', (49, 56))	('mutant', 'Var', (63, 69))	('thymomas', 'Disease', 'MESH:D013945', (49, 57))	('PLR', 'MPA', (17, 20))	('GTF2I', 'Gene', '2969', (174, 179))	('thymoma', 'Phenotype', 'HP:0100522', (151, 158))	('thymomas', 'Disease', 'MESH:D013945', (151, 159))	('GTF2I', 'Gene', '2969', (70, 75))	('GTF2I', 'Gene', '2969', (101, 106))	('thymomas', 'Disease', (49, 57))	('GTF2I', 'Gene', (174, 179))	('mutant', 'Var', (122, 128))	('GTF2I', 'Gene', (70, 75))	('thymoma', 'Phenotype', 'HP:0100522', (108, 115))
58274	32722121	Mutant GTF2I was not detected in other carcinomas, such as brain cancer, lung cancer, gastric cancer, colorectal cancer, hepatocellular carcinoma, and breast cancer, or in lymphomas (n = 20 for each, Table 3), indicating the specificity of mutant GTF2I in thymomas.	('breast cancer', 'Phenotype', 'HP:0003002', (151, 164))	('hepatocellular carcinoma', 'Disease', (121, 145))	('brain cancer', 'Phenotype', 'HP:0030692', (59, 71))	('carcinoma', 'Phenotype', 'HP:0030731', (136, 145))	('gastric cancer', 'Disease', (86, 100))	('cancer', 'Phenotype', 'HP:0002664', (113, 119))	('lung cancer', 'Disease', 'MESH:D008175', (73, 84))	('lymphomas', 'Disease', 'MESH:D008223', (172, 181))	('brain cancer', 'Disease', 'MESH:D001932', (59, 71))	('lymphomas', 'Phenotype', 'HP:0002665', (172, 181))	('mutant', 'Var', (240, 246))	('thymoma', 'Phenotype', 'HP:0100522', (256, 263))	('carcinomas', 'Disease', 'MESH:D009369', (39, 49))	('breast cancer', 'Disease', 'MESH:D001943', (151, 164))	('cancer', 'Phenotype', 'HP:0002664', (65, 71))	('carcinoma', 'Phenotype', 'HP:0030731', (39, 48))	('colorectal cancer', 'Disease', 'MESH:D015179', (102, 119))	('breast cancer', 'Disease', (151, 164))	('carcinomas', 'Phenotype', 'HP:0030731', (39, 49))	('lung cancer', 'Phenotype', 'HP:0100526', (73, 84))	('GTF2I', 'Gene', '2969', (247, 252))	('cancer', 'Phenotype', 'HP:0002664', (158, 164))	('gastric cancer', 'Disease', 'MESH:D013274', (86, 100))	('colorectal cancer', 'Disease', (102, 119))	('hepatocellular carcinoma', 'Phenotype', 'HP:0001402', (121, 145))	('cancer', 'Phenotype', 'HP:0002664', (94, 100))	('GTF2I', 'Gene', (247, 252))	('Mutant', 'Var', (0, 6))	('cancer', 'Phenotype', 'HP:0002664', (78, 84))	('brain cancer', 'Disease', (59, 71))	('thymomas', 'Disease', 'MESH:D013945', (256, 264))	('lymphomas', 'Disease', (172, 181))	('GTF2I', 'Gene', '2969', (7, 12))	('gastric cancer', 'Phenotype', 'HP:0012126', (86, 100))	('hepatocellular carcinoma', 'Disease', 'MESH:D006528', (121, 145))	('carcinomas', 'Disease', (39, 49))	('lung cancer', 'Disease', (73, 84))	('lymphoma', 'Phenotype', 'HP:0002665', (172, 180))	('GTF2I', 'Gene', (7, 12))	('colorectal cancer', 'Phenotype', 'HP:0003003', (102, 119))	('thymomas', 'Disease', (256, 264))
58275	32722121	In this study, we investigated the presence of point mutations in GTF2I in thymomas using targeted sequencing coupled with molecular barcoding to validate previous findings obtained by whole-exome sequencing.	('GTF2I', 'Gene', '2969', (66, 71))	('point mutations', 'Var', (47, 62))	('thymoma', 'Phenotype', 'HP:0100522', (75, 82))	('thymomas', 'Disease', (75, 83))	('GTF2I', 'Gene', (66, 71))	('thymomas', 'Disease', 'MESH:D013945', (75, 83))
58276	32722121	We demonstrated a widespread distribution of mutant GTF2I in all types of thymomas, including type B.	('GTF2I', 'Gene', '2969', (52, 57))	('mutant', 'Var', (45, 51))	('thymoma', 'Phenotype', 'HP:0100522', (74, 81))	('thymomas', 'Disease', 'MESH:D013945', (74, 82))	('thymomas', 'Disease', (74, 82))	('GTF2I', 'Gene', (52, 57))
58277	32722121	The SIFT and Polyphen 2 algorithms predicted that the GTF2I mutation (p.L424H) was somatic and altered protein structure and function.	('p.L424H', 'Var', (70, 77))	('GTF2I', 'Gene', (54, 59))	('GTF2I', 'Gene', '2969', (54, 59))	('altered', 'Reg', (95, 102))	('p.L424H', 'Mutation', 'p.L424H', (70, 77))	('function', 'MPA', (125, 133))	('protein structure', 'MPA', (103, 120))
58278	32722121	Mutant GTF2I did not induce anchorage-independent growth but accelerated cell proliferation in vitro.	('GTF2I', 'Gene', '2969', (7, 12))	('GTF2I', 'Gene', (7, 12))	('age', 'Gene', (34, 37))	('accelerated', 'PosReg', (61, 72))	('cell proliferation in vitro', 'CPA', (73, 100))	('age', 'Gene', '5973', (34, 37))	('Mutant', 'Var', (0, 6))
58280	32722121	The presence of mutant GTF2I in type B thymomas, in addition to type A thymomas, in this study, unlike previous studies, can be attributed to three reasons.	('GTF2I', 'Gene', (23, 28))	('type A thymomas', 'Disease', 'MESH:D013945', (64, 79))	('type A thymomas', 'Disease', (64, 79))	('thymoma', 'Phenotype', 'HP:0100522', (71, 78))	('type B thymomas', 'Disease', (32, 47))	('GTF2I', 'Gene', '2969', (23, 28))	('thymoma', 'Phenotype', 'HP:0100522', (39, 46))	('A thymomas', 'Phenotype', 'HP:0100522', (69, 79))	('mutant', 'Var', (16, 22))	('type B thymomas', 'Disease', 'MESH:D013945', (32, 47))
58284	32722121	Contamination with normal cells reduces the probability of detecting mutations in tumor cells.	('mutations', 'Var', (69, 78))	('tumor', 'Disease', 'MESH:D009369', (82, 87))	('tumor', 'Phenotype', 'HP:0002664', (82, 87))	('tumor', 'Disease', (82, 87))	('C', 'Chemical', 'MESH:D003596', (0, 1))
58285	32722121	We used laser-capture microdissection to select tumor cells to maximize the chances of detecting the point mutation.	('tumor', 'Phenotype', 'HP:0002664', (48, 53))	('point', 'Var', (101, 106))	('tumor', 'Disease', (48, 53))	('tumor', 'Disease', 'MESH:D009369', (48, 53))
58286	32722121	The sequence coverage was more extensive in our study compared to that in previous studies, and thus the sensitivity and specificity of detecting mutant GTF2I were theoretically much higher in our study.	('age', 'Gene', '5973', (18, 21))	('GTF2I', 'Gene', (153, 158))	('higher', 'PosReg', (183, 189))	('GTF2I', 'Gene', '2969', (153, 158))	('age', 'Gene', (18, 21))	('mutant', 'Var', (146, 152))
58287	32722121	Third, we excluded the influence of pseudogenes and manually counted the DNA strands harboring the mutation in the real GTF2I gene.	('GTF2I', 'Gene', '2969', (120, 125))	('GTF2I', 'Gene', (120, 125))	('mutation', 'Var', (99, 107))
58288	32722121	The pseudogenes could have potentially biased the measurement, thereby reducing the chance of detecting GTF2I since the heterozygous mutations were present in 1 out 6 (17%) of the amplicons.	('reducing', 'NegReg', (71, 79))	('GTF2I', 'Gene', '2969', (104, 109))	('pseudogenes', 'Var', (4, 15))	('measurement', 'MPA', (50, 61))	('biased', 'Reg', (39, 45))	('GTF2I', 'Gene', (104, 109))
58289	32722121	Thus, by eliminating such bias, we increased the chances of detecting mutations in GTF2I by approximately six-fold.	('GTF2I', 'Gene', (83, 88))	('increased', 'PosReg', (35, 44))	('GTF2I', 'Gene', '2969', (83, 88))	('mutations', 'Var', (70, 79))
58290	32722121	demonstrated that the GTF2I mutation was detected by quantitative real time PCR and the fraction of mutant GTF2I was the highest in type A and AB thymomas, followed by type B1, B2, and B3, consistent with our results.	('GTF2I', 'Gene', '2969', (107, 112))	('thymoma', 'Phenotype', 'HP:0100522', (146, 153))	('AB thymomas', 'Disease', 'MESH:D013945', (143, 154))	('highest', 'Reg', (121, 128))	('AB thymomas', 'Disease', (143, 154))	('GTF2I', 'Gene', (22, 27))	('mutant', 'Var', (100, 106))	('GTF2I', 'Gene', '2969', (22, 27))	('type A', 'Disease', (132, 138))	('GTF2I', 'Gene', (107, 112))	('C', 'Chemical', 'MESH:D003596', (77, 78))
58298	32722121	Thus, the GTF2I point mutation may serve as a neoantigen for use as a therapeutic target.	('GTF2I', 'Gene', (10, 15))	('GTF2I', 'Gene', '2969', (10, 15))	('point mutation', 'Var', (16, 30))
58300	32722121	In this study, PD-L1 expression and the presence of mutant GTF2I were inversely correlated; very few patients were positive for both PD-L1 and mutant GTF2I.	('patients', 'Species', '9606', (101, 109))	('PD-L1', 'Gene', (15, 20))	('mutant', 'Var', (52, 58))	('PD-L1', 'Gene', (133, 138))	('GTF2I', 'Gene', (150, 155))	('GTF2I', 'Gene', (59, 64))	('PD-L1', 'Gene', '29126', (15, 20))	('PD-L1', 'Gene', '29126', (133, 138))	('GTF2I', 'Gene', '2969', (150, 155))	('GTF2I', 'Gene', '2969', (59, 64))
58301	32722121	In addition, blood marker data (serum LDH and PLR) in our study suggested that thymomas without the GTF2I mutation exhibited a higher response rate to immunotherapy.	('GTF2I', 'Gene', '2969', (100, 105))	('thymomas', 'Disease', (79, 87))	('thymomas', 'Disease', 'MESH:D013945', (79, 87))	('mutation', 'Var', (106, 114))	('thymoma', 'Phenotype', 'HP:0100522', (79, 86))	('response', 'CPA', (134, 142))	('higher', 'PosReg', (127, 133))	('GTF2I', 'Gene', (100, 105))
58312	32722121	The GeneRead DNA FFPE Kit (Qiagen, Hilden, Germany) was used according to the manufacturer's instructions, and the DNA quality was checked using primers against ribonuclease P. There were two pseudogenes with 99.4% sequence homology within approximately 500 base pairs upstream and downstream of the mutation site in GTF2I that limited the detection of GTF2I mutations.	('GTF2I', 'Gene', '2969', (317, 322))	('Kit', 'Gene', (22, 25))	('age', 'Gene', '5973', (29, 32))	('GTF2I', 'Gene', (353, 358))	('mutation', 'Var', (300, 308))	('Kit', 'Gene', '3815', (22, 25))	('GTF2I', 'Gene', (317, 322))	('GTF2I', 'Gene', '2969', (353, 358))	('age', 'Gene', (29, 32))
58321	32722121	We manually counted the GTF2I DNA strands with C at the site of the single nucleotide variation.	('GTF2I', 'Gene', (24, 29))	('GTF2I', 'Gene', '2969', (24, 29))	('C', 'Chemical', 'MESH:D003596', (47, 48))	('single nucleotide', 'Var', (68, 85))
58322	32722121	In such DNA strands, the substitution of T>adenine (A) at the hotspot (c.74146970) was considered as a true mutation in GTF2I and used for analysis (Figure 3).	('GTF2I', 'Gene', (120, 125))	('substitution of T>adenine', 'Var', (25, 50))	('adenine', 'Chemical', 'MESH:D000225', (43, 50))	('GTF2I', 'Gene', '2969', (120, 125))	('c.74146970', 'Var', (71, 81))
58324	32722121	In this study, PyClone analysis was performed to estimate the fraction of cancer cells harboring mutant GTF2I.	('C', 'Chemical', 'MESH:D003596', (17, 18))	('GTF2I', 'Gene', '2969', (104, 109))	('cancer', 'Disease', 'MESH:D009369', (74, 80))	('mutant', 'Var', (97, 103))	('cancer', 'Disease', (74, 80))	('cancer', 'Phenotype', 'HP:0002664', (74, 80))	('GTF2I', 'Gene', (104, 109))
58330	32722121	After obtaining signed informed consent, their sample tissues were analyzed for the presence of the GTF2I mutation.	('GTF2I', 'Gene', (100, 105))	('GTF2I', 'Gene', '2969', (100, 105))	('mutation', 'Var', (106, 114))
58334	32722121	A missense mutation in GTF2I was detected with high prevalence in and specific to thymomas.	('GTF2I', 'Gene', (23, 28))	('GTF2I', 'Gene', '2969', (23, 28))	('thymomas', 'Disease', 'MESH:D013945', (82, 90))	('thymoma', 'Phenotype', 'HP:0100522', (82, 89))	('missense mutation', 'Var', (2, 19))	('thymomas', 'Disease', (82, 90))
58352	30949123	For patients with anti-Hu antibodies, treatment of the cancer was the only factor associated with the stabilization of neurological symptoms.	('antibodies', 'Var', (26, 36))	('cancer', 'Phenotype', 'HP:0002664', (55, 61))	('anti-Hu', 'Protein', (18, 25))	('patients', 'Species', '9606', (4, 12))	('cancer', 'Disease', 'MESH:D009369', (55, 61))	('stabilization of neurological symptoms', 'Phenotype', 'HP:0002344', (102, 140))	('cancer', 'Disease', (55, 61))
58554	31681591	PD-L1high was designated as >=50% of tumor proportion score; PD-1high and CD8high were defined as >=5% and 1% of tumoral immune cells, respectively.	('tumor', 'Disease', (113, 118))	('CD8', 'Gene', '925', (74, 77))	('tumor', 'Disease', 'MESH:D009369', (37, 42))	('tumoral', 'Disease', (113, 120))	('tumoral', 'Disease', 'MESH:D009369', (113, 120))	('tumor', 'Phenotype', 'HP:0002664', (37, 42))	('tumor', 'Disease', (37, 42))	('tumor', 'Disease', 'MESH:D009369', (113, 118))	('tumor', 'Phenotype', 'HP:0002664', (113, 118))	('PD-L1high', 'Var', (0, 9))	('CD8', 'Gene', (74, 77))
58558	31681591	The PD-L1high thymoma group was correlated with high Masaoka-Koga stage (p < 0.001), type B3 histology (p < 0.001), and myasthenia gravis (p < 0.001).	('myasthenia gravis', 'Disease', 'MESH:D009157', (120, 137))	('type B3 histology', 'CPA', (85, 102))	('myasthenia', 'Phenotype', 'HP:0003473', (120, 130))	('thymoma', 'Disease', 'MESH:D013945', (14, 21))	('thymoma', 'Disease', (14, 21))	('myasthenia gravis', 'Disease', (120, 137))	('thymoma', 'Phenotype', 'HP:0100522', (14, 21))	('PD-L1high', 'Var', (4, 13))
58560	31681591	Multivariate analysis revealed that PD-L1high expression was an independent poor prognostic factor (p = 0.047, HR 2.087, 95% CI, 1.009-4.318) in thymomas.	('PD-L1high expression', 'Var', (36, 56))	('thymomas', 'Disease', (145, 153))	('thymomas', 'Disease', 'MESH:D013945', (145, 153))	('thymoma', 'Phenotype', 'HP:0100522', (145, 152))
58619	31681591	However, other parameters, including tumor size (p = 0.138), lymph node metastasis (p = 0.083), and distant metastasis (p = 0.164), were not correlated with PD-L1high classification.	('tumor', 'Disease', 'MESH:D009369', (37, 42))	('lymph node metastasis', 'CPA', (61, 82))	('tumor', 'Phenotype', 'HP:0002664', (37, 42))	('tumor', 'Disease', (37, 42))	('PD-L1high', 'Var', (157, 166))	('distant metastasis', 'CPA', (100, 118))
58624	31681591	In thymomas, the PD-L1high group exhibited poorer DFS (p = 0.042, log-rank test, Figure 4A) and OS (p = 0.003, log-rank test, Figure 4B) than the PD-L1low group; no differences in DFS (p = 0.444, log-rank test, Figure 4C) and OS (p = 0.190, log-rank test, Figure 4D) were observed between the two groups in TC.	('thymomas', 'Disease', 'MESH:D013945', (3, 11))	('thymomas', 'Disease', (3, 11))	('thymoma', 'Phenotype', 'HP:0100522', (3, 10))	('poorer', 'NegReg', (43, 49))	('PD-L1high', 'Var', (17, 26))
58626	31681591	Analysis of the PD-L1 and PD-1 expression combinations in thymomas revealed that PD-L1low/PD-1high groups exhibited good OS (p = 0.009, log-rank, Supplemental Figure 1B) compared to PD-L1high/PD-1low group; however, no differences in DFS were observed (p = 0.082, log-rank, Supplemental Figure 1A).	('PD-L1low/PD-1high', 'Var', (81, 98))	('thymomas', 'Disease', 'MESH:D013945', (58, 66))	('thymomas', 'Disease', (58, 66))	('thymoma', 'Phenotype', 'HP:0100522', (58, 65))
58629	31681591	However, in the multivariate analysis, PD-L1high was an independent poor prognostic factor for OS (p = 0.047, HR 2.09, 95% CI, 1.009-4.318) of thymomas.	('thymomas', 'Disease', 'MESH:D013945', (143, 151))	('thymomas', 'Disease', (143, 151))	('thymoma', 'Phenotype', 'HP:0100522', (143, 150))	('PD-L1high', 'Var', (39, 48))
58633	31681591	High PD-L1 expression was correlated with higher Masaoka-Koga staging in six studies and associated with WHO classification of type B and/or thymic carcinoma in eight publications.	('Masaoka-Koga staging', 'CPA', (49, 69))	('associated', 'Reg', (89, 99))	('thymic carcinoma', 'Disease', 'MESH:D013945', (141, 157))	('High', 'Var', (0, 4))	('carcinoma', 'Phenotype', 'HP:0030731', (148, 157))	('PD-L1', 'Gene', (5, 10))	('expression', 'MPA', (11, 21))	('higher', 'PosReg', (42, 48))	('thymic carcinoma', 'Disease', (141, 157))
58639	31681591	We found that high PD-1 expression was correlated with lower Masaoka-Koga stage (p = 0.012) and absence of MG (p < 0.001) in thymoma, but, as in previous studies, no correlations with parameters were observed in TC.	('thymoma', 'Phenotype', 'HP:0100522', (125, 132))	('expression', 'MPA', (24, 34))	('Masaoka-Koga stage', 'CPA', (61, 79))	('absence', 'NegReg', (96, 103))	('high', 'Var', (14, 18))	('lower', 'NegReg', (55, 60))	('thymoma', 'Disease', 'MESH:D013945', (125, 132))	('PD-1', 'Gene', (19, 23))	('thymoma', 'Disease', (125, 132))
58643	31681591	Several studies have shown that high PD-L1 expression is correlated with a better response to anti-PD-L1 therapy in NSCLC.	('NSCLC', 'Disease', 'MESH:D002289', (116, 121))	('high', 'Var', (32, 36))	('PD-L1', 'Gene', (37, 42))	('NSCLC', 'Phenotype', 'HP:0030358', (116, 121))	('expression', 'MPA', (43, 53))	('NSCLC', 'Disease', (116, 121))
58644	31681591	In TETs, it may be expected that high PD-L1 expression would lead to a better response to anti-PD-L1 treatment, such as in NSCLC; however, the limited clinical trials of anti-PD-L1 therapy in TETs have shown controversial results.	('high', 'Var', (33, 37))	('NSCLC', 'Disease', (123, 128))	('NSCLC', 'Disease', 'MESH:D002289', (123, 128))	('expression', 'Var', (44, 54))	('response', 'MPA', (78, 86))	('NSCLC', 'Phenotype', 'HP:0030358', (123, 128))	('PD-L1', 'Gene', (38, 43))
58645	31681591	As the cutoff of SP263 is not yet proven by clinical trials in TETs, we determined the cut-off as 50% because it is more highly expressed in TETs than in NSCLC.	('NSCLC', 'Disease', 'MESH:D002289', (154, 159))	('SP263', 'Var', (17, 22))	('NSCLC', 'Phenotype', 'HP:0030358', (154, 159))	('TETs', 'Disease', (141, 145))	('highly', 'PosReg', (121, 127))	('NSCLC', 'Disease', (154, 159))
58646	31681591	We found that the average TPS of 753 patients with NSCLC for SP263 was 25.02 +- 33.14 (data not shown), whereas it was 38.06 +- 32.35 in TETs.	('patients', 'Species', '9606', (37, 45))	('NSCLC', 'Disease', (51, 56))	('NSCLC', 'Disease', 'MESH:D002289', (51, 56))	('SP263', 'Var', (61, 66))	('NSCLC', 'Phenotype', 'HP:0030358', (51, 56))
58649	31681591	Interestingly, SP263 IHC was deemed to be superior due to its strong staining intensity and higher sensitivity compared to E1L3N in NSCLC.	('SP263 IHC', 'Var', (15, 24))	('NSCLC', 'Phenotype', 'HP:0030358', (132, 137))	('staining intensity', 'MPA', (69, 87))	('NSCLC', 'Disease', (132, 137))	('NSCLC', 'Disease', 'MESH:D002289', (132, 137))	('sensitivity', 'MPA', (99, 110))
58650	31681591	We chose SP263 for the following reasons: first, we were unable to purchase the 22C3 antibody for research use because, at the time of our study, 22C3 was permitted only for use in companion diagnosis support by a global drug company in Korea; second, the positive rate for SP142 was very low in NSCLC; third, we considered it useful to choose a clinically validated and druggable antibody.	('NSCLC', 'Disease', (296, 301))	('NSCLC', 'Disease', 'MESH:D002289', (296, 301))	('SP142', 'Var', (274, 279))	('NSCLC', 'Phenotype', 'HP:0030358', (296, 301))
58663	31681591	In addition, the median PD-L1 mRNA level was higher in type B3 and TC than in the other thymomas, supporting the result that PD-L1high expression by IHC correlated with type B3 in thymoma.	('thymoma', 'Disease', 'MESH:D013945', (88, 95))	('thymoma', 'Phenotype', 'HP:0100522', (180, 187))	('thymoma', 'Disease', 'MESH:D013945', (180, 187))	('type B3', 'Var', (55, 62))	('thymoma', 'Disease', (88, 95))	('thymoma', 'Phenotype', 'HP:0100522', (88, 95))	('thymomas', 'Disease', (88, 96))	('thymomas', 'Disease', 'MESH:D013945', (88, 96))	('higher', 'PosReg', (45, 51))	('PD-L1 mRNA level', 'MPA', (24, 40))	('PD-L1high expression', 'Var', (125, 145))	('thymoma', 'Disease', (180, 187))
58724	26295375	Refined diagnostic criteria for type A, AB, B1-B3 thymomas and thymic squamous cell carcinoma are given and will hopefully improve the reproducibility of the classification and its clinical relevance.	('B1-B3', 'Var', (44, 49))	('squamous cell carcinoma', 'Phenotype', 'HP:0002860', (70, 93))	('squamous cell carcinoma', 'Disease', (70, 93))	('squamous cell carcinoma', 'Disease', 'MESH:D002294', (70, 93))	('improve', 'PosReg', (123, 130))	('thymoma', 'Phenotype', 'HP:0100522', (50, 57))	('carcinoma', 'Phenotype', 'HP:0030731', (84, 93))	('thymomas', 'Disease', 'MESH:D013945', (50, 58))	('thymomas', 'Disease', (50, 58))	('type A', 'Disease', (32, 38))
58750	26295375	The latter show mutations of epigenetic regulatory genes, methylation patterns and expression profiles of anti-apoptotic genes that clearly distinguish them from thymomas.	('methylation', 'MPA', (58, 69))	('thymoma', 'Phenotype', 'HP:0100522', (162, 169))	('thymomas', 'Disease', (162, 170))	('epigenetic regulatory genes', 'Gene', (29, 56))	('mutations', 'Var', (16, 25))	('thymomas', 'Disease', 'MESH:D013945', (162, 170))	('expression', 'MPA', (83, 93))	('anti-apoptotic genes', 'Gene', (106, 126))
58751	26295375	On the other hand, the identification of a highly recurrent point mutation in the GTF2I oncogene in all major thymoma subtypes and thymic carcinomas is a seminal finding that underlines the unique tumor biology of thymic epithelial tumors and lends strong support to the WHO-based subtyping of thymic tumors.	('tumor', 'Disease', 'MESH:D009369', (197, 202))	('carcinomas', 'Phenotype', 'HP:0030731', (138, 148))	('thymic tumors', 'Disease', (294, 307))	('GTF2I', 'Gene', '2969', (82, 87))	('tumor', 'Phenotype', 'HP:0002664', (301, 306))	('thymic tumors', 'Disease', 'MESH:D013953', (294, 307))	('thymic epithelial tumors', 'Disease', 'MESH:C536905', (214, 238))	('GTF2I', 'Gene', (82, 87))	('thymic carcinomas', 'Disease', 'MESH:D013945', (131, 148))	('tumor', 'Phenotype', 'HP:0002664', (197, 202))	('tumor', 'Disease', (232, 237))	('thymic carcinomas', 'Disease', (131, 148))	('thymoma subtypes', 'Disease', (110, 126))	('tumor', 'Disease', 'MESH:D009369', (232, 237))	('tumor', 'Disease', (301, 306))	('tumor', 'Disease', (197, 202))	('tumors', 'Phenotype', 'HP:0002664', (232, 238))	('thymoma', 'Phenotype', 'HP:0100522', (110, 117))	('thymoma subtypes', 'Disease', 'MESH:D013945', (110, 126))	('thymic epithelial tumors', 'Disease', (214, 238))	('point mutation', 'Var', (60, 74))	('carcinoma', 'Phenotype', 'HP:0030731', (138, 147))	('tumor', 'Disease', 'MESH:D009369', (301, 306))	('tumor', 'Phenotype', 'HP:0002664', (232, 237))	('tumors', 'Phenotype', 'HP:0002664', (301, 307))
58785	26295375	Translocation of the MAML2 gene is characteristic of almost all low-grade MECs and many high-grade MECs of salivary glands, bronchi and lung.	('MAML2', 'Gene', '84441', (21, 26))	('MAML2', 'Gene', (21, 26))	('bronchi', 'Disease', (124, 131))	('Translocation', 'Var', (0, 13))
58791	26295375	These tumors are now known to occur at all ages, outside the thorax (and rarely outside the midline) in ~40%, and to show variant NUT (nuclear protein in testis) translocations in ~30% of cases.	('NUT', 'Gene', '256646', (130, 133))	('tumors', 'Phenotype', 'HP:0002664', (6, 12))	('NUT', 'Gene', (130, 133))	('tumors', 'Disease', (6, 12))	('tumors', 'Disease', 'MESH:D009369', (6, 12))	('variant', 'Var', (122, 129))	('tumor', 'Phenotype', 'HP:0002664', (6, 11))	('translocations', 'Var', (162, 176))
58802	26295375	In advanced stage refractory disease, KIT mutations have exclusively been reported to occur in thymic carcinomas, but their potential role as biomarkers needs further studies; meanwhile, targeting angiogenesis using multikinase inhibitors is of higher relevance in carcinomas irrespective of their KIT mutational status.	('carcinomas', 'Disease', 'MESH:D002277', (102, 112))	('carcinomas', 'Phenotype', 'HP:0030731', (265, 275))	('carcinomas', 'Disease', (265, 275))	('thymic carcinomas', 'Disease', (95, 112))	('carcinomas', 'Disease', 'MESH:D002277', (265, 275))	('occur', 'Reg', (86, 91))	('carcinoma', 'Phenotype', 'HP:0030731', (102, 111))	('thymic carcinomas', 'Disease', 'MESH:D013945', (95, 112))	('mutations', 'Var', (42, 51))	('carcinomas', 'Phenotype', 'HP:0030731', (102, 112))	('carcinoma', 'Phenotype', 'HP:0030731', (265, 274))	('carcinomas', 'Disease', (102, 112))
58812	26295375	The progressive increase and overlap of genetic gains and losses from typical carcinoids through atypical carcinoids to LCNECs and small cell carcinomas lends support to the WHO classification.	('carcinoid', 'Phenotype', 'HP:0100570', (106, 115))	('LCNECs', 'Disease', (120, 126))	('carcinoids', 'Phenotype', 'HP:0100570', (78, 88))	('carcinoids', 'Phenotype', 'HP:0100570', (106, 116))	('carcinomas', 'Phenotype', 'HP:0030731', (142, 152))	('small cell carcinomas', 'Disease', 'MESH:D018288', (131, 152))	('carcinoma', 'Phenotype', 'HP:0030731', (142, 151))	('small cell carcinomas', 'Phenotype', 'HP:0030357', (131, 152))	('small cell carcinomas', 'Disease', (131, 152))	('carcinoid', 'Phenotype', 'HP:0100570', (78, 87))	('losses', 'NegReg', (58, 64))	('genetic', 'Var', (40, 47))	('small cell carcinoma', 'Phenotype', 'HP:0030357', (131, 151))	('gains', 'PosReg', (48, 53))
58826	26295375	Among the novel genetic alterations reported since 2004, the following are of special interest from a biological and potentially immunotherapeutic perspective: translocations of the HLA class II transactivator CIITA at 16p13.13 associated with down-regulation of HLA class II molecules; and the almost specific amplification and/or translocation of the 9p24.1 region including the loci coding for the immune checkpoint molecules PD-L1 and PD-L2, which are overexpressed and helpful immunohistochemical markers in PMBL.	('PD-L1', 'Gene', '29126', (429, 434))	('HLA class II molecules', 'Protein', (263, 285))	('translocations', 'Var', (160, 174))	('PD-L1', 'Gene', (429, 434))	('CIITA', 'Gene', (210, 215))	('CIITA', 'Gene', '4261', (210, 215))	('PD-L2', 'Gene', (439, 444))	('PD-L2', 'Gene', '80380', (439, 444))	('translocation', 'Var', (332, 345))	('down-regulation', 'NegReg', (244, 259))
58830	26295375	Among many novel genetic alterations detected, mutations of NOTCH1/FXBW are associated with a favourable outcome, while loss of heterozygocity (LOH) at 6q has a negative impact on prognosis.	('NOTCH1', 'Gene', '4851', (60, 66))	('NOTCH1', 'Gene', (60, 66))	('mutations', 'Var', (47, 56))
58835	26295375	Recognition that genetic and transcriptomic variation of the tumor cells, and tumor-associated T cells and macrophages have prognostic relevance is also new.	('variation', 'Var', (44, 53))	('tumor', 'Disease', 'MESH:D009369', (78, 83))	('tumor', 'Disease', 'MESH:D009369', (61, 66))	('tumor', 'Phenotype', 'HP:0002664', (78, 83))	('tumor', 'Phenotype', 'HP:0002664', (61, 66))	('tumor', 'Disease', (78, 83))	('tumor', 'Disease', (61, 66))
58849	26295375	A new finding is the detection of BRAF mutations in about 50% of all cases of Langerhans cell histiocytosis, including mediastinal cases.	('histiocytosis', 'Phenotype', 'HP:0100727', (94, 107))	('mutations', 'Var', (39, 48))	('BRAF', 'Gene', '673', (34, 38))	('mediastinal cases', 'Disease', (119, 136))	('Langerhans cell histiocytosis', 'Disease', (78, 107))	('detection', 'Reg', (21, 30))	('BRAF', 'Gene', (34, 38))
58869	25585350	Developmental Exposure To 2,3,7,8 Tetrachlorodibenzo-p-Dioxin Attenuates Later-Life Notch1-Mediated T Cell Development and Leukemogenesis Over half of T-cell acute lymphoblastic leukemia (T-ALL) patients have activating mutations in the Notch gene.	('T-cell acute lymphoblastic leukemia', 'Phenotype', 'HP:0006727', (151, 186))	('Leukemogenesis', 'CPA', (123, 137))	('ALL', 'Phenotype', 'HP:0006721', (190, 193))	('Notch', 'Gene', (237, 242))	('T-ALL', 'Phenotype', 'HP:0006727', (188, 193))	('lymphoblastic leukemia', 'Phenotype', 'HP:0005526', (164, 186))	('Notch1', 'Gene', (84, 90))	('Notch1', 'Gene', '18128', (84, 90))	('2,3,7,8 Tetrachlorodibenzo-p-Dioxin', 'Chemical', 'MESH:D000072317', (26, 61))	('acute lymphoblastic leukemia', 'Phenotype', 'HP:0006721', (158, 186))	('patients', 'Species', '9606', (195, 203))	('activating mutations', 'Var', (209, 229))	('Attenuates', 'NegReg', (62, 72))	('T-cell acute lymphoblastic leukemia', 'Disease', 'MESH:D054218', (151, 186))	('T-cell acute lymphoblastic leukemia', 'Disease', (151, 186))	('leukemia', 'Phenotype', 'HP:0001909', (178, 186))
58875	25585350	We found that the vehicle-exposed NotchICN-TG offspring have a peripheral T-cell pool heavily biased toward the CD4 lineage, while TCDD-exposed NotchICN-TG offspring were biased toward the CD8 lineage.	('NotchICN-TG', 'Var', (34, 45))	('TCDD', 'Chemical', 'MESH:D000072317', (131, 135))	('ICN', 'Chemical', '-', (39, 42))	('CD8', 'Gene', (189, 192))	('CD8', 'Gene', '925', (189, 192))	('ICN', 'Chemical', '-', (149, 152))
58882	25585350	For example, early mutations in hematopoietic stem cells can increase the risk for development of leukemia.	('early mutations', 'Var', (13, 28))	('leukemia', 'Disease', (98, 106))	('leukemia', 'Disease', 'MESH:D007938', (98, 106))	('leukemia', 'Phenotype', 'HP:0001909', (98, 106))
58883	25585350	Moreover, 60% of all cases of T cell acute lymphoblastic leukemia (T-ALL) are associated with activating genetic mutations in Notch1, a transmembrane receptor required for T cell development and function and regulation of CD4 vs. CD8 lineage commitment.	('T-ALL', 'Phenotype', 'HP:0006727', (67, 72))	('T cell acute lymphoblastic leukemia', 'Phenotype', 'HP:0006727', (30, 65))	('Notch1', 'Gene', '18128', (126, 132))	('lymphoblastic leukemia', 'Phenotype', 'HP:0005526', (43, 65))	('CD8', 'Gene', (230, 233))	('CD8', 'Gene', '925', (230, 233))	('mutations', 'Var', (113, 122))	('T cell acute lymphoblastic leukemia', 'Disease', (30, 65))	('ALL', 'Phenotype', 'HP:0006721', (69, 72))	('acute lymphoblastic leukemia', 'Phenotype', 'HP:0006721', (37, 65))	('leukemia', 'Phenotype', 'HP:0001909', (57, 65))	('Notch1', 'Gene', (126, 132))	('T cell acute lymphoblastic leukemia', 'Disease', 'MESH:D054218', (30, 65))
58889	25585350	This potential of developmental Notch1-AHR crosstalk during hematopoietic system disease initiation warrants further consideration given the genetic link to Notch1 mutations in T-ALL and continued production and persistence of TCDD and other environmental combustion by-products that act on the AHR, particularly in many developing countries undergoing rapid industrialization.	('T-ALL', 'Phenotype', 'HP:0006727', (177, 182))	('hematopoietic system disease initiation', 'Disease', (60, 99))	('Notch1', 'Gene', (157, 163))	('Notch1', 'Gene', '18128', (157, 163))	('ALL', 'Phenotype', 'HP:0006721', (179, 182))	('hematopoietic system disease', 'Phenotype', 'HP:0001871', (60, 88))	('Notch1', 'Gene', (32, 38))	('Notch1', 'Gene', '18128', (32, 38))	('mutations', 'Var', (164, 173))	('hematopoietic system disease initiation', 'Disease', 'MESH:D019337', (60, 99))	('TCDD', 'Chemical', 'MESH:D000072317', (227, 231))
58893	25585350	We hypothesized that developmental activation of AHR would produce a more severe form of Notch1- influenced thymoma in transgenic mice prone to disease than in unexposed control transgenic mice.	('AHR', 'Gene', (49, 52))	('Notch1', 'Gene', (89, 95))	('Notch1', 'Gene', '18128', (89, 95))	('transgenic mice', 'Species', '10090', (178, 193))	('thymoma', 'Disease', 'MESH:D013945', (108, 115))	('developmental activation', 'Var', (21, 45))	('transgenic mice', 'Species', '10090', (119, 134))	('thymoma', 'Disease', (108, 115))	('thymoma', 'Phenotype', 'HP:0100522', (108, 115))	('produce', 'Reg', (59, 66))
58899	25585350	C57BL/6-Tg(LckNotch1)9E mice, hereafter referred to as Notch1ICN-TG mice, were offspring of original pups that were a generous gift from B.J.	('mice', 'Species', '10090', (68, 72))	('mice', 'Species', '10090', (24, 28))	('Notch1ICN-TG', 'Gene', '18128', (55, 67))	('Notch1', 'Gene', (55, 61))	('Notch1', 'Gene', '18128', (55, 61))	('Notch1ICN-TG', 'Gene', (55, 67))	('Notch1', 'Gene', (14, 20))	('C57BL/6-Tg', 'Var', (0, 10))	('Notch1', 'Gene', '18128', (14, 20))
58920	25585350	CD5+ tumor cells were identified by first gating on CD3+ populations, then CD4+ and CD8+.	('CD4+', 'Var', (75, 79))	('CD8', 'Gene', '925', (84, 87))	('CD5', 'Gene', '12507', (0, 3))	('tumor', 'Disease', 'MESH:D009369', (5, 10))	('tumor', 'Phenotype', 'HP:0002664', (5, 10))	('CD3', 'Gene', (52, 55))	('tumor', 'Disease', (5, 10))	('CD3', 'Gene', '12503', (52, 55))	('CD8', 'Gene', (84, 87))	('CD5', 'Gene', (0, 3))
58929	25585350	Following exposure to TCDD, both C57BL/6 and Notch1ICN-TG mice showed a significant decrease in thymic weight and cellularity (Fig.	('decrease', 'NegReg', (84, 92))	('Notch1ICN-TG', 'Gene', (45, 57))	('Notch1ICN-TG', 'Gene', '18128', (45, 57))	('cellularity', 'CPA', (114, 125))	('TCDD', 'Var', (22, 26))	('TCDD', 'Chemical', 'MESH:D000072317', (22, 26))	('mice', 'Species', '10090', (58, 62))	('C57BL/6', 'Var', (33, 40))	('thymic weight', 'CPA', (96, 109))
58942	25585350	Moreover, 30mug/kg TCDD produces an excess of CD8 cells compared to DP cells thus yielding a ratio of CD8+ to CD4+CD8+ cells that is greater than one, indicating an increase in CD8 conversion efficiency in Notch1ICN-TG mice (Fig 1H; p <= 0.05).	('increase', 'PosReg', (165, 173))	('CD8', 'Gene', '925', (46, 49))	('Notch1ICN-TG', 'Gene', '18128', (206, 218))	('DP', 'Chemical', '-', (68, 70))	('CD8', 'Gene', (102, 105))	('mice', 'Species', '10090', (219, 223))	('TCDD', 'Var', (19, 23))	('CD8', 'Gene', '925', (102, 105))	('Notch1ICN-TG', 'Gene', (206, 218))	('TCDD', 'Chemical', 'MESH:D000072317', (19, 23))	('CD8', 'Gene', '925', (114, 117))	('CD8', 'Gene', (114, 117))	('CD8', 'Gene', (46, 49))	('CD8', 'Gene', (177, 180))	('CD8', 'Gene', '925', (177, 180))
58950	25585350	No significant difference was found between treatments at any time point in either C57BL/6 or Notch1ICN-TG mice in the percentage of macrophages and granulocytes, as evidenced by percent of CD11b+ or Gr1+CD11b+ cells, respectively (Fig.	('C57BL/6', 'Var', (83, 90))	('CD11b+', 'Var', (190, 196))	('mice', 'Species', '10090', (107, 111))	('Notch1ICN-TG', 'Gene', '18128', (94, 106))	('Notch1ICN-TG', 'Gene', (94, 106))
58960	25585350	4A), we found no significant difference in CD4 to CD8 ratios or percent of CD4+CD8+ cells at either 8 weeks or 12 weeks in C57BL/6 or in Notch1ICN-TG thymi (Supp.	('CD8', 'Gene', (50, 53))	('Notch1ICN-TG', 'Gene', (137, 149))	('CD8', 'Gene', '925', (50, 53))	('CD8', 'Gene', (79, 82))	('CD8', 'Gene', '925', (79, 82))	('Notch1ICN-TG', 'Gene', '18128', (137, 149))	('C57BL/6', 'Var', (123, 130))
58999	25585350	The moderate protection against splenomegaly by developmental TCDD is similar to autoimmune and inflammatory amelioration following AHR activation.	('developmental', 'Var', (48, 61))	('TCDD', 'Gene', (62, 66))	('splenomegaly', 'Disease', (32, 44))	('splenomegaly', 'Disease', 'MESH:D013163', (32, 44))	('splenomegaly', 'Phenotype', 'HP:0001744', (32, 44))	('TCDD', 'Chemical', 'MESH:D000072317', (62, 66))
59011	25585350	We found that Notch1ICN-TG mice developmentally exposed to TCDD showed a persistently lower CD4+ to CD8+ ratio in peripheral blood, suggesting a less favorable response to disease treatment.	('mice', 'Species', '10090', (27, 31))	('Notch1ICN-TG', 'Gene', '18128', (14, 26))	('lower', 'NegReg', (86, 91))	('CD8', 'Gene', (100, 103))	('Notch1ICN-TG', 'Gene', (14, 26))	('CD8', 'Gene', '925', (100, 103))	('TCDD', 'Chemical', 'MESH:D000072317', (59, 63))	('TCDD', 'Var', (59, 63))
59013	25585350	Future research to identify epigenetic changes influenced by exogenous stimulation of the AHR during development may facilitate identification of secondary stressors beyond Notch1 that vulnerable populations are burdened with that increase their propensity for later-life hematological and other immune deficiencies.	('Notch1', 'Gene', (173, 179))	('exogenous', 'Var', (61, 70))	('immune deficiencies', 'Disease', (296, 315))	('Notch1', 'Gene', '18128', (173, 179))	('immune deficiencies', 'Phenotype', 'HP:0002721', (296, 315))	('immune deficiencies', 'Disease', 'MESH:D007153', (296, 315))	('AHR', 'Gene', (90, 93))
59033	22475440	Histological examination showed a thymoma [B1 according to the World Health Organization (WHO) classification, CD3(+), CD5(+), CD1(+), keratine(+), CD20(-) and CD30(-)].	('CD5', 'Gene', '921', (119, 122))	('keratine(+', 'Var', (135, 145))	('CD30', 'Gene', (160, 164))	('CD1', 'Gene', '911', (127, 130))	('thymoma', 'Disease', 'MESH:D013945', (34, 41))	('CD30', 'Gene', '943', (160, 164))	('CD1', 'Gene', (127, 130))	('CD20', 'Gene', '54474', (148, 152))	('thymoma', 'Disease', (34, 41))	('CD20', 'Gene', (148, 152))	('thymoma', 'Phenotype', 'HP:0100522', (34, 41))	('CD3(+', 'Var', (111, 116))	('CD5', 'Gene', (119, 122))
59114	33907842	miR-525-5p inhibited the expression of HSPA9 protein by targeting the 3'-untranslated region (UTR) of HSPA9 mRNA.	('miR-525-5p', 'Var', (0, 10))	('protein', 'Protein', (45, 52))	('expression', 'MPA', (25, 35))	('miR-525-5p', 'Chemical', '-', (0, 10))	('HSPA9', 'Gene', (39, 44))	('HSPA9', 'Gene', (102, 107))	('inhibited', 'NegReg', (11, 20))
59116	33907842	Animal experiment results also showed that knockdown of miR-525-5p promoted cancer by promoting the expression of HSPA9.	('miR-525-5p', 'Var', (56, 66))	('HSPA9', 'Protein', (114, 119))	('promoted', 'PosReg', (67, 75))	('promoting', 'PosReg', (86, 95))	('miR-525-5p', 'Chemical', '-', (56, 66))	('knockdown', 'Var', (43, 52))	('cancer', 'Phenotype', 'HP:0002664', (76, 82))	('expression', 'MPA', (100, 110))	('cancer', 'Disease', (76, 82))	('cancer', 'Disease', 'MESH:D009369', (76, 82))
59117	33907842	In conclusion, LOXL1-AS1 and HSPA9 are highly expressed in thymoma and thymic carcinoma; miR-525-5p is expressed at low levels in thymoma and thymic carcinoma; and downregulation of miR-525-5p is associated with poor prognosis.	('miR-525-5p', 'Chemical', '-', (89, 99))	('thymoma', 'Phenotype', 'HP:0100522', (59, 66))	('miR-525-5p', 'Chemical', '-', (182, 192))	('LOXL1', 'Gene', (15, 20))	('thymoma and thymic carcinoma', 'Disease', 'MESH:D013953', (59, 87))	('carcinoma', 'Phenotype', 'HP:0030731', (78, 87))	('carcinoma', 'Phenotype', 'HP:0030731', (149, 158))	('HSPA9', 'Gene', (29, 34))	('thymoma', 'Phenotype', 'HP:0100522', (130, 137))	('downregulation', 'NegReg', (164, 178))	('miR-525-5p', 'Var', (89, 99))	('miR-525-5p', 'Var', (182, 192))	('AS1', 'Gene', '5729', (21, 24))	('AS1', 'Gene', (21, 24))	('thymoma and thymic carcinoma', 'Disease', 'MESH:D013953', (130, 158))	('LOXL1', 'Gene', '4016', (15, 20))
59130	33907842	TCGA data and clinical results revealed that LOXL1-AS1 and HSPA9 were highly expressed, miR-525-5p was expressed at low levels, and these findings were associated with the prognosis of TET patients.	('miR-525-5p', 'Var', (88, 98))	('HSPA9', 'Protein', (59, 64))	('TET', 'Chemical', '-', (185, 188))	('TET', 'Disease', (185, 188))	('miR-525-5p', 'Chemical', '-', (88, 98))	('associated with', 'Reg', (152, 167))	('LOXL1', 'Gene', (45, 50))	('patients', 'Species', '9606', (189, 197))	('AS1', 'Gene', '5729', (51, 54))	('AS1', 'Gene', (51, 54))	('LOXL1', 'Gene', '4016', (45, 50))
59136	33907842	The relationships between the levels of LOXL1-AS1, miR-525-5p, HSPA9 and the 5-year survival rate were analysed.	('miR-525-5p', 'Var', (51, 61))	('LOXL1', 'Gene', '4016', (40, 45))	('AS1', 'Gene', '5729', (46, 49))	('AS1', 'Gene', (46, 49))	('miR-525-5p', 'Chemical', '-', (51, 61))	('LOXL1', 'Gene', (40, 45))
59160	33907842	Through the TCGA database, we found that thymoma patients with low miR-525-5p levels had a lower 5-year survival rate (Fig.	('lower', 'NegReg', (91, 96))	('miR-525-5p levels', 'Var', (67, 84))	('5-year', 'MPA', (97, 103))	('thymoma', 'Disease', 'MESH:D013945', (41, 48))	('thymoma', 'Disease', (41, 48))	('low', 'NegReg', (63, 66))	('thymoma', 'Phenotype', 'HP:0100522', (41, 48))	('patients', 'Species', '9606', (49, 57))	('miR-525-5p', 'Chemical', '-', (67, 77))
59163	33907842	Ty-82 and Thy0517 cells were divided into 4 groups: Mimic-NC, mimic-miR-525-5p, inhibitor-NC and inhibitor-miR-525-5p.	('inhibitor-NC', 'Var', (80, 92))	('miR-525-5p', 'Chemical', '-', (68, 78))	('miR-525-5p', 'Chemical', '-', (107, 117))	('Ty', 'Chemical', '-', (0, 2))	('mimic-miR-525-5p', 'Var', (62, 78))	('inhibitor-miR-525-5p', 'Var', (97, 117))
59166	33907842	The results showed that the cell viability of the mimic-miR-525-5p group was significantly decreased, and the cell viability of the inhibitor-miR-525-5p group was significantly increased (Fig.	('cell viability', 'CPA', (28, 42))	('miR-525-5p', 'Chemical', '-', (56, 66))	('cell viability', 'CPA', (110, 124))	('increased', 'PosReg', (177, 186))	('miR-525-5p', 'Chemical', '-', (142, 152))	('decreased', 'NegReg', (91, 100))	('inhibitor-miR-525-5p', 'Var', (132, 152))	('mimic-miR-525-5p', 'Var', (50, 66))
59167	33907842	In addition, the upregulation of miR-525-5p levels inhibited cell invasion, while the downregulation of miR-525-5p levels promoted cell invasion (Fig.	('miR-525-5p', 'Var', (33, 43))	('miR-525-5p', 'Chemical', '-', (33, 43))	('promoted', 'PosReg', (122, 130))	('cell invasion', 'CPA', (131, 144))	('miR-525-5p', 'Chemical', '-', (104, 114))	('downregulation', 'NegReg', (86, 100))	('upregulation', 'PosReg', (17, 29))	('inhibited', 'NegReg', (51, 60))	('cell invasion', 'CPA', (61, 74))
59168	33907842	These results suggested that miR-525-5p exerted a tumour suppressor effect on thymoma and thymic carcinoma.	('tumour', 'Disease', 'MESH:D009369', (50, 56))	('carcinoma', 'Phenotype', 'HP:0030731', (97, 106))	('tumour', 'Disease', (50, 56))	('miR-525-5p', 'Var', (29, 39))	('thymoma', 'Phenotype', 'HP:0100522', (78, 85))	('miR-525-5p', 'Chemical', '-', (29, 39))	('tumour', 'Phenotype', 'HP:0002664', (50, 56))	('thymoma and thymic carcinoma', 'Disease', 'MESH:D013953', (78, 106))
59170	33907842	Further studies showed that the level of HSPA9 protein in the mimic-miR-525-5p group was significantly lower than that in the mimic-NC group, while the level of HSPA9 protein in the inhibitor-miR-525-5p group was significantly higher than that in the inhibitor-NC group (Fig.	('miR-525-5p', 'Chemical', '-', (68, 78))	('miR-525-5p', 'Chemical', '-', (192, 202))	('lower', 'NegReg', (103, 108))	('higher', 'PosReg', (227, 233))	('mimic-miR-525-5p', 'Var', (62, 78))	('level', 'MPA', (32, 37))	('HSPA9', 'Protein', (41, 46))
59171	33907842	This indicated that miR-525-5p could inhibit the level of HSPA9 protein by targeting HSPA9 mRNA.	('level of', 'MPA', (49, 57))	('miR-525-5p', 'Chemical', '-', (20, 30))	('targeting', 'Reg', (75, 84))	('inhibit', 'NegReg', (37, 44))	('HSPA9', 'Protein', (85, 90))	('HSPA9 protein', 'Protein', (58, 71))	('miR-525-5p', 'Var', (20, 30))
59172	33907842	To analyse the clinical significance of miR-525-5p targeting HSPA9 in TET, we analysed the transcriptional characteristics of HSPA9 in the TCGA database.	('miR-525-5p', 'Chemical', '-', (40, 50))	('TET', 'Chemical', '-', (70, 73))	('miR-525-5p', 'Var', (40, 50))	('HSPA9', 'Gene', (61, 66))
59175	33907842	In the TET tissues, the levels of miR-525-5p and HSPA9 were negatively correlated (Fig.	('miR-525-5p', 'Chemical', '-', (34, 44))	('TET', 'Chemical', '-', (7, 10))	('miR-525-5p', 'Var', (34, 44))	('negatively', 'NegReg', (60, 70))	('HSPA9', 'Protein', (49, 54))
59176	33907842	In addition, we detected the levels of LOXL1-AS1, miR-525-5p and HSPA9 mRNA and protein in the human embryonic thymocyte line HBT8810 and the thymoma cell lines Thy0517 and Ty-82.	('human', 'Species', '9606', (95, 100))	('Ty', 'Chemical', '-', (173, 175))	('LOXL1', 'Gene', '4016', (39, 44))	('LOXL1', 'Gene', (39, 44))	('miR-525-5p', 'Var', (50, 60))	('thymoma', 'Phenotype', 'HP:0100522', (142, 149))	('HSPA9', 'Protein', (65, 70))	('thymoma', 'Disease', 'MESH:D013945', (142, 149))	('thymoma', 'Disease', (142, 149))	('AS1', 'Gene', '5729', (45, 48))	('AS1', 'Gene', (45, 48))	('miR-525-5p', 'Chemical', '-', (50, 60))	('HBT8810', 'CellLine', 'CVCL:D281', (126, 133))
59178	33907842	This suggested that HSPA9 played a cancer-promoting role in TET, and its role may be targeted regulation by miR-525-5p.	('miR-525-5p', 'Var', (108, 118))	('TET', 'Chemical', '-', (60, 63))	('TET', 'Disease', (60, 63))	('cancer', 'Phenotype', 'HP:0002664', (35, 41))	('miR-525-5p', 'Chemical', '-', (108, 118))	('HSPA9', 'Protein', (20, 25))	('cancer', 'Disease', 'MESH:D009369', (35, 41))	('cancer', 'Disease', (35, 41))
59179	33907842	To demonstrate that miR-525-5p targeted HSPA9 in regulating the biological behaviour of thymoma and thymic carcinoma cells, Thy0517 and Ty-82 cells were divided into 4 groups: Inhibitor-NC+sh-NC, inhibitor-miR-525-5p+sh-NC, inhibitor-miR-525-5p+sh-HSPA9 and inhibitor-NC+sh-HSPA9.	('carcinoma', 'Phenotype', 'HP:0030731', (107, 116))	('inhibitor-miR-525-5p+sh-NC', 'Var', (196, 222))	('Ty', 'Chemical', '-', (136, 138))	('miR-525-5p', 'Chemical', '-', (20, 30))	('miR-525-5p', 'Chemical', '-', (206, 216))	('miR-525-5p', 'Chemical', '-', (234, 244))	('thymoma', 'Phenotype', 'HP:0100522', (88, 95))	('biological', 'MPA', (64, 74))	('inhibitor-miR-525-5p+sh-HSPA9', 'Var', (224, 253))	('inhibitor-NC+sh-HSPA9', 'Var', (258, 279))	('Inhibitor-NC+sh-NC', 'Var', (176, 194))	('thymoma and thymic carcinoma', 'Disease', 'MESH:D013953', (88, 116))
59183	33907842	In addition, the apoptosis rate of the inhibitor-miR-525-5p+sh-HSPA9 group was significantly higher than that of the inhibitor-miR-525-5p+sh-NC group, and the invasive ability was significantly lower than that of the inhibitor-miR-525-5p+sh-NC group (Fig.	('higher', 'PosReg', (93, 99))	('invasive ability', 'CPA', (159, 175))	('inhibitor-miR-525-5p+sh-HSPA9', 'Var', (39, 68))	('miR-525-5p', 'Chemical', '-', (227, 237))	('miR-525-5p', 'Chemical', '-', (127, 137))	('miR-525-5p', 'Chemical', '-', (49, 59))	('apoptosis rate', 'CPA', (17, 31))	('lower', 'NegReg', (194, 199))
59184	33907842	This suggested that downregulating HSPA9 reversed the inhibition of apoptosis and the promotion of invasion by downregulating miR-525-5p.	('miR-525-5p', 'Chemical', '-', (126, 136))	('downregulating', 'NegReg', (111, 125))	('promotion', 'PosReg', (86, 95))	('apoptosis', 'CPA', (68, 77))	('miR-525-5p', 'MPA', (126, 136))	('invasion', 'CPA', (99, 107))	('downregulating', 'Var', (20, 34))	('HSPA9', 'Protein', (35, 40))
59185	33907842	This suggested that HSPA9 had a role in promoting the growth and metastasis of thymoma and thymic carcinoma, and miR-525-5p inhibited the progression of thymoma and thymic carcinoma by targeting HSPA9.	('miR-525-5p', 'Chemical', '-', (113, 123))	('metastasis of thymoma and thymic carcinoma', 'Disease', 'MESH:D009362', (65, 107))	('thymoma and thymic carcinoma', 'Disease', 'MESH:D013953', (79, 107))	('carcinoma', 'Phenotype', 'HP:0030731', (98, 107))	('promoting', 'PosReg', (40, 49))	('miR-525-5p', 'Var', (113, 123))	('thymoma and thymic carcinoma', 'Disease', 'MESH:D013953', (153, 181))	('HSPA9', 'Gene', (195, 200))	('growth', 'CPA', (54, 60))	('thymoma', 'Phenotype', 'HP:0100522', (79, 86))	('inhibited', 'NegReg', (124, 133))	('carcinoma', 'Phenotype', 'HP:0030731', (172, 181))	('thymoma', 'Phenotype', 'HP:0100522', (153, 160))
59190	33907842	The results showed that downregulation of miR-525-5p levels promoted tumour growth, downregulating HSPA9 inhibited tumour growth and reversed the effect of the miR-525-5p inhibitor (Fig.	('tumour', 'Disease', (69, 75))	('miR-525-5p', 'Chemical', '-', (42, 52))	('promoted', 'PosReg', (60, 68))	('inhibited', 'NegReg', (105, 114))	('HSPA9', 'Protein', (99, 104))	('tumour', 'Phenotype', 'HP:0002664', (115, 121))	('downregulating', 'NegReg', (84, 98))	('downregulation', 'NegReg', (24, 38))	('tumour', 'Phenotype', 'HP:0002664', (69, 75))	('tumour', 'Disease', 'MESH:D009369', (69, 75))	('tumour', 'Disease', 'MESH:D009369', (115, 121))	('miR-525-5p', 'Var', (42, 52))	('miR-525-5p', 'Chemical', '-', (160, 170))	('tumour', 'Disease', (115, 121))
59191	33907842	Moreover, the HSPA9 protein level in the tumour tissues of the inhibitor-miR-525-5p+sh-NC group was significantly higher than that in the inhibitor-NC+sh-NC group.	('inhibitor-miR-525-5p+sh-NC', 'Var', (63, 89))	('HSPA9 protein level', 'MPA', (14, 33))	('tumour', 'Phenotype', 'HP:0002664', (41, 47))	('tumour', 'Disease', 'MESH:D009369', (41, 47))	('miR-525-5p', 'Chemical', '-', (73, 83))	('tumour', 'Disease', (41, 47))	('higher', 'PosReg', (114, 120))
59192	33907842	The level of HSPA9 protein in the inhibitor-miR-525-5p+sh-HSPA9 group was lower than that in the inhibitor-miR-525-5p+sh-NC group (Fig.	('HSPA9 protein', 'Protein', (13, 26))	('miR-525-5p', 'Chemical', '-', (107, 117))	('inhibitor-miR-525-5p+sh-HSPA9', 'Var', (34, 63))	('lower', 'NegReg', (74, 79))	('miR-525-5p', 'Chemical', '-', (44, 54))	('level of', 'MPA', (4, 12))
59199	33907842	RT-qPCR was applied to detect LOXL1-AS1 and miR-525-5p.	('AS1', 'Gene', '5729', (36, 39))	('AS1', 'Gene', (36, 39))	('LOXL1', 'Gene', '4016', (30, 35))	('LOXL1', 'Gene', (30, 35))	('miR-525-5p', 'Var', (44, 54))	('miR-525-5p', 'Chemical', '-', (44, 54))
59200	33907842	The results showed that LOXL1-AS1 reduced the level of miR-525-5p, and the overexpression of miR-525-5p also reduced the level of LOXL1-AS1 (Fig.	('miR-525-5p', 'Var', (93, 103))	('reduced', 'NegReg', (34, 41))	('LOXL1', 'Gene', '4016', (130, 135))	('level of miR-525-5p', 'MPA', (46, 65))	('AS1', 'Gene', '5729', (30, 33))	('AS1', 'Gene', (30, 33))	('LOXL1', 'Gene', (130, 135))	('miR-525-5p', 'Chemical', '-', (55, 65))	('miR-525-5p', 'Chemical', '-', (93, 103))	('LOXL1', 'Gene', '4016', (24, 29))	('LOXL1', 'Gene', (24, 29))	('reduced', 'NegReg', (109, 116))	('AS1', 'Gene', '5729', (136, 139))	('AS1', 'Gene', (136, 139))
59202	33907842	This suggested that the process by which miR-525-5p inhibited HSPA9 expression may be regulated by LOXL1-AS1.	('expression', 'MPA', (68, 78))	('miR-525-5p', 'Chemical', '-', (41, 51))	('AS1', 'Gene', '5729', (105, 108))	('AS1', 'Gene', (105, 108))	('LOXL1', 'Gene', '4016', (99, 104))	('LOXL1', 'Gene', (99, 104))	('miR-525-5p', 'Var', (41, 51))	('inhibited', 'NegReg', (52, 61))	('HSPA9', 'Gene', (62, 67))
59204	33907842	Silencing LOXL1-AS1 caused an increase in miR-525-5p and a decrease in HSPA9 mRNA/protein.	('AS1', 'Gene', '5729', (16, 19))	('AS1', 'Gene', (16, 19))	('miR-525-5p', 'Chemical', '-', (42, 52))	('HSPA9 mRNA/protein', 'MPA', (71, 89))	('decrease', 'NegReg', (59, 67))	('LOXL1', 'Gene', '4016', (10, 15))	('increase', 'PosReg', (30, 38))	('LOXL1', 'Gene', (10, 15))	('miR-525-5p', 'MPA', (42, 52))	('Silencing', 'Var', (0, 9))
59205	33907842	Inhibition of miR-525-5p also caused increases in LOXL1-AS1 and HSPA9 mRNA/protein (Fig.	('AS1', 'Gene', '5729', (56, 59))	('AS1', 'Gene', (56, 59))	('LOXL1', 'Gene', '4016', (50, 55))	('LOXL1', 'Gene', (50, 55))	('miR-525-5p', 'Gene', (14, 24))	('miR-525-5p', 'Chemical', '-', (14, 24))	('increases', 'PosReg', (37, 46))	('HSPA9 mRNA/protein', 'MPA', (64, 82))	('Inhibition', 'Var', (0, 10))
59206	33907842	The results showed that for Ty-82 cells, silencing LOXL1-AS1 inhibited cell viability and invasion and promoted apoptosis, and downregulated miR-525-5p reversed the inhibition of LOXL1-AS1 on cell growth and invasion (Fig.	('invasion', 'CPA', (208, 216))	('inhibited', 'NegReg', (61, 70))	('silencing', 'Var', (41, 50))	('apoptosis', 'CPA', (112, 121))	('LOXL1', 'Gene', '4016', (179, 184))	('miR-525-5p', 'Chemical', '-', (141, 151))	('AS1', 'Gene', (57, 60))	('downregulated', 'NegReg', (127, 140))	('AS1', 'Gene', '5729', (57, 60))	('Ty', 'Chemical', '-', (28, 30))	('LOXL1', 'Gene', (179, 184))	('promoted', 'PosReg', (103, 111))	('LOXL1', 'Gene', '4016', (51, 56))	('LOXL1', 'Gene', (51, 56))	('cell viability', 'CPA', (71, 85))	('AS1', 'Gene', '5729', (185, 188))	('AS1', 'Gene', (185, 188))	('invasion', 'CPA', (90, 98))
59207	33907842	This indicated that LOXL1-AS1 affected the inhibition of HSPA9 by miR-525-5p by targeting miR-525-5p, thereby exerting a cancer-promoting effect in thymoma and thymic carcinoma.	('miR-525-5p', 'MPA', (90, 100))	('inhibition', 'NegReg', (43, 53))	('AS1', 'Gene', (26, 29))	('LOXL1', 'Gene', '4016', (20, 25))	('cancer', 'Phenotype', 'HP:0002664', (121, 127))	('HSPA9', 'Protein', (57, 62))	('thymoma and thymic carcinoma', 'Disease', 'MESH:D013953', (148, 176))	('miR-525-5p', 'Chemical', '-', (66, 76))	('AS1', 'Gene', '5729', (26, 29))	('carcinoma', 'Phenotype', 'HP:0030731', (167, 176))	('LOXL1', 'Gene', (20, 25))	('miR-525-5p', 'Chemical', '-', (90, 100))	('cancer', 'Disease', 'MESH:D009369', (121, 127))	('targeting', 'Var', (80, 89))	('cancer', 'Disease', (121, 127))	('thymoma', 'Phenotype', 'HP:0100522', (148, 155))
59208	33907842	In this study, LOXL1-AS1 regulated the expression of HSPA9 by targeting miR-525-5p and regulated the cell growth, apoptosis and invasion of thymoma and thymic carcinoma cells.	('carcinoma', 'Phenotype', 'HP:0030731', (159, 168))	('LOXL1', 'Gene', (15, 20))	('cell growth', 'CPA', (101, 112))	('thymoma and thymic carcinoma', 'Disease', 'MESH:D013953', (140, 168))	('miR-525-5p', 'MPA', (72, 82))	('AS1', 'Gene', (21, 24))	('HSPA9', 'Gene', (53, 58))	('miR-525-5p', 'Chemical', '-', (72, 82))	('thymoma', 'Phenotype', 'HP:0100522', (140, 147))	('AS1', 'Gene', '5729', (21, 24))	('expression', 'MPA', (39, 49))	('targeting', 'Var', (62, 71))	('regulated', 'Reg', (87, 96))	('invasion', 'CPA', (128, 136))	('apoptosis', 'CPA', (114, 123))	('LOXL1', 'Gene', '4016', (15, 20))
59217	33907842	An in vitro experiment confirmed that miR-195a-5p inhibits the proliferation of medullary thymic epithelial cells by directly targeting Smad7.	('miR-195a-5p', 'Var', (38, 49))	('proliferation of medullary thymic epithelial cells', 'CPA', (63, 113))	('targeting', 'Reg', (126, 135))	('Smad7', 'Gene', (136, 141))	('Smad7', 'Gene', '4092', (136, 141))	('inhibits', 'NegReg', (50, 58))
59219	33907842	miR-525-5p is a newly identified tumour-associated miRNA, and miR-525-5p can block the UBE2C/ZEB1/2 signal axis by targeting the inhibition of UBE2C expression, impairing the invasive ability of cervical cancer cells.	('cancer', 'Disease', 'MESH:D009369', (204, 210))	('ZEB1/2', 'Gene', (93, 99))	('UBE2C', 'Gene', '11065', (143, 148))	('block', 'NegReg', (77, 82))	('ZEB1/2', 'Gene', '6935;9839', (93, 99))	('tumour', 'Phenotype', 'HP:0002664', (33, 39))	('tumour', 'Disease', 'MESH:D009369', (33, 39))	('cancer', 'Disease', (204, 210))	('tumour', 'Disease', (33, 39))	('UBE2C', 'Gene', (87, 92))	('cancer', 'Phenotype', 'HP:0002664', (204, 210))	('expression', 'MPA', (149, 159))	('UBE2C', 'Gene', '11065', (87, 92))	('miR-525-5p', 'Chemical', '-', (0, 10))	('UBE2C', 'Gene', (143, 148))	('miR-525-5p', 'Chemical', '-', (62, 72))	('inhibition', 'NegReg', (129, 139))	('miR-525-5p', 'Var', (62, 72))	('impairing', 'NegReg', (161, 170))
59220	33907842	miR-525-5p may also be used as a new prognostic biomarker and therapeutic target for lung squamous cell carcinoma.	('squamous cell carcinoma', 'Phenotype', 'HP:0002860', (90, 113))	('lung squamous cell carcinoma', 'Disease', (85, 113))	('carcinoma', 'Phenotype', 'HP:0030731', (104, 113))	('miR-525-5p', 'Chemical', '-', (0, 10))	('miR-525-5p', 'Var', (0, 10))	('lung squamous cell carcinoma', 'Disease', 'MESH:D002294', (85, 113))
59221	33907842	Moreover, miR-525-5p has a cancer-promoting effect in colorectal cancer.	('cancer', 'Phenotype', 'HP:0002664', (27, 33))	('colorectal cancer', 'Disease', 'MESH:D015179', (54, 71))	('cancer', 'Disease', (65, 71))	('cancer', 'Phenotype', 'HP:0002664', (65, 71))	('miR-525-5p', 'Chemical', '-', (10, 20))	('cancer', 'Disease', 'MESH:D009369', (65, 71))	('colorectal cancer', 'Phenotype', 'HP:0003003', (54, 71))	('cancer', 'Disease', (27, 33))	('cancer', 'Disease', 'MESH:D009369', (27, 33))	('colorectal cancer', 'Disease', (54, 71))	('miR-525-5p', 'Var', (10, 20))
59223	33907842	It has also been found that miR-525-5p may be carcinogenic in laryngeal squamous cell carcinoma.	('squamous cell carcinoma', 'Phenotype', 'HP:0002860', (72, 95))	('carcinoma', 'Phenotype', 'HP:0030731', (86, 95))	('miR-525-5p', 'Chemical', '-', (28, 38))	('squamous cell carcinoma', 'Disease', 'MESH:D002294', (72, 95))	('squamous cell carcinoma', 'Disease', (72, 95))	('carcinogenic', 'Disease', 'MESH:D063646', (46, 58))	('miR-525-5p', 'Var', (28, 38))	('carcinogenic', 'Disease', (46, 58))
59225	33907842	It was also found through clinical trials that miR-525-5p was underexpressed in thymic carcinoma tissues, and high levels of miR-525-5p predicted a better prognosis.	('thymic carcinoma', 'Disease', 'MESH:D013953', (80, 96))	('miR-525-5p', 'Var', (125, 135))	('carcinoma', 'Phenotype', 'HP:0030731', (87, 96))	('miR-525-5p', 'Chemical', '-', (125, 135))	('better', 'PosReg', (148, 154))	('miR-525-5p', 'Chemical', '-', (47, 57))	('thymic carcinoma', 'Disease', (80, 96))
59226	33907842	That preliminary study suggested the anticancer effects of miR-525-5p in thymic carcinoma.	('miR-525-5p', 'Var', (59, 69))	('carcinoma', 'Phenotype', 'HP:0030731', (80, 89))	('cancer', 'Phenotype', 'HP:0002664', (41, 47))	('miR-525-5p', 'Chemical', '-', (59, 69))	('cancer', 'Disease', (41, 47))	('cancer', 'Disease', 'MESH:D009369', (41, 47))	('thymic carcinoma', 'Disease', (73, 89))	('thymic carcinoma', 'Disease', 'MESH:D013953', (73, 89))
59227	33907842	Subsequently, thymoma and thymic carcinoma cells with low expression and overexpression of miR-525-5p were constructed, and the results showed that miR-525-5p inhibited cell growth and invasion and promoted apoptosis.	('promoted', 'PosReg', (198, 206))	('apoptosis', 'CPA', (207, 216))	('cell growth', 'CPA', (169, 180))	('miR-525-5p', 'Var', (148, 158))	('thymoma and thymic carcinoma', 'Disease', 'MESH:D013953', (14, 42))	('carcinoma', 'Phenotype', 'HP:0030731', (33, 42))	('invasion', 'CPA', (185, 193))	('thymoma', 'Phenotype', 'HP:0100522', (14, 21))	('miR-525-5p', 'Chemical', '-', (148, 158))	('miR-525-5p', 'Chemical', '-', (91, 101))	('inhibited', 'NegReg', (159, 168))
59228	33907842	This indicated that miR-525-5p exerted a tumour suppressor effect in thymoma and thymic carcinoma.	('miR-525-5p', 'Chemical', '-', (20, 30))	('tumour', 'Phenotype', 'HP:0002664', (41, 47))	('thymoma and thymic carcinoma', 'Disease', 'MESH:D013953', (69, 97))	('tumour', 'Disease', 'MESH:D009369', (41, 47))	('carcinoma', 'Phenotype', 'HP:0030731', (88, 97))	('miR-525-5p', 'Var', (20, 30))	('tumour', 'Disease', (41, 47))	('thymoma', 'Phenotype', 'HP:0100522', (69, 76))
59229	33907842	To further investigate the mechanism by which miR-525-5p exerted a tumour suppressor effect in thymoma and thymic carcinoma, we predicted and verified that miR-525-5p directly targeted inhibition of HSPA9 expression.	('tumour', 'Phenotype', 'HP:0002664', (67, 73))	('miR-525-5p', 'Chemical', '-', (46, 56))	('miR-525-5p', 'Var', (156, 166))	('tumour', 'Disease', (67, 73))	('carcinoma', 'Phenotype', 'HP:0030731', (114, 123))	('thymoma', 'Phenotype', 'HP:0100522', (95, 102))	('HSPA9', 'Protein', (199, 204))	('inhibition', 'NegReg', (185, 195))	('miR-525-5p', 'Chemical', '-', (156, 166))	('thymoma and thymic carcinoma', 'Disease', 'MESH:D013953', (95, 123))	('expression', 'MPA', (205, 215))	('tumour', 'Disease', 'MESH:D009369', (67, 73))
59234	33907842	In the present study, cell experiments also showed that silencing HSPA9 inhibited thymoma and thymic carcinoma cell growth and invasion and promoted apoptosis, and silencing HSPA9 reversed the effects of the miR-525-5p inhibitor on cell growth, invasion and apoptosis.	('silencing', 'Var', (56, 65))	('apoptosis', 'CPA', (149, 158))	('carcinoma', 'Phenotype', 'HP:0030731', (101, 110))	('promoted', 'PosReg', (140, 148))	('invasion', 'CPA', (127, 135))	('HSPA9', 'Gene', (174, 179))	('thymoma', 'Phenotype', 'HP:0100522', (82, 89))	('miR-525-5p', 'Chemical', '-', (208, 218))	('inhibited', 'NegReg', (72, 81))	('silencing', 'Var', (164, 173))	('HSPA9', 'Protein', (66, 71))	('thymoma and thymic carcinoma', 'Disease', 'MESH:D013953', (82, 110))
59235	33907842	This indicated that miR-525-5p could inhibit growth and invasion and promote apoptosis of thymoma and thymic carcinoma cells by targeting the inhibition of HSPA9 expression.	('inhibition', 'NegReg', (142, 152))	('miR-525-5p', 'Chemical', '-', (20, 30))	('apoptosis', 'CPA', (77, 86))	('HSPA9', 'Protein', (156, 161))	('thymoma and thymic carcinoma', 'Disease', 'MESH:D013953', (90, 118))	('inhibit', 'NegReg', (37, 44))	('carcinoma', 'Phenotype', 'HP:0030731', (109, 118))	('expression', 'MPA', (162, 172))	('miR-525-5p', 'Var', (20, 30))	('promote', 'PosReg', (69, 76))	('thymoma', 'Phenotype', 'HP:0100522', (90, 97))
59237	33907842	Kong et al found that MALAT can target miR-338-3p as a sponge and promote the expression of MSL2, which may become a new therapeutic target for myasthenia gravis with thymoma.	('thymoma', 'Disease', 'MESH:D013945', (167, 174))	('expression', 'MPA', (78, 88))	('myasthenia gravis', 'Disease', 'MESH:D009157', (144, 161))	('miR-338-3p', 'Var', (39, 49))	('MSL2', 'Gene', (92, 96))	('thymoma', 'Disease', (167, 174))	('MSL2', 'Gene', '55167', (92, 96))	('promote', 'PosReg', (66, 73))	('myasthenia', 'Phenotype', 'HP:0003473', (144, 154))	('thymoma', 'Phenotype', 'HP:0100522', (167, 174))	('myasthenia gravis', 'Disease', (144, 161))
59241	33907842	Similar results were obtained by testing clinical samples, and high levels of LOXL1-AS1 predicted a worse prognosis.	('LOXL1', 'Gene', '4016', (78, 83))	('LOXL1', 'Gene', (78, 83))	('AS1', 'Gene', '5729', (84, 87))	('AS1', 'Gene', (84, 87))	('high', 'Var', (63, 67))
59243	33907842	Cellular experiments also demonstrated that in Thy0517 and Ty-82 cells, silencing LOXL1-AS1 inhibited cell growth and invasion and promoted apoptosis by targeting miR-525-5p.	('inhibited', 'NegReg', (92, 101))	('silencing', 'Var', (72, 81))	('LOXL1', 'Gene', '4016', (82, 87))	('LOXL1', 'Gene', (82, 87))	('AS1', 'Gene', '5729', (88, 91))	('AS1', 'Gene', (88, 91))	('apoptosis', 'CPA', (140, 149))	('Ty', 'Chemical', '-', (59, 61))	('miR-525-5p', 'Chemical', '-', (163, 173))	('miR-525-5p', 'Protein', (163, 173))	('targeting', 'Reg', (153, 162))	('promoted', 'PosReg', (131, 139))
59244	33907842	In conclusion, LOXL1-AS1 and HSPA9 are highly expressed in thymoma and thymic carcinoma, miR-525-5p is expressed at low levels in thymoma and thymic carcinoma, and these expression levels are associated with poor prognosis.	('miR-525-5p', 'Chemical', '-', (89, 99))	('thymoma', 'Phenotype', 'HP:0100522', (59, 66))	('carcinoma', 'Phenotype', 'HP:0030731', (149, 158))	('LOXL1', 'Gene', (15, 20))	('thymoma and thymic carcinoma', 'Disease', 'MESH:D013953', (59, 87))	('carcinoma', 'Phenotype', 'HP:0030731', (78, 87))	('thymoma', 'Phenotype', 'HP:0100522', (130, 137))	('HSPA9', 'Gene', (29, 34))	('miR-525-5p', 'Var', (89, 99))	('AS1', 'Gene', '5729', (21, 24))	('AS1', 'Gene', (21, 24))	('thymoma and thymic carcinoma', 'Disease', 'MESH:D013953', (130, 158))	('LOXL1', 'Gene', '4016', (15, 20))
59304	33103369	In our analysis restricted to monotherapies, disease relapse was markedly lower in rituximab-treated patients (6.1%) compared with other immunotherapeutic agent groups in the Cox proportional hazards model (hazard ratio [HR] = 0.18, 95% confidence interval [CI] 0.06 to 0.56, P = .0030).	('patients', 'Species', '9606', (101, 109))	('rituximab', 'Chemical', 'MESH:D000069283', (83, 92))	('rituximab-treated', 'Var', (83, 100))	('disease relapse', 'CPA', (45, 60))	('lower', 'NegReg', (74, 79))
59312	33103369	Anti-MuSK positive patients had a higher risk of relapse (52.6%) than the anti-AChR sero-positive cohort (21.4%) (HR = 2.75, 95% CI 1.72 to 4.39, P < .0001); moreover, they also had a poor response to drug maintenance (34.2%) compared to anti-AChR positive patients (60.2%) (HR = 1.94, 95% CI 1.25 to 2.85, P = .0024).	('MuSK', 'Gene', (5, 9))	('MuSK', 'Gene', '4593', (5, 9))	('patients', 'Species', '9606', (19, 27))	('positive', 'Var', (10, 18))	('relapse', 'MPA', (49, 56))	('Anti-MuSK positive', 'Phenotype', 'HP:0030210', (0, 18))	('patients', 'Species', '9606', (257, 265))
59321	33103369	Likewise, monotherapy of azathioprine did not reduce the risk of relapses in the subgroup of patients with A/AB/B1 thymoma types and without thymoma (HR = 2.48, 95% CI 1.49 to 4.10, P = .0004).	('azathioprine', 'Chemical', 'MESH:D001379', (25, 37))	('thymoma', 'Phenotype', 'HP:0100522', (115, 122))	('A/AB/B1', 'Var', (107, 114))	('thymoma', 'Disease', 'MESH:D013945', (141, 148))	('thymoma', 'Phenotype', 'HP:0100522', (141, 148))	('thymoma', 'Disease', (141, 148))	('thymoma', 'Disease', 'MESH:D013945', (115, 122))	('thymoma', 'Disease', (115, 122))	('patients', 'Species', '9606', (93, 101))
59349	33103369	Most patients in our cohort who received rituximab were over 50 years old, and the efficacy of rituximab also contributed to reducing the risk of other concomitant immunotherapy in late-onset MG patients.	('rituximab', 'Chemical', 'MESH:D000069283', (95, 104))	('patients', 'Species', '9606', (5, 13))	('rituximab', 'Chemical', 'MESH:D000069283', (41, 50))	('reducing', 'NegReg', (125, 133))	('patients', 'Species', '9606', (195, 203))	('rituximab', 'Var', (95, 104))
59430	30042722	IL-4Ralpha Polymorphism Is Associated With Myasthenia Gravis in Chinese Han Population Interleukin-4 (IL-4) is a potent growth and differentiation factor for B cells which play a vital role in the pathogenesis of myasthenia gravis (MG).	('Myasthenia', 'Phenotype', 'HP:0003473', (43, 53))	('Associated', 'Reg', (27, 37))	('myasthenia gravis', 'Disease', 'MESH:D009157', (213, 230))	('IL-4Ralpha', 'Gene', (0, 10))	('IL-4Ralpha', 'Gene', '3566', (0, 10))	('myasthenia', 'Phenotype', 'HP:0003473', (213, 223))	('Polymorphism', 'Var', (11, 23))	('Interleukin-4', 'Gene', '3565', (87, 100))	('Myasthenia Gravis', 'Disease', 'MESH:D009157', (43, 60))	('Interleukin-4', 'Gene', (87, 100))	('myasthenia gravis', 'Disease', (213, 230))	('Myasthenia Gravis', 'Disease', (43, 60))
59433	30042722	We hypothesize that polymorphism of IL-4Ralpha gene may be associated with the susceptibility and severity of MG. A Chinese cohort of 480 MG patients and 487 healthy controls were recruited.	('IL-4Ralpha', 'Gene', '3566', (36, 46))	('patients', 'Species', '9606', (141, 149))	('polymorphism', 'Var', (20, 32))	('IL-4Ralpha', 'Gene', (36, 46))
59435	30042722	Rs2107356 and rs1805010 were found to be associated with adult thymoma associated MG, and rs1801275 was found to be associated with adult non-thymoma AChR-Ab positive MG. We did not found association between IL-4Ralpha polymorphism and the severity of MG. Genetic variations of IL-4Ralpha were found associated with the susceptibility of MG in Chinese Han population.	('IL-4Ralpha', 'Gene', (278, 288))	('rs1801275', 'Mutation', 'rs1801275', (90, 99))	('rs1805010', 'Mutation', 'rs1805010', (14, 23))	('associated', 'Reg', (300, 310))	('IL-4Ralpha', 'Gene', '3566', (278, 288))	('thymoma', 'Disease', 'MESH:D013945', (63, 70))	('adult thymoma', 'Disease', (57, 70))	('Genetic variations', 'Var', (256, 274))	('IL-4Ralpha', 'Gene', (208, 218))	('thymoma', 'Disease', (63, 70))	('thymoma', 'Disease', 'MESH:D013945', (142, 149))	('thymoma', 'Disease', (142, 149))	('IL-4Ralpha', 'Gene', '3566', (208, 218))	('adult thymoma', 'Disease', 'MESH:C536905', (57, 70))	('thymoma', 'Phenotype', 'HP:0100522', (63, 70))	('Rs2107356', 'Mutation', 'Rs2107356', (0, 9))	('thymoma', 'Phenotype', 'HP:0100522', (142, 149))
59437	30042722	Interleukin-4 (IL-4) is one of the Th2 cytokines which plays a vital role in the pathogenesis of MG. IL-4 is a potent growth and differentiation factor for B cells and stimulates class-switching and autoantibody production.	('Interleukin-4', 'Gene', '3565', (0, 13))	('class-switching', 'MPA', (179, 194))	('IL-4', 'Var', (101, 105))	('Interleukin-4', 'Gene', (0, 13))	('autoantibody', 'CPA', (199, 211))	('stimulates', 'PosReg', (168, 178))
59439	30042722	In mice genetically deficient in IL-4, long-lasting muscle weakness developed after a single immunization with acetylcholine receptor (AChR).	('muscle weakness', 'Disease', 'MESH:D018908', (52, 67))	('muscle weakness', 'Phenotype', 'HP:0001324', (52, 67))	('mice', 'Species', '10090', (3, 7))	('deficient', 'Var', (20, 29))	('acetylcholine receptor', 'MPA', (111, 133))	('muscle weakness', 'Disease', (52, 67))	('-lasting muscle weakness', 'Phenotype', 'HP:0003323', (43, 67))	('IL-4', 'Gene', (33, 37))
59447	30042722	In experimental MG, IL-4R is upregulated in the myocytes following exposure to anti-AChR antibody, and demonstrated an increased responsiveness to IL-4, which implies the role of IL-4R in disease progression of experimental MG. Till now, there was no evidence on the association of IL-4 gene polymorphism with MG. Polymorphisms of IL-4Ralpha were found to be associated with the susceptibility of autoimmune or inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus, Graves' disease, eczema and asthma, and with the severity and treatment effects of some of the diseases.	('asthma', 'Phenotype', 'HP:0002099', (521, 527))	("Graves' disease", 'Phenotype', 'HP:0100647', (493, 508))	('IL-4R', 'Gene', '3566', (20, 25))	('IL-4R', 'Gene', '3566', (179, 184))	('systemic lupus erythematosus', 'Disease', 'MESH:D008180', (463, 491))	('rheumatoid arthritis', 'Disease', (441, 461))	('asthma', 'Disease', (521, 527))	('IL-4R', 'Gene', (331, 336))	('eczema', 'Disease', 'MESH:D004485', (510, 516))	('rheumatoid arthritis', 'Disease', 'MESH:D001172', (441, 461))	('IL-4R', 'Gene', (20, 25))	('IL-4R', 'Gene', (179, 184))	("Graves' disease", 'Disease', 'MESH:D006111', (493, 508))	('IL-4Ralpha', 'Gene', (331, 341))	('systemic lupus erythematosus', 'Disease', (463, 491))	('IL-4Ralpha', 'Gene', '3566', (331, 341))	('rheumatoid arthritis', 'Phenotype', 'HP:0001370', (441, 461))	('eczema', 'Disease', (510, 516))	("Graves' disease", 'Disease', (493, 508))	('eczema', 'Phenotype', 'HP:0000964', (510, 516))	('associated', 'Reg', (359, 369))	('asthma', 'Disease', 'MESH:D001249', (521, 527))	('IL-4R', 'Gene', '3566', (331, 336))	('arthritis', 'Phenotype', 'HP:0001369', (452, 461))	('Polymorphisms', 'Var', (314, 327))	('systemic lupus erythematosus', 'Phenotype', 'HP:0002725', (463, 491))
59448	30042722	reported the frequency of rs1805010 GG genotype was significantly higher in MG patients than in healthy controls.	('rs1805010', 'Mutation', 'rs1805010', (26, 35))	('rs1805010 GG', 'Var', (26, 38))	('higher', 'PosReg', (66, 72))	('patients', 'Species', '9606', (79, 87))
59449	30042722	The association between the polymorphism of IL-4Ralpha and MG remains to be confirmed independently.	('IL-4Ralpha', 'Gene', '3566', (44, 54))	('polymorphism', 'Var', (28, 40))	('IL-4Ralpha', 'Gene', (44, 54))
59450	30042722	In the current study, we explore the potential association between polymorphism of IL-4Ralpha and the susceptibility and severity of MG in a Chinese cohort.	('IL-4Ralpha', 'Gene', '3566', (83, 93))	('polymorphism', 'Var', (67, 79))	('IL-4Ralpha', 'Gene', (83, 93))
59458	30042722	Based on previous reports till July, 2013 and Pubmed SNP database, six SNPs (rs2107356, rs1805010, rs1805011, rs1805015, rs1801275, and rs8832) were selected in IL-4Ralpha gene.	('rs1801275', 'Mutation', 'rs1801275', (121, 130))	('rs2107356', 'Mutation', 'rs2107356', (77, 86))	('IL-4Ralpha', 'Gene', (161, 171))	('rs1805010', 'Var', (88, 97))	('rs1805011', 'Var', (99, 108))	('IL-4Ralpha', 'Gene', '3566', (161, 171))	('rs2107356', 'Var', (77, 86))	('rs1805011', 'Mutation', 'rs1805011', (99, 108))	('rs1805015', 'Mutation', 'rs1805015', (110, 119))	('rs1805015', 'Var', (110, 119))	('rs8832', 'Mutation', 'rs8832', (136, 142))	('rs8832', 'Var', (136, 142))	('rs1805010', 'Mutation', 'rs1805010', (88, 97))	('rs1801275', 'Var', (121, 130))
59467	30042722	Frequency of rs1801275 G allele was higher in MG than that in HC (P = 0.036, OR = 1.293, 95%CI 1.017-1.643, PBon = 0.216).	('higher', 'PosReg', (36, 42))	('rs1801275 G', 'Var', (13, 24))	('rs1801275', 'Mutation', 'rs1801275', (13, 22))
59469	30042722	Frequencies of rs2107356 T allele and rs1805010 A allele were significantly higher in thymoma (+) subgroup than those in HC and in thymoma (-) subgroup both after Bonferonni correction.	('thymoma', 'Phenotype', 'HP:0100522', (131, 138))	('rs2107356 T', 'Var', (15, 26))	('rs1805010', 'Mutation', 'rs1805010', (38, 47))	('rs1805010 A', 'Var', (38, 49))	('thymoma', 'Disease', 'MESH:D013945', (86, 93))	('thymoma', 'Disease', (86, 93))	('thymoma', 'Disease', 'MESH:D013945', (131, 138))	('thymoma', 'Phenotype', 'HP:0100522', (86, 93))	('higher', 'PosReg', (76, 82))	('rs2107356', 'Mutation', 'rs2107356', (15, 24))	('thymoma', 'Disease', (131, 138))
59470	30042722	There were significant differences in genotype frequencies of rs2107356 and rs1805010 between thymoma (+) subgroup and HC and between thymoma (+) and thymoma (-) subgroups under codominant and additives models.	('rs1805010', 'Var', (76, 85))	('thymoma', 'Disease', 'MESH:D013945', (150, 157))	('thymoma', 'Disease', (150, 157))	('thymoma', 'Disease', (134, 141))	('thymoma', 'Phenotype', 'HP:0100522', (94, 101))	('thymoma', 'Phenotype', 'HP:0100522', (150, 157))	('thymoma', 'Phenotype', 'HP:0100522', (134, 141))	('thymoma', 'Disease', 'MESH:D013945', (94, 101))	('rs2107356', 'Mutation', 'rs2107356', (62, 71))	('rs1805010', 'Mutation', 'rs1805010', (76, 85))	('thymoma', 'Disease', (94, 101))	('thymoma', 'Disease', 'MESH:D013945', (134, 141))	('rs2107356', 'Var', (62, 71))
59471	30042722	There were no significant differences in frequencies of rs2107356 T allele and rs1805010 A allele between thymoma (-) subgroup and HC (Table 3).	('rs2107356 T', 'Var', (56, 67))	('thymoma', 'Disease', 'MESH:D013945', (106, 113))	('thymoma', 'Disease', (106, 113))	('rs1805010', 'Mutation', 'rs1805010', (79, 88))	('thymoma', 'Phenotype', 'HP:0100522', (106, 113))	('rs2107356', 'Mutation', 'rs2107356', (56, 65))	('rs1805010 A', 'Var', (79, 90))
59472	30042722	Frequency of rs1801275 G allele was significantly higher in AChR-Ab (+) subgroup than that in HC after Bonferonni correction.	('higher', 'PosReg', (50, 56))	('rs1801275 G', 'Var', (13, 24))	('rs1801275', 'Mutation', 'rs1801275', (13, 22))
59473	30042722	There were significant differences in genotype frequencies of rs1801275 between AChR-Ab (+) subgroup and HC under codominant and additive models of inheritance.	('AChR-Ab', 'Gene', (80, 87))	('rs1801275', 'Mutation', 'rs1801275', (62, 71))	('rs1801275', 'Var', (62, 71))	('differences', 'Reg', (23, 34))
59474	30042722	Frequency of rs1801275 G allele was significantly higher in male MG patients than that in male controls (P = 0.017, OR = 1.531, 95%CI 1.086-2.160), and higher in AChR-Ab (+) subgroup than that in AChR-Ab (-) subgroup (P = 0.039, OR = 1.522, 95%CI 1.020-2.271).	('higher', 'PosReg', (152, 158))	('higher', 'PosReg', (50, 56))	('AChR-Ab', 'Disease', (162, 169))	('rs1801275 G', 'Var', (13, 24))	('patients', 'Species', '9606', (68, 76))	('rs1801275', 'Mutation', 'rs1801275', (13, 22))
59475	30042722	Logistic regression analysis was performed with thymoma (+-) as dependent variables, and with onset age (<15/15-50/ > 50 years, <15 as reference), gender (male/female), AChR-Ab (+-), muscle involvement at onset (ocular/generalized) and genotypes of rs2107356 or rs1805010 separately (under codominant or additives model) as independent variables.	('thymoma', 'Phenotype', 'HP:0100522', (48, 55))	('rs2107356', 'Var', (249, 258))	('rs1805010', 'Mutation', 'rs1805010', (262, 271))	('thymoma', 'Disease', (48, 55))	('rs1805010 separately', 'Var', (262, 282))	('thymoma', 'Disease', 'MESH:D013945', (48, 55))	('AChR-Ab', 'Gene', (169, 176))	('rs2107356', 'Mutation', 'rs2107356', (249, 258))
59476	30042722	Onset age, AChR-Ab (+) and genotypes of rs2107356 and rs1805010 were found as independent risk factors for the presence of thymoma (Tables 4).	('rs1805010', 'Var', (54, 63))	('rs2107356', 'Mutation', 'rs2107356', (40, 49))	('thymoma', 'Disease', 'MESH:D013945', (123, 130))	('rs2107356', 'Var', (40, 49))	('thymoma', 'Disease', (123, 130))	('AChR-Ab', 'Gene', (11, 18))	('thymoma', 'Phenotype', 'HP:0100522', (123, 130))	('rs1805010', 'Mutation', 'rs1805010', (54, 63))
59478	30042722	Thymoma, ocular presenting and rs1801275 genotypes were found as independent risk factors for AChR-Ab positivity (Table 5).	('rs1801275', 'Mutation', 'rs1801275', (31, 40))	('Thymoma', 'Phenotype', 'HP:0100522', (0, 7))	('Thymoma', 'Disease', (0, 7))	('AChR-Ab', 'Gene', (94, 101))	('ocular presenting', 'Disease', (9, 26))	('Thymoma', 'Disease', 'MESH:D013945', (0, 7))	('rs1801275', 'Var', (31, 40))
59485	30042722	Frequencies of rs2107356 T allele and rs1805010 A allele in adult thymoma subgroup was significantly higher than those in HC and in adult non-thymoma subgroup after Bonferonni correction.	('higher', 'PosReg', (101, 107))	('rs2107356 T', 'Var', (15, 26))	('adult thymoma', 'Disease', (60, 73))	('rs1805010', 'Mutation', 'rs1805010', (38, 47))	('rs1805010 A', 'Var', (38, 49))	('thymoma', 'Disease', 'MESH:D013945', (66, 73))	('thymoma', 'Disease', (66, 73))	('thymoma', 'Disease', 'MESH:D013945', (142, 149))	('rs2107356', 'Mutation', 'rs2107356', (15, 24))	('thymoma', 'Disease', (142, 149))	('thymoma', 'Phenotype', 'HP:0100522', (66, 73))	('adult thymoma', 'Disease', 'MESH:C536905', (60, 73))	('thymoma', 'Phenotype', 'HP:0100522', (142, 149))
59486	30042722	There were significant differences in genotype frequencies of rs2107356 and rs1805010 between adult thymoma subgroup and HC and between adult thymoma subgroup and adult non-thymoma subgroup under codominant and additive models (p < 0.05, Table 6).	('rs1805010', 'Var', (76, 85))	('adult thymoma', 'Disease', 'MESH:C536905', (94, 107))	('adult thymoma', 'Disease', (94, 107))	('adult thymoma', 'Disease', (136, 149))	('adult thymoma', 'Disease', 'MESH:C536905', (136, 149))	('thymoma', 'Phenotype', 'HP:0100522', (142, 149))	('rs2107356', 'Mutation', 'rs2107356', (62, 71))	('thymoma', 'Disease', 'MESH:D013945', (100, 107))	('thymoma', 'Phenotype', 'HP:0100522', (173, 180))	('thymoma', 'Disease', (142, 149))	('rs1805010', 'Mutation', 'rs1805010', (76, 85))	('thymoma', 'Disease', 'MESH:D013945', (142, 149))	('thymoma', 'Disease', 'MESH:D013945', (173, 180))	('thymoma', 'Disease', (100, 107))	('thymoma', 'Disease', (173, 180))	('thymoma', 'Phenotype', 'HP:0100522', (100, 107))	('rs2107356', 'Var', (62, 71))
59488	30042722	Frequency of rs1801275 G allele was significantly higher in adult non-thymoma AChR-Ab positive subgroup than that in HC after Bonferonni correction.	('higher', 'PosReg', (50, 56))	('thymoma', 'Disease', 'MESH:D013945', (70, 77))	('rs1801275 G', 'Var', (13, 24))	('thymoma', 'Disease', (70, 77))	('thymoma', 'Phenotype', 'HP:0100522', (70, 77))	('rs1801275', 'Mutation', 'rs1801275', (13, 22))
59489	30042722	There were significant differences in genotype frequencies of rs1801275 between adult non-thymoma AChR-Ab positive subgroup and HC group under codominant and additive models (Table 6).	('rs1801275', 'Mutation', 'rs1801275', (62, 71))	('differences', 'Reg', (23, 34))	('thymoma', 'Disease', 'MESH:D013945', (90, 97))	('thymoma', 'Disease', (90, 97))	('thymoma', 'Phenotype', 'HP:0100522', (90, 97))	('rs1801275', 'Var', (62, 71))
59490	30042722	Frequency of rs1801275 G allele was significantly higher in adult non-thymoma AChR-Ab positive MG than in adult non-thymoma AChR-Ab negative MG (P = 0.023).	('higher', 'PosReg', (50, 56))	('thymoma', 'Disease', 'MESH:D013945', (116, 123))	('thymoma', 'Disease', (116, 123))	('thymoma', 'Disease', 'MESH:D013945', (70, 77))	('rs1801275 G', 'Var', (13, 24))	('thymoma', 'Disease', (70, 77))	('thymoma', 'Phenotype', 'HP:0100522', (116, 123))	('thymoma', 'Phenotype', 'HP:0100522', (70, 77))	('rs1801275', 'Mutation', 'rs1801275', (13, 22))
59491	30042722	There were no significantly difference in rs1801275 G allele and genotype frequencies between adult non-thymoma AChR-Ab negative subgroup and HC group.	('rs1801275', 'Mutation', 'rs1801275', (42, 51))	('thymoma', 'Disease', 'MESH:D013945', (104, 111))	('thymoma', 'Disease', (104, 111))	('thymoma', 'Phenotype', 'HP:0100522', (104, 111))	('rs1801275 G', 'Var', (42, 53))
59492	30042722	Frequency of rs1801275 G allele was higher in EOMG, LOMG, ocular presenting and generalized presenting subgroups than those in HC, but there were no allelic differences between EOMG subgroup and LOMG subgroup, and between ocular presenting subgroup and generalized presenting subgroup (Table 6).	('EOMG', 'Disease', (46, 50))	('higher', 'PosReg', (36, 42))	('EOMG', 'Chemical', '-', (46, 50))	('LOMG', 'Disease', (52, 56))	('EOMG', 'Chemical', '-', (177, 181))	('rs1801275 G', 'Var', (13, 24))	('generalized', 'Disease', (80, 91))	('ocular presenting', 'Disease', (58, 75))	('rs1801275', 'Mutation', 'rs1801275', (13, 22))
59493	30042722	Significant association was found between rs2107356 and rs1805010 and thymoma subgroup, and between rs1801275 and AChR-Ab positivie subgroup.	('rs1801275', 'Var', (100, 109))	('AChR-Ab', 'Disease', (114, 121))	('rs1801275', 'Mutation', 'rs1801275', (100, 109))	('thymoma', 'Disease', 'MESH:D013945', (70, 77))	('rs1805010', 'Mutation', 'rs1805010', (56, 65))	('rs2107356', 'Mutation', 'rs2107356', (42, 51))	('thymoma', 'Phenotype', 'HP:0100522', (70, 77))	('thymoma', 'Disease', (70, 77))	('rs1805010', 'Var', (56, 65))	('rs2107356', 'Var', (42, 51))
59494	30042722	We found the association of rs2107356 and rs1805010 with thymoma and association of rs1801275 with AChR-Ab positivity.	('thymoma', 'Disease', 'MESH:D013945', (57, 64))	('thymoma', 'Disease', (57, 64))	('rs1801275', 'Var', (84, 93))	('rs1805010', 'Mutation', 'rs1805010', (42, 51))	('rs2107356', 'Mutation', 'rs2107356', (28, 37))	('rs1801275', 'Mutation', 'rs1801275', (84, 93))	('thymoma', 'Phenotype', 'HP:0100522', (57, 64))	('association', 'Reg', (13, 24))	('rs2107356', 'Var', (28, 37))	('rs1805010', 'Var', (42, 51))
59495	30042722	We found association of rs2107356 and rs1805010 with adult thymoma associated MG; and found association of rs1801275 with adult non-thymoma AChR-Ab positivie MG.	('thymoma', 'Phenotype', 'HP:0100522', (132, 139))	('thymoma', 'Disease', (132, 139))	('rs1801275', 'Mutation', 'rs1801275', (107, 116))	('thymoma', 'Phenotype', 'HP:0100522', (59, 66))	('rs1805010', 'Mutation', 'rs1805010', (38, 47))	('thymoma', 'Disease', 'MESH:D013945', (59, 66))	('rs2107356', 'Mutation', 'rs2107356', (24, 33))	('adult thymoma', 'Disease', (53, 66))	('adult thymoma', 'Disease', 'MESH:C536905', (53, 66))	('thymoma', 'Disease', (59, 66))	('rs1805010', 'Var', (38, 47))	('thymoma', 'Disease', 'MESH:D013945', (132, 139))	('association', 'Interaction', (9, 20))	('rs2107356', 'Var', (24, 33))	('rs1801275', 'Var', (107, 116))	('association', 'Interaction', (92, 103))
59496	30042722	Although allele and genotype frequencies of rs2107356 and rs1805010 were significantly higher in the adult thymoma MG subgroup than those in HC and in adult non-thymoma MG subgroup, there was no difference between adult non-thymoma MG subgroup and HC.	('thymoma', 'Phenotype', 'HP:0100522', (107, 114))	('non-thymoma MG', 'Disease', 'MESH:D013945', (220, 234))	('rs2107356', 'Mutation', 'rs2107356', (44, 53))	('non-thymoma MG', 'Disease', (220, 234))	('adult thymoma', 'Disease', (101, 114))	('rs1805010', 'Mutation', 'rs1805010', (58, 67))	('thymoma', 'Phenotype', 'HP:0100522', (161, 168))	('adult thymoma', 'Disease', 'MESH:C536905', (101, 114))	('rs2107356', 'Var', (44, 53))	('rs1805010', 'Var', (58, 67))	('non-thymoma MG', 'Disease', 'MESH:D013945', (157, 171))	('thymoma', 'Phenotype', 'HP:0100522', (224, 231))	('non-thymoma MG', 'Disease', (157, 171))	('higher', 'PosReg', (87, 93))
59500	30042722	Rs2107356 is a promoter SNP which might increase the expression of IL-4R, which should be studied in the future.	('IL-4R', 'Gene', '3566', (67, 72))	('increase', 'PosReg', (40, 48))	('IL-4R', 'Gene', (67, 72))	('Rs2107356', 'Var', (0, 9))	('expression', 'MPA', (53, 63))	('Rs2107356', 'Mutation', 'Rs2107356', (0, 9))
59501	30042722	Rs2107356 was also found associated with gastric cancer and multiple myeloma.	('associated', 'Reg', (25, 35))	('gastric cancer', 'Phenotype', 'HP:0012126', (41, 55))	('cancer', 'Phenotype', 'HP:0002664', (49, 55))	('Rs2107356', 'Var', (0, 9))	('multiple myeloma', 'Disease', 'MESH:D009101', (60, 76))	('multiple myeloma', 'Phenotype', 'HP:0006775', (60, 76))	('gastric cancer', 'Disease', (41, 55))	('Rs2107356', 'Mutation', 'Rs2107356', (0, 9))	('multiple myeloma', 'Disease', (60, 76))	('gastric cancer', 'Disease', 'MESH:D013274', (41, 55))
59502	30042722	Rs1805010 is a gain-of-function mutation in the extracellular domain of IL-4Ralpha subunit.	('Rs1805010', 'Mutation', 'Rs1805010', (0, 9))	('gain-of-function', 'PosReg', (15, 31))	('IL-4Ralpha', 'Gene', (72, 82))	('IL-4Ralpha', 'Gene', '3566', (72, 82))	('Rs1805010', 'Var', (0, 9))
59503	30042722	This variant enhances IL-4 signaling by keeping STAT6 transcription factor abnormally active, which was thought not due to modulation of intracellular mechanisms.	('IL-4 signaling', 'MPA', (22, 36))	('STAT6', 'Gene', '6778', (48, 53))	('active', 'MPA', (86, 92))	('variant', 'Var', (5, 12))	('enhances', 'PosReg', (13, 21))	('STAT6', 'Gene', (48, 53))	('abnormally active', 'Phenotype', 'HP:0000752', (75, 92))
59504	30042722	Rs1805010 was also found associated with renal cell cancer and cervical cancer.	('Rs1805010', 'Mutation', 'Rs1805010', (0, 9))	('cancer', 'Phenotype', 'HP:0002664', (52, 58))	('associated', 'Reg', (25, 35))	('renal cell cancer', 'Phenotype', 'HP:0005584', (41, 58))	('cancer', 'Phenotype', 'HP:0002664', (72, 78))	('cervical cancer', 'Disease', 'MESH:D002583', (63, 78))	('renal cell cancer', 'Disease', (41, 58))	('cervical cancer', 'Disease', (63, 78))	('renal cell cancer', 'Disease', 'MESH:C538614', (41, 58))	('Rs1805010', 'Var', (0, 9))
59511	30042722	In our study, frequency of G allele in rs1801275 was higher in MG patients than that in HC group, especially in adult non-thymoma AChR-Ab positive MG subgroup.	('higher', 'PosReg', (53, 59))	('rs1801275', 'Var', (39, 48))	('thymoma', 'Disease', 'MESH:D013945', (122, 129))	('thymoma', 'Disease', (122, 129))	('rs1801275', 'Mutation', 'rs1801275', (39, 48))	('thymoma', 'Phenotype', 'HP:0100522', (122, 129))	('patients', 'Species', '9606', (66, 74))
59512	30042722	Genotypes of rs1801275 were found to be independent factors for the presence of AChR-Ab in MG.	('rs1801275', 'Var', (13, 22))	('AChR-Ab', 'Gene', (80, 87))	('presence', 'Reg', (68, 76))	('rs1801275', 'Mutation', 'rs1801275', (13, 22))
59513	30042722	The rs1801275 is another gain-of-function mutation in the intracellular domain of IL-4Ralpha, which enhancs IL-4Ralpha signal transduction via STAT6 pathway, which has important effects on immune modulating.	('IL-4Ralpha', 'Gene', (82, 92))	('enhancs', 'PosReg', (100, 107))	('STAT6', 'Gene', '6778', (143, 148))	('IL-4Ralpha', 'Gene', '3566', (82, 92))	('gain-of-function', 'PosReg', (25, 41))	('IL-4Ralpha', 'Gene', (108, 118))	('IL-4Ralpha', 'Gene', '3566', (108, 118))	('rs1801275', 'Var', (4, 13))	('rs1801275', 'Mutation', 'rs1801275', (4, 13))	('STAT6', 'Gene', (143, 148))
59514	30042722	This variant was also found associated with IL-4-directed and IL-6-dependent subversion of Treg cells into Th17-like cells.	('associated', 'Reg', (28, 38))	('variant', 'Var', (5, 12))	('IL-6', 'Gene', (62, 66))	('subversion of Treg cells into', 'CPA', (77, 106))	('IL-6', 'Gene', '3569', (62, 66))
59516	30042722	We did not enroll thymoma patients without MG, therefore, the association between IL-4Ralpha gene polymorphism and thymoma should be further confirmed.	('IL-4Ralpha', 'Gene', (82, 92))	('thymoma', 'Phenotype', 'HP:0100522', (18, 25))	('thymoma', 'Phenotype', 'HP:0100522', (115, 122))	('IL-4Ralpha', 'Gene', '3566', (82, 92))	('patients', 'Species', '9606', (26, 34))	('thymoma', 'Disease', 'MESH:D013945', (18, 25))	('polymorphism', 'Var', (98, 110))	('thymoma', 'Disease', 'MESH:D013945', (115, 122))	('thymoma', 'Disease', (115, 122))	('thymoma', 'Disease', (18, 25))
59519	30042722	In conclusion, in Chinese Han population, rs2107356 and rs1805010 were found to be associated with adult thymoma associated MG, and rs1801275 was found to be associated with adult non-thymoma AChR-Ab positive MG.	('thymoma', 'Disease', 'MESH:D013945', (105, 112))	('thymoma', 'Disease', (105, 112))	('rs1801275', 'Var', (132, 141))	('thymoma', 'Phenotype', 'HP:0100522', (184, 191))	('associated', 'Reg', (158, 168))	('adult thymoma', 'Disease', 'MESH:C536905', (99, 112))	('rs1801275', 'Mutation', 'rs1801275', (132, 141))	('rs1805010', 'Mutation', 'rs1805010', (56, 65))	('thymoma', 'Phenotype', 'HP:0100522', (105, 112))	('rs2107356', 'Mutation', 'rs2107356', (42, 51))	('associated', 'Reg', (83, 93))	('adult thymoma', 'Disease', (99, 112))	('rs1805010', 'Var', (56, 65))	('thymoma', 'Disease', 'MESH:D013945', (184, 191))	('rs2107356', 'Var', (42, 51))	('thymoma', 'Disease', (184, 191))
59570	29245252	Only necrotic keratinocytes were thinly scattered in the epidermis, but the immunohistochemical evaluation showed infiltration of more CD8+ than CD4+ T cells and a marked decrease in CD1a+ Langerhans cells in the epidermis, which correspond to observed characteristics of TAMA in our case.	('decrease', 'NegReg', (171, 179))	('CD1a', 'Gene', '909', (183, 187))	('CD8+', 'Var', (135, 139))	('necrotic keratinocytes', 'Phenotype', 'HP:0005540', (5, 27))	('TAMA', 'Chemical', '-', (272, 276))	('necrotic', 'Disease', (5, 13))	('necrotic', 'Disease', 'MESH:D009336', (5, 13))	('CD1a', 'Gene', (183, 187))
59730	23279873	To facilitate the statistical analysis, and since the original report did not give any percentage of different histotypes, combined histologies were re-classified according to the worst histotype (for example B2-B3, were considered B3 thymomas).	('thymomas', 'Disease', 'MESH:D013945', (235, 243))	('B2-B3', 'Var', (209, 214))	('thymoma', 'Phenotype', 'HP:0100522', (235, 242))	('thymomas', 'Disease', (235, 243))
59732	23279873	Paraneoplastic syndromes were observed in 33/129 (26%) cases: in 17 type B3, 5 type B2, 5 type B1, 5 type AB, and 1 type A.	('Paraneoplastic syndromes', 'Disease', (0, 24))	('Paraneoplastic syndromes', 'Disease', 'MESH:D010257', (0, 24))	('observed', 'Reg', (30, 38))	('type B3', 'Var', (68, 75))
59734	23279873	Briefly in most of the cases (9/23, 39%) the diagnostic difficulty rested in the proper recognition of type B thymomas; in this setting overlap between B1 and B2 was the most frequent occurrence (6/9).	('type B thymomas', 'Disease', (103, 118))	('thymoma', 'Phenotype', 'HP:0100522', (110, 117))	('overlap', 'Var', (136, 143))	('type B thymomas', 'Disease', 'MESH:D013945', (103, 118))
59736	23279873	In 7/23 (30%) cases the discrepancy involved fairly different histological subtypes: in four cases thymic carcinoma vs. type B3; in two cases type B3 vs. type A; and in one case thymic carcinoma vs. type A.	('type B3', 'Var', (142, 149))	('thymic carcinoma', 'Disease', (99, 115))	('thymic carcinoma', 'Disease', (178, 194))	('thymic carcinoma', 'Disease', 'MESH:D013945', (99, 115))	('carcinoma', 'Phenotype', 'HP:0030731', (106, 115))	('thymic carcinoma', 'Disease', 'MESH:D013945', (178, 194))	('carcinoma', 'Phenotype', 'HP:0030731', (185, 194))	('involved', 'Reg', (36, 44))
59774	26401511	Expression levels of the apoptosis inhibitor cellular FLICE-like inhibitory protein (c-FLIP) in blood T cells and intratumorous thymocytes were higher in TAMG(+) than in MG(-) thymomas and non-neoplastic thymic remnants.	('TAMG(+', 'Var', (154, 160))	('tumor', 'Disease', (119, 124))	('TAMG', 'Chemical', '-', (154, 158))	('neoplastic thymic remnants', 'Phenotype', 'HP:0100521', (193, 219))	('Expression levels', 'MPA', (0, 17))	('cellular FLICE-like inhibitory protein', 'Gene', (45, 83))	('thymomas', 'Disease', (176, 184))	('thymomas', 'Disease', 'MESH:D013945', (176, 184))	('higher', 'PosReg', (144, 150))	('tumor', 'Disease', 'MESH:D009369', (119, 124))	('c-FLIP', 'Gene', '8837', (85, 91))	('c-FLIP', 'Gene', (85, 91))	('tumor', 'Phenotype', 'HP:0002664', (119, 124))	('cellular FLICE-like inhibitory protein', 'Gene', '8837', (45, 83))	('thymoma', 'Phenotype', 'HP:0100522', (176, 183))
59821	26401511	Treatment of PBMCs from nine thymoma patients (four with AB, two with B2, and three B3 subtypes) with EF24 alone had little effect on survival, while EF24 pretreatment sensitized PBMCs in a dose-dependent manner for subsequent FASLG treatment with decreased survival (Fig.8A).	('FASLG', 'Gene', '356', (227, 232))	('thymoma', 'Phenotype', 'HP:0100522', (29, 36))	('patients', 'Species', '9606', (37, 45))	('EF24', 'Var', (150, 154))	('decreased', 'NegReg', (248, 257))	('thymoma', 'Gene', '7063', (29, 36))	('FASLG', 'Gene', (227, 232))	('thymoma', 'Gene', (29, 36))	('survival', 'MPA', (258, 266))
59823	26401511	Again, EF24 pretreatment lead to comparable apoptosis in PBMCs of blood donors and thymoma patients on subsequent FASLG treatment (Fig.8B).	('FASLG', 'Gene', (114, 119))	('patients', 'Species', '9606', (91, 99))	('thymoma', 'Gene', '7063', (83, 90))	('apoptosis', 'CPA', (44, 53))	('thymoma', 'Gene', (83, 90))	('FASLG', 'Gene', '356', (114, 119))	('EF24', 'Var', (7, 11))	('thymoma', 'Phenotype', 'HP:0100522', (83, 90))
59826	26401511	Nuclear expression was slightly higher in PBMCs of TAMG(+) than MG(-) thymoma patients (Fig.	('thymoma', 'Gene', '7063', (70, 77))	('TAMG', 'Chemical', '-', (51, 55))	('thymoma', 'Gene', (70, 77))	('higher', 'PosReg', (32, 38))	('patients', 'Species', '9606', (78, 86))	('thymoma', 'Phenotype', 'HP:0100522', (70, 77))	('Nuclear expression', 'MPA', (0, 18))	('TAMG', 'Var', (51, 55))
59830	26401511	TAMG was previously shown to be uniquely associated with the +49A/A CTLA4 genotype that confers protection in a variety of other autoimmune diseases.	('autoimmune diseases', 'Disease', (129, 148))	('CTLA4', 'Gene', '1493', (68, 73))	('associated', 'Reg', (41, 51))	('autoimmune diseases', 'Phenotype', 'HP:0002960', (129, 148))	('CTLA4', 'Gene', (68, 73))	('protection', 'NegReg', (96, 106))	('+49A/A', 'Var', (61, 67))	('autoimmune diseases', 'Disease', 'MESH:D001327', (129, 148))	('TAMG', 'Chemical', '-', (0, 4))
59831	26401511	In the present cohort of patients, we confirm this finding, since the CTLA4+49A/A genotype was significantly more prevalent in TAMG(+) than MG(-) thymoma patients (P = 0.0003 by chi2 Test; Table2).	('thymoma', 'Phenotype', 'HP:0100522', (146, 153))	('TAMG(+', 'Var', (127, 133))	('CTLA4', 'Gene', '1493', (70, 75))	('thymoma', 'Gene', '7063', (146, 153))	('prevalent', 'Reg', (114, 123))	('thymoma', 'Gene', (146, 153))	('CTLA4', 'Gene', (70, 75))	('patients', 'Species', '9606', (154, 162))	('patients', 'Species', '9606', (25, 33))	('TAMG', 'Chemical', '-', (127, 131))
59832	26401511	Surprisingly, cFLIP mRNA levels in thymoma tissue extracts were higher in TAMG patients with the +49A/A genotype than in TAMG with other genotypes, while no such association was obvious in MG(-) thymoma patients (Fig.	('thymoma', 'Gene', (195, 202))	('TAMG', 'Chemical', '-', (121, 125))	('thymoma', 'Gene', (35, 42))	('higher', 'PosReg', (64, 70))	('+49A/A', 'Var', (97, 103))	('patients', 'Species', '9606', (203, 211))	('patients', 'Species', '9606', (79, 87))	('cFLIP mRNA levels', 'MPA', (14, 31))	('TAMG', 'Chemical', '-', (74, 78))	('thymoma', 'Gene', '7063', (195, 202))	('thymoma', 'Phenotype', 'HP:0100522', (35, 42))	('thymoma', 'Gene', '7063', (35, 42))	('thymoma', 'Phenotype', 'HP:0100522', (195, 202))
59833	26401511	Export of CD4+ CD45RA+ effector T cells from thymomas to the blood is typical of TAMG(+) but not MG(-) thymomas, while export of CD8(+) T cells from MG(-) and TAMG(+) thymomas is similar.	('CD8', 'Gene', (129, 132))	('CD4+ CD45RA+', 'Var', (10, 22))	('thymomas', 'Disease', (45, 53))	('CD8', 'Gene', '925', (129, 132))	('thymomas', 'Disease', 'MESH:D013945', (45, 53))	('thymoma', 'Phenotype', 'HP:0100522', (45, 52))	('Export', 'MPA', (0, 6))	('thymomas', 'Disease', (103, 111))	('TAMG', 'Chemical', '-', (159, 163))	('thymomas', 'Disease', 'MESH:D013945', (167, 175))	('thymomas', 'Disease', 'MESH:D013945', (103, 111))	('thymoma', 'Phenotype', 'HP:0100522', (167, 174))	('TAMG', 'Chemical', '-', (81, 85))	('thymoma', 'Phenotype', 'HP:0100522', (103, 110))	('thymomas', 'Disease', (167, 175))
59834	26401511	The reason for the export of CD4+CD45RA+ T cells from TAMG(+) thymomas is poorly understood.	('thymomas', 'Disease', 'MESH:D013945', (62, 70))	('CD4+CD45RA+', 'Var', (29, 40))	('thymomas', 'Disease', (62, 70))	('TAMG', 'Chemical', '-', (54, 58))	('thymoma', 'Phenotype', 'HP:0100522', (62, 69))
59842	26401511	The reason for the latter observation is not clear; since cFLIP expression levels are increased in both CD8+ and CD4+ SP thymocytes of thymomas (Fig.4).	('increased', 'PosReg', (86, 95))	('CD4+ SP', 'Var', (113, 120))	('thymoma', 'Phenotype', 'HP:0100522', (135, 142))	('thymomas', 'Disease', (135, 143))	('CD8', 'Gene', (104, 107))	('thymomas', 'Disease', 'MESH:D013945', (135, 143))	('CD8', 'Gene', '925', (104, 107))	('cFLIP expression levels', 'MPA', (58, 81))
59844	26401511	Interestingly, CD40 deficiency has recently been observed in thymomas.	('deficiency', 'Var', (20, 30))	('CD40 deficiency', 'Phenotype', 'HP:0031384', (15, 30))	('CD40', 'Gene', (15, 19))	('thymoma', 'Phenotype', 'HP:0100522', (61, 68))	('thymomas', 'Disease', (61, 69))	('observed', 'Reg', (49, 57))	('thymomas', 'Disease', 'MESH:D013945', (61, 69))
59849	26401511	Our data now suggest that overexpression of cFLIP in TAMG(+) thymocytes during "priming" could be a mechanism to counteract negative selection and allow "primed" T cells to escape from the thymoma to the blood.	('overexpression', 'PosReg', (26, 40))	('thymoma', 'Gene', (189, 196))	('cFLIP', 'Var', (44, 49))	('thymoma', 'Phenotype', 'HP:0100522', (189, 196))	('TAMG', 'Chemical', '-', (53, 57))	('thymoma', 'Gene', '7063', (189, 196))
59866	26401511	The fact that cFLIP expression was highest in CD4+CD45RA+ blood T cells at the time of surgery and dropped thereafter hints to their derivation from the thymoma and shows that the cFLIPhigh phenotype is tumor dependent.	('CD4+CD45RA+', 'Var', (46, 57))	('tumor', 'Disease', (203, 208))	('tumor', 'Phenotype', 'HP:0002664', (203, 208))	('thymoma', 'Gene', '7063', (153, 160))	('thymoma', 'Gene', (153, 160))	('tumor', 'Disease', 'MESH:D009369', (203, 208))	('cFLIP expression', 'MPA', (14, 30))	('thymoma', 'Phenotype', 'HP:0100522', (153, 160))