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T1 Age 2 13 34-year-old T2 Personal_background 14 22 Japanese T3 Sex 23 28 woman T4 Disease_disorder 48 52 MCTD E1 Disease_disorder:T4 #1 AnnotatorNotes E1 mixed connective tissue disease T5 Disease_disorder 74 94 Raynaud's phenomenon E2 Disease_disorder:T5 T6 Sign_symptom 96 108 pancytopenia E3 Sign_symptom:T6 T7 Diagnostic_procedure 126 143 creatinine kinase E4 Diagnostic_procedure:T7 T8 Detailed_description 119 125 plasma R1 MODIFY Arg1:T8 Arg2:E4 T10 Diagnostic_procedure 168 188 U1-ribonucleoprotein E5 Diagnostic_procedure:T10 T12 Date 192 196 2005 E6 Date:T12 T13 Medication 219 231 prednisolone E7 Medication:T13 T14 Dosage 210 215 10 mg T15 Dosage 232 237 daily R4 MODIFY Arg1:T15 Arg2:E7 R5 MODIFY Arg1:T14 Arg2:E7 T9 Lab_value 110 118 elevated E8 Lab_value:T9 R2 MODIFY Arg1:E8 Arg2:E4 T11 Lab_value 149 167 antibodies against E9 Lab_value:T11 R3 MODIFY Arg1:E9 Arg2:E5 T16 Diagnostic_procedure 239 275 Pulmonary arterial systolic pressure E10 Diagnostic_procedure:T16 T18 Diagnostic_procedure 289 305 echocardiography E11 Diagnostic_procedure:T18 R7 SUB_PROCEDURE Arg1:E11 Arg2:E10 T19 Lab_value 310 327 slightly elevated E12 Lab_value:T19 T20 Lab_value 329 336 48 mmHg E13 Lab_value:T20 R8 MODIFY Arg1:E12 Arg2:E10 R9 MODIFY Arg1:E13 Arg2:E10 T21 Date 341 345 2006 E14 Date:T21 T22 Sign_symptom 368 387 shortness of breath E15 Sign_symptom:T22 T23 Activity 391 406 physical effort E16 Activity:T23 T24 Detailed_description 356 367 progressive R10 MODIFY Arg1:T24 Arg2:E15 T25 Date 410 414 2011 E17 Date:T25 T28 Diagnostic_procedure 478 510 mean pulmonary arterial pressure E19 Diagnostic_procedure:T28 T26 Disease_disorder 416 447 Pulmonary arterial hypertension E18 Disease_disorder:T26 T27 Lab_value 467 474 74 mmHg E20 Lab_value:T27 T30 Diagnostic_procedure 512 516 mPAP E21 Diagnostic_procedure:T30 R12 IDENTICAL Arg1:E21 Arg2:E19 R11 MODIFY Arg1:E20 Arg2:E19 T29 Diagnostic_procedure 531 558 right heart catheterization E22 Diagnostic_procedure:T29 T31 Diagnostic_procedure 560 563 RHC E23 Diagnostic_procedure:T31 R14 IDENTICAL Arg1:E23 Arg2:E22 T32 Date 568 572 2012 E24 Date:T32 T33 Medication 597 622 immunosuppressive therapy E25 Medication:T33 T34 Medication 574 590 Cyclophosphamide E26 Medication:T34 R15 SUB_PROCEDURE Arg1:E26 Arg2:E25 A1 POLARITY E25 NEG T35 Sign_symptom 674 693 menopausal symptoms E27 Sign_symptom:T35 A2 POLARITY E27 UNCERTAIN T36 Detailed_description 668 673 early R16 MODIFY Arg1:T36 Arg2:E27 T37 Dosage 710 720 250 mg/day T38 Medication 724 732 bosentan E28 Medication:T38 T39 Dosage 737 747 120 μg/day T40 Medication 751 760 beraprost E29 Medication:T40 R17 MODIFY Arg1:T39 Arg2:E29 R18 MODIFY Arg1:T37 Arg2:E28 T41 Date 788 800 January 2014 E30 Date:T41 T42 Sign_symptom 806 813 dyspnea E31 Sign_symptom:T42 A3 TREND E31 INC T43 Diagnostic_procedure 828 848 WHO functional class E32 Diagnostic_procedure:T43 T44 Lab_value 849 851 IV E33 Lab_value:T44 R19 MODIFY Arg1:E33 Arg2:E32 T45 Clinical_event 866 874 admitted E34 Clinical_event:T45 T46 Nonbiological_location 882 890 hospital R20 MODIFY Arg1:T46 Arg2:E34 T47 Diagnostic_procedure 894 914 physical examination E35 Diagnostic_procedure:T47 T48 Diagnostic_procedure 926 949 systemic blood pressure E36 Diagnostic_procedure:T48 T49 Lab_value 922 925 low E37 Lab_value:T49 T50 Lab_value 951 961 89/61 mmHg E38 Lab_value:T50 R21 MODIFY Arg1:E38 Arg2:E36 R22 MODIFY Arg1:E37 Arg2:E36 T51 Sign_symptom 964 975 tachycardia E39 Sign_symptom:T51 T52 Lab_value 977 984 104/min E40 Lab_value:T52 R23 MODIFY Arg1:E40 Arg2:E39 T53 Diagnostic_procedure 991 1009 blood oxygen level E41 Diagnostic_procedure:T53 T54 Lab_value 987 990 low E42 Lab_value:T54 R24 MODIFY Arg1:E42 Arg2:E41 T55 Diagnostic_procedure 1011 1041 percutaneous oxygen saturation E43 Diagnostic_procedure:T55 R25 SUB_PROCEDURE Arg1:E43 Arg2:E41 T56 Diagnostic_procedure 1043 1047 SpO2 E44 Diagnostic_procedure:T56 R26 IDENTICAL Arg1:E44 Arg2:E43 T57 Lab_value 1049 1052 95% E45 Lab_value:T57 R27 MODIFY Arg1:E45 Arg2:E43 T58 Sign_symptom 1070 1080 distension E46 Sign_symptom:T58 T59 Biological_structure 1055 1069 jugular venous R28 MODIFY Arg1:T59 Arg2:E46 T60 Sign_symptom 1102 1107 edema E47 Sign_symptom:T60 T61 Detailed_description 1093 1101 systemic T62 Severity 1086 1092 severe R29 MODIFY Arg1:T62 Arg2:E47 R30 MODIFY Arg1:T61 Arg2:E47 T63 Sign_symptom 1116 1124 crackles E48 Sign_symptom:T63 T64 Detailed_description 1109 1115 Coarse R31 MODIFY Arg1:T64 Arg2:E48 T65 Detailed_description 1129 1133 loud T66 Sign_symptom 1134 1163 pulmonic valve closure sounds E49 Sign_symptom:T66 R32 MODIFY Arg1:T65 Arg2:E49 T67 Diagnostic_procedure 1209 1227 6-minute walk test E50 Diagnostic_procedure:T67 A4 POLARITY E50 NEG T68 Sign_symptom 1242 1249 dyspnea E51 Sign_symptom:T68 T69 Severity 1235 1241 severe R33 MODIFY Arg1:T69 Arg2:E51 T70 Diagnostic_procedure 1251 1274 Laboratory examinations E52 Diagnostic_procedure:T70 T71 Diagnostic_procedure 1298 1323 brain natriuretic peptide E53 Diagnostic_procedure:T71 T72 Detailed_description 1291 1297 plasma R34 MODIFY Arg1:T72 Arg2:E53 T73 Lab_value 1282 1290 elevated E54 Lab_value:T73 T74 Diagnostic_procedure 1325 1328 BNP E55 Diagnostic_procedure:T74 R35 IDENTICAL Arg1:E55 Arg2:E53 R36 MODIFY Arg1:E54 Arg2:E53 T75 Lab_value 1337 1348 929.4 pg/mL E56 Lab_value:T75 R37 MODIFY Arg1:E56 Arg2:E53 T76 Sign_symptom 1351 1360 hypoxemia E57 Sign_symptom:T76 T77 Diagnostic_procedure 1362 1366 PaO2 E58 Diagnostic_procedure:T77 T78 Lab_value 1367 1376 62.5 mmHg E59 Lab_value:T78 R38 MODIFY Arg1:E59 Arg2:E58 T79 Diagnostic_procedure 1378 1383 PaCO2 E60 Diagnostic_procedure:T79 T80 Lab_value 1384 1393 27.1 mmHg E61 Lab_value:T80 R39 SUB_PROCEDURE Arg1:E53 Arg2:E52 R40 SUB_PROCEDURE Arg1:E58 Arg2:E52 R41 SUB_PROCEDURE Arg1:E60 Arg2:E52 R42 MODIFY Arg1:E61 Arg2:E60 T81 Lab_value 1404 1434 presence of antibodies against E62 Lab_value:T81 T82 Diagnostic_procedure 1435 1455 U1-ribonucleoprotein E63 Diagnostic_procedure:T82 R43 MODIFY Arg1:E62 Arg2:E63 T83 Lab_value 1457 1466 97.9 U/mL E64 Lab_value:T83 R44 MODIFY Arg1:E64 Arg2:E63 R45 SUB_PROCEDURE Arg1:E63 Arg2:E52 T84 Diagnostic_procedure 1479 1501 antinuclear antibodies E65 Diagnostic_procedure:T84 T85 Lab_value 1503 1508 1:640 E66 Lab_value:T85 T86 Lab_value 1510 1526 speckled pattern E67 Lab_value:T86 R46 MODIFY Arg1:E66 Arg2:E65 R47 MODIFY Arg1:E67 Arg2:E65 R48 SUB_PROCEDURE Arg1:E65 Arg2:E52 T87 Diagnostic_procedure 1537 1542 X-ray E68 Diagnostic_procedure:T87 T88 Biological_structure 1531 1536 chest R49 MODIFY Arg1:T88 Arg2:E68 T89 Sign_symptom 1550 1558 enlarged E69 Sign_symptom:T89 T90 Biological_structure 1559 1577 pulmonary arteries R50 MODIFY Arg1:T90 Arg2:E69 T91 Sign_symptom 1582 1594 cardiomegaly E70 Sign_symptom:T91 T92 Diagnostic_procedure 1605 1622 Electrocardiogram E71 Diagnostic_procedure:T92 T93 Sign_symptom 1630 1646 P wave elevation E72 Sign_symptom:T93 T94 Detailed_description 1654 1665 V1-V2 leads R51 MODIFY Arg1:T94 Arg2:E72 T95 Diagnostic_procedure 1667 1670 RHC E73 Diagnostic_procedure:T95 T96 Diagnostic_procedure 1693 1697 mPAP E74 Diagnostic_procedure:T96 T97 Lab_value 1684 1692 elevated E75 Lab_value:T97 T98 Lab_value 1699 1706 65 mmHg E76 Lab_value:T98 R52 MODIFY Arg1:E75 Arg2:E74 R53 MODIFY Arg1:E76 Arg2:E74 T99 Diagnostic_procedure 1720 1753 pulmonary arterial wedge pressure E77 Diagnostic_procedure:T99 T17 Lab_value 1755 1762 12 mmHg E78 Lab_value:T17 T100 Lab_value 1713 1719 normal E79 Lab_value:T100 R6 MODIFY Arg1:E79 Arg2:E77 R54 MODIFY Arg1:E78 Arg2:E77 T101 Lab_value 1765 1769 high E80 Lab_value:T101 T102 Diagnostic_procedure 1770 1799 pulmonary vascular resistance E81 Diagnostic_procedure:T102 T103 Lab_value 1801 1820 1,547 dyne・sec・cm-5 E82 Lab_value:T103 R55 MODIFY Arg1:E82 Arg2:E81 R56 MODIFY Arg1:E80 Arg2:E81 T104 Lab_value 1827 1836 decreased E83 Lab_value:T104 T105 Diagnostic_procedure 1837 1851 cardiac output E84 Diagnostic_procedure:T105 T106 Lab_value 1853 1880 cardiac index 1.69 L/min/m2 E85 Lab_value:T106 R13 MODIFY Arg1:E85 Arg2:E84 R57 MODIFY Arg1:E83 Arg2:E84 T107 Diagnostic_procedure 1885 1911 ventilation/perfusion scan E86 Diagnostic_procedure:T107 T108 Disease_disorder 1931 1956 pulmonary thromboembolism E87 Disease_disorder:T108 A5 POLARITY E87 NEG T109 Disease_disorder 1970 2007 chronic obstructive pulmonary disease E88 Disease_disorder:T109 A6 POLARITY E88 NEG T110 Disease_disorder 2011 2037 interstitial lung diseases E89 Disease_disorder:T110 A7 POLARITY E89 NEG T111 Diagnostic_procedure 2054 2073 computed tomography E90 Diagnostic_procedure:T111 T112 Sign_symptom 2079 2086 dyspnea E91 Sign_symptom:T112 T113 Disease_disorder 2141 2144 PAH E92 Disease_disorder:T113 #2 AnnotatorNotes E92 pulmonary arterial hypertension T114 Disease_disorder 2125 2129 MCTD E93 Disease_disorder:T114 R58 CAUSE Arg1:E93 Arg2:E92 R59 CAUSE Arg1:E92 Arg2:E91 T115 Medication 2169 2177 bosentan E94 Medication:T115 T116 Medication 2182 2191 beraprost E95 Medication:T116 T117 Therapeutic_procedure 2216 2234 supportive therapy E96 Therapeutic_procedure:T117 T118 Therapeutic_procedure 2240 2262 oxygen supplementation E97 Therapeutic_procedure:T118 R60 SUB_PROCEDURE Arg1:E97 Arg2:E96 T119 Medication 2267 2276 diuretics E98 Medication:T119 R61 SUB_PROCEDURE Arg1:E98 Arg2:E96 T120 Dosage 2278 2287 40 mg/day T121 Medication 2291 2301 furosemide E99 Medication:T121 R62 MODIFY Arg1:T120 Arg2:E99 T122 Dosage 2318 2327 60 mg/day T123 Medication 2331 2341 sildenafil E100 Medication:T123 R64 MODIFY Arg1:T122 Arg2:E100 T124 Medication 2386 2395 beraprost E101 Medication:T124 T125 Dosage 2353 2382 gradual increment in the dose R65 MODIFY Arg1:T125 Arg2:E101 T126 Sign_symptom 2448 2455 dyspnea E102 Sign_symptom:T126 A8 TREND E102 STAY T127 Diagnostic_procedure 2491 2494 BNP E103 Diagnostic_procedure:T127 T128 Detailed_description 2484 2490 plasma R66 MODIFY Arg1:T128 Arg2:E103 T129 Lab_value 2501 2510 increased E104 Lab_value:T129 R67 MODIFY Arg1:E104 Arg2:E103 T130 Medication 2512 2516 IVCY E105 Medication:T130 #3 AnnotatorNotes E105 Intravenous cyclophosphamide T131 Dosage 2518 2542 750 mg/m2, every 4 weeks R68 MODIFY Arg1:T131 Arg2:E105 T132 Medication 2575 2587 prednisolone E106 Medication:T132 T133 Dosage 2605 2616 60 mg daily R69 MODIFY Arg1:T133 Arg2:E106 T134 Sign_symptom 2622 2629 dyspnea E107 Sign_symptom:T134 A9 POLARITY E107 NEG T135 Diagnostic_procedure 2683 2701 6-minute walk test E108 Diagnostic_procedure:T135 T136 Lab_value 2703 2708 260 m E109 Lab_value:T136 T137 Diagnostic_procedure 2710 2722 minimum SpO2 E110 Diagnostic_procedure:T137 T138 Lab_value 2723 2727 95 % E111 Lab_value:T138 R70 MODIFY Arg1:E109 Arg2:E108 R71 MODIFY Arg1:E111 Arg2:E110 T139 Diagnostic_procedure 2741 2744 BNP E112 Diagnostic_procedure:T139 T140 Detailed_description 2734 2740 plasma R72 MODIFY Arg1:T140 Arg2:E112 T141 Lab_value 2756 2765 decreased E113 Lab_value:T141 R73 MODIFY Arg1:E113 Arg2:E112 T142 Medication 2790 2794 IVCY E114 Medication:T142 T143 Date 2805 2821 Six months after E115 Date:T143 T144 Clinical_event 2826 2835 admission E116 Clinical_event:T144 T145 Diagnostic_procedure 2849 2852 RHC E117 Diagnostic_procedure:T145 T146 Diagnostic_procedure 2871 2875 mPAP E118 Diagnostic_procedure:T146 T147 Lab_value 2862 2870 improved E119 Lab_value:T147 T148 Lab_value 2883 2890 53 mmHg E120 Lab_value:T148 R74 MODIFY Arg1:E120 Arg2:E118 R75 MODIFY Arg1:E119 Arg2:E118 T149 Diagnostic_procedure 2893 2922 pulmonary vascular resistance E121 Diagnostic_procedure:T149 R76 MODIFY Arg1:E119 Arg2:E121 T150 Lab_value 2933 2952 1,116 dyne・sec・cm-5 E122 Lab_value:T150 R77 MODIFY Arg1:E122 Arg2:E121 T151 Diagnostic_procedure 2959 2972 cardiac index E123 Diagnostic_procedure:T151 T152 Lab_value 2982 2995 1.83 L/min/m2 E124 Lab_value:T152 R78 MODIFY Arg1:E124 Arg2:E123 R79 MODIFY Arg1:E119 Arg2:E123 T153 Sign_symptom 3025 3031 stable E125 Sign_symptom:T153 T154 Date 3072 3087 18 months after E126 Date:T154 T155 Clinical_event 3092 3101 admission E127 Clinical_event:T155 T156 Medication 3134 3145 prostanoids E128 Medication:T156 A10 POLARITY E128 UNCERTAIN T157 Administration 3123 3133 parenteral R80 MODIFY Arg1:T157 Arg2:E128 T158 Therapeutic_procedure 3149 3169 lung transplantation E129 Therapeutic_procedure:T158 A11 POLARITY E129 UNCERTAIN * OVERLAP E1 E2 E3 E4 E5 E6 R81 BEFORE Arg1:E6 Arg2:E7 R82 BEFORE Arg1:E7 Arg2:E10 * OVERLAP E10 E14 R83 BEFORE Arg1:E14 Arg2:E15 R84 CAUSE Arg1:E16 Arg2:E15 * OVERLAP E15 E16 E17 R85 BEFORE Arg1:E17 Arg2:E18 * OVERLAP E18 E19 E22 E24 E26 E27 R86 BEFORE Arg1:E27 Arg2:E28 * OVERLAP E28 E29 R87 BEFORE Arg1:E29 Arg2:E30 * OVERLAP E30 E31 E32 E34 E35 E36 E39 E41 E46 E47 E48 E49 E50 E51 E52 E57 E68 E69 E70 E71 E72 E73 E74 E77 E81 E84 E86 E87 E88 E89 E90 E91 E93 E92 E94 E95 R88 BEFORE Arg1:E95 Arg2:E96 R63 SUB_PROCEDURE Arg1:E99 Arg2:E98 * OVERLAP E96 E100 E101 R89 BEFORE Arg1:E101 Arg2:E102 * OVERLAP E102 E103 R90 BEFORE Arg1:E103 Arg2:E105 * OVERLAP E105 E106 R91 BEFORE Arg1:E106 Arg2:E107 * OVERLAP E107 E108 E110 E112 R92 AFTER Arg1:E112 Arg2:E114 R93 BEFORE Arg1:E114 Arg2:E115 R94 AFTER Arg1:E115 Arg2:E116 R95 BEFORE Arg1:E116 Arg2:E117 * OVERLAP E117 E118 E121 E123 R96 BEFORE Arg1:E123 Arg2:E125 * OVERLAP E125 E126 R97 AFTER Arg1:E126 Arg2:E127 R98 BEFORE Arg1:E127 Arg2:E128 * OVERLAP E128 E129