{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:06:24Z","timestamp":1790856384456,"version":"4.1.0"},"reference-count":67,"publisher":"Japanese Society of Internal Medicine","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intern. Med."],"published-print":{"date-parts":[[2026]]},"DOI":"10.2169\/internalmedicine.7378-26","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T22:10:55Z","timestamp":1778883055000},"source":"Crossref","is-referenced-by-count":2,"title":["Small Molecules as Advanced Therapy for the Treatment of Inflammatory Bowel Disease, Particularly Regarding Ulcerative Colitis"],"prefix":"10.2169","author":[{"given":"Toshiyuki","family":"Sakurai","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Saruta","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"962","reference":[{"key":"1","doi-asserted-by":"crossref","unstructured":"1. Ng SC, Shi HY, Hamidi N, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet 390: 2769-2778, 2017.","DOI":"10.1016\/S0140-6736(17)32448-0"},{"key":"2","doi-asserted-by":"publisher","unstructured":"2. Turner D, Ricciuto A, Lewis A, et al. International Organization for the Study of IBD. STRIDE-II: an update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): determining therapeutic goals for treat-to-target strategies in IBD. Gastroenterology 160: 1570-1583, 2021.","DOI":"10.1053\/j.gastro.2020.12.031"},{"key":"3","doi-asserted-by":"crossref","unstructured":"3. Nakase H, Uchino M, Shinzaki S, et al. Evidence-based clinical practice guidelines for inflammatory bowel disease 2020. J Gastroenterol 56: 489-526, 2021.","DOI":"10.1007\/s00535-021-01784-1"},{"key":"4","unstructured":"4. Peyrin-Biroulet L. Anti-TNF therapy in inflammatory bowel disease: a huge review. Minerva Gastroenterol Dietol 56: 233-243, 2010."},{"key":"5","doi-asserted-by":"crossref","unstructured":"5. Deyhim T, Cheifetz AS, Papamichael K. Drug clearance in patients with inflammatory bowel disease treated with biologics. J Clin Med 12: 7132, 2023.","DOI":"10.3390\/jcm12227132"},{"key":"6","doi-asserted-by":"crossref","unstructured":"6. Ngo HX, Garneau-Tsodikova S. What are the drugs of the future? Medchemcomm 9: 757-758, 2018.","DOI":"10.1039\/C8MD90019A"},{"key":"7","doi-asserted-by":"crossref","unstructured":"7. Beck H, H\u00e4rter M, Ha\u00df B, Schmeck C, Baerfacker L. Small molecules and their impact in drug discovery: a perspective on the occasion of the 125th anniversary of the Bayer Chemical Research Laboratory. Drug Discov Tod 27: 1560-1574, 2022.","DOI":"10.1016\/j.drudis.2022.02.015"},{"key":"8","doi-asserted-by":"publisher","unstructured":"8. McLornan DP, Pope JE, Gotlib J, Harrison CN. Current and future status of JAK inhibitors. Lancet 398: 803-816, 2021.","DOI":"10.1016\/S0140-6736(21)00438-4"},{"key":"9","doi-asserted-by":"crossref","unstructured":"9. Salas A, Hernandez-Rocha C, Duijvestein M, et al. JAK-STAT pathway targeting for the treatment of inflammatory bowel disease. Nat Rev Gastroenterol Hepatol 17: 323-337, 2020.","DOI":"10.1038\/s41575-020-0273-0"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10. Schwartz DM, Kanno Y, Villarino A, Ward M, Gadina M, O'Shea JJ. JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat Rev Drug Discovery 16: 843-862, 2017.","DOI":"10.1038\/nrd.2017.201"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11. Clark JD, Flanagan ME, Telliez JB. Discovery and development of Janus kinase (JAK) inhibitors for inflammatory diseases. J Med Chem 57: 5023-5030, 2014.","DOI":"10.1021\/jm401490p"},{"key":"12","doi-asserted-by":"crossref","unstructured":"12. Dowty ME, Lin J, Ryder TF, et al. The pharmacokinetics, metabolism, and clearance mechanisms of tofacitinib, a Janus kinase inhibitor, in humans. Drug Metab Dispos 42: 759-773, 2014.","DOI":"10.1124\/dmd.113.054940"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13. Mohamed MF, Kl\u00fcnder B, Othman AA. Clinical pharmacokinetics of upadacitinib: review of data relevant to the rheumatoid arthritis indication. Clin Pharmacokinet 59: 531-544, 2020.","DOI":"10.1007\/s40262-019-00855-0"},{"key":"14","doi-asserted-by":"crossref","unstructured":"14. Yates M, Mootoo A, Adas M, et al. Venous thromboembolism risk with JAK inhibitors: a meta-analysis. Arthritis Rheumatol 73: 779-788, 2021.","DOI":"10.1002\/art.41580"},{"key":"15","unstructured":"15. XELJANZ (tofacitinib)-FDA Prescribing Information [Internet]. [cited 2025 Apr 1]. Available from: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2016\/208246s000lbl.pdf"},{"key":"16","unstructured":"16. Xeljanz (tofacitinib)-EMA Product Information [Internet]. [cited 2025 Apr 1]. Available from: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/xeljanz-epar-product-information_en.pdf"},{"key":"17","unstructured":"17. FDA requires warnings about increased risk of serious heart-related events, cancer, blood clots, and death for JAK inhibitors that treat certain chronic inflammatory conditions [Internet]. Available from: https:\/\/www.fda.gov\/drugs\/drug-safety-and-availability\/fda-requires-warnings-about-increased-risk-serious-heart-related-events-cancer-blood-clots-and-death"},{"key":"18","doi-asserted-by":"crossref","unstructured":"18. Olivera PA, Lasa JS, Bonovas S, Danese S, Peyrin-Biroulet L. Safety of Janus kinase inhibitors in patients with inflammatory bowel diseases or other immune-mediated diseases: a systematic review and meta-analysis. Gastroenterology 158: 1554-1573, 2020.","DOI":"10.1053\/j.gastro.2020.01.001"},{"key":"19","doi-asserted-by":"crossref","unstructured":"19. Olivera PA, Lasa JS, Peretto G, Zuily S, Danese S, Peyrin-Biroulet L. Review article: risk of cardiovascular events in patients with inflammatory bowel disease receiving small molecule drugs. Aliment Pharmacol Ther 57: 1231-1248, 2023.","DOI":"10.1111\/apt.17509"},{"key":"20","unstructured":"20. European Medicine Agency. EMA confirms measures to minimise risk of serious side effects with Janus kinase inhibitors for chronic inflammatory disorders. 11.11.2022 [Internet]. [cited 2023 May 9]. Available from: https:\/\/www.ema.europa.eu\/en\/news\/ema-confirms-measures-minimise-risk-serious-side-effects-janus-kinase-inhibitors-chronic"},{"key":"21","doi-asserted-by":"crossref","unstructured":"21. Sandborn WJ, Su C, Sands BE, et al. Tofacitinib as induction and maintenance therapy for ulcerative colitis. N Engl J Med 376: 1723-1736, 2017.","DOI":"10.1056\/NEJMoa1606910"},{"key":"22","doi-asserted-by":"crossref","unstructured":"22. Sandborn WJ, Ghosh S, Pan\u00e9s J, et al. Tofacitinib, an oral Janus kinase inhibitor, in active ulcerative colitis. N Engl J Med 367: 616-624, 2012.","DOI":"10.1056\/NEJMoa1112168"},{"key":"23","doi-asserted-by":"crossref","unstructured":"23. Feagan BG, Danese S, Loftus EV, et al. Filgotinib as induction and maintenance therapy for ulcerative colitis (SELECTION): a phase 2b\/3 double-Blind, randomised, placebo-controlled trial. Lancet 397: 2372-2384, 2021.","DOI":"10.1016\/S0140-6736(21)00666-8"},{"key":"24","doi-asserted-by":"crossref","unstructured":"24. Schreiber S, Roger G, Watanabe M, et al. Integrated safety analysis of filgotinib for ulcerative colitis: results from SELECTION and SELECTIONLTE. Aliment Pharmacol Ther 58: 874-887, 2023.","DOI":"10.1111\/apt.17674"},{"key":"25","doi-asserted-by":"crossref","unstructured":"25. Vermeire S, Danese S, Zhou W, et al. Efficacy and safety of upadacitinib maintenance therapy for moderately to severely active ulcerative colitis in patients responding to 8-week induction therapy (U-ACHIEVE maintenance): overall results from the randomised, placebo-controlled, double-blind, phase 3 maintenance study. Lancet Gastroenterol Hepatol 8: 976-989, 2023.","DOI":"10.1016\/S2468-1253(23)00208-X"},{"key":"26","doi-asserted-by":"crossref","unstructured":"26. Taxonera C, Olivares D, Rey E, Alba C. Real-world effectiveness and safety of tofacitinib in patients with ulcerative colitis: systematic review with meta-analysis. Inflamm Bowel Dis 28: 32-40, 2022.","DOI":"10.1093\/ibd\/izab011"},{"key":"27","doi-asserted-by":"crossref","unstructured":"27. Shimizu H, Matsuoka K, Hisamatsu T, et al. Long-term efficacy and safety of tofacitinib in patients with ulcerative colitis: 3-year results from a real-world study. Intest Res 22: 369-377, 2024.","DOI":"10.5217\/ir.2023.00194"},{"key":"28","doi-asserted-by":"crossref","unstructured":"28. Berinstein JA, Sheehan JL, Dias M, et al. Tofacitinib for Biologic-experienced hospitalized patients with acute severe ulcerative colitis: a retrospective case-control study. Clin Gastroenterol Hepatol 19: e2111, 2021.","DOI":"10.1016\/j.cgh.2021.05.038"},{"key":"29","doi-asserted-by":"crossref","unstructured":"29. Singh A, Goyal MK, Midha V, et al. Tofacitinib in Acute Severe Ulcerative Colitis (TACOS): A Rondomized Controlled Trial. Am J Gastroenterol 119: 1365-1372, 2023.","DOI":"10.14309\/ajg.0000000000002635"},{"key":"30","doi-asserted-by":"crossref","unstructured":"30. Narula N, Peertani F, Hansen T, et al. DOP46 Tofacitinib for hospitalized acute severe ulcerative colitis-the TRIUMPH study. J Crohns Colitis 18 (Supplement_1): i155-i155, 2024.","DOI":"10.1093\/ecco-jcc\/jjad212.0086"},{"key":"31","doi-asserted-by":"crossref","unstructured":"31. Tanaka Y, Kavanaugh A, Wicklund J, McInnes IB. Filgotinib, a novel JAK1-preferential inhibitor for the treatment of rheumatoid arthritis: an overview from clinical trials. Mod Rheumatol 32: 1-11, 2022.","DOI":"10.1080\/14397595.2021.1902617"},{"key":"32","doi-asserted-by":"crossref","unstructured":"32. Van Rompaey L, Galien R, van der Aar EM, et al. Preclinical characterization of GLPG0634, a selective inhibitor of JAK1, for the treatment of inflammatory diseases. J Immunol 191: 3568-3577, 2013.","DOI":"10.4049\/jimmunol.1201348"},{"key":"33","doi-asserted-by":"crossref","unstructured":"33. Traves PG, Murray B, Campigotto F, Galien R, Meng A, Di Paolo JA. JAK selectivity and the implications for clinical inhibition of pharmacodynamic cytokine signalling by filgotinib, upadacitinib, tofacitinib and baricitinib. Ann Rheum Dis 80: 865-875, 2021.","DOI":"10.1136\/annrheumdis-2020-219012"},{"key":"34","unstructured":"34. JYSELECA (filgotinib)-EMA Product Information [Internet]. [cited 2025 Apr 1]. Available from: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/jyseleca"},{"key":"35","doi-asserted-by":"crossref","unstructured":"35. Gros B, Engel T, Kopylov U, et al. Real-world cohort study on the effectiveness and safety of filgotinib use in ulcerative colitis. J Crohns Colitis 19: jjad187, 2025.","DOI":"10.1093\/ecco-jcc\/jjad187"},{"key":"36","doi-asserted-by":"crossref","unstructured":"36. Akiyama S, Yamamoto T, Ikeya T, et al. Efficacy and safety of filgotinib for ulcerative colitis: a real-world multicenter retrospective study in japan. Aliment Pharmacol Ther 59: 1413-1424, 2024.","DOI":"10.1111\/apt.17961"},{"key":"37","doi-asserted-by":"crossref","unstructured":"37. Young D, Bhamra R, Sebastian S, et al. Real-world assessment of effectiveness and safety of filgotinib in 286 patients with ulcerative colitis in 9 UK centres. Drugs Context 14: 2024-11-1, 2025.","DOI":"10.7573\/dic.2024-11-1"},{"key":"38","doi-asserted-by":"crossref","unstructured":"38. Traves PG, Murray B, Campigotto P, et al. JAK selectivity and the implications for clinical inhibition of pharmacodynamic cytokine signalling by filgotinib, upadacitinib, tofacitinib, and baricitinib. Ann Rheum Dis 80: 865-875, 2021.","DOI":"10.1136\/annrheumdis-2020-219012"},{"key":"39","doi-asserted-by":"crossref","unstructured":"39. Mohamed MF, Zeng J, Marroum PJ, Song IH, Othman AA. Pharmacokinetics of upadacitinib with the clinical regimens of the extended-release formulation utilized in rheumatoid arthritis phase 3 trials. Clin Pharmacol Drug Dev 8: 208-216, 2019.","DOI":"10.1002\/cpdd.462"},{"key":"40","unstructured":"40. RINVOQ (upadacitinib)-FDA Prescribing Information [Internet]. [cited 2025 Apr 1]. Available from: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2023\/211675s015lbl.pdf"},{"key":"41","doi-asserted-by":"publisher","unstructured":"41. Sandborn WJ, Ghosh S, Pan\u00e9s J, et al. Efficacy of upadacitinib in a randomized trial of patients with active ulcerative colitis. Gastroenterology 158: 2139-2149.e14, 2020.","DOI":"10.1053\/j.gastro.2020.02.030"},{"key":"42","doi-asserted-by":"crossref","unstructured":"42. Friedberg S, Rinawi F, Ben Hur D, et al. Upadacitinib is effective and safe in both ulcerative colitis and Crohn's disease: prospective real-world experience. Clin Gastroenterol Hepatol 21: 1913-1923.e2, 2023.","DOI":"10.1016\/j.cgh.2023.03.001"},{"key":"43","unstructured":"43. Berinstein JA, Karl T, Patel A, et al. Effectiveness of upadacitinib for patients with acute severe ulcerative colitis: a multicenter experience. Am J Gastroenterol 27: 2024. Online ahead of print."},{"key":"44","doi-asserted-by":"crossref","unstructured":"44. Damianos JA, Osikoya O, Brennan G. Upadacitinib for acute severe ulcerative colitis: a systematic review. Inflamm Bowel Dis 31: 1145-1149, 2025.","DOI":"10.1093\/ibd\/izae191"},{"key":"45","doi-asserted-by":"crossref","unstructured":"45. Loftus EV Jr, Pan\u00e9s J, Lacerda AP, et al. Upadacitinib induction and maintenance therapy for Crohn's disease. N Engl J Med 388: 1966-1980, 2023.","DOI":"10.1056\/NEJMoa2212728"},{"key":"46","doi-asserted-by":"crossref","unstructured":"46. Colombel JF, Hisamatsu T, Atreya R, et al. Upadacitinib reduces Crohn's disease symptoms within the first week of induction therapy. Clin Gastroenterol Hepatol 22: 1668-1677, 2024.","DOI":"10.1016\/j.cgh.2024.02.027"},{"key":"47","doi-asserted-by":"crossref","unstructured":"47. Colombel JF, Lacerda AP, Irving PM, et al. Efficacy and safety of upadacitinib for perianal fistulizing Crohn's disease: a post hoc analysis of 3 phase 3 trials. Clin Gastroenterol Hepatol 23: 1019-1029, 2025.","DOI":"10.1016\/j.cgh.2024.08.032"},{"key":"48","doi-asserted-by":"crossref","unstructured":"48. Devi J, Xu A, Stone M, et al. Real-world effectiveness and safety of upadacitinib in Crohn's disease: a multicenter study. Clin Gastroenterol Hepatol 23: 2281-2291.e4, 2025.","DOI":"10.1016\/j.cgh.2025.01.012"},{"key":"49","doi-asserted-by":"crossref","unstructured":"49. Shehab M, Alrashed F, Alsayegh A, et al. Comparative efficacy of biologics and small molecule in ulcerative colitis: a systematic review and network meta-analysis. Clin Gastroenterol Hepatol 23: 250-262, 2024.","DOI":"10.1016\/j.cgh.2024.07.033"},{"key":"50","doi-asserted-by":"crossref","unstructured":"50. Akiyama S, Shimizu H, Tamura A, et al. Comparative efficacy and safety of three Janus kinase inhibitors in ulcerative colitis: a real-world multicentre study in Japan. Aliment Pharmacol Ther 61: 524-537, 2025.","DOI":"10.1111\/apt.18406"},{"key":"51","doi-asserted-by":"crossref","unstructured":"51. Hasan F, Liaquat A, Raza A, et al. Effectiveness of upadacitinib in ulcerative colitis patients with prior tofacitinib exposure: a systematic review and meta-analysis. Ann Gastroenterol 38: 511-518, 2025.","DOI":"10.20524\/aog.2025.0991"},{"key":"52","doi-asserted-by":"crossref","unstructured":"52. Mendelson K, Evans T, Hla T. Sphingosine 1-phosphate signalling. Development 141: 5-9, 2014.","DOI":"10.1242\/dev.094805"},{"key":"53","doi-asserted-by":"crossref","unstructured":"53. Verstockt B, Vetrano S, Salas A, et al. Sphingosine 1-phosphate modulation and immune cell trafficking in inflammatory bowel disease. Nat Rev Gastroenterol Hepatol 19: 351-366, 2022.","DOI":"10.1038\/s41575-021-00574-7"},{"key":"54","doi-asserted-by":"crossref","unstructured":"54. Blaho VA, Hla T. Thematic review series: lysophospholipids and their receptors: an update on the biology of sphingosine 1-phosphate receptors. J Lipid Res 55: 1596-1608, 2014.","DOI":"10.1194\/jlr.R046300"},{"key":"55","doi-asserted-by":"crossref","unstructured":"55. Degagne E, Saba JD. S1ppingFire: Sphingosine-1-phosphate signaling as an emerging target in inflammatory bowel disease and colitis-associated cancer. Clin Exp Gastroenterol 7: 205-214, 2014.","DOI":"10.2147\/CEG.S43453"},{"key":"56","doi-asserted-by":"crossref","unstructured":"56. Sandborn WJ, Feagan BG, D'Haens G, et al. Ozanimod as induction and maintenance therapy for ulcerative colitis. N Engl J Med 385: 1280-1291, 2021.","DOI":"10.1056\/NEJMoa2033617"},{"key":"57","doi-asserted-by":"crossref","unstructured":"57. Danese S, Panaccione R, Abreu MT, et al. Efficacy and safety of approximately 3 years of continuous ozanimod in moderately to severely active ulcerative colitis: interim analysis of the true north open-label extension. J Crohns Colitis 18: 264-274, 2024.","DOI":"10.1093\/ecco-jcc\/jjad146"},{"key":"58","doi-asserted-by":"crossref","unstructured":"58. Tran JQ, Hartung JP, Olson AD, et al. Cardiac safety of ozanimod, a novel sphingosine-1-phosphate receptor modulator: results of a thorough QT\/QTc study. Clin Pharmacol Drug Dev 7: 263-276, 2017.","DOI":"10.1002\/cpdd.383"},{"key":"59","doi-asserted-by":"crossref","unstructured":"59. Fantini MC, Centonze D, Giacobazzi G, et al. Sphingosine-1-phosphate receptor modulators for the treatment of ulcerative colitis: a narrative review focusing on safety. United Eur Gastroenterol J 13: 1077-1091, 2025.","DOI":"10.1002\/ueg2.70026"},{"key":"60","unstructured":"60. Schreiber S, Morgan M, Christopher R, et al. P-180 Etrasimod (APD334), a potent, selective, oral S1P receptor modulator with autoimmune disease-modifying activity exhibiting favorable PK\/PD properties in healthy volunteers. Inflamm Bowel Dis 23: S61, 2017."},{"key":"61","doi-asserted-by":"crossref","unstructured":"61. Nakase H, Fujii T, Hisamatsu T, et al. Once-daily oral ozanimod for Japanese patients with ulcerative colitis: results from the phase 2\/3 J-True North study. Gastro Hep Adv 5: 100812, 2025.","DOI":"10.1016\/j.gastha.2025.100812"},{"key":"62","doi-asserted-by":"crossref","unstructured":"62. Kochhar GS, Khataniar H, Hashash JG, et al. Comparative effectiveness of ozanimod and vedolizumab as first-line advanced therapies in ulcerative colitis: a propensity-matched cohort analysis. Inflamm Bowel Dis 31: 1868-1875, 2025.","DOI":"10.1093\/ibd\/izae251"},{"key":"63","doi-asserted-by":"crossref","unstructured":"63. Cohen NA, Choi D, Garcia N, et al. Real world clinical effectiveness and safety of ozanimod in the treatment of ulcerative colitis: 1-year follow-up from a tertiary center. Dig Dis Sci 69: 579-587, 2024.","DOI":"10.1007\/s10620-023-08178-8"},{"key":"64","doi-asserted-by":"crossref","unstructured":"64. Sandborn WJ, Vermeire S, Peyrin-Biroulet L, et al. Etrasimod as induction and maintenance therapy for ulcerative colitis (ELEVATE): two randomised, double-blind, placebo-controlled, phase 3 studies. Lancet 401: 1159-1171, 2023.","DOI":"10.1016\/S0140-6736(23)00061-2"},{"key":"65","doi-asserted-by":"crossref","unstructured":"65. Matsuoka K, Watanabe M, Ohmori T, et al. AJM300 (carotegrast methyl), an oral antagonist of alpha4-integrin, as induction therapy for patients with moderately active ulcerative colitis: a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Gastroenterol Hepatol 7: 648-657, 2022.","DOI":"10.2139\/ssrn.3978554"},{"key":"66","doi-asserted-by":"crossref","unstructured":"66. Koshiba R, Kakimoto K, Inoue T, et al. Real-world effectiveness and safety of carotegrast methyl in patients with ulcerative colitis: a multicenter retrospective cohort study. Intest Res 2025. Online ahead of print.","DOI":"10.5217\/ir.2025.00066"},{"key":"67","doi-asserted-by":"crossref","unstructured":"67. Shimoyama T, Yamamoto T, Miyao H, Aota S, Morita S, Sakaguchi R. Efficacy and safety of carotegrast methyl in active ulcerative colitis: a real-world prospective cohort study. Intest Res 2025. Online ahead of print.","DOI":"10.5217\/ir.2025.00046"}],"container-title":["Internal Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/internalmedicine\/advpub\/0\/advpub_7378-26\/_pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T03:27:56Z","timestamp":1778902076000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/internalmedicine\/advpub\/0\/advpub_7378-26\/_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":67,"URL":"https:\/\/doi.org\/10.2169\/internalmedicine.7378-26","relation":{},"ISSN":["0918-2918","1349-7235"],"issn-type":[{"value":"0918-2918","type":"print"},{"value":"1349-7235","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026]]},"article-number":"7378-26"}}