{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:30:34Z","timestamp":1790803834536,"version":"4.1.0"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,5,4]],"date-time":"2024-05-04T00:00:00Z","timestamp":1714780800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,5,4]],"date-time":"2024-05-04T00:00:00Z","timestamp":1714780800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Respir Res"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Lipocalin-2 (LCN2) is a secretory glycoprotein upregulated by oxidative stress; moreover, patients with idiopathic pulmonary fibrosis (IPF) have shown increased LCN2 levels in bronchoalveolar lavage fluid (BALF). This study aimed to determine whether circulatory LCN2 could be a systemic biomarker in patients with IPF and to investigate the role of LCN2 in a bleomycin-induced lung injury mouse model.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We measured serum LCN2 levels in 99 patients with stable IPF, 27 patients with acute exacerbation (AE) of IPF, 51 patients with chronic hypersensitivity pneumonitis, and 67 healthy controls. Further, LCN2 expression in lung tissue was evaluated in a bleomycin-induced lung injury mouse model, and the role of LCN2 was investigated using LCN2-knockout (LCN2 -\/-) mice.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Serum levels of LCN2 were significantly higher in patients with AE-IPF than in the other groups. The multivariate Cox proportional hazards model showed that elevated serum LCN2 level was an independent predictor of poor survival in patients with AE-IPF. In the bleomycin-induced lung injury mouse model, a higher dose of bleomycin resulted in higher LCN2 levels and shorter survival. Bleomycin-treated LCN2 -\/- mice exhibited increased BALF cell and protein levels as well as hydroxyproline content. Moreover, compared with wild-type mice, LCN2-\/- mice showed higher levels of circulatory 8-isoprostane as well as lower Nrf-2, GCLC, and NQO1 expression levels in lung tissue following bleomycin administration.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our findings demonstrate that serum LCN2 might be a potential prognostic marker of AE-IPF. Moreover, LCN2 expression levels may reflect the severity of lung injury, and LCN2 may be a protective factor against bleomycin-induced acute lung injury and oxidative stress.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12931-024-02825-y","type":"journal-article","created":{"date-parts":[[2024,5,4]],"date-time":"2024-05-04T12:01:49Z","timestamp":1714824109000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Lipocalin-2 as a prognostic marker in patients with acute exacerbation of idiopathic pulmonary fibrosis"],"prefix":"10.1186","volume":"25","author":[{"given":"Hiroki","family":"Tanahashi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Iwamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kakuhiro","family":"Yamaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinjiro","family":"Sakamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Horimasu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Masuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taku","family":"Nakashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichiro","family":"Ohshimo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazunori","family":"Fujitaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironobu","family":"Hamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noboru","family":"Hattori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,4]]},"reference":[{"key":"2825_CR1","doi-asserted-by":"publisher","first-page":"e44","DOI":"10.1164\/rccm.201807-1255ST","volume":"198","author":"G Raghu","year":"2018","unstructured":"Raghu G, Remy-Jardin M, Myers JL, Richeldi L, Ryerson CJ, Lederer DJ, Behr J, Cottin V, Danoff SK, Morell F, et al. Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS\/ERS\/JRS\/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2018;198:e44\u201368.","journal-title":"Am J Respir Crit Care Med"},{"key":"2825_CR2","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1016\/j.resinv.2018.03.003","volume":"56","author":"S Homma","year":"2018","unstructured":"Homma S, Bando M, Azuma A, Sakamoto S, Sugino K, Ishii Y, Izumi S, Inase N, Inoue Y, Ebina M, et al. Japanese guideline for the treatment of idiopathic pulmonary fibrosis. Respir Investig. 2018;56:268\u201391.","journal-title":"Respir Investig"},{"key":"2825_CR3","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1164\/rccm.201604-0801CI","volume":"194","author":"HR Collard","year":"2016","unstructured":"Collard HR, Ryerson CJ, Corte TJ, Jenkins G, Kondoh Y, Lederer DJ, Lee JS, Maher TM, Wells AU, Antoniou KM, et al. Acute Exacerbation of Idiopathic Pulmonary Fibrosis. An International Working Group Report. Am J Respir Crit Care Med. 2016;194:265\u201375.","journal-title":"Am J Respir Crit Care Med"},{"key":"2825_CR4","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1164\/rccm.201006-0894CI","volume":"183","author":"B Ley","year":"2011","unstructured":"Ley B, Collard HR, King TE Jr. Clinical course and prediction of survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2011;183:431\u201340.","journal-title":"Am J Respir Crit Care Med"},{"key":"2825_CR5","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1164\/rccm.200501-017PP","volume":"172","author":"VL Kinnula","year":"2005","unstructured":"Kinnula VL, Fattman CL, Tan RJ, Oury TD. Oxidative stress in pulmonary fibrosis: a possible role for redox modulatory therapy. Am J Respir Crit Care Med. 2005;172:417\u201322.","journal-title":"Am J Respir Crit Care Med"},{"key":"2825_CR6","doi-asserted-by":"publisher","first-page":"1092","DOI":"10.1089\/ars.2019.7742","volume":"31","author":"C Veith","year":"2019","unstructured":"Veith C, Boots AW, Idris M, van Schooten FJ, van der Vliet A. Redox Imbalance in Idiopathic Pulmonary Fibrosis: A Role for Oxidant Cross-Talk Between NADPH Oxidase Enzymes and Mitochondria. Antioxid Redox Signal. 2019;31:1092\u2013115.","journal-title":"Antioxid Redox Signal"},{"key":"2825_CR7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.pupt.2015.03.005","volume":"32","author":"Y Matsuzawa","year":"2015","unstructured":"Matsuzawa Y, Kawashima T, Kuwabara R, Hayakawa S, Irie T, Yoshida T, Rikitake H, Wakabayashi T, Okada N, Kawashima K, et al. Change in serum marker of oxidative stress in the progression of idiopathic pulmonary fibrosis. Pulm Pharmacol Ther. 2015;32:1\u20136.","journal-title":"Pulm Pharmacol Ther"},{"key":"2825_CR8","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1183\/09031936.96.09020307","volume":"9","author":"AG Lenz","year":"1996","unstructured":"Lenz AG, Costabel U, Maier KL. Oxidized BAL fluid proteins in patients with interstitial lung diseases. Eur Respir J. 1996;9:307\u201312.","journal-title":"Eur Respir J"},{"key":"2825_CR9","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1183\/09031936.02.00262402","volume":"19","author":"KM Beeh","year":"2002","unstructured":"Beeh KM, Beier J, Haas IC, Kornmann O, Micke P, Buhl R. Glutathione deficiency of the lower respiratory tract in patients with idiopathic pulmonary fibrosis. Eur Respir J. 2002;19:1119\u201323.","journal-title":"Eur Respir J"},{"key":"2825_CR10","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1111\/j.1365-2362.2006.01636.x","volume":"36","author":"K Psathakis","year":"2006","unstructured":"Psathakis K, Mermigkis D, Papatheodorou G, Loukides S, Panagou P, Polychronopoulos V, Siafakas NM, Bouros D. Exhaled markers of oxidative stress in idiopathic pulmonary fibrosis. Eur J Clin Invest. 2006;36:362\u20137.","journal-title":"Eur J Clin Invest"},{"key":"2825_CR11","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1136\/thoraxjnl-2017-209967","volume":"73","author":"L Ses\u00e9","year":"2018","unstructured":"Ses\u00e9 L, Nunes H, Cottin V, Sanyal S, Didier M, Carton Z, Israel-Biet D, Crestani B, Cadranel J, Wallaert B, et al. Role of atmospheric pollution on the natural history of idiopathic pulmonary fibrosis. Thorax. 2018;73:145\u201350.","journal-title":"Thorax"},{"key":"2825_CR12","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1186\/s12931-021-01671-6","volume":"22","author":"M Tahara","year":"2021","unstructured":"Tahara M, Fujino Y, Yamasaki K, Oda K, Kido T, Sakamoto N, Kawanami T, Kataoka K, Egashira R, et al. Exposure to PM(2.5) is a risk factor for acute exacerbation of surgically diagnosed idiopathic pulmonary fibrosis: a case-control study. Respir Res. 2021;22:80.","journal-title":"Respir Res"},{"key":"2825_CR13","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1007\/s11604-008-0261-8","volume":"26","author":"A Takeda","year":"2008","unstructured":"Takeda A, Enomoto T, Sanuki N, Nakajima T, Takeda T, Sayama K, Kunieda E. Acute exacerbation of subclinical idiopathic pulmonary fibrosis triggered by hypofractionated stereotactic body radiotherapy in a patient with primary lung cancer and slightly focal honeycombing. Radiat Med. 2008;26:504\u20137.","journal-title":"Radiat Med"},{"key":"2825_CR14","doi-asserted-by":"publisher","first-page":"L726","DOI":"10.1152\/ajplung.00080.2021","volume":"321","author":"S Guardado","year":"2021","unstructured":"Guardado S, Ojeda-Ju\u00e1rez D, Kaul M, Nordgren TM. Comprehensive review of lipocalin 2-mediated effects in lung inflammation. Am J Physiol Lung Cell Mol Physiol. 2021;321:L726-l733.","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"2825_CR15","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1269\/jrr.06057","volume":"48","author":"MH Roudkenar","year":"2007","unstructured":"Roudkenar MH, Kuwahara Y, Baba T, Roushandeh AM, Ebishima S, Abe S, Ohkubo Y, Fukumoto M. Oxidative stress induced lipocalin 2 gene expression: addressing its expression under the harmful conditions. J Radiat Res. 2007;48:39\u201344.","journal-title":"J Radiat Res"},{"key":"2825_CR16","doi-asserted-by":"publisher","first-page":"e14026","DOI":"10.14814\/phy2.14026","volume":"7","author":"N Fuentes","year":"2019","unstructured":"Fuentes N, Cabello N, Nicoleau M, Chroneos ZC, Silveyra P. Modulation of the lung inflammatory response to ozone by the estrous cycle. Physiol Rep. 2019;7:e14026.","journal-title":"Physiol Rep"},{"key":"2825_CR17","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1007\/s12192-009-0154-5","volume":"15","author":"P Bahmani","year":"2010","unstructured":"Bahmani P, Halabian R, Rouhbakhsh M, Roushandeh AM, Masroori N, Ebrahimi M, Samadikuchaksaraei A, Shokrgozar MA, Roudkenar MH. Neutrophil gelatinase-associated lipocalin induces the expression of heme oxygenase-1 and superoxide dismutase 1, 2. Cell Stress Chaperones. 2010;15:395\u2013403.","journal-title":"Cell Stress Chaperones"},{"key":"2825_CR18","doi-asserted-by":"publisher","first-page":"888","DOI":"10.1378\/chest.09-2718","volume":"138","author":"TM Eagan","year":"2010","unstructured":"Eagan TM, Dam\u00e5s JK, Ueland T, Voll-Aanerud M, Mollnes TE, Hardie JA, Bakke PS, Aukrust P. Neutrophil gelatinase-associated lipocalin: a biomarker in COPD. Chest. 2010;138:888\u201395.","journal-title":"Chest"},{"key":"2825_CR19","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1183\/09031936.00024313","volume":"43","author":"H Iwamoto","year":"2014","unstructured":"Iwamoto H, Gao J, Koskela J, Kinnula V, Kobayashi H, Laitinen T, Mazur W. Differences in plasma and sputum biomarkers between COPD and COPD-asthma overlap. Eur Respir J. 2014;43:421\u20139.","journal-title":"Eur Respir J"},{"key":"2825_CR20","doi-asserted-by":"publisher","first-page":"7909","DOI":"10.1038\/s41598-022-12117-4","volume":"12","author":"E Son","year":"2022","unstructured":"Son E, Cho WH, Jang JH, Kim T, Jeon D, Kim YS, Yeo HJ. Neutrophil gelatinase-associated lipocalin as a prognostic biomarker of severe acute respiratory distress syndrome. Sci Rep. 2022;12:7909.","journal-title":"Sci Rep"},{"key":"2825_CR21","doi-asserted-by":"publisher","first-page":"1807","DOI":"10.1183\/09031936.00192613","volume":"43","author":"K Ikezoe","year":"2014","unstructured":"Ikezoe K, Handa T, Mori K, Watanabe K, Tanizawa K, Aihara K, Tsuruyama T, Miyagawa-Hayashino A, Sokai A, Kubo T, et al. Neutrophil gelatinase-associated lipocalin in idiopathic pulmonary fibrosis. Eur Respir J. 2014;43:1807\u20139.","journal-title":"Eur Respir J"},{"key":"2825_CR22","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1111\/resp.13634","volume":"25","author":"K Yamaguchi","year":"2020","unstructured":"Yamaguchi K, Iwamoto H, Sakamoto S, Horimasu Y, Masuda T, Miyamoto S, Nakashima T, Ohshimo S, Fujitaka K, Hamada H, Hattori N. Serum high-mobility group box 1 is associated with the onset and severity of acute exacerbation of idiopathic pulmonary fibrosis. Respirology. 2020;25:275\u201380.","journal-title":"Respirology"},{"key":"2825_CR23","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/S0091-6749(99)70507-5","volume":"103","author":"Y Yoshizawa","year":"1999","unstructured":"Yoshizawa Y, Ohtani Y, Hayakawa H, Sato A, Suga M, Ando M. Chronic hypersensitivity pneumonitis in Japan: a nationwide epidemiologic survey. J Allergy Clin Immunol. 1999;103:315\u201320.","journal-title":"J Allergy Clin Immunol"},{"key":"2825_CR24","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1186\/s13287-021-02574-5","volume":"12","author":"S Takao","year":"2021","unstructured":"Takao S, Nakashima T, Masuda T, Namba M, Sakamoto S, Yamaguchi K, Horimasu Y, Miyamoto S, Iwamoto H, Fujitaka K, et al. Human bone marrow-derived mesenchymal stromal cells cultured in serum-free media demonstrate enhanced antifibrotic abilities via prolonged survival and robust regulatory T cell induction in murine bleomycin-induced pulmonary fibrosis. Stem Cell Res Ther. 2021;12:506.","journal-title":"Stem Cell Res Ther"},{"key":"2825_CR25","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1186\/s13287-021-02549-6","volume":"12","author":"H Takahashi","year":"2021","unstructured":"Takahashi H, Nakashima T, Masuda T, Namba M, Sakamoto S, Yamaguchi K, Horimasu Y, Miyamoto S, Iwamoto H, Fujitaka K, et al. Antifibrotic effect of lung-resident progenitor cells with high aldehyde dehydrogenase activity. Stem Cell Res Ther. 2021;12:471.","journal-title":"Stem Cell Res Ther"},{"key":"2825_CR26","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1016\/j.pupt.2007.07.006","volume":"21","author":"KC Teixeira","year":"2008","unstructured":"Teixeira KC, Soares FS, Rocha LG, Silveira PC, Silva LA, Valen\u00e7a SS, Dal Pizzol F, Streck EL, Pinho RA. Attenuation of bleomycin-induced lung injury and oxidative stress by N-acetylcysteine plus deferoxamine. Pulm Pharmacol Ther. 2008;21:309\u201316.","journal-title":"Pulm Pharmacol Ther"},{"key":"2825_CR27","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1111\/liv.12073","volume":"33","author":"S Sultan","year":"2013","unstructured":"Sultan S, Cameron S, Ahmad S, Malik IA, Schultze FC, Hielscher R, Rave-Fr\u00e4nk M, Hess CF, Ramadori G, Christiansen H. Serum Lipocalin2 is a potential biomarker of liver irradiation damage. Liver Int. 2013;33:459\u201368.","journal-title":"Liver Int"},{"key":"2825_CR28","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.cca.2019.07.015","volume":"497","author":"DK Faria","year":"2019","unstructured":"Faria DK, Faria CS, Doi D, Acencio MM, Antonangelo L. Hybrid panel of biomarkers can be useful in the diagnosis of pleural and peritoneal effusions. Clinica Chimica Acta. 2019;497:48\u201353.","journal-title":"Clinica Chimica Acta"},{"key":"2825_CR29","doi-asserted-by":"publisher","first-page":"6253","DOI":"10.3390\/ijms21176253","volume":"21","author":"G Wang","year":"2020","unstructured":"Wang G, Weng Y-C, Chiang I-C, Huang Y-T, Liao Y-C, Chen Y-C, Kao C-Y, Liu Y-L, Lee T-H, Chou W-H. Neutralization of lipocalin-2 diminishes stroke-reperfusion injury. International Journal of Molecular Sciences. 2020;21:6253.","journal-title":"International Journal of Molecular Sciences"},{"key":"2825_CR30","doi-asserted-by":"publisher","first-page":"1911","DOI":"10.4049\/jimmunol.1200892","volume":"189","author":"G Srinivasan","year":"2012","unstructured":"Srinivasan G, Aitken JD, Zhang B, Carvalho FA, Chassaing B, Shashidharamurthy R, Borregaard N, Jones DP, Gewirtz AT, Vijay-Kumar M. Lipocalin 2 deficiency dysregulates iron homeostasis and exacerbates endotoxin-induced sepsis. J Immunol. 2012;189:1911\u20139.","journal-title":"J Immunol"},{"key":"2825_CR31","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1016\/j.arcmed.2008.05.003","volume":"39","author":"MH Roudkenar","year":"2008","unstructured":"Roudkenar MH, Halabian R, Ghasemipour Z, Roushandeh AM, Rouhbakhsh M, Nekogoftar M, Kuwahara Y, Fukumoto M, Shokrgozar MA. Neutrophil gelatinase-associated lipocalin acts as a protective factor against H(2)O(2) toxicity. Arch Med Res. 2008;39:560\u20136.","journal-title":"Arch Med Res"},{"key":"2825_CR32","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1172\/JCI23056","volume":"115","author":"K Mori","year":"2005","unstructured":"Mori K, Lee HT, Rapoport D, Drexler IR, Foster K, Yang J, Schmidt-Ott KM, Chen X, Li JY, Weiss S, et al. Endocytic delivery of lipocalin-siderophore-iron complex rescues the kidney from ischemia-reperfusion injury. J Clin Invest. 2005;115:610\u201321.","journal-title":"J Clin Invest"},{"key":"2825_CR33","doi-asserted-by":"publisher","first-page":"e0124429","DOI":"10.1371\/journal.pone.0124429","volume":"10","author":"GP Otto","year":"2015","unstructured":"Otto GP, Hurtado-Oliveros J, Chung HY, Knoll K, Neumann T, M\u00fcller HJ, Herbsleb M, Kohl M, Busch M, Sossdorf M, Claus RA. Plasma Neutrophil Gelatinase-Associated Lipocalin Is Primarily Related to Inflammation during Sepsis: A Translational Approach. PLoS One. 2015;10:e0124429.","journal-title":"PLoS One"}],"container-title":["Respiratory Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12931-024-02825-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12931-024-02825-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12931-024-02825-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,4]],"date-time":"2024-05-04T12:02:15Z","timestamp":1714824135000},"score":1,"resource":{"primary":{"URL":"https:\/\/respiratory-research.biomedcentral.com\/articles\/10.1186\/s12931-024-02825-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,4]]},"references-count":33,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["2825"],"URL":"https:\/\/doi.org\/10.1186\/s12931-024-02825-y","relation":{},"ISSN":["1465-993X"],"issn-type":[{"value":"1465-993X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,4]]},"assertion":[{"value":"6 July 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 April 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 May 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by the Ethics Committee of Hiroshima University Hospital (E2004-0326 and E2023-0185), and all participants provided written informed consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"195"}}