{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:48:20Z","timestamp":1787240900178,"version":"build-2736575974"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T00:00:00Z","timestamp":1752105600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T00:00:00Z","timestamp":1752105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"The University of Osaka"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Gastric Cancer"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Excessive surgical stress induces inflammatory cytokine release, negatively impacting prognosis in patients with malignancies. This study aimed to determine whether the anti-inflammatory effect of a corticosteroid (CS) would improve prognosis when administered intraoperatively to patients with resectable gastric cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this multicenter, randomized, open-label, phase II\/III study, patients with cStage II\u2013III gastric cancer were randomized to CS administration or non-administration (control) groups. Patients in the CS group received 5\u00a0mg\/kg of methylprednisolone just before the skin incision during surgery. The primary endpoints were the highest postoperative serum level of C-reactive protein (CRP\n                      <jats:sub>max<\/jats:sub>\n                      ) in the phase II portion, and recurrence-free survival (RFS) in the phase III portion.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Between December 2016 and February 2019, 410 patients were enrolled. In the phase II portion, CRP\n                      <jats:sub>max<\/jats:sub>\n                      was significantly lower in the CS group than in the control group (mean, 10.7 vs 14.3\u00a0mg\/dL, respectively;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.009). In the phase III portion, 3-year RFS rates in the CS (n\u2009=\u2009202) and control (n\u2009=\u2009204) groups were 67.2% and 63.0%, respectively, indicating no significant difference (hazard ratio, 0.807 [95% confidence interval, 0.590\u20131.105]; log-rank\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.182). Subgroup analysis showed that both histological type and clinical stage had significant interactions with RFS, suggesting a potential survival benefit of CS administration in patients with differentiated histological-type or cStage III gastric cancer.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Intraoperative CS administration mitigated postoperative CRP elevation but did not result in significantly improved survival in patients with cStage II\u2013III gastric cancer. The study is registered with UMIN-CTR, number UMIN000024465.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10120-025-01635-5","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T09:59:13Z","timestamp":1752141553000},"page":"993-1003","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Intraoperative corticosteroid administration for resectable gastric cancer: a multicenter, randomized, open-label, phase II\/III study"],"prefix":"10.1007","volume":"28","author":[{"given":"Takaomi","family":"Hagi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukinori","family":"Kurokawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Omori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Akamaru","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keijiro","family":"Sugimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaaki","family":"Motoori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Matsuyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuro","family":"Saito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyoshi","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuyoshi","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshio","family":"Shimokawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidetoshi","family":"Eguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichiro","family":"Doki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,10]]},"reference":[{"key":"1635_CR1","doi-asserted-by":"publisher","DOI":"10.1002\/ags3.12835","author":"T Higashi","year":"2024","unstructured":"Higashi T, Kurokawa Y. Incidence, mortality, survival, and treatment statistics of cancers in digestive organs\u2014Japanese cancer statistics. Ann Gastroenterol Surg. 2024. https:\/\/doi.org\/10.1002\/ags3.12835.","journal-title":"Ann Gastroenterol Surg"},{"issue":"5","key":"1635_CR2","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1002\/ags3.12711","volume":"7","author":"Y Yanagimoto","year":"2023","unstructured":"Yanagimoto Y, Kurokawa Y, Doki Y. Essential updates 2021\/2022: Perioperative and surgical treatments for gastric and esophagogastric junction cancer. Ann Gastroenterol Surg. 2023;7(5):698\u2013708.","journal-title":"Ann Gastroenterol Surg"},{"issue":"7","key":"1635_CR3","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1016\/S2468-1253(18)30090-6","volume":"3","author":"Y Kurokawa","year":"2018","unstructured":"Kurokawa Y, Doki Y, Mizusawa J, Terashima M, Katai H, Yoshikawa T, et al. Bursectomy versus omentectomy alone for resectable gastric cancer (JCOG1001): a phase 3, open-label, randomised controlled trial. Lancet Gastroenterol Hepatol. 2018;3(7):460\u20138.","journal-title":"Lancet Gastroenterol Hepatol"},{"issue":"5","key":"1635_CR4","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1001\/jamasurg.2023.0096","volume":"158","author":"T Etoh","year":"2023","unstructured":"Etoh T, Ohyama T, Sakuramoto S, Tsuji T, Lee SW, Yoshida K, Japanese Laparoscopic Surgery Study Group (JLSSG), et al. Five-year survival outcomes of laparoscopy-assisted vs open distal gastrectomy for advanced gastric cancer: the JLSSG0901 randomized clinical trial. JAMA Surg. 2023;158(5):445\u201354.","journal-title":"JAMA Surg"},{"issue":"2","key":"1635_CR5","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1007\/s10120-021-01257-7","volume":"25","author":"K Suda","year":"2022","unstructured":"Suda K, Yamamoto H, Nishigori T, Obama K, Yoda Y, Hikage M, et al. Safe implementation of robotic gastrectomy for gastric cancer under the requirements for universal health insurance coverage: a retrospective cohort study using a nationwide registry database in Japan. Gastric Cancer. 2022;25(2):438\u201349.","journal-title":"Gastric Cancer"},{"issue":"9","key":"1635_CR6","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1200\/JCO.20.01540","volume":"39","author":"A van der Veen","year":"2021","unstructured":"van der Veen A, Brenkman HJF, Seesing MFJ, Haverkamp L, Luyer MDP, Nieuwenhuijzen GAP, et al. Laparoscopic versus open gastrectomy for gastric cancer (LOGICA): a multicenter randomized clinical trial. J Clin Oncol. 2021;39(9):978\u201389.","journal-title":"J Clin Oncol"},{"issue":"20","key":"1635_CR7","doi-asserted-by":"publisher","first-page":"1983","DOI":"10.1001\/jama.2019.5359","volume":"321","author":"J Yu","year":"2019","unstructured":"Yu J, Huang C, Sun Y, Su X, Cao H, Hu J, et al. Effect of laparoscopic vs open distal gastrectomy on 3-year disease-free survival in patients with locally advanced gastric cancer: the CLASS-01 randomized clinical trial. JAMA. 2019;321(20):1983\u201392.","journal-title":"JAMA"},{"issue":"3","key":"1635_CR8","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1245\/s10434-013-3384-9","volume":"21","author":"T Kubota","year":"2014","unstructured":"Kubota T, Hiki N, Sano T, Nomura S, Nunobe S, Kumagai K, et al. Prognostic significance of complications after curative surgery for gastric cancer. Ann Surg Oncol. 2014;21(3):891\u20138.","journal-title":"Ann Surg Oncol"},{"issue":"5","key":"1635_CR9","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1007\/s10120-020-01073-5","volume":"23","author":"Y Kurokawa","year":"2020","unstructured":"Kurokawa Y, Yamashita K, Kawabata R, Fujita J, Imamura H, Takeno A, et al. Prognostic value of postoperative C-reactive protein elevation versus complication occurrence: a multicenter validation study. Gastric Cancer. 2020;23(5):937\u201343.","journal-title":"Gastric Cancer"},{"issue":"6","key":"1635_CR10","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1016\/0022-2828(92)91042-4","volume":"24","author":"U Ikeda","year":"1992","unstructured":"Ikeda U, Ohkawa F, Seino Y, Yamamoto K, Hidaka Y, Kasahara T, et al. Serum interleukin 6 levels become elevated in acute myocardial infarction. J Mol Cell Cardiol. 1992;24(6):579\u201384.","journal-title":"J Mol Cell Cardiol"},{"issue":"4","key":"1635_CR11","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1038\/nrclinonc.2018.8","volume":"15","author":"DE Johnson","year":"2018","unstructured":"Johnson DE, O\u2019Keefe RA, Grandis JR. Targeting the IL-6\/JAK\/STAT3 signalling axis in cancer. Nat Rev Clin Oncol. 2018;15(4):234\u201348.","journal-title":"Nat Rev Clin Oncol"},{"issue":"4","key":"1635_CR12","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1038\/nri.2017.1","volume":"17","author":"DW Cain","year":"2017","unstructured":"Cain DW, Cidlowski JA. Immune regulation by glucocorticoids. Nat Rev Immunol. 2017;17(4):233\u201347.","journal-title":"Nat Rev Immunol"},{"issue":"1","key":"1635_CR13","doi-asserted-by":"publisher","first-page":"6268","DOI":"10.1038\/s41598-021-85241-2","volume":"11","author":"T Hagi","year":"2021","unstructured":"Hagi T, Kurokawa Y, Kobayashi N, Takahashi T, Saito T, Yamashita K, et al. Anti-metastatic effect of methylprednisolone targeting vascular endothelial cells under surgical stress. Sci Rep. 2021;11(1):6268.","journal-title":"Sci Rep"},{"issue":"9","key":"1635_CR14","doi-asserted-by":"publisher","first-page":"2831","DOI":"10.1245\/s10434-019-07585-4","volume":"26","author":"Y Taniguchi","year":"2019","unstructured":"Taniguchi Y, Kurokawa Y, Hagi T, Takahashi T, Miyazaki Y, Tanaka K, et al. methylprednisolone inhibits tumor growth and peritoneal seeding induced by surgical stress and postoperative complications. Ann Surg Oncol. 2019;26(9):2831\u20138.","journal-title":"Ann Surg Oncol"},{"issue":"2","key":"1635_CR15","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1007\/s10120-011-0041-5","volume":"14","author":"Japanese Gastric Cancer Association","year":"2011","unstructured":"Japanese Gastric Cancer Association. Japanese classification of gastric carcinoma: 3rd English edition. Gastric Cancer. 2011;14(2):101\u201312.","journal-title":"Gastric Cancer"},{"issue":"1","key":"1635_CR16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s10120-016-0622-4","volume":"20","author":"Japanese Gastric Cancer Association","year":"2017","unstructured":"Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2014 (ver 4.). Gastric Cancer. 2017;20(1):1\u201319.","journal-title":"Gastric Cancer"},{"issue":"2","key":"1635_CR17","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1097\/01.sla.0000133083.54934.ae","volume":"240","author":"D Dindo","year":"2004","unstructured":"Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205\u201313.","journal-title":"Ann Surg"},{"issue":"6","key":"1635_CR18","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1007\/s00595-015-1236-x","volume":"46","author":"H Katayama","year":"2016","unstructured":"Katayama H, Kurokawa Y, Nakamura K, Ito H, Kanemitsu Y, Masuda N, et al. Extended Clavien-Dindo classification of surgical complications: Japan clinical oncology group postoperative complications criteria. Surg Today. 2016;46(6):668\u201385.","journal-title":"Surg Today"},{"issue":"8","key":"1635_CR19","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1002\/jso.24067","volume":"112","author":"T Saito","year":"2015","unstructured":"Saito T, Kurokawa Y, Miyazaki Y, Makino T, Takahashi T, Yamasaki M, et al. Which is a more reliable indicator of survival after gastric cancer surgery: Postoperative complication occurrence or C-reactive protein elevation? J Surg Oncol. 2015;112(8):894\u20139.","journal-title":"J Surg Oncol"},{"issue":"1","key":"1635_CR20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s10388-014-0465-1","volume":"12","author":"H Kuwano","year":"2015","unstructured":"Kuwano H, Nishimura Y, Oyama T, Kato H, Kitagawa Y, Kusano M, et al. Guidelines for diagnosis and treatment of carcinoma of the esophagus April 2012 edited by the Japan esophageal society. Esophagus. 2015;12(1):1\u201330.","journal-title":"Esophagus"},{"issue":"1","key":"1635_CR21","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1007\/s10388-018-0642-8","volume":"16","author":"Y Kitagawa","year":"2019","unstructured":"Kitagawa Y, Uno T, Oyama T, Kato K, Kato H, Kawakubo H, et al. Esophageal cancer practice guidelines 2017 edited by the Japan esophageal society: part 2. Esophagus. 2019;16(1):25\u201343.","journal-title":"Esophagus"},{"issue":"6","key":"1635_CR22","doi-asserted-by":"publisher","first-page":"e1247","DOI":"10.1097\/SLA.0000000000005502","volume":"277","author":"Y Hirano","year":"2023","unstructured":"Hirano Y, Konishi T, Kaneko H, Itoh H, Matsuda S, Kawakubo H, et al. Impact of prophylactic corticosteroid use on in-hospital mortality and respiratory failure after esophagectomy for esophageal cancer: nationwide inpatient data study in Japan. Ann Surg. 2023;277(6):e1247\u201353.","journal-title":"Ann Surg"},{"issue":"4","key":"1635_CR23","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1093\/icvts\/ivs167","volume":"15","author":"SY Park","year":"2012","unstructured":"Park SY, Lee HS, Jang HJ, Joo J, Zo JI. Efficacy of intraoperative, single-bolus corticosteroid administration to prevent postoperative acute respiratory failure after oesophageal cancer surgery. Interact Cardiovasc Thorac Surg. 2012;15(4):639\u201343.","journal-title":"Interact Cardiovasc Thorac Surg"},{"issue":"1","key":"1635_CR24","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1186\/s12885-022-09998-z","volume":"22","author":"J Magnin","year":"2022","unstructured":"Magnin J, Fournel I, Doussot A, R\u00e9gimbeau JM, Zerbib P, Piessen G, et al. Benefit of a flash dose of corticosteroids in digestive surgical oncology: a multicenter, randomized, double blind, placebo-controlled trial (CORTIFRENCH). BMC Cancer. 2022;22(1):913.","journal-title":"BMC Cancer"},{"issue":"2","key":"1635_CR25","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1097\/SLA.0b013e3182261118","volume":"254","author":"S Srinivasa","year":"2011","unstructured":"Srinivasa S, Kahokehr AA, Yu TC, Hill AG. Preoperative glucocorticoid use in major abdominal surgery: systematic review and meta-analysis of randomized trials. Ann Surg. 2011;254(2):183\u201391.","journal-title":"Ann Surg"},{"issue":"5","key":"1635_CR26","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1007\/s11605-010-1168-0","volume":"14","author":"E Engelman","year":"2010","unstructured":"Engelman E, Maeyens C. Effect of preoperative single-dose corticosteroid administration on postoperative morbidity following esophagectomy. J Gastrointest Surg. 2010;14(5):788\u2013804.","journal-title":"J Gastrointest Surg"},{"issue":"4","key":"1635_CR27","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1016\/j.ejso.2022.11.093","volume":"49","author":"T Toriumi","year":"2023","unstructured":"Toriumi T, Terashima M, Mizusawa J, Sato Y, Kurokawa Y, Takiguchi S, et al. Recurrence patterns after curative gastrectomy for pStage II\/III gastric cancer: Exploratory analysis of the randomized controlled JCOG1001 trial. Eur J Surg Oncol. 2023;49(4):838\u201344.","journal-title":"Eur J Surg Oncol"},{"issue":"1","key":"1635_CR28","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1038\/s41572-021-00326-6","volume":"7","author":"D Cort\u00e9s-Guiral","year":"2021","unstructured":"Cort\u00e9s-Guiral D, H\u00fcbner M, Alyami M, Bhatt A, Ceelen W, Glehen O, et al. Primary and metastatic peritoneal surface malignancies. Nat Rev Dis Primers. 2021;7(1):91.","journal-title":"Nat Rev Dis Primers"},{"issue":"4","key":"1635_CR29","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1172\/JCI200418975","volume":"113","author":"DC Tsitoura","year":"2004","unstructured":"Tsitoura DC, Rothman PB. Enhancement of MEK\/ERK signaling promotes glucocorticoid resistance in CD4+ T cells. J Clin Invest. 2004;113(4):619\u201327.","journal-title":"J Clin Invest"},{"issue":"2","key":"1635_CR30","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1016\/j.celrep.2014.03.004","volume":"7","author":"O Bereshchenko","year":"2014","unstructured":"Bereshchenko O, Coppo M, Bruscoli S, Biagioli M, Cimino M, Frammartino T, et al. GILZ promotes production of peripherally induced Treg cells and mediates the crosstalk between glucocorticoids and TGF-\u03b2 signaling. Cell Rep. 2014;7(2):464\u201375.","journal-title":"Cell Rep"},{"issue":"6","key":"1635_CR31","doi-asserted-by":"publisher","first-page":"1425","DOI":"10.1016\/j.jaci.2004.07.014","volume":"114","author":"C Karagiannidis","year":"2004","unstructured":"Karagiannidis C, Akdis M, Holopainen P, Woolley NJ, Hense G, R\u00fcckert B, et al. Glucocorticoids upregulate FOXP3 expression and regulatory T cells in asthma. J Allergy Clin Immunol. 2004;114(6):1425\u201333.","journal-title":"J Allergy Clin Immunol"},{"key":"1635_CR32","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.critrevonc.2016.03.011","volume":"101","author":"ST McSorley","year":"2016","unstructured":"McSorley ST, Horgan PG, McMillan DC. The impact of preoperative corticosteroids on the systemic inflammatory response and postoperative complications following surgery for gastrointestinal cancer: A systematic review and meta-analysis. Crit Rev Oncol Hematol. 2016;101:139\u201350.","journal-title":"Crit Rev Oncol Hematol"},{"issue":"5","key":"1635_CR33","doi-asserted-by":"publisher","first-page":"e393","DOI":"10.1097\/SLA.0000000000004547","volume":"276","author":"A Okamura","year":"2022","unstructured":"Okamura A, Yamamoto H, Watanabe M, Miyata H, Kanaji S, Kamiya K, et al. Association between preoperative HbA1c levels and complications after esophagectomy: analysis of 15,801 esophagectomies from the national clinical database in Japan. Ann Surg. 2022;276(5):e393\u20139.","journal-title":"Ann Surg"}],"container-title":["Gastric Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10120-025-01635-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10120-025-01635-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10120-025-01635-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T17:04:10Z","timestamp":1758819850000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10120-025-01635-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,10]]},"references-count":33,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["1635"],"URL":"https:\/\/doi.org\/10.1007\/s10120-025-01635-5","relation":{},"ISSN":["1436-3291","1436-3305"],"issn-type":[{"value":"1436-3291","type":"print"},{"value":"1436-3305","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,10]]},"assertion":[{"value":"7 March 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 June 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 July 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}