{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T14:06:07Z","timestamp":1789740367287,"version":"4.0.1"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Gastroenterol"],"DOI":"10.1186\/s12876-026-05180-y","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T13:14:15Z","timestamp":1789737255000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Leucine-rich alpha-2 glycoprotein as a predictor of primary non-response to anti-TNF-\u03b1 therapy in biologic-na\u00efve Egyptian IBD patients"],"prefix":"10.1186","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3778-8826","authenticated-orcid":false,"given":"Ibrahiem","family":"Amer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7929-3333","authenticated-orcid":false,"given":"Hassan","family":"El Batae","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5310-7635","authenticated-orcid":false,"given":"Yasmine A.","family":"Elshaer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1046-643X","authenticated-orcid":false,"given":"Dalia Elsayed","family":"Sherief","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2259-3209","authenticated-orcid":false,"given":"Mahmoud A.","family":"Elkerdawy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1504-7851","authenticated-orcid":false,"given":"Mohamed H.","family":"Emara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shimaa","family":"El Sharawy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"issue":"3","key":"5180_CR1","doi-asserted-by":"publisher","first-page":"e065186","DOI":"10.1136\/bmjopen-2022-065186","volume":"13","author":"R Wang","year":"2023","unstructured":"Wang R, Li Z, Liu S, Zhang D. Global, regional and national burden of inflammatory bowel disease in 204 countries and territories from 1990 to 2019: a systematic analysis based on the Global Burden of Disease Study 2019. BMJ Open. 2023;13(3):e065186.","journal-title":"BMJ Open"},{"key":"5180_CR2","doi-asserted-by":"publisher","unstructured":"Elbadry M, Nour MO, Hussien M, Ghoneem EA, Medhat MA, Shehab H et al. Clinico-Epidemiological Characteristics of Patients With Inflammatory Bowel Disease in Egypt: A Nationwide Multicenter Study. Front Med. 2022;9867293. https:\/\/doi.org\/10.3389\/fmed.2022.867293.","DOI":"10.3389\/fmed.2022.867293"},{"key":"5180_CR3","doi-asserted-by":"publisher","first-page":"209","DOI":"10.21608\/asmj.2025.348359.1356","volume":"76","author":"M Hamad","year":"2025","unstructured":"Hamad M, Hussein B, Aboali L, Elfert A, Abousaif S. Epidemiological and Clinical Characteristics of Inflammatory Bowel Disease in Egyptian Patients at the Nile Delta: A Single-Center Study. Ain Shams Med J. 2025;76:209\u201319.","journal-title":"Ain Shams Med J"},{"issue":"2","key":"5180_CR4","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1053\/j.gastro.2016.12.004","volume":"152","author":"JF Colombel","year":"2017","unstructured":"Colombel JF, Mahadevan U. Inflammatory Bowel Disease 2017: Innovations and Changing Paradigms. Gastroenterology. 2017;152(2):309\u201312.","journal-title":"Gastroenterology"},{"issue":"5","key":"5180_CR5","doi-asserted-by":"publisher","first-page":"1570","DOI":"10.1053\/j.gastro.2020.12.031","volume":"160","author":"D Turner","year":"2021","unstructured":"Turner D, Ricciuto A, Lewis A, D\u2019Amico F, Dhaliwal J, Griffiths AM, et al. 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. 2021;160(5):1570\u201383.","journal-title":"Gastroenterology"},{"key":"5180_CR6","doi-asserted-by":"publisher","first-page":"204062231983844","DOI":"10.1177\/2040622319838443","volume":"10","author":"K Papamichael","year":"2019","unstructured":"Papamichael K, Lin S, Moore M, Papaioannou G, Sattler L, Cheifetz AS. Infliximab in inflammatory bowel disease. Ther Adv Chronic Dis. 2019;10:2040622319838443.","journal-title":"Ther Adv Chronic Dis"},{"issue":"1","key":"5180_CR7","doi-asserted-by":"publisher","first-page":"e135","DOI":"10.1038\/ctg.2015.63","volume":"7","author":"G Roda","year":"2016","unstructured":"Roda G, Jharap B, Neeraj N, Colombel JF. Loss of Response to Anti-TNFs: Definition, Epidemiology, and Management. Clin Transl Gastroenterol. 2016;7(1):e135.","journal-title":"Clin Transl Gastroenterol"},{"issue":"Suppl 1","key":"5180_CR8","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1159\/000506898","volume":"101","author":"M Vulliemoz","year":"2020","unstructured":"Vulliemoz M, Brand S, Juillerat P, Mottet C, Ben-Horin S, Michetti P. TNF-Alpha Blockers in Inflammatory Bowel Diseases: Practical Recommendations and a User\u2019s Guide: An Update. Digestion. 2020;101(Suppl 1):16\u201326.","journal-title":"Digestion"},{"issue":"6","key":"5180_CR9","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1093\/ecco-jcc\/jjx008","volume":"11","author":"F Magro","year":"2017","unstructured":"Magro F, Gionchetti P, Eliakim R, Ardizzone S, Armuzzi A, Barreiro-de Acosta M, et al. Third European Evidence-based Consensus on Diagnosis and Management of Ulcerative Colitis. Part 1: Definitions, Diagnosis, Extra-intestinal Manifestations, Pregnancy, Cancer Surveillance, Surgery, and Ileo-anal Pouch Disorders. J Crohns Colitis. 2017;11(6):649\u201370.","journal-title":"J Crohns Colitis"},{"issue":"8","key":"5180_CR10","doi-asserted-by":"publisher","first-page":"1425","DOI":"10.1097\/MIB.0000000000001140","volume":"23","author":"A Buisson","year":"2017","unstructured":"Buisson A, Gonzalez F, Poullenot F, Nancey S, Sollellis E, Fumery M, et al. Comparative Acceptability and Perceived Clinical Utility of Monitoring Tools: A Nationwide Survey of Patients with Inflammatory Bowel Disease. Inflamm Bowel Dis. 2017;23(8):1425\u201333.","journal-title":"Inflamm Bowel Dis"},{"key":"5180_CR11","doi-asserted-by":"publisher","first-page":"15","DOI":"10.31689\/rmm.2021.29.1.15","volume":"29","author":"R Sadagurschi","year":"2022","unstructured":"Sadagurschi R, Dobromirescu A, Babiuc R, Negreanu L. Clinical Predictive Factors of Response to Biologics in IBD. Med Moderna - Mod Med. 2022;29:15\u201323.","journal-title":"Med Moderna - Mod Med"},{"issue":"8","key":"5180_CR12","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1002\/jgh3.12953","volume":"7","author":"M Kono","year":"2023","unstructured":"Kono M, Komeda Y, Tribonias G, Yoshida S, Nomura K, Handa K, et al. Serum leucine-rich alpha-2 glycoprotein in monitoring disease activity and intestinal mucosal healing for biotherapy-na\u00efve cases with ulcerative colitis. JGH Open. 2023;7(8):579\u201383.","journal-title":"JGH Open"},{"issue":"6","key":"5180_CR13","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1007\/s00535-021-01793-0","volume":"56","author":"S Shinzaki","year":"2021","unstructured":"Shinzaki S, Matsuoka K, Tanaka H, Takeshima F, Kato S, Torisu T, et al. Leucine-rich alpha-2 glycoprotein is a potential biomarker to monitor disease activity in inflammatory bowel disease receiving adalimumab: PLANET study. J Gastroenterol. 2021;56(6):560\u20139.","journal-title":"J Gastroenterol"},{"issue":"1","key":"5180_CR14","doi-asserted-by":"publisher","first-page":"29755","DOI":"10.1038\/s41598-024-80285-6","volume":"14","author":"T Amano","year":"2024","unstructured":"Amano T, Yoshihara T, Shinzaki S, Sakakibara Y, Yamada T, Osugi N, et al. Selection of anti-cytokine biologics by pretreatment levels of serum leucine-rich alpha-2 glycoprotein in patients with inflammatory bowel disease. Sci Rep. 2024;14(1):29755.","journal-title":"Sci Rep"},{"issue":"8","key":"5180_CR15","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1097\/MEG.0000000000002952","volume":"37","author":"F Ojaghi Shirmard","year":"2025","unstructured":"Ojaghi Shirmard F, Pourfaraji SM, Saeedian B, Bagheri T, Ismaiel A, Matsumoto S, Babajani N. The usefulness of serum leucine-rich alpha-2 glycoprotein as a novel biomarker in monitoring inflammatory bowel disease: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol. 2025;37(8):891\u2013904.","journal-title":"Eur J Gastroenterol Hepatol"},{"issue":"2","key":"5180_CR16","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1093\/ecco-jcc\/jjy113","volume":"13","author":"C Maaser","year":"2019","unstructured":"Maaser C, Sturm A, Vavricka SR, Kucharzik T, Fiorino G, Annese V, et al. ECCO-ESGAR Guideline for Diagnostic Assessment in IBD Part 1: Initial diagnosis, monitoring of known IBD, detection of complications. J Crohns Colitis. 2019;13(2):144\u201364.","journal-title":"J Crohns Colitis"},{"issue":"2","key":"5180_CR17","doi-asserted-by":"publisher","first-page":"175","DOI":"10.3758\/BF03193146","volume":"39","author":"F Faul","year":"2007","unstructured":"Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007;39(2):175\u201391.","journal-title":"Behav Res Methods"},{"issue":"8167","key":"5180_CR18","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1016\/S0140-6736(80)92767-1","volume":"1","author":"RF Harvey","year":"1980","unstructured":"Harvey RF, Bradshaw JM. A simple index of Crohn\u2019s-disease activity. Lancet. 1980;1(8167):514.","journal-title":"Lancet"},{"issue":"12","key":"5180_CR19","doi-asserted-by":"publisher","first-page":"1660","DOI":"10.1002\/ibd.20520","volume":"14","author":"JD Lewis","year":"2008","unstructured":"Lewis JD, Chuai S, Nessel L, Lichtenstein GR, Aberra FN, Ellenberg JH. Use of the noninvasive components of the Mayo score to assess clinical response in ulcerative colitis. Inflamm Bowel Dis. 2008;14(12):1660\u20136.","journal-title":"Inflamm Bowel Dis"},{"issue":"4","key":"5180_CR20","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/S0016-5107(04)01878-4","volume":"60","author":"M Daperno","year":"2004","unstructured":"Daperno M, D\u2019Haens G, Van Assche G, Baert F, Bulois P, Maunoury V, et al. Development and validation of a new, simplified endoscopic activity score for Crohn\u2019s disease: the SES-CD. Gastrointest Endosc. 2004;60(4):505\u201312.","journal-title":"Gastrointest Endosc"},{"issue":"26","key":"5180_CR21","doi-asserted-by":"publisher","first-page":"1625","DOI":"10.1056\/NEJM198712243172603","volume":"317","author":"KW Schroeder","year":"1987","unstructured":"Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N Engl J Med. 1987;317(26):1625\u20139.","journal-title":"N Engl J Med"},{"issue":"4","key":"5180_CR22","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1136\/gutjnl-2011-300486","volume":"61","author":"SP Travis","year":"2012","unstructured":"Travis SP, Schnell D, Krzeski P, Abreu MT, Altman DG, Colombel JF, et al. Developing an instrument to assess the endoscopic severity of ulcerative colitis: the Ulcerative Colitis Endoscopic Index of Severity (UCEIS). Gut. 2012;61(4):535\u201342.","journal-title":"Gut"},{"issue":"6","key":"5180_CR23","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1136\/gut.2005.082909","volume":"55","author":"J Satsangi","year":"2006","unstructured":"Satsangi J, Silverberg MS, Vermeire S, Colombel JF. The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications. Gut. 2006;55(6):749\u201353.","journal-title":"Gut"},{"issue":"3","key":"5180_CR24","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1136\/gut.47.3.404","volume":"47","author":"K Geboes","year":"2000","unstructured":"Geboes K, Riddell R, Ost A, Jensfelt B, Persson T, L\u00f6fberg R. A reproducible grading scale for histological assessment of inflammation in ulcerative colitis. Gut. 2000;47(3):404\u20139.","journal-title":"Gut"},{"issue":"18","key":"5180_CR25","doi-asserted-by":"publisher","first-page":"6091","DOI":"10.12998\/wjcc.v10.i18.6091","volume":"10","author":"HH Yang","year":"2022","unstructured":"Yang HH, Huang Y, Zhou XC, Wang RN. Efficacy and safety of adalimumab in comparison to infliximab for Crohn\u2019s disease: A systematic review and meta-analysis. World J Clin Cases. 2022;10(18):6091\u2013104.","journal-title":"World J Clin Cases"},{"issue":"9","key":"5180_CR26","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.1093\/ibd\/izac230","volume":"29","author":"T Shimoyama","year":"2023","unstructured":"Shimoyama T, Yamamoto T, Yoshiyama S, Nishikawa R, Umegae S. Leucine-Rich Alpha-2 Glycoprotein Is a Reliable Serum Biomarker for Evaluating Clinical and Endoscopic Disease Activity in Inflammatory Bowel Disease. Inflamm Bowel Dis. 2023;29(9):1399\u2013408.","journal-title":"Inflamm Bowel Dis"},{"issue":"3","key":"5180_CR27","doi-asserted-by":"publisher","first-page":"114677","DOI":"10.3748\/wjg.v32.i3.114677","volume":"32","author":"Y-C Chen","year":"2026","unstructured":"Chen Y-C, Weng M-T, Tsai F-P, Chen Z-C, Wu H-Y, Tung C-C, et al. Role of leucine-rich \u03b1-2-glycoprotein in Taiwanese patients with inflammatory bowel disease as a predictive biomarker for endoscopic activity. World J Gastroenterol. 2026;32(3):114677.","journal-title":"World J Gastroenterol"},{"issue":"5","key":"5180_CR28","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1016\/S2468-1253(19)30012-3","volume":"4","author":"NA Kennedy","year":"2019","unstructured":"Kennedy NA, Heap GA, Green HD, Hamilton B, Bewshea C, Walker GJ, et al. Predictors of anti-TNF treatment failure in anti-TNF-naive patients with active luminal Crohn\u2019s disease: a prospective, multicentre, cohort study. Lancet Gastroenterol Hepatol. 2019;4(5):341\u201353.","journal-title":"Lancet Gastroenterol Hepatol"},{"issue":"11","key":"5180_CR29","doi-asserted-by":"publisher","first-page":"1472","DOI":"10.1111\/apt.14665","volume":"47","author":"S Kurnool","year":"2018","unstructured":"Kurnool S, Nguyen NH, Proudfoot J, Dulai PS, Boland BS, Vande Casteele N, et al. High body mass index is associated with increased risk of treatment failure and surgery in biologic-treated patients with ulcerative colitis. Aliment Pharmacol Ther. 2018;47(11):1472\u20139.","journal-title":"Aliment Pharmacol Ther"},{"issue":"29","key":"5180_CR30","doi-asserted-by":"publisher","first-page":"4481","DOI":"10.3748\/wjg.v29.i29.4481","volume":"29","author":"LF Wang","year":"2023","unstructured":"Wang LF, Chen PR, He SK, Duan SH, Zhang Y. Predictors and optimal management of tumor necrosis factor antagonist nonresponse in inflammatory bowel disease: A literature review. World J Gastroenterol. 2023;29(29):4481\u201398.","journal-title":"World J Gastroenterol"},{"issue":"12","key":"5180_CR31","doi-asserted-by":"publisher","first-page":"1808","DOI":"10.1093\/ibd\/izaa031","volume":"26","author":"S Hamdeh","year":"2020","unstructured":"Hamdeh S, Aziz M, Altayar O, Olyaee M, Murad MH, Hanauer SB. Early vs Late Use of Anti-TNFa Therapy in Adult Patients With Crohn Disease: A Systematic Review and Meta-Analysis. Inflamm Bowel Dis. 2020;26(12):1808\u201318.","journal-title":"Inflamm Bowel Dis"},{"issue":"5","key":"5180_CR32","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1093\/ecco-jcc\/jjz195","volume":"14","author":"JP Gisbert","year":"2020","unstructured":"Gisbert JP, Chaparro M. Predictors of Primary Response to Biologic Treatment [Anti-TNF, Vedolizumab, and Ustekinumab] in Patients With Inflammatory Bowel Disease: From Basic Science to Clinical Practice. J Crohns Colitis. 2020;14(5):694\u2013709.","journal-title":"J Crohns Colitis"},{"issue":"7","key":"5180_CR33","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1007\/s00535-016-1274-1","volume":"52","author":"M Iborra","year":"2017","unstructured":"Iborra M, P\u00e9rez-Gisbert J, Bosca-Watts MM, L\u00f3pez-Garc\u00eda A, Garc\u00eda-S\u00e1nchez V, L\u00f3pez-Sanrom\u00e1n A, et al. Effectiveness of adalimumab for the treatment of ulcerative colitis in clinical practice: comparison between anti-tumour necrosis factor-na\u00efve and non-na\u00efve patients. J Gastroenterol. 2017;52(7):788\u201399.","journal-title":"J Gastroenterol"},{"issue":"3","key":"5180_CR34","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1093\/ecco-jcc\/jjx146","volume":"12","author":"L Beswick","year":"2018","unstructured":"Beswick L, Rosella O, Rosella G, Headon B, Sparrow MP, Gibson PR, van Langenberg DR. Exploration of Predictive Biomarkers of Early Infliximab Response in Acute Severe Colitis: A Prospective Pilot Study. J Crohns Colitis. 2018;12(3):289\u201397.","journal-title":"J Crohns Colitis"},{"issue":"1","key":"5180_CR35","doi-asserted-by":"publisher","first-page":"182","DOI":"10.3390\/life16010182","volume":"16","author":"I Faggiani","year":"2026","unstructured":"Faggiani I, Villaseca IL, D\u2019Amico F, Furfaro F, Zilli A, Massironi S, et al. Perianal Crohn\u2019s Disease in Inflammatory Bowel Disease: Diagnosis, Assessment and Treatment. Life. 2026;16(1):182.","journal-title":"Life"},{"issue":"4","key":"5180_CR36","doi-asserted-by":"publisher","first-page":"473","DOI":"10.5217\/ir.2023.00135","volume":"22","author":"R Karashima","year":"2024","unstructured":"Karashima R, Sagami S, Yamana Y, Maeda M, Hojo A, Miyatani Y, et al. Early change in serum leucine-rich \u03b1-2-glycoprotein predicts clinical and endoscopic response in ulcerative colitis. Intest Res. 2024;22(4):473\u201383.","journal-title":"Intest Res"}],"container-title":["BMC Gastroenterology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12876-026-05180-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12876-026-05180-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12876-026-05180-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T13:26:11Z","timestamp":1789737971000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12876-026-05180-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,18]]},"references-count":36,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["5180"],"URL":"https:\/\/doi.org\/10.1186\/s12876-026-05180-y","relation":{},"ISSN":["1471-230X"],"issn-type":[{"value":"1471-230X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,18]]},"assertion":[{"value":"26 April 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 September 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The study protocol was approved by the Kafrelsheikh University, Faculty of Medicine Institutional Review Board (IRB NO: KFSIRB200-169) and conformed to the 2013 revision of the Declaration of Helsinki. Written informed consent was obtained from all enrolled subjects.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not Applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"580"}}