{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T16:51:44Z","timestamp":1790095904029,"version":"4.0.1"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T00:00:00Z","timestamp":1739923200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T00:00:00Z","timestamp":1739923200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Spinoza 2008 Award of the Netherlands Organization for Scientific Research"},{"DOI":"10.13039\/501100005744","name":"Lastentautien Tutkimuss\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005744","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008376","name":"Helsingin ja Uudenmaan Sairaanhoitopiiri","doi-asserted-by":"publisher","award":["TYH2016224"],"award-info":[{"award-number":["TYH2016224"]}],"id":[{"id":"10.13039\/100008376","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Orofacial granulomatosis (OFG) is a rare chronic inflammatory condition. It is under debate, whether it is a condition of its own or merely a subtype of Crohn\u2019s disease (CD). We aimed to search for markers characteristic of patients with pediatric-onset OFG compared to patients with pediatric-onset CD. We recruited young patients with OFG (with or without CD, <jats:italic>n<\/jats:italic>\u2009=\u200929), CD (<jats:italic>n<\/jats:italic>\u2009=\u200924), and healthy controls (<jats:italic>n<\/jats:italic>\u2009=\u200920). All participants provided a fecal sample for microbiota and calprotectin analyses and saliva for DNA analysis of genes associated with OFG and kept a 3-day food diary. Oral disease activity was evaluated using The Oral Disease Activity Score by an otorhinolaryngologist and a dentist. We observed decreased relative abundance in class Clostridia and increased relative abundances of classes Actinobacteria and Bacilli in the feces of patients with OFG when compared to patients with CD and healthy controls. The relative abundances of <jats:italic>Bifidobacterium adolescentis<\/jats:italic> increased and <jats:italic>Faecalibacterium prausnitzii<\/jats:italic> decreased along with the increase in the Oral Disease Activity Score. We found the NOD2 gene rs8057341 allele A to be enriched in patients with OFG compared to patients with CD. These findings support the theory that OFG is a distinct disease phenotype.<\/jats:p>","DOI":"10.1038\/s41598-025-90243-5","type":"journal-article","created":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T08:16:43Z","timestamp":1739953003000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Fecal microbiota and genetics in pediatric-onset orofacial granulomatosis and Crohn\u00b4s disease"],"prefix":"10.1038","volume":"15","author":[{"given":"Miikka","family":"H\u00f6yhty\u00e4","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anu","family":"Haaramo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Nikkonen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecka","family":"Ventin-Holmberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nitin","family":"Agrawal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jarmo","family":"Ritari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon","family":"Hickman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jukka","family":"Partanen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heikki","family":"Alapulli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jetta","family":"Tuokkola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Salonen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willem M","family":"de Vos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaija-Leena","family":"Kolho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,19]]},"reference":[{"key":"90243_CR1","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1159\/000369810","volume":"24","author":"G Troiano","year":"2015","unstructured":"Troiano, G. et al. Orofacial granulomatosis: clinical signs of different pathologies. Med. Principles Pract. 24, 117\u2013122 (2015).","journal-title":"Med. Principles Pract."},{"key":"90243_CR2","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/j.jdin.2020.07.003","volume":"1","author":"M Wei","year":"2020","unstructured":"Wei, M. et al. Characterizing disease manifestations and treatment outcomes among patients with orofacial granulomatosis in China. JAAD Int. 1, 126\u2013134 (2020).","journal-title":"JAAD Int."},{"key":"90243_CR3","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1111\/j.1601-0825.2008.01500.x","volume":"15","author":"B Grave","year":"2009","unstructured":"Grave, B., McCullough, M. & Wiesenfeld, D. Orofacial granulomatosis - A 20-year review. Oral Dis. 15, 46\u201351 (2009).","journal-title":"Oral Dis."},{"key":"90243_CR4","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1159\/000513446","volume":"237","author":"CFB Gavioli","year":"2021","unstructured":"Gavioli, C. F. B. et al. Orofacial granulomatosis and Crohn Disease: coincidence or pattern? A systematic review. Dermatology 237, 635\u2013640 (2021).","journal-title":"Dermatology"},{"key":"90243_CR5","unstructured":"Haaramo, A. Oral Manifestations in Crohn\u00b4s Disease and Orofacial Granulomatosis. University of Helsinki http:\/\/hdl.handle.net\/10138\/301005 (2019)."},{"key":"90243_CR6","doi-asserted-by":"publisher","first-page":"e584","DOI":"10.4317\/medoral.20187","volume":"19","author":"G Gale","year":"2014","unstructured":"Gale, G., \u00d6stman, S., Saalman, R., Telemo, E. & Hass\u00e9us, B. Immunophenotype in orofacial granulomatosis with and without Crohn\u2019s disease. Med. Oral Patol. Oral Cir. Bucal. 19, e584\u2013e591 (2014).","journal-title":"Med. Oral Patol. Oral Cir. Bucal"},{"key":"90243_CR7","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1002\/ibd.21169","volume":"16","author":"P Patel","year":"2010","unstructured":"Patel, P. et al. Subepithelial dendritic B cells in orofacial granulomatosis. Inflamm. Bowel Dis. 16, 1051\u20131060 (2010).","journal-title":"Inflamm. Bowel Dis."},{"key":"90243_CR8","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1046\/j.1365-2133.2000.03877.x","volume":"143","author":"J Gibson","year":"2000","unstructured":"Gibson, J. & Wray, D. Human leucocyte antigen typing in orofacial granulomatosis. Br. J. Dermatol. 143, 1119\u20131121 (2000).","journal-title":"Br. J. Dermatol."},{"key":"90243_CR9","doi-asserted-by":"publisher","first-page":"e121","DOI":"10.1097\/MPG.0000000000001300","volume":"63","author":"R Paakkanen","year":"2016","unstructured":"Paakkanen, R., Haaramo, A., Kolho, K. L., Ruuska, T. & Lokki, M. L. HLA-B*44 May be a marker for Orofacial granulomatosis. J. Pediatr. Gastroenterol. Nutr. 63, e121\u2013e122 (2016).","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"90243_CR10","doi-asserted-by":"publisher","first-page":"1552","DOI":"10.1097\/MIB.0000000000000844","volume":"22","author":"A Mentzer","year":"2016","unstructured":"Mentzer, A. et al. Genetic Association Analysis Reveals Differences in the contribution of NOD2 variants to the clinical phenotypes of Orofacial Granulomatosis. Inflamm. Bowel Dis. 22, 1552\u20131558 (2016).","journal-title":"Inflamm. Bowel Dis."},{"key":"90243_CR11","doi-asserted-by":"publisher","first-page":"7497","DOI":"10.3748\/wjg.v20.i23.7497","volume":"20","author":"M Lazzerini","year":"2014","unstructured":"Lazzerini, M., Bramuzzo, M. & Ventura, A. Association between orofacial granulomatosis and Crohn\u2019s disease in children: systematic review. World J. Gastroenterol. 20, 7497\u20137504 (2014).","journal-title":"World J. Gastroenterol."},{"key":"90243_CR12","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1093\/ibd\/izz022","volume":"25","author":"RM Goel","year":"2019","unstructured":"Goel, R. M. et al. Streptococcus salivarius: a potential salivary biomarker for orofacial granulomatosis and Crohn\u2019s disease? Inflamm. Bowel Dis. 25, 1367\u20131374 (2019).","journal-title":"Inflamm. Bowel Dis."},{"key":"90243_CR13","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1097\/MPG.0000000000001554","volume":"65","author":"A Haaramo","year":"2017","unstructured":"Haaramo, A. et al. Detailed follow-up study of Pediatric Orofacial granulomatosis patients. J. Pediatr. Gastroenterol. Nutr. 65, 388\u2013393 (2017).","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"90243_CR14","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1093\/ecco-jcc\/jjx153","volume":"12","author":"Y Wang","year":"2018","unstructured":"Wang, Y. et al. Characteristics of faecal microbiota in paediatric Crohn\u2019s disease and their dynamic changes during infliximab therapy. J. Crohns Colitis. 12, 337\u2013346 (2018).","journal-title":"J. Crohns Colitis"},{"key":"90243_CR15","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1016\/j.chom.2015.09.008","volume":"18","author":"JD Lewis","year":"2015","unstructured":"Lewis, J. D. et al. Inflammation, antibiotics, and Diet as Environmental stressors of the gut Microbiome in Pediatric Crohn\u2019s Disease. Cell. Host Microbe. 18, 489\u2013500 (2015).","journal-title":"Cell. Host Microbe"},{"key":"90243_CR16","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1038\/ajg.2015.149","volume":"110","author":"KL Kolho","year":"2015","unstructured":"Kolho, K. L. et al. Fecal microbiota in pediatric inflammatory bowel disease and its relation to inflammation. Am. J. Gastroenterol. 110, 921\u2013930 (2015).","journal-title":"Am. J. Gastroenterol."},{"key":"90243_CR17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/19490976.2020.1826746","volume":"13","author":"L Fan","year":"2021","unstructured":"Fan, L. et al. B. adolescentis ameliorates chronic colitis by regulating Treg\/Th2 response and gut microbiota remodeling. Gut Microbes. 13, 1\u201317 (2021).","journal-title":"Gut Microbes"},{"key":"90243_CR18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1136\/rmdopen-2021-001755","volume":"7","author":"MC Ditto","year":"2021","unstructured":"Ditto, M. C. et al. Intestinal microbiota changes induced by TNF-inhibitors in IBD-related spondyloarthritis. RMD Open. 7, 1\u20139 (2021).","journal-title":"RMD Open."},{"key":"90243_CR19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s40168-023-01469-2","volume":"11","author":"I Bourdeau-Julien","year":"2023","unstructured":"Bourdeau-Julien, I. et al. The diet rapidly and differentially affects the gut microbiota and host lipid mediators in a healthy population. Microbiome 11, 1\u201316 (2023).","journal-title":"Microbiome"},{"key":"90243_CR20","unstructured":"Valsta, L., Kaartinen, N., Tapanainen, H., M\u00e4nnist\u00f6, S. & S\u00e4\u00e4ksj\u00e4rvi, K. Ravitsemus Suomessa - FinRavinto 2017 -Tutkimus. Terveyden ja hyvinvoinnin laitos (2018)."},{"key":"90243_CR21","unstructured":"Nordic council of Ministers. Nordic Nutrition Recommendations 2012. (2012)."},{"key":"90243_CR22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-021-84938-8","volume":"11","author":"JE Horowitz","year":"2021","unstructured":"Horowitz, J. E. et al. Mutation spectrum of NOD2 reveals recessive inheritance as a main driver of early onset Crohn\u2019s Disease. Sci. Rep. 11, 1\u201310 (2021).","journal-title":"Sci. Rep."},{"key":"90243_CR23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fnut.2020.606171","volume":"7","author":"O Giampaoli","year":"2020","unstructured":"Giampaoli, O., Conta, G., Calvani, R. & Miccheli, A. Can the FUT2 non-secretor phenotype Associated with Gut Microbiota increase the children susceptibility for type 1 diabetes? A Mini Review. Front. Nutr. 7, 1\u20139 (2020).","journal-title":"Front. Nutr."},{"key":"90243_CR24","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1111\/tan.12016","volume":"80","author":"AS Parmar","year":"2012","unstructured":"Parmar, A. S. et al. Association study of FUT2 (rs601338) with celiac disease and inflammatory bowel disease in the Finnish population. Tissue Antigens. 80, 488\u2013493 (2012).","journal-title":"Tissue Antigens"},{"key":"90243_CR25","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1111\/ijd.15912","volume":"61","author":"V Kiiski","year":"2022","unstructured":"Kiiski, V. et al. Atopic dermatitis in adults: a population-based study in Finland. Int. J. Dermatol. 61, 324\u2013330 (2022).","journal-title":"Int. J. Dermatol."},{"key":"90243_CR26","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1590\/abd1806-4841.20185828","volume":"93","author":"I Espinoza","year":"2018","unstructured":"Espinoza, I. et al. Orofacial granulomatosis and diet therapy: a review of the literature and two clinical cases. Bras. Dermatol. 93, 80\u201385 (2018).","journal-title":"Bras. Dermatol."},{"key":"90243_CR27","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1093\/ibd\/izac182","volume":"29","author":"M H\u00f6yhty\u00e4","year":"2023","unstructured":"H\u00f6yhty\u00e4, M. et al. Quantitative fecal microbiota profiles relate to therapy response during induction with tumor necrosis factor \u03b1 antagonist Infliximab in Pediatric Inflammatory Bowel Disease. Inflamm. Bowel Dis. 29, 116\u2013124 (2023).","journal-title":"Inflamm. Bowel Dis."},{"key":"90243_CR28","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1097\/MPG.0000000000000239","volume":"58","author":"A Levine","year":"2014","unstructured":"Levine, A. et al. ESPGHAN revised porto criteria for the diagnosis of inflammatory bowel disease in children and adolescents. J. Pediatr. Gastroenterol. Nutr. 58, 795\u2013806 (2014).","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"90243_CR29","doi-asserted-by":"publisher","first-page":"E269","DOI":"10.1097\/MCG.0000000000001074","volume":"53","author":"A Haaramo","year":"2019","unstructured":"Haaramo, A. et al. Oral and otorhinolaryngological findings in adults who were diagnosed with Pediatric Onset Crohn\u2019s Disease: a controlled study. J. Clin. Gastroenterol. 53, E269\u2013E275 (2019).","journal-title":"J. Clin. Gastroenterol."},{"key":"90243_CR30","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.mimet.2010.02.007","volume":"81","author":"A Salonen","year":"2010","unstructured":"Salonen, A. et al. Comparative analysis of fecal DNA extraction methods with phylogenetic microarray: effective recovery of bacterial and archaeal DNA using mechanical cell lysis. J. Microbiol. Methods. 81, 127\u2013134 (2010).","journal-title":"J. Microbiol. Methods"},{"key":"90243_CR31","doi-asserted-by":"publisher","first-page":"104695","DOI":"10.1016\/j.ebiom.2023.104695","volume":"94","author":"R Jokela","year":"2023","unstructured":"Jokela, R. et al. Sources of gut microbiota variation in a large longitudinal Finnish infant cohort. EBioMedicine 94, 104695 (2023).","journal-title":"EBioMedicine"},{"key":"90243_CR32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/nar\/gks808","volume":"41","author":"A Klindworth","year":"2013","unstructured":"Klindworth, A. et al. Evaluation of general 16S ribosomal RNA gene PCR primers for classical and next-generation sequencing-based diversity studies. Nucleic Acids Res. 41, 1\u201311 (2013).","journal-title":"Nucleic Acids Res."},{"key":"90243_CR33","doi-asserted-by":"publisher","first-page":"2311","DOI":"10.1007\/s00467-021-04955-7","volume":"36","author":"M Koskela","year":"2021","unstructured":"Koskela, M. et al. HLA-DQ and HLA-DRB1 alleles associated with Henoch-Sch\u00f6nlein purpura nephritis in Finnish pediatric population: a genome-wide association study. Pediatr. Nephrol. 36, 2311\u20132318 (2021).","journal-title":"Pediatr. Nephrol."},{"key":"90243_CR34","unstructured":"R Core Team. R: A language and environment for statistical computing. Preprint at (2018). https:\/\/www.r-project.org\/"},{"key":"90243_CR35","doi-asserted-by":"publisher","first-page":"1686","DOI":"10.21105\/joss.01686","volume":"4","author":"H Wickham","year":"2019","unstructured":"Wickham, H. et al. Welcome to the Tidyverse. J. Open. Source Softw. 4, 1686 (2019).","journal-title":"J. Open. Source Softw."},{"key":"90243_CR36","doi-asserted-by":"publisher","unstructured":"Wickham, H. & Bryan, J. Read Excel Files. Preprint at https:\/\/doi. (2019). https:\/\/doi.org\/10.21105\/joss.01686","DOI":"10.21105\/joss.01686"},{"key":"90243_CR37","doi-asserted-by":"publisher","first-page":"1184","DOI":"10.1038\/nprot.2009.97","volume":"4","author":"S Durinck","year":"2009","unstructured":"Durinck, S., Spellman, P. T., Birney, E. & Huber, W. Mapping identifiers for the integration of genomic datasets with the R\/Bioconductor package biomaRt. Nat. Protoc. 4, 1184\u20131191 (2009).","journal-title":"Nat. Protoc."},{"key":"90243_CR38","doi-asserted-by":"publisher","first-page":"3439","DOI":"10.1093\/bioinformatics\/bti525","volume":"21","author":"S Durinck","year":"2005","unstructured":"Durinck, S. et al. BioMart and Bioconductor: a powerful link between biological databases and microarray data analysis. Bioinformatics 21, 3439\u20133440 (2005).","journal-title":"Bioinformatics"},{"key":"90243_CR39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13742-015-0047-8","volume":"4","author":"CC Chang","year":"2015","unstructured":"Chang, C. C. et al. Second-generation PLINK: rising to the challenge of larger and richer datasets. Gigascience 4, 1\u201316 (2015).","journal-title":"Gigascience"},{"key":"90243_CR40","unstructured":"Purcell, S. & Chang, C. plink v2.00a3LM AVX2 Intel. Preprint at (2021). www.cog-genomics.org\/plink\/2.0\/"},{"key":"90243_CR41","doi-asserted-by":"crossref","unstructured":"Wacklin, P. et al. Secretor genotype (FUT2 gene) is strongly associated with the composition of bifidobacteria in the human intestine. PLoS One 6, (2011).","DOI":"10.1371\/journal.pone.0020113"},{"key":"90243_CR42","unstructured":"Korpela, K. mare: Microbiota analysis in R Easily. R package version 1.0. Preprint at (2016)."},{"key":"90243_CR43","doi-asserted-by":"publisher","first-page":"2460","DOI":"10.1093\/bioinformatics\/btq461","volume":"26","author":"RC Edgar","year":"2010","unstructured":"Edgar, R. C. Search and clustering orders of magnitude faster than BLAST. Bioinformatics 26, 2460\u20132461 (2010).","journal-title":"Bioinformatics"},{"key":"90243_CR44","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1093\/nar\/gks1219","volume":"41","author":"C Quast","year":"2013","unstructured":"Quast, C. et al. The SILVA ribosomal RNA gene database project: improved data processing and web-based tools. Nucleic Acids Res. 41, 590\u2013596 (2013).","journal-title":"Nucleic Acids Res."},{"key":"90243_CR45","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-21706-2","volume-title":"In Modern Applied Statistics with S","author":"W Venables","year":"2002","unstructured":"Venables, W. & Ripley, B. In Modern Applied Statistics with S (Springer, 2002)."},{"key":"90243_CR46","unstructured":"Oksanen, J. et al. vegan: Community Ecology Package. R package version 2. 0\u20132. Preprint at (2012)."},{"key":"90243_CR47","unstructured":"J, P. D, B., S, D., D, S. & R Core, T. nlme: Linear and Nonlinear Mixed Effects Models. R package version 3.1\u2013145. Preprint at (2020)."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-90243-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-90243-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-90243-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T08:16:48Z","timestamp":1739953008000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-90243-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,19]]},"references-count":47,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["90243"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-90243-5","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,19]]},"assertion":[{"value":"23 April 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 February 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 February 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"K-L.K. has received consultancy fees from AbbVie, Biocodex and Tillotts Pharma. The other authors report none.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"6020"}}