{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T11:38:45Z","timestamp":1790249925039,"version":"4.1.0"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2025,4,12]],"date-time":"2025-04-12T00:00:00Z","timestamp":1744416000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,4,12]],"date-time":"2025-04-12T00:00:00Z","timestamp":1744416000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100007537","name":"Freie Universit\u00e4t Berlin","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007537","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Mol Med"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:sec>\n            <jats:title>Abstract<\/jats:title>\n            <jats:p>The human chloride channel regulator, calcium-activated (CLCA) 4 is discussed as a driver of epithelial-to-mesenchymal transition as well as a biomarker for colorectal cancer (CRC) and ulcerative colitis. In contrast to humans, the <jats:italic>Clca4<\/jats:italic> gene is duplicated in the mouse, a common model species to study gene functions. However, the relevance of the functional murine Clca4 variants in healthy and diseased intestine is largely unknown. Here, we characterized the spatiotemporal expression patterns of the murine <jats:italic>Clca4a<\/jats:italic> and <jats:italic>Clca4b<\/jats:italic> genes in the healthy intestinal tract as well as in dextran sulfate sodium (DSS)-induced colitis and colitis-associated colon cancer (CAC) mouse model using RT-qPCR and in situ-hybridization. Similarly, we analyzed expression of the human <jats:italic>CLCA4<\/jats:italic> in healthy, inflamed and cancerous intestinal tracts at single cell level. Murine <jats:italic>Clca4a<\/jats:italic> and -<jats:italic>4b<\/jats:italic> but not the human <jats:italic>CLCA4<\/jats:italic> were detected in small intestine enterocytes of the respective species. Conversely, healthy colonocytes expressed the human <jats:italic>CLCA4<\/jats:italic> and its murine ortholog <jats:italic>Clca4a<\/jats:italic> but not the murine <jats:italic>Clca4b<\/jats:italic>. Under inflammatory conditions, de novo expression of <jats:italic>Clca4b<\/jats:italic> was observed with both murine homologs abundantly expressed in enterocytes adjacent to ulcerations. Neoplastic colonocytes expressed none or only minimal amounts of the <jats:italic>CLCA4<\/jats:italic> homologs both in humans and mice, whereas adjacent non-neoplastic colonocytes strongly up-regulated the human or both murine homologs, respectively. Our results suggest marked species- and homolog-specific differences in the expression patterns of the three CLCA4 homologs. Moreover, all three seem to play a role in reactive, non-neoplastic colonocytes adjacent to ulcerated and neoplastic lesions.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Key messages<\/jats:title>\n            <jats:p>\n              <jats:list list-type=\"bullet\">\n                <jats:list-item>\n                  <jats:p>Human <jats:italic>CLCA4<\/jats:italic> and murine <jats:italic>Clca4a<\/jats:italic>, but not <jats:italic>Clca4b<\/jats:italic>, are expressed in healthy colonocytes.<\/jats:p>\n                <\/jats:list-item>\n                <jats:list-item>\n                  <jats:p>Inflammation leads to a de novo expression of the murine <jats:italic>Clca4b<\/jats:italic> in colonocytes.<\/jats:p>\n                <\/jats:list-item>\n                <jats:list-item>\n                  <jats:p>Human and murine <jats:italic>CLCA4<\/jats:italic> homologs are absent from neoplastic enterocytes.<\/jats:p>\n                <\/jats:list-item>\n                <jats:list-item>\n                  <jats:p>Human and murine <jats:italic>CLCA4<\/jats:italic>s are highly expressed in tumor-adjacent, reactive colonocytes.<\/jats:p>\n                <\/jats:list-item>\n              <\/jats:list>\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s00109-025-02538-9","type":"journal-article","created":{"date-parts":[[2025,4,12]],"date-time":"2025-04-12T10:56:51Z","timestamp":1744455411000},"page":"687-697","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The impact of disease and species differences on the intestinal CLCA4 gene expression"],"prefix":"10.1007","volume":"103","author":[{"given":"K.","family":"Teske","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N. A.","family":"Erickson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Huck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Dzamukova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Fulde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Heinbokel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Horst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Klymiuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Pastille","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Mekes-Adamczyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"L\u00f6hning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. D.","family":"Gruber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Glauben","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9033-9360","authenticated-orcid":false,"given":"L.","family":"Mundhenk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,12]]},"reference":[{"issue":"6","key":"2538_CR1","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1089\/10445490152122442","volume":"20","author":"SA Bustin","year":"2001","unstructured":"Bustin SA, Li SR, Dorudi S (2001) Expression of the Ca2+-activated chloride channel genes CLCA1 and CLCA2 is downregulated in human colorectal cancer. DNA Cell Biol 20(6):331\u2013338","journal-title":"DNA Cell Biol"},{"issue":"1","key":"2538_CR2","doi-asserted-by":"publisher","first-page":"631","DOI":"10.3892\/ol.2020.11640","volume":"20","author":"L Wei","year":"2020","unstructured":"Wei L et al (2020) Downregulation of CLCA4 expression is associated with the development and progression of colorectal cancer. Oncol Lett 20(1):631\u2013638","journal-title":"Oncol Lett"},{"issue":"4","key":"2538_CR3","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1089\/dna.2019.5088","volume":"39","author":"X Gao","year":"2020","unstructured":"Gao X, Yang J (2020) Identification of Genes related to clinicopathological characteristics and prognosis of patients with colorectal cancer. DNA Cell Biol 39(4):690\u2013699","journal-title":"DNA Cell Biol"},{"issue":"4","key":"2538_CR4","doi-asserted-by":"publisher","first-page":"2942","DOI":"10.3934\/mbe.2019145","volume":"16","author":"ZW Zhao","year":"2019","unstructured":"Zhao ZW et al (2019) The identification of a common different gene expression signature in patients with colorectal cancer. Math Biosci Eng 16(4):2942\u20132958","journal-title":"Math Biosci Eng"},{"issue":"4","key":"2538_CR5","doi-asserted-by":"publisher","first-page":"e60861","DOI":"10.1371\/journal.pone.0060861","volume":"8","author":"B Yang","year":"2013","unstructured":"Yang B et al (2013) The transition from proliferation to differentiation in colorectal cancer is regulated by the calcium activated chloride channel A1. PLoS ONE 8(4):e60861","journal-title":"PLoS ONE"},{"issue":"9","key":"2538_CR6","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1007\/s12032-021-01543-5","volume":"38","author":"J Ebadfardzadeh","year":"2021","unstructured":"Ebadfardzadeh J et al (2021) Employing bioinformatics analysis to identify hub genes and microRNAs involved in colorectal cancer. Med Oncol 38(9):114","journal-title":"Med Oncol"},{"key":"2538_CR7","doi-asserted-by":"crossref","unstructured":"Han J et al (2020)\u00a0CLCA4 and MS4A12 as the significant gene biomarkers of primary colorectal cancer. Biosci Rep 40(8):BSR20200963","DOI":"10.1042\/BSR20200963"},{"key":"2538_CR8","doi-asserted-by":"publisher","first-page":"8082697","DOI":"10.1155\/2020\/8082697","volume":"2020","author":"H Xu","year":"2020","unstructured":"Xu H et al (2020) Identification and Verification of Core Genes in Colorectal Cancer. Biomed Res Int 2020:8082697","journal-title":"Biomed Res Int"},{"issue":"10","key":"2538_CR9","doi-asserted-by":"publisher","first-page":"2570","DOI":"10.18632\/aging.101571","volume":"10","author":"Z Liu","year":"2018","unstructured":"Liu Z et al (2018) CLCA4 inhibits cell proliferation and invasion of hepatocellular carcinoma by suppressing epithelial-mesenchymal transition via PI3K\/AKT signaling. Aging (Albany NY) 10(10):2570\u20132584","journal-title":"Aging (Albany NY)"},{"issue":"54","key":"2538_CR10","doi-asserted-by":"publisher","first-page":"93001","DOI":"10.18632\/oncotarget.21724","volume":"8","author":"T Hou","year":"2017","unstructured":"Hou T et al (2017) CLCA4 inhibits bladder cancer cell proliferation, migration, and invasion by suppressing the PI3K\/AKT pathway. Oncotarget 8(54):93001\u201393013","journal-title":"Oncotarget"},{"issue":"12","key":"2538_CR11","doi-asserted-by":"publisher","first-page":"e83943","DOI":"10.1371\/journal.pone.0083943","volume":"8","author":"Y Yu","year":"2013","unstructured":"Yu Y, Walia V, Elble RC (2013) Loss of CLCA4 promotes epithelial-to-mesenchymal transition in breast cancer cells. PLoS ONE 8(12):e83943","journal-title":"PLoS ONE"},{"key":"2538_CR12","doi-asserted-by":"publisher","first-page":"4176","DOI":"10.12659\/MSM.914195","volume":"25","author":"H Chen","year":"2019","unstructured":"Chen H et al (2019) Calcium-Activated Chloride Channel A4 (CLCA4) plays inhibitory roles in invasion and migration through suppressing epithelial-mesenchymal transition via PI3K\/AKT signaling in colorectal cancer. Med Sci Monit 25:4176\u20134185","journal-title":"Med Sci Monit"},{"issue":"8","key":"2538_CR13","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1007\/s00335-009-9212-7","volume":"20","author":"EM Comelli","year":"2009","unstructured":"Comelli EM et al (2009) Biomarkers of human gastrointestinal tract regions. Mamm Genome 20(8):516\u2013527","journal-title":"Mamm Genome"},{"issue":"4","key":"2538_CR14","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1053\/j.gastro.2013.01.067","volume":"144","author":"MK Washington","year":"2013","unstructured":"Washington MK et al (2013) Pathology of rodent models of intestinal cancer: progress report and recommendations. Gastroenterology 144(4):705\u2013717","journal-title":"Gastroenterology"},{"issue":"2","key":"2538_CR15","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1002\/path.4645","volume":"238","author":"R Jackstadt","year":"2016","unstructured":"Jackstadt R, Sansom OJ (2016) Mouse models of intestinal cancer. J Pathol 238(2):141\u2013151","journal-title":"J Pathol"},{"key":"2538_CR16","first-page":"7479540","volume":"2021","author":"Z Baydi","year":"2021","unstructured":"Baydi Z et al (2021) An Update of Research Animal Models of Inflammatory Bowel Disease. SciWorldJ 2021:7479540","journal-title":"SciWorldJ"},{"issue":"1","key":"2538_CR17","doi-asserted-by":"publisher","first-page":"e0191512","DOI":"10.1371\/journal.pone.0191512","volume":"13","author":"L Mundhenk","year":"2018","unstructured":"Mundhenk L et al (2018) Interspecies diversity of chloride channel regulators, calcium-activated 3 genes. PLoS ONE 13(1):e0191512","journal-title":"PLoS ONE"},{"issue":"4","key":"2538_CR18","doi-asserted-by":"publisher","first-page":"e0266937","DOI":"10.1371\/journal.pone.0266937","volume":"17","author":"F Bartenschlager","year":"2022","unstructured":"Bartenschlager F et al (2022) Evolutionarily conserved properties of CLCA proteins 1, 3 and 4, as revealed by phylogenetic and biochemical studies in avian homologues. PLoS ONE 17(4):e0266937","journal-title":"PLoS ONE"},{"key":"2538_CR19","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1146\/annurev.physiol.010908.163253","volume":"71","author":"AC Patel","year":"2009","unstructured":"Patel AC, Brett TJ, Holtzman MJ (2009) The role of CLCA proteins in inflammatory airway disease. Annu Rev Physiol 71:425\u2013449","journal-title":"Annu Rev Physiol"},{"issue":"4","key":"2538_CR20","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1203\/01.PDR.0000057204.51420.DC","volume":"53","author":"M Mall","year":"2003","unstructured":"Mall M et al (2003) Modulation of Ca2+-activated Cl- secretion by basolateral K+ channels in human normal and cystic fibrosis airway epithelia. Pediatr Res 53(4):608\u2013618","journal-title":"Pediatr Res"},{"issue":"6","key":"2538_CR21","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1007\/s00439-004-1190-y","volume":"115","author":"M Ritzka","year":"2004","unstructured":"Ritzka M et al (2004) The CLCA gene locus as a modulator of the gastrointestinal basic defect in cystic fibrosis. Hum Genet 115(6):483\u2013491","journal-title":"Hum Genet"},{"issue":"7","key":"2538_CR22","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1097\/PAI.0000000000000777","volume":"28","author":"HY Mo","year":"2020","unstructured":"Mo HY et al (2020) Frameshift mutations and loss of expression of CLCA4 gene are frequent in colorectal cancers with microsatellite instability. Appl Immunohistochem Mol Morphol 28(7):489\u2013494","journal-title":"Appl Immunohistochem Mol Morphol"},{"issue":"5","key":"2538_CR23","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1007\/s12264-007-0044-8","volume":"23","author":"M Al-Jumaily","year":"2007","unstructured":"Al-Jumaily M et al (2007) Expression of three distinct families of calcium-activated chloride channel genes in the mouse dorsal root ganglion. Neurosci Bull 23(5):293\u2013299","journal-title":"Neurosci Bull"},{"issue":"1","key":"2538_CR24","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1165\/rcmb.2010-0508OC","volume":"47","author":"L Mundhenk","year":"2012","unstructured":"Mundhenk L et al (2012) mCLCA3 does not contribute to calcium-activated chloride conductance in murine airways. Am J Respir Cell Mol Biol 47(1):87\u201393","journal-title":"Am J Respir Cell Mol Biol"},{"issue":"5","key":"2538_CR25","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1369\/jhc.2008.950592","volume":"56","author":"MK Bothe","year":"2008","unstructured":"Bothe MK et al (2008) Murine mCLCA6 is an integral apical membrane protein of non-goblet cell enterocytes and co-localizes with the cystic fibrosis transmembrane conductance regulator. J Histochem Cytochem 56(5):495\u2013509","journal-title":"J Histochem Cytochem"},{"issue":"7","key":"2538_CR26","doi-asserted-by":"publisher","first-page":"e0131991","DOI":"10.1371\/journal.pone.0131991","volume":"10","author":"NA Erickson","year":"2015","unstructured":"Erickson NA et al (2015) The Goblet Cell Protein Clca1 (Alias mClca3 or Gob-5) Is Not Required for Intestinal Mucus Synthesis, Structure and Barrier Function in Naive or DSS-Challenged Mice. PLoS ONE 10(7):e0131991","journal-title":"PLoS ONE"},{"key":"2538_CR27","doi-asserted-by":"publisher","first-page":"669747","DOI":"10.3389\/fimmu.2021.669747","volume":"12","author":"E Pastille","year":"2021","unstructured":"Pastille E et al (2021) Inhibition of TLR4 Signaling Impedes Tumor Growth in Colitis-Associated Colon Cancer. Front Immunol 12:669747","journal-title":"Front Immunol"},{"issue":"7","key":"2538_CR28","doi-asserted-by":"publisher","first-page":"e102606","DOI":"10.1371\/journal.pone.0102606","volume":"9","author":"K Dietert","year":"2014","unstructured":"Dietert K et al (2014) mCLCA3 modulates IL-17 and CXCL-1 induction and leukocyte recruitment in murine Staphylococcus aureus pneumonia. PLoS ONE 9(7):e102606","journal-title":"PLoS ONE"},{"key":"2538_CR29","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.jcpa.2019.10.193","volume":"174","author":"NA Erickson","year":"2020","unstructured":"Erickson NA, Gruber AD, Mundhenk L (2020) The Family of Chloride Channel Regulator, Calcium-activated Proteins in the Feline Respiratory Tract: A Comparative Perspective on Airway Diseases in Man and Animal Models. J Comp Pathol 174:39\u201353","journal-title":"J Comp Pathol"},{"issue":"2","key":"2538_CR30","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1016\/j.immuni.2023.01.002","volume":"56","author":"L Kong","year":"2023","unstructured":"Kong L et al (2023) The landscape of immune dysregulation in Crohn\u2019s disease revealed through single-cell transcriptomic profiling in the ileum and colon. Immunity 56(2):444-458.e5","journal-title":"Immunity"},{"issue":"10","key":"2538_CR31","doi-asserted-by":"publisher","first-page":"e14123","DOI":"10.15252\/emmm.202114123","volume":"13","author":"F Uhlitz","year":"2021","unstructured":"Uhlitz F et al (2021) Mitogen-activated protein kinase activity drives cell trajectories in colorectal cancer. EMBO Mol Med 13(10):e14123","journal-title":"EMBO Mol Med"},{"key":"2538_CR32","doi-asserted-by":"crossref","unstructured":"Wei TT et al (2024) High-confidence calling of normal epithelial cells allows identification of a novel stem-like cell state in the colorectal cancer microenvironment. Int J Cancer 155(9):1655\u20131669","DOI":"10.1002\/ijc.35079"},{"issue":"4","key":"2538_CR33","doi-asserted-by":"publisher","first-page":"1531","DOI":"10.1093\/genetics\/151.4.1531","volume":"151","author":"A Force","year":"1999","unstructured":"Force A et al (1999) Preservation of duplicate genes by complementary, degenerative mutations. Genetics 151(4):1531\u20131545","journal-title":"Genetics"},{"issue":"1346","key":"2538_CR34","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1098\/rspb.1994.0058","volume":"256","author":"AL Hughes","year":"1994","unstructured":"Hughes AL (1994) The evolution of functionally novel proteins after gene duplication. Proc Biol Sci 256(1346):119\u2013124","journal-title":"Proc Biol Sci"},{"issue":"7","key":"2538_CR35","doi-asserted-by":"publisher","first-page":"1322","DOI":"10.1007\/s00018-003-2289-3","volume":"60","author":"P de Santa Barbara","year":"2003","unstructured":"de Santa Barbara P, van den Brink GR, Roberts DJ (2003) Development and differentiation of the intestinal epithelium. Cell Mol Life Sci 60(7):1322\u201332","journal-title":"Cell Mol Life Sci"}],"container-title":["Journal of Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00109-025-02538-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00109-025-02538-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00109-025-02538-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T06:26:57Z","timestamp":1749104817000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00109-025-02538-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,12]]},"references-count":35,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["2538"],"URL":"https:\/\/doi.org\/10.1007\/s00109-025-02538-9","relation":{},"ISSN":["0946-2716","1432-1440"],"issn-type":[{"value":"0946-2716","type":"print"},{"value":"1432-1440","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,12]]},"assertion":[{"value":"21 October 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 March 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 March 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 April 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Euthanasia of mice was in accordance with the FELASA guidelines and acknowledged by the local governmental authorities (State Office of Health and Social Affairs Berlin, IDs: T 0181\/15, T 0104\/06). Tissues from mice were re-used from former approved studies (State Office of Health and Social Affairs Berlin, approval ID: G 0170\/12; State Agency for Nature, Environment and Consumer Protection in North Rhine-Westphalia, approval ID: 81\u201302.04.2017.A445). A detailed assignment can be found in the material and method section. The retrospective study on human samples was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Charit\u00e9 \u2013 University Medicine Berlin (04.04.2024\/No. EA1\/039\/24).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"The authors have no relevant financial or non-financial interests to disclose.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}