{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:18:20Z","timestamp":1790705900762,"version":"4.1.0"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2020,11,24]],"date-time":"2020-11-24T00:00:00Z","timestamp":1606176000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Wessex Investigational Sciences Hub, Faculty of Medicine, Cancer Sciences"},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["109377\/Z\/15\/Z"],"award-info":[{"award-number":["109377\/Z\/15\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"MRC","doi-asserted-by":"publisher","award":["MC_PC_15078"],"award-info":[{"award-number":["MC_PC_15078"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,5,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aims<\/jats:title><jats:p>Crohn\u2019s disease [CD] arises through host-environment interaction. Abnormal gene expression results from disturbed pathway activation or response to bacteria. We aimed to determine activated pathways and driving cell types in paediatric CD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We employed contemporary targeted autoimmune RNA sequencing, in parallel to single-cell sequencing, to ileal tissue derived from paediatric CD and controls. Weighted gene co-expression network analysis [WGCNA] was performed and differentially expressed genes [DEGs] were determined. We integrated clinical data to determine co-expression modules associated with outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In all, 27 treatment-naive CD [TN-CD], 26 established CD patients and 17 controls were included. WGCNA revealed a 31-gene signature characterising TN-CD patients, but not established CD, nor controls. The CSF3R gene is a hub within this module and is key in neutrophil expansion and differentiation. Antimicrobial genes, including S100A12 and the calprotectin subunit S100A9, were significantly upregulated in TN CD compared with controls [p = 2.61 x 10-15 and p = 9.13 x 10-14, respectively] and established CD [both p = 0.0055]. Gene-enrichment analysis confirmed upregulation of the IL17-, NOD- and Oncostatin-M-signalling pathways in TN-CD patients, identified in both WGCNA and DEG analyses. An upregulated gene signature was enriched for transcripts promoting Th17-cell differentiation and correlated with prolonged time to relapse [correlation-coefficient-0.36, p = 0.07]. Single-cell sequencing of TN-CD patients identified specialised epithelial cells driving differential expression of S100A9. Cell groups, determined by single-cell gene expression, demonstrated enrichment of IL17-signalling in monocytes and epithelial cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Ileal tissue from treatment-na\u00efve paediatric patients is significantly upregulated for genes driving IL17-, NOD- and Oncostatin-M-signalling. This signal is driven by a distinct subset of epithelial cells expressing antimicrobial gene transcripts.<\/jats:p><\/jats:sec>","DOI":"10.1093\/ecco-jcc\/jjaa236","type":"journal-article","created":{"date-parts":[[2020,11,18]],"date-time":"2020-11-18T05:52:48Z","timestamp":1605678768000},"page":"774-786","source":"Crossref","is-referenced-by-count":20,"title":["Ileal Transcriptomic Analysis in Paediatric Crohn\u2019s Disease Reveals<i>IL17-<\/i>and<i>NOD-<\/i>signalling Expression Signatures in Treatment-na\u00efve Patients and Identifies Epithelial Cells Driving Differentially Expressed Genes"],"prefix":"10.1093","volume":"15","author":[{"given":"James J","family":"Ashton","sequence":"first","affiliation":[{"name":"Department of Human Genetics and Genomic Medicine, University of Southampton, Southampton, UK"},{"name":"Department of Paediatric Gastroenterology, Southampton Children\u2019s Hospital, Southampton, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Boukas","sequence":"additional","affiliation":[{"name":"Wessex Investigational Sciences Hub, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Davies","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Sciences, Sir Henry Wellcome Laboratories, Faculty of Medicine, University of Southampton, Southampton, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imogen S","family":"Stafford","sequence":"additional","affiliation":[{"name":"Department of Human Genetics and Genomic Medicine, University of Southampton, Southampton, UK"},{"name":"Institute for Life Sciences, University of Southampton, Southampton, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andres F","family":"Vallejo","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Sciences, Sir Henry Wellcome Laboratories, Faculty of Medicine, University of Southampton, Southampton, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Haggarty","sequence":"additional","affiliation":[{"name":"NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy A F","family":"Coelho","sequence":"additional","affiliation":[{"name":"Department of Paediatric Gastroenterology, Southampton Children\u2019s Hospital, Southampton, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akshay","family":"Batra","sequence":"additional","affiliation":[{"name":"Department of Paediatric Gastroenterology, Southampton Children\u2019s Hospital, Southampton, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadeem A","family":"Afzal","sequence":"additional","affiliation":[{"name":"Department of Paediatric Gastroenterology, Southampton Children\u2019s Hospital, Southampton, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhumita","family":"Vadgama","sequence":"additional","affiliation":[{"name":"Department of Paediatric Histopathology, Southampton Children\u2019s Hospital, Southampton, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony P","family":"Williams","sequence":"additional","affiliation":[{"name":"Wessex Investigational Sciences Hub, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK"},{"name":"Institute for Life Sciences, University of Southampton, Southampton, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R Mark","family":"Beattie","sequence":"additional","affiliation":[{"name":"Department of Paediatric Gastroenterology, Southampton Children\u2019s Hospital, Southampton, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta E","family":"Polak","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Sciences, Sir Henry Wellcome Laboratories, Faculty of Medicine, University of Southampton, Southampton, UK"},{"name":"Department of Human Genetics and Genomic Medicine, University of Southampton, Southampton, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Ennis","sequence":"additional","affiliation":[{"name":"Department of Human Genetics and Genomic Medicine, University of Southampton, Southampton, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,11,24]]},"reference":[{"key":"2021050415275633600_CIT0001","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1038\/nature10209","article-title":"Genetics and pathogenesis of inflammatory bowel disease","volume":"474","author":"Khor","year":"2011","journal-title":"Nature"},{"key":"2021050415275633600_CIT0002","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1038\/s41586-020-2025-2","article-title":"Pathway paradigms revealed from the genetics of inflammatory bowel disease","volume":"578","author":"Graham","year":"2020","journal-title":"Nature"},{"key":"2021050415275633600_CIT0003","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1053\/j.gastro.2012.04.045","article-title":"Loss of interleukin-10 signaling and infantile inflammatory bowel disease: implications for diagnosis and therapy","volume":"143","author":"Kotlarz","year":"2012","journal-title":"Gastroenterology"},{"key":"2021050415275633600_CIT0004","doi-asserted-by":"crossref","first-page":"e00129","DOI":"10.14309\/ctg.0000000000000129","article-title":"Genetic sequencing of pediatric patients identifies mutations in monogenic inflammatory bowel disease genes that translate to distinct clinical phenotypes","volume":"11","author":"Ashton","year":"2020","journal-title":"Clin Transl Gastroenterol"},{"key":"2021050415275633600_CIT0005","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1053\/j.gastro.2018.02.016","article-title":"Clinical and genomic correlates of neutrophil reactive oxygen species production in pediatric patients with Crohn\u2019s disease","volume":"154","author":"Denson","year":"2018","journal-title":"Gastroenterology"},{"key":"2021050415275633600_CIT0006","doi-asserted-by":"crossref","first-page":"56","DOI":"10.21037\/tp.2018.12.03","article-title":"Personalising medicine in inflammatory bowel disease - current and future perspectives","volume":"8","author":"Ashton","year":"2019","journal-title":"Transl Pediatr"},{"key":"2021050415275633600_CIT0007","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1038\/nm0617-788d","article-title":"Erratum: oncostatin M drives intestinal inflammation and predicts response to tumor necrosis factor-neutralizing therapy in patients with inflammatory bowel disease","volume":"23","author":"West","year":"2017","journal-title":"Nat Med"},{"key":"2021050415275633600_CIT0008","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1172\/JCI79657","article-title":"Corrigendum. Pediatric Crohn disease patients exhibit specific ileal transcriptome and microbiome signature","volume":"125","author":"Haberman","year":"2015","journal-title":"J Clin Invest"},{"key":"2021050415275633600_CIT0009","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/j.ebiom.2019.01.027","article-title":"Low TREM1 expression in whole blood predicts anti-TNF response in inflammatory bowel disease","volume":"40","author":"Verstockt","year":"2019","journal-title":"EBioMedicine"},{"key":"2021050415275633600_CIT0010","doi-asserted-by":"crossref","first-page":"e0222952","DOI":"10.1371\/journal.pone.0222952","article-title":"Concordance between gene expression in peripheral whole blood and colonic tissue in children with inflammatory bowel disease","volume":"14","author":"Palmer","year":"2019","journal-title":"PLoS One"},{"key":"2021050415275633600_CIT0011","article-title":"Targeted RNA sequencing assay to characterize gene expression and genomic alterations","volume":"2016","author":"Martin","year":"2016","journal-title":"J Vis Exp"},{"key":"2021050415275633600_CIT0012","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/S1470-2045(19)30826-5","article-title":"Pazopanib for treatment of typical solitary fibrous tumours: a multicentre, single-arm, phase 2 trial","volume":"21","author":"Martin-Broto","year":"2020","journal-title":"Lancet Oncol"},{"key":"2021050415275633600_CIT0013","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.procbio.2019.10.022","article-title":"Next generation sequencing and functional pathway analysis to understand the mechanism of action of copper-tolfenamic acid against pancreatic cancer cells","volume":"89","author":"Hurtado","year":"2020","journal-title":"Process Biochem"},{"key":"2021050415275633600_CIT0014","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1016\/j.cell.2015.05.002","article-title":"Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets","volume":"161","author":"Macosko","year":"2015","journal-title":"Cell"},{"key":"2021050415275633600_CIT0015","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1016\/j.cell.2019.08.008","article-title":"Single-cell analysis of Crohn\u2019s disease lesions identifies a pathogenic cellular module associated with resistance to anti-TNF therapy","volume":"178","author":"Martin","year":"2019","journal-title":"Cell"},{"key":"2021050415275633600_CIT0016","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1097\/MPG.0000000000000239","article-title":"ESPGHAN revised Porto criteria for the diagnosis of inflammatory bowel disease in children and adolescents","volume":"58","author":"Levine","year":"2014","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"2021050415275633600_CIT0017","volume-title":"HTG Autoimmune"},{"key":"2021050415275633600_CIT0018","first-page":"4212","article-title":"Comparison of reproducibility, accuracy, sensitivity, and specificity of miRNA quantification platforms","volume-title":"Cell Rep","author":"Godoy","year":"2019"},{"key":"2021050415275633600_CIT0019","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1093\/bib\/bbs046","article-title":"A comprehensive evaluation of normalization methods for Illumina high-throughput RNA sequencing data analysis","volume":"14","author":"Dillies","year":"2013","journal-title":"Brief Bioinform"},{"key":"2021050415275633600_CIT0020","doi-asserted-by":"crossref","first-page":"R106","DOI":"10.1186\/gb-2010-11-10-r106","article-title":"Differential expression analysis for sequence count data","volume":"11","author":"Anders","year":"2010","journal-title":"Genome Biol"},{"key":"2021050415275633600_CIT0021","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s12859-018-2053-1","article-title":"CEMiTool: a Bioconductor package for performing comprehensive modular co-expression analyses","volume":"19","author":"Russo","year":"2018","journal-title":"BMC Bioinformatics"},{"key":"2021050415275633600_CIT0022","doi-asserted-by":"crossref","first-page":"bav117","DOI":"10.1093\/database\/bav117","article-title":"HitPredict version 4: comprehensive reliability scoring of physical protein-protein interactions from more than 100 species - PubMed","volume":"2015","author":"Lopez","year":"2015","journal-title":"Database"},{"key":"2021050415275633600_CIT0023","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1186\/1471-2105-9-559","article-title":"WGCNA: an R package for weighted correlation network analysis","volume":"9","author":"Langfelder","year":"2008","journal-title":"BMC Bioinformatics"},{"key":"2021050415275633600_CIT0024","doi-asserted-by":"crossref","first-page":"W305","DOI":"10.1093\/nar\/gkp427","article-title":"ToppGene Suite for gene list enrichment analysis and candidate gene prioritization","volume":"37","author":"Chen","year":"2009","journal-title":"Nucleic Acids Res"},{"key":"2021050415275633600_CIT0025","doi-asserted-by":"crossref","first-page":"W90","DOI":"10.1093\/nar\/gkw377","article-title":"Enrichr: a comprehensive gene set enrichment analysis web server 2016 update","volume":"44","author":"Kuleshov","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"2021050415275633600_CIT0026","doi-asserted-by":"crossref","first-page":"445","DOI":"10.3389\/fphar.2019.00445","article-title":"The NCATS BioPlanet \u2013 an integrated platform for exploring the universe of cellular signaling pathways for toxicology, systems biology, and chemical genomics","volume":"10","author":"Huang","year":"2019","journal-title":"Front Pharmacol"},{"key":"2021050415275633600_CIT0027","first-page":"800631","article-title":"Resolving cellular systems by ultra-sensitive and economical single-cell transcriptome filtering","author":"Vallejo","year":"2019","journal-title":"BioRxiv"},{"key":"2021050415275633600_CIT0028","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"2021050415275633600_CIT0029","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s13059-017-1382-0","article-title":"SCANPY: large-scale single-cell gene expression data analysis","volume":"19","author":"Wolf","year":"2018","journal-title":"Genome Biol"},{"key":"2021050415275633600_CIT0030","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1186\/s13059-019-1662-y","article-title":"EmptyDrops: distinguishing cells from empty droplets in droplet-based single-cell RNA sequencing data","volume":"20","author":"Lun","year":"2019","journal-title":"Genome Biol"},{"key":"2021050415275633600_CIT0031","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s13059-016-0947-7","article-title":"Pooling across cells to normalize single-cell RNA sequencing data with many zero counts","volume":"17","author":"Lun","year":"2016","journal-title":"Genome Biol"},{"key":"2021050415275633600_CIT0032","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1093\/bioinformatics\/btz625","article-title":"BBKNN: fast batch alignment of single cell transcriptomes","volume":"36","author":"Pola\u0144ski","year":"2020","journal-title":"Bioinformatics"},{"key":"2021050415275633600_CIT0033","doi-asserted-by":"crossref","first-page":"5233","DOI":"10.1038\/s41598-019-41695-z","article-title":"From Louvain to Leiden: guaranteeing well-connected communities","volume":"9","author":"Traag","year":"2019","journal-title":"Sci Rep"},{"key":"2021050415275633600_CIT0034","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1038\/s41590-018-0276-y","article-title":"Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage","volume":"20","author":"Aran","year":"2019","journal-title":"Nat Immunol"},{"key":"2021050415275633600_CIT0035","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1016\/j.immuni.2014.12.010","article-title":"NOD1 and NOD2: signaling, host defense, and inflammatory disease","volume":"41","author":"Caruso","year":"2014","journal-title":"Immunity"},{"key":"2021050415275633600_CIT0036","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1093\/ibd\/izz316","article-title":"Th17 cells in inflammatory bowel disease: an update for the clinician","volume":"26","author":"Hou","year":"2020","journal-title":"Inflamm Bowel Dis"},{"key":"2021050415275633600_CIT0037","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1038\/jid.2010.36","article-title":"Assessment of the psoriatic transcriptome in a large sample: additional regulated genes and comparisons with in vitro models","volume":"130","author":"Gudjonsson","year":"2010","journal-title":"J Invest Dermatol"},{"key":"2021050415275633600_CIT0038","doi-asserted-by":"crossref","first-page":"1992","DOI":"10.1002\/eji.200324807","article-title":"CXCR1-binding chemokines in inflammatory bowel diseases: down-regulated IL-8\/CXCL8 production by leukocytes in Crohn\u2019s disease and selective GCP-2\/CXCL6 expression in inflamed intestinal tissue","volume":"34","author":"Gijsbers","year":"2004","journal-title":"Eur J Immunol"},{"key":"2021050415275633600_CIT0039","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1053\/j.gastro.2014.07.023","article-title":"The diagnostic approach to monogenic very early onset inflammatory bowel disease","volume":"147","author":"Uhlig","year":"2014","journal-title":"Gastroenterology"},{"key":"2021050415275633600_CIT0040","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1016\/S0140-6736(17)30317-3","article-title":"Prediction of complicated disease course for children newly diagnosed with Crohn\u2019s disease: a multicentre inception cohort study","volume":"389","author":"Kugathasan","year":"2017","journal-title":"Lancet"},{"key":"2021050415275633600_CIT0041","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1136\/gut.52.1.65","article-title":"Increased expression of interleukin 17 in inflammatory bowel disease","volume":"52","author":"Fujino","year":"2003","journal-title":"Gut"},{"key":"2021050415275633600_CIT0042","doi-asserted-by":"crossref","first-page":"690853","DOI":"10.1155\/2014\/690853","article-title":"Serum interleukin 17 levels in patients with Crohn\u2019s disease: real life data","volume":"2014","author":"Sahin","year":"2014","journal-title":"Dis Markers"},{"key":"2021050415275633600_CIT0043","doi-asserted-by":"crossref","first-page":"6536","DOI":"10.4049\/jimmunol.181.9.6536","article-title":"Differential regulation of chemokines by IL-17 in colonic epithelial cells","volume":"181","author":"Lee","year":"2008","journal-title":"J Immunol"},{"key":"2021050415275633600_CIT0044","doi-asserted-by":"crossref","first-page":"353","DOI":"10.5114\/aoms.2014.43672","article-title":"Is faecal calprotectin equally useful in all Crohn\u2019s disease locations? A prospective, comparative study","volume":"11","author":"Stawczyk-Eder","year":"2015","journal-title":"Arch Med Sci"},{"key":"2021050415275633600_CIT0045","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1053\/j.gastro.2017.10.007","article-title":"DNA methylation and transcription patterns in intestinal epithelial cells from pediatric patients with inflammatory bowel diseases differentiate disease subtypes and associate with outcome","volume":"154","author":"Howell","year":"2018","journal-title":"Gastroenterology"},{"key":"2021050415275633600_CIT0046","first-page":"1","article-title":"Immunological profiling of paediatric inflammatory bowel disease using unsupervised machine learning","author":"Coelho","year":"2020","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"2021050415275633600_CIT0047","first-page":"20143085","article-title":"Evolution of the immune system in humans from infancy to old age","volume":"282","author":"Simon","year":"2015","journal-title":"Proc Biol Sci"},{"key":"2021050415275633600_CIT0048","doi-asserted-by":"crossref","first-page":"3566","DOI":"10.1200\/JCO.2020.38.15_suppl.3566","article-title":"Platform comparison of HTG EdgeSeq and RNA-Seq for gene expression profiling of tumor tissue specimens","volume":"38","author":"Ran","year":"2020","journal-title":"J Clin Oncol"}],"container-title":["Journal of Crohn's and Colitis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/ecco-jcc\/advance-article-pdf\/doi\/10.1093\/ecco-jcc\/jjaa236\/34479977\/jjaa236.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/ecco-jcc\/article-pdf\/15\/5\/774\/37790222\/jjaa236.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/ecco-jcc\/article-pdf\/15\/5\/774\/37790222\/jjaa236.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T15:16:21Z","timestamp":1697123781000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ecco-jcc\/article\/15\/5\/774\/6000068"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,24]]},"references-count":48,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2020,11,24]]},"published-print":{"date-parts":[[2021,5,4]]}},"URL":"https:\/\/doi.org\/10.1093\/ecco-jcc\/jjaa236","relation":{},"ISSN":["1873-9946","1876-4479"],"issn-type":[{"value":"1873-9946","type":"print"},{"value":"1876-4479","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,5,4]]},"published":{"date-parts":[[2020,11,24]]}}}