{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:49:03Z","timestamp":1790804943294,"version":"4.1.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2020,8,8]],"date-time":"2020-08-08T00:00:00Z","timestamp":1596844800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100011684","name":"Crohn's and Colitis Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011684","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Gene Analysis and Integrative Morphology"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32 DK007727"],"award-info":[{"award-number":["T32 DK007727"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DK098231"],"award-info":[{"award-number":["R01 DK098231"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Cincinnati Children\u2019s Hospital Research Foundation Digestive Health Center","award":["1P30DK078392-01"],"award-info":[{"award-number":["1P30DK078392-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Ileal strictures are the major indication for resective surgery in Crohn\u2019s disease [CD]. We aimed to define ileal gene programmes present at diagnosis and linked with future stricturing behaviour during 5-year follow-up, and to identify potential small molecules to reverse these gene signatures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Antimicrobial serologies and pre-treatment ileal gene expression were assessed in a representative subset of 249 CD patients within the RISK multicentre paediatric CD inception cohort study, including 113 that are unique to this report. These data were used to define genes associated with stricturing behaviour and for model testing to predict stricturing behaviour. A bioinformatics approach to define small molecules which may reverse the stricturing gene signature was applied.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 19 of the 249 patients developed isolated B2 stricturing behaviour during follow-up, while 218 remained B1 inflammatory. Using deeper RNA sequencing than in our previous report, we have now defined an inflammatory gene signature including an oncostatin M co-expression signature, tightly associated with extra-cellular matrix [ECM] gene expression, in those who developed stricturing complications. We further computationally prioritise small molecules targeting macrophage and fibroblast activation and angiogenesis which may reverse the stricturing gene signature. A model containing ASCA and CBir1 serologies and a refined eight ECM gene set was significantly associated with stricturing development by Year 5 after diagnosis {AUC (area under the curve) (95th CI [confidence interval])\u2005=\u20050.82 [0.7\u20130.94)}.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>An ileal gene programme for macrophage and fibroblast activation is linked to stricturing complications in treatment of na\u00efve pediatric CD, and may inform novel small molecule therapeutic approaches.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ecco-jcc\/jjaa166","type":"journal-article","created":{"date-parts":[[2020,8,4]],"date-time":"2020-08-04T15:31:18Z","timestamp":1596555078000},"page":"273-286","source":"Crossref","is-referenced-by-count":30,"title":["Mucosal Inflammatory and Wound Healing Gene Programmes Reveal Targets for Stricturing Behaviour in Paediatric Crohn\u2019s Disease"],"prefix":"10.1093","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2680-1570","authenticated-orcid":false,"given":"Yael","family":"Haberman","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Cincinnati Children\u2019s Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH, USA"},{"name":"Department of Pediatrics, Sheba Medical Center, Tel-HaShomer, affiliated with the Tel-Aviv University, Tel-Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip","family":"Minar","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Cincinnati Children\u2019s Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebekah","family":"Karns","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Cincinnati Children\u2019s Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip J","family":"Dexheimer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Cincinnati Children\u2019s Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudhir","family":"Ghandikota","sequence":"additional","affiliation":[{"name":"Department of Computer Science, University of Cincinnati College of Engineering, Cincinnati, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5950-0419","authenticated-orcid":false,"given":"Samuel","family":"Tegge","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Cincinnati Children\u2019s Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, 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affiliated with the Tel-Aviv University, Tel-Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison","family":"Ta","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Cincinnati Children\u2019s Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4184-4600","authenticated-orcid":false,"given":"Thomas D","family":"Walters","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert N","family":"Baldassano","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua D","family":"Noe","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Rosh","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Goryeb Children\u2019s Hospital\/Atlantic Health, Morristown, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Markowitz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Cohen Children\u2019s Medical Center of New York, New Hyde Park, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L","family":"Dotson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Nationwide Children\u2019s Hospital, Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R","family":"Mack","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Kellermayer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Texas Children\u2019s Hospital, Baylor College School of Medicine, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne M","family":"Griffiths","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melvin B","family":"Heyman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan S","family":"Baker","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University at Buffalo, 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