{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T11:24:20Z","timestamp":1784201060631,"version":"3.55.0"},"reference-count":82,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T00:00:00Z","timestamp":1763683200000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK131917"],"award-info":[{"award-number":["DK131917"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK133846"],"award-info":[{"award-number":["DK133846"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000056","name":"National Institute of Nursing Research","doi-asserted-by":"publisher","award":["NR\u2010015639"],"award-info":[{"award-number":["NR\u2010015639"]}],"id":[{"id":"10.13039\/100000056","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Wound Repair Regeneration"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Diabetic foot ulcers (DFUs) are common and difficult to treat because the mechanisms behind unsuccessful responses to treatment are poorly understood. The goals of this study were to identify differences in healing and non\u2010healing human DFUs using debrided tissue samples and to identify possible biomarkers of non\u2010healing. First, DFU tissue samples collected over 12\u2009weeks of treatment from 27 subjects (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200912 healing and\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200915 non\u2010healing) were analysed using a focused panel of 227 inflammation and wound healing\u2010related human genes and 16S ribosomal RNA amplicon sequence to identify microbial species. Gene expression and correlation with microbial species differed between healing and non\u2010healing DFUs. While no individual genes analysed at the initial time point could accurately predict healing outcome 12\u2009weeks later, several 2\u2010gene ratios were highly accurate. The ratio of\n                    <jats:italic>C3AR1\/CCL22<\/jats:italic>\n                    predicted healing outcome in the discovery cohort with an area under the receiver operator characteristic (ROC) curve (AUC) of 0.96. The AUC was 0.80 when tested on 74 unique samples collected at later time points from the discovery cohort, and the AUC was 0.69 when validated in a completely independent cohort of\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200951 subjects and using quantitative reverse transcription polymerase chain reaction (qRTPCR) as a more translational method of detection. The AUC increased to 0.75 when initial wound area was included. Overall, the results suggest that differences in inflammation contribute to differential healing outcomes in human chronic DFUs, and associated biomarkers may be used to predict healing outcome to guide treatment decisions.\n                  <\/jats:p>","DOI":"10.1111\/wrr.70113","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T09:56:07Z","timestamp":1763718967000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Differential Gene Expression in Healing and Non\u2010Healing Diabetic Foot Ulcers and Discovery of Novel Ratiometric Biomarker to Predict Healing Outcome"],"prefix":"10.1111","volume":"33","author":[{"given":"Jessica M.","family":"Eager","sequence":"first","affiliation":[{"name":"School of Biomedical Engineering, Science, and Health Systems Drexel University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Cortes\u2010Troncoso","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, Science, and Health Systems Drexel University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay","family":"Kalan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biomedical Sciences, Faculty of Health Sciences McMaster University  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Campbell","sequence":"additional","affiliation":[{"name":"Departments of Dermatology and Microbiology, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Department of Biology Haverford College  Haverford Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Northwell Health, New Hyde Park  New York New York USA"},{"name":"Donald and Barbara Zucker School of Medicine  New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Weingarten","sequence":"additional","affiliation":[{"name":"Department of Surgery Drexel University College of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Grice","sequence":"additional","affiliation":[{"name":"Departments of Dermatology and Microbiology, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alisha","family":"Oropallo","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Northwell Health, New Hyde Park  New York New York USA"},{"name":"Donald and Barbara Zucker School of Medicine  New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Margolis","sequence":"additional","affiliation":[{"name":"Departments of Dermatology and Biostatistics, Epidemiology and Biostatistics, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmet","family":"Sacan","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, Science, and Health Systems Drexel University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kara L.","family":"Spiller","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, Science, and Health Systems Drexel University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,21]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc17\u20101836"},{"key":"e_1_2_10_3_1","unstructured":"http:\/\/www.diabetes.org\/diabetes\u2010basics\/statistics\/."},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742\u2010481X.2007.00392.x"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc13\u20102176"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/iwj.12816"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmra1615439"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11892\u2010018\u20100970\u2010z"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010020\u201018276\u20100"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.2337\/db13\u20100927"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5309.75"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3009337"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2017.05.010"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.06.008"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2011.06.016"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.2337\/db12\u20101450"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009539"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.2147\/JPR.S164493"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125\u2010013\u20102885\u20101"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.prs.0000222737.09322.77"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a041218"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579\u2010024\u201001035\u2010z"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40257\u2010020\u201000536\u2010w"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.2337\/db12\u20100771"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2016.08.009"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11908\u2010023\u201000822\u20108"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2019.03.006"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2062"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.12.033"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1524\u2010475X.2012.00843.x"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1177\/19322968221121152"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2015.30"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.2217\/bmm\u20102018\u20100339"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464\u20105491.2008.02414.x"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423\u2010019\u20100233\u20101"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.2337\/db15\u20100863"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/2695436"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125\u2010014\u20103300\u20102"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdiacomp.2012.12.007"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1910"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2934"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2017.02.006"},{"key":"e_1_2_10_43_1","volume-title":"Reading and Understanding Multivariate Statistics","author":"Grimm L. G.","year":"1994"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4370"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1109\/5254.708428"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.26.6.1696"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3700303"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1524\u2010475X.2012.00849.x"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.26.6.1879"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1089\/wound.2024.0095"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1089\/wound.2021.0073"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.25.10.1835"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2014.10.017"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2025.113943"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsbiomaterials.1c01190"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1097\/SAP.0000000000003163"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00216\u2010020\u201002594\u20109"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1752\u20108062.2008.00075.x"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01875"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201027801\u20108"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2022.951491"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e14470"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010017\u201001526\u2010z"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073\u2010023\u201001250\u2010y"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44161\u2010024\u201000428\u2010w"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.09.005"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20170277"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.121.055888"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2019.07.015"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2018.10.039"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202314500"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1039\/c7ib00018a"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2011.11.031"},{"key":"e_1_2_10_74_1","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.2319"},{"key":"e_1_2_10_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2016.01.016"},{"key":"e_1_2_10_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.f.303"},{"key":"e_1_2_10_77_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq461"},{"key":"e_1_2_10_78_1","doi-asserted-by":"publisher","DOI":"10.1128\/aem.00062\u201007"},{"key":"e_1_2_10_79_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp636"},{"key":"e_1_2_10_80_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.112730.110"},{"key":"e_1_2_10_81_1","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbaa163"},{"key":"e_1_2_10_82_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btac757"},{"key":"e_1_2_10_83_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"}],"container-title":["Wound Repair and Regeneration"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/wrr.70113","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T16:32:52Z","timestamp":1767025972000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/wrr.70113"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11]]},"references-count":82,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1111\/wrr.70113"],"URL":"https:\/\/doi.org\/10.1111\/wrr.70113","archive":["Portico"],"relation":{},"ISSN":["1067-1927","1524-475X"],"issn-type":[{"value":"1067-1927","type":"print"},{"value":"1524-475X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11]]},"assertion":[{"value":"2025-08-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70113"}}