{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T17:50:51Z","timestamp":1786989051685,"version":"build-2736575974"},"reference-count":49,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Experimental Eye Research"],"published-print":{"date-parts":[[2025,10]]},"DOI":"10.1016\/j.exer.2025.110516","type":"journal-article","created":{"date-parts":[[2025,7,19]],"date-time":"2025-07-19T15:17:54Z","timestamp":1752938274000},"page":"110516","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"special_numbering":"C","title":["Exploring the oxidative stress-related molecular clusters in the cornea of patients with keratoconus"],"prefix":"10.1016","volume":"259","author":[{"given":"Chenfeng","family":"Gu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lumeng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuruo","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanhao","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinghao","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinmei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shihao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4643-6796","authenticated-orcid":false,"given":"Chenchen","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"4","key":"10.1016\/j.exer.2025.110516_bib1","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1111\/opo.12825","article-title":"Keratoconus in Africa: a systematic review and meta-analysis","volume":"41","author":"Akowuah","year":"2021","journal-title":"Ophthalmic Physiol. Opt.: J. Br. Coll. Ophthalmic Opt (optom)."},{"issue":"1","key":"10.1016\/j.exer.2025.110516_bib2","doi-asserted-by":"crossref","first-page":"44","DOI":"10.51329\/mehdiophthal1493","article-title":"Keratoconus: imaging modalities and management","volume":"13","author":"Alqudah","year":"2024","journal-title":"Med. Hypothesis, Discov. Innovation (MEHDI) Ophthalmol."},{"issue":"1","key":"10.1016\/j.exer.2025.110516_bib3","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s40662-022-00288-0","article-title":"Standardizing the measurement and classification of quality of life using the keratoconus end-points assessment questionnaire (KEPAQ): the ABCDEF keratoconus classification","volume":"9","author":"Balparda","year":"2022","journal-title":"Eye Vis (lond Engl)."},{"key":"10.1016\/j.exer.2025.110516_bib4","doi-asserted-by":"crossref","DOI":"10.1016\/j.redox.2023.102967","article-title":"Oxidative stress in the eye and its role in the pathophysiology of ocular diseases","volume":"68","author":"B\u00f6hm","year":"2023","journal-title":"Redox Biol."},{"issue":"D1","key":"10.1016\/j.exer.2025.110516_bib5","doi-asserted-by":"crossref","first-page":"D1227","DOI":"10.1093\/nar\/gkad1040","article-title":"DGIdb 5.0: rebuilding the drug-gene interaction database for precision medicine and drug discovery platforms","volume":"52","author":"Cannon","year":"2024","journal-title":"Nucleic Acids Res."},{"issue":"1\u20133","key":"10.1016\/j.exer.2025.110516_bib6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.schres.2006.05.023","article-title":"Schizophrenia susceptibility genes converge on interlinked pathways related to glutamatergic transmission and long-term potentiation, oxidative stress and oligodendrocyte viability","volume":"86","author":"Carter","year":"2006","journal-title":"Schizophr. Res."},{"key":"10.1016\/j.exer.2025.110516_bib7","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/978-1-4939-3578-9_5","article-title":"The gene expression omnibus database","volume":"1418","author":"Clough","year":"2016","journal-title":"Methods Mol. Biol."},{"issue":"3","key":"10.1016\/j.exer.2025.110516_bib8","doi-asserted-by":"crossref","first-page":"189","DOI":"10.3390\/nu9030189","article-title":"Pyridoxine (vitamin B6) and the glutathione peroxidase system; a link between one-carbon metabolism and antioxidation","volume":"9","author":"Dalto","year":"2017","journal-title":"Nutrients"},{"issue":"3","key":"10.1016\/j.exer.2025.110516_bib9","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.jtos.2020.03.006","article-title":"The keratoconus enigma: a review with emphasis on pathogenesis","volume":"18","author":"Ferrari","year":"2020","journal-title":"Ocul. Surf."},{"issue":"7","key":"10.1016\/j.exer.2025.110516_bib10","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1038\/eye.2015.63","article-title":"Keratoconus: an inflammatory disorder?","volume":"29","author":"Galvis","year":"2015","journal-title":"Eye (Lond)."},{"issue":"1","key":"10.1016\/j.exer.2025.110516_bib11","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/s12916-022-02296-2","article-title":"Loss of thymidine phosphorylase activity disrupts adipocyte differentiation and induces insulin-resistant lipoatrophic diabetes","volume":"20","author":"Gautheron","year":"2022","journal-title":"BMC Med."},{"key":"10.1016\/j.exer.2025.110516_bib12","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2021.744396","article-title":"Epidemiology of ocular manifestations in autoimmune disease","volume":"12","author":"Glover","year":"2021","journal-title":"Front. Immunol."},{"issue":"9","key":"10.1016\/j.exer.2025.110516_bib13","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1097\/ICO.0000000000000510","article-title":"Tear film and serum prolidase activity and oxidative stress in patients with keratoconus","volume":"34","author":"G\u00f6nc\u00fc","year":"2015","journal-title":"Cornea"},{"key":"10.1016\/j.exer.2025.110516_bib14","article-title":"PRDM1 drives human primary T cell hyporesponsiveness by altering the T cell transcriptome and epigenome","volume":"13","author":"Guo","year":"2022","journal-title":"Front. Immunol."},{"issue":"23","key":"10.1016\/j.exer.2025.110516_bib15","doi-asserted-by":"crossref","first-page":"2681","DOI":"10.3390\/cells12232681","article-title":"Animal models for the study of keratoconus","volume":"12","author":"Hadvina","year":"2023","journal-title":"Cells"},{"issue":"5","key":"10.1016\/j.exer.2025.110516_bib16","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1208\/s12249-024-02792-z","article-title":"Silk fibroin formed bioadhesive ophthalmic gel for dry eye syndrome treatment","volume":"25","author":"Hao","year":"2024","journal-title":"AAPS PharmSciTech"},{"issue":"2","key":"10.1016\/j.exer.2025.110516_bib17","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1097\/ICO.0000000000002150","article-title":"The prevalence and risk factors for keratoconus: a systematic review and meta-analysis","volume":"39","author":"Hashemi","year":"2020","journal-title":"Cornea"},{"issue":"4","key":"10.1016\/j.exer.2025.110516_bib18","doi-asserted-by":"crossref","first-page":"270","DOI":"10.3928\/1081597X-20200212-03","article-title":"A systematic review of subclinical keratoconus and forme fruste keratoconus","volume":"36","author":"Henriquez","year":"2020","journal-title":"J. Refract. Surg."},{"issue":"3","key":"10.1016\/j.exer.2025.110516_bib19","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.3390\/ijms23031255","article-title":"The pathomechanism, antioxidant biomarkers, and treatment of oxidative stress-related eye diseases","volume":"23","author":"Hsueh","year":"2022","journal-title":"Int. J. Mol. Sci."},{"issue":"1","key":"10.1016\/j.exer.2025.110516_bib20","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s13293-017-0152-8","article-title":"The protective role of estrogen and estrogen receptors in cardiovascular disease and the controversial use of estrogen therapy","volume":"8","author":"Iorga","year":"2017","journal-title":"Biol. Sex Differ."},{"issue":"Suppl. 2","key":"10.1016\/j.exer.2025.110516_bib21","doi-asserted-by":"crossref","first-page":"S57","DOI":"10.1097\/ICL.0000000000000668","article-title":"Role of matrix metalloproteinase 9 in ocular surface disorders","volume":"46","author":"Jamerson","year":"2020","journal-title":"Eye Contact Lens"},{"issue":"5","key":"10.1016\/j.exer.2025.110516_bib22","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1038\/ejhg.2017.4","article-title":"Collagen synthesis disruption and downregulation of core elements of TGF-\u03b2, hippo, and wnt pathways in keratoconus corneas","volume":"25","author":"Kabza","year":"2017","journal-title":"Eur. J. Hum. Genet.: EJHG (Eur. J. Hum. Genet.)"},{"key":"10.1016\/j.exer.2025.110516_bib23","doi-asserted-by":"crossref","first-page":"4608","DOI":"10.1038\/srep04608","article-title":"In vitro model suggests oxidative stress involved in keratoconus disease","volume":"4","author":"Karamichos","year":"2014","journal-title":"Sci. Rep."},{"issue":"3","key":"10.1016\/j.exer.2025.110516_bib24","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1097\/ICO.0000000000003362","article-title":"Effect of keratoconus stage and classification parameters on deep anterior lamellar keratoplasty outcomes","volume":"43","author":"Kemer","year":"2024","journal-title":"Cornea"},{"key":"10.1016\/j.exer.2025.110516_bib25","doi-asserted-by":"crossref","DOI":"10.1155\/2017\/7803029","article-title":"Molecular and histopathological changes associated with keratoconus","author":"Khaled","year":"2017","journal-title":"BioMed Res. Int."},{"key":"10.1016\/j.exer.2025.110516_bib26","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1007\/978-1-60761-987-1_18","article-title":"Cytoscape: software for visualization and analysis of biological networks","volume":"696","author":"Kohl","year":"2011","journal-title":"Methods Mol. Biol."},{"key":"10.1016\/j.exer.2025.110516_bib27","doi-asserted-by":"crossref","unstructured":"Lommers, K., Harzli, O.E., Kim, J., 2021. Confronting machine learning with financial research. arXiv preprint arXiv:2103.00366 IF: NA NA NA.","DOI":"10.2139\/ssrn.3788349"},{"issue":"4","key":"10.1016\/j.exer.2025.110516_bib28","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.optom.2019.11.001","article-title":"A review of corneal imaging methods for the early diagnosis of pre-clinical Keratoconus","volume":"13","author":"Masiwa","year":"2020","journal-title":"J. Opt."},{"issue":"11","key":"10.1016\/j.exer.2025.110516_bib29","first-page":"1640","article-title":"Histopathologic findings of keratoconus corneas underwent penetrating keratoplasty according to topographic measurements and keratoconus severity","volume":"10","author":"Naderan","year":"2017","journal-title":"Int. J. Ophthalmol."},{"issue":"5","key":"10.1016\/j.exer.2025.110516_bib30","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1177\/1073858412470168","article-title":"DISC1: a key lead in studying cortical development and associated brain disorders","volume":"19","author":"Narayan","year":"2013","journal-title":"Neuroscientist"},{"issue":"6","key":"10.1016\/j.exer.2025.110516_bib31","doi-asserted-by":"crossref","first-page":"e777","DOI":"10.1111\/aos.14714","article-title":"Oxidative and antioxidative stress markers in keratoconus: a systematic review and meta-analysis","volume":"99","author":"Navel","year":"2021","journal-title":"Acta Ophthalmol."},{"issue":"1","key":"10.1016\/j.exer.2025.110516_bib32","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1186\/s12886-018-0760-z","article-title":"A rabbit model of corneal ectasia generated by treatment with collagenase type II","volume":"18","author":"Qiao","year":"2018","journal-title":"BMC Ophthalmol."},{"issue":"4","key":"10.1016\/j.exer.2025.110516_bib33","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/S0039-6257(97)00119-7","volume":"42","author":"Rabinowitz","year":"1998","journal-title":"Keratoconus. Surv. Ophthalmol."},{"key":"10.1016\/j.exer.2025.110516_bib34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.artmed.2018.06.002","article-title":"A review of statistical and machine learning methods for modeling cancer risk using structured clinical data","volume":"90","author":"Richter","year":"2018","journal-title":"Artif. Intell. Med."},{"key":"10.1016\/j.exer.2025.110516_bib35","doi-asserted-by":"crossref","DOI":"10.1093\/database\/baq020","article-title":"GeneCards version 3: the human gene integrator","author":"Safran","year":"2010","journal-title":"Database"},{"issue":"2","key":"10.1016\/j.exer.2025.110516_bib36","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1167\/iovs.14-14831","article-title":"Elevated expression of matrix metalloproteinase-9 and inflammatory cytokines in keratoconus patients is inhibited by cyclosporine A","volume":"56","author":"Shetty","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"issue":"1","key":"10.1016\/j.exer.2025.110516_bib37","doi-asserted-by":"crossref","first-page":"9907","DOI":"10.1038\/s41598-020-66735-x","article-title":"RNA sequencing of corneas from two keratoconus patient groups identifies potential biomarkers and decreased NRF2-antioxidant responses","volume":"10","author":"Shinde","year":"2020","journal-title":"Sci. Rep."},{"issue":"6","key":"10.1016\/j.exer.2025.110516_bib38","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1097\/j.jcrs.0000000000001160","article-title":"Comparison of blood levels of vitamin B12, folic acid, riboflavin, and homocysteine in keratoconus and healthy subjects","volume":"49","author":"Sozer","year":"2023","journal-title":"J. Cataract Refract. Surg."},{"issue":"D1","key":"10.1016\/j.exer.2025.110516_bib39","doi-asserted-by":"crossref","first-page":"D605","DOI":"10.1093\/nar\/gkaa1074","article-title":"The STRING database in 2021: customizable protein-protein networks, and functional characterization of user-uploaded gene\/measurement sets","volume":"49","author":"Szklarczyk","year":"2021","journal-title":"Nucleic Acids Res."},{"issue":"3","key":"10.1016\/j.exer.2025.110516_bib40","doi-asserted-by":"crossref","first-page":"247","DOI":"10.2165\/00003088-200544030-00003","article-title":"Ocular pharmacokinetics and safety of ciclosporin, a novel topical treatment for dry eye","volume":"44","author":"Tang-Liu","year":"2005","journal-title":"Clin. Pharmacokinet."},{"issue":"13","key":"10.1016\/j.exer.2025.110516_bib41","first-page":"4478","article-title":"Keratoconus: the possible involvement of inflammatory cytokines in its pathogenesis. An experimental study and review of the literature","volume":"25","author":"Taurone","year":"2021","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"issue":"5","key":"10.1016\/j.exer.2025.110516_bib42","doi-asserted-by":"crossref","first-page":"352","DOI":"10.3109\/09273948.2010.498657","article-title":"Clinical review: topical ophthalmic use of cyclosporin A","volume":"18","author":"Utine","year":"2010","journal-title":"Ocul. Immunol. Inflamm."},{"issue":"11","key":"10.1016\/j.exer.2025.110516_bib43","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0224365","article-title":"Machine learning algorithm validation with a limited sample size","volume":"14","author":"Vabalas","year":"2019","journal-title":"PLoS One"},{"issue":"23","key":"10.1016\/j.exer.2025.110516_bib44","doi-asserted-by":"crossref","first-page":"2724","DOI":"10.2174\/138161209788923886","article-title":"Nanocarriers in ocular drug delivery: an update review","volume":"15","author":"Wadhwa","year":"2009","journal-title":"Current pharmaceutical design"},{"issue":"4","key":"10.1016\/j.exer.2025.110516_bib45","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.jtos.2015.04.006","article-title":"Cytokine expression in keratoconus and its corneal microenvironment: a systematic review","volume":"13","author":"Wisse","year":"2015","journal-title":"Ocul. Surf."},{"key":"10.1016\/j.exer.2025.110516_bib46","article-title":"Higher vitamin B6 dietary consumption is associated with a lower risk of glaucoma among United States adults","volume":"11","author":"Yang","year":"2024","journal-title":"Front. Nutr."},{"issue":"1","key":"10.1016\/j.exer.2025.110516_bib47","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/s41598-017-18480-x","article-title":"RNA-seq analysis and comparison of corneal epithelium in keratoconus and myopia patients","volume":"8","author":"You","year":"2018","journal-title":"Sci. Rep."},{"key":"10.1016\/j.exer.2025.110516_bib48","article-title":"Role of inflammation, immunity, and oxidative stress in hypertension: new insights and potential therapeutic targets","volume":"13","author":"Zhang","year":"2022","journal-title":"Front. Immunol."},{"issue":"5","key":"10.1016\/j.exer.2025.110516_bib49","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1177\/17085381211036549","article-title":"The protective mechanism of folic acid on hyperhomocysteinemia-related arterial injury in spontaneously hypertensive rats: folic acid against arterial inflammation","volume":"30","author":"Zhang","year":"2022","journal-title":"Vascular"}],"container-title":["Experimental Eye Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014483525002878?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014483525002878?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T10:06:05Z","timestamp":1770285965000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0014483525002878"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":49,"alternative-id":["S0014483525002878"],"URL":"https:\/\/doi.org\/10.1016\/j.exer.2025.110516","relation":{},"ISSN":["0014-4835"],"issn-type":[{"value":"0014-4835","type":"print"}],"subject":[],"published":{"date-parts":[[2025,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Exploring the oxidative stress-related molecular clusters in the cornea of patients with keratoconus","name":"articletitle","label":"Article Title"},{"value":"Experimental Eye Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.exer.2025.110516","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"110516"}}