{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T17:27:04Z","timestamp":1793035624940,"version":"4.5.0"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T00:00:00Z","timestamp":1778889600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":54,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/100000025","name":"U.S. Department of Health & Human Services | NIH | National Institute of Mental Health","doi-asserted-by":"publisher","award":["R01 MH119165"],"award-info":[{"award-number":["R01 MH119165"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"U.S. Department of Health & Human Services | NIH | National Institute of Mental Health","doi-asserted-by":"publisher","award":["R01 AG084710"],"award-info":[{"award-number":["R01 AG084710"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002975","name":"Dainippon Sumitomo Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002975","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Transl Psychiatry"],"DOI":"10.1038\/s41398-026-04067-6","type":"journal-article","created":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T14:44:35Z","timestamp":1778942675000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Postoperative delirium in hip fracture patients linked to epigenetic alterations in inflammatory and immune pathways: a genome-wide DNA methylation study"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2593-7118","authenticated-orcid":false,"given":"Tomoteru","family":"Seki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shota","family":"Nishitani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshitaka","family":"Nishizawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyosuke","family":"Yamanishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiyoshi","family":"Shimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuyoshi","family":"Nishiguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6026-8664","authenticated-orcid":false,"given":"Takaya","family":"Ishii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bun","family":"Aoyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Therese Anne","family":"Santiago","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8374-782X","authenticated-orcid":false,"given":"Nathan James","family":"Phuong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nipun","family":"Gorantla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hieu Dinh","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Takeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Kameoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5248-1289","authenticated-orcid":false,"given":"Takeshi","family":"Inoue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Sugiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Ueda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3881-8997","authenticated-orcid":false,"given":"Takehiko","family":"Yamanashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6129-2789","authenticated-orcid":false,"given":"Gen","family":"Shinozaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,16]]},"reference":[{"issue":"11","key":"4067_CR1","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1056\/NEJMra052321","volume":"354","author":"SK Inouye","year":"2006","unstructured":"Inouye SK. Delirium in older persons. N Engl J Med. 2006;354(11):1157\u201365.","journal-title":"N Engl J Med"},{"issue":"4","key":"4067_CR2","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1038\/nrneurol.2009.24","volume":"5","author":"TG Fong","year":"2009","unstructured":"Fong TG, Tulebaev SR, Inouye SK. Delirium in elderly adults: diagnosis, prevention and treatment. Nat Rev Neurol. 2009;5(4):210\u201320.","journal-title":"Nat Rev Neurol"},{"issue":"9920","key":"4067_CR3","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1016\/S0140-6736(13)60688-1","volume":"383","author":"SK Inouye","year":"2014","unstructured":"Inouye SK, Westendorp RGJ, Saczynski JS. Delirium in elderly people. The Lancet. 2014;383(9920):911\u201322.","journal-title":"The Lancet"},{"issue":"4","key":"4067_CR4","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1189\/jlb.0208108","volume":"84","author":"RN Dilger","year":"2008","unstructured":"Dilger RN, Johnson RW. Aging, microglial cell priming, and the discordant central inflammatory response to signals from the peripheral immune system. Journal of Leukocyte Biology. 2008;84(4):932\u20139.","journal-title":"Journal of Leukocyte Biology"},{"key":"4067_CR5","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1016\/j.bbi.2017.01.010","volume":"62","author":"L Schreuder","year":"2017","unstructured":"Schreuder L, Eggen BJ, Biber K, Schoemaker RG, Laman JD, de Rooij SE. Pathophysiological and behavioral effects of systemic inflammation in aged and diseased rodents with relevance to delirium: A systematic review. Brain Behav Immun. 2017;62:362\u201381.","journal-title":"Brain Behav Immun"},{"issue":"7370","key":"4067_CR6","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1038\/nature10523","volume":"478","author":"HJ Kang","year":"2011","unstructured":"Kang HJ, Kawasawa YI, Cheng F, Zhu Y, Xu X, Li M, et al. Spatio-temporal transcriptome of the human brain. Nature. 2011;478(7370):483\u20139.","journal-title":"Nature"},{"key":"4067_CR7","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.mad.2015.02.002","volume":"151","author":"M Zampieri","year":"2015","unstructured":"Zampieri M, Ciccarone F, Calabrese R, Franceschi C, B\u00fcrkle A, Caiafa P. Reconfiguration of DNA methylation in aging. Mechanisms of Ageing and Development. 2015;151:60\u201370.","journal-title":"Mechanisms of Ageing and Development"},{"issue":"10","key":"4067_CR8","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1038\/nbt.1685","volume":"28","author":"A Portela","year":"2010","unstructured":"Portela A, Esteller M. Epigenetic modifications and human disease. Nat Biotechnol. 2010;28(10):1057\u201368.","journal-title":"Nat Biotechnol"},{"issue":"2","key":"4067_CR9","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1016\/j.ajhg.2011.12.020","volume":"90","author":"S Numata","year":"2012","unstructured":"Numata S, Ye T, Hyde TM, Guitart-Navarro X, Tao R, Wininger M, et al. DNA methylation signatures in development and aging of the human prefrontal cortex. Am J Hum Genet. 2012;90(2):260\u201372.","journal-title":"Am J Hum Genet"},{"issue":"9","key":"4067_CR10","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2013-14-9-r102","volume":"14","author":"K Day","year":"2013","unstructured":"Day K, Waite LL, Thalacker-Mercer A, West A, Bamman MM, Brooks JD, et al. Differential DNA methylation with age displays both common and dynamic features across human tissues that are influenced by CpG landscape. Genome Biol. 2013;14(9):R102.","journal-title":"Genome Biol"},{"issue":"4","key":"4067_CR11","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1016\/j.cell.2016.07.050","volume":"166","author":"P Sen","year":"2016","unstructured":"Sen P, Shah PP, Nativio R, Berger SL. Epigenetic Mechanisms of Longevity and Aging. Cell. 2016;166(4):822\u201339.","journal-title":"Cell"},{"key":"4067_CR12","doi-asserted-by":"publisher","first-page":"311","DOI":"10.3389\/fnagi.2018.00311","volume":"10","author":"G Shinozaki","year":"2018","unstructured":"Shinozaki G, Braun PR, Hing BWQ, Ratanatharathorn A, Klisares MJ, Duncan GN, et al. Epigenetics of delirium and aging: potential role of DNA methylation change on cytokine genes in glia and blood along with aging. Front Aging Neurosci. 2018;10:311.","journal-title":"Front Aging Neurosci"},{"key":"4067_CR13","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.jpsychires.2020.06.005","volume":"129","author":"T Saito","year":"2020","unstructured":"Saito T, Toda H, Duncan GN, Jellison SS, Yu T, Klisares MJ, et al. Epigenetics of neuroinflammation: Immune response, inflammatory response and cholinergic synaptic involvement evidenced by genome-wide DNA methylation analysis of delirious inpatients. J Psychiatr Res. 2020;129:61\u20135.","journal-title":"J Psychiatr Res"},{"issue":"1","key":"4067_CR14","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-021-01752-6","volume":"11","author":"T Yamanashi","year":"2021","unstructured":"Yamanashi T, Nagao T, Wahba NE, Marra PS, Crutchley KJ, Meyer AA, et al. DNA methylation in the inflammatory genes after neurosurgery and diagnostic ability of post-operative delirium. Transl Psychiatry. 2021;11(1):627.","journal-title":"Transl Psychiatry"},{"issue":"1","key":"4067_CR15","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1111\/pcn.13495","volume":"77","author":"T Yamanashi","year":"2023","unstructured":"Yamanashi T, Crutchley KJ, Wahba NE, Nagao T, Marra PS, Akers CC, et al. The genome-wide DNA methylation profiles among neurosurgery patients with and without post-operative delirium. Psychiatry Clin Neurosci. 2023;77(1):48\u201355.","journal-title":"Psychiatry Clin Neurosci"},{"key":"4067_CR16","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/j.jpsychires.2024.07.013","volume":"177","author":"Y Nishizawa","year":"2024","unstructured":"Nishizawa Y, Yamanashi T, Nishiguchi T, Kajitani N, Miura A, Matsuo R, et al. The Genome-wide DNA methylation changes in gastrointestinal surgery patients with and without postoperative delirium: Evidence of immune process in its pathophysiology. J Psychiatr Res. 2024;177:249\u201355.","journal-title":"J Psychiatr Res"},{"issue":"21","key":"4067_CR17","doi-asserted-by":"publisher","first-page":"2703","DOI":"10.1001\/jama.286.21.2703","volume":"286","author":"EW Ely","year":"2001","unstructured":"Ely EW, Inouye SK, Bernard GR, Gordon S, Francis J, May L, et al. Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU). Jama. 2001;286(21):2703\u201310.","journal-title":"Jama"},{"issue":"2","key":"4067_CR18","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1176\/jnp.13.2.229","volume":"13","author":"PT Trzepacz","year":"2001","unstructured":"Trzepacz PT, Mittal D, Torres R, Kanary K, Norton J, Jimerson N. Validation of the Delirium Rating Scale-revised-98: comparison with the delirium rating scale and the cognitive test for delirium. J Neuropsychiatry Clin Neurosci. 2001;13(2):229\u201342.","journal-title":"J Neuropsychiatry Clin Neurosci"},{"issue":"2","key":"4067_CR19","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1111\/j.1532-5415.2005.53120.x","volume":"53","author":"SK Inouye","year":"2005","unstructured":"Inouye SK, Leo-Summers L, Zhang Y, Bogardus ST Jr., Leslie DL, Agostini JV. A chart-based method for identification of delirium: validation compared with interviewer ratings using the confusion assessment method. J Am Geriatr Soc. 2005;53(2):312\u20138.","journal-title":"J Am Geriatr Soc"},{"issue":"3","key":"4067_CR20","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1038\/bmt.2012.244","volume":"48","author":"Y Kanda","year":"2013","unstructured":"Kanda Y. Investigation of the freely available easy-to-use software \u2018EZR\u2019 for medical statistics. Bone Marrow Transplant. 2013;48(3):452\u20138.","journal-title":"Bone Marrow Transplant"},{"key":"4067_CR21","volume-title":"R: A Language and Environment for Statistical Computing","author":"Team RC.","year":"2019","unstructured":"Team RC. R: A Language and Environment for Statistical Computing. Vienna, Austria: R Foundation for Statistical Computing; 2019."},{"issue":"3","key":"4067_CR22","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1093\/bioinformatics\/btt684","volume":"30","author":"TJ Morris","year":"2014","unstructured":"Morris TJ, Butcher LM, Feber A, Teschendorff AE, Chakravarthy AR, Wojdacz TK, et al. ChAMP: 450k chip analysis methylation pipeline. Bioinformatics. 2014;30(3):428\u201330.","journal-title":"Bioinformatics"},{"issue":"24","key":"4067_CR23","doi-asserted-by":"publisher","first-page":"3982","DOI":"10.1093\/bioinformatics\/btx513","volume":"33","author":"Y Tian","year":"2017","unstructured":"Tian Y, Morris TJ, Webster AP, Yang Z, Beck S, Feber A, et al. ChAMP: updated methylation analysis pipeline for Illumina BeadChips. Bioinformatics. 2017;33(24):3982\u20134.","journal-title":"Bioinformatics"},{"issue":"10","key":"4067_CR24","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1093\/bioinformatics\/btu049","volume":"30","author":"MJ Aryee","year":"2014","unstructured":"Aryee MJ, Jaffe AE, Corrada-Bravo H, Ladd-Acosta C, Feinberg AP, Hansen KD, et al. Minfi: a flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays. Bioinformatics. 2014;30(10):1363\u20139.","journal-title":"Bioinformatics"},{"issue":"4","key":"4067_CR25","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1093\/bioinformatics\/btw691","volume":"33","author":"JP Fortin","year":"2017","unstructured":"Fortin JP, Triche TJ Jr., Hansen KD. Preprocessing, normalization and integration of the Illumina HumanMethylationEPIC array with minfi. Bioinformatics. 2017;33(4):558\u201360.","journal-title":"Bioinformatics"},{"issue":"2","key":"4067_CR26","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1093\/bioinformatics\/bts680","volume":"29","author":"AE Teschendorff","year":"2013","unstructured":"Teschendorff AE, Marabita F, Lechner M, Bartlett T, Tegner J, Gomez-Cabrero D, et al. A beta-mixture quantile normalization method for correcting probe design bias in Illumina Infinium 450 k DNA methylation data. Bioinformatics. 2013;29(2):189\u201396.","journal-title":"Bioinformatics"},{"issue":"1","key":"4067_CR27","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1093\/biostatistics\/kxj037","volume":"8","author":"WE Johnson","year":"2007","unstructured":"Johnson WE, Li C, Rabinovic A. Adjusting batch effects in microarray expression data using empirical Bayes methods. Biostatistics. 2007;8(1):118\u201327.","journal-title":"Biostatistics"},{"issue":"10","key":"4067_CR28","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2013-14-10-r115","volume":"14","author":"S Horvath","year":"2013","unstructured":"Horvath S. DNA methylation age of human tissues and cell types. Genome Biol. 2013;14(10):3156.","journal-title":"Genome Biol"},{"key":"4067_CR29","unstructured":"Horvath S DNA methylation age calculator 2019 [Available from: https:\/\/dnamage.genetics.ucla.edu\/home."},{"issue":"1","key":"4067_CR30","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-13-86","volume":"13","author":"EA Houseman","year":"2012","unstructured":"Houseman EA, Accomando WP, Koestler DC, Christensen BC, Marsit CJ, Nelson HH, et al. DNA methylation arrays as surrogate measures of cell mixture distribution. BMC Bioinformatics. 2012;13(1):86.","journal-title":"BMC Bioinformatics"},{"issue":"11","key":"4067_CR31","doi-asserted-by":"publisher","first-page":"1138","DOI":"10.1038\/nmeth.3115","volume":"11","author":"Y Assenov","year":"2014","unstructured":"Assenov Y, M\u00fcller F, Lutsik P, Walter J, Lengauer T, Bock C. Comprehensive analysis of DNA methylation data with RnBeads. Nat Methods. 2014;11(11):1138\u201340.","journal-title":"Nat Methods"},{"issue":"7","key":"4067_CR32","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkv007","volume":"43","author":"ME Ritchie","year":"2015","unstructured":"Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;43(7):e47.","journal-title":"Nucleic Acids Res"},{"issue":"2","key":"4067_CR33","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1093\/bioinformatics\/btv560","volume":"32","author":"B Phipson","year":"2016","unstructured":"Phipson B, Maksimovic J, Oshlack A. missMethyl: an R package for analyzing data from Illumina\u2019s HumanMethylation450 platform. Bioinformatics. 2016;32(2):286\u20138.","journal-title":"Bioinformatics"},{"issue":"1","key":"4067_CR34","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-021-02388-x","volume":"22","author":"J Maksimovic","year":"2021","unstructured":"Maksimovic J, Oshlack A, Phipson B. Gene set enrichment analysis for genome-wide DNA methylation data. Genome Biology. 2021;22(1):173.","journal-title":"Genome Biology"},{"key":"4067_CR35","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13561","volume":"7","author":"SV Iyer","year":"2016","unstructured":"Iyer SV, Ranjan A, Elias HK, Parrales A, Sasaki H, Roy BC, et al. Genome-wide RNAi screening identifies TMIGD3 isoform1 as a suppressor of NF-\u03baB and osteosarcoma progression. Nat Commun. 2016;7:13561.","journal-title":"Nat Commun"},{"issue":"7-8","key":"4067_CR36","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1016\/j.drudis.2011.10.007","volume":"17","author":"P Fishman","year":"2012","unstructured":"Fishman P, Bar-Yehuda S, Liang BT, Jacobson KA. Pharmacological and therapeutic effects of A3 adenosine receptor agonists. Drug Discov Today. 2012;17(7-8):359\u201366.","journal-title":"Drug Discov Today"},{"issue":"4","key":"4067_CR37","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1002\/med.21456","volume":"38","author":"KA Jacobson","year":"2018","unstructured":"Jacobson KA, Merighi S, Varani K, Borea PA, Baraldi S, Aghazadeh Tabrizi M, et al. A(3) Adenosine Receptors as Modulators of Inflammation: From Medicinal Chemistry to Therapy. Med Res Rev. 2018;38(4):1031\u201372.","journal-title":"Med Res Rev"},{"issue":"4","key":"4067_CR38","doi-asserted-by":"publisher","first-page":"462","DOI":"10.18632\/oncotarget.497","volume":"3","author":"D Jjingo","year":"2012","unstructured":"Jjingo D, Conley AB, Yi SV, Lunyak VV, Jordan IK. On the presence and role of human gene-body DNA methylation. Oncotarget. 2012;3(4):462\u201374.","journal-title":"Oncotarget"},{"issue":"4","key":"4067_CR39","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1016\/j.ccr.2014.07.028","volume":"26","author":"X Yang","year":"2014","unstructured":"Yang X, Han H, De Carvalho DD, Lay FD, Jones PA, Liang G. Gene body methylation can alter gene expression and is a therapeutic target in cancer. Cancer Cell. 2014;26(4):577\u201390.","journal-title":"Cancer Cell"},{"issue":"19","key":"4067_CR40","doi-asserted-by":"publisher","first-page":"2954","DOI":"10.3390\/cells11192954","volume":"11","author":"K Rump","year":"2022","unstructured":"Rump K, Adamzik M. Epigenetic mechanisms of postoperative cognitive impairment induced by anesthesia and neuroinflammation. Cells. 2022;11(19):2954.","journal-title":"Cells"},{"issue":"4","key":"4067_CR41","doi-asserted-by":"publisher","DOI":"10.1111\/acel.14458","volume":"24","author":"P Cong","year":"2025","unstructured":"Cong P, Huang X, Zhang Q, He M, Wan H, Wu Q, et al. DNMT3a deficiency contributes to anesthesia\/surgery-induced synaptic dysfunction and cognitive impairment in aged mice. Aging Cell. 2025;24(4):e14458.","journal-title":"Aging Cell"},{"issue":"4","key":"4067_CR42","doi-asserted-by":"publisher","first-page":"1226","DOI":"10.1016\/j.bja.2025.12.046","volume":"136","author":"M Thedim","year":"2026","unstructured":"Thedim M, Li H, Formanek A, Wiener-Kronish J, Saxena R, Vacas S. Genetic and epigenetic insights into perioperative neurocognitive disorders: a narrative review. Br J Anaesth. 2026;136(4):1226\u201334.","journal-title":"Br J Anaesth"},{"issue":"4","key":"4067_CR43","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1001\/jamasurg.2018.5093","volume":"154","author":"CA Austin","year":"2019","unstructured":"Austin CA, O\u2019Gorman T, Stern E, Emmett D, St\u00fcrmer T, Carson S, et al. Association between postoperative delirium and long-term cognitive function after major nonemergent surgery. JAMA Surgery. 2019;154(4):328\u201334.","journal-title":"JAMA Surgery"},{"issue":"1","key":"4067_CR44","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-62262-x","volume":"10","author":"R Sadahiro","year":"2020","unstructured":"Sadahiro R, Knight B, James F, Hannon E, Charity J, Daniels IR, et al. Major surgery induces acute changes in measured DNA methylation associated with immune response pathways. Sci Rep. 2020;10(1):5743.","journal-title":"Sci Rep"},{"issue":"1","key":"4067_CR45","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1186\/s12987-020-00230-3","volume":"17","author":"H Kadry","year":"2020","unstructured":"Kadry H, Noorani B, Cucullo L. A blood-brain barrier overview on structure, function, impairment, and biomarkers of integrity. Fluids Barriers CNS. 2020;17(1):69.","journal-title":"Fluids Barriers CNS"},{"key":"4067_CR46","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2022.1013933","volume":"15","author":"J Yang","year":"2022","unstructured":"Yang J, Ran M, Li H, Lin Y, Ma K, Yang Y, et al. New insight into neurological degeneration: Inflammatory cytokines and blood-brain barrier. Front Mol Neurosci. 2022;15:1013933.","journal-title":"Front Mol Neurosci"},{"issue":"2","key":"4067_CR47","doi-asserted-by":"publisher","first-page":"e370","DOI":"10.1016\/j.bja.2022.05.025","volume":"130","author":"T Yang","year":"2023","unstructured":"Yang T, Velagapudi R, Kong C, Ko U, Kumar V, Brown P, et al. Protective effects of omega-3 fatty acids in a blood-brain barrier-on-chip model and on postoperative delirium-like behaviour in mice. Br J Anaesth. 2023;130(2):e370\u2013e80.","journal-title":"Br J Anaesth"},{"issue":"8056","key":"4067_CR48","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1038\/s41586-025-08589-9","volume":"639","author":"SM Shi","year":"2025","unstructured":"Shi SM, Suh RJ, Shon DJ, Garcia FJ, Buff JK, Atkins M, et al. Glycocalyx dysregulation impairs blood-brain barrier in ageing and disease. Nature. 2025;639(8056):985\u201394.","journal-title":"Nature"},{"issue":"6","key":"4067_CR49","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1002\/ana.26771","volume":"94","author":"MJ Devinney","year":"2023","unstructured":"Devinney MJ, Wong MK, Wright MC, Marcantonio ER, Terrando N, Browndyke JN, et al. Role of blood-brain barrier dysfunction in delirium following non-cardiac surgery in older adults. Ann Neurol. 2023;94(6):1024\u201335.","journal-title":"Ann Neurol"},{"key":"4067_CR50","unstructured":"Association AP. Diagnostic and statistical manual of mental disorders. Text revision. 2000."}],"container-title":["Translational Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41398-026-04067-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41398-026-04067-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41398-026-04067-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T01:03:12Z","timestamp":1783558992000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41398-026-04067-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,16]]},"references-count":50,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["4067"],"URL":"https:\/\/doi.org\/10.1038\/s41398-026-04067-6","relation":{},"ISSN":["2158-3188"],"issn-type":[{"value":"2158-3188","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,16]]},"assertion":[{"value":"10 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 April 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 April 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 May 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"G.S. is a co-founder of Delight Health Inc and has pending patents: \u201cNon-invasive device for predicting and screening delirium,\u201d PCT application no. PCT\/US2016\/064937 and US provisional patent no. 62\/263,325; \u201cPrediction of patient outcomes with a novel electroencephalography device,\u201d US provisional patent no. 62\/829,411; and \u201cEpigenetic Biomarker of Delirium Risk,\u201d PCT application no. PCT\/US19\/51276 and US provisional patent no. 62\/731,599. T.I. is employed by Sumitomo Pharma Co., Ltd, and currently affiliated with RACTHERA Co., Ltd. The other authors declare no actual or potential conflicts of interest associated with this study.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"All methods were performed in accordance with the relevant guidelines and regulations. This study was approved by the Institutional Review Boards of Stanford University (study approval no.: 63791) and Kameda Medical Center (study approval no.: 19-171-230331). Written informed consent was obtained from all participants.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}],"article-number":"349"}}