{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T01:50:32Z","timestamp":1791597032524,"version":"4.3.4"},"reference-count":55,"publisher":"Elsevier BV","issue":"9","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["iScience"],"published-print":{"date-parts":[[2026,9]]},"DOI":"10.1016\/j.isci.2026.117440","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T15:10:11Z","timestamp":1788793811000},"page":"117440","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["CTLA-4 haploinsufficiency leads to late-onset autoimmune pathology in mice"],"prefix":"10.1016","volume":"29","author":[{"given":"Qingman","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhishan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yichi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lehui","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuexiao","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lize","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0171-4115","authenticated-orcid":false,"given":"Linrong","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.isci.2026.117440_bib1","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/nri1984","article-title":"Regulation of immune tolerance by anti-inflammatory neuropeptides","volume":"7","author":"Gonzalez-Rey","year":"2007","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.isci.2026.117440_bib2","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2022.972121","article-title":"Genetic basis of defects in immune tolerance underlying the development of autoimmunity","volume":"13","author":"Hocking","year":"2022","journal-title":"Front. Immunol."},{"key":"10.1016\/j.isci.2026.117440_bib3","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1046\/j.1365-3083.2001.00985.x","article-title":"Regulation of surface and intracellular expression of CTLA-4 on human peripheral T cells","volume":"54","author":"Wang","year":"2001","journal-title":"Scand. J. Immunol."},{"key":"10.1016\/j.isci.2026.117440_bib4","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/S1074-7613(02)00362-X","article-title":"The Interaction Properties of Costimulatory Molecules Revisited","volume":"17","author":"Collins","year":"2002","journal-title":"Immunity"},{"key":"10.1016\/j.isci.2026.117440_bib5","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1038\/nri3108","article-title":"The emerging role of CTLA4 as a cell-extrinsic regulator of T cell responses","volume":"11","author":"Walker","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.isci.2026.117440_bib6","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1111\/imr.12721","article-title":"What did we learn from CTLA-4 insufficiency on the human immune system?","volume":"287","author":"Mitsuiki","year":"2019","journal-title":"Immunol. Rev."},{"key":"10.1016\/j.isci.2026.117440_bib7","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2022.894648","article-title":"Cytotoxic T Lymphocyte Antigen 4 Haploinsufficiency Presenting As Refractory Celiac-Like Disease: Case Report","volume":"13","author":"Collen","year":"2022","journal-title":"Front. Immunol."},{"key":"10.1016\/j.isci.2026.117440_bib8","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1016\/j.jaci.2021.04.039","article-title":"Therapeutic options for CTLA-4 insufficiency","volume":"149","author":"Egg","year":"2022","journal-title":"J. Allergy Clin. Immunol."},{"key":"10.1016\/j.isci.2026.117440_bib9","doi-asserted-by":"crossref","first-page":"2232","DOI":"10.1002\/ppul.25373","article-title":"Pulmonary manifestations of immune dysregulation in CTLA-4 haploinsufficiency and LRBA deficiency","volume":"56","author":"Krone","year":"2021","journal-title":"Pediatr. Pulmonol."},{"key":"10.1016\/j.isci.2026.117440_bib10","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.it.2008.02.011","article-title":"CTLA-4 trafficking and surface expression","volume":"29","author":"Valk","year":"2008","journal-title":"Trends Immunol."},{"key":"10.1016\/j.isci.2026.117440_bib11","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1084\/jem.180.6.2049","article-title":"Complementarity determining region 1 (CDR1)- and CDR3-analogous regions in CTLA-4 and CD28 determine the binding to B7-1","volume":"180","author":"Peach","year":"1994","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.isci.2026.117440_bib12","doi-asserted-by":"crossref","DOI":"10.1126\/sciimmunol.aaw0902","article-title":"CTLA-4-mediated transendocytosis of costimulatory molecules primarily targets migratory dendritic cells","volume":"4","author":"Ovcinnikovs","year":"2019","journal-title":"Sci. Immunol."},{"key":"10.1016\/j.isci.2026.117440_bib13","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1038\/s41423-025-01348-w","article-title":"Dissection of the trans-endocytosis and signal inhibition functions of CTLA-4 through the study of a disease-associated Y139C mutation","volume":"22","author":"Zhao","year":"2025","journal-title":"Cell. Mol. Immunol."},{"key":"10.1016\/j.isci.2026.117440_bib14","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.jaci.2021.11.020","article-title":"The new quest in CTLA-4 insufficiency: How to immune modulate effectively?","volume":"149","author":"Westermann-Clark","year":"2022","journal-title":"J. Allergy Clin. Immunol."},{"key":"10.1016\/j.isci.2026.117440_bib15","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1182\/blood-2016-04-712612","article-title":"CHAI and LATAIE: new genetic diseases of CTLA-4 checkpoint insufficiency","volume":"128","author":"Lo","year":"2016","journal-title":"Blood"},{"key":"10.1016\/j.isci.2026.117440_bib16","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1186\/s12979-024-00489-2","article-title":"The role of autoantibodies in bridging obesity, aging, and immunosenescence","volume":"21","author":"Valentino","year":"2024","journal-title":"Immun. Ageing"},{"key":"10.1016\/j.isci.2026.117440_bib17","doi-asserted-by":"crossref","first-page":"4611","DOI":"10.1007\/s00018-016-2311-1","article-title":"Environmental factors in autoimmune diseases and their role in multiple sclerosis","volume":"73","author":"J\u00f6rg","year":"2016","journal-title":"Cell. Mol. Life Sci."},{"key":"10.1016\/j.isci.2026.117440_bib18","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1126\/science.1202947","article-title":"Trans-endocytosis of CD80 and CD86: a molecular basis for the cell extrinsic function of CTLA-4","volume":"332","author":"Qureshi","year":"2011","journal-title":"Science"},{"key":"10.1016\/j.isci.2026.117440_bib19","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1016\/j.bpj.2016.12.052","article-title":"Multiscale Modeling of Complex Formation and CD80 Depletion during Immune Synapse Development","volume":"112","author":"Sug\u00e1r","year":"2017","journal-title":"Biophys. J."},{"key":"10.1016\/j.isci.2026.117440_bib20","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/j.immuni.2025.03.004","article-title":"Soluble CTLA-4 regulates immune homeostasis and promotes resolution of inflammation by suppressing type 1 but allowing type 2 immunity","volume":"58","author":"Osaki","year":"2025","journal-title":"Immunity"},{"key":"10.1016\/j.isci.2026.117440_bib21","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.1016\/j.jaci.2018.02.055","article-title":"Phenotype, penetrance, and treatment of 133 cytotoxic T-lymphocyte antigen 4-insufficient subjects","volume":"142","author":"Schwab","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"10.1016\/j.isci.2026.117440_bib22","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/S1074-7613(00)80480-X","article-title":"Intracellular Trafficking of CTLA-4 and Focal Localization Towards Sites of TCR Engagement","volume":"4","author":"Linsley","year":"1996","journal-title":"Immunity"},{"key":"10.1016\/j.isci.2026.117440_bib23","doi-asserted-by":"crossref","first-page":"5062","DOI":"10.4049\/jimmunol.165.9.5062","article-title":"Regulation of cell surface expression of CTLA-4 by secretion of CTLA-4-containing lysosomes upon activation of CD4+ T cells","volume":"165","author":"Iida","year":"2000","journal-title":"J. Immunol."},{"key":"10.1016\/j.isci.2026.117440_bib24","doi-asserted-by":"crossref","first-page":"2282","DOI":"10.1097\/MIB.0b013e31829c32dd","article-title":"Therapeutic Evaluation of Ex Vivo-Generated Versus Natural Regulatory T-cells in a Mouse Model of Chronic Gut Inflammation","volume":"19","author":"Karlsson","year":"2013","journal-title":"Inflamm. Bowel Dis."},{"key":"10.1016\/j.isci.2026.117440_bib25","doi-asserted-by":"crossref","first-page":"29336","DOI":"10.1074\/jbc.M211973200","article-title":"IIGP1, an Interferon-\u03b3-inducible 47-kDa GTPase of the Mouse, Showing Cooperative Enzymatic Activity and GTP-dependent Multimerization","volume":"278","author":"Uthaiah","year":"2003","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.isci.2026.117440_bib26","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1002\/glia.24494","article-title":"Proteomic profiling of interferon-responsive reactive astrocytes in rodent and human","volume":"72","author":"Prakash","year":"2024","journal-title":"Glia"},{"key":"10.1016\/j.isci.2026.117440_bib27","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1084\/jem.20182031","article-title":"Interferon-induced guanylate-binding proteins: Guardians of host defense in health and disease","volume":"216","author":"Tretina","year":"2019","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.isci.2026.117440_bib28","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2021-002787","article-title":"GDF15 induces immunosuppression via CD48 on regulatory T cells in hepatocellular carcinoma","volume":"9","author":"Wang","year":"2021","journal-title":"J. Immunother. Cancer"},{"key":"10.1016\/j.isci.2026.117440_bib29","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.15252\/emmm.201303376","article-title":"Insulin-like growth factor-1 stimulates regulatory T cells and suppresses autoimmune disease","volume":"6","author":"Bilbao","year":"2014","journal-title":"EMBO Mol. Med."},{"key":"10.1016\/j.isci.2026.117440_bib30","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.celrep.2019.06.024","article-title":"Requirement of Mitochondrial Transcription Factor A in Tissue-Resident Regulatory T Cell Maintenance and Function","volume":"28","author":"Fu","year":"2019","journal-title":"Cell Rep."},{"key":"10.1016\/j.isci.2026.117440_bib31","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1002\/eji.201847935","article-title":"Helios+ and Helios- Treg subpopulations are phenotypically and functionally distinct and express dissimilar TCR repertoires","volume":"49","author":"Thornton","year":"2019","journal-title":"Eur. J. Immunol."},{"key":"10.1016\/j.isci.2026.117440_bib32","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1038\/s41590-021-00987-1","article-title":"TCF-1 controls Treg functions that regulate inflammation, CD8 T-cell cytotoxicity, and severity of colon cancer","volume":"22","author":"Osman","year":"2021","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.isci.2026.117440_bib33","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1038\/s41590-022-01289-w","article-title":"Differences in CD80 and CD86 transendocytosis reveal CD86 as a key target for CTLA-4 immune regulation","volume":"23","author":"Kennedy","year":"2022","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.isci.2026.117440_bib34","doi-asserted-by":"crossref","first-page":"5382","DOI":"10.1038\/s41467-023-40986-4","article-title":"Lrig1-expression confers suppressive function to CD4+ cells and is essential for averting autoimmunity via the Smad2\/3\/Foxp3 axis","volume":"14","author":"Moon","year":"2023","journal-title":"Nat. Commun."},{"key":"10.1016\/j.isci.2026.117440_bib35","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/s41598-024-51217-1","article-title":"FGL2 promotes tumour growth and attenuates infiltration of activated immune cells in melanoma and ovarian cancer models","volume":"14","author":"Galpin","year":"2024","journal-title":"Sci. Rep."},{"key":"10.1016\/j.isci.2026.117440_bib36","doi-asserted-by":"crossref","first-page":"13330","DOI":"10.1073\/pnas.1510045112","article-title":"IL-7R signaling in regulatory T cells maintains peripheral and allograft tolerance in mice","volume":"112","author":"Schmaler","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.isci.2026.117440_bib37","doi-asserted-by":"crossref","DOI":"10.1126\/sciimmunol.adg1487","article-title":"Lung tumor-infiltrating Treg have divergent transcriptional profiles and function linked to checkpoint blockade response","volume":"8","author":"Dykema","year":"2023","journal-title":"Sci. Immunol."},{"key":"10.1016\/j.isci.2026.117440_bib38","article-title":"Endocytic vesicles act as vehicles for glucose uptake in response to growth factor stimulation","author":"Tsutsumi","year":"2023","journal-title":"bioRxiv"},{"key":"10.1016\/j.isci.2026.117440_bib39","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2022.1054472","article-title":"Transcriptional inhibition of STAT1 functions in the nucleus alleviates Th1 and Th17 cell-mediated inflammatory diseases","volume":"13","author":"Park","year":"2022","journal-title":"Front. Immunol."},{"key":"10.1016\/j.isci.2026.117440_bib40","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1038\/cmi.2015.72","article-title":"Transcription factor IRF8 controls Th1-like regulatory T-cell function","volume":"13","author":"Lee","year":"2016","journal-title":"Cell. Mol. Immunol."},{"key":"10.1016\/j.isci.2026.117440_bib41","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1038\/s41590-023-01453-w","article-title":"IFN\u03b3-induction of TH1-like regulatory T cells controls antiviral responses","volume":"24","author":"Gocher-Demske","year":"2023","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.isci.2026.117440_bib42","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/s41423-018-0004-4","article-title":"When worlds collide: Th17 and Treg cells in cancer and autoimmunity","volume":"15","author":"Knochelmann","year":"2018","journal-title":"Cell. Mol. Immunol."},{"key":"10.1016\/j.isci.2026.117440_bib43","doi-asserted-by":"crossref","DOI":"10.1016\/j.jaut.2022.102859","article-title":"Th1-like Treg in vitiligo: An incompetent regulator in immune tolerance","volume":"131","author":"Chen","year":"2022","journal-title":"J. Autoimmun."},{"key":"10.1016\/j.isci.2026.117440_bib44","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1182\/blood-2016-10-745174","article-title":"Identifying functional defects in patients with immune dysregulation due to LRBA and CTLA-4 mutations","volume":"129","author":"Hou","year":"2017","journal-title":"Blood"},{"key":"10.1016\/j.isci.2026.117440_bib45","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1038\/nm.3746","article-title":"Autosomal dominant immune dysregulation syndrome in humans with CTLA4 mutations","volume":"20","author":"Schubert","year":"2014","journal-title":"Nat. Med."},{"key":"10.1016\/j.isci.2026.117440_bib46","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.3389\/fimmu.2019.01544","article-title":"Preponderance of CTLA4 Variation Associated With Autosomal Dominant Immune Dysregulation in the MYPPPY Motif","volume":"10","author":"Siggs","year":"2019","journal-title":"Front. Immunol."},{"key":"10.1016\/j.isci.2026.117440_bib47","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1182\/blood-2017-06-741033","article-title":"CTLA-4: a moving target in immunotherapy","volume":"131","author":"Rowshanravan","year":"2018","journal-title":"Blood"},{"key":"10.1016\/j.isci.2026.117440_bib48","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2015855118","article-title":"Primate innate immune responses to bacterial and viral pathogens reveals an evolutionary trade-off between strength and specificity","volume":"118","author":"Hawash","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.isci.2026.117440_bib49","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2022.1011646","article-title":"Do common infections trigger disease-onset or -severity in CTLA-4 insufficiency?","volume":"13","author":"Krausz","year":"2022","journal-title":"Front. Immunol."},{"key":"10.1016\/j.isci.2026.117440_bib50","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s40168-025-02028-7","article-title":"The intestinal microbiome and metabolome discern disease severity in cytotoxic T-lymphocyte-associated protein 4 deficiency","volume":"13","author":"Chandrasekaran","year":"2025","journal-title":"Microbiome"},{"key":"10.1016\/j.isci.2026.117440_bib51","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.3389\/fimmu.2017.01824","article-title":"An Activating Janus Kinase-3 Mutation Is Associated with Cytotoxic T Lymphocyte Antigen-4-Dependent Immune Dysregulation Syndrome","volume":"8","author":"Sic","year":"2017","journal-title":"Front. Immunol."},{"key":"10.1016\/j.isci.2026.117440_bib52","doi-asserted-by":"crossref","first-page":"974","DOI":"10.3390\/biom13060974","article-title":"Increased Serum Interleukin 10 Levels Are Associated with Increased Disease Activity and Increased Risk of Anti-SS-A\/Ro Antibody Positivity in Patients with Systemic Lupus Erythematosus","volume":"13","author":"Winikajtis-Burzy\u0144ska","year":"2023","journal-title":"Biomolecules"},{"key":"10.1016\/j.isci.2026.117440_bib53","doi-asserted-by":"crossref","first-page":"eabn5811","DOI":"10.1126\/scitranslmed.abn5811","article-title":"Therapeutic gene editing of T cells to correct CTLA-4 insufficiency","volume":"14","author":"Fox","year":"2022","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.isci.2026.117440_bib54","doi-asserted-by":"crossref","first-page":"7015","DOI":"10.3390\/ijms21197015","article-title":"Treg Enhancing Therapies to Treat Autoimmune Diseases","volume":"21","author":"Eggenhuizen","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.isci.2026.117440_bib55","doi-asserted-by":"crossref","first-page":"7797","DOI":"10.3390\/ijms24097797","article-title":"Enhancing Regulatory T Cells to Treat Inflammatory and Autoimmune Diseases","volume":"24","author":"Fiyouzi","year":"2023","journal-title":"Int. J. Mol. Sci."}],"container-title":["iScience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S258900422602818X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S258900422602818X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T01:16:07Z","timestamp":1791594967000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S258900422602818X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":55,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["S258900422602818X"],"URL":"https:\/\/doi.org\/10.1016\/j.isci.2026.117440","relation":{},"ISSN":["2589-0042"],"issn-type":[{"value":"2589-0042","type":"print"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"CTLA-4 haploinsufficiency leads to late-onset autoimmune pathology in mice","name":"articletitle","label":"Article Title"},{"value":"iScience","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.isci.2026.117440","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Author(s). Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"117440"}}