{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T12:17:19Z","timestamp":1788351439039,"version":"build-2803163510"},"reference-count":52,"publisher":"BMJ","issue":"8","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"unspecified","delay-in-days":11,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Research Project of Jiangsu Cancer Hospital","award":["ZJ202202"],"award-info":[{"award-number":["ZJ202202"]}]},{"name":"Yishan Research Project of Jiangsu Cancer Hospital","award":["YSZD202405"],"award-info":[{"award-number":["YSZD202405"]}]},{"name":"Qunfeng Project of Jiangsu Cancer Hospital","award":["No.GFXK202501"],"award-info":[{"award-number":["No.GFXK202501"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,7,23]]},"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Acquired resistance limits the durability of programmed cell death protein-1 (PD-1) blockade in lung adenocarcinoma, yet the tumor-intrinsic programs and immune circuits that drive acquired resistance relapse remain poorly defined. The purpose of this study was to identify tumor-intrinsic mediators of acquired resistance and determine how they remodel antitumor immunity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>An orthotopic bioluminescence-tracked Lewis lung carcinoma (LLC1) lung adenocarcinoma model was established in immunocompetent mice treated with anti-PD-1. Tumor-intrinsic regulators were identified by an in vivo genome-wide CRISPR loss-of-function screen and validated using inducible tetracycline-off knockdown. Prostaglandin E2 (PGE2) signaling was interrogated through tumor-cell Ptgs2 knockdown\/deletion, 16,16-dimethyl PGE2 administration, selective EP2\/EP4 antagonists, and celecoxib treatment. Natural killer (NK)-cell function was analyzed by flow cytometry, immunofluorescence, RNA sequencing, cAMP measurement, calcium flux assays, mouse and human NK-cell co-culture cytotoxicity assays, and NK-cell adoptive transfer. Celecoxib was used to evaluate the therapeutic potential of pharmacologic PGE2 blockade in vivo. Public immunotherapy datasets were analyzed to assess the clinical relevance of PTGS2.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The orthotopic LLC1 model captured key features of heterogeneous anti-PD-1 responses, including relapse after initial regression. The CRISPR screen identified Ptgs2 as a key driver of acquired resistance. Tumor-derived PGE2 progressively increased in resistant tumors, and its genetic silencing overcame resistance by restoring NK-cell infiltration and function. Mechanistically, PGE2 signaled through EP2\/EP4 receptors to elevate cAMP and induce CREM, thereby suppressing NK-cell cytotoxicity and cytokine production. This axis was validated in human NK cells. Pharmacologic inhibition of cyclooxygenase-2 with celecoxib reversed acquired resistance, an effect abrogated by NK-cell depletion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Tumor-derived PGE2 is an important contributor to acquired resistance to PD-1 blockade in lung adenocarcinoma. Therapeutic disruption of the EP2\/EP4\u2013cAMP\u2013CREM axis restores NK-cell function and overcomes acquired resistance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-014673","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T12:40:21Z","timestamp":1786538421000},"page":"e014673","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["PGE2-mediated NK cell reprogramming drives acquired immunotherapy resistance in lung adenocarcinoma"],"prefix":"10.1136","volume":"14","author":[{"given":"Yajing","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Oncology, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0494-9269","authenticated-orcid":false,"given":"Chen","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Oncology, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sitong","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Oncology, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7951-0123","authenticated-orcid":false,"given":"Shaodi","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Oncology, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Oncology, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyue","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Oncology, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Oncology, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renrui","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Oncology, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Oncology, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuejuan","family":"Ma","sequence":"additional","affiliation":[{"name":"Chengdu Women and Children\u2019s Central Hospital, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Oncology, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muxi","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Oncology, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9708-6098","authenticated-orcid":false,"given":"Bo","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Oncology, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"2026090204350954000_14.8.e014673.1","doi-asserted-by":"crossref","DOI":"10.3390\/cancers17132244","article-title":"Emerging Techniques of Translational Research in Immuno-Oncology: A Focus on Non-Small Cell Lung Cancer","volume":"17","author":"Guardamagna","year":"2025","journal-title":"Cancers (Basel)"},{"key":"2026090204350954000_14.8.e014673.2","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a037895","article-title":"Tumor Immunology and Immunotherapy of Non-Small-Cell Lung Cancer","volume":"12","author":"Cascone","year":"2022","journal-title":"Cold Spring Harb Perspect Med"},{"key":"2026090204350954000_14.8.e014673.3","article-title":"Role of the TME in immune checkpoint blockade resistance of non-small cell lung cancer","volume":"7","author":"Dai","year":"2024","journal-title":"Cancer Drug Resist"},{"key":"2026090204350954000_14.8.e014673.4","doi-asserted-by":"crossref","first-page":"218145","DOI":"10.1016\/j.canlet.2025.218145","article-title":"Current advances and future directions of combined ICIs and TILs in solid tumors","volume":"636","author":"Wang","year":"2026","journal-title":"Cancer Lett"},{"key":"2026090204350954000_14.8.e014673.5","doi-asserted-by":"crossref","unstructured":"Zhang Y , Liu Z . Insights into the Mechanisms of Immune\u2010Checkpoint Inhibitors Gained from Spatiotemporal Dynamics of the Tumor Microenvironment. Advanced Science 2025;12. doi:10.1002\/advs.202508692","DOI":"10.1002\/advs.202508692"},{"key":"2026090204350954000_14.8.e014673.6","doi-asserted-by":"publisher","DOI":"10.12968\/hmed.2024.0713"},{"key":"2026090204350954000_14.8.e014673.7","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2025-013110","article-title":"Categorizing immunotherapy resistance mechanisms in non-small cell lung cancer: how can we perform better?","volume":"13","author":"van der Geest","year":"2025","journal-title":"J Immunother Cancer"},{"key":"2026090204350954000_14.8.e014673.8","doi-asserted-by":"crossref","DOI":"10.1183\/16000617.0200-2023","article-title":"Complex situations in lung cancer: multifocal disease, oligoprogression and oligorecurrence","volume":"33","author":"Werner","year":"2024","journal-title":"Eur Respir Rev"},{"key":"2026090204350954000_14.8.e014673.9","doi-asserted-by":"crossref","DOI":"10.3390\/cancers17142293","article-title":"Characteristics of Oligo-Recurrence and Treatment Selection in Non-Small Cell Lung Cancer","volume":"17","author":"Sonoda","year":"2025","journal-title":"Cancers (Basel)"},{"key":"2026090204350954000_14.8.e014673.10","doi-asserted-by":"publisher","DOI":"10.12968\/hmed.2024.0713"},{"key":"2026090204350954000_14.8.e014673.11","doi-asserted-by":"publisher","DOI":"10.1124\/pharmrev.123.000901"},{"key":"2026090204350954000_14.8.e014673.12","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2021.09.059"},{"key":"2026090204350954000_14.8.e014673.13","doi-asserted-by":"crossref","first-page":"113745","DOI":"10.1016\/j.jconrel.2025.113745","article-title":"Reversing hypoxia-induced immune evasion in tumors to enhance cancer immunotherapy","volume":"382","author":"Sun","year":"2025","journal-title":"J Control Release"},{"key":"2026090204350954000_14.8.e014673.14","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1182\/blood.2024025706","article-title":"Two-layered immune escape in AML is overcome by Fc\u03b3 receptor activation and inhibition of PGE2 signaling in NK cells","volume":"145","author":"Rothfu\u00df","year":"2025","journal-title":"Blood"},{"key":"2026090204350954000_14.8.e014673.15","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0801548"},{"key":"2026090204350954000_14.8.e014673.16","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.cytogfr.2025.10.001","article-title":"Reprogramming natural killer cells in the tumor microenvironment: Challenges and therapeutic opportunities","volume":"86","author":"Ma","year":"2025","journal-title":"Cytokine Growth Factor Rev"},{"key":"2026090204350954000_14.8.e014673.17","doi-asserted-by":"crossref","DOI":"10.3390\/cells14231858","article-title":"Strategies for the Development of NK Cell-Based Therapies for Cancer Treatment","volume":"14","author":"Budagova","year":"2025","journal-title":"Cells"},{"key":"2026090204350954000_14.8.e014673.18","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.cytogfr.2025.10.009","article-title":"Natural killers or natural regulators? Dual roles of NK cells in checkpoint immunotherapy","volume":"86","author":"Ma","year":"2025","journal-title":"Cytokine Growth Factor Rev"},{"key":"2026090204350954000_14.8.e014673.19","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1158\/2159-8290.CD-23-0519","article-title":"NKG2A Is a Therapeutic Vulnerability in Immunotherapy Resistant MHC-I Heterogeneous Triple-Negative Breast Cancer","volume":"14","author":"Taylor","year":"2024","journal-title":"Cancer Discov"},{"key":"2026090204350954000_14.8.e014673.20","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.cytogfr.2025.10.003","article-title":"NK cell adaptation in the tumor microenvironment: Insights for NK cell-based immunotherapy","volume":"86","author":"Li","year":"2025","journal-title":"Cytokine Growth Factor Rev"},{"key":"2026090204350954000_14.8.e014673.21","doi-asserted-by":"crossref","first-page":"1654947","DOI":"10.3389\/fimmu.2025.1654947","article-title":"Dual roles of innate immune cells and cytokines in shaping the breast cancer microenvironment","volume":"16","author":"Zhang","year":"2025","journal-title":"Front Immunol"},{"key":"2026090204350954000_14.8.e014673.22","doi-asserted-by":"crossref","first-page":"1696102","DOI":"10.3389\/fimmu.2025.1696102","article-title":"Bidirectional regulation of lipid metabolism and the tumor microenvironment: new perspectives from mechanism to therapy","volume":"16","author":"Shi","year":"2025","journal-title":"Front Immunol"},{"key":"2026090204350954000_14.8.e014673.23","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2025-013072","article-title":"Second-event endpoints (EFS2, PRFS2 and PFS2) after anti-PD-(L)1-based RCTs: a systematic review and meta-analysis","volume":"13","author":"Jimenez-Labaig","year":"2025","journal-title":"J Immunother Cancer"},{"key":"2026090204350954000_14.8.e014673.24","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2019.12.013"},{"key":"2026090204350954000_14.8.e014673.25","doi-asserted-by":"publisher","DOI":"10.2174\/1566523216666160524144041"},{"key":"2026090204350954000_14.8.e014673.26","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1080\/13543776.2024.2373771","article-title":"Selective COX-2 inhibitors as anticancer agents: a patent review (2018-2023)","volume":"34","author":"Mahboubi-Rabbani","year":"2024","journal-title":"Expert Opin Ther Pat"},{"key":"2026090204350954000_14.8.e014673.27","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.86492"},{"key":"2026090204350954000_14.8.e014673.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2025.112617"},{"key":"2026090204350954000_14.8.e014673.29","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2021.637504","article-title":"Cyclooxygenase-2 Inhibitor: A Potential Combination Strategy With Immunotherapy in Cancer","volume":"11","author":"Pu","year":"2021","journal-title":"Front Oncol"},{"key":"2026090204350954000_14.8.e014673.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.08.015"},{"key":"2026090204350954000_14.8.e014673.31","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1111\/ijd.17711","article-title":"The Role of Prostaglandin Pathway and EP Receptors in Skin Cancer Development","volume":"64","author":"St. Denis","year":"2025","journal-title":"Int J Dermatology"},{"key":"2026090204350954000_14.8.e014673.32","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-20-4245"},{"key":"2026090204350954000_14.8.e014673.33","doi-asserted-by":"publisher","DOI":"10.1126\/science.1103478"},{"key":"2026090204350954000_14.8.e014673.34","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1038\/s41586-025-09087-8","article-title":"CREM is a regulatory checkpoint of CAR and IL-15 signalling in NK cells","volume":"643","author":"Rafei","year":"2025","journal-title":"Nature"},{"key":"2026090204350954000_14.8.e014673.35","doi-asserted-by":"crossref","DOI":"10.1038\/srep09482","article-title":"ADP-ribose\/TRPM2-mediated Ca2+ signaling is essential for cytolytic degranulation and antitumor activity of natural killer cells","volume":"5","author":"Rah","year":"2015","journal-title":"Sci Rep"},{"key":"2026090204350954000_14.8.e014673.36","doi-asserted-by":"crossref","DOI":"10.1002\/advs.202506336","article-title":"Contribution of Prostaglandin E2-Induced Neuronal Excitation to Drug Resistance in Glioblastoma Countered by a Novel Blood-Brain Barrier Crossing Celecoxib Derivative","volume":"12","author":"Shen","year":"2025","journal-title":"Adv Sci (Weinh)"},{"key":"2026090204350954000_14.8.e014673.37","doi-asserted-by":"publisher","DOI":"10.1124\/mol.105.011833"},{"key":"2026090204350954000_14.8.e014673.38","doi-asserted-by":"publisher","DOI":"10.1172\/JCI2872"},{"key":"2026090204350954000_14.8.e014673.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.05.011"},{"key":"2026090204350954000_14.8.e014673.40","doi-asserted-by":"crossref","DOI":"10.1186\/s11671-024-04070-0","article-title":"Advances, limitations and perspectives in the use of celecoxib-loaded nanocarriers in therapeutics of cancer","volume":"19","author":"Oliveira Santos","year":"2024","journal-title":"Discov Nano"},{"key":"2026090204350954000_14.8.e014673.41","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2024-010058","article-title":"Systemic chemokine-modulatory regimen combined with neoadjuvant chemotherapy in patients with triple-negative breast cancer","volume":"12","author":"Gandhi","year":"2024","journal-title":"J Immunother Cancer"},{"key":"2026090204350954000_14.8.e014673.42","doi-asserted-by":"crossref","first-page":"108826","DOI":"10.1016\/j.pharmthera.2025.108826","article-title":"The tumor suppressor role and epigenetic regulation of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in cancer and tumor microenvironment (TME)","volume":"268","author":"Tulimilli","year":"2025","journal-title":"Pharmacol Ther"},{"key":"2026090204350954000_14.8.e014673.43","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2025-012134","article-title":"Aberrant lipid metabolism reshapes the immune landscape in bone metastasis of nasopharyngeal carcinoma","volume":"13","author":"Feng","year":"2025","journal-title":"J Immunother Cancer"},{"key":"2026090204350954000_14.8.e014673.44","doi-asserted-by":"crossref","DOI":"10.1186\/s13046-025-03595-1","article-title":"Novel MAFG-METTL14-SCD1 axis regulates lipid metabolism mediating choroidal melanoma distant metastasis","volume":"44","author":"Zhang","year":"2025","journal-title":"J Exp Clin Cancer Res"},{"key":"2026090204350954000_14.8.e014673.45","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/s41568-024-00761-z","article-title":"Convergent inducers and effectors of T cell paralysis in the tumour microenvironment","volume":"25","author":"Hanahan","year":"2025","journal-title":"Nat Rev Cancer"},{"key":"2026090204350954000_14.8.e014673.46","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2022-004938","article-title":"Indomethacin-induced oxidative stress enhances death receptor 5 signaling and sensitizes tumor cells to adoptive T-cell therapy","volume":"10","author":"Aboelella","year":"2022","journal-title":"J Immunother Cancer"},{"key":"2026090204350954000_14.8.e014673.47","doi-asserted-by":"crossref","DOI":"10.1186\/s13045-024-01524-x","article-title":"cAMP-PKA\/EPAC signaling and cancer: the interplay in tumor microenvironment","volume":"17","author":"Zhang","year":"2024","journal-title":"J Hematol Oncol"},{"key":"2026090204350954000_14.8.e014673.48","doi-asserted-by":"crossref","DOI":"10.1186\/s12951-025-03842-9","article-title":"Targeting pre-metastatic niche with inhalable dendritic cell vesicles to prevent breast cancer lung metastasis","volume":"23","author":"Leng","year":"2025","journal-title":"J Nanobiotechnology"},{"key":"2026090204350954000_14.8.e014673.49","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/s41401-021-00654-z","article-title":"TNF-\u03b1 impairs EP4 signaling through the association of TRAF2-GRK2 in primary fibroblast-like synoviocytes","volume":"43","author":"Tai","year":"2022","journal-title":"Acta Pharmacol Sin"},{"key":"2026090204350954000_14.8.e014673.50","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.cytogfr.2022.07.006","article-title":"Cancer-associated fibroblasts: Vital suppressors of the immune response in the tumor microenvironment","volume":"67","author":"Xiang","year":"2022","journal-title":"Cytokine Growth Factor Rev"},{"key":"2026090204350954000_14.8.e014673.51","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1080\/17425247.2020.1714587","article-title":"Mesenchymal stromal cell based therapies for the treatment of immune disorders: recent milestones and future challenges","volume":"17","author":"Gonzalez-Pujana","year":"2020","journal-title":"Expert Opin Drug Deliv"},{"key":"2026090204350954000_14.8.e014673.52","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2021.119627"}],"container-title":["Journal for ImmunoTherapy of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jitc-2025-014673","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T11:35:23Z","timestamp":1788348923000},"score":1,"resource":{"primary":{"URL":"https:\/\/jitc.bmj.com\/lookup\/doi\/10.1136\/jitc-2025-014673"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":52,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8,12]]},"published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1136\/jitc-2025-014673"],"URL":"https:\/\/doi.org\/10.1136\/jitc-2025-014673","relation":{},"ISSN":["2051-1426"],"issn-type":[{"value":"2051-1426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8]]}}}