{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:07:16Z","timestamp":1791284836438,"version":"4.1.0"},"posted":{"date-parts":[[2025,6,7]]},"group-title":"Transplantation","reference-count":61,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,6,7]],"date-time":"2025-06-07T00:00:00Z","timestamp":1749254400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.medrxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,6,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Donation after circulatory death (DCD) offers a promising strategy to expand the donor pool by 20\u201330%. However, DCD heart grafts suffer from warm ischemia injury, making effective graft viability assessment before transplantation prudent. Current methods for assessing DCD hearts are impacted either by ethical concerns and regional limitations (thoracoabdominal normothermic regional perfusion - taNRP) or by the need for significant resources, expertise, and equipment, with limitations in functional assessment (direct procurement and reperfusion \u2013 DPP, via the Organ Care System (OCS) by TransMedics). This study explores an alternative approach to DCD heart preservation, using controlled hypothermia at 6-8 degrees Celsius for up to 7 hours, followed by reanimation using normothermic machine perfusion. DCD grafts were procured from porcine donors after 19 mins of functional warm ischemia, stored via controlled cold static preservation for up to 7 hours and evaluated via a novel method of ex vivo cardiac loading. No functional, biochemical or proteomic differences were observed between DCD cardiac grafts stored via controlled hypothermia for up to 7 hours and DCD grafts reperfused immediately after procurement. These results suggest that controlled hypothermia may be a viable alternative to current DCD preservation methods, eliminating ethical concerns of taNRP and reducing logistical complexity and costs associated with DPP. These findings provide a foundation for a potential shift in DCD heart preservation practices, offering a more effective and cost-efficient approach to expand the donor pool and improve transplantation outcomes.<\/jats:p>","DOI":"10.1101\/2025.06.04.25329001","type":"posted-content","created":{"date-parts":[[2025,6,7]],"date-time":"2025-06-07T21:45:14Z","timestamp":1749332714000},"source":"Crossref","is-referenced-by-count":2,"title":["Alternative preservation strategies of DCD hearts: Effect of cold ischemia time before normothermic machine perfusion"],"prefix":"10.64898","author":[{"given":"Manuela Lopera","family":"Higuita","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuella O.","family":"Ajenu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya","family":"Bolger-Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Olverson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soheila Ali","family":"Akbari Ghavimi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si Young","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8075-6099","authenticated-orcid":false,"given":"Taku","family":"Kasai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Michaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chukwudi","family":"Chijioke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhuban","family":"Ruidas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison","family":"Pitti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Minie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Catricala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doug","family":"Vincent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selena","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9693-7313","authenticated-orcid":false,"given":"David","family":"D\u2019Alessandro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7835-2135","authenticated-orcid":false,"given":"Elena","family":"Aikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0929-3164","authenticated-orcid":false,"given":"Sasha A","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7591-0362","authenticated-orcid":false,"given":"Marie","family":"Billaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1140-097X","authenticated-orcid":false,"given":"Asishana A.","family":"Osho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2373-232X","authenticated-orcid":false,"given":"Shannon N.","family":"Tessier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7888-6636","authenticated-orcid":false,"given":"S. Alireza","family":"Rabi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"issue":"1","key":"2025060923501043000_2025.06.04.25329001v1.1","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.cardfail.2024.07.001","article-title":"HF STATS 2024: Heart Failure Epidemiology and Outcomes Statistics An Updated 2024 Report from the Heart Failure Society of America","volume":"31","year":"2025","journal-title":"J Card Fail"},{"issue":"7","key":"2025060923501043000_2025.06.04.25329001v1.2","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1002\/clc.22124","article-title":"Heart transplantation and left ventricular assist device therapy: two comparable options in end-stage heart failure?","volume":"36","year":"2013","journal-title":"Clin Cardiol"},{"key":"2025060923501043000_2025.06.04.25329001v1.3","doi-asserted-by":"publisher","DOI":"10.1111\/jocs.14781"},{"issue":"5","key":"2025060923501043000_2025.06.04.25329001v1.4","doi-asserted-by":"crossref","first-page":"e307","DOI":"10.1016\/j.jtcvs.2019.09.080","article-title":"Increasing the United States heart transplant donor pool with donation after circulatory death","volume":"159","year":"2020","journal-title":"J Thorac Cardiovasc Surg"},{"issue":"4","key":"2025060923501043000_2025.06.04.25329001v1.5","doi-asserted-by":"crossref","first-page":"e211","DOI":"10.1016\/j.athoracsur.2018.04.017","article-title":"Direct Heart Procurement After Donation After Circulatory Death With Ex Situ Reperfusion","volume":"106","year":"2018","journal-title":"Ann Thorac Surg"},{"issue":"12","key":"2025060923501043000_2025.06.04.25329001v1.6","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1016\/j.healun.2016.07.004","article-title":"Functional assessment and transplantation of the donor heart after circulatory death","volume":"35","year":"2016","journal-title":"J Heart Lung Transplant"},{"key":"2025060923501043000_2025.06.04.25329001v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2021.06.022"},{"issue":"8","key":"2025060923501043000_2025.06.04.25329001v1.8","doi-asserted-by":"crossref","first-page":"3486","DOI":"10.1016\/S0041-1345(97)01117-2","article-title":"Changes in adenine nucleotides and lipid hydroperoxides during normothermic cardiopulmonary bypass in a porcine model of type II non-heart-beating donor","volume":"29","year":"1997","journal-title":"Transplant Proc"},{"issue":"4","key":"2025060923501043000_2025.06.04.25329001v1.9","doi-asserted-by":"crossref","first-page":"e15296","DOI":"10.1111\/ctr.15296","article-title":"Financial impact of donation after circulatory death heart transplantation: A single-center analysis","volume":"38","year":"2024","journal-title":"Clin Transplant"},{"key":"2025060923501043000_2025.06.04.25329001v1.10","doi-asserted-by":"crossref","unstructured":"Murphy, N.B. , et al., Ethical Issues in Normothermic Regional Perfusion in Controlled Organ Donation After Determination of Death by Circulatory Criteria: A Scoping Review. Transplantation, 2024.","DOI":"10.1097\/TP.0000000000005161"},{"issue":"1","key":"2025060923501043000_2025.06.04.25329001v1.11","first-page":"e0193","article-title":"The ethics surrounding normothermic regional perfusion in donors following circulatory death","volume":"23","year":"2024","journal-title":"Clin Liver Dis (Hoboken"},{"key":"2025060923501043000_2025.06.04.25329001v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)60261-6"},{"issue":"6","key":"2025060923501043000_2025.06.04.25329001v1.13","first-page":"e26281","article-title":"Is the Organ Care System (OCS) Still the First Choice With Emerging New Strategies for Donation After Circulatory Death (DCD) in Heart Transplant?","volume":"14","year":"2022","journal-title":"Cureus"},{"issue":"4","key":"2025060923501043000_2025.06.04.25329001v1.14","doi-asserted-by":"crossref","first-page":"S467","DOI":"10.1016\/j.healun.2023.02.1295","article-title":"(1084) Successful Heart Transplantation Using a Portable Normothermic Ex-Vivo Donor Heart Preservation System for Extended Criteria Donor after Circulatory Death: A Case Series with Extended Perfusion Times","volume":"42","year":"2023","journal-title":"The Journal of Heart and Lung Transplantation"},{"key":"2025060923501043000_2025.06.04.25329001v1.15","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.120.018966"},{"key":"2025060923501043000_2025.06.04.25329001v1.16","doi-asserted-by":"crossref","unstructured":"Pettit, S.J. and M.C. Petrie , Transplantation of hearts donated after circulatory-determined death: a song of fire and ice. 2019, Lippincott Williams & Wilkins Hagerstown, MD. p. e005991.","DOI":"10.1161\/CIRCHEARTFAILURE.119.005991"},{"issue":"9","key":"2025060923501043000_2025.06.04.25329001v1.17","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1016\/j.healun.2022.02.003","article-title":"Lactate during ex-situ heart perfusion does not predict the requirement for mechanical circulatory support following donation after circulatory death (DCD) heart transplants","volume":"41","year":"2022","journal-title":"J Heart Lung Transplant"},{"issue":"12","key":"2025060923501043000_2025.06.04.25329001v1.18","doi-asserted-by":"crossref","first-page":"2073","DOI":"10.1016\/j.jchf.2024.06.007","article-title":"Early U.S. Heart Transplant Experience With Normothermic Regional Perfusion Following Donation After Circulatory Death","volume":"12","year":"2024","journal-title":"JACC Heart Fail"},{"key":"2025060923501043000_2025.06.04.25329001v1.19","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.12994"},{"issue":"4","key":"2025060923501043000_2025.06.04.25329001v1.20","doi-asserted-by":"crossref","first-page":"S73","DOI":"10.1016\/j.healun.2023.02.160","article-title":"(144) Cold Static Storage of Donation after Circulatory Death (DCD) Hearts Procured via Normothermic Region Perfusion (NRP): Effect of Ischemic Time on Outcomes","volume":"42","year":"2023","journal-title":"The Journal of Heart and Lung Transplantation"},{"issue":"4","key":"2025060923501043000_2025.06.04.25329001v1.21","doi-asserted-by":"crossref","first-page":"e005364","DOI":"10.1161\/CIRCHEARTFAILURE.118.005364","article-title":"Hearts Donated After Circulatory Death and Reconditioned Using Normothermic Regional Perfusion Can Be Successfully Transplanted Following an Extended Period of Static Storage","volume":"12","year":"2019","journal-title":"Circ Heart Fail"},{"issue":"11","key":"2025060923501043000_2025.06.04.25329001v1.22","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1016\/j.healun.2024.07.018","article-title":"Successful clinical transplantation of hearts donated after circulatory death using direct procurement followed by hypothermic oxygenated perfusion: A report of the first 3 cases","volume":"43","year":"2024","journal-title":"J Heart Lung Transplant"},{"issue":"3","key":"2025060923501043000_2025.06.04.25329001v1.23","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1111\/ajt.16258","article-title":"Hypothermic, oxygenated perfusion (HOPE) provides cardioprotection via succinate oxidation prior to normothermic perfusion in a rat model of donation after circulatory death (DCD)","volume":"21","year":"2021","journal-title":"Am J Transplant"},{"key":"2025060923501043000_2025.06.04.25329001v1.24","doi-asserted-by":"publisher","DOI":"10.1016\/S1053-2498(03)00211-0"},{"issue":"8","key":"2025060923501043000_2025.06.04.25329001v1.25","doi-asserted-by":"crossref","first-page":"e010326","DOI":"10.1161\/CIRCINTERVENTIONS.120.010326","article-title":"Hypothermia for Reduction of Myocardial Reperfusion Injury in Acute Myocardial Infarction: Closing the Translational Gap","volume":"14","year":"2021","journal-title":"Circ Cardiovasc Interv"},{"key":"2025060923501043000_2025.06.04.25329001v1.26","doi-asserted-by":"crossref","first-page":"642843","DOI":"10.3389\/fcvm.2021.642843","article-title":"Effects of Therapeutic Hypothermia on Normal and Ischemic Heart","volume":"8","year":"2021","journal-title":"Front Cardiovasc Med"},{"key":"2025060923501043000_2025.06.04.25329001v1.27","doi-asserted-by":"crossref","unstructured":"Ali, A. , et al., Static lung storage at 10 degrees C maintains mitochondrial health and preserves donor organ function. Sci Transl Med, 2021. 13(611): p. eabf7601.","DOI":"10.1126\/scitranslmed.abf7601"},{"issue":"12","key":"2025060923501043000_2025.06.04.25329001v1.28","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1016\/j.healun.2022.08.025","article-title":"Evaluation of 10 degrees C as the optimal storage temperature for aspiration-injured donor lungs in a large animal transplant model","volume":"41","year":"2022","journal-title":"J Heart Lung Transplant"},{"key":"2025060923501043000_2025.06.04.25329001v1.29","doi-asserted-by":"crossref","unstructured":"Olverson, G.t. , et al., Cardiac Loading using Passive Left Atrial Pressurization and Passive Afterload for Graft Assessment. J Vis Exp, 2024(210).","DOI":"10.3791\/66624"},{"key":"2025060923501043000_2025.06.04.25329001v1.30","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0223-y"},{"key":"2025060923501043000_2025.06.04.25329001v1.31","doi-asserted-by":"crossref","unstructured":"Ajenu, E.O. , et al., Advancing Cardiac Graft Assessment Methods During Normothermic Machine Perfusion to Achieve Improved Transplantation Outcomes. bioRxiv, 2025: p. 2025.02. 20.639392.","DOI":"10.1101\/2025.02.20.639392"},{"issue":"1","key":"2025060923501043000_2025.06.04.25329001v1.32","doi-asserted-by":"crossref","first-page":"4008","DOI":"10.1038\/s41467-022-31490-2","article-title":"Partial freezing of rat livers extends preservation time by 5-fold","volume":"13","year":"2022","journal-title":"Nat Commun"},{"key":"2025060923501043000_2025.06.04.25329001v1.33","doi-asserted-by":"crossref","first-page":"22415","DOI":"10.1038\/srep22415","article-title":"Metabolic profiling during ex vivo machine perfusion of the human liver","volume":"6","year":"2016","journal-title":"Sci Rep"},{"key":"2025060923501043000_2025.06.04.25329001v1.34","doi-asserted-by":"crossref","unstructured":"Lam, J. , et al., A Universal Approach to Analyzing Transmission Electron Microscopy with ImageJ. Cells, 2021. 10(9).","DOI":"10.3390\/cells10092177"},{"key":"2025060923501043000_2025.06.04.25329001v1.35","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-13-S16-S12"},{"key":"2025060923501043000_2025.06.04.25329001v1.36","doi-asserted-by":"publisher","DOI":"10.1093\/NAR\/GKAC194"},{"key":"2025060923501043000_2025.06.04.25329001v1.37","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"},{"key":"2025060923501043000_2025.06.04.25329001v1.38","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr260"},{"key":"2025060923501043000_2025.06.04.25329001v1.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.echo.2014.10.003"},{"key":"2025060923501043000_2025.06.04.25329001v1.40","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2012.04086.x"},{"key":"2025060923501043000_2025.06.04.25329001v1.41","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2024.01.011"},{"key":"2025060923501043000_2025.06.04.25329001v1.42","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-010715-103335"},{"issue":"1","key":"2025060923501043000_2025.06.04.25329001v1.43","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.healun.2023.09.004","article-title":"Acute rejection in donation after circulatory death (DCD) heart transplants","volume":"43","year":"2024","journal-title":"J Heart Lung Transplant"},{"key":"2025060923501043000_2025.06.04.25329001v1.44","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2022.02.005"},{"key":"2025060923501043000_2025.06.04.25329001v1.45","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1501686"},{"key":"2025060923501043000_2025.06.04.25329001v1.46","doi-asserted-by":"crossref","first-page":"667834","DOI":"10.3389\/fimmu.2021.667834","article-title":"The Impact of Inflammation on the Immune Responses to Transplantation: Tolerance or Rejection?","volume":"12","year":"2021","journal-title":"Front Immunol"},{"issue":"1","key":"2025060923501043000_2025.06.04.25329001v1.47","doi-asserted-by":"crossref","first-page":"5456","DOI":"10.1038\/s41467-021-25745-7","article-title":"C3 complement inhibition prevents antibody-mediated rejection and prolongs renal allograft survival in sensitized non-human primates","volume":"12","year":"2021","journal-title":"Nat Commun"},{"issue":"1","key":"2025060923501043000_2025.06.04.25329001v1.48","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s40560-024-00774-8","article-title":"Impact of hyper- and hypothermia on cellular and whole-body physiology","volume":"13","year":"2025","journal-title":"J Intensive Care"},{"key":"2025060923501043000_2025.06.04.25329001v1.49","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.101297"},{"key":"2025060923501043000_2025.06.04.25329001v1.50","doi-asserted-by":"crossref","first-page":"107276","DOI":"10.1016\/j.phrs.2024.107276","article-title":"Action and therapeutic targets of myosin light chain kinase, an important cardiovascular signaling mechanism","volume":"206","year":"2024","journal-title":"Pharmacol Res"},{"key":"2025060923501043000_2025.06.04.25329001v1.51","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2020.08.021"},{"issue":"3","key":"2025060923501043000_2025.06.04.25329001v1.52","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1097\/TP.0000000000000926","article-title":"Cold Crystalloid Perfusion Provides Cardiac Preservation Superior to Cold Storage for Donation After Circulatory Death","volume":"100","year":"2016","journal-title":"Transplantation"},{"key":"2025060923501043000_2025.06.04.25329001v1.53","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.119.006552"},{"issue":"1","key":"2025060923501043000_2025.06.04.25329001v1.54","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/1054-8807(95)00057-7","article-title":"Myocardial vacuolization, a marker of ischemic injury, in surveillance cardiac biopsies posttransplant: Correlations with morphologic vascular disease and endothelial dysfunction","volume":"5","year":"1996","journal-title":"Cardiovasc Pathol"},{"key":"2025060923501043000_2025.06.04.25329001v1.55","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2020.11.006"},{"issue":"1","key":"2025060923501043000_2025.06.04.25329001v1.56","doi-asserted-by":"crossref","first-page":"e12636","DOI":"10.1111\/xen.12636","article-title":"Cold non-ischemic heart preservation with continuous perfusion prevents early graft failure in orthotopic pig-to-baboon xenotransplantation","volume":"28","year":"2021","journal-title":"Xenotransplantation"},{"issue":"5","key":"2025060923501043000_2025.06.04.25329001v1.57","first-page":"432","article-title":"A comparative anatomic and physiologic overview of the porcine heart","volume":"53","year":"2014","journal-title":"J Am Assoc Lab Anim Sci"},{"key":"2025060923501043000_2025.06.04.25329001v1.58","unstructured":"Boyette, L. and B. Manna , Physiology, myocardial oxygen demand. StatPearls. 2019, StatPearls Publishing, Treasure Island, FL."},{"issue":"3","key":"2025060923501043000_2025.06.04.25329001v1.59","first-page":"217","article-title":"Reperfusion injury in ischemic myocardium: protective effect of controlled reperfusion","volume":"3","year":"1990","journal-title":"Am J Cardiovasc Pathol"},{"key":"2025060923501043000_2025.06.04.25329001v1.60","doi-asserted-by":"crossref","unstructured":"Hutin, A. , et al., Early Coronary Reperfusion Facilitates Return of Spontaneous Circulation and Improves Cardiovascular Outcomes After Ischemic Cardiac Arrest and Extracorporeal Resuscitation in Pigs. J Am Heart Assoc, 2016. 5(12).","DOI":"10.1161\/JAHA.116.004588"},{"issue":"2","key":"2025060923501043000_2025.06.04.25329001v1.61","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1097\/HCO.0000000000001109","article-title":"Heart transplant donation after circulatory death: current status and implications","volume":"39","year":"2024","journal-title":"Curr Opin Cardiol"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.06.04.25329001","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:37:45Z","timestamp":1768509465000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.1101\/2025.06.04.25329001"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,7]]},"references-count":61,"URL":"https:\/\/doi.org\/10.1101\/2025.06.04.25329001","relation":{},"subject":[],"published":{"date-parts":[[2025,6,7]]},"subtype":"preprint"}}