{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:04:02Z","timestamp":1785405842278,"version":"3.56.0"},"posted":{"date-parts":[[2026,7,27]]},"group-title":"Microbiology","reference-count":46,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["R01 AI080607"],"award-info":[{"award-number":["R01 AI080607"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R21 AI190589"],"award-info":[{"award-number":["R21 AI190589"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R21 AI163910"],"award-info":[{"award-number":["R21 AI163910"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["RFGA2022-010-22"],"award-info":[{"award-number":["RFGA2022-010-22"]}],"id":[{"id":"https:\/\/ror.org\/022fhzr29","id-type":"ROR","asserted-by":"publisher"}]},{"award":["PG16459"],"award-info":[{"award-number":["PG16459"]}],"id":[{"id":"https:\/\/ror.org\/03efmqc40","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Myxoma virus (MYXV), a member of the\n                  <jats:italic>Leporipoxvirus<\/jats:italic>\n                  genus (species\n                  <jats:italic>Leporipoxvirus myxoma;<\/jats:italic>\n                  family\n                  <jats:italic>Poxviridae<\/jats:italic>\n                  ), causes a highly lethal disease known as myxomatosis in European rabbits. In late 2018, a new natural MYXV isolate, MYXV-Tol (a.k.a. hare MYXV; ha-MYXV), emerged and caused myxomatosis-like disease with high mortality in Iberian hares, European brown hares, and European rabbits. This variant contains an approximately 2.8-kb insertion of a recombination cassette within the\n                  <jats:italic>M009L<\/jats:italic>\n                  gene encoding four additional genes, including the C7-like host range gene,\n                  <jats:italic>M159L<\/jats:italic>\n                  . M159 is essential for replication of MYXV-Tol in hare cells and is likely a key determinant of its pathogenicity in both hares and rabbits. Here, we compared the pathogenicity of wild-type MYXV-Tol (vMyx-Tol), an M159 deletion strain (vMyx-Tol-M159KO), and the classical MYXV-Lau strain (vMyx-Lau) in European rabbits. All three viruses caused systemic disease; however, vMyx-Tol and vMyx-Tol-M159KO produced clinical signs distinct from classical myxomatosis. Infection with vMyx-Tol and vMyx-Tol-M159KO was characterized by the absence of the typical primary and secondary nodular lesions, and caused severe edema, marked fluid accumulation, lymphocyte infection, and significantly reduced or no virus-neutralizing antibody responses. The disease caused by both vMyx-Tol and vMyx-Tol-M159KO progressed rapidly within 9-11 days, resulting in animals reaching humane euthanasia endpoints like vMyx-Lau. Deletion of M159 did not significantly alter MYXV-Tol pathogenicity in rabbits. Collectively, these findings demonstrate that MYXV-Tol has evolved to cause an atypical, amyxomatous-like acute to hyperacute disease in European rabbits and likely in hares.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Significance<\/jats:title>\n                  <jats:p>Natural evolution enables viruses to cross species barriers and adapt to new hosts. Myxoma virus (MYXV), released in the 1950s in Australia and Europe as a biocontrol agent against European rabbits, became a classic model for real-time monitoring of virus evolution, virulence, and host adaptation. Although MYXV is typically host-restricted, a newly emerged natural isolate, MYXV-Tol, causes lethal disease in both hares and rabbits. Here, we show that MYXV-Tol induces an atypical, amyxomatous-like disease characterized by the absence of nodular lesions, severe edema, lymphocyte infection, and markedly reduced virus-neutralizing antibody responses. These findings reveal previously unrecognized virus\u2013host interactions that shape disease outcome and provide new insight into the mechanisms driving viral adaptation and evolution.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.07.25.740729","type":"posted-content","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T05:15:21Z","timestamp":1785215721000},"source":"Crossref","is-referenced-by-count":0,"title":["Atypical myxomatosis in European rabbits is caused by the recombinant myxoma virus involved in species jumping into hares"],"prefix":"10.64898","author":[{"given":"Jacqueline","family":"Carmona","sequence":"first","affiliation":[{"name":"Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ 85281, USA"},{"name":"School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4631-6989","authenticated-orcid":false,"given":"Junior A.","family":"Enow","sequence":"additional","affiliation":[{"name":"Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ 85281, USA"},{"name":"School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethan","family":"Ramsey","sequence":"additional","affiliation":[{"name":"Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ 85281, USA"},{"name":"School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabeeha M.","family":"Reshi","sequence":"additional","affiliation":[{"name":"Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ 85281, USA"},{"name":"School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mackenzie","family":"Cashen","sequence":"additional","affiliation":[{"name":"Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ 85281, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ami D.","family":"Gutierrez-Jensen","sequence":"additional","affiliation":[{"name":"Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ 85281, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saige","family":"Munig","sequence":"additional","affiliation":[{"name":"Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ 85281, USA"},{"name":"School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Reed","sequence":"additional","affiliation":[{"name":"Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ 85281, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Lowe","sequence":"additional","affiliation":[{"name":"Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ 85281, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacquelyn","family":"Kilbourne","sequence":"additional","affiliation":[{"name":"Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ 85281, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grant","family":"McFadden","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Kraberger","sequence":"additional","affiliation":[{"name":"Center for Fundamental & Applied Microbiomics, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4111-2415","authenticated-orcid":false,"given":"Arvind","family":"Varsani","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA"},{"name":"Center for Fundamental & Applied Microbiomics, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA"},{"name":"Center of Evolution and Medicine, Arizona State University, Tempe, AZ 85287, USA"},{"name":"Structural Biology Research Unit, Department of Integrative Biomedical Sciences, University of Cape Town, Observatory, Cape Town, 7925, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7177-819X","authenticated-orcid":false,"given":"Masmudur M.","family":"Rahman","sequence":"additional","affiliation":[{"name":"Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ 85281, USA"},{"name":"School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026073002350528000_2026.07.25.740729v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1099"},{"key":"2026073002350528000_2026.07.25.740729v1.2","unstructured":"F. Fenner , F. Ratcliffe , Myxomatosis (Cambridge: University Press, 1965), pp. xiv + 379 pp."},{"key":"2026073002350528000_2026.07.25.740729v1.3","first-page":"400","article-title":"The pathogenesis of infectious myxomatosis; the mechanism of infection and the immunological response in the European rabbit (Oryctolagus cuniculus)","volume":"34","year":"1953","journal-title":"Br J Exp Pathol"},{"key":"2026073002350528000_2026.07.25.740729v1.4","doi-asserted-by":"publisher","DOI":"10.3390\/v7031020"},{"key":"2026073002350528000_2026.07.25.740729v1.5","doi-asserted-by":"crossref","first-page":"256","DOI":"10.20506\/rst.17.1.1081","article-title":"Myxoma virus in rabbits","volume":"17","year":"1998","journal-title":"Rev Sci Tech"},{"key":"2026073002350528000_2026.07.25.740729v1.6","first-page":"865","article-title":"Das myxomatogene virus","volume":"23","year":"1898","journal-title":"Beitrag zum Stadium der Krankheit-serreger ausserhalbdes Sichtbaren Zbl Bakt"},{"key":"2026073002350528000_2026.07.25.740729v1.7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002950"},{"key":"2026073002350528000_2026.07.25.740729v1.8","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1999.0104"},{"key":"2026073002350528000_2026.07.25.740729v1.9","first-page":"417","article-title":"Myxomatosis: the virulence of field strains of myxoma virus in a population of wild rabbits (Oryctolagus cuniculus L","volume":"74","year":"1975","journal-title":"with high resistance to myxomatosis. J Hyg (Lond"},{"key":"2026073002350528000_2026.07.25.740729v1.10","doi-asserted-by":"crossref","unstructured":"J. Ross , M. F. Sanders , The development of genetic resistance to myxomatosis in wild rabbits in Britain. J Hyg (Lond ) 92 , 255\u2013261 (1984).","DOI":"10.1017\/S0022172400064494"},{"key":"2026073002350528000_2026.07.25.740729v1.11","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1126\/science.aau7285","article-title":"Parallel adaptation of rabbit populations to myxoma virus. Science (New York","volume":"363","year":"2019","journal-title":"N.Y"},{"key":"2026073002350528000_2026.07.25.740729v1.12","doi-asserted-by":"publisher","DOI":"10.1136\/vr.g4621"},{"key":"2026073002350528000_2026.07.25.740729v1.13","doi-asserted-by":"crossref","unstructured":"A. \u00c1gueda-Pinto et al., Genetic Characterization of a Recombinant Myxoma Virus in the Iberian Hare (Lepus granatensis). Viruses 11 (2019).","DOI":"10.3390\/v11060530"},{"key":"2026073002350528000_2026.07.25.740729v1.14","doi-asserted-by":"crossref","first-page":"2204","DOI":"10.1111\/tbed.13289","article-title":"First outbreak of myxomatosis in Iberian hares (Lepus granatensis)","volume":"66","year":"2019","journal-title":"Transbound Emerg Dis"},{"key":"2026073002350528000_2026.07.25.740729v1.15","doi-asserted-by":"crossref","first-page":"2218","DOI":"10.1111\/tbed.13296","article-title":"Myxoma virus jumps species to the Iberian hare","volume":"66","year":"2019","journal-title":"Transbound Emerg Dis"},{"key":"2026073002350528000_2026.07.25.740729v1.16","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1111\/tbed.13781","article-title":"Monitoring of emerging myxoma virus epidemics in Iberian hares (Lepus granatensis) in Spain, 2018-2020","volume":"68","year":"2021","journal-title":"Transbound Emerg Dis"},{"key":"2026073002350528000_2026.07.25.740729v1.17","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1111\/tbed.14540","article-title":"Co-infection by classic MYXV and ha-MYXV in Iberian hare (Lepus granatensis) and European wild rabbit (Oryctolagus cuniculus algirus)","volume":"69","year":"2022","journal-title":"Transbound Emerg Dis"},{"key":"2026073002350528000_2026.07.25.740729v1.18","doi-asserted-by":"crossref","first-page":"1754249","DOI":"10.3389\/fvets.2026.1754249","article-title":"First evidence of recombinant Myxomavirus (ha-MYXV) in European hare (Lepus europaeus) in the Czech Republic and Slovakia","volume":"13","year":"2026","journal-title":"Front Vet Sci"},{"key":"2026073002350528000_2026.07.25.740729v1.19","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1556\/004.2025.01264","article-title":"First detection of myxomatosis in European brown hares (Lepus europaeus) in West-Hungary","volume":"74","year":"2026","journal-title":"Acta Vet Hung"},{"key":"2026073002350528000_2026.07.25.740729v1.20","first-page":"1608","article-title":"Recombinant Myxoma Virus in European Brown Hares, 2023-2024.","volume":"31","year":"2025","journal-title":"Emerg Infect Dis"},{"key":"2026073002350528000_2026.07.25.740729v1.21","doi-asserted-by":"crossref","unstructured":"B. Cardoso et al., Epidemiological surveillance of myxoma virus in European hares (Lepus europaeus) in the Iberian Peninsula: First evidence of infection by the emerging ha-MYXV. Vet Microbiol 302, 110405 (2025).","DOI":"10.1016\/j.vetmic.2025.110405"},{"key":"2026073002350528000_2026.07.25.740729v1.22","doi-asserted-by":"crossref","unstructured":"E. Rossini et al., Identification and Characterisation of a Myxoma Virus Detected in the Italian Hare (Lepus corsicanus). Viruses 16 (2024).","DOI":"10.3390\/v16030437"},{"key":"2026073002350528000_2026.07.25.740729v1.23","doi-asserted-by":"crossref","first-page":"9374702","DOI":"10.1155\/tbed\/9374702","article-title":"Emergence of Recombinant Myxoma Virus in Algerian Farmed Rabbits: Molecular and Phylogenetic Evidence","volume":"2026","year":"2026","journal-title":"Transbound Emerg Dis"},{"key":"2026073002350528000_2026.07.25.740729v1.24","doi-asserted-by":"crossref","unstructured":"F. A . Abade Dos Santos et al., Detection of recombinant Hare Myxoma Virus in wild rabbits (Oryctolagus cuniculus algirus). Viruses 12 (2020).","DOI":"10.20944\/preprints202009.0244.v1"},{"key":"2026073002350528000_2026.07.25.740729v1.25","doi-asserted-by":"crossref","first-page":"e0346121","DOI":"10.1128\/mbio.03461-21","article-title":"Identification of a Novel Myxoma Virus C7-Like Host Range Factor That Enabled a Species Leap from Rabbits to Hares","volume":"13","year":"2022","journal-title":"mBio"},{"key":"2026073002350528000_2026.07.25.740729v1.26","doi-asserted-by":"crossref","unstructured":"F. A . Abade Dos Santos et al., Evaluation of Commercial Myxomatosis Vaccines against Recombinant Myxoma Virus (ha-MYXV) in Iberian Hare and Wild Rabbit. Vaccines 10 (2022).","DOI":"10.3390\/vaccines10030356"},{"key":"2026073002350528000_2026.07.25.740729v1.27","doi-asserted-by":"crossref","first-page":"280","DOI":"10.30802\/AALAS-CM-18-000024","article-title":"Refinement and Successful Implementation of a Scoring System for Myxomatosis in a Susceptible Rabbit (Oryctolagus cuniculus) Model","volume":"68","year":"2018","journal-title":"Comp Med"},{"key":"2026073002350528000_2026.07.25.740729v1.28","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.virol.2014.06.021","article-title":"Recombinant myxoma virus lacking all poxvirus ankyrin-repeat proteins stimulates multiple cellular anti-viral pathways and exhibits a severe decrease in virulence","volume":"464-465","year":"2014","journal-title":"Virology"},{"key":"2026073002350528000_2026.07.25.740729v1.29","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/S0195-5616(87)50103-6","article-title":"Rabbit husbandry and medicine","volume":"17","year":"1987","journal-title":"Vet Clin North Am Small Anim Pract"},{"key":"2026073002350528000_2026.07.25.740729v1.30","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.01526-22"},{"key":"2026073002350528000_2026.07.25.740729v1.31","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.meegid.2009.10.001","article-title":"The evolutionary biology of poxviruses","volume":"10","year":"2010","journal-title":"Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases"},{"key":"2026073002350528000_2026.07.25.740729v1.32","doi-asserted-by":"crossref","unstructured":"C. H. Yang , A. L. Song , Y. \u01eaiu , X. Y. Ge , Cross-species transmission and host range genes in poxviruses. Virol Sin 39 , 177\u2013193 (2024).","DOI":"10.1016\/j.virs.2024.01.007"},{"key":"2026073002350528000_2026.07.25.740729v1.33","doi-asserted-by":"crossref","unstructured":"M. M. Rahman , G. McFadden , Role of cytokines in poxvirus host tropism and adaptation. Current opinion in virology 57, 101286 (2022).","DOI":"10.1016\/j.coviro.2022.101286"},{"key":"2026073002350528000_2026.07.25.740729v1.34","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1017\/S0022172400045083","article-title":"EVOLUTIONARY CHANGES IN MYXOMA VIRUS IN BRITAIN. AN EXAMINATION OF 222 NATURALLY OCCURRING STRAINS OBTAINED FROM 80 COUNTIES DURING THE PERIOD OCTOBER-NOVEMBER 1962","volume":"63","year":"1965","journal-title":"J Hyg (Lond)"},{"key":"2026073002350528000_2026.07.25.740729v1.35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006252"},{"key":"2026073002350528000_2026.07.25.740729v1.36","doi-asserted-by":"crossref","first-page":"e0088622","DOI":"10.1128\/jvi.00886-22","article-title":"Divergent Evolutionary Pathways of Myxoma Virus in Australia: Virulence Phenotypes in Susceptible and Partially Resistant Rabbits Indicate Possible Selection for Transmissibility","volume":"96","year":"2022","journal-title":"J Virol"},{"key":"2026073002350528000_2026.07.25.740729v1.37","doi-asserted-by":"crossref","unstructured":"M. M. Rahman , J. Liu , W. M. Chan , S. Rothenburg , G. McFadden , Myxoma virus protein M029 is a dual function immunomodulator that inhibits PKR and also conscripts RHA\/DHX9 to promote expanded host tropism and viral replication. PLoS Pathog 9 , e1003465 (2013).","DOI":"10.1371\/journal.ppat.1003465"},{"key":"2026073002350528000_2026.07.25.740729v1.38","doi-asserted-by":"crossref","unstructured":"K. P. Dalton , I. Nicieza , A. Baraga\u00f1o , J. M. Alonso , F. Parra , Molecular characterisation of virulence graded field isolates of myxoma virus. Virology journal 7, 49 (2010).","DOI":"10.1186\/1743-422X-7-49"},{"key":"2026073002350528000_2026.07.25.740729v1.39","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-82-6-1407"},{"key":"2026073002350528000_2026.07.25.740729v1.40","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01923-13"},{"key":"2026073002350528000_2026.07.25.740729v1.41","doi-asserted-by":"crossref","unstructured":"F. A . Abade Dos Santos et al., Retrospective serological and molecular survey of myxoma or antigenically related virus in the Iberian hare, Lepus granatensis. Transbound Emerg Dis 69 , 3637\u20133650 (2022).","DOI":"10.1111\/tbed.14734"},{"key":"2026073002350528000_2026.07.25.740729v1.42","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2005.12.007"},{"key":"2026073002350528000_2026.07.25.740729v1.43","doi-asserted-by":"publisher","DOI":"10.1038\/nri3152"},{"key":"2026073002350528000_2026.07.25.740729v1.44","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.vetmic.2009.09.031","article-title":"Host-specificity of myxoma virus: Pathogenesis of South American and North American strains of myxoma virus in two North American lagomorph species","volume":"141","year":"2010","journal-title":"Vet Microbiol"},{"key":"2026073002350528000_2026.07.25.740729v1.45","doi-asserted-by":"crossref","first-page":"e2182","DOI":"10.1002\/vetr.2182","article-title":"Pathological changes and viral antigen distribution in tissues of Iberian hare (Lepus granatensis) naturally infected with the emerging recombinant myxoma virus (ha-MYXV)","volume":"192","year":"2023","journal-title":"Vet Rec"},{"key":"2026073002350528000_2026.07.25.740729v1.46","doi-asserted-by":"crossref","first-page":"2616","DOI":"10.1111\/tbed.13899","article-title":"Recombinant myxoma virus infection associated with high mortality in rabbit farming (Oryctolagus cuniculus)","volume":"68","year":"2021","journal-title":"Transbound Emerg Dis"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.07.25.740729","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:35:17Z","timestamp":1785404117000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.07.25.740729"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,27]]},"references-count":46,"URL":"https:\/\/doi.org\/10.64898\/2026.07.25.740729","relation":{},"subject":[],"published":{"date-parts":[[2026,7,27]]},"subtype":"preprint"}}