{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T10:35:33Z","timestamp":1772015733545,"version":"3.50.1"},"reference-count":126,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:00:00Z","timestamp":1770681600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001250","name":"Morris Animal Foundation","doi-asserted-by":"publisher","award":["D10ZO-003"],"award-info":[{"award-number":["D10ZO-003"]}],"id":[{"id":"10.13039\/100001250","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NC State Cancer Genomics Fund"},{"name":"Genetics and Genomics Fellowship"},{"name":"US Department of Education Graduate Assistance in Areas of National Need","award":["P200A210002"],"award-info":[{"award-number":["P200A210002"]}]},{"DOI":"10.13039\/100000066","name":"NIEHS","doi-asserted-by":"crossref","award":["R01ES033243"],"award-info":[{"award-number":["R01ES033243"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Human-driven environmental change can promote cancer development in wild species, yet the pathophysiology of wildlife cancers remain largely unexplored. Urogenital carcinoma (UGC) in the California sea lion (CSL) (Zalophus californianus) is one of the most common cancer types documented in any wild mammal. The pathogenesis of UGC in CSLs is known to be multifactorial, with links to environmental contaminant exposure and infection by Otarine Herpesvirus-1 (OtHV-1); however, the genomic features of these cancers have not been thoroughly explored. Understanding UGC pathogenesis in the CSL has important implications for the health of humans and other species that share environment and diet. Methods: We leveraged the evolutionary conservation between the domestic dog and CSL genomes to perform cross-species whole-exome sequencing (WES) of CSL UGC tumors and matched normal tissue pairs. We also used PCR and Sanger sequencing to investigate the prevalence of DNA from OtHV-1. Results: Bioinformatic analyses identified shared somatic variants and DNA copy number aberrations in UGC tumor samples, including recurrent exonic single-nucleotide variants in CD274\/PD-L1, and recurrent copy number gains in CD274\/PD-L1, TNFRSF14, CD200, CDK4, and PLCG2. In an extended cohort of 70 CSLs (tumor, matched normals, and controls), a recurrent C &gt; T single-nucleotide variant in exon 4 of CD274\/PD-L1 was identified in 54 of 68 (79.4%) CSLs with diagnosed UGC. OtHV-1 DNA was detected in 67 of 70 individuals (95.8%). Conclusions: These results demonstrate that cross-species exome capture provides a means to identify genomic alterations that may play a role in the molecular pathogenesis of UGC in the CSL and adds to the body of evidence for an association between OtHV-1 and UGC in this species.<\/jats:p>","DOI":"10.3390\/genes17020222","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T17:10:52Z","timestamp":1770743452000},"page":"222","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cross-Species Exome Sequencing Reveals Recurrent Genomic Alterations in California Sea Lion (Zalophus californianus) Urogenital Carcinoma and Highlights a Recurrent PD-L1 Variant"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3951-6525","authenticated-orcid":false,"given":"Isabella G.","family":"Livingston","sequence":"first","affiliation":[{"name":"Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6294-0426","authenticated-orcid":false,"given":"Catherine F.","family":"Wise","sequence":"additional","affiliation":[{"name":"Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7466-2870","authenticated-orcid":false,"given":"Allison N.","family":"Dickey","sequence":"additional","affiliation":[{"name":"Bioinformatics Research Center, North Carolina State University, Raleigh, NC 27607, USA"},{"name":"Center for Human Health and the Environment, North Carolina State University, Raleigh, NC 27607, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3029-8798","authenticated-orcid":false,"given":"Rachael","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607, USA"},{"name":"Comparative Medicine Institute, North Carolina State University, Raleigh, NC 27607, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3281-5701","authenticated-orcid":false,"given":"Alissa C.","family":"Deming","sequence":"additional","affiliation":[{"name":"Department of Conservation Medicine and Science, Pacific Marine Mammal Center, Laguna Beach, CA 92651, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbie","family":"Halaska","sequence":"additional","affiliation":[{"name":"The Marine Mammal Center, Sausalito, CA 94965, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6416-0156","authenticated-orcid":false,"given":"Frances M. D.","family":"Gulland","sequence":"additional","affiliation":[{"name":"The Marine Mammal Center, Sausalito, CA 94965, USA"},{"name":"School of Veterinary Medicine, University of California, Davis, CA 95616, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen M.","family":"Colegrove","sequence":"additional","affiliation":[{"name":"Zoological Pathology Program, Veterinary Diagnostic Laboratory, College of Veterinary Medicine, University of Illinois, Brookfield, IL 61802, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6565-4799","authenticated-orcid":false,"given":"P\u00e1draig","family":"Duignan","sequence":"additional","affiliation":[{"name":"The Marine Mammal Center, Sausalito, CA 94965, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8901-4155","authenticated-orcid":false,"given":"Matthew","family":"Breen","sequence":"additional","affiliation":[{"name":"Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607, USA"},{"name":"Center for Human Health and the Environment, North Carolina State University, Raleigh, NC 27607, USA"},{"name":"Comparative Medicine Institute, North Carolina State University, Raleigh, NC 27607, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1038\/s41559-018-0558-7","article-title":"Human activities might influence oncogenic processes in wild animal populations","volume":"2","author":"Giraudeau","year":"2018","journal-title":"Nat. Ecol. Evol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1038\/s41568-018-0045-0","article-title":"Cancer in wildlife: Patterns of emergence","volume":"18","author":"Pesavento","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_3","first-page":"20182434","article-title":"Urban environment and cancer in wildlife: Available evidence and future research avenues","volume":"286","author":"Sepp","year":"2019","journal-title":"Proc. Biol. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"142955","DOI":"10.1016\/j.scitotenv.2020.142955","article-title":"Cancer risk landscapes: A framework to study cancer in ecosystems","volume":"763","author":"Dujon","year":"2021","journal-title":"Sci. Total Environ."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/nrc2665","article-title":"Wildlife cancer: A conservation perspective","volume":"9","author":"McAloose","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"ref_6","first-page":"7","article-title":"Cancer statistics, 2022","volume":"72","author":"Siegel","year":"2022","journal-title":"CA Cancer J. Clin."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1111\/ele.12726","article-title":"A framework for how environment contributes to cancer risk","volume":"20","author":"Hochberg","year":"2017","journal-title":"Ecol. Lett."},{"key":"ref_8","first-page":"239","article-title":"Climate change and cancer","volume":"70","author":"Nogueira","year":"2020","journal-title":"CA Cancer J. Clin."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/j.biopha.2007.10.006","article-title":"Lifestyle-related factors and environmental agents causing cancer: An overview","volume":"61","author":"Irigaray","year":"2007","journal-title":"Biomed. Pharmacother."},{"key":"ref_10","first-page":"562","article-title":"Endocrine disrupting chemicals as potential risk factor for estrogen-dependent cancers","volume":"126","author":"Rutkowska","year":"2016","journal-title":"Pol. Arch. Med. Wewn."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1158\/2159-8290.CD-24-0573","article-title":"Cancer Prevalence across Vertebrates","volume":"15","author":"Compton","year":"2025","journal-title":"Cancer Discov."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1111\/vco.70006","article-title":"Genomic Evaluation of Canine Prostatic Carcinomas as a Model for the Human Disease: Or \u2018UC or not UC\u2014That is the question\u2019","volume":"23","author":"Thomas","year":"2025","journal-title":"Vet. Comp. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Burlibasa, L., Nicu, A.T., Chifiriuc, M.C., Medar, C., Petrescu, A., Jinga, V., and Stoica, I. (2023). H3 histone methylation landscape in male urogenital cancers: From molecular mechanisms to epigenetic biomarkers and therapeutic targets. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1181764"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Khan, A.A., Al-Mahrouqi, N., Al-Yahyaee, A., Al-Sayegh, H., Al-Harthy, M., and Al-Zadjali, S. (2023). Deciphering Urogenital Cancers through Proteomic Biomarkers: A Systematic Review and Meta-Analysis. Cancers, 16.","DOI":"10.3390\/cancers16010022"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Holtedahl, K., Borgquist, L., Donker, G.A., Buntinx, F., Weller, D., Campbell, C., Mansson, J., Hammersley, V., Braaten, T., and Parajuli, R. (2023). Symptoms and signs of urogenital cancer in primary care. BMC Prim. Care, 24.","DOI":"10.1186\/s12875-023-02063-z"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"20140228","DOI":"10.1098\/rstb.2014.0228","article-title":"Common cancer in a wild animal: The California sea lion (Zalophus californianus) as an emerging model for carcinogenesis","volume":"370","author":"Browning","year":"2015","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Gulland, F.M.D., Hall, A.J., Ylitalo, G.M., Colegrove, K.M., Norris, T., Duignan, P.J., Halaska, B., Acevedo Whitehouse, K., Lowenstine, L.J., and Deming, A.C. (2020). Persistent Contaminants and Herpesvirus OtHV1 Are Positively Associated with Cancer in Wild California Sea Lions (Zalophus californianus). Front. Mar. Sci., 7.","DOI":"10.3389\/fmars.2020.602565"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S0378-1135(01)00497-7","article-title":"Otarine herpesvirus-1: A novel gammaherpesvirus associated with urogenital carcinoma in California sea lions (Zalophus californianus)","volume":"86","author":"King","year":"2002","journal-title":"Vet. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1177\/0300985810388525","article-title":"Marine mammals as sentinel species for oceans and human health","volume":"48","author":"Bossart","year":"2011","journal-title":"Vet. Pathol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.jcpa.2006.06.007","article-title":"Otarine Herpesvirus-1, not papillomavirus, is associated with endemic tumours in California sea lions (Zalophus californianus)","volume":"135","author":"Buckles","year":"2006","journal-title":"J. Comp. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1354\/vp.43-6-865","article-title":"Marine mammal neoplasia: A review","volume":"43","author":"Newman","year":"2006","journal-title":"Vet. Pathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"581","DOI":"10.7589\/2017-08-208","article-title":"Prevalence of Urogenital Carcinoma in Stranded California Sea Lions (Zalophus californianus) from 2005\u20132015","volume":"54","author":"Deming","year":"2018","journal-title":"J. Wildl. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"250","DOI":"10.7589\/0090-3558-32.2.250","article-title":"Metastatic carcinoma of probable transitional cell origin in 66 free-living California sea lions (Zalophus californianus), 1979 to 1994","volume":"32","author":"Gulland","year":"1996","journal-title":"J. Wildl. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.vetmic.2006.10.002","article-title":"Age-prevalence of Otarine Herpesvirus-1, a tumor-associated virus, and possibility of its sexual transmission in California sea lions","volume":"120","author":"Buckles","year":"2007","journal-title":"Vet. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.marpolbul.2004.08.005","article-title":"The role of organochlorines in cancer-associated mortality in California sea lions (Zalophus californianus)","volume":"50","author":"Ylitalo","year":"2005","journal-title":"Mar. Pollut. Bull."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1354\/vp.37-6-609","article-title":"Common metastatic carcinoma of California sea lions (Zalophus californianus): Evidence of genital origin and association with novel gammaherpesvirus","volume":"37","author":"Lipscomb","year":"2000","journal-title":"Vet. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Fujiwara, S., and Nakamura, H. (2020). Animal Models for Gammaherpesvirus Infections: Recent Development in the Analysis of Virus-Induced Pathogenesis. Pathogens, 9.","DOI":"10.3390\/pathogens9020116"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1897\/05-609R.1","article-title":"Transplacental transfer of organochlorines in California sea lions (Zalophus californianus)","volume":"26","author":"Greig","year":"2007","journal-title":"Environ. Toxicol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1007\/s00244-008-9181-y","article-title":"Organochlorine pesticides and polychlorinated biphenyls in California sea lions (Zalophus californianus californianus) from the Gulf of California, Mexico","volume":"56","author":"Gardner","year":"2009","journal-title":"Arch. Environ. Contam. Toxicol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.onehlt.2015.08.003","article-title":"Sentinel California sea lions provide insight into legacy organochlorine exposure trends and their association with cancer and infectious disease","volume":"1","author":"Randhawa","year":"2015","journal-title":"One Health"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/j.chemosphere.2019.01.050","article-title":"Apex marine predators and ocean health: Proactive screening of halogenated organic contaminants reveals ecosystem indicator species","volume":"221","author":"Cossaboon","year":"2019","journal-title":"Chemosphere"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"124804","DOI":"10.1016\/j.envpol.2024.124804","article-title":"Unveiling mercury levels: Trophic habits influence on bioaccumulation in two Otariid species","volume":"361","year":"2024","journal-title":"Environ. Pollut."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"166412","DOI":"10.1016\/j.scitotenv.2023.166412","article-title":"Associations between urogenital carcinoma and DECA-BDE (BDE-209) among wild California Sea lions (Zalophus californianus) and Steller Sea lions (Eumetopias jubatus)","volume":"900","author":"Rothenberg","year":"2023","journal-title":"Sci. Total Environ."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1111\/1755-0998.13443","article-title":"Hi-C scaffolded short- and long-read genome assemblies of the California sea lion are broadly consistent for syntenic inference across 45 million years of evolution","volume":"21","author":"Peart","year":"2021","journal-title":"Mol. Ecol. Resour."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e2200188","DOI":"10.1002\/bies.202200188","article-title":"Wild animals as an underused treasure trove for studying the genetics of cancer","volume":"45","author":"Sepp","year":"2023","journal-title":"Bioessays"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1080\/13590840500535396","article-title":"Environmental influences in cancer aetiology","volume":"15","author":"Newby","year":"2009","journal-title":"J. Nutr. Environ. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1111\/his.12034","article-title":"Pathways of vulvar intraepithelial neoplasia and squamous cell carcinoma","volume":"62","author":"Ordi","year":"2013","journal-title":"Histopathology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/1750-9378-7-35","article-title":"The role of infectious agents in urogenital cancers","volume":"7","author":"Alibek","year":"2012","journal-title":"Infect. Agent. Cancer"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e609","DOI":"10.1016\/S2214-109X(16)30143-7","article-title":"Global burden of cancers attributable to infections in 2012: A synthetic analysis","volume":"4","author":"Plummer","year":"2016","journal-title":"Lancet Glob. Health"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.ejca.2011.10.031","article-title":"Incidence and survival of rare urogenital cancers in Europe","volume":"48","author":"Visser","year":"2012","journal-title":"Eur. J. Cancer"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1002\/gcc.20908","article-title":"Characterization of canine osteosarcoma by array comparative genomic hybridization and RT-qPCR: Signatures of genomic imbalance in canine osteosarcoma parallel the human counterpart","volume":"50","author":"Angstadt","year":"2011","journal-title":"Genes. Chromosomes Cancer"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/j.cancergen.2012.09.005","article-title":"A genome-wide approach to comparative oncology: High-resolution oligonucleotide aCGH of canine and human osteosarcoma pinpoints shared microaberrations","volume":"205","author":"Angstadt","year":"2012","journal-title":"Cancer Genet."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/s10577-019-09606-0","article-title":"Genome-wide DNA copy number analysis and targeted transcriptional analysis of canine histiocytic malignancies identifies diagnostic signatures and highlights disruption of spindle assembly complex","volume":"27","author":"Kennedy","year":"2019","journal-title":"Chromosome Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1002\/gcc.22441","article-title":"Cross-species analysis of the canine and human bladder cancer transcriptome and exome","volume":"56","author":"Ramsey","year":"2017","journal-title":"Genes. Chromosomes Cancer"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/s10577-015-9471-y","article-title":"Canine urothelial carcinoma: Genomically aberrant and comparatively relevant","volume":"23","author":"Shapiro","year":"2015","journal-title":"Chromosome Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s10577-014-9406-z","article-title":"Genomic profiling reveals extensive heterogeneity in somatic DNA copy number aberrations of canine hemangiosarcoma","volume":"22","author":"Thomas","year":"2014","journal-title":"Chromosome Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.3109\/10428194.2011.559802","article-title":"Refining tumor-associated aneuploidy through \u2018genomic recoding\u2019 of recurrent DNA copy number aberrations in 150 canine non-Hodgkin lymphomas","volume":"52","author":"Thomas","year":"2011","journal-title":"Leuk. Lymphoma"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.pharmthera.2018.01.012","article-title":"Canine sarcomas as a surrogate for the human disease","volume":"188","author":"Gustafson","year":"2018","journal-title":"Pharmacol. Ther."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1038\/nrg2382","article-title":"Leader of the pack: Gene mapping in dogs and other model organisms","volume":"9","author":"Karlsson","year":"2008","journal-title":"Nat. Rev. Genet."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.tig.2007.08.013","article-title":"Lessons learned from the dog genome","volume":"23","author":"Wayne","year":"2007","journal-title":"Trends Genet."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Tawa, G.J., Braisted, J., Gerhold, D., Grewal, G., Mazcko, C., Breen, M., Sittampalam, G., and LeBlanc, A.K. (2021). Transcriptomic profiling in canines and humans reveals cancer specific gene modules and biological mechanisms common to both species. PLoS Comput. Biol., 17.","DOI":"10.1371\/journal.pcbi.1009450"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1158\/2767-9764.CRC-23-0441","article-title":"Hemangiosarcoma Cells Promote Conserved Host-derived Hematopoietic Expansion","volume":"4","author":"Kim","year":"2024","journal-title":"Cancer Res. Commun."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"105517","DOI":"10.1016\/j.rvsc.2024.105517","article-title":"Environmental exposure and cancer occurrence in dogs: A critical appraisal of evidence","volume":"184","author":"Owada","year":"2025","journal-title":"Res. Vet. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Thomas, R., Wiley, C.A., Droste, E.L., Robertson, J., Inman, B.A., and Breen, M. (2023). Whole exome sequencing analysis of canine urothelial carcinomas without BRAF V595E mutation: Short in-frame deletions in BRAF and MAP2K1 suggest alternative mechanisms for MAPK pathway disruption. PLoS Genet., 19.","DOI":"10.1371\/journal.pgen.1010575"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/j.dci.2011.10.011","article-title":"Health status, infection and disease in California sea lions (Zalophus californianus) studied using a canine microarray platform and machine-learning approaches","volume":"36","author":"Mancia","year":"2012","journal-title":"Dev. Comp. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1126\/science.1188046","article-title":"Targeted investigation of the Neandertal genome by array-based sequence capture","volume":"328","author":"Burbano","year":"2010","journal-title":"Science"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Cosart, T., Beja-Pereira, A., Chen, S., Ng, S.B., Shendure, J., and Luikart, G. (2011). Exome-wide DNA capture and next generation sequencing in domestic and wild species. BMC Genom., 12.","DOI":"10.1186\/1471-2164-12-347"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1007\/s00442-006-0489-x","article-title":"How seals divide up the world: Environment, life history, and conservation","volume":"150","author":"Ferguson","year":"2006","journal-title":"Oecologia"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/BF02198839","article-title":"Phylogenetic analyses of complete cytochrome b genes of the order carnivora with particular emphasis on the caniformia","volume":"42","author":"Ledje","year":"1996","journal-title":"J. Mol. Evol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1354\/vp.08-VP-0214-C-FL","article-title":"Tumor morphology and immunohistochemical expression of estrogen receptor, progesterone receptor, p53, and Ki67 in urogenital carcinomas of California sea lions (Zalophus californianus)","volume":"46","author":"Colegrove","year":"2009","journal-title":"Vet. Pathol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Deming, A.C., Wellehan, J.F.X., Colegrove, K.M., Hall, A., Luff, J., Lowenstine, L., Duignan, P., Cortes-Hinojosa, G., and Gulland, F.M.D. (2021). Unlocking the Role of a Genital Herpesvirus, Otarine Herpesvirus 1, in California Sea Lion Cervical Cancer. Animals, 11.","DOI":"10.3390\/ani11020491"},{"key":"ref_62","unstructured":"Wise, C.F. (2020). One Health Approach to Environmental Health and Genomics of Sporadic Disease Models for Urogenital Cancers. [Ph.D. Thesis, North Carolina State University]."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"i884","DOI":"10.1093\/bioinformatics\/bty560","article-title":"fastp: An ultra-fast all-in-one FASTQ preprocessor","volume":"34","author":"Chen","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_64","unstructured":"Li, H. (2013). Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM. arXiv."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"giab008","DOI":"10.1093\/gigascience\/giab008","article-title":"Twelve years of SAMtools and BCFtools","volume":"10","author":"Danecek","year":"2021","journal-title":"Gigascience"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Benjamin, D., Sato, T., Cibulskis, K., Getz, G., Stewart, C., and Lichtenstein, L. (2019). Calling Somatic SNVs and Indels with Mutect2. bioRxiv, 861054.","DOI":"10.1101\/861054"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"D590","DOI":"10.1093\/nar\/gkj144","article-title":"The UCSC Genome Browser Database: Update 2006","volume":"34","author":"Hinrichs","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Wickham, H. (2016). ggplot2: Elegant Graphics for Data Analysis, Springer.","DOI":"10.1007\/978-3-319-24277-4_9"},{"key":"ref_69","unstructured":"Van der Auwera, G.A., and O\u2019Connor, B.D. (2020). Genomics in the Cloud: Using Docker, GATK, and WDL in Terra, O\u2019Reilly Media."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1101\/gr.107524.110","article-title":"The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data","volume":"20","author":"McKenna","year":"2010","journal-title":"Genome Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1750-9378-9-3","article-title":"Implication of human herpesviruses in oncogenesis through immune evasion and supression","volume":"9","author":"Alibek","year":"2014","journal-title":"Infect. Agent. Cancer"},{"key":"ref_72","unstructured":"Baron, S. (1996). Herpesviruses. Medical Microbiology, University of Texas Medical Branch at Galveston. [4th ed.]."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Weidner-Glunde, M., Kruminis-Kaszkiel, E., and Savanagouder, M. (2020). Herpesviral Latency-Common Themes. Pathogens, 9.","DOI":"10.3390\/pathogens9020125"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.tim.2016.11.009","article-title":"Herpesviruses and Their Host Cells: A Successful Liaison","volume":"25","author":"Adler","year":"2017","journal-title":"Trends Microbiol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1038\/sj.cr.7290347","article-title":"Regulation of survivin and CDK4 by Epstein-Barr virus encoded latent membrane protein 1 in nasopharyngeal carcinoma cell lines","volume":"15","author":"Ai","year":"2005","journal-title":"Cell Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.ebiom.2019.04.002","article-title":"Immune checkpoint molecule herpes virus entry mediator is overexpressed and associated with poor prognosis in human glioblastoma","volume":"43","author":"Han","year":"2019","journal-title":"EBioMedicine"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.jss.2019.07.009","article-title":"Herpes Virus Entry Mediator (HVEM): A Novel Potential Mediator of Trauma-Induced Immunosuppression","volume":"245","author":"Wakeley","year":"2020","journal-title":"J. Surg. Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/978-3-030-91836-1_3","article-title":"Somatic and Germline Variant Calling from Next-Generation Sequencing Data","volume":"1361","author":"Chang","year":"2022","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.cell.2020.08.006","article-title":"Distinct Classes of Complex Structural Variation Uncovered across Thousands of Cancer Genome Graphs","volume":"183","author":"Hadi","year":"2020","journal-title":"Cell"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1038\/s41576-023-00663-0","article-title":"Scrambling the genome in cancer: Causes and consequences of complex chromosome rearrangements","volume":"25","author":"Krupina","year":"2024","journal-title":"Nat. Rev. Genet."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/s41698-021-00155-6","article-title":"Structural variant detection in cancer genomes: Computational challenges and perspectives for precision oncology","volume":"5","author":"Schonhuth","year":"2021","journal-title":"NPJ Precis. Oncol."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Zheng, S., Guerrero-Haughton, E., and Foijer, F. (2023). Chromosomal Instability-Driven Cancer Progression: Interplay with the Tumour Microenvironment and Therapeutic Strategies. Cells, 12.","DOI":"10.3390\/cells12232712"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1373\/clinchem.2019.308213","article-title":"Using Machine Learning to Identify True Somatic Variants from Next-Generation Sequencing","volume":"66","author":"Wu","year":"2020","journal-title":"Clin. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1093\/bioinformatics\/bts271","article-title":"Strelka: Accurate somatic small-variant calling from sequenced tumor-normal sample pairs","volume":"28","author":"Saunders","year":"2012","journal-title":"Bioinformatics"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Kondo, R., Kondo, K., Nabeshima, K., Nishikimi, A., Ishida, Y., Shigeoka, T., and Dijkstra, J.M. (2025). PD-1 is conserved from sharks to humans: New insights into PD-1, PD-L1, PD-L2, and SHP-2 evolution. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1573492"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Flies, A.S., Blackburn, N.B., Lyons, A.B., Hayball, J.D., and Woods, G.M. (2017). Comparative Analysis of Immune Checkpoint Molecules and Their Potential Role in the Transmissible Tasmanian Devil Facial Tumor Disease. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.00513"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"msaf016","DOI":"10.1093\/molbev\/msaf016","article-title":"Positive Selection on Mammalian Immune Genes-Effects of Gene Function and Selective Constraint","volume":"42","author":"Nandakumar","year":"2025","journal-title":"Mol. Biol. Evol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1093\/bioinformatics\/btt771","article-title":"Bias from removing read duplication in ultra-deep sequencing experiments","volume":"30","author":"Zhou","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1016\/j.trecan.2023.08.011","article-title":"Variant allele frequency: A decision-making tool in precision oncology?","volume":"9","author":"Trapani","year":"2023","journal-title":"Trends Cancer"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1038\/s41467-025-56670-8","article-title":"Breakage fusion bridge cycles drive high oncogene number with moderate intratumoural heterogeneity","volume":"16","author":"Wong","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"3908","DOI":"10.1038\/s41467-019-11857-8","article-title":"Identification of somatic mutations in single cell DNA-seq using a spatial model of allelic imbalance","volume":"10","author":"Luquette","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Pande, S., Dawood, M., and Grochowski, C.M. (2025). Structural Variants: Mechanisms, Mapping, and Interpretation in Human Genetics. Genes, 16.","DOI":"10.3390\/genes16080905"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/nrg3117","article-title":"Repetitive DNA and next-generation sequencing: Computational challenges and solutions","volume":"13","author":"Treangen","year":"2011","journal-title":"Nat. Rev. Genet."},{"key":"ref_94","unstructured":"O\u2019Sullivan, B. (2024). Computational Approaches to Identify and Explain Sources of Error in Cancer Somatic Mutation Data. [Ph.D. Thesis, University of Galway, NUI Galway]."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Jin, X., He, M., Ferguson, B., Meng, Y., Ouyang, L., Ren, J., Mailund, T., Sun, F., Sun, L., and Shen, J. (2012). An effort to use human-based exome capture methods to analyze chimpanzee and macaque exomes. PLoS ONE, 7.","DOI":"10.1371\/annotation\/450f85d8-03c6-4bd4-aa8e-b5b5894b4593"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"R87","DOI":"10.1186\/gb-2011-12-9-r87","article-title":"Expanding whole exome resequencing into non-human primates","volume":"12","author":"Vallender","year":"2011","journal-title":"Genome Biol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"6309","DOI":"10.1038\/s41388-021-02022-x","article-title":"Codon optimality in cancer","volume":"40","author":"Gillen","year":"2021","journal-title":"Oncogene"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/s41525-021-00229-1","article-title":"Estimating the predictive power of silent mutations on cancer classification and prognosis","volume":"6","author":"Gutman","year":"2021","journal-title":"NPJ Genom. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"7593","DOI":"10.1038\/s41598-023-34452-w","article-title":"Possible involvement of silent mutations in cancer pathogenesis and evolution","volume":"13","author":"Kikutake","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.1038\/s41467-019-10489-2","article-title":"A pan-cancer analysis of synonymous mutations","volume":"10","author":"Sharma","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Li, Q., Li, J., Yu, C.P., Chang, S., Xie, L.L., and Wang, S. (2021). Synonymous mutations that regulate translation speed might play a non-negligible role in liver cancer development. BMC Cancer, 21.","DOI":"10.1186\/s12885-021-08131-w"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1093\/nar\/15.3.1281","article-title":"The codon Adaptation Index--a measure of directional synonymous codon usage bias, and its potential applications","volume":"15","author":"Sharp","year":"1987","journal-title":"Nucleic Acids Res."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1016\/j.cell.2014.08.011","article-title":"A dual program for translation regulation in cellular proliferation and differentiation","volume":"158","author":"Gingold","year":"2014","journal-title":"Cell"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1016\/j.cell.2016.05.046","article-title":"Modulated Expression of Specific tRNAs Drives Gene Expression and Cancer Progression","volume":"165","author":"Goodarzi","year":"2016","journal-title":"Cell"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/s41698-021-00147-6","article-title":"PD-L1 immunohistochemistry for canine cancers and clinical benefit of anti-PD-L1 antibody in dogs with pulmonary metastatic oral malignant melanoma","volume":"5","author":"Maekawa","year":"2021","journal-title":"NPJ Precis. Oncol."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Maekawa, N., Konnai, S., Okagawa, T., Nishimori, A., Ikebuchi, R., Izumi, Y., Takagi, S., Kagawa, Y., Nakajima, C., and Suzuki, Y. (2016). Immunohistochemical Analysis of PD-L1 Expression in Canine Malignant Cancers and PD-1 Expression on Lymphocytes in Canine Oral Melanoma. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0157176"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"5023","DOI":"10.2147\/OTT.S105862","article-title":"PD-L1 expression in human cancers and its association with clinical outcomes","volume":"9","author":"Wang","year":"2016","journal-title":"Onco Targets Ther."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Mazzone, E., and Aresu, L. (2024). Comprehensive Analysis of Microsatellite Instability in Canine Cancers: Implications for Comparative Oncology and Personalized Veterinary Medicine. Animals, 14.","DOI":"10.20944\/preprints202407.0300.v1"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Choi, J.W., Withers, S.S., Chang, H., Spanier, J.A., De La Trinidad, V.L., Panesar, H., Fife, B.T., Sciammas, R., Sparger, E.E., and Moore, P.F. (2020). Development of canine PD-1\/PD-L1 specific monoclonal antibodies and amplification of canine T cell function. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0235518"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Maekawa, N., Konnai, S., Ikebuchi, R., Okagawa, T., Adachi, M., Takagi, S., Kagawa, Y., Nakajima, C., Suzuki, Y., and Murata, S. (2014). Expression of PD-L1 on canine tumor cells and enhancement of IFN-\u03b3 production from tumor-infiltrating cells by PD-L1 blockade. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0098415"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"395","DOI":"10.3233\/BLC-201532","article-title":"CD274 (PD-L1) Copy Number Changes (Gain) & Response to Immune Checkpoint Blockade Therapy in Carcinomas of the Urinary Tract","volume":"7","author":"Gupta","year":"2021","journal-title":"Bladder Cancer"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1158\/2767-9764.CRC-22-0468","article-title":"Development of an Anti-canine PD-L1 Antibody and Caninized PD-L1 Mouse Model as Translational Research Tools for the Study of Immunotherapy in Humans","volume":"3","author":"Oh","year":"2023","journal-title":"Cancer Res. Commun."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1111\/jog.13411","article-title":"Expressions of programmed death (PD)-1 and PD-1 ligand (PD-L1) in cervical intraepithelial neoplasia and cervical squamous cell carcinomas are of prognostic value and associated with human papillomavirus status","volume":"43","author":"Yang","year":"2017","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1158\/1078-0432.CCR-16-1069","article-title":"Genomic Amplification of CD274 (PD-L1) in Small-Cell Lung Cancer","volume":"23","author":"George","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"e002680","DOI":"10.1136\/jitc-2021-002680","article-title":"Pan-cancer landscape of CD274 (PD-L1) copy number changes in 244,584 patient samples and the correlation with PD-L1 protein expression","volume":"9","author":"Huang","year":"2021","journal-title":"J. Immunother. Cancer"},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Lee, W.H., Seo, D., Lim, S.G., and Suk, K. (2019). Reverse Signaling of Tumor Necrosis Factor Superfamily Proteins in Macrophages and Microglia: Superfamily Portrait in the Neuroimmune Interface. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00262"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"21","DOI":"10.18632\/genesandcancer.221","article-title":"CDK4: A master regulator of the cell cycle and its role in cancer","volume":"13","author":"Baker","year":"2022","journal-title":"Genes. Cancer"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"226","DOI":"10.4161\/cbt.72","article-title":"Cycling to cancer with cyclin D1","volume":"1","author":"Diehl","year":"2002","journal-title":"Cancer Biol. Ther."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.trecan.2016.11.006","article-title":"The Strange Case of CDK4\/6 Inhibitors: Mechanisms, Resistance, and Combination Strategies","volume":"3","author":"Knudsen","year":"2017","journal-title":"Trends Cancer"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.1126\/science.274.5293.1672","article-title":"Cancer cell cycles","volume":"274","author":"Sherr","year":"1996","journal-title":"Science"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.ctrv.2016.03.002","article-title":"Targeting CDK4\/6 in patients with cancer","volume":"45","author":"Hamilton","year":"2016","journal-title":"Cancer Treat. Rev."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"5689464","DOI":"10.1155\/2019\/5689464","article-title":"Interaction of CD200 Overexpression on Tumor Cells with CD200R1 Overexpression on Stromal Cells: An Escape from the Host Immune Response in Rectal Cancer Patients","volume":"2019","author":"Bisgin","year":"2019","journal-title":"J. Oncol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"971","DOI":"10.4161\/onci.20034","article-title":"The role of tumor expression of CD200 in tumor formation, metastasis and susceptibility to T lymphocyte adoptive transfer therapy","volume":"1","author":"Talebian","year":"2012","journal-title":"Oncoimmunology"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1158\/1541-7786.MCR-20-0075","article-title":"Phosphorylation of PLCgamma1 by EphA2 Receptor Tyrosine Kinase Promotes Tumor Growth in Lung Cancer","volume":"18","author":"Song","year":"2020","journal-title":"Mol. Cancer Res."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1038\/s41419-023-05755-7","article-title":"PLCG2 can exist in eccDNA and contribute to the metastasis of non-small cell lung cancer by regulating mitochondrial respiration","volume":"14","author":"Yang","year":"2023","journal-title":"Cell Death Dis."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Zhang, H., Qin, C., Gan, H., Guo, X., and Zhang, L. (2020). Construction of an Immunogenomic Risk Score for Prognostication in Colon Cancer. Front. Genet., 11.","DOI":"10.3389\/fgene.2020.00499"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/2\/222\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T09:55:08Z","timestamp":1772013308000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/2\/222"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,10]]},"references-count":126,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["genes17020222"],"URL":"https:\/\/doi.org\/10.3390\/genes17020222","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,10]]}}}