{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T12:37:43Z","timestamp":1758631063569,"version":"3.41.2"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T00:00:00Z","timestamp":1701043200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["773830"],"award-info":[{"award-number":["773830"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002911","name":"Universidad Complutense de Madrid","doi-asserted-by":"publisher","award":["CT42\/18-CT43\/18"],"award-info":[{"award-number":["CT42\/18-CT43\/18"]}],"id":[{"id":"10.13039\/501100002911","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Parasitol."],"abstract":"<jats:p><jats:italic>Toxoplasma gondii<\/jats:italic> is a zoonotic parasite infecting all warm-blooded animals, including humans. The contribution of environmental contamination by <jats:italic>T. gondii<\/jats:italic> oocysts to infections is understudied. The aim of the current work was to explore <jats:italic>T. gondii<\/jats:italic> serology as a means of attributing the source of infection using a robust stepwise approach. We identified <jats:italic>in silico<\/jats:italic> thirty-two promising oocyst-specific antigens from <jats:italic>T. gondii<\/jats:italic> \u00b4omics data, recombinantly expressed and purified them and validated whether serology based on these proteins could discriminate oocyst- from tissue cyst-driven experimental infections. For this, three well-characterized serum panels, sampled from 0 to 6 weeks post-infection, from pigs and sheep experimentally infected with <jats:italic>T. gondii<\/jats:italic> oocysts or tissue cysts, were used. Candidate proteins were initially screened by Western blot with sera from pigs or sheep, infected for different times, either with oocysts or tissue cysts, as well as non-infected animals. Only the recombinant proteins TgCCp5A and TgSR1 provoked seroconversion upon infection and appeared to discriminate between oocyst- and tissue cyst-driven infections with pig sera. They were subsequently used to develop an enzyme-linked immunosorbent assay test for pigs. Based on this assay and Western blot analyses, a lack of stage specificity and low antigenicity was observed with all pig sera. The same was true for proteins TgERP, TgSporoSAG, TgOWP1 and TgOWP8, previously described as source-attributing antigens, when analyzed using the whole panels of sera. We conclude that there is currently no antigen that allows the discrimination of <jats:italic>T. gondii<\/jats:italic> infections acquired from either oocysts or tissue cysts by serological tests. This work provides robust new knowledge that can inform further research and development toward source-attributing <jats:italic>T. gondii<\/jats:italic> serology.<\/jats:p>","DOI":"10.3389\/fpara.2023.1292322","type":"journal-article","created":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T06:53:35Z","timestamp":1701068015000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Limited value of current and new in silico predicted oocyst-specific proteins of Toxoplasma gondii for source-attributing serology"],"prefix":"10.3389","volume":"2","author":[{"given":"Nadia-Mar\u00eda","family":"L\u00f3pez-Ure\u00f1a","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael","family":"Calero-Bernal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bretislav","family":"Koudela","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona","family":"Cherchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessia","family":"Possenti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabio","family":"Tosini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Klein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"San Juan-Casero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Jara-Herrera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pikka","family":"Jokelainen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"Regidor-Cerrillo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis-Miguel","family":"Ortega-Mora","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Furio","family":"Spano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Seeber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gema","family":"\u00c1lvarez-Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,11,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms9112346","article-title":"Identification of Oocyst-Driven Toxoplasma gondii Infections in Humans and Animals through Stage-Specific Serology-Current Status and Future Perspectives","volume":"9","author":"\u00c1lvarez Garc\u00eda","year":"2021","journal-title":"Microorganisms"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.621738","article-title":"Toxoplasma GRA peptide-specific serologic fingerprints discriminate among major strains causing toxoplasmosis","volume":"11","author":"Arranz-Sol\u00eds","year":"2021","journal-title":"Front. Cell Infect. Microbiol."},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2019.00408","article-title":"Serotyping of Toxoplasma gondii infection using peptide membrane arrays","volume":"9","author":"Arranz-Sol\u00eds","year":"2019","journal-title":"Front. Cell Infect. Microbiol."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.02868-22","article-title":"Late Embryogenesis Abundant Proteins Contribute to the Resistance of Toxoplasma gondii Oocysts against Environmental Stresses","volume":"14","author":"Arranz-Sol\u00eds","year":"2023","journal-title":"mBio"},{"key":"B5","doi-asserted-by":"publisher","first-page":"2021","DOI":"10.1111\/tbed.14214","article-title":"Epidemiological study of toxoplasmosis outbreaks in Brazil","volume":"69","author":"Balbino","year":"2022","journal-title":"Transbound Emerg. Dis."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0011210","article-title":"Antigen discovery by bioinformatics analysis and peptide microarray for the diagnosis of cystic echinococcosis","volume":"17","author":"Batisti Biffignandi","year":"2023","journal-title":"PloS Negl. Trop. Dis."},{"key":"B7","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1186\/s13071-016-1610-6","article-title":"The prevalence and genotypic analysis of Toxoplasma gondii from individuals in Scotland 2006-2012","volume":"9","author":"Burrells","year":"2016","journal-title":"Parasit. Vectors"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.2807\/1560-7917.Es.2018.23.16.17-00454","article-title":"Impact of infectious diseases on population health using incidence-based disability-adjusted life years (DALYs): results from the Burden of Communicable Diseases in Europe study, European Union and European Economic Area countries 2009 to 2013","volume":"23","author":"Cassini","year":"2018","journal-title":"Euro. Surveill."},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbac567","article-title":"Critical review of conformational B-cell epitope prediction methods","volume":"24","author":"Cia","year":"2023","journal-title":"Brief Bioinform."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1002\/pro.4497","article-title":"BepiPred-3.0: Improved B-cell epitope prediction using protein language models","volume":"31","author":"Clifford","year":"2022","journal-title":"Protein Sci."},{"key":"B11","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1093\/bioinformatics\/btaa773","article-title":"EpiDope: a deep neural network for linear B-cell epitope prediction","volume":"37","author":"Collatz","year":"2021","journal-title":"Bioinformatics"},{"key":"B12","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1136\/bmj.321.7254.142","article-title":"Sources of Toxoplasma infection in pregnant women: European multicentre case-control study. European Research Network on Congenital Toxoplasmosis","volume":"321","author":"Cook","year":"2000","journal-title":"Bmj"},{"key":"B13","doi-asserted-by":"publisher","first-page":"12063","DOI":"10.1074\/jbc.M109.054866","article-title":"Structural and functional characterization of SporoSAG: a SAG2-related surface antigen from Toxoplasma gondii","volume":"285","author":"Crawford","year":"2010","journal-title":"J. Biol. Chem."},{"volume-title":"Toxoplasma gondii in pork production: a stable to table approach (Doctoral dissertation)","year":"2023","author":"D\u00e1mek","key":"B14"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2019.00046","article-title":"From entry to early dissemination-Toxoplasma gondii's initial encounter with its host","volume":"9","author":"Delgado Betancourt","year":"2019","journal-title":"Front. Cell Infect. Microbiol."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0108329","article-title":"Diagnostic value of a rec-ELISA using Toxoplasma gondii recombinant SporoSAG, BAG1, and GRA1 proteins in murine models infected orally with tissue cysts and oocysts","volume":"9","author":"D\u00f6\u015fkaya","year":"2014","journal-title":"PloS One"},{"key":"B17","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1186\/s13071-018-2934-1","article-title":"Discovery of new Toxoplasma gondii antigenic proteins using a high throughput protein microarray approach screening sera of murine model infected orally with oocysts and tissue cysts","volume":"11","author":"D\u00f6\u015fkaya","year":"2018","journal-title":"Parasit. Vectors"},{"key":"B18","doi-asserted-by":"crossref","DOI":"10.1201\/9781003199373","volume-title":"Toxoplasmosis of Animals and Humans","author":"Dubey","year":"2021"},{"key":"B19","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1186\/s13071-021-04769-4","article-title":"Outbreaks of clinical toxoplasmosis in humans: five decades of personal experience, perspectives and lessons learned","volume":"14","author":"Dubey","year":"2021","journal-title":"Parasit. Vectors"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.2903\/j.efsa.2018.5495","article-title":"Public health risks associated with food-borne parasites","volume":"16","author":"Koutsoumanis","year":"2018","journal-title":"EFSA. J."},{"key":"B21","doi-asserted-by":"publisher","first-page":"e01341","DOI":"10.1128\/mSphere.01341-20","article-title":"Expanding the known repertoire of C-type lectin receptors binding to Toxoplasma gondii oocysts using a modified high-resolution immunofluorescence assay","volume":"6","author":"Fabian","year":"2021","journal-title":"mSphere"},{"key":"B22","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1017\/s0031182014001978","article-title":"Identification of Toxoplasma gondii antigens associated with different types of infection by serum antibody profiling","volume":"142","author":"Felgner","year":"2015","journal-title":"Parasitology"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1017\/s0950268823000808","article-title":"Risk factors for acute toxoplasmosis in the Netherlands","volume":"151","author":"Friesema","year":"2023","journal-title":"Epidemiol. Infect."},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0029955","article-title":"Proteomic analysis of fractionated Toxoplasma oocysts reveals clues to their environmental resistance","volume":"7","author":"Fritz","year":"2012","journal-title":"PloS One"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0029998","article-title":"Transcriptomic analysis of Toxoplasma development reveals many novel functions and structures specific to sporozoites and oocysts","volume":"7","author":"Fritz","year":"2012","journal-title":"PloS One"},{"key":"B26","doi-asserted-by":"publisher","first-page":"3210","DOI":"10.3390\/ijms22063210","article-title":"Linear B-cell epitope prediction for in silico vaccine design: A performance review of methods available via command-line interface","volume":"22","author":"Galanis","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B27","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/B978-0-12-815041-2.00005-0","article-title":"Ocular disease due to Toxoplasma gondii","volume-title":"Toxoplasma gondii: The Model Apicomplexan - Perspectives and Methods","author":"Gomez-Marin","year":"2020"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0145839","article-title":"World Health organization estimates of the relative contributions of food to the burden of disease due to selected foodborne hazards: A structured expert elicitation","volume":"11","author":"Hald","year":"2016","journal-title":"PloS One"},{"key":"B29","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/978-1-4939-9857-9_2","article-title":"ToxoDB: functional genomics resource for Toxoplasma and related organisms","volume":"2071","author":"Harb","year":"2020","journal-title":"Methods Mol. Biol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"3098","DOI":"10.1093\/bioinformatics\/btx345","article-title":"Protein\u2013Sol: a web tool for predicting protein solubility from sequence","volume":"33","author":"Hebditch","year":"2017","journal-title":"Bioinf. (Oxford. England)."},{"key":"B31","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1645\/ge-2782.1","article-title":"Identification of a sporozoite-specific antigen from Toxoplasma gondii","volume":"97","author":"Hill","year":"2011","journal-title":"J. Parasitol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"2002.2005.527174","DOI":"10.1101\/2023.02.05.527174","article-title":"DiscoTope-3.0 - Improved B-cell epitope prediction using AlphaFold2 modeling and inverse folding latent representations","volume":"2023","author":"H\u00f8ie","year":"2023","journal-title":"bioRxiv"},{"key":"B33","doi-asserted-by":"publisher","first-page":"W24","DOI":"10.1093\/nar\/gkx346","article-title":"BepiPred-2.0: improving sequence-based B-cell epitope prediction using conformational epitopes","volume":"45","author":"Jespersen","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"B34","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"B35","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1186\/s12896-020-00646-7","article-title":"Expression of in vivo biotinylated recombinant antigens SAG1 and SAG2A from Toxoplasma gondii for improved seroepidemiological bead-based multiplex assays","volume":"20","author":"Klein","year":"2020","journal-title":"BMC Biotechnol."},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1021556","article-title":"Archetypal type II and III Toxoplasma gondii oocysts induce different immune responses and clinical outcomes in experimentally infected piglets","volume":"13","author":"Largo-de la Torre","year":"2022","journal-title":"Front. Immunol."},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M110.006916","article-title":"Identification of potential serodiagnostic and subunit vaccine antigens by antibody profiling of toxoplasmosis cases in Turkey","volume":"10","author":"Liang","year":"2011","journal-title":"Mol. Cell Proteomics"},{"key":"B38","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1097\/qco.0000000000000193","article-title":"A systems biology approach for diagnostic and vaccine antigen discovery in tropical infectious diseases","volume":"28","author":"Liang","year":"2015","journal-title":"Curr. Opin. Infect. Dis."},{"key":"B39","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1186\/s12917-019-2121-4","article-title":"Toxoplasma gondii oocyst-driven infection in pigs, chickens and humans in northeastern China","volume":"15","author":"Liu","year":"2019","journal-title":"BMC Vet. Res."},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2023.110024","article-title":"Optimization of the most widely used serological tests for a harmonized diagnosis of Toxoplasma gondii infection in domestic pigs","volume":"322","author":"L\u00f3pez-Ure\u00f1a","year":"2023","journal-title":"Vet. Parasitol."},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.rvsc.2023.105052","article-title":"A comparative study of serological tests used in the diagnosis of Toxoplasma gondii infection in small ruminants evidenced the importance of cross-reactions for harmonizing diagnostic performance","volume":"165","author":"L\u00f3pez-Ure\u00f1a","year":"2023","journal-title":"Res. Vet. Sci."},{"key":"B42","doi-asserted-by":"publisher","first-page":"517","DOI":"10.3390\/microorganisms10030517","article-title":"Contamination of soil, water, fresh produce, and bivalve mollusks with Toxoplasma gondii oocysts: A systematic review","volume":"10","author":"L\u00f3pez-Ure\u00f1a","year":"2022","journal-title":"Microorganisms"},{"key":"B43","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/j.str.2015.10.028","article-title":"Antibody recognition of disordered antigens","volume":"24","author":"MacRaild","year":"2016","journal-title":"Structure"},{"key":"B44","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1128\/cvi.00119-12","article-title":"Peptide microarray analysis of in silico-predicted epitopes for serological diagnosis of Toxoplasma gondii infection in humans","volume":"19","author":"Maksimov","year":"2012","journal-title":"Clin. Vaccine Immunol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"2568","DOI":"10.1017\/s0950268816000960","article-title":"Salivary IgA against sporozoite-specific embryogenesis-related protein (TgERP) in the study of horizontally transmitted toxoplasmosis via T. gondii oocysts in endemic settings","volume":"144","author":"Mangiavacchi","year":"2016","journal-title":"Epidemiol. Infect."},{"key":"B46","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1186\/s12859-017-1995-z","article-title":"fDETECT webserver: fast predictor of propensity for protein production, purification, and crystallization","volume":"18","author":"Meng","year":"2017","journal-title":"BMC Bioinf."},{"key":"B47","doi-asserted-by":"publisher","first-page":"227","DOI":"10.20506\/rst.40.1.3220","article-title":"Quality standards and guidelines for test validation for infectious diseases in veterinary laboratories","volume":"40","author":"Newberry","year":"2021","journal-title":"Rev. Sci. Tech."},{"key":"B48","doi-asserted-by":"publisher","first-page":"2177","DOI":"10.3201\/eid2512.181565","article-title":"Patterns of transmission and sources of infection in outbreaks of human toxoplasmosis","volume":"25","author":"Pinto-Ferreira","year":"2019","journal-title":"Emerg. Infect. Dis."},{"key":"B49","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1093\/nar\/gkaa1058","article-title":"MobiDB: intrinsically disordered proteins in 2021","volume":"54","author":"Piovesan","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1639","DOI":"10.1016\/j.ijpara.2010.06.009","article-title":"Molecular characterisation of a novel family of cysteine-rich proteins of Toxoplasma gondii and ultrastructural evidence of oocyst wall localisation","volume":"40","author":"Possenti","year":"2010","journal-title":"Int. J. Parasitol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1111\/j.1365-2958.2003.03967.x","article-title":"Identification of a sporozoite-specific member of the Toxoplasma SAG superfamily via genetic complementation","volume":"52","author":"Radke","year":"2004","journal-title":"Mol. Microbiol."},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.702552","article-title":"APRANK: computational prioritization of antigenic proteins and peptides from complete pathogen proteomes","volume":"12","author":"Ricci","year":"2021","journal-title":"Front. Immunol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1016\/j.parint.2017.05.009","article-title":"Evaluation of novel oocyst wall protein candidates of Toxoplasma gondii","volume":"66","author":"Salman","year":"2017","journal-title":"Parasitol. Int."},{"key":"B54","doi-asserted-by":"publisher","first-page":"1518","DOI":"10.3390\/pathogens10111518","article-title":"Dynamics of Neospora caninum-associated abortions in a dairy sheep flock and results of a test-and-cull control programme","volume":"10","author":"S\u00e1nchez-S\u00e1nchez","year":"2021","journal-title":"Pathogens"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2015.01305","article-title":"CCp5A Protein from Toxoplasma gondii as a serological marker of oocyst-driven infections in humans and domestic animals","volume":"6","author":"Santana","year":"2015","journal-title":"Front. Microbiol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1080\/10409238.2020.1869683","article-title":"Mobility and disorder in antibody and antigen binding sites do not prevent immunochemical recognition","volume":"56","author":"Uversky","year":"2021","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2023.109889","article-title":"Experimental infection of sheep at mid-pregnancy with archetypal type II and type III Toxoplasma gondii isolates exhibited different phenotypic traits","volume":"315","author":"Vallejo","year":"2023","journal-title":"Vet. Parasitol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1590\/0074-02760150262","article-title":"Waterborne toxoplasmosis investigated and analysed under hydrogeological assessment: new data and perspectives for further research","volume":"110","author":"Vieira","year":"2015","journal-title":"Mem. Inst. Oswaldo. Cruz."}],"container-title":["Frontiers in Parasitology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpara.2023.1292322\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T06:53:43Z","timestamp":1701068023000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpara.2023.1292322\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,27]]},"references-count":58,"alternative-id":["10.3389\/fpara.2023.1292322"],"URL":"https:\/\/doi.org\/10.3389\/fpara.2023.1292322","relation":{},"ISSN":["2813-2424"],"issn-type":[{"type":"electronic","value":"2813-2424"}],"subject":[],"published":{"date-parts":[[2023,11,27]]},"article-number":"1292322"}}