{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T23:29:49Z","timestamp":1771975789756,"version":"3.50.1"},"reference-count":57,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T00:00:00Z","timestamp":1634083200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Human noroviruses are a common pathogen causing acute gastroenteritis worldwide. Among all norovirus genotypes, GII.3 is particularly prevalent in the pediatric population. Here we report the identification of two distinct blockade antibody epitopes on the GII.3 capsid. We generated a panel of monoclonal antibodies (mAbs) from mice immunized with virus-like particle (VLP) of a GII.3 cluster 3 strain. Two of these mAbs, namely 8C7 and 8D1, specifically bound the parental GII.3 VLP but not VLPs of GII.4, GII.17, or GI.1. In addition, 8C7 and 8D1 efficiently blocked GII.3 VLP binding with its ligand, histo-blood group antigens (HBGA). These data demonstrate that 8C7 and 8D1 are GII.3-specific blockade antibodies. By using a series of chimeric VLPs, we mapped the epitopes of 8C7 and 8D1 to residues 385\u2013400 and 401\u2013420 of the VP1 capsid protein, respectively. These two blockade antibody epitopes are highly conserved among GII.3 cluster 3 strains. Structural modeling shows that the 8C7 epitope partially overlaps with the HBGA binding site (HBS) while the 8D1 epitope is spatially adjacent to HBS. These findings may enhance our understanding of the immunology and evolution of GII.3 noroviruses.<\/jats:p>","DOI":"10.3390\/v13102058","type":"journal-article","created":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T21:55:02Z","timestamp":1634162102000},"page":"2058","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Identification of Human Norovirus GII.3 Blockade Antibody Epitopes"],"prefix":"10.3390","volume":"13","author":[{"given":"Yufang","family":"Yi","sequence":"first","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Medical University, Haikou 571199, China"},{"name":"Hainan Medical University\u2014The University of Hong Kong Joint Laboratory of Tropical Infectious Diseases, Hainan Medical University, Haikou 571199, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuxia","family":"Wang","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoli","family":"Wang","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pei","family":"Xiong","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingwei","family":"Liu","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8658-9009","authenticated-orcid":false,"given":"Chao","family":"Zhang","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6195-0614","authenticated-orcid":false,"given":"Feifei","family":"Yin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Medical University, Haikou 571199, China"},{"name":"Hainan Medical University\u2014The University of Hong Kong Joint Laboratory of Tropical Infectious Diseases, Hainan Medical University, Haikou 571199, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2161-1359","authenticated-orcid":false,"given":"Zhong","family":"Huang","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1038\/nm860","article-title":"Human susceptibility and resistance to Norwalk virus infection","volume":"9","author":"Lindesmith","year":"2003","journal-title":"Nat. Med."},{"key":"ref_2","first-page":"153","article-title":"The role of human caliciviruses in epidemic gastroenteritis","volume":"13","author":"Green","year":"1997","journal-title":"Arch. Virol. Suppl."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1099\/jgv.0.001318","article-title":"Updated classification of norovirus genogroups and genotypes","volume":"100","author":"Chhabra","year":"2019","journal-title":"J. Gen. Virol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1006\/viro.1993.1345","article-title":"Sequence and genomic organization of Norwalk virus","volume":"195","author":"Jiang","year":"1993","journal-title":"Virology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1006\/viro.2002.1568","article-title":"Phylogenetic analysis of the complete genome of 18 Norwalk-like viruses","volume":"299","author":"Katayama","year":"2002","journal-title":"Virology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.femsle.2005.08.031","article-title":"Norovirus protein structure and function","volume":"253","author":"Hardy","year":"2005","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1126\/science.286.5438.287","article-title":"X-ray crystallographic structure of the Norwalk virus capsid","volume":"286","author":"Prasad","year":"1999","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"14017","DOI":"10.1128\/JVI.79.22.14017-14030.2005","article-title":"The p domain of norovirus capsid protein forms a subviral particle that binds to histo-blood group antigen receptors","volume":"79","author":"Tan","year":"2005","journal-title":"J. Virol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5949","DOI":"10.1128\/JVI.00219-07","article-title":"Structural basis for the recognition of blood group trisaccharides by norovirus","volume":"81","author":"Cao","year":"2007","journal-title":"J. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"8048","DOI":"10.1073\/pnas.0600421103","article-title":"X-ray structure of a native calicivirus: Structural insights into antigenic diversity and host specificity","volume":"103","author":"Chen","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.tim.2005.04.004","article-title":"Norovirus and its histo-blood group antigen receptors: An answer to a historical puzzle","volume":"13","author":"Tan","year":"2005","journal-title":"Trends Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Tan, M., and Jiang, X. (2010). Norovirus gastroenteritis, carbohydrate receptors, and animal models. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1000983"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.tim.2011.05.007","article-title":"Norovirus-host interaction: Multi-selections by human histo-blood group antigens","volume":"19","author":"Tan","year":"2011","journal-title":"Trends Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.1007\/s00705-013-1708-5","article-title":"Proposal for a unified norovirus nomenclature and genotyping","volume":"158","author":"Kroneman","year":"2013","journal-title":"Arch. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1128\/JCM.02680-13","article-title":"Genotypic and epidemiologic trends of norovirus outbreaks in the United States, 2009 to 2013","volume":"52","author":"Vega","year":"2014","journal-title":"J. Clin. Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.tim.2011.01.002","article-title":"Mechanisms of GII.4 norovirus evolution","volume":"19","author":"Bull","year":"2011","journal-title":"Trends Microbiol."},{"key":"ref_17","first-page":"8","article-title":"Indications for worldwide increased norovirus activity associated with emergence of a new variant of genotype II.4, late 2012","volume":"18","author":"Botteldoorn","year":"2013","journal-title":"Euro Surveill."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Siebenga, J.J., Lemey, P., Kosakovsky Pond, S.L., Rambaut, A., Vennema, H., and Koopmans, M. (2010). Phylodynamic reconstruction reveals norovirus GII.4 epidemic expansions and their molecular determinants. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1000884"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"9932","DOI":"10.1128\/JVI.00674-07","article-title":"Epochal evolution of GGII.4 norovirus capsid proteins from 1995 to 2006","volume":"81","author":"Siebenga","year":"2007","journal-title":"J. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1086\/314783","article-title":"Identification of a distinct common strain of \"Norwalk-like viruses\" having a global distribution","volume":"179","author":"Noel","year":"1999","journal-title":"J. Infect. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8656","DOI":"10.1128\/JVI.00472-11","article-title":"Comparative evolution of GII.3 and GII.4 norovirus over a 31-year period","volume":"85","author":"Boon","year":"2011","journal-title":"J. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3687","DOI":"10.1128\/JVI.03056-12","article-title":"The importance of intergenic recombination in norovirus GII.3 evolution","volume":"87","author":"Mahar","year":"2013","journal-title":"J. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Wangchuk, S., Matsumoto, T., Iha, H., and Ahmed, K. (2017). Surveillance of norovirus among children with diarrhea in four major hospitals in Bhutan: Replacement of GII.21 by GII.3 as a dominant genotype. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0184826"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.meegid.2018.02.028","article-title":"The dynamics of norovirus genotypes and genetic analysis of a novel recombinant GII.P12-GII.3 among infants and children in Bangkok, Thailand between 2014 and 2016","volume":"60","author":"Boonchan","year":"2018","journal-title":"Infect. Genet. Evol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2737","DOI":"10.1007\/s00705-018-3905-8","article-title":"Genomic characterization of GII.3 noroviruses isolated from children in Zhengzhou city, China, 2015\/16","volume":"163","author":"Liu","year":"2018","journal-title":"Arch. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"11507","DOI":"10.1038\/srep11507","article-title":"Virus Genotype Distribution and Virus Burden in Children and Adults Hospitalized for Norovirus Gastroenteritis, 2012\u20132014, Hong Kong","volume":"5","author":"Chan","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Li, H.Y., Zhang, Y.G., Lei, X., Song, J., and Duan, Z.J. (2019). Prevalence of noroviruses in children hospitalized for acute gastroenteritis in Hohhot, China, 2012\u20132017. BMC Infect. Dis., 19.","DOI":"10.1186\/s12879-019-4230-x"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11684-019-0733-5","article-title":"The epidemiology of norovirus gastroenteritis in China: Disease burden and distribution of genotypes","volume":"14","author":"Zhou","year":"2020","journal-title":"Front. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"104703","DOI":"10.1016\/j.meegid.2020.104703","article-title":"Molecular epidemiology and genetic diversity of norovirus infection in children hospitalized with acute gastroenteritis in East Java, Indonesia in 2015-2019","volume":"88","author":"Utsumi","year":"2021","journal-title":"Infect. Genet. Evol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1097\/INF.0000000000002989","article-title":"Hospital-based Surveillance for Pediatric Norovirus Gastroenteritis in Bangladesh, 2012\u20132016","volume":"40","author":"Satter","year":"2021","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1002\/jmv.1890460305","article-title":"Enzyme immunoassay using baculovirus-expressed human calicivirus (Mexico) for the measurement of IgG responses and determining its seroprevalence in London, UK","volume":"46","author":"Parker","year":"1995","journal-title":"J. Med. Virol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1002\/jmv.24068","article-title":"Molecular epidemiology of noroviruses associated with sporadic gastroenteritis in children in Novosibirsk, Russia, 2003\u20132012","volume":"87","author":"Zhirakovskaia","year":"2015","journal-title":"J. Med. Virol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e03835","DOI":"10.1016\/j.heliyon.2020.e03835","article-title":"Molecular evolution of the capsid (VP1) region in human norovirus genogroup II genotype 3","volume":"6","author":"Saito","year":"2020","journal-title":"Heliyon"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1007\/s11262-016-1359-1","article-title":"Characterization of virus-like particles derived from a GII.3 norovirus strain distantly related with current dominating strains","volume":"52","author":"Huo","year":"2016","journal-title":"Virus Genes"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Song, C., Takai-Todaka, R., Miki, M., Haga, K., Fujimoto, A., Ishiyama, R., Oikawa, K., Yokoyama, M., Miyazaki, N., and Iwasaki, K. (2020). Dynamic rotation of the protruding domain enhances the infectivity of norovirus. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008619"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1080\/22221751.2019.1686335","article-title":"Structural basis of host ligand specificity change of GII porcine noroviruses from their closely related GII human noroviruses","volume":"8","author":"Yang","year":"2019","journal-title":"Emerg. Microbes Infect."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.micpath.2015.11.022","article-title":"Biological and immunological characterization of norovirus major capsid proteins from three different genotypes","volume":"90","author":"Huo","year":"2016","journal-title":"Microb. Pathog."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1080\/22221751.2021.1925162","article-title":"Identification of a blockade epitope of human norovirus GII.17","volume":"10","author":"Yi","year":"2021","journal-title":"Emerg. Microbes Infect."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2335","DOI":"10.1016\/j.vaccine.2015.03.034","article-title":"High-yield production of recombinant virus-like particles of enterovirus 71 in Pichia pastoris and their protective efficacy against oral viral challenge in mice","volume":"33","author":"Zhang","year":"2015","journal-title":"Vaccine"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2904","DOI":"10.1038\/s41467-021-23199-5","article-title":"Functional and structural characterization of a two-MAb cocktail for delayed treatment of enterovirus D68 infections","volume":"12","author":"Zhang","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1038\/s41467-020-20465-w","article-title":"Development and structural basis of a two-MAb cocktail for treating SARS-CoV-2 infections","volume":"12","author":"Zhang","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/s41421-019-0140-8","article-title":"A new class of broadly neutralizing antibodies that target the glycan loop of Zika virus envelope protein","volume":"6","author":"Qu","year":"2020","journal-title":"Cell Discov."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1086\/427779","article-title":"Association of histo-blood group antigens and susceptibility to norovirus infections","volume":"191","author":"Rockx","year":"2005","journal-title":"J. Infect. Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1086\/339883","article-title":"Norwalk virus infection and disease is associated with ABO histo-blood group type","volume":"185","author":"Hutson","year":"2002","journal-title":"J. Infect. Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5842","DOI":"10.1016\/j.vaccine.2020.06.011","article-title":"A phase 2 study of the bivalent VLP norovirus vaccine candidate in older adults; impact of MPL adjuvant or a second dose","volume":"38","author":"Treanor","year":"2020","journal-title":"Vaccine"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"6442","DOI":"10.1016\/j.vaccine.2020.07.069","article-title":"Efficacy of an intramuscular bivalent norovirus GI.1\/GII.4 virus-like particle vaccine candidate in healthy US adults","volume":"38","author":"Sherwood","year":"2020","journal-title":"Vaccine"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Zhang, M., Fu, M., and Hu, Q. (2021). Advances in Human Norovirus Vaccine Research. Vaccines, 9.","DOI":"10.3390\/vaccines9070732"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1586\/erv.12.145","article-title":"Norovirus virus-like particle vaccines for the prevention of acute gastroenteritis","volume":"12","author":"Richardson","year":"2013","journal-title":"Expert Rev. Vaccines"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Lindesmith, L.C., Beltramello, M., Donaldson, E.F., Corti, D., Swanstrom, J., Debbink, K., Lanzavecchia, A., and Baric, R.S. (2012). Immunogenetic mechanisms driving norovirus GII.4 antigenic variation. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002705"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1128\/JVI.06189-11","article-title":"Genetic mapping of a highly variable norovirus GII.4 blockade epitope: Potential role in escape from human herd immunity","volume":"86","author":"Debbink","year":"2012","journal-title":"J. Virol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1128\/JVI.06200-11","article-title":"Monoclonal antibody-based antigenic mapping of norovirus GII.4-2002","volume":"86","author":"Lindesmith","year":"2012","journal-title":"J. Virol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Mallory, M.L., Lindesmith, L.C., Graham, R.L., and Baric, R.S. (2019). GII.4 Human Norovirus: Surveying the Antigenic Landscape. Viruses, 11.","DOI":"10.3390\/v11020177"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1002\/jmv.25001","article-title":"Characterization of a Norovirus-specific monoclonal antibody that exhibits wide spectrum binding activities","volume":"90","author":"Zheng","year":"2018","journal-title":"J. Med. Virol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Parra, G.I., Azure, J., Fischer, R., Bok, K., Sandoval-Jaime, C., Sosnovtsev, S.V., Sander, P., and Green, K.Y. (2013). Identification of a Broadly Cross-Reactive Epitope in the Inner Shell of the Norovirus Capsid. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0067592"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Lindesmith, L.C., Brewer-Jensen, P.D., Mallory, M.L., Yount, B., Collins, M.H., Debbink, K., Graham, R.L., and Baric, R.S. (2019). Human Norovirus Epitope D Plasticity Allows Escape from Antibody Immunity without Loss of Capacity for Binding Cellular Ligands. J. Virol., 93.","DOI":"10.1128\/JVI.01813-18"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"7703","DOI":"10.1128\/JVI.01023-16","article-title":"Characterization of a Novel Conformational GII.4 Norovirus Epitope: Implications for Norovirus-Host Interactions","volume":"90","author":"Allen","year":"2016","journal-title":"J. Virol"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Koromyslova, A.D., Morozov, V.A., Hefele, L., and Hansman, G.S. (2019). Human Norovirus Neutralized by a Monoclonal Antibody Targeting the Histo-Blood Group Antigen Pocket. J. Virol., 93.","DOI":"10.1128\/JVI.02174-18"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/10\/2058\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:12:40Z","timestamp":1760166760000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/10\/2058"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,13]]},"references-count":57,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["v13102058"],"URL":"https:\/\/doi.org\/10.3390\/v13102058","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,13]]}}}