{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:41:05Z","timestamp":1787312465056,"version":"build-2736575974"},"reference-count":47,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T00:00:00Z","timestamp":1650931200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The competitive State research financing of the responsible area of Tampere","award":["9AA050 and 9AB046"],"award-info":[{"award-number":["9AA050 and 9AB046"]}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["308613"],"award-info":[{"award-number":["308613"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["321809"],"award-info":[{"award-number":["321809"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006306","name":"Sigrid Jus\u00e9lius Foundation","doi-asserted-by":"publisher","award":["0220205"],"award-info":[{"award-number":["0220205"]}],"id":[{"id":"10.13039\/501100006306","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003756","name":"Helsinki University Hospital","doi-asserted-by":"publisher","award":["TYH2021343"],"award-info":[{"award-number":["TYH2021343"]}],"id":[{"id":"10.13039\/501100003756","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004012","name":"Jane and Aatos Erkko Foundation","doi-asserted-by":"publisher","award":["Olli Vapalahti"],"award-info":[{"award-number":["Olli Vapalahti"]}],"id":[{"id":"10.13039\/501100004012","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Nephropathia epidemica (NE), a mild form of haemorrhagic fever with renal syndrome (HFRS), is an acute febrile illness caused by Puumala orthohantavirus (PUUV). NE manifests typically with acute kidney injury (AKI), with a case fatality rate of about 0.1%. The treatment and management of hantavirus infections are mainly supportive, although neutralizing monoclonal antibodies and immune sera therapeutics are under investigation. In order to assess the potential use of antibody therapeutics in NE, we sought to determine the relationship between circulating PUUV neutralizing antibodies, PUUV nucleocapsid protein (N) IgG antibodies, and viral loads with markers of disease severity. The study included serum samples of extensively characterized patient cohorts (n = 116) from Tampere University Hospital, Finland. The results showed that upon hospitalization, most patients already had considerable neutralizing and anti-PUUV-N IgG antibody levels. However, contrary to expectations, neutralizing antibody titers from the first day of hospitalization did not appear to protect from AKI or correlate with more favorable disease outcomes. This indicates that further studies are needed to investigate the applicability of neutralizing antibodies as a therapy for hospitalized NE patients.<\/jats:p>","DOI":"10.3390\/v14050901","type":"journal-article","created":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T21:37:53Z","timestamp":1651009073000},"page":"901","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Neutralizing Antibody Titers in Hospitalized Patients with Acute Puumala Orthohantavirus Infection Do Not Associate with Disease Severity"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7654-5515","authenticated-orcid":false,"given":"Rommel","family":"Iheozor-Ejiofor","sequence":"first","affiliation":[{"name":"Department of Virology, Medicum, University of Helsinki, 00014 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katariina","family":"Vapalahti","sequence":"additional","affiliation":[{"name":"Department of Veterinary Biosciences, University of Helsinki, 00014 Helsinki, Finland"},{"name":"Diagnostic Center, Virology and Immunology, HUSLAB, Helsinki University Hospital, 00029 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2344-2755","authenticated-orcid":false,"given":"Tarja","family":"Sironen","sequence":"additional","affiliation":[{"name":"Department of Virology, Medicum, University of Helsinki, 00014 Helsinki, Finland"},{"name":"Department of Veterinary Biosciences, University of Helsinki, 00014 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lev","family":"Levanov","sequence":"additional","affiliation":[{"name":"Department of Virology, Medicum, University of Helsinki, 00014 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5699-214X","authenticated-orcid":false,"given":"Jussi","family":"Hepojoki","sequence":"additional","affiliation":[{"name":"Department of Virology, Medicum, University of Helsinki, 00014 Helsinki, Finland"},{"name":"Vetsuisse Faculty, Institute of Veterinary Pathology, University of Z\u00fcrich, CH-8057 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8608-6551","authenticated-orcid":false,"given":"\u00c5ke","family":"Lundkvist","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Microbiology, Zoonosis Science Center, Uppsala University, SE-751 05 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6967-2401","authenticated-orcid":false,"given":"Satu","family":"M\u00e4kel\u00e4","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Tampere University Hospital, 33520 Tampere, Finland"},{"name":"Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2670-2345","authenticated-orcid":false,"given":"Antti","family":"Vaheri","sequence":"additional","affiliation":[{"name":"Department of Virology, Medicum, University of Helsinki, 00014 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3462-2129","authenticated-orcid":false,"given":"Jukka","family":"Mustonen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Tampere University Hospital, 33520 Tampere, Finland"},{"name":"Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Plyusnin","sequence":"additional","affiliation":[{"name":"Department of Virology, Medicum, University of Helsinki, 00014 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2454-7479","authenticated-orcid":false,"given":"Tomas M.","family":"Strandin","sequence":"additional","affiliation":[{"name":"Department of Virology, Medicum, University of Helsinki, 00014 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2270-6824","authenticated-orcid":false,"given":"Olli","family":"Vapalahti","sequence":"additional","affiliation":[{"name":"Department of Virology, Medicum, University of Helsinki, 00014 Helsinki, Finland"},{"name":"Department of Veterinary Biosciences, University of Helsinki, 00014 Helsinki, Finland"},{"name":"Diagnostic Center, Virology and Immunology, HUSLAB, Helsinki University Hospital, 00029 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1016\/0140-6736(91)92235-T","article-title":"Rapid diagnosis of hantavirus disease with an IgG-avidity assay","volume":"338","author":"Hedman","year":"1991","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/nrmicro3066","article-title":"Uncovering the mysteries of hantavirus infections","volume":"11","author":"Vaheri","year":"2013","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_3","first-page":"47","article-title":"Virus evolution and genetic diversity of hantaviruses and their rodent hosts","volume":"256","author":"Plyusnin","year":"2001","journal-title":"Curr. Top Microbiol. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"773","DOI":"10.2174\/156652405774962317","article-title":"Hantaviruses: Molecular biology, evolution and pathogenesis","volume":"5","author":"Khaiboullina","year":"2005","journal-title":"Curr. Mol. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1128\/jvi.55.1.34-38.1985","article-title":"Experimental infection with Puumala virus, the etiologic agent of nephropathia epidemica, in bank voles (Clethrionomys glareolus)","volume":"55","author":"Yanagihara","year":"1985","journal-title":"J. Virol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.3201\/eid1311.070221","article-title":"Characterization of hemorrhagic fever with renal syndrome caused by hantaviruses, Estonia","volume":"13","author":"Golovljova","year":"2007","journal-title":"Emerg. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1080\/003655400750045204","article-title":"Clinical aspects of nephropathia epidemica (Puumala virus infection) in Europe: A review","volume":"32","author":"Settergren","year":"2000","journal-title":"Scand. J. Infect. Dis."},{"key":"ref_8","unstructured":"European Centre for Disease Prevention and Control (2022, January 17). Hantavirus Infection, on ECDC. Available online: https:\/\/www.ecdc.europa.eu\/en\/publications-data\/hantavirus-infection-annual-epidemiological-report-2018."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"727","DOI":"10.3389\/fmicb.2014.00727","article-title":"The fundamental role of endothelial cells in hantavirus pathogenesis","volume":"5","author":"Hepojoki","year":"2014","journal-title":"Front. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"13837","DOI":"10.1073\/pnas.192298899","article-title":"Pathogenic and nonpathogenic hantaviruses differentially regulate endothelial cell responses","volume":"99","author":"Geimonen","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1128\/CMR.00062-09","article-title":"A global perspective on hantavirus ecology, epidemiology, and disease","volume":"23","author":"Jonsson","year":"2010","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1099\/jgv.0.000437","article-title":"Vaccinia virus-free rescue of Fluorescent replication-defective Vesicular Stomatitis virus and pseudotyping with Puumala virus glycoproteins for use in neutralization tests","volume":"97","author":"Levanov","year":"2016","journal-title":"J. Gen. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"377","DOI":"10.3851\/IMP2875","article-title":"A non-randomized multicentre trial of human immune plasma for treatment of hantavirus cardiopulmonary syndrome caused by Andes virus","volume":"20","author":"Vial","year":"2015","journal-title":"Antivir. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1038\/nri.2017.148","article-title":"Passive immunotherapy of viral infections: \u2018super-antibodies\u2019 enter the fray","volume":"18","author":"Walker","year":"2018","journal-title":"Nat. Rev. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Habjan, M., Andersson, I., Klingstrom, J., Schumann, M., Martin, A., Zimmermann, P., Wagner, V., Pichlmair, A., Schneider, U., and Muhlberger, E. (2008). Processing of genome 5\u2032 termini as a strategy of negative-strand RNA viruses to avoid RIG-I-dependent interferon induction. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0002032"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2157","DOI":"10.1099\/vir.0.2008\/002097-0","article-title":"T7 RNA polymerase-dependent and -independent systems for cDNA-based rescue of Rift Valley fever virus","volume":"89","author":"Habjan","year":"2008","journal-title":"J. Gen. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4185","DOI":"10.1128\/JVI.01853-08","article-title":"A chimeric A2 strain of respiratory syncytial virus (RSV) with the fusion protein of RSV strain line 19 exhibits enhanced viral load, mucus, and airway dysfunction","volume":"83","author":"Moore","year":"2009","journal-title":"J. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/S1386-6532(01)00191-3","article-title":"Comparison of a new immunochromatographic rapid test with a commercial EIA for the detection of Puumala virus specific IgM antibodies","volume":"23","author":"Hujakka","year":"2001","journal-title":"J. Clin. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1002\/jmv.1890460402","article-title":"Human B-cell epitopes of Puumala virus nucleocapsid protein, the major antigen in early serological response","volume":"46","author":"Vapalahti","year":"1995","journal-title":"J. Med. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1128\/jcm.34.1.119-125.1996","article-title":"Antigenic properties and diagnostic potential of puumala virus nucleocapsid protein expressed in insect cells","volume":"34","author":"Vapalahti","year":"1996","journal-title":"J. Clin. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1053\/j.ajkd.2021.08.003","article-title":"A Unifying Approach for GFR Estimation: Recommendations of the NKF-ASN Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease","volume":"79","author":"Delgado","year":"2022","journal-title":"Am. J. Kidney. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2994","DOI":"10.1681\/ASN.2021070988","article-title":"A Unifying Approach for GFR Estimation: Recommendations of the NKF-ASN Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease","volume":"32","author":"Delgado","year":"2021","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"604","DOI":"10.7326\/0003-4819-150-9-200905050-00006","article-title":"A new equation to estimate glomerular filtration rate","volume":"150","author":"Levey","year":"2009","journal-title":"Ann. Intern. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"461","DOI":"10.7326\/0003-4819-130-6-199903160-00002","article-title":"A more accurate method to estimate glomerular filtration rate from serum creatinine: A new prediction equation. Modification of Diet in Renal Disease Study Group","volume":"130","author":"Levey","year":"1999","journal-title":"Ann. Intern. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1097\/CCM.0000000000000324","article-title":"The highs and lows of blood pressure: Toward meaningful clinical targets in patients with shock","volume":"42","author":"Magder","year":"2014","journal-title":"Crit. Care Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2098","DOI":"10.3389\/fimmu.2018.02098","article-title":"Neutrophil Activation in Acute Hemorrhagic Fever With Renal Syndrome Is Mediated by Hantavirus-Infected Microvascular Endothelial Cells","volume":"9","author":"Strandin","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.antiviral.2014.08.007","article-title":"Pathophysiology of a severe case of Puumala hantavirus infection successfully treated with bradykinin receptor antagonist icatibant","volume":"111","author":"Vaheri","year":"2014","journal-title":"Antivir. Res."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Niskanen, S., Jaaskelainen, A., Vapalahti, O., and Sironen, T. (2019). Evaluation of Real-Time RT-PCR for Diagnostic Use in Detection of Puumala Virus. Viruses, 11.","DOI":"10.3390\/v11070661"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/BF01309687","article-title":"Bank vole monoclonal antibodies against Puumala virus envelope glycoproteins: Identification of epitopes involved in neutralization","volume":"126","author":"Lundkvist","year":"1992","journal-title":"Arch. Virol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1080\/01621459.1987.10478551","article-title":"Fine-Tuning Some Resistant Rules for Outlier Labeling","volume":"82","author":"Hoaglin","year":"1987","journal-title":"J. Am. Stat. Assoc."},{"key":"ref_31","unstructured":"IBM Corp (2016). Release IBM SPSS Statistics for Windows, IBM Corp. v24.0."},{"key":"ref_32","unstructured":"SAS Institute Inc (2013). SAS 9.4, SAS Institute Inc."},{"key":"ref_33","unstructured":"R Core Team (2021, November 23). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing, Vienna, Austria. Available online: https:\/\/www.R-project.org\/."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s00705-004-0389-5","article-title":"Delayed viremia and antibody responses in Puumala hantavirus challenged passively immunized cynomolgus macaques","volume":"150","author":"Klingstrom","year":"2005","journal-title":"Arch. Virol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1177\/135965350801300114","article-title":"Passive immunization protects cynomolgus macaques against Puumala hantavirus challenge","volume":"13","author":"Klingstrom","year":"2008","journal-title":"Antivir. Ther."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Brocato, R.L., and Hooper, J.W. (2019). Progress on the Prevention and Treatment of Hantavirus Disease. Viruses, 11.","DOI":"10.3390\/v11070610"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1093\/infdis\/164.6.1119","article-title":"Prospective, double-blind, concurrent, placebo-controlled clinical trial of intravenous ribavirin therapy of hemorrhagic fever with renal syndrome","volume":"164","author":"Huggins","year":"1991","journal-title":"J. Infect. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1080\/23744235.2017.1293841","article-title":"Insufficient efficacy and safety of intravenous ribavirin in treatment of haemorrhagic fever with renal syndrome caused by Puumala virus","volume":"49","author":"Malinin","year":"2017","journal-title":"Infect. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2909","DOI":"10.12688\/f1000research.9092.1","article-title":"Agents to reduce cytokine storm","volume":"5","author":"Gerlach","year":"2016","journal-title":"F1000Research"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1086\/315657","article-title":"Humoral immune responses in the hantavirus cardiopulmonary syndrome","volume":"182","author":"Bharadwaj","year":"2000","journal-title":"J. Infect. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Hepojoki, J., Cabrera, L.E., Hepojoki, S., Bellomo, C., Kareinen, L., Andersson, L.C., Vaheri, A., Makela, S., Mustonen, J., and Vapalahti, O. (2021). Hantavirus infection-induced B cell activation elevates free light chains levels in circulation. PLoS Pathog., 17.","DOI":"10.1371\/journal.ppat.1009843"},{"key":"ref_42","first-page":"121","article-title":"Renal biopsy findings and clinicopathologic correlations in nephropathia epidemica","volume":"41","author":"Mustonen","year":"1994","journal-title":"Clin. Nephrol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1111\/1469-0691.12259","article-title":"Viral load and humoral immune response in association with disease severity in Puumala hantavirus-infected patients\u2014Implications for treatment","volume":"20","author":"Pettersson","year":"2014","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1080\/23744235.2016.1192719","article-title":"Thrombocytopenia associates with the severity of inflammation and variables reflecting capillary leakage in Puumala Hantavirus infection, an analysis of 546 Finnish patients","volume":"48","author":"Outinen","year":"2016","journal-title":"Infect. Dis."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Vangeti, S., Strandin, T., Liu, S., Tauriainen, J., Raisanen-Sokolowski, A., Cabrera, L., Hassinen, A., Makela, S., Mustonen, J., and Vaheri, A. (2021). Monocyte subset redistribution from blood to kidneys in patients with Puumala virus caused hemorrhagic fever with renal syndrome. PLoS Pathog., 17.","DOI":"10.1371\/journal.ppat.1009876"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1186\/s13054-016-1478-z","article-title":"Acute kidney injury 2016: Diagnosis and diagnostic workup","volume":"20","author":"Ostermann","year":"2016","journal-title":"Crit. Care"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1017\/S0950268817002904","article-title":"Population-based seroprevalence of Puumala hantavirus in Finland: Smoking as a risk factor","volume":"146","author":"Latronico","year":"2018","journal-title":"Epidemiol. Infect."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/5\/901\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:01:26Z","timestamp":1760137286000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/5\/901"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,26]]},"references-count":47,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["v14050901"],"URL":"https:\/\/doi.org\/10.3390\/v14050901","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,26]]}}}