{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T02:36:47Z","timestamp":1773196607041,"version":"3.50.1"},"reference-count":52,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T00:00:00Z","timestamp":1746576000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2012-02088, 2017-01026, 2020-00896, 2021-03046, 2023-01776"],"award-info":[{"award-number":["2012-02088, 2017-01026, 2020-00896, 2021-03046, 2023-01776"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003793","name":"Hj\u00e4rt-Lungfonden","doi-asserted-by":"publisher","award":["20160243, 20190177"],"award-info":[{"award-number":["20160243, 20190177"]}],"id":[{"id":"10.13039\/501100003793","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Seasonal influenza continues to be a global health problem. Current existing vaccines and antivirals against influenza have limited effectiveness, and typically do not stay ahead of the viral evolutionary curve. Broad-spectrum antiviral agents that are effective therapeutically and prophylactically are much needed. We have created a promising new broad-spectrum anti-influenza agent using molecular engineering of a lectin from bananas, H84T, which is well-tolerated and protective in small animal models. However, the potency and effect of H84T on human immune cells and influenza-specific immune responses are undetermined. We found that H84T efficiently inhibited influenza A virus (IAV) replication in primary human dendritic cells (DCs) isolated from blood and tonsil, preserved DC viability and allowed acquisition and presentation of viral antigen. Excitingly, H84T-treated DCs subsequently initiated effective expansion of IAV-specific CD8 T cells. Furthermore, H84T preserved the capacity of IAV-exposed DCs to present a second non-IAV antigen and induce robust antigen-specific CD8 T cell expansion. Our data support H84T as a potent antiviral in humans as it not only effectively inhibits IAV infection, but also preserves induction of robust pathogen-specific adaptive immune responses against diverse antigens, which likely is clinically beneficial.<\/jats:p>","DOI":"10.1371\/journal.ppat.1013112","type":"journal-article","created":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T13:28:53Z","timestamp":1746624533000},"page":"e1013112","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["A genetically engineered therapeutic lectin inhibits human influenza A virus infection and sustains robust virus-specific CD8 T cell expansion"],"prefix":"10.1371","volume":"21","author":[{"given":"Meng","family":"Yu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ang","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Faezzah","family":"Baharom","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuijie","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maureen","family":"Legendre","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evelyn","family":"Cov\u00e9s-Datson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ebba","family":"Sohlberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne","family":"Schlisio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin","family":"Lor\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David M.","family":"Markovitz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6966-7039","authenticated-orcid":true,"given":"Anna","family":"Smed-S\u00f6rensen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,5,7]]},"reference":[{"key":"ppat.1013112.ref001","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1146\/annurev.med.51.1.407","article-title":"Global epidemiology of influenza: past and present","volume":"51","author":"NJ Cox","year":"2000","journal-title":"Annu Rev Med"},{"issue":"9348","key":"ppat.1013112.ref002","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.1016\/S0140-6736(02)11772-7","article-title":"Induction of proinflammatory cytokines in human macrophages by influenza A (H5N1) viruses: a mechanism for the unusual severity of human disease?","volume":"360","author":"CY Cheung","year":"2002","journal-title":"Lancet"},{"issue":"5","key":"ppat.1013112.ref003","doi-asserted-by":"crossref","first-page":"2403","DOI":"10.1128\/JVI.02749-15","article-title":"Hemagglutinin of Influenza A Virus Antagonizes Type I Interferon (IFN) Responses by Inducing Degradation of Type I IFN Receptor 1","volume":"90","author":"C Xia","year":"2015","journal-title":"J Virol"},{"issue":"5","key":"ppat.1013112.ref004","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.chom.2009.04.006","article-title":"Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade recognition by the host viral RNA sensor RIG-I","volume":"5","author":"MU Gack","year":"2009","journal-title":"Cell Host Microbe"},{"issue":"3","key":"ppat.1013112.ref005","doi-asserted-by":"crossref","first-page":"e1002572","DOI":"10.1371\/journal.ppat.1002572","article-title":"Influenza A virus infection of human primary dendritic cells impairs their ability to cross-present antigen to CD8 T cells","volume":"8","author":"A Smed-S\u00f6rensen","year":"2012","journal-title":"PLoS Pathog"},{"issue":"13","key":"ppat.1013112.ref006","doi-asserted-by":"crossref","first-page":"6295","DOI":"10.1128\/JVI.02381-05","article-title":"Influenza virus evades innate and adaptive immunity via the NS1 protein","volume":"80","author":"A Fernandez-Sesma","year":"2006","journal-title":"J Virol"},{"issue":"Pt 9","key":"ppat.1013112.ref007","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.1099\/vir.0.032060-0","article-title":"The NS1 protein of influenza A virus suppresses interferon-regulated activation of antigen-presentation and immune-proteasome pathways","volume":"92","author":"JR Tisoncik","year":"2011","journal-title":"J Gen Virol"},{"issue":"13","key":"ppat.1013112.ref008","doi-asserted-by":"crossref","first-page":"6849","DOI":"10.1128\/JVI.02323-08","article-title":"The NS1 protein of a human influenza virus inhibits type I interferon production and the induction of antiviral responses in primary human dendritic and respiratory epithelial cells","volume":"83","author":"K Haye","year":"2009","journal-title":"J Virol"},{"issue":"1","key":"ppat.1013112.ref009","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/S1473-3099(11)70295-X","article-title":"Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis","volume":"12","author":"MT Osterholm","year":"2012","journal-title":"Lancet Infect Dis"},{"issue":"6","key":"ppat.1013112.ref010","doi-asserted-by":"crossref","first-page":"180","DOI":"10.15585\/mmwr.mm6706a2","article-title":"Interim Estimates of 2017-18 Seasonal Influenza Vaccine Effectiveness - United States, February 2018","volume":"67","author":"B Flannery","year":"2018","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"ppat.1013112.ref011","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.3389\/fimmu.2018.01547","article-title":"Advancements in Host-Based Interventions for Influenza Treatment","volume":"9","author":"T-F Yip","year":"2018","journal-title":"Front Immunol"},{"issue":"4","key":"ppat.1013112.ref012","doi-asserted-by":"crossref","first-page":"2122","DOI":"10.1073\/pnas.1915152117","article-title":"A molecularly engineered antiviral banana lectin inhibits fusion and is efficacious against influenza virus infection in vivo","volume":"117","author":"EM Cov\u00e9s-Datson","year":"2020","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"24","key":"ppat.1013112.ref013","first-page":"30258","article-title":"Influenza A (H1N1) pdm09 virus exhibiting enhanced cross-resistance to oseltamivir and peramivir due to a dual H275Y\/G147R substitution, Japan, March 2016","volume":"2016","author":"E Takashita","journal-title":"Eurosurveillance"},{"issue":"2","key":"ppat.1013112.ref014","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1111\/irv.12534","article-title":"Five years of monitoring for the emergence of oseltamivir resistance in patients with influenza A infections in the Influenza Resistance Information Study","volume":"12","author":"B Lina","year":"2018","journal-title":"Influenza Other Respir Viruses"},{"issue":"2","key":"ppat.1013112.ref015","first-page":"44","article-title":"High levels of adamantane resistance among influenza A (H3N2) viruses and interim guidelines for use of antiviral agents--United States, 2005-06 influenza season","volume":"55","author":"Control CfD","year":"2006","journal-title":"MMWR Morbidity and mortality weekly report"},{"issue":"11","key":"ppat.1013112.ref016","doi-asserted-by":"crossref","first-page":"53R-62R","DOI":"10.1093\/glycob\/cwh122","article-title":"History of lectins: from hemagglutinins to biological recognition molecules","volume":"14","author":"N Sharon","year":"2004","journal-title":"Glycobiology"},{"issue":"3","key":"ppat.1013112.ref017","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1016\/j.cell.2015.09.056","article-title":"Engineering a therapeutic lectin by uncoupling mitogenicity from antiviral activity","volume":"163","author":"MD Swanson","year":"2015","journal-title":"Cell"},{"issue":"18","key":"ppat.1013112.ref018","doi-asserted-by":"crossref","first-page":"8709","DOI":"10.1128\/JVI.74.18.8709-8719.2000","article-title":"Influenza virus assembly: effect of influenza virus glycoproteins on the membrane association of M1 protein","volume":"74","author":"A Ali","year":"2000","journal-title":"J Virol"},{"issue":"10","key":"ppat.1013112.ref019","doi-asserted-by":"crossref","first-page":"6653","DOI":"10.1128\/jvi.70.10.6653-6657.1996","article-title":"Influenza virus hemagglutinin and neuraminidase glycoprotein s stimulate the membrane association of the matrix protein","volume":"70","author":"M Enami","year":"1996","journal-title":"J Virol"},{"key":"ppat.1013112.ref020","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.lfs.2018.06.003","article-title":"Lectins as mitosis stimulating factors: Briefly reviewed","volume":"207","author":"EVMM Carvalho","year":"2018","journal-title":"Life Sci"},{"issue":"12","key":"ppat.1013112.ref021","doi-asserted-by":"crossref","first-page":"2802","DOI":"10.1016\/j.biocel.2008.05.023","article-title":"Safety concerns for the potential use of cyanovirin-N as a microbicidal anti-HIV agent","volume":"40","author":"D Huskens","year":"2008","journal-title":"Int J Biochem Cell Biol"},{"key":"ppat.1013112.ref022","doi-asserted-by":"crossref","first-page":"e77345","DOI":"10.7554\/eLife.77345","article-title":"Human influenza virus infection elicits distinct patterns of monocyte and dendritic cell mobilization in blood and the nasopharynx","volume":"12","author":"S Vangeti","year":"2023","journal-title":"Elife"},{"issue":"7","key":"ppat.1013112.ref023","doi-asserted-by":"crossref","first-page":"3494","DOI":"10.4049\/jimmunol.164.7.3494","article-title":"Calcitonin gene-related peptide decreases expression of HLA-DR and CD86 by human dendritic cells and dampens dendritic cell-driven T cell-proliferative responses via the type I calcitonin gene-related peptide receptor","volume":"164","author":"JA Carucci","year":"2000","journal-title":"The Journal of Immunology"},{"issue":"6","key":"ppat.1013112.ref024","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1002\/eji.1830260603","article-title":"Human dendritic cells activate T lymphocytes via a CD40: CD40 ligand-dependent pathway","volume":"26","author":"AD McLellan","year":"1996","journal-title":"Eur J Immunol"},{"issue":"4","key":"ppat.1013112.ref025","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/nrmicro3231","article-title":"The co-pathogenesis of influenza viruses with bacteria in the lung","volume":"12","author":"JA McCullers","year":"2014","journal-title":"Nat Rev Microbiol"},{"issue":"3","key":"ppat.1013112.ref026","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.ijantimicag.2017.11.005","article-title":"Co-infection with influenza-associated acute respiratory distress syndrome requiring extracorporeal membrane oxygenation","volume":"51","author":"S Rozencwajg","year":"2018","journal-title":"Int J Antimicrob Agents"},{"issue":"3","key":"ppat.1013112.ref027","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1042\/bj2720721","article-title":"Isolation and characterization of BanLec-I, a mannoside-binding lectin from Musa paradisiac (banana)","volume":"272","author":"VL Koshte","year":"1990","journal-title":"Biochem J"},{"issue":"1","key":"ppat.1013112.ref028","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1159\/000236090","article-title":"The potent IgG4-inducing antigen in banana is a mannose-binding lectin, BanLec-I","volume":"97","author":"VL Koshte","year":"1992","journal-title":"Int Arch Allergy Immunol"},{"key":"ppat.1013112.ref029","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.ijbiomac.2016.04.049","article-title":"Oral administration of banana lectin modulates cytokine profile and abundance of T-cell populations in mice","volume":"89","author":"ACMB Sansone","year":"2016","journal-title":"Int J Biol Macromol"},{"issue":"5","key":"ppat.1013112.ref030","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1084\/jem.182.5.1573","article-title":"Cross-linking of major histocompatibility complex class II molecules by staphylococcal enterotoxin A superantigen is a requirement for inflammatory cytokine gene expression","volume":"182","author":"K Mehindate","year":"1995","journal-title":"J Exp Med"},{"issue":"11","key":"ppat.1013112.ref031","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1099\/vir.0.045021-0","article-title":"The fate of influenza A virus after infection of human macrophages and dendritic cells","volume":"93","author":"KR Short","year":"2012","journal-title":"Journal of general virology"},{"issue":"10","key":"ppat.1013112.ref032","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1038\/nm.3971","article-title":"Antigen-presenting cells look within during influenza infection","volume":"21","author":"JD Mintern","year":"2015","journal-title":"Nat Med"},{"key":"ppat.1013112.ref033","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.3389\/fimmu.2018.01521","article-title":"Respiratory Mononuclear Phagocytes in Human Influenza A Virus Infection: Their Role in Immune Protection and As Targets of the Virus","volume":"9","author":"S Vangeti","year":"2018","journal-title":"Front Immunol"},{"issue":"22","key":"ppat.1013112.ref034","doi-asserted-by":"crossref","first-page":"11955","DOI":"10.1128\/JVI.05830-11","article-title":"Major histocompatibility complex class II expression and hemagglutinin subtype influence the infectivity of type A influenza virus for respiratory dendritic cells","volume":"85","author":"KM Hargadon","year":"2011","journal-title":"J Virol"},{"issue":"10","key":"ppat.1013112.ref035","doi-asserted-by":"crossref","first-page":"4908","DOI":"10.1128\/JVI.02367-07","article-title":"Differential response of respiratory dendritic cell subsets to influenza virus infection","volume":"82","author":"X Hao","year":"2008","journal-title":"J Virol"},{"issue":"11","key":"ppat.1013112.ref036","doi-asserted-by":"crossref","first-page":"4037","DOI":"10.1172\/JCI60659","article-title":"Cross-presenting CD103+ dendritic cells are protected from influenza virus infection","volume":"122","author":"J Helft","year":"2012","journal-title":"J Clin Invest"},{"key":"ppat.1013112.ref037","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1146\/annurev.immunol.20.100301.064828","article-title":"Antigen presentation and T cell stimulation by dendritic cells","volume":"20","author":"P Guermonprez","year":"2002","journal-title":"Annu Rev Immunol"},{"issue":"3","key":"ppat.1013112.ref038","first-page":"160","article-title":"Dendritic cells and the control of immunity: enhancing the efficiency of antigen presentation","volume":"68","author":"RM Steinman","year":"2001","journal-title":"The Mount Sinai journal of medicine, New York"},{"issue":"8","key":"ppat.1013112.ref039","doi-asserted-by":"crossref","first-page":"223","DOI":"10.3390\/v9080223","article-title":"Influenza Virus Infection, Interferon Response, Viral Counter-Response, and Apoptosis","volume":"9","author":"JM Shim","year":"2017","journal-title":"Viruses"},{"issue":"1\u20132","key":"ppat.1013112.ref040","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10495-019-01575-3","article-title":"Influenza A virus-induced apoptosis and virus propagation","volume":"25","author":"PB Ampomah","year":"2020","journal-title":"Apoptosis"},{"issue":"5","key":"ppat.1013112.ref041","doi-asserted-by":"crossref","first-page":"e1768","DOI":"10.1038\/cddis.2015.131","article-title":"The nucleoprotein of influenza A virus induces p53 signaling and apoptosis via attenuation of host ubiquitin ligase RNF43","volume":"6","author":"H Nailwal","year":"2015","journal-title":"Cell Death Dis"},{"issue":"12","key":"ppat.1013112.ref042","doi-asserted-by":"crossref","first-page":"8624","DOI":"10.1128\/jvi.70.12.8624-8629.1996","article-title":"Influenza virus neuraminidase activates latent transforming growth factor beta","volume":"70","author":"S Schultz-Cherry","year":"1996","journal-title":"J Virol"},{"issue":"10","key":"ppat.1013112.ref043","doi-asserted-by":"crossref","first-page":"e1001136","DOI":"10.1371\/journal.ppat.1001136","article-title":"Transforming growth factor-\u03b2: activation by neuraminidase and role in highly pathogenic H5N1 influenza pathogenesis","volume":"6","author":"CM Carlson","year":"2010","journal-title":"PLoS Pathog"},{"issue":"9","key":"ppat.1013112.ref044","doi-asserted-by":"crossref","first-page":"e197","DOI":"10.1038\/cddis.2011.75","article-title":"Cell death regulation during influenza A virus infection by matrix (M1) protein: a model of viral control over the cellular survival pathway","volume":"2","author":"UC Halder","year":"2011","journal-title":"Cell Death Dis"},{"issue":"1","key":"ppat.1013112.ref045","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/cmi.2015.74","article-title":"The cytokine storm of severe influenza and development of immunomodulatory therapy","volume":"13","author":"Q Liu","year":"2016","journal-title":"Cell Mol Immunol"},{"issue":"12","key":"ppat.1013112.ref046","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.3390\/genes12121914","article-title":"TNFA and IL10 Polymorphisms and IL-6 and IL-10 Levels Influence Disease Severity in Influenza A(H1N1)pdm09 Virus Infected Patients","volume":"12","author":"K Alagarasu","year":"2021","journal-title":"Genes (Basel)"},{"issue":"7","key":"ppat.1013112.ref047","doi-asserted-by":"crossref","first-page":"e0007595","DOI":"10.1371\/journal.pntd.0007595","article-title":"Inhibition of Ebola Virus by a Molecularly Engineered Banana Lectin","volume":"13","author":"EM Cov\u00e9s-Datson","year":"2019","journal-title":"PLoS Negl Trop Dis"},{"issue":"1","key":"ppat.1013112.ref048","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1038\/s41598-022-05580-6","article-title":"H84T BanLec has broad spectrum antiviral activity against human herpesviruses in cells, skin, and mice","volume":"12","author":"MG Lloyd","year":"2022","journal-title":"Sci Rep"},{"issue":"10","key":"ppat.1013112.ref049","doi-asserted-by":"crossref","first-page":"100774","DOI":"10.1016\/j.xcrm.2022.100774","article-title":"A molecularly engineered, broad-spectrum anti-coronavirus lectin inhibits SARS-CoV-2 and MERS-CoV infection in vivo","volume":"3","author":"JF-W Chan","year":"2022","journal-title":"Cell Reports Medicine"},{"key":"ppat.1013112.ref050","doi-asserted-by":"crossref","first-page":"763460","DOI":"10.3389\/fimmu.2021.763460","article-title":"Glycoprotein targeted CAR-NK cells for the treatment of SARS-CoV-2 infection","volume":"12","author":"I Christodoulou","year":"2021","journal-title":"Frontiers in immunology"},{"issue":"Supplement 1","key":"ppat.1013112.ref051","doi-asserted-by":"crossref","first-page":"2803","DOI":"10.1182\/blood-2021-146865","article-title":"CAR-NK Cells Targeting Sars-Cov-2 Glycosites As COVID-19 Treatment","volume":"138","author":"I Christodoulou","year":"2021","journal-title":"Blood"},{"issue":"7","key":"ppat.1013112.ref052","doi-asserted-by":"crossref","first-page":"2069","DOI":"10.4049\/jimmunol.1801191","article-title":"Human Blood and Tonsil Plasmacytoid Dendritic Cells Display Similar Gene Expression Profiles but Exhibit Differential Type I IFN Responses to Influenza A Virus Infection","volume":"202","author":"S Vangeti","year":"2019","journal-title":"J Immunol"}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1013112","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T13:29:01Z","timestamp":1746624541000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1013112"}},"subtitle":[],"editor":[{"given":"Peter","family":"Palese","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,5,7]]},"references-count":52,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,5,7]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1013112","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.08.15.608041","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,7]]}}}