{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:37:04Z","timestamp":1760146624177,"version":"build-2065373602"},"reference-count":51,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T00:00:00Z","timestamp":1732492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq)","award":["408725\/2022-2","306942\/2023-2","E-26\/210.875\/2016","E-26\/211.554\/2019","E-26\/064,210\/2020","E-26\/203.941\/2024","001","INV-007641"],"award-info":[{"award-number":["408725\/2022-2","306942\/2023-2","E-26\/210.875\/2016","E-26\/211.554\/2019","E-26\/064,210\/2020","E-26\/203.941\/2024","001","INV-007641"]}]},{"name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro (FAPERJ)","award":["408725\/2022-2","306942\/2023-2","E-26\/210.875\/2016","E-26\/211.554\/2019","E-26\/064,210\/2020","E-26\/203.941\/2024","001","INV-007641"],"award-info":[{"award-number":["408725\/2022-2","306942\/2023-2","E-26\/210.875\/2016","E-26\/211.554\/2019","E-26\/064,210\/2020","E-26\/203.941\/2024","001","INV-007641"]}]},{"name":"Funda\u00e7\u00e3o Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)","award":["408725\/2022-2","306942\/2023-2","E-26\/210.875\/2016","E-26\/211.554\/2019","E-26\/064,210\/2020","E-26\/203.941\/2024","001","INV-007641"],"award-info":[{"award-number":["408725\/2022-2","306942\/2023-2","E-26\/210.875\/2016","E-26\/211.554\/2019","E-26\/064,210\/2020","E-26\/203.941\/2024","001","INV-007641"]}]},{"name":"Bill and Melinda Gates Foundation","award":["408725\/2022-2","306942\/2023-2","E-26\/210.875\/2016","E-26\/211.554\/2019","E-26\/064,210\/2020","E-26\/203.941\/2024","001","INV-007641"],"award-info":[{"award-number":["408725\/2022-2","306942\/2023-2","E-26\/210.875\/2016","E-26\/211.554\/2019","E-26\/064,210\/2020","E-26\/203.941\/2024","001","INV-007641"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background\/Objective: The anti-restriction protein ArdA-H1, found in multiresistant Staphylococcus aureus (MRSA) strains from the ST239-SCCmecIII lineage, inhibits restriction\u2013modification systems, fostering horizontal gene transfer (HGT) and supporting genetic adaptability and resistance. This study investigates the regulatory mechanisms controlling ardA-H1 expression in S. aureus under various stress conditions, including acidic pH, iron limitation, and vancomycin exposure, and explores the roles of the Agr quorum sensing system. Methods: The expression of ardA-H1 was analyzed in S. aureus strains exposed to environmental stressors using real-time quantitative reverse transcription PCR. Comparisons were made between Agr-functional and Agr-deficient strains. In addition, Agr inhibition was achieved using a heterologous Agr autoinducing peptide. Results: The Agr system upregulated ardA-H1 expression in acidic and iron-limited conditions. However, vancomycin induced ardA-H1 activation specifically in the Agr-deficient strain GV69, indicating that an alternative regulatory pathway controls ardA-H1 expression in the absence of agr. The vancomycin response in GV69 suggests that diminished quorum sensing may offer a survival advantage by promoting persistence and HGT-related adaptability. Conclusion: Overall, our findings provide new insights into the intricate relationships between quorum-sensing, stress responses, bacterial virulence, and genetic plasticity, enhancing our understanding of S. aureus adaptability in challenging environments.<\/jats:p>","DOI":"10.3390\/antibiotics13121131","type":"journal-article","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T05:21:32Z","timestamp":1732512092000},"page":"1131","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Survival Strategies of Staphylococcus aureus: Adaptive Regulation of the Anti-Restriction Gene ardA-H1 Under Stress Conditions"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8216-9023","authenticated-orcid":false,"given":"Flavia Costa Carvalho","family":"de Andrade","sequence":"first","affiliation":[{"name":"Departamento de Microbiologia M\u00e9dica, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2492-3317","authenticated-orcid":false,"given":"Mariana Fernandes","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia M\u00e9dica, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8229-6957","authenticated-orcid":false,"given":"Agnes Marie S\u00e1","family":"Figueiredo","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia M\u00e9dica, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Patologia, Faculdade de Medicina, Universidade Federal Fluminense, Niter\u00f3i 24033-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"113267","DOI":"10.1016\/j.envres.2022.113267","article-title":"Detection and various environmental factors of antibiotic resistance gene horizontal transfer","volume":"212","author":"Li","year":"2022","journal-title":"Environ. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/s41579-020-00497-1","article-title":"Beyond horizontal gene transfer: The role of plasmids in bacterial evolution","volume":"19","author":"DelaFuente","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"von Wintersdorff, C.J., Penders, J., van Niekerk, J.M., Mills, N.D., Majumder, S., van Alphen, L.B., Savelkoul, P.H., and Wolffs, P.F. (2016). Dissemination of antimicrobial resistance in microbial ecosystems through horizontal gene transfer. Front. Microbiol., 7.","DOI":"10.3389\/fmicb.2016.00173"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1038\/s41396-023-01514-w","article-title":"Oxytetracycline and heavy metals promote the migration of resistance genes in the intestinal microbiome by plasmid transfer","volume":"17","author":"Lin","year":"2023","journal-title":"ISME J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"107714","DOI":"10.1016\/j.envint.2022.107714","article-title":"Industrial effluents boosted antibiotic resistome risk in coastal environments","volume":"171","author":"Su","year":"2023","journal-title":"Environ. Int."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Michaelis, C., and Grohmann, E. (2023). Horizontal gene transfer of antibiotic resistance genes in biofilms. Antibiotics, 12.","DOI":"10.3390\/antibiotics12020328"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1038\/nature02241","article-title":"SOS response promotes horizontal dissemination of antibiotic resistance genes","volume":"427","author":"Beaber","year":"2004","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4737","DOI":"10.1007\/s11033-022-07323-2","article-title":"Azithromycin can induce SOS response and horizontal gene transfer of SXT element in Vibrio cholerae","volume":"49","author":"Mohanraj","year":"2022","journal-title":"Mol. Biol. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/j.mib.2012.08.001","article-title":"Induction of competence for genetic transformation by antibiotics: Convergent evolution of stress responses in distant bacterial species lacking SOS?","volume":"15","author":"Charpentier","year":"2012","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.watres.2018.11.019","article-title":"Antibiotic-resistance gene transfer in antibiotic-resistance bacteria under different light irradiation: Implications from oxidative stress and gene expression","volume":"149","author":"Chen","year":"2019","journal-title":"Water Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1038\/s44221-023-00110-8","article-title":"Impact of chemicals and physical stressors on horizontal gene transfer via natural transformation","volume":"1","author":"Wang","year":"2023","journal-title":"Nat. Water"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1093\/nar\/gkt847","article-title":"Type I restriction enzymes and their relatives","volume":"42","author":"Loenen","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1146\/annurev.bi.41.070172.002311","article-title":"Restriction and modification of DNA","volume":"41","author":"Meselson","year":"1972","journal-title":"Annu. Rev. Biochem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1128\/MMBR.64.2.412-434.2000","article-title":"Type I restriction systems: Sophisticated molecular machines (a legacy of Bertani and Weigle)","volume":"64","author":"Murray","year":"2000","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Goryanin, I.I., Kudryavtseva, A.A., Balabanov, V.P., Biryukova, V.S., Manukhov, I.V., and Zavilgelsky, G.B. (2018). Anti-restriction activities of KlcA (RP4) and ArdB (R64) proteins. FEMS Microbiol. Lett., 365.","DOI":"10.1093\/femsle\/fny227"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Kudryavtseva, A.A., Cs\u00e9falvay, E., Gnuchikh, E.Y., Yanovskaya, D.D., Skutel, M.A., Isaev, A.B., Bazhenov, S.V., Utkina, A.A., and Manukhov, I.V. (2023). Broadness and specificity: ArdB, ArdA, and Ocr against various restriction-modification systems. Front. Microbiol., 14.","DOI":"10.3389\/fmicb.2023.1133144"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Liang, W., Xie, Y., Xiong, W., Tang, Y., Li, G., Jiang, X., and Lu, Y. (2017). Anti-restriction protein, KlcAHS, promotes dissemination of carbapenem resistance. Front. Cell. Infect. Microbiol., 27.","DOI":"10.3389\/fcimb.2017.00150"},{"key":"ref_18","first-page":"906","article-title":"Comparative analysis of anti-restriction activities of ArdA (ColIb-P9) and Ocr (T7) proteins","volume":"73","author":"Zavilgelsky","year":"2008","journal-title":"Biochemistry"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Silva, D.N.S., Beltrame, C.O., Botelho, A.M.N., Martini, C.L., Esteves, M.A.C., Guedes, I.A., Dardenne, L.E., and Figueiredo, A.M.S. (2022). Anti-Restriction gene homologs are highly represented in methicillin-resistant and multidrug-resistant Staphylococcus aureus ST239 and ST398: Implications for resistance gene acquisitions. Antibiotics, 11.","DOI":"10.3390\/antibiotics11091217"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e22986","DOI":"10.1016\/j.heliyon.2023.e22986","article-title":"ArdA genes from pKM101 and from B. bifidum chromosome have a different range of regulated genes","volume":"9","author":"Sharko","year":"2023","journal-title":"Heliyon"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Horton, J.S., and Taylor, T.B. (2023). Mutation bias and adaptation in bacteria. Microbiology, 169.","DOI":"10.1099\/mic.0.001404"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"147170","DOI":"10.1016\/j.gene.2023.147170","article-title":"The role of oxidative stress in genome destabilization and adaptive evolution of bacteria","volume":"857","author":"Sazykin","year":"2023","journal-title":"Gene"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1126\/science.287.5452.391a","article-title":"Activation and inhibition of the staphylococcal agr system","volume":"287","author":"Novick","year":"2000","journal-title":"Science"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Barraza, I., Pajon, C., Diaz-Tang, G., Marin Meneses, E., Abu-Rumman, F., Garc\u00eda-Di\u00e9guez, L., Castro, V., Lopatkin, A.J., and Smith, R.P. (2023). Disturbing the spatial organization of biofilm communities affects expression of agr-regulated virulence factors in Staphylococcus aureus. Appl. Environ. Microbiol., 89.","DOI":"10.1128\/aem.01932-22"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2027","DOI":"10.1126\/science.276.5321.2027","article-title":"Bacterial interference caused by autoinducing peptide variants","volume":"276","author":"Ji","year":"1997","journal-title":"Science"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"8407","DOI":"10.1128\/JB.186.24.8407-8423.2004","article-title":"Effect of mild acid on gene expression in Staphylococcus aureus","volume":"186","author":"Weinrick","year":"2004","journal-title":"J. Bacteriol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"RP89098","DOI":"10.7554\/eLife.89098","article-title":"Quorum-sensing agr system of Staphylococcus aureus primes gene expression for protection from lethal oxidative stress","volume":"12","author":"Podkowik","year":"2024","journal-title":"eLife"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/BF00395935","article-title":"Lactococcus lactis and stress","volume":"70","author":"Rallu","year":"1996","journal-title":"Antonie Van Leeuwenhoek"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2483","DOI":"10.1128\/AAC.00428-08","article-title":"Antibiotic resistance in Pseudomonas aeruginosa strains with increased mutation frequency due to inactivation of the DNA oxidative repair system","volume":"53","author":"Mandsberg","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Nandy, P. (2022). The role of sigma factor competition in bacterial adaptation under prolonged starvation. Microbiology, 168.","DOI":"10.1099\/mic.0.001195"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e55640","DOI":"10.15252\/embr.202255640","article-title":"Adaptation delay causes a burst of mutations in bacteria responding to oxidative stress","volume":"24","author":"Lagage","year":"2023","journal-title":"EMBO Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1038\/s41590-022-01231-0","article-title":"pH sensing controls tissue inflammation by modulating cellular metabolism and endo-lysosomal function of immune cells","volume":"23","author":"Chen","year":"2022","journal-title":"Nat. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1128\/IAI.01635-07","article-title":"Iron-regulated biofilm formation in Staphylococcus aureus Newman requires ica and the secreted protein","volume":"76","author":"Johnson","year":"2008","journal-title":"Emp. Infect. Immun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1016\/j.micinf.2006.01.022","article-title":"Transcriptional modulation of some Staphylococcus aureus iron-regulated genes during growth in vitro and in a tissue cage model in vivo","volume":"8","author":"Allard","year":"2006","journal-title":"Microbes Infect."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.ijmm.2010.05.003","article-title":"Fur is required for the activation of virulence gene expression through the induction of the sae regulatory system in Staphylococcus aureus","volume":"301","author":"Johnson","year":"2011","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Ghssein, G., and Ezzeddine, Z. (2022). The key element role of metallophores in the pathogenicity and virulence of Staphylococcus aureus: A review. Biology, 11.","DOI":"10.3390\/biology11101525"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00203-015-1148-6","article-title":"Biofilm, pathogenesis and prevention\u2014A journey to break the wall: A review","volume":"198","author":"Gupta","year":"2016","journal-title":"Arch. Microbiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3480","DOI":"10.1099\/mic.0.2007\/016014-0","article-title":"agr RNAIII divergently regulates glucose-induced biofilm formation in clinical isolates of Staphylococcus aureus","volume":"154","author":"Coelho","year":"2008","journal-title":"Microbiology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.1038\/s41467-022-29877-2","article-title":"Natural transformation allows transfer of SCCmec-mediated methicillin resistance in Staphylococcus aureus biofilms","volume":"13","author":"Maree","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Brothers, K.M., Parker, D.M., Taguchi, M., Ma, D., Mandell, J.B., Thurlow, L.L., Byrapogu, V.C., and Urish, K.L. (2023). Dose optimization in surgical prophylaxis: Sub-inhibitory dosing of vancomycin increases rates of biofilm formation and the rates of surgical site infection. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-30951-y"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2687","DOI":"10.1128\/AAC.49.7.2687-2692.2005","article-title":"Reduced susceptibility of Staphylococcus aureus to vancomycin and platelet microbicidal protein correlates with defective autolysis and loss of accessory gene regulator (agr) function","volume":"49","author":"Sakoulas","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e00576-13","DOI":"10.1128\/genomeA.00576-13","article-title":"Complete genome sequence of a variant of the methicillin-resistant Staphylococcus aureus ST239 lineage, strain BMB9393, displaying superior ability to accumulate ica-independent biofilm","volume":"1","author":"Costa","year":"2013","journal-title":"Genome Announc."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s40793-016-0154-x","article-title":"genome sequence of an agr-dysfunctional variant of the ST239 lineage of the methicillin-resistant Staphylococcus aureus strain GV69 from Brazil","volume":"11","author":"Botelho","year":"2016","journal-title":"Stand. Genom. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1139\/W10-057","article-title":"Responses of Staphylococcus aureus exposed to HCl and organic acid stress","volume":"56","author":"Rode","year":"2010","journal-title":"Can. J. Microbiol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Mesquita-Rodrigues, C., Menna-Barreto, R.F., Sab\u00f3ia-Vahia, L., Da-Silva, S.A., de Souza, E.M., Waghabi, M.C., Cuervo, P., and De Jesus, J.B. (2013). Cellular growth and mitochondrial ultrastructure of leishmania (Viannia) braziliensis promastigotes are affected by the iron chelator 2,2-dipyridyl. PLoS Negl. Trop. Dis., 7.","DOI":"10.1371\/journal.pntd.0002481"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.mimet.2012.01.007","article-title":"Comparison of in vitro and in vivo systems to study ica-independent Staphylococcus aureus biofilms","volume":"88","author":"Ferreira","year":"2012","journal-title":"J. Microbiol. Methods"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Novais, J.S., Carvalho, M.F., Ramundo, M.S., Beltrame, C.O., Geraldo, R.B., Jord\u00e3o, A.K., Ferreira, V.F., Castro, H.C., and Figueiredo, A.M.S. (2020). Antibiofilm effects of N,O-acetals derived from 2-amino-1,4-naphthoquinone are associated with downregulation of important global virulence regulators in methicillin-resistant Staphylococcus aureus. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-76372-z"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1590\/1414-431x20154734","article-title":"Optimization of the RNeasy Mini Kit to obtain high-quality total RNA from sessile cells of Staphylococcus aureus","volume":"48","author":"Beltrame","year":"2015","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2155","DOI":"10.1128\/AAC.46.7.2155-2161.2002","article-title":"Multiplex PCR strategy for rapid identification of structural types and variants of the mec element in methicillin-resistant Staphylococcus aureus","volume":"46","author":"Oliveira","year":"2002","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3967","DOI":"10.1002\/j.1460-2075.1993.tb06074.x","article-title":"Synthesis of staphylococcal virulence factors is controlled by a regulatory RNA molecule","volume":"12","author":"Novick","year":"1993","journal-title":"EMBO J."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Dienes, Z. (2014). Using Bayes to get the most out of non-significant results. Front. Psychol., 45.","DOI":"10.3389\/fpsyg.2014.00781"}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/13\/12\/1131\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:38:53Z","timestamp":1760114333000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/13\/12\/1131"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,25]]},"references-count":51,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["antibiotics13121131"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics13121131","relation":{},"ISSN":["2079-6382"],"issn-type":[{"type":"electronic","value":"2079-6382"}],"subject":[],"published":{"date-parts":[[2024,11,25]]}}}