{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T09:48:39Z","timestamp":1782380919031,"version":"3.54.5"},"reference-count":49,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Background: Torque teno virus (TTV) is a ubiquitous, non-pathogenic component of the human virome whose role in people living with HIV (PLWH), particularly during antiretroviral therapy (ART)-mediated immune reconstitution, remains unclear. This systematic review aimed to synthesize available evidence on TTV viral load in PLWH, focusing on its relationship with immunological markers. Methods: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. A comprehensive literature search was conducted in MEDLINE, Web of Science, and Scopus in January 2026 to identify studies assessing plasma TTV viral load before and\/or during ART and reporting immunological outcomes. Eligible studies included prospective and retrospective longitudinal studies, cross-sectional studies, and mixed designs assessing plasma TTV viral load in relation to ART status and immune recovery markers. Results: Thirteen studies (n = 1700 PLWH) were included, predominantly observational and conducted in adult populations. Most studies (76.9%) reported a significant inverse association between TTV viral load and CD4 T-cell count, while all studies assessing HIV viral load found a direct correlation with TTV levels. An inverse relationship with the CD4\/CD8 ratio was consistently observed where evaluated. Higher TTV loads were reported in ART-na\u00efve individuals and in those with advanced immunosuppression, with longitudinal studies indicating a general decline during ART. Overall, methodological heterogeneity and moderate risk of bias were common. Conclusions: TTV viral load shows a consistent inverse association with CD4 cell count and may reflect global immune dysfunction in PLWH beyond conventional markers. However, its clinical utility remains investigational due to the heterogeneity in the study design, limited data on longitudinal dynamics, and lack of standardized assays and thresholds.<\/jats:p>","DOI":"10.3390\/microorganisms14061386","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T06:13:37Z","timestamp":1782195217000},"page":"1386","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Torque Teno Virus (TTV) Plasma Load and Immune Reconstitution in People Living with HIV: A Systematic Review"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-4327-7305","authenticated-orcid":false,"given":"Federico","family":"Cesanelli","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Sciences, Unit of Infectious and Tropical Diseases, University of Brescia and ASST Spedali Civili di Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ottavia","family":"Nozza","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Sciences, Unit of Infectious and Tropical Diseases, University of Brescia and ASST Spedali Civili di Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Salvi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Sciences, Unit of Infectious and Tropical Diseases, University of Brescia and ASST Spedali Civili di Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Alberti","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Sciences, Unit of Infectious and Tropical Diseases, University of Brescia and ASST Spedali Civili di Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Scarvaglieri","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Sciences, Unit of Infectious and Tropical Diseases, University of Brescia and ASST Spedali Civili di Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7366-871X","authenticated-orcid":false,"given":"Giorgio","family":"Tiecco","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Sciences, Unit of Infectious and Tropical Diseases, University of Brescia and ASST Spedali Civili di Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Mosti","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Sciences, Unit of Infectious and Tropical Diseases, University of Brescia and ASST Spedali Civili di Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2221-6286","authenticated-orcid":false,"given":"Maria Antonia","family":"De Francesco","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"},{"name":"Highly Specialized Laboratory, ASST Spedali Civili of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1452-9100","authenticated-orcid":false,"given":"Eugenia","family":"Quiros-Roldan","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Sciences, Unit of Infectious and Tropical Diseases, University of Brescia and ASST Spedali Civili di Brescia, 25123 Brescia, Italy"},{"name":"Department of Global Public Health, Karolinska Institute, 17177 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2943","DOI":"10.1007\/s00705-021-05192-x","article-title":"Taxonomic update for mammalian anelloviruses (family Anelloviridae)","volume":"166","author":"Varsani","year":"2021","journal-title":"Arch. Virol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Cesanelli, F., Scarvaglieri, I., De Francesco, M.A., Alberti, M., Salvi, M., Tiecco, G., Castelli, F., and Quiros-Roldan, E. (2025). The Human Virome in Health and Its Remodeling During HIV Infection and Antiretroviral Therapy: A Narrative Review. Microorganisms, 14.","DOI":"10.3390\/microorganisms14010050"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1007\/s00705-015-2363-9","article-title":"Human anelloviruses: An update of molecular, epidemiological and clinical aspects","volume":"160","author":"Spandole","year":"2015","journal-title":"Arch. Virol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/S0042-6822(02)00049-1","article-title":"Distribution of TT virus (TTV), TTV-like minivirus, and related viruses in humans and nonhuman primates","volume":"306","author":"Thom","year":"2003","journal-title":"Virology"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"V\u00e4is\u00e4nen, E., Kuisma, I., M\u00e4kinen, M., Ilonen, J., Veijola, R., Toppari, J., Hedman, K., and S\u00f6derlund-Venermo, M. (2022). Torque Teno Virus Primary Infection Kinetics in Early Childhood. Viruses, 14.","DOI":"10.3390\/v14061277"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/s12985-018-1007-6","article-title":"Torque teno virus dynamics during the first year of life","volume":"15","author":"Tyschik","year":"2018","journal-title":"Virol. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e70473","DOI":"10.1002\/jmv.70473","article-title":"Deep Characterisation of Circulating Torque Teno Virus DNA Load in Crohn\u2019s Disease Patients","volume":"97","author":"Goens","year":"2025","journal-title":"J. Med. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1620\/tjem.191.203","article-title":"Detection rates of TT virus DNA in serum of umbilical cord blood, breast milk and saliva","volume":"191","author":"Goto","year":"2000","journal-title":"Tohoku J. Exp. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2073","DOI":"10.1016\/j.cmi.2025.07.035","article-title":"Clinical significance of respiratory torque teno virus in immunocompromised patients with acute respiratory failure","volume":"31","author":"Maillard","year":"2025","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2749","DOI":"10.1007\/s00705-020-04841-x","article-title":"Constant companion: Clinical and developmental aspects of torque teno virus infections","volume":"165","author":"Lolomadze","year":"2020","journal-title":"Arch. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.3748\/wjg.v26.i15.1691","article-title":"Torque teno virus in liver diseases: On the way towards unity of view","volume":"26","author":"Reshetnyak","year":"2020","journal-title":"World J. Gastroenterol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"40857","DOI":"10.1038\/s41598-025-24543-1","article-title":"Clinical characteristics of Torquetenovirus infected immunocompromised patients explored by metagenomic next-generation sequencing","volume":"15","author":"Zhang","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e70068","DOI":"10.1111\/eci.70068","article-title":"Torque teno virus as a marker of immune status in immunocompromised patients: A systematic review","volume":"55","author":"Medina","year":"2025","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e70743","DOI":"10.1002\/jmv.70743","article-title":"Association of Torque Teno Virus with Corticosteroids, Rejection, and Infection in Adult and Pediatric Kidney Transplant Recipients","volume":"97","author":"Gramkow","year":"2025","journal-title":"J. Med. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Mouton, W., Conrad, A., Bal, A., Boccard, M., Malcus, C., Ducastelle-Lepretre, S., Balsat, M., Barraco, F., Larcher, M.V., and Fossard, G. (2020). Torque Teno Virus Viral Load as a Marker of Immune Function in Allogeneic Haematopoietic Stem Cell Transplantation Recipients. Viruses, 12.","DOI":"10.3390\/v12111292"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1093\/cid\/ciy176","article-title":"Incomplete Recovery of CD4 Cell Count, CD4 Percentage, and CD4\/CD8 Ratio in Patients with Human Immunodeficiency Virus Infection and Suppressed Viremia During Long-term Antiretroviral Therapy","volume":"67","author":"Mutoh","year":"2018","journal-title":"Clin. Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Milan\u00e9s-Guisado, Y., Guti\u00e9rrez-Valencia, A., Trujillo-Rodr\u00edguez, M., Espinosa, N., Viciana, P., and L\u00f3pez-Cort\u00e9s, L.F. (2018). Absolute CD4+ T cell count overstate immune recovery assessed by CD4+\/CD8+ ratio in HIV-infected patients on treatment. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0205777"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"24691","DOI":"10.1038\/s41598-024-73870-2","article-title":"Torque teno virus: A potential marker of immune reconstitution in youths with vertically acquired HIV","volume":"14","author":"Carrasco","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e437","DOI":"10.1093\/infdis\/jiae014","article-title":"Torque Teno Virus Load Is Associated with Centers for Disease Control and Prevention Stage and CD4+ Cell Count in People Living with Human Immunodeficiency Virus but Seems Unrelated to AIDS-Defining Events and Human Pegivirus Load","volume":"230","author":"Esser","year":"2024","journal-title":"J. Infect. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Abbate, I., Rozera, G., Cimini, E., Carletti, F., Tartaglia, E., Rubino, M., Pittalis, S., Esvan, R., Gagliardini, R., and Mondi, A. (2023). Kinetics of TTV Loads in Peripheral Blood Mononuclear Cells of Early Treated Acute HIV Infections. Viruses, 15.","DOI":"10.3390\/v15091931"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_22","unstructured":"(2026, April 01). JBI Manual for Evidence Synthesis. Available online: https:\/\/jbi-global-wiki.refined.site\/space\/MANUAL."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1002\/jrsm.1411","article-title":"Risk-of-bias VISualization (robvis): An R package and Shiny web app for visualizing risk-of-bias assessments","volume":"12","author":"McGuinness","year":"2021","journal-title":"Res. Synth. Methods"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Lapa, D., Del Porto, P., Minosse, C., D\u2019Offizi, G., Antinori, A., Capobianchi, M.R., Visco-Comandini, U., McPhee, F., Garbuglia, A.R., and Zaccarelli, M. (2021). Clinical Relevance of Torque Teno Virus (TTV) in HIV\/HCV Coinfected and HCV Monoinfected Patients Treated with Direct-Acting Antiviral Therapy. J. Clin. Med., 10.","DOI":"10.3390\/jcm10102092"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Honorato, L., Witkin, S.S., Mendes-Correa, M.C., Conde Toscano, A.L.C., Linhares, I.M., de Paula, A.V., Pai\u00e3o, H.G.O., de Paula, V.S., Lopes, A.O., and Lima, S.H. (2022). The Torque Teno Virus Titer in Saliva Reflects the Level of Circulating CD4+ T Lymphocytes and HIV in Individuals Undergoing Antiretroviral Maintenance Therapy. Front. Med., 8.","DOI":"10.3389\/fmed.2021.809312"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1007\/s00705-009-0440-7","article-title":"Variations in the frequencies of torque teno virus subpopulations during HAART treatment in HIV-1-coinfected patients","volume":"154","author":"Devalle","year":"2009","journal-title":"Arch. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1007\/s00705-020-04538-1","article-title":"Prevalence of torque viruses in HIV-infected and non-HIV-infected Nigerian subjects: Analysis of near-full-length genome sequences","volume":"165","author":"Elesinnla","year":"2020","journal-title":"Arch. Virol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/jmv.20756","article-title":"Progression towards AIDS leads to increased Torque teno virus and Torque teno minivirus titers in tissues of HIV infected individuals","volume":"79","author":"Thom","year":"2007","journal-title":"J. Med. Virol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.bsheal.2025.05.006","article-title":"Clinical prognostic value of TTV and HCMV but not EBV for outcomes in hospitalized HIV-positive patients","volume":"7","author":"Fan","year":"2025","journal-title":"Biosaf. Health"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1097\/00002030-200103300-00004","article-title":"Inverse relationship between the titre of TT virus DNA and the CD4 cell count in patients infected with HIV","volume":"15","author":"Shibayama","year":"2001","journal-title":"AIDS"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1086\/315440","article-title":"Prevalence and prognostic significance of infection with TT virus in patients infected with human immunodeficiency virus","volume":"181","author":"Christensen","year":"2000","journal-title":"J. Infect. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1310\/8C94-VYPQ-NG1H-4CNW","article-title":"TTV viral load as a marker for immune reconstitution after initiation of HAART in HIV-infected patients","volume":"3","author":"Madsen","year":"2002","journal-title":"HIV Clin. Trials"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1007\/s15010-020-01573-7","article-title":"Torque Teno Virus plasma level as novel biomarker of retained immunocompetence in HIV-infected patients","volume":"49","author":"Schmidt","year":"2021","journal-title":"Infection"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e176","DOI":"10.1016\/S2352-3018(23)00272-2","article-title":"Longitudinal trends in causes of death among adults with HIV on antiretroviral therapy in Europe and North America from 1996 to 2020: A collaboration of cohort studies","volume":"11","author":"Trickey","year":"2024","journal-title":"Lancet HIV"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1093\/cid\/ciae014","article-title":"Swiss HIV Cohort Study. Time Trends in Causes of Death in People with HIV: Insights From the Swiss HIV Cohort Study","volume":"79","author":"Weber","year":"2024","journal-title":"Clin. Infect. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/S0140-6736(23)01381-8","article-title":"HIV epidemiology, prevention, treatment, and implementation strategies for public health","volume":"403","author":"Mody","year":"2024","journal-title":"Lancet"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e207954","DOI":"10.1001\/jamanetworkopen.2020.7954","article-title":"Comparison of Overall and Comorbidity-Free Life Expectancy Between Insured Adults with and Without HIV Infection, 2000-2016","volume":"3","author":"Marcus","year":"2020","journal-title":"JAMA Netw. Open"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Jin, J., Xu, Q., Zhang, X., Zhu, A., Xia, W., Moog, C., Chan, A.S.W., Zhang, T., and Su, B. (2025). HIV infection and immunosenescence: Challenges and intervention strategies. BMC Med., 24.","DOI":"10.1186\/s12916-025-04545-6"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1111\/andr.70050","article-title":"Penile vascular status in young men living with HIV experiencing erectile dysfunction: A comparative cross-sectional pilot study","volume":"14","author":"Tiecco","year":"2026","journal-title":"Andrology"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Gotti, D., Raffetti, E., Albini, L., Sighinolfi, L., Maggiolo, F., Di Filippo, E., Ladisa, N., Angarano, G., Lapadula, G., and Pan, A. (2014). Survival in HIV-infected patients after a cancer diagnosis in the cART Era: Results of an italian multicenter study. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0094768"},{"key":"ref_41","unstructured":"(2026, April 01). Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV, Available online: https:\/\/clinicalinfo.hiv.gov\/sites\/default\/files\/guidelines\/documents\/adult-adolescent-arv\/guidelines-adult-adolescent-arv.pdf."},{"key":"ref_42","unstructured":"(2026, April 01). EACS Guidelines, Version 13.0. Available online: https:\/\/www.eacsociety.org\/guidelines\/eacs-guidelines\/."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Quiros-Roldan, E., Salvi, M., Alberti, M., Tiecco, G., Biasiotto, G., Bresciani, R., Bertoli, D., Sottini, A., and De Francesco, M.A. (2026). Torque Teno Virus (TTV) Plasma Load and Immune Reconstitution Post-Transplantation in Patients with Lymphoproliferative Disorders: A Systematic Review. Pathogens, 15.","DOI":"10.3390\/pathogens15010105"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1159\/000528169","article-title":"Association of Torquetenovirus Viremia with Physical Frailty and Cognitive Impairment in Three Independent European Cohorts","volume":"69","author":"Giacconi","year":"2023","journal-title":"Gerontology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.exger.2018.09.003","article-title":"Torquetenovirus (TTV) load is associated with mortality in Italian elderly subjects","volume":"112","author":"Giacconi","year":"2018","journal-title":"Exp. Gerontol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1838","DOI":"10.1093\/gerona\/glz293","article-title":"Prevalence and Loads of Torquetenovirus in the European MARK-AGE Study Population","volume":"75","author":"Giacconi","year":"2020","journal-title":"J. Gerontol. Biol. Sci. Med. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2815","DOI":"10.1093\/rheumatology\/keab839","article-title":"Torque Teno Virus quantification for monitoring of immunomodulation with biologic compounds in the treatment of rheumatoid arthritis","volume":"61","author":"Studenic","year":"2022","journal-title":"Rheumatology"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Zhang, X., Chen, L., Wang, F., Xu, X., Wu, Y., Xu, J., Xu, Y., and He, X. (2026). Torque teno virus in the lower respiratory tract: Association with immunosuppression but not mortality in severe pneumonia-a multicenter retrospective cohort study. Eur. J. Clin. Microbiol. Infect. Dis.","DOI":"10.1007\/s10096-026-05488-3"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e70831","DOI":"10.1002\/jmv.70831","article-title":"Torque Teno Virus Levels During Viral Respiratory Infections: The Interplay with Immune Dysregulation and Coagulopathy Biomarkers","volume":"98","author":"Ferrarese","year":"2026","journal-title":"J. Med. Virol."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/14\/6\/1386\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T09:32:33Z","timestamp":1782379953000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/14\/6\/1386"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,22]]},"references-count":49,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["microorganisms14061386"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms14061386","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,22]]}}}