{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T04:46:08Z","timestamp":1784263568737,"version":"3.55.0"},"reference-count":53,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001322","name":"Medical Research Council of South Africa","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001322","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004765","name":"University of the Free State","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004765","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection results in dysregulated inflammatory and coagulation pathways that drive immunothrombosis and contribute to adverse clinical outcomes. While individual cytokines and endothelial biomarkers have been associated with disease severity and mortality, the prognostic relevance of combined inflammatory and endothelial signatures remains incompletely characterised. To identify inflammatory cytokines and markers of endothelial activation associated with mortality in patients with severe COVID-19 requiring supplemental oxygen. This retrospective observational study included 73 consecutive adults admitted to a dedicated supplemental oxygen unit with severe COVID-19. Plasma concentrations of IL-1\u03b1, IL-1\u03b2, IL-6, IL-8, IL-10, TNF-\u03b1, von Willebrand factor (VWF) antigen and propeptide, ADAMTS13 antigen and activity, and ADAMTS13 autoantibodies were measured on admission using ELISA-based assays. Associations with mortality were assessed using non-parametric analyses, age-adjusted logistic regression, multivariable logistic regression, and receiver operating characteristic (ROC) curve analysis. Increasing age was independently associated with mortality. After adjustment for age, higher IL-1\u03b1 concentrations were associated with increased odds of death, whereas a higher IL-6\/IL-10 ratio was independently protective. In multivariable models, including non-ratio variables, ADAMTS13 autoantibody levels remained independently associated with mortality. In ratio-based multivariable analysis, both the ADAMTS13 activity\/autoantibody ratio and the IL-6\/IL-10 ratio were independently protective, while age was no longer significant. IL-10 and ADAMTS13 autoantibodies demonstrated moderate discriminative performance for mortality prediction (AUC ~0.70). A combined biomarker model incorporating IL-1\u03b1, IL-8, IL-10, and ADAMTS13 autoantibodies yielded very high predicted mortality probabilities. Our findings highlight IL-1\u03b1 and ADAMTS13 autoantibodies as independent predictors of mortality in severe COVID-19, reflecting the interplay between inflammatory and endothelial pathways. Biomarker ratios capturing immune and endothelial balance\u2014particularly the ADAMTS13 activity\/autoantibody ratio\u2014may enhance risk stratification and support integrated prognostic models.<\/jats:p>","DOI":"10.3390\/ijms27031272","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T15:41:56Z","timestamp":1769528516000},"page":"1272","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Endothelial Biomarkers and Cytokine Profiles: Signatures of Mortality in Severe COVID-19"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5004-2490","authenticated-orcid":false,"given":"Quintin A.","family":"van Staden","sequence":"first","affiliation":[{"name":"Department of Haematology and Cell Biology, School of Pathology, Faculty of Health Sciences, University of the Free State, Bloemfontein 9300, South Africa"},{"name":"Department of Haematology and Cell Biology, Universitas Academic Laboratories, National Health Laboratory Service, Bloemfontein 9300, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5202-7702","authenticated-orcid":false,"given":"Muriel","family":"Meiring","sequence":"additional","affiliation":[{"name":"Department of Haematology and Cell Biology, School of Pathology, Faculty of Health Sciences, University of the Free State, Bloemfontein 9300, South Africa"},{"name":"Department of Haematology and Cell Biology, Universitas Academic Laboratories, National Health Laboratory Service, Bloemfontein 9300, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermanus A.","family":"Hanekom","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, School of Clinical Medicine, Faculty of Health Sciences, University of the Free State, Bloemfontein 9300, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vongani","family":"Nkuna","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, School of Clinical Medicine, Faculty of Health Sciences, University of the Free State, Bloemfontein 9300, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7614-900X","authenticated-orcid":false,"given":"Lezelle","family":"Botes","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, School of Clinical Medicine, Faculty of Health Sciences, University of the Free State, Bloemfontein 9300, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6483-5320","authenticated-orcid":false,"given":"Francis E.","family":"Smit","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, School of Clinical Medicine, Faculty of Health Sciences, University of the Free State, Bloemfontein 9300, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/s41577-021-00536-9","article-title":"Endothelial dysfunction and immunothrombosis as key pathogenic mechanisms in COVID-19","volume":"21","author":"Bonaventura","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1007\/s11239-021-02475-7","article-title":"Incidence of thrombotic complications in COVID-19: On behalf of ICODE: The International COVID-19 Thrombosis Biomarkers Colloquium","volume":"52","author":"Jenner","year":"2021","journal-title":"J. Thromb. Thrombolysis"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/s41435-021-00140-w","article-title":"Role of DAMPs in respiratory virus-induced acute respiratory distress syndrome\u2014With a preliminary reference to SARS-CoV-2 pneumonia","volume":"22","author":"Land","year":"2021","journal-title":"Genes Immun."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Chen, R., Lan, Z., Ye, J., Pang, L., Liu, Y., Wu, W., Qin, X., Guo, Y., and Zhang, P. (2021). Cytokine Storm: The Primary Determinant for the Pathophysiological Evolution of COVID-19 Deterioration. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.589095"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1515\/cclm-2020-0369","article-title":"Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): A meta-analysis","volume":"58","author":"Henry","year":"2020","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"m1328","DOI":"10.1136\/bmj.m1328","article-title":"Prediction models for diagnosis and prognosis of COVID-19: Systematic review and critical appraisal","volume":"369","author":"Wynants","year":"2020","journal-title":"BMJ"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"155190","DOI":"10.1016\/j.cyto.2020.155190","article-title":"Cytokine prediction of mortality in COVID19 patients","volume":"134","author":"Mandel","year":"2020","journal-title":"Cytokine"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1038\/s41591-020-1051-9","article-title":"An inflammatory cytokine signature predicts COVID-19 severity and survival","volume":"26","author":"Huang","year":"2020","journal-title":"Nat. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.1172\/JCI116122","article-title":"Hypoxia-mediated induction of endothelial cell interleukin-1 alpha. An autocrine mechanism promoting expression of leukocyte adhesion molecules on the vessel surface","volume":"90","author":"Shreeniwas","year":"1992","journal-title":"J. Clin. Investig."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/imr.12621","article-title":"Overview of the IL-1 family in innate inflammation and acquired immunity","volume":"281","author":"Dinarello","year":"2018","journal-title":"Immunol. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"eabe3024","DOI":"10.1126\/sciadv.abe3024","article-title":"Distinct inflammatory profiles distinguish COVID-19 from influenza with limited contributions from cytokine storm","volume":"6","author":"Mudd","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/s41586-020-2588-y","article-title":"Longitudinal analyses reveal immunological misfiring in severe COVID-19","volume":"584","author":"Lucas","year":"2020","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e16985","DOI":"10.1016\/j.heliyon.2023.e16985","article-title":"IL-10\/IL-6 ratio from nasal & oral swab samples, acts as an inflammatory indicator for COVID-19 patients infected with the delta variant","volume":"9","author":"Biswas","year":"2023","journal-title":"Heliyon"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1111\/bjh.17273","article-title":"Von Willebrand factor propeptide in severe coronavirus disease 2019 (COVID-19): Evidence of acute and sustained endothelial cell activation","volume":"192","author":"Ward","year":"2021","journal-title":"Br. J. Haematol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.thromres.2022.08.017","article-title":"Prognostic value of von Willebrand factor and ADAMTS13 in patients with COVID-19: A systematic review and meta-analysis","volume":"218","author":"Xu","year":"2022","journal-title":"Thromb. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1111\/jth.15191","article-title":"The ADAMTS13-von Willebrand factor axis in COVID-19 patients","volume":"19","author":"Mancini","year":"2021","journal-title":"J. Thromb. Haemost."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2429","DOI":"10.1111\/jth.15830","article-title":"Sustained VWF-ADAMTS-13 axis imbalance and endotheliopathy in long COVID syndrome is related to immune dysfunction","volume":"20","author":"Fogarty","year":"2022","journal-title":"J. Thromb. Haemostasis"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e512","DOI":"10.1097\/CCM.0000000000004918","article-title":"von Willebrand Factor Multimer Formation Contributes to Immunothrombosis in Coronavirus Disease 2019","volume":"49","author":"Doevelaar","year":"2021","journal-title":"Crit Care Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"10501","DOI":"10.1038\/s41598-023-37405-5","article-title":"Generation of potentially inhibitory autoantibodies to ADAMTS13 in coronavirus disease 2019","volume":"13","author":"Doevelaar","year":"2023","journal-title":"Sci Rep."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Molina, F.J., Botero, L.E., Isaza, J.P., Cano, L.E., L\u00f3pez, L., Hoyos, L.M., Correa, E., and Torres, A. (2022). Cytokine levels as predictors of mortality in critically ill patients with severe COVID-19 pneumonia: Case-control study nested within a cohort in Colombia. Front. Med., 9.","DOI":"10.3389\/fmed.2022.1005636"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/j.1600-0854.2008.00840.x","article-title":"The dynamics and mechanisms of interleukin-1alpha and beta nuclear import","volume":"10","author":"Luheshi","year":"2009","journal-title":"Traffic"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"14209","DOI":"10.1038\/s41598-025-98505-y","article-title":"Cytokine profiles dynamics in COVID-19 patients: A longitudinal analysis of disease severity and outcomes","volume":"15","author":"Ghaffarpour","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Tamayo-Velasco, \u00c1., Mart\u00ednez-Paz, P., Pe\u00f1arrubia-Ponce, M.J., de la Fuente, I., P\u00e9rez-Gonz\u00e1lez, S., Fern\u00e1ndez, I., Due\u00f1as, C., G\u00f3mez-S\u00e1nchez, E., Lorenzo-L\u00f3pez, M., and G\u00f3mez-Pesquera, E. (2021). HGF, IL-1\u03b1, and IL-27 Are Robust Biomarkers in Early Severity Stratification of COVID-19 Patients. J. Clin. Med., 10.","DOI":"10.21203\/rs.3.rs-374650\/v1"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e202400672","DOI":"10.1002\/cmdc.202400672","article-title":"Inflammaging and Immunosenescence in the Post-COVID Era: Small Molecules, Big Challenges","volume":"20","author":"Francavilla","year":"2025","journal-title":"ChemMedChem"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"M\u00fcller, L., and Di Benedetto, S. (2024). The impact of COVID-19 on accelerating of immunosenescence and brain aging. Front. Cell. Neurosci., 18.","DOI":"10.3389\/fncel.2024.1471192"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.cger.2022.03.003","article-title":"Inflammaging at the Time of COVID-19","volume":"38","author":"Zazzara","year":"2022","journal-title":"Clin. Geriatr. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"111685","DOI":"10.1016\/j.mad.2022.111685","article-title":"Inflammaging: The lesson of COVID-19 pandemic","volume":"205","author":"Olivieri","year":"2022","journal-title":"Mech. Ageing Dev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"17","DOI":"10.3109\/01902149109063278","article-title":"Interleukin-8 (IL-8): The major neutrophil chemotactic factor in the lung","volume":"17","author":"Kunkel","year":"1991","journal-title":"Exp. Lung Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/S0140-6736(20)30183-5","article-title":"Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China","volume":"395","author":"Huang","year":"2020","journal-title":"Lancet"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.it.2020.10.012","article-title":"A Potential Role of Interleukin 10 in COVID-19 Pathogenesis","volume":"42","author":"Lu","year":"2021","journal-title":"Trends Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e108","DOI":"10.1097\/MJT.0000000000001603","article-title":"Anakinra-An Interleukin-1 Receptor Antagonist for COVID-19","volume":"30","author":"Nguyen","year":"2023","journal-title":"Am. J. Ther."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"817","DOI":"10.2217\/fvl-2020-0168","article-title":"Relationship Between IL-6 and COVID-19: To Be Considered During Treatment","volume":"15","author":"Vatansever","year":"2020","journal-title":"Future Virol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1080\/22221751.2020.1770129","article-title":"Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors","volume":"9","author":"Han","year":"2020","journal-title":"Emerg. Microbes Infect."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Nilsonne, G., Lekander, M., \u00c5kerstedt, T., Axelsson, J., and Ingre, M. (2016). Diurnal Variation of Circulating Interleukin-6 in Humans: A Meta-Analysis. PLoS ONE, 11.","DOI":"10.1101\/042507"},{"key":"ref_35","first-page":"CD011811","article-title":"Plasma interleukin-6 concentration for the diagnosis of sepsis in critically ill adults","volume":"4","author":"Nuvials","year":"2019","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1161\/CIRCULATIONAHA.107.710509","article-title":"Visceral and subcutaneous adipose tissue volumes are cross-sectionally related to markers of inflammation and oxidative stress: The Framingham Heart Study","volume":"116","author":"Pou","year":"2007","journal-title":"Circulation"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"103026","DOI":"10.1016\/j.ebiom.2020.103026","article-title":"A linear prognostic score based on the ratio of interleukin-6 to interleukin-10 predicts outcomes in COVID-19","volume":"61","author":"McElvaney","year":"2020","journal-title":"EBioMedicine"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"110323","DOI":"10.1016\/j.clim.2024.110323","article-title":"Aberrant innate immune profile associated with COVID-19 mortality in Pretoria, South Africa","volume":"266","author":"Steel","year":"2024","journal-title":"Clin. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2415","DOI":"10.2147\/IJGM.S356547","article-title":"Secondary Infections in Patients with COVID-19 Pneumonia Treated with Tocilizumab Compared to Those Not Treated with Tocilizumab: A Retrospective Study at a Tertiary Hospital in Kenya","volume":"15","author":"Shah","year":"2022","journal-title":"Int. J. Gen. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/s10456-021-09789-3","article-title":"Von Willebrand factor collagen-binding capacity predicts in-hospital mortality in COVID-19 patients: Insight from VWF\/ADAMTS13 ratio imbalance","volume":"24","author":"Philippe","year":"2021","journal-title":"Angiogenesis"},{"key":"ref_41","first-page":"O152","article-title":"Increased von Willebrand factor antigen and low ADAMTS13 activity are related to poor prognosis in COVID-19 patients","volume":"43","author":"Ayala","year":"2021","journal-title":"Int. J. Lab. Hematol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"100182","DOI":"10.1016\/j.rpth.2023.100182","article-title":"Von Willebrand factor and the thrombophilia of severe COVID-19: In situ evidence from autopsies","volume":"7","author":"Berg","year":"2023","journal-title":"Res. Pract. Thromb. Haemost."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1007\/s10238-021-00769-x","article-title":"High levels of Von Willebrand factor markers in COVID-19: A systematic review and meta-analysis","volume":"22","author":"Rostami","year":"2022","journal-title":"Clin. Exp. Med."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Mejia-Pailles, G., Berrington, A., McGrath, N., and Hosegood, V. (2020). Trends in the prevalence and incidence of orphanhood in children and adolescents <20 years in rural KwaZulu-Natal South Africa, 2000\u20132014. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0238563"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.ijid.2020.06.064","article-title":"Therapeutic plasma exchange in adults with severe COVID-19 infection","volume":"99","author":"Khamis","year":"2020","journal-title":"Int. J. Infect. Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1016\/j.ebiom.2015.06.007","article-title":"Pathogenicity of Anti-ADAMTS13 Autoantibodies in Acquired Thrombotic Thrombocytopenic Purpura","volume":"2","author":"Thomas","year":"2015","journal-title":"EBioMedicine"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1161\/ATVBAHA.122.318232","article-title":"Cardiovascular Disease and Thrombosis in HIV Infection","volume":"43","author":"Perkins","year":"2023","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_48","unstructured":"World Health Organization (2020). Estimating Mortality from COVID-19: Scientific Brief, 4 August 2020, World Health Organization. Available online: https:\/\/iris.who.int\/handle\/10665\/333642."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2451","DOI":"10.1056\/NEJMcp2009575","article-title":"Severe COVID-19","volume":"383","author":"Berlin","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_50","first-page":"227","article-title":"Multicollinearity in Regression Analyses Conducted in Epidemiologic Studies","volume":"6","author":"Vatcheva","year":"2016","journal-title":"Epidemiology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1148\/radiology.143.1.7063747","article-title":"The meaning and use of the area under a receiver operating characteristic (ROC) curve","volume":"143","author":"Hanley","year":"1982","journal-title":"Radiology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1002\/1097-0142(1950)3:1<32::AID-CNCR2820030106>3.0.CO;2-3","article-title":"Index for rating diagnostic tests","volume":"3","author":"Youden","year":"1950","journal-title":"Cancer"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1080\/03610928008827941","article-title":"Goodness of fit tests for the multiple logistic regression model","volume":"9","author":"Hosmer","year":"1980","journal-title":"Commun. Stat. Theory Methods"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/3\/1272\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T05:11:06Z","timestamp":1769663466000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/3\/1272"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,27]]},"references-count":53,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["ijms27031272"],"URL":"https:\/\/doi.org\/10.3390\/ijms27031272","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,27]]}}}