{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:04:51Z","timestamp":1790701491508,"version":"4.1.0"},"reference-count":53,"publisher":"IMR Press","issue":"3","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Heart, Lung, and Blood Institute","award":["2R15HL143545-02"],"award-info":[{"award-number":["2R15HL143545-02"]}],"id":[{"id":"https:\/\/ror.org\/012pb6c26","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Front. Biosci. (Elite Ed)"],"abstract":"<jats:p>Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a major global health challenge, particularly in low- and middle-income countries. The Bacillus Calmette\u2013Gu\u00e9rin (BCG) vaccine, developed from attenuated Mycobacterium bovis (M. bovis) and introduced in 1921, is the only licensed vaccine for TB prevention. Although BCG provides strong protection against morbid forms of pediatric TB, its efficacy against adult pulmonary TB is variable. Emerging evidence indicates that BCG exerts broader immunological effects beyond TB prevention, including non-specific immune protection mediated through trained immunity. BCG-induced trained immunity induces epigenetic reprogramming of innate immune cells which enhances host defense against heterologous pathogens. Advances in pharmacological biotechnology, including recombinant BCG platforms, genetic modification, and novel delivery systems, have demonstrated improved antigen presentation, durability of immune memory, and expanded clinical utility. Beyond TB, BCG remains a cornerstone immunotherapy for non\u2013muscle-invasive bladder cancer and shows promising immunomodulatory potential in autoimmune diseases such as type 1 diabetes and multiple sclerosis. While adverse effects are generally mild, they tend to be more pronounced in immunocompromised individuals. This review examines the historical development, biotechnological production, immunological mechanisms, and expanding therapeutic applications of BCG. We synthesized findings on strain variability, manufacturing processes, and immune responses, highlighting the induction of T helper 1 (Th1)\u2013mediated cellular immunity through interferon gamma (IFN-\u03b3) and interleukin-12 (IL-12), macrophage activation, and granuloma formation. Overall, BCG represents both a critical public health intervention and a model system for advancing immune-based therapies.<\/jats:p>","DOI":"10.31083\/fbe49594","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:24:22Z","timestamp":1790699062000},"source":"Crossref","is-referenced-by-count":0,"title":["The BCG Vaccine: Pharmacological Biotechnology and Expanding Immunological Horizons"],"prefix":"10.31083","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-7533-9570","authenticated-orcid":true,"given":"Yibo","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Kansas College of Osteopathic Medicine, Wichita, KS 67202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3189-3175","authenticated-orcid":true,"given":"Melodie","family":"Pepper","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Kansas College of Osteopathic Medicine, Wichita, KS 67202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1652-1452","authenticated-orcid":true,"given":"Christopher","family":"Khatchadourian","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Southern California, Los Angeles, CA 90033, USA"},{"name":"Department of Pathology, Los Angeles General Medical Center, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5442-4850","authenticated-orcid":true,"given":"Luke","family":"Sanders","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Kansas College of Osteopathic Medicine, Wichita, KS 67202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7887-0346","authenticated-orcid":true,"given":"Jackson","family":"Lewis","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Kansas College of Osteopathic Medicine, Wichita, KS 67202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3484-7011","authenticated-orcid":true,"given":"Morgan","family":"Trapp","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Kansas College of Osteopathic Medicine, Wichita, KS 67202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2586-1160","authenticated-orcid":true,"given":"Vishwanath","family":"Venketaraman","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, Western University of Health Sciences, Pomona, CA 91766, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"ref1","unstructured":"World Health Organization. Global tuberculosis report 2024. 2024. Available at: https:\/\/www.who.int\/teams\/global-programme-on-tuberculosis-and-lung-health\/tb-reports\/global-tuberculosis-report-2024 (Accessed: 14 December 2025)."},{"key":"ref2","doi-asserted-by":"publisher","unstructured":"Lange C, Aaby P, Behr MA, Donald PR, Kaufmann SHE, Netea MG, et al. 100 years of Mycobacterium bovis bacille Calmette-Gu\u00e9rin. The Lancet. Infectious Diseases. 2022; 22: e2\u2013e12.","DOI":"10.1016\/S1473-3099(21)00403-5"},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"Cobelens F, Suri RK, Helinski M, Makanga M, Weinberg AL, Schaffmeister B, et al. Accelerating research and development of new vaccines against tuberculosis: a global roadmap. The Lancet. Infectious Diseases. 2022; 22: e108\u2013e120.","DOI":"10.1016\/S1473-3099(21)00810-0"},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"Puvaci\u0107 S, Dizdarevi\u0107 J, Santi\u0107 Z, Mulaomerovi\u0107 M. Protective effect of neonatal BCG vaccines against tuberculous meningitis. Bosnian Journal of Basic Medical Sciences. 2004; 4: 46\u201349.","DOI":"10.17305\/bjbms.2004.3460"},{"key":"ref5","doi-asserted-by":"publisher","unstructured":"Fatima S, Kumari A, Das G, Dwivedi VP. Tuberculosis vaccine: A journey from BCG to present. Life Sciences. 2020; 252: 117594.","DOI":"10.1016\/j.lfs.2020.117594"},{"key":"ref6","doi-asserted-by":"publisher","unstructured":"Gopalaswamy R, Subbian S. An Update on Tuberculosis Vaccines. Methods in Molecular Biology (Clifton, N.J.). 2022; 2410: 387\u2013409.","DOI":"10.1007\/978-1-0716-1884-4_20"},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"Srivastava S, Dey S, Mukhopadhyay S. Vaccines against Tuberculosis: Where Are We Now? Vaccines. 2023; 11: 1013.","DOI":"10.3390\/vaccines11051013"},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"Ferluga J, Yasmin H, Bhakta S, Kishore U. Vaccination Strategies Against Mycobacterium tuberculosis: BCG and Beyond. Advances in Experimental Medicine and Biology. 2021; 1313: 217\u2013240.","DOI":"10.1007\/978-3-030-67452-6_10"},{"key":"ref9","doi-asserted-by":"publisher","unstructured":"Singh S, Saavedra-Avila NA, Tiwari S, Porcelli SA. A century of BCG vaccination: Immune mechanisms, animal models, non-traditional routes and implications for COVID-19. Frontiers in Immunology. 2022; 13: 959656.","DOI":"10.3389\/fimmu.2022.959656"},{"key":"ref10","doi-asserted-by":"publisher","unstructured":"Trunz BB, Fine P, Dye C. Effect of BCG vaccination on childhood tuberculous meningitis and miliary tuberculosis worldwide: a meta-analysis and assessment of cost-effectiveness. Lancet (London, England). 2006; 367: 1173\u20131180.","DOI":"10.1016\/S0140-6736(06)68507-3"},{"key":"ref11","doi-asserted-by":"publisher","unstructured":"Kaufmann SHE. Vaccination Against Tuberculosis: Revamping BCG by Molecular Genetics Guided by Immunology. Frontiers in Immunology. 2020; 11: 316.","DOI":"10.3389\/fimmu.2020.00316"},{"key":"ref12","doi-asserted-by":"publisher","unstructured":"Calmette A. Preventive Vaccination Against Tuberculosis with BCG. Proceedings of the Royal Society of Medicine. 1931; 24: 1481\u20131490.","DOI":"10.1177\/003591573102401109"},{"key":"ref13","doi-asserted-by":"publisher","unstructured":"Locht C. Highlights of the 3rd international BCG symposium: 100th anniversary of the first administration of BCG. Microbes and Infection. 2022; 24: 105043.","DOI":"10.1016\/j.micinf.2022.105043"},{"key":"ref14","doi-asserted-by":"publisher","unstructured":"Wallgren A. INTRADERMAL VACCINATIONS WITH B C G VIRUS: PRELIMINARY NOTE. The Journal of the American Medical Association. 1928; 91: 1876.","DOI":"10.1001\/jama.1928.02700240030008"},{"key":"ref15","doi-asserted-by":"publisher","unstructured":"Fox GJ, Orlova M, Schurr E. Tuberculosis in Newborns: The Lessons of the \u201cL\u00fcbeck Disaster\u201d (1929-1933). PLoS Pathogens. 2016; 12: e1005271.","DOI":"10.1371\/journal.ppat.1005271"},{"key":"ref16","doi-asserted-by":"publisher","unstructured":"Nakayama DK. A Novel Microbe, Immunization Deaths, and Vaccination on Trial: BCG and the L\u00fcbeck Disaster of 1930. The American Surgeon. 2025; 91: 672\u2013676.","DOI":"10.1177\/00031348251313994"},{"key":"ref17","doi-asserted-by":"publisher","unstructured":"Moliva JI, Turner J, Torrelles JB. Prospects in Mycobacterium bovis Bacille Calmette et Gu\u00e9rin (BCG) vaccine diversity and delivery: why does BCG fail to protect against tuberculosis? Vaccine. 2015; 33: 5035\u20135041.","DOI":"10.1016\/j.vaccine.2015.08.033"},{"key":"ref18","unstructured":"Luca S, Mihaescu T. History of BCG Vaccine. Maedica. 2013; 8: 53\u201358."},{"key":"ref19","unstructured":"World Health Organization. Recommendations to assure the quality, safety and Efficacy of BCG Vaccines. annex 3(TRS no 979). 2013. Available at: https:\/\/www.who.int\/publications\/m\/item\/trs-979-annex-3-bcg-vax (Accessed: 14 December 2025)."},{"key":"ref20","doi-asserted-by":"publisher","unstructured":"Lobo N, Brooks NA, Zlotta AR, Cirillo JD, Boorjian S, Black PC, et al. 100 years of Bacillus Calmette-Gu\u00e9rin immunotherapy: from cattle to COVID-19. Nature Reviews. Urology. 2021; 18: 611\u2013622.","DOI":"10.1038\/s41585-021-00481-1"},{"key":"ref21","doi-asserted-by":"publisher","unstructured":"Cernuschi T, Malvolti S, Nickels E, Friede M. Bacillus Calmette-Gu\u00e9rin (BCG) vaccine: A global assessment of demand and supply balance. Vaccine. 2018; 36: 498\u2013506.","DOI":"10.1016\/j.vaccine.2017.12.010"},{"key":"ref22","doi-asserted-by":"publisher","unstructured":"Chen J, Gao L, Wu X, Fan Y, Liu M, Peng L, et al. BCG-induced trained immunity: history, mechanisms and potential applications. Journal of Translational Medicine. 2023; 21: 106.","DOI":"10.1186\/s12967-023-03944-8"},{"key":"ref23","unstructured":"Sharma S, Bose M. Role of cytokines in immune response to pulmonary tuberculosis. Asian Pacific Journal of Allergy and Immunology. 2001; 19: 213\u2013219."},{"key":"ref24","doi-asserted-by":"publisher","unstructured":"Suen TK, Moorlag SJCFM, Li W, de Bree LCJ, Koeken VACM, Mourits VP, et al. BCG vaccination induces innate immune memory in \u03b3\u03b4 T cells in humans. Journal of Leukocyte Biology. 2024; 115: 149\u2013163.","DOI":"10.1093\/jleuko\/qiad103"},{"key":"ref25","doi-asserted-by":"publisher","unstructured":"Zhu J. T helper 2 (Th2) cell differentiation, type 2 innate lymphoid cell (ILC2) development and regulation of interleukin-4 (IL-4) and IL-13 production. Cytokine. 2015; 75: 14\u201324.","DOI":"10.1016\/j.cyto.2015.05.010"},{"key":"ref26","doi-asserted-by":"publisher","unstructured":"Mosmann TR, Moore KW. The role of IL-10 in crossregulation of TH1 and TH2 responses. Immunology Today. 1991; 12: A49\u2013A53.","DOI":"10.1016\/S0167-5699(05)80015-5"},{"key":"ref27","doi-asserted-by":"publisher","unstructured":"Arts RJW, Carvalho A, La Rocca C, Palma C, Rodrigues F, Silvestre R, et al. Immunometabolic Pathways in BCG-Induced Trained Immunity. Cell Reports. 2016; 17: 2562\u20132571.","DOI":"10.1016\/j.celrep.2016.11.011"},{"key":"ref28","doi-asserted-by":"publisher","unstructured":"Ritz N, Casalaz D, Donath S, Tebruegge M, Dutta B, Connell TG, et al. Comparable CD4 and CD8 T cell responses and cytokine release after at-birth and delayed BCG immunisation in infants born in Australia. Vaccine. 2016; 34: 4132\u20134139.","DOI":"10.1016\/j.vaccine.2016.06.077"},{"key":"ref29","doi-asserted-by":"publisher","unstructured":"Schmidt AC, Fairlie L, Hellstr\u00f6m E, Luabeya Kany Kany A, Middelkoop K, Naidoo K, et al. BCG Revaccination for the Prevention of Mycobacterium tuberculosis Infection. The New England Journal of Medicine. 2025; 392: 1789\u20131800.","DOI":"10.1056\/NEJMoa2412381"},{"key":"ref30","unstructured":"Implementing the WHO Stop TB Strategy: A Handbook for National Tuberculosis Control Programmes. Geneva: World Health Organization; 2008. 8. BCG vaccination. Available at: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK310750\/ (Accessed: 14 December 2025)."},{"key":"ref31","doi-asserted-by":"publisher","unstructured":"Venkataraman A, Yusuff M, Liebeschuetz S, Riddell A, Prendergast AJ. Management and outcome of Bacille Calmette-Gu\u00e9rin vaccine adverse reactions. Vaccine. 2015; 33: 5470\u20135474.","DOI":"10.1016\/j.vaccine.2015.07.103"},{"key":"ref32","doi-asserted-by":"publisher","unstructured":"Turnbull FM, McIntyre PB, Achat HM, Wang H, Stapledon R, Gold M, et al. National study of adverse reactions after vaccination with bacille Calmette-Gu\u00e9rin. Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2002; 34: 447\u2013453.","DOI":"10.1086\/338462"},{"key":"ref33","doi-asserted-by":"publisher","unstructured":"Rermruay R, Rungmaitree S, Chatpornvorarux S, Brukesawan C, Wittawatmongkol O, Lapphra K, et al. Clinical features and outcomes of Bacille Calmette-Gu\u00e9rin (BCG)-induced diseases following neonatal BCG Tokyo-172 strain immunization. Vaccine. 2018; 36: 4046\u20134053.","DOI":"10.1016\/j.vaccine.2018.05.098"},{"key":"ref34","doi-asserted-by":"publisher","unstructured":"Nunes-Santos CDJ, Rosenzweig SD. Bacille Calmette-Guerin Complications in Newly Described Primary Immunodeficiency Diseases: 2010-2017. Frontiers in Immunology. 2018; 9: 1423.","DOI":"10.3389\/fimmu.2018.01423"},{"key":"ref35","doi-asserted-by":"publisher","unstructured":"Fekrvand S, Yazdani R, Olbrich P, Gennery A, Rosenzweig SD, Condino-Neto A, et al. Primary Immunodeficiency Diseases and Bacillus Calmette-Gu\u00e9rin (BCG)-Vaccine-Derived Complications: A Systematic Review. The Journal of Allergy and Clinical Immunology. in Practice. 2020; 8: 1371\u20131386.","DOI":"10.1016\/j.jaip.2020.01.038"},{"key":"ref36","doi-asserted-by":"publisher","unstructured":"Fazlollahi MR, Goudarzi A, Nourizadeh M, Alizadeh Z, Tajik S, Badalzadeh M, et al. Complications of the Bacillus Calmette-Guerin vaccine as an early warning sign of inborn errors of immunity: a report of 197 patients. Frontiers in Immunology. 2024; 15: 1477499.","DOI":"10.3389\/fimmu.2024.1477499"},{"key":"ref37","doi-asserted-by":"publisher","unstructured":"Chen H, Yang X, Huang Y, Jiao F, Bai H, Zhu Y, et al. Clinical characteristics and genetic features of 35 cases of adverse reactions to Bacillus Calmette-Gu\u00e9rin vaccine in children. Frontiers in Cellular and Infection Microbiology. 2025; 15: 1570382.","DOI":"10.3389\/fcimb.2025.1570382"},{"key":"ref38","doi-asserted-by":"publisher","unstructured":"Huang W, Chiu NC, Chi H, Huang FY, Huang CY. Inoculation Age of Bacillus Calmette-Gu\u00e9rin Tokyo-172 Strain and Vaccine-related Adverse Reactions in Taiwan Birth Cohort of 2012-2017. Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2021; 73: e1554\u2013e1559.","DOI":"10.1093\/cid\/ciaa1235"},{"key":"ref39","doi-asserted-by":"publisher","unstructured":"Badurdeen S, Marshall A, Daish H, Hatherill M, Berkley JA. Safety and Immunogenicity of Early Bacillus Calmette-Gu\u00e9rin Vaccination in Infants Who Are Preterm and\/or Have Low Birth Weights: A Systematic Review and Meta-analysis. JAMA Pediatrics. 2019; 173: 75\u201385.","DOI":"10.1001\/jamapediatrics.2018.4038"},{"key":"ref40","unstructured":"World Health Organization. Module 5: Management of tuberculosis in children and adolescents. 2022. Available at: https:\/\/www.who.int\/publications\/i\/item\/9789240046832 (Accessed: 11 December 2025)."},{"key":"ref41","doi-asserted-by":"publisher","unstructured":"Lamm DL, Morales A. A BCG success story: From prevention of tuberculosis to optimal bladder cancer treatment. Vaccine. 2021; 39: 7308\u20137318.","DOI":"10.1016\/j.vaccine.2021.08.026"},{"key":"ref42","doi-asserted-by":"publisher","unstructured":"Gan C, Mostafid H, Khan MS, Lewis DJM. BCG immunotherapy for bladder cancer--the effects of substrain differences. Nature Reviews. Urology. 2013; 10: 580\u2013588.","DOI":"10.1038\/nrurol.2013.194"},{"key":"ref43","doi-asserted-by":"publisher","unstructured":"Ji N, Mukherjee N, Reyes RM, Gelfond J, Javors M, Meeks JJ, et al. Rapamycin enhances BCG-specific \u03b3\u03b4 T cells during intravesical BCG therapy for non-muscle invasive bladder cancer: a randomized, double-blind study. Journal for Immunotherapy of Cancer. 2021; 9: e001941.","DOI":"10.1136\/jitc-2020-001941"},{"key":"ref44","doi-asserted-by":"publisher","unstructured":"Singh AK, Srikrishna G, Bivalacqua TJ, Bishai WR. Recombinant BCGs for tuberculosis and bladder cancer. Vaccine. 2021; 39: 7321\u20137331.","DOI":"10.1016\/j.vaccine.2021.09.040"},{"key":"ref45","doi-asserted-by":"publisher","unstructured":"Yamazaki-Nakashimada MA, Unzueta A, Berenise G\u00e1mez-Gonz\u00e1lez L, Gonz\u00e1lez-Salda\u00f1a N, Sorensen RU. BCG: a vaccine with multiple faces. Human Vaccines & Immunotherapeutics. 2020; 16: 1841\u20131850.","DOI":"10.1080\/21645515.2019.1706930"},{"key":"ref46","doi-asserted-by":"publisher","unstructured":"Ilijazi D, Pulverer W, Ertl IE, Lemberger U, Kimura S, Abufaraj M, et al. Discovery of Molecular DNA Methylation-Based Biomarkers through Genome-Wide Analysis of Response Patterns to BCG for Bladder Cancer. Cells. 2020; 9: 1839.","DOI":"10.3390\/cells9081839"},{"key":"ref47","doi-asserted-by":"publisher","unstructured":"Faustman DL, Lee A, Hostetter ER, Aristarkhova A, Ng NC, Shpilsky GF, et al. Multiple BCG vaccinations for the prevention of COVID-19 and other infectious diseases in type 1 diabetes. Cell Reports. Medicine. 2022; 3: 100728.","DOI":"10.1016\/j.xcrm.2022.100728"},{"key":"ref48","doi-asserted-by":"publisher","unstructured":"Amato MP, De Stefano N, Inglese M, Morena E, Ristori G, Salvetti M, et al. Secondary Prevention in Radiologically Isolated Syndromes and Prodromal Stages of Multiple Sclerosis. Frontiers in Neurology. 2022; 13: 787160.","DOI":"10.3389\/fneur.2022.787160"},{"key":"ref49","doi-asserted-by":"publisher","unstructured":"Ristori G, Romano S, Cannoni S, Visconti A, Tinelli E, Mendozzi L, et al. Effects of Bacille Calmette-Guerin after the first demyelinating event in the CNS. Neurology. 2014; 82: 41\u201348.","DOI":"10.1212\/01.wnl.0000438216.93319.ab"},{"key":"ref50","doi-asserted-by":"publisher","unstructured":"Sewell DL, Reinke EK, Co DO, Hogan LH, Fritz RB, Sandor M, et al. Infection with Mycobacterium bovis BCG diverts traffic of myelin oligodendroglial glycoprotein autoantigen-specific T cells away from the central nervous system and ameliorates experimental autoimmune encephalomyelitis. Clinical and Diagnostic Laboratory Immunology. 2003; 10: 564\u2013572.","DOI":"10.1128\/cdli.10.4.564-572.2003"},{"key":"ref51","doi-asserted-by":"publisher","unstructured":"Zhuang L, Ye Z, Li L, Yang L, Gong W. Next-Generation TB Vaccines: Progress, Challenges, and Prospects. Vaccines. 2023; 11: 1304.","DOI":"10.3390\/vaccines11081304"},{"key":"ref52","doi-asserted-by":"publisher","unstructured":"Tait DR, Hatherill M, Van Der Meeren O, Ginsberg AM, Van Brakel E, Salaun B, et al. Final Analysis of a Trial of M72\/AS01E Vaccine to Prevent Tuberculosis. The New England Journal of Medicine. 2019; 381: 2429\u20132439.","DOI":"10.1056\/NEJMoa1909953"},{"key":"ref53","doi-asserted-by":"publisher","unstructured":"Zwerling A, Behr MA, Verma A, Brewer TF, Menzies D, Pai M. The BCG World Atlas: a database of global BCG vaccination policies and practices. PLoS Medicine. 2011; 8: e1001012.","DOI":"10.1371\/journal.pmed.1001012"}],"container-title":["Frontiers in Bioscience-Elite"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.imrpress.com\/journal\/FBE\/18\/3\/10.31083\/FBE49594","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:24:28Z","timestamp":1790699068000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.imrpress.com\/journal\/FBE\/18\/3\/10.31083\/FBE49594"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,15]]},"references-count":53,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026]]}},"alternative-id":["S1945-0508(26)03974-0"],"URL":"https:\/\/doi.org\/10.31083\/fbe49594","relation":{},"ISSN":["1945-0494","1945-0508"],"issn-type":[{"value":"1945-0494","type":"print"},{"value":"1945-0508","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,15]]},"article-number":"49594"}}