{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:55:39Z","timestamp":1791924939984,"version":"4.3.4"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2022,8,9]],"date-time":"2022-08-09T00:00:00Z","timestamp":1660003200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Fonds de Recherche du Qu\u00e9bec\u2013Sant\u00e9"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,2,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Toxoplasmic encephalitis (TE) is an opportunistic infection of people with human immunodeficiency virus (HIV) or other causes of immunosuppression. Guideline-recommended treatments for TE are pyrimethamine and sulfadiazine (P-S) or pyrimethamine and clindamycin (P-C); however, a substantial price increase has limited access to pyrimethamine. Consequently, some centers have transitioned to trimethoprim-sulfamethoxazole (TMP-SMX), an inexpensive alternative treatment. We aimed to review the evidence on the efficacy and safety of pyrimethamine-containing therapies vs TMP-SMX.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We searched for and included randomized controlled trials (RCTs) and observational studies of TE treatments, regardless of HIV status. Data for each therapy were pooled by meta-analysis to assess the proportions of patients who experienced clinical and radiologic responses to treatment, all-cause mortality, and discontinuation due to toxicity. Sensitivity analyses limited to RCTs directly compared therapies.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We identified 6 RCTs\/dose-escalation studies and 26 single-arm\/observational studies. Identified studies included only persons with HIV, and most predated modern antiretroviral treatment. Pooled proportions of clinical and radiologic response and mortality were not significantly different between TMP-SMX and pyrimethamine-containing regimens (P &amp;gt; .05). Treatment discontinuation due to toxicity was significantly lower in TMP-SMX (7.3%; 95% confidence interval [CI], 4.7\u201311.4; I2 = 0.0%) vs P-S (30.5%; 95% CI, 27.1\u201334.2; I2 = 0.0%; P &amp;lt; .01) or P-C (13.7%; 95% CI, 9.8\u201318.8; I2 = 32.0%; P = .031). These results were consistent in analyses restricted to RCT data.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>TMP-SMX appears to be as effective and safer than pyrimethamine-containing regimens for TE. These findings support modern RCTs comparing TMP-SMX to pyrimethamine-based therapies and a revisiting of the guidelines.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciac645","type":"journal-article","created":{"date-parts":[[2022,8,9]],"date-time":"2022-08-09T18:38:25Z","timestamp":1660070305000},"page":"e1302-e1319","source":"Crossref","is-referenced-by-count":29,"title":["Revisiting the Evidence Base for Modern-Day Practice of the Treatment of Toxoplasmic Encephalitis: A Systematic Review and Meta-Analysis"],"prefix":"10.1093","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6790-220X","authenticated-orcid":false,"given":"Connor","family":"Prosty","sequence":"first","affiliation":[{"name":"Faculty of Medicine, McGill University , Montr\u00e9al, Qu\u00e9bec , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Hanula","sequence":"additional","affiliation":[{"name":"Division of Experimental Medicine, Department of Medicine, McGill University , Montr\u00e9al, Qu\u00e9bec , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yossef","family":"Levin","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, McGill University , Montr\u00e9al, Qu\u00e9bec , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac I","family":"Bogoch","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, University of Toronto , Toronto, Ontario , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily G","family":"McDonald","sequence":"additional","affiliation":[{"name":"Division of Experimental Medicine, Department of Medicine, McGill University , Montr\u00e9al, Qu\u00e9bec , Canada"},{"name":"Division of General Internal Medicine, Department of Medicine, McGill University Health Centre , Montr\u00e9al, Qu\u00e9bec , Canada"},{"name":"Clinical Practice Assessment Unit, Department of Medicine, McGill University Health Centre , Montr\u00e9al, Qu\u00e9bec , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd C","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Experimental Medicine, Department of Medicine, McGill University , Montr\u00e9al, Qu\u00e9bec , Canada"},{"name":"Clinical Practice Assessment Unit, Department of Medicine, McGill University Health Centre , Montr\u00e9al, Qu\u00e9bec , Canada"},{"name":"Division of Infectious Diseases, Department of Medicine, McGill University Health Centre , Qu\u00e9bec, Montr\u00e9al , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,8,9]]},"reference":[{"key":"2023020817095138200_ciac645-B1","doi-asserted-by":"crossref","DOI":"10.1177\/2325958219867315","article-title":"HIV-related cerebral toxoplasmosis revisited: current concepts and controversies of an old disease","volume":"18","author":"Vidal","year":"2019","journal-title":"J Int Assoc Provid AIDS Care"},{"key":"2023020817095138200_ciac645-B2","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.bjid.2012.10.030","article-title":"AIDS-related cerebral toxoplasmosis in S\u00e3o Paulo State, Brazil: marked improvements in the highly active antiretroviral therapy-era but the challenges continue","volume":"17","author":"Vidal","year":"2013","journal-title":"Braz J Infect Dis"},{"key":"2023020817095138200_ciac645-B3","doi-asserted-by":"crossref","first-page":"755","DOI":"10.7326\/0003-4819-122-10-199505150-00004","article-title":"Intermittent trimethoprim-sulfamethoxazole compared with dapsone-pyrimethamine for the simultaneous primary prophylaxis of Pneumocystis pneumonia and toxoplasmosis in patients infected with HIV","volume":"122","author":"Podzamczer","year":"1995","journal-title":"Ann Intern Med"},{"key":"2023020817095138200_ciac645-B4","doi-asserted-by":"crossref","first-page":"e13546","DOI":"10.1111\/ctr.13546","article-title":"Tissue and blood protozoa including toxoplasmosis, Chagas disease, leishmaniasis, Babesia, Acanthamoeba, Balamuthia, and Naegleria in solid organ transplant recipients","volume":"33","author":"La Hoz","year":"2019","journal-title":"Clin Transplant"},{"key":"2023020817095138200_ciac645-B5","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1086\/317548","article-title":"Toxoplasmosis, a severe complication in allogeneic hematopoietic stem cell transplantation: successful treatment strategies during a 5-year single-center experience","volume":"32","author":"Roemer","year":"2001","journal-title":"Clin Infect Dis"},{"key":"2023020817095138200_ciac645-B6","doi-asserted-by":"crossref","first-page":"193","DOI":"10.7326\/0003-4819-84-2-193","article-title":"Toxoplasmosis in the compromised host","volume":"84","author":"Ruskin","year":"1976","journal-title":"Ann Intern Med"},{"key":"2023020817095138200_ciac645-B7","year":"2017"},{"key":"2023020817095138200_ciac645-B8","doi-asserted-by":"crossref","first-page":"ofv177","DOI":"10.1093\/ofid\/ofv177","article-title":"Get rich quick with old generic drugs! The pyrimethamine pricing scandal","volume":"2","author":"Gallant","year":"2015","journal-title":"Open Forum Infect Dis"},{"key":"2023020817095138200_ciac645-B9","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1097\/XEB.0000000000000141","article-title":"A new improved graphical and quantitative method for detecting bias in meta-analysis","volume":"16","author":"Furuya-Kanamori","year":"2018","journal-title":"Int J Evid Based Healthc"},{"key":"2023020817095138200_ciac645-B10","first-page":"1","article-title":"Conducting meta-analyses in R with the metafor package","volume":"36","author":"Viechtbauer","year":"2008","journal-title":"J Stat Softw"},{"key":"2023020817095138200_ciac645-B11","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1136\/ebmental-2019-300117","article-title":"How to perform a meta-analysis with R: a practical tutorial","volume":"22","author":"Balduzzi","year":"2019","journal-title":"Evid Based Ment Health"},{"key":"2023020817095138200_ciac645-B12","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1007\/s11121-013-0377-7","article-title":"Meta-analysis and subgroups","volume":"14","author":"Borenstein","year":"2013","journal-title":"Prev Sci"},{"key":"2023020817095138200_ciac645-B13","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1007\/BF02230867","article-title":"Comparison of two medications in central nervous system toxoplasmosis in patients with AIDS","volume":"13","author":"Antinori","year":"1992","journal-title":"Ital J Neurol Sci"},{"key":"2023020817095138200_ciac645-B14","first-page":"956","article-title":"Treating AIDS-associated cerebral toxoplasmosis","volume":"97","author":"Arens","year":"2007","journal-title":"S Afr Med J"},{"key":"2023020817095138200_ciac645-B15","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/0303-8467(89)90004-8","article-title":"Cerebral toxoplasmosis in the acquired immune deficiency syndrome","volume":"91","author":"Carrazana","year":"1989","journal-title":"Clin Neurol Neurosurg"},{"key":"2023020817095138200_ciac645-B16","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/0002-9343(89)90378-1","article-title":"Evaluation of the policy of empiric treatment of suspected Toxoplasma encephalitis in patients with the acquired immunodeficiency syndrome","volume":"86","author":"Cohn","year":"1989","journal-title":"Am J Med"},{"key":"2023020817095138200_ciac645-B17","first-page":"4","article-title":"Cerebral toxoplasmosis in patients with human immunodeficiency virus (HIV) infection. Clinico-radiological and therapeutic aspects in 63 patients","volume":"13","author":"Ferrer","year":"1996","journal-title":"An Med Interna"},{"key":"2023020817095138200_ciac645-B18","first-page":"71","article-title":"Toxoplasmosi cerebrale nella sindrome da immunodeficienza acquisita","volume":"3","author":"Gervasoni","year":"1995","journal-title":"Infez Med"},{"key":"2023020817095138200_ciac645-B19","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1177\/0956462414560594","article-title":"Alternative treatment approach to cerebral toxoplasmosis in HIV\/AIDS: experience from a resource-poor setting","volume":"26","author":"Goswami","year":"2015","journal-title":"Int J STD AIDS"},{"key":"2023020817095138200_ciac645-B20","first-page":"22","article-title":"Cerebral toxoplasmosis in a hospital environment in Lome (Togo)","volume":"88","author":"Grunitzky","year":"1995","journal-title":"Bull Soc Pathol Exo"},{"key":"2023020817095138200_ciac645-B21","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/0002-9343(88)90014-9","article-title":"Treatment of central nervous system toxoplasmosis with pyrimethamine\/sulfadiazine combination in 35 patients with the acquired immunodeficiency syndrome. Efficacy of long-term continuous therapy","volume":"84","author":"Leport","year":"1988","journal-title":"Am J Med"},{"key":"2023020817095138200_ciac645-B22","first-page":"258","article-title":"Clinical characteristics of toxoplasmic encephalopathy in 57 patients with acquired immunodeficiency syndrome","volume":"6","author":"Liu","year":"2018","journal-title":"Chinese J Infect Chemother"},{"key":"2023020817095138200_ciac645-B23","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1056\/NEJM199212033272306","article-title":"Toxoplasmosis of the central nervous system in the acquired immunodeficiency syndrome","volume":"327","author":"Porter","year":"1992","journal-title":"N Engl J Med"},{"key":"2023020817095138200_ciac645-B24","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/BF01964457","article-title":"Role of clindamycin in the treatment of acute toxoplasmosis of the central nervous system","volume":"10","author":"Ruf","year":"1991","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"2023020817095138200_ciac645-B25","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/S0163-4453(98)90217-1","article-title":"A retrospective study of treatment of cerebral toxoplasmosis in AIDS patients with trimethoprim-sulphamethoxazole","volume":"37","author":"Torre","year":"1998","journal-title":"J Infect"},{"key":"2023020817095138200_ciac645-B26","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1097\/00002030-199605000-00009","article-title":"Reasons for failure of prevention of Toxoplasma encephalitis. Swiss HIV Cohort Study","volume":"10","author":"Van Delden","year":"1996","journal-title":"AIDS"},{"key":"2023020817095138200_ciac645-B27","doi-asserted-by":"crossref","first-page":"583","DOI":"10.4269\/ajtmh.2009.80.583","article-title":"Cotrimoxazole for treatment of cerebral toxoplasmosis: an observational cohort study during 1994\u20132006","volume":"80","author":"B\u00e9raud","year":"2009","journal-title":"Am J Trop Med Hyg"},{"key":"2023020817095138200_ciac645-B28","first-page":"259","article-title":"Cerebral toxoplasmosis and AIDS in Martinique","volume":"57","author":"Bouree","year":"1997","journal-title":"Med Trop (Mars)"},{"key":"2023020817095138200_ciac645-B29","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/BF01967063","article-title":"Cotrimoxazole therapy of Toxoplasma gondii encephalitis in AIDS patients","volume":"11","author":"Canessa","year":"1992","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"2023020817095138200_ciac645-B30","first-page":"51","article-title":"Oral trimethoprim-sulfamethoxazole in the treatment of cerebral toxoplasmosis in AIDS patients","volume":"94","author":"Francis","year":"2004","journal-title":"S Afr Med J"},{"key":"2023020817095138200_ciac645-B31","first-page":"441","article-title":"Encephalic toxoplasmosis in patients with the acquired immunodeficiency syndrome. A clinico-radiological study and the therapeutic results in 78 cases","volume":"95","author":"Gonz\u00e1lez-Clemente","year":"1990","journal-title":"Med Clin (Barc)"},{"key":"2023020817095138200_ciac645-B32","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1017\/S0950268814001253","article-title":"Incidence, immunological and clinical characteristics of reactivation of latent Toxoplasma gondii infection in HIV-infected patients","volume":"143","author":"Kodym","year":"2015","journal-title":"Epidemiol Infect"},{"key":"2023020817095138200_ciac645-B33","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1097\/00002030-199006000-00003","article-title":"Central nervous system toxoplasmosis in AIDS patients: efficacy of an intermittent maintenance therapy","volume":"4","author":"Pedrol","year":"1990","journal-title":"AIDS"},{"key":"2023020817095138200_ciac645-B34","first-page":"1315","article-title":"Efficacy and good tolerance of cotrimoxazole as treatment of cerebral toxoplasmosis in AIDS","volume":"27","author":"Smadja","year":"1998","journal-title":"Presse Med"},{"key":"2023020817095138200_ciac645-B35","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1089\/apc.2005.19.626","article-title":"Cerebral toxoplasmosis in HIV-positive patients in Brazil: clinical features and predictors of treatment response in the HAART era","volume":"19","author":"Vidal","year":"2005","journal-title":"AIDS Patient Care STDS"},{"key":"2023020817095138200_ciac645-B36","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1086\/339551","article-title":"Randomized phase II trial of atovaquone with pyrimethamine or sulfadiazine for treatment of toxoplasmic encephalitis in patients with acquired immunodeficiency syndrome: ACTG 237\/ANRS 039 Study. AIDS Clinical Trials Group 237\/Agence Nationale de Recherche sur le SIDA, Essai 039","volume":"34","author":"Chirgwin","year":"2002","journal-title":"Clin Infect Dis"},{"key":"2023020817095138200_ciac645-B37","doi-asserted-by":"crossref","first-page":"33","DOI":"10.7326\/0003-4819-116-1-33","article-title":"Treatment of toxoplasmic encephalitis in patients with AIDS. A randomized trial comparing pyrimethamine plus clindamycin to pyrimethamine plus sulfadiazine. The California Collaborative Treatment Group","volume":"116","author":"Dannemann","year":"1992","journal-title":"Ann Intern Med"},{"key":"2023020817095138200_ciac645-B38","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1093\/clinids\/22.2.268","article-title":"Pyrimethamine-clindamycin vs. pyrimethamine-sulfadiazine as acute and long-term therapy for toxoplasmic encephalitis in patients with AIDS","volume":"22","author":"Katlama","year":"1996","journal-title":"Clin Infect Dis"},{"key":"2023020817095138200_ciac645-B39","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1177\/1545109707301244","article-title":"Randomized controlled trial of pyrimethamine plus sulfadiazine versus trimethoprim plus sulfamethoxazole for treatment of toxoplasmic encephalitis in AIDS patients","volume":"7","author":"Kongsaengdao","year":"2008","journal-title":"J Int Assoc Physicians AIDS Care (Chic)"},{"key":"2023020817095138200_ciac645-B40","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1128\/AAC.42.6.1346","article-title":"Randomized trial of trimethoprim-sulfamethoxazole versus pyrimethamine-sulfadiazine for therapy of toxoplasmic encephalitis in patients with AIDS. Italian Collaborative Study Group","volume":"42","author":"Torre","year":"1998","journal-title":"Antimicrob Agents Chemother"},{"key":"2023020817095138200_ciac645-B41","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1056\/NEJM199309303291403","article-title":"Toxoplasmic encephalitis in patients with the acquired immunodeficiency syndrome","volume":"329","author":"Luft","year":"1993","journal-title":"N Engl J Med"},{"key":"2023020817095138200_ciac645-B42","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1177\/0956462419865829","article-title":"Efficacy and safety of trimethoprim-sulfamethoxazole in HIV-infected patients with cerebral toxoplasmosis in Brazil: a single-arm open-label clinical trial","volume":"30","author":"Pellegrino","year":"2019","journal-title":"Int J STD AIDS"},{"key":"2023020817095138200_ciac645-B43","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1093\/clinids\/24.3.422","article-title":"Atovaquone for salvage treatment and suppression of toxoplasmic encephalitis in patients with AIDS","volume":"24","author":"Torres","year":"1997","journal-title":"Clin Infect Dis"},{"key":"2023020817095138200_ciac645-B44","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1097\/00002030-200103300-00007","article-title":"Dose-escalation, phase I\/II study of azithromycin and pyrimethamine for the treatment of toxoplasmic encephalitis in AIDS","volume":"15","author":"Jacobson","year":"2001","journal-title":"AIDS"},{"key":"2023020817095138200_ciac645-B45","article-title":"Management of toxoplasmic encephalitis in HIV-infected adults (with an emphasis on resource-poor settings)","volume":"3","author":"Dedicoat","year":"2006","journal-title":"Cochrane Database Syst Rev"},{"key":"2023020817095138200_ciac645-B46","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1111\/hiv.12402","article-title":"A systematic review and meta-analysis of the relative efficacy and safety of treatment regimens for HIV-associated cerebral toxoplasmosis: is trimethoprim-sulfamethoxazole a real option?","volume":"18","author":"Hernandez","year":"2017","journal-title":"HIV Med"},{"key":"2023020817095138200_ciac645-B47","first-page":"414","article-title":"Prevalence of Toxoplasma infection in a cohort of homosexual men at risk of AIDS and toxoplasmic encephalitis","volume":"6","author":"Israelski","year":"1993","journal-title":"J Acquir Immune Defic Syndr"},{"key":"2023020817095138200_ciac645-B48","doi-asserted-by":"crossref","first-page":"36","DOI":"10.7326\/0003-4819-100-1-36","article-title":"Central-nervous-system toxoplasmosis in homosexual men and parenteral drug abusers","volume":"100","author":"Wong","year":"1984","journal-title":"Ann Intern Med"},{"key":"2023020817095138200_ciac645-B49","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/S0140-6736(83)91847-0","article-title":"Outbreak of central-nervous-system toxoplasmosis in western Europe and North America","volume":"1","author":"Luft","year":"1983","journal-title":"Lancet"},{"key":"2023020817095138200_ciac645-B50","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1080\/20477724.2018.1552644","article-title":"Patient and treatment pathways for toxoplasmosis in the United States: data analysis of the Vizient Health Systems data from 2011 to 2017","volume":"112","author":"Belk","year":"2018","journal-title":"Pathog Glob Health"}],"container-title":["Clinical Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/cid\/advance-article-pdf\/doi\/10.1093\/cid\/ciac645\/45634283\/ciac645.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cid\/article-pdf\/76\/3\/e1302\/49125537\/ciac645.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cid\/article-pdf\/76\/3\/e1302\/49125537\/ciac645.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T17:51:02Z","timestamp":1675878662000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cid\/article\/76\/3\/e1302\/6659053"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,9]]},"references-count":50,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,8,9]]},"published-print":{"date-parts":[[2023,2,8]]}},"URL":"https:\/\/doi.org\/10.1093\/cid\/ciac645","relation":{},"ISSN":["1058-4838","1537-6591"],"issn-type":[{"value":"1058-4838","type":"print"},{"value":"1537-6591","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,2,1]]},"published":{"date-parts":[[2022,8,9]]}}}