{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T22:42:45Z","timestamp":1778712165633,"version":"3.51.4"},"reference-count":51,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T00:00:00Z","timestamp":1664496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"INSTITUT PASTEUR INTERNATIONAL NETWORK","award":["N\/R\u00e9f: PA\/MLH\/N\u00b0 11\/22"],"award-info":[{"award-number":["N\/R\u00e9f: PA\/MLH\/N\u00b0 11\/22"]}]},{"name":"INSTITUT PASTEUR INTERNATIONAL NETWORK","award":["PCI027"],"award-info":[{"award-number":["PCI027"]}]},{"name":"INSTITUT PASTEUR DE TUNIS","award":["N\/R\u00e9f: PA\/MLH\/N\u00b0 11\/22"],"award-info":[{"award-number":["N\/R\u00e9f: PA\/MLH\/N\u00b0 11\/22"]}]},{"name":"INSTITUT PASTEUR DE TUNIS","award":["PCI027"],"award-info":[{"award-number":["PCI027"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>The contaminant responsible for the atypical toxicity reported in mussels from Bizerte Lagoon (Northern Tunisia) during the last decade has been characterized as C17-sphinganine analog mycotoxin (C17-SAMT). This neurotoxin showed common mouse toxic symptoms, including flaccid paralysis and severe dyspnea, followed by rapid death. For hazard assessment on human health, in this work we aimed to evaluate the in vivo genotoxic effects of this marine biotoxin using the classical alkaline and modified Fpg comet assays performed to detect DNA breaks and alkali-labile sites as well as oxidized bases. The micronucleus assay was used on bone marrow to detect chromosome and genome damage. C17-SAMT induces a statistically insignificant increase in DNA tail intensity at all doses in the duodenum, and in the spleen contrary to the liver, the percentage of tail DNA increased significantly at the mid dose of 300 \u00b5g\/kg b.w\/d. C17-SAMT did not affect the number of micronuclei in the bone marrow. Microscopic observations of the liver showed an increase in the number of mitosis and hepatocytes\u2019 cytoplasm clarification. At this level of study, we confirm that C17-SAMT induced DNA damage in the liver but there was no evidence of effects causing DNA oxidation or chromosome and genome damage.<\/jats:p>","DOI":"10.3390\/md20100619","type":"journal-article","created":{"date-parts":[[2022,10,9]],"date-time":"2022-10-09T01:43:11Z","timestamp":1665279791000},"page":"619","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Investigation of the Genotoxic Potential of the Marine Toxin C17-SAMT Using the In Vivo Comet and Micronucleus Assays"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7398-3816","authenticated-orcid":false,"given":"Zeineb","family":"Marzougui","sequence":"first","affiliation":[{"name":"Laboratoire des Venins et Biomol\u00e9cules Th\u00e9rapeutiques, Institut Pasteur de Tunis, Universit\u00e9 Tunis El Manar, 13 Place Pasteur, B.P. 74, Tunis-Belv\u00e9d\u00e8re, Tunis 1002, Tunisia"},{"name":"National Institute of Agronomy, University of Carthage, Tunis 1082, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvie","family":"Huet","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Toxicologie des Contaminants, Agence Nationale de S\u00e9curit\u00e9 Sanitaire (ANSES), 10 B rue Claude Bourgelat, 35306 Foug\u00e8res, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne-Louise","family":"Blier","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Toxicologie des Contaminants, Agence Nationale de S\u00e9curit\u00e9 Sanitaire (ANSES), 10 B rue Claude Bourgelat, 35306 Foug\u00e8res, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3494-4109","authenticated-orcid":false,"given":"Ludovic Le","family":"H\u00e9garat","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Toxicologie des Contaminants, Agence Nationale de S\u00e9curit\u00e9 Sanitaire (ANSES), 10 B rue Claude Bourgelat, 35306 Foug\u00e8res, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ha\u00effa","family":"Tounsi-Kettiti","sequence":"additional","affiliation":[{"name":"Laboratoire d\u2019Anatomie Pathologique Humaine et Exp\u00e9rimentale, Institut Pasteur de Tunis, Universit\u00e9 Tunis El Manar, 13 Place Pasteur, B.P. 74, Tunis-Belv\u00e9d\u00e8re, Tunis 1002, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riadh","family":"Kharrat","sequence":"additional","affiliation":[{"name":"Laboratoire des Venins et Biomol\u00e9cules Th\u00e9rapeutiques, Institut Pasteur de Tunis, Universit\u00e9 Tunis El Manar, 13 Place Pasteur, B.P. 74, Tunis-Belv\u00e9d\u00e8re, Tunis 1002, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2311-576X","authenticated-orcid":false,"given":"Riadh","family":"Marrouchi","sequence":"additional","affiliation":[{"name":"Laboratoire des Venins et Biomol\u00e9cules Th\u00e9rapeutiques, Institut Pasteur de Tunis, Universit\u00e9 Tunis El Manar, 13 Place Pasteur, B.P. 74, Tunis-Belv\u00e9d\u00e8re, Tunis 1002, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9046-9117","authenticated-orcid":false,"given":"Val\u00e9rie","family":"Fessard","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Toxicologie des Contaminants, Agence Nationale de S\u00e9curit\u00e9 Sanitaire (ANSES), 10 B rue Claude Bourgelat, 35306 Foug\u00e8res, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1039\/c5tx00293a","article-title":"Mycotoxins: Cytotoxicity and Biotransformation in Animal Cells","volume":"5","author":"Wen","year":"2016","journal-title":"Toxicol. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7034","DOI":"10.1021\/acs.jafc.6b04847","article-title":"Worldwide Occurrence of Mycotoxins in Cereals and Cereal-Derived Food Products: Public Health Perspectives of Their Co-Occurrence","volume":"65","author":"Lee","year":"2017","journal-title":"J. Agric. Food Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.tifs.2021.03.031","article-title":"Climate Change and Its Implications for Food Safety and Spoilage","volume":"126","author":"Misiou","year":"2021","journal-title":"Trends Food Sci. Technol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Alshannaq, A., and Yu, J.-H. (2017). Occurrence, Toxicity, and Analysis of Major Mycotoxins in Food. Int. J. Environ. Res. Public Health, 14.","DOI":"10.3390\/ijerph14060632"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.toxicon.2020.07.004","article-title":"Genotoxic Effects of Mycotoxins","volume":"185","author":"Yilmaz","year":"2020","journal-title":"Toxicon"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Habschied, K., Kani\u017eai \u0160ari\u0107, G., Krstanovi\u0107, V., and Mastanjevi\u0107, K. (2021). Mycotoxins\u2014Biomonitoring and Human Exposure. Toxins, 13.","DOI":"10.3390\/toxins13020113"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/BF00769561","article-title":"Mycotoxins, Mycotoxicoses, Mycotoxicology and Mycopathologia","volume":"100","author":"Bennett","year":"1987","journal-title":"Mycopathologia"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.fct.2013.07.047","article-title":"Mycotoxins: Occurrence, Toxicology, and Exposure Assessment","volume":"60","author":"Marin","year":"2013","journal-title":"Food Chem. Toxicol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/j.1574-6968.1997.tb12745.x","article-title":"Growth and Mycotoxin Production by Aspergillus fumigatus Strains Isolated from a Saltern","volume":"157","author":"Frisvad","year":"1997","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.fct.2012.11.037","article-title":"New Mycotoxins from Marine-Derived Fungus Aspergillus sp. SCSGAF0093","volume":"53","author":"Xu","year":"2013","journal-title":"Food Chem. Toxicol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.aquaculture.2015.08.022","article-title":"Mycotoxins and Their Consequences in Aquaculture: A Review","volume":"451","author":"Anater","year":"2016","journal-title":"Aquaculture"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/S0041-0101(03)00146-6","article-title":"Accumulation of Gliotoxin, a Cytotoxic Mycotoxin from Aspergillus fumigatus, in Blue Mussel (Mytilus edulis)","volume":"42","author":"Grovel","year":"2003","journal-title":"Toxicon"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"559","DOI":"10.3390\/encyclopedia2010037","article-title":"Marine Fungi: Opportunities and Challenges","volume":"2","author":"Esteves","year":"2022","journal-title":"Encyclopedia"},{"key":"ref_14","unstructured":"Amzil, Z., Marcaillou-Le Baut, C., and Bohec, M. (1996). Unexplained Toxicity in Molluscs Gathered during Phytoplankton Monitoring. Harmful Toxic Algal Blooms, 543\u2013546."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1023\/A:1007259810190","article-title":"Toxigenic Saprophytic Fungi in Marine Shellfish Farming Areas","volume":"149","author":"Pouchus","year":"2000","journal-title":"Mycopathologia"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"110976","DOI":"10.1016\/j.marpolbul.2020.110976","article-title":"The Fungus Pestalotiopsis sp., Isolated from Perna perna (Bivalvia:Mytilidae) Cultured on Marine Farms in Southeastern Brazil and Destined for Human Consumption","volume":"153","author":"Grault","year":"2020","journal-title":"Mar. Pollut. Bull."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1017\/S0025315418000644","article-title":"Variation of Parasite and Fungi Infection between Farmed and Wild Mussels (Mytilus galloprovincialis Lamarck, 1819) from the Adriatic Sea","volume":"98","author":"Pustijanac","year":"2018","journal-title":"J. Mar. Biol. Assoc. U. K."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1515\/bot-2017-0088","article-title":"Fungal Assemblages Associated with Commercial Bivalve Species in Coastal Waters of the Sea of Japan, Russia","volume":"61","author":"Borzykh","year":"2018","journal-title":"Bot. Mar."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4724","DOI":"10.3390\/md11124724","article-title":"Toxic C17-Sphinganine Analogue Mycotoxin, Contaminating Tunisian Mussels, Causes Flaccid Paralysis in Rodents","volume":"11","author":"Marrouchi","year":"2013","journal-title":"Mar. Drugs"},{"key":"ref_20","unstructured":"OCDE (2016). Test No. 489: In vivo Mammalian Alkaline Comet Assay, OECD Guidelines for the Testing of Chemicals, Section 4. \u00c9ditions OCDE, OCDE."},{"key":"ref_21","unstructured":"OCDE (2016). Test No. 474: Mammalian Erythrocyte Micronucleus Test, OECD Guidelines for the Testing of Chemicals, Section 4. \u00c9ditions OCDE, OCDE."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"933S","DOI":"10.1093\/jn\/133.3.933S","article-title":"Antioxidant Nutrients and Chronic Disease: Use of Biomarkers of Exposure and Oxidative Stress Status in Epidemiologic Research","volume":"133","author":"Mayne","year":"2003","journal-title":"J. Nutr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.toxlet.2020.03.016","article-title":"The Role of the Enzyme-Modified Comet Assay in In vivo Studies","volume":"327","author":"Collins","year":"2020","journal-title":"Toxicol. Lett."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.toxicon.2017.12.041","article-title":"Fumonisin B1 Induces Oxidative Stress in Oesophageal (SNO) Cancer Cells","volume":"141","author":"Khan","year":"2018","journal-title":"Toxicon"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.chemosphere.2019.05.004","article-title":"Toxicity of Nanosilver and Fumonisin B1 and Their Interactions on Duckweed (Lemna minor L.)","volume":"229","author":"Domijan","year":"2019","journal-title":"Chemosphere"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.foodchem.2014.08.036","article-title":"In Vitro Genotoxicity of Mycotoxins Ochratoxin A and Fumonisin B1 Could Be Prevented by Sodium Copper Chlorophyllin\u2014Implication to Their Genotoxic Mechanism","volume":"170","author":"Domijan","year":"2015","journal-title":"Food Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.tox.2012.08.012","article-title":"Reactive Oxygen Species Sources and Biomolecular Oxidative Damage Induced by Aflatoxin B1 and Fumonisin B1 in Rat Spleen Mononuclear Cells","volume":"302","author":"Mary","year":"2012","journal-title":"Toxicology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.aquaculture.2018.01.020","article-title":"Fumonisins B1 + B2 Change the Expression of Genes in Apoptosis Balance in Nile Tilapia Fingerlings","volume":"488","author":"Lala","year":"2018","journal-title":"Aquaculture"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"EFSA Panel on Contaminants in the Food Chain (CONTAM) (2011). Scientific Opinion on the Risks for Animal and Public Health Related to the Presence of Alternaria Toxins in Feed and Food. EFSA J., 9, 2407.","DOI":"10.2903\/j.efsa.2011.2407"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.tox.2009.12.007","article-title":"Subchronic Mycotoxicoses in Wistar Rats: Assessment of the In vivo and In Vitro Genotoxicity Induced by Fumonisins and Aflatoxin B1, and Oxidative Stress Biomarkers Status","volume":"268","author":"Theumer","year":"2010","journal-title":"Toxicology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1385\/MB:26:3:249","article-title":"The Comet Assay for DNA Damage and Repair","volume":"26","author":"Collins","year":"2004","journal-title":"Mol. Biotechnol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0300-483X(98)00123-1","article-title":"Oxidative Damage and Fumonisin B1-Induced Toxicity in Primary Rat Hepatocytes and Rat Liver in Vivo","volume":"131","author":"Abel","year":"1998","journal-title":"Toxicology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1016\/j.biocel.2011.03.003","article-title":"Fumonisin B1 Inhibits Mitochondrial Respiration and Deregulates Calcium Homeostasis\u2014Implication to Mechanism of Cell Toxicity","volume":"43","author":"Domijan","year":"2011","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.tox.2007.01.007","article-title":"Fumonisin B(1): Oxidative Status and DNA Damage in Rats","volume":"232","author":"Domijan","year":"2007","journal-title":"Toxicology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1006\/taap.2000.8893","article-title":"Epigenetic Properties of Fumonisin B1: Cell Cycle Arrest and DNA Base Modification in C6 Glioma Cells","volume":"164","author":"Mobio","year":"2000","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_36","unstructured":"(2002). IARC Some Traditional Herbal Medicines, Some Mycotoxins, Naphthalene and Styrene. IARC Monogr. Eval. Carcinog. Risks Hum., 82, 1\u2013556."},{"key":"ref_37","first-page":"679E","article-title":"Combined Toxicokinetic and In vivo Genotoxicity Study on Alternaria Toxins","volume":"11","author":"Schuchardt","year":"2014","journal-title":"EFSA Support. Publ."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.cbi.2005.11.004","article-title":"Effects of Fumonisins on Liver and Kidney Sphinganine and the Sphinganine to Sphingosine Ratio during Chronic Exposure in Ducks","volume":"160","author":"Tardieu","year":"2006","journal-title":"Chem. Biol. Interact."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/S1382-6689(97)00015-X","article-title":"Disruption of Sphingolipid Metabolism and Induction of Equine Leukoencephalomalacia by Fusarium proliferatum Culture Material Containing Fumonisin B2 or B3","volume":"3","author":"Riley","year":"1997","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_40","first-page":"283","article-title":"Sphingolipid Metabolism: Roles in Signal Transduction and Disruption by Fumonisins","volume":"109","author":"Merrill","year":"2001","journal-title":"Environ. Health Perspect."},{"key":"ref_41","first-page":"259","article-title":"An Overview of Rodent Toxicities: Liver and Kidney Effects of Fumonisins and Fusarium moniliforme","volume":"109","author":"Voss","year":"2001","journal-title":"Environ. Health Perspect."},{"key":"ref_42","first-page":"251","article-title":"Fumonisin Toxicosis in Swine: An Overview of Porcine Pulmonary Edema and Current Perspectives","volume":"109","author":"Haschek","year":"2001","journal-title":"Environ. Health Perspect."},{"key":"ref_43","first-page":"277","article-title":"Fumonisin B1 Carcinogenicity in a Two-Year Feeding Study Using F344 Rats and B6C3F1 Mice","volume":"109","author":"Howard","year":"2001","journal-title":"Environ. Health Perspect."},{"key":"ref_44","first-page":"309","article-title":"Compensatory Regeneration as a Mechanism for Renal Tubule Carcinogenesis of Fumonisin B1 in the F344\/N\/Nctr BR Rat","volume":"109","author":"Howard","year":"2001","journal-title":"Environ. Health Perspect."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/S0304-3835(01)00542-0","article-title":"Cancer Initiation by Fumonisin B1 in Rat Liver\u2014Role of Cell Proliferation","volume":"169","author":"Gelderblom","year":"2001","journal-title":"Cancer Lett."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"14486","DOI":"10.1016\/S0021-9258(18)98712-0","article-title":"Inhibition of Sphingolipid Biosynthesis by Fumonisins. Implications for Diseases Associated with Fusarium moniliforme","volume":"266","author":"Wang","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1006\/taap.1996.0119","article-title":"Elevated Sphingoid Bases and Complex Sphingolipid Depletion as Contributing Factors in Fumonisin-Induced Cytotoxicity","volume":"138","author":"Yoo","year":"1996","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1006\/taap.1997.8356","article-title":"Induction of Apoptosis by Fumonisin B1in HT29 Cells Is Mediated by the Accumulation of Endogenous Free Sphingoid Bases","volume":"148","author":"Schmelz","year":"1998","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1002\/em.21935","article-title":"Genotoxicity of Synthetic Amorphous Silica Nanoparticles in Rats following Short-Term Exposure. Part 1: Oral Route","volume":"56","author":"Tarantini","year":"2015","journal-title":"Environ. Mol. Mutagen."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Jalili, P., Huet, S., Lanceleur, R., Jarry, G., Hegarat, L.L., Nesslany, F., Hogeveen, K., and Fessard, V. (2020). Genotoxicity of Aluminum and Aluminum Oxide Nanomaterials in Rats Following Oral Exposure. Nanomaterials, 10.","DOI":"10.3390\/nano10020305"},{"key":"ref_51","first-page":"1406E","article-title":"In vivo Toxicity and Genotoxicity of Beauvericin and Enniatins. Combined Approach to Study In vivo Toxicity and Genotoxicity of Mycotoxins Beauvericin (BEA) and Enniatin B (ENNB)","volume":"15","author":"Maranghi","year":"2018","journal-title":"EFSA Support. Publ."}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/20\/10\/619\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:44:19Z","timestamp":1760143459000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/20\/10\/619"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,30]]},"references-count":51,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["md20100619"],"URL":"https:\/\/doi.org\/10.3390\/md20100619","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,30]]}}}