{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T08:08:41Z","timestamp":1781078921961,"version":"3.54.1"},"reference-count":42,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T00:00:00Z","timestamp":1616371200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T00:00:00Z","timestamp":1616371200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2016\/23\/B\/NZ1\/01928"],"award-info":[{"award-number":["2016\/23\/B\/NZ1\/01928"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2016\/23\/B\/NZ1\/01928"],"award-info":[{"award-number":["2016\/23\/B\/NZ1\/01928"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2016\/23\/B\/NZ1\/01928"],"award-info":[{"award-number":["2016\/23\/B\/NZ1\/01928"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The effect of capric acid, secreted by the probiotic yeasts <jats:italic>Saccharomyces boulardii<\/jats:italic>, was evaluated on the activities of fluconazole (FLC) and amphotericin B (AMB) against pathogenic <jats:italic>Candida albicans<\/jats:italic> fungus. The findings indicated that capric acid may be a promising additive for use in combination with FLC. A FLC-capric acid combination led to reduced efflux activity of multidrug resistance (MDR) transporter Cdr1p by causing it to relocalize from the plasma membrane (PM) to the interior of the cell. The above effect occurred due to inhibitory effect of FLC-capric acid combination of ergosterol biosynthesis. However, capric acid alone stimulated ergosterol production in <jats:italic>C. albicans<\/jats:italic>, which in turn generated cross resistance towards AMB and inhibited its action (PM permeabilization and cytoplasm leakage) against <jats:italic>C. albicans<\/jats:italic> cells. This concluded that AMB should not be administered among dietary supplements containing capric acid or <jats:italic>S. boulardii<\/jats:italic> cells.<\/jats:p>","DOI":"10.1038\/s41598-021-86012-9","type":"journal-article","created":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T11:03:43Z","timestamp":1616411023000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Capric acid secreted by Saccharomyces boulardii influences the susceptibility of Candida albicans to fluconazole and amphotericin B"],"prefix":"10.1038","volume":"11","author":[{"given":"Jakub","family":"Suchodolski","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria","family":"Derkacz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Przemys\u0142aw","family":"Bernat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Krasowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,22]]},"reference":[{"key":"86012_CR1","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1126\/science.1200439","volume":"332","author":"A Puel","year":"2011","unstructured":"Puel, A. et al. Chronic mucocutaneous candidiasis in humans with inborn errors of interleukin-17 immunity. Science (80-) 332, 65\u201368 (2011).","journal-title":"Science (80-)"},{"key":"86012_CR2","doi-asserted-by":"publisher","first-page":"2173","DOI":"10.3389\/fmicb.2016.02173","volume":"7","author":"SG Whaley","year":"2017","unstructured":"Whaley, S. G. et al. Azole antifungal resistance in Candida albicans and emerging non-albicans Candida Species. Front. Microbiol. 7, 2173 (2017).","journal-title":"Front. Microbiol."},{"key":"86012_CR3","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.micpath.2018.02.028","volume":"117","author":"M Dadar","year":"2018","unstructured":"Dadar, M. et al. Candida albicans - Biology, molecular characterization, pathogenicity, and advances in diagnosis and control \u2013 An update. Microb. Pathog. 117, 128\u2013138 (2018).","journal-title":"Microb. Pathog."},{"key":"86012_CR4","first-page":"13","volume":"3","author":"F Alizadeh","year":"2017","unstructured":"Alizadeh, F., Khodavandi, A. & Zalakian, S. Quantitation of ergosterol content and gene expression profile of ERG11 gene in fluconazole-resistant Candida albicans. Curr. Med. Mycol. 3, 13\u201319 (2017).","journal-title":"Curr. Med. Mycol."},{"key":"86012_CR5","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.2217\/fmb-2018-0059","volume":"13","author":"J Beardsley","year":"2018","unstructured":"Beardsley, J., Halliday, C. L., Chen, S. C. A. & Sorrell, T. C. Responding to the emergence of antifungal drug resistance: perspectives from the bench and the bedside. Future Microbiol. 13, 1175\u20131191 (2018).","journal-title":"Future Microbiol."},{"key":"86012_CR6","doi-asserted-by":"publisher","first-page":"555777","DOI":"10.19080\/AIBM.2018.10.555777","volume":"10","author":"C Ortiz","year":"2018","unstructured":"Ortiz, C. & Torres, R. Antifungal resistance and its evolution: an increasing concern. Adv. Biotechnol. Microbiol. 10, 555777 (2018).","journal-title":"Adv. Biotechnol. Microbiol."},{"key":"86012_CR7","doi-asserted-by":"publisher","first-page":"249","DOI":"10.2147\/IDR.S124918","volume":"10","author":"NP Wiederhold","year":"2017","unstructured":"Wiederhold, N. P. Antifungal resistance: current trends and future strategies to combat. Infect. Drug Resist. 10, 249\u2013259 (2017).","journal-title":"Infect. Drug Resist."},{"key":"86012_CR8","first-page":"1","volume":"17","author":"YQ Wu","year":"2017","unstructured":"Wu, Y. Q., Gao, N., Li, C., Gao, J. & Ying, C. M. A newly identified amino acid substitution T123I in the 14\u03b1-demethylase (Erg11p) of Candida albicans confers azole resistance. FEMS Yeast Res. 17, 1\u20136 (2017).","journal-title":"FEMS Yeast Res."},{"key":"86012_CR9","doi-asserted-by":"publisher","first-page":"143","DOI":"10.3389\/fphys.2014.00143","volume":"5","author":"S Paul","year":"2014","unstructured":"Paul, S. & Moye-Rowley, W. S. Multidrug resistance in fungi: regulation of transporter-encoding gene expression. Front. Physiol. 5, 143 (2014).","journal-title":"Front. Physiol."},{"key":"86012_CR10","doi-asserted-by":"publisher","first-page":"2234","DOI":"10.1073\/pnas.1117280109","volume":"109","author":"KC Gray","year":"2012","unstructured":"Gray, K. C. et al. Amphotericin primarily kills yeast by simply binding ergosterol. Proc. Natl. Acad. Sci. U. S. A. 109, 2234\u20132239 (2012).","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"86012_CR11","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1097\/FAD.0b013e32831844cb","volume":"2","author":"NJ Gogtay","year":"2008","unstructured":"Gogtay, N. J., Kulkarni, U. P. & Panchabhai, T. S. Adverse reactions to antifungal agents. Adverse Drug React. Bull. 2, 963\u2013966 (2008).","journal-title":"Adverse Drug React. Bull."},{"key":"86012_CR12","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.3389\/fmicb.2018.01351","volume":"9","author":"GCDO Santos","year":"2018","unstructured":"Santos, G. C. D. O. et al. Candida infections and therapeutic strategies: Mechanisms of action for traditional and alternative agents. Front. Microbiol. 9, 1351 (2018).","journal-title":"Front. Microbiol."},{"key":"86012_CR13","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1099\/00221287-73-1-201","volume":"73","author":"JM Hamilton-Miller","year":"1972","unstructured":"Hamilton-Miller, J. M. Sterols from polyene-resistant mutants of Candida albicans. J. Gen. Microbiol. 73, 201\u2013203 (1972).","journal-title":"J. Gen. Microbiol."},{"key":"86012_CR14","doi-asserted-by":"publisher","first-page":"802","DOI":"10.1016\/j.drudis.2018.01.003","volume":"23","author":"TP Salci","year":"2018","unstructured":"Salci, T. P., Negri, M., Abadio, A. K. R., Svidzinski, T. I. E. & Kioshima, \u00c9. S. Targeting Candida spp. to develop antifungal agents. Drug Discov. Today 23, 802\u2013814 (2018).","journal-title":"Drug Discov. Today"},{"key":"86012_CR15","doi-asserted-by":"publisher","first-page":"1206","DOI":"10.4315\/0362-028X-70.5.1206","volume":"70","author":"C Altieri","year":"2007","unstructured":"Altieri, C., Cardillo, D., Bevilacqua, A. & Sinigaglia, M. Inhibition of Aspergillus spp. and Penicillium spp. by fatty acids and their monoglycerides. J. Food Prot. 70, 1206\u20131212 (2007).","journal-title":"J. Food Prot."},{"key":"86012_CR16","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.plipres.2007.10.002","volume":"47","author":"NM Carballeira","year":"2008","unstructured":"Carballeira, N. M. New advances in fatty acids as antimalarial, antimycobacterial and antifungal agents. Prog. Lipid Res. 47, 50\u201361 (2008).","journal-title":"Prog. Lipid Res."},{"key":"86012_CR17","first-page":"61","volume":"1","author":"CH Pohl","year":"2011","unstructured":"Pohl, C. H., Kock, J. L. F. & Thibane, V. S. Antifungal free fatty acids: a review. Sci. Against Microb. Pathog. Curr. Res. Technol. Adv. 1, 61\u201371 (2011).","journal-title":"Sci. Against Microb. Pathog. Curr. Res. Technol. Adv."},{"key":"86012_CR18","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1371\/journal.pone.0012050","volume":"5","author":"A Murzyn","year":"2010","unstructured":"Murzyn, A., Krasowska, A., Stefanowicz, P., Dziadkowiec, D. & \u0141ukaszewicz, M. Capric acid secreted by S. boulardii inhibits C. albicans filamentous growth, adhesion and biofilm formation. PLoS ONE 5, 2\u20138 (2010).","journal-title":"PLoS ONE"},{"key":"86012_CR19","doi-asserted-by":"publisher","first-page":"3209","DOI":"10.1128\/AAC.45.11.3209-3212.2001","volume":"45","author":"G Bergsson","year":"2001","unstructured":"Bergsson, G., Arnfinnsson, J., Steingr\u00edmsson, \u00d3. & Thormar, H. In vitro killing of Candida albicans by fatty acids and monoglycerides. Antimicrob. Agents Chemother. 45, 3209\u20133212 (2001).","journal-title":"Antimicrob. Agents Chemother."},{"key":"86012_CR20","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1002\/pds.1473","volume":"16","author":"F Depont","year":"2007","unstructured":"Depont, F. et al. Drug\u2013drug interactions with systemic antifungals in clinical practice. Pharmacoepidemiol. Drug Saf. 16, 1227\u20131233 (2007).","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"86012_CR21","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1111\/myc.12786","volume":"61","author":"OA Cornely","year":"2018","unstructured":"Cornely, O. A. & Kontoyiannis, D. P. How to prophylax against invasive fungal infections in adult ALL? An unmet need. Mycoses 61, 646\u2013649 (2018).","journal-title":"Mycoses"},{"key":"86012_CR22","doi-asserted-by":"publisher","first-page":"378","DOI":"10.3390\/microorganisms7100378","volume":"7","author":"J Suchodolski","year":"2019","unstructured":"Suchodolski, J., Muraszko, J., Bernat, P. & Krasowska, A. A crucial role for ergosterol in plasma membrane composition, localisation, and activity of Cdr1p and H + -ATPase in Candida albicans. Microorganisms 7, 378 (2019).","journal-title":"Microorganisms"},{"key":"86012_CR23","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1002\/yea.3455","volume":"37","author":"J Suchodolski","year":"2020","unstructured":"Suchodolski, J., Muraszko, J., Korba, A., Bernat, P. & Krasowska, A. Lipid composition and cell surface hydrophobicity of Candida albicans influence the efficacy of fluconazole-gentamicin treatment. Yeast 37, 117\u2013129 (2020).","journal-title":"Yeast"},{"key":"86012_CR24","doi-asserted-by":"publisher","first-page":"314","DOI":"10.3390\/pharmaceutics12040314","volume":"12","author":"J Suchodolski","year":"2020","unstructured":"Suchodolski, J., Derkacz, D., Muraszko, J., Panek, J. J. & Jezierska, A. Fluconazole and lipopeptide surfactin interplay during Candida albicans plasma membrane and cell wall remodeling increases fungal immune system exposure. Pharmaceutics 12, 314 (2020).","journal-title":"Pharmaceutics"},{"key":"86012_CR25","doi-asserted-by":"publisher","first-page":"E103252","DOI":"10.1016\/j.fgb.2019.103252","volume":"132","author":"R Prasad","year":"2019","unstructured":"Prasad, R., Nair, R. & Banerjee, A. Multidrug transporters of Candida species in clinical azole resistance. Fungal Genet. Biol. 132, E103252 (2019).","journal-title":"Fungal Genet. Biol."},{"key":"86012_CR26","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1002\/yea.3356","volume":"36","author":"R Prasad","year":"2019","unstructured":"Prasad, R., Balzi, E., Banerjee, A. & Khandelwal, N. K. All about CDR transporters: Past, present, and future. Yeast 36, 223\u2013233 (2019).","journal-title":"Yeast"},{"key":"86012_CR27","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.ijantimicag.2017.01.044","volume":"50","author":"J Szczepaniak","year":"2017","unstructured":"Szczepaniak, J., Cie\u015blik, W., Romanowicz, A., Musio\u0142, R. & Krasowska, A. Blocking and dislocation of Candida albicans Cdr1p transporter by styrylquinolines. Int. J. Antimicrob. Agents 50, 171\u2013176 (2017).","journal-title":"Int. J. Antimicrob. Agents"},{"key":"86012_CR28","doi-asserted-by":"publisher","first-page":"4333","DOI":"10.1128\/IAI.71.8.4333-4340.2003","volume":"71","author":"PK Mukherjee","year":"2003","unstructured":"Mukherjee, P. K., Chandra, J., Kuhn, D. M. & Ghannoum, M. A. Mechanism of fluconazole resistance in Candida albicans biofilms: phase-specific role of efflux pumps and membrane sterols. Infect. Immun. 71, 4333\u20134340 (2003).","journal-title":"Infect. Immun."},{"key":"86012_CR29","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1128\/AAC.03470-14","volume":"59","author":"SA Flowers","year":"2015","unstructured":"Flowers, S. A., Col\u00f3n, B., Whaley, S. G., Schuler, M. A. & David Rogers, P. Contribution of clinically derived mutations in ERG11 to azole resistance in Candida albicans. Antimicrob. Agents Chemother. 59, 450\u2013460 (2015).","journal-title":"Antimicrob. Agents Chemother."},{"key":"86012_CR30","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.memsci.2017.09.032","volume":"545","author":"HC Wu","year":"2018","unstructured":"Wu, H. C. et al. Preparation of Amphotericin B-Ergosterol structures and molecular simulation of water adsorption and diffusion. J. Memb. Sci. 545, 229\u2013239 (2018).","journal-title":"J. Memb. Sci."},{"key":"86012_CR31","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.memsci.2019.04.021","volume":"583","author":"HC Wu","year":"2019","unstructured":"Wu, H. C. et al. Molecular simulation of a modified amphotericin B-Ergosterol artificial water channel to evaluate structure and water molecule transport performance. J. Memb. Sci. 583, 49\u201358 (2019).","journal-title":"J. Memb. Sci."},{"key":"86012_CR32","doi-asserted-by":"publisher","first-page":"1454","DOI":"10.1021\/acs.bioconjchem.8b00136","volume":"29","author":"AS Skwarecki","year":"2018","unstructured":"Skwarecki, A. S. et al. Molecular umbrellas modulate the selective toxicity of polyene macrolide antifungals. Bioconjug. Chem. 29, 1454\u20131465 (2018).","journal-title":"Bioconjug. Chem."},{"key":"86012_CR33","doi-asserted-by":"publisher","first-page":"172937","DOI":"10.1016\/j.ejphar.2020.172937","volume":"871","author":"M J\u00f3\u017awiak","year":"2020","unstructured":"J\u00f3\u017awiak, M., Filipowska, A., Fiorino, F. & Struga, M. Anticancer activities of fatty acids and their heterocyclic derivatives. Eur. J. Pharmacol. 871, 172937 (2020).","journal-title":"Eur. J. Pharmacol."},{"key":"86012_CR34","doi-asserted-by":"publisher","first-page":"5014","DOI":"10.3390\/ijms16035014","volume":"16","author":"A Narayanan","year":"2015","unstructured":"Narayanan, A., Baskaran, S. A., Amalaradjou, M. A. R. & Venkitanarayanan, K. Anticarcinogenic properties of medium chain fatty acids on human colorectal, skin and breast cancer cells in vitro. Int. J. Mol. Sci. 16, 5014\u20135027 (2015).","journal-title":"Int. J. Mol. Sci."},{"key":"86012_CR35","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1128\/AEM.67.2.956-960.2001","volume":"67","author":"TJ Avis","year":"2001","unstructured":"Avis, T. J. & B\u00e9langer, R. R. Specificity and mode of action of the antifungal fatty acid cis-9-heptadecenoic acid produced by Pseudozyma flocculosa. Appl. Environ. Microbiol. 67, 956\u2013960 (2001).","journal-title":"Appl. Environ. Microbiol."},{"key":"86012_CR36","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/S1388-1981(02)00127-0","volume":"1581","author":"V McDonough","year":"2002","unstructured":"McDonough, V., Stukey, J. & Cavanagh, T. Mutations in erg4 affect the sensitivity of Saccharomyces cerevisiae to medium-chain fatty acids. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1581, 109\u2013118 (2002).","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"86012_CR37","first-page":"E176","volume":"6","author":"J Szczepaniak","year":"2015","unstructured":"Szczepaniak, J., Lukaszewicz, M. & Krasowska, A. Detection of inhibitors of Candida albicans Cdr transporters using a diS-C3(3) fluorescence. Front. Microbiol. 6, E176 (2015).","journal-title":"Front. Microbiol."},{"key":"86012_CR38","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.tox.2010.07.001","volume":"276","author":"AA Tonshin","year":"2010","unstructured":"Tonshin, A. A., Teplova, V. V., Andersson, M. A. & Salkinoja-Salonen, M. S. The Fusarium mycotoxins enniatins and beauvericin cause mitochondrial dysfunction by affecting the mitochondrial volume regulation, oxidative phosphorylation and ion homeostasis. Toxicology 276, 49\u201357 (2010).","journal-title":"Toxicology"},{"key":"86012_CR39","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1128\/AAC.17.5.861","volume":"17","author":"RC Iannitelli","year":"1980","unstructured":"Iannitelli, R. C. & Ikawa, M. Effect of fatty acids on action of polyene antibiotics. Antimicrob. Agents Chemother. 17, 861\u2013864 (1980).","journal-title":"Antimicrob. Agents Chemother."},{"key":"86012_CR40","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1093\/genetics\/134.3.717","volume":"134","author":"WA Fonzi","year":"1993","unstructured":"Fonzi, W. A. & Irwin, M. Y. Isogenic strain construction and gene mapping in Candida albicans. Genetis 134, 717\u2013728 (1993).","journal-title":"Genetis"},{"key":"86012_CR41","first-page":"E1382","volume":"6","author":"J Szczepaniak","year":"2015","unstructured":"Szczepaniak, J., \u0141ukaszewicz, M. & Krasowska, A. Estimation of Candida albicans ABC transporter behavior in real-time via fluorescence. Front. Microbiol. 6, E1382 (2015).","journal-title":"Front. Microbiol."},{"key":"86012_CR42","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.micres.2016.12.008","volume":"197","author":"J Suchodolski","year":"2017","unstructured":"Suchodolski, J., Feder-Kubis, J. & Krasowska, A. Antifungal activity of ionic liquids based on (\u2212)-menthol: a mechanism study. Microbiol. Res. 197, 56\u201364 (2017).","journal-title":"Microbiol. Res."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-86012-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-86012-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-86012-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T05:37:04Z","timestamp":1670045824000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-86012-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,22]]},"references-count":42,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["86012"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-86012-9","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,22]]},"assertion":[{"value":"11 November 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 March 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 March 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"6519"}}