{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T21:03:32Z","timestamp":1777064612452,"version":"3.51.4"},"reference-count":51,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,4,19]],"date-time":"2021-04-19T00:00:00Z","timestamp":1618790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Spanish Ministry of Economy and Competitiveness","award":["SAF2013-47570-P, SAF2017-86188-P"],"award-info":[{"award-number":["SAF2013-47570-P, SAF2017-86188-P"]}]},{"name":"Regional Government of Castilla-La Mancha (JCCM)","award":["SBPLY\/19\/180501\/000114"],"award-info":[{"award-number":["SBPLY\/19\/180501\/000114"]}]},{"name":"FEDER","award":["SAF2013-47570-P, SAF2017-86188-P, SBPLY\/19\/180501\/000114"],"award-info":[{"award-number":["SAF2013-47570-P, SAF2017-86188-P, SBPLY\/19\/180501\/000114"]}]},{"name":"Consejer\u00eda de Educaci\u00f3n, Universidades e Investigaci\u00f3n of Gobierno Vasco-Eusko Jaurlaritza","award":["GIC15\/78 IT-990-16"],"award-info":[{"award-number":["GIC15\/78 IT-990-16"]}]},{"DOI":"10.13039\/100011264","name":"FP7 People: Marie-Curie Actions","doi-asserted-by":"publisher","award":["MC-ITN-606786"],"award-info":[{"award-number":["MC-ITN-606786"]}],"id":[{"id":"10.13039\/100011264","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Candida parapsilosis is among the most frequent causes of candidiasis. Clinical isolates of this species show large variations in colony morphotype, ranging from round and smooth to a variety of non-smooth irregular colony shapes. A non-smooth appearance is related to increased formation of pseudohyphae, higher capacity to form biofilms on abiotic surfaces, and invading agar. Here, we present a comprehensive study of the cell wall proteome of C. parapsilosis reference strain CDC317 and seven clinical isolates under planktonic and sessile conditions. This analysis resulted in the identification of 40 wall proteins, most of them homologs of known Candida albicans cell wall proteins, such as Gas, Crh, Bgl2, Cht2, Ecm33, Sap, Sod, Plb, Pir, Pga30, Pga59, and adhesin family members. Comparative analysis of exponentially growing and stationary phase planktonic cultures of CDC317 at 30 \u00b0C and 37 \u00b0C revealed only minor variations. However, comparison of smooth isolates to non-smooth isolates with high biofilm formation capacity showed an increase in abundance and diversity of putative wall adhesins from Als, Iff\/Hyr, and Hwp families in the latter. This difference depended more strongly on strain phenotype than on the growth conditions, as it was observed in planktonic as well as biofilm cells. Thus, in the set of isolates analyzed, the high biofilm formation capacity of non-smooth C. parapsilosis isolates with elongated cellular phenotypes correlates with the increased surface expression of putative wall adhesins in accordance with their proposed cellular function.<\/jats:p>","DOI":"10.3390\/pathogens10040493","type":"journal-article","created":{"date-parts":[[2021,4,19]],"date-time":"2021-04-19T11:21:38Z","timestamp":1618831298000},"page":"493","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["High Biofilm Formation of Non-Smooth Candida parapsilosis Correlates with Increased Incorporation of GPI-Modified Wall Adhesins"],"prefix":"10.3390","volume":"10","author":[{"given":"Ana Esther","family":"Moreno-Mart\u00ednez","sequence":"first","affiliation":[{"name":"Albacete Regional Center for Biomedical Research, Castilla\u2014La Mancha Science &amp; Technology Park, University of Castilla-La Mancha, 02008 Albacete, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emilia","family":"G\u00f3mez-Molero","sequence":"additional","affiliation":[{"name":"Albacete Regional Center for Biomedical Research, Castilla\u2014La Mancha Science &amp; Technology Park, University of Castilla-La Mancha, 02008 Albacete, Spain"},{"name":"Institute for Medical Microbiology, University Medical Center G\u00f6ttingen, Kreuzbergring 57, 37075 G\u00f6ttingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pablo","family":"S\u00e1nchez-Virosta","sequence":"additional","affiliation":[{"name":"Albacete Regional Center for Biomedical Research, Castilla\u2014La Mancha Science &amp; Technology Park, University of Castilla-La Mancha, 02008 Albacete, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henk L.","family":"Dekker","sequence":"additional","affiliation":[{"name":"Mass Spectrometry of Biomolecules, Swammerdam Institute for Life Sciences, University of Amsterdam, 1098 XH Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albert","family":"de Boer","sequence":"additional","affiliation":[{"name":"Albacete Regional Center for Biomedical Research, Castilla\u2014La Mancha Science &amp; Technology Park, University of Castilla-La Mancha, 02008 Albacete, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9043-9265","authenticated-orcid":false,"given":"Elena","family":"Eraso","sequence":"additional","affiliation":[{"name":"Department of Immunology, Microbiology and Parasitology, Faculty of Medicine and Nursing, University of the Basque Country (UPV\/EHU), 48940 Bilbao, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1534-440X","authenticated-orcid":false,"given":"Oliver","family":"Bader","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology, University Medical Center G\u00f6ttingen, Kreuzbergring 57, 37075 G\u00f6ttingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3112-6947","authenticated-orcid":false,"given":"Piet W. J.","family":"de Groot","sequence":"additional","affiliation":[{"name":"Albacete Regional Center for Biomedical Research, Castilla\u2014La Mancha Science &amp; Technology Park, University of Castilla-La Mancha, 02008 Albacete, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1056\/NEJMra1315399","article-title":"Invasive Candidiasis","volume":"373","author":"Kullberg","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1177\/1093526618798773","article-title":"Pathology of neonatal non-albicans candidiasis: Autopsy study and literature review","volume":"22","author":"Hemedez","year":"2019","journal-title":"Pediatr. Dev. Pathol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.3201\/eid1006.030873","article-title":"Candida parapsilosis characterization in an outbreak setting","volume":"10","author":"Kuhn","year":"2004","journal-title":"Emerg. Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e206","DOI":"10.1097\/INF.0b013e3182863a1c","article-title":"Candida parapsilosis is a significant neonatal pathogen: A systematic review and meta-analysis","volume":"32","author":"Pammi","year":"2013","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1128\/CMR.00013-08","article-title":"Candida parapsilosis, an emerging fungal pathogen","volume":"21","author":"Trofa","year":"2008","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Zuo, X.S., Liu, Y., Cai, X., Zhan, L., and Hu, K. (2021). Association of different Candida species with catheter-related candidemia, and the potential antifungal treatments against their adhesion properties and biofilm-forming capabilities. J. Clin. Lab. Anal., e23738.","DOI":"10.1002\/jcla.23738"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1994","DOI":"10.3389\/fmicb.2020.01994","article-title":"Phenotypic variability in a coinfection with three independent Candida parapsilosis lineages","volume":"11","author":"Willis","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1111\/j.1469-0691.2010.03302.x","article-title":"Characterization of Candida parapsilosis complex isolates","volume":"17","author":"Torres","year":"2011","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.ijmm.2009.09.001","article-title":"Characterization of biofilms formed by Candida parapsilosis, C. metapsilosis, and C. orthopsilosis","volume":"300","author":"Lattif","year":"2010","journal-title":"Int. J. Med. Microbiol"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"fov111","DOI":"10.1093\/femsyr\/fov111","article-title":"Biofilm formation in Candida glabrata: What have we learnt from functional genomics approaches?","volume":"16","author":"Janbon","year":"2016","journal-title":"FEMS Yeast Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1128\/AAC.46.6.1773-1780.2002","article-title":"Antifungal susceptibility of Candida biofilms: Unique efficacy of amphotericin B lipid formulations and echinocandins","volume":"46","author":"Kuhn","year":"2002","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"G\u00f3mez-Molero, E., De-la-Pinta, I., Fern\u00e1ndez-Pereira, J., Gro\u00df, U., Weig, M., Quind\u00f3s, G., De Groot, P.W.J., and Bader, O. (2021). Candida parapsilosis colony morphotype forecasts biofilm formation of clinical isolates. J. Fungi, 7.","DOI":"10.3390\/jof7010033"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1099\/mic.0.27739-0","article-title":"Phenotype switching affects biofilm formation by Candida parapsilosis","volume":"151","author":"Laffey","year":"2005","journal-title":"Microbiology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/nrmicro2711","article-title":"Candida albicans morphogenesis and host defence: Discriminating invasion from colonization","volume":"10","author":"Gow","year":"2011","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/mmy.39.1.1.8-0","article-title":"Molecular organization of the cell wall of Candida albicans","volume":"39","author":"Klis","year":"2001","journal-title":"Med. Mycol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1111\/j.1567-1364.2009.00541.x","article-title":"Covalently linked cell wall proteins of Candida albicans and their role in fitness and virulence","volume":"9","author":"Klis","year":"2009","journal-title":"FEMS Yeast Res."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Satala, D., Karkowska-Kuleta, J., Zelazna, A., Rapala-Kozik, M., and Kozik, A. (2020). Moonlighting proteins at the candidal cell surface. Microorganisms, 8.","DOI":"10.3390\/microorganisms8071046"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1128\/EC.00364-12","article-title":"Adhesins in human fungal pathogens: Glue with plenty of stick","volume":"12","author":"Bader","year":"2013","journal-title":"Eukaryot. Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"280","DOI":"10.3389\/fmicb.2016.00280","article-title":"Candida albicans agglutinin-like sequence (Als) family vignettes: A review of Als protein structure and function","volume":"7","author":"Hoyer","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"40737","DOI":"10.1074\/jbc.M406005200","article-title":"Expression of transglutaminase substrate activity on Candida albicans germ tubes through a coiled, disulfide-bonded N-terminal domain of Hwp1 requires C-terminal glycosylphosphatidylinositol modification","volume":"279","author":"Staab","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"12512","DOI":"10.1074\/jbc.RA120.013968","article-title":"Functional reprogramming of Candida glabrata epithelial adhesins: The role of conserved and variable structural motifs in ligand binding","volume":"295","author":"Hoffmann","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1111\/j.1365-2958.2008.06184.x","article-title":"Glycan microarray analysis of Candida glabrata adhesin ligand specificity","volume":"68","author":"Zupancic","year":"2008","journal-title":"Mol. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1038\/nature08064","article-title":"Evolution of pathogenicity and sexual reproduction in eight Candida genomes","volume":"459","author":"Butler","year":"2009","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"807","DOI":"10.18388\/abp.2015_1140","article-title":"Surfaceome of pathogenic yeasts, Candida parapsilosis and Candida tropicalis, revealed with the use of cell surface shaving method and shotgun proteomic approach","volume":"62","author":"Zajac","year":"2015","journal-title":"Acta Biochim. Pol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e00892-17","DOI":"10.1128\/IAI.00892-17","article-title":"Role of the inducible adhesin CpAls7 in binding of Candida parapsilosis to the extracellular matrix under fluid shear","volume":"86","author":"Neale","year":"2018","journal-title":"Infect. Immun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1128\/EC.00350-08","article-title":"Correlation between biofilm formation and the hypoxic response in Candida parapsilosis","volume":"8","author":"Rossignol","year":"2009","journal-title":"Eukaryot. Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"S69","DOI":"10.4103\/0974-8490.150528","article-title":"Performance of chromogenic media for Candida in rapid presumptive identification of Candida species from clinical materials","volume":"7","author":"Kali","year":"2015","journal-title":"Pharmacogn. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"E246","DOI":"10.1111\/j.1469-0691.2012.03880.x","article-title":"EUCAST technical note on the EUCAST definitive document EDef 7.2: Method for the determination of broth dilution minimum inhibitory concentrations of antifungal agents for yeasts EDef 7.2 (EUCAST-AFST)","volume":"18","author":"Arendrup","year":"2012","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1128\/EC.3.4.955-965.2004","article-title":"Proteomic analysis of Candida albicans cell walls reveals covalently bound carbohydrate-active enzymes and adhesins","volume":"3","author":"Cunningham","year":"2004","journal-title":"Eukaryot. Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1128\/EC.00284-08","article-title":"The cell wall of the human pathogen Candida glabrata: Differential incorporation of novel adhesin-like wall proteins","volume":"7","author":"Kraneveld","year":"2008","journal-title":"Eukaryot. Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"fov098","DOI":"10.1093\/femsyr\/fov098","article-title":"Proteomic analysis of hyperadhesive Candida glabrata clinical isolates reveals a core wall proteome and differential incorporation of adhesins","volume":"15","author":"Dekker","year":"2015","journal-title":"FEMS Yeast Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"20894","DOI":"10.1074\/jbc.M500334200","article-title":"Comprehensive proteomic analysis of Saccharomyces cerevisiae cell walls: Identification of proteins covalently attached via glycosylphosphatidylinositol remnants or mild alkali-sensitive linkages","volume":"280","author":"Yin","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.fgb.2011.12.009","article-title":"ProFASTA: A pipeline web server for fungal protein scanning with integration of cell surface prediction software","volume":"49","author":"Brandt","year":"2012","journal-title":"Fungal. Genet. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.fgb.2005.04.002","article-title":"Features and functions of covalently linked proteins in fungal cell walls","volume":"42","author":"Ram","year":"2005","journal-title":"Fungal Genet. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/S0968-0004(03)00025-2","article-title":"An eight-cysteine-containing CFEM domain unique to a group of fungal membrane proteins","volume":"28","author":"Kulkarni","year":"2003","journal-title":"Trends Biochem. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"S72","DOI":"10.1016\/j.fgb.2008.07.022","article-title":"Comprehensive genomic analysis of cell wall genes in Aspergillus nidulans","volume":"46","author":"Brandt","year":"2009","journal-title":"Fungal Genet. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"11523","DOI":"10.1074\/jbc.M600314200","article-title":"Pir-proteins of Saccharomyces cerevisiae are attached to b-1,3-glucan by a new protein-carbohydrate linkage","volume":"281","author":"Ecker","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1111\/j.1365-2958.2011.07626.x","article-title":"Contribution of the glycolytic flux and hypoxia adaptation to efficient biofilm formation by Candida albicans","volume":"80","author":"Bonhomme","year":"2011","journal-title":"Mol. Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.cell.2011.10.048","article-title":"A recently evolved transcriptional network controls biofilm development in Candida albicans","volume":"148","author":"Nobile","year":"2012","journal-title":"Cell"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Chaudhuri, R., Ansari, F.A., Raghunandanan, M.V., and Ramachandran, S. (2011). FungalRV: Adhesin prediction and immunoinformatics portal for human fungal pathogens. BMC Genomics, 12.","DOI":"10.1186\/1471-2164-12-192"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1099\/mic.0.044206-0","article-title":"Mass spectrometric quantitation of the adaptations in the wall proteome of Candida albicans in response to ambient pH","volume":"157","author":"Sosinska","year":"2011","journal-title":"Microbiology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3164","DOI":"10.1002\/pmic.201200228","article-title":"Carbon source-induced reprogramming of the cell wall proteome and secretome modulates the adherence and drug resistance of the fungal pathogen Candida albicans","volume":"12","author":"Ene","year":"2012","journal-title":"Proteomics"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1128\/EC.05011-11","article-title":"Effects of fluconazole on the secretome, the wall proteome, and wall integrity of the clinical fungus Candida albicans","volume":"10","author":"Sorgo","year":"2011","journal-title":"Eukaryot. Cell"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2297","DOI":"10.1099\/mic.0.049395-0","article-title":"Hyphal induction in the human fungal pathogen Candida albicans reveals a characteristic wall protein profile","volume":"157","author":"Heilmann","year":"2011","journal-title":"Microbiology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1046\/j.1439-0507.2001.00611.x","article-title":"Adhesion of Candida parapsilosis to epithelial and acrylic surfaces correlates with cell surface hydrophobicity","volume":"44","author":"Panagoda","year":"2001","journal-title":"Mycoses"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1093\/infdis\/171.4.967","article-title":"Biotype diversity of Candida parapsilosis and its relationship to the clinical source and experimental pathogenicity","volume":"171","author":"Cassone","year":"1995","journal-title":"J. Infect. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1093\/emboj\/18.5.1257","article-title":"MAP kinase and cAMP filamentation signaling pathways converge on the unusually large promoter of the yeast FLO11 gene","volume":"18","author":"Rupp","year":"1999","journal-title":"EMBO J."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Timmermans, B., De Las Pe\u00f1as, A., Castano, I., and Van Dijck, P. (2018). Adhesins in Candida glabrata. J. Fungi, 4.","DOI":"10.3390\/jof4020060"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"781","DOI":"10.3389\/fmicb.2019.00781","article-title":"Agglutinin-like sequence (ALS) genes in the Candida parapsilosis species complex: Blurring the boundaries between gene families that encode cell-wall proteins","volume":"10","author":"Oh","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Bliss, J.M., Tollefson, G.A., Cuevas, A., Longley, S.J., Neale, M.N., Uzun, A., and Shaw, S.K. (2021). Transcription Profiles Associated with Inducible Adhesion in Candida parapsilosis. mSphere, 6.","DOI":"10.1128\/mSphere.01071-20"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1099\/mic.0.27663-0","article-title":"Yeast wall protein 1 of Candida albicans","volume":"151","author":"Granger","year":"2005","journal-title":"Microbiology"}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/10\/4\/493\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:49:51Z","timestamp":1760161791000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/10\/4\/493"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,19]]},"references-count":51,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["pathogens10040493"],"URL":"https:\/\/doi.org\/10.3390\/pathogens10040493","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,19]]}}}