{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:01:32Z","timestamp":1760234492193,"version":"build-2065373602"},"reference-count":55,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T00:00:00Z","timestamp":1621468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Internal Project of The Children\u2019s Memorial Health Institute","award":["S141\/2014","G8\/2020"],"award-info":[{"award-number":["S141\/2014","G8\/2020"]}]},{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["UMO-2016\/21\/N\/NZ1\/00278"],"award-info":[{"award-number":["UMO-2016\/21\/N\/NZ1\/00278"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["IG-23670"],"award-info":[{"award-number":["IG-23670"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002426","name":"Fondazione Telethon","doi-asserted-by":"publisher","award":["GGP11139B"],"award-info":[{"award-number":["GGP11139B"]}],"id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Progetti di Rilevante Interesse Nazionale","award":["PRIN, 2017 E5L5P3"],"award-info":[{"award-number":["PRIN, 2017 E5L5P3"]}]},{"DOI":"10.13039\/501100007109","name":"Universit\u00e0 degli Studi di Ferrara","doi-asserted-by":"publisher","award":["local funds"],"award-info":[{"award-number":["local funds"]}],"id":[{"id":"10.13039\/501100007109","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Numerous papers have reported altered expression patterns of Ras and\/or ShcA proteins in different types of cancers. Their level can be potentially associated with oncogenic processes. We analyzed samples of pediatric brain tumors reflecting different groups such as choroid plexus tumors, diffuse astrocytic and oligodendroglial tumors, embryonal tumors, ependymal tumors, and other astrocytic tumors as well as tumor malignancy grade, in order to characterize the expression profile of Ras, TrkB, and three isoforms of ShcA, namely, p66Shc, p52Shc, and p46Shc proteins. The main aim of our study was to evaluate the potential correlation between the type of pediatric brain tumors, tumor malignancy grade, and the expression patterns of the investigated proteins.<\/jats:p>","DOI":"10.3390\/jcm10102219","type":"journal-article","created":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T11:45:57Z","timestamp":1621511157000},"page":"2219","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ras, TrkB, and ShcA Protein Expression Patterns in Pediatric Brain Tumors"],"prefix":"10.3390","volume":"10","author":[{"given":"Monika","family":"Prill","sequence":"first","affiliation":[{"name":"Laboratory of Mitochondrial Biology and Metabolism, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4936-1571","authenticated-orcid":false,"given":"Agnieszka","family":"Karkucinska-Wieckowska","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Children\u2019s Memorial Health Institute, 04-730 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2725-5551","authenticated-orcid":false,"given":"Magdalena","family":"Lebiedzinska-Arciszewska","sequence":"additional","affiliation":[{"name":"Laboratory of Mitochondrial Biology and Metabolism, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giampaolo","family":"Morciano","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Section of Experimental Medicine, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agata","family":"Charzynska","sequence":"additional","affiliation":[{"name":"Laboratory of Bioinformatics, Nencki Institute of Experimental Biology, 02-093 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5335-158X","authenticated-orcid":false,"given":"Michal","family":"Dabrowski","sequence":"additional","affiliation":[{"name":"Laboratory of Bioinformatics, Nencki Institute of Experimental Biology, 02-093 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maciej","family":"Pronicki","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Children\u2019s Memorial Health Institute, 04-730 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7108-6508","authenticated-orcid":false,"given":"Paolo","family":"Pinton","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Section of Experimental Medicine, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wieslawa","family":"Grajkowska","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Children\u2019s Memorial Health Institute, 04-730 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0789-4521","authenticated-orcid":false,"given":"Mariusz R.","family":"Wieckowski","sequence":"additional","affiliation":[{"name":"Laboratory of Mitochondrial Biology and Metabolism, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,20]]},"reference":[{"key":"ref_1","first-page":"633","article-title":"A family of Shc related proteins with conserved PTB, CH1 and SH2 regions","volume":"13","author":"Pelicci","year":"1996","journal-title":"Oncogene"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.cell.2017.06.009","article-title":"RAS Proteins and Their Regulators in Human Disease","volume":"170","author":"Simanshu","year":"2017","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s12943-015-0354-9","article-title":"p66Shc as a switch in bringing about contrasting responses in cell growth: Implications on cell proliferation and apoptosis","volume":"14","author":"Bhat","year":"2015","journal-title":"Mol. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5839","DOI":"10.1038\/onc.2010.318","article-title":"A Rac-Pak signaling pathway is essential for ErbB2-mediated transformation of human breast epithelial cancer cells","volume":"29","author":"Pacheco","year":"2010","journal-title":"Oncogene"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Samuel, M.S., Louren\u00e7o, F.C., and Olson, M.F. (2011). K-Ras mediated murine epidermal tumorigenesis is dependent upon and associated with elevated Rac1 activity. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0017143"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1158\/1541-7786.MCR-12-0082","article-title":"Group I p21-activated kinases (PAKs) promote tumor cell proliferation and survival through the AKT1 and Raf-MAPK pathways","volume":"10","author":"Menges","year":"2012","journal-title":"Mol. Cancer Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6322","DOI":"10.1038\/sj.onc.1204776","article-title":"Signaling via Shc family adapter proteins","volume":"20","author":"Ravichandran","year":"2001","journal-title":"Oncogene"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.1128\/MCB.16.5.1946","article-title":"Shc proteins are localized on endoplasmic reticulum membranes and are redistributed after tyrosine kinase receptor activation","volume":"16","author":"Lotti","year":"1996","journal-title":"Mol. Cell. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1093\/emboj\/16.4.706","article-title":"Opposite effects of the p52shc\/p46shc and p66shc splicing isoforms on the EGF receptor-MAP kinase-fos signalling pathway","volume":"16","author":"Migliaccio","year":"1997","journal-title":"EMBO J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/46311","article-title":"The p66shc adaptor protein controls oxidative stress response and life span in mammals","volume":"402","author":"Migliaccio","year":"1999","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1111\/jphp.13043","article-title":"The PKC\u03b2-p66shc-NADPH oxidase pathway plays a crucial role in diabetic nephropathy","volume":"71","author":"Cheng","year":"2019","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s00395-019-0738-x","article-title":"P66shc and its role in ischemic cardiovascular diseases","volume":"114","author":"Boengler","year":"2019","journal-title":"Basic Res. Cardiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"719407","DOI":"10.1155\/2013\/719407","article-title":"The P66Shc\/mitochondrial permeability transition pore pathway determines neurodegeneration","volume":"2013","author":"Savino","year":"2013","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1016\/j.bbabio.2010.03.005","article-title":"Oxidative stress-dependent p66Shc phosphorylation in skin fibroblasts of children with mitochondrial disorders","volume":"1797","author":"Lebiedzinska","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.abb.2009.03.007","article-title":"Age-related changes in levels of p66Shc and serine 36-phosphorylated p66Shc in organs and mouse tissues","volume":"486","author":"Lebiedzinska","year":"2009","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5057","DOI":"10.1038\/onc.2008.143","article-title":"Mitochondrial redox signaling by p66Shc is involved in regulating androgenic growth stimulation of human prostate cancer cells","volume":"27","author":"Veeramani","year":"2008","journal-title":"Oncogene"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1002\/ijc.11621","article-title":"p66Shc protein is upregulated by steroid hormones in hormone-sensitive cancer cells and in primary prostate carcinomas","volume":"108","author":"Lee","year":"2004","journal-title":"Int. J. Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/s10555-010-9213-8","article-title":"p66Shc\u2014A longevity redox protein in human prostate cancer progression and metastasis: p66Shc in cancer progression and metastasis","volume":"29","author":"Rajendran","year":"2010","journal-title":"Cancer Metastasis Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1677\/ERC-08-0179","article-title":"A novel role of Shc adaptor proteins in steroid hormone-regulated cancers","volume":"16","author":"Alam","year":"2009","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5559","DOI":"10.1038\/onc.2010.326","article-title":"p66(Shc) restrains Ras hyperactivation and suppresses metastatic behavior","volume":"29","author":"Ma","year":"2010","journal-title":"Oncogene"},{"key":"ref_21","first-page":"899","article-title":"Constitutive phosphorylation of Shc proteins in human tumors","volume":"11","author":"Pelicci","year":"1995","journal-title":"Oncogene"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2","DOI":"10.4161\/sgtp.1.1.12178","article-title":"Ras history: The saga continues","volume":"1","author":"Cox","year":"2010","journal-title":"Small GTPases"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1126\/science.2406906","article-title":"Molecular switch for signal transduction: Structural differences between active and inactive forms of protooncogenic ras proteins","volume":"247","author":"Milburn","year":"1990","journal-title":"Science"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.ccr.2005.10.014","article-title":"Reduction in the requirement of oncogenic Ras signaling to activation of PI3K\/AKT pathway during tumor maintenance","volume":"8","author":"Lim","year":"2005","journal-title":"Cancer Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"D777","DOI":"10.1093\/nar\/gkw1121","article-title":"COSMIC: Somatic cancer genetics at high-resolution","volume":"45","author":"Forbes","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_26","first-page":"4682","article-title":"Ras oncogenes in human cancer: A review","volume":"49","author":"Bos","year":"1989","journal-title":"Cancer Res."},{"key":"ref_27","first-page":"6772","article-title":"Shc proteins are strong, independent prognostic markers for both node-negative and node-positive primary breast cancer","volume":"63","author":"Davol","year":"2003","journal-title":"Cancer Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"R73","DOI":"10.1186\/bcr1631","article-title":"p66 Shc and tyrosine-phosphorylated Shc in primary breast tumors identify patients likely to relapse despite tamoxifen therapy","volume":"8","author":"Frackelton","year":"2006","journal-title":"Breast Cancer Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5798","DOI":"10.1158\/1078-0432.CCR-07-0073","article-title":"p66 Shc tumor levels show a strong prognostic correlation with disease outcome in stage IIA colon cancer","volume":"13","author":"Grossman","year":"2007","journal-title":"Clin. Cancer Res."},{"key":"ref_30","first-page":"1135","article-title":"Elevated levels of p66 Shc are found in breast cancer cell lines and primary tumors with high metastatic potential","volume":"6","author":"Jackson","year":"2000","journal-title":"Clin. Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5687","DOI":"10.1074\/jbc.M113.516047","article-title":"The adaptor proteins p66Shc and Grb2 regulate the activation of the GTPases ARF1 and ARF6 in invasive breast cancer cells","volume":"289","author":"Haines","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/S0896-6273(00)00156-2","article-title":"The mammalian ShcB and ShcC phosphotyrosine docking proteins function in the maturation of sensory and sympathetic neurons","volume":"28","author":"Sakai","year":"2000","journal-title":"Neuron"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1038\/88395","article-title":"Shc signaling in differentiating neural progenitor cells","volume":"4","author":"Conti","year":"2001","journal-title":"Nat. Neurosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2923","DOI":"10.1038\/bjc.2014.228","article-title":"Tropomyosin-related receptor kinase B at the invasive front and tumour cell dedifferentiation in gastric cancer","volume":"110","author":"Tanaka","year":"2014","journal-title":"Br. J. Cancer"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/bjc.2012.499","article-title":"Brain-derived neurotrophic factor\/tropomyosin-related kinase B pathway in gastric cancer","volume":"108","author":"Okugawa","year":"2013","journal-title":"Br. J. Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1159\/000151615","article-title":"Overexpression of tyrosine kinase B protein as a predictor for distant metastases and prognosis in gastric carcinoma","volume":"75","author":"Zhang","year":"2008","journal-title":"Oncology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1007\/s10495-014-0968-1","article-title":"Tropomyosin-related kinase B promotes distant metastasis of colorectal cancer through protein kinase B-mediated anoikis suppression and correlates with poor prognosis","volume":"19","author":"Fan","year":"2014","journal-title":"Apoptosis"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1111\/his.12603","article-title":"Tyrosine kinase receptor B (TrkB) expression in colorectal cancers highlights anoikis resistance as a survival mechanism of tumour budding cells","volume":"66","author":"Dawson","year":"2015","journal-title":"Histopathology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.lungcan.2012.07.011","article-title":"Expression of TrkB and BDNF is associated with poor prognosis in non-small cell lung cancer","volume":"78","author":"Okamura","year":"2012","journal-title":"Lung Cancer"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.canlet.2009.02.025","article-title":"Tyrosine kinase B receptor and BDNF expression in ovarian cancers\u2014Effect on cell migration, angiogenesis and clinical outcome","volume":"281","author":"Au","year":"2009","journal-title":"Cancer Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"665","DOI":"10.3892\/or.2013.2878","article-title":"Clinical significance of TrkB expression in nasopharyngeal carcinoma","volume":"31","author":"Li","year":"2014","journal-title":"Oncol. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/s10585-012-9525-x","article-title":"Trks are novel oncogenes involved in the induction of neovascularization, tumor progression, and nodal metastasis in oral squamous cell carcinoma","volume":"30","author":"Sasahira","year":"2013","journal-title":"Clin. Exp. Metastasis"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.ijom.2016.09.027","article-title":"Expression and clinical significance of TrkB in sinonasal squamous cell carcinoma: A pilot study","volume":"46","author":"Li","year":"2017","journal-title":"Int. J. Oral. Maxillofac. Surg."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"99394","DOI":"10.18632\/oncotarget.19561","article-title":"The prognostic value of over-expressed TrkB in solid tumors: A systematic review and meta-analysis","volume":"8","author":"Zhang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1007\/s00401-016-1545-1","article-title":"The 2016 World Health Organization Classification of Tumors of the Central Nervous System: A summary","volume":"131","author":"Louis","year":"2016","journal-title":"Acta Neuropathol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1042\/BST0340607","article-title":"Mechanisms of neurotrophin receptor signalling","volume":"34","author":"Zampieri","year":"2006","journal-title":"Biochem. Soc. Trans."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3280","DOI":"10.1158\/1078-0432.CCR-04-1681","article-title":"Shc family expression in neuroblastoma: High expression of shcC is associated with a poor prognosis in advanced neuroblastoma","volume":"11","author":"Terui","year":"2005","journal-title":"Clin. Cancer Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1056\/NEJM199303253281205","article-title":"Association between high levels of expression of the TRK gene and favorable outcome in human neuroblastoma","volume":"328","author":"Nakagawara","year":"1993","journal-title":"N. Engl. J. Med."},{"key":"ref_49","first-page":"6756","article-title":"Brain-derived neurotrophic factor activation of TrkB protects neuroblastoma cells from chemotherapy-induced apoptosis via phosphatidylinositol 3\u2019-kinase pathway","volume":"62","author":"Jaboin","year":"2002","journal-title":"Cancer Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.3389\/fonc.2019.01088","article-title":"A Comparative Analysis of Individual RAS Mutations in Cancer Biology","volume":"9","author":"Zimmer","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"261","DOI":"10.3171\/2018.10.PEDS18377","article-title":"Childhood brain tumors: Current management, biological insights, and future directions","volume":"23","author":"Pollack","year":"2019","journal-title":"J. Neurosurg. Pediatr."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1177\/0883073820937225","article-title":"Pilocytic Astrocytoma: A Review of General, Clinical, and Molecular Characteristics","volume":"35","author":"Salles","year":"2020","journal-title":"J. Child Neurol."},{"key":"ref_53","first-page":"138","article-title":"Case-based review: Pediatric medulloblastoma","volume":"4","author":"Kline","year":"2017","journal-title":"Neurooncol. Pract."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"353","DOI":"10.3171\/2019.5.PEDS18381","article-title":"Medulloblastoma in the age of molecular subgroups: A review","volume":"24","author":"Juraschka","year":"2019","journal-title":"J. Neurosurg. Pediatr."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1186\/1476-4598-12-127","article-title":"R-RAS2 overexpression in tumors of the human central nervous system","volume":"12","author":"Fresno","year":"2013","journal-title":"Mol. Cancer"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/10\/2219\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:04:58Z","timestamp":1760162698000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/10\/2219"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,20]]},"references-count":55,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["jcm10102219"],"URL":"https:\/\/doi.org\/10.3390\/jcm10102219","relation":{},"ISSN":["2077-0383"],"issn-type":[{"type":"electronic","value":"2077-0383"}],"subject":[],"published":{"date-parts":[[2021,5,20]]}}}