{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T22:26:49Z","timestamp":1789165609761,"version":"build-2803163510"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T00:00:00Z","timestamp":1644969600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003197","name":"Agenzia Italiana del Farmaco, Ministero della Salute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003197","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018225","name":"EuroNanoMed III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018225","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002803","name":"Fondazione Cariplo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002803","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>There is a lack of effective biomarkers for neurodegenerative diseases (NDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia. Extracellular vesicle (EV) RNA cargo can have an interesting potential as a non-invasive biomarker for NDs. However, the knowledge about the abundance of EV-mRNAs and their contribution to neurodegeneration is not clear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Large and small EVs (LEVs and SEVs) were isolated from plasma of patients and healthy volunteers (control, CTR) by differential centrifugation and filtration, and RNA was extracted. Whole transcriptome was carried out using next generation sequencing (NGS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Coding RNA (i.e., mRNA) but not long non-coding RNAs (lncRNAs) in SEVs and LEVs of patients with ALS could be distinguished from healthy CTRs and from other NDs using the principal component analysis (PCA). Some mRNAs were found in commonly deregulated between SEVs of patients with ALS and frontotemporal dementia (FTD), and they were classified in mRNA processing and splicing pathways. In LEVs, instead, one mRNA and one antisense RNA (i.e., MAP3K7CL and AP003068.3) were found to be in common among ALS, FTD, and PD. No deregulated mRNAs were found in EVs of patients with AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Different RNA regulation occurs in LEVs and SEVs of NDs. mRNAs and lncRNAs are present in plasma-derived EVs of NDs, and there are common and specific transcripts that characterize LEVs and SEVs from the NDs considered in this study.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnagi.2022.785741","type":"journal-article","created":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T02:24:04Z","timestamp":1644978244000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":33,"title":["Extracellular Vesicles Derived From Plasma of Patients With Neurodegenerative Disease Have Common Transcriptomic Profiling"],"prefix":"10.3389","volume":"14","author":[{"given":"Daisy","family":"Sproviero","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stella","family":"Gagliardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna","family":"Zucca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maddalena","family":"Arigoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Giannini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Garofalo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Fantini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orietta","family":"Pansarasa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micol","family":"Avenali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo Cotta","family":"Ramusino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Diamanti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigida","family":"Minafra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Perini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Zangaglia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Costa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Ceroni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaele A.","family":"Calogero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Cereda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1016\/j.bbrc.2006.10.093","article-title":"TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis","volume":"351","author":"Arai","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B2","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1080\/146608200300079536","article-title":"El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis","volume":"1","author":"Brooks","year":"2000","journal-title":"Amyotroph. Lateral Scler"},{"key":"B3","doi-asserted-by":"publisher","first-page":"2576","DOI":"10.3390\/ijms21072576","article-title":"Lysosomal exocytosis, exosome release and secretory autophagy: The autophagic- and endo-lysosomal systems go extracellular","volume":"21","author":"Buratta","year":"2020","journal-title":"Int. J. Mol. Sci"},{"key":"B4","doi-asserted-by":"publisher","first-page":"e94839","DOI":"10.1371\/journal.pone.0094839","article-title":"Profiles of extracellular miRNA in cerebrospinal fluid and serum from patients with Alzheimer's and Parkinson's diseases correlate with disease status and features of pathology","volume":"9","author":"Burgos","year":"2014","journal-title":"PLoS ONE"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.3389\/fnins.2019.01208","article-title":"miR-212 and miR-132 are downregulated in neurally derived plasma exosomes of Alzheimer's patients","volume":"13","author":"Cha","year":"2019","journal-title":"Front. Neurosci."},{"key":"B6","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/1471-2105-14-128","article-title":"Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool","volume":"128","author":"Chen","year":"2013","journal-title":"BMC Bioinform."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1766822","DOI":"10.1080\/20013078.2020.1766822","article-title":"Small RNA fingerprinting of Alzheimer's disease frontal cortex extracellular vesicles and their comparison with peripheral extracellular vesicles","volume":"9","author":"Cheng","year":"2020","journal-title":"J. Extracell. Vesicles"},{"key":"B8","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1016\/j.tcb.2015.01.004","article-title":"Ectosomes and exosomes: shedding the confusion between extracellular vesicles","volume":"25","author":"Cocucci","year":"2015","journal-title":"Trends Cell Biol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1016\/j.jalz.2014.06.008","article-title":"Identification of preclinical Alzheimer's disease by a profile of pathogenic proteins in neurally derived blood exosomes: a case-control study","volume":"11","author":"Fiandaca","year":"2015","journal-title":"Alzheimers Dement"},{"key":"B10","doi-asserted-by":"publisher","first-page":"2378","DOI":"10.1038\/s41598-018-20679-5","article-title":"Long non-coding and coding RNAs characterization in peripheral blood mononuclear cells and spinal cord from amyotrophic lateral sclerosis patients","volume":"8","author":"Gagliardi","year":"2018","journal-title":"Sci. Rep."},{"key":"B11","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/s40035-019-0169-5","article-title":"Exploratory study on microRNA profiles from plasma-derived extracellular vesicles in Alzheimer's disease and dementia with Lewy bodies","volume":"8","author":"G\u00e1mez-Valero","year":"2019","journal-title":"Transl. Neurodegener."},{"key":"B12","doi-asserted-by":"publisher","first-page":"9500","DOI":"10.3390\/ijms21249500","article-title":"Alzheimer's, Parkinson's disease and amyotrophic lateral sclerosis gene expression patterns divergence reveals different grade of RNA metabolism involvement","volume":"21","author":"Garofalo","year":"2020","journal-title":"Int. J. Mol. Sci"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1002\/cbin.10301","article-title":"Long non-coding RNAs with low expression levels in cells are enriched in secreted exosomes","volume":"38","author":"Gezer","year":"2014","journal-title":"Cell Biol. Int"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.3233\/JAD-170953","article-title":"Innovative biomarkers for Alzheimer's disease: focus on the hidden disease biomarkers","volume":"62","author":"Ghidoni","year":"2018","journal-title":"J. Alzheimers Dis"},{"key":"B15","doi-asserted-by":"publisher","first-page":"888","DOI":"10.1096\/fj.201700731R","article-title":"Declining levels of functionally specialized synaptic proteins in plasma neuronal exosomes with progression of Alzheimer's disease","volume":"32","author":"Goetzl","year":"2018","journal-title":"FASEB J"},{"key":"B16","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1002\/acn3.211","article-title":"Low neural exosomal levels of cellular survival factors in Alzheimer's disease","volume":"2","author":"Goetzl","year":"2015","journal-title":"Ann. Clin. Transl. Neurol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1002\/ana.20513","article-title":"Functional anatomy of the basal ganglia in X-linked recessive dystonia-Parkinsonism","volume":"58","author":"Goto","year":"2005","journal-title":"Ann. Neurol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"37043","DOI":"10.18632\/oncotarget.6158","article-title":"Altered microRNA profiles in cerebrospinal fluid exosome in Parkinson disease and Alzheimer disease","volume":"6","author":"Gui","year":"2015","journal-title":"Oncotarget"},{"key":"B19","doi-asserted-by":"publisher","first-page":"300","DOI":"10.2174\/1389202918666171005100549","article-title":"Decoding common features of neurodegenerative disorders: from differentially expressed genes to pathways","volume":"19","author":"Habib","year":"2018","journal-title":"Curr. Genom"},{"key":"B20","doi-asserted-by":"publisher","first-page":"3187","DOI":"10.1093\/brain\/aww237","article-title":"Exosome secretion is a key pathway for clearance of pathological TDP-43","volume":"139","author":"Iguchi","year":"2016","journal-title":"Brain"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aah5436","article-title":"RNA binding proteins and the pathological cascade in ALS\/FTD neurodegeneration","volume":"9","author":"Ito","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"B22","doi-asserted-by":"publisher","first-page":"146331","DOI":"10.1016\/j.brainres.2019.146331","article-title":"Serum secreted miR-137-containing exosomes affects oxidative stress of neurons by regulating OXR1 in Parkinson's disease","volume":"1722","author":"Jiang","year":"2019","journal-title":"Brain Res"},{"key":"B23","doi-asserted-by":"publisher","first-page":"581882","DOI":"10.3389\/fcell.2020.581882","article-title":"Mitochondrial RNA in Alzheimer's disease circulating extracellular vesicles","volume":"8","author":"Kim","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"W90","DOI":"10.1093\/nar\/gkw377","article-title":"Enrichr: a comprehensive gene set enrichment analysis web server 2016 update","volume":"44","author":"Kuleshov","year":"2016","journal-title":"Nucleic acids research"},{"key":"B25","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1186\/s12859-018-2296-x","article-title":"Reproducible bioinformatics project: a community for reproducible bioinformatics analysis pipelines","volume":"19","author":"Kulkarni","year":"2018","journal-title":"BMC Bioinform."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1126\/science.1166066","article-title":"Mutations in the FUS\/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis","volume":"323","author":"Kwiatkowski","year":"2009","journal-title":"Science"},{"key":"B27","doi-asserted-by":"publisher","first-page":"R46","DOI":"10.1093\/hmg\/ddq137","article-title":"TDP-43 and FUS\/TLS: emerging roles in RNA processing and neurodegeneration","volume":"19","author":"Lagier-Tourenne","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"B28","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1186\/1471-2105-9-559","article-title":"WGCNA: an R package for weighted correlation network analysis","volume":"9","author":"Langfelder","year":"2008","journal-title":"BMC Bioinform."},{"key":"B29","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1016\/j.neuron.2013.07.033","article-title":"Converging mechanisms in ALS and FTD: disrupted RNA and protein homeostasis","volume":"79","author":"Ling","year":"2013","journal-title":"Neuron"},{"key":"B30","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1242\/dmm.028613","article-title":"RNA metabolism in neurodegenerative disease","volume":"10","author":"Liu","year":"2017","journal-title":"Dis. Models Mech."},{"key":"B31","doi-asserted-by":"publisher","first-page":"e0139233","DOI":"10.1371\/journal.pone.0139233","article-title":"Plasma exosomal miRNAs in persons with and without Alzheimer disease: altered expression and prospects for biomarkers","volume":"10","author":"Lugli","year":"2015","journal-title":"PLoS ONE"},{"key":"B32","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.jalz.2011.03.005","article-title":"The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease","volume":"7","author":"McKhann","year":"2011","journal-title":"Alzheimers Dement."},{"key":"B33","doi-asserted-by":"publisher","first-page":"2477","DOI":"10.1016\/j.celrep.2019.02.003","article-title":"Cell-type-specific gene expression profiling in adult mouse brain reveals normal and disease-state signatures","volume":"26","author":"Merienne","year":"2019","journal-title":"Cell Rep"},{"key":"B34","doi-asserted-by":"publisher","first-page":"102249","DOI":"10.1016\/j.nano.2020.102249","article-title":"Raman spectroscopy reveals biochemical differences in plasma derived extracellular vesicles from sporadic Amyotrophic Lateral Sclerosis patients","volume":"29","author":"Morasso","year":"2020","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"B35","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1126\/science.1134108","article-title":"Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis","volume":"314","author":"Neumann","year":"2006","journal-title":"Science"},{"key":"B36","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1038\/s41580-020-0251-y","article-title":"RNA delivery by extracellular vesicles in mammalian cells and its applications","volume":"21","author":"O'Brien","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.1002\/mds.26424","article-title":"MDS clinical diagnostic criteria for Parkinson's disease","volume":"30","author":"Postuma","year":"2015","journal-title":"Movement Disord."},{"key":"B38","doi-asserted-by":"publisher","first-page":"15482","DOI":"10.1523\/JNEUROSCI.3258-14.2014","article-title":"Emerging roles of extracellular vesicles in the nervous system","volume":"34","author":"Rajendran","year":"2014","journal-title":"J. Neurosci"},{"key":"B39","doi-asserted-by":"publisher","first-page":"323","DOI":"10.3389\/fnagi.2017.00323","article-title":"miRNA in circulating microvesicles as biomarkers for age-related cognitive decline","volume":"9","author":"Rani","year":"2017","journal-title":"Front. Aging. Neurosci."},{"key":"B40","doi-asserted-by":"publisher","first-page":"2456","DOI":"10.1093\/brain\/awr179","article-title":"Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia","volume":"134","author":"Rascovsky","year":"2011","journal-title":"Brain J. Neurol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"5733","DOI":"10.1073\/pnas.85.15.5733","article-title":"Differential loss of striatal projection neurons in Huntington disease","volume":"85","author":"Reiner","year":"1988","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B42","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1093\/jnen\/nlw053","article-title":"Marked involvement of the striatal efferent system in TAR DNA-binding protein 43 kDa-related frontotemporal lobar degeneration and amyotrophic lateral sclerosis","volume":"75","author":"Riku","year":"2016","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"3842","DOI":"10.1074\/jbc.M111.277061","article-title":"Exosome-associated tau is secreted in tauopathy models and is selectively phosphorylated in cerebrospinal fluid in early Alzheimer disease","volume":"287","author":"Saman","year":"2012","journal-title":"J. Biol. Chem"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1470","DOI":"10.1038\/ncb1800","article-title":"Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers","volume":"10","author":"Skog","year":"2008","journal-title":"Nat. Cell Biol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1111\/jnc.15112","article-title":"Diagnostic and therapeutic potential of exosomes in Alzheimer's disease","volume":"156","author":"Soares Martins","year":"2021","journal-title":"J. Neurochem."},{"key":"B46","doi-asserted-by":"publisher","first-page":"2737","DOI":"10.3390\/ijms22052737","article-title":"Different miRNA profiles in plasma derived small and large extracellular vesicles from patients with neurodegenerative diseases","volume":"22","author":"Sproviero","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B47","doi-asserted-by":"publisher","first-page":"344","DOI":"10.3389\/fnins.2019.00344","article-title":"Leukocyte derived microvesicles as disease progression biomarkers in slow progressing amyotrophic lateral sclerosis patients","volume":"13","author":"Sproviero","year":"2019","journal-title":"Front. Neurosci."},{"key":"B48","doi-asserted-by":"publisher","first-page":"487","DOI":"10.3389\/fnins.2018.00487","article-title":"Pathological proteins are transported by extracellular vesicles of sporadic amyotrophic lateral sclerosis patients","volume":"12","author":"Sproviero","year":"2018","journal-title":"Front. Neurosci."},{"key":"B49","doi-asserted-by":"publisher","first-page":"2508","DOI":"10.1002\/mds.28639","article-title":"\u03b1-synuclein in plasma-derived extracellular vesicles is a potential biomarker of Parkinson's disease","volume":"36","author":"Stuendl","year":"2021","journal-title":"Movement Disord."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.3233\/JAD-132144","article-title":"Genome-wide serum microRNA expression profiling identifies serum biomarkers for Alzheimer's disease","volume":"40","author":"Tan","year":"2014","journal-title":"J. Alzheimers Dis."},{"key":"B51","doi-asserted-by":"publisher","first-page":"1535750","DOI":"10.1080\/20013078.2018.1461450","article-title":"Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines","volume":"7","author":"Th\u00e9ry","year":"2018","journal-title":"J. Extracell. Vesicles"},{"key":"B52","doi-asserted-by":"publisher","first-page":"590034","DOI":"10.3389\/fncel.2020.590034","article-title":"Extracellular vesicles loaded miRNAs as potential modulators shared between glioblastoma, and Parkinson's and Alzheimer's diseases","volume":"14","author":"Thomas","year":"2020","journal-title":"Front. Cell. Neurosci."},{"key":"B53","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/s12014-020-09294-7","article-title":"CSF extracellular vesicle proteomics demonstrates altered protein homeostasis in amyotrophic lateral sclerosis","volume":"17","author":"Thompson","year":"2020","journal-title":"Clin. Proteomics"},{"key":"B54","doi-asserted-by":"publisher","first-page":"2442","DOI":"10.7150\/ijbs.46751","article-title":"Serine\/arginine-rich splicing factors: the bridge linking alternative splicing and cancer","volume":"16","author":"Zheng","year":"2020","journal-title":"Int. J. Biol. Sci."},{"key":"B55","doi-asserted-by":"publisher","first-page":"190006","DOI":"10.1038\/sdata.2019.6","article-title":"RNA-Seq profiling in peripheral blood mononuclear cells of amyotrophic lateral sclerosis patients and controls","volume":"6","author":"Zucca","year":"2019","journal-title":"Sci. Data"}],"container-title":["Frontiers in Aging Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2022.785741\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T02:24:09Z","timestamp":1644978249000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2022.785741\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,16]]},"references-count":55,"alternative-id":["10.3389\/fnagi.2022.785741"],"URL":"https:\/\/doi.org\/10.3389\/fnagi.2022.785741","relation":{},"ISSN":["1663-4365"],"issn-type":[{"value":"1663-4365","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,16]]},"article-number":"785741"}}