{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,7,22]],"date-time":"2023-07-22T05:11:20Z","timestamp":1690002680369},"posted":{"date-parts":[[2023]]},"group-title":"SSRN","reference-count":82,"publisher":"Elsevier BV","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"DOI":"10.2139\/ssrn.4512951","type":"posted-content","created":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T18:35:57Z","timestamp":1689964557000},"source":"Crossref","is-referenced-by-count":0,"title":["Purinergic Preconditioning Induces Epigenomic and Transcriptomic-Mediated Training Resembling Epilepsy-Associated Microglial States"],"prefix":"10.2139","author":[{"given":"Ricardo","family":"Martins-Ferreira","sequence":"first","affiliation":[]},{"given":"Josep","family":"Calafell-Segura","sequence":"additional","affiliation":[]},{"given":"Jo\u00e3o","family":"Chaves","sequence":"additional","affiliation":[]},{"given":"Laura","family":"Ciudad","sequence":"additional","affiliation":[]},{"given":"Ant\u00f3nio","family":"Martins da Silva","sequence":"additional","affiliation":[]},{"given":"Paulo","family":"Pinho Costa","sequence":"additional","affiliation":[]},{"given":"B\u00e1rbara","family":"Leal","sequence":"additional","affiliation":[]},{"given":"Esteban","family":"Ballestar","sequence":"additional","affiliation":[]}],"member":"78","reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.neuron.2012.12.023","article-title":"Microglia: new roles for the synaptic stripper","volume":"77","author":"H Kettenmann","year":"2013","journal-title":"Neuron"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/s004010000284","article-title":"Local distribution of microglia in the normal adult human central nervous system differs by up to one order of magnitude","volume":"101","author":"M Mittelbronn","year":"2001","journal-title":"Acta Neuropathol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.biocel.2017.11.012","article-title":"Microglia: Key players in neurodevelopment and neuronal plasticity","volume":"94","author":"L Sominsky","year":"2018","journal-title":"Int. J. Biochem. Cell Biol"},{"key":"ref4","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0026317","article-title":"Absence of colony stimulation factor-1 receptor results in loss of microglia, disrupted brain development and olfactory deficits","volume":"6","author":"B Erblich","year":"2011","journal-title":"PLoS One"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1038\/nn.3641","article-title":"Deficient neuron-microglia signaling results in impaired functional brain connectivity and social behavior","volume":"17","author":"Y Zhan","year":"2014","journal-title":"Nat. Neurosci"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/nrneurol.2010.17-c1","article-title":"Nasu-Hakola disease and primary microglial dysfunction","volume":"6","author":"M M Bianchin","year":"2010","journal-title":"Nat. Rev. Neurol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1038\/ng.3916","article-title":"Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease","volume":"49","author":"R Sims","year":"2017","journal-title":"Nat. Genet"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.it.2019.02.001","article-title":"Priming Microglia for Innate Immune Memory in the Brain","volume":"40","author":"J J Neher","year":"2019","journal-title":"Trends Immunol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.bbi.2015.03.013","article-title":"Long-lasting proinflammatory suppression of microglia by LPS-preconditioning is mediated by RelBdependent epigenetic silencing","volume":"48","author":"W Schaafsma","year":"2015","journal-title":"Brain. Behav. Immun"},{"key":"ref10","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2019.02492","article-title":"Memory-Like Inflammatory Responses of Microglia to Rising Doses of LPS: Key Role of PI3K?","volume":"10","author":"T Lajqi","year":"2019","journal-title":"Front. Immunol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1038\/s41586-018-0023-4","article-title":"Innate immune memory in the brain shapes neurological disease hallmarks","volume":"556","author":"A.-C Wendeln","year":"2018","journal-title":"Nature"},{"key":"ref12","doi-asserted-by":"crossref","DOI":"10.1186\/s12974-022-02463-5","article-title":"Epigenetic regulation of innate immune memory in microglia","volume":"19","author":"X Zhang","year":"2022","journal-title":"J. Neuroinflammation"},{"key":"ref13","doi-asserted-by":"crossref","DOI":"10.1016\/j.pneurobio.2021.102105","article-title":"ATP and adenosine-Two players in the control of seizures and epilepsy development","volume":"204","author":"E Beamer","year":"2021","journal-title":"Prog. Neurobiol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.yebeh.2016.05.036","article-title":"Effects of A1 receptor agonist\/antagonist on spontaneous seizures in pilocarpine-induced epileptic rats","volume":"61","author":"B O Amorim","year":"2016","journal-title":"Epilepsy Behav"},{"key":"ref15","doi-asserted-by":"crossref","DOI":"10.3390\/molecules22040676","article-title":"Adenosine A1 and A2A Receptors in the Brain: Current Research and Their Role in Neurodegeneration","volume":"22","author":"J Stockwell","year":"2017","journal-title":"Molecules"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1111\/j.1528-1167.2009.02382.x","article-title":"Adenosine A1 receptor blockage mediates theophylline-associated seizures","volume":"51","author":"M Fukuda","year":"2010","journal-title":"Epilepsia"},{"key":"ref17","article-title":"Neuronal and glial purinergic receptors functions in neuron development and brain disease","volume":"7","author":"A Del Puerto","year":"2013","journal-title":"Front. Cell. Neurosci"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1002\/ana.410320504","article-title":"Adenosine: a potential mediator of seizure arrest and postictal refractoriness","volume":"32","author":"M J During","year":"1992","journal-title":"Ann. Neurol"},{"key":"ref19","article-title":"Pannexin-1 channels contribute to seizure generation in human epileptic brain tissue and in a mouse model of epilepsy","author":"E Dossi","year":"2018","journal-title":"Sci. Transl. Med"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.neulet.2015.11.028","article-title":"Extracellular levels of ATP and acetylcholine during lithium-pilocarpine induced status epilepticus in rats","volume":"611","author":"J Lietsche","year":"2016","journal-title":"Neurosci. Lett"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"160","DOI":"10.2174\/157015909789152146","article-title":"Release of adenosine and ATP during ischemia and epilepsy","volume":"7","author":"N Dale","year":"2009","journal-title":"Curr. Neuropharmacol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1002\/glia.21251","article-title":"An optimized protocol for the acute isolation of human microglia from autopsy brain samples","volume":"60","author":"M Olah","year":"2012","journal-title":"Glia"},{"key":"ref23","doi-asserted-by":"crossref","DOI":"10.1126\/science.aal3222","article-title":"An environment-dependent transcriptional network specifies human microglia identity","volume":"356","author":"D Gosselin","year":"2017","journal-title":"Science"},{"key":"ref24","doi-asserted-by":"crossref","DOI":"10.1186\/s40478-017-0418-8","article-title":"Isolation of primary microglia from the human post-mortem brain: effects of ante-and post-mortem variables","volume":"5","author":"M R Mizee","year":"2017","journal-title":"Acta Neuropathol. Commun"},{"key":"ref25","article-title":"A human microglia-like cellular model for assessing the effects of neurodegenerative disease gene variants","author":"K J Ryan","year":"2017","journal-title":"Sci. Transl. Med"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/nn.3599","article-title":"Identification of a unique TGF-?-dependent molecular and functional signature in microglia","volume":"17","author":"O Butovsky","year":"2014","journal-title":"Nat. Neurosci"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.jneumeth.2012.05.025","article-title":"A novel in vitro human microglia model: characterization of human monocyte-derived microglia","volume":"209","author":"S Etemad","year":"2012","journal-title":"J. Neurosci. Methods"},{"key":"ref28","article-title":"Comparative analysis of human microglial models for studies of HIV replication and pathogenesis","volume":"17","author":"M A Rai","year":"2020","journal-title":"Retrovirology"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.molmed.2018.11.004","article-title":"Transcriptional and Epigenetic Regulation of Microglia in Health and Disease","volume":"25","author":"H Yeh","year":"2019","journal-title":"Trends Mol. Med"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.neuron.2014.02.040","article-title":"Colony-stimulating factor 1 receptor signaling is necessary for microglia viability, unmasking a microglia progenitor cell in the adult brain","volume":"82","author":"M R P Elmore","year":"2014","journal-title":"Neuron"},{"key":"ref31","doi-asserted-by":"crossref","DOI":"10.1126\/science.1251086","article-title":"Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity","volume":"345","author":"S Saeed","year":"2014","journal-title":"Science"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"3088","DOI":"10.1016\/j.neuron.2021.09.001","article-title":"Single-nucleus transcriptome analysis reveals cell-type-specific molecular signatures across reward circuitry in the human brain","volume":"109","author":"M N Tran","year":"2021","journal-title":"Neuron"},{"key":"ref33","doi-asserted-by":"crossref","DOI":"10.1126\/sciimmunol.abb8786","article-title":"Transcriptomic and clonal characterization of T cells in the human central nervous system","volume":"5","author":"J L Pappalardo","year":"2020","journal-title":"Sci. Immunol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.neuron.2021.10.036","article-title":"Transcriptomic taxonomy and neurogenic trajectories of adult human, macaque, and pig hippocampal and entorhinal cells","volume":"110","author":"D Franjic","year":"2022","journal-title":"Neuron"},{"key":"ref35","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2020.108189","article-title":"Single-Nucleus RNA-Seq Is Not Suitable for Detection of Microglial Activation Genes in Humans","volume":"32","author":"N Thrupp","year":"2020","journal-title":"Cell Rep"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1016\/j.immuni.2022.07.004","article-title":"Dual ontogeny of disease-associated microglia and disease inflammatory macrophages in aging and neurodegeneration","volume":"55","author":"A Silvin","year":"2022","journal-title":"Immunity"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.cell.2007.02.006","article-title":"Epigenetics: a landscape takes shape","volume":"128","author":"A D Goldberg","year":"2007","journal-title":"Cell"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1038\/nature05913","article-title":"Perceptions of epigenetics","volume":"447","author":"A Bird","year":"2007","journal-title":"Nature"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1126\/science.1194637","article-title":"Fate mapping analysis reveals that adult microglia derive from primitive macrophages","volume":"330","author":"F Ginhoux","year":"2010","journal-title":"Science"},{"key":"ref40","doi-asserted-by":"crossref","DOI":"10.3389\/fncel.2013.00045","article-title":"Origin and differentiation of microglia","volume":"7","author":"F Ginhoux","year":"2013","journal-title":"Front. Cell. Neurosci"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1002\/glia.23781","article-title":"Human iPSC-derived microglia: A growing toolset to study the brain's innate immune cells","volume":"68","author":"J Hasselmann","year":"2020","journal-title":"Glia"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.bbi.2022.09.015","article-title":"Human monocyte-derived microglia-like cell models: A review of the benefits, limitations and recommendations","volume":"107","author":"T J Sargeant","year":"2023","journal-title":"Brain. Behav. Immun"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1002\/glia.20372","article-title":"Characterization of human monocyte-derived microglia-like cells","volume":"54","author":"C Leone","year":"2006","journal-title":"Glia"},{"key":"ref44","doi-asserted-by":"crossref","DOI":"10.3389\/fncel.2021.629279","article-title":"Validation of Induced Microglia-Like Cells (iMG Cells) for Future Studies of Brain Diseases","volume":"15","author":"A Banerjee","year":"2021","journal-title":"Front. Cell. Neurosci"},{"key":"ref45","first-page":"31268","article-title":"Principles of DNA methylation and their implications for biology and medicine","volume":"392","author":"Y Dor","year":"2018","journal-title":"Lancet"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1111\/j.0013-9580.2004.09004.x","article-title":"Mesial temporal lobe epilepsy with hippocampal sclerosis","volume":"45","author":"H.-G Wieser","year":"2004","journal-title":"Epilepsia"},{"issue":"Suppl 1","key":"ref47","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1111\/j.1528-1167.2008.01969.x","article-title":"Prognostic factors in patients with mesial temporal lobe epilepsy","volume":"50","author":"F Pittau","year":"2009","journal-title":"Epilepsia"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1111\/j.1528-1157.1993.tb02105.x","article-title":"Temporal lobe epilepsy after prolonged febrile convulsions: excellent outcome after surgical treatment","volume":"34","author":"B Abou-Khalil","year":"1993","journal-title":"Epilepsia"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1002\/jnr.22829","article-title":"Understanding the basic mechanisms underlying seizures in mesial temporal lobe epilepsy and possible therapeutic targets: a review","volume":"90","author":"C M O'dell","year":"2012","journal-title":"J. Neurosci. Res"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.pneurobio.2007.12.002","article-title":"The adenosine kinase hypothesis of epileptogenesis","volume":"84","author":"D Boison","year":"2008","journal-title":"Prog. Neurobiol"},{"issue":"Suppl 9","key":"ref51","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/epi.12031","article-title":"The emerging role of DNA methylation in epileptogenesis","volume":"53","author":"K Kobow","year":"2012","journal-title":"Epilepsia"},{"key":"ref52","doi-asserted-by":"crossref","DOI":"10.1016\/j.neuint.2021.105054","article-title":"Adenosine kinase: An epigenetic modulator in development and disease","volume":"147","author":"M Murugan","year":"2021","journal-title":"Neurochem. Int"},{"key":"ref53","article-title":"Epilepsy progression is associated with cumulative DNA methylation changes in inflammatory genes","volume":"209","author":"R Martins-Ferreira","year":"2021","journal-title":"Prog. Neurobiol"},{"key":"ref54","doi-asserted-by":"crossref","DOI":"10.1038\/srep04957","article-title":"Direct induction of ramified microglia-like cells from human monocytes: dynamic microglial dysfunction in Nasu-Hakola disease","volume":"4","author":"M Ohgidani","year":"2014","journal-title":"Sci. Rep"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/mp.2016.220","article-title":"Patientspecific models of microglia-mediated engulfment of synapses and neural progenitors","volume":"22","author":"C M Sellgren","year":"2017","journal-title":"Mol. Psychiatry"},{"key":"ref56","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-017-11506-4","article-title":"Fibromyalgia and microglial TNF-?: Translational research using human blood induced microglia-like cells","volume":"7","author":"M Ohgidani","year":"2017","journal-title":"Sci. Rep"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1038\/s41593-018-0334-7","article-title":"Increased synapse elimination by microglia in schizophrenia patient-derived models of synaptic pruning","volume":"22","author":"C M Sellgren","year":"2019","journal-title":"Nat. Neurosci"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.bbi.2020.08.012","article-title":"A characterization of the molecular phenotype and inflammatory response of schizophrenia patient-derived microglia-like cells","volume":"90","author":"P R Ormel","year":"2020","journal-title":"Brain. Behav. Immun"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1093\/bioinformatics\/btm091","article-title":"Enhancements and modifications of primer design program Primer3","volume":"23","author":"T Koressaar","year":"2007","journal-title":"Bioinformatics"},{"key":"ref60","article-title":"shiny\ufffdPICo: A graphical pipeline to analyze Illumina DNA methylation arrays","author":"O Morante-Palacios","year":"2021","journal-title":"Bioinformatics"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1093\/bioinformatics\/btu049","article-title":"Minfi: a flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays","volume":"30","author":"M J Aryee","year":"2014","journal-title":"Bioinformatics"},{"key":"ref62","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"M E Ritchie","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"ref63","article-title":"Comparison of Beta-value and M-value methods for quantifying methylation levels by microarray analysis","volume":"11","author":"P Du","year":"2010","journal-title":"BMC Bioinformatics"},{"key":"ref64","author":"J T Leek","year":"2022","journal-title":"sva: Surrogate Variable Analysis"},{"key":"ref65","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.3317","article-title":"HISAT: a fast spliced aligner with low memory requirements","volume":"12","author":"D Kim","year":"2015","journal-title":"Nat. Methods"},{"key":"ref66","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","article-title":"featureCounts: an efficient general purpose program for assigning sequence reads to genomic features","volume":"30","author":"Y Liao","year":"2014","journal-title":"Bioinformatics"},{"key":"ref67","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"M I Love","year":"2014","journal-title":"Genome Biol"},{"key":"ref68","doi-asserted-by":"crossref","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","article-title":"Integrated analysis of multimodal single-cell data","volume":"184","author":"Y Hao","year":"2021","journal-title":"Cell"},{"key":"ref69","article-title":"Systematic analysis of gene expression patterns associated with postmortem interval in human tissues","volume":"7","author":"Y Zhu","year":"2017","journal-title":"Sci. Rep"},{"key":"ref70","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.cels.2019.03.003","article-title":"DoubletFinder: Doublet Detection in Single-Cell RNA Sequencing Data Using Artificial Nearest Neighbors","volume":"8","author":"C S Mcginnis","year":"2019","journal-title":"Cell Syst"},{"key":"ref71","doi-asserted-by":"crossref","DOI":"10.1186\/s13059-019-1874-1","article-title":"Normalization and variance stabilization of single-cell RNA-seq data using regularized negative binomial regression","volume":"20","author":"C Hafemeister","year":"2019","journal-title":"Genome Biol"},{"key":"ref72","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","article-title":"Comprehensive Integration of Single-Cell Data","volume":"177","author":"T Stuart","year":"2019","journal-title":"Cell"},{"key":"ref73","author":"G R Warnes","year":"2022","journal-title":"gplots: Various R Programming Tools for Plotting Data"},{"key":"ref74","doi-asserted-by":"crossref","first-page":"2847","DOI":"10.1093\/bioinformatics\/btw313","article-title":"Complex heatmaps reveal patterns and correlations in multidimensional genomic data","volume":"32","author":"Z Gu","year":"2016","journal-title":"Bioinformatics"},{"key":"ref75","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/978-1-4939-3578-9_16","article-title":"Visualizing Genomic Data Using Gviz and Bioconductor","volume":"1418","author":"F Hahne","year":"2016","journal-title":"Methods Mol. Biol"},{"key":"ref76","article-title":"_VennDiagram: Generate High-Resolution Venn and Euler Plots","author":"H Chen","year":"2022","journal-title":"R Packag"},{"key":"ref77","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.molcel.2010.05.004","article-title":"Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities","volume":"38","author":"S Heinz","year":"2010","journal-title":"Mol. Cell"},{"key":"ref78","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/nbt.1630","article-title":"GREAT improves functional interpretation of cis-regulatory regions","volume":"28","author":"C Y Mclean","year":"2010","journal-title":"Nat. Biotechnol"},{"key":"ref79","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1158\/0008-5472.CAN-17-1679","article-title":"Transcription Factor Activities Enhance Markers of Drug Sensitivity in Cancer","volume":"78","author":"L Garcia-Alonso","year":"2018","journal-title":"Cancer Res"},{"key":"ref80","article-title":"A universal enrichment tool for interpreting omics data","author":"T Wu","year":"2021","journal-title":"Innov"},{"key":"ref81","author":"L Shen","year":"2021","journal-title":"GeneOverlap: Test and visualize gene overlaps"},{"key":"ref82","article-title":"Fast gene set enrichment analysis","author":"G Korotkevich","year":"2021","journal-title":"bioRxiv"}],"container-title":[],"original-title":[],"deposited":{"date-parts":[[2023,7,22]],"date-time":"2023-07-22T04:07:41Z","timestamp":1689998861000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ssrn.com\/abstract=4512951"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023]]},"references-count":82,"URL":"https:\/\/doi.org\/10.2139\/ssrn.4512951","relation":{},"subject":[],"published":{"date-parts":[[2023]]},"subtype":"preprint"}}