{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T17:43:29Z","timestamp":1788371009556,"version":"build-2803163510"},"reference-count":56,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T00:00:00Z","timestamp":1711324800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2019\/33\/B\/NZ4\/03000"],"award-info":[{"award-number":["2019\/33\/B\/NZ4\/03000"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"crossref","award":["310030_172870, 314730_153380"],"award-info":[{"award-number":["310030_172870, 314730_153380"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Acidosis is one of the hallmarks of demyelinating central nervous system (CNS) lesions in multiple sclerosis (MS). The response to acidic pH is primarily mediated by a family of G protein-coupled proton-sensing receptors: OGR1, GPR4 and TDAG8. These receptors are inactive at alkaline pH, reaching maximal activation at acidic pH. Genome-wide association studies have identified a locus within the TDAG8 gene associated with several autoimmune diseases, including MS. Accordingly, we here found that expression of<jats:italic>TDAG8<\/jats:italic>, as opposed to<jats:italic>GPR4<\/jats:italic>or<jats:italic>OGR1<\/jats:italic>, is upregulated in MS plaques. This led us to investigate the expression of TDAG8 in oligodendrocytes using mouse and human<jats:italic>in vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>models. We observed significant upregulation of TDAG8 in human MO3.13 oligodendrocytes during maturation and in response to acidic conditions. However, its deficiency did not impact normal myelination in the mouse CNS, and its expression remained unaltered under demyelinating conditions in mouse organotypic cerebellar slices. Notably, our data revealed no expression of TDAG8 in primary mouse oligodendrocyte progenitor cells (OPCs), in contrast to its expression in primary human OPCs. Our investigations have revealed substantial species differences in the expression of proton-sensing receptors in oligodendrocytes, highlighting the limitations of the employed experimental models in fully elucidating the role of TDAG8 in myelination and oligodendrocyte biology. Consequently, the study does not furnish robust evidence for the role of TDAG8 in such processes. Nonetheless, our findings tentatively point towards a potential association between TDAG8 and myelination processes in humans, hinting at a potential link between TDAG8 and the pathophysiology of MS and warrants further research.<\/jats:p>","DOI":"10.1371\/journal.pone.0283060","type":"journal-article","created":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T17:34:48Z","timestamp":1711388088000},"page":"e0283060","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["The proton-sensing receptors TDAG8 and GPR4 are differentially expressed in human and mouse oligodendrocytes: Exploring their role in neuroinflammation and multiple sclerosis"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9315-8568","authenticated-orcid":true,"given":"Fion\u00e4","family":"Caratis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3423-3745","authenticated-orcid":true,"given":"Miko\u0142aj","family":"Opie\u0142ka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Hausmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2886-122X","authenticated-orcid":true,"given":"Maria","family":"Velasco-Estevez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart\u0142omiej","family":"Rojek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl","family":"de Valli\u00e8re","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Seuwen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard","family":"Rogler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bartosz","family":"Karaszewski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7318-0597","authenticated-orcid":true,"given":"Aleksandra","family":"Rutkowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,3,25]]},"reference":[{"key":"pone.0283060.ref001","doi-asserted-by":"crossref","first-page":"9083","DOI":"10.1074\/jbc.M407832200","article-title":"Identification of T Cell Death-associated Gene 8 (TDAG8) as a Novel Acid Sensing G-protein-coupled Receptor","volume":"280","author":"S Ishii","year":"2005","journal-title":"J Biol Chem"},{"key":"pone.0283060.ref002","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/nature01905","article-title":"Proton-sensing G-protein-coupled receptors","volume":"425","author":"M-G Ludwig","year":"2003","journal-title":"Nature"},{"key":"pone.0283060.ref003","doi-asserted-by":"crossref","first-page":"123","DOI":"10.3389\/fimmu.2016.00123","article-title":"The cAMP Pathway as Therapeutic Target in Autoimmune and Inflammatory Diseases","volume":"7","author":"VK Raker","year":"2016","journal-title":"Front Immunol"},{"key":"pone.0283060.ref004","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1016\/j.cellsig.2010.11.018","article-title":"Cyclic AMP-mediated immune regulation\u2014Overview of mechanisms of action in T cells","volume":"23","author":"R Mosenden","year":"2011","journal-title":"Cell Signal"},{"key":"pone.0283060.ref005","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1093\/ecco-jcc\/jjy152","article-title":"Lack of the pH-sensing Receptor TDAG8 [GPR65] in Macrophages Plays a Detrimental Role in Murine Models of Inflammatory Bowel Disease","volume":"13","author":"I Tcymbarevich","year":"2019","journal-title":"J Crohns Colitis"},{"key":"pone.0283060.ref006","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1016\/j.tips.2008.08.002","article-title":"G12\/G13-mediated signalling in mammalian physiology and disease","volume":"29","author":"T Worzfeld","year":"2008","journal-title":"Trends Pharmacol Sci"},{"key":"pone.0283060.ref007","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.neurobiolaging.2020.12.007","article-title":"Decreased pH in the aging brain and Alzheimer\u2019s disease","volume":"101","author":"Y Decker","year":"2021","journal-title":"Neurobiol Aging"},{"key":"pone.0283060.ref008","first-page":"1619","article-title":"Inflammatory CNS demyelination: histopathologic correlation with in vivo quantitative proton MR spectroscopy","volume":"20","author":"A Bitsch","year":"1999","journal-title":"AJNR Am J Neuroradiol"},{"key":"pone.0283060.ref009","first-page":"1","article-title":"Tissue Acidosis Associated with Ischemic Stroke to Guide Neuroprotective Drug Delivery","volume":"9","author":"OM T\u00f3th","year":"2020","journal-title":"Biology (Basel)"},{"key":"pone.0283060.ref010","first-page":"1","article-title":"The protective role of proton-sensing TDAG8 in the brain injury in a mouse ischemia reperfusion model","volume":"10","author":"K Sato","year":"2020","journal-title":"Sci Reports"},{"key":"pone.0283060.ref011","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1038\/nm1668","article-title":"Acid-sensing ion channel-1 contributes to axonal degeneration in autoimmune inflammation of the central nervous system","volume":"13","author":"MA Friese","year":"2007","journal-title":"Nat Med"},{"key":"pone.0283060.ref012","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1093\/brain\/awq337","article-title":"Acid-sensing ion channel 1 is involved in both axonal injury and demyelination in multiple sclerosis and its animal model","volume":"134","author":"S Vergo","year":"2011","journal-title":"Brain"},{"key":"pone.0283060.ref013","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1038\/ng.2770","article-title":"Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis","volume":"45","author":"AH Beecham","year":"2013","journal-title":"Nat Genet"},{"key":"pone.0283060.ref014","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1038\/nature10251","article-title":"Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis","volume":"476","author":"S Sawcer","year":"2011","journal-title":"Nature"},{"key":"pone.0283060.ref015","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.biopsych.2016.04.022","article-title":"Microglial Acid Sensing Regulates Carbon Dioxide-Evoked Fear","volume":"80","author":"LL Vollmer","year":"2016","journal-title":"Biol Psychiatry"},{"key":"pone.0283060.ref016","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1111\/jnc.12661","article-title":"Inhibition of interleukin-1\u03b2 production by extracellular acidification through the TDAG8\/cAMP pathway in mouse microglia","volume":"129","author":"Y Jin","year":"2014","journal-title":"J Neurochem"},{"key":"pone.0283060.ref017","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s12974-017-0825-6","article-title":"Astrocyte-specific overexpressed gene signatures in response to methamphetamine exposure in vitro","volume":"14","author":"N Bortell","year":"2017","journal-title":"J Neuroinflammation"},{"key":"pone.0283060.ref018","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.mcn.2007.06.010","article-title":"Nociceptors of dorsal root ganglion express proton-sensing G-protein-coupled receptors","volume":"36","author":"CW Huang","year":"2007","journal-title":"Mol Cell Neurosci"},{"key":"pone.0283060.ref019","article-title":"Expression and function of proton-sensing G-protein-coupled receptors in inflammatory pain","volume":"5","author":"YJ Chen","year":"2009","journal-title":"Mol Pain"},{"key":"pone.0283060.ref020","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1016\/j.cell.2015.11.009","article-title":"Single-Cell Genomics Unveils Critical Regulators of Th17 Cell Pathogenicity","volume":"163","author":"JT Gaublomme","year":"2015","journal-title":"Cell"},{"key":"pone.0283060.ref021","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.cell.2012.09.016","article-title":"A validated regulatory network for Th17 cell specification","volume":"151","author":"M Ciofani","year":"2012","journal-title":"Cell"},{"key":"pone.0283060.ref022","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1111\/imcb.1031","article-title":"GPR65 inhibits experimental autoimmune encephalomyelitis through CD4+ T cell independent mechanisms that include effects on iNKT cells","volume":"96","author":"RC Wirasinha","year":"2018","journal-title":"Immunol Cell Biol"},{"key":"pone.0283060.ref023","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1194\/jlr.M600084-JLR200","article-title":"Krabbe disease: psychosine-mediated activation of phospholipase A2 in oligodendrocyte cell death","volume":"47","author":"S Giri","year":"2006","journal-title":"J Lipid Res"},{"key":"pone.0283060.ref024","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1186\/s12974-017-1025-0","article-title":"EBI2 receptor regulates myelin development and inhibits LPC-induced demyelination","volume":"14","author":"A Rutkowska","year":"2017","journal-title":"J Neuroinflammation"},{"key":"pone.0283060.ref025","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1002\/glia.22272","article-title":"S1P1 receptor subtype inhibits demyelination and regulates chemokine release in cerebellar slice cultures","volume":"60","author":"GK Sheridan","year":"2012","journal-title":"Glia"},{"key":"pone.0283060.ref026","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1002\/glia.23148","article-title":"Demyelination induced by oxidative stress is regulated by sphingosine 1-phosphate receptors","volume":"65","author":"SA O\u2019Sullivan","year":"2017","journal-title":"Glia"},{"key":"pone.0283060.ref027","doi-asserted-by":"crossref","DOI":"10.3390\/ijms22094342","article-title":"Ebi2 is temporarily upregulated in mo3.13 oligodendrocytes during maturation and regulates remyelination in the organotypic cerebellar slice model","volume":"22","author":"M Velasco-Estevez","year":"2021","journal-title":"Int J Mol Sci"},{"key":"pone.0283060.ref028","doi-asserted-by":"crossref","DOI":"10.3389\/fncel.2022.914985","article-title":"Mechanoreceptor Piezo1 Is Downregulated in Multiple Sclerosis Brain and Is Involved in the Maturation and Migration of Oligodendrocytes in vitro","volume":"16","author":"M Velasco-Estevez","year":"2022","journal-title":"Front Cell Neurosci"},{"key":"pone.0283060.ref029","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1242\/jcs.198564","article-title":"Neuronal hyperactivity causes Na +\/H + exchanger-induced extracellular acidification at active synapses","volume":"130","author":"M Chiacchiaretta","year":"2017","journal-title":"J Cell Sci"},{"key":"pone.0283060.ref030","doi-asserted-by":"crossref","DOI":"10.1186\/s12974-016-0747-8","article-title":"Acute neuroinflammation provokes intracellular acidification in mouse hippocampus","volume":"13","author":"AA Tyrtyshnaia","year":"2016","journal-title":"J Neuroinflammation"},{"key":"pone.0283060.ref031","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1038\/jcbfm.2012.15","article-title":"pH as a biomarker of neurodegeneration in Huntington\u2019s disease: a translational rodent-human MRS study","volume":"32","author":"MM Chaumeil","year":"2012","journal-title":"J Cereb Blood Flow Metab"},{"key":"pone.0283060.ref032","author":"X-M Zha","journal-title":"pH and proton-sensitive receptors in brain ischemia"},{"key":"pone.0283060.ref033","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.neuropharm.2018.01.029","article-title":"EBI2 regulates pro-inflammatory signalling and cytokine release in astrocytes","volume":"133","author":"A Rutkowska","year":"2018","journal-title":"Neuropharmacology"},{"key":"pone.0283060.ref034","doi-asserted-by":"crossref","first-page":"17309","DOI":"10.1073\/pnas.1001165107","article-title":"The G protein-coupled receptor T-cell death-associated gene 8 (TDAG8) facilitates tumor development by serving as an extracellular pH sensor","volume":"107","author":"Y Ihara","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0283060.ref035","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1006\/cimm.1996.0051","article-title":"Identification of a putative G protein-coupled receptor induced during activation-induced apoptosis of T cells","volume":"168","author":"JW Choi","year":"1996","journal-title":"Cell Immunol"},{"key":"pone.0283060.ref036","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1016\/j.cellsig.2005.06.002","article-title":"Proton-sensing and lysolipid-sensitive G-protein-coupled receptors: a novel type of multi-functional receptors","volume":"17","author":"H Tomura","year":"2005","journal-title":"Cell Signal"},{"key":"pone.0283060.ref037","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.ejphar.2011.01.005","article-title":"Activation of T cell death-associated gene 8 attenuates inflammation by negatively regulating the function of inflammatory cells","volume":"654","author":"Y Onozawa","year":"2011","journal-title":"Eur J Pharmacol"},{"key":"pone.0283060.ref038","doi-asserted-by":"crossref","DOI":"10.3390\/cells10082050","article-title":"Proton-Sensing GPCRs in Health and Disease","volume":"10","author":"M Sisignano","year":"2021","journal-title":"Cells"},{"key":"pone.0283060.ref039","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1002\/glia.22637","article-title":"The selective anti-IL17A monoclonal antibody secukinumab (AIN457) attenuates IL17A-induced levels of IL6 in human astrocytes","volume":"62","author":"G Elain","year":"2014","journal-title":"Glia"},{"key":"pone.0283060.ref040","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0076048","article-title":"Extracellular Acidic pH Inhibits Oligodendrocyte Precursor Viability, Migration, and Differentiation","volume":"8","author":"A Jagielska","year":"2013","journal-title":"PLoS One"},{"key":"pone.0283060.ref041","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1002\/glia.22757","article-title":"EBI2 regulates intracellular signaling and migration in human astrocyte","volume":"63","author":"A Rutkowska","year":"2015","journal-title":"Glia"},{"key":"pone.0283060.ref042","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1016\/j.celrep.2017.01.020","article-title":"EBI2 Is Highly Expressed in Multiple Sclerosis Lesions and Promotes Early CNS Migration of Encephalitogenic CD4 T Cells","volume":"18","author":"F Wanke","year":"2017","journal-title":"Cell Rep"},{"key":"pone.0283060.ref043","doi-asserted-by":"crossref","first-page":"10130","DOI":"10.1073\/pnas.1821306116","article-title":"Gene expression in oligodendrocytes during remyelination reveals cholesterol homeostasis as a therapeutic target in multiple sclerosis","volume":"116","author":"RR Voskuhl","year":"2019","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0283060.ref044","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/j.bbadis.2016.12.005","article-title":"GPR4 deficiency alleviates intestinal inflammation in a mouse model of acute experimental colitis","volume":"1863","author":"EJ Sanderlin","year":"2017","journal-title":"Biochim Biophys acta Mol basis Dis"},{"key":"pone.0283060.ref045","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1111\/j.1471-4159.2010.07136.x","article-title":"Synergistic Activity of Interleukin-17 and Tumor Necrosis Factor-\u03b1 Enhances Oxidative Stress-Mediated Oligodendrocyte Apoptosis","volume":"116","author":"MK Paintlia","year":"2011","journal-title":"J Neurochem"},{"key":"pone.0283060.ref046","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1309\/AJCP7UBK8IBVMVNR","article-title":"Analysis of proinflammatory and anti-inflammatory cytokine serum concentrations in patients with multiple sclerosis by using a multiplexed immunoassay","volume":"136","author":"TB Martins","year":"2011","journal-title":"Am J Clin Pathol"},{"key":"pone.0283060.ref047","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1056\/NEJM199108153250704","article-title":"Association between tumor necrosis factor-alpha and disease progression in patients with multiple sclerosis","volume":"325","author":"MK Sharief","year":"1991","journal-title":"N Engl J Med"},{"key":"pone.0283060.ref048","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.cellimm.2005.11.002","article-title":"Therapeutic efficacy of IL-17 neutralization in murine experimental autoimmune encephalomyelitis","volume":"237","author":"HH Hofstetter","year":"2005","journal-title":"Cell Immunol"},{"key":"pone.0283060.ref049","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.it.2011.02.007","article-title":"IL-17 receptor signaling and T helper 17-mediated autoimmune demyelinating disease","volume":"32","author":"J Zepp","year":"2011","journal-title":"Trends Immunol"},{"key":"pone.0283060.ref050","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1038\/ni1261","article-title":"A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17","volume":"6","author":"H Park","year":"2005","journal-title":"Nat Immunol"},{"key":"pone.0283060.ref051","doi-asserted-by":"crossref","first-page":"3243","DOI":"10.4049\/jimmunol.0803466","article-title":"Involvement of Proton-Sensing TDAG8 in Extracellular Acidification-Induced Inhibition of Proinflammatory Cytokine Production in Peritoneal Macrophages","volume":"182","author":"C Mogi","year":"2009","journal-title":"J Immunol"},{"key":"pone.0283060.ref052","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.ejphar.2012.03.007","article-title":"Activation of T cell death-associated gene 8 regulates the cytokine production of T cells and macrophages in vitro","volume":"683","author":"Y Onozawa","year":"2012","journal-title":"Eur J Pharmacol"},{"key":"pone.0283060.ref053","doi-asserted-by":"crossref","first-page":"28931","DOI":"10.3390\/ijms161226145","article-title":"Protective Role of Proton-Sensing TDAG8 in Lipopolysaccharide-Induced Acute Lung Injury","volume":"16","author":"H Tsurumaki","year":"2015","journal-title":"Int J Mol Sci"},{"key":"pone.0283060.ref054","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1002\/jnr.21051","article-title":"pH is an intracellular effector controlling differentiation of oligodendrocyte precursors in culture via activation of the ERK1\/2 pathway","volume":"84","author":"F Bernard","year":"2006","journal-title":"J Neurosci Res"},{"key":"pone.0283060.ref055","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1038\/s41586-019-1484-9","article-title":"Niche stiffness underlies the aging of central nervous system progenitor cells","volume":"573","author":"M Segel","year":"2019","journal-title":"Nature"},{"key":"pone.0283060.ref056","doi-asserted-by":"crossref","first-page":"5167","DOI":"10.1074\/jbc.M114.604033","article-title":"Protonation of the Human PIEZO1 Ion Channel Stabilizes Inactivation","volume":"290","author":"C Bae","year":"2015","journal-title":"J Biol Chem"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0283060","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T00:23:37Z","timestamp":1731630217000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0283060"}},"subtitle":[],"editor":[{"given":"Belgin","family":"Sever","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,3,25]]},"references-count":56,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,3,25]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0283060","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,25]]}}}