{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T05:17:39Z","timestamp":1777871859527,"version":"3.51.4"},"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R21DE027873-01A1"],"award-info":[{"award-number":["R21DE027873-01A1"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R01DE030296"],"award-info":[{"award-number":["R01DE030296"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["F31DE031967-01A1"],"award-info":[{"award-number":["F31DE031967-01A1"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R21DE027873-01A1"],"award-info":[{"award-number":["R21DE027873-01A1"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R01DE030296 (awarded"],"award-info":[{"award-number":["R01DE030296 (awarded"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Osteoarthritis is a degenerative joint disease that disrupts the cellular homeostasis within cartilage tissues, promoting further disease progression that can lead to debilitating pain. Cartilage of the temporomandibular joint (TMJ) is unique among diarthrodial joints because they are of neural crest origin, rather than the mesoderm germ layer. TMJ cartilage also has different cellular architecture, where it is composed of a superficial fibrous layer, a proliferative layer, and a fibrocartilage layer overlying subchondral bone. Understanding of the cytopathological changes that occur during TMJ osteoarthritis (TMJOA) could potentiate therapies to mitigate disease progression and repair diseased tissues. Here, we analyzed the unique cell populations present in healthy and OA-induced condylar cartilage of adult rats through single-cell RNA-sequencing. TMJOA was established via our previous rat model to study the changes in the cellular composition of the condyle in response to OA. Several cell types could be uniquely identified, and the prominent matrix producing cells were fibroblasts and chondrocyte subsets. Our trajectory and pseudotime analysis revealed three cell fates stemming from a fibrochondrocyte-like population and two chondrocyte cell fates that stem from a shared progenitor population. We also found that Pleiotrophin is uniquely expressed in the proliferative zone by cells with a chondrocyte progenitor phenotype. In OA cartilage, differential gene expression in the fibroblast group revealed responses to inflammation, possibly through activation of chondrocyte differentiation. The chondrocyte group was highly metabolically active, indicative of rapid repair or remodeling. Cell-cell signaling analysis revealed that chondrocyte and chondrocyte progenitor communication became highly activated. Additionally, intracellular pathways that may contribute to cellular dysfunction and tissue remodeling were highly active, while pathways related to tissue catabolism appeared less active.<\/jats:p>","DOI":"10.1371\/journal.pone.0348175","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T17:32:11Z","timestamp":1777570331000},"page":"e0348175","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Single-cell RNA sequencing of healthy and diseased rat temporomandibular joint condyle cartilage"],"prefix":"10.1371","volume":"21","author":[{"given":"Sara","family":"Trbojevic","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xudong","family":"Dong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Lafyatis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael S.","family":"Gold","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan M.","family":"Taboas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4602-9258","authenticated-orcid":true,"given":"Alejandro J.","family":"Almarza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"pone.0348175.ref001","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1111\/j.1469-7580.2008.01009.x","article-title":"Development of the mandibular condylar cartilage in human specimens of 10-15 weeks\u2019 gestation","volume":"214","author":"JR M\u00e9rida Velasco","year":"2009","journal-title":"J Anat"},{"key":"pone.0348175.ref002","article-title":"Temporomandibular disorders: priorities for research and care","author":"O Yost","year":"2020","journal-title":"Washington (DC): National Academies Press (US)"},{"key":"pone.0348175.ref003","unstructured":"Trbojevic S, Pineda-Farias JB, Gold MS, Verdelis K, Lukshova L, Almarza AJ. Mechanically induced osteoarthritis rat model to study the development of pain. 2025."},{"key":"pone.0348175.ref004","doi-asserted-by":"crossref","first-page":"46","DOI":"10.22203\/eCM.v045a04","article-title":"Mandibular condylar process remodeling in rats with different bite-altering devices","volume":"45","author":"W Li","year":"2023","journal-title":"Eur Cell Mater"},{"key":"pone.0348175.ref005","article-title":"CellMarker 2.0: an updated database of manually curated cell markers in human\/mouse and web tools based on scRNA-seq data","volume":"51","author":"C Hu","year":"2023","journal-title":"Nucleic Acids Res"},{"key":"pone.0348175.ref006","article-title":"PanglaoDB: a web server for exploration of mouse and human single-cell RNA sequencing data","author":"O Franz\u00e9n","year":"2019","journal-title":"Database (Oxford)"},{"issue":"2","key":"pone.0348175.ref007","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.joca.2011.12.004","article-title":"Molecular differentiation between osteophytic and articular cartilage--clues for a transient and permanent chondrocyte phenotype","volume":"20","author":"K Gelse","year":"2012","journal-title":"Osteoarthr Cartil"},{"key":"pone.0348175.ref008","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1186\/s13578-019-0344-5","article-title":"KIF5B modulates central spindle organization in late-stage cytokinesis in chondrocytes","volume":"9","author":"H Gan","year":"2019","journal-title":"Cell Biosci"},{"issue":"7","key":"pone.0348175.ref009","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0180856","article-title":"Functional analysis of the zebrafish ortholog of HMGCS1 reveals independent functions for cholesterol and isoprenoids in craniofacial development","volume":"12","author":"AM Quintana","year":"2017","journal-title":"PLoS One"},{"issue":"4","key":"pone.0348175.ref010","doi-asserted-by":"crossref","first-page":"590","DOI":"10.3390\/ijms17040590","article-title":"Matrilin-3 Role in Cartilage Development and Osteoarthritis","volume":"17","author":"MS Muttigi","year":"2016","journal-title":"Int J Mol Sci"},{"issue":"2","key":"pone.0348175.ref011","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.cellsig.2007.10.028","article-title":"The RGK family of GTP-binding proteins: regulators of voltage-dependent calcium channels and cytoskeleton remodeling","volume":"20","author":"RN Correll","year":"2008","journal-title":"Cell Signal"},{"issue":"4","key":"pone.0348175.ref012","doi-asserted-by":"crossref","first-page":"688","DOI":"10.3390\/biom13040688","article-title":"The Multifaceted Role of Glutathione S-Transferases in Health and Disease","volume":"13","author":"AMA Mazari","year":"2023","journal-title":"Biomolecules"},{"issue":"809","key":"pone.0348175.ref013","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.adm9488","article-title":"NFIA regulates articular chondrocyte fatty acid metabolism and joint homeostasis","volume":"17","author":"C Wang","year":"2025","journal-title":"Sci Transl Med"},{"issue":"12","key":"pone.0348175.ref014","doi-asserted-by":"crossref","DOI":"10.1111\/cpr.13156","article-title":"Osteoblasts impair cholesterol synthesis in chondrocytes via Notch1 signalling","volume":"54","author":"Y Yang","year":"2021","journal-title":"Cell Prolif"},{"issue":"1","key":"pone.0348175.ref015","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1186\/s13075-020-02295-9","article-title":"The alarmins S100A8 and S100A9 mediate acute pain in experimental synovitis","volume":"22","author":"AB Blom","year":"2020","journal-title":"Arthritis Res Ther"},{"issue":"1","key":"pone.0348175.ref016","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s40246-021-00321-8","article-title":"Cathelicidin antimicrobial peptide (CAMP) gene promoter methylation induces chondrocyte apoptosis","volume":"15","author":"G Wang","year":"2021","journal-title":"Hum Genomics"},{"issue":"6","key":"pone.0348175.ref017","doi-asserted-by":"crossref","first-page":"2156","DOI":"10.1002\/jcb.24089","article-title":"Ski inhibits TGF-\u03b2\/phospho-Smad3 signaling and accelerates hypertrophic differentiation in chondrocytes","volume":"113","author":"K-O Kim","year":"2012","journal-title":"J Cell Biochem"},{"issue":"1","key":"pone.0348175.ref018","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1038\/s42003-021-02793-9","article-title":"Zfhx4 regulates endochondral ossification as the transcriptional platform of Osterix in mice","volume":"4","author":"E Nakamura","year":"2021","journal-title":"Commun Biol"},{"key":"pone.0348175.ref019","doi-asserted-by":"crossref","first-page":"16050","DOI":"10.1038\/celldisc.2016.50","article-title":"RNA-binding protein SAMD4 regulates skeleton development through translational inhibition of Mig6 expression","volume":"3","author":"N Niu","year":"2017","journal-title":"Cell Discov"},{"issue":"1","key":"pone.0348175.ref020","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.joca.2019.10.011","article-title":"Lumican is upregulated in osteoarthritis and contributes to TLR4-induced pro-inflammatory activation of cartilage degradation and macrophage polarization","volume":"28","author":"G Barreto","year":"2020","journal-title":"Osteoarthr Cartil"},{"issue":"2","key":"pone.0348175.ref021","doi-asserted-by":"crossref","DOI":"10.1186\/ar2153","article-title":"Microenvironmental changes during differentiation of mesenchymal stem cells towards chondrocytes","volume":"9","author":"F Djouad","year":"2007","journal-title":"Arthritis Res Ther"},{"issue":"1","key":"pone.0348175.ref022","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1302\/2046-3758.121.BJR-2022-0231.R1","article-title":"CircStrn3 targeting microRNA-9-5p is involved in the regulation of cartilage degeneration and subchondral bone remodelling in osteoarthritis","volume":"12","author":"B Li","year":"2023","journal-title":"Bone Joint Res"},{"key":"pone.0348175.ref023","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.bone.2018.08.017","article-title":"The study of GPX3 methylation in patients with Kashin-Beck Disease and its mechanism in chondrocyte apoptosis","volume":"117","author":"L Han","year":"2018","journal-title":"Bone"},{"key":"pone.0348175.ref024","doi-asserted-by":"crossref","first-page":"116076","DOI":"10.1016\/j.bone.2021.116076","article-title":"Cholesterol metabolism related genes in osteoarthritis","volume":"152","author":"I Papathanasiou","year":"2021","journal-title":"Bone"},{"issue":"4","key":"pone.0348175.ref025","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/j.joca.2008.08.004","article-title":"Complement 1s is the serine protease that cleaves IGFBP-5 in human osteoarthritic joint fluid","volume":"17","author":"WH Busby","year":"2009","journal-title":"Osteoarthr Cartil"},{"issue":"3","key":"pone.0348175.ref026","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1136\/annrheumdis-2020-218344","article-title":"OATargets: a knowledge base of genes associated with osteoarthritis joint damage in animals","volume":"80","author":"J Soul","year":"2021","journal-title":"Ann Rheum Dis"},{"issue":"2","key":"pone.0348175.ref027","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1002\/sctm.19-0190","article-title":"Neural cell adhesion molecule regulates chondrocyte hypertrophy in chondrogenic differentiation and experimental osteoarthritis","volume":"9","author":"B-F Cheng","year":"2020","journal-title":"Stem Cells Transl Med"},{"issue":"5","key":"pone.0348175.ref028","doi-asserted-by":"crossref","first-page":"3044","DOI":"10.3390\/ijms25053044","article-title":"Molecular Mechanisms Linking Osteoarthritis and Alzheimer\u2019s Disease: Shared Pathways, Mechanisms and Breakthrough Prospects","volume":"25","author":"IO Umoh","year":"2024","journal-title":"Int J Mol Sci"},{"issue":"2","key":"pone.0348175.ref029","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.stemcr.2016.07.003","article-title":"MIF Plays a Key Role in Regulating Tissue-Specific Chondro-Osteogenic Differentiation Fate of Human Cartilage Endplate Stem Cells under Hypoxia","volume":"7","author":"Y Yao","year":"2016","journal-title":"Stem Cell Reports"},{"issue":"4","key":"pone.0348175.ref030","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1152\/physrev.00027.2021","article-title":"Adhesion G protein-coupled receptors: structure, signaling, physiology, and pathophysiology","volume":"102","author":"T Lala","year":"2022","journal-title":"Physiol Rev"},{"issue":"11","key":"pone.0348175.ref031","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.3390\/biom14111469","article-title":"Advances in the Regulation of Periostin for Osteoarthritic Cartilage Repair Applications","volume":"14","author":"SY Shih","year":"2024","journal-title":"Biomolecules"},{"issue":"22","key":"pone.0348175.ref032","article-title":"Single-cell transcriptomics identifies chondrocyte differentiation dynamics in vivo and in vitro","volume":"60","author":"JEG Lawrence","year":"2025","journal-title":"Dev Cell"},{"issue":"12","key":"pone.0348175.ref033","doi-asserted-by":"crossref","first-page":"2735","DOI":"10.1016\/j.ajhg.2024.10.019","article-title":"Primary cartilage transcriptional signatures reflect cell-type-specific molecular pathways underpinning osteoarthritis","volume":"111","author":"G Katsoula","year":"2024","journal-title":"Am J Hum Genet"},{"issue":"1","key":"pone.0348175.ref034","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1136\/annrheumdis-2017-212863","article-title":"Single-cell RNA-seq analysis reveals the progression of human osteoarthritis","volume":"78","author":"Q Ji","year":"2019","journal-title":"Ann Rheum Dis"},{"issue":"9","key":"pone.0348175.ref035","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1016\/j.joca.2021.06.010","article-title":"Single-cell RNA-seq analysis identifies unique chondrocyte subsets and reveals involvement of ferroptosis in human intervertebral disc degeneration","volume":"29","author":"Y Zhang","year":"2021","journal-title":"Osteoarthr Cartil"},{"issue":"17","key":"pone.0348175.ref036","doi-asserted-by":"crossref","first-page":"13137","DOI":"10.3390\/ijms241713137","article-title":"Osteoarthritis: Role of Peroxisome Proliferator-Activated Receptors","volume":"24","author":"W Sheng","year":"2023","journal-title":"Int J Mol Sci"},{"issue":"1","key":"pone.0348175.ref037","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/s41392-023-01330-w","article-title":"Osteoarthritis: pathogenic signaling pathways and therapeutic targets","volume":"8","author":"Q Yao","year":"2023","journal-title":"Signal Transduct Target Ther"},{"issue":"2","key":"pone.0348175.ref038","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1111\/1756-185X.13061","article-title":"Cholesterol metabolism in pathogenesis of osteoarthritis disease","volume":"20","author":"S Farnaghi","year":"2017","journal-title":"Int J Rheum Dis"},{"issue":"4","key":"pone.0348175.ref039","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.joca.2020.02.027","article-title":"The PI3K\/AKT\/mTOR signaling pathway in osteoarthritis: a narrative review","volume":"28","author":"K Sun","year":"2020","journal-title":"Osteoarthr Cartil"},{"issue":"1","key":"pone.0348175.ref040","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1136\/annrheumdis-2013-203901","article-title":"Inhibition of Rac1 activity by controlled release of NSC23766 from chitosan microspheres effectively ameliorates osteoarthritis development in vivo","volume":"74","author":"S Zhu","year":"2015","journal-title":"Ann Rheum Dis"},{"issue":"9","key":"pone.0348175.ref041","doi-asserted-by":"crossref","first-page":"4672","DOI":"10.3390\/ijms23094672","article-title":"Regulatory Mechanisms of Prg4 and Gdf5 Expression in Articular Cartilage and Functions in Osteoarthritis","volume":"23","author":"Y Takahata","year":"2022","journal-title":"Int J Mol Sci"},{"issue":"1","key":"pone.0348175.ref042","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1186\/s13075-019-2041-5","article-title":"Wnt\/\u03b2-catenin signaling contributes to articular cartilage homeostasis through lubricin induction in the superficial zone","volume":"21","author":"F Xuan","year":"2019","journal-title":"Arthritis Res Ther"},{"issue":"1","key":"pone.0348175.ref043","doi-asserted-by":"crossref","first-page":"10568","DOI":"10.1038\/s41598-024-61502-8","article-title":"Histological and immunohistochemical analyses of articular cartilage during onset and progression of pre- and early-stage osteoarthritis in a rodent model","volume":"14","author":"I Takahashi","year":"2024","journal-title":"Sci Rep"},{"issue":"1","key":"pone.0348175.ref044","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.joca.2016.07.021","article-title":"Lubricin\/proteoglycan 4 increases in both experimental and naturally occurring equine osteoarthritis","volume":"25","author":"HL Reesink","year":"2017","journal-title":"Osteoarthr Cartil"},{"key":"pone.0348175.ref045","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1089\/scd.2021.0324","article-title":"An Updated View on Temporomandibular Joint Degeneration: Insights from the Cell Subsets of Mandibular Condylar Cartilage","volume":"31","author":"M Xu","year":"2022","journal-title":"Stem Cells Dev"},{"issue":"7743","key":"pone.0348175.ref046","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1038\/s41586-019-0920-1","article-title":"The CH25H-CYP7B1-ROR\u03b1 axis of cholesterol metabolism regulates osteoarthritis","volume":"566","author":"W-S Choi","year":"2019","journal-title":"Nature"},{"issue":"6","key":"pone.0348175.ref047","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1038\/nm.3143","article-title":"Inhibition of TGF-\u03b2 signaling in mesenchymal stem cells of subchondral bone attenuates osteoarthritis","volume":"19","author":"G Zhen","year":"2013","journal-title":"Nat Med"},{"key":"pone.0348175.ref048","doi-asserted-by":"crossref","first-page":"1407679","DOI":"10.3389\/fimmu.2024.1407679","article-title":"Single-cell RNA sequencing reveals different chondrocyte states in femoral cartilage between osteoarthritis and healthy individuals","volume":"15","author":"Z Sun","year":"2024","journal-title":"Front Immunol"},{"issue":"19","key":"pone.0348175.ref049","doi-asserted-by":"crossref","first-page":"3984","DOI":"10.3390\/nu14193984","article-title":"Lipid Metabolism in Cartilage Development, Degeneration, and Regeneration","volume":"14","author":"Z Su","year":"2022","journal-title":"Nutrients"},{"issue":"2","key":"pone.0348175.ref050","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.stem.2024.01.003","article-title":"Metabolic regulation of the hallmarks of stem cell biology","volume":"31","author":"BT Jackson","year":"2024","journal-title":"Cell Stem Cell"},{"issue":"1","key":"pone.0348175.ref051","doi-asserted-by":"crossref","DOI":"10.1186\/ar4443","article-title":"Induction of nerve growth factor expression and release by mechanical and inflammatory stimuli in chondrocytes: possible involvement in osteoarthritis pain","volume":"16","author":"E Pecchi","year":"2014","journal-title":"Arthritis Res Ther"},{"issue":"1","key":"pone.0348175.ref052","doi-asserted-by":"crossref","first-page":"3225","DOI":"10.1038\/s41467-024-47633-6","article-title":"Nerve growth factor receptor limits inflammation to promote remodeling and repair of osteoarthritic joints","volume":"15","author":"L Zhao","year":"2024","journal-title":"Nat Commun"},{"issue":"6","key":"pone.0348175.ref053","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1111\/odi.12045","article-title":"Nerve growth factor induced after temporomandibular joint inflammation decelerates chondrocyte differentiation","volume":"19","author":"H Huang","year":"2013","journal-title":"Oral Dis"},{"key":"pone.0348175.ref054","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1186\/s13075-015-0840-x","article-title":"Cartilage stem\/progenitor cells are activated in osteoarthritis via interleukin-1\u03b2\/nerve growth factor signaling","volume":"17","author":"Y Jiang","year":"2015","journal-title":"Arthritis Res Ther"},{"issue":"5","key":"pone.0348175.ref055","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1097\/BOR.0b013e328349c2b1","article-title":"Inflammation in osteoarthritis","volume":"23","author":"MB Goldring","year":"2011","journal-title":"Curr Opin Rheumatol"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0348175","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T17:32:20Z","timestamp":1777570340000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0348175"}},"subtitle":[],"editor":[{"given":"James J","family":"Cray Jr","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2026,4,30]]},"references-count":55,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4,30]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0348175","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,30]]}}}