{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T14:15:34Z","timestamp":1781360134419,"version":"3.54.1"},"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2020,11,19]],"date-time":"2020-11-19T00:00:00Z","timestamp":1605744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"name":"Canadian Institutes of Health Research Grant-Regional partnership fund - Innovation PEI","award":["97027"],"award-info":[{"award-number":["97027"]}]},{"DOI":"10.13039\/501100005202","name":"University of Prince Edward Island","doi-asserted-by":"publisher","award":["Companion Animal Trust Fund Award 2012"],"award-info":[{"award-number":["Companion Animal Trust Fund Award 2012"]}],"id":[{"id":"10.13039\/501100005202","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>The purpose of this study was to evaluate matrix metalloproteinases (MMP) -2 and MMP-3 in serum, and keratinocyte-derived chemoattractant (KC), interleukin 8 (IL-8) and monocyte chemoattractant 1 (MCP-1) in synovial fluid (SF) as stifle osteoarthritis (OA) biomarkers in dogs. Dogs with naturally occurring cranial cruciate ligament (CrCL) rupture (OA group) and healthy controls were recruited. Stifles with CrCL deficiency were surgically stabilized. Serum, SF, and synovial biopsy samples were collected from the OA group preoperatively, whereas samples were collected once from control dogs. A blinded veterinary pathologist graded synovial biopsies. Serum and SF analyses were performed using xMAP technology. General linear regression was used for statistical comparisons of serum biomarkers, and mixed linear regression for SF biomarkers and temporal concentration changes. The overall discriminative ability was quantified using area under curve (AUC). Spearman\u2019s correlation coefficient was used to assess correlations between synovial histology grades and the biomarkers. Samples from 62 dogs in the OA group and 50 controls were included. The MMP-2 and MMP-3 concentrations between the OA and control groups were not significantly different, and both with an AUC indicating a poor discriminative ability. All three SF biomarker concentrations were significantly different between the OA group and controls (<jats:italic>P<\/jats:italic>&lt;0.05). The MCP-1 was the only biomarker showing an acceptable discriminative performance with an AUC of 0.91 (95% confidence interval: 0.83\u20130.98). The sum of the inflammatory infiltrate score was significantly correlated with all three SF biomarkers (<jats:italic>P<\/jats:italic>&lt;0.01). Summed synovial stroma, and all scores combined were significantly correlated with IL-8 and MCP-1 concentrations (<jats:italic>P<\/jats:italic>&lt;0.003), and the summed synoviocyte scores were significantly correlated with MCP-1 concentrations (<jats:italic>P<\/jats:italic>&lt;0.001). Correlations between MCP-1 concentrations and synovial histopathologic grading and its discriminative ability suggest its potential as a synovitis biomarker in canine stifle OA associated with CrCL rupture.<\/jats:p>","DOI":"10.1371\/journal.pone.0242614","type":"journal-article","created":{"date-parts":[[2020,11,19]],"date-time":"2020-11-19T19:09:31Z","timestamp":1605812971000},"page":"e0242614","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Evaluation of serum MMP-2 and MMP-3, synovial fluid IL-8, MCP-1, and KC concentrations as biomarkers of stifle osteoarthritis associated with naturally occurring cranial cruciate ligament rupture in dogs"],"prefix":"10.1371","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8809-8388","authenticated-orcid":true,"given":"Sarah","family":"Malek","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsin-Yi","family":"Weng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon A.","family":"Martinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark C.","family":"Rochat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"B\u00e9raud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher B.","family":"Riley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2020,11,19]]},"reference":[{"issue":"12","key":"pone.0242614.ref001","doi-asserted-by":"crossref","first-page":"1818","DOI":"10.2460\/javma.232.12.1818","article-title":"Prevalence of and risk factors for hip dysplasia and cranial cruciate ligament deficiency in dogs","volume":"232","author":"TH Witsberger","year":"2008","journal-title":"J Am Vet Med Assoc"},{"key":"pone.0242614.ref002","first-page":"109","volume-title":"Advances In The Canine Cruciate Ligament 1","author":"P. Baker LAM","year":"2018","edition":"2"},{"issue":"10","key":"pone.0242614.ref003","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.2460\/javma.2005.227.1604","article-title":"Estimate of the annual economic impact of treatment of cranial cruciate ligament injury in dogs in the United States","volume":"227","author":"VL Wilke","year":"2005","journal-title":"J Am Vet Med Assoc"},{"issue":"10","key":"pone.0242614.ref004","doi-asserted-by":"crossref","first-page":"e25331","DOI":"10.1371\/journal.pone.0025331","article-title":"Contralateral cruciate survival in dogs with unilateral non-contact cranial cruciate ligament rupture","volume":"6","author":"P Muir","year":"2011","journal-title":"PLoS One"},{"issue":"6","key":"pone.0242614.ref005","doi-asserted-by":"crossref","first-page":"889","DOI":"10.2460\/javma.232.6.889","article-title":"Comparison of tibial plateau angles in dogs with unilateral versus bilateral cranial cruciate ligament rupture: 150 cases (2000\u20132006)","volume":"232","author":"SY Cabrera","year":"2008","journal-title":"J Am Vet Med Assoc"},{"key":"pone.0242614.ref006","first-page":"115","volume-title":"Advances in the Canine Cranial Cruciate Ligament","author":"P Muir","year":"2018","edition":"2"},{"issue":"14","key":"pone.0242614.ref007","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1136\/vr.164.14.418","article-title":"Systematic review of the management of canine osteoarthritis","volume":"164","author":"RO Sanderson","year":"2009","journal-title":"Vet Rec"},{"issue":"13","key":"pone.0242614.ref008","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1136\/vr.103982","article-title":"Canine synovial fluid biomarkers for early detection and monitoring of osteoarthritis","volume":"180","author":"E de Bakker","year":"2017","journal-title":"Vet Rec"},{"issue":"2","key":"pone.0242614.ref009","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1111\/j.1532-950X.2007.00363.x","article-title":"Osteophytosis, subchondral bone sclerosis, joint effusion and soft tissue thickening in canine experimental stifle osteoarthritis: comparison between 1.5 T magnetic resonance imaging and computed radiography","volume":"37","author":"MA D'Anjou","year":"2008","journal-title":"Vet Surg"},{"issue":"2","key":"pone.0242614.ref010","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.joca.2018.09.016","article-title":"Models of osteoarthritis: the good, the bad and the promising","volume":"27","author":"PJ Cope","year":"2019","journal-title":"Osteoarthritis and Cartilage"},{"issue":"8","key":"pone.0242614.ref011","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1016\/j.joca.2015.03.036","article-title":"Call for standardized definitions of osteoarthritis and risk stratification for clinical trials and clinical use","volume":"23","author":"VB Kraus","year":"2015","journal-title":"Osteoarthritis Cartilage"},{"issue":"5","key":"pone.0242614.ref012","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1002\/art.24473","article-title":"Association of biomarkers with pre-radiographically defined and radiographically defined knee osteoarthritis in a population-based study","volume":"60","author":"J Cibere","year":"2009","journal-title":"Arthritis Rheum"},{"issue":"1","key":"pone.0242614.ref013","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.berh.2014.01.007","article-title":"Biomarkers for osteoarthritis: current position and steps towards further validation","volume":"28","author":"DJ Hunter","year":"2014","journal-title":"Best Pract Res Clin Rheumatol"},{"key":"pone.0242614.ref014","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1146\/annurev.pharmtox.41.1.347","article-title":"Use of biomarkers and surrogate endpoints in drug development and regulatory decision making: Criteria, validation, strategies","volume":"41","author":"LJ Lesko","year":"2001","journal-title":"Annu Rev Pharmacol"},{"issue":"4","key":"pone.0242614.ref015","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1055\/s-0031-1297361","article-title":"Using animal models in osteoarthritis biomarker research","volume":"24","author":"BC Garner","year":"2011","journal-title":"J Knee Surg"},{"issue":"3","key":"pone.0242614.ref016","doi-asserted-by":"crossref","first-page":"429","DOI":"10.2460\/ajvr.67.3.429","article-title":"Serum and synovial fluid concentrations of keratan sulfate and hyaluronan in dogs with induced stifle joint osteoarthritis following cranial cruciate ligament transection","volume":"67","author":"SC Budsberg","year":"2006","journal-title":"Am J Vet Res"},{"issue":"1","key":"pone.0242614.ref017","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1136\/ard.2002.003624","article-title":"Treatment with licofelone prevents abnormal subchondral bone cell metabolism in experimental dog osteoarthritis","volume":"63","author":"D Lajeunesse","year":"2004","journal-title":"Ann Rheum Dis"},{"issue":"2","key":"pone.0242614.ref018","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1053\/joca.2001.0491","article-title":"The canine 'groove' model, compared with the ACLT model of osteoarthritis","volume":"10","author":"AC Marijnissen","year":"2002","journal-title":"Osteoarthritis Cartilage"},{"issue":"2","key":"pone.0242614.ref019","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1002\/jor.1100180216","article-title":"Longitudinal characterization of synovial fluid biomarkers in the canine meniscectomy model of osteoarthritis","volume":"18","author":"E Lindhorst","year":"2000","journal-title":"J Orthop Res"},{"issue":"4","key":"pone.0242614.ref020","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1016\/S0736-0266(03)00002-0","article-title":"Spontaneous and experimental osteoarthritis in dog: similarities and differences in proteoglycan levels","volume":"21","author":"W Liu","year":"2003","journal-title":"J Orthop Res"},{"issue":"2","key":"pone.0242614.ref021","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1208\/s12248-013-9454-x","article-title":"Animal models of osteoarthritis: challenges of model selection and analysis.","volume":"15","author":"E Teeple","year":"2013","journal-title":"AAPS J"},{"issue":"9","key":"pone.0242614.ref022","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.2460\/ajvr.1997.58.09.1027","article-title":"Synovial fluid interleukin 6, tumor necrosis factor, and nitric oxide values in dogs with osteoarthritis secondary to cranial cruciate ligament rupture","volume":"58","author":"CW Hay","year":"1997","journal-title":"Am J Vet Res"},{"issue":"2","key":"pone.0242614.ref023","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/s11259-017-9680-2","article-title":"Correlation between osteoarthritic changes in the stifle joint in dogs and the results of orthopedic, radiographic, ultrasonographic and arthroscopic examinations","volume":"41","author":"GI Ramirez-Flores","year":"2017","journal-title":"Vet Res Commun"},{"key":"pone.0242614.ref024","first-page":"217","volume-title":"Advances in the canine cranial cruciate ligament","author":"SL Schafer","year":"2018"},{"key":"pone.0242614.ref025","first-page":"189","volume-title":"Advances in the canine cranial cruciate ligament","author":"S.E. Tinga SK","year":"2018","edition":"2"},{"issue":"3","key":"pone.0242614.ref026","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1111\/j.1532-950X.2010.00675.x","article-title":"Detection and evaluation of matrix metalloproteinases involved in cruciate ligament disease in dogs using multiplex bead technology","volume":"39","author":"LA Breshears","year":"2010","journal-title":"Vet Surg"},{"key":"pone.0242614.ref027","first-page":"396","volume-title":"Piermattei\u2019s Atlas of Surgical Approaches to the Bones and Joints of Dog and Cat","author":"K. Johnson","year":"2014","edition":"5"},{"issue":"Suppl 3","key":"pone.0242614.ref028","doi-asserted-by":"crossref","first-page":"S53","DOI":"10.1016\/j.joca.2010.05.029","article-title":"The OARSI histopathology initiative\u2014recommendations for histological assessments of osteoarthritis in the rabbit","volume":"18","author":"S Laverty","year":"2010","journal-title":"Osteoarthritis Cartilage"},{"issue":"Suppl 3","key":"pone.0242614.ref029","doi-asserted-by":"crossref","first-page":"S66","DOI":"10.1016\/j.joca.2010.04.017","article-title":"The OARSI histopathology initiative\u2014recommendations for histological assessments of osteoarthritis in the dog","volume":"18","author":"JL Cook","year":"2010","journal-title":"Osteoarthritis Cartilage"},{"key":"pone.0242614.ref030","doi-asserted-by":"crossref","first-page":"834208","DOI":"10.1155\/2012\/834208","article-title":"Recent findings on the role of gelatinases (matrix metalloproteinase-2 and -9) in osteoarthritis","volume":"2012","author":"O Galasso","year":"2012","journal-title":"Adv Orthop"},{"issue":"4","key":"pone.0242614.ref031","doi-asserted-by":"crossref","first-page":"14811","DOI":"10.4238\/2015.November.18.46","article-title":"High MMP-1, MMP-2, and MMP-9 protein levels in osteoarthritis","volume":"14","author":"GQ Zeng","year":"2015","journal-title":"Genet Mol Res"},{"issue":"3","key":"pone.0242614.ref032","doi-asserted-by":"crossref","first-page":"210","DOI":"10.3415\/VCOT-13-06-0082","article-title":"MMP-2 as an early synovial biomarker for cranial cruciate ligament disease in dogs","volume":"27","author":"L Boland","year":"2014","journal-title":"Vet Comp Orthop Traumatol"},{"issue":"1","key":"pone.0242614.ref033","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.tvjl.2011.10.028","article-title":"Matrix metalloproteinase activity in stifle synovial fluid of cranial cruciate ligament deficient dogs and effect of postoperative doxycycline treatment","volume":"193","author":"M Rabillard","year":"2012","journal-title":"Vet J"},{"issue":"3","key":"pone.0242614.ref034","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1002\/art.1780330312","article-title":"The role of stromelysin in the cartilage destruction that accompanies inflammatory arthritis","volume":"33","author":"KA Hasty","year":"1990","journal-title":"Arthritis Rheum"},{"issue":"10","key":"pone.0242614.ref035","doi-asserted-by":"crossref","first-page":"2625","DOI":"10.1002\/art.10547","article-title":"Significant increases in serum and plasma concentrations of matrix metalloproteinases 3 and 9 in patients with rapidly destructive osteoarthritis of the hip","volume":"46","author":"K Masuhara","year":"2002","journal-title":"Arthritis Rheum"},{"issue":"3\u20134","key":"pone.0242614.ref036","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/S0165-2427(03)00005-9","article-title":"Synovial MMP-3 and TIMP-1 levels and their correlation with cytokine expression in canine rheumatoid arthritis","volume":"91","author":"N Hegemann","year":"2003","journal-title":"Vet Immunol Immunopathol"},{"issue":"5","key":"pone.0242614.ref037","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1111\/j.1532-950X.2005.00073.x","article-title":"Collagenolytic protease expression in cranial cruciate ligament and stifle synovial fluid in dogs with cranial cruciate ligament rupture","volume":"34","author":"P Muir","year":"2005","journal-title":"Vet Surg"},{"issue":"2","key":"pone.0242614.ref038","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1093\/oxfordjournals.molbev.a026101","article-title":"Isolation of novel GRO genes and a phylogenetic analysis of the CXC chemokine subfamily in mammals","volume":"16","author":"WS Modi","year":"1999","journal-title":"Mol Biol Evol"},{"issue":"3","key":"pone.0242614.ref039","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/S0014-5793(99)00886-8","article-title":"Flow cytometric analysis of intracellular chemokines in chondrocytes in vivo: constitutive expression and enhancement in osteoarthritis and rheumatoid arthritis","volume":"455","author":"RM Borzi","year":"1999","journal-title":"FEBS Lett"},{"issue":"5","key":"pone.0242614.ref040","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1111\/j.1532-950X.2011.00841.x","article-title":"Synovitis in dogs with stable stifle joints and incipient cranial cruciate ligament rupture: a cross-sectional study","volume":"40","author":"JA Bleedorn","year":"2011","journal-title":"Vet Surg"},{"issue":"6","key":"pone.0242614.ref041","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1089\/jir.2008.0027","article-title":"Monocyte chemoattractant protein-1 (MCP-1): an overview","volume":"29","author":"SL Deshmane","year":"2009","journal-title":"Journal of interferon & cytokine research: the official journal of the International Society for Interferon and Cytokine Research"},{"issue":"8","key":"pone.0242614.ref042","doi-asserted-by":"crossref","first-page":"4406","DOI":"10.4049\/jimmunol.171.8.4406","article-title":"IL-8\/CXCL8 and growth-related oncogene alpha\/CXCL1 induce chondrocyte hypertrophic differentiation","volume":"171","author":"D Merz","year":"2003","journal-title":"J Immunol"},{"issue":"3","key":"pone.0242614.ref043","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1046\/j.1365-2249.1998.00530.x","article-title":"Tenidap decreases IL-8 and monocyte chemotactic peptide-1 (MCP-1) mRNA expression in the synovial tissue of rabbits with antigen arthritis and in cultured synovial cells","volume":"111","author":"I Palacios","year":"1998","journal-title":"Clin Exp Immunol"},{"issue":"1","key":"pone.0242614.ref044","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/ar141","article-title":"The development of clinical signs of rheumatoid synovial inflammation is associated with increased synthesis of the chemokine CXCL8 (interleukin-8)","volume":"3","author":"MC Kraan","year":"2001","journal-title":"Arthritis Res"},{"issue":"4","key":"pone.0242614.ref045","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1128\/IAI.65.4.1273-1285.1997","article-title":"Borrelia burgdorferi migrates into joint capsules and causes an up-regulation of interleukin-8 in synovial membranes of dogs experimentally infected with ticks","volume":"65","author":"RK Straubinger","year":"1997","journal-title":"Infect Immun"},{"issue":"3","key":"pone.0242614.ref046","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1111\/j.1939-165X.2010.00228.x","article-title":"Serum concentrations of monocyte chemoattractant protein-1 in healthy and critically ill dogs","volume":"39","author":"AL Duffy","year":"2010","journal-title":"Vet Clin Pathol"},{"issue":"1","key":"pone.0242614.ref047","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1111\/j.1939-1676.2010.0642.x","article-title":"Use of Serum Concentrations of Interleukin-18 and Monocyte Chemoattractant Protein-1 as Prognostic Indicators in Primary Immune-Mediated Hemolytic Anemia in Dogs","volume":"25","author":"M Kjelgaard-Hansen","year":"2011","journal-title":"Journal of Veterinary Internal Medicine"},{"issue":"9","key":"pone.0242614.ref048","doi-asserted-by":"crossref","first-page":"e106389","DOI":"10.1371\/journal.pone.0106389","article-title":"Radiographic risk factors for contralateral rupture in dogs with unilateral cranial cruciate ligament rupture","volume":"9","author":"C Chuang","year":"2014","journal-title":"PLoS One"},{"issue":"6","key":"pone.0242614.ref049","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0178086","article-title":"Radiographic and magnetic resonance imaging predicts severity of cruciate ligament fiber damage and synovitis in dogs with cranial cruciate ligament rupture","volume":"12","author":"SJ Sample","year":"2017","journal-title":"PLoS One"},{"issue":"4","key":"pone.0242614.ref050","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1111\/j.1532-950X.2010.00662.x","article-title":"Effect of transection of the caudal menisco-tibial ligament on medial femorotibial contact mechanics","volume":"39","author":"A Pozzi","year":"2010","journal-title":"Vet Surg"},{"issue":"2\u20134","key":"pone.0242614.ref051","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.vetmic.2010.09.011","article-title":"Are bacterial load and synovitis related in dogs with inflammatory stifle arthritis?","volume":"148","author":"Z Schwartz","year":"2011","journal-title":"Vet Microbiol"},{"issue":"12","key":"pone.0242614.ref052","first-page":"2893","article-title":"Carprofen simultaneously reduces progression of morphological changes in cartilage and subchondral bone in experimental dog osteoarthritis","volume":"27","author":"JP Pelletier","year":"2000","journal-title":"J Rheumatol"},{"issue":"5","key":"pone.0242614.ref053","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1053\/joca.2000.0406","article-title":"Effects of non-steroidal antiinflammatory drugs and dexamethasone on the activity and expression of matrix metalloproteinase-1, matrix metalloproteinase-3 and tissue inhibitor of metalloproteinases-1 by bovine articular chondrocytes","volume":"9","author":"T Sadowski","year":"2001","journal-title":"Osteoarthritis and Cartilage"},{"issue":"3","key":"pone.0242614.ref054","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1211\/jpp.58.3.0010","article-title":"Suppression of matrix metalloproteinase production from synovial fibroblasts by meloxicam in-vitro","volume":"58","author":"K Asano","year":"2006","journal-title":"J Pharm Pharmacol"},{"issue":"3","key":"pone.0242614.ref055","doi-asserted-by":"crossref","first-page":"133","DOI":"10.31138\/mjr.28.3.133","article-title":"The effect of non-steroidal anti-inflammatory drugs on matrix metalloproteinases levels in patients with osteoarthritis","volume":"28","author":"M Efstathiou","year":"2017","journal-title":"Mediterr J Rheumatol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0242614","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,17]],"date-time":"2024-08-17T18:58:07Z","timestamp":1723921087000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0242614"}},"subtitle":[],"editor":[{"given":"Chi","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2020,11,19]]},"references-count":55,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,11,19]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0242614","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,19]]}}}