{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:32:24Z","timestamp":1789086744267,"version":"build-2803163510"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T00:00:00Z","timestamp":1678147200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T00:00:00Z","timestamp":1678147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2020R1A2C2005364"],"award-info":[{"award-number":["2020R1A2C2005364"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2020R1A2C2005364"],"award-info":[{"award-number":["2020R1A2C2005364"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2020R1A2C2005364"],"award-info":[{"award-number":["2020R1A2C2005364"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2020R1A2C2005364"],"award-info":[{"award-number":["2020R1A2C2005364"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Vet Res"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Myxomatous mitral valve degeneration (MMVD) is the most common degenerative heart disease in dogs and is associated with irreversible changes in the valve tissue. Although traditional cardiac biomarkers are efficient for diagnosing MMVD, there are limitations, therefore, it is important to find novel biomarkers. Cartilage intermediate layer protein 1 (CILP1), an extracellular matrix-derived protein, acts as a transforming growth factor-\u03b2 antagonist and is involved in myocardial fibrosis. This study aimed to evaluate serum CILP1 levels in canines with MMVD. Dogs with MMVD were staged according to the American College of Veterinary Internal Medicine consensus guidelines. Data analysis was performed using the Mann\u2013Whitney U test, Spearman\u2019s correlation, and receiver operating characteristic (ROC) curves.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CILP1 levels were elevated in dogs with MMVD (<jats:italic>n<\/jats:italic>\u2009=\u200927) compared to healthy controls (<jats:italic>n<\/jats:italic>\u2009=\u20098). Furthermore, results showed that CILP1 levels were significantly higher in stage C group dogs compared to healthy controls. The ROC curve of CILP1 and NT-proBNP were good predictors of MMVD, although no similarity was observed between the two. Left ventricular end-diastolic diameter normalized to the body weight (LVIDdn) and left atrial to aorta dimension (LA\/Ao) showed a strong association with CILP1 levels; however, no correlation was observed between CILP1 levels and vertebral heart size (VHS) and vertebral left atrial score (VLAS). The optimal cut-off value was selected from the ROC curve and dogs were classified according to the cut-off value (1.068\u00a0ng\/mL, sensitivity 51.9%, specificity 100%). Results showed a significant association of CILP1 with cardiac remodeling indicators, such as VHS, VLAS, LA\/Ao, and LVIDdn.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>CILP1 can be an indicator of cardiac remodeling in canines with MMVD and therefore, can be used as an MMVD biomarker.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12917-023-03583-7","type":"journal-article","created":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T09:20:18Z","timestamp":1678180818000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Can cartilage intermediate layer protein 1 (CILP1) use as a novel biomarker for canine myxomatous mitral valve degeneration levels or not?"],"prefix":"10.1186","volume":"19","author":[{"given":"Hyeon-Jin","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihyun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soomin","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ha-Jung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,3,7]]},"reference":[{"key":"3583_CR1","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1111\/j.1749-6632.1965.tb49421.x","volume":"127","author":"DK Detweiler","year":"1965","unstructured":"Detweiler DK, Patterson DF. The prevalence and types of cardiovascular disease in dogs. Ann N Y Acad Sci. 1965;127:481. https:\/\/doi.org\/10.1111\/j.1749-6632.1965.tb49421.x.","journal-title":"Ann N Y Acad Sci"},{"key":"3583_CR2","doi-asserted-by":"publisher","unstructured":"Thrusfield MV, Aitken CGG, Darke PGG. Observations on breed and sex in relation to canine heart valve incompetence. J Small Anim Pract. 1985. https:\/\/doi.org\/10.1111\/j.1748-5827.1985.tb02199.x.","DOI":"10.1111\/j.1748-5827.1985.tb02199.x"},{"key":"3583_CR3","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1136\/vr.120.15.365","volume":"120","author":"PG Darke","year":"1987","unstructured":"Darke PG. Valvular incompetence in cavalier King Charles spaniels. Vet Rec. 1987;120:365. https:\/\/doi.org\/10.1136\/vr.120.15.365.","journal-title":"Vet Rec"},{"key":"3583_CR4","doi-asserted-by":"publisher","first-page":"198","DOI":"10.2460\/ajvr.2004.65.198","volume":"65","author":"BM Corcoran","year":"2004","unstructured":"Corcoran BM, Black A, Anderson H, McEwan JD, French A, Smith P, et al. Identification of surface morphologic changes in the mitral valve leaflets and chordae tendineae of dogs with myxomatous degeneration. Am J Vet Res. 2004;65:198. https:\/\/doi.org\/10.2460\/ajvr.2004.65.198.","journal-title":"Am J Vet Res"},{"key":"3583_CR5","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/S0008-6363(00)00113-9","volume":"47","author":"HD Pedersen","year":"2000","unstructured":"Pedersen HD, H\u00e4ggstr\u00f6m J. Mitral valve prolapse in the dog: a model of mitral valve prolapse in man. Cardiovasc Res. 2000;47:234. https:\/\/doi.org\/10.1016\/S0008-6363(00)00113-9.","journal-title":"Cardiovasc Res"},{"key":"3583_CR6","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1111\/j.1748-5827.1974.tb06529.x","volume":"15","author":"JC Whitney","year":"1974","unstructured":"Whitney JC. Observations on the effect of age on the severity of heart valve lesions in the dog. J Small Anim Pract. 1974;15:511. https:\/\/doi.org\/10.1111\/j.1748-5827.1974.tb06529.x.","journal-title":"J Small Anim Pract"},{"key":"3583_CR7","doi-asserted-by":"publisher","first-page":"23463","DOI":"10.1074\/jbc.273.36.23463","volume":"273","author":"P Lorenzo","year":"1998","unstructured":"Lorenzo P, Bayliss MT, Heineg\u00e5rd D. A novel cartilage protein (CILP) present in the mid-zone of human articular cartilage increases with age. J Biol Chem. 1998;273:23463. https:\/\/doi.org\/10.1074\/jbc.273.36.23463.","journal-title":"J Biol Chem"},{"key":"3583_CR8","doi-asserted-by":"publisher","first-page":"37758","DOI":"10.1074\/jbc.M111.248039","volume":"286","author":"BC Bernardo","year":"2011","unstructured":"Bernardo BC, Belluoccio D, Rowley L, Little CB, Hansen U, Bateman JF. Cartilage intermediate layer protein 2 (CILP-2) is expressed in articular and meniscal cartilage and down-regulated in experimental osteoarthritis. J Biol Chem. 2011;286:37758. https:\/\/doi.org\/10.1074\/jbc.M111.248039.","journal-title":"J Biol Chem"},{"key":"3583_CR9","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.yjmcc.2018.02.006","volume":"116","author":"CL Zhang","year":"2018","unstructured":"Zhang CL, Zhao Q, Liang H, Qiao X, Wang JY, Wu D, et al. Cartilage intermediate layer protein-1 alleviates pressure overload-induced cardiac fibrosis via interfering TGF-\u03b21 signaling. J Mol Cell Cardiol. 2018;116:135. https:\/\/doi.org\/10.1016\/j.yjmcc.2018.02.006.","journal-title":"J Mol Cell Cardiol"},{"key":"3583_CR10","doi-asserted-by":"publisher","first-page":"1901192","DOI":"10.1183\/13993003.01192-2019","volume":"57","author":"S Keranov","year":"2021","unstructured":"Keranov S, D\u00f6rr O, Jafari L, Troidl C, Liebetrau C, Kriechbaum S, et al. CILP1 as a biomarker for right ventricular maladaptation in pulmonary hypertension. Eur Respir J. 2021;57:1901192. https:\/\/doi.org\/10.1183\/13993003.01192-2019.","journal-title":"Eur Respir J"},{"key":"3583_CR11","doi-asserted-by":"publisher","first-page":"16042","DOI":"10.1038\/s41598-017-16201-y","volume":"7","author":"FA van Nieuwenhoven","year":"2017","unstructured":"van Nieuwenhoven FA, Munts C, Op\u2019t Veld RC, Gonz\u00e1lez A, D\u00edez J, Heymans S, et al. Cartilage intermediate layer protein 1 (CILP1): A novel mediator of cardiac extracellular matrix remodelling. Sci Rep. 2017;7:16042. https:\/\/doi.org\/10.1038\/s41598-017-16201-y.","journal-title":"Sci Rep"},{"key":"3583_CR12","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1080\/10408360490460933","volume":"41","author":"M Hyyti\u00e4inen","year":"2004","unstructured":"Hyyti\u00e4inen M, Penttinen C, Keski-Oja J. Latent TGF-beta binding proteins: extracellular matrix association and roles in TGF-beta activation. Crit Rev Clin Lab Sci. 2004;41:233. https:\/\/doi.org\/10.1080\/10408360490460933.","journal-title":"Crit Rev Clin Lab Sci"},{"key":"3583_CR13","doi-asserted-by":"publisher","first-page":"372","DOI":"10.3389\/fgene.2020.00372","volume":"11","author":"GR Markby","year":"2020","unstructured":"Markby GR, Macrae VE, Summers KM, Corcoran BM. Disease severity-associated gene expression in canine Myxomatous mitral valve disease is dominated by TGF\u03b2 Signaling. Front Genet. 2020;11:372. https:\/\/doi.org\/10.3389\/fgene.2020.00372.","journal-title":"Front Genet"},{"key":"3583_CR14","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.jcpa.2008.05.007","volume":"139","author":"H Aupperle","year":"2008","unstructured":"Aupperle H, M\u00e4rz I, Thielebein J, Schoon HA. Expression of transforming growth factor-beta1, -beta2 and -beta3 in normal and diseased canine mitral valves. J Comp Pathol. 2008;139:97. https:\/\/doi.org\/10.1016\/j.jcpa.2008.05.007.","journal-title":"J Comp Pathol"},{"key":"3583_CR15","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.jvc.2016.08.006","volume":"19","author":"M H\u00f6llmer","year":"2017","unstructured":"H\u00f6llmer M, Willesen JL, Tolver A, Koch J. Left atrial volume and function in dogs with naturally occurring myxomatous mitral valve disease. J Vet Cardiol. 2017;19:24. https:\/\/doi.org\/10.1016\/j.jvc.2016.08.006.","journal-title":"J Vet Cardiol"},{"key":"3583_CR16","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1038\/ng1557","volume":"37","author":"S Seki","year":"2005","unstructured":"Seki S, Kawaguchi Y, Chiba K, Mikami Y, Kizawa H, Oya T, et al. A functional SNP in CILP, encoding cartilage intermediate layer protein, is associated with susceptibility to lumbar disc disease. Nat Genet. 2005;37:607. https:\/\/doi.org\/10.1038\/ng1557.","journal-title":"Nat Genet"},{"key":"3583_CR17","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1016\/j.yjmcc.2010.07.014","volume":"49","author":"KG Kreymborg","year":"2010","unstructured":"Kreymborg KG, Uchida S, Gellert P, Schneider A, Boettger T, Voswinckel R, et al. Identification of right heart-enriched genes in a murine model of chronic outflow tract obstruction. J Mol Cell Cardiol. 2010;49:598. https:\/\/doi.org\/10.1016\/j.yjmcc.2010.07.014.","journal-title":"J Mol Cell Cardiol"},{"key":"3583_CR18","doi-asserted-by":"publisher","first-page":"320","DOI":"10.3389\/fvets.2020.00320","volume":"7","author":"A Gavazza","year":"2020","unstructured":"Gavazza A, Fruganti A, Turinelli V, Marchegiani A, Spaterna A, Tesei B, et al. Canine traditional laboratory tests and cardiac biomarkers. Front Vet Sci. 2020;7:320. https:\/\/doi.org\/10.3389\/fvets.2020.00320.","journal-title":"Front Vet Sci"},{"key":"3583_CR19","doi-asserted-by":"publisher","first-page":"551","DOI":"10.2478\/v10181-011-0082-z","volume":"14","author":"A Noszczyk-Nowak","year":"2011","unstructured":"Noszczyk-Nowak A. NT-pro-BNP and troponin I as predictors of mortality in dogs with heart failure. Pol J Vet Sci. 2011;14:551. https:\/\/doi.org\/10.2478\/v10181-011-0082-z.","journal-title":"Pol J Vet Sci"},{"key":"3583_CR20","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1111\/jvim.13801","volume":"30","author":"R Langhorn","year":"2016","unstructured":"Langhorn R, Willesen JL. Cardiac troponins in dogs and cats. J Vet Intern Med. 2016;30:36. https:\/\/doi.org\/10.1111\/jvim.13801.","journal-title":"J Vet Intern Med"},{"key":"3583_CR21","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1016\/j.cll.2015.05.005","volume":"33","author":"MA Oyama","year":"2015","unstructured":"Oyama MA. Using cardiac biomarkers in veterinary practice. Clin Lab Med. 2015;33:555. https:\/\/doi.org\/10.1016\/j.cll.2015.05.005.","journal-title":"Clin Lab Med"},{"key":"3583_CR22","doi-asserted-by":"publisher","first-page":"767","DOI":"10.2460\/javma.234.6.767","volume":"234","author":"LC Sharkey","year":"2009","unstructured":"Sharkey LC, Berzina I, Ferasin L, Tobias AH, Lulich JP, Hegstad-Davies RL. Evaluation of serum cardiac troponin I concentration in dogs with renal failure. J Am Vet Med Assoc. 2009;234:767. https:\/\/doi.org\/10.2460\/javma.234.6.767.","journal-title":"J Am Vet Med Assoc"},{"key":"3583_CR23","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.jvc.2011.04.003","volume":"13","author":"HB Kellihan","year":"2011","unstructured":"Kellihan HB, Mackie BA, Stepien RL. NT-proBNP, NT-proANP and cTnI concentrations in dogs with pre-capillary pulmonary hypertension. J Vet Cardiol. 2011;13:171. https:\/\/doi.org\/10.1016\/j.jvc.2011.04.003.","journal-title":"J Vet Cardiol"},{"key":"3583_CR24","doi-asserted-by":"publisher","first-page":"1768","DOI":"10.1161\/CIRCULATIONAHA.109.849166","volume":"121","author":"DM Lloyd-Jones","year":"2010","unstructured":"Lloyd-Jones DM. Cardiovascular risk prediction: basic concepts, current status, and future directions. Circulation. 2010;121:1768. https:\/\/doi.org\/10.1161\/CIRCULATIONAHA.109.849166.","journal-title":"Circulation"},{"key":"3583_CR25","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1111\/j.1939-1676.2012.00894.x","volume":"26","author":"MJ Hezzell","year":"2012","unstructured":"Hezzell MJ, Boswood A, Chang YM, Moonarmart W, Souttar K, Elliott J. The combined prognostic potential of serum high-sensitivity cardiac troponin I and N-terminal pro-B-type natriuretic peptide concentrations in dogs with degenerative mitral valve disease. J Vet Intern Med. 2012;26:302. https:\/\/doi.org\/10.1111\/j.1939-1676.2012.00894.x.","journal-title":"J Vet Intern Med"},{"key":"3583_CR26","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1186\/s12863-017-0585-4","volume":"18","author":"M Taipale","year":"2017","unstructured":"Taipale M, Solovieva S, Leino-Arjas P, M\u00e4nnikk\u00f6 M. Functional polymorphisms in asporin and CILP together with joint loading predispose to hand osteoarthritis. BMC Genet. 2017;18:108. https:\/\/doi.org\/10.1186\/s12863-017-0585-4.","journal-title":"BMC Genet"},{"key":"3583_CR27","doi-asserted-by":"publisher","first-page":"E203","DOI":"10.1097\/BRS.0b013e31822dcf47","volume":"37","author":"Z Wang","year":"2012","unstructured":"Wang Z, Kim JH, Higashino K, Kim SS, Yang S, Seki S, et al. Cartilage intermediate layer protein (CILP) regulation in intervertebral discs. The effect of age, degeneration, and bone morphogenetic protein-2. Spine. 2012;37:E203. https:\/\/doi.org\/10.1097\/BRS.0b013e31822dcf47.","journal-title":"Spine"},{"key":"3583_CR28","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1093\/jmcb\/mjz016","volume":"11","author":"T Wu","year":"2019","unstructured":"Wu T, Zhang Q, Wu S, Hu W, Zhou T, Li K, et al. CILP-2 is a novel secreted protein and associated with insulin resistance. J Mol Cell Biol. 2019;11:1083. https:\/\/doi.org\/10.1093\/jmcb\/mjz016.","journal-title":"J Mol Cell Biol"},{"key":"3583_CR29","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1111\/jvim.15488","volume":"33","author":"BW Keene","year":"2019","unstructured":"Keene BW, Atkins CE, Bonagura JD, Fox PR, H\u00e4ggstr\u00f6m J, Fuentes VL, et al. ACVIM consensus guidelines for the diagnosis and treatment of myxomatous mitral valve disease in dogs. J Vet Intern Med. 2019;33:1127. https:\/\/doi.org\/10.1111\/jvim.15488.","journal-title":"J Vet Intern Med"},{"key":"3583_CR30","doi-asserted-by":"crossref","first-page":"194","DOI":"10.2460\/javma.1995.206.02.194","volume":"206","author":"JW Buchanan","year":"1995","unstructured":"Buchanan JW, B\u00fccheler J. Vertebral scale system to measure canine heart size in radiographs. J Am Vet Med Assoc. 1995;206:194.","journal-title":"J Am Vet Med Assoc."},{"key":"3583_CR31","doi-asserted-by":"publisher","first-page":"1038","DOI":"10.2460\/javma.253.8.1038","volume":"253","author":"EL Malcolm","year":"2018","unstructured":"Malcolm EL, Visser LC, Phillips KL, Johnson LR. Diagnostic value of vertebral left atrial size as determined from thoracic radiographs for assessment of left atrial size in dogs with myxomatous mitral valve disease. J Am Vet Med Assoc. 2018;253:1038. https:\/\/doi.org\/10.2460\/javma.253.8.1038.","journal-title":"J Am Vet Med Assoc"},{"key":"3583_CR32","doi-asserted-by":"publisher","unstructured":"Cornell CC, Kittleson MD, Della Torre P, et al. Allometric scaling of M-mode cardiac measurements in normal adult dogs. J Vet Intern Med. 2004;18:311.\u00a0https:\/\/doi.org\/10.1111\/j.1939-1676.2004.tb02551.x.","DOI":"10.1111\/j.1939-1676.2004.tb02551.x"},{"key":"3583_CR33","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1111\/j.1740-8261.2002.tb01051.x","volume":"43","author":"K Hansson","year":"2002","unstructured":"Hansson K, H\u00e4ggstr\u00f6m J, Kvart C, Lord P. Left atrial to aortic root indices using two-dimensional and M-mode echocardiography in cavalier King Charles spaniels with and without left atrial enlargement. Vet Radiol Ultrasound. 2002;43:568. https:\/\/doi.org\/10.1111\/j.1740-8261.2002.tb01051.x.","journal-title":"Vet Radiol Ultrasound"},{"key":"3583_CR34","doi-asserted-by":"publisher","first-page":"1358","DOI":"10.1111\/j.1939-1676.2010.0592.x","volume":"24","author":"KE Schober","year":"2010","unstructured":"Schober KE, Hart TM, Stern JA, et al. Detection of congestive heart failure in dogs by Doppler echocardiography. J Vet Intern Med. 2010;24:1358. https:\/\/doi.org\/10.1111\/j.1939-1676.2010.0592.x.","journal-title":"J Vet Intern Med"}],"container-title":["BMC Veterinary Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12917-023-03583-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12917-023-03583-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12917-023-03583-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T22:27:40Z","timestamp":1729031260000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcvetres.biomedcentral.com\/articles\/10.1186\/s12917-023-03583-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,7]]},"references-count":34,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["3583"],"URL":"https:\/\/doi.org\/10.1186\/s12917-023-03583-7","relation":{},"ISSN":["1746-6148"],"issn-type":[{"value":"1746-6148","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,7]]},"assertion":[{"value":"6 September 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 January 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 March 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study protocol was approved by the Institutional Animal Care and Use Committee of Chonnam National University (CNU IACUC-YB-2019\u201323). Owners of all included dogs provided written informed consent. All diagnostic procedures were clinically indicated, meant for the benefit of the animals, and performed according to the highest standards of veterinary practice.The authors confirm that all methods were carried out in accordance with relevant guidelines and veterinary regulations, and reported in accordance with the ARRIVE guidelines as applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"59"}}