{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:50:09Z","timestamp":1790833809531,"version":"4.1.0"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,4,15]],"date-time":"2020-04-15T00:00:00Z","timestamp":1586908800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,4,15]],"date-time":"2020-04-15T00:00:00Z","timestamp":1586908800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AR50245, AG15768, AG46927, AR074992, AR073752"],"award-info":[{"award-number":["AR50245, AG15768, AG46927, AR074992, AR073752"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AR075899"],"award-info":[{"award-number":["AR075899"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000980","name":"Arthritis Foundation","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100000980","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007253","name":"Nancy Taylor Foundation for Chronic Diseases","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100007253","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010002","name":"Ministry of Education","doi-asserted-by":"publisher","award":["GSSA Scholarship"],"award-info":[{"award-number":["GSSA Scholarship"]}],"id":[{"id":"10.13039\/100010002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthritis Res Ther"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Dietary fatty acid (FA) content has been shown to influence the development of post-traumatic osteoarthritis (PTOA) in obesity. We used the <jats:italic>fat-1<\/jats:italic> transgenic mouse to examine the hypothesis that endogenous reduction of \u03c9-6 to \u03c9-3 FA ratio, under the same dietary conditions, would mitigate metabolic inflammation and the pathogenesis of PTOA in obese male and female mice.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Male and female <jats:italic>fat-1<\/jats:italic> and wild-type littermates were fed either a control diet or an \u03c9-6 FA-rich high-fat diet and underwent destabilization of the medial meniscus (DMM) surgery to induce PTOA. OA severity, synovitis, and osteophyte formation were determined histologically, while biomarker and lipidomic analyses were performed to evaluate levels of adipokines, insulin, pro-\/anti-inflammatory cytokines, and FAs in serum and joint synovial fluid. Multivariable models were performed to elucidate the associations of dietary, metabolic, and mechanical factors with PTOA.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>We found that elevated serum levels of \u03c9-3 FAs in <jats:italic>fat-1<\/jats:italic> mice as compared to wild-type controls fed the same diet resulted in reduced OA and synovitis in a sex- and diet-dependent manner, despite comparable body weights. The <jats:italic>fat-1<\/jats:italic> mice showed trends toward decreased serum pro-inflammatory cytokines and increased anti-inflammatory cytokines. Multivariable analysis for variables predicting OA severity in mice resulted in correlations with serum FA levels, but not with body weight.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>This study provides further evidence that circulating FA composition and systemic metabolic inflammation, rather than body weight, may be the major risk factor for obesity-associated OA. We also demonstrate the potential genetic use of \u03c9-3 FA desaturase in mitigating PTOA in obese patients following injury.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s13075-020-02170-7","type":"journal-article","created":{"date-parts":[[2020,4,15]],"date-time":"2020-04-15T17:02:39Z","timestamp":1586970159000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Transgenic conversion of \u03c9-6 to \u03c9-3 polyunsaturated fatty acids via fat-1 reduces the severity of post-traumatic osteoarthritis"],"prefix":"10.1186","volume":"22","author":[{"given":"Kelly A.","family":"Kimmerling","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara J.","family":"Oswald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet L.","family":"Huebner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianne","family":"Little","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia B.","family":"Kraus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing X.","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Lung","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farshid","family":"Guilak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,4,15]]},"reference":[{"issue":"10","key":"2170_CR1","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1097\/01.bot.0000246468.80635.ef","volume":"20","author":"TD Brown","year":"2006","unstructured":"Brown TD, Johnston RC, Saltzman CL, et al. Posttraumatic osteoarthritis: a first estimate of incidence, prevalence, and burden of disease. J Orthop Trauma. 2006;20(10):739\u201344.","journal-title":"J Orthop Trauma"},{"issue":"2","key":"2170_CR2","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1016\/j.addr.2006.01.008","volume":"58","author":"SB Abramson","year":"2006","unstructured":"Abramson SB, Yazici Y. Biologics in development for rheumatoid arthritis: relevance to osteoarthritis. Adv Drug Deliv Rev. 2006;58(2):212\u201325.","journal-title":"Adv Drug Deliv Rev"},{"issue":"1","key":"2170_CR3","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1186\/s13075-019-2081-x","volume":"21","author":"BM Dickson","year":"2019","unstructured":"Dickson BM, Roelofs AJ, Rochford JJ, et al. The burden of metabolic syndrome on osteoarthritic joints. Arthritis Res Ther. 2019;21(1):289.","journal-title":"Arthritis Res Ther."},{"issue":"1","key":"2170_CR4","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1038\/nrrheum.2010.123","volume":"7","author":"RM Aspden","year":"2011","unstructured":"Aspden RM. Obesity punches above its weight in osteoarthritis. Nat Rev Rheumatol. 2011;7(1):65\u20138.","journal-title":"Nat Rev Rheumatol"},{"issue":"11","key":"2170_CR5","doi-asserted-by":"publisher","first-page":"1890","DOI":"10.1016\/j.joca.2015.02.009","volume":"23","author":"HN Daghestani","year":"2015","unstructured":"Daghestani HN, Kraus VB. Inflammatory biomarkers in osteoarthritis. Osteoarthr Cartil. 2015;23(11):1890\u20136.","journal-title":"Osteoarthr Cartil"},{"issue":"5","key":"2170_CR6","doi-asserted-by":"publisher","first-page":"248","DOI":"10.7150\/ijms.5.248","volume":"5","author":"H Inadera","year":"2008","unstructured":"Inadera H. The usefulness of circulating adipokine levels for the assessment of obesity-related health problems. Int J Med Sci. 2008;5(5):248\u201362.","journal-title":"Int J Med Sci"},{"issue":"11","key":"2170_CR7","doi-asserted-by":"publisher","first-page":"1302","DOI":"10.1016\/j.joca.2012.07.021","volume":"20","author":"P Sward","year":"2012","unstructured":"Sward P, Frobell R, Englund M, et al. Cartilage and bone markers and inflammatory cytokines are increased in synovial fluid in the acute phase of knee injury (hemarthrosis)--a cross-sectional analysis. Osteoarthr Cartil. 2012;20(11):1302\u20138.","journal-title":"Osteoarthr Cartil"},{"issue":"3","key":"2170_CR8","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1002\/art.37796","volume":"65","author":"JS Lewis Jr","year":"2013","unstructured":"Lewis JS Jr, Furman BD, Zeitler E, et al. Genetic and cellular evidence of decreased inflammation associated with reduced incidence of posttraumatic arthritis in MRL\/MpJ mice. Arthritis Rheum. 2013;65(3):660\u201370.","journal-title":"Arthritis Rheum"},{"issue":"1","key":"2170_CR9","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1007\/s00264-005-0023-5","volume":"30","author":"H Higuchi","year":"2006","unstructured":"Higuchi H, Shirakura K, Kimura M, et al. Changes in biochemical parameters after anterior cruciate ligament injury. Int Orthop. 2006;30(1):43\u20137.","journal-title":"Int Orthop"},{"issue":"2","key":"2170_CR10","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1002\/jor.22208","volume":"31","author":"M Bigoni","year":"2013","unstructured":"Bigoni M, Sacerdote P, Turati M, et al. Acute and late changes in intraarticular cytokine levels following anterior cruciate ligament injury. J Orthop Res. 2013;31(2):315\u201321.","journal-title":"J Orthop Res"},{"key":"2170_CR11","doi-asserted-by":"crossref","unstructured":"Liddle DM, Hutchinson AL, Wellings HR, et al. Integrated immunomodulatory mechanisms through which long-chain n-3 polyunsaturated fatty acids attenuate obese adipose tissue dysfunction. Nutrients. 2017;9(12):1289\u2013331.","DOI":"10.3390\/nu9121289"},{"issue":"7","key":"2170_CR12","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1007\/s00592-018-1110-6","volume":"55","author":"AR Farimani","year":"2018","unstructured":"Farimani AR, Hariri M, Azimi-Nezhad M, et al. The effect of n-3 PUFAs on circulating adiponectin and leptin in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials. Acta Diabetol. 2018;55(7):641\u201352.","journal-title":"Acta Diabetol"},{"key":"2170_CR13","doi-asserted-by":"crossref","unstructured":"Huang CW, Chien YS, Chen YJ, et al. Role of n-3 polyunsaturated fatty acids in ameliorating the obesity-induced metabolic syndrome in animal models and humans. Int J Mol Sci. 2016;17(10):1689\u2013718.","DOI":"10.3390\/ijms17101689"},{"issue":"5\u20136","key":"2170_CR14","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.plefa.2007.10.010","volume":"77","author":"JX Kang","year":"2007","unstructured":"Kang JX. Fat-1 transgenic mice: a new model for omega-3 research. Prostaglandins Leukot Essent Fatty Acids. 2007;77(5\u20136):263\u20137.","journal-title":"Prostaglandins Leukot Essent Fatty Acids"},{"issue":"9","key":"2170_CR15","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.1016\/j.joca.2014.06.033","volume":"22","author":"A Cai","year":"2014","unstructured":"Cai A, Hutchison E, Hudson J, et al. Metabolic enrichment of omega-3 polyunsaturated fatty acids does not reduce the onset of idiopathic knee osteoarthritis in mice. Osteoarthr Cartil. 2014;22(9):1301\u20139.","journal-title":"Osteoarthr Cartil"},{"key":"2170_CR16","doi-asserted-by":"crossref","unstructured":"Huang MJ, Wang L, Jin DD, Zhang ZM, et al. Enhancement of the synthesis of n-3 PUFAs in fat-1 transgenic mice inhibits mTORC1 signalling and delays surgically induced osteoarthritis in comparison with wild-type mice. Ann Rheum Dis. 2014;73:1719\u201327.","DOI":"10.1136\/annrheumdis-2013-203231"},{"issue":"11","key":"2170_CR17","doi-asserted-by":"publisher","first-page":"2076","DOI":"10.1136\/annrheumdis-2014-205601","volume":"74","author":"C-L Wu","year":"2015","unstructured":"Wu C-L, Jain D, McNeill JN, et al. Dietary fatty acid content regulates wound repair and the pathogenesis of osteoarthritis following joint injury. Ann Rheum Dis. 2015;74(11):2076\u201383.","journal-title":"Ann Rheum Dis"},{"issue":"10","key":"2170_CR18","doi-asserted-by":"publisher","first-page":"2935","DOI":"10.1002\/art.24854","volume":"60","author":"TM Griffin","year":"2009","unstructured":"Griffin TM, Huebner JL, Kraus VB, et al. Extreme obesity due to impaired leptin signaling in mice does not cause knee osteoarthritis. Arthritis Rheumatism. 2009;60(10):2935\u201344.","journal-title":"Arthritis Rheumatism"},{"issue":"4","key":"2170_CR19","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1016\/j.joca.2009.11.013","volume":"18","author":"A Malfait","year":"2010","unstructured":"Malfait A, Ritchie J, Gil A, et al. ADAMTS-5 deficient mice do not develop mechanical allodynia associated with osteoarthritis following medial meniscal destabilization. Osteoarthr Cartil. 2010;18(4):572\u201380.","journal-title":"Osteoarthr Cartil"},{"issue":"2","key":"2170_CR20","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1002\/art.33332","volume":"64","author":"TM Griffin","year":"2012","unstructured":"Griffin TM, Huebner JL, Kraus VB, et al. Induction of osteoarthritis and metabolic inflammation by a very high-fat diet in mice: effects of short-term exercise. Arthritis Rheum. 2012;64(2):443\u201353.","journal-title":"Arthritis Rheum"},{"issue":"5","key":"2170_CR21","doi-asserted-by":"publisher","first-page":"1234","DOI":"10.1002\/art.39064","volume":"67","author":"BD Furman","year":"2015","unstructured":"Furman BD, Kimmerling KA, Zura RD, et al. Brief report: articular ankle fracture results in increased synovitis, synovial macrophage infiltration, and synovial fluid concentrations of inflammatory cytokines and chemokines. Arthritis Rheumatol. 2015;67(5):1234\u20139.","journal-title":"Arthritis Rheumatol"},{"issue":"8","key":"2170_CR22","doi-asserted-by":"publisher","first-page":"1316","DOI":"10.1210\/me.2014-1011","volume":"28","author":"J Li","year":"2014","unstructured":"Li J, Li FR, Wei D, et al. Endogenous omega-3 polyunsaturated fatty acid production confers resistance to obesity, dyslipidemia, and diabetes in mice. Mol Endocrinol. 2014;28(8):1316\u201328.","journal-title":"Mol Endocrinol"},{"issue":"7","key":"2170_CR23","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1016\/j.jnutbio.2015.01.011","volume":"26","author":"SJ Woo","year":"2015","unstructured":"Woo SJ, Lim K, Park SY, et al. Endogenous conversion of n-6 to n-3 polyunsaturated fatty acids attenuates K\/BxN serum-transfer arthritis in fat-1 mice. J Nutr Biochem. 2015;26(7):713\u201320.","journal-title":"J Nutr Biochem"},{"issue":"4","key":"2170_CR24","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1016\/j.bbalip.2014.08.010","volume":"1851","author":"PC Calder","year":"2015","unstructured":"Calder PC. Marine omega-3 fatty acids and inflammatory processes: effects, mechanisms and clinical relevance. Biochim Biophys Acta Mol Cell Biol Lipids. 2015;1851(4):469\u201384.","journal-title":"Biochim Biophys Acta Mol Cell Biol Lipids"},{"key":"2170_CR25","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/j.lfs.2018.04.049","volume":"203","author":"RK Saini","year":"2018","unstructured":"Saini RK, Keum Y-S. Omega-3 and omega-6 polyunsaturated fatty acids: dietary sources, metabolism, and significance\u2014a review. Life Sci. 2018;203:255\u201367.","journal-title":"Life Sci"},{"issue":"1","key":"2170_CR26","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1111\/nyas.13999","volume":"1440","author":"NS Harasymowicz","year":"2019","unstructured":"Harasymowicz NS, Dicks A, Wu CL, et al. Physiologic and pathologic effects of dietary free fatty acids on cells of the joint. Ann N Y Acad Sci. 2019;1440(1):36\u201353.","journal-title":"Ann N Y Acad Sci"},{"issue":"7","key":"2170_CR27","doi-asserted-by":"publisher","first-page":"1789","DOI":"10.1002\/art.10356","volume":"46","author":"MM Hardy","year":"2002","unstructured":"Hardy MM, Seibert K, Manning PT, et al. Cyclooxygenase 2-dependent prostaglandin E2 modulates cartilage proteoglycan degradation in human osteoarthritis explants. Arthritis Rheum. 2002;46(7):1789\u2013803.","journal-title":"Arthritis Rheum"},{"issue":"5","key":"2170_CR28","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1016\/j.cell.2010.07.041","volume":"142","author":"S Talukdar","year":"2010","unstructured":"Talukdar S, Bae EJ, Imamura T, et al. GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell. 2010;142(5):687\u201398.","journal-title":"Cell."},{"issue":"1","key":"2170_CR29","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1186\/s13075-018-1660-6","volume":"20","author":"Y Chen","year":"2018","unstructured":"Chen Y, Zhang D, Ho KW, et al. GPR120 is an important inflammatory regulator in the development of osteoarthritis. Arthritis Res Ther. 2018;20(1):163.","journal-title":"Arthritis Res Ther."},{"issue":"5","key":"2170_CR30","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1016\/j.joca.2012.01.021","volume":"20","author":"KR Baker","year":"2012","unstructured":"Baker KR, Matthan N, Lichtenstein A, et al. Association of plasma n-6 and n-3 polyunsaturated fatty acids with synovitis in the knee: the MOST study. Osteoarthr Cartil. 2012;20(5):382\u20137.","journal-title":"Osteoarthr Cartil"},{"issue":"12","key":"2170_CR31","doi-asserted-by":"publisher","first-page":"1750","DOI":"10.1093\/hmg\/ddn066","volume":"17","author":"S Hein","year":"2008","unstructured":"Hein S, Sch\u00f6nfeld P, Kahlert S, et al. Toxic effects of X-linked adrenoleukodystrophy-associated, very long chain fatty acids on glial cells and neurons from rat hippocampus in culture. Hum Mol Genet. 2008;17(12):1750\u201361.","journal-title":"Hum Mol Genet"},{"key":"2170_CR32","doi-asserted-by":"publisher","first-page":"44315","DOI":"10.1038\/srep44315","volume":"7","author":"C-L Wu","year":"2017","unstructured":"Wu C-L, Kimmerling KA, Little D, et al. Serum and synovial fluid lipidomic profiles predict obesity-associated osteoarthritis, synovitis, and wound repair. Sci Rep. 2017;7:44315.","journal-title":"Sci Rep"},{"issue":"6","key":"2170_CR33","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1016\/j.joca.2006.11.005","volume":"15","author":"H-L Ma","year":"2007","unstructured":"Ma H-L, Blanchet T, Peluso D, et al. Osteoarthritis severity is sex dependent in a surgical mouse model. Osteoarthr Cartil. 2007;15(6):695\u2013700.","journal-title":"Osteoarthr Cartil"},{"issue":"4","key":"2170_CR34","doi-asserted-by":"publisher","first-page":"R130","DOI":"10.1186\/ar3068","volume":"12","author":"TM Griffin","year":"2010","unstructured":"Griffin TM, Fermor B, Huebner JL, et al. Diet-induced obesity differentially regulates behavioral, biomechanical, and molecular risk factors for osteoarthritis in mice. Arthritis Res Ther. 2010;12(4):R130.","journal-title":"Arthritis Res Ther."},{"issue":"9","key":"2170_CR35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0046057","volume":"7","author":"US Pettersson","year":"2012","unstructured":"Pettersson US, Wald\u00e9n TB, Carlsson P-O, et al. Female mice are protected against high-fat diet induced metabolic syndrome and increase the regulatory T cell population in adipose tissue. PLoS One. 2012;7(9):e46057.","journal-title":"PLoS One"},{"issue":"2","key":"2170_CR36","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1530\/eje.0.1390198","volume":"139","author":"E Mannucci","year":"1998","unstructured":"Mannucci E, Ognibene A, Becorpi A, et al. Relationship between leptin and oestrogens in healthy women. Eur J Endocrinol. 1998;139(2):198\u2013201.","journal-title":"Eur J Endocrinol"},{"issue":"5","key":"2170_CR37","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1186\/ar2791","volume":"11","author":"JA Roman-Blas","year":"2009","unstructured":"Roman-Blas JA, Castaneda S, Largo R, et al. Osteoarthritis associated with estrogen deficiency. Arthritis Res Ther. 2009;11(5):241.","journal-title":"Arthritis Res Ther"}],"container-title":["Arthritis Research &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13075-020-02170-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13075-020-02170-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13075-020-02170-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T00:27:52Z","timestamp":1618446472000},"score":1,"resource":{"primary":{"URL":"https:\/\/arthritis-research.biomedcentral.com\/articles\/10.1186\/s13075-020-02170-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,15]]},"references-count":37,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["2170"],"URL":"https:\/\/doi.org\/10.1186\/s13075-020-02170-7","relation":{},"ISSN":["1478-6362"],"issn-type":[{"value":"1478-6362","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,15]]},"assertion":[{"value":"28 October 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 March 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 April 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"83"}}