{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T19:09:39Z","timestamp":1790622579200,"version":"4.1.0"},"reference-count":53,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T00:00:00Z","timestamp":1631577600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JND"],"published-print":{"date-parts":[[2021,9,14]]},"abstract":"<jats:p>Duchenne muscular dystrophy is an X-linked, recessive muscular dystrophy in which the absence of the dystrophin protein leads to fibrosis, inflammation and oxidative stress, resulting in loss of muscle tissue. Drug repurposing, i.e. using drugs already approved for other disorders, is attractive as it decreases development time. Recent studies suggested that simvastatin, a cholesterol lowering drug used for cardiovascular diseases, has beneficial effects on several parameters in mdx mice. To validate properly the effectiveness of simvastatin, two independent labs tested the effects of 12-week simvastatin treatment in either young (starting at 4 weeks of age) or adult (starting at 12 weeks of age) mdx mice. In neither study were benefits of simvastatin treatment observed on muscle function, histology or expression of genes involved in fibrosis, regeneration, oxidative stress and autophagy. Unexpectedly, although the treatment protocol was similar, simvastatin plasma levels were found to be much lower than observed in a previous study. In conclusion, in two laboratories, simvastatin did not ameliorate disease pathology in mdx mice, which could either be due to the ineffectiveness of simvastatin itself or due to the low simvastatin plasma levels following oral administration via the food.<\/jats:p>","DOI":"10.3233\/jnd-200524","type":"journal-article","created":{"date-parts":[[2020,10,6]],"date-time":"2020-10-06T13:15:30Z","timestamp":1601990130000},"page":"845-863","source":"Crossref","is-referenced-by-count":16,"title":["Simvastatin Treatment Does Not Ameliorate Muscle Pathophysiology in a Mouse Model for Duchenne Muscular Dystrophy"],"prefix":"10.1177","volume":"8","author":[{"given":"Ingrid E.C.","family":"Verhaart","sequence":"first","affiliation":[{"name":"Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ornella","family":"Cappellari","sequence":"additional","affiliation":[{"name":"Department of Comparative Biomedical Sciences, Neuromuscular Diseases Group, Royal Veterinary College, London, United Kingdom"},{"name":"Current address: Department of Pharmacy-Drug Sciences, University of Bari \u201cAldo Moro\u201d, Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christa L.","family":"Tanganyika-de Winter","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaap J.","family":"Plomp","sequence":"additional","affiliation":[{"name":"Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Nnorom","sequence":"additional","affiliation":[{"name":"Department of Comparative Biomedical Sciences, Neuromuscular Diseases Group, Royal Veterinary College, London, United Kingdom"},{"name":"Current address: Cancer Clinical Trials Unit, University College London Hospital, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim E.","family":"Wells","sequence":"additional","affiliation":[{"name":"Department of Comparative Biomedical Sciences, Neuromuscular Diseases Group, Royal Veterinary College, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.W.","family":"Hildyard","sequence":"additional","affiliation":[{"name":"Department of Comparative Biomedical Sciences, Neuromuscular Diseases Group, Royal Veterinary College, London, United Kingdom"},{"name":"Current address: Department of Clinical Science and Services, Comparative Neuromuscular Diseases, Royal Veterinary College, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Bull","sequence":"additional","affiliation":[{"name":"Duchenne UK, Unit G20, Charecroft Way, Hammersmith, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemieke","family":"Aartsma-Rus","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominic J.","family":"Wells","sequence":"additional","affiliation":[{"name":"Department of Comparative Biomedical Sciences, Neuromuscular Diseases Group, Royal Veterinary College, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"issue":"1","key":"10.3233\/JND-200524_ref1","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1002\/mus.23810","article-title":"Report of MDA muscle disease symposium on newborn screening for Duchenne muscular dystrophy","volume":"48","author":"Mendell","year":"2013","journal-title":"Muscle Nerve"},{"issue":"10","key":"10.3233\/JND-200524_ref2","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1038\/ejhg.2012.301","article-title":"Newborn bloodspot screening for Duchenne muscular dystrophy: 21 years experience in Wales (UK)","volume":"21","author":"Moat","year":"2013","journal-title":"Eur J Hum Genet"},{"key":"10.3233\/JND-200524_ref3","doi-asserted-by":"crossref","unstructured":"Emery AEH , Muntoni F , Quinlivan RCM . Duchenne muscular dystrophy. 4th ed: Oxford University Press; 2015May 2015.","DOI":"10.1093\/med\/9780199681488.001.0001"},{"issue":"6","key":"10.3233\/JND-200524_ref4","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/0092-8674(87)90579-4","article-title":"Dystrophin: The protein product of the Duchenne muscular dystrophy locus","volume":"51","author":"Hoffman","year":"1987","journal-title":"Cell"},{"issue":"2","key":"10.3233\/JND-200524_ref5","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/0092-8674(88)90383-2","article-title":"The complete sequence of dystrophin predicts a rod-shaped cytoskeletal protein","volume":"53","author":"Koenig","year":"1988","journal-title":"Cell"},{"issue":"2","key":"10.3233\/JND-200524_ref6","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1152\/physrev.00028.2001","article-title":"Function and genetics of dystrophin and dystrophin-related proteins in muscle","volume":"82","author":"Blake","year":"2002","journal-title":"Physiol Rev"},{"issue":"11","key":"10.3233\/JND-200524_ref7","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1016\/j.nmd.2018.07.004","article-title":"Longitudinal pulmonary function testing outcome measures in Duchenne muscular dystrophy: Long-term natural history with and without glucocorticoids","volume":"28","author":"McDonald","year":"2018","journal-title":"Neuromuscul Disord"},{"issue":"10119","key":"10.3233\/JND-200524_ref8","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/S0140-6736(17)32160-8","article-title":"Long-term effects of glucocorticoids on function, quality of life, and survival in patients with Duchenne muscular dystrophy: A prospective cohort study","volume":"391","author":"McDonald","year":"2018","journal-title":"Lancet (London, England)"},{"issue":"7","key":"10.3233\/JND-200524_ref9","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/s41582-019-0203-3","article-title":"Therapeutic developments for Duchenne muscular dystrophy","volume":"15","author":"Verhaart","year":"2019","journal-title":"Nature reviews Neurology"},{"issue":"2","key":"10.3233\/JND-200524_ref10","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1089\/nat.2020.0845","article-title":"The 10th Oligonucleotide Therapy Approved: Golodirsen for Duchenne Muscular Dystrophy","volume":"30","author":"Aartsma-Rus","year":"2020","journal-title":"Nucleic Acid Ther"},{"issue":"10","key":"10.3233\/JND-200524_ref11","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1016\/j.drudis.2019.06.014","article-title":"Drug repurposing: A promising tool to accelerate the drug discovery process","volume":"24","author":"Parvathaneni","year":"2019","journal-title":"Drug Discov Today"},{"issue":"1","key":"10.3233\/JND-200524_ref12","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s13023-015-0258-1","article-title":"The TREAT-NMD advisory committee for therapeutics (TACT): An innovative de-risking model to foster orphan drug development","volume":"10","author":"Heslop","year":"2015","journal-title":"Orphanet J Rare Dis"},{"key":"10.3233\/JND-200524_ref13","doi-asserted-by":"crossref","unstructured":"Vuorio A , Kuoppala J , Kovanen PT , Humphries SE , Tonstad S , Wiegman A , et al. Statins for children with familial hypercholesterolemia. Cochrane Database Syst Rev. 2019;2019(11).","DOI":"10.1002\/14651858.CD006401.pub5"},{"issue":"11","key":"10.3233\/JND-200524_ref14","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1161\/hq1101.098486","article-title":"Pleiotropic effects of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors","volume":"21","author":"Takemoto","year":"2001","journal-title":"Arteriosclerosis, thrombosis, and vascular biology"},{"issue":"1","key":"10.3233\/JND-200524_ref15","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1161\/CIRCRESAHA.116.308537","article-title":"Pleiotropic Effects of Statins on the Cardiovascular System","volume":"120","author":"Oesterle","year":"2017","journal-title":"Circulation research"},{"issue":"3","key":"10.3233\/JND-200524_ref16","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1111\/resp.12926","article-title":"Simvastatin alleviates airway inflammation and remodelling through up-regulation of autophagy in mouse models of asthma","volume":"22","author":"Gu","year":"2017","journal-title":"Respirology (Carlton, Vic)"},{"issue":"41","key":"10.3233\/JND-200524_ref17","doi-asserted-by":"crossref","first-page":"12864","DOI":"10.1073\/pnas.1509536112","article-title":"A new therapeutic effect of simvastatin revealed by functional improvement in muscular dystrophy","volume":"112","author":"Whitehead","year":"2015","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"10.3233\/JND-200524_ref18","doi-asserted-by":"crossref","first-page":"e1156286","DOI":"10.1080\/21675511.2016.1156286","article-title":"Simvastatin offers new prospects for the treatment of Duchenne muscular dystrophy","volume":"4","author":"Whitehead","year":"2016","journal-title":"Rare Dis"},{"issue":"7604","key":"10.3233\/JND-200524_ref19","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/533452a","article-title":"1,500 scientists lift the lid on reproducibility","volume":"533","author":"Baker","year":"2016","journal-title":"Nature"},{"issue":"7796","key":"10.3233\/JND-200524_ref20","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/d41586-020-00530-6","article-title":"In praise of replication studies and null results","volume":"578","author":"editors N","year":"2020","journal-title":"Nature"},{"issue":"2","key":"10.3233\/JND-200524_ref21","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1001\/jama.294.2.218","article-title":"Contradicted and initially stronger effects in highly cited clinical research","volume":"294","author":"Ioannidis","year":"2005","journal-title":"JAMA"},{"issue":"15","key":"10.3233\/JND-200524_ref24","doi-asserted-by":"crossref","first-page":"4225","DOI":"10.1093\/hmg\/ddv155","article-title":"How much dystrophin is enough: The physiological consequences of different levels of dystrophin in the mdx mouse","volume":"24","author":"Godfrey","year":"2015","journal-title":"Hum Mol Genet"},{"issue":"1","key":"10.3233\/JND-200524_ref25","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1038\/mt.2010.213","article-title":"Physiological characterization of muscle strength with variable levels of dystrophin restoration in mdx mice following local antisense therapy","volume":"19","author":"Sharp","year":"2011","journal-title":"Mol Ther"},{"issue":"3","key":"10.3233\/JND-200524_ref26","doi-asserted-by":"crossref","first-page":"e91221","DOI":"10.1371\/journal.pone.0091221","article-title":"Poloxamer [corrected] 188 has a deleterious effect on dystrophic skeletal muscle function","volume":"9","author":"Terry","year":"2014","journal-title":"PLoS One"},{"issue":"2","key":"10.3233\/JND-200524_ref27","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1002\/jmor.1052210207","article-title":"Relationship between muscle fiber types and sizes and muscle architectural properties in the mouse hindlimb","volume":"221","author":"Burkholder","year":"1994","journal-title":"J Morphol"},{"issue":"3","key":"10.3233\/JND-200524_ref28","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/0009-9120(96)00003-6","article-title":"A simplified method for the analysis of hydroxyproline in biological tissues","volume":"29","author":"Reddy","year":"1996","journal-title":"Clin Biochem"},{"key":"10.3233\/JND-200524_ref29","unstructured":"RStudio Team. RStudio: Integrated Development for R. In: RStudio Inc., editor. Boston, MA: RStudio Inc.; 2019."},{"issue":"1","key":"10.3233\/JND-200524_ref30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v067.i01","article-title":"Fitting Linear Mixed-Effects Models Using lme4","volume":"67","author":"Bates","year":"2015","journal-title":"Journal of Statistical Software"},{"issue":"3","key":"10.3233\/JND-200524_ref31","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1096\/fj.07-9574LSF","article-title":"Dose translation from animal to human studies revisited","volume":"22","author":"Reagan-Shaw","year":"2008","journal-title":"FASEB J"},{"issue":"4","key":"10.3233\/JND-200524_ref32","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1007\/s00246-008-9364-3","article-title":"Systematic review and metaanalysis of statins for heterozygous familial hypercholesterolemia in children: Evaluation of cholesterol changes and side effects","volume":"30","author":"O\u2019Gorman","year":"2009","journal-title":"Pediatr Cardiol"},{"issue":"6335","key":"10.3233\/JND-200524_ref33","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1038\/352536a0","article-title":"The mdx mouse diaphragm reproduces the degenerative changes of Duchenne muscular dystrophy","volume":"352","author":"Stedman","year":"1991","journal-title":"Nature"},{"issue":"2","key":"10.3233\/JND-200524_ref34","doi-asserted-by":"crossref","first-page":"e31937","DOI":"10.1371\/journal.pone.0031937","article-title":"The effects of low levels of dystrophin on mouse muscle function and pathology","volume":"7","author":"van Putten","year":"2012","journal-title":"PLoS One"},{"issue":"6","key":"10.3233\/JND-200524_ref35","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1002\/1097-0029(20000915)50:6<500::AID-JEMT7>3.0.CO;2-7","article-title":"Myosin isoforms, muscle fiber types, and transitions","volume":"50","author":"Pette","year":"2000","journal-title":"Microscopy research and technique"},{"issue":"4","key":"10.3233\/JND-200524_ref36","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1152\/physrev.00031.2010","article-title":"Fiber types in mammalian skeletal muscles","volume":"91","author":"Schiaffino","year":"2011","journal-title":"Physiol Rev"},{"key":"10.3233\/JND-200524_ref37","doi-asserted-by":"crossref","first-page":"e418","DOI":"10.1038\/cddis.2012.159","article-title":"Autophagy as a new therapeutic target in Duchenne muscular dystrophy","volume":"3","author":"De Palma","year":"2012","journal-title":"Cell Death Dis"},{"issue":"12","key":"10.3233\/JND-200524_ref38","first-page":"3940","article-title":"The muscle-specific ubiquitin ligase atrogin-1\/MAFbx mediates statin-induced muscle toxicity","volume":"117","author":"Hanai","year":"2007","journal-title":"J Clin Invest"},{"issue":"6","key":"10.3233\/JND-200524_ref39","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1159\/000350111","article-title":"Enhancement of autophagy by simvastatin through inhibition of Rac1-mTOR signaling pathway in coronary arterial myocytes","volume":"31","author":"Wei","year":"2013","journal-title":"Cellular physiology and biochemistry: International journal of experimental cellular physiology, biochemistry, and pharmacology"},{"issue":"1","key":"10.3233\/JND-200524_ref40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10974-012-9330-9","article-title":"Contribution of oxidative stress to pathology in diaphragm and limb muscles with Duchenne muscular dystrophy","volume":"34","author":"Kim","year":"2013","journal-title":"Journal of muscle research and cell motility"},{"key":"10.3233\/JND-200524_ref41","doi-asserted-by":"crossref","first-page":"4425","DOI":"10.1038\/ncomms5425","article-title":"Src-dependent impairment of autophagy by oxidative stress in a mouse model of Duchenne muscular dystrophy","volume":"5","author":"Pal","year":"2014","journal-title":"Nat Commun"},{"issue":"1","key":"10.3233\/JND-200524_ref42","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1152\/physrev.00044.2005","article-title":"The NOX family of ROS-generating NADPH oxidases: Physiology and pathophysiology","volume":"87","author":"Bedard","year":"2007","journal-title":"Physiol Rev"},{"issue":"4","key":"10.3233\/JND-200524_ref43","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1507\/endocrj.EJ15-0480","article-title":"Simvastatin rescues homo-cysteine-induced apoptosis of osteocytic MLO-Y4 cells by decreasing the expressions of NADPH oxidase 1 and 2","volume":"63","author":"Takeno","year":"2016","journal-title":"Endocrine journal"},{"issue":"4","key":"10.3233\/JND-200524_ref44","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.1159\/000495720","article-title":"Simvastatin Protects Dopaminergic Neurons Against MPP+-Induced Oxidative Stress and Regulates the Endogenous Anti-Oxidant System Through ERK","volume":"51","author":"Yan","year":"2018","journal-title":"Cellular physiology and biochemistry: International journal of experimental cellular physiology, biochemistry, and pharmacology"},{"issue":"1-2","key":"10.3233\/JND-200524_ref45","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s11010-011-1045-5","article-title":"Simvastatin protects osteoblast against H2O2-induced oxidative damage via inhibiting the upregulation of Nox4","volume":"360","author":"Huang","year":"2012","journal-title":"Molecular and cellular biochemistry"},{"key":"10.3233\/JND-200524_ref46","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1186\/1471-2164-6-98","article-title":"Muscle regeneration in dystrophin-deficient mdx mice studied by gene expression profiling","volume":"6","author":"Turk","year":"2005","journal-title":"BMC genomics"},{"key":"10.3233\/JND-200524_ref47","doi-asserted-by":"crossref","first-page":"104201","DOI":"10.1016\/j.phrs.2019.03.010","article-title":"Mechanisms of statin-associated skeletal muscle-associated symptoms","volume":"154","author":"Bouitbir","year":"2020","journal-title":"Pharmacol Res"},{"issue":"12","key":"10.3233\/JND-200524_ref48","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1111\/ejn.13249","article-title":"Characterization of neuromuscular synapse function abnormalities in multiple Duchenne muscular dystrophy mouse models","volume":"43","author":"van der Pijl","year":"2016","journal-title":"Eur J Neurosci"},{"issue":"71","key":"10.3233\/JND-200524_ref49","first-page":"e50036","article-title":"Isometric and eccentric force generation assessment of skeletal muscles isolated from murine models of muscular dystrophies","author":"Moorwood","year":"2013","journal-title":"J Vis Exp"},{"issue":"4","key":"10.3233\/JND-200524_ref50","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1080\/15548627.2016.1144005","article-title":"Enhanced autophagy as a potential mechanism for the improved physiological function by simvastatin in muscular dystrophy","volume":"12","author":"Whitehead","year":"2016","journal-title":"Autophagy"},{"issue":"6","key":"10.3233\/JND-200524_ref51","doi-asserted-by":"crossref","first-page":"e14018","DOI":"10.14814\/phy2.14018","article-title":"Simvastatin provides long-term improvement of left ventricular function and prevents cardiac fibrosis in muscular dystrophy","volume":"7","author":"Kim","year":"2019","journal-title":"Physiol Rep"},{"issue":"5","key":"10.3233\/JND-200524_ref52","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.nmd.2011.10.025","article-title":"Assessment of cardiac function in three mouse dystrophinopathies by magnetic resonance imaging","volume":"22","author":"Verhaart","year":"2012","journal-title":"Neuromuscul Disord"},{"issue":"2","key":"10.3233\/JND-200524_ref53","doi-asserted-by":"crossref","first-page":"334","DOI":"10.2165\/00003495-199550020-00009","article-title":"Simvastatin. A reappraisal of its pharmacology and therapeutic efficacy in hypercholesterolaemia","volume":"50","author":"Plosker","year":"1995","journal-title":"Drugs"},{"issue":"4","key":"10.3233\/JND-200524_ref54","doi-asserted-by":"crossref","first-page":"e13402","DOI":"10.1111\/apha.13402","article-title":"PGC-1alpha plays a pivotal role in simvastatin-induced exercise impairment in mice","volume":"228","author":"Panajatovic","year":"2020","journal-title":"Acta Physiol (Oxf)"},{"key":"10.3233\/JND-200524_ref55","doi-asserted-by":"crossref","first-page":"2507","DOI":"10.2147\/DDDT.S114826","article-title":"Quantification of simvastatin in mice plasma by near-infrared and chemometric analysis of spectral data","volume":"10","author":"Fahmy","year":"2016","journal-title":"Drug Des Devel Ther"}],"container-title":["Journal of Neuromuscular Diseases"],"original-title":[],"link":[{"URL":"https:\/\/content.iospress.com\/download?id=10.3233\/JND-200524","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T23:49:44Z","timestamp":1777506584000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.3233\/JND-200524"}},"subtitle":[],"editor":[{"given":"Virginia","family":"Arechavala-Gomeza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]},{"given":"Annemieke","family":"Aartsma-Rus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,9,14]]},"references-count":53,"journal-issue":{"issue":"5"},"URL":"https:\/\/doi.org\/10.3233\/jnd-200524","relation":{},"ISSN":["2214-3599","2214-3602"],"issn-type":[{"value":"2214-3599","type":"print"},{"value":"2214-3602","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,14]]}}}