{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:07:45Z","timestamp":1790842065224,"version":"4.1.0"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"13","license":[{"start":{"date-parts":[[2019,3,5]],"date-time":"2019-03-05T00:00:00Z","timestamp":1551744000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011724","name":"Muscular Dystrophy UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011724","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Summit Therapeutics"},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Duchenne muscular dystrophy (DMD) is a lethal neuromuscular disorder caused by loss of dystrophin. Several therapeutic modalities are currently in clinical trials but none will achieve maximum functional rescue and full disease correction. Therefore, we explored the potential of combining the benefits of dystrophin with increases of utrophin, an autosomal paralogue of dystrophin. Utrophin and dystrophin can be co-expressed and co-localized at the same muscle membrane. Wild-type (wt) levels of dystrophin are not significantly affected by a moderate increase of utrophin whereas higher levels of utrophin reduce wt dystrophin, suggesting a finite number of actin binding sites at the sarcolemma. Thus, utrophin upregulation strategies may be applied to the more mildly affected Becker patients with lower dystrophin levels. Whereas increased dystrophin in wt animals does not offer functional improvement, overexpression of utrophin in wt mice results in a significant supra-functional benefit over wt. These findings highlight an additive benefit of the combined therapy and potential new unique roles of utrophin. Finally, we show a 30% restoration of wt dystrophin levels, using exon-skipping, together with increased utrophin levels restores dystrophic muscle function to wt levels offering greater therapeutic benefit than either single approach alone. Thus, this combination therapy results in additive functional benefit and paves the way for potential future combinations of dystrophin- and utrophin-based strategies.<\/jats:p>","DOI":"10.1093\/hmg\/ddz049","type":"journal-article","created":{"date-parts":[[2019,3,4]],"date-time":"2019-03-04T20:12:21Z","timestamp":1551730341000},"page":"2189-2200","source":"Crossref","is-referenced-by-count":54,"title":["The potential of utrophin and dystrophin combination therapies for Duchenne muscular dystrophy"],"prefix":"10.1093","volume":"28","author":[{"given":"Simon","family":"Guiraud","sequence":"first","affiliation":[{"name":"MDUK Oxford Neuromuscular Centre, Department of Physiology , Anatomy and Genetics, Oxford,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Edwards","sequence":"additional","affiliation":[{"name":"MDUK Oxford Neuromuscular Centre, Department of Physiology , Anatomy and Genetics, Oxford,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arran","family":"Babbs","sequence":"additional","affiliation":[{"name":"MDUK Oxford Neuromuscular Centre, Department of Physiology , Anatomy and Genetics, Oxford,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E","family":"Squire","sequence":"additional","affiliation":[{"name":"MDUK Oxford Neuromuscular Centre, Department of Physiology , Anatomy and Genetics, Oxford,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Berg","sequence":"additional","affiliation":[{"name":"MDUK Oxford Neuromuscular Centre, Department of Physiology , Anatomy and Genetics, Oxford,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee","family":"Moir","sequence":"additional","affiliation":[{"name":"MDUK Oxford Neuromuscular Centre, Department of Physiology , Anatomy and Genetics, Oxford,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J","family":"Wood","sequence":"additional","affiliation":[{"name":"MDUK Oxford Neuromuscular Centre, Department of Physiology , Anatomy and Genetics, Oxford,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kay E","family":"Davies","sequence":"additional","affiliation":[{"name":"MDUK Oxford Neuromuscular Centre, Department of Physiology , Anatomy and Genetics, Oxford,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,3,5]]},"reference":[{"key":"2024102212523145000_ref1","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1146\/annurev-genom-090314-025003","article-title":"The pathogenesis and therapy of muscular dystrophies","volume":"16","author":"Guiraud","year":"2015","journal-title":"Annu. Rev. Genomics Hum. Genet."},{"key":"2024102212523145000_ref2","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1038\/323646a0","article-title":"Isolation of candidate cDNAs for portions of the Duchenne muscular dystrophy gene","volume":"323","author":"Monaco","year":"1986","journal-title":"Nature"},{"key":"2024102212523145000_ref3","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.nmd.2014.03.008","article-title":"A systematic review and meta-analysis on the epidemiology of Duchenne and Becker muscular dystrophy","volume":"24","author":"Mah","year":"2014","journal-title":"Neuromuscul. Disord.: NMD"},{"key":"2024102212523145000_ref4","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."},{"key":"2024102212523145000_ref5","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1038\/343180a0","article-title":"Very mild muscular dystrophy associated with the deletion of 46% of dystrophin","volume":"343","author":"England","year":"1990","journal-title":"Nature"},{"key":"2024102212523145000_ref6","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/0960-8966(93)90018-F","article-title":"Duchenne muscular dystrophy\u2014Meryon\u2019s disease","volume":"3","author":"Emery","year":"1993","journal-title":"Neuromuscul. Disord.: NMD"},{"key":"2024102212523145000_ref7","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1002\/mus.880100212","article-title":"Management of end stage respiratory failure in Duchenne muscular dystrophy","volume":"10","author":"Bach","year":"1987","journal-title":"Muscle Nerve"},{"key":"2024102212523145000_ref8","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1002\/ana.24555","article-title":"Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy","volume":"79","author":"Mendell","year":"2016","journal-title":"Ann. Neurol."},{"key":"2024102212523145000_ref9","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1002\/mus.24332","article-title":"Ataluren treatment of patients with nonsense mutation dystrophinopathy","volume":"50","author":"Bushby","year":"2014","journal-title":"Muscle Nerve"},{"key":"2024102212523145000_ref10","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1016\/j.ymthe.2017.02.019","article-title":"Progress toward gene therapy for Duchenne muscular dystrophy","volume":"25","author":"Chamberlain","year":"2017","journal-title":"Mol. Ther."},{"key":"2024102212523145000_ref11","doi-asserted-by":"crossref","first-page":"2337","DOI":"10.1016\/j.ymthe.2018.07.011","article-title":"Systemic AAV micro-dystrophin gene therapy for Duchenne muscular dystrophy","volume":"26","author":"Duan","year":"2018","journal-title":"Mol. Ther."},{"key":"2024102212523145000_ref12","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1080\/21678707.2018.1438261","article-title":"The potential of utrophin modulators for the treatment of Duchenne muscular dystrophy","volume":"6","author":"Guiraud","year":"2018","journal-title":"Expert Opin. Orphan Drugs"},{"key":"2024102212523145000_ref13","doi-asserted-by":"crossref","first-page":"44","DOI":"10.3390\/jfmk2040044","article-title":"Insights into the pathogenic secondary symptoms caused by the primary loss of Dystrophin","volume":"2","author":"Forcina","year":"2017","journal-title":"J. Funct. Morphol. Kinesiol."},{"key":"2024102212523145000_ref14","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.coph.2017.04.002","article-title":"Pharmacological advances for treatment in Duchenne muscular dystrophy","volume":"34","author":"Guiraud","year":"2017","journal-title":"Curr. Opin. Pharmacol."},{"key":"2024102212523145000_ref15","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1089\/hum.2018.151","article-title":"Gene and cell therapy for muscular dystrophies: are we getting there?","volume":"29","author":"Galli","year":"2018","journal-title":"Hum. Gene Ther."},{"key":"2024102212523145000_ref16","doi-asserted-by":"crossref","first-page":"114","DOI":"10.3389\/fgene.2018.00114","article-title":"Combined therapies for Duchenne muscular dystrophy to optimize treatment efficacy","volume":"9","author":"Cordova","year":"2018","journal-title":"Front. Genet."},{"key":"2024102212523145000_ref17","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.ymthe.2005.04.001","article-title":"Phenotypic improvement of dystrophic muscles by rAAV\/microdystrophin vectors is augmented by Igf1 codelivery","volume":"12","author":"Abmayr","year":"2005","journal-title":"Mol. Ther."},{"key":"2024102212523145000_ref18","doi-asserted-by":"crossref","first-page":"4929","DOI":"10.1093\/hmg\/ddt342","article-title":"Micro-dystrophin and follistatin co-delivery restores muscle function in aged DMD model","volume":"22","author":"Rodino-Klapac","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"2024102212523145000_ref19","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/387083a0","article-title":"Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member","volume":"387","author":"McPherron","year":"1997","journal-title":"Nature"},{"key":"2024102212523145000_ref20","doi-asserted-by":"crossref","first-page":"3555","DOI":"10.1093\/hmg\/ddw201","article-title":"Antisense pre-treatment increases gene therapy efficacy in dystrophic muscles","volume":"25","author":"Peccate","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"2024102212523145000_ref21","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1038\/360591a0","article-title":"Primary structure of dystrophin-related protein","volume":"360","author":"Tinsley","year":"1992","journal-title":"Nature"},{"key":"2024102212523145000_ref22","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/339055a0","article-title":"An autosomal transcript in skeletal muscle with homology to dystrophin","volume":"339","author":"Love","year":"1989","journal-title":"Nature"},{"key":"2024102212523145000_ref23","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/0960-8966(94)90070-1","article-title":"Expression of dystrophin-associated glycoproteins during human fetal muscle development: a preliminary immunocytochemical study","volume":"4","author":"Tome","year":"1994","journal-title":"Neuromuscul. Disord.: NMD"},{"key":"2024102212523145000_ref24","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1007\/BF02388063","article-title":"Dystrophin-related protein, utrophin, in normal and dystrophic human fetal skeletal muscle","volume":"25","author":"Clerk","year":"1993","journal-title":"Histochem. J."},{"key":"2024102212523145000_ref25","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1002\/aja.1001980403","article-title":"Expression of the dystrophin-related protein (utrophin) gene during mouse embryogenesis","volume":"198","author":"Schofield","year":"1993","journal-title":"Dev. Dyn."},{"key":"2024102212523145000_ref26","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1083\/jcb.115.6.1695","article-title":"Localization of the DMDL gene-encoded dystrophin-related protein using a panel of nineteen monoclonal antibodies: presence at neuromuscular junctions, in the sarcolemma of dystrophic skeletal muscle, in vascular and other smooth muscles, and in proliferating brain cell lines","volume":"115","author":"Nguyen","year":"1991","journal-title":"J. Cell Biol."},{"key":"2024102212523145000_ref27","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/0960-8966(92)90004-P","article-title":"The dystrophin-related protein, utrophin, is expressed on the sarcolemma of regenerating human skeletal muscle fibres in dystrophies and inflammatory myopathies","volume":"2","author":"Helliwell","year":"1992","journal-title":"Neuromuscul Disord.: NMD"},{"key":"2024102212523145000_ref28","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1111\/j.1365-2990.2009.01056.x","article-title":"Immunohistological intensity measurements as a tool to assess sarcolemma-associated protein expression","volume":"36","author":"Arechavala-Gomeza","year":"2010","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"2024102212523145000_ref29","doi-asserted-by":"crossref","first-page":"45285","DOI":"10.1074\/jbc.M205177200","article-title":"A- and B-utrophin have different expression patterns and are differentially up-regulated in mdx muscle","volume":"277","author":"Weir","year":"2002","journal-title":"J. Biol. Chem."},{"key":"2024102212523145000_ref30","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.bbadis.2006.05.010","article-title":"Dystrophin, its interactions with other proteins, and implications for muscular dystrophy","volume":"1772","author":"Ervasti","year":"2007","journal-title":"Biochim. Biophys. Acta"},{"key":"2024102212523145000_ref31","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1023\/A:1014964127156","article-title":"Immunogold confirmation that utrophin is localized to the normal position of dystrophin in dystrophin-negative transgenic mouse muscle","volume":"33","author":"Cullen","year":"2001","journal-title":"Histochem. J."},{"key":"2024102212523145000_ref32","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1038\/4033","article-title":"Expression of full-length utrophin prevents muscular dystrophy in mdx mice","volume":"4","author":"Tinsley","year":"1998","journal-title":"Nat. Med."},{"key":"2024102212523145000_ref33","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/S0960-8966(01)00220-6","article-title":"Non-toxic ubiquitous over-expression of utrophin in the mdx mouse","volume":"11","author":"Fisher","year":"2001","journal-title":"Neuromuscul. Disord.: NMD"},{"key":"2024102212523145000_ref34","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1111\/j.1365-2990.1997.tb01314.x","article-title":"The abnormal expression of utrophin in Duchenne and Becker muscular dystrophy is age related","volume":"23","author":"Taylor","year":"1997","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"2024102212523145000_ref35","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/0960-8966(94)90079-5","article-title":"Expression of dystrophin-associated glycoproteins and utrophin in carriers of Duchenne muscular dystrophy","volume":"4","author":"Sewry","year":"1994","journal-title":"Neuromuscul. Disord.: NMD"},{"key":"2024102212523145000_ref36","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1002\/(SICI)1097-0029(20000201\/15)48:3\/4<142::AID-JEMT3>3.0.CO;2-9","article-title":"Immunocytochemical analysis of human muscular dystrophy","volume":"48","author":"Sewry","year":"2000","journal-title":"Microsc. Res. Tech."},{"key":"2024102212523145000_ref37","doi-asserted-by":"crossref","first-page":"15","DOI":"10.3349\/ymj.2003.44.1.15","article-title":"Relationship between utrophin and regenerating muscle fibers in duchenne muscular dystrophy","volume":"44","author":"Shim","year":"2003","journal-title":"Yonsei Med. J."},{"key":"2024102212523145000_ref38","doi-asserted-by":"crossref","DOI":"10.1038\/mtm.2016.45","article-title":"100-fold but not 50-fold dystrophin overexpression aggravates electrocardiographic defects in the mdx model of Duchenne muscular dystrophy","volume":"3","author":"Yue","year":"2016","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"2024102212523145000_ref39","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1038\/364725a0","article-title":"Overexpression of dystrophin in transgenic mdx mice eliminates dystrophic symptoms without toxicity","volume":"364","author":"Cox","year":"1993","journal-title":"Nature"},{"key":"2024102212523145000_ref40","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."},{"key":"2024102212523145000_ref41","doi-asserted-by":"crossref","DOI":"10.1038\/srep43697","article-title":"Identification of serum protein biomarkers for utrophin based DMD therapy","volume":"7","author":"Guiraud","year":"2017","journal-title":"Sci. Rep."},{"key":"2024102212523145000_ref42","first-page":"307","article-title":"Embryonic myosin is a regeneration marker to monitor utrophin based therapies for DMD","volume":"28","author":"Guiraud","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"2024102212523145000_ref43","doi-asserted-by":"crossref","DOI":"10.1038\/mtna.2012.30","article-title":"Pip6-PMO, a new generation of peptide-oligonucleotide conjugates with improved cardiac exon skipping activity for DMD treatment","volume":"1","author":"Betts","year":"2012","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"2024102212523145000_ref44","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/j.nmd.2018.06.009","article-title":"Personalized gene and cell therapy for Duchenne muscular dystrophy","volume":"28","author":"Barthelemy","year":"2018","journal-title":"Neuromuscul. Disord.: NMD"},{"key":"2024102212523145000_ref45","doi-asserted-by":"crossref","first-page":"2864","DOI":"10.1091\/mbc.e06-12-1069","article-title":"Ets-2 repressor factor silences extrasynaptic utrophin by N-box mediated repression in skeletal muscle","volume":"18","author":"Perkins","year":"2007","journal-title":"Mol. Biol. Cell"},{"key":"2024102212523145000_ref46","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/S0165-3806(99)00165-0","article-title":"Utrophin may be a precursor of dystrophin during skeletal muscle development","volume":"119","author":"Lin","year":"2000","journal-title":"Brain Res. Dev. Brain Res."},{"key":"2024102212523145000_ref47","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/2044-5040-2-8","article-title":"Inducible Cre transgenic mouse strain for skeletal muscle-specific gene targeting","volume":"2","author":"McCarthy","year":"2012","journal-title":"Skeletal Muscle"},{"key":"2024102212523145000_ref48","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1083\/jcb.136.4.883","article-title":"Postsynaptic abnormalities at the neuromuscular junctions of utrophin-deficient mice","volume":"136","author":"Deconinck","year":"1997","journal-title":"J. Cell Biol."},{"key":"2024102212523145000_ref49","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.nmd.2018.02.013","article-title":"Low dystrophin levels are insufficient to normalize the neuromuscular synaptic abnormalities of mdx mice","volume":"28","author":"Pijl","year":"2018","journal-title":"Neuromuscul. Disord.: NMD"},{"key":"2024102212523145000_ref50","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.tins.2012.04.005","article-title":"Molecular mechanisms underlying maturation and maintenance of the vertebrate neuromuscular junction","volume":"35","author":"Shi","year":"2012","journal-title":"Trends Neurosci."},{"key":"2024102212523145000_ref51","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.omtn.2018.09.017","article-title":"NS-065\/NCNP-01: an antisense oligonucleotide for potential treatment of exon 53 skipping in Duchenne muscular dystrophy","volume":"13","author":"Watanabe","year":"2018","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"2024102212523145000_ref52","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0195850","article-title":"Use of capillary Western immunoassay (Wes) for quantification of dystrophin levels in skeletal muscle of healthy controls and individuals with Becker and Duchenne muscular dystrophy","volume":"13","author":"Beekman","year":"2018","journal-title":"PLoS One"},{"key":"2024102212523145000_ref53","doi-asserted-by":"crossref","first-page":"4212","DOI":"10.1093\/hmg\/ddv154","article-title":"Second-generation compound for the modulation of utrophin in the therapy of DMD","volume":"24","author":"Guiraud","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"2024102212523145000_ref54","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1038\/mt.2008.149","article-title":"Microutrophin delivery through rAAV6 increases lifespan and improves muscle function in dystrophic dystrophin\/utrophin-deficient mice","volume":"16","author":"Odom","year":"2008","journal-title":"Mol. Ther."}],"container-title":["Human Molecular Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/hmg\/article-pdf\/28\/13\/2189\/59959007\/hmg_28_13_2189.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/hmg\/article-pdf\/28\/13\/2189\/59959007\/hmg_28_13_2189.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T12:54:14Z","timestamp":1729601654000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/hmg\/article\/28\/13\/2189\/5369669"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,5]]},"references-count":54,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2019,3,5]]},"published-print":{"date-parts":[[2019,7,1]]}},"URL":"https:\/\/doi.org\/10.1093\/hmg\/ddz049","relation":{},"ISSN":["0964-6906","1460-2083"],"issn-type":[{"value":"0964-6906","type":"print"},{"value":"1460-2083","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,7,1]]},"published":{"date-parts":[[2019,3,5]]}}}