{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T23:44:52Z","timestamp":1790639092607,"version":"4.1.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T00:00:00Z","timestamp":1638835200000},"content-version":"vor","delay-in-days":1477,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Beta-thalassemia is one of the most common recessive genetic diseases, caused by mutations in the HBB gene. Over 200 different types of mutations in the HBB gene containing three exons have been identified in patients with \u03b2-thalassemia (\u03b2-thal) whereas a homozygous mutation in exon 1 causes sickle cell disease (SCD). Novel therapeutic strategies to permanently correct the HBB mutation in stem cells that are able to expand and differentiate into erythrocytes producing corrected HBB proteins are highly desirable. Genome editing aided by CRISPR\/Cas9 and other site-specific engineered nucleases offers promise to precisely correct a genetic mutation in the native genome without alterations in other parts of the human genome. Although making a sequence-specific nuclease to enhance correction of a specific HBB mutation by homology-directed repair (HDR) is becoming straightforward, targeting various HBB mutations of \u03b2-thal is still challenging because individual guide RNA as well as a donor DNA template for HDR of each type of HBB gene mutation have to be selected and validated. Using human induced pluripotent stem cells (iPSCs) from two \u03b2-thal patients with different HBB gene mutations, we devised and tested a universal strategy to achieve targeted insertion of the HBB cDNA in exon 1 of HBB gene using Cas9 and two validated guide RNAs. We observed that HBB protein production was restored in erythrocytes derived from iPSCs of two patients. This strategy of restoring functional HBB gene expression will be able to correct most types of HBB gene mutations in \u03b2-thal and SCD.<\/jats:p>","DOI":"10.1002\/sctm.17-0066","type":"journal-article","created":{"date-parts":[[2017,11,22]],"date-time":"2017-11-22T04:52:45Z","timestamp":1511326365000},"page":"87-97","source":"Crossref","is-referenced-by-count":82,"title":["A Universal Approach to Correct Various <i>HBB<\/i> Gene Mutations in Human Stem Cells for Gene Therapy of Beta-Thalassemia and Sickle Cell Disease"],"prefix":"10.1093","volume":"7","author":[{"given":"Liuhong","family":"Cai","sequence":"first","affiliation":[{"name":"a Center for Reproductive Medicine The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China"},{"name":"b Division of Hematology, Department of Medicine, Baltimore, Maryland, USA"},{"name":"c Stem Cell Program in the Institute for Cell Engineering Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Bai","sequence":"additional","affiliation":[{"name":"b Division of Hematology, Department of Medicine, Baltimore, Maryland, USA"},{"name":"c Stem Cell Program in the Institute for Cell Engineering Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasiliki","family":"Mahairaki","sequence":"additional","affiliation":[{"name":"c Stem Cell Program in the Institute for Cell Engineering Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"},{"name":"d Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongxing","family":"Gao","sequence":"additional","affiliation":[{"name":"b Division of Hematology, Department of Medicine, Baltimore, Maryland, USA"},{"name":"c Stem Cell Program in the Institute for Cell Engineering Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoxia","family":"He","sequence":"additional","affiliation":[{"name":"b Division of Hematology, Department of Medicine, Baltimore, Maryland, USA"},{"name":"c Stem Cell Program in the Institute for Cell Engineering Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanfei","family":"Wen","sequence":"additional","affiliation":[{"name":"a Center for Reproductive Medicine The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China"},{"name":"e Center for Reproductive Medicine Jiangmen Hospital, Sun Yat-sen University, Jiangmen, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You-Chuan","family":"Jin","sequence":"additional","affiliation":[{"name":"c Stem Cell Program in the Institute for Cell Engineering Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"},{"name":"f Li Ka Shing Faculty of Medicine The University of Hong Kong, Hong Kong, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You","family":"Wang","sequence":"additional","affiliation":[{"name":"c Stem Cell Program in the Institute for Cell Engineering Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"},{"name":"g Department of Public Health Studies Johns Hopkins University Krieger School of Art and Science, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel L.","family":"Pan","sequence":"additional","affiliation":[{"name":"c Stem Cell Program in the Institute for Cell Engineering Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"},{"name":"h Department of Biology Emory University, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armaan","family":"Qasba","sequence":"additional","affiliation":[{"name":"c Stem Cell Program in the Institute for Cell Engineering Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"},{"name":"i Department of Biology McDaniel College, Westminster, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaohui","family":"Ye","sequence":"additional","affiliation":[{"name":"b Division of Hematology, Department of Medicine, Baltimore, Maryland, USA"},{"name":"j Division of Cellular and Gene Therapies, Gene Transfer and Immunogenicity Branch Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linzhao","family":"Cheng","sequence":"additional","affiliation":[{"name":"b Division of Hematology, Department of Medicine, Baltimore, Maryland, USA"},{"name":"c Stem Cell Program in the Institute for Cell Engineering Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,11,21]]},"reference":[{"key":"2022022808492915900_sct312237-bib-0001","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/35066048","article-title":"Phenotype-genotype relationships in monogenic disease: Lessons from the thalassaemias","volume":"2","author":"Weatherall","year":"2001","journal-title":"Nat Rev Genet"},{"key":"2022022808492915900_sct312237-bib-0002","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1007\/s11684-011-0159-1","article-title":"Stem cell gene therapy: The risks of insertional mutagenesis and approaches to minimize genotoxicity","volume":"5","author":"Wu","year":"2011","journal-title":"Front Med"},{"key":"2022022808492915900_sct312237-bib-0003","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1038\/nrg2985","article-title":"Ex vivo gene transfer and correction for cell-based therapies","volume":"12","author":"Naldini","year":"2011","journal-title":"Nat Rev Genet"},{"key":"2022022808492915900_sct312237-bib-0004","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1182\/blood-2011-09-349993","article-title":"Hematopoietic stem cell engineering at a crossroads","volume":"119","author":"Rivi\u00e8re","year":"2012","journal-title":"Blood"},{"key":"2022022808492915900_sct312237-bib-0005","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1177\/2040620716653729","article-title":"The potential of gene therapy approaches for the treatment of hemoglobinopathies: Achievements and challenges","volume":"7","author":"Goodman","year":"2016","journal-title":"Ther Adv Hematol"},{"key":"2022022808492915900_sct312237-bib-0006","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1007\/s00439-016-1696-0","article-title":"Treating hemoglobinopathies using gene-correction approaches: Promises and challenges","volume":"135","author":"Cottle","year":"2016","journal-title":"Hum Genet"},{"key":"2022022808492915900_sct312237-bib-0007","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1089\/hum.2016.107","article-title":"Gene editing of human hematopoietic stem and progenitor cells: Promise and potential hurdles","volume":"27","author":"Yu","year":"2016","journal-title":"Hum Gene Ther"},{"key":"2022022808492915900_sct312237-bib-0008","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1038\/nbt1125","article-title":"Gene targeting using zinc finger nucleases","volume":"23","author":"Porteus","year":"2005","journal-title":"Nat Biotechnol"},{"key":"2022022808492915900_sct312237-bib-0009","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1634\/stemcells.2008-0346","article-title":"Improved efficiency and pace of generating induced pluripotent stem cells from human adult and fetal fibroblasts","volume":"26","author":"Mali","year":"2008","journal-title":"Stem Cells"},{"key":"2022022808492915900_sct312237-bib-0010","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1038\/cr.2009.100","article-title":"Generation of induced pluripotent stem cells from human beta-thalassemia fibroblast cells","volume":"19","author":"Wang","year":"2009","journal-title":"Cell Res"},{"key":"2022022808492915900_sct312237-bib-0011","doi-asserted-by":"crossref","first-page":"9826","DOI":"10.1073\/pnas.0904689106","article-title":"Induced pluripotent stem cells offer new approach to therapy in thalassemia and sickle cell anemia and option in prenatal diagnosis in genetic diseases","volume":"106","author":"Ye","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"key":"2022022808492915900_sct312237-bib-0012","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1038\/cr.2011.12","article-title":"Efficient human iPS cell derivation by a non-integrating plasmid from blood cells with unique epigenetic and gene expression signatures","volume":"21","author":"Chou","year":"2011","journal-title":"Cell Res"},{"key":"2022022808492915900_sct312237-bib-0013","doi-asserted-by":"crossref","first-page":"4599","DOI":"10.1182\/blood-2011-02-335554","article-title":"Site-specific gene correction of a point mutation in human iPS cells derived from sickle cell disease patient","volume":"118","author":"Zou","year":"2011","journal-title":"Blood"},{"key":"2022022808492915900_sct312237-bib-0014","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1002\/stem.718","article-title":"In situ genetic correction of the sickle cell anemia mutation in human induced pluripotent stem cells using engineered zinc finger nucleases","volume":"29","author":"Sebastiano","year":"2011","journal-title":"Stem Cells"},{"key":"2022022808492915900_sct312237-bib-0015","doi-asserted-by":"crossref","first-page":"2376","DOI":"10.1038\/srep02376","article-title":"Expanded activity of dimer nucleases by combining ZFN and TALEN for genome editing","volume":"3","author":"Yan","year":"2013","journal-title":"Sci Rep"},{"key":"2022022808492915900_sct312237-bib-0016","doi-asserted-by":"crossref","first-page":"34671","DOI":"10.1074\/jbc.M113.496174","article-title":"Transcription activator-like effector nuclease (TALEN)-mediated gene correction in integration-free \u03b2-thalassemia induced pluripotent stem cells","volume":"288","author":"Ma","year":"2013","journal-title":"J Biol Chem"},{"key":"2022022808492915900_sct312237-bib-0017","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1101\/gr.173427.114","article-title":"Seamless gene correction of \u03b2-thalassemia mutations in patient-specific iPSCs using CRISPR\/Cas9 and piggyBac","volume":"24","author":"Xie","year":"2014","journal-title":"Genome Res"},{"key":"2022022808492915900_sct312237-bib-0018","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1002\/stem.1969","article-title":"Corrected adult \u03b2-globin protein production in mature erythrocytes differentiated from patient iPSCs after genome editing of the sickle point mutation","volume":"33","author":"Huang","year":"2015","journal-title":"Stem Cells"},{"key":"2022022808492915900_sct312237-bib-0019","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1089\/scd.2014.0347","article-title":"Improved hematopoietic differentiation efficiency of gene-corrected beta-thalassemia induced pluripotent stem cells by CRISPR\/Cas9 system","volume":"24","author":"Song","year":"2015","journal-title":"Stem Cells Dev"},{"key":"2022022808492915900_sct312237-bib-0020","doi-asserted-by":"crossref","first-page":"12065","DOI":"10.1038\/srep12065","article-title":"Both TALENs and CRISPR\/Cas9 directly target the HBB IVS2\u2013654 (C\u2009&gt;\u2009T) mutation in \u03b2-thalassemia-derived iPSCs","volume":"5","author":"Xu","year":"2015","journal-title":"Sci Rep"},{"key":"2022022808492915900_sct312237-bib-0021","doi-asserted-by":"crossref","first-page":"32463","DOI":"10.1038\/srep32463","article-title":"The combination of CRISPR\/Cas9 and iPSC technologies in the gene therapy of human \u03b2-thalassemia in mice","volume":"6","author":"Ou","year":"2016","journal-title":"Sci Rep"},{"key":"2022022808492915900_sct312237-bib-0022","doi-asserted-by":"crossref","first-page":"16576","DOI":"10.1074\/jbc.M116.719237","article-title":"Combining single strand oligodeoxynucleotides and CRISPR\/Cas9 to correct gene mutations in \u03b2-thalassemia-induced pluripotent stem cells","volume":"291","author":"Niu","year":"2016","journal-title":"J Biol Chem"},{"key":"2022022808492915900_sct312237-bib-0023","doi-asserted-by":"crossref","first-page":"267","DOI":"10.5966\/sctm.2015-0157erratum","article-title":"Na\u00efve induced pluripotent stem cells generated from \u03b2-thalassemia fibroblasts allow efficient gene correction with CRISPR\/Cas9","volume":"5","author":"Yang","year":"2016","journal-title":"Stem Cells Translational Medicine"},{"key":"2022022808492915900_sct312237-bib-0024","doi-asserted-by":"crossref","first-page":"320","DOI":"10.5966\/sctm.2014-0214","article-title":"A facile method to establish human iPS cells from adult blood cells under feeder-free and xeno-free culture conditions: A clinically compliant approach","volume":"4","author":"Chou","year":"2015","journal-title":"Stem Cells Translational Medicine"},{"key":"2022022808492915900_sct312237-bib-0025","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1016\/j.scr.2013.07.011","article-title":"Scalable expansion of human induced pluripotent stem cells in the defined xeno-free E8 medium under adherent and suspension culture conditions","volume":"11","author":"Wang","year":"2013","journal-title":"Stem Cell Res"},{"key":"2022022808492915900_sct312237-bib-0026","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1126\/science.1232033","article-title":"RNA-guided human genome engineering via Cas9","volume":"339","author":"Mali","year":"2013","journal-title":"Science"},{"key":"2022022808492915900_sct312237-bib-0027","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1038\/mt.2014.226","article-title":"Efficient and allele-specific genome editing of disease loci in human iPSCs","volume":"23","author":"Smith","year":"2014","journal-title":"Mol Ther"},{"key":"2022022808492915900_sct312237-bib-0028","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/nbt.1927","article-title":"Genetic engineering of human pluripotent cells using TALE nucleases","volume":"29","author":"Hockemeyer","year":"2011","journal-title":"Nat Biotechnol"},{"key":"2022022808492915900_sct312237-bib-0029","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1038\/nprot.2012.121","article-title":"Generation of integration-free human induced pluripotent stem cells from postnatal blood mononuclear cells by plasmid vector expression","volume":"7","author":"Dowey","year":"2012","journal-title":"Nat Protoc"},{"key":"2022022808492915900_sct312237-bib-0030","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1097\/GIM.0b013e3181cd68ed","article-title":"Beta-thalassemia","volume":"12","author":"Cao","year":"2010","journal-title":"Genet Med"},{"key":"2022022808492915900_sct312237-bib-0031","doi-asserted-by":"crossref","first-page":"3513","DOI":"10.1182\/blood-2009-03-191304","article-title":"Toward clinical therapies using hematopoietic cells derived from human pluripotent stem cells","volume":"114","author":"Kaufman","year":"2009","journal-title":"Blood"},{"key":"2022022808492915900_sct312237-bib-0032","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/nature10761","article-title":"The promise of induced pluripotent stem cells in research and therapy","volume":"481","author":"Robinton","year":"2012","journal-title":"Nature"},{"key":"2022022808492915900_sct312237-bib-0033","doi-asserted-by":"crossref","first-page":"4035","DOI":"10.1182\/blood-2013-07-474825","article-title":"Hematopoietic specification from human pluripotent stem cells: Current advances and challenges toward de novo generation of hematopoietic stem cells","volume":"122","author":"Slukvin","year":"2013","journal-title":"Blood"},{"key":"2022022808492915900_sct312237-bib-0034","doi-asserted-by":"crossref","first-page":"927","DOI":"10.5966\/sctm.2012-0097","article-title":"Concise review: Production of cultured red blood cells from stem cells","volume":"1","author":"Bouhassira","year":"2012","journal-title":"Stem Cells Translational Medicine"},{"key":"2022022808492915900_sct312237-bib-0035","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.stem.2012.01.001","article-title":"The potential of stem cells as an in vitro source of red blood cells for transfusion","volume":"10","author":"Migliaccio","year":"2012","journal-title":"Cell Stem Cell"},{"key":"2022022808492915900_sct312237-bib-0036","doi-asserted-by":"crossref","first-page":"346","DOI":"10.5966\/sctm.2013-0054","article-title":"Stem cell-based approaches of red blood cell production for transfusion","volume":"3","author":"Shah","year":"2014","journal-title":"Stem Cells Translational Medicine"},{"key":"2022022808492915900_sct312237-bib-0037","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.3324\/haematol.2011.055566","article-title":"Human induced pluripotent stem cells can reach complete terminal maturation: In vivo and in vitro evidence in the erythropoietic differentiation model","volume":"97","author":"Kobari","year":"2012","journal-title":"Haematologica"},{"key":"2022022808492915900_sct312237-bib-0038","doi-asserted-by":"crossref","first-page":"e100874","DOI":"10.1371\/journal.pone.0100874","article-title":"Qualitative and quantitative comparison of the proteome of erythroid cells differentiated from human iPSCs and adult erythroid cells by multiplex TMT labelling and nanoLC-MS\/MS","volume":"9","author":"Trakarnsanga","year":"2014","journal-title":"PLoS One"},{"key":"2022022808492915900_sct312237-bib-0039","doi-asserted-by":"crossref","first-page":"3466","DOI":"10.1182\/blood-2014-01-548305","article-title":"Global transcriptome analyses of human and murine terminal erythroid differentiation","volume":"123","author":"An","year":"2014","journal-title":"Blood"},{"key":"2022022808492915900_sct312237-bib-0040","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.stem.2015.09.015","article-title":"Targeted application of human genetic variation can improve red blood cell production from stem cells","volume":"18","author":"Giani","year":"2016","journal-title":"Cell Stem Cell"},{"key":"2022022808492915900_sct312237-bib-0041","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1093\/nar\/gkt947","article-title":"Nuclease-mediated gene editing by homologous recombination of the human globin locus","volume":"42","author":"Voit","year":"2014","journal-title":"Nucleic Acids Res"},{"key":"2022022808492915900_sct312237-bib-0042","doi-asserted-by":"crossref","first-page":"360ra134","DOI":"10.1126\/scitranslmed.aaf9336","article-title":"Selection-free genome editing of the sickle mutation in human adult hematopoietic stem\/progenitor cells","volume":"8","author":"DeWitt","year":"2016","journal-title":"Sci Transl Med"},{"key":"2022022808492915900_sct312237-bib-0043","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1038\/nature20134","article-title":"CRISPR\/Cas9 \u03b2-globin gene targeting in human haematopoietic stem cells","volume":"539","author":"Dever","year":"2016","journal-title":"Nature"},{"key":"2022022808492915900_sct312237-bib-0044","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1038\/mt.2016.148","article-title":"CRISPR\/Cas9-mediated correction of the sickle mutation in human CD34+ cells","volume":"24","author":"Hoban","year":"2016","journal-title":"Mol Ther"},{"key":"2022022808492915900_sct312237-bib-0045","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1038\/nature15521","article-title":"BCL11A enhancer dissection by Cas9-mediated in situ saturating mutagenesis","volume":"527","author":"Canver","year":"2015","journal-title":"Nature"},{"key":"2022022808492915900_sct312237-bib-0046","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1038\/nm.4170","article-title":"A genome-editing strategy to treat \u03b2-hemoglobinopathies that recapitulates a mutation associated with a benign genetic condition","volume":"22","author":"Traxler","year":"2016","journal-title":"Nat Med"}],"container-title":["Stem Cells Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fsctm.17-0066","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/stcltm\/article-pdf\/7\/1\/87\/42625622\/stcltm_7_1_87.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/stcltm\/article-pdf\/7\/1\/87\/42625622\/stcltm_7_1_87.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T08:50:53Z","timestamp":1646038253000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/stcltm\/article\/7\/1\/87\/6454813"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,21]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,11,21]]},"published-print":{"date-parts":[[2018,1,1]]}},"URL":"https:\/\/doi.org\/10.1002\/sctm.17-0066","relation":{},"ISSN":["2157-6564","2157-6580"],"issn-type":[{"value":"2157-6564","type":"print"},{"value":"2157-6580","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2018,1,1]]},"published":{"date-parts":[[2017,11,21]]}}}