{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T22:11:00Z","timestamp":1785276660051,"version":"3.55.0"},"reference-count":45,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2015,12,3]],"date-time":"2015-12-03T00:00:00Z","timestamp":1449100800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"},{"start":{"date-parts":[[2015,12,3]],"date-time":"2015-12-03T00:00:00Z","timestamp":1449100800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"},{"start":{"date-parts":[[2015,12,3]],"date-time":"2015-12-03T00:00:00Z","timestamp":1449100800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000070","name":"National Institute of Biomedical Imaging and Bioengineering","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000070","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000093","name":"Center for Information Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000093","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["61427807"],"award-info":[{"award-number":["61427807"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["61271083"],"award-info":[{"award-number":["61271083"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["61525106"],"award-info":[{"award-number":["61525106"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LR12F03001"],"award-info":[{"award-number":["LR12F03001"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006049","name":"Marine Biological Laboratory","doi-asserted-by":"publisher","award":["Whitman Research Award"],"award-info":[{"award-number":["Whitman Research Award"]}],"id":[{"id":"10.13039\/100006049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UO1 HD075602"],"award-info":[{"award-number":["UO1 HD075602"]}],"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":["R24OD016474"],"award-info":[{"award-number":["R24OD016474"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>The nematode Caenorhabditis elegans possesses a simple embryonic nervous system with few enough neurons that the growth of each cell could be followed to provide a systems-level view of development. However, studies of single cell development have largely been conducted in fixed or pre-twitching live embryos, because of technical difficulties associated with embryo movement in late embryogenesis. We present open-source untwisting and annotation software (http:\/\/mipav.cit.nih.gov\/plugin_jws\/mipav_worm_plugin.php) that allows the investigation of neurodevelopmental events in late embryogenesis and apply it to track the 3D positions of seam cell nuclei, neurons, and neurites in multiple elongating embryos. We also provide a tutorial describing how to use the software (&lt;xref ref-type=\"supplementary-material\" rid=\"SD1-data\"&gt;Supplementary file 1&lt;\/xref&gt;) and a detailed description of the untwisting algorithm (Appendix). The detailed positional information we obtained enabled us to develop a composite model showing movement of these cells and neurites in an 'average' worm embryo. The untwisting and cell tracking capabilities of our method provide a foundation on which to catalog C. elegans neurodevelopment, allowing interrogation of developmental events in previously inaccessible periods of embryogenesis.<\/jats:p>","DOI":"10.7554\/elife.10070","type":"journal-article","created":{"date-parts":[[2015,12,3]],"date-time":"2015-12-03T07:58:45Z","timestamp":1449129525000},"source":"Crossref","is-referenced-by-count":38,"title":["Untwisting the Caenorhabditis elegans embryo"],"prefix":"10.7554","volume":"4","author":[{"given":"Ryan Patrick","family":"Christensen","sequence":"first","affiliation":[{"name":"Section on High Resolution Optical Imaging, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Bokinsky","sequence":"additional","affiliation":[{"name":"Biomedical Imaging Research Services Section, Center for Information Technology, National Institutes of Health, Bethesda, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Santella","sequence":"additional","affiliation":[{"name":"Developmental Biology Program, Sloan-Kettering Institute, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yicong","family":"Wu","sequence":"additional","affiliation":[{"name":"Section on High Resolution Optical Imaging, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Marquina-Solis","sequence":"additional","affiliation":[{"name":"Program in Cellular Neuroscience, Neurodegeneration and Repair, Department of Cell Biology, Yale University School of Medicine, New Haven, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Guo","sequence":"additional","affiliation":[{"name":"Section on High Resolution Optical Imaging, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, United States"},{"name":"State Key Laboratory of Modern Optical Instrumentation, College of Optical Science and Engineering, Zhejiang University, Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismar","family":"Kovacevic","sequence":"additional","affiliation":[{"name":"Developmental Biology Program, Sloan-Kettering Institute, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhishek","family":"Kumar","sequence":"additional","affiliation":[{"name":"Section on High Resolution Optical Imaging, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, United States"},{"name":"Program in Cellular Neuroscience, Neurodegeneration and Repair, Department of Cell Biology, Yale University School of Medicine, New Haven, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter W","family":"Winter","sequence":"additional","affiliation":[{"name":"Section on High Resolution Optical Imaging, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Tashakkori","sequence":"additional","affiliation":[{"name":"Section on High Resolution Optical Imaging, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan","family":"McCreedy","sequence":"additional","affiliation":[{"name":"Biomedical Imaging Research Services Section, Center for Information Technology, National Institutes of Health, Bethesda, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huafeng","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Modern Optical Instrumentation, College of Optical Science and Engineering, Zhejiang University, Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"McAuliffe","sequence":"additional","affiliation":[{"name":"Biomedical Imaging Research Services Section, Center for Information Technology, National Institutes of Health, Bethesda, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Mohler","sequence":"additional","affiliation":[{"name":"Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel A","family":"Col\u00f3n-Ramos","sequence":"additional","affiliation":[{"name":"Program in Cellular Neuroscience, Neurodegeneration and Repair, Department of Cell Biology, Yale University School of Medicine, New Haven, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhirong","family":"Bao","sequence":"additional","affiliation":[{"name":"Developmental Biology Program, Sloan-Kettering Institute, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hari","family":"Shroff","sequence":"additional","affiliation":[{"name":"Section on High Resolution Optical Imaging, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2015,12,3]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1038\/nmeth.2434","article-title":"Whole-brain functional imaging at cellular resolution using light-sheet microscopy","volume":"10","author":"Ahrens","year":"2013","journal-title":"Nature Methods"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1038\/nmeth.3036","article-title":"Fast, accurate reconstruction of cell lineages from large-scale fluorescence microscopy data","volume":"11","author":"Amat","year":"2014","journal-title":"Nature Methods"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"2651","DOI":"10.1534\/genetics.107.074369","article-title":"Temporal control of cell-specific transgene expression in caenorhabditis elegans","volume":"176","author":"Bacaj","year":"2007","journal-title":"Genetics"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"2707","DOI":"10.1073\/pnas.0511111103","article-title":"Automated cell lineage tracing in caenorhabditis elegans","volume":"103","author":"Bao","year":"2006","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"bib5","author":"Bao","year":"2010"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"2012","DOI":"10.1126\/science.282.5396.2012","article-title":"Genome sequence of the nematode c. elegans: a platform for investigating biology","volume":"282","author":"C. elegans Sequencing Consortium","year":"1998","journal-title":"Science"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.ydbio.2005.12.048","article-title":"Molecular mechanisms of axon guidance","volume":"292","author":"Chilton","year":"2006","journal-title":"Developmental Biology"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1016\/S0168-9525(00)02143-0","article-title":"Form of the worm: genetics of epidermal morphogenesis in c. elegans","volume":"16","author":"Chin-Sang","year":"2000","journal-title":"Trends in Genetics"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"93340C","DOI":"10.1117\/12.2082394","article-title":"An imaging and analysis toolset for the study of caenorhabditis elegans neurodevelopment","volume":"9334","author":"Christensen","year":"2015","journal-title":"\u00a0SPIE BIOS"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"3379","DOI":"10.1098\/rsta.2009.0088","article-title":"Continuum model of epithelial morphogenesis during caenorhabditis elegans embryonic elongation","volume":"367","author":"Ciarletta","year":"2009","journal-title":"Philosophical Transactions of the Royal Society A"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.yexcr.2004.08.017","article-title":"The cytoskeleton and epidermal morphogenesis in","volume":"301","author":"Ding","year":"2004","journal-title":"Experimental Cell Research"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/j.tins.2013.01.007","article-title":"Integration of guidance cues: parallel signaling and crosstalk","volume":"36","author":"Dudanova","year":"2013","journal-title":"Trends in Neurosciences"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"3109","DOI":"10.1242\/dev.039412","article-title":"Myosin II regulation during c. elegans embryonic elongation: LET-502\/ROCK, MRCK-1 and PAK-1, three kinases with different roles","volume":"136","author":"Gally","year":"2009","journal-title":"Development"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"4271","DOI":"10.1242\/dev.086256","article-title":"Quantitative semi-automated analysis of morphogenesis with single-cell resolution in complex embryos","volume":"139","author":"Giurumescu","year":"2012","journal-title":"Development"},{"key":"bib15","doi-asserted-by":"publisher","DOI":"10.1007\/s10278-015-9833-1","article-title":"A survey of DICOM viewer software to integrate clinical research and medical imaging","author":"Haak","year":"2015","journal-title":"Journal of Digital Imaging"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"6255","DOI":"10.1073\/pnas.94.12.6255","article-title":"Targeted gene expression without a tissue-specific promoter: creating mosaic embryos using laser-induced single-cell heat shock","volume":"94","author":"Halfon","year":"1997","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1016\/j.neuron.2008.01.011","article-title":"Fast three-dimensional fluorescence imaging of activity in neural populations by objective-coupled planar illumination microscopy","volume":"57","author":"Holekamp","year":"2008","journal-title":"Neuron"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1126\/science.1100035","article-title":"Optical sectioning deep inside live embryos by selective plane illumination microscopy","volume":"305","author":"Huisken","year":"2004","journal-title":"Science"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fncir.2013.00001","article-title":"Error detection and representation in the olivo-cerebellar system","volume":"7","author":"Ito","year":"2013","journal-title":"Frontiers in Neural Circuits"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1126\/science.1162493","article-title":"Reconstruction of zebrafish early embryonic development by scanned light sheet microscopy","volume":"322","author":"Keller","year":"2008","journal-title":"Science"},{"key":"bib21","doi-asserted-by":"crossref","first-page":"2867","DOI":"10.1242\/dev.128.15.2867","article-title":"ELT-5 and ELT-6 are required continuously to regulate epidermal seam cell differentiation and cell fusion in C. elegans","volume":"128","author":"Koh","year":"2001","journal-title":"Development"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"a001727","DOI":"10.1101\/cshperspect.a001727","article-title":"Mechanisms and molecules of neuronal wiring: a primer","volume":"3","author":"Kolodkin","year":"2011","journal-title":"Cold Spring Harbor Perspectives in Biology"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1063\/PT.3.2856","article-title":"Watching a roundworm develop with a sheet of light","volume":"68","author":"Kumar","year":"2015","journal-title":"Physics Today"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"2555","DOI":"10.1038\/nprot.2014.172","article-title":"Dual-view plane illumination microscopy for rapid and spatially isotropic imaging","volume":"9","author":"Kumar","year":"2014","journal-title":"Nature Protocols"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"e30826","DOI":"10.1371\/journal.pone.0030826","article-title":"3D multicolor super-resolution imaging offers improved accuracy in neuron tracing","volume":"7","author":"Lakadamyali","year":"2012","journal-title":"PloS One"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/nature06293","article-title":"Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system","volume":"450","author":"Livet","year":"2007","journal-title":"Nature"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1038\/nmeth.1366","article-title":"A 3D digital atlas of C. elegans and its application to single-cell analyses","volume":"6","author":"Long","year":"2009","journal-title":"Nature Methods"},{"key":"bib28","first-page":"381","article-title":"Medical image processing, analysis, and visualization in clinical research","author":"McAuliffe","year":"2001","journal-title":"Proc. 14th IEEE Symp. Computer-Based Medical Systems"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1083\/jcb.200111051","article-title":"Alpha spectrin is essential for morphogenesis and body wall muscle formation in caenorhabditis elegans","volume":"157","author":"Norman","year":"2002","journal-title":"The Journal of Cell Biology"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1146\/annurev.neuro.051508.135614","article-title":"Axon growth and guidance: receptor regulation and signal transduction","volume":"32","author":"O'Donnell","year":"2009","journal-title":"Annual Review of Neuroscience"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1093\/bioinformatics\/btm569","article-title":"Straightening caenorhabditis elegans images","volume":"24","author":"Peng","year":"2008","journal-title":"Bioinformatics"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/0012-1606(86)90358-1","article-title":"Caenorhabditis elegans morphogenesis: the role of the cytoskeleton in elongation of the embryo","volume":"117","author":"Priess","year":"1986","journal-title":"Developmental Biology"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1186\/s12859-015-0627-8","article-title":"WormGUIDES: an interactive single cell developmental atlas and tool for collaborative multidimensional data exploration","volume":"16","author":"Santella","year":"2015","journal-title":"BMC Bioinformatics"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1186\/1471-2105-11-580","article-title":"A hybrid blob-slice model for accurate and efficient detection of fluorescence labeled nuclei in 3D","volume":"11","author":"Santella","year":"2010","journal-title":"BMC Bioinformatics"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1369\/0022155410394857","article-title":"Light sheet fluorescence microscopy: a review","volume":"59","author":"Santi","year":"2011","journal-title":"The Journal of Histochemistry and Cytochemistry\u00a0"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/0012-1606(83)90201-4","article-title":"The embryonic cell lineage of the nematode caenorhabditis elegans","volume":"100","author":"Sulston","year":"1983","journal-title":"Developmental Biology"},{"key":"bib37","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1093\/genetics\/146.1.185","article-title":"A deficiency screen for zygotic loci required for establishment and patterning of the epidermis in caenorhabditis elegans","volume":"146","author":"Terns","year":"1997","journal-title":"Genetics"},{"key":"bib38","article-title":"EM image 2-fold_993, from 2-fold image set","author":"Thomson","unstructured":"Thomson N. EM image 2-fold_993, from 2-fold image set. http:\/\/www.wormimage.org."},{"key":"bib39","doi-asserted-by":"publisher","first-page":"1259","DOI":"10.1242\/dev.02833","article-title":"PAR-6 is required for junction formation but not apicobasal polarization in c. elegans embryonic epithelial cells","volume":"134","author":"Totong","year":"2007","journal-title":"Development"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1016\/j.devcel.2004.05.004","article-title":"Genomic cis-regulatory architecture and trans-acting regulators of a single interneuron-specific gene battery in c. elegans","volume":"6","author":"Wenick","year":"2004","journal-title":"Developmental Cell"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1098\/rstb.1986.0056","article-title":"The structure of the nervous system of the nematode caenorhabditis elegans","volume":"314","author":"White","year":"1986","journal-title":"Philosophical Transactions of the Royal Society B"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1364\/OPTICA.1.000181","article-title":"Two-photon instant structured illumination microscopy improves the depth penetration of super-resolution imaging in thick scattering samples","volume":"1","author":"Winter","year":"2014","journal-title":"Optica"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"1090","DOI":"10.1016\/j.conb.2013.06.008","article-title":"Advanced optical imaging techniques for neurodevelopment","volume":"23","author":"Wu","year":"2013","journal-title":"Current Opinion in Neurobiology"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"17708","DOI":"10.1073\/pnas.1108494108","article-title":"Inverted selective plane illumination microscopy (iSPIM) enables coupled cell identity lineaging and neurodevelopmental imaging in caenorhabditis elegans","volume":"108","author":"Wu","year":"2011","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"1032","DOI":"10.1038\/nbt.2713","article-title":"Spatially isotropic four-dimensional imaging with dual-view plane illumination microscopy","volume":"31","author":"Wu","year":"2013","journal-title":"Nature Biotechnology"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/10070\/elife-10070-v2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/10070\/elife-10070-v2.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/10070","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T20:53:02Z","timestamp":1697057582000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/10070"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,12,3]]},"references-count":45,"alternative-id":["10.7554\/eLife.10070"],"URL":"https:\/\/doi.org\/10.7554\/elife.10070","archive":["CLOCKSS"],"relation":{"has-review":[{"id-type":"doi","id":"10.7554\/eLife.10070.057","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.10070.058","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,12,3]]},"article-number":"e10070"}}