{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T14:27:17Z","timestamp":1791642437993,"version":"4.3.4"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2017,6,5]],"date-time":"2017-06-05T00:00:00Z","timestamp":1496620800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Genet"],"published-print":{"date-parts":[[2017,7]]},"DOI":"10.1038\/ng.3878","type":"journal-article","created":{"date-parts":[[2017,6,5]],"date-time":"2017-06-05T11:04:21Z","timestamp":1496660661000},"page":"1035-1044","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":189,"title":["Hyperactivation of HUSH complex function by Charcot\u2013Marie\u2013Tooth disease mutation in MORC2"],"prefix":"10.1038","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0477-0956","authenticated-orcid":false,"given":"Iva A","family":"Tchasovnikarova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard T","family":"Timms","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher H","family":"Douse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0008-4649","authenticated-orcid":false,"given":"Rhys C","family":"Roberts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon","family":"Dougan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert E","family":"Kingston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6084-0429","authenticated-orcid":false,"given":"Yorgo","family":"Modis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J","family":"Lehner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,6,5]]},"reference":[{"key":"BFng3878_CR1","doi-asserted-by":"publisher","first-page":"4841","DOI":"10.1007\/s00018-014-1725-x","volume":"71","author":"J Wang","year":"2014","unstructured":"Wang, J., Lawry, S.T., Cohen, A.L. & Jia, S. Chromosome boundary elements and regulation of heterochromatin spreading. Cell. Mol. Life Sci. 71, 4841\u20134852 (2014).","journal-title":"Cell. Mol. Life Sci."},{"key":"BFng3878_CR2","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/nature09784","volume":"469","author":"R Margueron","year":"2011","unstructured":"Margueron, R. & Reinberg, D. The Polycomb complex PRC2 and its mark in life. Nature 469, 343\u2013349 (2011).","journal-title":"Nature"},{"key":"BFng3878_CR3","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.tig.2015.11.001","volume":"32","author":"JS Becker","year":"2016","unstructured":"Becker, J.S., Nicetto, D. & Zaret, K.S. H3K9me3-dependent heterochromatin: barrier to cell fate changes. Trends Genet. 32, 29\u201341 (2016).","journal-title":"Trends Genet."},{"key":"BFng3878_CR4","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1038\/nrg1920","volume":"7","author":"PB Talbert","year":"2006","unstructured":"Talbert, P.B. & Henikoff, S. Spreading of silent chromatin: inaction at a distance. Nat. Rev. Genet. 7, 793\u2013803 (2006).","journal-title":"Nat. Rev. Genet."},{"key":"BFng3878_CR5","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/S1084-9521(02)00138-6","volume":"14","author":"G Schotta","year":"2003","unstructured":"Schotta, G., Ebert, A., Dorn, R. & Reuter, G. Position-effect variegation and the genetic dissection of chromatin regulation in Drosophila. Semin. Cell Dev. Biol. 14, 67\u201375 (2003).","journal-title":"Semin. Cell Dev. Biol."},{"key":"BFng3878_CR6","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1016\/j.cell.2013.07.018","volume":"154","author":"W Akhtar","year":"2013","unstructured":"Akhtar, W. et al. Chromatin position effects assayed by thousands of reporters integrated in parallel. Cell 154, 914\u2013927 (2013).","journal-title":"Cell"},{"key":"BFng3878_CR7","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1006\/excr.1999.4656","volume":"252","author":"M Kotecki","year":"1999","unstructured":"Kotecki, M., Reddy, P.S. & Cochran, B.H. Isolation and characterization of a near-haploid human cell line. Exp. Cell Res. 252, 273\u2013280 (1999).","journal-title":"Exp. Cell Res."},{"key":"BFng3878_CR8","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1126\/science.1178955","volume":"326","author":"JE Carette","year":"2009","unstructured":"Carette, J.E. et al. Haploid genetic screens in human cells identify host factors used by pathogens. Science 326, 1231\u20131235 (2009).","journal-title":"Science"},{"key":"BFng3878_CR9","doi-asserted-by":"publisher","first-page":"1481","DOI":"10.1126\/science.aaa7227","volume":"348","author":"IA Tchasovnikarova","year":"2015","unstructured":"Tchasovnikarova, I.A. et al. Epigenetic silencing by the HUSH complex mediates position-effect variegation in human cells. Science 348, 1481\u20131485 (2015).","journal-title":"Science"},{"key":"BFng3878_CR10","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1101\/gad.973302","volume":"16","author":"DC Schultz","year":"2002","unstructured":"Schultz, D.C., Ayyanathan, K., Negorev, D., Maul, G.G. & Rauscher, F.J. III. SETDB1: a novel KAP-1-associated histone H3, lysine 9-specific methyltransferase that contributes to HP1-mediated silencing of euchromatic genes by KRAB zinc-finger proteins. Genes Dev. 16, 919\u2013932 (2002).","journal-title":"Genes Dev."},{"key":"BFng3878_CR11","doi-asserted-by":"publisher","first-page":"3673","DOI":"10.1038\/emboj.2010.239","volume":"29","author":"K Kokura","year":"2010","unstructured":"Kokura, K., Sun, L., Bedford, M.T. & Fang, J. Methyl-H3K9-binding protein MPP8 mediates E-cadherin gene silencing and promotes tumour cell motility and invasion. EMBO J. 29, 3673\u20133687 (2010).","journal-title":"EMBO J."},{"key":"BFng3878_CR12","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1007\/s00335-014-9516-0","volume":"25","author":"SK Harten","year":"2014","unstructured":"Harten, S.K. et al. The first mouse mutants of D14Abb1e (Fam208a) show that it is critical for early development. Mamm. Genome 25, 293\u2013303 (2014).","journal-title":"Mamm. Genome"},{"key":"BFng3878_CR13","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1002\/dvg.20553","volume":"47","author":"AS Soehn","year":"2009","unstructured":"Soehn, A.S. et al. Periphilin is strongly expressed in the murine nervous system and is indispensable for murine development. Genesis 47, 697\u2013707 (2009).","journal-title":"Genesis"},{"key":"BFng3878_CR14","doi-asserted-by":"publisher","first-page":"11786","DOI":"10.1038\/ncomms11786","volume":"7","author":"RT Timms","year":"2016","unstructured":"Timms, R.T. et al. Genetic dissection of mammalian ERAD through comparative haploid and CRISPR forward genetic screens. Nat. Commun. 7, 11786 (2016).","journal-title":"Nat. Commun."},{"key":"BFng3878_CR15","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1016\/j.celrep.2016.09.050","volume":"17","author":"RT Timms","year":"2016","unstructured":"Timms, R.T., Tchasovnikarova, I.A., Antrobus, R., Dougan, G. & Lehner, P.J. ATF7IP-mediated stabilization of the histone methyltransferase setdb1 is essential for heterochromatin formation by the HUSH complex. Cell Rep. 17, 653\u2013659 (2016).","journal-title":"Cell Rep."},{"key":"BFng3878_CR16","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1126\/science.1246981","volume":"343","author":"T Wang","year":"2014","unstructured":"Wang, T., Wei, J.J., Sabatini, D.M. & Lander, E.S. Genetic screens in human cells using the CRISPR-Cas9 system. Science 343, 80\u201384 (2014).","journal-title":"Science"},{"key":"BFng3878_CR17","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1126\/science.1247005","volume":"343","author":"O Shalem","year":"2014","unstructured":"Shalem, O. et al. Genome-scale CRISPR-Cas9 knockout screening in human cells. Science 343, 84\u201387 (2014).","journal-title":"Science"},{"key":"BFng3878_CR18","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1038\/nmeth.3047","volume":"11","author":"NE Sanjana","year":"2014","unstructured":"Sanjana, N.E., Shalem, O. & Zhang, F. Improved vectors and genome-wide libraries for CRISPR screening. Nat. Methods 11, 783\u2013784 (2014).","journal-title":"Nat. Methods"},{"key":"BFng3878_CR19","doi-asserted-by":"publisher","first-page":"685","DOI":"10.4161\/epi.24976","volume":"8","author":"D-Q Li","year":"2013","unstructured":"Li, D.-Q., Nair, S.S. & Kumar, R. The MORC family: new epigenetic regulators of transcription and DNA damage response. Epigenetics 8, 685\u2013693 (2013).","journal-title":"Epigenetics"},{"key":"BFng3878_CR20","doi-asserted-by":"publisher","first-page":"1448","DOI":"10.1126\/science.1221472","volume":"336","author":"G Moissiard","year":"2012","unstructured":"Moissiard, G. et al. MORC family ATPases required for heterochromatin condensation and gene silencing. Science 336, 1448\u20131451 (2012).","journal-title":"Science"},{"key":"BFng3878_CR21","doi-asserted-by":"publisher","first-page":"5795","DOI":"10.1038\/ncomms6795","volume":"5","author":"WA Pastor","year":"2014","unstructured":"Pastor, W.A. et al. MORC1 represses transposable elements in the mouse male germline. Nat. Commun. 5, 5795 (2014).","journal-title":"Nat. Commun."},{"key":"BFng3878_CR22","doi-asserted-by":"publisher","first-page":"9000","DOI":"10.1074\/jbc.M116.718973","volume":"291","author":"Y Liu","year":"2016","unstructured":"Liu, Y. et al. Family-wide characterization of histone binding abilities of human CW domain-containing proteins. J. Biol. Chem. 291, 9000\u20139013 (2016).","journal-title":"J. Biol. Chem."},{"key":"BFng3878_CR23","doi-asserted-by":"publisher","first-page":"497","DOI":"10.2174\/1389203717666160125115130","volume":"17","author":"Y Liu","year":"2016","unstructured":"Liu, Y. et al. Structure and function of CW domain containing proteins. Curr. Protein Pept. Sci. 17, 497\u2013506 (2016).","journal-title":"Curr. Protein Pept. Sci."},{"key":"BFng3878_CR24","doi-asserted-by":"publisher","first-page":"E5108","DOI":"10.1073\/pnas.1609709113","volume":"113","author":"S Li","year":"2016","unstructured":"Li, S. et al. Mouse MORC3 is a GHKL ATPase that localizes to H3K4me3 marked chromatin. Proc. Natl. Acad. Sci. USA 113, E5108\u2013E5116 (2016).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFng3878_CR25","doi-asserted-by":"publisher","first-page":"1657","DOI":"10.1016\/j.celrep.2012.11.018","volume":"2","author":"D-Q Li","year":"2012","unstructured":"Li, D.-Q. et al. MORC2 signaling integrates phosphorylation-dependent, ATPase-coupled chromatin remodeling during the DNA damage response. Cell Rep. 2, 1657\u20131669 (2012).","journal-title":"Cell Rep."},{"key":"BFng3878_CR26","doi-asserted-by":"publisher","first-page":"1213","DOI":"10.1038\/nmeth.2688","volume":"10","author":"JD Buenrostro","year":"2013","unstructured":"Buenrostro, J.D., Giresi, P.G., Zaba, L.C., Chang, H.Y. & Greenleaf, W.J. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat. Methods 10, 1213\u20131218 (2013).","journal-title":"Nat. Methods"},{"key":"BFng3878_CR27","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1038\/nature18606","volume":"534","author":"J Wu","year":"2016","unstructured":"Wu, J. et al. The landscape of accessible chromatin in mammalian preimplantation embryos. Nature 534, 652\u2013657 (2016).","journal-title":"Nature"},{"key":"BFng3878_CR28","doi-asserted-by":"publisher","first-page":"10209","DOI":"10.1093\/nar\/gku769","volume":"42","author":"M Kvaratskhelia","year":"2014","unstructured":"Kvaratskhelia, M., Sharma, A., Larue, R.C., Serrao, E. & Engelman, A. Molecular mechanisms of retroviral integration site selection. Nucleic Acids Res. 42, 10209\u201310225 (2014).","journal-title":"Nucleic Acids Res."},{"key":"BFng3878_CR29","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1093\/brain\/awv311","volume":"139","author":"T Sevilla","year":"2016","unstructured":"Sevilla, T. et al. Mutations in the MORC2 gene cause axonal Charcot-Marie-Tooth disease. Brain 139, 62\u201372 (2016).","journal-title":"Brain"},{"key":"BFng3878_CR30","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1002\/ana.24575","volume":"79","author":"OM Albulym","year":"2016","unstructured":"Albulym, O.M. et al. MORC2 mutations cause axonal Charcot-Marie-Tooth disease with pyramidal signs. Ann. Neurol. 79, 419\u2013427 (2016).","journal-title":"Ann. Neurol."},{"key":"BFng3878_CR31","doi-asserted-by":"publisher","first-page":"e26","DOI":"10.1093\/brain\/awv411","volume":"139","author":"P La\u0161\u0161uthov\u00e1","year":"2016","unstructured":"La\u0161\u0161uthov\u00e1, P. et al. Severe axonal Charcot-Marie-Tooth disease with proximal weakness caused by de novo mutation in the MORC2 gene. Brain 139, e26 (2016).","journal-title":"Brain"},{"key":"BFng3878_CR32","doi-asserted-by":"publisher","first-page":"e40","DOI":"10.1093\/brain\/aww082","volume":"139","author":"YS Hyun","year":"2016","unstructured":"Hyun, Y.S., Hong, Y.B., Choi, B.O. & Chung, K.W. Clinico-genetics in Korean Charcot-Marie-Tooth disease type 2Z with MORC2 mutations. Brain 139, e40 (2016).","journal-title":"Brain"},{"key":"BFng3878_CR33","doi-asserted-by":"publisher","first-page":"e56","DOI":"10.1093\/brain\/aww156","volume":"139","author":"X Zhao","year":"2016","unstructured":"Zhao, X. et al. MORC2 mutations in a cohort of Chinese patients with Charcot-Marie-Tooth disease type 2. Brain 139, e56 (2016).","journal-title":"Brain"},{"key":"BFng3878_CR34","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1126\/science.aac7041","volume":"350","author":"T Wang","year":"2015","unstructured":"Wang, T. et al. Identification and characterization of essential genes in the human genome. Science 350, 1096\u2013101 (2015).","journal-title":"Science"},{"key":"BFng3878_CR35","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1038\/nbt.3437","volume":"34","author":"JG Doench","year":"2016","unstructured":"Doench, J.G. et al. Optimized sgRNA design to maximize activity and minimize off-target effects of CRISPR-Cas9. Nat. Biotechnol. 34, 184\u2013191 (2016).","journal-title":"Nat. Biotechnol."},{"key":"BFng3878_CR36","doi-asserted-by":"publisher","first-page":"e19760","DOI":"10.7554\/eLife.19760","volume":"5","author":"MA Horlbeck","year":"2016","unstructured":"Horlbeck, M.A. et al. Compact and highly active next-generation libraries for CRISPR-mediated gene repression and activation. eLife 5, e19760 (2016).","journal-title":"eLife"},{"key":"BFng3878_CR37","doi-asserted-by":"publisher","first-page":"1574","DOI":"10.1126\/science.1100576","volume":"306","author":"NJ Francis","year":"2004","unstructured":"Francis, N.J., Kingston, R.E. & Woodcock, C.L. Chromatin compaction by a polycomb group protein complex. Science 306, 1574\u20131577 (2004).","journal-title":"Science"},{"key":"BFng3878_CR38","doi-asserted-by":"publisher","first-page":"2210","DOI":"10.1101\/gad.17288211","volume":"25","author":"DJ Grau","year":"2011","unstructured":"Grau, D.J. et al. Compaction of chromatin by diverse Polycomb group proteins requires localized regions of high charge. Genes Dev. 25, 2210\u20132221 (2011).","journal-title":"Genes Dev."},{"key":"BFng3878_CR39","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1146\/annurev.biochem.77.062706.153223","volume":"78","author":"CR Clapier","year":"2009","unstructured":"Clapier, C.R. & Cairns, B.R. The biology of chromatin remodeling complexes. Annu. Rev. Biochem. 78, 273\u2013304 (2009).","journal-title":"Annu. Rev. Biochem."},{"key":"BFng3878_CR40","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/S0092-8674(00)81758-4","volume":"95","author":"Y Zhang","year":"1998","unstructured":"Zhang, Y., LeRoy, G., Seelig, H.P., Lane, W.S. & Reinberg, D. The dermatomyositis-specific autoantigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities. Cell 95, 279\u2013289 (1998).","journal-title":"Cell"},{"key":"BFng3878_CR41","doi-asserted-by":"publisher","first-page":"e70","DOI":"10.1093\/brain\/aww252","volume":"139","author":"G Schottmann","year":"2016","unstructured":"Schottmann, G., Wagner, C., Seifert, F., Stenzel, W. & Schuelke, M. MORC2 mutation causes severe spinal muscular atrophy-phenotype, cerebellar atrophy, and diaphragmatic paralysis. Brain 139, e70 (2016).","journal-title":"Brain"},{"key":"BFng3878_CR42","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/S0092-8674(00)80203-2","volume":"89","author":"CE Stebbins","year":"1997","unstructured":"Stebbins, C.E. et al. Crystal structure of an Hsp90-geldanamycin complex: targeting of a protein chaperone by an antitumor agent. Cell 89, 239\u2013250 (1997).","journal-title":"Cell"},{"key":"BFng3878_CR43","doi-asserted-by":"publisher","first-page":"2639","DOI":"10.1038\/sj.onc.1201790","volume":"16","author":"SV Sharma","year":"1998","unstructured":"Sharma, S.V., Agatsuma, T. & Nakano, H. Targeting of the protein chaperone, HSP90, by the transformation suppressing agent, radicicol. Oncogene 16, 2639\u20132645 (1998).","journal-title":"Oncogene"},{"key":"BFng3878_CR44","doi-asserted-by":"publisher","first-page":"E3535","DOI":"10.1073\/pnas.1504232112","volume":"112","author":"K Chen","year":"2015","unstructured":"Chen, K. et al. Genome-wide binding and mechanistic analyses of Smchd1-mediated epigenetic regulation. Proc. Natl. Acad. Sci. USA 112, E3535\u2013E3544 (2015).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFng3878_CR45","doi-asserted-by":"publisher","first-page":"2281","DOI":"10.1038\/nprot.2013.143","volume":"8","author":"FA Ran","year":"2013","unstructured":"Ran, F.A. et al. Genome engineering using the CRISPR-Cas9 system. Nat. Protoc. 8, 2281\u20132308 (2013).","journal-title":"Nat. Protoc."},{"key":"BFng3878_CR46","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1038\/nbt.2800","volume":"32","author":"H Koike-Yusa","year":"2014","unstructured":"Koike-Yusa, H., Li, Y., Tan, E.-P., Velasco-Herrera, Mdel.C. & Yusa, K. Genome-wide recessive genetic screening in mammalian cells with a lentiviral CRISPR-guide RNA library. Nat. Biotechnol. 32, 267\u2013273 (2014).","journal-title":"Nat. Biotechnol."},{"key":"BFng3878_CR47","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1038\/nsmb.3180","volume":"23","author":"M Lerdrup","year":"2016","unstructured":"Lerdrup, M., Johansen, J.V., Agrawal-Singh, S. & Hansen, K. An interactive environment for agile analysis and visualization of ChIP-sequencing data. Nat. Struct. Mol. Biol. 23, 349\u2013357 (2016).","journal-title":"Nat. Struct. Mol. Biol."}],"container-title":["Nature Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/ng.3878.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/ng.3878","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/doifinder\/10.1038\/ng.3878","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"http:\/\/www.nature.com\/articles\/ng.3878.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T17:20:57Z","timestamp":1684430457000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/ng.3878"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,6,5]]},"references-count":47,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2017,7]]}},"alternative-id":["BFng3878"],"URL":"https:\/\/doi.org\/10.1038\/ng.3878","relation":{},"ISSN":["1061-4036","1546-1718"],"issn-type":[{"value":"1061-4036","type":"print"},{"value":"1546-1718","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,6,5]]},"assertion":[{"value":"15 January 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 April 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 June 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}