{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T21:02:02Z","timestamp":1764277322191,"version":"3.40.5"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T00:00:00Z","timestamp":1747094400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T00:00:00Z","timestamp":1747094400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100021171","name":"Guangdong Basic and Applied Basic Research Foundation","doi-asserted-by":"crossref","award":["2019A1515011134"],"award-info":[{"award-number":["2019A1515011134"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100015956","name":"Special Project for Research and Development in Key areas of Guangdong Province","doi-asserted-by":"publisher","award":["2018B020203003"],"award-info":[{"award-number":["2018B020203003"]}],"id":[{"id":"10.13039\/501100015956","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Biol Res"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>A splice mutation that causes skipping of exon 17 in the <jats:italic>KIT<\/jats:italic> gene is a major reason for the dominant white phenotype of pigs. Exon 17 of the <jats:italic>KIT<\/jats:italic> gene may be related to differences in testis size and sperm quality among different pig breeds. Investigating the effects of exon 17 of the <jats:italic>KIT<\/jats:italic> gene on spermatogonia differentiation and testicular development is essential for understanding the genetic causes of reduced fertility and semen quality in pigs. To better understand the effects of the splice mutation of <jats:italic>KIT<\/jats:italic> on porcine spermatogenesis, we described an exon 17 deletion mouse model (<jats:italic>Kit<\/jats:italic>\n              <jats:sup>D17\/+<\/jats:sup>) constructed by simulating splice mutations in <jats:italic>KIT<\/jats:italic> for functional verification.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Deletion of exon 17 of <jats:italic>Kit<\/jats:italic> severely impaired the differentiation of spermatogonia and promoted the apoptosis of germ cells, resulting in testicular dysplasia and decreased sperm quality and male fertility. Further transcriptomic analysis revealed inhibited expression of genes involved in meiosis and spermatogenesis and attenuated MAPK-ERK signaling in the testicular tissues of <jats:italic>Kit<\/jats:italic>\n              <jats:sup>D17\/+<\/jats:sup> mice. The attenuated MAPK-ERK signaling caused by impaired Kit phosphorylation was confirmed by western blotting.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Our study demonstrated that deletion of exon 17 of <jats:italic>Kit<\/jats:italic> severely impaired spermatogenesis and testicular development, leading to decreased semen quality and male fertility. These findings verified the function of exon 17 in the <jats:italic>Kit<\/jats:italic> gene and provide a theoretical basis for improving the semen quality of dominant white pigs through correction of the splice mutation of <jats:italic>KIT<\/jats:italic>.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s40659-025-00609-2","type":"journal-article","created":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T02:35:49Z","timestamp":1747103749000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Heterozygous deletion of exon 17 of the Kit gene impairs mouse spermatogenesis by attenuating MAPK-ERK signaling"],"prefix":"10.1186","volume":"58","author":[{"given":"Siyuan","family":"Lin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weipeng","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changqi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaosheng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peiqing","family":"Cong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3644-9080","authenticated-orcid":false,"given":"Zuyong","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,5,13]]},"reference":[{"issue":"9","key":"609_CR1","doi-asserted-by":"publisher","first-page":"1641","DOI":"10.3390\/genes13091641","volume":"13","author":"F Avila","year":"2022","unstructured":"Avila F, Hughes SS, Magdesian KG, Penedo MCT, Bellone RR. Breed distribution and allele frequencies of base coat color, dilution, and white patterning variants across 28 horse breeds. Genes. 2022;13(9):1641.","journal-title":"Genes"},{"key":"609_CR2","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1016\/S0888-7543(05)80118-1","volume":"14","author":"M Johansson","year":"1992","unstructured":"Johansson M, Ellegren H, Marklund L, Gustavsson U, Ringmar-Cederberg E, Andersson K, et al. The gene for dominant white color in the pig is closely linked to ALB and PDGFRA on chromosome 8. Genomics. 1992;14:965\u20139.","journal-title":"Genomics"},{"issue":"5","key":"609_CR3","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1111\/j.1365-2052.2009.01893.x","volume":"40","author":"B Haase","year":"2009","unstructured":"Haase B, Brooks SA, Tozaki T, Burger D, Poncet PA, Rieder S, et al. Seven novel KIT mutations in horses with white coat colour phenotypes. Anim Genet. 2009;40(5):623\u20139.","journal-title":"Anim Genet"},{"issue":"8","key":"609_CR4","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1101\/gr.8.8.826","volume":"8","author":"S Marklund","year":"1998","unstructured":"Marklund S, Kijas J, Rodriguez-Martinez H, R\u00f6nnstrand L, Funa K, Moller M, et al. Molecular basis for the dominant white phenotype in the domestic pig. Genome Res. 1998;8(8):826\u201333.","journal-title":"Genome Res"},{"issue":"11","key":"609_CR5","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1007\/s003359900244","volume":"7","author":"M Johansson Moller","year":"1996","unstructured":"Johansson Moller M, Chaudhary R, Hellm\u00e9n E, H\u00f6yheim B, Chowdhary B, Andersson L. Pigs with the dominant white coat color phenotype carry a duplication of the KIT gene encoding the mast\/stem cell growth factor receptor. Mamm Genome. 1996;7(11):822\u201330.","journal-title":"Mamm Genome"},{"issue":"6","key":"609_CR6","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1089\/crispr.2022.0039","volume":"5","author":"X Liang","year":"2022","unstructured":"Liang X, Lan J, Xu M, Qin K, Liu H, Sun G, et al. Impact of KIT editing on coat pigmentation and fresh meat color in Yorkshire pigs. CRISPR J. 2022;5(6):825\u201342.","journal-title":"CRISPR J"},{"issue":"3","key":"609_CR7","doi-asserted-by":"publisher","first-page":"186","DOI":"10.4161\/spmg.1.3.17760","volume":"1","author":"L Zhang","year":"2014","unstructured":"Zhang L, Tang J, Haines CJ, Feng HL, Lai L, Teng X, et al. c-kit and its related genes in spermatogonial differentiation. Spermatogenesis. 2014;1(3):186\u201394.","journal-title":"Spermatogenesis"},{"issue":"11","key":"609_CR8","doi-asserted-by":"publisher","first-page":"3341","DOI":"10.1002\/j.1460-2075.1987.tb02655.x","volume":"6","author":"Y Yarden","year":"1987","unstructured":"Yarden Y, Kuang WJ, Yang-Feng T, Coussens L, Munemitsu S, Dull TJ, et al. Human proto-oncogene c-kit: a new cell surface receptor tyrosine kinase for an unidentified ligand. EMBO J. 1987;6(11):3341\u201351.","journal-title":"EMBO J"},{"issue":"6185","key":"609_CR9","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1038\/335088a0","volume":"335","author":"B Chabot","year":"1988","unstructured":"Chabot B, Stephenson DA, Chapman VM, Besmer P, Bernstein A. The proto-oncogene c-kit encoding a transmembrane tyrosine kinase receptor maps to the mouse W locus. Nature. 1988;335(6185):88\u20139.","journal-title":"Nature"},{"issue":"1","key":"609_CR10","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/0092-8674(95)90455-7","volume":"80","author":"JM Blechman","year":"1995","unstructured":"Blechman JM, Lev S, Barg J, Eisenstein M, Vaks B, Vogel Z, et al. The fourth Immunoglobulin domain of the stem cell factor receptor couples ligand binding to signal transduction. Cell. 1995;80(1):103\u201313.","journal-title":"Cell"},{"issue":"2","key":"609_CR11","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1016\/j.cell.2007.05.055","volume":"130","author":"S Yuzawa","year":"2007","unstructured":"Yuzawa S, Opatowsky Y, Zhang Z, Mandiyan V, Lax I, Schlessinger J, et al. Structural basis for activation of the receptor tyrosine kinase KIT by stem cell factor. Cell. 2007;130(2):323\u201334.","journal-title":"Cell"},{"issue":"2","key":"609_CR12","first-page":"12","volume":"11","author":"JM Blechman","year":"1993","unstructured":"Blechman JM, Lev S, Givol D, Yarden Y. Structure-Function analyses of the kit receptor for the steel factor. Stem Cells. 1993;11(2):12\u201321.","journal-title":"Stem Cells"},{"issue":"4","key":"609_CR13","doi-asserted-by":"publisher","first-page":"1619","DOI":"10.1152\/physrev.00046.2011","volume":"92","author":"J Lennartsson","year":"2012","unstructured":"Lennartsson J, R\u00f6nnstrand L. Stem cell factor Receptor\/c-Kit: from basic science to clinical implications. Physiol Rev. 2012;92(4):1619\u201349.","journal-title":"Physiol Rev"},{"issue":"2","key":"609_CR14","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1093\/genetics\/97.2.337","volume":"97","author":"EN Geissler","year":"1981","unstructured":"Geissler EN, McFarland EC, Russell ES. Analysis of pleiotropism at the dominant white-spotting (W) locus of the house mouse: a description of ten new W alleles. Genetics. 1981;97(2):337\u201361.","journal-title":"Genetics"},{"issue":"1","key":"609_CR15","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/0092-8674(88)90020-7","volume":"55","author":"EN Geissler","year":"1988","unstructured":"Geissler EN, Ryan MA, Housman DE. The dominant-white spotting (W) locus of the mouse encodes the c-kit proto-oncogene. Cell. 1988;55(1):185\u201392.","journal-title":"Cell"},{"issue":"3","key":"609_CR16","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1101\/gad.4.3.390","volume":"4","author":"R Reith","year":"1990","unstructured":"Reith R, Rottapel AD, Giddens R, Brady E, Forrester C, Bernstein L. W mutant mice with mild or severe developmental defects contain distinct point mutations in the kinase domain of the c-kit receptor. Genes Dev. 1990;4(3):390\u2013400.","journal-title":"Genes Dev"},{"issue":"7","key":"609_CR17","first-page":"61","volume":"22","author":"YX ZHAO","year":"2020","unstructured":"ZHAO YX, FANG GGX, ZHU C, LI L, YANG XH. Developmental rule and correlation of testicular and semen quality in different breeds of boars. J Agric Sci Technol. 2020;22(7):61\u20138.","journal-title":"J Agric Sci Technol"},{"issue":"10","key":"609_CR18","first-page":"3879","volume":"49","author":"XK ZHANG","year":"2022","unstructured":"ZHANG XK, LI LW, WU Y, ZHUANG YW, JIA RB. Effects of breeds, seasons, parity, mouth ages and interval of semen collection for semen quality in pigs. Chin Anim Husb Vet Med. 2022;49(10):3879\u201390.","journal-title":"Chin Anim Husb Vet Med"},{"issue":"3","key":"609_CR19","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1111\/jbg.12393","volume":"136","author":"X Li","year":"2019","unstructured":"Li X, Jiang B, Wang X, Liu X, Zhang Q, Chen Y. Estimation of genetic parameters and season effects for semen traits in three pig breeds of South China. J Anim Breed Genet. 2019;136(3):183\u20139.","journal-title":"J Anim Breed Genet"},{"key":"609_CR20","doi-asserted-by":"crossref","unstructured":"Morimoto H, Kanatsu-Shinohara M, Takashima S, Chuma S, Nakatsuji N, Takehashi M et al. Phenotypic Plasticity of Mouse Spermatogonial Stem Cells. PLoS ONE. 2009; 4(11).","DOI":"10.1371\/journal.pone.0007909"},{"issue":"2","key":"609_CR21","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1242\/dev.113.2.689","volume":"113","author":"K Yoshinaga","year":"1991","unstructured":"Yoshinaga K, Nishikawa S, Ogawa M, Hayashi S, Kunisada T, Fujimoto T. Role of c-kit in mouse spermatogenesis: identification of spermatogonia as a specific site of c-kit expression and function. Development. 1991;113(2):689\u201399.","journal-title":"Development"},{"issue":"2","key":"609_CR22","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1089\/oli.2008.0108","volume":"18","author":"AP Sikarwar","year":"2008","unstructured":"Sikarwar AP, Reddy KV. siRNA-Mediated Silencing of c-kit in mouse primary spermatogonial cells induces cell cycle arrest. Oligonucleotides. 2008;18(2):145\u201360.","journal-title":"Oligonucleotides"},{"key":"609_CR23","doi-asserted-by":"crossref","unstructured":"Sun G, Liang X, Qin K, Qin Y, Shi X, Cong P, et al. Functional analysis of KIT gene structural mutations causing the porcine dominant white phenotype using genome edited mouse models. Front Genet. 2020;11:138.","DOI":"10.3389\/fgene.2020.00138"},{"issue":"5","key":"609_CR24","doi-asserted-by":"publisher","first-page":"892","DOI":"10.1016\/j.stemcr.2014.09.003","volume":"3","author":"HH Chen","year":"2014","unstructured":"Chen HH, Welling M, Bloch DB, Mu\u00f1oz J, Mientjes E, Chen X, et al. DAZL limits pluripotency, differentiation, and apoptosis in developing primordial germ cells. Stem Cell Rep. 2014;3(5):892\u2013904.","journal-title":"Stem Cell Rep"},{"issue":"10","key":"609_CR25","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1007\/s10815-012-9828-5","volume":"29","author":"B Heidari","year":"2012","unstructured":"Heidari B, Rahmati-Ahmadabadi M, Akhondi MM, Zarnani AH, Jeddi-Tehrani M, Shirazi A, et al. Isolation, identification, and culture of goat spermatogonial stem cells using c-kit and PGP9.5 markers. J Assist Reprod Genet. 2012;29(10):1029\u201338.","journal-title":"J Assist Reprod Genet"},{"key":"609_CR26","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.anireprosci.2017.12.020","volume":"190","author":"R Lee","year":"2018","unstructured":"Lee R, Lee WY, Park HJ, Ha WT, Woo JS, Chung HJ, et al. Stage-specific expression of DDX4 and c-kit at different developmental stages of the Porcine testis. Anim Reprod Sci. 2018;190:18\u201326.","journal-title":"Anim Reprod Sci"},{"key":"609_CR27","doi-asserted-by":"crossref","unstructured":"Tian P, Zhao Z, Fan Y, Cui N, Shi B, Hao G. Changes in expressions of spermatogenic marker genes and spermatogenic cell population caused by stress. Front Endocrinol. 2021;12:584125.","DOI":"10.3389\/fendo.2021.584125"},{"issue":"6","key":"609_CR28","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1016\/j.fertnstert.2018.07.018","volume":"110","author":"JV Medrano","year":"2018","unstructured":"Medrano JV, Vilanova-P\u00e9rez T, Forn\u00e9s-Ferrer V, Navarro-Gomezlechon A, Mart\u00ednez-Triguero ML, Garc\u00eda S, et al. Influence of temperature, serum, and gonadotropin supplementation in short- and long-term organotypic culture of human immature testicular tissue. Fertil Steril. 2018;110(6):1045\u2013e10571043.","journal-title":"Fertil Steril"},{"issue":"5","key":"609_CR29","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1093\/humupd\/5.5.535","volume":"5","author":"C Mauduit","year":"1999","unstructured":"Mauduit C, Hamamah S, Benahmed M. Stem cell factor\/c-kit system in spermatogenesis. Hum Reprod Update. 1999;5(5):535\u201345.","journal-title":"Hum Reprod Update"},{"issue":"12","key":"609_CR30","doi-asserted-by":"publisher","first-page":"5894","DOI":"10.1210\/endo.140.12.7172","volume":"140","author":"BH Schrans-Stassen","year":"1999","unstructured":"Schrans-Stassen BH, van de Kant HJ, de Rooij DG, van Pelt AM. Differential expression of c-kit in mouse undifferentiated and differentiating type A spermatogonia. Endocrinology. 1999;140(12):5894\u2013900.","journal-title":"Endocrinology"},{"issue":"1","key":"609_CR31","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1095\/biolreprod67.1.70","volume":"67","author":"F Guerif","year":"2002","unstructured":"Guerif F, Cadoret V, Rahal-Perola V, Lansac J, Bernex F, Panthier JJ, Hochereau-de Reviers MT, et al. Apoptosis, onset and maintenance of spermatogenesis: evidence for the involvement of kit in kit-haplodeficient mice. Biol Reprod. 2002;67(1):70\u20139.","journal-title":"Biol Reprod"},{"issue":"6","key":"609_CR32","doi-asserted-by":"publisher","first-page":"1815","DOI":"10.1095\/biolreprod.103.019323","volume":"69","author":"H Ohta","year":"2003","unstructured":"Ohta H, Tohda A, Nishimune Y. Proliferation and differentiation of spermatogonial stem cells in the W\/Wv mutant mouse testis. Biol Reprod. 2003;69(6):1815\u201321.","journal-title":"Biol Reprod"},{"issue":"1","key":"609_CR33","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/sj.cr.7290105","volume":"12","author":"W Zhang","year":"2002","unstructured":"Zhang W, Liu HT. MAPK signal pathways in the regulation of cell proliferation in mammalian cells. Cell Res. 2002;12(1):9\u201318.","journal-title":"Cell Res"},{"issue":"5","key":"609_CR34","doi-asserted-by":"publisher","first-page":"435","DOI":"10.7150\/ijbs.6087","volume":"9","author":"J Liang","year":"2013","unstructured":"Liang J, Wu YL, Chen BJ, Zhang W, Tanaka Y, Sugiyama H. The C-Kit Receptor-Mediated signal transduction and Tumor-Related diseases. Int J Biol Sci. 2013;9(5):435\u201343.","journal-title":"Int J Biol Sci"},{"issue":"4","key":"609_CR35","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1007\/s12079-017-0399-1","volume":"11","author":"HJ Cardoso","year":"2017","unstructured":"Cardoso HJ, Figueira MI, Socorro S. The stem cell factor (SCF)\/c-KIT signalling in testis and prostate cancer. J Cell Commun Signal. 2017;11(4):297\u2013307.","journal-title":"J Cell Commun Signal"},{"issue":"9","key":"609_CR36","doi-asserted-by":"publisher","first-page":"1004","DOI":"10.1002\/mrd.22875","volume":"84","author":"LJ Zak","year":"2017","unstructured":"Zak LJ, Gaustad AH, Bolarin A, Broekhuijse MLWJ, Walling GA, Knol EF. Genetic control of complex traits, with a focus on reproduction in pigs. Mol Reprod Dev. 2017;84(9):1004\u201311.","journal-title":"Mol Reprod Dev"},{"key":"609_CR37","doi-asserted-by":"crossref","unstructured":"Zhao Y, Yang L, Su G, Wei Z, Liu X, Song L, et al. Growth traits and sperm proteomics analyses of myostatin gene-edited Chinese yellow cattle. Life. 2022;12(5):627.","DOI":"10.3390\/life12050627"}],"container-title":["Biological Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40659-025-00609-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40659-025-00609-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40659-025-00609-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T02:35:54Z","timestamp":1747103754000},"score":1,"resource":{"primary":{"URL":"https:\/\/biolres.biomedcentral.com\/articles\/10.1186\/s40659-025-00609-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,13]]},"references-count":37,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["609"],"URL":"https:\/\/doi.org\/10.1186\/s40659-025-00609-2","relation":{},"ISSN":["0717-6287"],"issn-type":[{"value":"0717-6287","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,13]]},"assertion":[{"value":"29 October 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 April 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 May 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All the experimental animal operations involved strictly follow the animal experiment scheme approved by the Animal Ethics Committee of Sun Yat-sen University (approval number: SYSU-IACUC-2023-B0617).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"28"}}