{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T05:24:59Z","timestamp":1786944299040,"version":"build-2736575974"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T00:00:00Z","timestamp":1786752000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":2,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100008131","name":"Rheinische Friedrich-Wilhelms-Universit\u00e4t Bonn","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008131","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Head Face Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Studies on animal models and fibroblast growth factor receptor (FGFR2)-associated craniosynostosis syndromes suggest that FGFR2 plays a crucial role in craniofacial development. Therefore, the present exploratory study aims to investigate the relationship between functional genetic polymorphisms of\n                      <jats:italic>FGFR2<\/jats:italic>\n                      and variations in facial morphology.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Frontal and lateral photographs of healthy boys (aged 9 to 14 years) and girls (aged 9 to 13 years), taken before the start of orthodontic treatment, were used for the study. Saliva samples from the patients were also analyzed. Patients with syndromes, skull trauma, or cleft lip and palate were excluded from the study. The measurements and determinations of proportions were performed using the Image J image processing program. DNA was extracted from the saliva samples to investigate seven genetic polymorphisms in\n                      <jats:italic>FGFR2<\/jats:italic>\n                      using real-time PCR (rs2162540, rs2981578, rs10736303, rs1078806, rs11200014, rs1219648, and rs4752566). ANOVA and t-tests were used to investigate the relationship between the genotypes and the horizontal as well as lateral facial proportions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 102 children (60 boys and 42 girls) were included in the analysis. No significant sex-related differences in relative facial dimensions or angles were observed.\n                      <jats:italic>FGFR2<\/jats:italic>\n                      polymorphisms were significantly associated with distinct facial parameters. The rs10736303 variant was associated with frontal facial proportions related to the eye and midface region, with larger relative dimensions observed in carriers of the AA genotype compared to the AG genotype. The rs2162540 polymorphism was associated with lateral profile measurements, including the relative vermilion height of the lower lip and the mentolabial angle. In addition, rs11200014 showed a significant association with the mentolabial angle, with larger angles observed in AA genotype carriers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This exploratory study suggested that\n                      <jats:italic>FGFR2<\/jats:italic>\n                      polymorphisms may be involved in specific facial parameters, supporting a role of\n                      <jats:italic>FGFR2<\/jats:italic>\n                      in facial development.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13005-026-00649-3","type":"journal-article","created":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T10:44:14Z","timestamp":1786790654000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring the association between genetic polymorphisms in FGFR2 and children\u2019s facial morphology"],"prefix":"10.1186","volume":"22","author":[{"given":"Christian","family":"Rinnert","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svenja","family":"Beisel-Memmert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Proff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristiano Miranda","family":"de Araujo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Julia Pugsley","family":"Baratto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila","family":"Paiva Perin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliane","family":"Cor\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Kirschneck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika Calvano","family":"K\u00fcchler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,15]]},"reference":[{"key":"649_CR1","doi-asserted-by":"publisher","first-page":"1192","DOI":"10.1038\/ejhg.2011.110","volume":"19","author":"S Boehringer","year":"2011","unstructured":"Boehringer S, Van Der Lijn F, Liu F, G\u00fcnther M, Sinigerova S, Nowak S, et al. Genetic determination of human facial morphology: links between cleft-lips and normal variation. Eur J Hum Genet. 2011;19:1192\u20137. https:\/\/doi.org\/10.1038\/ejhg.2011.110.","journal-title":"Eur J Hum Genet"},{"key":"649_CR2","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1111\/j.1601-6343.2009.01462.x","volume":"12","author":"S Weinberg","year":"2009","unstructured":"Weinberg S, Naidoo S, Bardi K, Brandon C, Neiswanger K, Resick J, et al. Face shape of unaffected parents with cleft affected offspring: combining three-dimensional surface imaging and geometric morphometrics. Orthod Craniofac Res. 2009;12:271\u201381. https:\/\/doi.org\/10.1111\/j.1601-6343.2009.01462.x.","journal-title":"Orthod Craniofac Res"},{"key":"649_CR3","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1016\/j.ajhg.2011.12.021","volume":"90","author":"L Paternoster","year":"2012","unstructured":"Paternoster L, Zhurov AI, Toma AM, Kemp JP, St. Pourcain B, Timpson NJ, et al. Genome-wide Association Study of Three-Dimensional Facial Morphology Identifies a Variant in PAX3 Associated with Nasion Position. Am J Hum Genet. 2012;90:478\u201385. https:\/\/doi.org\/10.1016\/j.ajhg.2011.12.021.","journal-title":"Am J Hum Genet"},{"key":"649_CR4","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1002\/ajhb.22331","volume":"25","author":"JA G\u00f3mez-Vald\u00e9s","year":"2013","unstructured":"G\u00f3mez-Vald\u00e9s JA, H\u00fcnemeier T, Contini V, Acu\u00f1a\u2010Alonzo V, Macin G, Ballesteros\u2010Romero M, et al. Fibroblast growth factor receptor 1 (FGFR1) variants and craniofacial variation in Amerindians and related populations. Am J Hum Biol. 2013;25:12\u20139. https:\/\/doi.org\/10.1002\/ajhb.22331.","journal-title":"Am J Hum Biol"},{"key":"649_CR5","doi-asserted-by":"publisher","first-page":"10815","DOI":"10.1038\/ncomms10815","volume":"7","author":"K Adhikari","year":"2016","unstructured":"Adhikari K, Fontanil T, Cal S, Mendoza-Revilla J, Fuentes-Guajardo M, Chac\u00f3n-Duque J-C, et al. A genome-wide association scan in admixed Latin Americans identifies loci influencing facial and scalp hair features. Nat Commun. 2016;7:10815. https:\/\/doi.org\/10.1038\/ncomms10815.","journal-title":"Nat Commun"},{"key":"649_CR6","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/s41588-020-00741-7","volume":"53","author":"JD White","year":"2021","unstructured":"White JD, Indencleef K, Naqvi S, Eller RJ, Hoskens H, Roosenboom J, et al. Insights into the genetic architecture of the human face. Nat Genet. 2021;53:45\u201353. https:\/\/doi.org\/10.1038\/s41588-020-00741-7.","journal-title":"Nat Genet"},{"key":"649_CR7","doi-asserted-by":"publisher","first-page":"7832","DOI":"10.1038\/s41467-022-35328-9","volume":"13","author":"Z Xiong","year":"2022","unstructured":"Xiong Z, Gao X, Chen Y, Feng Z, Pan S, Lu H, et al. Combining genome-wide association studies highlight novel loci involved in human facial variation. Nat Commun. 2022;13:7832. https:\/\/doi.org\/10.1038\/s41467-022-35328-9.","journal-title":"Nat Commun"},{"key":"649_CR8","doi-asserted-by":"publisher","first-page":"626403","DOI":"10.3389\/fgene.2021.626403","volume":"12","author":"K Indencleef","year":"2021","unstructured":"Indencleef K, Hoskens H, Lee MK, White JD, Liu C, Eller RJ, et al. The Intersection of the Genetic Architectures of Orofacial Clefts and Normal Facial Variation. Front Genet. 2021;12:626403. https:\/\/doi.org\/10.3389\/fgene.2021.626403.","journal-title":"Front Genet"},{"key":"649_CR9","doi-asserted-by":"publisher","first-page":"1546295","DOI":"10.3389\/fdmed.2025.1546295","volume":"6","author":"EC K\u00fcchler","year":"2025","unstructured":"K\u00fcchler EC, Meger MN, Pires BCR, Beisel-Memmert S, Hemming D, Coletta RD, et al. Investigating possible shared single nucleotide polymorphisms in isolated oral cleft and non-cleft facial morphology. Front Dent Med. 2025;6:1546295. https:\/\/doi.org\/10.3389\/fdmed.2025.1546295.","journal-title":"Front Dent Med"},{"key":"649_CR10","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1016\/S0168-9525(00)89088-5","volume":"11","author":"M Muenke","year":"1995","unstructured":"Muenke M, Schell U. Fibroblast-growth-factor receptor mutations in human skeletal disorders. Trends Genet. 1995;11:308\u201313. https:\/\/doi.org\/10.1016\/S0168-9525(00)89088-5.","journal-title":"Trends Genet"},{"key":"649_CR11","doi-asserted-by":"publisher","first-page":"1446","DOI":"10.1101\/gad.990702","volume":"16","author":"DM Ornitz","year":"2002","unstructured":"Ornitz DM, Marie PJ. FGF signaling pathways in endochondral and intramembranous bone development and human genetic disease. Genes Dev. 2002;16:1446\u201365. https:\/\/doi.org\/10.1101\/gad.990702.","journal-title":"Genes Dev"},{"key":"649_CR12","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/1471-213X-14-8","volume":"14","author":"SM Motch Perrine","year":"2014","unstructured":"Motch Perrine SM, Cole TM, Mart\u00ednez-Abad\u00edas N, Aldridge K, Jabs EW, Richtsmeier JT. Craniofacial divergence by distinct prenatal growth patterns in Fgfr2 mutant mice. BMC Dev Biol. 2014;14:8. https:\/\/doi.org\/10.1186\/1471-213X-14-8.","journal-title":"BMC Dev Biol"},{"key":"649_CR13","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1038\/nrg2933","volume":"12","author":"MJ Dixon","year":"2011","unstructured":"Dixon MJ, Marazita ML, Beaty TH, Murray JC. Cleft lip and palate: understanding genetic and environmental influences. Nat Rev Genet. 2011;12:167\u201378. https:\/\/doi.org\/10.1038\/nrg2933.","journal-title":"Nat Rev Genet"},{"key":"649_CR14","first-page":"321","volume":"57","author":"WJ Park","year":"1995","unstructured":"Park WJ, Theda C, Maestri NE, Meyers GA, Fryburg JS, Dufresne C, et al. Analysis of phenotypic features and FGFR2 mutations in Apert syndrome. Am J Hum Genet. 1995;57:321\u20138.","journal-title":"Am J Hum Genet"},{"key":"649_CR15","doi-asserted-by":"publisher","first-page":"1647","DOI":"10.1093\/hmg\/6.10.1647","volume":"6","author":"A Wilkie","year":"1997","unstructured":"Wilkie A. Craniosynostosis: genes and mechanisms. Hum Mol Genet. 1997;6:1647\u201356. https:\/\/doi.org\/10.1093\/hmg\/6.10.1647.","journal-title":"Hum Mol Genet"},{"key":"649_CR16","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1002\/(SICI)1096-8628(19980113)75:2<211::AID-AJMG19>3.0.CO;2-S","volume":"75","author":"E Lajeunie","year":"1998","unstructured":"Lajeunie E, Merrer ML, Marchac D, Renier D. Syndromal and nonsyndromal primary trigonocephaly: Analysis of a series of 237 patients. Am J Med Genet. 1998;75:211\u20135.","journal-title":"Am J Med Genet"},{"key":"649_CR17","first-page":"5","volume":"2","author":"AV Ciurea","year":"2009","unstructured":"Ciurea AV, Toader C. Genetics of craniosynostosis: review of the literature. J Med Life. 2009;2:5\u201317.","journal-title":"J Med Life"},{"key":"649_CR18","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1186\/s12920-015-0115-z","volume":"8","author":"R Karki","year":"2015","unstructured":"Karki R, Pandya D, Elston RC, Ferlini C. Defining mutation and polymorphism in the era of personal genomics. BMC Med Genomics. 2015;8:37. https:\/\/doi.org\/10.1186\/s12920-015-0115-z.","journal-title":"BMC Med Genomics"},{"key":"649_CR19","doi-asserted-by":"publisher","first-page":"6562","DOI":"10.1038\/s41467-025-61761-7","volume":"16","author":"Z Xiong","year":"2025","unstructured":"Xiong Z, Li Y, Liu X, Lu H, Hysi PG, Pardo LM, et al. Combined genome-wide association study of facial traits in Europeans increases explained variance and improves prediction. Nat Commun. 2025;16:6562. https:\/\/doi.org\/10.1038\/s41467-025-61761-7.","journal-title":"Nat Commun"},{"key":"649_CR20","doi-asserted-by":"publisher","first-page":"1340","DOI":"10.1177\/0022034519872951","volume":"98","author":"Q Jiang","year":"2019","unstructured":"Jiang Q, Mei L, Zou Y, Ding Q, Cannon RD, Chen H, et al. Genetic Polymorphisms in FGFR2 Underlie Skeletal Malocclusion. J Dent Res. 2019;98:1340\u20137. https:\/\/doi.org\/10.1177\/0022034519872951.","journal-title":"J Dent Res"},{"key":"649_CR21","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1055\/s-0042-1744371","volume":"17","author":"IGAW Ardani","year":"2023","unstructured":"Ardani IGAW, Budipramana M, Rachmawati E, Nugraha AP, Ardana IKKG, Budhy TI, et al. COL1A1 and FGFR2 Single-Nucleotide Polymorphisms Found in Class II and Class III Skeletal Malocclusions in Javanese Population. Eur J Dent. 2023;17:183\u201390. https:\/\/doi.org\/10.1055\/s-0042-1744371.","journal-title":"Eur J Dent"},{"key":"649_CR22","doi-asserted-by":"publisher","first-page":"346","DOI":"10.2174\/1874210601509010346","volume":"9","author":"V Moshkelgosha","year":"2015","unstructured":"Moshkelgosha V, Fathinejad S, Pakizeh Z, Shamsa M, Golkari A. Photographic Facial Soft Tissue Analysis by Means of Linear and Angular Measurements in an Adolescent Persian Population. TODENTJ. 2015;9:346\u201356. https:\/\/doi.org\/10.2174\/1874210601509010346.","journal-title":"TODENTJ"},{"key":"649_CR23","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1093\/ejo\/25.4.393","volume":"25","author":"P Fernandez-Riveiro","year":"2003","unstructured":"Fernandez-Riveiro P. Angular photogrammetric analysis of the soft tissue facial profile. Eur J Orthod. 2003;25:393\u20139. https:\/\/doi.org\/10.1093\/ejo\/25.4.393.","journal-title":"Eur J Orthod"},{"key":"649_CR24","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1067\/mod.2002.125236","volume":"122","author":"P Fern\u00e1ndez-Riveiro","year":"2002","unstructured":"Fern\u00e1ndez-Riveiro P, Su\u00e1rez-Quintanilla D, Smyth-Chamosa E, Su\u00e1rez-Cunqueiro M. Linear photogrammetric analysis of the soft tissue facial profile. Am J Orthod Dentofac Orthop. 2002;122:59\u201366. https:\/\/doi.org\/10.1067\/mod.2002.125236.","journal-title":"Am J Orthod Dentofac Orthop"},{"key":"649_CR25","volume-title":"Zahn\u00e4rztliche Prop\u00e4deutik","author":"KM Lehmann","year":"2005","unstructured":"Lehmann KM, Hellwig E. Zahn\u00e4rztliche Prop\u00e4deutik. M\u00fcnchen: Urban & Fischer; 2005."},{"key":"649_CR26","unstructured":"Speckmann A. Longitudinale zweidimensionale Weichteilanalyse elektronisch vermessener Profilfotos bei westf\u00e4lischen Schulkindern im Alter von 7 bis 10 Jahren."},{"key":"649_CR27","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1177\/0022034512468750","volume":"92","author":"EC K\u00fcchler","year":"2013","unstructured":"K\u00fcchler EC, Lips A, Tannure PN, Ho B, Costa MC, Granjeiro JM, et al. Tooth Agenesis Association with Self-reported Family History of Cancer. J Dent Res. 2013;92:149\u201355. https:\/\/doi.org\/10.1177\/0022034512468750.","journal-title":"J Dent Res"},{"key":"649_CR28","doi-asserted-by":"publisher","DOI":"10.1111\/ocr.70081","author":"CLB Reis","year":"2026","unstructured":"Reis CLB, Kirschneck C, Hemming D, Paddenberg-Schubert E, Proff P, De Oliveira DSB, et al. Intronic Single Nucleotide Polymorphisms in FGFR2 Gene Association With Non\u2010Syndromic Mandibular Retrognathism. Orthod Craniofac Res. 2026. https:\/\/doi.org\/10.1111\/ocr.70081. ocr.70081.","journal-title":"Orthod Craniofac Res"},{"key":"649_CR29","doi-asserted-by":"publisher","unstructured":"Meyfarth SRS, Baratto-Filho F, Locks MEN, Proff P, Zandon\u00e1 GO, Fernandes TDO et al. Fibroblast growth factor receptor 2 (FGFR2) genetic polymorphisms contribute to fused roots in human molars. Stein GS, editor. PLoS ONE. 2025;20:e0316904. https:\/\/doi.org\/10.1371\/journal.pone.0316904","DOI":"10.1371\/journal.pone.0316904"},{"key":"649_CR30","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1016\/0002-9416(55)90156-1","volume":"41","author":"MM Stoner","year":"1955","unstructured":"Stoner MM. A photometric analysis of the facial profile. Am J Orthod. 1955;41:453\u201369. https:\/\/doi.org\/10.1016\/0002-9416(55)90156-1.","journal-title":"Am J Orthod"},{"key":"649_CR31","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1043\/0003","volume":"51","author":"LG Farkas","year":"1981","unstructured":"Farkas LG, Cheung G. Facial asymmetry in healthy North American Caucasians. An anthropometrical study. Angle Orthod. 1981;51:70\u20137. https:\/\/doi.org\/10.1043\/0003.","journal-title":"Angle Orthod"},{"key":"649_CR32","volume-title":"Proportions of the aesthetic face","author":"N Powell","year":"1984","unstructured":"Powell N, Humphreys B. Proportions of the aesthetic face. New York: Thieme-Stratton; 1984."},{"key":"649_CR33","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/0889-5406(93)70010-L","volume":"103","author":"GW Arnett","year":"1993","unstructured":"Arnett GW, Bergman RT. Facial keys to orthodontic diagnosis and treatment planning. Part I. Am J Orthod Dentofac Orthop. 1993;103:299\u2013312. https:\/\/doi.org\/10.1016\/0889-5406(93)70010-L.","journal-title":"Am J Orthod Dentofac Orthop"},{"key":"649_CR34","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1093\/ejo\/cjm116","volume":"30","author":"S Anicy-Milosevicy","year":"2008","unstructured":"Anicy-Milosevicy S, Lapter-Varga M, Slaj M. Analysis of the soft tissue facial profile by means of angular measurements. Eur J Orthod. 2008;30:135\u201340. https:\/\/doi.org\/10.1093\/ejo\/cjm116.","journal-title":"Eur J Orthod"}],"container-title":["Head &amp; Face Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13005-026-00649-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13005-026-00649-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13005-026-00649-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T04:45:44Z","timestamp":1786941944000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s13005-026-00649-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,15]]},"references-count":34,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["649"],"URL":"https:\/\/doi.org\/10.1186\/s13005-026-00649-3","relation":{},"ISSN":["1746-160X"],"issn-type":[{"value":"1746-160X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,15]]},"assertion":[{"value":"5 March 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 August 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 August 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This project received the approval of the Local Research Ethics committee of Regensburg University, Germany (number: 19-1549-101) and the study was performed in accordance with the latest version of Helsinki Declaration guidelines.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Written informed consent was obtained from all the participants and their legal guardians.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"67"}}