{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T09:21:22Z","timestamp":1787908882695,"version":"build-2784847793"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100012352","name":"Universit\u00e0 degli Studi di Milano","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100012352","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Cell Biochem"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Skeletal muscle is crucial for glucose regulation and amino acid storage, significantly influencing overall metabolic balance. Its function is tightly regulated by complex mechanisms, with histone acetylation as a key epigenetic control point. Our previous work identified eIF6 as a key regulator of muscle energy homeostasis and demonstrated its role in modulating histone acetylation in the liver. However, whether similar epigenetic mechanisms underpin eIF6\u2019s effects in muscle remains undetermined. To investigate this, we measured H3K9 acetylation levels and HDAC activity both in vivo, using eIF6\n                    <jats:sup>+\/\u2013<\/jats:sup>\n                    mice, and in vitro, following eIF6 depletion. Our findings demonstrate that eIF6 downregulation in C2C12 myoblasts drives an increase in histone acetylation, a pattern also evident in heterozygous eIF6 primary satellite cells, both in their undifferentiated state and following differentiation. In vivo, eIF6\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    mice show pronounced histone hyperacetylation, especially in younger animals, which correlates with a specific decrease in class II HDACs, particularly HDAC4 and HDAC5. This trend is further supported by in vitro data and findings from Drosophila eIF6\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    mutants, both of which exhibit decreased HDAC activity. Importantly, the reduction in HDAC4 and HDAC5 activity appears to result from decreased protein levels, driven by eIF6-dependent translational regulation of their mRNAs. All together, these findings establish a link between mRNA translation and histone acetylation in muscle, underpinning translational control as a master regulator of histone acetylation.\n                  <\/jats:p>","DOI":"10.1007\/s11010-026-05637-4","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T08:58:14Z","timestamp":1785315494000},"page":"3933-3943","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["eIF6 links histone acetylation with translational control of HDAC in skeletal muscle"],"prefix":"10.1007","volume":"481","author":[{"given":"Alessandra","family":"Scagliola","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annarita","family":"Miluzio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Ferrari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Brina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Ricciardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3780-1050","authenticated-orcid":false,"given":"Stefano","family":"Biffo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"5637_CR1","doi-asserted-by":"publisher","DOI":"10.1093\/jas\/skac035","volume":"100","author":"MD Zumbaugh","year":"2022","unstructured":"Zumbaugh MD, Johnson SE, Shi TH, Gerrard DE (2022) Molecular and biochemical regulation of skeletal muscle metabolism. J Anim Sci 100:skac035","journal-title":"J Anim Sci"},{"key":"5637_CR2","doi-asserted-by":"publisher","DOI":"10.1002\/wsbm.1462","volume":"12","author":"K Mukund","year":"2020","unstructured":"Mukund K, Subramaniam S (2020) Skeletal muscle: a review of molecular structure and function, in health and disease. Wiley Interdiscip Rev Syst Biol Med 12:e1462","journal-title":"Wiley Interdiscip Rev Syst Biol Med"},{"key":"5637_CR3","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1113\/jphysiol.2007.134593","volume":"582","author":"S Fujita","year":"2007","unstructured":"Fujita S, Dreyer HC, Drummond MJ, Glynn EL, Cadenas JG, Yoshizawa F, Volpi E, Rasmussen BB (2007) Nutrient signalling in the regulation of human muscle protein synthesis. J Physiol 582:813\u2013823","journal-title":"J Physiol"},{"key":"5637_CR4","doi-asserted-by":"publisher","first-page":"1428","DOI":"10.1111\/febs.15820","volume":"289","author":"M Attwaters","year":"2022","unstructured":"Attwaters M, Hughes SM (2022) Cellular and molecular pathways controlling muscle size in response to exercise. FEBS J 289:1428\u20131456","journal-title":"FEBS J"},{"key":"5637_CR5","doi-asserted-by":"publisher","first-page":"3219S","DOI":"10.1093\/jn\/131.10.3219S","volume":"132","author":"RR Wolfe","year":"2002","unstructured":"Wolfe RR (2002) Regulation of muscle protein by amino acids. J Nutr 132:3219S\u20133224S","journal-title":"J Nutr"},{"key":"5637_CR6","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1111\/j.1475-097X.1983.tb00847.x","volume":"3","author":"M Rennie","year":"1983","unstructured":"Rennie M, Edwards R, Emery P, Halliday D, Lundholm K, Millward D (1983) Depressed protein synthesis is the dominant characteristic of muscle wasting and cachexia. Clin Physiol 3:387\u2013398","journal-title":"Clin Physiol"},{"key":"5637_CR7","doi-asserted-by":"publisher","first-page":"572","DOI":"10.3390\/antiox10040572","volume":"10","author":"PC Bradshaw","year":"2021","unstructured":"Bradshaw PC (2021) Acetyl-CoA metabolism and histone acetylation in the regulation of aging and lifespan. Antioxidants 10:572","journal-title":"Antioxidants"},{"key":"5637_CR8","doi-asserted-by":"publisher","DOI":"10.3390\/metabo11110792","volume":"11","author":"J King","year":"2021","unstructured":"King J, Patel M, Chandrasekaran S (2021) Metabolism, HDACs, and HDAC inhibitors: a systems biology perspective. Metabolites 11:792","journal-title":"Metabolites"},{"key":"5637_CR9","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2023.1267456","volume":"14","author":"J Xu","year":"2023","unstructured":"Xu J, Li C, Kang X (2023) The epigenetic regulatory effect of histone acetylation and deacetylation on skeletal muscle metabolism-a review. Front Physiol 14:1267456","journal-title":"Front Physiol"},{"key":"5637_CR10","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1038\/nature10098","volume":"473","author":"B Schwanh\u00e4usser","year":"2011","unstructured":"Schwanh\u00e4usser B, Busse D, Li N, Dittmar G, Schuchhardt J, Wolf J, Chen W, Selbach M (2011) Global quantification of mammalian gene expression control. Nature 473:337\u2013342","journal-title":"Nature"},{"issue":"e5","key":"5637_CR11","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1016\/j.cmet.2018.08.009","volume":"28","author":"S Ricciardi","year":"2018","unstructured":"Ricciardi S, Manfrini N, Alfieri R, Calamita P, Crosti MC, Gallo S, Muller R, Pagani M, Abrignani S, Biffo S (2018) The Translational Machinery of Human CD4(+) T Cells Is Poised for Activation and Controls the Switch from Quiescence to Metabolic Remodeling. Cell Metab 28(e5):895\u2013906. https:\/\/doi.org\/10.1016\/j.cmet.2018.08.009","journal-title":"Cell Metab"},{"key":"5637_CR12","doi-asserted-by":"publisher","first-page":"1945","DOI":"10.1016\/j.cmet.2024.07.022","volume":"36","author":"S Biffo","year":"2024","unstructured":"Biffo S, Ruggero D, Santoro MM (2024) The crosstalk between metabolism and translation. Cell Metab 36:1945\u20131962. https:\/\/doi.org\/10.1016\/j.cmet.2024.07.022","journal-title":"Cell Metab"},{"key":"5637_CR13","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.gde.2017.11.003","volume":"48","author":"LM Lindqvist","year":"2018","unstructured":"Lindqvist LM, Tandoc K, Topisirovic I, Furic L (2018) Cross-talk between protein synthesis, energy metabolism and autophagy in cancer. Curr Opin Genet Dev 48:104\u2013111","journal-title":"Curr Opin Genet Dev"},{"key":"5637_CR14","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1038\/nature07267","volume":"455","author":"V Gandin","year":"2008","unstructured":"Gandin V, Miluzio A, Barbieri AM, Beugnet A, Kiyokawa H, Marchisio PC, Biffo S (2008) Eukaryotic initiation factor 6 is rate-limiting in translation, growth and transformation. Nature 455:684\u20138. https:\/\/doi.org\/10.1038\/nature07267","journal-title":"Nature"},{"key":"5637_CR15","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1016\/j.ccr.2011.04.018","volume":"19","author":"A Miluzio","year":"2011","unstructured":"Miluzio A, Beugnet A, Grosso S, Brina D, Mancino M, Campaner S, Amati B, de Marco A, Biffo S (2011) Impairment of cytoplasmic eIF6 activity restricts lymphomagenesis and tumor progression without affecting normal growth. Cancer Cell 19:765\u201375. https:\/\/doi.org\/10.1016\/j.ccr.2011.04.018","journal-title":"Cancer Cell"},{"key":"5637_CR16","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1038\/nature02160","volume":"426","author":"M Ceci","year":"2003","unstructured":"Ceci M, Gaviraghi C, Gorrini C, Sala LA, Offenhauser N, Marchisio PC, Biffo S (2003) Release of eIF6 (p27BBP) from the 60S subunit allows 80S ribosome assembly. Nature 426:579\u201384. https:\/\/doi.org\/10.1038\/nature02160","journal-title":"Nature"},{"key":"5637_CR17","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9261","volume":"6","author":"D Brina","year":"2015","unstructured":"Brina D, Miluzio A, Ricciardi S, Clarke K, Davidsen PK, Viero G, Tebaldi T, Offenh\u00e4user N, Rozman J, Rathkolb B, Neschen S, Klingenspor M, Wolf E, Gailus-Durner V, Fuchs H, Hrabe de Angelis M, Quattrone A, Falciani F, Biffo S (2015) eIF6 coordinates insulin sensitivity and lipid metabolism by coupling translation to transcription. Nat Commun 6:8261. https:\/\/doi.org\/10.1038\/ncomms9261","journal-title":"Nat Commun"},{"key":"5637_CR18","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.1016\/j.celrep.2017.10.040","volume":"21","author":"K Clarke","year":"2017","unstructured":"Clarke K, Ricciardi S, Pearson T, Bharudin I, Davidsen PK, Bonomo M, Brina D, Scagliola A, Simpson DM, Beynon RJ, Khanim F, Ankers J, Sarzynski MA, Ghosh S, Pisconti A, Rozman J, Hrabe de Angelis M, Bunce C, Stewart C, Egginton S, Caddick M, Jackson M, Bouchard C, Biffo S, Falciani F (2017) The role of Eif6 in skeletal muscle homeostasis revealed by endurance training co-expression networks. Cell Rep 21:1507\u20131520. https:\/\/doi.org\/10.1016\/j.celrep.2017.10.040","journal-title":"Cell Rep"},{"issue":"1","key":"5637_CR19","doi-asserted-by":"publisher","first-page":"7108","DOI":"10.1038\/s41467-022-34831-3","volume":"13","author":"A Osseni","year":"2022","unstructured":"Osseni A, Ravel-Chapuis A, Belotti E, Scionti I, Gangloff Y-G, Moncollin V, Mazelin L, Mounier R, Leblanc P, Jasmin BJ, Schaeffer L (2022) Pharmacological inhibition of HDAC6 improves muscle phenotypes in dystrophin-deficient mice by downregulating TGF-\u03b2 via Smad3 acetylation. Nat Commun 13:7108. https:\/\/doi.org\/10.1038\/s41467-022-34831-3","journal-title":"Nat Commun"},{"key":"5637_CR20","doi-asserted-by":"publisher","first-page":"4410","DOI":"10.1016\/j.molcel.2025.11.002","volume":"85","author":"A Miluzio","year":"2025","unstructured":"Miluzio A, Scagliola A, Ferrari I, Yilmaz H, D\u2019Andrea G, Cassina L, Oliveto S, Ricciardi S, Boletta A, Biffo S (2025) Recycling of ribosomes at stop codons drives the rate of translation and the transition from proliferation to RESt. Mol Cell 85:4410\u20134425e11. https:\/\/doi.org\/10.1016\/j.molcel.2025.11.002","journal-title":"Mol Cell"},{"key":"5637_CR21","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-025-02810-3","author":"MI \u015awirski","year":"2025","unstructured":"\u015awirski MI, Tierney JA, Alb\u00e0 MM, Andreev DE, Aspden JL, Atkins JF, Bassani-Sternberg M, Berry MJ, Biffo S, Boris-Lawrie K (2025) Translon: a single term for translated regions. Nat Methods. https:\/\/doi.org\/10.1038\/s41592-025-02810-3","journal-title":"Nat Methods"},{"key":"5637_CR22","doi-asserted-by":"publisher","first-page":"139","DOI":"10.2217\/epi.13.73","volume":"6","author":"Z Wang","year":"2014","unstructured":"Wang Z, Qin G, Zhao TC (2014) HDAC4: mechanism of regulation and biological functions. Epigenomics 6:139\u2013150. https:\/\/doi.org\/10.2217\/epi.13.73","journal-title":"Epigenomics"},{"key":"5637_CR23","doi-asserted-by":"publisher","DOI":"10.3390\/genes11050556","author":"G Milazzo","year":"2020","unstructured":"Milazzo G, Mercatelli D, Di Muzio G, Triboli L, De Rosa P, Perini G, Giorgi FM (2020) Histone deacetylases (HDACs): evolution, specificity, role in transcriptional complexes, and pharmacological actionability. Genes (Basel). https:\/\/doi.org\/10.3390\/genes11050556","journal-title":"Genes (Basel)"},{"key":"5637_CR24","doi-asserted-by":"publisher","DOI":"10.3390\/cells10061380","author":"E Domi","year":"2021","unstructured":"Domi E, Hoxha M, Prendi E, Zappacosta B (2021) A systematic review on the role of SIRT1 in Duchenne muscular dystrophy. Cells. https:\/\/doi.org\/10.3390\/cells10061380","journal-title":"Cells"},{"key":"5637_CR25","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24054306","author":"M Sandona","year":"2023","unstructured":"Sandona M, Cavioli G, Renzini A, Cedola A, Gigli G, Coletti D, McKinsey TA, Moresi V, Saccone V (2023) Histone deacetylases: molecular mechanisms and therapeutic implications for muscular dystrophies. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms24054306","journal-title":"Int J Mol Sci"},{"issue":"1","key":"5637_CR26","doi-asserted-by":"publisher","first-page":"4878","DOI":"10.1038\/s41467-021-25195-1","volume":"12","author":"A Scagliola","year":"2021","unstructured":"Scagliola A, Miluzio A, Ventura G, Oliveto S, Cordiglieri C, Manfrini N, Cirino D, Ricciardi S, Valenti L, Baselli G (2021) Targeting of eIF6-driven translation induces a metabolic rewiring that reduces NAFLD and the consequent evolution to hepatocellular carcinoma. Nat Commun 12:4878","journal-title":"Nat Commun"},{"key":"5637_CR27","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1002\/jcp.21714","volume":"219","author":"J Krejci","year":"2009","unstructured":"Krejci J, Uhlirova R, Galiova G, Kozubek S, Smigova J, Bartova E (2009) Genome-wide reduction in H3K9 acetylation during human embryonic stem cell differentiation. J Cell Physiol 219:677\u2013687. https:\/\/doi.org\/10.1002\/jcp.21714","journal-title":"J Cell Physiol"},{"key":"5637_CR28","doi-asserted-by":"publisher","first-page":"1168","DOI":"10.4161\/cc.6.10.4230","volume":"6","author":"N Tavernarakis","year":"2007","unstructured":"Tavernarakis N (2007) Protein synthesis and aging: eIF4E and the soma vs. germline distinction. Cell Cycle 6:1168\u20131171. https:\/\/doi.org\/10.4161\/cc.6.10.4230","journal-title":"Cell Cycle"},{"key":"5637_CR29","doi-asserted-by":"publisher","first-page":"2778","DOI":"10.1038\/s41388-022-02272-3","volume":"41","author":"C Wang","year":"2022","unstructured":"Wang C, Leavenworth J, Zhang C, Liu Z, Yuan KY, Wang Y, Zhang G, Wang S, Cui X, Zhang Y, Bae S, Zhou J, Wang L, Liu R (2022) Epigenetic regulation of EIF4A1 through DNA methylation and an oncogenic role of eIF4A1 through BRD2 signaling in prostate cancer. Oncogene 41:2778\u20132785. https:\/\/doi.org\/10.1038\/s41388-022-02272-3","journal-title":"Oncogene"},{"key":"5637_CR30","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1002\/dneu.20763","volume":"70","author":"T Kisliouk","year":"2010","unstructured":"Kisliouk T, Ziv M, Meiri N (2010) Epigenetic control of translation regulation: alterations in histone H3 lysine 9 post-translation modifications are correlated with the expression of the translation initiation factor 2B (Eif2b5) during thermal control establishment. Dev Neurobiol 70:100\u2013113. https:\/\/doi.org\/10.1002\/dneu.20763","journal-title":"Dev Neurobiol"},{"key":"5637_CR31","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10071689","author":"M Dvoran","year":"2022","unstructured":"Dvoran M, Nemcova L, Kalous J (2022) An interplay between epigenetics and translation in oocyte maturation and embryo development: assisted reproduction perspective. Biomedicines. https:\/\/doi.org\/10.3390\/biomedicines10071689","journal-title":"Biomedicines"},{"key":"5637_CR32","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.628415","volume":"9","author":"S Kumar","year":"2021","unstructured":"Kumar S, Mohapatra T (2021) Deciphering epitranscriptome: modification of mRNA bases provides a new perspective for post-transcriptional regulation of gene expression. Front Cell Dev Biol 9:628415. https:\/\/doi.org\/10.3389\/fcell.2021.628415","journal-title":"Front Cell Dev Biol"},{"key":"5637_CR33","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24054885","author":"A Scagliola","year":"2023","unstructured":"Scagliola A, Miluzio A, Biffo S (2023) Translational control of metabolism and cell cycle progression in hepatocellular carcinoma. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms24054885","journal-title":"Int J Mol Sci"},{"key":"5637_CR34","doi-asserted-by":"publisher","DOI":"10.1093\/narcan\/zcae026","volume":"6","author":"M Mahe","year":"2024","unstructured":"Mahe M, Rios-Fuller T, Katsara O, Schneider RJ (2024) Non-canonical mRNA translation initiation in cell stress and cancer. NAR Cancer 6:zcae026. https:\/\/doi.org\/10.1093\/narcan\/zcae026","journal-title":"NAR Cancer"},{"key":"5637_CR35","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.ydbio.2019.05.013","volume":"455","author":"A Russo","year":"2019","unstructured":"Russo A, Gatti G, Alfieri R, Pesce E, Soanes K, Ricciardi S, Mancino M, Cheroni C, Vaccari T, Biffo S (2019) Modulating eIF6 levels unveils the role of translation in ecdysone biosynthesis during Drosophila development. Dev Biol 455:100\u2013111","journal-title":"Dev Biol"},{"key":"5637_CR36","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.scr.2014.10.007","volume":"14","author":"L Boldrin","year":"2015","unstructured":"Boldrin L, Zammit PS, Morgan JE (2015) Satellite cells from dystrophic muscle retain regenerative capacity. Stem Cell Res 14:20\u201329. https:\/\/doi.org\/10.1016\/j.scr.2014.10.007","journal-title":"Stem Cell Res"},{"key":"5637_CR37","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1038\/s41419-025-08399-x","volume":"17","author":"A Scagliola","year":"2025","unstructured":"Scagliola A, Miluzio A, Pauselli M, Ceci M, Biffo S, Ricciardi S (2025) Prime editing links the split integrated stress response to pathogenic eIF2B mutations and white matter degeneration. Cell Death Dis 17:141. https:\/\/doi.org\/10.1038\/s41419-025-08399-x","journal-title":"Cell Death Dis"}],"container-title":["Molecular and Cellular Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11010-026-05637-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11010-026-05637-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11010-026-05637-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T09:14:44Z","timestamp":1787908484000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11010-026-05637-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,29]]},"references-count":37,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["5637"],"URL":"https:\/\/doi.org\/10.1007\/s11010-026-05637-4","relation":{},"ISSN":["1573-4919"],"issn-type":[{"value":"1573-4919","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,29]]},"assertion":[{"value":"25 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}}]}}