{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T10:38:15Z","timestamp":1785839895041,"version":"3.56.0"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Death Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    N6-methyladenosine (m\n                    <jats:sup>6<\/jats:sup>\n                    A) modification has emerged as a common chemical modification in epigenetic regulation. However, whether this m\n                    <jats:sup>6<\/jats:sup>\n                    A modification is involved in glycolysis metabolism in pancreatic ductal adenocarcinoma (PDAC) remains elusive. Multiomics integration strategies, including metabolomics, m\n                    <jats:sup>6<\/jats:sup>\n                    A-seq and transcriptome sequencing, were utilized to evaluate the associations between m\n                    <jats:sup>6<\/jats:sup>\n                    A modifications and key processes of glucose metabolism in PDAC. Spontaneous PDAC mice (LSLKras\n                    <jats:sup>G12D\/+<\/jats:sup>\n                    , LSL-Trp53\n                    <jats:sup>R172H\/+<\/jats:sup>\n                    , Pdx1-Cre; KPC) with FTO-conditional knockout and organoids were used to evaluate the effects of FTO stimulation on PDAC cell glycolysis and tumorigenesis. Series of in vivo and vitro functional analysis revealed that FTO promoted migratory capacity and glycolysis of PDAC cells. Mechanistically, FTO elevates the mRNA expression of the transcription factor C-Jun in a m\n                    <jats:sup>6<\/jats:sup>\n                    A-YTHDF2-dependent manner and further transcriptionally upregulates PFKM expression. Translational studies involving organoid models and xenograft tumor models revealed that the use of FTO inhibitors significantly suppressed PDAC growth. Our findings uncover that targeting the m\n                    <jats:sup>6<\/jats:sup>\n                    A-dependent FTO\/C-Jun\/PFKM glycolysis regulatory axis may be essential for the prevention and treatment of PDAC.\n                  <\/jats:p>","DOI":"10.1038\/s41419-025-08049-2","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T14:00:27Z","timestamp":1762178427000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["m6A demethylase FTO drives pancreatic ductal adenocarcinoma tumorigenesis and metastasis through remodeling PFKM mediated glycolysis"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6188-209X","authenticated-orcid":false,"given":"Zhen","family":"Tan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhui","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueyue","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomeng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7433-3121","authenticated-orcid":false,"given":"Qingcai","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0862-2501","authenticated-orcid":false,"given":"Mingming","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyin","family":"Rong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6697-7143","authenticated-orcid":false,"given":"Xianjun","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0578-7589","authenticated-orcid":false,"given":"Chen","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,3]]},"reference":[{"key":"8049_CR1","doi-asserted-by":"publisher","first-page":"1729","DOI":"10.1016\/j.cell.2023.02.014","volume":"186","author":"CJ Halbrook","year":"2023","unstructured":"Halbrook CJ, Lyssiotis CA, Pasca di Magliano M, Maitra A. Pancreatic cancer: advances and challenges. Cell. 2023;186:1729\u201354.","journal-title":"Cell"},{"key":"8049_CR2","first-page":"7","volume":"72","author":"RL Siegel","year":"2022","unstructured":"Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022;72:7\u201333.","journal-title":"CA Cancer J Clin"},{"key":"8049_CR3","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/j.ccell.2018.12.010","volume":"35","author":"AA Connor","year":"2019","unstructured":"Connor AA, Denroche RE, Jang GH, Lemire M, Zhang A, Chan-Seng-Yue M, et al. Integration of genomic and transcriptional features in pancreatic cancer reveals increased cell cycle progression in metastases. Cancer Cell. 2019;35:267\u2013282.e7.","journal-title":"Cancer Cell"},{"key":"8049_CR4","doi-asserted-by":"publisher","first-page":"6119","DOI":"10.1016\/j.cell.2021.11.017","volume":"184","author":"S Raghavan","year":"2021","unstructured":"Raghavan S, Winter PS, Navia AW, Williams HL, DenAdel A, Lowder KE, et al. Microenvironment drives cell state, plasticity, and drug response in pancreatic cancer. Cell. 2021;184:6119\u201337.e26.","journal-title":"Cell"},{"key":"8049_CR5","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1126\/science.aay6018","volume":"367","author":"J Liu","year":"2020","unstructured":"Liu J, Dou X, Chen C, Chen C, Liu C, Xu MM, et al. N (6)-methyladenosine of chromosome-associated regulatory RNA regulates chromatin state and transcription. Science. 2020;367:580\u20136.","journal-title":"Science"},{"key":"8049_CR6","doi-asserted-by":"publisher","first-page":"1346","DOI":"10.1126\/science.aau1646","volume":"361","author":"M Frye","year":"2018","unstructured":"Frye M, Harada BT, Behm M, He C. RNA modifications modulate gene expression during development. Science. 2018;361:1346\u20139.","journal-title":"Science"},{"key":"8049_CR7","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1186\/s13045-022-01384-3","volume":"15","author":"Y Tong","year":"2022","unstructured":"Tong Y, Sun M, Chen L, Wang Y, Li Y, Li L, et al. Proteogenomic insights into the biology and treatment of pancreatic ductal adenocarcinoma. J Hematol Oncol. 2022;15:168.","journal-title":"J Hematol Oncol"},{"key":"8049_CR8","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1158\/2159-8290.CD-19-0297","volume":"10","author":"P Dey","year":"2020","unstructured":"Dey P, Li J, Zhang J, Chaurasiya S, Strom A, Wang H, et al. Oncogenic KRAS-driven metabolic reprogramming in pancreatic cancer cells utilizes cytokines from the tumor microenvironment. Cancer Discov. 2020;10:608\u201325.","journal-title":"Cancer Discov"},{"key":"8049_CR9","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.1016\/j.cmet.2021.04.001","volume":"33","author":"Y Liu","year":"2021","unstructured":"Liu Y, Liang G, Xu H, Dong W, Dong Z, Qiu Z, et al. Tumors exploit FTO-mediated regulation of glycolytic metabolism to evade immune surveillance. Cell Metab. 2021;33:1221\u201333.e11.","journal-title":"Cell Metab"},{"key":"8049_CR10","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-020-01190-w","volume":"19","author":"C Shen","year":"2020","unstructured":"Shen C, Xuan B, Yan T, Ma Y, Xu P, Tian X, et al. m(6)A-dependent glycolysis enhances colorectal cancer progression. Mol Cancer. 2020;19:72.","journal-title":"Mol Cancer"},{"key":"8049_CR11","doi-asserted-by":"publisher","first-page":"2329","DOI":"10.1136\/gutjnl-2022-329349","volume":"72","author":"X Liu","year":"2023","unstructured":"Liu X, Tang R, Xu J, Tan Z, Liang C, Meng Q, et al. CRIP1 fosters MDSC trafficking and resets tumour microenvironment via facilitating NF-kappaB\/p65 nuclear translocation in pancreatic ductal adenocarcinoma. Gut. 2023;72:2329\u201343.","journal-title":"Gut"},{"key":"8049_CR12","doi-asserted-by":"publisher","first-page":"15995","DOI":"10.1002\/anie.201807942","volume":"57","author":"Y Xiao","year":"2018","unstructured":"Xiao Y, Wang Y, Tang Q, Wei L, Zhang X, Jia G. An elongation- and ligation-based qPCR amplification method for the radiolabeling-free detection of locus-specific N(6) -methyladenosine modification. Angew Chem Int Ed Engl. 2018;57:15995\u201316000.","journal-title":"Angew Chem Int Ed Engl"},{"key":"8049_CR13","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1016\/j.ccell.2019.03.006","volume":"35","author":"Y Huang","year":"2019","unstructured":"Huang Y, Su R, Sheng Y, Dong L, Dong Z, Xu H, et al. Small-molecule targeting of oncogenic FTO demethylase in acute myeloid leukemia. Cancer Cell. 2019;35:677\u201391.e10.","journal-title":"Cancer Cell"},{"key":"8049_CR14","doi-asserted-by":"publisher","first-page":"3010","DOI":"10.1021\/acs.accounts.3c00451","volume":"56","author":"Y Huang","year":"2023","unstructured":"Huang Y, Xia W, Dong Z, Yang CG. Chemical inhibitors targeting the oncogenic m(6)A modifying proteins. Acc Chem Res. 2023;56:3010\u201322.","journal-title":"Acc Chem Res"},{"key":"8049_CR15","doi-asserted-by":"publisher","first-page":"4480","DOI":"10.1016\/j.cell.2021.07.004","volume":"184","author":"N Amara","year":"2021","unstructured":"Amara N, Cooper MP, Voronkova MA, Webb BA, Lynch EM, Kollman JM, et al. Selective activation of PFKL suppresses the phagocytic oxidative burst. Cell. 2021;184:4480\u201394.e15.","journal-title":"Cell"},{"key":"8049_CR16","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1093\/neuonc\/noac135","volume":"25","author":"YC Lim","year":"2023","unstructured":"Lim YC, Jensen KE, Aguilar-Morante D, Vardouli L, Vitting-Seerup K, Gimple RC, et al. Non-metabolic functions of phosphofructokinase-1 orchestrate tumor cellular invasion and genome maintenance under bevacizumab therapy. Neuro Oncol. 2023;25:248\u201360.","journal-title":"Neuro Oncol"},{"key":"8049_CR17","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.cmet.2006.04.015","volume":"4","author":"F Gachon","year":"2006","unstructured":"Gachon F, Olela FF, Schaad O, Descombes P, Schibler U. The circadian PAR-domain basic leucine zipper transcription factors DBP, TEF, and HLF modulate basal and inducible xenobiotic detoxification. Cell Metab. 2006;4:25\u201336.","journal-title":"Cell Metab"},{"key":"8049_CR18","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1038\/nature12730","volume":"505","author":"X Wang","year":"2014","unstructured":"Wang X, Lu Z, Gomez A, Hon GC, Yue Y, Han D, et al. N6-methyladenosine-dependent regulation of messenger RNA stability. Nature. 2014;505:117\u201320.","journal-title":"Nature"},{"key":"8049_CR19","doi-asserted-by":"publisher","first-page":"1582","DOI":"10.1016\/j.cell.2020.05.012","volume":"181","author":"S Zaccara","year":"2020","unstructured":"Zaccara S, Jaffrey SR. A unified model for the function of YTHDF proteins in regulating m(6)A-modified mRNA. Cell. 2020;181:1582\u201395.e18.","journal-title":"Cell"},{"key":"8049_CR20","doi-asserted-by":"publisher","first-page":"eadf3208","DOI":"10.1126\/science.adf3208","volume":"382","author":"G Snieckute","year":"2023","unstructured":"Snieckute G, Ryder L, Vind AC, Wu Z, Arendrup FS, Stoneley M, et al. ROS-induced ribosome impairment underlies ZAKalpha-mediated metabolic decline in obesity and aging. Science. 2023;382:eadf3208 p.","journal-title":"Science"},{"key":"8049_CR21","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1186\/s13045-020-00912-3","volume":"13","author":"X Xiao","year":"2020","unstructured":"Xiao X, Liu P, Li D, Xia Z, Wang P, Zhang X, et al. Combination therapy of BCR-ABL-positive B cell acute lymphoblastic leukemia by tyrosine kinase inhibitor dasatinib and c-JUN N-terminal kinase inhibition. J Hematol Oncol. 2020;13:80.","journal-title":"J Hematol Oncol"},{"key":"8049_CR22","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1001\/jama.2021.13027","volume":"326","author":"W Park","year":"2021","unstructured":"Park W, Chawla A, O\u2019Reilly EM. Pancreatic cancer: a review. JAMA. 2021;326:851\u201362.","journal-title":"JAMA"},{"key":"8049_CR23","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1038\/s41571-020-0363-5","volume":"17","author":"WJ Ho","year":"2020","unstructured":"Ho WJ, Jaffee EM, Zheng L. The tumour microenvironment in pancreatic cancer\u2014clinical challenges and opportunities. Nat Rev Clin Oncol. 2020;17:527\u201340.","journal-title":"Nat Rev Clin Oncol"},{"key":"8049_CR24","doi-asserted-by":"publisher","first-page":"3602","DOI":"10.1158\/0008-5472.CAN-24-0927","volume":"84","author":"Z Xu","year":"2024","unstructured":"Xu Z, Zhou Y, Liu S, Zhao H, Chen Z, Li R, et al. KHSRP stabilizes m6A-modified transcripts to activate FAK signaling and promote pancreatic ductal adenocarcinoma progression. Cancer Res. 2024;84:3602\u201316.","journal-title":"Cancer Res"},{"key":"8049_CR25","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1038\/nature11112","volume":"485","author":"D Dominissini","year":"2012","unstructured":"Dominissini D, Moshitch-Moshkovitz S, Schwartz S, Salmon-Divon M, Ungar L, Osenberg S, et al. Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature. 2012;485:201\u20136.","journal-title":"Nature"},{"key":"8049_CR26","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1146\/annurev-cellbio-100616-060758","volume":"33","author":"KD Meyer","year":"2017","unstructured":"Meyer KD, Jaffrey SR. Rethinking m(6)A readers, writers, and erasers. Annu Rev Cell Dev Biol. 2017;33:319\u201342.","journal-title":"Annu Rev Cell Dev Biol"},{"key":"8049_CR27","doi-asserted-by":"publisher","first-page":"964","DOI":"10.1056\/NEJMe1508683","volume":"373","author":"CJ Rosen","year":"2015","unstructured":"Rosen CJ, Ingelfinger JR. Unraveling the function of FTO variants. N Engl J Med. 2015;373:964\u20135.","journal-title":"N Engl J Med"},{"key":"8049_CR28","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.cell.2017.11.031","volume":"172","author":"R Su","year":"2018","unstructured":"Su R, Dong L, Li C, Nachtergaele S, Wunderlich M, Qing Y, et al. R-2HG exhibits anti-tumor activity by targeting FTO\/m(6)A\/MYC\/CEBPA signaling. Cell. 2018;172:90\u2013105.e23.","journal-title":"Cell"},{"key":"8049_CR29","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.ccell.2020.04.017","volume":"38","author":"R Su","year":"2020","unstructured":"Su R, Dong L, Li Y, Gao M, Han L, Wunderlich M, et al. Targeting FTO suppresses cancer stem cell maintenance and immune evasion. Cancer Cell. 2020;38:79\u201396.e11.","journal-title":"Cancer Cell"},{"key":"8049_CR30","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/s13046-022-02254-z","volume":"41","author":"J Huang","year":"2022","unstructured":"Huang J, Sun W, Wang Z, Lv C, Zhang T, Zhang D, et al. FTO suppresses glycolysis and growth of papillary thyroid cancer via decreasing stability of APOE mRNA in an N6-methyladenosine-dependent manner. J Exp Clin Cancer Res. 2022;41:42.","journal-title":"J Exp Clin Cancer Res"},{"key":"8049_CR31","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1039\/D2CS00479H","volume":"52","author":"J Chen","year":"2023","unstructured":"Chen J, Zhu Y, Wu C, Shi J. Engineering lactate-modulating nanomedicines for cancer therapy. Chem Soc Rev. 2023;52:973\u20131000.","journal-title":"Chem Soc Rev"},{"key":"8049_CR32","doi-asserted-by":"publisher","first-page":"3824","DOI":"10.1016\/j.cell.2024.06.026","volume":"187","author":"SM Fendt","year":"2024","unstructured":"Fendt SM. 100 years of the Warburg effect: a cancer metabolism endeavor. Cell. 2024;187:3824\u20138.","journal-title":"Cell"},{"key":"8049_CR33","doi-asserted-by":"publisher","first-page":"1905","DOI":"10.1016\/j.molcel.2021.02.033","volume":"81","author":"AA Jourdain","year":"2021","unstructured":"Jourdain AA, Begg BE, Mick E, Shah H, Calvo SE, Skinner OS, et al. Loss of LUC7L2 and U1 snRNP subunits shifts energy metabolism from glycolysis to OXPHOS. Mol Cell. 2021;81:1905\u201319.e12.","journal-title":"Mol Cell"},{"key":"8049_CR34","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-021-03681-0","volume":"12","author":"W Gao","year":"2021","unstructured":"Gao W, Huang M, Chen X, Chen J, Zou Z, Li L, et al. The role of S-nitrosylation of PFKM in regulation of glycolysis in ovarian cancer cells. Cell Death Dis. 2021;12:408.","journal-title":"Cell Death Dis"},{"key":"8049_CR35","doi-asserted-by":"publisher","first-page":"5926","DOI":"10.7150\/thno.56490","volume":"11","author":"Y Zhou","year":"2021","unstructured":"Zhou Y, Lin F, Wan T, Chen A, Wang H, Jiang B, et al. ZEB1 enhances Warburg effect to facilitate tumorigenesis and metastasis of HCC by transcriptionally activating PFKM. Theranostics. 2021;11:5926\u201338.","journal-title":"Theranostics"},{"key":"8049_CR36","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1038\/s41568-024-00706-6","volume":"24","author":"R Polak","year":"2024","unstructured":"Polak R, Zhang ET, Kuo CJ. Cancer organoids 2.0: modelling the complexity of the tumour immune microenvironment. Nat Rev Cancer. 2024;24:523\u201339.","journal-title":"Nat Rev Cancer"},{"key":"8049_CR37","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/j.ccell.2024.03.004","volume":"42","author":"H Yang","year":"2024","unstructured":"Yang H, Cheng J, Zhuang H, Xu H, Wang Y, Zhang T, et al. Pharmacogenomic profiling of intra-tumor heterogeneity using a large organoid biobank of liver cancer. Cancer Cell. 2024;42:535\u201351.e8.","journal-title":"Cancer Cell"}],"container-title":["Cell Death &amp; Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41419-025-08049-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41419-025-08049-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41419-025-08049-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T14:00:27Z","timestamp":1762178427000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41419-025-08049-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,3]]},"references-count":37,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["8049"],"URL":"https:\/\/doi.org\/10.1038\/s41419-025-08049-2","relation":{},"ISSN":["2041-4889"],"issn-type":[{"value":"2041-4889","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,3]]},"assertion":[{"value":"23 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 August 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 September 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 November 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"This study involved human participants and was approved by the Institutional Research Ethics Committee of Fudan University Shanghai Cancer Center (Project identification code: 2410-Exp085), and written informed consent was obtained from all patients. All animal care and experimental procedures were conducted in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and were approved by Fudan University\u2019s Animal Care and Ethics Committee (FUSCC-IACUC-2024334).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}],"article-number":"784"}}