{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T03:56:13Z","timestamp":1778644573541,"version":"3.51.4"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100008702","name":"Kagoshima University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008702","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Forensic Sci Med Pathol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>\n                      The lack of specific autopsy findings for carbon dioxide (CO\n                      <jats:sub>2<\/jats:sub>\n                      ) intoxication hinders the determination of cause of death based on autopsy findings alone. In addition, when death occurs in a space is filled with CO\n                      <jats:sub>2<\/jats:sub>\n                      or other gases, the cause of death must be distinguished between intoxication and asphyxia due to oxygen deficiency, which also has no specific autopsy findings. In this study, we aimed to identify diagnostic markers of mRNA expression in the brainstem that indicate cause of death in cases of suspected CO\n                      <jats:sub>2<\/jats:sub>\n                      intoxication.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Mouse models of CO\n                      <jats:sub>2<\/jats:sub>\n                      intoxication (composition of ambient gases at 70% CO\n                      <jats:sub>2<\/jats:sub>\n                      , 20% O\n                      <jats:sub>2<\/jats:sub>\n                      , and 10% N\n                      <jats:sub>2<\/jats:sub>\n                      ) and asphyxia due to oxygen deficiency (5% O\n                      <jats:sub>2<\/jats:sub>\n                      , 95% N\n                      <jats:sub>2<\/jats:sub>\n                      ) were used to identify mRNA markers specific to intoxication or asphyxia.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Using RNA-Sequence analysis, we identified 7 candidate genes for qRT-PCR analysis: Acid-sensing ion channel 4 (Asic4), Early growth response protein 1 (Egr1), Neurogranin (Nrgn), Opioid receptor delta 1 (Oprd1), Semaphorin 3f (Sema3f), Transthyretin (Ttr), and Tryptophan hydroxylase 2 (Tph2). We observed a significant increase of Nrgn mRNA expression in the brainstem of CO\n                      <jats:sub>2<\/jats:sub>\n                      intoxication and a significant increase of Ttr mRNA expression in the brainstem of asphyxia due to oxygen deficiency.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Assays for the expression of Nrgn and Ttr in the human brainstem may assist in the diagnosis\/differential diagnosis of CO\n                      <jats:sub>2<\/jats:sub>\n                      intoxication and asphyxia due to oxygen deficiency, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s12024-025-00981-1","type":"journal-article","created":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T11:31:13Z","timestamp":1743679873000},"page":"1607-1616","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["New molecular markers to differentiate carbon dioxide intoxication from asphyxia due to oxygen deficiency"],"prefix":"10.1007","volume":"21","author":[{"given":"Masahiko","family":"Yatsushiro","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Midori","family":"Katsuyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takuma","family":"Nakamae","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kotomi","family":"Imahara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Machiko","family":"Miyamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3390-5135","authenticated-orcid":false,"given":"Takahito","family":"Hayashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,4,1]]},"reference":[{"key":"981_CR1","first-page":"83","volume":"4\u20135","author":"AA La Verne","year":"1973","unstructured":"La Verne AA, DiMaio DJ, Fernandez AJ. Occupational, accidental, explorational carbon dioxide inhalation poisonings, and prevention. PDM. 1973;4\u20135:83\u201394.","journal-title":"PDM"},{"key":"981_CR2","first-page":"46","volume":"7","author":"H Kuroki","year":"2001","unstructured":"Kuroki H, Yamazaki M, Nakamura M, Inoue H, Iino M, Honda K, Tuchihashi H, Matoba R. An autopsy case of CO2 (Carbon Dioxide) intoxication and the physiological mechanism. Jpn J Forensic Pathol. 2001;7:46\u201353. (In Japanese with English Abstract).","journal-title":"Jpn J Forensic Pathol"},{"key":"981_CR3","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1111\/j.1556-4029.2009.01057.x","volume":"54","author":"S Srisont","year":"2009","unstructured":"Srisont S, Chirachariyavej T, Peonim AV. A carbon dioxide fatality from dry ice. J Forensic Sci. 2009;54:961\u20132.","journal-title":"J Forensic Sci"},{"key":"981_CR4","doi-asserted-by":"publisher","unstructured":"Kettner M, Ramsthaler F, Juhnke C, Bux R, Schmidt P. A fatal case of CO2 intoxication in a fermentation tank. J Forensic Sci 20135;8:556\u20138. https:\/\/doi.org\/10.1111\/1556-4029.12058.12058","DOI":"10.1111\/1556-4029.12058"},{"key":"981_CR5","doi-asserted-by":"publisher","unstructured":"Rupp WR, Thierauf A, Nadjem H, Vogt S. Suicide by carbon dioxide. Forensic Sci Int. 2013;231(1\u20133): e30-2. https:\/\/doi.org\/10.1016\/j.forsciint.2013.05.013","DOI":"10.1016\/j.forsciint.2013.05.013"},{"key":"981_CR6","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1007\/s00414-018-1856-y","volume":"133","author":"K Murakami","year":"2019","unstructured":"Murakami K, Kawaguchi T, Hashizume Y, Kitamura K, Okada M, Okumoto K, Sakamoto S, Ishida Y, Nosaka M, Kimura A, Takatsu A, Kondo T. Suicide by plastic bag suffocation combined with the mixture of citric acid and baking soda in an adolescent. Int J Legal Med. 2019;133:177\u201380.","journal-title":"Int J Legal Med"},{"key":"981_CR7","doi-asserted-by":"publisher","unstructured":"Yatsushiro M, Nakamae T, Katsuyama M, Miyamoto M, Hayashi T. A forensic autopsy case of suicide using baking soda and citric acid in a bathtub. Forensic Sci Med Pathol. 2024 Dec;6. https:\/\/doi.org\/10.1007\/s12024-024-00927-z.","DOI":"10.1007\/s12024-024-00927-z"},{"key":"981_CR8","first-page":"352","volume":"37","author":"M Takahashi","year":"1998","unstructured":"Takahashi M. Effects of carbon dioxide on human body. J Japan Soc Saf Eng. 1998;37:352\u20137.","journal-title":"J Japan Soc Saf Eng"},{"key":"981_CR9","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1097\/01.paf.0000097856.31249.ac","volume":"24","author":"KE Gallagher","year":"2003","unstructured":"Gallagher KE, Smith DM, Mellen PF. Suicidal asphyxiation Byusing pure helium gas: case report, review, and discussion of the influence of the internet. Am J Forensic Med Pathol. 2003;24:361\u20133. https:\/\/doi.org\/10.1097\/01.paf.0000097856.31249.ac.","journal-title":"Am J Forensic Med Pathol"},{"key":"981_CR10","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1027\/0227-5910\/a000326","volume":"36","author":"D Gunnell","year":"2015","unstructured":"Gunnell D, Derges J, Chang SS, Biddle L. Searching for suicide methods: accessibility of information about helium as a method of suicide on the internet. Crisis. 2015;36:325\u201331. https:\/\/doi.org\/10.1027\/0227-5910\/a000326.","journal-title":"Crisis"},{"issue":"21","key":"981_CR11","doi-asserted-by":"publisher","first-page":"11607","DOI":"10.3390\/ijms252111607","volume":"25","author":"MA Sacco","year":"2024","unstructured":"Sacco MA, Aquila I. Post mortem molecular biomarkers of asphyxia: A literature review. Int J Mol Sci. 2024;25(21):11607. https:\/\/doi.org\/10.3390\/ijms252111607.","journal-title":"Int J Mol Sci"},{"key":"981_CR12","doi-asserted-by":"publisher","first-page":"110548","DOI":"10.1016\/j.forsciint.2020.110548","volume":"317","author":"A Giorgetti","year":"2020","unstructured":"Giorgetti A, Pelletti G, Barone R, Garagnani M, Rossi F, Guadagnini G, Fais P, Pelotti S. Deaths related to nitrogen inhalation: analytical challenges. Forensic Sci Int. 2020;317:110548. https:\/\/doi.org\/10.1016\/j.forsciint.2020.110548.","journal-title":"Forensic Sci Int"},{"key":"981_CR13","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2020.584743","author":"Y Xiang","year":"2020","unstructured":"Xiang Y, Xin J, Le W, Yang Y. Neurogranin: a potential biomarker of neurological and mental diseases. Front Aging Neurosci. 2020. https:\/\/doi.org\/10.3389\/fnagi.2020.584743.","journal-title":"Front Aging Neurosci"},{"key":"981_CR14","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2022.104815","author":"AN Jorgensen","year":"2022","unstructured":"Jorgensen AN, Abdullah CS, Bhuiyan MS, Watt M, Dominic P, Kolluru GK, Kevil CG, Nam HW. Neurogranin regulates calcium-dependent cardiac hypertrophy. Exp Mol Pathol. 2022. https:\/\/doi.org\/10.1016\/j.yexmp.2022.104815.","journal-title":"Exp Mol Pathol"},{"key":"981_CR15","unstructured":"Tissue expression of NRGN - The. Human Protein Atlas. https:\/\/www.proteinatlas.org\/ENSG00000154146-NRGN\/tissue\/"},{"key":"981_CR16","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1017\/S1041610298005110","volume":"10","author":"P Davidsson","year":"1998","unstructured":"Davidsson P, Blennow K. Neurochemical dissection of synaptic pathology in Alzheimer\u2019s disease. Int Psychogeriatr. 1998;10:11\u201323. https:\/\/doi.org\/10.1017\/S1041610298005110.","journal-title":"Int Psychogeriatr"},{"key":"981_CR17","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.brainres.2014.10.013","volume":"1591","author":"AO Koob","year":"2014","unstructured":"Koob AO, Shaked GM, Bender A, Bisquertt A, Rockenstein E, Masliah E. Neurogranin binds \u03b1-synuclein in the human superior Temporal cortex and interaction is decreased in Parkinson\u2019s disease. Brain Res. 2014;1591:102\u201310. https:\/\/doi.org\/10.1016\/j.brainres.2014.10.013.","journal-title":"Brain Res"},{"issue":"3","key":"981_CR18","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1038\/npp.2017.167","volume":"43","author":"H Hagihara","year":"2018","unstructured":"Hagihara H, Catts VS, Katayama Y, Shoji H, Takagi T, Huang FL, Nakao A, Mori Y, Huang KP, Ishii S, Graef IA, Nakayama KI, Shannon Weickert C, Miyakawa T. Decreased brain pH as a shared endophenotype of psychiatric disorders. Neuropsychopharmacology. 2018;43(3):459\u201368. https:\/\/doi.org\/10.1038\/npp.2017.167.","journal-title":"Neuropsychopharmacology"},{"key":"981_CR19","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1136\/jnnp-2018-320155","volume":"90","author":"K Blennow","year":"2019","unstructured":"Blennow K, Diaz-Lucena D, Zetterberg H, Villar-Pique A, Karch A, Vidal E, Hermann P, Schmitz M, Ferrer Abizanda I, Zerr I. Llorens FCSF neurogranin as a neuronal damage marker in CJD: A comparative study with AD. J Neurol Neurosurg Psychiatry. 2019;90:846\u201353. https:\/\/doi.org\/10.1136\/jnnp-2018-320155.","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"981_CR20","doi-asserted-by":"publisher","first-page":"584743","DOI":"10.3389\/fnagi.2020.584743","volume":"12","author":"Y Xiang","year":"2020","unstructured":"Xiang Y, Xin J, Le W, Yang Y, Neurogranin. A potential biomarker of neurological and mental diseases. Front Aging Neurosci. 2020;12:584743. https:\/\/doi.org\/10.3389\/fnagi.2020.584743.","journal-title":"Front Aging Neurosci"},{"issue":"6","key":"981_CR21","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1093\/ps\/81.6.869","volume":"81","author":"MR Fedde","year":"2002","unstructured":"Fedde MR, Nelson PI, Kuhlmann WD. Ventilatory sensitivity to changes in inspired and arterial carbon dioxide partial pressures in the chicken. Poult Sci. 2002;81(6):869\u201376. https:\/\/doi.org\/10.1093\/ps\/81.6.869.","journal-title":"Poult Sci"},{"issue":"5","key":"981_CR22","first-page":"440","volume":"64","author":"T Ogasawara","year":"1994","unstructured":"Ogasawara T. Pathophysiology of various oxygen-deprived conditions: medico-legal discussions from blood gas acid-base balance and blood flow values. J Tokyo Wom Med Univ. 1994;64(5):440\u201355.","journal-title":"J Tokyo Wom Med Univ"},{"key":"981_CR23","doi-asserted-by":"publisher","first-page":"1162662","DOI":"10.3389\/fcvm.2023.1162662","volume":"10","author":"Y Xie","year":"2023","unstructured":"Xie Y, Li Y, Chen J, Ding H, Zhang X. Early growth response-1: key mediators of cell death and novel targets for cardiovascular disease therapy. Front Cardiovasc Med. 2023;10:1162662. https:\/\/doi.org\/10.3389\/fcvm.2023.1162662.","journal-title":"Front Cardiovasc Med"},{"key":"981_CR24","unstructured":"EGR1 protein expression summary -. The Human Protein Atlas. https:\/\/www.proteinatlas.org\/ENSG00000120738-EGR1\/brain"},{"issue":"7","key":"981_CR25","doi-asserted-by":"publisher","first-page":"141","DOI":"10.31083\/j.jin2307141","volume":"23","author":"J Wen","year":"2024","unstructured":"Wen J, Jiang Q, Yang L, Cui H. Transcriptomic hallmarks of hypoxic-ischemic brain injury: insights from an in vitro model. J Integr Neurosci. 2024;23(7):141. https:\/\/doi.org\/10.31083\/j.jin2307141.","journal-title":"J Integr Neurosci"},{"key":"981_CR26","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2022.105313","author":"M Ueda","year":"2022","unstructured":"Ueda M. Transthyretin: its function and amyloid formation. Neurochem Int. 2022. https:\/\/doi.org\/10.1016\/j.neuint.2022.105313.","journal-title":"Neurochem Int"},{"key":"981_CR27","doi-asserted-by":"crossref","unstructured":"Santos SD, Lambertsen KL, Clausen BH, Akinc A, Alvarez R, Finsen B et al. CSF transthyretin neuroprotection in a mouse model of brain ischemia. J Neurochem. 2010;115: 1434-44. pmid:21044072.","DOI":"10.1111\/j.1471-4159.2010.07047.x"},{"key":"981_CR28","doi-asserted-by":"publisher","unstructured":"Talhada D, Gon\u00e7alves I, Gomes JC, Saraiva MJ, Reis Santos C, Ruscher K. Transthyretin expression in the postischemic brain. PLoS One. 2019;14(9): e0221555. https:\/\/doi.org\/10.1371\/journal.pone.0221555. eCollection 2019.","DOI":"10.1371\/journal.pone.0221555"},{"key":"981_CR29","doi-asserted-by":"publisher","DOI":"10.1038\/srep18242","author":"V Schwartz","year":"2015","unstructured":"Schwartz V, Friedrich K, Polleichtner G, Gr\u00fcnder S. Acid-sensing ion channel (ASIC) 4 predominantly localizes to an early endosome-related organelle upon heterologous expression. Sci Rep. 2015. https:\/\/doi.org\/10.1038\/srep18242.","journal-title":"Sci Rep"},{"issue":"6","key":"981_CR30","doi-asserted-by":"publisher","first-page":"fcac256","DOI":"10.1093\/braincomms\/fcac256","volume":"4","author":"M Papalampropoulou-Tsiridou","year":"2022","unstructured":"Papalampropoulou-Tsiridou M, Shiers S, Wang F, Godin AG, Price TJ, De Koninck Y. Distribution of acid-sensing ion channel subunits in human sensory neurons contrasts with that in rodents. Brain Commun. 2022;4(6):fcac256. https:\/\/doi.org\/10.1093\/braincomms\/fcac256.","journal-title":"Brain Commun"},{"issue":"9","key":"981_CR31","doi-asserted-by":"publisher","first-page":"1570","DOI":"10.2174\/1570159X19666210125151824","volume":"19","author":"M Storozhuk","year":"2021","unstructured":"Storozhuk M, Cherninskyi A, Maximyuk O, Isaev D, Krishtal O. Acid-sensing ion channels: focus on physiological and some pathological roles in the brain. Curr Neuropharmacol. 2021;19(9):1570\u201389. https:\/\/doi.org\/10.2174\/1570159X19666210125151824.","journal-title":"Curr Neuropharmacol"},{"key":"981_CR32","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2013.06.003","author":"P Chung","year":"2013","unstructured":"Chung P, Chu Sin, Kieffer BL. Delta opioid receptors in brain function and diseases. Pharmacol Ther. 2013. https:\/\/doi.org\/10.1016\/j.pharmthera.2013.06.003.","journal-title":"Pharmacol Ther"},{"key":"981_CR33","doi-asserted-by":"publisher","DOI":"10.14952\/SEIKAGAKU.2015.870428","author":"I Oinuma","year":"2015","unstructured":"Oinuma I. Signaling mechanism for axonal guidance factors, semaphorins. J Jpn Biochem Soc. 2015. https:\/\/doi.org\/10.14952\/SEIKAGAKU.2015.870428. [in Japanese with English Abstract].","journal-title":"J Jpn Biochem Soc"},{"issue":"5","key":"981_CR34","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1002\/cne.21073","volume":"498","author":"MS Clark","year":"2006","unstructured":"Clark MS, McDevitt RA, Neumaier JF. Quantitative mapping of Tryptophan hydroxylase-2, 5-HT1A, 5-HT1B, and serotonin transporter expression across the anteroposterior axis of the rat dorsal and median Raphe nuclei. J Comp Neurol. 2006;498(5):611\u201323. https:\/\/doi.org\/10.1002\/cne.21073.","journal-title":"J Comp Neurol"},{"issue":"5","key":"981_CR35","doi-asserted-by":"publisher","first-page":"2224","DOI":"10.1152\/jn.2001.85.5.2224","volume":"85","author":"W Wang","year":"2001","unstructured":"Wang W, Tiwari JK, Bradley SR, Zaykin RV, Richerson GB. Acidosis-stimulated neurons of the medullary Raphe are serotonergic. Neurophysiol. 2001;85(5):2224\u201335. https:\/\/doi.org\/10.1152\/jn.2001.85.5.2224.","journal-title":"Neurophysiol"},{"issue":"6","key":"981_CR36","doi-asserted-by":"publisher","first-page":"1981","DOI":"10.1523\/JNEUROSCI.4639-10.2011","volume":"31","author":"SD Depuy","year":"2011","unstructured":"Depuy SD, Kanbar R, Coates MB, Stornetta RL, Guyenet PG. Control of breathing by Raphe obscurus serotonergic neurons in mice. J Neurosci. 2011;31(6):1981\u201390. https:\/\/doi.org\/10.1523\/JNEUROSCI.4639-10.2011.","journal-title":"J Neurosci"},{"key":"981_CR37","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.legalmed.2015.07.014","volume":"19","author":"K Sato","year":"2016","unstructured":"Sato K, Tsuji A, Usumoto Y, Kudo K, Yokoyama T, Ikeda N. Expression of mRNA in the frontal cortex and hypothalamus in a rat model of acute carbon dioxide poisoning. Leg Med. 2016;19:101\u20136. https:\/\/doi.org\/10.1016\/j.legalmed.2015.07.014.","journal-title":"Leg Med"}],"container-title":["Forensic Science, Medicine and Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12024-025-00981-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12024-025-00981-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12024-025-00981-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T03:13:37Z","timestamp":1768360417000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12024-025-00981-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,1]]},"references-count":37,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["981"],"URL":"https:\/\/doi.org\/10.1007\/s12024-025-00981-1","relation":{},"ISSN":["1556-2891"],"issn-type":[{"value":"1556-2891","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,1]]},"assertion":[{"value":"4 March 2025","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 April 2025","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no known competing financial interests or personal relatonships that could have appeared to influence the work reported in this paper.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}