{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T12:10:42Z","timestamp":1785499842769,"version":"3.56.0"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T00:00:00Z","timestamp":1722816000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T00:00:00Z","timestamp":1722816000000},"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":["Pediatr Res"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>The optimal rate to rewarm infants after therapeutic hypothermia is unclear. In this study we examined whether slow rewarming after 72\u2009h of hypothermia would attenuate white matter injury.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Near-term fetal sheep received sham occlusion (<jats:italic>n<\/jats:italic>\u2009=\u20098) or cerebral ischemia for 30\u2009min, followed by normothermia (<jats:italic>n<\/jats:italic>\u2009=\u20097) or hypothermia from 3\u201372\u2009h, with either spontaneous fast rewarming (<jats:italic>n<\/jats:italic>\u2009=\u20098) within 1\u2009h, or slow rewarming at ~0.5\u2009\u00b0C\/h (<jats:italic>n<\/jats:italic>\u2009=\u20098) over 10\u2009h. Fetuses were euthanized 7 days later.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Ischemia was associated with loss of total and mature oligodendrocytes, reduced expression of myelin proteins and induction of microglia and astrocytes, compared with sham controls (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). Both hypothermia protocols were associated with a significant increase in numbers of total and mature oligodendrocytes, area fraction of myelin proteins and reduced numbers of microglia and astrocytes, compared with ischemia-normothermia (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). There was no difference in the number of oligodendrocytes, microglia or astrocytes or expression of myelin proteins between fast and slow rewarming after hypothermia.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>The rate of rewarming after a clinically relevant duration of hypothermia had no apparent effect on white matter protection by hypothermia after cerebral ischemia in near-term fetal sheep.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Impact<\/jats:title>\n            <jats:p>\n              <jats:list list-type=\"bullet\">\n                <jats:list-item>\n                  <jats:p>Persistent white matter injury is a major contributor to long-term disability after neonatal encephalopathy despite treatment with therapeutic hypothermia.<\/jats:p>\n                <\/jats:list-item>\n                <jats:list-item>\n                  <jats:p>The optimal rate to rewarm infants after therapeutic hypothermia is unclear; current protocols were developed on a precautionary basis.<\/jats:p>\n                <\/jats:list-item>\n                <jats:list-item>\n                  <jats:p>We now show that slow rewarming at 0.5\u2009\u00b0C\/h did not improve histological white matter injury compared with rapid spontaneous rewarming after a clinically established duration of hypothermia in near-term fetal sheep.<\/jats:p>\n                <\/jats:list-item>\n              <\/jats:list>\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1038\/s41390-024-03332-y","type":"journal-article","created":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T15:03:41Z","timestamp":1722870221000},"page":"1209-1219","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Slow rewarming after hypothermia does not ameliorate white matter injury after hypoxia-ischemia in near-term fetal sheep"],"prefix":"10.1038","volume":"97","author":[{"given":"Alice","family":"McDouall","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly Q.","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Davies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Wassink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy L. M.","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Bennet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alistair J.","family":"Gunn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne O.","family":"Davidson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,8,5]]},"reference":[{"key":"3332_CR1","doi-asserted-by":"publisher","first-page":"1004","DOI":"10.1542\/peds.2004-0222","volume":"114","author":"M Rutherford","year":"2004","unstructured":"Rutherford, M. et al. Diffusion-weighted magnetic resonance imaging in term perinatal brain injury: a comparison with site of lesion and time from birth. Pediatrics 114, 1004\u20131014 (2004).","journal-title":"Pediatrics"},{"key":"3332_CR2","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1016\/S0140-6736(03)12658-X","volume":"361","author":"F Cowan","year":"2003","unstructured":"Cowan, F. et al. Origin and timing of brain lesions in term infants with neonatal encephalopathy. Lancet 361, 736\u2013742 (2003).","journal-title":"Lancet"},{"key":"3332_CR3","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1203\/PDR.0b013e31818912d2","volume":"65","author":"AM Li","year":"2009","unstructured":"Li, A. M. et al. White matter injury in term newborns with neonatal encephalopathy. Pediatr. Res. 65, 85\u201389 (2009).","journal-title":"Pediatr. Res."},{"key":"3332_CR4","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1016\/j.jpeds.2012.04.054","volume":"161","author":"M Martinez-Biarge","year":"2012","unstructured":"Martinez-Biarge, M. et al. White matter and cortical injury in hypoxic-ischemic encephalopathy: antecedent factors and 2-year outcome. J. Pediatr. 161, 799\u2013807 (2012).","journal-title":"J. Pediatr."},{"key":"3332_CR5","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2021.100885","volume":"36","author":"M Thoresen","year":"2021","unstructured":"Thoresen, M. et al. MRI combined with early clinical variables are excellent outcome predictors for newborn infants undergoing therapeutic hypothermia after perinatal asphyxia. EClinicalMedicine 36, 100885 (2021).","journal-title":"EClinicalMedicine"},{"key":"3332_CR6","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/S1474-4422(09)70295-9","volume":"9","author":"M Rutherford","year":"2010","unstructured":"Rutherford, M. et al. Assessment of brain tissue injury after moderate hypothermia in neonates with hypoxic-ischaemic encephalopathy: a nested substudy of a randomised controlled trial. Lancet Neurol. 9, 39\u201345 (2010).","journal-title":"Lancet Neurol."},{"key":"3332_CR7","first-page":"F398","volume":"97","author":"S Shankaran","year":"2012","unstructured":"Shankaran, S. et al. Brain injury following trial of hypothermia for neonatal hypoxic-ischaemic encephalopathy. Arch. Dis. Child. Fetal Neonatal Ed. 97, F398\u2013F404 (2012).","journal-title":"Arch. Dis. Child. Fetal Neonatal Ed."},{"key":"3332_CR8","doi-asserted-by":"publisher","first-page":"634","DOI":"10.1001\/archpediatrics.2012.284","volume":"166","author":"JL Cheong","year":"2012","unstructured":"Cheong, J. L. et al. Prognostic utility of magnetic resonance imaging in neonatal hypoxic-ischemic encephalopathy: substudy of a randomized trial. Arch. Pediatr. Adolesc. Med. 166, 634\u2013640 (2012).","journal-title":"Arch. Pediatr. Adolesc. Med."},{"key":"3332_CR9","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1038\/pr.2012.40","volume":"72","author":"N Tusor","year":"2012","unstructured":"Tusor, N. et al. Prediction of neurodevelopmental outcome after hypoxic-ischemic encephalopathy treated with hypothermia by diffusion tensor imaging analyzed using tract-based spatial statistics. Pediatr. Res 72, 63\u201369 (2012).","journal-title":"Pediatr. Res"},{"key":"3332_CR10","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2021.102582","volume":"30","author":"APC Spencer","year":"2021","unstructured":"Spencer, A. P. C. et al. Disrupted brain connectivity in children treated with therapeutic hypothermia for neonatal encephalopathy. NeuroImage Clin. 30, 102582 (2021).","journal-title":"NeuroImage Clin."},{"key":"3332_CR11","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1177\/0271678X17707671","volume":"38","author":"JO Davidson","year":"2018","unstructured":"Davidson, J. O. et al. How long is sufficient for optimal neuroprotection with cerebral cooling after ischemia in fetal sheep? J. Cereb. Blood Flow. Metab. 38, 1047\u20131059 (2018).","journal-title":"J. Cereb. Blood Flow. Metab."},{"key":"3332_CR12","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1203\/00006450-199909000-00005","volume":"46","author":"AJ Gunn","year":"1999","unstructured":"Gunn, A. J., Bennet, L., Gunning, M. I., Gluckman, P. D. & Gunn, T. R. Cerebral hypothermia is not neuroprotective when started after postischemic seizures in fetal sheep. Pediatr. Res. 46, 274\u2013280 (1999).","journal-title":"Pediatr. Res."},{"key":"3332_CR13","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1172\/JCI119153","volume":"99","author":"AJ Gunn","year":"1997","unstructured":"Gunn, A. J., Gunn, T. R., de Haan, H. H., Williams, C. E. & Gluckman, P. D. Dramatic neuronal rescue with prolonged selective head cooling after ischemia in fetal lambs. J. Clin. Investig. 99, 248\u2013256 (1997).","journal-title":"J. Clin. Investig."},{"key":"3332_CR14","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1038\/jcbfm.2014.259","volume":"35","author":"JO Davidson","year":"2015","unstructured":"Davidson, J. O. et al. How long is too long for cerebral cooling after ischemia in fetal sheep? J. Cereb. Blood Flow. Metab. 35, 751\u2013758 (2015).","journal-title":"J. Cereb. Blood Flow. Metab."},{"key":"3332_CR15","doi-asserted-by":"publisher","first-page":"1678","DOI":"10.4103\/1673-5374.257512","volume":"14","author":"A Davies","year":"2019","unstructured":"Davies, A., Wassink, G., Bennet, L., Gunn, A. J. & Davidson, J. O. Can we further optimize therapeutic hypothermia for hypoxic-ischemic encephalopathy? Neural Regen. Res. 14, 1678\u20131683 (2019).","journal-title":"Neural Regen. Res."},{"key":"3332_CR16","doi-asserted-by":"publisher","first-page":"198","DOI":"10.3389\/fneur.2015.00198","volume":"6","author":"JO Davidson","year":"2015","unstructured":"Davidson, J. O., Wassink, G., van den Heuij, L. G., Bennet, L. & Gunn, A. J. Therapeutic hypothermia for neonatal hypoxic\u2013ischemic encephalopathy\u2013where to from here? Front. Neurol. 6, 198 (2015).","journal-title":"Front. Neurol."},{"key":"3332_CR17","doi-asserted-by":"publisher","first-page":"5641","DOI":"10.1113\/JP274928","volume":"596","author":"G Wassink","year":"2018","unstructured":"Wassink, G. et al. A working model for hypothermic neuroprotection. J. Physiol. 596, 5641\u20135654 (2018).","journal-title":"J. Physiol."},{"key":"3332_CR18","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-46505-0","volume":"9","author":"V Draghi","year":"2019","unstructured":"Draghi, V. et al. Differential effects of slow rewarming after cerebral hypothermia on white matter recovery after global cerebral ischemia in near-term fetal sheep. Sci. Rep. 9, 10142 (2019).","journal-title":"Sci. Rep."},{"key":"3332_CR19","doi-asserted-by":"crossref","unstructured":"Davidson, J. O. et al. Limited benefit of slow rewarming after cerebral hypothermia for global cerebral ischemia in near-term fetal sheep. J. Cereb. Blood Flow. Metab. 39, 2246\u20132257 (2019).","DOI":"10.1177\/0271678X18791631"},{"key":"3332_CR20","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.neuroscience.2015.12.046","volume":"316","author":"B Wang","year":"2016","unstructured":"Wang, B. et al. White matter apoptosis is increased by delayed hypothermia and rewarming in a neonatal piglet model of hypoxic ischemic encephalopathy. Neuroscience 316, 296\u2013310 (2016).","journal-title":"Neuroscience"},{"key":"3332_CR21","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1038\/s41390-019-0475-8","volume":"88","author":"KQ Zhou","year":"2020","unstructured":"Zhou, K. Q. et al. Protection of axonal integrity with 48 or 72 H of cerebral hypothermia in near-term fetal sheep. Pediatr. Res 88, 48\u201356 (2020).","journal-title":"Pediatr. Res"},{"key":"3332_CR22","doi-asserted-by":"crossref","unstructured":"Yang, P. et al. Therapeutic hypothermia attenuates cortical interneuron loss after cerebral ischemia in near-term fetal sheep. Int. J. Mol. Sci. 24, 3706 (2023).","DOI":"10.3390\/ijms24043706"},{"key":"3332_CR23","doi-asserted-by":"publisher","first-page":"3793","DOI":"10.1113\/JP280389","volume":"598","author":"N Percie du Sert","year":"2020","unstructured":"Percie du Sert, N. et al. The arrive guidelines 2.0: updated guidelines for reporting animal research. J. Physiol. 598, 3793\u20133801 (2020).","journal-title":"J. Physiol."},{"key":"3332_CR24","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1542\/peds.102.5.1098","volume":"102","author":"AJ Gunn","year":"1998","unstructured":"Gunn, A. J., Gunn, T. R., Gunning, M. I., Williams, C. E. & Gluckman, P. D. Neuroprotection with prolonged head cooling started before postischemic seizures in fetal sheep. Pediatrics 102, 1098\u20131106 (1998).","journal-title":"Pediatrics"},{"key":"3332_CR25","doi-asserted-by":"publisher","DOI":"10.1038\/srep25178","volume":"6","author":"JO Davidson","year":"2016","unstructured":"Davidson, J. O. et al. Extending the duration of hypothermia does not further improve white matter protection after ischemia in term-equivalent fetal sheep. Sci. Rep. 6, 25178 (2016).","journal-title":"Sci. Rep."},{"key":"3332_CR26","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcab172","volume":"3","author":"G Wassink","year":"2021","unstructured":"Wassink, G. et al. Recombinant erythropoietin does not augment hypothermic white matter protection after global cerebral ischaemia in near-term fetal sheep. Brain Commun. 3, fcab172 (2021).","journal-title":"Brain Commun."},{"key":"3332_CR27","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1097\/01.WCB.0000123904.17746.92","volume":"24","author":"V Roelfsema","year":"2004","unstructured":"Roelfsema, V. et al. Window of opportunity of cerebral hypothermia for postischemic white matter injury in the near-term fetal sheep. J. Cereb. Blood Flow. Metab. 24, 877\u2013886 (2004).","journal-title":"J. Cereb. Blood Flow. Metab."},{"key":"3332_CR28","doi-asserted-by":"publisher","first-page":"2052","DOI":"10.1038\/jcbfm.2015.171","volume":"35","author":"JO Davidson","year":"2015","unstructured":"Davidson, J. O. et al. Non-additive effects of delayed connexin hemichannel blockade and hypothermia after cerebral ischemia in near-term fetal sheep. J. Cereb. Blood Flow. Metab. 35, 2052\u20132061 (2015).","journal-title":"J. Cereb. Blood Flow. Metab."},{"key":"3332_CR29","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1097\/01.WCB.0000123904.17746.92","volume":"24","author":"V Roelfsema","year":"2004","unstructured":"Roelfsema, V. et al. The window of opportunity for cerebral hypothermia and white matter injury after cerebral ischemia in near-term fetal sheep. J. Cereb. Blood Flow. Metab. 24, 877\u2013886 (2004).","journal-title":"J. Cereb. Blood Flow. Metab."},{"key":"3332_CR30","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.neulet.2013.10.046","volume":"565","author":"J Romero","year":"2014","unstructured":"Romero, J. et al. Dual role of astrocytes in perinatal asphyxia injury and neuroprotection. Neurosci. Lett. 565, 42\u201346 (2014).","journal-title":"Neurosci. Lett."},{"key":"3332_CR31","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1016\/j.brainres.2010.01.010","volume":"1319","author":"SM Sullivan","year":"2010","unstructured":"Sullivan, S. M., Bjorkman, S. T., Miller, S. M., Colditz, P. B. & Pow, D. V. Morphological changes in white matter astrocytes in response to hypoxia\/ischemia in the neonatal pig. Brain Res. 1319, 164\u2013174 (2010).","journal-title":"Brain Res."},{"key":"3332_CR32","doi-asserted-by":"publisher","first-page":"1574","DOI":"10.1056\/NEJMcps050929","volume":"353","author":"S Shankaran","year":"2005","unstructured":"Shankaran, S. et al. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N. Engl. J. Med. 353, 1574\u20131584 (2005).","journal-title":"N. Engl. J. Med."},{"key":"3332_CR33","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1056\/NEJMoa0900854","volume":"361","author":"DV Azzopardi","year":"2009","unstructured":"Azzopardi, D. V. et al. Moderate hypothermia to treat perinatal asphyxial encephalopathy. N. Engl. J. Med. 361, 1349\u20131358 (2009).","journal-title":"N. Engl. J. Med."},{"key":"3332_CR34","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1016\/S0140-6736(05)17946-X","volume":"365","author":"PD Gluckman","year":"2005","unstructured":"Gluckman, P. D. et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet 365, 663\u2013670 (2005).","journal-title":"Lancet"},{"key":"3332_CR35","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1542\/peds.106.1.92","volume":"106","author":"M Thoresen","year":"2000","unstructured":"Thoresen, M. & Whitelaw, A. Cardiovascular changes during mild therapeutic hypothermia and rewarming in infants with hypoxic-ischaemic encephalopathy. Pediatrics 106, 92\u201399 (2000).","journal-title":"Pediatrics"},{"key":"3332_CR36","doi-asserted-by":"publisher","first-page":"1369","DOI":"10.1542\/peds.2004-1695","volume":"114","author":"M Battin","year":"2004","unstructured":"Battin, M., Bennet, L. & Gunn, A. J. Rebound seizures during rewarming. Pediatrics 114, 1369 (2004).","journal-title":"Pediatrics"},{"key":"3332_CR37","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1007\/s00234-010-0674-9","volume":"52","author":"LS de Vries","year":"2010","unstructured":"de Vries, L. S. & Groenendaal, F. Patterns of neonatal hypoxic-ischaemic brain injury. Neuroradiology 52, 555\u2013566 (2010).","journal-title":"Neuroradiology"},{"key":"3332_CR38","doi-asserted-by":"publisher","first-page":"1484","DOI":"10.1001\/jamaneurol.2021.3723","volume":"78","author":"LF Chalak","year":"2021","unstructured":"Chalak, L. F. et al. Association between increased seizures during rewarming after hypothermia for neonatal hypoxic ischemic encephalopathy and abnormal neurodevelopmental outcomes at 2-year follow-up: a nested multisite cohort study. JAMA Neurol. 78, 1484\u20131493 (2021).","journal-title":"JAMA Neurol."},{"key":"3332_CR39","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1016\/j.pediatrneurol.2024.01.023","volume":"153","author":"JF Langeslag","year":"2024","unstructured":"Langeslag, J. F. et al. Association between seizures and neurodevelopmental outcome at two and five years in asphyxiated newborns with therapeutic hypothermia. Pediatr. Neurol. 153, 152\u2013158 (2024).","journal-title":"Pediatr. Neurol."}],"container-title":["Pediatric Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41390-024-03332-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41390-024-03332-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41390-024-03332-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T12:35:16Z","timestamp":1747226116000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41390-024-03332-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,5]]},"references-count":39,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["3332"],"URL":"https:\/\/doi.org\/10.1038\/s41390-024-03332-y","relation":{},"ISSN":["0031-3998","1530-0447"],"issn-type":[{"value":"0031-3998","type":"print"},{"value":"1530-0447","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,5]]},"assertion":[{"value":"10 January 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 April 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 May 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 August 2024","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"}}]}}