{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T18:38:06Z","timestamp":1774895886233,"version":"3.50.1"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,9,22]],"date-time":"2020-09-22T00:00:00Z","timestamp":1600732800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2020,9,22]],"date-time":"2020-09-22T00:00:00Z","timestamp":1600732800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81570081"],"award-info":[{"award-number":["81570081"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81770083"],"award-info":[{"award-number":["81770083"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The National Key Research and Development Program of China","award":["2018YFC1313600"],"award-info":[{"award-number":["2018YFC1313600"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Psychopharmacology"],"published-print":{"date-parts":[[2021,1]]},"DOI":"10.1007\/s00213-020-05663-0","type":"journal-article","created":{"date-parts":[[2020,9,22]],"date-time":"2020-09-22T21:51:03Z","timestamp":1600811463000},"page":"121-131","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Impact of histaminergic H3 receptor antagonist on hypoglossal nucleus in chronic intermittent hypoxia conditions"],"prefix":"10.1007","volume":"238","author":[{"given":"Liang","family":"Xie","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qinhan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiping","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xu","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guiling","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shengyu","family":"Hao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8096-9780","authenticated-orcid":false,"given":"Shanqun","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,9,22]]},"reference":[{"key":"5663_CR1","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.nlm.2010.10.008","volume":"95","author":"ME Bardgett","year":"2011","unstructured":"Bardgett ME, Davis NN, Schultheis PJ, Griffith MS (2011) Ciproxifan, an H3 receptor antagonist, alleviates hyperactivity and cognitive deficits in the APP Tg2576 mouse model of Alzheimer\u2019s disease. Neurobiol Learn Mem 95:64\u201372. https:\/\/doi.org\/10.1016\/j.nlm.2010.10.008","journal-title":"Neurobiol Learn Mem"},{"key":"5663_CR2","doi-asserted-by":"publisher","first-page":"1313","DOI":"10.1093\/sleep\/32.10.1313","volume":"32","author":"T Bastedo","year":"2009","unstructured":"Bastedo T, Chan E, Park E, Liu H, Horner RL (2009) Modulation of genioglossus muscle activity across sleep-wake states by histamine at the hypoglossal motor pool. Sleep 32:1313\u20131324. https:\/\/doi.org\/10.1093\/sleep\/32.10.1313","journal-title":"Sleep"},{"key":"5663_CR3","doi-asserted-by":"publisher","first-page":"2919","DOI":"10.1101\/gad.841400","volume":"14","author":"M Bibel","year":"2000","unstructured":"Bibel M, Barde YA (2000) Neurotrophins: key regulators of cell fate and cell shape in the vertebrate nervous system. Genes Dev 14:2919\u20132937. https:\/\/doi.org\/10.1101\/gad.841400","journal-title":"Genes Dev"},{"key":"5663_CR4","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1002\/cne.902960402","volume":"296","author":"E Bullitt","year":"1990","unstructured":"Bullitt E (1990) Expression of c-fos-like protein as a marker for neuronal activity following noxious stimulation in the rat. J Comp Neurol 296:517\u2013530. https:\/\/doi.org\/10.1002\/cne.902960402","journal-title":"J Comp Neurol"},{"key":"5663_CR5","first-page":"234","volume":"49","author":"AA Chiang","year":"2006","unstructured":"Chiang AA (2006) Obstructive sleep apnea and chronic intermittent hypoxia: a review. Chin J Phys 49:234\u2013243","journal-title":"Chin J Phys"},{"key":"5663_CR6","doi-asserted-by":"publisher","first-page":"1492","DOI":"10.1183\/09031936.00141511","volume":"39","author":"R Del Rio","year":"2012","unstructured":"Del Rio R, Moya EA, Parga MJ, Madrid C, Iturriaga R (2012) Carotid body inflammation and cardiorespiratory alterations in intermittent hypoxia. Eur Respir J 39:1492\u20131500. https:\/\/doi.org\/10.1183\/09031936.00141511","journal-title":"Eur Respir J"},{"key":"5663_CR7","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1152\/physrev.00043.2008","volume":"90","author":"JA Dempsey","year":"2010","unstructured":"Dempsey JA, Veasey SC, Morgan BJ, O\u2019Donnell CP (2010) Pathophysiology of sleep apnea. Physiol Rev 90:47\u2013112. https:\/\/doi.org\/10.1152\/physrev.00043.2008","journal-title":"Physiol Rev"},{"key":"5663_CR8","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1007\/s00424-002-0904-z","volume":"445","author":"M Dutschmann","year":"2003","unstructured":"Dutschmann M, Bischoff AM, Busselberg D, Richter DW (2003) Histaminergic modulation of the intact respiratory network of adult mice. Pflugers Arch 445:570\u2013576. https:\/\/doi.org\/10.1007\/s00424-002-0904-z","journal-title":"Pflugers Arch"},{"key":"5663_CR9","doi-asserted-by":"publisher","unstructured":"Eastwood PR et al (2019) Bilateral hypoglossal nerve stimulation for treatment of adult obstructive sleep apnea. Eur Respir J. https:\/\/doi.org\/10.1183\/13993003.01320-2019","DOI":"10.1183\/13993003.01320-2019"},{"key":"5663_CR10","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1124\/jpet.104.078303","volume":"313","author":"TA Esbenshade","year":"2005","unstructured":"Esbenshade TA, Fox GB, Krueger KM, Miller TR, Kang CH, Denny LI, Witte DG, Yao BB, Pan L, Wetter J, Marsh K, Bennani YL, Cowart MD, Sullivan JP, Hancock AA (2005) Pharmacological properties of ABT-239 [4-(2-{2-[(2R)-2-methylpyrrolidinyl]ethyl}-benzofuran-5-yl)benzonitrile]: I. Potent and selective histamine H3 receptor antagonist with drug-like properties. J Pharmacol Exp Ther 313:165\u2013175. https:\/\/doi.org\/10.1124\/jpet.104.078303","journal-title":"J Pharmacol Exp Ther"},{"key":"5663_CR11","doi-asserted-by":"publisher","first-page":"2025","DOI":"10.1164\/ajrccm.164.11.2102048","volume":"164","author":"RB Fogel","year":"2001","unstructured":"Fogel RB, Malhotra A, Pillar G, Edwards JK, Beauregard J, Shea SA, White DP (2001) Genioglossal activation in patients with obstructive sleep apnea versus control subjects. Mechanisms of muscle control. Am J Respir Crit Care Med 164:2025\u20132030. https:\/\/doi.org\/10.1164\/ajrccm.164.11.2102048","journal-title":"Am J Respir Crit Care Med"},{"key":"5663_CR12","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1113\/jphysiol.2005.083659","volume":"564","author":"RB Fogel","year":"2005","unstructured":"Fogel RB et al (2005) The effect of sleep onset on upper airway muscle activity in patients with sleep apnoea versus controls. J Physiol 564:549\u2013562. https:\/\/doi.org\/10.1113\/jphysiol.2005.083659","journal-title":"J Physiol"},{"key":"5663_CR13","doi-asserted-by":"publisher","first-page":"2538","DOI":"10.1152\/jn.1994.72.5.2538","volume":"72","author":"GD Funk","year":"1994","unstructured":"Funk GD, Smith JC, Feldman JL (1994) Development of thyrotropin-releasing hormone and norepinephrine potentiation of inspiratory-related hypoglossal motoneuron discharge in neonatal and juvenile mice in vitro. J Neurophysiol 72:2538\u20132541. https:\/\/doi.org\/10.1152\/jn.1994.72.5.2538","journal-title":"J Neurophysiol"},{"key":"5663_CR14","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1016\/s0006-8993(98)01222-0","volume":"816","author":"HE Greenberg","year":"1999","unstructured":"Greenberg HE, Sica AL, Scharf SM, Ruggiero DA (1999) Expression of c-fos in the rat brainstem after chronic intermittent hypoxia. Brain Res 816:638\u2013645. https:\/\/doi.org\/10.1016\/s0006-8993(98)01222-0","journal-title":"Brain Res"},{"key":"5663_CR15","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1038\/nrn1034","volume":"4","author":"H Haas","year":"2003","unstructured":"Haas H, Panula P (2003) The role of histamine and the tuberomamillary nucleus in the nervous system. Nat Rev Neurosci 4:121\u2013130. https:\/\/doi.org\/10.1038\/nrn1034","journal-title":"Nat Rev Neurosci"},{"key":"5663_CR16","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.resp.2008.06.012","volume":"164","author":"RL Horner","year":"2008","unstructured":"Horner RL (2008) Neuromodulation of hypoglossal motoneurons during sleep. Respir Physiol Neurobiol 164:179\u2013196. https:\/\/doi.org\/10.1016\/j.resp.2008.06.012","journal-title":"Respir Physiol Neurobiol"},{"key":"5663_CR17","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1124\/jpet.110.171264","volume":"336","author":"LB Hough","year":"2011","unstructured":"Hough LB, Rice FL (2011) H3 receptors and pain modulation: peripheral, spinal, and brain interactions. J Pharmacol Exp Ther 336:30\u201337. https:\/\/doi.org\/10.1124\/jpet.110.171264","journal-title":"J Pharmacol Exp Ther"},{"key":"5663_CR18","doi-asserted-by":"publisher","first-page":"4687","DOI":"10.1073\/pnas.0600451103","volume":"103","author":"ZL Huang","year":"2006","unstructured":"Huang ZL, Mochizuki T, Qu WM, Hong ZY, Watanabe T, Urade Y, Hayaishi O (2006) Altered sleep-wake characteristics and lack of arousal response to H3 receptor antagonist in histamine H1 receptor knockout mice. Proc Natl Acad Sci U S A 103:4687\u20134692. https:\/\/doi.org\/10.1073\/pnas.0600451103","journal-title":"Proc Natl Acad Sci U S A"},{"key":"5663_CR19","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.neuropharm.2015.09.025","volume":"106","author":"RL Hudkins","year":"2016","unstructured":"Hudkins RL et al (2016) 3-(1\u2032-Cyclobutylspiro[4H-1,3-benzodioxine-2,4\u2032-piperidine]-6-yl)-5,5-dimethyl-1,4 -dihydropyridazin-6-one (CEP-32215), a new wake-promoting histamine H3 antagonist\/inverse agonist. Neuropharmacology 106:37\u201345. https:\/\/doi.org\/10.1016\/j.neuropharm.2015.09.025","journal-title":"Neuropharmacology"},{"key":"5663_CR20","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1002\/cne.902730302","volume":"273","author":"N Inagaki","year":"1988","unstructured":"Inagaki N, Yamatodani A, Ando-Yamamoto M, Tohyama M, Watanabe T, Wada H (1988) Organization of histaminergic fibers in the rat brain. J Comp Neurol 273:283\u2013300. https:\/\/doi.org\/10.1002\/cne.902730302","journal-title":"J Comp Neurol"},{"key":"5663_CR21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.resp.2007.07.009","volume":"160","author":"AS Jordan","year":"2008","unstructured":"Jordan AS, White DP (2008) Pharyngeal motor control and the pathogenesis of obstructive sleep apnea. Respir Physiol Neurobiol 160:1\u20137. https:\/\/doi.org\/10.1016\/j.resp.2007.07.009","journal-title":"Respir Physiol Neurobiol"},{"key":"5663_CR22","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1152\/physiologyonline.1998.13.2.91","volume":"13","author":"L Kubin","year":"1998","unstructured":"Kubin L, Davies RO, Pack AI (1998) Control of upper airway motoneurons during REM sleep. News Physiol Sci 13:91\u201397. https:\/\/doi.org\/10.1152\/physiologyonline.1998.13.2.91","journal-title":"News Physiol Sci"},{"key":"5663_CR23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.brainres.2003.10.033","volume":"1001","author":"T Ladewig","year":"2004","unstructured":"Ladewig T, Lalley PM, Keller BU (2004) Serotonergic modulation of intracellular calcium dynamics in neonatal hypoglossal motoneurons from mouse. Brain Res 1001:1\u201312. https:\/\/doi.org\/10.1016\/j.brainres.2003.10.033","journal-title":"Brain Res"},{"key":"5663_CR24","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1016\/j.stemcr.2019.01.004","volume":"12","author":"R Liao","year":"2019","unstructured":"Liao R et al (2019) Histamine H1 receptors in neural stem cells are required for the promotion of neurogenesis conferred by H3 receptor antagonism following traumatic brain injury. Stem Cell Rep 12:532\u2013544. https:\/\/doi.org\/10.1016\/j.stemcr.2019.01.004","journal-title":"Stem Cell Rep"},{"key":"5663_CR25","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1111\/jnc.13548","volume":"137","author":"ZL Liu","year":"2016","unstructured":"Liu ZL, Wu X, Luo YJ, Wang L, Qu WM, Li SQ, Huang ZL (2016) Signaling mechanism underlying the histamine-modulated action of hypoglossal motoneurons. J Neurochem 137:277\u2013286. https:\/\/doi.org\/10.1111\/jnc.13548","journal-title":"J Neurochem"},{"key":"5663_CR26","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1111\/cns.12675","volume":"23","author":"T Luo","year":"2017","unstructured":"Luo T, Wang Y, Qin J, Liu ZG, Liu M (2017) Histamine H3 receptor antagonist prevents memory deficits and synaptic plasticity disruption following isoflurane exposure. CNS Neurosci Ther 23:301\u2013309. https:\/\/doi.org\/10.1111\/cns.12675","journal-title":"CNS Neurosci Ther"},{"key":"5663_CR27","doi-asserted-by":"publisher","first-page":"1880","DOI":"10.1164\/ajrccm.153.6.8665050","volume":"153","author":"WS Mezzanotte","year":"1996","unstructured":"Mezzanotte WS, Tangel DJ, White DP (1996) Influence of sleep onset on upper-airway muscle activity in apnea patients versus normal controls. Am J Respir Crit Care Med 153:1880\u20131887. https:\/\/doi.org\/10.1164\/ajrccm.153.6.8665050","journal-title":"Am J Respir Crit Care Med"},{"key":"5663_CR28","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1093\/sleep\/28.6.754","volume":"28","author":"E Mignot","year":"2005","unstructured":"Mignot E, Nishino S (2005) Emerging therapies in narcolepsy-cataplexy. Sleep 28:754\u2013763. https:\/\/doi.org\/10.1093\/sleep\/28.6.754","journal-title":"Sleep"},{"key":"5663_CR29","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1111\/j.1365-2869.2008.00708.x","volume":"18","author":"PC Neuzeret","year":"2009","unstructured":"Neuzeret PC et al (2009) Application of histamine or serotonin to the hypoglossal nucleus increases genioglossus muscle activity across the wake-sleep cycle. J Sleep Res 18:113\u2013121. https:\/\/doi.org\/10.1111\/j.1365-2869.2008.00708.x","journal-title":"J Sleep Res"},{"key":"5663_CR30","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1124\/mol.59.3.427","volume":"59","author":"T Nguyen","year":"2001","unstructured":"Nguyen T et al (2001) Discovery of a novel member of the histamine receptor family. Mol Pharmacol 59:427\u2013433. https:\/\/doi.org\/10.1124\/mol.59.3.427","journal-title":"Mol Pharmacol"},{"key":"5663_CR31","volume-title":"The mouse brain in stereotaxic coordinates","author":"G Paxinos","year":"2001","unstructured":"Paxinos G, Franklin KBJ, Franklin KBJ (2001) The mouse brain in stereotaxic coordinates, 2nd edn. Academic, San Diego","edition":"2"},{"key":"5663_CR32","doi-asserted-by":"publisher","first-page":"1321","DOI":"10.1164\/rccm.200912-1884OC","volume":"182","author":"I Rukhadze","year":"2010","unstructured":"Rukhadze I, Fenik VB, Benincasa KE, Price A, Kubin L (2010) Chronic intermittent hypoxia alters density of aminergic terminals and receptors in the hypoglossal motor nucleus. Am J Respir Crit Care Med 182:1321\u20131329. https:\/\/doi.org\/10.1164\/rccm.200912-1884OC","journal-title":"Am J Respir Crit Care Med"},{"key":"5663_CR33","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1186\/1465-9921-10-74","volume":"10","author":"F Series","year":"2009","unstructured":"Series F, Wang W, Similowski T (2009) Corticomotor control of the genioglossus in awake OSAS patients: a transcranial magnetic stimulation study. Respir Res 10:74. https:\/\/doi.org\/10.1186\/1465-9921-10-74","journal-title":"Respir Res"},{"key":"5663_CR34","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/s0034-5687(00)00126-2","volume":"121","author":"AL Sica","year":"2000","unstructured":"Sica AL, Greenberg HE, Ruggiero DA, Scharf SM (2000) Chronic-intermittent hypoxia: a model of sympathetic activation in the rat. Respir Physiol 121:173\u2013184. https:\/\/doi.org\/10.1016\/s0034-5687(00)00126-2","journal-title":"Respir Physiol"},{"key":"5663_CR35","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1517\/14728214.2015.1115480","volume":"20","author":"SS Sullivan","year":"2015","unstructured":"Sullivan SS, Guilleminault C (2015) Emerging drugs for common conditions of sleepiness: obstructive sleep apnea and narcolepsy. Expert Opin Emerg Drugs 20:571\u2013582. https:\/\/doi.org\/10.1517\/14728214.2015.1115480","journal-title":"Expert Opin Emerg Drugs"},{"key":"5663_CR36","doi-asserted-by":"publisher","first-page":"1583","DOI":"10.3389\/fphar.2019.01583","volume":"10","author":"N Wang","year":"2019","unstructured":"Wang N, Ma J, Liu J, Wang J, Liu C, Wang H, Liu Y, Yan H, Jiang S (2019) Histamine H3 receptor antagonist enhances neurogenesis and improves chronic cerebral hypoperfusion-induced cognitive impairments. Front Pharmacol 10:1583. https:\/\/doi.org\/10.3389\/fphar.2019.01583","journal-title":"Front Pharmacol"},{"key":"5663_CR37","first-page":"546","volume":"9","author":"X Wu","year":"2017","unstructured":"Wu X et al (2017) Chronic intermittent hypoxia affects endogenous serotonergic inputs and expression of synaptic proteins in rat hypoglossal nucleus. Am J Transl Res 9:546\u2013557","journal-title":"Am J Transl Res"},{"key":"5663_CR38","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1038\/aps.2011.184","volume":"33","author":"H Xie","year":"2012","unstructured":"Xie H, Yung WH (2012) Chronic intermittent hypoxia-induced deficits in synaptic plasticity and neurocognitive functions: a role for brain-derived neurotrophic factor. Acta Pharmacol Sin 33:5\u201310. https:\/\/doi.org\/10.1038\/aps.2011.184","journal-title":"Acta Pharmacol Sin"}],"container-title":["Psychopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00213-020-05663-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00213-020-05663-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00213-020-05663-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,22]],"date-time":"2021-09-22T00:18:17Z","timestamp":1632269897000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00213-020-05663-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,22]]},"references-count":38,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["5663"],"URL":"https:\/\/doi.org\/10.1007\/s00213-020-05663-0","relation":{},"ISSN":["0033-3158","1432-2072"],"issn-type":[{"value":"0033-3158","type":"print"},{"value":"1432-2072","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,22]]},"assertion":[{"value":"1 June 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 September 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 September 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This experiment was conducted according to the guidelines implemented by the National Institutes of Health Guide for the Care and the Use of Laboratory Animals, approved by the Medical Experimental Animal Administrative Committee of the Shanghai Medical College of Fudan University. All effects were made to minimize animal suffering.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}