{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T18:45:20Z","timestamp":1789497920112,"version":"build-2803163510"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,7,7]],"date-time":"2021-07-07T00:00:00Z","timestamp":1625616000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,7,7]],"date-time":"2021-07-07T00:00:00Z","timestamp":1625616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["FA4600-12-D-9000"],"award-info":[{"award-number":["FA4600-12-D-9000"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Respir Res"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Acute respiratory distress syndrome (ARDS) is multifactorial and can result from sepsis, trauma, or pneumonia, amongst other primary pathologies. It is one of the major causes of death in critically ill patients with a reported mortality rate up to 45%. The present study focuses on the development of a large animal model of smoke inhalation-induced ARDS in an effort to provide the scientific community with a reliable, reproducible large animal model of isolated toxic inhalation injury-induced ARDS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Animals (n\u2009=\u200921) were exposed to smoke under general anesthesia for 1 to 2\u00a0h (median smoke exposure\u2009=\u20090.5 to 1 L of oak wood smoke) after the ultrasound-guided placement of carotid, pulmonary, and femoral artery catheters. Peripheral oxygen saturation (SpO\n                      <jats:sub>2<\/jats:sub>\n                      ), vital signs, and ventilator parameters were monitored throughout the procedure. Chest x-ray, carotid, femoral and pulmonary artery blood samples were collected before, during, and after smoke exposure. Animals were euthanized and lung tissue collected for analysis 48\u00a0h after smoke inhalation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Animals developed ARDS 48\u00a0h after smoke inhalation as reflected by a decrease in SpO\n                      <jats:sub>2<\/jats:sub>\n                      by approximately 31%, PaO\n                      <jats:sub>2<\/jats:sub>\n                      \/FiO\n                      <jats:sub>2<\/jats:sub>\n                      ratio by approximately 208 (50%), and development of bilateral, diffuse infiltrates on chest x-ray. Study animals also demonstrated a significant increase in IL-6 level, lung tissue injury score and wet\/dry ratio, as well as changes in other arterial blood gas (ABG) parameters.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study reports, for the first time, a novel large animal model of isolated smoke inhalation-induced ARDS without confounding variables such as cutaneous burn injury. Use of this unique model may be of benefit in studying the pathophysiology of inhalation injury or for development of novel therapeutics.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12931-021-01788-8","type":"journal-article","created":{"date-parts":[[2021,7,7]],"date-time":"2021-07-07T03:03:14Z","timestamp":1625626994000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["A novel large animal model of smoke inhalation-induced acute respiratory distress syndrome"],"prefix":"10.1186","volume":"22","author":[{"given":"Premila D.","family":"Leiphrakpam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah R.","family":"Weber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"McCain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roser Romaguera","family":"Matas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernesto Martinez","family":"Duarte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8461-1938","authenticated-orcid":false,"given":"Keely L.","family":"Buesing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,7]]},"reference":[{"issue":"1","key":"1788_CR1","doi-asserted-by":"publisher","first-page":"113","DOI":"10.4187\/respcare.04716","volume":"62","author":"J M\u00e1ca","year":"2017","unstructured":"M\u00e1ca J, Jor O, Holub M, Sklienka P, Bur\u0161a F, Burda M, et al. Past and present ARDS mortality rates: a systematic review. Respir Care. 2017;62(1):113\u201322.","journal-title":"Respir Care"},{"issue":"3","key":"1788_CR2","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1164\/rccm.200805-722OC","volume":"179","author":"J Phua","year":"2009","unstructured":"Phua J, Badia JR, Adhikari NKJ, Friedrich JO, Fowler RA, Singh JM, et al. Has mortality from acute respiratory distress syndrome decreased over time? Am J Respir Crit Care Med. 2009;179(3):220\u20137.","journal-title":"Am J Respir Crit Care Med"},{"key":"1788_CR3","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1186\/1757-7241-20-54","volume":"20","author":"M Bakowitz","year":"2012","unstructured":"Bakowitz M, Bruns B, McCunn M. Acute lung injury and the acute respiratory distress syndrome in the injured patient. Scand J Trauma Resuscit Emerg Med. 2012;20:54\u201354.","journal-title":"Scand J Trauma Resuscit Emerg Med"},{"issue":"2","key":"1788_CR4","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1042\/CS20040135","volume":"107","author":"P Enkhbaatar","year":"2004","unstructured":"Enkhbaatar P, Traber DL. Pathophysiology of acute lung injury in combined burn and smoke inhalation injury. Clin Sci. 2004;107(2):137\u201343.","journal-title":"Clin Sci"},{"issue":"1","key":"1788_CR5","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1097\/00000658-198701000-00015","volume":"205","author":"KZ Shirani","year":"1987","unstructured":"Shirani KZ, Pruitt BAJ, Mason ADJ. The influence of inhalation injury and pneumonia on burn mortality. Ann Surg. 1987;205(1):82\u20137.","journal-title":"Ann Surg"},{"issue":"7511","key":"1788_CR6","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/S0140-6736(67)90168-7","volume":"290","author":"D Ashbaugh","year":"1967","unstructured":"Ashbaugh D, Boyd Bigelow D, Petty T, Levine B. Acute respiratory distress in adults. Lancet. 1967;290(7511):319\u201323.","journal-title":"Lancet"},{"issue":"23","key":"1788_CR7","first-page":"2526","volume":"307","author":"TADT Force","year":"2012","unstructured":"Force TADT. Acute respiratory distress syndrome: the berlin definition. JAMA. 2012;307(23):2526\u201333.","journal-title":"JAMA."},{"key":"1788_CR8","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1146\/annurev-pathol-011110-130158","volume":"6","author":"MA Matthay","year":"2011","unstructured":"Matthay MA, Zemans RL. The acute respiratory distress syndrome: pathogenesis and treatment. Annu Rev Pathol. 2011;6:147\u201363.","journal-title":"Annu Rev Pathol"},{"issue":"7","key":"1788_CR9","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1056\/NEJM196702162760702","volume":"276","author":"G Nash","year":"1967","unstructured":"Nash G, Blennerhassett JB, Pontoppidan H. Pulmonary lesions associated with oxygen therapy and artificial ventilation. N Engl J Med. 1967;276(7):368\u201374.","journal-title":"N Engl J Med"},{"issue":"5","key":"1788_CR10","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1016\/S2213-2600(13)70053-5","volume":"1","author":"AW Thille","year":"2013","unstructured":"Thille AW, Esteban A, Fern\u00e1ndez-Segoviano P, Rodriguez J-M, Aramburu J-A, Vargas-Err\u00e1zuriz P, et al. Chronology of histological lesions in acute respiratory distress syndrome with diffuse alveolar damage: a prospective cohort study of clinical autopsies. Lancet Respir Med. 2013;1(5):395\u2013401.","journal-title":"Lancet Respir Med"},{"issue":"5","key":"1788_CR11","doi-asserted-by":"publisher","first-page":"1162","DOI":"10.1183\/09031936.00093911","volume":"39","author":"BV Patel","year":"2012","unstructured":"Patel BV, Wilson MR, Takata M. Resolution of acute lung injury and inflammation: a translational mouse model. Eur Respir J. 2012;39(5):1162\u201370.","journal-title":"Eur Respir J"},{"issue":"10","key":"1788_CR12","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1111\/1440-1681.12283","volume":"41","author":"MT Voelker","year":"2014","unstructured":"Voelker MT, Fichtner F, Kasper M, Kamprad M, Sack U, Kaisers UX, et al. Characterization of a double-hit murine model of acute respiratory distress syndrome. Clin Exp Pharmacol Physiol. 2014;41(10):844\u201353.","journal-title":"Clin Exp Pharmacol Physiol"},{"issue":"8","key":"1788_CR13","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1001\/jama.1961.63040080006011","volume":"175","author":"RF McLaughlin Jr","year":"1961","unstructured":"McLaughlin RF Jr, Tyler WS, Canada RO. Subgross pulmonary anatomy in various mammals and man. JAMA. 1961;175(8):694\u20137.","journal-title":"JAMA"},{"issue":"3","key":"1788_CR14","doi-asserted-by":"publisher","first-page":"1281","DOI":"10.1152\/japplphysiol.00632.2006","volume":"102","author":"RW Glenny","year":"2007","unstructured":"Glenny RW, Bernard SL, Luchtel DL, Neradilek B, Polissar NL. The spatial-temporal redistribution of pulmonary blood flow with postnatal growth. J Appl Physiol. 2007;102(3):1281\u20138.","journal-title":"J Appl Physiol"},{"issue":"4","key":"1788_CR15","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1203\/PDR.0b013e31814625a0","volume":"62","author":"TV Brogan","year":"2007","unstructured":"Brogan TV, Mellema JD, Martin LD, Krueger M, Redding GJ, Glenny RW. Spatial and temporal heterogeneity of regional pulmonary blood flow in piglets. Pediatr Res. 2007;62(4):434\u20139.","journal-title":"Pediatr Res"},{"issue":"5","key":"1788_CR16","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1183\/09031936.01.00049201","volume":"18","author":"Y Gushima","year":"2001","unstructured":"Gushima Y, Ichikado K, Suga M, Okamoto T, Iyonaga K, Sato K, et al. Expression of matrix metalloproteinases in pigs with hyperoxia-induced acute lung injury. Eur Respir J. 2001;18(5):827\u201337.","journal-title":"Eur Respir J"},{"issue":"1","key":"1788_CR17","doi-asserted-by":"publisher","first-page":"e155","DOI":"10.1016\/j.jss.2010.05.042","volume":"164","author":"C Ballard-Croft","year":"2010","unstructured":"Ballard-Croft C, Sumpter LR, Broaddus R, Alexander J, Wang D, Zwischenberger JB. Ovine smoke\/burn ARDS model: a new ventilator-controlled smoke delivery system. J Surg Res. 2010;164(1):e155\u201362.","journal-title":"J Surg Res"},{"issue":"1","key":"1788_CR18","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.burns.2003.07.003","volume":"30","author":"RE Barrow","year":"2004","unstructured":"Barrow RE, Spies M, Barrow LN, Herndon DN. Influence of demographics and inhalation injury on burn mortality in children. Burns. 2004;30(1):72\u20137.","journal-title":"Burns"},{"issue":"11","key":"1788_CR19","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1007\/PL00003763","volume":"25","author":"DR Dancey","year":"1999","unstructured":"Dancey DR, Hayes J, Gomez M, Schouten D, Fish J, Peters W, et al. ARDS in patients with thermal injury. Intensive Care Med. 1999;25(11):1231\u20136.","journal-title":"Intensive Care Med"},{"issue":"5","key":"1788_CR20","doi-asserted-by":"publisher","first-page":"1469","DOI":"10.1097\/00003246-200005000-00036","volume":"28","author":"SK Alpard","year":"2000","unstructured":"Alpard SK, Zwischenberger JB, Tao W, Deyo DJ, Traber DL, Bidani A. New clinically relevant sheep model of severe respiratory failure secondary to combined smoke inhalation\/cutaneous flame burn injury. Crit Care Med. 2000;28(5):1469\u201376.","journal-title":"Crit Care Med"},{"issue":"3","key":"1788_CR21","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1097\/SLA.0b013e318148c6e6","volume":"246","author":"FC Schmalstieg","year":"2007","unstructured":"Schmalstieg FC, Keeney SE, Rudloff HE, Palkowetz KH, Cevallos M, Zhou X, et al. Arteriovenous CO2 removal improves survival compared to high frequency percussive and low tidal volume ventilation in a smoke\/burn sheep acute respiratory distress syndrome model. Ann Surg. 2007;246(3):512\u201323.","journal-title":"Ann Surg"},{"issue":"6","key":"1788_CR22","first-page":"L1233","volume":"280","author":"K Soejima","year":"2001","unstructured":"Soejima K, Schmalstieg FC, Sakurai H, Traber LD, Traber DL. Pathophysiological analysis of combined burn and smoke inhalation injuries in sheep. Am J Physiol. 2001;280(6):L1233\u201341.","journal-title":"Am J Physiol"},{"issue":"3","key":"1788_CR23","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1164\/ajrccm.163.3.2003065","volume":"163","author":"Y Kitamura","year":"2001","unstructured":"Kitamura Y, Hashimoto S, Mizuta N, Kobayashi A, Kooguchi K, Fujiwara I, et al. Fas\/FasL-dependent apoptosis of alveolar cells after lipopolysaccharide-induced lung injury in mice. Am J Respir Crit Care Med. 2001;163(3):762\u20139.","journal-title":"Am J Respir Crit Care Med"},{"issue":"2","key":"1788_CR24","first-page":"173","volume":"10","author":"S Katalan","year":"2017","unstructured":"Katalan S, Falach R, Rosner A, Goldvaser M, Brosh-Nissimov T, Dvir A, et al. A novel swine model of ricin-induced acute respiratory distress syndrome. Dis Model Mech. 2017;10(2):173\u201383.","journal-title":"Dis Model Mech"},{"issue":"7","key":"1788_CR25","doi-asserted-by":"publisher","first-page":"1468","DOI":"10.1016\/j.burns.2015.04.010","volume":"41","author":"Z Yilin","year":"2015","unstructured":"Yilin Z, Yandong N, Faguang J. Role of angiotensin-converting enzyme (ACE) and ACE2 in a rat model of smoke inhalation induced acute respiratory distress syndrome. Burns. 2015;41(7):1468\u201377.","journal-title":"Burns"},{"issue":"8","key":"1788_CR26","first-page":"8797","volume":"8","author":"T Wang","year":"2015","unstructured":"Wang T, Chen X, Zhang W, Xiang X, Leng C, Jia Q. Roles of macrophage stimulating protein and tyrosine kinase receptor RON in smoke-induced airway inflammation of rats. Int J Clin Exp Pathol. 2015;8(8):8797\u2013808.","journal-title":"Int J Clin Exp Pathol"},{"issue":"7","key":"1788_CR27","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1001\/jama.2017.21907","volume":"319","author":"E Fan","year":"2018","unstructured":"Fan E, Brodie D, Slutsky AS. Acute respiratory distress syndrome: advances in diagnosis and treatment. JAMA. 2018;319(7):698\u2013710.","journal-title":"JAMA"},{"issue":"2","key":"1788_CR28","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1152\/jappl.1986.60.2.433","volume":"60","author":"M Julien","year":"1986","unstructured":"Julien M, Hoeffel JM, Flick MR. Oleic acid lung injury in sheep. J Appl Physiol. 1986;60(2):433\u201340.","journal-title":"J Appl Physiol"},{"issue":"4","key":"1788_CR29","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1007\/BF01700456","volume":"22","author":"HP Grotjohan","year":"1996","unstructured":"Grotjohan HP, Van Der Heijde RMJL, Jansen JRC, Wagenvoort CA, Versprille A. A stable model of respiratory distress by small injections of oleic acid in pigs. Intensive Care Med. 1996;22(4):336\u201344.","journal-title":"Intensive Care Med"},{"key":"1788_CR30","doi-asserted-by":"crossref","unstructured":"Lewis JF, Tabor B, Ikegami M, Jobe AH, Joseph M, Absolom D. Lung function and surfactant distribution in saline-lavaged sheep given instilled vs. nebulized surfactant. Journal of Applied Physiology. 1993;74(3):1256\u20131264.","DOI":"10.1152\/jappl.1993.74.3.1256"},{"issue":"3","key":"1788_CR31","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1080\/01902140802534975","volume":"35","author":"RM Muellenbach","year":"2009","unstructured":"Muellenbach RM, Kredel M, Bernd Z, Johannes A, Kuestermann J, Schuster F, et al. Acute respiratory distress induced by repeated saline lavage provides stable experimental conditions for 24 hours in pigs. Exp Lung Res. 2009;35(3):222\u201333.","journal-title":"Exp Lung Res"},{"issue":"3","key":"1788_CR32","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/j.resp.2009.04.015","volume":"167","author":"Z Guo","year":"2009","unstructured":"Guo Z, Lu G, Ren T, Zheng Y, Gong J, Yu J, et al. Partial liquid ventilation confers protection against acute lung injury induced by endotoxin in juvenile piglets. Respir Physiol Neurobiol. 2009;167(3):221\u20136.","journal-title":"Respir Physiol Neurobiol."},{"issue":"4","key":"1788_CR33","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1097\/00024382-200204000-00010","volume":"17","author":"K Kabir","year":"2002","unstructured":"Kabir K, Gelinas J-P, Chen M, Chen D, Zhang D, Luo X, et al. Characterization of a murine model of endotoxin-induced acute lung injury. Shock. 2002;17(4):300\u20133.","journal-title":"Shock"},{"key":"1788_CR34","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.carres.2015.07.003","volume":"417","author":"A Le Floch","year":"2015","unstructured":"Le Floch A, Jourdes M, Teissedre P-L. Polysaccharides and lignin from oak wood used in cooperage: composition, interest, assays: A review. Carbohyd Res. 2015;417:94\u2013102.","journal-title":"Carbohyd Res"},{"key":"1788_CR35","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1089\/ees.2004.21.705","volume":"21","author":"P Fine","year":"2004","unstructured":"Fine P, Cass G, Simoneit B. Chemical characterization of fine particle emissions from the wood stove combustion of prevalent US tree species. Environ Eng Sci. 2004;21:705\u201321.","journal-title":"Environ Eng Sci"},{"issue":"6","key":"1788_CR36","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1097\/SHK.0b013e318292c331","volume":"39","author":"S Belenkiy","year":"2013","unstructured":"Belenkiy S, Ivey KM, Batchinsky AI, Langer T, Necsoiu C, Baker W, et al. Noninvasive carbon dioxide monitoring in a porcine model of acute lung injury due to smoke inhalation and burns. Shock. 2013;39(6):495\u2013500.","journal-title":"Shock"},{"issue":"2","key":"1788_CR37","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1136\/jim-2016-000253","volume":"65","author":"T Yousuf","year":"2017","unstructured":"Yousuf T, Brinton T, Murtaza G, Wozniczka D, Ahmad K, Iskandar J, et al. Establishing a gradient between partial pressure of arterial carbon dioxide and end-tidal carbon dioxide in patients with acute respiratory distress syndrome. J Investig Med. 2017;65(2):338\u201341.","journal-title":"J Investig Med"}],"container-title":["Respiratory Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12931-021-01788-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12931-021-01788-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12931-021-01788-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,7]],"date-time":"2021-07-07T03:03:21Z","timestamp":1625627001000},"score":1,"resource":{"primary":{"URL":"https:\/\/respiratory-research.biomedcentral.com\/articles\/10.1186\/s12931-021-01788-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,7]]},"references-count":37,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["1788"],"URL":"https:\/\/doi.org\/10.1186\/s12931-021-01788-8","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-297210\/v1","asserted-by":"object"}]},"ISSN":["1465-993X"],"issn-type":[{"value":"1465-993X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,7]]},"assertion":[{"value":"3 March 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 June 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 July 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All the experiments involving animals were approved by University of Nebraska Lincoln (UNL) Institutional Animal Care and Use Committee (IACUC) (protocol # 1674).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing or financial interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"198"}}