{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T14:00:42Z","timestamp":1792936842333,"version":"4.5.0"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T00:00:00Z","timestamp":1750809600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T00:00:00Z","timestamp":1750809600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004047","name":"Karolinska Institute","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004047","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Sepsis is associated with substantial mortality rates. Traditional treatment strategies often fail to address the underlying dysregulation in immune response, necessitating novel therapeutic approaches. Ozone (O<jats:sub>3<\/jats:sub>) is an inorganic molecule with no evident function in the body. We investigated the properties of ozone, using a system of extracorporeal ozone blood treatment in <jats:italic>Pseudomonas aeruginosa<\/jats:italic> septic shock. We hypothesized that extracorporeal ozonation would decrease bacteria in blood, have immunomodulating properties, and improve organ function. In this 4-h sepsis model swine were allocated to <jats:italic>P. aeruginosa<\/jats:italic> (PA-103, ATCC 29260, CCUG31589) infusion and ozone treatment (n\u2009=\u20097) or <jats:italic>P. aeruginosa<\/jats:italic> infusion and no ozone treatment (n\u2009=\u20096). Bacteria were infused in a peripheral vein. Mean (SD) duration of ozone treatment was 134 (67)\u00a0min. A single pass through the system decreased viable <jats:italic>P. aeruginosa<\/jats:italic> by 53%, mean 2193 to 1023 colony forming units\/mL, mean of differences -1170 (95% CI \u2212\u20091689 to \u2212\u2009651, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.0001). No difference in viable bacterial concentration was detected in peripheral venous blood between groups (<jats:italic>P<\/jats:italic>\u2009=\u20090.68). IL-1\u03b2, IL-4, IL-6, IL-8 and IFN-\u03b3 decreased by ozonation. Classical and alternative complement pathways were not affected. Blood hemoglobin, hematocrit and noradrenaline doses decreased in the treatment group. Breathing frequency and pulmonary peak airway pressure decreased in the ozone treatment group. Median survival in ozone treatment was 134\u00a0min and no treatment 159\u00a0min, with no statistical difference. Extracorporeal ozone blood treatment modulated the immune response in <jats:italic>P. aeruginosa<\/jats:italic> septic shock, which decreased mostly proinflammatory cytokines and was associated with indications of decreased vascular permeability and improved lung function and warrants further investigation for potential use in clinical settings.<\/jats:p>","DOI":"10.1038\/s41598-025-07408-5","type":"journal-article","created":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T08:42:39Z","timestamp":1750840959000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Immunomodulation by extracorporeal ozone-based bactericide system in porcine Pseudomonas aeruginosa septic shock"],"prefix":"10.1038","volume":"15","author":[{"given":"Henrik","family":"Rundgren","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Sj\u00f6holm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanja","family":"Juric","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pellina","family":"Janson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joline","family":"Kolerud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Wallin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Skorup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miklos","family":"Lipcsey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattias","family":"G\u00fcnther","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,25]]},"reference":[{"issue":"3","key":"7408_CR1","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1007\/s00134-017-4683-6","volume":"43","author":"A Rhodes","year":"2017","unstructured":"Rhodes, A. et al. Surviving sepsis campaign: International guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 43(3), 304\u2013377 (2017).","journal-title":"Intensive Care Med."},{"issue":"2","key":"7408_CR2","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1007\/s00134-009-1738-3","volume":"36","author":"MM Levy","year":"2010","unstructured":"Levy, M. M. et al. The Surviving Sepsis Campaign: Results of an international guideline-based performance improvement program targeting severe sepsis. Intensive Care Med. 36(2), 222\u2013231 (2010).","journal-title":"Intensive Care Med."},{"key":"7408_CR3","unstructured":"WorldHealthOrganization. Antimicrobial resistance: global report on surveillance: (WorldHealthOrganization, 2014)."},{"key":"7408_CR4","unstructured":"WorldHealthOrganization. Newsroom Antimicrobial resistance; 13 October 2020 https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/antimicrobial-resistance2020 [updated 2020 October 13."},{"issue":"3","key":"7408_CR5","volume":"16","author":"A Jain","year":"2024","unstructured":"Jain, A., Singam, A. & Mudiganti, V. Recent advances in immunomodulatory therapy in sepsis: A comprehensive review. Cureus 16(3), e57309 (2024).","journal-title":"Cureus"},{"issue":"1","key":"7408_CR6","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/2045-9912-1-6","volume":"1","author":"V Bocci","year":"2011","unstructured":"Bocci, V., Zanardi, I. & Travagli, V. Oxygen\/ozone as a medical gas mixture. A critical evaluation of the various methods clarifies positive and negative aspects. Med. Gas Res. 1(1), 6 (2011).","journal-title":"Med. Gas Res."},{"issue":"5647","key":"7408_CR7","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1126\/science.1089525","volume":"302","author":"P Wentworth Jr","year":"2003","unstructured":"Wentworth, P. Jr. et al. Evidence for ozone formation in human atherosclerotic arteries. Science 302(5647), 1053\u20131056 (2003).","journal-title":"Science"},{"issue":"11","key":"7408_CR8","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1056\/NEJMoa0803894","volume":"360","author":"M Jerrett","year":"2009","unstructured":"Jerrett, M. et al. Long-term ozone exposure and mortality. N. Engl. J. Med. 360(11), 1085\u20131095 (2009).","journal-title":"N. Engl. J. Med."},{"key":"7408_CR9","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1007\/978-90-481-9234-2","volume-title":"OZONE: A New Medical Drug","author":"V Bocci","year":"2011","unstructured":"Bocci, V. The clinical application of ozonetherapy. In OZONE: A New Medical Drug (ed. Bocci, V.) 97\u2013232 (Springer, 2011)."},{"issue":"11","key":"7408_CR10","doi-asserted-by":"publisher","first-page":"Br339","DOI":"10.12659\/MSM.882044","volume":"17","author":"D Bialoszewski","year":"2011","unstructured":"Bialoszewski, D. et al. Activity of ozonated water and ozone against Staphylococcus aureus and Pseudomonas aeruginosa biofilms. Med. Sci. Monit. 17(11), Br339\u2013Br344 (2011).","journal-title":"Med. Sci. Monit."},{"issue":"2","key":"7408_CR11","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1111\/1471-0307.12302","volume":"69","author":"L Varga","year":"2016","unstructured":"Varga, L. & Szigeti, J. Use of ozone in the dairy industry: A review. Int. J. Dairy Technol. 69(2), 157\u2013168 (2016).","journal-title":"Int. J. Dairy Technol."},{"issue":"5","key":"7408_CR12","doi-asserted-by":"publisher","first-page":"1715","DOI":"10.1111\/j.1365-2672.2008.04141.x","volume":"106","author":"S Burgassi","year":"2009","unstructured":"Burgassi, S., Zanardi, I., Travagli, V., Montomoli, E. & Bocci, V. How much ozone bactericidal activity is compromised by plasma components?. J. Appl. Microbiol. 106(5), 1715\u20131721 (2009).","journal-title":"J. Appl. Microbiol."},{"issue":"1","key":"7408_CR13","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/s40635-022-00443-w","volume":"10","author":"P Skorup","year":"2022","unstructured":"Skorup, P. et al. Evaluation of an extracorporeal ozone-based bactericide system for the treatment of Escherichia coli sepsis. Intensive Care Med. Exp. 10(1), 14 (2022).","journal-title":"Intensive Care Med. Exp."},{"issue":"4","key":"7408_CR14","doi-asserted-by":"publisher","first-page":"1306","DOI":"10.1128\/AAC.49.4.1306-1311.2005","volume":"49","author":"ST Micek","year":"2005","unstructured":"Micek, S. T. et al. Pseudomonas aeruginosa bloodstream infection: Importance of appropriate initial antimicrobial treatment. Antimicrob Agents Chemother. 49(4), 1306\u20131311 (2005).","journal-title":"Antimicrob Agents Chemother."},{"issue":"4","key":"7408_CR15","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1128\/CMR.00002-14","volume":"27","author":"KB Laupland","year":"2014","unstructured":"Laupland, K. B. & Church, D. L. Population-based epidemiology and microbiology of community-onset bloodstream infections. Clin. Microbiol. Rev. 27(4), 647\u2013664 (2014).","journal-title":"Clin. Microbiol. Rev."},{"issue":"2","key":"7408_CR16","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1063\/1.555680","volume":"12","author":"R Battino","year":"1983","unstructured":"Battino, R., Rettich, T. R. & Tominaga, T. The solubility of oxygen and ozone in liquids. J. Phys. Chem. Ref. Data 12(2), 163\u2013178 (1983).","journal-title":"J. Phys. Chem. Ref. Data"},{"key":"7408_CR17","doi-asserted-by":"crossref","unstructured":"Sven, B. The oxygen deficit of arterial blood caused by non-ventilating parts of the lung. Acta Physiol. Scand. 11(4) (1942).","DOI":"10.1111\/j.1365-201X.1942.tb11004.x"},{"issue":"1","key":"7408_CR18","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1097\/CCM.0000000000000555","volume":"43","author":"C Ani","year":"2015","unstructured":"Ani, C., Farshidpanah, S., Bellinghausen Stewart, A. & Nguyen, H. B. Variations in organism-specific severe sepsis mortality in the United States: 1999\u20132008. Crit Care Med. 43(1), 65\u201377 (2015).","journal-title":"Crit Care Med."},{"issue":"1","key":"7408_CR19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13054-019-2478-6","volume":"23","author":"J-L Vincent","year":"2019","unstructured":"Vincent, J.-L., Jones, G., David, S., Olariu, E. & Cadwell, K. K. Frequency and mortality of septic shock in Europe and North America: A systematic review and meta-analysis. Crit Care 23(1), 1\u201311 (2019).","journal-title":"Crit Care"},{"issue":"2","key":"7408_CR20","doi-asserted-by":"publisher","first-page":"e90441","DOI":"10.1371\/journal.pone.0090441","volume":"9","author":"P Skorup","year":"2014","unstructured":"Skorup, P. et al. Beneficial antimicrobial effect of the addition of an aminoglycoside to a \u03b2-lactam antibiotic in an E. coli porcine intensive care severe sepsis model. PLoS ONE 9(2), e90441 (2014).","journal-title":"PLoS ONE"},{"issue":"7","key":"7408_CR21","doi-asserted-by":"publisher","first-page":"e634","DOI":"10.1097\/CCM.0000000000003139","volume":"46","author":"P Skorup","year":"2018","unstructured":"Skorup, P. et al. Dynamics of endotoxin, inflammatory variables, and organ dysfunction after treatment with antibiotics in an Escherichia coli Porcine intensive care sepsis model. Crit Care Med. 46(7), e634\u2013e641 (2018).","journal-title":"Crit Care Med."},{"issue":"3","key":"7408_CR22","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1128\/CMR.3.3.269","volume":"3","author":"P Yagupsky","year":"1990","unstructured":"Yagupsky, P. & Nolte, F. S. Quantitative aspects of septicemia. Clin. Microbiol. Rev. 3(3), 269\u2013279 (1990).","journal-title":"Clin. Microbiol. Rev."},{"issue":"1","key":"7408_CR23","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1093\/cvr\/cvaa070","volume":"117","author":"EV Dolmatova","year":"2021","unstructured":"Dolmatova, E. V., Wang, K., Mandavilli, R. & Griendling, K. K. The effects of sepsis on endothelium and clinical implications. Cardiovasc. Res. 117(1), 60\u201373 (2021).","journal-title":"Cardiovasc. Res."},{"issue":"23","key":"7408_CR24","doi-asserted-by":"publisher","first-page":"6008","DOI":"10.3390\/ijms20236008","volume":"20","author":"S Kany","year":"2019","unstructured":"Kany, S., Vollrath, J. T. & Relja, B. Cytokines in inflammatory disease. Int. J. Mol. Sci. 20(23), 6008 (2019).","journal-title":"Int. J. Mol. Sci."},{"issue":"5","key":"7408_CR25","doi-asserted-by":"publisher","first-page":"2528","DOI":"10.3390\/ijms23052528","volume":"23","author":"A De Sire","year":"2022","unstructured":"De Sire, A. et al. Oxygen-ozone therapy for reducing pro-inflammatory cytokines serum levels in musculoskeletal and temporomandibular disorders: A comprehensive review. Int. J. Mol. Sci. 23(5), 2528 (2022).","journal-title":"Int. J. Mol. Sci."},{"key":"7408_CR26","doi-asserted-by":"crossref","unstructured":"Diaz-Luis, J., Menendez-Cepero, S., Diaz-Luis, A., Ascanio-Garcia, Y. In vitro effect of ozone in phagocytic function of leucocytes in peripheral blood. J. Ozone Therapy 1(1) (2015).","DOI":"10.7203\/jo3t.1.1.2015.10627"},{"issue":"1\u20132","key":"7408_CR27","doi-asserted-by":"publisher","DOI":"10.4161\/21688370.2014.974448","volume":"3","author":"A K\u00e1sa","year":"2015","unstructured":"K\u00e1sa, A., Csortos, C. & Verin, A. D. Cytoskeletal mechanisms regulating vascular endothelial barrier function in response to acute lung injury. Tissue Barriers 3(1\u20132), e974448 (2015).","journal-title":"Tissue Barriers"},{"issue":"6","key":"7408_CR28","doi-asserted-by":"publisher","first-page":"L1107","DOI":"10.1152\/ajplung.2000.278.6.L1107","volume":"278","author":"T Ferro","year":"2000","unstructured":"Ferro, T., Neumann, P., Gertzberg, N., Clements, R. & Johnson, A. Protein kinase C-alpha mediates endothelial barrier dysfunction induced by TNF-alpha. Am. J. Physiol. Lung Cell Mol. Physiol. 278(6), L1107\u2013L1117 (2000).","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"7408_CR29","doi-asserted-by":"publisher","first-page":"1289194","DOI":"10.3389\/fmed.2023.1289194","volume":"10","author":"B Sun","year":"2023","unstructured":"Sun, B. et al. Acute lung injury caused by sepsis: how does it happen?. Front Med. (Lausanne) 10, 1289194 (2023).","journal-title":"Front Med. (Lausanne)"},{"issue":"1","key":"7408_CR30","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/s44158-024-00147-5","volume":"4","author":"D Raimondi Cominesi","year":"2024","unstructured":"Raimondi Cominesi, D. et al. Pulmonary shunt in critical care: A practical approach with clinical scenarios. J. Anesth. Analg Crit Care 4(1), 18 (2024).","journal-title":"J. Anesth. Analg Crit Care"},{"issue":"1","key":"7408_CR31","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.redox.2012.12.003","volume":"1","author":"GM Hare","year":"2013","unstructured":"Hare, G. M., Tsui, A. K., Crawford, J. H. & Patel, R. P. Is methemoglobin an inert bystander, biomarker or a mediator of oxidative stress\u2013The example of anemia?. Redox Biol. 1(1), 65\u201369 (2013).","journal-title":"Redox Biol."},{"issue":"5","key":"7408_CR32","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1016\/S0891-5849(97)00351-1","volume":"24","author":"S Mendiratta","year":"1998","unstructured":"Mendiratta, S., Qu, Z. C. & May, J. M. Erythrocyte ascorbate recycling: Antioxidant effects in blood. Free Radic. Biol. Med. 24(5), 789\u2013797 (1998).","journal-title":"Free Radic. Biol. Med."},{"issue":"2","key":"7408_CR33","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1177\/1091581809360069","volume":"29","author":"V Travagli","year":"2010","unstructured":"Travagli, V. et al. Effects of ozone blood treatment on the metabolite profile of human blood. Int. J. Toxicol. 29(2), 165\u2013174 (2010).","journal-title":"Int. J. Toxicol."},{"issue":"5","key":"7408_CR34","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1016\/j.freeradbiomed.2008.11.008","volume":"46","author":"B Halliwell","year":"2009","unstructured":"Halliwell, B. The wanderings of a free radical. Free Radic. Biol. Med. 46(5), 531\u2013542 (2009).","journal-title":"Free Radic. Biol. Med."},{"issue":"1","key":"7408_CR35","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/S1383-5718(98)00155-7","volume":"438","author":"M Foksinski","year":"1999","unstructured":"Foksinski, M. et al. Evaluation of 8-oxodeoxyguanosine, typical oxidative DNA damage, in lymphocytes of ozone-treated arteriosclerotic patients. Mutat. Res. 438(1), 23\u201327 (1999).","journal-title":"Mutat. Res."},{"issue":"2","key":"7408_CR36","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/j.dci.2014.03.022","volume":"45","author":"K Mair","year":"2014","unstructured":"Mair, K. et al. The porcine innate immune system: An update. Dev. Comp. Immunol. 45(2), 321\u2013343 (2014).","journal-title":"Dev. Comp. Immunol."},{"issue":"1","key":"7408_CR37","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.tim.2011.11.002","volume":"20","author":"F Meurens","year":"2012","unstructured":"Meurens, F., Summerfield, A., Nauwynck, H., Saif, L. & Gerdts, V. The pig: a model for human infectious diseases. Trends Microbiol. 20(1), 50\u201357 (2012).","journal-title":"Trends Microbiol."},{"issue":"2","key":"7408_CR38","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1177\/0300985811402846","volume":"49","author":"MM Swindle","year":"2012","unstructured":"Swindle, M. M., Makin, A., Herron, A. J., Clubb, F. J. Jr. & Frazier, K. S. Swine as models in biomedical research and toxicology testing. Vet. Pathol. 49(2), 344\u2013356 (2012).","journal-title":"Vet. Pathol."},{"issue":"7","key":"7408_CR39","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1097\/SHK.0b013e318181a343","volume":"30","author":"LF Poli-de-Figueiredo","year":"2008","unstructured":"Poli-de-Figueiredo, L. F., Garrido, A. G., Nakagawa, N. & Sannomiya, P. Experimental models of sepsis and their clinical relevance. Shock (Augusta, Ga) 30(7), 53\u201359 (2008).","journal-title":"Shock (Augusta, Ga)"},{"key":"7408_CR40","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1159\/000499520","volume":"47","author":"C Monard","year":"2019","unstructured":"Monard, C., Rimmel\u00e9, T. & Ronco, C. Extracorporeal blood purification therapies for sepsis. Blood Purific. 47, 2\u201315 (2019).","journal-title":"Blood Purific."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-07408-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-07408-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-07408-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T21:02:14Z","timestamp":1750885334000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-07408-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,25]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["7408"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-07408-5","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,25]]},"assertion":[{"value":"2 December 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 June 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 June 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was funded by an unrestricted grant from Sangair (Sweden). J.S. and H.R. are owners of\/employed by Sangair. All other authors declare no conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"All animal studies have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}],"article-number":"20295"}}