{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T17:13:24Z","timestamp":1790097204345,"version":"4.0.1"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2020,6,15]],"date-time":"2020-06-15T00:00:00Z","timestamp":1592179200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,6,15]],"date-time":"2020-06-15T00:00:00Z","timestamp":1592179200000},"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":["Herz"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cardiovascular diseases and cancer are major causes of mortality in industrialized societies. They share common risk factors (e.g., genetics, lifestyle, age, infection, toxins, and pollution) and might also mutually promote the onset of the respective other disease. Cancer can affect cardiac function directly while antitumor therapies may have acute- and\/or late-onset cardiotoxic effects. Recent studies suggest that heart failure might promote tumorigenesis and tumor progression. In both cancer and cardiovascular diseases, genetic predisposition is implicated in the disease onset and development. In this regard, genetic variants classically associated with cardiomyopathies increase the risk for toxic side effects on the cardiovascular system. Genetic variants associated with increased cancer risk are frequent in patients with peripartum cardiomyopathy complicated by cancer, pointing to a\u00a0common genetic predisposition for both diseases. Common risk factors, cardiotoxic antitumor treatment, genetic variants (associated with cardiomyopathies and\/or cancer), and increased cardiac stress lead us to propose the \u201cmulti-hit hypothesis\u201d linking cancer and cardiovascular diseases. In the present review, we summarize the current knowledge on potential connecting factors between cancer and cardiovascular diseases with a\u00a0major focus on the role of genetic predisposition and its implication for individual therapeutic strategies and risk assessment in the novel field of oncocardiology.<\/jats:p>","DOI":"10.1007\/s00059-020-04953-9","type":"journal-article","created":{"date-parts":[[2020,6,15]],"date-time":"2020-06-15T16:03:12Z","timestamp":1592236992000},"page":"632-636","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Common genetic predisposition for heart failure and cancer","Gemeinsame genetische Pr\u00e4disposition f\u00fcr Herzinsuffizienz und Krebs"],"prefix":"10.1007","volume":"45","author":[{"given":"Tobias J.","family":"Pfeffer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Pietzsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Hilfiker-Kleiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,6,15]]},"reference":[{"key":"4953_CR1","volume-title":"Global health estimates 2015: deaths by cause, age, sex, by country and by region, 2000\u20132015","author":"World Health Organisation","year":"2016","unstructured":"World Health Organisation (2016) Global health estimates 2015: deaths by cause, age, sex, by country and by region, 2000\u20132015"},{"issue":"14","key":"4953_CR2","doi-asserted-by":"publisher","first-page":"2059","DOI":"10.2217\/fon.15.89","volume":"11","author":"BJ Petek","year":"2015","unstructured":"Petek\u00a0BJ, Greenman\u00a0C, Herrmann\u00a0J, Ewer\u00a0MS, Jones\u00a0RL (2015) Cardio-oncology: an ongoing evolution. Future Oncol 11(14):2059\u20132066","journal-title":"Future Oncol"},{"issue":"Suppl M","key":"4953_CR3","doi-asserted-by":"publisher","first-page":"M44","DOI":"10.1093\/eurheartj\/suz230","volume":"21","author":"M Habibian","year":"2019","unstructured":"Habibian\u00a0M, Lyon\u00a0AR (2019) Monitoring the heart during cancer therapy. Eur Heart J Suppl 21(Suppl M):M44\u2013M49","journal-title":"Eur Heart J Suppl"},{"issue":"7","key":"4953_CR4","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1161\/CIRCULATIONAHA.117.030816","volume":"138","author":"WC Meijers","year":"2018","unstructured":"Meijers\u00a0WC, Maglione\u00a0M, Bakker\u00a0SJL et\u00a0al (2018) Heart failure stimulates tumor growth by circulating factors. Circulation 138(7):678\u2013691","journal-title":"Circulation"},{"issue":"2","key":"4953_CR5","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1016\/j.jaccao.2019.09.008","volume":"1","author":"TJ Pfeffer","year":"2019","unstructured":"Pfeffer\u00a0TJ, Schlothauer\u00a0S, Pietzsch\u00a0S et\u00a0al (2019) Increased cancer prevalence in peripartum cardiomyopathy. JACC CardioOncol 1(2):196\u2013205","journal-title":"JACC CardioOncol"},{"key":"4953_CR6","doi-asserted-by":"publisher","DOI":"10.1007\/s00392-020-01636-7","author":"T Rassaf","year":"2020","unstructured":"Rassaf\u00a0T, Totzeck\u00a0M, Backs\u00a0J et al (2020) Onco-cardiology: consensus paper of the German Cardiac Society, the German Society for Pediatric Cardiology and Congenital Heart Defects and the German Society for Hematology and Medical Oncology. Clin Res Cardiol. https:\/\/doi.org\/10.1007\/s00392-020-01636-7","journal-title":"Clin Res Cardiol"},{"issue":"35\u201336","key":"4953_CR7","first-page":"586","volume":"115","author":"T Gredner","year":"2018","unstructured":"Gredner\u00a0T, Behrens\u00a0G, Stock\u00a0C et\u00a0al (2018) Cancers due to infection and selected environmental factors. Dtsch Arztebl Int 115(35\u201336):586\u2013593","journal-title":"Dtsch Arztebl Int"},{"issue":"11","key":"4953_CR8","doi-asserted-by":"publisher","first-page":"3502","DOI":"10.1200\/JCO.1998.16.11.3502","volume":"16","author":"M Ryberg","year":"1998","unstructured":"Ryberg\u00a0M, Nielsen\u00a0D, Skovsgaard\u00a0T et\u00a0al (1998) Epirubicin cardiotoxicity: an analysis of 469 patients with metastatic breast cancer. J\u00a0Clin Oncol 16(11):3502\u20133508","journal-title":"J Clin Oncol"},{"key":"4953_CR9","doi-asserted-by":"publisher","first-page":"231","DOI":"10.3389\/fgene.2013.00231","volume":"4","author":"JM Lubieniecka","year":"2013","unstructured":"Lubieniecka\u00a0JM, Graham\u00a0J, Heffner\u00a0D et\u00a0al (2013) A discovery study of daunorubicin induced cardiotoxicity in a\u00a0sample of acute myeloid leukemia patients prioritizes P450 oxidoreductase polymorphisms as a\u00a0potential risk factor. Front Genet 4:231","journal-title":"Front Genet"},{"issue":"2","key":"4953_CR10","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1159\/000265166","volume":"115","author":"K Chatterjee","year":"2010","unstructured":"Chatterjee\u00a0K, Zhang\u00a0J, Honbo\u00a0N, Karliner\u00a0JS (2010) Doxorubicin cardiomyopathy. Cardiology 115(2):155\u2013162","journal-title":"Cardiology"},{"issue":"11","key":"4953_CR11","doi-asserted-by":"publisher","first-page":"2827","DOI":"10.1200\/JCO.1995.13.11.2827","volume":"13","author":"P Anderlini","year":"1995","unstructured":"Anderlini\u00a0P, Benjamin\u00a0RS, Wong\u00a0FC et\u00a0al (1995) Idarubicin cardiotoxicity: a\u00a0retrospective study in acute myeloid leukemia and myelodysplasia. J\u00a0Clin Oncol 13(11):2827\u20132834","journal-title":"J Clin Oncol"},{"issue":"1","key":"4953_CR12","first-page":"13","volume":"1","author":"N Mohan","year":"2018","unstructured":"Mohan\u00a0N, Jiang\u00a0J, Dokmanovic\u00a0M, Wu\u00a0WJ (2018) Trastuzumab-mediated cardiotoxicity: current understanding, challenges, and frontiers. Antib Ther 1(1):13\u201317","journal-title":"Antib Ther"},{"issue":"6","key":"4953_CR13","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1200\/JCO.2010.31.9129","volume":"29","author":"TK Choueiri","year":"2011","unstructured":"Choueiri\u00a0TK, Mayer\u00a0EL, Je\u00a0Y et\u00a0al (2011) Congestive heart failure risk in patients with breast cancer treated with bevacizumab. J\u00a0Clin Oncol 29(6):632\u2013638","journal-title":"J Clin Oncol"},{"key":"4953_CR14","doi-asserted-by":"publisher","first-page":"293","DOI":"10.2147\/VHRM.S108874","volume":"13","author":"N Aghel","year":"2017","unstructured":"Aghel\u00a0N, Delgado\u00a0DH, Lipton\u00a0JH (2017) Cardiovascular toxicities of BCR-ABL tyrosine kinase inhibitors in chronic myeloid leukemia: preventive strategies and cardiovascular surveillance. Vasc Health Risk Manag 13:293\u2013303","journal-title":"Vasc Health Risk Manag"},{"issue":"2","key":"4953_CR15","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1111\/bcpt.13318","volume":"126","author":"W Ma","year":"2020","unstructured":"Ma\u00a0W, Liu\u00a0M, Liang\u00a0F et\u00a0al (2020) Cardiotoxicity of sorafenib is mediated through elevation of ROS level and CaMKII activity and dysregulation of calcium homoeostasis. Basic Clin Pharmacol Toxicol 126(2):166\u2013180","journal-title":"Basic Clin Pharmacol Toxicol"},{"issue":"1","key":"4953_CR16","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1097\/HCO.0000000000000034","volume":"29","author":"SE Lipshultz","year":"2014","unstructured":"Lipshultz\u00a0SE, Karnik\u00a0R, Sambatakos\u00a0P et al (2014) Anthracycline-related cardiotoxicity in childhood cancer survivors. Curr Opin Cardiol 29(1):103\u2013112","journal-title":"Curr Opin Cardiol"},{"issue":"3","key":"4953_CR17","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1007\/s40778-018-0133-9","volume":"4","author":"SJ Park","year":"2018","unstructured":"Park\u00a0SJ, Bejar\u00a0R (2018) Clonal hematopoiesis in aging. Curr Stem Cell Rep 4(3):209\u2013219","journal-title":"Curr Stem Cell Rep"},{"issue":"10","key":"4953_CR18","doi-asserted-by":"publisher","first-page":"e93098","DOI":"10.1172\/jci.insight.93098","volume":"2","author":"JT Thackeray","year":"2017","unstructured":"Thackeray\u00a0JT, Pietzsch\u00a0S, Stapel\u00a0B et al (2017) Insulin supplementation attenuates cancer-induced cardiomyopathy and slows tumor disease progression. JCI Insight 2(10):e93098","journal-title":"JCI Insight"},{"issue":"37","key":"4953_CR19","doi-asserted-by":"publisher","first-page":"10436","DOI":"10.1073\/pnas.1601650113","volume":"113","author":"A Karlstaedt","year":"2016","unstructured":"Karlstaedt\u00a0A, Zhang\u00a0X, Vitrac\u00a0H et al (2016) Oncometabolite d\u20112-hydroxyglutarate impairs alpha-ketoglutarate dehydrogenase and contractile function in rodent heart. Proc Natl Acad Sci USA 113(37):10436\u201310441","journal-title":"Proc Natl Acad Sci USA"},{"issue":"11","key":"4953_CR20","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1016\/j.jacc.2011.11.040","volume":"59","author":"S Ather","year":"2012","unstructured":"Ather\u00a0S, Chan\u00a0W, Bozkurt\u00a0B et\u00a0al (2012) Impact of noncardiac comorbidities on morbidity and mortality in a\u00a0predominantly male population with heart failure and preserved versus reduced ejection fraction. J\u00a0Am Coll Cardiol 59(11):998\u20131005","journal-title":"J Am Coll Cardiol"},{"issue":"10","key":"4953_CR21","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1016\/j.jacc.2013.04.088","volume":"62","author":"T Hasin","year":"2013","unstructured":"Hasin\u00a0T, Gerber\u00a0Y, McNallan\u00a0SM et\u00a0al (2013) Patients with heart failure have an increased risk of incident cancer. J\u00a0Am Coll Cardiol 62(10):881\u2013886","journal-title":"J Am Coll Cardiol"},{"issue":"3","key":"4953_CR22","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1002\/ejhf.472","volume":"18","author":"A Banke","year":"2016","unstructured":"Banke\u00a0A, Schou\u00a0M, Videbaek\u00a0L et al (2016) Incidence of cancer in patients with chronic heart failure: a\u00a0long-term follow-up study. Eur J Heart Fail 18(3):260\u2013266","journal-title":"Eur J Heart Fail"},{"issue":"3","key":"4953_CR23","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/j.jacc.2016.04.053","volume":"68","author":"T Hasin","year":"2016","unstructured":"Hasin\u00a0T, Gerber\u00a0Y, Weston\u00a0SA et\u00a0al (2016) Heart failure after myocardial infarction is associated with increased risk of cancer. J\u00a0Am Coll Cardiol 68(3):265\u2013271","journal-title":"J Am Coll Cardiol"},{"issue":"4","key":"4953_CR24","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1016\/j.jacc.2019.06.007","volume":"74","author":"P Libby","year":"2019","unstructured":"Libby\u00a0P, Sidlow\u00a0R, Lin\u00a0AE et\u00a0al (2019) Clonal hematopoiesis: crossroads of aging, cardiovascular disease, and cancer: JACC review topic of the week. J\u00a0Am Coll Cardiol 74(4):567\u2013577","journal-title":"J Am Coll Cardiol"},{"issue":"11","key":"4953_CR25","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.1038\/ng.2413","volume":"44","author":"L Busque","year":"2012","unstructured":"Busque\u00a0L, Patel\u00a0JP, Figueroa\u00a0ME et\u00a0al (2012) Recurrent somatic TET2 mutations in normal elderly individuals with clonal hematopoiesis. Nat Genet 44(11):1179\u20131181","journal-title":"Nat Genet"},{"issue":"6327","key":"4953_CR26","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1126\/science.aag1381","volume":"355","author":"JJ Fuster","year":"2017","unstructured":"Fuster\u00a0JJ, MacLauchlan\u00a0S, Zuriaga\u00a0MA et\u00a0al (2017) Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice. Science 355(6327):842\u2013847","journal-title":"Science"},{"issue":"26","key":"4953_CR27","doi-asserted-by":"publisher","first-page":"2488","DOI":"10.1056\/NEJMoa1408617","volume":"371","author":"S Jaiswal","year":"2014","unstructured":"Jaiswal\u00a0S, Fontanillas\u00a0P, Flannick\u00a0J et al (2014) Age-related clonal hematopoiesis associated with adverse outcomes. N\u00a0Engl J Med 371(26):2488\u20132498","journal-title":"N Engl J Med"},{"issue":"7","key":"4953_CR28","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1097\/FPC.0000000000000284","volume":"27","author":"QS Wells","year":"2017","unstructured":"Wells\u00a0QS, Veatch\u00a0OJ, Fessel\u00a0JP et al (2017) Genome-wide association and pathway analysis of left ventricular function after anthracycline exposure in adults. Pharmacogenet Genomics 27(7):247\u2013254","journal-title":"Pharmacogenet Genomics"},{"issue":"1","key":"4953_CR29","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1161\/CIRCULATIONAHA.118.037934","volume":"140","author":"P Garcia-Pavia","year":"2019","unstructured":"Garcia-Pavia\u00a0P, Kim\u00a0Y, Restrepo-Cordoba\u00a0MA, Lunde\u00a0IG, Wakimoto\u00a0H, Smith\u00a0AM et al (2019) Genetic variants associated with cancer therapy-induced cardiomyopathy. Circulation 140(1):31\u201341","journal-title":"Circulation"},{"issue":"32","key":"4953_CR30","doi-asserted-by":"publisher","first-page":"11809","DOI":"10.1073\/pnas.0404580101","volume":"101","author":"JW Watters","year":"2004","unstructured":"Watters\u00a0JW, Kraja\u00a0A, Meucci\u00a0MA et al (2004) Genome-wide discovery of loci influencing chemotherapy cytotoxicity. Proc Natl Acad Sci USA 101(32):11809\u201311814","journal-title":"Proc Natl Acad Sci USA"},{"issue":"3","key":"4953_CR31","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1056\/NEJMoa1505517","volume":"374","author":"JS Ware","year":"2016","unstructured":"Ware\u00a0JS, Li\u00a0J, Mazaika\u00a0E et\u00a0al (2016) Shared genetic predisposition in peripartum and dilated cardiomyopathies. N\u00a0Engl J Med 374(3):233\u2013241","journal-title":"N Engl J Med"},{"issue":"2","key":"4953_CR32","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1667\/RR13515.1","volume":"181","author":"CG Broustas","year":"2014","unstructured":"Broustas\u00a0CG, Lieberman\u00a0HB (2014) DNA damage response genes and the development of cancer metastasis. Radiat Res 181(2):111\u2013130","journal-title":"Radiat Res"},{"issue":"2","key":"4953_CR33","doi-asserted-by":"publisher","first-page":"59","DOI":"10.3390\/genes8020059","volume":"8","author":"M Sajjad","year":"2017","unstructured":"Sajjad\u00a0M, Fradley\u00a0M, Sun\u00a0W et\u00a0al (2017) An exploratory study to determine whether BRCA1 and BRCA2 mutation carriers have higher risk of cardiac toxicity. Genes (Basel) 8(2):59","journal-title":"Genes (Basel)"},{"issue":"6","key":"4953_CR34","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1093\/biolre\/ioy038","volume":"98","author":"J Yang","year":"2018","unstructured":"Yang\u00a0J, Zhang\u00a0Y, Tong\u00a0J et al (2018) Dysfunction of DNA damage-inducible transcript 4 in the decidua is relevant to the pathogenesis of preeclampsia. Biol Reprod 98(6):821\u2013833","journal-title":"Biol Reprod"},{"issue":"4","key":"4953_CR35","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1073\/pnas.68.4.820","volume":"68","author":"AG Knudson Jr","year":"1971","unstructured":"Knudson\u00a0AG Jr (1971) Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci USA 68(4):820\u2013823","journal-title":"Proc Natl Acad Sci USA"},{"issue":"3","key":"4953_CR36","first-page":"1063","volume":"36","author":"R Dobrila-Dintinjana","year":"2012","unstructured":"Dobrila-Dintinjana\u00a0R, Vanis\u00a0N, Dintinjana\u00a0M, Radi\u0107\u00a0M (2012) Etiology and oncogenesis of pancreatic carcinoma. Coll Antropol 36(3):1063\u20131067","journal-title":"Coll Antropol"},{"issue":"12","key":"4953_CR37","doi-asserted-by":"publisher","first-page":"1983","DOI":"10.1007\/s00277-017-3161-0","volume":"96","author":"S Nassereddine","year":"2017","unstructured":"Nassereddine\u00a0S, Lap\u00a0CJ, Haroun\u00a0F, Tabbara\u00a0I (2017) The role of mutant IDH1 and IDH2 inhibitors in the treatment of acute myeloid leukemia. Ann Hematol 96(12):1983\u20131991","journal-title":"Ann Hematol"},{"key":"4953_CR38","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1146\/annurev-med-070213-054849","volume":"66","author":"SE Lipshultz","year":"2015","unstructured":"Lipshultz\u00a0SE, Franco\u00a0VI, Miller\u00a0TL et\u00a0al (2015) Cardiovascular disease in adult survivors of childhood cancer. Annu Rev Med 66:161\u2013176","journal-title":"Annu Rev Med"},{"issue":"6","key":"4953_CR39","doi-asserted-by":"publisher","first-page":"719","DOI":"10.2174\/1389450117666160401125404","volume":"18","author":"R Madonna","year":"2017","unstructured":"Madonna\u00a0R, Cadeddu\u00a0C, Deidda\u00a0M et al (2017) Modelling chemotherapy-induced cardiotoxicity by human pluripotent stem cells. Curr Drug Targets 18(6):719\u2013723","journal-title":"Curr Drug Targets"},{"issue":"7","key":"4953_CR40","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1007\/s11912-018-0696-8","volume":"20","author":"VY Chang","year":"2018","unstructured":"Chang\u00a0VY, Wang\u00a0JJ (2018) Pharmacogenetics of chemotherapy-induced cardiotoxicity. Curr Oncol Rep 20(7):52","journal-title":"Curr Oncol Rep"}],"container-title":["Herz"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00059-020-04953-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00059-020-04953-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00059-020-04953-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,14]],"date-time":"2021-06-14T23:06:13Z","timestamp":1623711973000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00059-020-04953-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,15]]},"references-count":40,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2020,11]]}},"alternative-id":["4953"],"URL":"https:\/\/doi.org\/10.1007\/s00059-020-04953-9","relation":{},"ISSN":["0340-9937","1615-6692"],"issn-type":[{"value":"0340-9937","type":"print"},{"value":"1615-6692","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,15]]},"assertion":[{"value":"15 June 2020","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical guidelines"}},{"value":"T.J.\u00a0Pfeffer, S.\u00a0Pietzsch and D.\u00a0Hilfiker-Kleiner declare that they have no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"For this article no studies with human participants or animals were performed by any of the authors. All cited studies in which authors of this manuscript were involved were in accordance with the ethical standards indicated in each case.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}