{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T15:31:40Z","timestamp":1779377500918,"version":"3.53.1"},"reference-count":91,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,10,5]],"date-time":"2020-10-05T00:00:00Z","timestamp":1601856000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,10,5]],"date-time":"2020-10-05T00:00:00Z","timestamp":1601856000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Sz\u00e9chenyi 2020 Programme","award":["GINOP-2.3.2\u201315\u20132016-00042"],"award-info":[{"award-number":["GINOP-2.3.2\u201315\u20132016-00042"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Fungal infections represent a worrisome complication in hematologic cancer patients and in the absence of disease specific symptoms, it is important to establish new biological indicators, which can be used during mould-active prophylaxis. Recently, miRNAs have appeared as candidate diagnostic and prognostic markers of several diseases. A pilot clinical study was performed to evaluate the diagnostic utility of 14 microRNAs which can be related to invasive fungal infections. Based on our data miR-142-3p, miR-142-5p, miR-26b-5p and miR-21-5p showed significant overexpression (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.005) due to invasive aspergillosis in hemato-oncology patients with profound neutropenia. A tetramiR assay was designed to monitor peripheral blood specimens. Optimal cut-off was estimated by using the median value (fold change 1.1) of the log10 transformed gene expressions. The biomarker panel was evaluated on two independent sample cohorts implementing different antimicrobial prophylactic strategies. The receiver operating characteristic analysis with area under the curve proved to be 0.97. Three miRNAs (miR-142-5p, miR-142-3p, miR-16-5p) showed significant expression alterations in episodes with sepsis. In summary, the tetramiR assay proved to be a promising diagnostic adjunct with sufficient accuracy and sensitivity to trace invasive aspergillosis in hemato-oncology patients.<\/jats:p>","DOI":"10.1038\/s41598-020-73556-5","type":"journal-article","created":{"date-parts":[[2020,10,5]],"date-time":"2020-10-05T10:05:05Z","timestamp":1601892305000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Free circulating mircoRNAs support the diagnosis of invasive aspergillosis in patients with hematologic malignancies and neutropenia"],"prefix":"10.1038","volume":"10","author":[{"given":"Emese","family":"Tolnai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e1bor","family":"Fidler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00f3bert","family":"Sz\u00e1sz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e1szl\u00f3","family":"Rejt\u0151","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kingsley Okechukwu","family":"Nwozor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e1ndor","family":"Bir\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melinda","family":"Paholcsek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,10,5]]},"reference":[{"key":"73556_CR1","doi-asserted-by":"publisher","first-page":"ofy187","DOI":"10.1093\/ofid\/ofy187","volume":"5","author":"BJ Webb","year":"2018","unstructured":"Webb, B. J. et al. Epidemiology and clinical features of invasive fungal infection in a US health care network. Open Forum Infect Dis. 5, ofy187 (2018).","journal-title":"Open Forum Infect Dis."},{"key":"73556_CR2","doi-asserted-by":"publisher","first-page":"2521","DOI":"10.1007\/s00520-013-1816-5","volume":"9","author":"G Samonis","year":"2013","unstructured":"Samonis, G. et al. A prospective study of characteristics and outcomes of bacteremia in patients with solid organ or hematologic malignancies. Support Care Cancer 9, 2521\u20132526 (2013).","journal-title":"Support Care Cancer"},{"key":"73556_CR3","doi-asserted-by":"publisher","first-page":"1608","DOI":"10.1093\/cid\/cis774","volume":"12","author":"D Dix","year":"2012","unstructured":"Dix, D. et al. Association between corticosteroids and infection, sepsis, and infectious death in pediatric acute myeloid leukemia (AML): results from the Canadian infections in AML research group. Clin. Infect. Dis. 12, 1608\u20131614 (2012).","journal-title":"Clin. Infect. Dis."},{"key":"73556_CR4","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.1086\/522189","volume":"9","author":"L Pagano","year":"2007","unstructured":"Pagano, L. et al. Fungal infections in recipients of hematopoietic stem cell transplants: results of the SEIFEM B-2004 study-Sorveglianza Epidemiologica Infezioni Fungine Nelle Emopatie Maligne. Clin. Infect. Dis. 9, 1161\u20131170 (2007).","journal-title":"Clin. Infect. Dis."},{"key":"73556_CR5","first-page":"195","volume":"2","author":"P Badiee","year":"2014","unstructured":"Badiee, P. & Hashemizadeh, Z. Opportunistic invasive fungal infections: diagnosis & clinical management. Indian J. Med. Res. 2, 195\u2013204 (2014).","journal-title":"Indian J. Med. Res."},{"key":"73556_CR6","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1111\/myc.12838","volume":"11","author":"M Ruhnke","year":"2018","unstructured":"Ruhnke, M. et al. Diagnosis of invasive fungal diseases in haematology and oncology: 2018 update of the recommendations of the infectious diseases working party of the German society for hematology and medical oncology (AGIHO). Mycoses 11, 796\u2013813 (2018).","journal-title":"Mycoses"},{"key":"73556_CR7","doi-asserted-by":"publisher","first-page":"1644","DOI":"10.1378\/chest.101.6.1644","volume":"6","author":"RC Bone","year":"1992","unstructured":"Bone, R. C. et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP\/SCCM Consensus Conference Committee. American College of Chest Physicians\/Society of Critical Care Medicine. Chest 6, 1644\u20131655 (1992).","journal-title":"Chest"},{"key":"73556_CR8","first-page":"220","volume":"4","author":"Z Salih","year":"2013","unstructured":"Salih, Z. et al. Prognostic factors for mortality with fungal blood stream infections in patients with hematological and non-hematological malignancies. South Asian J. Cancer 4, 220\u2013224 (2013).","journal-title":"South Asian J. Cancer"},{"key":"73556_CR9","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s13054-014-0722-7","volume":"19","author":"FS Taccone","year":"2015","unstructured":"Taccone, F. S. et al. Epidemiology of invasive aspergillosis in critically ill patients: clinical presentation, underlying conditions, and outcomes. Crit. Care 19, 7 (2015).","journal-title":"Crit. Care"},{"key":"73556_CR10","doi-asserted-by":"publisher","first-page":"e0186422","DOI":"10.1371\/journal.pone.0186422","volume":"12","author":"KS Sun","year":"2017","unstructured":"Sun, K. S., Tsai, C. F., Chen, S. C. & Huang, W. C. Clinical outcome and prognostic factors associated with invasive pulmonary aspergillosis: an 11-year follow-up report from Taiwan. PLoS ONE 12, e0186422 (2017).","journal-title":"PLoS ONE"},{"key":"73556_CR11","doi-asserted-by":"publisher","first-page":"53","DOI":"10.2174\/1871526515666150320161804","volume":"1","author":"D Stubljar","year":"2015","unstructured":"Stubljar, D. & Skvarc, M. Effective strategies for diagnosis of systemic inflammatory response syndrome (SIRS) due to bacterial infection in surgical patients. Infect. Disord. Drug Targets 1, 53\u201356 (2015).","journal-title":"Infect. Disord. Drug Targets"},{"key":"73556_CR12","doi-asserted-by":"publisher","first-page":"3139","DOI":"10.3390\/ijms19103139","volume":"19","author":"M Di Marco","year":"2018","unstructured":"Di Marco, M. et al. MicroRNAs in autoimmunity and hematological malignancies. Int. J. Mol. Sci. 19, 3139 (2018).","journal-title":"Int. J. Mol. Sci."},{"key":"73556_CR13","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1093\/cid\/ciy181","volume":"5","author":"MD Zilberberg","year":"2018","unstructured":"Zilberberg, M. D., Nathanson, B. H., Harrington, R., Spalding, J. R. & Shorr, A. F. Epidemiology and outcomes of hospitalizations with invasive aspergillosis in the United States, 2009\u20132013. Clin. Infect. Dis. 5, 727\u2013735 (2018).","journal-title":"Clin. Infect. Dis."},{"key":"73556_CR14","doi-asserted-by":"publisher","first-page":"1524","DOI":"10.1086\/317487","volume":"6","author":"EJ Dasbach","year":"2000","unstructured":"Dasbach, E. J., Davies, G. M. & Teutsch, S. M. Burden of aspergillosis-related hospitalizations in the United States. Clin. Infect. Dis. 6, 1524\u20131528 (2000).","journal-title":"Clin. Infect. Dis."},{"key":"73556_CR15","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1086\/318483","volume":"3","author":"SJ Lin","year":"2001","unstructured":"Lin, S. J., Schranz, J. & Teutsch, S. M. Aspergillosis case-fatality rate: systematic review of the literature. Clin. Infect. Dis. 3, 358\u2013366 (2001).","journal-title":"Clin. Infect. Dis."},{"key":"73556_CR16","doi-asserted-by":"publisher","first-page":"113","DOI":"10.3324\/haematol.11665","volume":"1","author":"OA Cornely","year":"2009","unstructured":"Cornely, O. A. et al. Primary prophylaxis of invasive fungal infections in patients with hematologic malignancies. Recommendations of the Infectious Diseases Working Party of the German Society for Haematology and Oncology. Haematologica 1, 113\u2013122 (2009).","journal-title":"Haematologica"},{"key":"73556_CR17","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/j.omtn.2017.12.016","volume":"10","author":"P Shanxin","year":"2018","unstructured":"Shanxin, P. et al. Endogenous cellular MicroRNAs mediate antiviral defense against influenza A virus. Mol. Ther. Nucl. Acids 10, 361\u2013375 (2018).","journal-title":"Mol. Ther. Nucl. Acids"},{"key":"73556_CR18","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/S0092-8674(04)00045-5","volume":"2","author":"DP Bartel","year":"2004","unstructured":"Bartel, D. P. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2, 281\u2013297 (2004).","journal-title":"Cell"},{"key":"73556_CR19","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1007\/978-1-4939-7046-9_4","volume":"1617","author":"W Huang","year":"2017","unstructured":"Huang, W. MicroRNAs: biomarkers, diagnostics, and therapeutics. Methods Mol. Biol. 1617, 57\u201367 (2017).","journal-title":"Methods Mol. Biol."},{"key":"73556_CR20","first-page":"8","volume":"23","author":"A Dix","year":"2017","unstructured":"Dix, A. et al. Specific and novel microRNAs are regulated as response to fungal infection in human dendritic cells. Front Microbiol. 23, 8\u2013270 (2017).","journal-title":"Front Microbiol."},{"key":"73556_CR21","doi-asserted-by":"publisher","first-page":"801","DOI":"10.2217\/fon-2018-0812","volume":"8","author":"K Saliminejad","year":"2019","unstructured":"Saliminejad, K., Khorram Khorshid, H. R. & Ghaffari, S. H. Why have microRNA biomarkers not been translated from bench to clinic?. Future Oncol. 8, 801\u2013803 (2019).","journal-title":"Future Oncol."},{"key":"73556_CR22","doi-asserted-by":"publisher","first-page":"1373","DOI":"10.3892\/mmr.2017.6139","volume":"3","author":"X Xu","year":"2017","unstructured":"Xu, X., Liu, C. & Bao, J. Hypoxia-induced hsa-miR-101 promotes glycolysis by targeting TIGAR mRNA in clear cell renal cell carcinoma. Mol. Med. Rep. 3, 1373\u20131378 (2017).","journal-title":"Mol. Med. Rep."},{"key":"73556_CR23","doi-asserted-by":"publisher","first-page":"28006","DOI":"10.1038\/srep28006","volume":"6","author":"S Caserta","year":"2016","unstructured":"Caserta, S. et al. Circulating plasma microRNAs can differentiate human sepsis and systemic inflammatory response syndrome (SIRS). Sci. Rep. 6, 28006 (2016).","journal-title":"Sci. Rep."},{"key":"73556_CR24","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1016\/j.ijmm.2014.04.005","volume":"304","author":"M Gupta","year":"2014","unstructured":"Gupta, M. et al. Aspergillus fumigatus induces microRNA-132 in human monocytes and dendritic cells. Int. J. Med. Microbiol. 304, 592\u2013596 (2014).","journal-title":"Int. J. Med. Microbiol."},{"key":"73556_CR25","doi-asserted-by":"publisher","first-page":"e0136454","DOI":"10.1371\/journal.pone.0136454","volume":"10","author":"SA Muhammad","year":"2015","unstructured":"Muhammad, S. A. et al. MicroRNA expression profiling of human respiratory epithelium affected by invasive Candida infection. PLoS ONE 10, e0136454 (2015).","journal-title":"PLoS ONE"},{"key":"73556_CR26","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1097\/SHK.0000000000000766","volume":"47","author":"CX Wu","year":"2017","unstructured":"Wu, C. X. et al. Microrna expression profiling of macrophage line raw 264.7 infected by Candida albicans. Shock 47, 520\u2013530 (2017).","journal-title":"Shock"},{"key":"73556_CR27","doi-asserted-by":"publisher","first-page":"1445","DOI":"10.1128\/JCM.03322-12","volume":"5","author":"J Springer","year":"2013","unstructured":"Springer, J. et al. Multicenter comparison of serum and whole-blood specimens for detection of Aspergillus DNA in high-risk hematological patients. J. Clin. Microbiol. 5, 1445\u20131450 (2013).","journal-title":"J. Clin. Microbiol."},{"key":"73556_CR28","doi-asserted-by":"publisher","first-page":"2735","DOI":"10.1073\/pnas.0811073106","volume":"8","author":"M Ceppi","year":"2009","unstructured":"Ceppi, M. et al. MicroRNA-155 modulates the interleukin-1 signaling pathway in activated human monocyte-derived dendritic cells. Proc. Natl. Acad. Sci. USA 8, 2735\u20132740 (2009).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"73556_CR29","doi-asserted-by":"publisher","first-page":"e8508","DOI":"10.1371\/journal.pone.0008508","volume":"4","author":"TJ Cremer","year":"2009","unstructured":"Cremer, T. J. et al. MiR-155 induction by F. novicida but not the virulent F. tularensis results in SHIP down-regulation and enhanced pro-inflammatory cytokine response. PLoS ONE 4, e8508 (2009).","journal-title":"PLoS ONE"},{"key":"73556_CR30","doi-asserted-by":"publisher","first-page":"186716","DOI":"10.1155\/2015\/186716","volume":"2015","author":"R Dumache","year":"2015","unstructured":"Dumache, R. et al. Use of miRNAs as biomarkers in sepsis. Anal. Cell Pathol. 2015, 186716 (2015).","journal-title":"Anal. Cell Pathol."},{"key":"73556_CR31","doi-asserted-by":"publisher","first-page":"2403","DOI":"10.1111\/jcmm.13162","volume":"21","author":"M Reithmar","year":"2017","unstructured":"Reithmar, M. et al. Cellular and extracellular miRNAs are blood-compartment-specific diagnostic targets in sepsis. J. Cell Mol. Med. 21, 2403\u20132411 (2017).","journal-title":"J. Cell Mol. Med."},{"key":"73556_CR32","doi-asserted-by":"publisher","first-page":"118","DOI":"10.3389\/fimmu.2017.00118","volume":"8","author":"CN Correia","year":"2017","unstructured":"Correia, C. N. et al. Circulating microRNAs as potential biomarkers of infectious disease. Front. Immunol. 8, 118 (2017).","journal-title":"Front. Immunol."},{"key":"73556_CR33","first-page":"1331","volume":"781","author":"JGP Juan","year":"2016","unstructured":"Juan, J. G. P. Current roles of microRNAs in infectious diseases\u2014advancing into healthcare. Redni broj lanka 781, 1331\u20132820 (2016).","journal-title":"Redni broj lanka"},{"key":"73556_CR34","first-page":"8","volume":"25","author":"RE Drury","year":"2017","unstructured":"Drury, R. E., O\u2019Connor, D. & Pollard, A. J. The clinical application of MicroRNAs in infectious disease. Front. Immunol. 25, 8\u20131182 (2017).","journal-title":"Front. Immunol."},{"key":"73556_CR35","doi-asserted-by":"publisher","first-page":"35114","DOI":"10.18632\/oncotarget.26210","volume":"9","author":"D Lacedonia","year":"2018","unstructured":"Lacedonia, D. et al. MicroRNA expression profile during different conditions of hypoxia. Oncotarget 9, 35114\u201335122 (2018).","journal-title":"Oncotarget"},{"key":"73556_CR36","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1007\/BF01967060","volume":"2","author":"G Bodey","year":"1992","unstructured":"Bodey, G. et al. Fungal infections in cancer patients: an international autopsy survey. Eur. J. Clin. Microbiol. Infect. Dis. 2, 99\u2013109 (1992).","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"73556_CR37","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1086\/520192","volume":"2","author":"MB Edmond","year":"1999","unstructured":"Edmond, M. B. et al. Nosocomial bloodstream infections in United States hospitals: a three-year analysis. Clin. Infect. Dis. 2, 239\u2013244 (1999).","journal-title":"Clin. Infect. Dis."},{"key":"73556_CR38","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1093\/cid\/civ885","volume":"3","author":"PE Verweij","year":"2016","unstructured":"Verweij, P. E., Chowdhary, A., Melchers, W. J. & Meis, J. F. Azole resistance in Aspergillus fumigatus: can we retain the clinical use of mold-active antifungal azoles?. Clin. Infect. Dis. 3, 362\u2013368 (2016).","journal-title":"Clin. Infect. Dis."},{"key":"73556_CR39","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1086\/315193","volume":"1","author":"KA Marr","year":"2000","unstructured":"Marr, K. A., Seidel, K., White, T. C. & Bowden, R. A. Candidemia in allogeneic blood and marrow transplant recipients: evolution of risk factors after the adoption of prophylactic fluconazole. J. Infect. Dis. 1, 309\u2013316 (2000).","journal-title":"J. Infect. Dis."},{"key":"73556_CR40","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1185\/030079903125001884","volume":"4","author":"AJ Ullmann","year":"2003","unstructured":"Ullmann, A. J. Review of the safety, tolerability, and drug interactions of the new antifungal agents caspofungin and voriconazole. Curr. Med. Res. Opin. 4, 263\u2013271 (2003).","journal-title":"Curr. Med. Res. Opin."},{"key":"73556_CR41","first-page":"549","volume":"4","author":"PR Daniel","year":"2001","unstructured":"Daniel, P. R. et al. Impact of bloodstream infection on outcomes among infected surgical inpatients. Ann. Surg. 4, 549\u2013555 (2001).","journal-title":"Ann. Surg."},{"key":"73556_CR42","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1007\/s001340050041","volume":"2","author":"MW Wichmann","year":"2000","unstructured":"Wichmann, M. W., Inthorn, D., Andress, H. J. & Schildberg, F. W. Incidence and mortality of severe sepsis in surgical intensive care patients: the influence of patient gender on disease process and outcome. Intensive Care Med. 2, 167\u2013172 (2000).","journal-title":"Intensive Care Med."},{"key":"73556_CR43","doi-asserted-by":"publisher","first-page":"1232","DOI":"10.1086\/496922","volume":"9","author":"TE Zaoutis","year":"2005","unstructured":"Zaoutis, T. E. et al. The epidemiology and attributable outcomes of candidemia in adults and children hospitalized in the United States: a propensity analysis. Clin. Infect Dis. 9, 1232\u20131239 (2005).","journal-title":"Clin. Infect Dis."},{"key":"73556_CR44","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1086\/502581","volume":"6","author":"J Morgan","year":"2005","unstructured":"Morgan, J. et al. Excess mortality, hospital stay, and cost due to candidemia: a case-control study using data from population-based candidemia surveillance. Infect. Control Hosp. Epidemiol. 6, 540\u2013547 (2005).","journal-title":"Infect. Control Hosp. Epidemiol."},{"key":"73556_CR45","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1093\/mmy\/myw121","volume":"1","author":"S Pasupneti","year":"2017","unstructured":"Pasupneti, S., Manouvakhova, O., Nicolls, M. R. & Hsu, J. L. Aspergillus-related pulmonary diseases in lung transplantation. Med. Mycol. 1, 96\u2013102 (2017).","journal-title":"Med. Mycol."},{"key":"73556_CR46","first-page":"44","volume":"1","author":"S Nina","year":"2005","unstructured":"Nina, S. & David, L. P. Aspergillus Infections in transplant recipients. Clin. Microbiol. Rev. 1, 44\u201369 (2005).","journal-title":"Clin. Microbiol. Rev."},{"key":"73556_CR47","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1007\/s00134-017-4683-6","volume":"3","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. 3, 304\u2013377 (2017).","journal-title":"Intensive Care Med."},{"key":"73556_CR48","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1097\/01.CCM.0000298158.12101.41","volume":"1","author":"RP Dellinger","year":"2008","unstructured":"Dellinger, R. P. et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit. Care Med. 1, 296\u2013327 (2008).","journal-title":"Crit. Care Med."},{"key":"73556_CR49","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1017\/S148180350001054X","volume":"5","author":"RS Green","year":"2008","unstructured":"Green, R. S. et al. Critical Care Interest Group. Canadian Association of Emergency Physicians Sepsis Guidelines: the optimal management of severe sepsis in Canadian emergency departments. CJEM 5, 443\u2013459 (2008).","journal-title":"CJEM"},{"key":"73556_CR50","doi-asserted-by":"publisher","first-page":"1937","DOI":"10.1097\/CCM.0b013e31817603ba","volume":"6","author":"PE Marik","year":"2008","unstructured":"Marik, P. E. et al. Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: consensus statements from an international task force by the American College of Critical Care Medicine. Crit. Care Med. 6, 1937\u20131949 (2008).","journal-title":"Crit. Care Med."},{"key":"73556_CR51","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/cc4965","volume":"10","author":"T Pottecher","year":"2006","unstructured":"Pottecher, T., Calvat, S., Dupont, H., Durand-Gasselin, J. & Gerbeaux, P. Haemodynamic management of severe sepsis: recommendations of the French Intensive Care Societies (SFAR\/SRLF) Consensus Conference, 13 October 2005, Paris France. Crit. Care 10, 4\u2013311 (2006).","journal-title":"Crit. Care"},{"key":"73556_CR52","first-page":"347","volume":"59","author":"K Reinhart","year":"2010","unstructured":"Reinhart, K. et al. Prevention, diagnosis, therapy and follow-up care of sepsis: 1st revision of S-2k guidelines of the German Sepsis Society (Deutsche Sepsis-Gesellschaft e.V. (DSG)) and the German Interdisciplinary Association of Intensive Care and Emergency Medicine (Deutsche Interdisziplin\u00e4re Vereinigung f\u00fcr Intensiv- und Notfallmedizin (DIVI)). Ger. Med. Sci. 59, 347\u2013370 (2010).","journal-title":"Ger. Med. Sci."},{"key":"73556_CR53","doi-asserted-by":"publisher","first-page":"R5","DOI":"10.1186\/cc6766","volume":"12","author":"GH Xie","year":"2008","unstructured":"Xie, G. H. et al. Impact of invasive fungal infection on outcomes of severe sepsis: a multicenter matched cohort study in critically ill surgical patients. Crit. Care 12, R5 (2008).","journal-title":"Crit. Care"},{"key":"73556_CR54","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1007\/s15010-013-0468-1","volume":"5","author":"MM Bos","year":"2013","unstructured":"Bos, M. M., Smeets, L. S., Dumay, I. & de Jonge, E. Bloodstream infections in patients with or without cancer in a large community hospital. Infection 5, 949\u2013958 (2013).","journal-title":"Infection"},{"key":"73556_CR55","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1086\/374339","volume":"29","author":"H Wisplinghoff","year":"2003","unstructured":"Wisplinghoff, H., Seifert, H., Wenzel, R. P. & Edmond, M. B. Current trends in the epidemiology of nosocomial bloodstream infections in patients with hematological malignancies and solid neoplasms in hospitals in the United States. Clin. Infect. Dis. 29, 1103\u20131110 (2003).","journal-title":"Clin. Infect. Dis."},{"key":"73556_CR56","doi-asserted-by":"publisher","first-page":"1726","DOI":"10.1086\/504328","volume":"12","author":"II Raad","year":"2006","unstructured":"Raad, I. I. et al. Safety of long-term oral posaconazole use in the treatment of refractory invasive fungal infections. Clin. Infect. Dis. 12, 1726\u20131734 (2006).","journal-title":"Clin. Infect. Dis."},{"key":"73556_CR57","doi-asserted-by":"publisher","first-page":"16","DOI":"10.3109\/08830185.2010.529976","volume":"30","author":"H Kumar","year":"2011","unstructured":"Kumar, H., Kawai, T. & Akira, S. Pathogen recognition by the innate immune system. Int. Rev. Immunol. 30, 16\u201334 (2011).","journal-title":"Int. Rev. Immunol."},{"key":"73556_CR58","doi-asserted-by":"publisher","first-page":"12481","DOI":"10.1073\/pnas.0605298103","volume":"33","author":"KD Taganov","year":"2006","unstructured":"Taganov, K. D., Boldin, M. P., Chang, K. J. & Baltimore, D. NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc. Natl. Acad. Sci. USA 33, 12481\u201312486 (2006).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"73556_CR59","doi-asserted-by":"publisher","first-page":"1604","DOI":"10.1073\/pnas.0610731104","volume":"5","author":"RM O'Connell","year":"2007","unstructured":"O\u2019Connell, R. M., Taganov, K. D., Boldin, M. P., Cheng, G. & Baltimore, D. MicroRNA-155 is induced during the macrophage inflammatory response. Proc. Natl. Acad. Sci. USA 5, 1604\u20131609 (2007).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"73556_CR60","doi-asserted-by":"publisher","first-page":"5082","DOI":"10.4049\/jimmunol.179.8.5082","volume":"8","author":"E Tili","year":"2007","unstructured":"Tili, E. et al. Modulation of miR-155 and miR-125b levels following lipopolysaccharide\/TNF-alpha stimulation and their possible roles in regulating the response to endotoxin shock. J. Immunol. 8, 5082\u20135089 (2007).","journal-title":"J. Immunol."},{"key":"73556_CR61","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1038\/s41392-017-0003-4","volume":"25","author":"X Zhou","year":"2018","unstructured":"Zhou, X., Li, X. & Wu, M. miRNAs reshape immunity and inflammatory responses in bacterial infection. Signal Transduct. Target Ther. 25, 3\u201314 (2018).","journal-title":"Signal Transduct. Target Ther."},{"key":"73556_CR62","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.3389\/fphar.2018.01509","volume":"9","author":"Y He","year":"2019","unstructured":"He, Y. et al. miR-26 induces apoptosis and inhibits autophagy in non-small cell lung cancer cells by suppressing TGF-\u03b21-JNK signaling pathway. Front Pharmacol. 9, 1509 (2019).","journal-title":"Front Pharmacol."},{"key":"73556_CR63","doi-asserted-by":"publisher","first-page":"1532","DOI":"10.1086\/320514","volume":"11","author":"C Viscoli","year":"2001","unstructured":"Viscoli, C. et al. Association between antifungal prophylaxis and rate of documented bacteremia in febrile neutropenic cancer patients. Clin. Infect. Dis. 11, 1532\u20131537 (2001).","journal-title":"Clin. Infect. Dis."},{"key":"73556_CR64","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1128\/CMR.00029-06","volume":"1","author":"MA Pfaller","year":"2007","unstructured":"Pfaller, M. A. & Diekema, D. J. Epidemiology of invasive candidiasis: a persistent public health problem. Clin. Microbiol. Rev. 1, 133\u2013163 (2007).","journal-title":"Clin. Microbiol. Rev."},{"key":"73556_CR65","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.1007\/s10096-010-0984-1","volume":"10","author":"H Syrj\u00e4l\u00e4","year":"2010","unstructured":"Syrj\u00e4l\u00e4, H. et al. Blood stream infections during chemotherapy-induced neutropenia in adult patients with acute myeloid leukemia: treatment cycle matters. Eur. J. Clin. Microbiol. Infect. Dis. 10, 1211\u20131218 (2010).","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"73556_CR66","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1038\/bmt.2009.187","volume":"3","author":"C Orasch","year":"2010","unstructured":"Orasch, C. et al. Comparison of infectious complications during induction\/consolidation chemotherapy versus allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 3, 521\u2013526 (2010).","journal-title":"Bone Marrow Transplant."},{"key":"73556_CR67","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1007\/s15010-013-0525-9","volume":"1","author":"L Nesher","year":"2014","unstructured":"Nesher, L. & Rolston, K. V. The current spectrum of infection in cancer patients with chemotherapy related neutropenia. Infection 1, 5\u201313 (2014).","journal-title":"Infection"},{"key":"73556_CR68","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1016\/j.ajic.2013.03.299","volume":"11","author":"KY Ibrahim","year":"2013","unstructured":"Ibrahim, K. Y. et al. Health care-associated infections in hematology-oncology patients with neutropenia: a method of surveillance. Am. J. Infect. Control 11, 1131\u20131133 (2013).","journal-title":"Am. J. Infect. Control"},{"key":"73556_CR69","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1016\/0959-8049(94)90412-X","volume":"4","author":"C Viscoli","year":"1994","unstructured":"Viscoli, C. et al. Factors associated with bacteraemia in febrile, granulocytopenic cancer patients. The International Antimicrobial Therapy Cooperative Group (IATCG) of the European Organization for Research and Treatment of Cancer (EORTC). Eur. J. Cancer 4, 430\u2013437 (1994).","journal-title":"Eur. J. Cancer"},{"key":"73556_CR70","doi-asserted-by":"publisher","first-page":"1584","DOI":"10.1038\/s41598-019-38505-x","volume":"9","author":"M Faraldi","year":"2019","unstructured":"Faraldi, M. et al. Normalization strategies differently affect circulating miRNA profile associated with the training status. Sci. Rep. 9, 1584 (2019).","journal-title":"Sci. Rep."},{"key":"73556_CR71","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1038\/ncb2210","volume":"4","author":"KC Vickers","year":"2011","unstructured":"Vickers, K. C. et al. MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nat. Cell Biol. 4, 423\u2013433 (2011).","journal-title":"Nat. Cell Biol."},{"key":"73556_CR72","doi-asserted-by":"publisher","first-page":"2638","DOI":"10.1158\/1055-9965.EPI-14-0503","volume":"12","author":"E Miotto","year":"2014","unstructured":"Miotto, E. et al. Quantification of circulating miRNAs by droplet digital PCR: comparison of EvaGreen- and TaqMan-based chemistries. Cancer Epidemiol. Biomark. Prev. 12, 2638\u20132642 (2014).","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"73556_CR73","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1111\/jcmm.12236","volume":"3","author":"L Moldovan","year":"2014","unstructured":"Moldovan, L. et al. Methodological challenges in utilizing miRNAs as circulating biomarkers. J. Cell Mol. Med. 3, 371\u2013390 (2014).","journal-title":"J. Cell Mol. Med."},{"key":"73556_CR74","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1213\/ANE.0000000000002444","volume":"2","author":"S Kreth","year":"2018","unstructured":"Kreth, S., H\u00fcbner, M. & Hinske, L. C. MicroRNAs as clinical biomarkers and therapeutic tools in perioperative medicine. Anesth Analg. 2, 670\u2013681 (2018).","journal-title":"Anesth Analg."},{"key":"73556_CR75","doi-asserted-by":"publisher","first-page":"916","DOI":"10.1086\/605443","volume":"6","author":"B Xiao","year":"2009","unstructured":"Xiao, B. et al. Induction of microRNA-155 during Helicobacter pylori infection and its negative regulatory role in the inflammatory response. J. Infect. Dis. 6, 916\u2013925 (2009).","journal-title":"J. Infect. Dis."},{"key":"73556_CR76","doi-asserted-by":"publisher","first-page":"984","DOI":"10.1093\/annonc\/mdm571","volume":"5","author":"O Penack","year":"2008","unstructured":"Penack, O., Rempf, P., Graf, B., Blau, I. W. & Thiel, E. Aspergillus galactomannan testing in patients with long-term neutropenia: implications for clinical management. Ann. Oncol. 5, 984\u2013989 (2008).","journal-title":"Ann. Oncol."},{"key":"73556_CR77","doi-asserted-by":"publisher","first-page":"1417","DOI":"10.1086\/503427","volume":"15","author":"CD Pfeiffer","year":"2006","unstructured":"Pfeiffer, C. D., Fine, J. P. & Safdar, N. Diagnosis of invasive aspergillosis using a galactomannan assay: a meta-analysis. Clin. Infect. Dis. 15, 1417\u20131427 (2006).","journal-title":"Clin. Infect. Dis."},{"key":"73556_CR78","first-page":"149","volume":"3","author":"SA Sarrafzadeh","year":"2010","unstructured":"Sarrafzadeh, S. A. et al. The accuracy of serum galactomannan assay in diagnosing invasive pulmonary aspergillosis. Iran. J. Allergy Asthma Immunol. 3, 149\u2013155 (2010).","journal-title":"Iran. J. Allergy Asthma Immunol."},{"key":"73556_CR79","doi-asserted-by":"publisher","first-page":"1629","DOI":"10.1056\/NEJMoa1415236","volume":"17","author":"KM Kaukonen","year":"2015","unstructured":"Kaukonen, K. M., Bailey, M., Pilcher, D., Cooper, D. J. & Bellomo, R. Systemic inflammatory response syndrome criteria in defining severe sepsis. N. Engl. J. Med. 17, 1629\u20131638 (2015).","journal-title":"N. Engl. J. Med."},{"key":"73556_CR80","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1373\/jalm.2018.028472","volume":"4","author":"AB Chambliss","year":"2019","unstructured":"Chambliss, A. B., Butler-Wu, S. M. & Dien Bard, J. Diagnosis and management of sepsis and blood stream infections. J. Appl. Lab. Med. 4, 525\u2013526 (2019).","journal-title":"J. Appl. Lab. Med."},{"key":"73556_CR81","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1016\/S1473-3099(04)01205-8","volume":"12","author":"RP Peters","year":"2004","unstructured":"Peters, R. P., van Agtmael, M. A., Danner, S. A., Savelkoul, P. H. & Vandenbroucke-Grauls, C. M. New developments in the diagnosis of bloodstream infections. Lancet Infect. Dis. 12, 751\u2013760 (2004).","journal-title":"Lancet Infect. Dis."},{"key":"73556_CR82","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1128\/CMR.00043-09","volume":"1","author":"N Mancini","year":"2010","unstructured":"Mancini, N. et al. The era of molecular and other non-culture-based methods in diagnosis of sepsis. Clin. Microbiol. Rev. 1, 235\u2013251 (2010).","journal-title":"Clin. Microbiol. Rev."},{"key":"73556_CR83","doi-asserted-by":"publisher","first-page":"1168","DOI":"10.1038\/sj.bjc.6606076","volume":"7","author":"HE Gee","year":"2011","unstructured":"Gee, H. E. et al. The small-nucleolar RNAs commonly used for microRNA normalisation correlate with tumour pathology and prognosis. Br. J Cancer. 7, 1168\u20131177 (2011).","journal-title":"Br. J Cancer."},{"key":"73556_CR84","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1056\/NEJMoa061094","volume":"4","author":"OA Cornely","year":"2007","unstructured":"Cornely, O. A. et al. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N. Engl. J. Med. 4, 348\u2013359 (2007).","journal-title":"N. Engl. J. Med."},{"key":"73556_CR85","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1086\/321805","volume":"2","author":"CA Dykewicz","year":"2001","unstructured":"Dykewicz, C. A. Summary of the guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients. Clin. Infect. Dis. 2, 139\u2013144 (2001).","journal-title":"Clin. Infect. Dis."},{"key":"73556_CR86","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1056\/NEJM199203263261301","volume":"13","author":"JL Goodman","year":"1992","unstructured":"Goodman, J. L. et al. A controlled trial of fluconazole to prevent fungal infections in patients undergoing bone marrow transplantation. N. Engl. J. Med. 13, 845\u2013851 (1992).","journal-title":"N. Engl. J. Med."},{"key":"73556_CR87","doi-asserted-by":"publisher","first-page":"1813","DOI":"10.1086\/588660","volume":"12","author":"B De Pauw","year":"2008","unstructured":"De Pauw, B. et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer\/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC\/MSG) Consensus Group. Clin. Infect. Dis. 12, 1813\u20131821 (2008).","journal-title":"Clin. Infect. Dis."},{"key":"73556_CR88","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1097\/00003246-198905000-00002","volume":"5","author":"RC Bone","year":"1989","unstructured":"Bone, R. C. et al. Sepsis syndrome: a valid clinical entity. Methylprednisolone Severe Sepsis Study Group. Crit. Care Med. 5, 389\u2013393 (1989).","journal-title":"Crit. Care Med."},{"key":"73556_CR89","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1261\/rna.939908","volume":"5","author":"HJ Peltier","year":"2008","unstructured":"Peltier, H. J. & Latham, G. J. Normalization of microRNA expression levels in quantitative RT-PCR assays: identification of suitable reference RNA targets in normal and cancerous human solid tissues. RNA 5, 844\u2013852 (2008).","journal-title":"RNA"},{"key":"73556_CR90","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1186\/s12879-015-0995-8","volume":"15","author":"M Paholcsek","year":"2015","unstructured":"Paholcsek, M. et al. Combining standard clinical methods with PCR showed improved diagnosis of invasive pulmonary aspergillosis in patients with hematological malignancies and prolonged neutropenia. BMC Infect. Dis. 15, 251 (2015).","journal-title":"BMC Infect. Dis."},{"key":"73556_CR91","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/j.jinf.2010.06.018","volume":"3","author":"T Lehrnbecher","year":"2010","unstructured":"Lehrnbecher, T. et al. Trends in the postmortem epidemiology of invasive fungal infections at a university hospital. J. Infect. 3, 259\u2013265 (2010).","journal-title":"J. Infect."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-73556-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-73556-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-73556-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T20:15:17Z","timestamp":1670357717000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-73556-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,5]]},"references-count":91,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["73556"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-73556-5","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,5]]},"assertion":[{"value":"9 December 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 September 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 October 2020","order":3,"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"}}],"article-number":"16532"}}