{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T06:12:47Z","timestamp":1793686367822,"version":"4.5.1"},"reference-count":224,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,10,3]],"date-time":"2022-10-03T00:00:00Z","timestamp":1664755200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The human innate and adaptive immune systems consist of effector cells producing cytokines (interleukins, interferons, chemokines, and numerous other mediators). Usually, a fragile equilibrium of pro- and anti-inflammation effects is maintained by complex regulatory mechanisms. Disturbances of this homeostasis can lead to intricate chain reactions resulting in a massive release of cytokines. This may result in a drastic self-reinforcement of various feedback mechanisms, which can ultimately lead to systemic damage, multi-organ failure, or death. Not only pathogens can initiate such disturbances, but also congenital diseases or immunomodulatory therapies. Due to the complex and diverse interactions within the innate and adaptive immune systems, the understanding of this important clinical syndrome is incomplete to date and effective therapeutic approaches remain scarce.<\/jats:p>","DOI":"10.3390\/ijms231911740","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T23:39:31Z","timestamp":1665272371000},"page":"11740","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":316,"title":["Cytokine Storm\u2014Definition, Causes, and Implications"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0480-2089","authenticated-orcid":false,"given":"Dominik","family":"Jarczak","sequence":"first","affiliation":[{"name":"Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5493-7964","authenticated-orcid":false,"given":"Axel","family":"Nierhaus","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,3]]},"reference":[{"key":"ref_1","first-page":"1216","article-title":"Cytokine storm of graft-versus-host disease: A critical effector role for interleukin-1","volume":"25","author":"Ferrara","year":"1993","journal-title":"Transplant. Proc."},{"key":"ref_2","first-page":"121","article-title":"The anti-CD3-induced syndrome: A consequence of massive in vivo cell activation","volume":"174","author":"Chatenoud","year":"1991","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global, regional, and national sepsis incidence and mortality, 1990-2017: Analysis for the Global Burden of Disease Study","volume":"395","author":"Rudd","year":"2020","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1007\/s00281-017-0639-8","article-title":"Cytokine storm and sepsis disease pathogenesis","volume":"39","author":"Chousterman","year":"2017","journal-title":"Semin. Immunopathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2255","DOI":"10.1056\/NEJMra2026131","article-title":"Cytokine Storm","volume":"383","author":"Fajgenbaum","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1128\/MMBR.05015-11","article-title":"Into the eye of the cytokine storm","volume":"76","author":"Tisoncik","year":"2012","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2290","DOI":"10.1097\/CCM.0b013e3181a02afc","article-title":"Biomarkers of sepsis","volume":"37","author":"Marshall","year":"2009","journal-title":"Crit. Care Med."},{"key":"ref_8","first-page":"7","article-title":"Biomarkers for Sepsis: What Is and What Might Be?","volume":"10","author":"Biron","year":"2015","journal-title":"Biomark Insights"},{"key":"ref_9","first-page":"151","article-title":"Compartmentalization of the inflammatory response in sepsis and SIRS","volume":"12","author":"Cavaillon","year":"2006","journal-title":"J. Endotoxin. Res."},{"key":"ref_10","first-page":"145","article-title":"Circulating cytokines: The tip of the iceberg?","volume":"38","author":"Cavaillon","year":"1992","journal-title":"Circ. Shock."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1016\/j.jcrc.2014.06.014","article-title":"Usefulness of presepsin (sCD14 subtype) measurements as a new marker for the diagnosis and prediction of disease severity of sepsis in the Korean population","volume":"29","author":"Kweon","year":"2014","journal-title":"J. Crit. Care"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1016\/j.ajem.2017.12.038","article-title":"The utility of presepsin in diagnosis and risk stratification for the emergency patients with sepsis","volume":"36","author":"Lu","year":"2018","journal-title":"Am. J. Emerg. Med."},{"key":"ref_13","first-page":"175","article-title":"Diagnostic value of sTREM-1 and procalcitonin levels in the early diagnosis of sepsis","volume":"3","author":"Aksaray","year":"2016","journal-title":"N. Clin. Istanb."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1080\/1354750X.2016.1204005","article-title":"Soluble TREM-1 as a diagnostic and prognostic biomarker in patients with septic shock: An observational clinical study","volume":"22","author":"Brenner","year":"2017","journal-title":"Biomarkers"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1556\/1886.2016.00011","article-title":"Role of suPAR and Lactic Acid in Diagnosing Sepsis and Predicting Mortality in Elderly Patients","volume":"6","author":"Khater","year":"2016","journal-title":"Eur. J. Microbiol. Immunol. (Bp.)"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"79","DOI":"10.5847\/wjem.j.1920-8642.2020.02.003","article-title":"Effect of neutrophil CD64 for diagnosing sepsis in emergency department","volume":"11","author":"Yin","year":"2020","journal-title":"World J. Emerg. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1080\/00365513.2019.1703216","article-title":"Calprotectin is superior to procalcitonin as a sepsis marker and predictor of 30-day mortality in intensive care patients","volume":"80","author":"Larsson","year":"2020","journal-title":"Scand. J. Clin. Lab. Investig."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1097\/SHK.0000000000001023","article-title":"Procalcitonin and MR-Proadrenomedullin Combination with SOFA and qSOFA Scores for Sepsis Diagnosis and Prognosis: A Diagnostic Algorithm","volume":"50","author":"Spoto","year":"2018","journal-title":"Shock"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Hamed, S., Behnes, M., Pauly, D., Lepiorz, D., Barre, M., Becher, T., Lang, S., Akin, I., Borggrefe, M., and Bertsch, T. (2017). Diagnostic value of Pentraxin-3 in patients with sepsis and septic shock in accordance with latest sepsis-3 definitions. BMC Infect. Dis., 17.","DOI":"10.1186\/s12879-017-2606-3"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1007\/s11739-015-1268-7","article-title":"Usefulness of suPAR in the risk stratification of patients with sepsis admitted to the emergency department","volume":"10","author":"Casagranda","year":"2015","journal-title":"Intern. Emerg. Med."},{"key":"ref_21","first-page":"933","article-title":"Significance of high mobility group box 1, von Willebrand factor and other cytokines in the evaluation of severity and prognosis of sepsis patients","volume":"32","author":"Chen","year":"2020","journal-title":"Zhonghua Wei Zhong Bing Ji Jiu Yi Xue"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s13613-017-0238-9","article-title":"Superior accuracy of mid-regional proadrenomedullin for mortality prediction in sepsis with varying levels of illness severity","volume":"7","author":"Nguyen","year":"2017","journal-title":"Ann. Intensive Care"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"454","DOI":"10.3343\/alm.2019.39.5.454","article-title":"Circulating Biologically Active Adrenomedullin Predicts Organ Failure and Mortality in Sepsis","volume":"39","author":"Kim","year":"2019","journal-title":"Ann. Lab. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"155029","DOI":"10.1016\/j.cyto.2020.155029","article-title":"The ratio of plasma angiopoietin-2 to angiopoietin-1 as a prognostic biomarker in patients with sepsis","volume":"129","author":"Seol","year":"2020","journal-title":"Cytokine"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1186\/s13054-015-1075-6","article-title":"Prognostic significance of the angiopoietin-2\/angiopoietin-1 and angiopoietin-1\/Tie-2 ratios for early sepsis in an emergency department","volume":"19","author":"Fang","year":"2015","journal-title":"Crit. Care"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1182\/blood-2014-05-552729","article-title":"Current concepts in the diagnosis and management of cytokine release syndrome","volume":"124","author":"Lee","year":"2014","journal-title":"Blood"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.bbmt.2018.12.758","article-title":"ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells","volume":"25","author":"Lee","year":"2019","journal-title":"Biol. Blood Marrow Transpl."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1182\/blood.2019003618","article-title":"The earlier the better: Timely mitigation of CRS","volume":"134","author":"Rouce","year":"2019","journal-title":"Blood"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1152\/physrev.00037.2012","article-title":"Sepsis: Multiple abnormalities, heterogeneous responses, and evolving understanding","volume":"93","author":"Iskander","year":"2013","journal-title":"Physiol. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"796","DOI":"10.3389\/fimmu.2020.00796","article-title":"Concurrent Immune Suppression and Hyperinflammation in Patients With Community-Acquired Pneumonia","volume":"11","author":"Brands","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1080\/00365540310015935","article-title":"Cytokine cascade in sepsis","volume":"35","author":"Cavaillon","year":"2003","journal-title":"Scand. J. Infect. Dis."},{"key":"ref_32","first-page":"1264","article-title":"Towards precision medicine in sepsis: A position paper from the European Society of Clinical Microbiology and Infectious Diseases","volume":"24","author":"Rello","year":"2018","journal-title":"Clin. Microbiol. Infect. Off. Publ. Eur. Soc. Clin. Microbiol. Infect. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1517\/17425255.2011.558190","article-title":"Eritoran tetrasodium (E5564) treatment for sepsis: Review of preclinical and clinical studies","volume":"7","author":"Barochia","year":"2011","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1001\/archinte.167.15.1655","article-title":"Understanding the inflammatory cytokine response in pneumonia and sepsis: Results of the Genetic and Inflammatory Markers of Sepsis (GenIMS) Study","volume":"167","author":"Kellum","year":"2007","journal-title":"Arch. Intern. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2450","DOI":"10.1016\/j.immuni.2021.10.012","article-title":"The immunology of sepsis","volume":"54","author":"Wiersinga","year":"2021","journal-title":"Immunity"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"15353702221090454","DOI":"10.1177\/15353702221090454","article-title":"Hyperinflammation, apoptosis, and organ damage","volume":"247","author":"Kuypers","year":"2022","journal-title":"Exp. Biol. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1182\/blood.2019000931","article-title":"Overview of Castleman disease","volume":"135","author":"Dispenzieri","year":"2020","journal-title":"Blood"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1146\/annurev-pathol-011110-130327","article-title":"The pathogenesis of sepsis","volume":"6","author":"Osuchowski","year":"2011","journal-title":"Annu. Rev. Pathol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1182\/blood-2010-12-324533","article-title":"Perforin is a critical physiologic regulator of T-cell activation","volume":"118","author":"Lykens","year":"2011","journal-title":"Blood"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"628302","DOI":"10.3389\/fmed.2021.628302","article-title":"Sepsis-Pathophysiology and Therapeutic Concepts","volume":"8","author":"Jarczak","year":"2021","journal-title":"Front. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1684\/ecn.2011.0281","article-title":"Pro- and anti-inflammatory responses are regulated simultaneously from the first moments of septic shock","volume":"22","author":"Tamayo","year":"2011","journal-title":"Eur. Cytokine Netw."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"16045","DOI":"10.1038\/nrdp.2016.45","article-title":"Sepsis and septic shock","volume":"2","author":"Hotchkiss","year":"2016","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Walton, A.H., Muenzer, J.T., Rasche, D., Boomer, J.S., Sato, B., Brownstein, B.H., Pachot, A., Brooks, T.L., Deych, E., and Shannon, W.D. (2014). Reactivation of multiple viruses in patients with sepsis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0098819"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1038\/nri3552","article-title":"Sepsis-induced immunosuppression: From cellular dysfunctions to immunotherapy","volume":"13","author":"Hotchkiss","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"85","DOI":"10.3389\/fcvm.2019.00085","article-title":"Platelet-Neutrophil Interplay: Insights Into Neutrophil Extracellular Trap (NET)-Driven Coagulation in Infection","volume":"6","author":"Zucoloto","year":"2019","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2689","DOI":"10.4049\/jimmunol.1201719","article-title":"Neutrophil extracellular traps: Double-edged swords of innate immunity","volume":"189","author":"Kaplan","year":"2012","journal-title":"J. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"365","DOI":"10.3389\/fimmu.2012.00365","article-title":"A NET Outcome","volume":"3","author":"Lu","year":"2012","journal-title":"Front. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Czaikoski, P.G., Mota, J.M., Nascimento, D.C., Sonego, F., Castanheira, F.V., Melo, P.H., Scortegagna, G.T., Silva, R.L., Barroso-Sousa, R., and Souto, F.O. (2016). Neutrophil Extracellular Traps Induce Organ Damage during Experimental and Clinical Sepsis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0148142"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1016\/j.chest.2018.03.058","article-title":"Multicentric Standardized Flow Cytometry Routine Assessment of Patients With Sepsis to Predict Clinical Worsening","volume":"154","author":"Daix","year":"2018","journal-title":"Chest"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Cox, L.E., Walstein, K., Vollger, L., Reuner, F., Bick, A., Dotsch, A., Engler, A., Peters, J., von Kockritz-Blickwede, M., and Schafer, S.T. (2020). Neutrophil extracellular trap formation and nuclease activity in septic patients. BMC Anesthesiol., 20.","DOI":"10.1186\/s12871-019-0911-7"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Keshari, R.S., Jyoti, A., Dubey, M., Kothari, N., Kohli, M., Bogra, J., Barthwal, M.K., and Dikshit, M. (2012). Cytokines induced neutrophil extracellular traps formation: Implication for the inflammatory disease condition. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0048111"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4154","DOI":"10.1111\/j.1582-4934.2009.00893.x","article-title":"Sepsis, complement and the dysregulated inflammatory response","volume":"13","author":"Ward","year":"2009","journal-title":"J. Cell. Mol. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1038\/ni.1923","article-title":"Complement: A key system for immune surveillance and homeostasis","volume":"11","author":"Ricklin","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1111\/sji.12580","article-title":"Complement C5a-Induced Changes in Neutrophil Morphology During Inflammation","volume":"86","author":"Denk","year":"2017","journal-title":"Scand. J. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"312","DOI":"10.3389\/fimmu.2018.00312","article-title":"Interaction of the Human Contact System with Pathogens-An Update","volume":"9","author":"Kohler","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/nri3345","article-title":"Thrombosis as an intravascular effector of innate immunity","volume":"13","author":"Engelmann","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2367","DOI":"10.1182\/blood-2009-05-199208","article-title":"Coagulation and innate immune responses: Can we view them separately?","volume":"114","author":"Delvaeye","year":"2009","journal-title":"Blood"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1055\/s-0037-1616068","article-title":"Scientific Subcommittee on Disseminated Intravascular Coagulation (DIC) of the International Society on Thrombosis and Haemostasis (ISTH). Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation","volume":"86","author":"Taylor","year":"2001","journal-title":"Thromb. Haemost."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1055\/s-0039-1694995","article-title":"Sepsis-Induced Coagulopathy and Disseminated Intravascular Coagulation","volume":"46","author":"Iba","year":"2020","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1097\/SHK.0000000000000473","article-title":"The Endothelium in Sepsis","volume":"45","author":"Ince","year":"2016","journal-title":"Shock"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1161\/ATVBAHA.117.309846","article-title":"Tissue Factor: An Essential Mediator of Hemostasis and Trigger of Thrombosis","volume":"38","author":"Grover","year":"2018","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1186\/s13054-019-2478-6","article-title":"Frequency and mortality of septic shock in Europe and North America: A systematic review and meta-analysis","volume":"23","author":"Vincent","year":"2019","journal-title":"Crit. Care"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1078\/1438-4221-00232","article-title":"Staphylococcal and streptococcal superantigens: Molecular, biological and clinical aspects","volume":"292","author":"Alouf","year":"2003","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_65","unstructured":"Ferretti, J.J., Stevens, D.L., and Fischetti, V.A. (2016). Streptococcal Superantigens: Biological properties and potential role in disease. Streptococcus Pyogenes: Basic Biology to Clinical Manifestations, University of Oklahoma City Science Center."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1016\/S0140-6736(05)65800-X","article-title":"Detection of circulating bacterial superantigen and lymphotoxin-alpha in patients with streptococcal toxic-shock syndrome","volume":"348","author":"Sriskandan","year":"1996","journal-title":"Lancet"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2492","DOI":"10.4049\/jimmunol.1501284","article-title":"A Heterozygous RAB27A Mutation Associated with Delayed Cytolytic Granule Polarization and Hemophagocytic Lymphohistiocytosis","volume":"196","author":"Zhang","year":"2016","journal-title":"J. Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"5184","DOI":"10.1182\/blood-2013-04-495309","article-title":"Perforin deficiency impairs a critical immunoregulatory loop involving murine CD8(+) T cells and dendritic cells","volume":"121","author":"Terrell","year":"2013","journal-title":"Blood"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e67","DOI":"10.1161\/CIR.0000000000000558","article-title":"Heart Disease and Stroke Statistics-2018 Update: A Report From the American Heart Association","volume":"137","author":"Benjamin","year":"2018","journal-title":"Circulation"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1001\/jama.300.12.1423","article-title":"Regional variation in out-of-hospital cardiac arrest incidence and outcome","volume":"300","author":"Nichol","year":"2008","journal-title":"JAMA"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.resuscitation.2008.09.017","article-title":"Post-cardiac arrest syndrome: Epidemiology, pathophysiology, treatment, and prognostication. A Scientific Statement from the International Liaison Committee on Resuscitation; the American Heart Association Emergency Cardiovascular Care Committee; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care; the Council on Clinical Cardiology; the Council on Stroke","volume":"79","author":"Nolan","year":"2008","journal-title":"Resuscitation"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1161\/01.CIR.0000023891.80661.AD","article-title":"Successful cardiopulmonary resuscitation after cardiac arrest as a \u201csepsis-like\u201d syndrome","volume":"106","author":"Adrie","year":"2002","journal-title":"Circulation"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.resuscitation.2016.01.006","article-title":"Inflammatory markers following resuscitation from out-of-hospital cardiac arrest-A prospective multicenter observational study","volume":"103","author":"Peberdy","year":"2016","journal-title":"Resuscitation"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/0006-8993(93)90400-H","article-title":"Trophic effects of interleukin-4, -7 and -8 on hippocampal neuronal cultures: Potential involvement of glial-derived factors","volume":"600","author":"Araujo","year":"1993","journal-title":"Brain Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.resuscitation.2016.08.006","article-title":"Endothelial activation\/injury and associations with severity of post-cardiac arrest syndrome and mortality after out-of-hospital cardiac arrest","volume":"107","author":"Johansson","year":"2016","journal-title":"Resuscitation"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1089\/jir.2009.0035","article-title":"Cardiac function and the proinflammatory cytokine response after recovery from cardiac arrest in swine","volume":"29","author":"Niemann","year":"2009","journal-title":"J. Interferon Cytokine Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1016\/j.resuscitation.2013.01.004","article-title":"Procalcitonin after cardiac arrest\u2014An indicator of severity of illness, ischemia-reperfusion injury and outcome","volume":"84","author":"Annborn","year":"2013","journal-title":"Resuscitation"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s13054-015-0741-z","article-title":"Glycocalyx and sepsis-induced alterations in vascular permeability","volume":"19","author":"Chelazzi","year":"2015","journal-title":"Crit. Care"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"332","DOI":"10.7326\/0003-4819-114-4-332","article-title":"Sepsis, the sepsis syndrome, multi-organ failure: A plea for comparable definitions","volume":"114","author":"Bone","year":"1991","journal-title":"Ann. Intern. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1146\/annurev.me.38.020187.002221","article-title":"Endotoxins and disease mechanisms","volume":"38","author":"Morrison","year":"1987","journal-title":"Annu. Rev. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1128\/CMR.13.1.144","article-title":"Update on meningococcal disease with emphasis on pathogenesis and clinical management","volume":"13","author":"Brandtzaeg","year":"2000","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1182\/blood.V77.8.1627.1627","article-title":"Interleukin-1 and interleukin-1 antagonism","volume":"77","author":"Dinarello","year":"1991","journal-title":"Blood"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/nrmicro1068","article-title":"LPS, TLR4 and infectious disease diversity","volume":"3","author":"Miller","year":"2005","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1002\/glia.20467","article-title":"Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration","volume":"55","author":"Qin","year":"2007","journal-title":"Glia"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"H2281","DOI":"10.1152\/ajpheart.2001.280.5.H2281","article-title":"Effects of soluble TNF receptor treatment on lipopolysaccharide-induced myocardial cytokine expression","volume":"280","author":"Kadokami","year":"2001","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1006\/cyto.1995.0004","article-title":"Complementary organ expression of IL-1 vs. IL-6 and CSF-1 activities in normal and LPS-injected mice","volume":"8","author":"Hacham","year":"1996","journal-title":"Cytokine"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1056\/NEJM199305203282005","article-title":"Brief report: Shock and multiple-organ dysfunction after self-administration of Salmonella endotoxin","volume":"328","author":"Kaulbach","year":"1993","journal-title":"N. Engl. J. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"e002892","DOI":"10.1161\/CIRCGEN.119.002892","article-title":"SOS1 Gain-of-Function Variants in Dilated Cardiomyopathy","volume":"13","author":"Cowan","year":"2020","journal-title":"Circ. Genom. Precis. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1126\/science.1698311","article-title":"CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein","volume":"249","author":"Wright","year":"1990","journal-title":"Science"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Feng, C., Stamatos, N.M., Dragan, A.I., Medvedev, A., Whitford, M., Zhang, L., Song, C., Rallabhandi, P., Cole, L., and Nhu, Q.M. (2012). Sialyl residues modulate LPS-mediated signaling through the Toll-like receptor 4 complex. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0032359"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.cyto.2008.01.006","article-title":"LPS\/TLR4 signal transduction pathway","volume":"42","author":"Lu","year":"2008","journal-title":"Cytokine"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1093\/infdis\/172.2.433","article-title":"Correlation between proinflammatory cytokines and antiinflammatory mediators and the severity of disease in meningococcal infections","volume":"172","author":"Bartelink","year":"1995","journal-title":"J. Infect. Dis."},{"key":"ref_93","first-page":"401","article-title":"Neisseria meningitidis lipopolysaccharides in human pathology","volume":"7","author":"Brandtzaeg","year":"2001","journal-title":"J. Endotoxin. Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1084\/jem.184.1.51","article-title":"Net inflammatory capacity of human septic shock plasma evaluated by a monocyte-based target cell assay: Identification of interleukin-10 as a major functional deactivator of human monocytes","volume":"184","author":"Brandtzaeg","year":"1996","journal-title":"J. Exp. Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1086\/427514","article-title":"Chemokine patterns in meningococcal disease","volume":"191","author":"Moller","year":"2005","journal-title":"J. Infect. Dis."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1046\/j.1365-2249.2002.01953.x","article-title":"The dual function of the splenic marginal zone: Essential for initiation of anti-TI-2 responses but also vital in the general first-line defense against blood-borne antigens","volume":"130","author":"Zandvoort","year":"2002","journal-title":"Clin. Exp. Immunol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1111\/j.1365-2141.2011.08843.x","article-title":"British Committee for Standards in Health Care, Review of guidelines for the prevention and treatment of infection in patients with an absent or dysfunctional spleen: Prepared on behalf of the British Committee for Standards in Haematology by a working party of the Haemato-Oncology task force","volume":"155","author":"Davies","year":"2011","journal-title":"Br. J. Haematol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2839","DOI":"10.2147\/IDR.S179902","article-title":"Post-splenectomy sepsis: Preventative strategies, challenges, and solutions","volume":"12","author":"Luu","year":"2019","journal-title":"Infect. Drug Resist."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"11008","DOI":"10.1073\/pnas.0803237105","article-title":"Splenic nerve is required for cholinergic antiinflammatory pathway control of TNF in endotoxemia","volume":"105","author":"Ochani","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1084\/jem.20052362","article-title":"Splenectomy inactivates the cholinergic antiinflammatory pathway during lethal endotoxemia and polymicrobial sepsis","volume":"203","author":"Huston","year":"2006","journal-title":"J. Exp. Med."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Cameron, P.U., Jones, P., Gorniak, M., Dunster, K., Paul, E., Lewin, S., Woolley, I., and Spelman, D. (2011). Splenectomy associated changes in IgM memory B cells in an adult spleen registry cohort. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0023164"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1128\/iai.65.6.2299-2305.1997","article-title":"The decrease in nonsplenic interleukin-6 (IL-6) production after splenectomy indicates the existence of a positive feedback loop of IL-6 production during endotoxemia in dogs","volume":"65","author":"Moeniralam","year":"1997","journal-title":"Infect. Immun."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1159\/000129522","article-title":"The role of splenic macrophages in plasma tumor necrosis factor levels in endotoxemia","volume":"29","author":"Kohno","year":"1997","journal-title":"Eur. Surg. Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S0039-6109(16)42339-X","article-title":"Postsplenectomy infection","volume":"61","author":"Francke","year":"1981","journal-title":"Surg. Clin. N. Am."},{"key":"ref_105","unstructured":"Lyczko, K., and Borger, J. (2021). Meningococcal Prophylaxis. StatPearls, StatPearls Publishing."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.molmed.2014.08.002","article-title":"Invasive meningococcal disease: A disease of the endothelial cells","volume":"20","author":"Coureuil","year":"2014","journal-title":"Trends Mol. Med."},{"key":"ref_107","first-page":"1971289","article-title":"Global epidemiology and changing clinical presentations of invasive meningococcal disease: A narrative review","volume":"54","author":"Deghmane","year":"2021","journal-title":"Infect. Dis."},{"key":"ref_108","first-page":"E116","article-title":"Epidemiology of Neisseria meningitidis infections: Case distribution by age and relevance of carriage","volume":"56","author":"Gabutti","year":"2015","journal-title":"J. Prev. Med. Hyg."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1016\/S1473-3099(15)00217-0","article-title":"Global incidence of serogroup B invasive meningococcal disease: A systematic review","volume":"15","author":"Sridhar","year":"2015","journal-title":"Lancet Infect. Dis."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2507","DOI":"10.1016\/j.vaccine.2018.03.087","article-title":"A rare case of septic shock due to Neisseria meningitidis serogroup B infection despite prior vaccination in a young adult with paroxysmal nocturnal haemoglobinuria receiving eculizumab","volume":"36","author":"Reher","year":"2018","journal-title":"Vaccine"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1084\/jem.169.1.333","article-title":"The complex pattern of cytokines in serum from patients with meningococcal septic shock. Association between interleukin 6, interleukin 1, and fatal outcome","volume":"169","author":"Waage","year":"1989","journal-title":"J. Exp. Med."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1111\/j.1365-3083.1986.tb02194.x","article-title":"Detection of tumour necrosis factor-like cytotoxicity in serum from patients with septicaemia but not from untreated cancer patients","volume":"24","author":"Waage","year":"1986","journal-title":"Scand. J. Immunol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1056\/NEJM198808183190703","article-title":"Tumor necrosis factor and interleukin-1 in the serum of children with severe infectious purpura","volume":"319","author":"Girardin","year":"1988","journal-title":"N. Engl. J. Med."},{"key":"ref_114","first-page":"20","article-title":"Imbalance between tumour necrosis factor-alpha and soluble TNF receptor concentrations in severe meningococcaemia. The J5 Study Group","volume":"76","author":"Girardin","year":"1992","journal-title":"Immunology"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1182\/blood.V90.3.1101","article-title":"The pattern of interleukin-1beta (IL-1beta) and its modulating agents IL-1 receptor antagonist and IL-1 soluble receptor type II in acute meningococcal infections","volume":"90","author":"Vannier","year":"1997","journal-title":"Blood"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1136\/adc.75.5.453","article-title":"Proinflammatory and anti-inflammatory cytokines in meningococcal disease","volume":"75","author":"Riordan","year":"1996","journal-title":"Arch. Dis. Child"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"a012393","DOI":"10.1101\/cshperspect.a012393","article-title":"Pathogenesis of meningococcemia","volume":"3","author":"Coureuil","year":"2013","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Bille, E., Ure, R., Gray, S.J., Kaczmarski, E.B., McCarthy, N.D., Nassif, X., Maiden, M.C., and Tinsley, C.R. (2008). Association of a bacteriophage with meningococcal disease in young adults. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0003885"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1808","DOI":"10.1080\/21505594.2017.1391446","article-title":"Peripheral blood vessels are a niche for blood-borne meningococci","volume":"8","author":"Capel","year":"2017","journal-title":"Virulence"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1093\/femsre\/fuu001","article-title":"Exceptionally widespread nanomachines composed of type IV pilins: The prokaryotic Swiss Army knives","volume":"39","author":"Berry","year":"2015","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"127","DOI":"10.5802\/crbiol.56","article-title":"Meningococcus, this famous unknown","volume":"344","author":"Ziveri","year":"2021","journal-title":"C. R. Biol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1038\/nm.3563","article-title":"Pathogenic Neisseria meningitidis utilizes CD147 for vascular colonization","volume":"20","author":"Bernard","year":"2014","journal-title":"Nat. Med."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Xiong, L., Edwards, C.K., and Zhou, L. (2014). The biological function and clinical utilization of CD147 in human diseases: A review of the current scientific literature. Int. J. Mol. Sci., 15.","DOI":"10.3390\/ijms151017411"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.1002\/pro.3519","article-title":"The molecular details of cytokine signaling via the JAK\/STAT pathway","volume":"27","author":"Morris","year":"2018","journal-title":"Protein. Sci."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1002\/jmv.20255","article-title":"An interferon-gamma-related cytokine storm in SARS patients","volume":"75","author":"Huang","year":"2005","journal-title":"J. Med. Virol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.resp.2010.11.004","article-title":"Three fatal cases of pandemic 2009 influenza A virus infection in Shenzhen are associated with cytokine storm","volume":"175","author":"Cheng","year":"2011","journal-title":"Respir. Physiol. Neurobiol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1164\/rccm.201311-2071OC","article-title":"Low titers of serum antibodies inhibiting hemagglutination predict fatal fulminant influenza A(H1N1) 2009 infection","volume":"189","author":"Guihot","year":"2014","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1093\/infdis\/jis452","article-title":"Host cytokine storm is associated with disease severity of severe fever with thrombocytopenia syndrome","volume":"206","author":"Sun","year":"2012","journal-title":"J. Infect. Dis."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1007\/s11010-021-04326-8","article-title":"Integrated view of molecular diagnosis and prognosis of dengue viral infection: Future prospect of exosomes biomarkers","volume":"477","author":"Rana","year":"2022","journal-title":"Mol. Cell. Biochem."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Mandala, W.L., Msefula, C.L., Gondwe, E.N., Drayson, M.T., Molyneux, M.E., and MacLennan, C.A. (2017). Cytokine Profiles in Malawian Children Presenting with Uncomplicated Malaria, Severe Malarial Anemia, and Cerebral Malaria. Clin. Vaccine Immunol. CVI, 24.","DOI":"10.1128\/CVI.00533-16"},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Santos-Oliveira, J.R., Regis, E.G., Leal, C.R., Cunha, R.V., Bozza, P.T., and Da-Cruz, A.M. (2011). Evidence that lipopolisaccharide may contribute to the cytokine storm and cellular activation in patients with visceral leishmaniasis. PLoS Negl. Trop. Dis., 5.","DOI":"10.1371\/journal.pntd.0001198"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1056\/NEJMc2011400","article-title":"Multiorgan and Renal Tropism of SARS-CoV-2","volume":"383","author":"Puelles","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"593223","DOI":"10.3389\/fphys.2021.593223","article-title":"Pathogenesis of Multiple Organ Injury in COVID-19 and Potential Therapeutic Strategies","volume":"12","author":"Silva","year":"2021","journal-title":"Front. Physiol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1097\/SHK.0000000000001769","article-title":"Cytokine Drizzle-The Rationale for Abandoning \u201cCytokine Storm\u201d","volume":"56","author":"Stolarski","year":"2021","journal-title":"Shock"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"e140329","DOI":"10.1172\/jci.insight.140329","article-title":"Severe immunosuppression and not a cytokine storm characterizes COVID-19 infections","volume":"5","author":"Remy","year":"2020","journal-title":"JCI Insight"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1001\/jama.2020.17052","article-title":"Cytokine Levels in Critically Ill Patients With COVID-19 and Other Conditions","volume":"324","author":"Kox","year":"2020","journal-title":"JAMA"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1515\/cclm-2020-1761","article-title":"Cytokine \u201cstorm\u201d, cytokine \u201cbreeze\u201d, or both in COVID-19?","volume":"59","author":"Lippi","year":"2020","journal-title":"Clin. Chem. Lab Med."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.chom.2020.04.017","article-title":"Heightened Innate Immune Responses in the Respiratory Tract of COVID-19 Patients","volume":"27","author":"Zhou","year":"2020","journal-title":"Cell Host Microbe"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1080\/22221751.2020.1747363","article-title":"Transcriptomic characteristics of bronchoalveolar lavage fluid and peripheral blood mononuclear cells in COVID-19 patients","volume":"9","author":"Xiong","year":"2020","journal-title":"Emerg Microbes Infect."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1016\/S2213-2600(20)30404-5","article-title":"Cytokine elevation in severe and critical COVID-19: A rapid systematic review, meta-analysis, and comparison with other inflammatory syndromes","volume":"8","author":"Leisman","year":"2020","journal-title":"Lancet. Respir. Med."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"e754","DOI":"10.1016\/S2665-9913(20)30343-X","article-title":"Clinical criteria for COVID-19-associated hyperinflammatory syndrome: A cohort study","volume":"2","author":"Webb","year":"2020","journal-title":"Lancet Rheumatol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1056\/NEJMoa063842","article-title":"Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412","volume":"355","author":"Suntharalingam","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1097\/00007890-199110000-00018","article-title":"Evidence that pentoxifylline reduces anti-CD3 monoclonal antibody-induced cytokine release syndrome","volume":"52","author":"Alegre","year":"1991","journal-title":"Transplantation"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"2217","DOI":"10.1182\/blood.V94.7.2217.419k02_2217_2224","article-title":"Cytokine-release syndrome in patients with B-cell chronic lymphocytic leukemia and high lymphocyte counts after treatment with an anti-CD20 monoclonal antibody (rituximab, IDEC-C2B8)","volume":"94","author":"Winkler","year":"1999","journal-title":"Blood"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.retram.2017.08.003","article-title":"Chimeric antigen-receptor T-cell therapy for hematological malignancies and solid tumors: Clinical data to date, current limitations and perspectives","volume":"65","author":"Gauthier","year":"2017","journal-title":"Curr. Res. Transl. Med."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1056\/NEJMoa1215134","article-title":"Chimeric antigen receptor-modified T cells for acute lymphoid leukemia","volume":"368","author":"Grupp","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"2625","DOI":"10.1182\/blood-2013-11-492231","article-title":"Antibody-modified T cells: CARs take the front seat for hematologic malignancies","volume":"123","author":"Maus","year":"2014","journal-title":"Blood"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"303ra139","DOI":"10.1126\/scitranslmed.aac5415","article-title":"Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia","volume":"7","author":"Porter","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1007\/s005340200049","article-title":"Cytokine storm in acute pancreatitis","volume":"9","author":"Makhija","year":"2002","journal-title":"J. Hepatobiliary Pancreat. Surg"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/s41392-021-00764-4","article-title":"Signaling pathways in the regulation of cytokine release syndrome in human diseases and intervention therapy","volume":"6","author":"Li","year":"2021","journal-title":"Signal. Transduct. Target Ther."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.jinf.2016.01.010","article-title":"Defining immunological dysfunction in sepsis: A requisite tool for precision medicine","volume":"72","author":"Almansa","year":"2016","journal-title":"J. Infect."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"6952","DOI":"10.4049\/jimmunol.166.11.6952","article-title":"Sepsis-induced apoptosis causes progressive profound depletion of B and CD4+ T lymphocytes in humans","volume":"166","author":"Hotchkiss","year":"2001","journal-title":"J. Immunol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1002\/cytob.21123","article-title":"An extended leukocyte differential count (16 types of circulating leukocytes) using the cytodiff flow cytometric system can provide informations for the discrimination of sepsis severity and prediction of outcome in sepsis patients","volume":"86","author":"Park","year":"2013","journal-title":"Cytom. B Clin. Cytom."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"R105","DOI":"10.1186\/cc12750","article-title":"Early alterations of B cells in patients with septic shock","volume":"17","author":"Monserrat","year":"2013","journal-title":"Crit. Care"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1097\/SHK.0000000000001671","article-title":"Single Cell RNA-SEQ of Human Myeloid Derived Suppressor Cells in Late Sepsis Reveals Multiple Subsets with Unique Transcriptional Responses: A Pilot Study","volume":"55","author":"Darden","year":"2020","journal-title":"Shock"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.it.2004.03.007","article-title":"What is the importance of the immunological synapse?","volume":"25","author":"Davis","year":"2004","journal-title":"Trends Immunol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1836","DOI":"10.1007\/s00134-018-5389-0","article-title":"Early PREdiction of sepsis using leukocyte surface biomarkers: The ExPRES-sepsis cohort study","volume":"44","author":"Datta","year":"2018","journal-title":"Intens. Care Med."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.ebiom.2014.10.003","article-title":"An Endotoxin Tolerance Signature Predicts Sepsis and Organ Dysfunction at Initial Clinical Presentation","volume":"1","author":"Pena","year":"2014","journal-title":"EBioMedicine"},{"key":"ref_159","first-page":"26","article-title":"Depressed Monocytic Activity may be a Predictor for Sepsis","volume":"7","author":"Bhardwaj","year":"2015","journal-title":"J. Lab. Phys."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/nri.2017.36","article-title":"The immunopathology of sepsis and potential therapeutic targets","volume":"17","author":"Scicluna","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.immuni.2014.04.001","article-title":"Sepsis: Current dogma and new perspectives","volume":"40","author":"Deutschman","year":"2014","journal-title":"Immunity"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1097\/TA.0b013e318256e000","article-title":"Persistent inflammation and immunosuppression: A common syndrome and new horizon for surgical intensive care","volume":"72","author":"Gentile","year":"2012","journal-title":"J. Trauma Acute Care Surg."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1016\/S0140-6736(14)60687-5","article-title":"The systemic immune response to trauma: An overview of pathophysiology and treatment","volume":"384","author":"Lord","year":"2014","journal-title":"Lancet"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.virol.2010.12.003","article-title":"Influenza virus assembly and budding","volume":"411","author":"Rossman","year":"2011","journal-title":"Virology"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/nri3665","article-title":"Innate immunity to influenza virus infection","volume":"14","author":"Iwasaki","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1111\/imr.12101","article-title":"Interferon induction and function at the mucosal surface","volume":"255","author":"Durbin","year":"2013","journal-title":"Immunol. Rev."},{"key":"ref_167","doi-asserted-by":"crossref","unstructured":"Pothlichet, J., Meunier, I., Davis, B.K., Ting, J.P., Skamene, E., von Messling, V., and Vidal, S.M. (2013). Type I IFN triggers RIG-I\/TLR3\/NLRP3-dependent inflammasome activation in influenza A virus infected cells. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003256"},{"key":"ref_168","doi-asserted-by":"crossref","unstructured":"Gu, Y., Zuo, X., Zhang, S., Ouyang, Z., Jiang, S., Wang, F., and Wang, G. (2021). The Mechanism behind Influenza Virus Cytokine Storm. Viruses, 13.","DOI":"10.3390\/v13071362"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1159\/000484258","article-title":"Interferon-Stimulated Genes as Enhancers of Antiviral Innate Immune Signaling","volume":"10","author":"Crosse","year":"2018","journal-title":"J. Innate. Immun."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1146\/annurev-virology-092818-015756","article-title":"Interferon-Stimulated Genes: What Do They All Do?","volume":"6","author":"Schoggins","year":"2019","journal-title":"Annu. Rev. Virol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/j.chom.2016.05.016","article-title":"The Roles of Type I Interferon in Bacterial Infection","volume":"19","author":"Boxx","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"652","DOI":"10.3389\/fimmu.2016.00652","article-title":"Type I Interferons in Bacterial Infections: A Balancing Act","volume":"7","author":"Kovarik","year":"2016","journal-title":"Front. Immunol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1128\/microbiolspec.VMBF-0012-2015","article-title":"Bacterial Secretion Systems: An Overview","volume":"4","author":"Green","year":"2016","journal-title":"Microbiol. Spectr."},{"key":"ref_174","first-page":"68","article-title":"Immunosenescence and Challenges of Vaccination against Influenza in the Aging Population","volume":"3","author":"Reber","year":"2012","journal-title":"Aging Dis."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"1960","DOI":"10.3389\/fimmu.2017.01960","article-title":"Immunosenescence and Inflamm-Aging As Two Sides of the Same Coin: Friends or Foes?","volume":"8","author":"Fulop","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"aaq1564","DOI":"10.1126\/scitranslmed.aaq1564","article-title":"TORC1 inhibition enhances immune function and reduces infections in the elderly","volume":"10","author":"Mannick","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"9234","DOI":"10.18632\/aging.102438","article-title":"Age-associated changes in human CD4(+) T cells point to mitochondrial dysfunction consequent to impaired autophagy","volume":"11","author":"Bektas","year":"2019","journal-title":"Aging"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"100998","DOI":"10.1016\/j.arr.2019.100998","article-title":"Activation of immunosuppressive network in the aging process","volume":"57","author":"Salminen","year":"2020","journal-title":"Ageing Res. Rev."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"277","DOI":"10.14336\/AD.2020.0627","article-title":"Immune Cell Number, Phenotype, and Function in the Elderly with Sepsis","volume":"12","author":"He","year":"2021","journal-title":"Aging Dis."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1038\/s41569-018-0064-2","article-title":"Inflammageing: Chronic inflammation in ageing, cardiovascular disease, and frailty","volume":"15","author":"Ferrucci","year":"2018","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1038\/s41574-018-0059-4","article-title":"Inflammaging: A new immune-metabolic viewpoint for age-related diseases","volume":"14","author":"Franceschi","year":"2018","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1111\/j.1365-2567.2007.02555.x","article-title":"Immunosenescence: Emerging challenges for an ageing population","volume":"120","author":"Aw","year":"2007","journal-title":"Immunology"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/S1473-3099(02)00437-1","article-title":"Ageing and infection","volume":"2","author":"Gavazzi","year":"2002","journal-title":"Lancet. Infect. Dis."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1007\/s003910070031","article-title":"Infection in the elderly--what is different?","volume":"33","author":"Werner","year":"2000","journal-title":"Z. Gerontol. Geriatr."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1086\/427876","article-title":"Insights into severe sepsis in older patients: From epidemiology to evidence-based management","volume":"40","author":"Girard","year":"2005","journal-title":"Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.cger.2007.05.003","article-title":"Bacteremia and sepsis in older adults","volume":"23","author":"Girard","year":"2007","journal-title":"Clin. Geriatr. Med."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1086\/313896","article-title":"Fever in the elderly","volume":"31","author":"Norman","year":"2000","journal-title":"Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1038\/nri1943","article-title":"Apoptosis and caspases regulate death and inflammation in sepsis","volume":"6","author":"Hotchkiss","year":"2006","journal-title":"Nat. Rev. Immunol."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1111\/imr.12499","article-title":"The immune system\u2019s role in sepsis progression, resolution, and long-term outcome","volume":"274","author":"Delano","year":"2016","journal-title":"Immunol. Rev."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.arr.2014.12.002","article-title":"A review of the equine age-related changes in the immune system: Comparisons between human and equine aging, with focus on lung-specific immune-aging","volume":"20","author":"Hansen","year":"2015","journal-title":"Ageing Res. Rev."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.exger.2017.12.020","article-title":"Inflammation and neutrophil immunosenescence in health and disease: Targeted treatments to improve clinical outcomes in the elderly","volume":"105","author":"Drew","year":"2018","journal-title":"Exp. Gerontol."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/nrneph.2017.165","article-title":"Advances in the understanding and treatment of sepsis-induced immunosuppression","volume":"14","author":"Venet","year":"2018","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.exger.2014.01.007","article-title":"Elevated A20 contributes to age-dependent macrophage dysfunction in the lungs","volume":"54","author":"Hinojosa","year":"2014","journal-title":"Exp. Gerontol."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.humimm.2011.01.009","article-title":"Age-related changes in natural killer cell receptors from childhood through old age","volume":"72","author":"Porto","year":"2011","journal-title":"Hum. Immunol."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.exger.2014.01.008","article-title":"Effect of age and CMV on NK cell subpopulations","volume":"54","author":"Campos","year":"2014","journal-title":"Exp. Gerontol."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1742-4933-3-10","article-title":"Ageing is associated with a decline in peripheral blood CD56bright NK cells","volume":"3","author":"Chidrawar","year":"2006","journal-title":"Immun. Ageing"},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1111\/j.1474-9726.2010.00584.x","article-title":"Human NK cells display major phenotypic and functional changes over the life span","volume":"9","author":"Beziat","year":"2010","journal-title":"Aging Cell"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1111\/j.1474-9726.2012.00839.x","article-title":"Reduced release and binding of perforin at the immunological synapse underlies the age-related decline in natural killer cell cytotoxicity","volume":"11","author":"Hazeldine","year":"2012","journal-title":"Aging Cell"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1189\/jlb.0912461","article-title":"Blood CD33(+)HLA-DR(-) myeloid-derived suppressor cells are increased with age and a history of cancer","volume":"93","author":"Verschoor","year":"2013","journal-title":"J. Leukoc. Biol."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"917293","DOI":"10.3389\/fimmu.2022.917293","article-title":"Immunosenescence: A Critical Factor Associated With Organ Injury After Sepsis","volume":"13","author":"Lu","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/S2213-2600(16)00046-1","article-title":"Genomic landscape of the individual host response and outcomes in sepsis: A prospective cohort study","volume":"4","author":"Davenport","year":"2016","journal-title":"Lancet. Respir. Med."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1007\/s00134-003-1666-6","article-title":"Reversal of immunoparalysis by recombinant human granulocyte-macrophage colony-stimulating factor in patients with severe sepsis","volume":"29","author":"Nierhaus","year":"2003","journal-title":"Intensive Care Med."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1007\/s00134-006-0204-8","article-title":"Persisting low monocyte human leukocyte antigen-DR expression predicts mortality in septic shock","volume":"32","author":"Monneret","year":"2006","journal-title":"Intensive Care Med."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1164\/rccm.200903-0363OC","article-title":"Granulocyte-macrophage colony-stimulating factor to reverse sepsis-associated immunosuppression: A double-blind, randomized, placebo-controlled multicenter trial","volume":"180","author":"Meisel","year":"2009","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1016\/S2213-2600(17)30294-1","article-title":"Classification of patients with sepsis according to blood genomic endotype: A prospective cohort study","volume":"5","author":"Scicluna","year":"2017","journal-title":"Lancet. Respir. Med."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"930043","DOI":"10.3389\/fmed.2022.930043","article-title":"Mortality Prediction in Sepsis With an Immune-Related Transcriptomics Signature: A Multi-Cohort Analysis","volume":"9","author":"Kreitmann","year":"2022","journal-title":"Front. Med."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1164\/rccm.201410-1864OC","article-title":"Developing a clinically feasible personalized medicine approach to pediatric septic shock","volume":"191","author":"Wong","year":"2015","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"3074902","DOI":"10.1155\/2016\/3074902","article-title":"The Early Expression of HLA-DR and CD64 Myeloid Markers Is Specifically Compartmentalized in the Blood and Lungs of Patients with Septic Shock","volume":"2016","author":"Skirecki","year":"2016","journal-title":"Mediat. Inflamm."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.micinf.2017.12.008","article-title":"Compartment diversity in innate immune reprogramming","volume":"20","author":"Rasid","year":"2018","journal-title":"Microbes Infect."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1038\/ni.2419","article-title":"Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages","volume":"13","author":"Gautier","year":"2012","journal-title":"Nat. Immunol."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1097\/CCM.0000000000003084","article-title":"Unsupervised Analysis of Transcriptomics in Bacterial Sepsis Across Multiple Datasets Reveals Three Robust Clusters","volume":"46","author":"Sweeney","year":"2018","journal-title":"Crit. Care Med."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"607217","DOI":"10.3389\/fimmu.2021.607217","article-title":"Use of IFNgamma\/IL10 Ratio for Stratification of Hydrocortisone Therapy in Patients With Septic Shock","volume":"12","author":"Konig","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1097\/CCM.0000000000001402","article-title":"Interleukin-1 Receptor Blockade Is Associated With Reduced Mortality in Sepsis Patients With Features of Macrophage Activation Syndrome: Reanalysis of a Prior Phase III Trial","volume":"44","author":"Shakoory","year":"2016","journal-title":"Crit. Care Med."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"2173","DOI":"10.1097\/01.CCM.0000145229.59014.6C","article-title":"Efficacy and safety of the monoclonal anti-tumor necrosis factor antibody F(ab\u2019)2 fragment afelimomab in patients with severe sepsis and elevated interleukin-6 levels","volume":"32","author":"Panacek","year":"2004","journal-title":"Crit. Care Med."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1164\/rccm.201807-1419OC","article-title":"Transcriptomic Signatures in Sepsis and a Differential Response to Steroids. From the VANISH Randomized Trial","volume":"199","author":"Antcliffe","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1086\/314015","article-title":"Diagnostic virology","volume":"31","author":"Storch","year":"2000","journal-title":"Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"104","DOI":"10.2174\/1874357901206010104","article-title":"Application of molecular diagnostic techniques for viral testing","volume":"6","author":"Cobo","year":"2012","journal-title":"Open Virol. J."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1007\/s00134-022-06769-z","article-title":"Presymptomatic diagnosis of postoperative infection and sepsis using gene expression signatures","volume":"48","author":"Lukaszewski","year":"2022","journal-title":"Intensive Care Med."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jinf.2021.01.028","article-title":"Distinguishing bacterial versus non-bacterial causes of febrile illness\u2014A systematic review of host biomarkers","volume":"82","author":"Escadafal","year":"2021","journal-title":"J. Infect."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"346ra391","DOI":"10.1126\/scitranslmed.aaf7165","article-title":"Robust classification of bacterial and viral infections via integrated host gene expression diagnostics","volume":"8","author":"Sweeney","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"12792","DOI":"10.1073\/pnas.1302968110","article-title":"Gene expression profiles in febrile children with defined viral and bacterial infection","volume":"110","author":"Hu","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"R157","DOI":"10.1186\/cc11477","article-title":"A distinct influenza infection signature in the blood transcriptome of patients with severe community-acquired pneumonia","volume":"16","author":"Parnell","year":"2012","journal-title":"Crit. Care"},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"2914","DOI":"10.1038\/s41598-017-02325-8","article-title":"A Four-Biomarker Blood Signature Discriminates Systemic Inflammation Due to Viral Infection Versus Other Etiologies","volume":"7","author":"Sampson","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"e507","DOI":"10.1016\/S2589-7500(21)00102-3","article-title":"A two-transcript biomarker of host classifier genes for discrimination of bacterial from viral infection in acute febrile illness: A multicentre discovery and validation study","volume":"3","author":"Xu","year":"2021","journal-title":"Lancet Digit Health"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/19\/11740\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:46:08Z","timestamp":1760143568000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/19\/11740"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,3]]},"references-count":224,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["ijms231911740"],"URL":"https:\/\/doi.org\/10.3390\/ijms231911740","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,3]]}}}