{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T20:14:55Z","timestamp":1767212095819,"version":"build-2065373602"},"reference-count":70,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2017,11,1]],"date-time":"2017-11-01T00:00:00Z","timestamp":1509494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Sepsis represents a dysregulated immune response to infection, with a continuum of severity progressing to septic shock. This dysregulated response generally follows a pattern by which an initial hyperinflammatory phase is followed by a state of sepsis-associated immunosuppression. Major challenges in improving sepsis care include developing strategies to ensure early and accurate identification and diagnosis of the disease process, improving our ability to predict outcomes and stratify patients, and the need for novel sepsis-specific treatments such as immunomodulation. Biomarkers offer promise with all three of these challenges and are likely also to be the solution to determining a patient\u2019s immune status; something that is critical in guiding effective and safe immunomodulatory therapy. Currently available biomarkers used in sepsis lack sensitivity and specificity, among other significant shortcomings. The endocannabinoid system (ECS) is an emerging topic of research with evidence suggesting a ubiquitous presence on both central and peripheral tissues, including an intrinsic link with immune function. This review will first discuss the state of sepsis biomarkers and lack of available treatments, followed by an introduction to the ECS and a discussion of its potential to provide novel biomarkers and treatments.<\/jats:p>","DOI":"10.3390\/metabo7040055","type":"journal-article","created":{"date-parts":[[2017,11,1]],"date-time":"2017-11-01T16:01:19Z","timestamp":1509552079000},"page":"55","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Parameters of the Endocannabinoid System as Novel Biomarkers in Sepsis and Septic Shock"],"prefix":"10.3390","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8181-1822","authenticated-orcid":false,"given":"J.","family":"Lafreniere","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Dalhousie University, Halifax, NS B3H 4R2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Lehmann","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Dalhousie University, Halifax, NS B3H 4R2, Canada"},{"name":"Department of Anesthesia & Perioperative Medicine, Dalhousie University, Halifax, NS B3H 4R2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2017,11,1]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/S1473-3099(13)70001-X","article-title":"Immunosuppression in sepsis: A novel understanding of the disorder and a new therapeutic approach","volume":"13","author":"Hotchkiss","year":"2013","journal-title":"Lancet Infect. Dis."},{"key":"ref_3","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_4","doi-asserted-by":"crossref","first-page":"4","DOI":"10.4161\/viru.27372","article-title":"Epidemiology of severe sepsis","volume":"5","author":"Mayr","year":"2014","journal-title":"Virulence"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1097\/01.CCM.0000261890.41311.E9","article-title":"Rapid increase in hospitalization and mortality rates for severe sepsis in the United States: A trend analysis from 1993 to 2003","volume":"35","author":"Dombrovskiy","year":"2007","journal-title":"Crit. Care Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.1001\/jama.2009.1754","article-title":"International study of the prevalence and outcomes of infection in intensive care units","volume":"302","author":"Vincent","year":"2009","journal-title":"JAMA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.1213\/ane.0b013e318195e11d","article-title":"Macroscopic postmortem findings in 235 surgical intensive care patients with sepsis","volume":"108","author":"Torgersen","year":"2009","journal-title":"Anesth. Analg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1093\/bja\/aep128","article-title":"Immunomodulation in the critically ill","volume":"103","author":"Webster","year":"2009","journal-title":"Br. J. Anaesth."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1056\/NEJM200103083441001","article-title":"Efficacy and safety of recombinant human activated protein C for severe sepsis","volume":"344","author":"Bernard","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.1056\/NEJMoa1202290","article-title":"Drotrecogin alfa (activated) in adults with septic shock","volume":"366","author":"Ranieri","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1097\/00003246-199707000-00010","article-title":"Confirmatory interleukin-1 receptor antagonist trial in severe sepsis: A phase III, randomized, double-blind, placebo-controlled, multicenter trial. The Interleukin-1 Receptor Antagonist Sepsis Investigator Group","volume":"25","author":"Opal","year":"1997","journal-title":"Crit. Care Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1056\/NEJMra021333","article-title":"The pathophysiology and treatment of sepsis","volume":"348","author":"Hotchkiss","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"R15","DOI":"10.1186\/cc8872","article-title":"Sepsis biomarkers: A review","volume":"14","author":"Pierrakos","year":"2010","journal-title":"Crit. Care"},{"key":"ref_14","unstructured":"Schmidt, M., and Mandel, J. (2017, September 29). Evaluation and Management of Suspected Sepsis and Septic Shock in Adults. Available online: https:\/\/www.uptodate.com\/contents\/evaluation-and-management-of-suspected-sepsis-and-septic-shock-in-adults."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"23","DOI":"10.3109\/10408363.2013.764490","article-title":"Biomarkers of sepsis","volume":"50","author":"Faix","year":"2013","journal-title":"Crit. Rev. Clin. Lab. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"R116","DOI":"10.1186\/cc13908","article-title":"Prognostic and diagnostic value of eosinopenia, C-reactive protein, procalcitonin, and circulating cell-free DNA in critically ill patients admitted with suspicion of sepsis","volume":"18","author":"Macher","year":"2014","journal-title":"Crit. Care"},{"key":"ref_17","first-page":"14","article-title":"Oswald Avery and the Pneumococcus","volume":"74","author":"Kushner","year":"2011","journal-title":"Pharos Alpha Omega Alpha Honor Med. Soc."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1084\/jem.52.4.561","article-title":"Serological reactions in pneumonia with a non-protein somatic fraction of the pneumococcus","volume":"52","author":"Tillett","year":"1930","journal-title":"J. Exp. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1111\/j.1749-6632.1982.tb22124.x","article-title":"The phenomenon of the acute phase response","volume":"389","author":"Kushner","year":"1982","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1056\/NEJM199902113400607","article-title":"Acute-phase proteins and other systemic responses to inflammation","volume":"340","author":"Gabay","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_21","first-page":"396","article-title":"Ubiquitous expression of the calcitonin-I gene in multiple tissues in response to sepsis","volume":"86","author":"Muller","year":"2001","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/0140-6736(93)90277-N","article-title":"High serum procalcitonin concentrations in patients with sepsis and infection","volume":"341","author":"Assicot","year":"1993","journal-title":"Lancet"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/BF01740811","article-title":"Procalcitonin: A new indicator of the systemic response to severe infections","volume":"25","author":"Karzai","year":"1997","journal-title":"Infection"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1016\/j.burns.2008.01.014","article-title":"Comparison of WBC, ESR, CRP and PCT serum levels in septic and non-septic burn cases","volume":"34","author":"Barati","year":"2008","journal-title":"Burns"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1046\/j.1469-0691.2002.00349.x","article-title":"Procalcitonin, C-reactive protein and APACHE II score for risk evaluation in patients with severe pneumonia","volume":"8","author":"Brunkhorst","year":"2002","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Bele, N., Darmon, M., Coquet, I., Feugeas, J.P., Legriel, S., Adaoui, N., Schlemmer, B., and Azoulay, E. (2011). Diagnostic accuracy of procalcitonin in critically ill immunocompromised patients. BMC Infect. Dis., 11.","DOI":"10.1186\/1471-2334-11-224"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1086\/421997","article-title":"Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: A systematic review and meta-analysis","volume":"39","author":"Simon","year":"2004","journal-title":"Clin. Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1111\/j.1469-0691.2004.01044.x","article-title":"C-reactive protein as a marker of infection in critically ill patients","volume":"11","author":"Coelho","year":"2005","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1159\/000336629","article-title":"An update on the use of C-reactive protein in early-onset neonatal sepsis: Current insights and new tasks","volume":"102","author":"Hofer","year":"2012","journal-title":"Neonatology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.annemergmed.2004.12.006","article-title":"Serum lactate as a predictor of mortality in emergency department patients with infection","volume":"45","author":"Shapiro","year":"2005","journal-title":"Ann. Emerg. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2309","DOI":"10.1056\/NEJMra1309483","article-title":"Lactic acidosis","volume":"371","author":"Kraut","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.1001\/jama.1993.03510140084034","article-title":"Identification of the critical oxygen delivery for anaerobic metabolism in critically ill septic and nonseptic humans","volume":"270","author":"Ronco","year":"1993","journal-title":"JAMA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1186\/s13054-014-0503-3","article-title":"Sepsis-associated hyperlactatemia","volume":"18","author":"Marik","year":"2014","journal-title":"Crit. Care"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"253","DOI":"10.3109\/10408369109106865","article-title":"Blood lactate: Biochemistry, laboratory methods, and clinical interpretation","volume":"28","author":"Toffaletti","year":"1991","journal-title":"Crit. Rev. Clin. Lab. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1186\/cc13179","article-title":"Monocyte HLA-DR in sepsis: Shall we stop following the flow?","volume":"18","author":"Monneret","year":"2014","journal-title":"Crit. Care"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.1007\/s00134-010-1965-7","article-title":"Measurement of monocytic HLA-DR (mHLA-DR) expression in patients with severe sepsis and septic shock: Assessment of immune organ failure","volume":"36","author":"Schefold","year":"2010","journal-title":"Intensive Care Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1002\/cbdv.200790144","article-title":"History of cannabis and its preparations in saga, science, and sobriquet","volume":"4","author":"Russo","year":"2007","journal-title":"Chem. Biodivers."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/365061a0","article-title":"Molecular characterization of a peripheral receptor for cannabinoids","volume":"365","author":"Munro","year":"1993","journal-title":"Nature"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1124\/pr.54.2.161","article-title":"International Union of Pharmacology: XXVII. Classification of cannabinoid receptors","volume":"54","author":"Howlett","year":"2002","journal-title":"Pharmacol. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.2174\/092986710790980050","article-title":"Receptors and channels targeted by synthetic cannabinoid receptor agonists and antagonists","volume":"17","author":"Pertwee","year":"2010","journal-title":"Curr. Med. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.irn.2015.10.001","article-title":"The endocannabinoid signaling System in the CNS: A primer","volume":"125","author":"Hillard","year":"2015","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/S0026-895X(25)09876-1","article-title":"Determination and Characterization of a cannabinoid receptor in rat brain","volume":"34","author":"Devane","year":"1998","journal-title":"Mol. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1111\/j.1582-4934.2008.00530.x","article-title":"Reduced ligand affinity leads to an impaired function of the adenosine A2A receptor of human granulocytes in sepsis","volume":"13","author":"Kreth","year":"2009","journal-title":"J. Cell. Mol. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"499","DOI":"10.4049\/jimmunol.0900203","article-title":"The cannabinoid receptor 2 is critical for the host response to sepsis","volume":"183","author":"Kasten","year":"2009","journal-title":"J. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1007\/s11481-005-9007-x","article-title":"Cannabinoid-induced immune suppression and modulation of antigen-presenting cells","volume":"1","author":"Klein","year":"2006","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/S0006-2952(98)00314-1","article-title":"Enzymes of porcine brain hydrolyzing 2-arachidonoylglycerol, an endogenous ligand of cannabinoid receptors","volume":"57","author":"Goparaju","year":"1999","journal-title":"Biochem. Pharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1038\/42015","article-title":"A second endogenous cannabinoid that modulates long-term potentiation","volume":"388","author":"Stella","year":"1997","journal-title":"Nature"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1006\/nbdi.1998.0221","article-title":"Endogenous cannabinoid signaling","volume":"5","author":"Piomelli","year":"1998","journal-title":"Neurobiol. Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"9371","DOI":"10.1073\/pnas.161191698","article-title":"Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolase","volume":"98","author":"Cravatt","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1208\/s12248-009-9084-5","article-title":"Cannabinoids, Endocannabinoids, and Related Analogs in Inflammation","volume":"11","author":"Burstein","year":"2009","journal-title":"AAPS J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1038\/nrgastro.2013.245","article-title":"Patients with IBD find symptom relief in the Cannabis field","volume":"11","author":"Schicho","year":"2014","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Kelly, M.E.M., Lehmann, C., and Zhou, J. (2017). The Endocannabinoid System in Local and Systemic Inflammation, Morgan & Claypool.","DOI":"10.4199\/C00151ED1V01Y201702ISP074"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1111\/j.1432-1033.1995.tb20780.x","article-title":"Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations","volume":"232","author":"Mary","year":"1995","journal-title":"Eur. J. Biochem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"224","DOI":"10.2174\/187153010791936874","article-title":"The cannabinoid 2 receptor as a potential therapeutic target for sepsis","volume":"10","author":"Kasten","year":"2010","journal-title":"Endocr. Metab. Immune Disord. Drug Targets"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1124\/jpet.102.041095","article-title":"Potentiation of anandamide effects in mesenteric beds isolated from endotoxemic rats","volume":"304","author":"Orliac","year":"2003","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1111\/j.1476-5381.2012.02042.x","article-title":"Targeting cannabinoid receptor CB2 in cardiovascular disorders: Promises and controversies","volume":"167","author":"Steffens","year":"2012","journal-title":"Br. J. Pharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1007\/s11481-013-9445-9","article-title":"Cannabinoid receptor 2: Potential role in immunomodulation and neuroinflammation","volume":"8","author":"Rom","year":"2013","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1002\/glia.10177","article-title":"Cannabinoids ablate release of TNF-alpha in rat microglial cells stimulated with lypopolysaccharide","volume":"41","author":"Facchinetti","year":"2003","journal-title":"Glia"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1124\/mol.53.4.676","article-title":"Suppression of interleukin-2 by the putative endogenous cannabinoid 2-arachidonyl-glycerol is mediated through down-regulation of the nuclear factor of activated T cells","volume":"53","author":"Ouyang","year":"1998","journal-title":"Mol. Pharmacol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"R5","DOI":"10.1016\/S0014-2999(00)00653-1","article-title":"2-Arachidonylglycerol, an endogenous cannabinoid, inhibits tumor necrosis factor-alpha production in murine macrophages, and in mice","volume":"406","author":"Gallily","year":"2000","journal-title":"Eur. J. Pharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2899","DOI":"10.1016\/j.febslet.2007.05.037","article-title":"Inhibition of microglial fatty acid amide hydrolase modulates LPS stimulated release of inflammatory mediators","volume":"581","author":"Tham","year":"2007","journal-title":"FEBS. Lett."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1124\/jpet.109.164806","article-title":"Regulation of Inflammatory Pain by Inhibition of Fatty Acid Amide Hydrolase","volume":"334","author":"Naidu","year":"2010","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Hillard, C.J. (2017). Circulating Endocannabinoids: From Whence Do They Come and Where are They Going?. Neuropsychopharmacology.","DOI":"10.1038\/npp.2017.130"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1021\/ac403352e","article-title":"Development and validation of a sensitive UPLC-ESI-MS\/MS method for the simultaneous quantification of 15 endocannabinoids and related compounds in milk and other biofluids","volume":"86","author":"Nording","year":"2014","journal-title":"Anal. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.neuroscience.2011.11.020","article-title":"Contributions of endocannabinoid signaling to psychiatric disorders in humans: Genetic and biochemical evidence","volume":"204","author":"Hillard","year":"2012","journal-title":"Neuroscience"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1007\/s00216-010-4103-z","article-title":"Simultaneous measurement of three. N-acylethanolamides in human bio-matrices using ultra performance liquid chromatography-tandem mass spectrometry","volume":"398","author":"Lam","year":"2010","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1515\/CCLM.2006.065","article-title":"Release of anandamide from blood cells","volume":"44","author":"Vogeser","year":"2006","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.jbbm.2004.04.020","article-title":"A simple stopped assay for fatty acid amide hydrolase avoiding the use of a chloroform extraction phase","volume":"60","author":"Boldrup","year":"2004","journal-title":"J. Biochem. Biophys. Methods"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1186\/1476-511X-10-129","article-title":"The activity of the endocannabinoid metabolising enzyme fatty acid amide hydrolase in subcutaneous adipocytes correlates with BMI in metabolically healthy humans","volume":"10","author":"Cable","year":"2011","journal-title":"Lipids Health Dis."},{"key":"ref_70","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."}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/7\/4\/55\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:49:04Z","timestamp":1760208544000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/7\/4\/55"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,1]]},"references-count":70,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["metabo7040055"],"URL":"https:\/\/doi.org\/10.3390\/metabo7040055","relation":{},"ISSN":["2218-1989"],"issn-type":[{"type":"electronic","value":"2218-1989"}],"subject":[],"published":{"date-parts":[[2017,11,1]]}}}