{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T11:09:58Z","timestamp":1793272198980,"version":"4.5.0"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"10","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:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Critically ill patients typically present with hyperglycemia. Treatment with conventional insulin therapy (targeting 144\u2013180 mg\/dl) improves patient survival; however, intensive insulin therapy (IIT) targeting normal blood glucose levels (81\u2013108 mg\/dl) increases the incidence of moderate and severe hypoglycemia, and increases mortality. Septic patients are especially prone to IIT-induced hypoglycemia, but the mechanism remains unknown. Here, we show that codelivery of insulin with otherwise sublethal doses of LPS induced hypoglycemic shock in mice within 1\u20132 h. LPS impaired clearance of insulin, which amplified insulin receptor signaling. These effects were mediated by caspase-11, TLR4, and complement, each of which trigger eicosanoid production that potentiates insulin signaling. Finally, in an animal model of sepsis, we observed that Salmonella typhimurium\u2013infected mice exhibited simultaneous impaired insulin clearance coexisting with insulin resistance. Our results raise the possibility that septic patients have impaired insulin clearance, which could increase their susceptibility to hypoglycemia during IIT, contraindicating its use.<\/jats:p>","DOI":"10.4049\/jimmunol.1700820","type":"journal-article","created":{"date-parts":[[2017,10,17]],"date-time":"2017-10-17T00:40:38Z","timestamp":1508200838000},"page":"3634-3643","source":"Crossref","is-referenced-by-count":27,"title":["Lipopolysaccharide Potentiates Insulin-Driven Hypoglycemic Shock"],"prefix":"10.1093","volume":"199","author":[{"given":"Jon A","family":"Hagar","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of North Carolina at Chapel Hill , Chapel Hill, NC 27599"},{"name":"Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill , Chapel Hill, NC 27599"},{"name":"Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill , Chapel Hill, NC 27599"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew L","family":"Edin","sequence":"additional","affiliation":[{"name":"Division of Intramural Research, National Institute for Environmental Health Sciences, National Institutes of Health , Research Triangle Park, NC 27709"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2260-816X","authenticated-orcid":false,"given":"Fred B","family":"Lih","sequence":"additional","affiliation":[{"name":"Division of Intramural Research, National Institute for Environmental Health Sciences, National Institutes of Health , Research Triangle Park, NC 27709"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lance R","family":"Thurlow","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Pittsburgh , Pittsburgh, PA 15219"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beverly H","family":"Koller","sequence":"additional","affiliation":[{"name":"Department of Genetics, University of North Carolina at Chapel Hill , Chapel Hill, NC 27599"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce A","family":"Cairns","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of North Carolina at Chapel Hill , Chapel Hill, NC 27599"},{"name":"Department of Surgery, University of North Carolina at Chapel Hill , Chapel Hill, NC 27599"},{"name":"North Carolina Jaycee Burn Center, University of North Carolina at Chapel Hill , Chapel Hill, NC 27599"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darryl C","family":"Zeldin","sequence":"additional","affiliation":[{"name":"Division of Intramural Research, National Institute for Environmental Health Sciences, National Institutes of Health , Research Triangle Park, NC 27709"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7295-3490","authenticated-orcid":false,"given":"Edward A","family":"Miao","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of North Carolina at Chapel Hill , Chapel Hill, NC 27599"},{"name":"Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill , Chapel Hill, NC 27599"},{"name":"Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill , Chapel Hill, NC 27599"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,11,15]]},"reference":[{"key":"2025030614522673000_r1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1038\/41131","article-title":"A human homologue of the Drosophila Toll protein signals activation of adaptive immunity","volume":"388","author":"Medzhitov","year":"1997","journal-title":"Nature"},{"key":"2025030614522673000_r2","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1126\/science.282.5396.2085","article-title":"Defective LPS signaling in C3H\/HeJ and C57BL\/10ScCr mice: mutations in Tlr4 gene","volume":"282","author":"Poltorak","year":"1998","journal-title":"Science"},{"key":"2025030614522673000_r3","doi-asserted-by":"crossref","first-page":"3749","DOI":"10.4049\/jimmunol.162.7.3749","article-title":"Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product","volume":"162","author":"Hoshino","year":"1999","journal-title":"J. Immunol."},{"key":"2025030614522673000_r4","doi-asserted-by":"crossref","first-page":"3233","DOI":"10.1182\/blood-2002-01-0252","article-title":"LPS-induced platelet response and rapid shock in mice: contribution of O-antigen region of LPS and involvement of the lectin pathway of the complement system","volume":"100","author":"Zhao","year":"2002","journal-title":"Blood"},{"key":"2025030614522673000_r5","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1126\/science.1240988","article-title":"Cytoplasmic LPS activates caspase-11: implications in TLR4-independent endotoxic shock","volume":"341","author":"Hagar","year":"2013","journal-title":"Science"},{"key":"2025030614522673000_r6","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1126\/science.1240248","article-title":"Noncanonical inflammasome activation by intracellular LPS independent of TLR4","volume":"341","author":"Kayagaki","year":"2013","journal-title":"Science"},{"key":"2025030614522673000_r7","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/nature13683","article-title":"Inflammatory caspases are innate immune receptors for intracellular LPS","volume":"514","author":"Shi","year":"2014","journal-title":"Nature"},{"key":"2025030614522673000_r8","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1126\/science.1230751","article-title":"Caspase-11 protects against bacteria that escape the vacuole","volume":"339","author":"Aachoui","year":"2013","journal-title":"Science"},{"key":"2025030614522673000_r9","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.chom.2015.07.016","article-title":"Canonical inflammasomes drive IFN-\u03b3 to prime caspase-11 in defense against a cytosol-invasive bacterium","volume":"18","author":"Aachoui","year":"2015","journal-title":"Cell Host Microbe"},{"key":"2025030614522673000_r10","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/S1074-7613(00)80119-3","article-title":"Differential roles of TLR2 and TLR4 in recognition of gram-negative and gram-positive bacterial cell wall components","volume":"11","author":"Takeuchi","year":"1999","journal-title":"Immunity"},{"key":"2025030614522673000_r11","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/S0092-8674(00)80943-5","article-title":"Murine caspase-11, an ICE-interacting protease, is essential for the activation of ICE","volume":"92","author":"Wang","year":"1998","journal-title":"Cell"},{"key":"2025030614522673000_r12","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/nature10558","article-title":"Non-canonical inflammasome activation targets caspase-11","volume":"479","author":"Kayagaki","year":"2011","journal-title":"Nature"},{"key":"2025030614522673000_r13","doi-asserted-by":"crossref","first-page":"41624","DOI":"10.1074\/jbc.M207852200","article-title":"Caspase-11 gene expression in response to lipopolysaccharide and interferon-gamma requires nuclear factor-kappa B and signal transducer and activator of transcription (STAT) 1","volume":"277","author":"Schauvliege","year":"2002","journal-title":"J. Biol. Chem."},{"key":"2025030614522673000_r14","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/j.immuni.2015.10.009","article-title":"Caspase-11 requires the Pannexin-1 channel and the purinergic P2X7 pore to mediate pyroptosis and endotoxic shock","volume":"43","author":"Yang","year":"2015","journal-title":"Immunity"},{"key":"2025030614522673000_r15","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/nrm1837","article-title":"Critical nodes in signalling pathways: insights into insulin action","volume":"7","author":"Taniguchi","year":"2006","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2025030614522673000_r16","first-page":"608","article-title":"Insulin degradation: progress and potential","volume":"19","author":"Duckworth","year":"1998","journal-title":"Endocr. Rev."},{"key":"2025030614522673000_r17","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/nature13297","article-title":"Anti-diabetic activity of insulin-degrading enzyme inhibitors mediated by multiple hormones","volume":"511","author":"Maianti","year":"2014","journal-title":"Nature"},{"key":"2025030614522673000_r18","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1083\/jcb.110.1.35","article-title":"Selective degradation of insulin within rat liver endosomes","volume":"110","author":"Doherty","year":"1990","journal-title":"J. Cell Biol."},{"key":"2025030614522673000_r19","doi-asserted-by":"crossref","first-page":"26833","DOI":"10.1074\/jbc.272.43.26833","article-title":"Chloroquine extends the lifetime of the activated insulin receptor complex in endosomes","volume":"272","author":"Bevan","year":"1997","journal-title":"J. Biol. Chem."},{"key":"2025030614522673000_r20","doi-asserted-by":"crossref","first-page":"9044","DOI":"10.1073\/pnas.1332766100","article-title":"Impaired inflammatory and pain responses in mice lacking an inducible prostaglandin E synthase","volume":"100","author":"Trebino","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030614522673000_r21","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/S1097-2765(05)00015-8","article-title":"Loss of insulin signaling in hepatocytes leads to severe insulin resistance and progressive hepatic dysfunction","volume":"6","author":"Michael","year":"2000","journal-title":"Mol. Cell"},{"key":"2025030614522673000_r22","doi-asserted-by":"crossref","first-page":"2124","DOI":"10.1194\/jlr.M053199","article-title":"Functional characterization of cytochrome P450-derived epoxyeicosatrienoic acids in adipogenesis and obesity","volume":"55","author":"Zha","year":"2014","journal-title":"J. Lipid Res."},{"key":"2025030614522673000_r23","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1210\/jcem-65-3-494","article-title":"Renal metabolism of C-peptide in man","volume":"65","author":"Zavaroni","year":"1987","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2025030614522673000_r24","doi-asserted-by":"crossref","first-page":"19545","DOI":"10.1074\/jbc.274.28.19545","article-title":"Enhancement by adenosine of insulin-induced activation of phosphoinositide 3-kinase and protein kinase B in rat adipocytes","volume":"274","author":"Takasuga","year":"1999","journal-title":"J. Biol. Chem."},{"key":"2025030614522673000_r25","doi-asserted-by":"crossref","first-page":"C226","DOI":"10.1152\/ajpcell.1985.249.3.C226","article-title":"Dissociation of effects of insulin and contraction on glucose transport in rat epitrochlearis muscle","volume":"249","author":"Nesher","year":"1985","journal-title":"Am. J. Physiol."},{"key":"2025030614522673000_r26","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/0006-291X(77)91039-7","article-title":"Interaction between insulin receptors and glucose transport: effect of prostaglandin E2","volume":"75","author":"Olefsky","year":"1977","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2025030614522673000_r27","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/0167-4889(87)90164-9","article-title":"Inhibition of glucagon-stimulated cAMP accumulation and fatty acid oxidation by E-series prostaglandins in isolated rat hepatocytes","volume":"930","author":"Brass","year":"1987","journal-title":"Biochim. Biophys. Acta"},{"key":"2025030614522673000_r28","doi-asserted-by":"crossref","first-page":"R332","DOI":"10.1152\/ajpregu.00567.2004","article-title":"LPS-activated complement, not LPS per se, triggers the early release of PGE2 by Kupffer cells","volume":"289","author":"Perlik","year":"2005","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"2025030614522673000_r29","doi-asserted-by":"crossref","first-page":"6953","DOI":"10.1016\/S0021-9258(18)68587-4","article-title":"Endotoxin stimulates glycogenolysis in the liver by means of intercellular communication","volume":"263","author":"Casteleijn","year":"1988","journal-title":"J. Biol. Chem."},{"key":"2025030614522673000_r30","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/nature11351","article-title":"Rapid induction of inflammatory lipid mediators by the inflammasome in vivo","volume":"490","author":"Von Moltke","year":"2012","journal-title":"Nature"},{"key":"2025030614522673000_r31","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/j.ccm.2008.06.002","article-title":"Glucose control in sepsis","volume":"29","author":"Thompson","year":"2008","journal-title":"Clin. Chest Med."},{"key":"2025030614522673000_r32","doi-asserted-by":"crossref","first-page":"2392","DOI":"10.2337\/db06-0391","article-title":"Molecular mechanisms of insulin resistance: serine phosphorylation of insulin receptor substrate-1 and increased expression of p85alpha: the two sides of a coin","volume":"55","author":"Draznin","year":"2006","journal-title":"Diabetes"},{"key":"2025030614522673000_r33","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1097\/00075197-200207000-00005","article-title":"Mediators of cytokine-induced insulin resistance in obesity and other inflammatory settings","volume":"5","author":"Marette","year":"2002","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"2025030614522673000_r34","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1056\/NEJMoa011300","article-title":"Intensive insulin therapy in critically ill patients","volume":"345","author":"Van den Berghe","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"2025030614522673000_r35","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1056\/NEJMoa052521","article-title":"Intensive insulin therapy in the medical ICU","volume":"354","author":"Van den Berghe","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"2025030614522673000_r36","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1001\/jama.300.8.933","article-title":"Benefits and risks of tight glucose control in critically ill adults: a meta-analysis","volume":"300","author":"Wiener","year":"2008","journal-title":"JAMA"},{"key":"2025030614522673000_r37","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1056\/NEJMoa070716","article-title":"Intensive insulin therapy and pentastarch resuscitation in severe sepsis","volume":"358","author":"Brunkhorst","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"2025030614522673000_r38","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1056\/NEJMoa0810625","article-title":"Intensive versus conventional glucose control in critically ill patients","volume":"360","author":"NICE-SUGAR Study Investigators","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"2025030614522673000_r39","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1056\/NEJMoa1204942","article-title":"Hypoglycemia and risk of death in critically ill patients","volume":"367","author":"NICE-SUGAR Study Investigators","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"2025030614522673000_r40","doi-asserted-by":"crossref","first-page":"R189","DOI":"10.1186\/cc11674","article-title":"Mild hypoglycemia is independently associated with increased risk of mortality in patients with sepsis: a 3-year retrospective observational study","volume":"16","author":"Park","year":"2012","journal-title":"Crit. Care"},{"key":"2025030614522673000_r41","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1056\/NEJMe058304","article-title":"Intensive insulin in intensive care","volume":"354","author":"Malhotra","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"2025030614522673000_r42","doi-asserted-by":"crossref","first-page":"2262","DOI":"10.1097\/01.CCM.0000282073.98414.4B","article-title":"Severe hypoglycemia in critically ill patients: risk factors and outcomes","volume":"35","author":"Krinsley","year":"2007","journal-title":"Crit. Care Med."},{"key":"2025030614522673000_r43","doi-asserted-by":"crossref","first-page":"e30160","DOI":"10.1371\/journal.pone.0030160","article-title":"Disassociation of muscle insulin signaling and insulin-stimulated glucose uptake during endotoxemia","volume":"7","author":"Mulligan","year":"2012","journal-title":"PLoS One"},{"key":"2025030614522673000_r44","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1097\/SHK.0000000000000550","article-title":"Enhanced glucose transport, but not phosphorylation capacity, ameliorates lipopolysaccharide-induced impairments in insulin-stimulated muscle glucose uptake","volume":"45","author":"Otero","year":"2016","journal-title":"Shock"},{"key":"2025030614522673000_r45","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1038\/ni.1960","article-title":"Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria","volume":"11","author":"Miao","year":"2010","journal-title":"Nat. Immunol."},{"key":"2025030614522673000_r46","doi-asserted-by":"crossref","first-page":"34005","DOI":"10.1074\/jbc.M109.030627","article-title":"Protective role of Cys-178 against the inactivation and oligomerization of human insulin-degrading enzyme by oxidation and nitrosylation","volume":"284","author":"Ralat","year":"2009","journal-title":"J. Biol. Chem."},{"key":"2025030614522673000_r47","doi-asserted-by":"crossref","first-page":"12822","DOI":"10.1021\/bi801192h","article-title":"Molecular bases for the recognition of short peptide substrates and cysteine-directed modifications of human insulin-degrading enzyme","volume":"47","author":"Malito","year":"2008","journal-title":"Biochemistry"},{"key":"2025030614522673000_r48","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.cmet.2009.08.009","article-title":"Reactive oxygen species enhance insulin sensitivity","volume":"10","author":"Loh","year":"2009","journal-title":"Cell Metab."},{"key":"2025030614522673000_r49","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1089\/ars.2005.7.1021","article-title":"Role of insulin-induced reactive oxygen species in the insulin signaling pathway","volume":"7","author":"Goldstein","year":"2005","journal-title":"Antioxid. Redox Signal."},{"key":"2025030614522673000_r50","first-page":"318","article-title":"Regulation of luminal acidification by the V-ATPase","volume":"28","author":"Breton","year":"2013","journal-title":"Physiology (Bethesda)"},{"key":"2025030614522673000_r51","doi-asserted-by":"crossref","first-page":"2072","DOI":"10.1210\/endo.134.5.8156907","article-title":"Mechanisms of insulin resistance during acute endotoxemia","volume":"134","author":"Virkam\u00e4ki","year":"1994","journal-title":"Endocrinology"},{"key":"2025030614522673000_r52","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1002\/hep.22999","article-title":"Lipopolysaccharide inhibition of glucose production through the Toll-like receptor-4, myeloid differentiation factor 88, and nuclear factor kappa b pathway","volume":"50","author":"Raetzsch","year":"2009","journal-title":"Hepatology"},{"key":"2025030614522673000_r53","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1016\/0026-0495(93)90137-D","article-title":"Effect of high-dose endotoxin on glucose production and utilization","volume":"42","author":"Lang","year":"1993","journal-title":"Metabolism"},{"key":"2025030614522673000_r54","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.2337\/dc06-1964","article-title":"Intensive insulin therapy in critical care: a review of 12 protocols","volume":"30","author":"Wilson","year":"2007","journal-title":"Diabetes Care"},{"key":"2025030614522673000_r55","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/0885-4505(87)90010-7","article-title":"Liver glycogen metabolism in endotoxin shock. I. Endotoxin administration decreases glycogen synthase activities in dog livers","volume":"37","author":"Liu","year":"1987","journal-title":"Biochem. Med. Metab. Biol."},{"key":"2025030614522673000_r56","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/0026-0495(91)90048-2","article-title":"Sepsis-induced increases in glucose uptake by macrophage-rich tissues persist during hypoglycemia","volume":"40","author":"Lang","year":"1991","journal-title":"Metabolism"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/199\/10\/3634\/61533719\/ji1700820.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/199\/10\/3634\/61533719\/ji1700820.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T16:53:59Z","timestamp":1741280039000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/199\/10\/3634\/7966250"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11]]},"references-count":56,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2017,11,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1700820","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2017,11]]},"published":{"date-parts":[[2017,11]]}}}