{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:25:30Z","timestamp":1781105130098,"version":"3.54.1"},"reference-count":59,"publisher":"National Academy of Sciences","issue":"13","license":[{"start":{"date-parts":[[2016,9,14]],"date-time":"2016-09-14T00:00:00Z","timestamp":1473811200000},"content-version":"vor","delay-in-days":184,"URL":"http:\/\/www.pnas.org\/preview_site\/misc\/userlicense.xhtml"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["138488"],"award-info":[{"award-number":["138488"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["145014"],"award-info":[{"award-number":["145014"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["149511"],"award-info":[{"award-number":["149511"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["144054"],"award-info":[{"award-number":["144054"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"EC | European Research Council","doi-asserted-by":"publisher","award":["starting grant 281156"],"award-info":[{"award-number":["starting grant 281156"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001826","name":"Netherlands Organization for Health Research and Development","doi-asserted-by":"crossref","award":["Vidi grant 016.116.358"],"award-info":[{"award-number":["Vidi grant 016.116.358"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001826","name":"Netherlands Organization for Health Research and Development","doi-asserted-by":"crossref","award":["NWOVeni grant 916.13.078"],"award-info":[{"award-number":["NWOVeni grant 916.13.078"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Porphyrogenis Foundation","award":["none"],"award-info":[{"award-number":["none"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2016,3,29]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Pneumococcal meningitis, the most frequent cause of bacterial meningitis in adults, is associated with substantial morbidity and mortality. In a prospective, nationwide cohort of patients with pneumococcal meningitis, macrophage migration inhibitory factor (MIF), a proinflammatory mediator, was identified as a previously unidentified genetic marker of patient\u2019s outcome. High-expression\n                    <jats:italic>MIF<\/jats:italic>\n                    alleles were associated with disease severity and death, a finding consistent with the harmful consequences of robust proinflammatory cytokine responses on brain edema and neuronal damage in the course of bacterial meningitis. These results provide strong evidence that functional\n                    <jats:italic>MIF<\/jats:italic>\n                    polymorphisms are genetic predictors of morbidity and mortality of pneumococcal meningitis and suggest that MIF is a potential target for immune-modulating adjunctive therapies.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1520727113","type":"journal-article","created":{"date-parts":[[2016,3,14]],"date-time":"2016-03-14T23:24:27Z","timestamp":1457997867000},"page":"3597-3602","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":47,"title":["Functional polymorphisms of macrophage migration inhibitory factor as predictors of morbidity and mortality of pneumococcal meningitis"],"prefix":"10.1073","volume":"113","author":[{"given":"Athina","family":"Savva","sequence":"first","affiliation":[{"name":"Infectious Diseases Service, Centre Hospitalier Universitaire Vaudois and University of Lausanne, CH-10111 Lausanne, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthijs C.","family":"Brouwer","sequence":"additional","affiliation":[{"name":"Department of Neurology, Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9358-0109","authenticated-orcid":false,"given":"Thierry","family":"Roger","sequence":"additional","affiliation":[{"name":"Infectious Diseases Service, Centre Hospitalier Universitaire Vaudois and University of Lausanne, CH-10111 Lausanne, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercedes","family":"Valls Ser\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Neurology, Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didier","family":"Le Roy","sequence":"additional","affiliation":[{"name":"Infectious Diseases Service, Centre Hospitalier Universitaire Vaudois and University of Lausanne, CH-10111 Lausanne, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart","family":"Ferwerda","sequence":"additional","affiliation":[{"name":"Department of Neurology, Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arie","family":"van der Ende","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, the Netherlands Reference Laboratory for Bacterial Meningitis, CINIMA, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre-Yves","family":"Bochud","sequence":"additional","affiliation":[{"name":"Infectious Diseases Service, Centre Hospitalier Universitaire Vaudois and University of Lausanne, CH-10111 Lausanne, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diederik","family":"van de Beek","sequence":"additional","affiliation":[{"name":"Department of Neurology, Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Calandra","sequence":"additional","affiliation":[{"name":"Infectious Diseases Service, Centre Hospitalier Universitaire Vaudois and University of Lausanne, CH-10111 Lausanne, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2016,3,14]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61728-0"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(08)70261-5"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00070-09"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1005384"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(10)70048-7"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2011.03668.x"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2010.04.008"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-030409-101335"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0b013e328360415c"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0506-499"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)08516-1"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1976"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200702-169OC"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.153.3731.80"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.56.1.72"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/377068a0"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.012511599"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200535413"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/414920a"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-012-9781-1"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1200"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1286-4579(02)01560-5"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gene.6363867"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200108)44:8<1782::AID-ART314>3.0.CO;2-#"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1086\/432009"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00008-11"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1567"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2010.12.010"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1186\/cc7933"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1086\/600894"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-7-100"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.09-129445"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.11-195065"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jit571"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(07)70185-8"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3114"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/72262"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.86.6.7570"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1086\/514344"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.shk.0000246898.65692.34"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI32218"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaa4304"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.19.11383"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jis673"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1400133"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/365756a0"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1007\/s001340101022"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1177\/09680519010070061101"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1086\/374752"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiv262"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.329664"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-05-284711"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2009.09.007"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI57522"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a000179"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(75)92830-5"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa040845"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200737357"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000480"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.1520727113","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1520727113","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T01:52:16Z","timestamp":1649814736000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1520727113"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,3,14]]},"references-count":59,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2016,3,29]]}},"alternative-id":["10.1073\/pnas.1520727113"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1520727113","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,3,14]]},"assertion":[{"value":"2016-03-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}