{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T05:32:11Z","timestamp":1785216731257,"version":"3.55.0"},"reference-count":57,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100005220","name":"Agency for Toxic Substances and Disease Registry","doi-asserted-by":"publisher","award":["R01TS000339"],"award-info":[{"award-number":["R01TS000339"]}],"id":[{"id":"10.13039\/100005220","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005220","name":"Agency for Toxic Substances and Disease Registry","doi-asserted-by":"publisher","award":["U01TS000351"],"award-info":[{"award-number":["U01TS000351"]}],"id":[{"id":"10.13039\/100005220","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["F31NS139629"],"award-info":[{"award-number":["F31NS139629"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01ES030049"],"award-info":[{"award-number":["R01ES030049"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01NS120926"],"award-info":[{"award-number":["R01NS120926"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01NS127188"],"award-info":[{"award-number":["R01NS127188"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32AI007413"],"award-info":[{"award-number":["T32AI007413"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Peripheral neutrophil levels in amyotrophic lateral sclerosis (ALS) inversely correlate with survival, suggesting a role for neutrophils in disease progression. Here, we characterize markers of several neutrophil activation pathways and evaluate their associations with survival to identify potential mechanisms of disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Blood samples were obtained from participants at the University of Michigan ALS Clinic or from healthy controls. Ex\u00a0vivo neutrophil extracellular trap (NET) formation was quantified via image analysis of primary neutrophils. Neutrophil function markers of general activation (calprotectin), migration (matrix\u2010metalloproteinase 9 [MMP9]), and degranulation (neutrophil gelatinase\u2010associated lipocalin [NGAL]) were then quantified in plasma via ELISA; NET formation (double\u2010stranded DNA [dsDNA]) was assessed via fluorescence assay. These markers were then associated with ALS survival using Cox proportional hazard regression models, and analyses were stratified by sex.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Spontaneous ex\u00a0vivo NET formation (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u200920 controls, 66 ALS) was increased in ALS (1.0% vs. 9.7%;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.017). In plasma (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u2009233 controls, 178 ALS), calprotectin (294 vs. 372\u2009ng\/mL;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), MMP9 (106 vs. 152\u2009ng\/mL;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), and NGAL (61 vs. 66\u2009ng\/mL;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.01) were elevated in ALS. Calprotectin, MMP9, and NGAL levels were not associated with ALS survival; however, dsDNA was associated with poorer ALS survival but only in females (HR\u2009=\u20091.77 [95% CI, 1.20\u20132.61];\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.004).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Neutrophil function is altered in ALS, and NET formation is a potential mechanism by which neutrophils contribute to ALS, particularly in females.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.70431","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T04:25:07Z","timestamp":1778819107000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Peripheral Neutrophil Activation and Extracellular Trap Formation in Amyotrophic Lateral Sclerosis"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3209-8754","authenticated-orcid":false,"given":"Lillia A.","family":"Baird","sequence":"first","affiliation":[{"name":"Department of Neurology University of Michigan  Ann Arbor Michigan USA"},{"name":"Graduate Program in Immunology University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haley","family":"McQuown","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihyun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel J.","family":"Teener","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian F.","family":"Webber\u2010Davis","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7953-8998","authenticated-orcid":false,"given":"Andrew D.","family":"Carter","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7966-1322","authenticated-orcid":false,"given":"Dae\u2010Gyu","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9162-2694","authenticated-orcid":false,"given":"Eva L.","family":"Feldman","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8780-6637","authenticated-orcid":false,"given":"Stephen A.","family":"Goutman","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3543-4007","authenticated-orcid":false,"given":"Benjamin J.","family":"Murdock","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1016\/S0140-6736(22)01272-7","article-title":"Amyotrophic Lateral Sclerosis","volume":"400","author":"Feldman E. 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