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School","award":["K24AG035075"],"award-info":[{"award-number":["K24AG035075"]}]},{"name":"Hebrew SeniorLife\/Harvard Medical School","award":["R03AG061582"],"award-info":[{"award-number":["R03AG061582"]}]},{"name":"Hebrew SeniorLife\/Harvard Medical School","award":["K01AG057836"],"award-info":[{"award-number":["K01AG057836"]}]},{"name":"Hebrew SeniorLife\/Harvard Medical School","award":["R01AG062509"],"award-info":[{"award-number":["R01AG062509"]}]},{"name":"Hebrew SeniorLife\/Harvard Medical School","award":["AARF-18-560786"],"award-info":[{"award-number":["AARF-18-560786"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Delirium is a common postoperative complication among older patients with many adverse outcomes. Due to a lack of validated biomarkers, prediction and monitoring of delirium by biological testing is not currently feasible. Circulating proteins in cerebrospinal fluid (CSF) may reflect biological processes causing delirium. Our goal was to discover and investigate candidate protein biomarkers in preoperative CSF that were associated with the development of postoperative delirium in older surgical patients. We employed a nested case\u2013control study design coupled with high multiplex affinity proteomics analysis to measure 1305 proteins in preoperative CSF. Twenty-four matched delirium cases and non-delirium controls were selected from the Healthier Postoperative Recovery (HiPOR) cohort, and the associations between preoperative protein levels and postoperative delirium were assessed using t-test statistics with further analysis by systems biology to elucidate delirium pathophysiology. Proteomics analysis identified 32 proteins in preoperative CSF that significantly associate with delirium (t-test p &lt; 0.05). Due to the limited sample size, these proteins did not remain significant by multiple hypothesis testing using the Benjamini\u2013Hochberg correction and q-value method. Three algorithms were applied to separate delirium cases from non-delirium controls. Hierarchical clustering classified 40\/48 case\u2013control samples correctly, and principal components analysis separated 43\/48. The receiver operating characteristic curve yielded an area under the curve [95% confidence interval] of 0.91 [0.80\u20130.97]. Systems biology analysis identified several key pathways associated with risk of delirium: inflammation, immune cell migration, apoptosis, angiogenesis, synaptic depression and neuronal cell death. Proteomics analysis of preoperative CSF identified 32 proteins that might discriminate individuals who subsequently develop postoperative delirium from matched control samples. These proteins are potential candidate biomarkers for delirium and may play a role in its pathophysiology.<\/jats:p>","DOI":"10.3390\/biom13091395","type":"journal-article","created":{"date-parts":[[2023,9,17]],"date-time":"2023-09-17T06:12:21Z","timestamp":1694931141000},"page":"1395","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Aptamer-Based Proteomics Measuring Preoperative Cerebrospinal Fluid Protein Alterations Associated with Postoperative Delirium"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4417-178X","authenticated-orcid":false,"given":"Simon T.","family":"Dillon","sequence":"first","affiliation":[{"name":"Division of Interdisciplinary Medicine and Biotechnology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA"},{"name":"Beth Israel Deaconess Medical Center Genomics, Proteomics, Bioinformatics and Systems Biology Center, Boston, MA 02215, USA"},{"name":"Harvard Medical School, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarinnapha M.","family":"Vasunilashorn","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA 02215, USA"},{"name":"Divisions of General Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA"},{"name":"Departments of Epidemiology and Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasan H.","family":"Otu","sequence":"additional","affiliation":[{"name":"Department of Electrical and Computer Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Ngo","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA 02215, USA"},{"name":"Divisions of General Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Fong","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA 02215, USA"},{"name":"Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA"},{"name":"Aging Brain Center, Marcus Institute for Aging Research, Hebrew Senior Life, Boston, MA 02131, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuesong","family":"Gu","sequence":"additional","affiliation":[{"name":"Division of Interdisciplinary Medicine and Biotechnology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA"},{"name":"Beth Israel Deaconess Medical Center Genomics, Proteomics, Bioinformatics and Systems Biology Center, Boston, MA 02215, USA"},{"name":"Harvard Medical School, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Cavallari","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA 02215, USA"},{"name":"Center for Neurological Imaging, Department of Radiology, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Touroutoglou","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA 02215, USA"},{"name":"Frontotemporal Disorders Unit, Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mouhsin","family":"Shafi","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA 02215, USA"},{"name":"Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA"},{"name":"Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon K.","family":"Inouye","sequence":"additional","affiliation":[{"name":"Aging Brain Center, Marcus Institute for Aging Research, Hebrew Senior Life, Boston, MA 02131, USA"},{"name":"Divisions of Gerontology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0720-1759","authenticated-orcid":false,"given":"Zhongcong","family":"Xie","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA 02215, USA"},{"name":"Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward R.","family":"Marcantonio","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA 02215, USA"},{"name":"Divisions of General Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA"},{"name":"Divisions of Gerontology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4006-8179","authenticated-orcid":false,"given":"Towia A.","family":"Libermann","sequence":"additional","affiliation":[{"name":"Division of Interdisciplinary Medicine and Biotechnology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA"},{"name":"Beth Israel Deaconess Medical Center Genomics, Proteomics, Bioinformatics and Systems Biology Center, Boston, MA 02215, USA"},{"name":"Harvard Medical School, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1056\/NEJMcp1605501","article-title":"Delirium in hospitalized older adults","volume":"377","author":"Marcantonio","year":"2017","journal-title":"N. 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