Browsing by Author "Nguyen, Thuy"
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Item Blood-based gene and co-expression network levels are associated with AD/MCI diagnosis and cognitive phenotypes(Wiley, 2025-01-09) Chen, Xuan; Reddy, Joseph S.; Wang, Xue; Quicksall, Zachary; Nguyen, Thuy; Reyes, Denise A.; Graff-Radford, Jonathan; Jack, Clifford R., Jr.; Lowe, Val J.; Knopman, David S.; Petersen, Ronald C.; Kantarci, Kejal; Nho, Kwangsik; Allen, Mariet; Carrasquillo, Minerva M.; Saykin, Andrew J.; Ertekin-Taner, Nilüfer; Radiology and Imaging Sciences, School of MedicineBackground: Alzheimer’s disease (AD) patients have decline in cognitive domains including memory, language, visuospatial, and/or executive function and brain pathology including amyloid‐β and tau deposition, neurodegeneration, and frequent vascular co‐pathologies detectable by neuroimaging and/or cerebrospinal fluid biomarkers. However, molecular disease mechanisms are complex and heterogeneous. It is necessary to develop cost‐effective blood‐based biomarkers reflecting brain molecular perturbations in AD. We identified blood‐based gene and co‐expression network level changes associated with AD/mild cognitive impairment (MCI) diagnosis and AD‐related phenotypes. Method: We performed differential gene expression and weighted gene co‐expression network analysis, followed by meta‐analysis, using blood transcriptome data of 391 participants from the Mayo Clinic Study of Aging and 654 participants from the Alzheimer's Disease Neuroimaging Initiative. The neuroimaging phenotypes include microhemorrhages, infarcts, amyloid burden, hippocampal volume, and white matter hyperintensities. The cognitive phenotypes include standardized cognitive subtest scores and composite scores for memory, language, visuospatial, and executive function. Result: Five out of 18 modules(M) are significantly associated with diagnosis or cognition (FDR‐adjusted p<0.05). M1 and M15 both positively associates with memory, M1 positively associated with language and M15 with visuospatial function. M1 and M15 are enriched in differentially expressed genes (DEGs) associated with language and executive function, respectively. M2 negatively associates with logical memory delayed recall scores(LMDR), memory, executive, and language functions and is enriched in DEGs for these phenotypes. M8 negatively associates with memory, language and executive functions and is enriched in DEGs for memory and language. M12 positively associates with LMDR. M1 and M15 are down‐regulated while M2 and M8 are up‐regulated in AD/MCI patients. Cell‐type enrichment analysis showed M2 is enriched in monocytes and neutrophils; M8 in monocytes; M15 in B cells (FDR <0.05). Gene ontology terms enriched in these modules indicated broad consistency with their cell types. Conclusion: We identified five modules significantly associated with AD/MCI or cognitive phenotypes using blood transcriptome data. These findings nominate blood transcriptome changes and their enriched biological processes as potential pathomechanisms in cognitive decline and AD/MCI development. We aim to investigate these blood transcripts as potential biomarkers for AD or AD‐related phenotypes and therapeutic targets through additional replication and experimental validation studies.Item Effects of social distancing policy on labor market outcomes(Wiley, 2023) Gupta, Sumedha; Montenovo, Laura; Nguyen, Thuy; Lozano-Rojas, Felipe; Schmutte, Ian; Simon, Kosali; Weinberg, Bruce A.; Wing, Coady; Economics, School of Liberal ArtsUS workers receive unemployment benefits if they lose their job, but not for reduced working hours. In alignment with the benefits incentives, we find that the labor market responded to COVID-19 and related closure-policies mostly on the extensive (12 pp outright job loss) margin. Exploiting timing variation in state closure-policies, difference-in-differences (DiD) estimates show, between March 12 and April 12, 2020, employment rate fell by 1.7 pp for every 10 extra days of state stay-at-home orders (SAH), with little effect on hours worked/earnings among those employed. Forty percentage of the unemployment was due to a nationwide shock, rest due to social-distancing policies, particularly among "non-essential" workers.Item Gliovascular transcriptional perturbations in Alzheimer's disease reveal molecular mechanisms of blood brain barrier dysfunction(Springer Nature, 2024-06-20) İş, Özkan; Wang, Xue; Reddy, Joseph S.; Min, Yuhao; Yilmaz, Elanur; Bhattarai, Prabesh; Patel, Tulsi; Bergman, Jeremiah; Quicksall, Zachary; Heckman, Michael G.; Tutor-New, Frederick Q.; Demirdogen, Birsen Can; White, Launia; Koga, Shunsuke; Krause, Vincent; Inoue, Yasuteru; Kanekiyo, Takahisa; Cosacak, Mehmet Ilyas; Nelson, Nastasia; Lee, Annie J.; Vardarajan, Badri; Mayeux, Richard; Kouri, Naomi; Deniz, Kaancan; Carnwath, Troy; Oatman, Stephanie R.; Lewis-Tuffin, Laura J.; Nguyen, Thuy; Alzheimer’s Disease Neuroimaging Initiative; Carrasquillo, Minerva M.; Graff-Radford, Jonathan; Petersen, Ronald C.; Jack, Clifford R., Jr.; Kantarci, Kejal; Murray, Melissa E.; Nho, Kwangsik; Saykin, Andrew J.; Dickson, Dennis W.; Kizil, Caghan; Allen, Mariet; Ertekin-Taner, Nilüfer; Radiology and Imaging Sciences, School of MedicineTo uncover molecular changes underlying blood-brain-barrier dysfunction in Alzheimer’s disease, we performed single nucleus RNA sequencing in 24 Alzheimer’s disease and control brains and focused on vascular and astrocyte clusters as main cell types of blood-brain-barrier gliovascular-unit. The majority of the vascular transcriptional changes were in pericytes. Of the vascular molecular targets predicted to interact with astrocytic ligands, SMAD3, upregulated in Alzheimer’s disease pericytes, has the highest number of ligands including VEGFA, downregulated in Alzheimer’s disease astrocytes. We validated these findings with external datasets comprising 4,730 pericyte and 150,664 astrocyte nuclei. Blood SMAD3 levels are associated with Alzheimer’s disease-related neuroimaging outcomes. We determined inverse relationships between pericytic SMAD3 and astrocytic VEGFA in human iPSC and zebrafish models. Here, we detect vast transcriptome changes in Alzheimer’s disease at the gliovascular-unit, prioritize perturbed pericytic SMAD3-astrocytic VEGFA interactions, and validate these in cross-species models to provide a molecular mechanism of blood-brain-barrier disintegrity in Alzheimer’s disease.Item Racial and Ethnic Disparities in Buprenorphine and Extended-Release Naltrexone Filled Prescriptions During the COVID-19 Pandemic(American Medical Association, 2022) Nguyen, Thuy; Ziedan, Engy; Simon, Kosali; Miles, Jennifer; Crystal, Stephen; Samples, Hillary; Gupta, Sumedha; Economics, School of Liberal ArtsImportance: COVID-19 disrupted delivery of buprenorphine and naltrexone treatment for opioid use disorder (OUD), and during the pandemic, members of racial and ethnic minority groups experienced increased COVID-19 and opioid overdose risks compared with White individuals. However, whether filled buprenorphine and naltrexone prescriptions varied across racial and ethnic groups during the COVID-19 pandemic remains unknown. Objective: To investigate whether disruptions in filled buprenorphine and naltrexone prescriptions differed by race and ethnicity and insurance status or payer type. Design, setting, and participants: This cross-sectional study used retail pharmacy claims from May 2019 to June 2021 from the Symphony Health database, which includes 92% of US retail pharmacy claims, with race and ethnicity data spanning all insurance status and payer categories. Interrupted time series were used to estimate levels and trends of dispensed buprenorphine and naltrexone prescriptions before and after pandemic onset. Included individuals were those who filled buprenorphine and extended-release naltrexone prescriptions. Data were analyzed from July 2021 through March 2022. Main outcomes and measures: Weekly rates of dispensed buprenorphine and extended-release naltrexone prescription fills per 1000 patients and proportion of longer (ie, ≥14 days' supply) buprenorphine prescription fills were calculated. Analyses were stratified by patient race and ethnicity and further by insurance status and payer type for White and Black patients. Results: A total of 1 556 860 individuals who filled buprenorphine prescriptions (4359 Asian [0.3%], 94 657 Black [6.1%], 55 369 Hispanic [3.6%], and 664 779 White [42.7%]) and 127 506 individuals who filled extended-release naltrexone prescriptions (344 Asian [0.3%], 8186 Black [6.4%], 5343 Hispanic [4.2%], and 53 068 White [41.6%]) from May 6, 2019, to June 5, 2021, were analyzed. Prepandemic increases in buprenorphine fill rate flattened for all groups after COVID-19 onset (30.5 percentage point difference in trend; P < .001) compared with prepandemic trends. Significant level decreases in buprenorphine fills (ranging from 2.5% for Black patients; P = .009 to 4.0% for Hispanic patients; P = .009) at pandemic onset were observed for members of racial and ethnic minority groups but not White patients. At pandemic onset, rate of buprenorphine fills decreased in level for Medicare and cash-paying patients but with greater decreases for Black patients (Medicare: 10.0%; P < .001; cash: 20.0%; P < .001) than White patients (Medicare: 3.5%; P = .004; cash: 15.0%; P < .001). No decreases were found among Medicaid patients. Unlike buprenorphine, extended-release naltrexone had uniform level (from 10.0% for White patients with private insurance; P < .001 to 23.3% for Black patients with Medicare; P < .001) and trend (from 15.5 percentage points for White patients with Medicaid; P = .001 to 52.0 percentage points for Black patients with private insurance; P < .001) decreases across groups. Conclusions and relevance: This study found that the COVID-19 pandemic was associated with immediate decreases in filled buprenorphine prescriptions by members of racial and ethnic minority groups but not White individuals. These findings suggest that members of racial and ethnic minority groups had larger losses in buprenorphine access during the pandemic across payer types.