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Genetic Architecture Of Cerebrospinal Fluid And Brain Metabolite Levels And The Genetic Colocalization Of Metabolites With Human Traits, Ciyang Wang, Chengran Yang, Daniel Western, Muhammad Ali, Yueyao Wang, Chia-Ling Phuah, John Budde, Lihua Wang, Priyanka Gorijala, Jigyasha Timsina, Agustin Ruiz, Pau Pastor, Maria Victoria Fernandez, Dominantly Inherited Alzheimer Network (Dian), Alzheimer’S Disease Neuroimaging Initiative (Adni), Daniel J Panyard, Corinne D Engelman, Yuetiva Deming, Merce Boada, Amanda Cano, Pablo Garcia-Gonzalez, Neill R Graff-Radford, Hiroshi Mori, Jae-Hong Lee, Richard J Perrin, Laura Ibanez, Yun Ju Sung, Carlos Cruchaga Dec 2024

Genetic Architecture Of Cerebrospinal Fluid And Brain Metabolite Levels And The Genetic Colocalization Of Metabolites With Human Traits, Ciyang Wang, Chengran Yang, Daniel Western, Muhammad Ali, Yueyao Wang, Chia-Ling Phuah, John Budde, Lihua Wang, Priyanka Gorijala, Jigyasha Timsina, Agustin Ruiz, Pau Pastor, Maria Victoria Fernandez, Dominantly Inherited Alzheimer Network (Dian), Alzheimer’S Disease Neuroimaging Initiative (Adni), Daniel J Panyard, Corinne D Engelman, Yuetiva Deming, Merce Boada, Amanda Cano, Pablo Garcia-Gonzalez, Neill R Graff-Radford, Hiroshi Mori, Jae-Hong Lee, Richard J Perrin, Laura Ibanez, Yun Ju Sung, Carlos Cruchaga

Faculty, Staff and Student Publications

Brain metabolism perturbation can contribute to traits and diseases. We conducted a genome-wide association study for cerebrospinal fluid (CSF) and brain metabolite levels, identifying 205 independent associations (47.3% new signals, containing 11 new loci) for 139 CSF metabolites, and 32 independent associations (43.8% new signals, containing 4 new loci) for 31 brain metabolites. Of these, 96.9% (CSF) and 71.4% (brain) of the new signals belonged to previously analyzed metabolites in blood or urine. We integrated the metabolite quantitative trait loci (MQTLs) with 23 neurological, psychiatric and common human traits and diseases through colocalization to identify metabolites and biological processes implicated …


Evaluating The Stress System Of The Grieving Brain: Corticotropin-Releasing Factors And Partner Loss In Female Coyotes, Rachel Tong Xin Ning Dec 2024

Evaluating The Stress System Of The Grieving Brain: Corticotropin-Releasing Factors And Partner Loss In Female Coyotes, Rachel Tong Xin Ning

Undergraduate Honors Capstone Projects

Forming social bonds is fundamental in helping us foster connections with others. The loss of a loved one often results in grief, stress, and loneliness, and the stress response system of the body has been implicated in the physiological symptoms associated with grieving. Corticotropin releasing factor (CRF) is the hormone that initiates the stress response in the body and acts at two different receptor subtypes CRF receptor (CRFR)1 and CRFF2. Many studies on CRF and social loss have been conducted in monogamous prairie voles, but studies in longer-lived monogamous mammals could improve understanding of the effects of losing pair bonds. …


Prediagnostic Amino Acid Metabolites And Risk Of Gout, Accounting For Serum Urate: Prospective Cohort Study And Mendelian Randomization, Natalie Mccormick, Amit D Joshi, Chio Yokose, Bing Yu, Adrienne Tin, Robert Terkeltaub, Tony R Merriman, Oana Zeleznik, A Heather Eliassen, Gary C Curhan, Hang-Korng Ea, Matthew Nayor, Laura M Raffield, Hyon K Choi Dec 2024

Prediagnostic Amino Acid Metabolites And Risk Of Gout, Accounting For Serum Urate: Prospective Cohort Study And Mendelian Randomization, Natalie Mccormick, Amit D Joshi, Chio Yokose, Bing Yu, Adrienne Tin, Robert Terkeltaub, Tony R Merriman, Oana Zeleznik, A Heather Eliassen, Gary C Curhan, Hang-Korng Ea, Matthew Nayor, Laura M Raffield, Hyon K Choi

Faculty, Staff and Student Publications

Objective: Our objective was to prospectively investigate prediagnostic population-based metabolome for risk of hospitalized gout (ie, most accurate, severe, and costly cases), accounting for serum urate.

Methods: We conducted prediagnostic metabolome-wide analyses among 249,677 UK Biobank participants with nuclear magnetic resonance metabolomic profiling (N = 168 metabolites, including eight amino acids) from baseline blood samples (2006-2010) without a history of gout. We calculated multivariable hazard ratios (HRs) for hospitalized incident gout, before and after adjusting for serum urate levels; we included patients with nonhospitalized incident gout in a sensitivity analysis. Potential causal effects were evaluated with two-sample Mendelian randomization.

Results: …


The Role Of Lifr Signaling In Innate Immunity, Laura Kahn Serrudo Dec 2024

The Role Of Lifr Signaling In Innate Immunity, Laura Kahn Serrudo

Dissertations and Theses (Open Access)

The localized signals that bone marrow (BM) hematopoietic stem cells (HSCs) and immune cells receive are critical in regulating their responses in the steady state and inflammation. Monocytes are an abundant and key population in the innate immune response that originates in the BM, and they circulate to monitor the periphery. Monocytes are composed of many subsets that have essential and specific functions, including swift egress from the BM, production of pro-inflammatory cytokines, and differentiation into monocyte-derived dendritic cells (MoDCs), which are required for efficient pathogen eradication.

Here, we uncovered LIFR (leukemia inhibitory factor receptor) restrains low-grade chronic inflammation in …


A Pan-Cancer Single-Cell Analysis Of Intratumoral Copy Number Diversity And Evolution, Hanghui Ye Dec 2024

A Pan-Cancer Single-Cell Analysis Of Intratumoral Copy Number Diversity And Evolution, Hanghui Ye

Dissertations and Theses (Open Access)

Aneuploidy is a hallmark of human cancers, with many copy number aberrations (CNAs) being associated with disease progression. Previous studies have revealed extensive inter-patient heterogeneity (IPH) in copy number profiles. However, the extent of intratumoral heterogeneity (ITH) and its evolutionary dynamics remain poorly understood.

To address these gaps, we developed Acoustic Cell Tagmentation (ACT), an advanced single-cell single-molecule DNA sequencing (scDNA-seq) technology, to resolve the copy number substructure of human tumors and investigate the evolution of aneuploidy. Applying ACT to eight triple-negative breast cancer (TNBC) patients to profile 9,765 aneuploid tumor cells, we discovered that following initial punctuated copy number …


Investigating The Rare Aneuploid Cells In Normal Breast And Therapeutic Resistance In Triple Negative Breast Cancer Using Single Cell Genomics, Yiyun Lin Dec 2024

Investigating The Rare Aneuploid Cells In Normal Breast And Therapeutic Resistance In Triple Negative Breast Cancer Using Single Cell Genomics, Yiyun Lin

Dissertations and Theses (Open Access)

Aneuploid epithelial cells are common in breast cancer, however their presence in normal breast tissues is not well understood. To address this question, we applied single cell DNA sequencing to profile copy number alterations (CNAs) in 83,206 epithelial cells from breast tissues of 49 healthy women and single cell DNA&ATAC co-assays to 19 women. Our data shows that all women harbored rare aneuploid epithelial cells (median 3.19%) that increased with age. Many aneuploid epithelial cells (median 82.22%) in normal breast tissues underwent clonal expansions and harbored CNAs reminiscent of invasive breast cancers (gains of 1q, losses of 10q, 16q and …


Economic Disadvantage During Childhood, Obesity, And Diabetes Across Three Birth Cohorts Of Older Mexicans, Jesús-Daniel Zazueta-Borboa, Rafael Samper-Ternent, Rebeca Wong, Neil Mehta Dec 2024

Economic Disadvantage During Childhood, Obesity, And Diabetes Across Three Birth Cohorts Of Older Mexicans, Jesús-Daniel Zazueta-Borboa, Rafael Samper-Ternent, Rebeca Wong, Neil Mehta

Faculty, Staff and Student Publications

OBJECTIVES: Diabetes prevalence has increased markedly in Mexico. We examined the individual and joint contributions of economic disadvantage during childhood (EDDC) and elevated body weight on diabetes prevalence in 3 cohorts of Mexican adults.

METHODS: Data on those 60-69 years old from the 1930-1939, 1940-1949, and 1950-1959 birth cohorts in Waves 1 (2001), 3 (2012), and 5 (2018) of the Mexican Health and Aging Study were used. EDDC was defined as the absence of a toilet in the household before age 10. Body mass status was defined using self-reported perceived body image at age 50. Diabetes was based on respondent …


The Role Of Ganglioside Gd2 And Gd3 Synthase (St8sia1) In The Regulation Of Immune Suppression In Breast Cancer, Bolutyfe Oderinde Dec 2024

The Role Of Ganglioside Gd2 And Gd3 Synthase (St8sia1) In The Regulation Of Immune Suppression In Breast Cancer, Bolutyfe Oderinde

Dissertations and Theses (Open Access)

Gangliosides are acidic glycosphingolipids involved in cell adhesion, proliferation, and modulation of signal transduction pathways. It has been reported that tumor-shed gangliosides influence the activity of immune cells including macrophages, NK cells, and T cells. GD3 synthase (GD3S) is the key enzyme that regulates the biosynthesis of the b and c series gangliosides, particularly GD3 and GD2, and studies have shown that GD3S is upregulated in most tumors and plays a role in tumor progression. Similarly, we have previously found GD3S to be significantly upregulated in GD2+ breast cancer stem cells (BCSC) compared to GD2- cells, and the knockdown of …


Smooth Muscle Cell Stress Response: Essential In Atherosclerotic Pathogenesis, Pujun Guan Dec 2024

Smooth Muscle Cell Stress Response: Essential In Atherosclerotic Pathogenesis, Pujun Guan

Dissertations and Theses (Open Access)

Atherosclerosis remains the leading cause of death worldwide. Recent research using lineage tracing and single-cell RNA sequencing unveiled a previously undescribed and prominent role of smooth muscle cells (SMCs) in atherosclerotic plaque formation. SMCs undergo complex phenotypic modulation characterized by de-differentiation of SMCs and heterogeneously increased expression of markers for macrophages, fibroblasts, chondrocytes, and mesenchymal stem cells as plaques form. Cultured SMCs exposed to exogenous cholesterol mimic many of the phenotypic changes associated with plaque formation, and our lab determined this SMC modulation is driven by cholesterol entering the endoplasmic reticulum (ER) and triggering ER stress and PERK signaling. Further, …


Assessing The Temporal Role Of Mir-200 Loss In Murine Models Of Nsclc, Jared Fradette Dec 2024

Assessing The Temporal Role Of Mir-200 Loss In Murine Models Of Nsclc, Jared Fradette

Dissertations and Theses (Open Access)

Lung cancer is the leading cause of cancer related deaths in the United States, with non-small cell lung cancer (NSCLC) making up a majority of new diagnoses. Metastasis is the big killer in NSCLC and is driven by epithelial-mesenchymal transition (EMT) and immune evasion. The microRNA 200 family is a master regulator of EMT and is implicated in immune regulation. In this study we have developed a novel genetically engineered mouse model (GEMM) and derived primary cell lines from them to explore the role of microRNA-200 in early EMT and immune changes. Our model combines conditional activation of KrasG12D …


Manufacturing Enterprises' Gross Margins And Performance: A Study On The Moderating Effect Of Management Expenses And R&D Expenses, Jiuliu Zhang Dec 2024

Manufacturing Enterprises' Gross Margins And Performance: A Study On The Moderating Effect Of Management Expenses And R&D Expenses, Jiuliu Zhang

Dissertations and Theses Collection (Open Access)

In the context of globalization, manufacturing enterprises are integral to national economies, with their financial stability closely related to increasingly fierce market competition. Among various financial metrics, gross margin stands out as a key indicator of product profitability, significantly impacting production decisions, cost control, and pricing strategies. Understanding the relationship between the gross margins of manufacturing enterprises and their performance is essential for optimizing their financial structures and enhancing their market competitiveness. The study aims to investigate the correlation between gross margin and enterprise performance by developing complex, scientifically sound models and utilizing big data analysis technology. Additionally, it examines …


The Unconscious At Work: A Psychosocial Study Of Leaders' Unconscious Processes Impacting Participatory Change Leadership, Vanessa Hills Dec 2024

The Unconscious At Work: A Psychosocial Study Of Leaders' Unconscious Processes Impacting Participatory Change Leadership, Vanessa Hills

Dissertations

This dissertation explores the varied dynamics impacting how organizational leaders conceptualize and enact their roles in participatory change processes. To that end, a multiple-case study informed by a psycho-social approach and using Free Association Narrative Interview (FANI) methods was conducted. Each case was comprised of a single business leader. The findings, presented through individual case analyses and cross-case comparisons, reveal a discrepancy between leaders’ rhetoric and the reality of their change leadership behaviors. While leaders express support for collaborative change, factors such as a desire for control, fear of failure, and bias toward their own capabilities lead them to adopt …


Gamma Sigma Delta, Nebraska Chapter Newsletter, Issue #66 December 2024 Dec 2024

Gamma Sigma Delta, Nebraska Chapter Newsletter, Issue #66 December 2024

Gamma Sigma Delta, Nebraska Chapter: Newsletters

Nominations Solicitations Issue

President's Message, John R. Ruberson

Members

Grad Student Award

Teaching Award

Research Award

Extension Award

Award of Merit

Annual Membership Info

Student Award Fund

In Memoriam: John L. Lambert (April 25, 1942-July 3, 2024), Larry Elmer Germer (April 24, 1941-October 25, 2024), Leo Lucas (1931-November 13, 2024)

Pledge


The Life And Discoveries Of Yellapragada Subbarow, Nikhil R, Varuni Pragya, Subramanian Ramaswamy, Shiva Prasad B N, Mahabaleshwar Mamadapur Dec 2024

The Life And Discoveries Of Yellapragada Subbarow, Nikhil R, Varuni Pragya, Subramanian Ramaswamy, Shiva Prasad B N, Mahabaleshwar Mamadapur

Digital Journal of Clinical Medicine

Dr. Yellapragada Subbarow was a researcher, teacher, and a wizard of wonder drugs who constantly made efforts in the discoveries/ inventions such as vitamins, anti-vitamins, antibiotics, and many more by disentangling the mysteries of nature for the betterment of the people. He inspired the youngsters to take up the challenges and to stand up above mediocrity. The reward for his achievement was delayed. The article describes a true humanist's journey, discoveries, and his achievements that are largely unknown to date.


Elevation And Population Size Effects On The Survival Of Drosera Rotundifolia, Jessica Williams Dec 2024

Elevation And Population Size Effects On The Survival Of Drosera Rotundifolia, Jessica Williams

Electronic Theses and Dissertations

Carnivorous plants face significant conservation challenges due to habitat destruction, climate change, and illegal harvesting. This study explores how elevation and population size influence key-life history traits of D. rotundifolia, such as flowering phenology, prey capture efficiency, seed production, and germination rates. Higher elevations and larger populations are associated with extended flowering durations and increased prey capture. However, seed production and germination rates show complex patterns that are likely influenced by genetic diversity, resource availability, or environmental conditions. These insights inform targeted conservation strategies, emphasizing habitat preservation, enhancing prey availability, and maintaining genetic diversity. Public education and community engagement …


Fabrication And Charcaterization Of Pullulan-Collagen Nanofibers Via Forcespinning, Valeria Leon Leal Dec 2024

Fabrication And Charcaterization Of Pullulan-Collagen Nanofibers Via Forcespinning, Valeria Leon Leal

Theses and Dissertations

Extensive research on collagen has spurred advancements in tissue engineering and biomaterial development, given collagen´s pivotal role in regulating various tissue structures across diverse organisms. This study delves into fabricating nanocomposites utilizing collagen, along with silver nanoparticles, chondroitin sulfate and pullulan, for potential applications in antibacterial medical devices, and cell regeneration. Collagen, abundant in the extracellular matrix, provides essential structural support, while silver nanoparticles and chondroitin confer antimicrobial properties, crucial for combating infections. Pullulan, a polysaccharide polymer, serves as a biocompatible carrier for silver nanoparticles whilst being the starting nanofiber forming material. Utilizing Forcespinning® technology, composite nanofibers were successfully synthesized. …


Exploring The Potential Of Epiregulin And Amphiregulin As Prognostic, Predictive, And Therapeutic Targets In Colorectal Cancer, Cara Guernsey-Biddle, Peyton High, Kendra S Carmon Dec 2024

Exploring The Potential Of Epiregulin And Amphiregulin As Prognostic, Predictive, And Therapeutic Targets In Colorectal Cancer, Cara Guernsey-Biddle, Peyton High, Kendra S Carmon

The Brown Foundation: Institute of Molecular Medicine

The epidermal growth factor receptor (EGFR) plays a critical role in regulating essential cellular processes that are frequently hijacked to promote cancer. In colorectal cancer (CRC) in particular, the EGFR signaling pathway is frequently hyperactivated via receptor and/or ligand overexpression and downstream oncogenic mutations. Current EGFR-targeted therapies for metastatic CRC (mCRC) include the monoclonal antibodies (mAbs) cetuximab and panitumumab. However, intrinsic and acquired resistance to EGFR-targeted mAbs are commonly observed. Thus, additional biomarkers are necessary to better understand patient sensitivity to EGFR-targeted therapies. Furthermore, therapeutic targeting of alternative EGFR pathway components may serve as one mechanism to overcome EGFR-targeted mAb …


Three Decades Of Rat Genomics: Approaching The Finish(Ed) Line, Theodore S Kalbfleisch, Melissa L Smith, Julia L Ciosek, Kai Li, Peter A Doris Dec 2024

Three Decades Of Rat Genomics: Approaching The Finish(Ed) Line, Theodore S Kalbfleisch, Melissa L Smith, Julia L Ciosek, Kai Li, Peter A Doris

The Brown Foundation: Institute of Molecular Medicine

The rat, Rattus norvegicus, has provided an important model for investigation of a range of characteristics of biomedical importance. Here we survey the origins of this species, its introduction into laboratory research, and the emergence of genetic and genomic methods that utilize this model organism. Genomic studies have yielded important progress and provided new insight into several biologically important traits. However, some studies have been impeded by the lack of a complete and accurate reference genome for this species. New sequencing and genome assembly methods applied to the rat have resulted in a new reference genome assembly, GRCr8, which …


Anxiety-Like Behaviors In Mice Unmasked: Revealing Sex Differences In Anxiety Using A Novel Light-Heat Conflict Test, Sydney E Lee, Sung-Hoon Park, John C Aldrich, Laura K Fonken, Andrew D Gaudet Dec 2024

Anxiety-Like Behaviors In Mice Unmasked: Revealing Sex Differences In Anxiety Using A Novel Light-Heat Conflict Test, Sydney E Lee, Sung-Hoon Park, John C Aldrich, Laura K Fonken, Andrew D Gaudet

The Brown Foundation: Institute of Molecular Medicine

Anxiety and chronic pain afflict hundreds of millions worldwide. Anxiety and pain are more prevalent in females compared to males. Unfortunately, robust sex differences in human anxiety are not recapitulated in rodent tests, and results from rodent pain studies frequently fail to translate clinically. Therefore, there is a need to develop tests that reflect the differential salience of anxiety or pain-related stimuli between the sexes. Accordingly, here we introduce the Thermal Increments Dark-Light (TIDAL) conflict test. The TIDAL test places an anxiety-relevant stimulus (dark vs. illuminated chamber) in conflict with a heat-related stimulus (incrementally heated vs. isothermic chamber); mice freely …


Three-Dimensional Environmentally Sustainable Neuromorphic Computing System Based On Natural Organic Memristor, Mohammed Rafeeq Khan Dec 2024

Three-Dimensional Environmentally Sustainable Neuromorphic Computing System Based On Natural Organic Memristor, Mohammed Rafeeq Khan

Graduate Theses and Dissertations (2019 - present)

A three-dimensional neuromorphic (3D) computing architecture based on environmentally sustainable natural organic honey memristors is proposed in this thesis. A set of comprehensive and experimental results indicate that the proposed systems exhibit remarkable inference accuracy, consistently surpassing the 90% threshold, even with different challenges such as device variations and nonlinearity. This study also considers four different conductance drift situations, the effects of analog-to-digital converter (ADC) quantization, and multiple algorithms, such as VGG8 and DenseNet-40. The deliverable of this thesis will test the stability of the proposed systems and explore their potential applications and scalability in real-world situations.


Covid-19 Risk Assessment Among Vulnerable Small Business Owners In El Paso County, Texas, Sadie H Conway, Denise Vasquez, Kristina D Mena, Louis D Brown, Soyoung Kwon, Janelle Rios Dec 2024

Covid-19 Risk Assessment Among Vulnerable Small Business Owners In El Paso County, Texas, Sadie H Conway, Denise Vasquez, Kristina D Mena, Louis D Brown, Soyoung Kwon, Janelle Rios

Faculty, Staff and Student Publications

Background: Our objective was to deliver actionable, worksite-specific COVID-19 risk assessments and mitigation strategies tailored to vulnerable workers in one of the highest-risk areas in the US.

Methods: Four trained, bilingual (English/Spanish) community health workers (CHWs) recruited small businesses (ie, ≤20 employees) across various industries and executed novel on-site infectious disease risk assessment surveys of at least one employer and one employee.

Results: Of 102 participating businesses (95% Hispanic-owned), 96% were characterized as "high risk" or "very high risk" for disease transmission. All businesses reported implementing at least one practice to reduce disease transmission; however, almost half of businesses lacked …


Bivariate Genome-Wide Association Study Of Circulating Fibrinogen And C-Reactive Protein Levels, Julie Hahn, Gerard Temprano-Sagrera, Natalie R Hasbani, Symen Ligthart, Abbas Dehghan, Alisa S Wolberg, Nicholas L Smith, Maria Sabater-Lleal, Alanna C Morrison, Paul S De Vries Dec 2024

Bivariate Genome-Wide Association Study Of Circulating Fibrinogen And C-Reactive Protein Levels, Julie Hahn, Gerard Temprano-Sagrera, Natalie R Hasbani, Symen Ligthart, Abbas Dehghan, Alisa S Wolberg, Nicholas L Smith, Maria Sabater-Lleal, Alanna C Morrison, Paul S De Vries

Faculty, Staff and Student Publications

Background: Fibrinogen and C-reactive protein (CRP) play an important role in inflammatory pathways and share multiple genetic loci reported in previously published genome-wide association studies (GWAS), highlighting their common genetic background. Leveraging the shared biology may identify further loci pleiotropically associated with both fibrinogen and CRP.

Objectives: To identify novel genetic variants that are pleiotropic and associated with both fibrinogen and CRP, by integrating both phenotypes in a bivariate GWAS by using a multitrait GWAS.

Methods: We performed a bivariate GWAS to identify further pleiotropic genetic loci, using summary statistics of previously published GWAS on fibrinogen (n = 120 246) …


Identification Of Proteins Associated With Type 2 Diabetes Risk In Diverse Racial And Ethnic Populations, Shuai Liu, Jingjing Zhu, Hua Zhong, Chong Wu, Haoran Xue, Burcu F Darst, Xiuqing Guo, Peter Durda, Russell P Tracy, Yongmei Liu, W Craig Johnson, Kent D Taylor, Ani W Manichaikul, Mark O Goodarzi, Robert E Gerszten, Clary B Clish, Yii-Der Ida Chen, Heather Highland, Christopher A Haiman, Christopher R Gignoux, Leslie Lange, David V Conti, Laura M Raffield, Lynne Wilkens, Loïc Le Marchand, Kari E North, Kristin L Young, Ruth J Loos, Steve Buyske, Tara Matise, Ulrike Peters, Charles Kooperberg, Alexander P Reiner, Bing Yu, Eric Boerwinkle, Quan Sun, Mary R Rooney, Justin B Echouffo-Tcheugui, Martha L Daviglus, Qibin Qi, Nicholas Mancuso, Changwei Li, Youping Deng, Alisa Manning, James B Meigs, Stephen S Rich, Jerome I Rotter, Lang Wu Dec 2024

Identification Of Proteins Associated With Type 2 Diabetes Risk In Diverse Racial And Ethnic Populations, Shuai Liu, Jingjing Zhu, Hua Zhong, Chong Wu, Haoran Xue, Burcu F Darst, Xiuqing Guo, Peter Durda, Russell P Tracy, Yongmei Liu, W Craig Johnson, Kent D Taylor, Ani W Manichaikul, Mark O Goodarzi, Robert E Gerszten, Clary B Clish, Yii-Der Ida Chen, Heather Highland, Christopher A Haiman, Christopher R Gignoux, Leslie Lange, David V Conti, Laura M Raffield, Lynne Wilkens, Loïc Le Marchand, Kari E North, Kristin L Young, Ruth J Loos, Steve Buyske, Tara Matise, Ulrike Peters, Charles Kooperberg, Alexander P Reiner, Bing Yu, Eric Boerwinkle, Quan Sun, Mary R Rooney, Justin B Echouffo-Tcheugui, Martha L Daviglus, Qibin Qi, Nicholas Mancuso, Changwei Li, Youping Deng, Alisa Manning, James B Meigs, Stephen S Rich, Jerome I Rotter, Lang Wu

Faculty, Staff and Student Publications

Aims/hypothesis: Several studies have reported associations between specific proteins and type 2 diabetes risk in European populations. To better understand the role played by proteins in type 2 diabetes aetiology across diverse populations, we conducted a large proteome-wide association study using genetic instruments across four racial and ethnic groups: African; Asian; Hispanic/Latino; and European.

Methods: Genome and plasma proteome data from the Multi-Ethnic Study of Atherosclerosis (MESA) study involving 182 African, 69 Asian, 284 Hispanic/Latino and 409 European individuals residing in the USA were used to establish protein prediction models by using potentially associated cis- and trans-SNPs. The models were …


Perceived Stigma's Influence On The Association Between Suicide Risk Severity And Help-Seeking For Suicidal Crises, Donna Zastrow Dec 2024

Perceived Stigma's Influence On The Association Between Suicide Risk Severity And Help-Seeking For Suicidal Crises, Donna Zastrow

Electronic Theses and Dissertations

Introduction: Unfortunately, research examining help-seeking for suicide is limited. This study examined age, race, gender, suicide risk severity, and perceived stigma as predictors of formal and informal help-seeking behaviors individuals engage in during suicidal crises, and explored perceived stigma as a moderator of the relationship between risk severity and help-seeking. Method: Data from 80 college students who had experienced a past suicidal crisis were analyzed using two moderation analyses. Results: Rates of formal (67.5%) and informal (86.2%) help-seeking were high in the study sample. Higher suicide risk severity was positively associated with formal help-seeking (b = …


Association Of Common And Rare Variants With Alzheimer’S Disease In More Than 13,000 Diverse Individuals With Whole-Genome Sequencing From The Alzheimer’S Disease Sequencing Project, Wan-Ping Lee, Seung Hoan Choi, Margaret G Shea, Po-Liang Cheng, Beth A Dombroski, Achilleas N Pitsillides, Nancy L Heard-Costa, Hui Wang, Katia Bulekova, Amanda B Kuzma, Yuk Yee Leung, John J Farrell, Honghuang Lin, Brian W Kunkle, Adam Naj, Elizabeth E Blue, Frederick Nusetor, Dongyu Wang, Eric Boerwinkle, William S Bush, Xiaoling Zhang, Philip L De Jager, Josée Dupuis, Lindsay A Farrer, Myriam Fornage, Eden Martin, Margaret Pericak-Vance, Sudha Seshadri, Ellen M Wijsman, Li-San Wang, Alzheimer's Disease Sequencing Project;, Gerard D Schellenberg, Anita L Destefano, Jonathan L Haines, Gina M Peloso Dec 2024

Association Of Common And Rare Variants With Alzheimer’S Disease In More Than 13,000 Diverse Individuals With Whole-Genome Sequencing From The Alzheimer’S Disease Sequencing Project, Wan-Ping Lee, Seung Hoan Choi, Margaret G Shea, Po-Liang Cheng, Beth A Dombroski, Achilleas N Pitsillides, Nancy L Heard-Costa, Hui Wang, Katia Bulekova, Amanda B Kuzma, Yuk Yee Leung, John J Farrell, Honghuang Lin, Brian W Kunkle, Adam Naj, Elizabeth E Blue, Frederick Nusetor, Dongyu Wang, Eric Boerwinkle, William S Bush, Xiaoling Zhang, Philip L De Jager, Josée Dupuis, Lindsay A Farrer, Myriam Fornage, Eden Martin, Margaret Pericak-Vance, Sudha Seshadri, Ellen M Wijsman, Li-San Wang, Alzheimer's Disease Sequencing Project;, Gerard D Schellenberg, Anita L Destefano, Jonathan L Haines, Gina M Peloso

Faculty, Staff and Student Publications

INTRODUCTION: Alzheimer's disease (AD) is a common disorder of the elderly that is both highly heritable and genetically heterogeneous.

METHODS: We investigated the association of AD with both common variants and aggregates of rare coding and non-coding variants in 13,371 individuals of diverse ancestry with whole genome sequencing (WGS) data.

RESULTS: Pooled-population analyses of all individuals identified genetic variants at apolipoprotein E (APOE) and BIN1 associated with AD (p < 5 × 10

DISCUSSION: We observed that complementary pooled-population and subgroup-specific analyses offered unique insights into the genetic architecture of AD.

HIGHLIGHTS: We determine the association of genetic variants with Alzheimer's disease (AD) using …


Relative Muscular Effort In The Older Adults During The Sit-To-Stand Task: Monitoring Neuromuscular Reserve And Movement Limitations, Nayun Ahn, Michael H. Haischer, Cara L. Lewis, Kristof Kipp Dec 2024

Relative Muscular Effort In The Older Adults During The Sit-To-Stand Task: Monitoring Neuromuscular Reserve And Movement Limitations, Nayun Ahn, Michael H. Haischer, Cara L. Lewis, Kristof Kipp

Exercise Science Faculty Research and Publications

Background

Due to lower maximum strength, older adults purportedly need to exert greater muscular effort to stand up from a chair. This study investigated joint-specific muscular effort during a sit-to-stand by calculating relative-muscular-effort and investigating differences between healthy older and young adults.

Methods

Fifteen older (age: 69.9 ± 3.5 years) and 15 young (age: 22.2 ± 2.6 years) adults performed five self-paced sit-to-stand trials. Kinematic and kinetic data were collected and used to calculate inverse dynamics net joint moment. Peak isometric knee and hip extensor torques were measured and used as inputs to regression models that predicted angle- and velocity-dependent …


Equitable Community-Based Participatory Research Engagement With Communities Of Color Drives All Of Us Wisconsin Genomic Research Priorities, Sheikh Iqbal Ahamed, Praveen Madiraju Dec 2024

Equitable Community-Based Participatory Research Engagement With Communities Of Color Drives All Of Us Wisconsin Genomic Research Priorities, Sheikh Iqbal Ahamed, Praveen Madiraju

Computer Science Faculty Research and Publications

Objective

The NIH All of Us Research Program aims to advance personalized medicine by not only linking patient records, surveys, and genomic data but also engaging with participants, particularly from groups traditionally underrepresented in biomedical research (UBR). This study details how the dialogue between scientists and community members, including many from communities of color, shaped local research priorities.

Materials and Methods

We recruited area quantitative, basic, and clinical scientists as well as community members from our Community and Participant Advisory Boards with a predetermined interest in All of Us research as members of a Special Interest Group (SIG). An expert …


Low Intensity Mechanical Signals Promote Proliferation In A Cell-Specific Manner: Tailoring A Non-Drug Strategy To Enhance Biomanufacturing Yields, M Ete Chan, Christopher Ashdown, Lia Strait, Sishir Pasumarthy, Abdullah Hassan, Steven Crimarco, Chanpreet Singh, Vihitaben S Patel, Gabriel Pagnotti, Omor Khan, Gunes Uzer, Clinton T Rubin Dec 2024

Low Intensity Mechanical Signals Promote Proliferation In A Cell-Specific Manner: Tailoring A Non-Drug Strategy To Enhance Biomanufacturing Yields, M Ete Chan, Christopher Ashdown, Lia Strait, Sishir Pasumarthy, Abdullah Hassan, Steven Crimarco, Chanpreet Singh, Vihitaben S Patel, Gabriel Pagnotti, Omor Khan, Gunes Uzer, Clinton T Rubin

Faculty, Staff and Student Publications

Biomanufacturing relies on living cells to produce biotechnology-based therapeutics, tissue engineering constructs, vaccines, and a vast range of agricultural and industrial products. With the escalating demand for these bio-based products, any process that could improve yields and shorten outcome timelines by accelerating cell proliferation would have a significant impact across the discipline. While these goals are primarily achieved using biological or chemical strategies, harnessing cell mechanosensitivity represents a promising - albeit less studied - physical pathway to promote bioprocessing endpoints, yet identifying which mechanical parameters influence cell activities has remained elusive. We tested the hypothesis that mechanical signals, delivered non-invasively …


Healthcare Disparities, Screening, And Molecular Testing In The Changing Landscape Of Non-Small Cell Lung Cancer In The United States: A Review, Razelle Kurzrock, Aadel A Chaudhuri, David Feller-Kopman, Narjust Florez, Jed Gorden, Ignacio I Wistuba Dec 2024

Healthcare Disparities, Screening, And Molecular Testing In The Changing Landscape Of Non-Small Cell Lung Cancer In The United States: A Review, Razelle Kurzrock, Aadel A Chaudhuri, David Feller-Kopman, Narjust Florez, Jed Gorden, Ignacio I Wistuba

Faculty, Staff and Student Publications

Inequitable access to care continues to hinder improvements in diagnosis and treatment of lung cancer. This review describes healthcare disparities in the changing landscape of non-small cell lung cancer (NSCLC) in the United States, focusing on racial, ethnic, sex-based, and socioeconomic trends. Furthermore, strategies to address disparities, overcome challenges, and improve patient outcomes are proposed. Barriers exist across lung cancer screening, diagnosis, and treatment regimens, varying by sex, age, race and ethnicity, geography, and socioeconomic status. Incidence and mortality rates of lung cancer are higher among Black men than White men, and incidences in young women are substantially greater than …


Demystifying Research Paradigms: Navigating Ontology, Epistemology, And Axiology In Research, Lynette Pretorius Dec 2024

Demystifying Research Paradigms: Navigating Ontology, Epistemology, And Axiology In Research, Lynette Pretorius

The Qualitative Report

A sound understanding of research paradigms is crucial for developing coherent and philosophically grounded research designs, particularly in the humanities and social sciences. This paper offers an accessible overview of the most common research paradigms: positivism, post-positivism, constructivism, social constructionism, interpretivism, pragmatism, and critical realism. These paradigms differ in their approaches to ontology (the nature of reality), epistemology (the nature of knowledge), and axiology (the role of values in research). The paper also discusses the methodological and ethical implications of these paradigms. Reflexivity and ethical responsibility are emphasised, where researchers must account for how their own biases and values influence …