Digital Commons Network^™

Genetic Diversity And Expanded Phenotypes In Dystonia: Insights From Large-Scale Exome Sequencing, Mirja Thomsen, Joel S Perlmutter, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Dystonia is one of the most prevalent movement disorders, characterized by significant clinical and etiological heterogeneity. Despite considerable heritability (~25%), the etiology in most patients remains elusive. Moreover, understanding correlations between clinical manifestations and genetic variants has become increasingly complex.

METHODS: Exome sequencing was conducted on 1924 genetically unsolved, mainly late-onset isolated dystonia patients, recruited primarily from two dystonia registries (DysTract and the Dystonia Coalition). Rare variants in genes previously linked to dystonia (n = 406) were examined, confirmed via Sanger sequencing, and analyzed for segregation when possible.

RESULTS: We identified 137 distinct likely pathogenic/pathogenic variants (according to ACMG …

High-Density Lipoprotein-Associated Cholesterol Abnormalities In A Clinical Outcomes Study Of Dysferlin-Deficient Limb-Girdle Muscular Dystrophy Type R2, Zoe White, Alan Pestronk, Et Al.

2020-Current year OA Pubs

BACKGROUND: Limb-girdle muscular dystrophy (MD) type R2 (LGMDR2, formerly LGMD2B) is an autosomal recessive form of MD caused by variants in the dysferlin gene, DYSF. It leads to slow proximal and distal muscle weakening that generally results in loss of ambulation around early adulthood but without the lethal cardiorespiratory dysfunction observed in the more severe Duchenne MD. How loss of dysferlin causes muscle fibre death is poorly understood, but recent evidence suggests a link between muscle wasting and loss of muscle cholesterol homeostasis with circulating lipoprotein abnormalities in many forms of MD.

METHODS: Cross-sectional circulating total cholesterol (CHOL), high-density lipoprotein-associated …

Formation Control Between Leader And Migratory Follower Tissues Allows Coordinated Growth, Toru Kawanishi, Takamichi Sushida, Tony Y-C Tsai, Hiroyuki Takeda, Sean G Megason

2020-Current year OA Pubs

Coordinated growth of multiple tissues is fundamental to shaping our body, but the underlying mechanisms remain underexplored. In zebrafish embryos, midline tissues composed of the notochord, floorplate, and hypochord elongate synchronously with their lengths aligned. We show that floorplate and hypochord cells collectively migrate posteriorly along the nascent notochord extracellular matrix as it extends posteriorly, maintaining the tripartite configuration. Fibroblast growth factor-mediated migration in a spatially graded manner causes cell stretching, which triggers Yap-dependent proliferation and controls floorplate and hypochord growth. Supported by mathematical modeling, we further suggest that their growth is fine-tuned by mechanical tethering to the notochord via …

Dissemination And Implementation Of A Telehealth-Enabled Program For Providing Infectious Disease Expertise In Rural Settings, Robin L P Jump, Jason P Burnham, Et Al.

2020-Current year OA Pubs

BACKGROUND: Telehealth can facilitate improving antibiotic use and related antimicrobial stewardship activities in facilities underserved by infectious diseases (IDs) expertise. We describe implementation of the Department of Veterans Affairs (VA) videoconference antimicrobial stewardship team (VAST) to connect multidisciplinary teams from rural VA medical centers (VAMCs) with geographically distant ID experts.

METHODS: We implemented VASTs at 10 rural VAMCs from September 2021 to February 2024. VASTs consisted of regular meetings between rural VAMCs and an off-site ID expert who met by videoconference to discuss clinical cases, emphasizing recommendations for antibiotic prescribing. The VA Corporate Data Warehouse was used to collect information …

Tau Pet Positivity In Individuals With And Without Cognitive Impairment Varies With Age, Amyloid-Β Status, Apoe Genotype And Sex, Rik Ossenkoppele, Tammy L S Benzinger, Et Al.

2020-Current year OA Pubs

Tau positron emission tomography (PET) imaging allows in vivo detection of tau proteinopathy in Alzheimer's disease, which is associated with neurodegeneration and cognitive decline. Understanding how demographic, clinical and genetic factors relate to tau PET positivity will facilitate its use for clinical practice and research. Here we conducted an analysis of 42 cohorts worldwide (N = 12,048), including 7,394 cognitively unimpaired (CU) participants, 2,177 participants with mild cognitive impairment (MCI) and 2,477 participants with dementia. We found that from age 60 years to 80 years, tau PET positivity in a temporal composite region increased from 1.1% to 4.4% among CU …

Human Thalamocortical Structural Connectivity Develops In Line With A Hierarchical Axis Of Cortical Plasticity, Valerie J Sydnor, Deanna M Barch, Et Al.

2020-Current year OA Pubs

Human cortical development follows a hierarchical, sensorimotor-to-association sequence. The brain's capacity to enact this sequence indicates that it relies on unknown mechanisms to regulate regional differences in the timing of cortical maturation. Given evidence from animal systems that thalamic axons mechanistically regulate periods of cortical plasticity, here we evaluate in humans whether the development of structural connections between the thalamus and cortex aligns with cortical maturational heterochronicity. By deriving a new tractography atlas of human thalamic connections and applying it to diffusion data from three youth samples (8-23 years; total n = 2,676), we demonstrate that thalamocortical connectivity matures in …

The Global Neurodegeneration Proteomics Consortium: Biomarker And Drug Target Discovery For Common Neurodegenerative Diseases And Aging, Farhad Imam, Muhammad Ali, Carlos Cruchaga, Chengran Yang, Et Al.

2020-Current year OA Pubs

More than 57 million people globally suffer from neurodegenerative diseases, a figure expected to double every 20 years. Despite this growing burden, there are currently no cures, and treatment options remain limited due to disease heterogeneity, prolonged preclinical and prodromal phases, poor understanding of disease mechanisms, and diagnostic challenges. Identifying novel biomarkers is crucial for improving early detection, prognosis, staging and subtyping of these conditions. High-dimensional molecular studies in biofluids ('omics') offer promise for scalable biomarker discovery, but challenges in assembling large, diverse datasets hinder progress. To address this, the Global Neurodegeneration Proteomics Consortium (GNPC)-a public-private partnership-established one of the …

The Microrna Mir-30a Blocks Adipose Tissue Fibrosis Accumulation In Obesity, Pradip K Saha, Robert Sharp, Aaron R. Cox, Rabie Habib, Michael J. Bolt, Jessica B. Felix, Claudia E. Ramirez Bustamante, Xin Li, Sung Yun Jung, Kang Ho Kim, Kai Sun, Huaizhu Wu, Samuel Klein, Sean M. Hartig

2020-Current year OA Pubs

White adipose tissue (WAT) fibrosis occurring in obesity contributes to the inflammatory and metabolic comorbidities of insulin resistance and type 2 diabetes, yet the mechanisms involved remain poorly understood. Here, we report a role for the broadly conserved miRNA miR-30a as a regulator of WAT fibrosis and systemic glucose metabolism. Mice modified to express miR-30a at elevated levels in adipose tissues maintain insulin sensitivity coupled with reduced fatty liver disease when fed a high-fat diet. These effects were attributable to cell-autonomous functions of miR-30a that potently increase expression of adipocyte-specific genes. Proteomic screening revealed miR-30a limits profibrotic programs in subcutaneous …

Longer Scans Boost Prediction And Cut Costs In Brain-Wide Association Studies, Leon Qi Rong Ooi, Scott Marek, Nico U F Dosenbach, Timothy O Laumann, Evan M Gordon, Et Al.

2020-Current year OA Pubs

A pervasive dilemma in brain-wide association studies

Active Dna Demethylation Upstream Of Rod-Photoreceptor Fate Determination Is Required For Retinal Development, Ismael Hernández-Núñez, Alaina Urman, Xiaodong Zhang, William Jacobs, Christy Hoffmann, Ellen G. Harding, Shiming Chen, Meelad M. Dawlaty, Philip A. Ruzycki, John R. Edwards, Brian S. Clark

2020-Current year OA Pubs

Retinal cell fate specification from multipotent retinal progenitors is governed by dynamic changes in chromatin structure and gene expression. Methylation at cytosines in DNA (5mC) is actively regulated for proper control of gene expression and chromatin architecture. Numerous genes display active DNA demethylation across retinal development; a process that requires oxidation of 5mC to 5-hydroxymethylcytosine (5hmC) and is controlled by the ten-eleven translocation (TET) methylcytosine dioxygenase enzymes. Using an allelic series of conditional TET enzyme mutants in mice, we determine that DNA demethylation is required upstream of NRL and NR2E3 expression for the establishment of rod-photoreceptor fate. Using histological, behavioral, …

Disruption Of The Cerebrospinal Fluid-Plasma Protein Balance In Cognitive Impairment And Aging, Amelia Farinas, Daniel Western, Jigyasha Timsina, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

The brain barrier system, including the choroid plexus, meninges and brain vasculature, regulates substrate transport and maintains differential protein concentrations between blood and cerebrospinal fluid (CSF). Aging and neurodegeneration disrupt brain barrier function, but proteomic studies of the effects on blood-CSF protein balance are limited. Here we used SomaScan proteomics to characterize paired CSF and plasma samples from 2,171 healthy or cognitively impaired older individuals from multiple cohorts, including the Global Neurodegeneration Proteomics Consortium. We identified proteins with correlated CSF and plasma levels that are produced primarily outside the brain and are enriched for structural domains that may enable their …

The Impact Of Gender, Training Year, Medical Specialty And The Covid-19 Pandemic On Resident Wellness, Sara Beachy, Jessica Luzier, Chantel Weisenmuller, Kathleen Bors, Mary Ann Maurer, Amna Anees, Tiffany Lasky, Lisa Calderwood

Department of Family & Community Medicine Faculty Papers

INTRODUCTION: Data are limited as to which factors most strongly impact medical trainees' well-being, and few studies have assessed trainee's wellness at multiple time points during the COVID-19 pandemic. Additionally, much research has not taken an intersectional approach to understanding the ways in which different facets of a resident's identity impact their wellness. Thus, more person-centred, probability-driven statistical approaches that can produce distinct heterogenous groups of individuals are warranted to understand the way in which different identities are associated with resident wellness scores.

METHODS: A latent profile analysis was conducted using institutional data from resident surveys administered from 2019 to …

Experiences Of Discrimination During Pregnancy Predict Altered Neonatal Hair Cortisol At Birth, Kimberly D'Anna-Hernandez, Lillybelle K. Deer, Özlü Aran, Kenia M. Rivera, Melissa Nevarez-Brewster, Jenalee R. Doom, Benjamin L. Hankin, M. Camille Hoffman, Elysia Poggi Davis

Psychology Faculty Research and Publications

Objective

Prenatal glucocorticoids (e.g., cortisol) are a widely proposed prenatal programming mechanism, yet few studies directly measure fetal cortisol. Neonatal hair provides a non-invasive method to assess fetal cortisol. The current studies test the association between maternal exposure to discrimination and fetal cortisol, as measured in neonatal hair, in two cohorts.

Methods

Study 1: Pregnant individuals (N = 65) and their neonates (61.8 % female) participated in study 1 between 2017 and 2021. Participants self-identified as Asian (6.2 %), Black (21.5 %), Latinx (35.4 %), Multiracial or Multiethnic (35.4 %), and Native Hawaiian or Pacific Islander (1.5 %). Experiences …

Diversity Training In Clinical Child And Pediatric Psychology Programs: Results From A Survey Of Training Directors., Mary Louise Cashel, Shalonda Brooks, Trista Perez Crawford, Omar G. Gudiño, Sharnita Harris, Astrida S. Kaugars, Noriel Lim, Jerlym Porter

Psychology Faculty Research and Publications

This survey study presents satisfaction ratings completed by training directors of graduate, predoctoral internship, and postdoctoral programs in clinical child and pediatric psychology with respect to their culture and diversity training. The approaches to training and areas of diversity focus are also reported. All respondents (n = 42, 71% response rate) were from member programs of the Clinical Child and Pediatric Psychology Training Council, in geographical locations ranging from small towns to large cities across the United States. Over 90% of directors of graduate programs indicated that completing a course on multicultural psychology was a requirement for the program. …

The Effects Of Temperature And Cardiotonic Steroids On Cardiac Function And Metabolism In Snakes, Hannah Wilson

All Graduate Theses and Dissertations, Fall 2023 to Present

The function of the heart provides a window into the physiology of vertebrates and a means of evaluating their response to the stresses imposed by diverse activities. I developed a miniaturized instrument to record electrocardiograms (ECGs), using open-source Arduino technology, that a snake can wear as a backpack. The backpack can also be used when the snake is in a metabolic chamber, to record the metabolic rate and ECG simultaneously. I first used the ECG backpack to record the physiology of snakes under different temperature conditions, to verify that the system worked as expected. the backpack was then used on …

Geochemical And Stratigraphic Characterization Of The Morrison Formation And Cedar Mountain Formation Contact In The Island Park Quadrangle, Uintah County, Utah, Emily Mcdermott

All Graduate Theses and Dissertations, Fall 2023 to Present

The Upper Jurassic Morrison Formation and Lower Cretaceous Cedar Mountain Formation are among the richest sources of dinosaur fossils. Despite a 24-million-year gap in time (the Jurassic–Cretaceous unconformity), these formations are difficult to distinguish due to their similar rock types and colors. In Utah's Island Park quadrangle (IPQ), these formations are not separated on existing geological maps. This study focuses on identifying and understanding the formational boundary between them using field observations, stable isotope analysis, clay mineralogy, and chemical techniques such as X-ray diffraction (XRD) and X-ray fluorescence (XRF).

Unlike other areas where a conglomerate layer marks the boundary, the …

Gender-Diverse Individuals' Mathematics Self-Efficacy, Aliya Halterman

All Graduate Theses and Dissertations, Fall 2023 to Present

Many factors influence how well someone learns and achieve in school and daily living, with motivation being especially important. One key part of motivation is something called self-efficacy, which refers to how much someone believes they can successfully do a specific task (Bandura, 1986; 1997). Research has shown that self-efficacy plays a major role in how well people do, and the quality of their efforts (Pintrich & Schrauben, 1992; Weinstein & Mayer, 1986; Zimmermann, 2000). Additionally, mathematics skills are tied to better outcomes in school, careers, and in daily life. Mathematics also has also had a complex history when it …

Graph-Based Machine Learning: Higher-Order Interactions, Guided Generation, And Knowledge-Graph Tools, Thomas J. Kerby

All Graduate Theses and Dissertations, Fall 2023 to Present

This dissertation brings the power of graph thinking to three key challenges in modern AI, making complex data more transparent, generative design more controllable, and scholarly exploration more intuitive. First, we introduce Local CorEx, a new machine learning technique that uncovers hidden relationships among variables, making it easier to understand complex datasets without heavy computation. Next, we show how to guide the creation of new molecules by viewing the generation process itself as a walk through a "state graph," letting researchers steer outcomes toward desired chemical properties—without any extra model training. Finally, we deliver an open-source toolkit that builds interactive …

Risk Perceptions And Water Governance: Experiences Of Irrigation Companies In The Great Salt Lake Basin Of Northern Utah, United States, Bailey M. Holdaway

All Graduate Theses and Dissertations, Fall 2023 to Present

Irrigation companies are important water management entities in the Western US. However, these companies often face barriers when managing water. Particularly as the state of Utah grows and water resources are drying, there is much finger pointing at those in irrigation and agriculture for better water management. However, pointing fingers without the participation of these companies often does not lead to effective water management outcomes. Therefore, it is important to understand the role of these irrigation companies, and particularly how they are approaching water management.

I set out to understand the role of these irrigation companies, specifically in the Great …

The Validation Of The Patient’S Endorsement Of The Biopsychosocial Model Of Chronic Pain (Peb) Scale In Young Adults, Mathias M. Sanyer

All Graduate Theses and Dissertations, Fall 2023 to Present

This research examined a new tool designed to measure how patients view their chronic pain. While healthcare providers increasingly recognize that chronic pain involves biological, psychological, and social factors (a "biopsychosocial approach"), no previous tool existed to assess whether patients share this perspective. This study tested the reliability and effectiveness of the Patient's Endorsement of a Biopsychosocial Model of Chronic Pain (PEB) Scale in young adults with chronic pain. Results confirmed the scale accurately measures a single, consistent concept and correlates with patients' willingness to consider new pain management approaches. Unlike in older adults, the scale didn't predict active maintenance …

Examining The Development Of Collective Classroom Efficacy At The Secondary Level, Bradley K. Dutson

All Graduate Theses and Dissertations, Fall 2023 to Present

How can educators develop cohesive and productive learning communities at the secondary level? Prior research has investigated how classrooms develop collective classroom efficacy (CCE) or the shared belief that, as a classroom, they can achieve their learning goals together as a community. Previous studies suggest that CCE at the elementary level is developed with a teacher acting in the role of a community organizer. The teacher employs social and academic practices which incorporate the use of relevance, relationship, and responsibility. These help to establish four key elements of developing CCE which include: 1) a positive classroom environment, (2) persistence and …

Evaluating The Effects Of 3d User Interactions And Virtual Displays On Human Cognition And Perception For Immersive Analytics, Dongyun Han

All Graduate Theses and Dissertations, Fall 2023 to Present

This research investigates how virtual reality (VR) can be utilized effectively for users to explore data. Traditional data analysis typically takes place on flat, two-dimensional computer screens. In contrast, immersive technologies like VR offer a three-dimensional environment where users can engage with data more naturally and intuitively. Such immersive experiences have the potential to improve comprehension, memory, and insight during data analysis tasks. Despite this potential, several challenges remain in making immersive analytics practical and effective. Key questions include which types of 3D interaction techniques are most helpful and how accurately people perceive visual information in immersive environments. To address …

A Provable Semi-Infinite Programming Approach For Solving Dynamic Nash Games, Tyler C. Gardner

All Graduate Theses and Dissertations, Fall 2023 to Present

Many engineering problems must account for the non-cooperative decisions and actions of multiple players. These problems can be modeled within a game-theoretic framework. The approach herein is to model problems as Nash games, convert them to semi-infinite programs, and leverage provable semi-infinite algorithms to solve the original problem. A particular algorithm that leverages off-the-shelf solvers is used to solve four low-dimensional benchmark problems successfully. Two types of linear quadratic dynamic games are then investigated: ones where each player’s problem is convex and ones where at least one player’s problem is nonconvex. Within each type, variations based on information structure, communication …

Optimization Of The Root Zone In Controlled Environment Agriculture, Brendan Fatzinger

All Graduate Theses and Dissertations, Fall 2023 to Present

Controlled environment agriculture (CEA) helps grow plants in spaces where resources like water and nutrients are limited, such as deserts or spacecraft. Effective management of water in the root zone, the area where plant roots grow, is vital to keeping plants healthy, especially in closed-loop systems where water cannot be wasted, as will be necessary for long-duration space missions.

An improved automated watering system designed for use in space-like environments was developed over several trials. Early designs using suction to draw water through tubes faced problems with uneven watering and roots blocking the tubes. Switching to a system that pushed …

Alevi-Bektashi Ballads: Malady, Melody And Remedy, Mustafa Cingoz

All Graduate Theses and Dissertations, Fall 2023 to Present

This research focuses on how ballads play a central role in the cultural and spiritual life of the Alevi-Bektashi community in Türkiye. These ballads, performed by folk poets known as aşık (minstrel) with the stringed instrument bağlama are the inseparable elements of their daily life and sacred rituals. As rooted in the path of Ali, the fourth Caliph of Islam, and the teachings of 13th-century Sufi saint Haji Bektash Veli, Alevi-Bektashi ballads express shared emotions, struggles, and hopes. Therefore, my point of view argues that these ballads do more than preserve the Anatolian ballad tradition. They create a sense of …

Evaluating Cyanotoxins In Surface Water And Aerosols Near Utah Lake, Dylan R. Mcpeake

All Graduate Theses and Dissertations, Fall 2023 to Present

Utah Lake is a freshwater lake in Utah County near Provo, Utah. It is the third- largest lake in Utah and is important for recreation and local businesses. However, from June to October, the lake often has cyanobacteria harmful algal blooms (cHABs), which contain a toxin called cyanotoxin. These toxins can be dangerous to people who come into contact with the water. Government agencies regularly check for cHABs and warn people when the water is unsafe for activities like swimming. Collecting water samples to test for cHABs can be risky because it can possibly result in direct contact with the …

Adapting To Change In Amenity-Oriented Communities: Innovative Strategies For Shifting Social And Environmental Needs, Emma L. R. Epperson

All Graduate Theses and Dissertations, Fall 2023 to Present

Amenity-oriented communities are places with significant and desirable natural amenities that are highly visited and plentiful within the Intermountain West. These high rates of visitation create complex challenges such as congestion in recreation spaces and in towns and increase costs of living. These communities are typically rural and often do not have the resources, funding, or infrastructure to combat these challenges. Although tourists provide financial stability and other amenities to these towns, local wellbeing is highly impacted. Outdoor recreation and the nature connections derived from outdoor experiences are major contributors to wellbeing in amenity communities. This research investigates the changes …

Cutting Propagation And Out-Planting Of White-Margined Beardtongue (Penstemon Albomarginatus M.E. Jones), A Vulnerable Herbaceous Perennial Of The Mojave Desert), Alexander Stosich

All Graduate Theses and Dissertations, Fall 2023 to Present

Plant biodiversity is crucial for the proper functioning of ecosystems, with many species needed to maintain the variety of functions provided, especially with increasing environmental change. However, plant biodiversity is threatened in many different ecosystems, primarily through habitat loss. Species can be conserved by protecting their original habitat and mitigating for threats such as invasive species or altered disturbance regimes (plant conservation); however, with declining population numbers and continued habitat loss and/or disturbance, it may be necessary to actively move plants (plant restoration). Plant restoration is dependent on developing the capacity to a) reliably propagate plants in a nursery and …

From Rifles To Running Shoes: How Outdoor Recreation Trends Are Reshaping Conservation Efforts, Lane James Arthur

All Graduate Theses and Dissertations, Fall 2023 to Present

Parks and protected areas (PPAs) serve a dual purpose: they conserve wildlife and natural habitats while providing spaces for people to enjoy outdoor recreation. However, balancing conservation with recreation can be challenging, especially as outdoor activities continue to grow and evolve. In Utah, Wildlife Management Areas (WMAs) are set aside to protect important wildlife habitats and provide opportunities for hunting and fishing. Recently, these areas have seen an increase in activities such as mountain biking, trail running, and dog walking, some of which take place in areas which prohibit recreational activity in effort to protect wildlife. These shifts in recreation …

Effects Of Elevation, Fire Age, Burn Severity, And Pre-Fire Vegetation On Post-Fire Sagebrush Songbird Communities, William D. Harrod

All Graduate Theses and Dissertations, Fall 2023 to Present

The Sagebrush Biome of western North America has been threatened by a combination of interconnected threats. In the Great and Columbian Basins, a large portion of sagebrush loss has been due to an increase in higher-severity wildfires, caused by invasive annual grasses. As sagebrush declines, numerous wildlife species that rely on the biome have experienced similar trends. Sagebrush-adapted songbirds such as sage thrasher, Brewer's sparrow, and sagebrush sparrow as well as steppe-songbirds, have all experienced population declines. Currently, limited information exists as to how fire severity or recovery affect these songbirds or what resource managers can do to improve their …