Digital Commons Network^™

Whole-Genome Sequencing In 333,100 Individuals Reveals Rare Non-Coding Single Variant And Aggregate Associations With Height, Gareth Hawkes, Robin N. Beaumont, Zilin Li, Ravi Mandla, Xihao Li, Christine M. Albert, Donna K. Arnett, Allison E. Ashley-Koch, Aneel A. Ashrani, Joanne E. Curran

School of Medicine Publications

The role of rare non-coding variation in complex human phenotypes is still largely unknown. To elucidate the impact of rare variants in regulatory elements, we performed a whole-genome sequencing association analysis for height using 333,100 individuals from three datasets: UK Biobank (N = 200,003), TOPMed (N = 87,652) and All of Us (N = 45,445). We performed rare ( < 0.1% minor-allele-frequency) single-variant and aggregate testing of non-coding variants in regulatory regions based on proximal-regulatory, intergenic-regulatory and deep-intronic annotation. We observed 29 independent variants associated with height at P <  after conditioning on previously reported variants, with effect sizes ranging from −7cm to +4.7 cm. We also identified and replicated non-coding aggregate-based associations proximal to HMGA1 containing variants associated with a 5 cm taller height and of highly-conserved variants in MIR497HG on chromosome 17. We have developed an approach for identifying non-coding rare variants in regulatory regions with large effects from whole-genome sequencing data associated with complex traits.

Semi-Supervised Machine Learning Method For Predicting Homogeneous Ancestry Groups To Assess Hardy-Weinberg Equilibrium In Diverse Whole-Genome Sequencing Studies, Derek Shyr, Rounak Dey, Xihao Li, Hufeng Zhou, Eric Boerwinkle, Steve Buyske, Mark Daly, Richard A Gibbs, Ira Hall, Tara Matise, Catherine Reeves, Nathan O Stitziel, Michael Zody, Benjamin M Neale, Xihong Lin

Faculty, Staff and Student Publications

Large-scale, multi-ethnic whole-genome sequencing (WGS) studies, such as the National Human Genome Research Institute Genome Sequencing Program's Centers for Common Disease Genomics (CCDG), play an important role in increasing diversity for genetic research. Before performing association analyses, assessing Hardy-Weinberg equilibrium (HWE) is a crucial step in quality control procedures to remove low quality variants and ensure valid downstream analyses. Diverse WGS studies contain ancestrally heterogeneous samples; however, commonly used HWE methods assume that the samples are homogeneous. Therefore, directly applying these to the whole dataset can yield statistically invalid results. To account for this heterogeneity, HWE can be tested on …

Evaluation Of An Educational Intervention Focused On Intake And Output Documentation, Ingrid Lea Bloomfield

Walden Dissertations and Doctoral Studies

Heart failure (HF) is the primary reason for hospital admissions in the United States, accounting for almost 6.5 million hospital days per year and for 8.5% of cardiovascular deaths. As part of care delivery and supported by the evidence, providers use intake and output (I&O) to guide a HF patient’s overall treatment plan. Following several reviews in the local organization, it was determined that I&O documentation sheets were incomplete or not completed at all. Thus, organizational leadership determined that an educational intervention focused on I&O monitoring and documentation as part of the HF patient treatment plan would address this gap-in-practice. …

The Impact Of Covid-19 Response Measures On The Mental Health And Well-Being Of Teachers At Predominately Black Schools, Llewellyn Cooper

Walden Dissertations and Doctoral Studies

Teachers in predominately Black schools had limited access to mental health resources during the COVID-19 pandemic. The purpose of this generic qualitative study was to explore how the response to COVID-19 affected the mental health and well-being (MHWB) of teachers at predominately Black schools during the pandemic to gain an in-depth understanding of their experiences regarding MHWB. The study participants were eight teachers at various schools in the state of Alabama. The goal was to understand how teachers experienced MHWB support during the COVID-19 pandemic, how teachers’ MHWB were affected when there were rapid adjustments to curricula changes, and how …

Categorical Differences: Social Identity Heuristics Predict Differences In Cognitive Empathy, Corey Ronald Sims

Walden Dissertations and Doctoral Studies

The current study aimed to identify if there was a relationship between cross-ethnic racial identity and cognitive empathy for others and whether social and personal identities mediated this effect. Self-categorization theory was used as the theoretical framework. In this study, it was hypothesized that cross-ethnic racial identity significantly predicts empathic accuracy, and that social and personal identities mediate this relationship. A non-experimental, researcher-designed survey was used to collect participant data and demographic characteristics. Participant inclusion criteria were an age between 18 and 55, U.S. citizenship, and a self-identification as Asian American, Black American, Hispanic American, or White American. The Cross-Ethnic …

The Effectiveness Of Aleks To Address Grade 8 Students’ Math Deficiencies, Joseph Evans

Walden Dissertations and Doctoral Studies

The math intervention program, Assessment and Learning in Knowledge Spaces (ALEKS), at a Public Middle School (pseudonym) in the Northeast United States, was implemented for eighth grade middle school math students, but researchers have not measured its effectiveness. Grounded in the cultural relevance pedagogy, the purpose of this quantitative quasi-experimental study was to determine the efficacy of ALEKS intervention for eighth grade students in improving their smarter balanced assessment consortium (SBAC) mathematics scores. The research question focused on the ALEKS intervention program effects on eighth grade math scores at the study site. An independent samples t-test revealed that the SBAC …

The Perspective Of Formerly Incarcerated African American Men During The Covid-19 Pandemic, Iyesha Shauntae' Franklin

Walden Dissertations and Doctoral Studies

The confluence of two devastating circumstances—the COVID-19 pandemic and the crowded, insalubrious living conditions in American jails as a result of mass incarceration, brought about an epidemic of an unprecedented magnitude. The large jail population, highly susceptible to infections due to overcrowded conditions, experienced exponential spread of the virus. While earlier research examined unhealthy situations related to the prison environment and their effects on inmates, the focus of such studies was not typically major crises or disease outbreaks in prisons. This qualitative phenomenological study used 10 participants located in the southeastern United States as a case study to better understand …

Head Start Teachers’ And Administrators’ Perceptions Of Reasons For Elevated Teacher Turnover Rates, Amanda Renea Lankford

Walden Dissertations and Doctoral Studies

Many Head Start programs have closed classrooms due to staff shortages, with up to 30% of teacher positions unfilled. Reducing the elevated teacher turnover rate in Head Start centers is critical to maintaining program effectiveness and controlling costs; however, a limiting factor may be differences in administrators’ and teachers’ perceptions of reasons Head Start teachers leave their positions. Guided by Herzberg’s two-factor theory, this qualitative study was conducted to explore perceptions of Head Start administrators, current teachers, and exiting teachers regarding reasons for the elevated teacher turnover rates in Head Start programs. Semistructured interviews with open-ended questions were conducted with …

The Relationship Between Parental Political Intensity And Gay Individuals' Mental Health, And The Moderation Of Parental Age, Aaron Whipple

Walden Dissertations and Doctoral Studies

During periods of heightened political intensity, gay individuals experience increases in discrimination and prejudice, impacting their mental health, making the need for advocacy and support, particularly from parents and guardians, vital. Recent research shows that parent–child relationships can be heavily influenced by politics and the intensity of their political beliefs. Historically, conservative views have been associated with anti-gay sentiment, which can exacerbate gay individuals’ mental health, leading to familial discord, depression, self-harm, and suicide, whereas liberal views have been associated with supporting gay rights and decreasing mental health disparities. However, prior research has not explored the specific role of parental …

Vintage Truck Donation Fuels Titan Spirit, Julia Perez

News and Events (Discontinued Series)

No abstract provided.

Arid1a-Baf Coordinates Zic2 Genomic Occupancy For Epithelial-To-Mesenchymal Transition In Cranial Neural Crest Specification, Samantha M. Barnada, Aida Giner De Gracia, Cruz Morenilla-Palao, Maria Teresa López-Cascales, Chiara Scopa, Francis J. Waltrich, Harald M.M. Mikkers, Maria Elena Cicardi, Jonathan Karlin, Davide Trotti, Kevin A. Peterson, Samantha A. Brugmann, Gijs W.E. Santen, Steven B. Mcmahon, Eloísa Herrera, Marco Trizzino

Department of Biochemistry and Molecular Biology Faculty Papers

The BAF chromatin remodeler regulates lineage commitment including cranial neural crest cell (CNCC) specification. Variants in BAF subunits cause Coffin-Siris syndrome (CSS), a congenital disorder characterized by coarse craniofacial features and intellectual disability. Approximately 50% of individuals with CSS harbor variants in one of the mutually exclusive BAF subunits, ARID1A/ARID1B. While Arid1a deletion in mouse neural crest causes severe craniofacial phenotypes, little is known about the role of ARID1A in CNCC specification. Using CSS-patient-derived ARID1A induced pluripotent stem cells to model CNCC specification, we discovered that ARID1A-haploinsufficiency impairs epithelial-to-mesenchymal transition (EMT), a process necessary for CNCC delamination and migration from …

Public-Private Partnership: A New Policy To Ameliorate The Quality Of Public Utility Services To The Public, Karem Sayed Aboelazm, Fady Tawakol, Khalid Mohamed Dganni, Nada Zuhair Alfil

All Works

Objective: The paper aims to determine why the government resorts to partnerships with the private sector, in addition to the advantages and disadvantages of the public-private partnership system, and explain the types and forms of public-private partnerships. Theoretical Framework: This paper presented the concept of partnership and the reasons for partnership with the private sector. It also presented the types of partnerships with the private sector and, more specifically, the different BOT systems. Method: The study relied mainly on the descriptive approach to understand the concept of partnership, determine the forms of partnership between the public and private sectors, and …

Unh Ocean Discovery Lego Model Instructions - C2402 R/V Gulf Surveyor - Unh Ccom/Jhc, William F. Fessenden, Colleen Mitchell

Center for Coastal and Ocean Mapping

Commissioned in 2016, R/V Gulf Surveyor, or “RVGS" for short, is 48-foot research vessel operated by the UNH Center for Coastal and Ocean Mapping / NOAA-UNH Joint Hydrographic Center (CCOM/JHC). A vital tool for the Center’s research and academic programs, her twin screw propulsion and catamaran-style hull, combined with a state-of-the-art hull design, provide for excellent maneuverability and stability, and is an optimal launch for nearshore ocean mapping. In addition to its multibeam sonar mapping systems, the RVGS can also be equipped with sidescan sonar, seismic systems, and thanks to its A-frame and portside crane, is an effective platform for …

Romi: A Randomized Two-Stage Basket Trial Design To Optimize Doses For Multiple Indications, Shuqi Wang, Peter F Thall, Kentaro Takeda, Ying Yuan

Faculty, Staff and Student Publications

Optimizing doses for multiple indications is challenging. The pooled approach of finding a single optimal biological dose (OBD) for all indications ignores that dose-response or dose-toxicity curves may differ between indications, resulting in varying OBDs. Conversely, indication-specific dose optimization often requires a large sample size. To address this challenge, we propose a Randomized two-stage basket trial design that Optimizes doses in Multiple Indications (ROMI). In stage 1, for each indication, response and toxicity are evaluated for a high dose, which may be a previously obtained maximum tolerated dose, with a rule that stops accrual to indications where the high dose …

Syntaxin 3b: A Snare Protein Required For Vision, Himani Dey, Mariajose Perez-Hurtado, Ruth Heidelberger

Faculty, Staff and Student Publications

Syntaxin 3 is a member of a large protein family of syntaxin proteins that mediate fusion between vesicles and their target membranes. Mutations in the ubiquitously expressed syntaxin 3A splice form give rise to a serious gastrointestinal disorder in humans called microvillus inclusion disorder, while mutations that additionally involve syntaxin 3B, a splice form that is expressed primarily in retinal photoreceptors and bipolar cells, additionally give rise to an early onset severe retinal dystrophy. In this review, we discuss recent studies elucidating the roles of syntaxin 3B and the regulation of syntaxin 3B functionality in membrane fusion and neurotransmitter release …

Whole-Exome Sequencing Uncovers The Genetic Complexity Of Bicuspid Aortic Valve In Families With Early-Onset Complications, Sara Mansoorshahi, Anji T Yetman, Malenka M Bissell, Yuli Y Kim, Hector I Michelena, Julie De Backer, Laura Muiño Mosquera, Dawn S Hui, Anthony Caffarelli, Maria G Andreassi, Ilenia Foffa, Dongchuan Guo, Rodolfo Citro, Margot De Marco, Justin T Tretter, Shaine A Morris, Simon C Body, Jessica X Chong, Michael J Bamshad, Dianna M Milewicz, Siddharth K Prakash

Faculty, Staff and Student Publications

Bicuspid aortic valve (BAV) is the most common congenital heart lesion with an estimated population prevalence of 1%. We hypothesize that specific gene variants predispose to early-onset complications of BAV (EBAV). We analyzed whole-exome sequences (WESs) to identify rare coding variants that contribute to BAV disease in 215 EBAV-affected families. Predicted damaging variants in candidate genes with moderate or strong supportive evidence to cause developmental cardiac phenotypes were present in 107 EBAV-affected families (50% of total), including genes that cause BAV (9%) or heritable thoracic aortic disease (HTAD, 19%). After appropriate filtration, we also identified 129 variants in 54 candidate …

Likelihood Adaptively Incorporated External Aggregate Information With Uncertainty For Survival Data, Ziqi Chen, Yu Shen, Jing Qin, Jing Ning

Faculty, Staff and Student Publications

Population-based cancer registry databases are critical resources to bridge the information gap that results from a lack of sufficient statistical power from primary cohort data with small to moderate sample size. Although comprehensive data associated with tumor biomarkers often remain either unavailable or inconsistently measured in these registry databases, aggregate survival information sourced from these repositories has been well documented and publicly accessible. An appealing option is to integrate the aggregate survival information from the registry data with the primary cohort to enhance the evaluation of treatment impacts or prediction of survival outcomes across distinct tumor subtypes. Nevertheless, for rare …

Hydrogen Underground Storage For Grid Electricity Storage: An Optimization Study On Techno-Economic Analysis, Yunzhi Chen, Daniel Hill, Blake Billings, John Hedengren, Kody Powell

Faculty Publications

This study performs a techno-economic analysis of hydrogen underground storage systems for grid electricity storage, evaluating their economic viability at the plant scale using dynamic optimization. It explores the feasibility of various system configurations and revenue models in the context of volatile electricity prices and the necessity for multiple revenue streams. The hypothesis tested is that large-scale hydrogen storage, despite its low round-trip efficiency, can be economically viable with the right mix of revenue streams. This study uses scenario-based analysis to assess the impacts of different system configurations, including engaging in time-shifting arbitrage, ancillary service markets and blending hydrogen with …

The Biological Significance Of Tumor Grade, Age, Enhancement, And Extent Of Resection In Idh-Mutant Gliomas: How Should They Inform Treatment Decisions In The Era Of Idh Inhibitors?, Martin J Van Den Bent, Pim J French, Daniel Brat, Joerg C Tonn, Mehdi Touat, Benjamin M Ellingson, Robert J Young, Johan Pallud, Andreas Von Deimling, Felix Sahm, Dominique Figarella Branger, Raymond Y Huang, Michael Weller, Ingo K Mellinghoff, Tim F Cloughsey, Jason T Huse, Kenneth Aldape, Guido Reifenberger, Gilbert Youssef, Philipp Karschnia, Houtan Noushmehr, Katherine B Peters, Francois Ducray, Matthias Preusser, Patrick Y Wen

Faculty, Staff and Student Publications

The 2016 and 2021 World Health Organization 2021 Classification of central nervous system tumors have resulted in a major improvement in the classification of isocitrate dehydrogenase (IDH)-mutant gliomas. With more effective treatments many patients experience prolonged survival. However, treatment guidelines are often still based on information from historical series comprising both patients with IDH wild-type and IDH-mutant tumors. They provide recommendations for radiotherapy and chemotherapy for so-called high-risk patients, usually based on residual tumor after surgery and age over 40. More up-to-date studies give a better insight into clinical, radiological, and molecular factors associated with the outcome of patients with …

The Cochlear Dose And The Age At Radiotherapy Predict Severe Hearing Loss After Passive Scattering Proton Therapy And Cisplatin In Children With Medulloblastoma, Mohammad H Abu-Arja, Austin L Brown, Jack M Su, M Fatih Okcu, Holly B Lindsay, Susan L Mcgovern, Mary Frances Mcaleer, David R Grosshans, Murali M Chintagumpala, Arnold C Paulino

Faculty, Staff and Student Publications

Background: Hearing loss (HL) is associated with worse neurocognitive outcomes among patients with medulloblastoma. We aimed to identify risk factors associated with severe HL and to evaluate the generalizability of a published HL calculator among patients treated with passive scattering proton therapy (PSPT) and cisplatin.

Methods: We identified patients aged 3-21 years who were treated at our centers between 2007 and 2022. Audiograms were graded using the International Society of Pediatric Oncology (SIOP) Boston scale. Time to grades 3-4 HL was evaluated using Kaplan-Meier and multivariable Cox models to estimate hazard ratios and 95% confidence intervals (CI).

Results: Seventy-nine patients …

Identification Of A Single-Dose, Low-Flip-Angle-Based Cbv Threshold For Fractional Tumor Burden Mapping In Recurrent Glioblastoma, Aliya Anil, Ashley M Stokes, John P Karis, Laura C Bell, Jennifer Eschbacher, Kristofer Jennings, Melissa A Prah, Leland S Hu, Jerrold L Boxerman, Kathleen M Schmainda, C Chad Quarles

Faculty, Staff and Student Publications

Background and purpose: DSC-MR imaging can be used to generate fractional tumor burden (FTB) maps via application of relative CBV thresholds to spatially differentiate glioblastoma recurrence from posttreatment radiation effects (PTRE). Image-localized histopathology was previously used to validate FTB maps derived from a reference DSC-MR imaging protocol by using preload, a moderate flip angle (MFA, 60°), and postprocessing leakage correction. Recently, a DSC-MR imaging protocol with a low flip angle (LFA, 30°) with no preload was shown to provide leakage-corrected relative CBV (rCBV) equivalent to the reference protocol. This study aimed to identify the rCBV thresholds for the LFA protocol …

The Status Of Women Leaders In Utah Business: A 2024 Update, Shirlayne Quayle, Susan R. Madsen, Robyn Blackburn

Marketing and Strategy Faculty Publications

In 2014, the Utah Women & Leadership Project (UWLP) released a research and policy brief titled “The Status of Women Leaders in Utah Business.”¹ The brief was updated in 2018 to determine what, if any, progress had been made in women’s leadership within Utah’s business sector.² Unfortunately, in most areas, instead of making progress, the percentage had decreased. Now, six years later, we are providing yet another update. In each brief, we compare Utah data with national data and review the applicable literature addressing women in the highest levels of business leadership, including C-level positions and presence on …

Kenyon Collegian - October 3, 2024

The Kenyon Collegian

No abstract provided.

The Pace Of Life For Forest Trees, Lalasia Bialic-Murphy, Robert M. Mcelderry, Adriane Esquivel-Muelbert, Johan Van Den Hoogen, Pieter A. Zuidema, Oliver L. Phillips, Edmar Almeida De Oliveira, Patricia Alvarez Loayza, Esteban Alvarez-Davila, Luciana F. Alves, Vinícius Andrade Maia, Simone Aparecida Vieira, Lidiany Carolina Arantes Da Silva, Alejandro Araujo-Murakami, Eric Arets, Julen Astigarraga, Fabrício Baccaro, Timothy Baker, Olaf Banki, Jorcely Barroso, Lilian Blanc, Damien Bonal, Frans Bongers, Kauane Maiara Bordin, Roel Brienen, Marcelo Brilhante De Medeiros, José Luís Camargo, Felipe Carvalho Araújo, Carolina V. Castilho, Wendeson Castro

School of Geography, Earth and Environmental Sciences

Tree growth and longevity trade-offs fundamentally shape the terrestrial carbon balance. Yet, we lack a unified understanding of how such trade-offs vary across the world's forests. By mapping life history traits for a wide range of species across the Americas, we reveal considerable variation in life expectancies from 10 centimeters in diameter (ranging from 1.3 to 3195 years) and show that the pace of life for trees can be accurately classified into four demographic functional types. We found emergent patterns in the strength of trade-offs between growth and longevity across a temperature gradient. Furthermore, we show that the diversity of …

October 3, 2024, James Madison University

The Breeze, 2020-

The Breeze is the student newspaper of James Madison University in Harrisonburg, Virginia.

Eugene Coleman

African American Funeral Programs

No abstract provided.

Inflammation-Induced Epigenetic Imprinting Regulates Intestinal Stem Cells, Dongchang Zhao, Visweswaran Ravikumar, Tyler J Leach, Daniel Kraushaar, Emma Lauder, Lu Li, Yaping Sun, Katherine Oravecz-Wilson, Evan T Keller, Fengju Chen, Laure Maneix, Robert R Jenq, Robert Britton, Katherine Y King, Ana E Santibanez, Chad J Creighton, Arvind Rao, Pavan Reddy

Faculty, Staff and Students Publications

It remains unknown whether, and how intestinal stem cells (ISC) adapt to inflammatory exposure, and if the adaptation leaves scars will affect their subsequent regeneration. We investigated the consequences of inflammation on Lgr5+ISCs in well-defined clinically relevant models of gastrointestinal acute graft-versus-host disease (GI GVHD). Utilizing single cell transcriptomics, organoid, metabolic, epigenomic and in vivo models we found that Lgr5+ISCs undergo metabolic changes that lead to accumulation of succinate, which reprograms its epigenome. These changes reduced the ability of ISCs to differentiate and regenerate ex vivo in serial organoid cultures and also in vivo following serial transplantation. Furthermore, ISCs demonstrated …

A Ligation-Independent Sequencing Method Reveals Trna-Derived Rnas With Blocked 3′ Termini, Alessandro Scacchetti, Emily J Shields, Natalie A Trigg, Grace S Lee, Jeremy E Wilusz, Colin C Conine, Roberto Bonasio

Faculty, Staff and Students Publications

Despite the numerous sequencing methods available, the diversity in RNA size and chemical modification makes it difficult to capture all RNAs in a cell. We developed a method that combines quasi-random priming with template switching to construct sequencing libraries from RNA molecules of any length and with any type of 3' modifications, allowing for the sequencing of virtually all RNA species. Our ligation-independent detection of all types of RNA (LIDAR) is a simple, effective tool to identify and quantify all classes of coding and non-coding RNAs. With LIDAR, we comprehensively characterized the transcriptomes of mouse embryonic stem cells, neural progenitor …

Penicillin Susceptibility Among Staphylococcus Aureus Skin And Soft Tissue Infections At A Children’S Hospital, J Chase Mcneil, Lauren M Sommer, Marritta Joseph, Kristina G Hulten, Sheldon L Kaplan

Faculty, Staff and Students Publications

Shortly after its introduction into clinical practice, Staphylococcus aureus isolates gained resistance to penicillin via the acquisition of β-lactamases. A number of centers have recently described an increase in the proportion of invasive methicillin-susceptible S. aureus (MSSA), which are also susceptible to penicillin (PSSA). Little data are available regarding the prevalence or impact of PSSA in skin and soft tissue infections (SSTI). Community-acquired MSSA SSTI isolates were obtained through a surveillance study at Texas Children’s Hospital from January 2017 to December 2021. A total of 200 random isolates underwent PCR for blaZ β-lactamase; blaZ-negative isolates then underwent penicillin susceptibility …

In Acute Severe Ulcerative Colitis Patients Who Receive Rescue Therapy, Prior Maintenance Therapy And Day 3 C-Reactive Protein After Rescue Therapy Are Associated With 12-Month Colectomy Risk, Jared A Sninsky, Ana-Maria Staicu, Edward L Barnes

Faculty, Staff and Students Publications

No abstract provided.