Digital Commons Network^™

De Novo Complex Genomic Rearrangement Spanning 2q31.1 In A Proband With Congenital Malformations: Genotype-Phenotype Correlation And Development Of A Cgr Detection Pipeline, Katherine Helle, Jesse D Bengtsson, Mira Gandhi, Christopher M Grochowski, Ming Yin Lun, Neha Sudhir, Shalini N Jhangiani, Fritz J Sedlazeck, Seema R Lalani, Neil A Hanchard, Claudia M B Carvalho

Faculty, Staff and Students Publications

The 2q31 region is commonly associated with pathogenic alleles of the HOXD cluster leading to various clinical phenotypes related to skeletal development. We present a proband with tetralogy of Fallot and multiple congenital anomalies. Genomic variant screening including an in-house CGR detection pipeline pairing genome sequencing (GS) structural variant calls with read-depth data revealed a de novo complex genomic rearrangement (CGR) spanning 2.7 Mb across 2q31 characterized by a series of duplications and triplications including the HOXD gene cluster. The genomic structure was assembled by applying combined methodologies including short-read and long-read GS, and optical genome mapping (OGM). This in-house …

Proteomic Signatures Of 3-Year Progression From Impaired Fasting Glucose To Diabetes: The Atherosclerosis Risk In Communities (Aric) Study, Mary R Rooney, Justin B Echouffo Tcheugui, Jingsha Chen, Keenan A Walker, Christie M Ballantyne, Eric Boerwinkle, Tanika N Kelly, Chiadi E Ndumele, James S Pankow, Morgan E Grams, Wendy S Post, Peter J Ganz, Alexis C Wood, Jerome I Rotter, Elizabeth Selvin, Josef Coresh

Faculty, Staff and Students Publications

Objective: To identify proteomic signatures underlying 3-year progression from impaired fasting glucose (IFG) to diabetes.

Research design and methods: We examined IFG progression in the Atherosclerosis Risk in Communities (ARIC) study from visit 2 (1990-1992) to visit 3 (1993-1995). We tested associations of 4,955 plasma proteins (SomaScan version 4.0) with ∼3-year progression from IFG (FG 100-125 mg/dL without diabetes) to diabetes (diagnosis, medication, or FG ≥126 mg/dL) using logistic regression models adjusted for demographics, cardiometabolic risk factors, and baseline glucose with Bonferroni correction (P < 10-5). We explored biological pathways enriched among the top proteins and calculated improvements in prediction (ΔAUC and net reclassification using 3-year risk thresholds of 6% and 15% in 80% training and 20% internal validation subsamples). We validated results in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort.

Results: There were 3,786 ARIC participants with IFG (mean [SD] age 57 [6] years, 52% female, …

Improving Clostridioides Difficile Prevention Practices Through Standardized Stool Collection And Hand Hygiene, Dunya Khateeb, Laura Martin, Jessica Zhang

ELMSN E-Portfolio. A collection of Scholarly and Creative Works

Healthcare-associated Clostridioides difficile (C. diff) infections increase patient morbidity, length of stay, and healthcare costs (Simor, 2010). Our quality improvement project seeks to reduce C. diff infection rates and enhance prevention practices on the Med-Acute Unit at Sutter Medical Center Sacramento (SMCS) by utilizing the Plan-Do-Study-Act (PDSA) framework. Interventions will be implemented between March 2026 and July 2026. The project examined whether introducing a standardized stool collection tote and improving hand hygiene compliance would reduce C. diff infection rates. Participants included all nursing staff on the unit. Data is being collected through observational hand hygiene audits, collaboration with the SMCS …

Improving Knowledge Of Obesity-Related Risks And Healthy Lifestyle Behaviors In Adolescents, Tehroop Notra, Samreet Kaur, Karina Heredia

ELMSN E-Portfolio. A collection of Scholarly and Creative Works

This quality improvement project evaluated the effectiveness of a school-based educational intervention aimed at improving ninth-grade students’ knowledge and understanding of obesity prevention, nutrition, and physical activity. Adolescent obesity remains a significant public health concern, showcasing the need for early, evidence-based education. A total of 57 students participated in the two classroom sessions. Of these students, 49 completed the pre-intervention survey, and 48 completed the post-intervention survey. The intervention included an interactive presentation, group discussions, and educational materials. Student knowledge was assessed using a six-item survey administered before and after the session. The results demonstrated improvements across multiple knowledge areas, …

Id-More Vision: Real-Data Machine-Learning Assessment For A Digital-Twin-Inspired, Xr-Ready Rehabilitation Prototype, Rickey L. Clark

Master's Theses

Rehabilitation assessment often relies on periodic observation, while many XR prototypes show scripted rather than recorded-motion evidence. iD-MORE Vision is an offline pipeline trained on KIMORE and IRDS and linked through JSON packets to a two-mode Unity desktop prototype. Both datasets include controls and rehabilitation participants with neurologic, musculoskeletal, or mobility impairments. This improves relevance but does not clinically validate the system.

Under fixed subject-wise splits, the primary five-seed Random Forest predicted KIMORE clinician scores with MAE 6.087 ± 0.044 cTS and R² 0.568 ± 0.006; the subject-level R² interval crossed zero. The primary IRDS five-run CUDA GRU averaged 0.877 …

Characterization Of Catechol-Type Siderophore(S) From P. Mosselii Cfml 90-83, Kemper R. Rasnake

Electronic Theses and Dissertations

Iron is essential for many biological processes, where it is used as a cofactor. Even though it is abundant in the Earth’s crust, it is in an insoluble form unavailable to microorganisms in the soil. To overcome this, bacteria produce siderophores, which are secondary metabolites that have a high affinity for iron. This allows bacterial cells to obtain insoluble iron that is essential for survival. Pseudomonas mosselii, a Gram negative bacterium, was isolated from soil. It was selected for further analysis as it was found to produce siderophore(s) under iron-limited conditions, which have not been characterized previously. Therefore, we aimed …

A Geometric Morphometric Analysis Of Acetabular Shape Variation Across Bat Families, Jordan L. Huff

Electronic Theses and Dissertations

Bats are the only mammals capable of powered flight, and research is concentrated on this adaptation. Their non-flight locomotion has received comparatively little attention. Previous studies show that non-flight locomotor behaviors vary across families. Members of Pteropodidae are efficient climbers but cannot effectively walk, whereas Phyllostomidae and Vespertilionidae are better at terrestrial locomotion but show reduced arboreal capabilities. The non-flight locomotion of Hipposideridae and Rhinolophidae is less understood, although rhinolophids exhibit limited terrestrial locomotion. This study examined whether differences in locomotor behavior are associated with variation in acetabular morphology. A geometric morphometric analysis of acetabular shape was conducted across multiple …

Weathering More Than Storms: Understanding The Mental Health Disparities Of Black Farmers In The Appalachian Region, Aliyah Smith

Electronic Theses and Dissertations

Black farmers in Appalachia represent a vital and historically marginalized population within one of America’s most economically distressed regions. Black farmers have endured generations of systemic racism, resulting in land loss, economic hardship, and mental stressors. This study examines the intersection of race, agriculture, and behavioral health to illustrate how structural barriers and cultural stigmas shape the mental well-being of Black farmers across Appalachia.

Findings from the analysis will guide the development of a conceptual model based on constructs from the Social-Ecological Model (SEM), Intersectionality Theory, and Critical Race Theory (CRT). This study will use Key Informant Interviews (KIIs) conducted …

Wisdom In Counseling And Psychotherapy: A Conceptual Model For Practice, Mitchell Waters

Papers

Wisdom is increasingly recognized as a critical construct in counseling and psychotherapy, yet it remains conceptually diffuse and underdeveloped for clinical application. This article proposes an integrative conceptual model of wisdom that extends the Dialectical Behavior Therapy (DBT) WISE MIND framework by incorporating temporal and self-transcendent dimensions. Wisdom is defined as a dynamic, context-sensitive capacity to coordinate cognitive, affective, temporal, and spiritual processes in response to complex life demands. The model includes four components: (a) cognitive–affective integration, reflecting the synthesis of emotion and reason; (b) temporal integration, involving adaptive coordination of past experiences and future possibilities; (c) self-transcendent orientation, conceptualized …

The Rpm-1/Phr Signaling Hub Modulates Tau-Induced Neurodegeneration Through Regulation Of Microtubule Stability And Mapk Pathways In C. Elegans, Xinxing Ding

Theses and Dissertations

Neurodegenerative diseases, including Alzheimer's disease and frontotemporal dementia, are characterized by the accumulation of pathological tau proteins and progressive neuronal loss. Although research regarding tau-mediated toxicity is extensive, the specific pathology that determine whether neurons maintain homeostasis or succumb to collapse under tau-induced stress remain incompletely elucidated. A central, yet still insufficiently understood, feature of these diseases is the disruption of the microtubule (MT) cytoskeleton . The PHR protein family is evolutionarily highly conserved; within this family, RPM-1 in C. elegans functions as an intracellular signaling hub that regulates axon development, synapse formation, axon termination, and various microtubule-associated processes. This …

Agent-Based Modeling Of Cellular Dynamics In Adoptive Cell Therapies, Yujia Wang

Dissertations and Theses (Open Access)

Adoptive cell therapies (ACT) have shown promising progress in combating cancer, but clinical responses remain heterogeneous. Key determinants, including the functional states of infused cells, tumor–immune interactions, and dosing strategies, are difficult to resolve experimentally in the dynamic and heterogeneous tumor microenvironment, limiting optimization of ACT products and treatment regimens. To address the gap, we developed ABMACT (Agent-Based Model for Adoptive Cell Therapies), a computational framework that reconstruct key cellular functions, interactions, and molecular signatures to recapitulate cell population dynamics associated with differential treatment responses. ABMACT encodes autonomous “virtual cells” using literature-informed rules calibrated with experimental data, enabling simulation of …

Ai-Driven Segmentation And Volumetric Response Modeling Of Liver Regions To Radiotherapy, Aashish Chandra Gupta

Dissertations and Theses (Open Access)

In liver-directed radiotherapy (RT), liver regions receiving higher doses typically undergo atrophy while contralateral/adjacent lower-dose regions may exhibit compensatory hypertrophy through regeneration of healthy tissue. Optimizing the RT plan to promote regional hypertrophy while minimizing the risk of developing atrophy has the potential to enhance post-RT liver function and long-term survivorship. However, current clinical practice largely relies on global liver dose-volume metrics during RT-planning, which may obscure favorable dose-response correlation and limit actionable guidance for clinicians. Therefore, we hypothesized that post-RT regional liver response is governed by a combination of region-specific dose-volume and patient clinical features, and that these responses …

Developing A Deep-Learning Model To Segment White Matter Lesions In Cerebral Palsy, Varsha Kumar, Hyukjin Yun, Rose N. Gelineau-Morel, Avner Meoded

Posters

No abstract provided.

Understanding Hypertensive Renal Injury: A Well-Structured Approach, Peter A Doris

The Brown Foundation: Institute of Molecular Medicine

No abstract provided.

Computable Phenotypes For Research Using Real-World Data: Experiences From The Nih Pragmatic Trials Collaboratory, Marisa L Conte, Judith M Schlaeger, Guilherme Del Fiol, James R Campbell, Andrea L Cheville, Keith Marsolo, Kari A Stephens, Miriam O Ezenwa, Andrew D Boyd, Juanita E Darby, Nadine S Matthie, P Michael Ho, Alice Pressman, Morgan Justice, Carol Reynolds Geary, Keturah R Faurot, Alex Fist, Karen Staman, Hulin Wu, Rachel L Richesson

Faculty, Staff and Student Publications

Objectives: Embedded pragmatic clinical trials (ePCTs) are conducted as part of routine clinical care and therefore use data collected from real-world data sources, such as electronic health record systems and administrative claims. A common approach for using these types of data across all phases of trial conduct is to create a computable phenotype (an explicitly defined data query data, including specified data types, data codes, and logical parameters) to capture patients with a clinical condition, exposure, symptom, characteristic, treatment, or outcome of interest.

Materials and methods: The Electronic Health Record (EHR) Core Working Group of the NIH Pragmatic Trials Collaboratory …

Fuimos Olvidados Y Descuidados [Forgotten And Neglected]: Lessons Learned And Findings From On-Farm Covid-19 Education And Vaccine Clinics For Agricultural Workers And Their Multigenerational Families In Texas, Anabel Rodriguez, David I Douphrate, Ana L Pineda Reyes, Susana Zavala, Lus Chavez, Sofia Nicole Lopez, Andrea V Cabrera Cruz, Annie J Keeney, Nora Hernandez, Brenda Berumen-Flucker, Eva M Shipp, Matthew W Nonnenmann, Shannon P Guillot-Wright, Bethany Boggess Alcauter, G Lopez Ixta, Paula M Cuccaro, Higinio Fernandez-Sanchez, David Gimeno Ruiz De Porras

Faculty, Staff and Student Publications

Background: Despite being deemed essential non-healthcare workers, agricultural workers were excluded from COVID-19 vaccine prioritization in Texas. This professional practice report describes the multifaceted worker health and safety approaches to protecting agricultural workers and their families during the COVID-19 pandemic.

Methods: Between March 2020 and January 2025, several outreach, education, and training grants from various funding agencies were leveraged to deliver training, personal protective equipment, vaccines, and economic relief to agricultural workers in partnership with community-based organizations, industry, local public health departments, and academic institutions.

Findings: Timely funding efforts led to the distribution of 1,000 PPE kits, with more than …

The Effects Of Education And Training On Clinical Staff’S Knowledge, Perception, And Clinical Practice Of The Medication Reconciliation Process, Stephanie A. Williams

Doctor of Nursing Practice Projects

Medication-related harm affects approximately one in 30 patients in healthcare settings. Accurate medication reconciliation (MedRec) is essential for identifying medication discrepancies, preventing medication errors, and reducing adverse drug events. Clinical staff play a critical role in ensuring the accuracy of medication lists in primary care settings.

This evidence-based quality improvement project evaluated the effect of a structured MedRec training intervention on MedRec knowledge, perceptions, and practices among clinical staff in a primary care clinic in Southeast Texas. The project used a single-group, quantitative, quasi-experimental design. A convenience sample of 32 clinical staff members completed knowledge and perception assessments before and …

A Misplaced Pocket Of Air: Intramural Gastric Air Most Consistent With Gastric Emphysema, Priyanka Panwar, Lavender Otom, Subo Marsa, Gerald Odong, Steven Idet, Irene Muchiri, Hussein Abdulsamad, John Odhiambo, Christopher Opio, Amos Mwasamwaja, Saleem Abdulkarim

Internal Medicine, East Africa

Background Gastric emphysema (GE), or gastric pneumatosis, is a rare, noninfectious cause of intramural gastric air that must be distinguished from emphysematous gastritis (EG), a highly lethal infectious entity. Despite similar radiographic appearances, these conditions differ substantially in etiology, clinical course, management, and prognosis.

Cases We report three hemodynamically stable patients with CT-confirmed intramural gastric air most consistent with GE. Two had associated portal venous gas. The cases occurred in distinct clinical contexts: infectious gastroenteritis with retching, transient midgut volvulus with obstructive gastric overdistension, and alcohol-related upper gastrointestinal bleeding with forceful vomiting and a Mallory–Weiss tear. Although early EG could …

Prevalence Of Type 2 Diabetes Risk Factors Among Landscaping Workers In El Paso, Texas, Valeria Fontes

Open Access Theses & Dissertations

Type 2 diabetes mellitus (T2DM) is a significant public health challenge worldwide, yet little is known about the prevalence of diabetes risk factors among landscaping workers, an understudied occupational group. The purpose of this pilot study was to estimate the prevalence of type 2 diabetes risk factors among landscaping workers in El Paso, Texas. A descriptive cross-sectional study was conducted using a convenience sample of 20 landscaping workers. Participants completed a structured questionnaire and underwent anthropometric measurements, blood pressure assessment, point-of-care lipid and glucose testing, and vitamin D screening. Sixteen type 2 diabetes risk factors were assessed across seven domains: …

Balancing War And Peace In Taekwondo Athlete Development: A Multi-Criteria Coaching Decision Support Framework Using Leadership Scale For Sports And Fuzzy Ahp, King Harold A. Recto, Hazel Jade L. Antonio, Jhyrald Anthony P. Dalida

Electronics, Computer, and Communications Engineering Faculty Publications

Coaching effectiveness is frequently evaluated through competitive outcomes, with the assumption that coaching behaviors directly influence athlete performance. This study examined the relationship between perceived coaching behaviors and individual win percentage among collegiate Taekwondo athletes using the Leadership Scale for Sports (LSS). Descriptive statistics, correlation analysis, and regression analysis were conducted across five coaching dimensions: Training and Instruction, Democratic Behavior, Autocratic Behavior, Social Support, and Positive Feedback. Results showed that none of the coaching dimensions demonstrated a statistically significant relationship with win percentage. Although coaching behaviors did not significantly predict win percentage, the findings suggest that athlete development is shaped …

The Effect Of Cerebellar Transcranial Direct Current Stimulation On Anxiety, Shivangi Bhardwaj

All-Inclusive List of Electronic Theses and Dissertations

Anxiety is one of the most prevalent mental health disorders in the U.S. Individuals of all ages are affected by anxiety. Therefore, research into anxiety and its potential treatment has constantly been an area of interest. Newer approaches to managing anxiety include non-invasive stimulation techniques, such as Transcranial Direct Current Stimulation (tDCS), because of its accessibility and effectiveness. Past tDCS work typically focused on regions in the frontal lobe. However, tDCS over the cerebellum has not received as much attention compared to the cerebrum, despite recent work demonstrating cerebellar involvement in emotion processing. Thus, a better understanding of how cerebellar …

Surgeon Health And Well-Being Initiative: A Survey Of General And Orthopedic Surgery Residents' Reports Of Musculoskeletal Pain., Maryam Mohamed, Grace J Kim, Kristen Conrad-Schnetz, Zhan Yang, Mary Carneval

Ambulatory and Primary Care Articles

Background Musculoskeletal (MSK) pain is a well-known risk among surgeons, resulting from the multifactorial physical demands of the occupation. Because of the demands faced by resident surgeons, many individuals find themselves with sometimes debilitating MSK pain. Although these risks are well documented and there have been proposed solutions, there is little discussion on the role that osteopathic manipulative treatment (OMT) can play in relief of MSK pain over time in this population. Objective The purpose of this study is to determine the prevalence and distribution of MSK pain among general and orthopedic surgery residents at Cleveland Clinic Foundation (CCF). Based …

Musical Training Increases Anticipatory Responding And Predictive Control In Sequence Learning, Li Ann Leow, Jarrad Lum, Sara Johnson, Emily Corti, Welber Marinovic

Research outputs 2022 to 2026

Musicians demonstrate advantages in acquiring motor sequences, showing faster learning and better explicit sequence knowledge than non-musicians. However, it is unclear whether this advantage extends beyond acquisition to the consolidation phase, which is when newly learned skills stabilize and become resistant to interference. Additionally, while interference from executing competing motor tasks is well-established, less is known about whether purely sensory information presented after learning can disrupt consolidation of a bimodal motor sequence. We investigated how post-acquisition sensory interference affects performance of a learned audio-visual sequence, and whether musical training moderates this vulnerability. Participants first learned an explicit sequence in a …

Dietary Patterns And Cognitive Decline In Older Adults: Findings From The Western Australia Memory Study, Carolina Blagojevic Castro, Samantha L. Gardener, Farzana Jahan, Juliana Chen, Belinda M. Brown, Ruey L. Loo, Kevin Taddei, Stephanie R. Rainey-Smith, Michael Weinborn, Ana Caroline R.Dos Reis, Manohar L. Garg, Ralph N. Martins, Hamid R. Sohrabi

Research outputs 2022 to 2026

Background: Preventive strategies, including adherence to specific dietary patterns, have received increasing attention as approaches to reduce cognitive decline and dementia risk. However, findings remain inconsistent, partly due to differences in dietary assessment methods, cognitive outcomes, and THE consideration of genetic susceptibility factors such as apolipoprotein E (APOE) genotype.

Methods: This study examined associations between dietary patterns and longitudinal cognitive change in 185 older adults without dementia from the Western Australia Memory Study. Participants completed a food frequency questionnaire at baseline and underwent comprehensive neuropsychological assessments at baseline and up to five follow-up visits at 18-month intervals. Composite scores were …

Early-Onset Colorectal Cancer With Liver-Only Metastases: A Retrospective Cohort Study Integrating Prospectively Collected Real-World Clinical And Molecular Data From An Australian National Database (2009–2024) To Guide Treatment Planning, Savio G. Barreto, Christos S. Karapetis, Shahid Ullah, Matthew Burge, Susan Caird, Angus Campbell, Azim Jalali, Ross Jennens, Muhammad A. Khattak, Belinda Lee, Stephanie H. Lim, Shehara Mendis, Louise Nott, Timothy J. Price, Jeremy D. Shapiro, Jeanne Tie, Javier Torres, Colin Williams, Rachel Wong, Vanessa Wong, Peter Gibbs

Research outputs 2022 to 2026

Objective: To leverage the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry (an Australian cancer database) to explore the ideal timing and sequence of therapies and the factors influencing these decisions in colorectal cancer (CRC) patients with liver-only metastases to inform contemporary decision-making and future trials.

Study Type: Retrospective registry-based cohort study using the TRACC registry.

Setting and Participants: Consecutive patients with liver-only metastatic CRC enrolled in the TRACC registry.

Main Outcome Measures: To explore cancer biology, intended treatment at presentation, actual treatment received and the resultant outcomes for early-onset CRC (EOCRC) (≤ 50 years) and late-onset CRC (LOCRC) …

Estimation Of Persistent Inward Currents Contribution To Inspiratory Motoneuron Firing In Humans, Ricardo N.O. Mesquita, Simon C. Gandevia, Janet L. Taylor, Anna L. Hudson, Jane E. Butler

Research outputs 2022 to 2026

Persistent inward currents (PICs) are known to prolong firing of limb-muscle motoneurons. Although there is immunohistochemical evidence of PIC channels in respiratory motoneurons, it is unknown whether PICs contribute to their firing prolongation. Intramuscular electromyographic signals were recorded from human inspiratory muscles to identify motor unit (MU) activity. Diaphragm MUs were identified during quiet breathing (n = 7; one female) and MUs from the 1st, 3rd, and 5th parasternal intercostal muscles during quiet (no lung volume feedback) and voluntary (triangular-shaped lung volume feedback) breathing (n = 5 males). PIC contribution to firing prolongation was estimated via quantification of firing hysteresis …

The Reliability And Validity Of Manual Palpation To Assess Lower Limb Arterial Occlusion Pressure In Older Adults, For Application In Blood Flow Restriction Exercise, Michael Beere, Isaac Selva Raj, Jeremiah J. Peiffer, Keith D. Hill, Peter K. Edwards, Belinda Brown, Brendan R. Scott

Research outputs 2022 to 2026

(A) Investigate test-retest reliability of posterior tibial pulse palpation to determine arterial occlusion pressure (AOP) and examine validity against hand-held Doppler ultrasound. (B) Investigate the suitability of using 130% systolic brachial blood pressure for prescribing cuff inflation pressure for blood flow restriction (BFR) exercise. Repeated measures, crossover design. Lower limb AOP was assessed in 20 adults ≥ 60 years using hand-held Doppler ultrasound and posterior tibial pulse palpation. Brachial systolic blood pressure (bSBP) was measured to predict cuff inflation pressures (bSBP130%). On three occasions > 24 hours apart, three AOP measurements were recorded by the same blinded rater to determine intra-rater …

Unilateral Numbers Need Context: Reference Values For Single-Leg Cmj Performance Relative To Bilateral Cmj Capacity, Karol Kruczek, Tim Gabbett, Jason Lake, Michał Nowak

Research outputs 2022 to 2026

The single-leg countermovement jump (SL CMJ) is widely used to assess limb-specific neuromuscular function, with interpretation commonly centred on inter-limb asymmetry. However, contextualising unilateral performance relative to bilateral capacity remains less clearly defined. This retrospective cross-sectional study aimed to develop exploratory descriptive benchmarks for SL CMJ kinetic, kinematic, and temporal variables expressed as a percentage of bilateral CMJ performance in a heterogeneous athletic cohort. A total of 348 athletes completed bilateral and unilateral CMJs using dual force plate sampling at 1000 Hz. The best trials were selected using the modified reactive strength index (mRSI), and averaged unilateral variables were expressed …

Sez6-Targeting Antibody-Drug Conjugate Abbv-706 In Advanced Small Cell Lung Cancer And Solid Tumors: A Phase 1 Trial, Lauren Averett Byers, Daniel Morgensztern, Et Al.

2020-Current year OA Pubs

Seizure-related homolog 6 (SEZ6) is expressed in small cell lung cancer (SCLC) and neuroendocrine neoplasms. In an open label, phase 1 trial, ABBV-706, an antibody-drug conjugate with a SEZ6-directed antibody linked to topoisomerase-1 inhibitor (Top1i), was administered intravenously every 3 weeks (Q3W) to 288 patients with advanced solid tumors; 240 received monotherapy, including 124 with relapsed/refractory (R/R) SCLC. Primary objectives of dose escalation (part 1, advanced solid tumors), dose optimization and expansion (part 2, R/R SCLC only) and dose expansion (part 4, central nervous system tumors and high-grade neuroendocrine neoplasms only) were to evaluate the safety, tolerability, pharmacokinetics (PK), immunogenicity …

Colocalization Of Eqtls With Type 2 Diabetes And Glycemic Traits Using Whole-Genome Sequences In Diverse Populations From The Nhlbi Trans-Omics In Precision Medicine (Topmed) Program, Ningyuan Wang, Daniel A Dicorpo, Yixin Zhang, Erica Kleinbrink, Donna K Arnett, John Barnard, John Blangero, Donald W Bowden, April P Carson, Yii-Der Ida Chen, Mina K Chung, Joanne E Curran, Dawood Darbar, Ravindranath Duggirala, Patrick T Ellinor, Diane Fatkin, Myriam Fornage, Nancy Heard-Costa, Jiang He, Lifang Hou, Sharon L R Kardia, Charles Kooperberg, Ruth J F Loos, David D Mcmanus, Braxton D Mitchell, Ryan L Minster, Kari E North, Bruce M Psaty, Laura M Raffield, Susan Redline, Stephen S Rich, Dan Roden, Jerome I Rotter, Moore B Shoemaker, Jonathan D Smith, David R Van Wagoner, Francois Aguet, Kristin Ardlie, Joshua C Bis, Jennifer A Brody, Brian E Cade, Clary B Clish, Paul S De Vries, James S Floyd, Barry I Freedman, Stacey Gabriel, Robert E Gerzsten, Mark O Goodarzi, Charles Gu, Xiuqing Guo, Namrata Gupta, Susan R Heckbert, Sarah Hsu, Yi-Jen Hung, Rita R Kalyani, Tanika N Kelly, Gregory L Kinney, Changwei Li, Simin Liu, Yongmei Liu, Donald M Lloyd-Jones, Joann E Manson, Rasika A Mathias, Josep M Mercader, Alanna C Morrison, Take Naseri, Suna Onengut, Nicholette D Palmer, Patricia A Peyser, Qibin Qi, Sridharan Raghavan, Alex P Reiner, Mary R Rooney, Magdalena Sevilla-Gonzalez, Chloe Sarnowski, Joshua D Smith, Jennifer A Smith, Nicole L Spartano, Usman Tahir, Kent D Taylor, Deirdre K Tobias, Russel P Tracy, Satupa'itea Viali, Heming Wang, Alexis C Wood, Lisa R Yanek, Wei Zhao, Yinan Zheng, Josée Dupuis, Ching-Ti Liu, Robert Sladek, Jennifer Wessel, James B Meigs, Alisa K Manning, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium

Faculty, Staff and Students Publications

Large-scale multiancestry genome-wide association studies have identified hundreds of loci associated with type 2 diabetes (T2D) and glycemic traits, yet imputed genotyping arrays limit the detection of low-frequency and rare variants. Whole-genome sequencing (WGS) offers a more complete view of genetic variation, especially across diverse populations. We analyzed high-coverage (38×) WGS data from 21,913 T2D case subjects, 61,036 control subjects, and up to 50,011 individuals with no diabetes with fasting glucose, fasting insulin, and HbA1c from the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine Program. We performed single-variant association testing, conditional analysis, fine-mapping, and Bayesian colocalization to …