Digital Commons Network^™

Are We Winning At Twinning? Persistent Cni Use In Identical Kidney Transplants., Nicholas S. Herrera, Shivani Wadnerkar, Diane M. Cibrik

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Calcineurin inhibitors (CNIs) revolutionized kidney transplantation by reducing acute rejection rates. Identical twin kidney transplantation is the only setting in which the allograft is immunologically indistinguishable from self, yet CNI use persists. We characterized CNI utilization across end-stage kidney disease etiologies and examined whether CNI exposure was associated with reduced rejection or improved death-censored graft survival (DCGS).

METHODS: We performed a retrospective cohort study using scientific registry of transplant recipients data (January 2000-August 2025). Among 255 adult identical twin kidney transplant recipients, discharge regimens were categorized by CNI use; Firth penalized Cox regression was the primary method for 10-year …

Impact Of Trisomy 21 On Post Pull-Through Enterocolitis And Bowel Function In Children With Hirschsprung Disease: A Pcplc Analysis., Marshall W. Wallace, Scott S. Short, Rachel C. Crady, Ron W. Reeder, Hira Ahmad, Kelly Austin, Andrea Badillo, Casey M. Calkins, Megan M. Durham, Julie R. Fuchs, Christopher Gayer, Julia E. Grabowski, Jamie C. Harris, Charles R. Hong, Ankur Rana, Rebecca M. Rentea, Nelson Rosen, Payam Saadai, Caitlin A. Smith, K Elizabeth Speck, Cristine S. Velazco, Richard J. Wood, Michael D. Rollins

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: We evaluated whether Trisomy 21 (T21) affected bowel management use, ability to toilet train for stool, and rates of Hirschsprung-Associated Enterocolitis (HAEC) in children with Hirschsprung disease (HD). We hypothesized that T21 would be associated with increased rates of HAEC, bowel management program (BMP) use, and delayed toilet training for stool.

METHODS: Children with HD in the Pediatric Colorectal and Pelvic Learning Consortium (PCPLC) database who underwent primary pull-through were included and stratified by T21 status: HD only versus HD + T21. Children requiring a redo pull-through, initially managed with a stoma, or those who had inadequate follow-up were …

Assessing The Feasibility Of A Self-Management Intervention For Individuals With Advanced Prostate Cancer And Comorbid Type Ii Diabetes Mellitus, Amy L. Shaver, Christina Steinbock-Malfer, William Tester, Patrick Mille, William K. Kelly, Kevin K. Zarrabi, Costas D. Lallas, Mihir M. Shah, Rose Dimarco, Emily Brand, Shawntel Brown, Swapnil Sharma, Nikita Nikita, Cindy Cogen, Scott W. Keith, Grace Lu-Yao

Kimmel Cancer Center Faculty Papers

BACKGROUND: Many older adults with cancer have at least one comorbidity. Type II diabetes mellitus (T2DM) is a common comorbidity among patients with prostate cancer (PC) and represents an important consideration in this population. Comorbid T2DM can negatively impact cancer-specific outcomes for patients, suggesting the need for better glycemic management, especially for patients on active cancer treatment. The goal of this modified Diabetes Self-Management Education Services (mDSMES) pilot study was to provide patients with the opportunity to learn methods of diabetes self-management, including how to manage their glucose levels, improve their understanding and utilization of medication to promote improvements in …

Association Between Stress Mindset, Psychological Symptoms, And Psychosocial Risk In Liver Transplant Patients, Sarah Kay Brill

Dissertations

Psychosocial functioning is a central component of liver transplant evaluation, yet less is known about how cognitive factors, such as stress mindset, relate to transplant readiness. The present study examined the association between stress mindset and psychosocial risk, as well as its relationship with depressive symptoms, anxiety, and perceived stress among patients undergoing liver transplant evaluation. Patients included 62 adults completing standard pre-transplant assessment measures, including the Stress Mindset Measure–Specific (SMM-S), Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Perceived Stress Scale (PSS). Hierarchical logistic regression analyses indicated that stress mindset was …

Machine Learning In Flow Cytometry For Acute Myeloid Leukemia Diagnosis: A Scoping Review, Katrina Jezzela M. Dela Pena Md, Mls (Ascp)

Other Specialties

Manuscript version:

Introduction: Flow cytometry is essential for the diagnosis of acute myeloid leukemia (AML), but conventional analysis is labor-intensive, operator-dependent, and increasingly complex. Machine learning (ML) may support automated analysis; however, its readiness for clinical implementation remains unclear. This scoping review mapped ML approaches applied to flow cytometry for AML-related diagnosis.

Methods: PubMed was searched for English-language primary studies applying artificial intelligence, ML, or deep learning to human flow cytometry data for AML diagnosis or classification. Eligible studies reported diagnostic performance metrics. Study characteristics, preprocessing, data representation, model architecture, validation strategy, performance metrics, interpretability, and implementation considerations were descriptively …

Small But Mighty: How Can Pediatric Psychologists Harness The Power Of Digital Single-Session Interventions?, Christina Amaro, Alexandra Monzon, Melissa Alderfer, Kimberly Canter, Michael Amylon, Stephanie Fooks-Parker, Jessica Schleider, Susana Patton, Katie Devine

Department of Pediatrics Faculty Papers

OBJECTIVE: Single-session interventions (SSIs) are an innovative, scalable approach for addressing the unmet behavioral and mental health needs of pediatric patients and their families. Specifically, digital SSIs, which are self-guided and delivered online, offer a low-cost and accessible approach but are currently underutilized in pediatric psychology.

METHODS: This topical review aims to describe SSIs broadly and the specific need for digital SSIs, explore potential applications within pediatric psychology, outline future directions and considerations, and present two examples of community-engaged digital SSI design.

RESULTS: SSIs evidence small to medium effects across a range of mental health concerns, including distress, anxiety, and …

Dnp Final Report: Improving Diabetes Self-Efficacy Through Nutrition Education: A Quality Improvement Project, Lakimberely S. Wooten

DNP Final Reports

Diabetes affects 12.7% of residents in Northeast Texas and is the 7th leading cause of death. Internal evidence indicates low health literacy and a heavy disease burden in the service area, underscoring the need for a standardized, low-cost, and feasible approach to nutrition education. This quality improvement project evaluated the feasibility of implementing an instructor-led nutrition education session. Guided by the Johns Hopkins Evidence-Based Practice Framework and the ADKAR behavioral change model, adult participants with Type 2 diabetes received instruction on the Plate Method. Participants enrolled in a 4-week, instructor-led diabetes education class completed a 1-hour, nutrition education session using …

Transfusion Intensity In The Icu: Reasons And Triggers, Merijn Reuland, Senta Raasveld, Jimmy Schenk, Claudia Oord, Sanne Bruin, Caroline Schaap, Andrew Flint, Jan Bakker, Maurizio Cecconi, Marcus Lance

Anaesthesiology, East Africa

Background The reasons and physiological triggers for blood transfusion in critically ill patients are not well characterized. Beyond hemoglobin levels, hemodynamic instability is frequently cited, but its role across clinical contexts remains unclear.

Aims (1) To determine whether reasons and triggers for RBC transfusion differ across intensive care unit (ICU) days with varying transfusion intensity. (2) To describe reasons for non-RBC transfusions across these intensity groups.

Methods This sub-study of the prospective International Point Prevalence Study of Intensive Care Unit Transfusion Practices (InPUT) classified ICU days by transfusion intensity: nonmajor (1 RBC unit), major (≥2 units), and massive (≥6 units …

Hyperadhesive Von Willebrand Factor Contributes To Pathogenesis Of Preeclampsia, Yajuan Wang, Chenyu Wang, Katie L Houck, Xiaoli Gao, Yuanyuan Chen, Xin Xu, Xue Zhao, Miguel A Cruz, Shu Zhang, Chester Q Li, Fengxia Xue, Min Li, Swati Shree, Jing-Fei Dong, Cha Han

Children’s Nutrition Research Center Staff Publications

Background: Preeclampsia is the most common complication of pregnancy, significantly affecting maternal and fetal health, and is characterized by placental and systemic endotheliopathy. Patients with preeclampsia have elevated levels of VWF (von Willebrand Factor), which is associated with poor clinical outcomes. However, whether VWF serves as a marker for endotheliopathy or contributes to the pathogenesis of preeclampsia remains poorly understood.

Methods: We investigated the role of hyperadhesive VWF in the development of preeclampsia by studying patients, evaluating mouse models, and performing in vitro experiments.

Results: We show that patients develop VWF- and fibrin-rich thrombosis in the placenta and have significantly …

All-Cause And Cause-Specific Mortality In Gambling Disorder: Evidence From A Nation-Wide Matched And Sibling Cohort Study In Taiwan, Yang-Chieh Brian Chen, Chih-Wei Hsu, Liang-Jen Wang, Mu-Hong Chen, Yao-Hsu Yang, Chih-Sung Liang, Edward Chia-Cheng Lai

Children’s Nutrition Research Center Staff Publications

Background and aims: Gambling disorder (GD) has been linked to suicidal ideation and suicide deaths; however, evidence on all-cause and cause-specific mortality-particularly in Asian populations-remains limited. Using a retrospective cohort study based on nationwide matched and sibling cohort, we investigated all-cause and cause-specific mortality risk in patients with GD.

Design, setting and participants: A retrospective cohort study was conducted using 2000-2022 data from Taiwan's National Health Insurance Research Database. A cohort of 961 individuals diagnosed with GD was identified. An age- and sex-matched control cohort (n = 3,844) and an unaffected sibling cohort (n = 675) were constructed. Cumulative survival …

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 …

“We’Re Just Always There For Each Other”: Examining Social Support For African American Caregivers Of Oncology Patients, Madeleine Lee, Keisha White Makinde

Posters

No abstract provided.

Advancing Health Equity In Global Oncology: A Collaborative Academic-Cancer Society-Industry Program To Address Health Disparities In Sub-Saharan Africa, Kenneth Merrell, Ben Kamdem-Talom, Hannah Anie, Christine Wekesa, Nomsa Tsikai, Miriam Mutebi, Rakiya Saidu, Nwamaka Lasebikan, Adamu Bojude, Randiak Alaro

General Surgery, East Africa

Purpose Cancer care capacity in sub-Saharan Africa (SSA) is constrained by late diagnosis and limited treatment access. Few funding mechanisms support innovative, locally led programs to address these challenges. A collaborative initiative was developed to strengthen oncology care through quality improvement (QI) projects.

Materials and Methods The program was developed by Global Bridges Oncology (GBO) at Mayo Clinic, Pfizer Global Medical Grants, and the African Organisation for Research and Training in Cancer. A committee composed primarily of African oncology experts guided the process. An RFP was disseminated across SSA in English, French, and Portuguese, inviting applications to improve diagnostic and …

Expanding Cleft Surgical Workforce Capacity In Low- And Middle-Income Countries Through Competency-Based Training, Daniel Bradley, Jonathan Diaz, Emily Jones, Kealani Unkel, Atenas Bustamante, Zenebe Gebremariyam, Daniel Abate, Mamy Andriamanarivo, Mekonen Abebe, Armando Siu

General Surgery, East Africa

Objective To evaluate a competency-based cleft surgery training pathway designed to expand local surgical capacity in low- and middle-income countries (LMICs).

Design Prospective observational study of cleft surgery training outcomes between July 2022 and September 2024.

Setting Operation Smile cleft surgery programs and partner hospitals in LMICs, with integrated virtual education.

Patients/Participants Twenty trainee cleft surgeons from 11 countries.

Interventions A competency-based training pathway combining virtual education and mentored operative experience, with assessment using a validated surgical competency tool.

Main Outcome Measures Changes in self-reported surgical confidence and educator-rated surgical competency

Results Trainee cleft surgeons participated in 1168 cleft lip …

Emergency Medical Services Mental Health: Causes Of Providers Leaving The Industry, Brian C. Selke

Graduate Theses and Dissertations (2019 - present)

Employee resilience and mental health have become critical concerns in Emergency Medical Services (EMS) as workforce shortages increasingly threaten staffing stability and patient care. National Registry of Emergency Medical Technicians (NREMT) data indicates that more than 30% of eligible EMS providers did not recertify between 2020 and 2023, raising concerns about workforce sustainability. This study examines EMS providers’ intentions to leave the profession and identifies workplace factors associated with turnover. A statewide survey of more than 1,200 licensed EMS providers in Alabama was analyzed using regression techniques to evaluate the relationship between workplace conditions and turnover intentions. Results demonstrate that …

"I Can See Where This Is Taking Me": Medical Students' Perceptions Of Humanities Courses At Aga Khan University, Kenya, Catherine Gathu, Marthaclaire Zammit, Urvi Saboo, Robert Opoka

Family Medicine, East Africa

Background Humanities courses in medical training are increasingly recognized as essential for developing empathetic, reflective and socially responsive physicians. Although well-established globally, their integration into medical education in African contexts remains limited. In Kenya, humanities are often peripheral within curricula dominated by biomedical sciences and clinical medicine. Aga Khan University (AKU), Nairobi, has introduced a novel medical curriculum that embeds seven core humanities courses as central components of the initial phase of its MBChB program. This study explored students’ perceptions and lived experiences of these humanities courses.

Methods A retrospective descriptive study using an embedded mixed-methods design was conducted among …

Maternal, Perinatal, Neonatal, And Postpartum Outcomes Following Severe Acute Respiratory Syndrome - Coronavirus-2 Infection In Pregnancy: A World Health Organization Multi-Country Prospective Cohort Study, Edna Kara, Sami Gottlieb, Nathalie Broutet, Anna Thorson, Marie Delnord, Ibukun-Oluwa Abejirinde, Ronaldo Silva, Marleen Temmerman, Rodney Adam, Ingrid Gichere

Pathology, East Africa

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has raised global concerns regarding its impact on pregnant women and their infants, particularly across evolving variants. This study aimed to determine if infection during pregnancy increased the risk of adverse maternal, perinatal, neonatal, or postpartum outcomes during pre-Omicron and Omicron periods.

Methods We conducted a prospective cohort study in 10 primarily low- and middle-income countries, comprising public and private maternity hospitals in rural and urban areas. Maternal age and comorbidity adjusted mixed-effects models with country-specific random intercepts were used to estimate relative risks (RRs) comparing participants with and without infection …

Demographic And Clinical Characteristics Of Participants In The Neuropsychiatric Genetics Of African Populations-Psychosis (Neurogap-Psychosis) Study: A Descriptive Analysis, Rocky Stroud, Kimberly Hook, Melkam Alemayehu, Lukoye Atwoli, Mark Baker, Lori Chibnik, Bizu Gelaye, Stella Gichuru, Symon Kariuki, Rehema Mwema

Internal Medicine, East Africa

Background Approximately 1.3 million individuals in sub-Saharan Africa, as well as millions of others worldwide, live with psychotic disorders. However, there is limited mental health research based on these populations and even less of a focus on neuropsychiatric genetics research within these settings.

Methods To address this gap, the Neuropsychiatric Genetics of African Populations-Psychosis (NeuroGAP-Psychosis), a case-control study, collected data identifying genetic and environmental risk factors associated with psychotic disorders in Ethiopia, Kenya, South Africa, and Uganda. This paper describes baseline demographic and clinical characteristics of the 42,953 participants recruited between 2018–2023 and compares these characteristics by country and case …

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 …

Acute And Chronic Leukemia In Sub-Saharan Africa: A Systematic Review, Allwell A. Ayirebi, Stephen Twumasi, Linda K. Olaga, Benedict Sackey, Daniel N.M. Antonio, Richard O. Ansah, Eugene A. Ansah, John A. Sah, Enoch O. Anto, Yvonne Anang-Quartey, Antoinette Koomson, Angela Opoku, Godfred A. Donkor, Paulina Duah, Ama G. Boadu, Samuel Essien-Baidoo, Wina I.O. Boadu, Lilian A. Boateng

Research outputs 2022 to 2026

Background: The four primary subgroups of leukemia include chronic myeloid leukemia (CML), acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic lymphocytic leukemia (CLL). Very little is known about the regional variation of leukemia and subtypes in sub-Saharan Africa (SSA).

Aims: This systematic review focused on the prevalent cases reported in sub-Saharan Africa, throwing more emphasis on treatment outcomes, follow up time and survival rates.

Methods: A systematic review of studies on acute and chronic leukemia in sub-Saharan Africa (SSA) was conducted using articles retrieved from PubMed, Scopus, Google Scholar, Embase and African-specific databases such as African Journals Online …

Global Disparities In Neurosurgical Literature: A Narrative Review Of Underrepresentation Of Low- And Middle-Income Countries And Pathways To Research Equity, Tirath Patel, Naveed Ahmad, Abbas Hussain, Bisma Faraz, Amna Binte Naeem, Urooj Sheraz, Laiba Noor, Saleha Khan, Muhammad Seerat Ali, Nikhilesh Anand

School of Medicine Publications

The global neurosurgical literature is dominated by high-income countries, with low- and middle-income countries (LMICs) contributing minimally despite bearing the most significant share of the neurosurgical disease burden. Underrepresentation limits equitable knowledge dissemination and the relevance of guidelines. The objective of this review was to assess neurosurgical publication disparities, identify deterrents to LMIC participation, and outline initiatives that foster equity and inclusion in research. This narrative review synthesized evidence on global disparities in neurosurgical literature through a structured search of PubMed, Scopus, and Google Scholar (2010–2025). Eligible studies examined research output, authorship trends, publication barriers, or equity initiatives. Findings mapped …

Defining The Value Of Elective Lumbar Fusion: A Systematic Review Of Existing Methodologies And Framework For The Operative Value Index, Advith Sarikonda, Anthony Chen, Theo S. Biddle, Danyal A. Quraishi, Preston Carey, Arbaz A. Momin, Matthews Lan, Dwight Mitchell Self, Ashmal S. Kabani, Ahilan Sivaganesan

Department of Neurosurgery Faculty Papers

BACKGROUND: Despite wide variation in the outcomes and costs of lumbar fusion, few studies have integrated these domains together within a single metric to assess "value" (outcomes achieved per dollar spent). In this review, we sought to 1) characterize existing metrics of cost-effectiveness for lumbar fusion, 2) evaluate all applications of time-driven activity-based costing (TDABC) in spine surgery, and 3) outline the conceptual foundation for a standardized Operative Value Index (OVI).

METHODS: Two PRISMA-concordant systematic reviews were performed on PubMed and Scopus databases. The first review examined all studies which reported a cost-effectiveness metric for lumbar fusion. The second review …

Diabetter Together: Outcomes Of A Randomized Controlled Trial Evaluating A Peer Mentor Behavioral Intervention For Young Adults With Type 1 Diabetes During The Transfer From Pediatric To Adult Care, Marisa E Hilliard, Charles G Minard, Samantha A Carreon, Wendy L Levy, Sarah K Lyons, Randi Streisand, Tricia S Tang, Siripoom V Mckay, Sridevi Devaraj, Barbara J Anderson

Faculty, Staff and Students Publications

Objective: Transition between pediatric and adult health care is complex, with high risk for loss to follow-up and suboptimal health outcomes for young adults with type 1 diabetes. This trial evaluated the efficacy of DiaBetter Together, a 12-month strengths-based behavioral intervention delivered by trained peer mentors. The intervention aimed to help young adults navigate the transfer process to promote optimal glycemic outcomes, shorten time to adult care follow-up, and improve psychosocial outcomes.

Research design and methods: Using a single-site randomized clinical trial design, we compared the 12-month intervention to usual care among n = 100 young adults aged 17-25 years …

Cost-Effectiveness Of Hes V2.0 And Galad For Hepatocellular Carcinoma Surveillance In Patients With Cirrhosis, Mert Sahinkoc, Gizem S Nemutlu, Hashem B El-Serag, Mary Linton B Peters, Ali Hajjar, Anthony E Samir, Leigh Anne Dageforde, Fasiha Kanwal, Jagpreet Chhatwal

Faculty, Staff and Students Publications

Background: Ultrasound-based surveillance for HCC is limited by suboptimal sensitivity and low adherence. Blood-based biomarkers are potential alternatives for routine HCC surveillance. We aimed to define optimal sensitivity, specificity, and cost parameters under which blood-based biomarkers could serve as cost-effective alternatives in patients with cirrhosis.

Methods: We developed a microsimulation model of the natural history of HCC in individuals with compensated cirrhosis. We compared the cost-effectiveness of biannual surveillance using 2 blood-based biomarkers-HES V2.0 and GALAD-versus ultrasound-based surveillance across a range of sensitivity, specificity, test costs, and adherence levels. Outcomes included quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios …

Dupilumab Versus Placebo In Adults And Adolescents With Eosinophilic Gastritis (Degas): A Double-Blind, Placebo-Controlled, Phase 2, Multicentre, Randomised Controlled Trial, Nirmala P Gonsalves, Evan S Dellon, Kara L Kliewer, Tetsuo Shoda, Regina Yearout, Seema S Aceves, Nicoleta C Arva, John A Besse, Julie M Caldwell, Mirna Chehade, Amaziah Coleman, Margaret H Collins, Sara Anvari, Gary W Falk, Sandeep K Gupta, Girish Hiremath, David A Katzka, Paneez Khoury, John Leung, Calies Menard-Katcher, Paul Menard-Katcher, Kathryn A Peterson, Maria A Pletneva, Amanda K Rudman Spergel, Jonathan M Spergel, Tatyana Vaysman, Joshua B Wechsler, Benjamin L Wright, Guang-Yu Yang, Xue Zhang, Meijian Zhou, Ashish Bansal, Bram P Raphael, Amr Radwan, Jennifer Maloney, Antonio Martin, Yamo Deniz, Glenn T Furuta, Lisa J Martin, Marc E Rothenberg

Faculty, Staff and Students Publications

Background: Eosinophilic gastritis currently has no approved treatments and is postulated to be driven by type 2 inflammation. Dupilumab blocks type 2 cytokines IL-4 and IL-13 and has efficacy in multiple diseases characterised by type 2 inflammation, including eosinophilic oesophagitis. We aimed to assess the efficacy and safety of dupilumab in patients with eosinophilic gastritis.

Methods: DEGAS was a proof-of-concept, phase 2, multicentre, randomised controlled trial consisting of a 12-week, double-blind, placebo-controlled period, followed by a 24-week open-label extension period. Patients aged 12-70 years from 11 hospitals in the USA with histologically active eosinophilic gastritis (≥30 eosinophils per high-power field …

Rates Of, Reasons For, And Reactions To Discontinuation Of Glp-1 Receptor Agonists: A Narrative Review, Henry D Heisey, L Parker Gregg, Christopher D Verrico, Dennis T Villareal, Terri L Fletcher

Faculty, Staff and Students Publications

GLP-1RAs are increasingly used for their glucose-lowering and weight-management effects, but many patients discontinue them. In this narrative review we aim to review real-world, quantitative and qualitative GLP-1RA discontinuation, adherence, and persistence evidence as it aligns with an established conceptual framework for understanding medication adherence in noncommunicable chronic disease. Many inconsistencies exist in how discontinuation, adherence, and persistence are studied in this literature. Few qualitative studies have focused on discontinuation of GLP-1RAs. Quantitative approaches often focus on medication-related factors and more superficial aspects of socioeconomic and condition-related factors. Very few studies encompass all 5 dimensions of the medication adherence conceptual …

Quantitative Imaging Of Pyruvate Metabolism In A Patient With Anaplastic Thyroid Cancer, James A Bankson, Joshua S Niedzielski, Collin J Harlan, Yunyun Chen, Christopher M Walker, Philip L Lorenzi, Lin Tan, Vikas Kundra, Matthew E Merritt, Mukundan Ragavan, Dawid Schellingerhout, Renjie He, Yao Ding, Sahana Datar, Qing Wang, Christine B Peterson, Clifton D Fuller, Vlad C Sandulache, Stephen Y Lai

Faculty, Staff and Students Publications

Purpose: Magnetic resonance imaging using hyperpolarized (HP) [1-13C]-pyruvate enables assessment of pyruvate metabolism in vivo and offers new insight into metabolic changes in response to cancer therapy. Widely used semi-quantitative metrics of pyruvate metabolism can be affected by physiological factors that are extrinsic to intracellular metabolism. A validated pharmacokinetic (PK) model for analysis of intracellular pyruvate metabolism is needed to enhance the accuracy of quantitative metrics and clinical translation of metabolic MRI using HP pyruvate.

Methods: A PK model with two physical compartments and two chemical pools was developed to analyze the conversion of labeled pyruvate into lactate in vitro. …

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 …

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, …

Extending Genome-Wide Association Studies To Admixed Cohorts With High Degrees Of Relatedness, Taotao Tan, Alejandra Vergara-Lope, José Jaime Martínez-Magaña, Nirav N Shah, Yi-Sian Lin, Kai Yuan, Jaime Berumen, Jesus Alegre-Díaz, Pablo Kuri-Morales, Roberto Tapia-Conyer, Joel Gelenter, Janitza L Montalvo-Ortiz, Wei Zhou, Jason M Torres, Elizabeth G Atkinson

Duncan NRI Faculty and Staff Publications

Admixed populations comprise a large portion of the human population worldwide, but are often excluded from genome-wide association studies (GWASs) due to analytic challenges. Our group developed Tractor, a local-ancestry-informed GWAS tool designed for admixed samples that produces accurate ancestry-specific effect sizes and boosts the discovery power to identify ancestry-enriched loci. However, Tractor operates under an assumption of unrelated samples. Here, to address this gap, we propose Tractor-Mix, which allows for well-calibrated association studies in datasets containing admixed samples with relatedness. Extensive simulations show that this method is competitive with other state-of-the-art approaches that do not produce ancestry-specific results. Empirical …