Digital Commons Network^™

Using Randomization To Compare Ai And Expert-Generated Formative Assessment Questions In Medical Education, Akshat Kumar, Katie Stinson, Litao Wang, Elizabeth Nugent, Yongsu Lee, Mark Hormann, Latanya Jones Love, Toufeeq Ahmed Syed

Faculty, Staff and Student Publications

Background: AI-generated content is being used across the education spectrum and is beneficial for creating complex multiple-choice questions, such as those used in medical education. However, evaluating AI-generated content is challenging, and existing testing and evaluation methods are falling short. This study uses randomization to compare medical students' performance on and subjective evaluation of AI versus expert-generated questions. We hypothesized that there would be no difference in student performance or subjective evaluation of AI vs expert-generated questions.

Methods: We designed a single-center, randomized study where medical student participants received either one AI- or expert-generated question per day over four weeks. …

Impact Of School Nurse Education On Factors Influencing Hpv Vaccine Communication With Parents, Jihye Choi, Efrat K Gabay, Jeanette Deason, Elizabeth Baumler, Diane Santa Maria, Daisy Mullassery, Lara S Savas, Erika Thompson, Sanghamitra M Misra, Paula M Cuccaro

Faculty, Staff and Student Publications

Human papillomavirus (HPV) can cause six cancer types but can be prevented with timely vaccination in early adolescence. However, despite the wide availability of the HPV vaccine, uptake remains suboptimal among US adolescents. School nurses are invaluable resources to students and their families regarding adolescent immunization needs. As part of the All for Them vaccination program, we assessed the impact of the continued nurse education (CNE) intervention on school nurses’ HPV vaccine communication with parents. Seventy-two school nurses and nurse administrators in Texas participated in the study. Using a single-arm study design, we measured participants’ potential barriers to and self-efficacy …

Emotional Urgency And Lack Of Perseverance Are Linked To Anxiety Sensitivity And Improve During Early Recovery From Opioid Use Disorder., Breanna A. Mcnaughton-Long, Abigail J. Pleiman, Carmen Buchfink, Chrysantha B. Davis, Rayus Kuplicki, Martin P. Paulus, Hung-Wen Yeh, Maëlle C M Gueguen, Jennifer L. Stewart

Manuscripts, Articles, Book Chapters and Other Papers

Few studies have identified how facets of impulsivity relate to recovery in opioid use disorder (OUD). Treatment-enrolled individuals with OUD (n = 167) and healthy controls (CTL; n = 46) completed the Urgency, Premeditation, Perseverance, Sensation Seeking, Positive Urgency (UPPS-P) Impulsive Behavior Scale along with demographic and clinical measures at visit 1. Over the next three months, abstinence and return to use were documented for participants with OUD (via self-report, alcohol breathalyzer, urine drug screen, and secondary contact communication). Participants with OUD who returned to use (n = 59) did not complete further study visits, whereas those who remained abstinent …

Glial Dysfunction And Memory Impairments In A Model Of Pediatric Obstructive Sleep Apnea, Michael R Williamson, Jorge Botas, Mahyar J Hedayatpour, Thea Zlatkov, Akdes Serin Harmanci, Christopher J Yates, Kenneth Nobleza, Roshan Ailani, Adam C Adler, Farrah Kheradmand, Hyun Kyoung Lee, Benjamin Deneen, Hyun-Hwan Jeong, Arvind Chandrakantan

Faculty, Staff and Students Publications

Pediatric obstructive sleep apnea (POSA) is a common childhood disease that often causes aberrant brain development and cognitive deficits. The pathophysiological underpinnings of cognitive impairments in POSA remain unclear. Here, we examined cellular and molecular aspects of pathology in a mouse model of POSA that features learning and memory deficits. We performed single-nucleus RNA-sequencing (snRNA-seq) of the hippocampus to examine gene expression changes in an unbiased and cell type-specific manner. This dataset revealed a striking perturbation of transcriptomes across all brain cell types, particularly within glia and neural stem cells. We validated reduced expression of several differentially expressed genes at …

The Epidemiology Of Kidney And Urinary Tract Infections In Pediatric Chronic Kidney Disease: Prevalence, Risk Factors And Association With Gfr Decline In The Chronic Kidney Disease In Children Study., Derek K. Ng, Andrea R. Molino, Siyao Zhang, Emily J. Stonebrook, Craig S. Wong, Pratyush Gyawali, Kimberly J. Reidy, Susan L. Furth, Bradley A. Warady, Jeffrey J. Fadrowski, Ckid Study Investigators

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Urinary tract and kidney infections are potential complications in pediatric chronic kidney disease (CKD), especially among patients with congenital anomalies of the kidney and urinary tract (CAKUT). We characterized the prevalence of self-reported infections from childhood through young adulthood; evaluated risk factors; and quantified the association with CKD progression.

METHODS: Infections in the past year were self-reported at annual Chronic Kidney Disease in Children (CKiD) study visits. Age-specific infection prevalences were stratified by sex and CKD diagnoses (glomerular, non-glomerular non-CAKUT, CAKUT low-risk for infections, and three CAKUT high-risk categories: reflux nephropathy, obstructive uropathy, and other high-risk). Repeated measures logistic …

Early Hands-On Surgical Exposure: Outcomes Of A Student-Led Surgical Externship Program For Preclinical Students, Meryem C. Guler, Elizabeth Spitz, Jennifer E. Geller, Talar Tatarian, Renee Tholey

Department of Surgery Faculty Papers

Objective: Early surgical exposure may potentially influence medical students' decision to pursue a surgical career. At our urban, academic medical school, senior medical students developed a Surgical Externship Program (SEP) to provide first-years with hands-on OR experience. This program is a structured 1- to 2-week immersive experience in which first-year students scrubbed into operations, participated in rounds, and engaged with surgical teams under resident and attending supervision. This study evaluates the SEP's impact on surgical interest, OR confidence, and clinical exposure.

Setting: Academic tertiary care hospital.

Participants: First-year medical students.

Design: First-year students participated in a 1- or 2-week SEP …

Validation Of Next‑Generation Sequencing‑Derived Circulating Mrna Variants As Potential Diagnostic Tools In Hepatocellular Carcinoma And Cholangiocarcinoma, Daniel Zezulinski, Maarouf A. Hoteit, David E. Kaplan, Tingting Zhan, Cataldo Doria, Timothy M. Block, Aejaz Sayeed

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Liquid biopsy can transform oncology practice through early detection and real‑time monitoring of cancer progression and response to treatment. Circulating cell‑free tumor RNA offers promise as a novel and emerging alternative to circulating cell‑free tumor DNA for detecting the presence and understanding the biology of liver tumors. Both circulating DNA and RNA, which predominantly reside in extracellular vesicles, carry evidence of vital germline and somatic mutations. High impact single nucleotide changes, insertions and deletions in circulating RNA (ctRNA) serve a key role in cancer development and progression. Tumor cells exploit the RNA splicing machinery to induce structural and functional changes …

Androgens Mediate Sexual Dimorphism In Pilarowski-Bjornsson Syndrome., Kimberley Jade Anderson, Eirny Tholl Thorolfsdottir, Ilana M. Nodelman, Sara Tholl Halldorsdottir, Stefania Benonisdottir, Malak A. Alghamdi, Naif A M Almontashiri, Brenda J. Barry, Matthias Begemann, Jacquelyn F. Britton, Sarah Burke, Benjamin Cogne, Ana S A Cohen, Carles De Diego Boguñá, Evan E. Eichler, Elizabeth C. Engle, Jill A. Fahrner, Laurence Faivre, Mélanie Fradin, Nico Fuhrmann, Christine W. Gao, Gunjan Garg, Dagmar Grečmalová, Mina Grippa, Jacqueline R. Harris, Kendra Hoekzema, Tova Hershkovitz, Sydney Hubbard, Katrien Janssens, Julie A. Jurgens, Stanislav Kmoch, Cordula Knopp, Meral Aktas Koptagel, Farah A. Ladha, Pablo Lapunzina, Tobias Lindau, Marije Meuwissen, Andreina Minicucci, Emily Neuhaus, Mathilde Nizon, Lenka Nosková, Kristen Park, Chirag Patel, Rolph Pfundt, Pankaj Prasun, Nils Rahner, Nathaniel H. Robin, Carey Ronspies, Jasmin Roohi, Jill Rosenfeld, Margarita Saenz, Carol J. Saunders, Zornitza Stark, Isabelle Thiffault, Sarah Thull, Danita Velasco, Clara Velmans, Jolijn Verseput, Antonio Vitobello, Tianyun Wang, Karin Weiss, Ingrid M. Wentzensen, Genay Pilarowski, Thor Eysteinsson, Madelyn Gillentine, Kári Stefánsson, Agnar Helgason, Gregory D. Bowman, Hans Tomas Bjornsson

Manuscripts, Articles, Book Chapters and Other Papers

Sex-specific penetrance in autosomal-dominant Mendelian conditions is largely understudied. The neurodevelopmental disorder Pilarowski-Bjornsson syndrome (PILBOS) was initially described in females. Here, we describe the clinical and genetic characteristics of the largest PILBOS cohort to date, showing that both sexes can exhibit PILBOS features, although males are overrepresented. A mouse model carrying a human-derived Chd1 missense variant (Chd1^R616Q/+) displays female-restricted phenotypes, including growth deficiency, anxiety, and hypotonia. Orchiectomy unmasks a growth-deficiency phenotype in male Chd1^R616Q/+ mice, while testosterone rescues the phenotype in females, implicating androgens in phenotype modulation. In the gnomAD and UK Biobank databases, rare missense variants …

Complementary Vertebrate Wac Models Exhibit Phenotypes Relevant To Desanto-Shinawi Syndrome, Kang-Han Lee, Marwan Shinawi, Et Al.

2020-Current year OA Pubs

Monogenic syndromes are associated with neurodevelopmental changes that result in cognitive impairments and neurobehavioral phenotypes, including autism and seizures. Limited studies and resources are available to make meaningful headway into the underlying molecular mechanisms that result in these symptoms. One such example is DeSanto-Shinawi Syndrome (DESSH), a rare disorder caused by pathogenic variants in the

Assessment Of Timp1, Transgelin-2, And Procalcitonin As Protein Biomarkers For Diagnosis And Prognosis Of Bloodstream Infection In A Critically Ill Cohort, Sajal Tiwary, Caroline A O'Neil, Sydney Lawless, Olivia Arter, Meghan Brown, Brittany Roemmich, Carleigh Samuels, Jennie H Kwon, Christopher W Farnsworth

2020-Current year OA Pubs

BACKGROUND: Bloodstream infections (BSI) are a significant contributor to morbidity and mortality among hospitalized patients. Rapid diagnosis of BSI is critical for timely and appropriate clinical management, but current diagnostic strategies have a prolonged turnaround time or only identify select pathogens with minimal prognostic information.

METHODS: We examined serial serologic samples from 77 intensive care unit (ICU) patients at time points before, during, and after diagnosis of presumptive BSI to identify host-derived protein biomarkers associated with specific organisms and with clinical outcomes in BSI. ICU patients with and without BSI were included. Two candidate biomarkers, tissue metalloproteinase 1 (TIMP-1) and …

Inosine-Triphosphate-Pyrophosphatase Activity As A Potential Predictor Of Methotrexate Remission In Juvenile Idiopathic Arthritis., Sofia Sindici Forgiarini, Marianna Lucafò, Debora Curci, Davide Selvestrel, Valentina Moressa, Sofia Pagarin, Barbara Bellich, Martina Franzin, Alberto Tommasini, Mara L. Becker, Laura Ramsey, Susan D. Thompson, Carl D. Langefeld, Federica Corba, Edoardo Marrani, Gabriele Simonini, Gabriele Stocco, Giuliana Decorti, Andrea Taddio, Serena Pastore

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Methotrexate (MTX) is the first-line therapy for juvenile idiopathic arthritis (JIA), but up to 40% of patients do not respond to it. Low inosine triphosphate pyrophosphatase (ITPA) activity has been associated with reduced clinical remission. We investigated the role and underlying mechanisms of ITPA in vitro.

METHODS: ITPA enzymatic activity was measured by high-performance liquid chromatography with ultraviolet detection in erythrocyte lysates from patients with JIA (enrolled in Trieste, Italy; Florence, Italy; and Kansas City, Missouri) receiving weekly MTX (10-15 mg/m²) for at least 12 months. Remission was evaluated by Wallace et al criteria. ITPA rs1127354, which …

Postoperative Complications In Patients With Sickle Cell Disease After Total Shoulder Arthroplasty, Katie Zehner, Gwyneth C. Maloy, John Slevin, Wesley Day, Mitchell K. Ng, Xuan Luo, Jonathan N. Grauer, Arya G. Varthi

Rothman Institute Papers

BACKGROUND: Sickle cell disease (SCD) encompasses a spectrum of genetic hematologic disorders characterized by erythrocyte sickling. Patients may experience musculoskeletal manifestations, such as osteonecrosis, which may warrant consideration for total shoulder arthroplasty (TSA). While prior literature suggests patients with SCD more frequently suffer complications after orthopaedic procedures, this is not well characterized for TSA.

METHODS: Adult TSA patients (older than 18 years) were identified in the 2010 to 2023 PearlDiver M170 database. Patients with SCD were matched 1:4 to patients without SCD based on age, sex, and Elixhauser Comorbidity Index (ECI). Ninety-day postoperative complications, emergency department (ED) visits, and readmissions …

Lidocaine Combined With Low-Dose Esketamine For Movement-Evoked Pain After Hepatectomy: A Double-Blind Randomised Controlled Trial, Yan Xu, Li Zhou, Qianqian Tang, Feng Yu, Jingwen Wu, Siyu Yan, Min Cai, Jialu Wan, Yi Kang, Lajing Luowu, Mengmeng Zhou, Lulong Bo, Daniel I Sessler, Chunling Jiang

Faculty, Staff and Student Publications

Introduction: Pain following hepatectomy may delay recovery and increase opioid use. We tested the primary hypothesis that combining lidocaine and low-dose esketamine would reduce movement-evoked pain 24 h after hepatic resection. We also evaluated whether this approach reduced opioid consumption and improved quality of recovery.

Methods: Patients having elective hepatic resections were allocated randomly to receive lidocaine-esketamine or placebo from induction of anaesthesia until the end of surgery. After surgery, patients allocated to lidocaine-esketamine were given a continuous infusion of lidocaine with esketamine for 72 h. All patients received transversus abdominis plane blocks with ropivacaine 2 mg.kg-1 after induction of …

Cracking The Code: Genotype-Phenotype Correlation Models In Sarcoglycanopathies, Leonela Luce, Conrad C Weihl, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Sarcoglycanopathies are among the most severe limb-girdle muscular dystrophies (LGMD), though milder presentations have been described. These diseases are primarily caused by missense variants, but the limited predictability of their effect on protein maturation, complex formation, and transport has hindered reliable genotype-phenotype correlations. This study aimed to establish accurate genotype-phenotype correlations for LGMDR3, LGMDR4, and LGMDR5.

METHODS: We analyzed the largest sarcoglycanopathy cohort to date (n = 541). Clinical data, including age at symptom onset and loss of ambulation, were collected and used to define phenotype severity. Predictive models were developed considering the impact of non-truncating variants on secondary …

Predictors Of Complete Obliteration And Favourable Outcome After Single-Modality Treatment For Low-Grade Arteriovenous Malformations: A Multicentre Study, Angelica Fuentes, Salem Tos, Natasha Ironside, Georgios Mantziaris, Yuki Shinya, Basel Musmar, Hamza Adel Salim, Nimer Adeeb, Christopher Ogilvy, Douglas Kondziolka, Ali Alaraj, Min Park, Adam Dmytriw, Hussein Zeineddine, Finn Mccarthy, Hussam Abou-Al-Shaar, Ahmed Abdelsalam, Mustafa Baskaya, Cagdas Ataoglu, Anthony Sanchez-Forteza, Muhammed Amir Essibayi, Abdullah Keles, Sandeep Muram, Howard Riina, Arwin Rezai, Sahin Hanalioglu, Ufuk Erginoglu, Johannes Pöppe, Davide Simonato, Yan-Lin Li, Sandeep Kandregula, Dhairya Lakhani, Christoph Griessenauer, Rahim Abo Kasem, Alejandro Spiotta, Ajit Puri, Jasmeet Singh, Anna Luisa Kuhn, Jan Karl Burkhardt, Robert Starke, Laligam Sekhar, Michael Levitt, David Altschul, Neil Haranhalli, Malia Mcavoy, Paul Foreman, Osama Zaidat, Mohammad Almajali, Hakeem Shakir, Alfred Pokmeng See, Adib Abla, Aashay Patel, Andrew Nguyen, Matthew Koch, Visish Srinivasan, Peng Roc Chen, Spiros Blackburn, Ketan Bulsara, Peter Kan, Louis Kim, Omar Choudhri, Stavropoula Tjoumakaris, Pascal Jabbour, Amey Savardekar, Hugo Cuellar, Michael Lawton, Bharat Guthikonda, Jacques Morcos, Jason Sheehan

Department of Neurology Faculty Papers

INTRODUCTION: Patient and arteriovenous malformation (AVM) characteristics that portend success after treatment for low-grade brain AVMs remain unknown.

PATIENTS AND METHODS: We utilised the MISTA multicentre registry to identify patients with Spetzler-Martin (SM) grade I or II AVMs treated with stand-alone curative-intent intervention (resection, stereotactic radiosurgery [SRS] or endovascular embolisation). Bivariate and multivariable analyses were performed to identify patient and AVM characteristics predictive of complete obliteration or favourable outcome (complete obliteration without new permanent deficit or post-treatment haemorrhage).

RESULTS: A total of 522 patients were included (292 microsurgery, 152 SRS, 78 embolisation). Complete obliteration rates differed between microsurgery (95.9%), SRS …

Mitochondrial Trna-Derived Fragments As Candidate Metastasis-Modifying Rna, Katy L. Swancutt, R. Mckinnon Walsh, Sydney Quijano, Emily Schueddig, Devin C. Koestler, Adam D. Scheid, Tony Vanden Bush, Yi Jing, Isidore Rigoutsos, Danny R. Welch

Computational Medicine Center Faculty Papers

UNLABELLED: How mitochondrial DNA (mtDNA) polymorphisms influence complex phenotypes remains poorly understood. Using mitochondrial-nuclear exchange mice, we previously showed that mtDNA single-nucleotide polymorphisms (SNP) modify metastasis, cardiovascular disease, and epigenetic marks independently of metabolic differences. The only mtDNA SNP correlating with these phenotypes resides in the gene encoding mitochondrial transfer RNA (tRNA)-arginine [mt-tRNAArg (UCG), mt-TR], suggesting a role for non-protein-coding loci. In this study, we identify and preliminarily characterize previously undescribed tRNA-derived fragments (tRF) generated from mt-TRs. Northern blotting revealed distinct tRF that are differentially expressed among mtDNA SNPs, between lung and liver, and between sexes. Surprisingly, small RNA sequencing …

Altered Postnatal Chromatin Development In The Nucleus Accumbens Primes Enduring Stress Sensitivity, Rebekah L Rashford, Lisa Z Fang, Michael Deberardine, Hye Ji J Kim, Laura W Hirschfield, Ella Cervi, Mason R Barrett, Jeremy M Thompson, Meaghan C Creed, Catherine Jensen Peña

2020-Current year OA Pubs

Early life stress (ELS) sensitizes individuals to subsequent stressors to increase lifetime risk for psychiatric disorders. Within the nucleus accumbens (NAc)-a key limbic and reward-associated brain region-ELS sensitizes both cellular and transcriptional response to later stress, which are programmed by enduring epigenetic changes. Among the histone modifications persistently enriched by ELS in NAc is H3K4me1, which is associated with open chromatin and epigenetic priming of genomic enhancers. Here, we sought to determine whether H3K4me1 enrichment in NAc was sufficient to prime cellular and behavioral responses to adult stress. Viral-mediated overexpression of the histone H3 monomethyltransferase

Redo-Transcatheter Aortic Valve Replacement With Self-Expanding Valves: A U.S. Registry Analysis., Toby Rogers, Vinayak N Bapat, Stanley J Chetcuti, Harold L Dauerman, John K Forrest, Sachin S Goel, Kendra J Grubb, Wah Wah Htun, Rishi Puri, Michael J Reardon, Gilbert H L Tang, Amit N Vora, Steven J Yakubov, Ruth Eisenberg, Guilherme F Attizzani

Heart and Vascular Articles

BACKGROUND: Redo-transcatheter aortic valve replacement (TAVR) for failed transcatheter heart valves is expected to increase, but data on outcomes with self-expanding valves remain limited.

OBJECTIVES: The aims of this study were to evaluate procedural, clinical, and quality-of-life outcomes following redo-TAVR using self-expanding Evolut valves and to compare these outcomes with those among a contemporary native TAVR cohort.

METHODS: Outcomes after redo-TAVR with Evolut R, Evolut PRO, and Evolut PRO+ valves in the Society of Thoracic Surgeons/American College of Cardiology TVT (Transcatheter Valve Therapy) Registry were analyzed and compared with outcomes after native-valve TAVR using the same valve platform during the …

Hemodynamic Characterization Of Cardiac Dysfunction After Traumatic Brain Injury Using A Controlled Cortical Impact Model In Male Rats, Preston So, Amit Iyengar, Noah Weingarten, Mrinal Patel, Jessica Dominic, Andrew Belec, Joyce Ho, Samuel Shin, Pavan Atluri

Division of Cardiology Faculty Papers

Traumatic brain injury (TBI) is associated with cardiovascular dysfunction that worsens clinical outcomes, yet the underlying mechanisms are poorly under stood. Clinical studies are limited by heterogeneity, highlighting the need for con trolled experimental models. Controlled cortical impact (CCI) provides precise control of injury severity, and invasive pressure- volume (PV) loop analysis allows detailed hemodynamic assessment. Adult male Wistar rats underwent sham op eration or mild or severe CCI- induced TBI. PV- loop assessment and transtho racic echocardiography were performed at 8 or 24 h after TBI or sham. Serum epinephrine (EPI) and norepinephrine (NE) were quantified by ELISA. At …

A Distinct Form Of Fat Fibrosis Is Linked To Insulin Resistance In People With Hiv, Diana L Alba, Alaa Abdellatif, Moon Kyung Choi, Stephen M Brown Mayfield, Thuy An T Pham, David I Berrios, Antonio E Rodriguez, Marin Ewing, Tony R Figueroa, Judy Gonzalez-Vargas, Ningyan Zhang, Zhiqiang An, Dawei Bu, Steven G Deeks, Philipp E Scherer, Peter W Hunt, Suneil K Koliwad

The Brown Foundation: Institute of Molecular Medicine

BACKGROUND

Despite antiretroviral therapy (ART), people with HIV (PWH) are at heightened risk for insulin resistance (IR) and type 2 diabetes (T2D). Subcutaneous adipose tissue (SAT) fibrosis contributes to metabolic disease, but its role in IR among PWH is unknown. We investigated the relationship between SAT fibrosis and IR in PWH, along with transcriptional signatures to distinguish it from SAT fibrosis due to obesity.

METHODS

We analyzed body composition and SAT fibrosis (hydroxyproline) in 46 PWH and 74 people without HIV (PWoH), excluding individuals with T2D. We examined fibrosis-related gene transcription in the SAT using a targeted panel and measured …

Shared Neural Geometries For Bilingual Semantic Representations In Human Hippocampal Neurons, Xinyuan Yan, Ana G Chavez, Melissa Franch, Kalman A Katlowitz, Ivy Gautam, Brian Kim, Aaditya Krishna, Aadit Shrivastava, Katie Van Arsdel, James Belanger, Assia Chericoni, Taha Ismail, Elizabeth A Mickiewicz, Danika Paulo, Hanlin Zhu, Alica M Goldman, Vaishnav Krishnan, Atul Maheshwari, Eleonora Bartoli, Nicole R Provenza, Seng Bum Michael Yoo, Benjamin Y Hayden, Sameer A Sheth

Duncan NRI Faculty and Staff Publications

The human brain has the remarkable ability to comprehend and express similar concepts in multiple languages. To understand how it does so, we examined responses of hippocampal neurons during passive listening, directed speaking, and spontaneous conversation in both English and Spanish in a small group of balanced bilinguals. We found a small number of putative "cross-language neurons," whose responses to equivalent words (e.g., "tierra" and "earth") are correlated. However, neurons' semantic tunings differed substantially by language, suggesting language-specific neural implementations. Instead, the crucial driver of translation was a preserved geometric organization of neural responses between the two languages, one that …

An Online Epilepsy Self-Management Tool For Patients With Epilepsy: A Formative Usability Study, Katarzyna Czerniak, Ross Shegog, Refugio Sepulveda, Robert Addy, Youngran Kim, Sahiti Myneni, Alejandra Garcia-Quintana, Kimberly Martin, David M Labiner

Faculty, Staff and Student Publications

Background: Epilepsy is a serious chronic neurological condition with no permanent cure. Continual self-management is important to mitigate seizure frequency and optimize quality of life in people with epilepsy who have greater disparities in accessing epilepsy care. The Management Information & Decision Support Epilepsy Tool (MINDSET [UTHealth, University of Arizona, and Radiant Digital]) was developed to enhance accessibility to epilepsy self-management (ESM) assessment and treatment. The purpose of this formative usability pilot study was to assess the user experience and functionality of MINDSET 2.0, an enhanced cross-platform online version of MINDSET, among a sample of patients with epilepsy prior to …

Sex-Aware Causal Inference Assessment Of The Immune System In Complex Neurodegenerative Diseases, Frida Lona-Durazo, Ross P Byrne, Marc-Olivier Pilon, Michael D Greicius, Marie-Pierre Dubé, Michael E Belloy, Russell L Mclaughlin, Sarah A Gagliano Taliun

2020-Current year OA Pubs

Sex differences, in terms of prevalence, symptoms and disease progression, are established in the aetiology of complex neurodegenerative diseases, including amyotrophic lateral sclerosis, Parkinson's disease and Alzheimer's disease, but the underlying biology driving these differences remains poorly understood. There is emerging evidence from genetic and functional analyses affirming the role of the immune system in such diseases, but a thorough assessment of sex differences in the link between the immune system and neurodegenerative diseases remains lacking. Here, we applied a robust causal inference approach, two-sample Mendelian randomization, to evaluate the causal effect of immune-related protein levels on three neurodegenerative diseases …

A Cooking Skills Intervention For Long-Term Weight Loss In Young Adults With Intellectual Disabilities: Rationale And Design For A Randomized Trial., Lauren T. Ptomey, Jessica C. Danon, Delwyn Catley, Richard A. Washburn, Amy Bodde, Francisco J. Diaz, Brian C. Helsel, Anna M. Rice, Joseph R. Sherman, Madison Koester, Walker S. Mckinney Ph.D., Joseph E. Donnelly

Manuscripts, Articles, Book Chapters and Other Papers

Young adults with intellectual disability (ID) are an underserved population with a high prevalence of obesity, obesity-related health conditions, and reduced ability to complete instrumental and basic activities of daily living (I/ADLs). After leaving the structured environment of public school, many young adults with ID spend more time at home or in day programs, begin living more independently, or enter the workforce. These transitions may increase reliance on fast or processed foods and reduce opportunities for physical activity, contributing to accelerated weight gain. Previous research has demonstrated clinically meaningful short- and long-term weight loss (18-24 months) in adults with mild-to-moderate …

Decision-Making Criteria In Polygenic Embryo Screening: A Survey Of Reproductive Medicine Physicians, Rémy A Furrer, Aayushi Gandhi, Dorit Barlevy, Shai Carmi, Todd Lencz, Stacey Pereira, Gabriel Lázaro-Muñoz

Center for Medical Ethics and Health Policy Staff Publications

Purpose: Polygenic embryo screening (PES) examines embryos for their genetic likelihood of developing complex conditions and traits. The commercialization of PES places reproductive endocrinologists and infertility specialists (REIs) as the primary decision-makers in its use, despite professional guidelines cautioning that PES is not ready for clinical use.

Methods: This survey examines how 152 US REIs perceive and approach potential clinical decision-making scenarios regarding the use of PES.

Results: REIs were more likely to offer PES for medical conditions (up to 62% for cancer) than for traits (eg, 0% for skin color, 10% for body mass index). When evaluating 11 potential …

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 …

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, …

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 …

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 …