Digital Commons Network^™

Malt1 Protease Inhibition Restrains Glioblastoma Progression By Reversing Tumor-Associated Macrophage-Dependent Immunosuppression In Mice, Juliana Hofstätter Azambuja, Saigopalakrishna Yerneni, Lisa Maurer, Hannah Crentsil, Gabriela Debom, Linda Klei, Mei Smyers, Chaim Sneiderman, Kristina Schwab, Rajesh Acharya, Aivi Nguyen, Josie Emery, John Little, Jeffrey Meridew, Yijen Lin Wu, Prasanna Ekambaram, Dong Hu, Pete Gough, John Bertin, Ari Melnick, Gary Kohanbash, Riyue Bao, Peter Lucas, Linda Mcallister-Lucas

College of Life Sciences Faculty Papers

MALT1 protease is an intracellular signaling molecule that promotes tumor progression via cancer cell-intrinsic and cancer cell-extrinsic mechanisms. MALT1 has been mostly studied in lymphocytes, and little is known about its role in tumor-associated macrophages. We show that MALT1 is expressed in glioblastoma (GBM)-associated macrophages. Mechanistically, GBM tumor cells induce a MALT1-NF-κB signaling axis in macrophages, leading to enhanced macrophage migration and polarization toward an immunosuppressive ('M2-like') phenotype. Inactivation of MALT1 protease promotes transcriptional reprogramming that reduces migration and restores a macrophage anti-tumor 'M1-like' phenotype. Preclinical in vivo analysis shows that MALT1 inhibitor treatment results in immuno-reactivity of GBM-associated macrophages …

Surgical Outcomes Of Hidradenitis Suppurativa Excision: Factors Impacting Wound Healing Time, Christina Huang, Scott H. Koeneman, Sherry Yang, Sami Tannour

Department of Surgery Faculty Papers

Hidradenitis suppurativa (HS) can be treated surgically to excise recurrent and recalcitrant regions of disease activity. However, surgical outcomes are highly variable depending on closure method, concomitant medical management and area of excision. In this study, we aim to characterise the healing courses from HS excision in a case series. To reduce operator variability, we opted to conduct a case series from a single surgeon. Surgeries conducted from June 2024-December 2025 by surgeon S.T. were included, and the postoperative course was followed until February 2026. Surgical details and postoperative course for 34 sites of HS across 20 patients were analysed. …

Long-Term Poverty, Rurality, And Geographic Disparities In Colorectal Cancer: A Spatial Analysis In Texas, Ryan Ramphul, Tracey Farrigan, Yixiao Chen, Yanchen Liu, Jooyeon Lee, Ruth Rechis, Karen Basen-Engquist, Lorna Mcneill

Faculty, Staff and Student Publications

Purpose: Colorectal cancer (CRC) remains a leading cause of cancer morbidity and mortality in the United States and shows substantial geographic variation. Socioeconomically disadvantaged communities experience elevated CRC incidence, yet few studies have analyzed multi-decade poverty measures for long-term structural disadvantage.

Methods: We analyzed CRC incidence from 2017 to 2021 across Texas using Texas Cancer Registry data. Age-sex-race/ethnicity standardized cases were incorporated as offsets in Bayesian spatial models to generate tract-level posterior mean relative risks. We evaluated four tract-level poverty measures (high poverty in 2021; persistent poverty since 1990; enduring poverty since 1980 and 1970), Rural-Urban Commuting Area (RUCA) classifications, …

Young-Onset Stroke In The Uae: A Single-Centre Retrospective Analysis Of Risk Factors And Outcomes, Sobia Siddiq, Saryia Adra, Kamel A. Samara, Batool Aldaher, Mohamad Emad Aldeen Mahfouz, Nour Sakan, Fathima Musfira, Roomiyah Riyaz Assadi, Ahlam Mohamed Almarzooqi, Hiba Jawdat Barqawi, Eman Abu-Gharbieh

Abington Jefferson Health Papers

BACKGROUND: Young-onset stroke represents a growing public health concern, yet data from the United Arab Emirates (UAE) remain limited. This study aimed to examine the risk factors and clinical outcomes associated with young-onset stroke in the UAE.

METHODS: A retrospective chart review was conducted on 419 patients aged below 50 years who were admitted at Al Qassimi Hospital, Sharjah, UAE, with a diagnosis of stroke between 2016 and 2022. Data on demographics, comorbidities, stroke subtype, management, and outcomes were collected and analyzed using Python-based statistical libraries.

RESULTS: The study population comprised predominantly of male individuals (78.28%), with most patients originating …

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 …

Larotrectinib In Trk Fusion Differentiated Thyroid Carcinoma: Updated Trial Data, Steven Waguespack, Marcia Brose, Jessica J Lin, Ray Mcdermott, Mohammed Almubarak, Jessica Bauman, Michela Casanova, Shivaani Kummar, Se-Hoon Lee, Damian Rieke, Do-Youn Oh, Changsong Qi, Natascha Neu, Domnita-Ileana Burcoveanu, Chiara Mussi, Alexander Drilon, David Hong, Maria Cabanillas

Department of Medical Oncology Faculty Papers

Larotrectinib is a first-in-class, highly selective, central nervous system-active tropomyosin receptor kinase (TRK) inhibitor approved for tumour-agnostic use in TRK fusion cancer. It has previously demonstrated rapid and durable disease control and favourable safety in patients with advanced TRK fusion thyroid carcinoma (TC). After an additional 4 years of follow-up with the inclusion of two additional patients, and utilising an independent review committee (IRC) to assess overall response rate (ORR), we report updated pooled analyses from three phase 1-2 larotrectinib clinical trials, focusing only on patients with TRK fusion differentiated TC (DTC). The primary endpoint was the IRC-determined ORR per …

Recognition Of Autism Characteristics In Females: An Examination Of Stakeholders, Laurel Lyn Bishop

Theses and Dissertations

Autism is a neurodevelopmental communication disorder, characterized by differences in social communication, attention, interests, and sensory perception. Diagnostic criteria have historically applied to males, but clinical diagnostic criteria beginning in 2022 now include slight differences in traits comprising the female phenotype. Until recently, autistic females may be missed by the professional and education community or diagnosed later than males. Like their autistic male counterparts, they face an increased risk of suicidal ideation, but they also face more difficulties in peer relationships, academic problems, and increased anxiety and depressive symptoms, but may not get supports. School-age girls spend their days with …

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 …

Attrition Of The Midwifery Workforce: Understanding Factors Associated With Leaving The Profession, E. Brie Thumm, Amy H. Goh, Elizabeth G. Phillips, Zachary Giano

College of Health Professions Faculty Papers

OBJECTIVE: To understand why advanced practice midwives (certified nurse-midwives and certified midwives) leave the workforce.

STUDY SETTING AND DESIGN: A multi-method, multi-source investigation included secondary analysis of certification data of advanced practice midwives and a cross-sectional online survey with closed- and open-ended items. Advanced practice midwives' active certification data were used to compare self-reported demographic characteristics of advanced practice midwives who reported working in the discipline of midwifery to those who did not (n = 9704). A survey was conducted in 2022 with individuals who allowed their certification to lapse between 2017 and 2021 (n = 303) and individuals who …

Leveraging Administrative Health Data To Capture Rare Adverse Drug Reactions: Identifying Pediatric Patients With Trimethoprim-Sulfamethoxazole Acute Respiratory Distress Syndrome., Keith Feldman, Jenna Miller, Katherine Doane, Laura Loftis, James W. Antoon, Kevin J. Downes, Jennifer Goldman

Manuscripts, Articles, Book Chapters and Other Papers

Rare adverse drug reactions (ADRs) are underrecognized and underreported in the electronic medical record (EMR). These events often require clinical review, making systematic identification challenging. The study aim was to develop an approach to prioritize identification and validation of a rare ADR to trimethoprim-sulfamethoxazole causing acute respiratory distress syndrome (TMP-SMX ARDS) across medical institutions. We developed a clinical phenotype based on 2 local TMP-SMX ARDS cases mapped to standardized elements of a national comparative healthcare database (PHIS). We validated identification of TMP-SMX ARDS at scale across medical institutions. A set of scoring criteria was created to prioritize cases and generate …

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 …

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 …

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 …

Adamts13 And Von Willebrand Factor In Relation To Vascular Cognitive Impairment And Cerebral Small Vessel Disease: The Heart-Brain Connection Study, Amos C Pomp, Mathijs T Rosbergen, Moniek P M De Maat, Paul S De Vries, M Arfan Ikram, Mat J A P Daemen, Imo E Hoefer, Wiro J Niessen, Jeroen De Bresser, Esther E Bron, Charlotte E Teunissen, Geert Jan Biessels, Robert J Van Oostenbrugge, Frank J Wolters

Faculty, Staff and Student Publications

Background: Reduced activity of a disintegrin-like and metalloprotease with thrombospondin type 1 repeats 13 (ADAMTS13) is associated with an increased risk of dementia, independent of Von Willebrand factor (VWF) levels. Pathways underlying this association remain poorly understood.

Objectives: Investigate the associations of VWF levels and ADAMTS13 activity with vascular cognitive impairment (VCI) and cerebral small vessel disease (CSVD).

Methods: In this cross-sectional study, we included 147 participants with VCI and 120 reference subjects (mean age: 67.5 years, 41% women). Using multivariable logistic regression, we determined the cross-sectional association of ADAMTS13 activity and VWF levels in plasma with VCI. Additionally, across …

Clinical Machine Learning Model For Predicting Pathological Complete Response In Patients With Esophageal And Gastroesophageal Junction Adenocarcinoma After Trimodality Therapy, Kohei Yamashita, Evan Kwiatkowski, Matheus Sewastjanow-Silva, Jane E Rogers, Katsuhiro Yoshimura, Melissa Pool Pizzi, Qiong Gan, Jenny J Li, Rebecca E Waters, Mariela Blum Murphy, Masaaki Iwatsuki, Wayne L Hofstetter, Aileen Chen, Ying Yuan, Jaffer A Ajani

Faculty, Staff and Student Publications

Background: Accurate prediction of pathological complete response (pCR) after preoperative chemoradiation therapy, followed by surgery (trimodality therapy) in esophageal adenocarcinoma (EAC) and gastroesophageal junction adenocarcinoma (GEJAC) may improve clinical decision-making and patient counseling before esophagectomy. This study aimed to develop predictive models for pCR after trimodality using machine learning (ML) approaches.

Patients and methods: A total of 569 patients with EAC and GEJAC who received trimodality therapy at MD Anderson Cancer Center between 2002 and 2022 were included. Clinicopathological characteristics and survival benefit of patients who achieved a pCR were reviewed via descriptive and survival analyses. Subsequently, ML models based …

Safety And Efficacy Of Tranexamic Acid In Urologic Surgery: Results From The International, Randomized, Placebo-Controlled Poise-3 Trial, Kari A O Tikkinen, Maura Marcucci, Alex L E Halme, Sandra N Ofori, Flavia K Borges, Charlotte T B Kanstrup, Lily J Park, Farhad Tondroanamag, Tuomas P Kilpeläinen, Sara V Tornberg, Thomas W Painter, David Conen, Vladimir Lomivorotov, Daniel I Sessler, Matthew T V Chan, Maria Jose Martinez-Zapata, Chew Y Wang, Denis B Xavier, Michael K Wang, Wojciech Szczeklik, Kate Leslie, Luke T Lavallee, Rodney H Breau, Kumar Balasubramanian, P J Devereaux

Faculty, Staff and Student Publications

Background and objective: Perioperative bleeding is common. Evidence for tranexamic acid (TXA) in urology remains limited and conflicting, and major urologic guidelines provide no recommendations. In an a priori planned analysis, we evaluated TXA among patients undergoing urologic surgery in POISE-3.

Methods: POISE-3 was an international randomized trial of patients undergoing surgery with bleeding and cardiovascular risk factors. Participants received TXA (1 g intravenous bolus at surgery start and end) or placebo. The primary efficacy outcome was a 30-day bleeding composite (life-threatening/major/critical organ), and the primary safety outcome was a 30-day thrombosis composite (myocardial injury after noncardiac surgery [MINS], nonhemorrhagic …

Effects Of Concurrent Neuropathologies With Alzheimer Disease Neuropathologic Change On Cognitive Decline: Minimal Impact Of Vascular Brain Injury Compared With Other Combinations, Sarah M Yasuda, Charles Mock, Kathryn Gauthreaux, Kwun C G Chan, C Dirk Keene, Jessica E Culhane, Yen-Chi Chen, Walter Kukull

2020-Current year OA Pubs

We examined cognitive changes associated with several neuropathologic entities, alone and in combination. We studied 808 participants from the National Alzheimer's Coordinating Center to assess associations between neuropathologic diagnoses (from autopsy) and neuropsychologic test scores (trajectories over time for 5 domains: overall cognition, episodic memory, attention, language, executive function). Neuropathologies included: Alzheimer disease neuropathologic change (ADNC), Lewy body disease (LBD), vascular brain injury (VBI), and limbic-predominant age-related TDP43 encephalopathy neuropathologic change (LATE-NC). Using linear mixed-effects models, we examined trajectories of cognitive decline for ADNC alone compared to ADNC plus LBD, VBI, or LATE-NC. We also examined differences between observed trajectories …

Navigating Undone Science: The Search For Adequate Endometriosis Care, Heather Welty, Melanie Jeske

Center for Medical Ethics and Health Policy Staff Publications

Endometriosis is an estrogen-dependent disease in which tissue similar to the lining of the uterus grows elsewhere in the body leading to a variety of symptoms including heavy and prolonged menstruation, chronic pain, cysts, infertility, and gastrointestinal issues. Despite being one of the most common gynecologic conditions, much remains unknown about potential risk factors for endometriosis, its etiology, and treatment options. First and second-line biomedical treatment options, complementary and alternative medicine, and lifestyle changes are all treatment options that people living with endometriosis (PLE) leverage to manage their symptoms. This article draws on in-depth interviews with 52 people living with …

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 …

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 …

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 …

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 …

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 …

Blood-Based Circular Rnas For Early Diagnosis Of Alzheimer's Disease, Bridget Phillips, Jessie Sanford, Menghan Liu, Matt Johnson, Katherine Gong, Kristy Bergmann, Joseph Lowery, Allison Flynn, William Brock, Brenda Sanchez Montejo, Nicholas Sykora, John Budde, John C Morris, Joel S Perlmutter, Paul T Kotzbauer, Richard J Perrin, Laura Ibanez, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

Detection of Alzheimer's disease (AD) before the development of clinical symptoms is critical for enabling the use of new treatments. Circular RNAs (circRNAs) are highly stable non-coding RNAs enriched in the brain that can cross the blood-brain barrier. Here, analyzing blood data from 1,221 individuals with AD and healthy individuals, we identified 34 circRNAs associated with AD status. A predictive model including these 34 circRNAs was comparable to plasma phosphorylated Tau-217 (pTau217) in classifying AD based on biomarker-confirmed (amyloid-β and Tau) status and replicated in independent samples from the Knight-Alzheimer Disease Research Center (n = 551: 76 AD, 475 cognitively …