Digital Commons Network^™

The Future Of Epilepsy Care In The United Kingdom: A Roadmap For Technology-Enabled Transformation, Rohit Shankar, John Terry

Peninsula Medical School

Epilepsy is recognized to be a significant cause of premature mortality, socio-economic distress and poor quality of life in economically developed countries. Despite clear clinical guidelines, epilepsy care is marked by delayed diagnosis, fragmented management, high emergency admission rates, and pronounced health inequalities affecting rural populations, ethnic minority groups, and people with intellectual disabilities. Diagnostic pathways remain inefficient, with prolonged waits for electroencephalography (EEG), low sensitivity of routine investigations, and repeated inconclusive testing. Long-term management continues to depend on infrequent hospital visits and unreliable patient recall, contributing to suboptimal seizure control, avoidable morbidity, and preventable mortality. In the United Kingdom, …

Rethinking Ethics For An Era Of Trusted Computational Tools, Kristin M Kostick-Quenet, Meghan Hurley, John Herrington, Eric A Storch

Center for Medical Ethics and Health Policy Staff Publications

Computer perception (CP) technologies are poised to deliver near real-time behavioral insights with high precision. As technical barriers recede, our field's ethical focus must shift from "Can we trust the data?" to "Should we use it here, and how?" We propose a contextual ethics framework that: (1) defines the appropriate scope of CP integration; (2) advocates codesigned roadmaps to manage expectations and epistemic conflict; (3) expands evaluation beyond performance metrics to humanistic outcomes; and (4) anticipates future high performance systems to safeguard dignity, empathy, and shared decision-making in clinical care.

How To … Coach Problem Representation To Strengthen Diagnostic Reasoning In Trainees, Cody Clary, Adam Cohen, Satid Thammasitboon

Faculty, Staff and Students Publications

Problem representation (PR) is a concise synthesis of clinical information that captures the core diagnostic problem in a single statement, often referred to as a 'one-liner'. Although central to diagnostic reasoning, this skill is frequently underdeveloped in medical training. Many trainees struggle to transform clinical data into meaningful representations, which can hinder communication, diagnostic reasoning and patient safety. The Assessment of Reasoning Tool-Reconstructed (ART-R) provides a structured framework that educators can adapt as a coaching rubric to strengthen PR during clinical teaching. Using the ART-R, faculty can guide trainees to refine their PR by focusing on three elements: (1) clarity …

Plasma Biomarkers Of Brain Injury In Critically Ill Children Receiving Extracorporeal Membrane Oxygenation, Matthew L Friedman, Michael J Bell, Bonnie A Brooks, Adam S Himebauch, Asavari Kamerkar, Kerri Larovere, Laura L Loftis, Jose A Pineda, Ahmed Said, Hitesh S Sandhu, Martin Stengelin, Catherine Demos, Mark S Wainwright, Alina N West, Allan Barnes, Allen D Everett, Ryan J Felling, Sue J Hong, Jennifer L Roem, Cynthia F Salorio, Derek K Ng, Melania M Bembea

Faculty, Staff and Students Publications

Importance: Timely identification of acute brain injury (ABI) in children receiving extracorporeal membrane oxygenation (ECMO) support is critical for early neuroprotective interventions.

Objectives: To determine if elevations in plasma glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and tau levels in children receiving ECMO precede new ABI confirmed by neuroimaging, and if they are associated with mortality and functional outcomes.

Design, setting, and participants: This was a prospective observational cohort study conducted from 2019 to 2023, with 18-month follow-up completed in 2025. Children aged 2 days to younger than 18 years at ECMO cannulation were recruited from 11 US …

Association Of Infection Frequency And Incident Clonal Hematopoiesis Of Indeterminant Potential, Ajibike Lapite, Vernon A Burk, James Decuir, Junichi Ishigami, Seyedmohammad Saadatagah, Pradeep Natarajan, Christie M Ballantyne, Elizabeth A Platz, Katherine Y King

Faculty, Staff and Students Publications

Clonal hematopoiesis of indeterminant potential (CHIP) is an age-related phenomenon associated with increased risk of hematologic malignancy. Preclinical studies have shown that infection is a driver of CHIP; clinical studies in people living with HIV suggest a relationship between chronic infection and CHIP, but the association between infection frequency and incident CHIP in the general population remains unknown. We leveraged the atherosclerosis risk in communities study to design a closed prospective cohort study. CHIP was determined based on whole-exome sequencing at 2 time points 20 years apart. Included were 3,367 individuals without cancer or CHIP at time 1 and without …

Non-Isolated Dandy-Walker Malformation: Exome Sequencing Efficacy And Phenotypic Expansions, Sarah Araji, Xiaonan Zhao, Jill A Rosenfeld, Seema R Lalani, Daryl A Scott

Faculty, Staff and Students Publications

Dandy-Walker malformation (DWM) is a rare congenital abnormality of the posterior fossa and the cerebellum and has an incidence of 1 in 10 000 to 30 000 births. Although DWM can present in isolation, it is often associated with other central nervous system (CNS) abnormalities or extra-CNS anomalies (DWM+). A molecular cause is not identified in the majority of individuals with DWM+. This is due, in part, to uncertainty regarding optimal testing strategies and an incomplete understanding of the genetic causes of DWM+. In this study, we analyzed clinical exome sequencing (cES) data from 91 individuals with DWM+ to determine …

Barrett’S Esophagus-Associated Genetic Loci In African Americans: A Case-Control Study Using The All Of Us Research Program, Ashwin Rao, Jinyoung Byun, Aaron P Thrift, Hashem B El-Serag

Faculty, Staff and Students Publications

Background and aims: Barrett's esophagus is the only known precursor lesion to esophageal adenocarcinoma (EAC). Barrett's esophagus and EAC are less common in African Americans than in non-Hispanic Whites. Studies in European populations have identified Barrett's esophagus-associated risk loci; however, none have examined loci in African Americans cohorts. We conducted a case-control targeted replication study to investigate previously identified Barrett's esophagus risk loci in an African Americans cohort in the All of Us (AoU) Research Program.

Methods: We abstracted phenomic and genomic data from 108 African Americans with Barrett's esophagus and 778 African Americans controls in the AoU database. We …

Treatment Of Obsessive-Compulsive Disorder Via Mental Health Technology, Erika S Trent, Nisha Jagannathan, Eric A Storch

Faculty, Staff and Students Publications

Obsessive-compulsive disorder (OCD) is a debilitating neuropsychiatric disorder that remains chronic unless intervened with evidence-based intervention. Cognitive behavioral therapy (CBT) with exposure and response prevention is the gold-standard psychological intervention for OCD, but many individuals do not receive this intervention due to barriers to accessing treatment. Mental health technology tools such as telehealth, computerized programs, internet-delivered CBT, and mobile applications have been adopted to expand the accessibility of CBT. An up-to-date summary of the evidence base of technology-mediated formats of CBT for OCD treatment is provided. Clinical benefits offered by such approaches, current limitations, and future research directions are discussed.

Functional Genomics Studies Of Psychiatric Disorders In Individuals Of Latin American Populations: A Scoping Review, Luz M Porras, Isabelle Rodríguez-Lausell, Gabriel Iglesias-Maldonado, Emily Val F Tuliao, Gabriela Martínez, Chelsey Leveque, Julian Tobon, Rachel Eloy, Sintia Belangero, Cynthia M Bulik, Camila M Loureiro, Carolina Muniz Carvalho, Vanessa Ota, Diego Luiz Rovaris, Eric A Storch, Eva Maria Trujillo-Chi Vacuan, Maria M Velasquez, Latin American Genomics Consortium, Marcos L Santoro, Humberto Nicolini, Elizabeth G Atkinson, Janitza L Montalvo-Ortiz, Paola Giusti-Rodríguez

Faculty, Staff and Students Publications

Over the past 15 years, genetic studies of psychiatric disorders have provided important insight into the contribution of both common variants of small effect, as well as rare exonic and copy number variants with large effect sizes. Genome-wide association studies (GWAS) allow us to understand the intricate polygenicity characteristic of many psychiatric disorders. However, a considerable proportion of single nucleotide polymorphisms (SNPs) implicated in these disorders localize to the non-coding regions of the genome. Unraveling the molecular mechanisms that underlie the etiology of psychiatric illnesses requires integration using functional genomics approaches. Functional genomics methods are critical for developing a mechanistic …

Ilae-Yes Global Webinar Series: Integrating Clinical And Basic Science In Epilepsy Research, Cecilie G Nome, Parthvi Ravat, Fabrice Bartolomei, Marco De Curtis, Rossella Di Sapia, Marian Galovic, Maria Gogou, Lukas Imbach, Julia Jacobs, Katja Kobow, Alice D Lam, Christos Panagiotis Lisgaras, Elisa Micalizzi, Eleni Nikalexi, Jeffrey L Noebels, Jeanne T Paz, Avtar Singh Roopra, Sally Shaaban, Laurent Sheybani, Shobi Sivathamboo, Ana Suller Marti, Adam Williamson, Naoto Kuroda

Faculty, Staff and Students Publications

Bridging clinical and basic research is increasingly recognized as a priority in the epilepsy field, yet opportunities for integration remain limited by the time, space, and financial constraints of scientific meetings. To address this gap, the Research Task Force of the Young Epilepsy Section of the International League Against Epilepsy (ILAE-YES) organized a free global webinar series designed to promote translational dialogue and provide accessible research education for early-career clinicians, researchers, and physician-scientists. Based on a preliminary ILAE-YES community survey, eight topics of high interest were selected: (1) epigenetics, (2) EEG biomarkers, (3) ictogenesis, (4) thalamo-cortical network, (5) sudden unexpected …

Corneal Innervation Research At A Crossroads: A Tool-Driven Roadmap For The Future, Anna Matynia, Ian D Meng, Brian M Davis, Stephen C Pflugfelder, Anat Galor, Victor L Perez, Elizabeth R Felix, Pedram Hamrah, Pantelimon Rompolas, Raul E Ruiz-Lozano, Shamsuddin A Bhuiyan, Kaveh Moghbeli, Evangelia Semizoglou, William Renthal, Harinder Singh, Jishnu Das, Marcin Golczak, Mary Ann Stepp, Catherine W Morgans, Cintia S De Paiva, Carl Y Saab, Igor Spigelman, Rony R Sayegh, Tally M Largent-Milnes, Hao Wu, Wenqin Luo, Sreya Mitra, Heesuk Yoo, Sina Farsiu, Sejiro Littleton, Eden Jacob, Matthew T Mcpheeters, Maryse Lapierre-Landry, Jordan J Smith, Xi Wang, Roxana Florea, Made Airanthi K Widjaja-Adhi, Scott Holmes, Zane Zemborain, Kate E T Laise, Nicholas J Pondelis, Ki-Soo Jeong, Rui Chen, Michael W Jenkins, Vivian Lee, Eric A Moulton, Deborah S Jacobs, Sue A Aicher, Anthony J St Leger, Daniel R Saban

Faculty, Staff and Students Publications

Corneal innervation research has faced long-standing clinical challenges that only recent technological breakthroughs now make tractable. Advances in single-cell analysis, viral vectors, clinical imaging, and artificial intelligence provide integrated approaches for uncovering molecular mechanisms underlying functional outcomes and facilitating clinical applications. The National Eye Institute's U01-funded consortium on ocular surface innervation addresses major knowledge gaps in characterizing corneal-projecting neurons, understanding neuroimmune and epithelial interactions in the cornea, and translating animal model findings to human pathology. The unique properties of the cornea (transparent, avascular, and densely innervated) make it ideal for neurobiology research on peripheral and central sensory processing. Through a …

Systematic Identification Of Cell-Cell Interactions Associated With The Severity Of Patients With Alzheimer’S Disease, Zijian Zhang, Naail Chowdhury, Jing Dong, Lang Wu, Chao Cheng

Faculty, Staff and Students Publications

Background

Alzheimer's disease (AD) is a complex, multifactorial neurodegenerative disorder involving dysfunction across multiple brain regions. While accumulating evidence has implicated the roles of diverse cell types, including neurons, glia, and vascular cells in AD pathogenesis, it is still poorly understood how cell type interactions drive or respond to the disease progression and severity.

Objective

This study aimed to systematically characterize cell-type–specific alterations and intercellular communication changes associated with AD progression.

Methods

We leveraged the transcriptome profiling and a previously established statistical framework to present a comprehensive mapping of the cellular interaction landscape in the human brain of AD.

Results …

Initial Injury Type And Violent Reinjury, Nicholas Szoko, Daphne Lew, Taylor Kaser, Zoe M Miller, Matt Vogel, Michael A Mancini, Lindsay M Kranker, Christopher Behr, Vicki Moran, Rachel Ancona, Kristen Mueller

2020-Current year OA Pubs

IMPORTANCE: Violent injuries are the leading cause of death among children and young adults in the United States. Violent injury may increase the risk of subsequent injury (ie, violent reinjury), but it is unclear how this risk varies across different injury types (eg, blunt assault, stabbing, firearm).

OBJECTIVE: To describe patterns of violent reinjury across different injury types to inform tailored prevention strategies.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter cohort study included patients who presented with violent injuries to 2 adult and 2 pediatric level I trauma centers in St Louis, Missouri, from January 2016 to December 2023.

EXPOSURES: Violent …

Can Behavioral Interventions Promote Health Equity In Pediatric Type 1 Diabetes? A Narrative Review Of Promising Treatments, Paul T. Enlow, Jaquelin Flores Garcia, Julia Price, Kristen A. Torres, David V. Wagner

Department of Pediatrics Faculty Papers

Purpose of review: Synthesize data on whether existing behavioral interventions can improve health equity among youth with type 1 diabetes.

Recent findings: While existing behavioral interventions demonstrated efficacy in improving health and/or psychosocial outcomes, evidence that these same interventions may improve health equity were lacking. Most interventions were evaluated using predominantly White and affluent samples and some studies did not report on racial, ethnic, or sociodemographic characteristics of their sample. Only a few interventions have been adapted for youth from minoritized backgrounds. Recent multisystemic and technology/mHealth interventions recruited samples that were sociodemographically representative of youth experiencing disparities, suggesting that these …

Coxfa4l2 Upregulation Preserves Residual Cytochrome C Oxidase Activity In Coxfa4-Related Leigh-Like Encephalopathy, Micol Falabella, Sandra Lopez Calcerrada, Jana Aref, Jiaze Gao, William L Macken, Chiara Pizzamiglio, Renata Kabiljo, Anna Lucia Francavilla, Pauline Gaignard, Antoine Pouzet, Jonathan Levy, Giulia Barcia, Jamie K Leighton, Efstathia Chronopoulou, Germaine Pierre, Riza Köksal Özgül, Ali Dursun, Rebecca Halligan, Helen Mundy, Javeria Raza Alvi, Tipu Sultan, William James Craigen, Lisa Emrick, Jill A Rosenfeld, Gehad Elmakkawy, Jihye Kim, Joseph J Gleeson, Aboulfazl Rad, Gabriela Oprea, Maqbool Hussain, Khalil Ur Rehman, Sadia Riaz, Robert W Taylor, Vincent Procaccio, Maha S Zaki, Erika Fernandez-Vizarra, Ciro Leonardo Pierri, Michael G Hanna, Henry Houlden, Reza Maroofian, Cristina Ugalde, Jan-Willem Taanman, Robert D S Pitceathly

Faculty, Staff and Students Publications

Primary mitochondrial diseases (PMDs) affect approximately 1 in 4300 individuals and cause early-onset neuromuscular and multisystem dysfunction with reduced lifespan. They result from pathogenic variants in mitochondrial or nuclear DNA that impair oxidative phosphorylation. Cytochrome c oxidase (COX; complex IV) deficiency is a well-established cause of PMD, leading to a broad spectrum of phenotypes. COXFA4 (cytochrome c oxidase subunit FA4), formerly NDUFA4, is a nuclear-encoded COX subunit, but its role in disease remains poorly defined. We report the largest genetically confirmed cohort of COXFA4-related PMD to date, comprising 13 individuals from 12 families with biallelic pathogenic COXFA4 variants. All present …

Gastrointestinal Symptoms After Sport-Related Concussion: Prevalence And Patterns In A Multi-Cohort Analysis, Emma Finnegan, Ed Daly, Katherine J. Hunzinger, Lisa Ryan

Department of Exercise Science Faculty Papers

Background/Objectives: Concussions occur across all sports globally; however, inconsistent symptom recognition continues to challenge diagnosis, management, and recovery. Although concussion effects extend beyond neurological dysfunction, gastrointestinal (GI) symptoms remain insufficiently captured within current assessment frameworks and may influence athletes’ fuelling choices and food tolerance during recovery. This study aimed to describe the prevalence and patterns of GI symptoms reported among athletes with a history of concussion and to explore whether symptom prevalence and burden differed by sex and country. Methods: A total of 401 adult athletes (225 males; mean age 32.4 ± 11.3 years) with a history of concussion were …

Pregnancy Outcomes After In Utero Exposure To Immune Checkpoint Inhibitors, Morgan Bou Zerdan, Bruna Kfoury, Eliane Aoun, Sarah Diane Hmaidan, Roni Nitecki Wilke, Jeffrey A How, Terri L Woodard, Pamela T Soliman, Laurie J Mckenzie

Faculty, Staff and Students Publications

Importance: Immune checkpoint inhibitors (ICIs) have transformed the management of cancers affecting reproductive-age patients, yet their impact on pregnancy outcomes remains incompletely understood. We describe two cases of maternal and fetal outcomes associated with ICI exposure during pregnancy and present a comprehensive literature review.

Methods: A retrospective chart review was conducted at MD Anderson Cancer Center (1 January 2015 to 31 December 2024) to identify patients exposed to ICIs during pregnancy. Clinical data including cancer type, treatment timing, pregnancy course, and maternal and neonatal outcomes were collected. A narrative literature review was also performed using PubMed to identify reported cases …

Unbiased Niche Labeling Maps Immune-Excluded Niche In Bone Metastasis, Zhan Xu, Fengshuo Liu, Yunfeng Ding, Tianhong Pan, Yi-Hsuan Wu, Yujiao Han, Jun Liu, Igor L Bado, Weijie Zhang, Ling Wu, Yang Gao, Xiaoxin Hao, Liqun Yu, Xuan Li, David G Edwards, Hilda L Chan, Sergio Aguirre, Michael Warren Dieffenbach, Elina Chen, Siyue Wang, Yichao Shen, Dane Hoffman, Luis Becerra Dominguez, Charlotte Helena Rivas, Xiang Chen, Hai Wang, Yibin Kang, Zbigniew Gugala, Robert L Satcher, Xiang H-F Zhang

Faculty, Staff and Students Publications

Metastatic cancer cell fate is shaped by the local microenvironment niches. To unbiasedly define the cellular and molecular features of metastatic niches, we developed sortase A-based microenvironment niche tagging (SAMENT), which selectively labels cells encountered by cancer cells during metastasis. Applying SAMENT across multiple cancer models and target organs revealed shared niche features, including macrophage enrichment and T cell depletion, alongside marked organ-specific phenotype heterogeneity in niche macrophages. In bone, metastatic niches are enriched for macrophages expressing estrogen receptor alpha (ERα) with active ERα signaling. Conditional deletion of Esr1 in macrophages significantly impaired bone colonization by enabling T cell infiltration. …

Mitochondria-Er Contact Sites (Mercs) In The Cell Cycle: Molecular Architecture And Functional Remodeling Across Cellular States, Eduardo Silva-Pavez, Bruno Torres-Gonzalez, Michelle Sotomayor, Benjamín Cartes-Saavedra, Dorian V. Ziegler, Yessia Hidalgo-Fadic, Ulises Ahumada-Castro

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Mitochondria–endoplasmic reticulum (ER) contact sites (MERCS) are nanoscopic, dynamic platforms integrating metabolism, signaling, and stress responses to regulate cell fate. These nanoscopic interfaces remodel continuously to meet the demands of proliferating, quiescent, and senescent cells. We synthesize evidence that MERCS actively coordinate local Ca2+ signaling, non-vesicular lipid transfer, and proteostasis to shape mitochondrial function and cellular homeostasis. We discuss how MERCS architecture changes across the cell cycle and during arrest, distinguishing adaptive from maladaptive remodeling, and consider therapeutic potential in aging and age-related disease.

Evaluating Stroke Recognition And Prehospital Quality Metrics In Emergency Dispatch: A Retrospective Cohort Study Comparing Mimics And Confirmed Strokes, Nedim Leto, Elisabeth Farbu, Paul Barach, Conrad Arnfinn Bjørshol, Martin Kurz, Soffien Ajmi, Annette Fromm, Christopher Kalhagen Bjerkvig, Thomas Lindner

College of Population Health Faculty Papers

OBJECTIVES: Accurate identification of acute stroke by the Emergency Medical Dispatch Centre (EMDC) is essential for timely treatment and efficient resource use. However, stroke mimics-conditions resembling stroke can often lead to overtriage, complicating emergency care. We aimed to quantify EMDC stroke overtriage and compare characteristics of stroke mimics with confirmed stroke cases.

DESIGN: Retrospective cohort study.

SETTING: Patients with suspected stroke identified by the EMDC in Western Norway between 1 January 2021 and 31 December 2022.

PARTICIPANTS: A total of 8,261 patients with EMDC suspected stroke were included. Stroke suspicion was determined using the Norwegian Medical Priority Dispatch System, which …

Modulate Obesity And Related Metabolic Complications For Yielding Improvements In Ibd Outcomes (Modify-Ibd): Consensus On Obesity And Cardiometabolic Comorbidities In Inflammatory Bowel Disease Using Systematic Reviews And The Rand/Ucla Appropriateness Method, Jalpa Devi, Sami Samaan, Priya Sehgal, Mouhand Mohamed, Matthew Vincent, Shannon Coombs, Michelle Doering, Edward L. Barnes, Amanda M. Johnson, Andres J. Yarur, Parakkal Deepak

Division of Gastroenterology and Hepatology Faculty Papers

INTRODUCTION: Obesity and related cardiometabolic comorbidities, including hypertension, dyslipidaemia, diabetes, metabolic dysfunction-associated steatotic liver disease and atherosclerotic cardiovascular disease, are increasingly prevalent among individuals with inflammatory bowel disease (IBD). These conditions influence disease activity, therapeutic response, surgical outcomes and overall quality of life, yet evidence remains fragmented. The Modulate Obesity and relateD metabolic complIcations For Yielding improvements in IBD outcomes (MODIFY-IBD) initiative aims to synthesise evidence and generate consensus recommendations to guide practice and future research in this area. This study describes a protocol for a structured evidence synthesis and Research And Development/University of California, Los …

Benchmarking Genome Choice In Functional Genomics Analyses, Juan F Macias-Velasco, Xiaoyu Zhuo, Chad Tomlinson, Eddie A Belter, Milinn Kremitzki, Derek Albracht, Tina Lindsay, Xiaoyun Xing, Nina Tekkey, Wenjin Zhang, John E Garza, Zheng Xu, Zilan Xin, Qichen Fu, Heather A Lawson, Nathan O Stitziel, Robert S Fulton, Daofeng Li, Human Pangenome Reference Consortium, Ting Wang

2020-Current year OA Pubs

The human genome reference established a shared coordinate system for genome function, but it is incomplete and not fully representative of human diversity. Here, we benchmark how genome representation and corresponding analytical frameworks for each representation shape functional genomics using chromatin accessibility sequencing (ATAC-seq), RNA sequencing, whole-genome bisulfite sequencing, and chromosome conformation capture (Hi-C) data from lymphoblastoid cell lines derived from five individuals with fully phased genome assemblies. We compare results across hg38, CHM13, the draft human pangenome, and each individual's maternal and paternal assemblies. Because current pipelines and quality control conventions are tuned to hg38, several of these comparisons …

Holistic Management Of Epilepsy In Adults With Intellectual Development Disorders, Elena Fonseca, Antonella Riva, Samuel López‐Maza, Malin Zaddach, Marie‐Claire Porter, Ingo Borggraefe, Lance Watkins, Andreas Schulze‐Bonhage, Rohit Shankar, Pasquale Striano, Lina Nashef

Peninsula Medical School

This seminar addresses the complexity of the management of epilepsy in adults with intellectual development disorders (IDD), advocating holistic and multidisciplinary care aligned with the learning objectives of the International League Against Epilepsy. Epilepsy is significantly more prevalent in people with IDD, presenting unique diagnostic, therapeutic, and psychosocial challenges. Accurate diagnosis is hampered by limitations in communication, necessitating reliance on caregivers' observations. In adults with IDD and epilepsy, utilization of diagnostic tools, e.g., video electroencephalograph (EEG) monitoring, is helpful but can be challenging. Management requires careful consideration of cognitive and behavioral comorbidities and the effects of antiseizure medications (ASMs) on …

Axitinib-Pembrolizumab And Adverse Event Management In Patients With Advanced Renal Cell Carcinoma, Neil Shah, Yaa Ababio, Anthony Eccleston, Dharanija Rao, Scott Kelly, Jane Chang, Sarah Lucht, Caleb Paydar, Bryce Van Doren, Emily Bland, William John, Sarah Giegerich, Jalyna Laney, Bruce Feinberg, Kevin Zarrabi

Kimmel Cancer Center Faculty Papers

IMPORTANCE: Understanding approaches to managing treatment-related adverse events (AEs) in immunotherapy and tyrosine kinase inhibitor-based treatments in a clinical setting is critical for reaching optimal patient outcomes.

OBJECTIVE: To investigate the management of AEs in community practices during first-line axitinib plus pembrolizumab therapy for advanced renal cell carcinoma (aRCC).

DESIGN, SETTING, AND PARTICIPANTS: This study comprised a cross-sectional electronic physician survey and a multisite, retrospective cohort study of the medical records of US patients with aRCC who initiated first-line axitinib-pembrolizumab between April 22, 2019, and January 31, 2024. Data were analyzed from September 18 to December 20, 2024.

EXPOSURE: First-line …

Co-Occurring Clonal Hematopoiesis Exhibits Strong Selection And High Leukemia Risk, Kara M Barnao, Aubrey K Hubbard, Irenaeus C C Chan, Weiyin Zhou, Yasminka A Jakubek, Giulio Genovese, Wendy S W Wong, Rebecca L Kelly, Corey D Young, Derek W Brown, Wen-Yi Huang, Neal D Freedman, Kristine Jones, Amy Hutchinson, Belynda Hicks, Duc Tran, Donna Arnett, Kathleen C Barnes, Joshua C Bis, Eric Boerwinkle, Jennifer A Brody, April P Carson, Daniel I Chasman, Michael H Cho, Pinkal Desai, Margaret F Doyle, Myriam Fornage, Xiuqing Guo, Nancy Heard-Costa, Marguerite Ryan Irvin, Andrew D Johnson, Sharon L R Kardia, Charles Kooperberg, Daniel Levy, Joshua P Lewis, Yun Li, Ruth J F Loos, Taralynn M Mack, Rasika A Mathias, Braxton D Mitchell, Kari E North, Nathan Pankratz, Patricia A Peyser, Michael H Preuss, Bruce M Psaty, Laura M Raffield, Susan Redline, Stephen S Rich, Jerome I Rotter, Edwin K Silverman, Albert V Smith, Jennifer A Smith, Adrienne Stilp, Yin Cao, Paul Scheet, Alexander P Reiner, Alexander G Bick, Stephen J Chanock, Paul L Auer, Kelly L Bolton, Mitchell J Machiela

Faculty, Staff and Student Publications

Clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) are two types of clonal hematopoiesis (CH) associated with hematological parameters and malignancy risk. Here we show, in genomic data from 546,090 biobank participants, that co-occurring CH (≥2 CH mutations detected) is present in 1.6% of cancer-free individuals and shows strong evidence for selection (up to 804x enrichment). Co-occurrence is more frequent in those with a prior cancer (3.6%), suggesting treatment-induced selection. Acquisition of CHIP usually precedes mCAs with co-occurrences manifesting stronger phenotypic disruptions in telomere attrition and hematologic parameters than component CH events. Individuals with co-occurring CH have …

Co-Occurring Clonal Hematopoiesis Exhibits Strong Selection And High Leukemia Risk, Kara M Barnao, Irenaeus C C Chan, Duc Tran, Yin Cao, Kelly L Bolton, Et Al.

2020-Current year OA Pubs

Clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) are two types of clonal hematopoiesis (CH) associated with hematological parameters and malignancy risk. Here we show, in genomic data from 546,090 biobank participants, that co-occurring CH (≥2 CH mutations detected) is present in 1.6% of cancer-free individuals and shows strong evidence for selection (up to 804x enrichment). Co-occurrence is more frequent in those with a prior cancer (3.6%), suggesting treatment-induced selection. Acquisition of CHIP usually precedes mCAs with co-occurrences manifesting stronger phenotypic disruptions in telomere attrition and hematologic parameters than component CH events. Individuals with co-occurring CH have …

Mitochondrial Ca2+ Uniporter (Mcu) Variants Form Plasma-Membrane Channels, Iuliia Polina, Jyotsna Mishra, Michael Cypress, Maria Landherr, Nedyalka Valkov, Isabel Chaput, Bridget Nieto, Brian Rhee, Ameneh Ahrari, Nathan Demichaelis, Kye-Im Jeon, Ulrike Mende, Peng Zhang, Bong Sook Jhun, Jin O-Uchi

Center for Translational Medicine Faculty Papers

MCU, originally known as CCDC109A, is widely recognized as the gene responsible for encoding a pore-forming subunit of a Ca2+-selective channel, mitochondrial Ca2+ uniporter complex (mtCUC). While MCU expression is typically highly mitochondrial-specific, we report here a protein variant derived from the MCU gene, termed MCU-S, which lacks the mitochondria-targeting sequence (MTS) and forms a Ca2+-permeable channel outside of mitochondria. The mRNA of MCU-S was ubiquitously expressed in all cell types/tissues tested, with particularly high expression in human platelets. MCU-S protein formed Ca2+ channels at the plasma membrane, which exhibited similar channel properties to those observed in mtCUC. MCU-S channels …

Repurposing Semaglutide As An Adjunctive Treatment For Cocaine Use Disorder: Protocol For A Randomised Controlled Trial, Luba Yammine, Francesco Versace, Charles E Green, Heather E Webber, Jin Ho Yoon, Absalon D Gutierrez, Samuel J Leonard, Michael F Weaver, Joy Schmitz

Faculty, Staff and Student Publications

Introduction: Cocaine use disorder (CUD) is a significant public health concern in the USA, with considerable prevalence and mortality and no Food and Drug Administration (FDA)-approved pharmacotherapies. Recent advances in addiction science emphasise the need for novel, mechanism-based treatments. Glucagon-like peptide-1 receptor agonists, such as semaglutide, have shown promise in modulating reward-related behaviours and may offer therapeutic benefits for CUD. We present a study protocol evaluating semaglutide, as an adjunct to cognitive behavioural therapy (CBT), as a novel approach for treating CUD.

Methods and analysis: This is a randomised, double-blind, placebo-controlled trial enrolling 75 treatment-seeking adults with CUD. Participants will …

Human Papillomavirus Vaccine Discourse And Sentiment On Reddit Before And After Covid-19: Mixed Methods Retrospective Cross-Sectional Study, Marcin Marciniak, Sean A Setzen, Deeya Bhattacharya, Jamie Masliah, Robin Powszok, Erich M Sturgis, Vanessa C Stubbs, Mihir K Bhayani

Faculty, Staff and Students Publications

Background: Human papillomavirus (HPV) is a sexually transmitted virus that causes various oropharyngeal and anogenital cancers. The HPV vaccine provides protection against several strains of HPV and is a key preventative tool against HPV-related cancers; however, vaccination rates remain suboptimal in the United States due to variable state mandates and misperceptions of vaccine efficacy and risks. As social media becomes an increasingly popular avenue for health discussions, platforms such as Reddit offer opportunities to understand public vaccine discourse, particularly among underrepresented groups. Furthermore, vaccine hesitancy and mistrust generally increased during the COVID-19 pandemic, potentially impacting HPV vaccination rates.

Objective: This …

Vaccination-Related Applications And Health Care Professionals' Observed Changes In Human Papillomavirus Vaccine Hesitancy: Cross-Sectional Survey, Manali Desai, Shreela Sharma, Joel Fokom-Domgue, Robert Yu, Wenyaw Chan, Onyema G Chido-Amajuoyi, Charles Darkoh, Sanjay Shete

Faculty, Staff and Student Publications

Background: Digital tools are known to promote public health interventions such as vaccine delivery. The recommendation that health care professionals (HCPs) use vaccination-related mobile apps or web-based applications has contributed to improving vaccine awareness and acceptance in the United States. The state of Texas, which has one of the lowest human papillomavirus (HPV) vaccination rates, has seen a significant increase in HPV vaccine hesitancy, particularly during the COVID-19 pandemic.

Objective: This study aimed to examine the association between changes in HPV vaccine hesitancy observed by HCPs among patients in Texas and promotion of vaccination-related applications at the health care facilities …