Medicine and Health Sciences Commons^™

Intersection Of Pediatric Hypertension And Cardiovascular-Kidney-Metabolic Disease, Jessica O'Keeffe, Christina Kingshill, Jack Tompson, Andrew M. South, Carissa M. Baker-Smith

Department of Medicine Faculty Papers

PURPOSE OF REVIEW: The purpose of this review is to describe the intersection between pediatric hypertension and advancing stages of cardiovascular, kidney metabolic syndrome in children and adolescents.

RECENT FINDINGS: Cardiovascular-kidney-metabolic syndrome is highly prevalent in the pediatric population. The onset of CKM in childhood is influenced by the presence of antenatal risk factors such as maternal hypertensive disorders of pregnancy. Advancing stages of CKM in children and adolescents are strongly influenced by food insecurity and social determinants of health that impact the risk for childhood obesity. Activation of the renin-angiotensin-aldosterone system is a key mediator in the relationship between …

Improving Procedural Confidence: Outcomes Of A Surgical Skills Workshop For Medical Students, Mary Arden G Guillory, Jennifer Escamilla, Anika Doppalapudi, Ashlyn Holubar, Kaitlyn Ybanez, Mark Manickath, Maci Oestreich, Mckenna Stallworth, Kelsey Baker

School of Medicine Publications

Introduction Introducing surgical skills early in medical training may enhance students' confidence and readiness for clinical training. Simulation-based skill workshops provide students with a comfortable learning environment, resulting in effective learning. The goal of the Surgical Skills Workshop was to provide first- and second-year medical students with hands-on exposure to essential surgical skills. The educational impact on medical students' confidence in performing the respective surgical skills and changes in surgical career interest was assessed.

Methods: First- and second-year medical students at the University of Texas Rio Grande Valley School of Medicine participated in a hands-on surgical skills workshop comprising eight …

From Fly On The Wall To Future Colleagues: Best Practice Recommendations For Medical Student Shadowing Programs, Molly Estes, Danielle Matonis, Mckenna Knych, Brian Barbas, Ronnie Ren, William Dixon, Michael Pasirstein, Xiao C. Zhang, Kaitlin Bowers, Ravi R. Chauhan, Laryssa A. Patti

Department of Emergency Medicine Faculty Papers

BACKGROUND: Physician shadowing is a common component of early medical education and frequently represents students' first exposure to clinical practice. Despite its prevalence, existing guidance primarily targets learners rather than physicians supervising shadowing experiences. This gap is especially relevant in the emergency department (ED), where high patient acuity, workflow demands, and complex clinical environments create challenges for providing safe and meaningful observational learning. We sought to develop consensus-based best practice recommendations for ED faculty supervising medical student shadowing.

METHODS: We conducted a modified Delphi study using an online survey platform to achieve panelist consensus. Ten emergency medicine educators with a …

Reflections On Inclusive Qualitative Research With Autistic Emerging Adults: Lessons Learned And Practical Recommendations, Acadia W. Buro, Heidi Rishel Brakey, Monica F. Asencio Pimentel, Elizabeth Yakes Jimenez

Population Health Research and Scholarship

We explored inclusive qualitative data collection strategies for autistic emerging adults (ages 18–25) to identify nutrition-related resource needs and inform intervention development. We conducted Zoom interviews with autistic emerging adults, their caregivers, and service providers. We co-developed recruitment materials with a community advisory board of autistic advocates and offered and adapted interview accommodations in real time to align with participants’ preferences. Common accommodations included receiving questions in advance and in the chat, having a caregiver present, and simplifying questions. Some techniques used with neurotypical participants translated well to our participants, such as reflective listening, a conversational tone, and allowing pauses; …

Meeting Report From The 2025 Cure Ocular Melanoma (Cure Om) Global Science Meeting, Amsterdam, The Netherlands, October 2025, Andrew E. Aplin, Katherina Alsina, Allison S. Betof, Joseph Birkett, Marcus O. Butler, George Cole, Rizwan Haq, Florian A. Karreth, Vinit B. Mahajan, Rahul Marpadga, Prithvi Mruthyunjaya, Paul Nathan, Jonas A. Nilsson, Gary Palmer, Joseph J. Sacco, Takami Sato, Sarah Stanhope, Pang-Ning Teng, Kyleigh Lipira

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

The 2025 Cure Ocular Melanoma (CURE OM) Global Science Meeting took place in Amsterdam, The Netherlands on October 25th, 2025. Several promising drug candidates are in development; however, there is still an urgent need for better prevention, detection, and treatment of uveal melanoma. The purpose of this meeting was to promote international collaboration and idea exchange between scientists, industry, and patient advocates.

Qualitative Evaluation Of The Seated Physical Activity Intervention (Spin) Randomized Controlled Trial For Wheelchair Users With Multiple Sclerosis (Ms): Formative Feedback And Future Directions, Angela J Piasecki, Robert W Motl, Katherine Froehlich-Grobe, Stephanie L Silveira

Faculty, Staff and Student Publications

Background/objectives: Wheelchair users with multiple sclerosis (MS) often face barriers that restrict participation in physical activity and exercise training. This manuscript reports on participant feedback to guide evaluating and refining a novel exercise training program, Seated Physical activity INtervention (SPIN). SPIN was adapted from the Guidelines for Exercise in MS (GEMS) approach using a three-step community-engaged research framework based on meeting the needs of wheelchair users with MS.

Methods: Semi-structured interviews were conducted with 9 participants who completed the 16-week SPIN intervention. The key SPIN intervention components were the exercise prescription, exercise equipment, and behavioral coaching grounded in Social Cognitive …

The Roots Of Sexual Violence In Utah: A Framework For Understanding Harm, Susan R. Madsen

Marketing and Strategy Faculty Publications

Sexual violence in Utah is not an anomaly, a private tragedy, or the result of individual deviance. It is a patterned, predictable outcome of cultural norms, social systems, and power structures that shape how people understand gender, authority, and worth. Despite Utah’s reputation for strong families, close‑knit communities, and deep religious commitment, the state continues to report higher‑than‑national‑average rates of rape, child sexual abuse, and other forms of gender‑based harm. These realities demand a deeper understanding of why violence persists—and what can be done to prevent it.

This white paper synthesizes decades of national and international research, Utah‑specific data, and …

Self-Perceived Burden And Mental Health Outcomes In Adults With Osteogenesis Imperfecta, Emily R Strouphauer, Camille Villar, Ryan J Mccarty, Danqi Li, Gianna M Colombo, Brendan Lee, Chaya N Murali, Dianne Nguyen, Sarah Sadek, Marie-Eve Robinson, Jocelyn Gomez, Michelle Fynan, V Reid Sutton, Andrew D Wiese, Eric A Storch

Faculty, Staff and Students Publications

Osteogenesis Imperfecta (OI) is a rare disorder causing bone fragility, pain, and functional impairment that causes substantial psychosocial burden. This study examined how self-perceived burden (SPB), or distress from feelings of dependence on caregivers, relates to depression, anxiety, and suicidality in adults with OI. A total of 208 adults (M age = 42.9, predominately White and female) with OI were recruited to complete a cross-sectional survey assessing SPB, psychological symptoms, health, and sociodemographics. Results indicated that SPB was significantly higher among younger individuals, those not living with a partner, those living with adult family members, lower-income groups, and individuals …

Evaluating The Reproducibility And Verifiability Of Nutrition Research: A Case Study Of Studies Assessing The Relationship Between Potatoes And Colorectal Cancer, Yasaman Jamshidi-Naeini, Colby J Vorland, Pranav Kapoor, Bailey Ortyl, Jocelyn Mineo, Luke Still, Korlu Sorsor, Shelby Rodney, Xander Tooze, Brent Flickinger, Beate Henschel, Stephanie L Dickinson, David B Allison

Faculty, Staff and Students Publications

The credibility of nutritional research is dependent on the rigor with which studies are conducted and the ability for independent assessment to be performed. Despite the importance of these, more work is needed in the field of nutrition to buttress the trustworthiness of nutrition research. To develop and apply a process for evaluating the rigor, reproducibility, and verifiability of nutritional research, using the relationship between potato consumption and Colorectal Cancer (CRC) as a case study. We updated existing systematic reviews to include studies on potatoes and CRC, assessing their design, execution, and reporting quality. We attempted to reproduce and verify …

Point-Of-Care Hrhpv Mrna Detection With Reverse Transcription Recombinase Polymerase Amplification On A Portable Fluorimeter From Provider-Collected Cervical Samples In Maputo, Mozambique, Emilie Newsham Novak, Cannon J Hansen, Zoha Wazir, Ariel Ma, Jennifer Carns, Hira Atif, Jane R Montealegre, Michael E Scheurer, Cesaltina Lorenzoni, Daniel G Rosen, Mila P Salcedo, Kathleen M Schmeler, Rebecca R Richards-Kortum

Faculty, Staff and Students Publications

Background: Cervical cancer is the most common cancer in women in Mozambique, where limited screening infrastructure contributes to high disease burden. While testing for high-risk human papillomavirus (hrHPV) DNA can identify women at risk for cervical cancer, its limited specificity may lead to overtreatment in screen-and-treat programs, straining resources. We performed a pilot study to evaluate preliminary feasibility of a novel, accessible test to detect hrHPV mRNA, a more specific biomarker for cervical cancer risk, from 22 women who previously screened positive for visual inspection with acetic acid at Maputo Central Hospital in Mozambique.

Methods: Cervicovaginal samples were analyzed for …

Elevated Phagocytic Capacity Directs Innate Spinal Cord Repair, Dana Klatt Shaw, Vishnu Muraleedharan Saraswathy, Anthony R Mcadow, Lili Zhou, Dongkook Park, Ridim Mote, Amulya Saini, Ashley J Douthitt, Katerina Stepankova, Brittney Unverzagt, Cédric G Geoffroy, Aaron N Johnson, Mayssa H Mokalled

2020-Current year OA Pubs

Immune cells elicit a continuum of transcriptional states after spinal cord injury (SCI). In mammals, inefficient debris clearance and chronic inflammation impede recovery and overshadow pro-regenerative immune functions. We found that zebrafish SCI elicits transient immune activation and efficient debris clearance. Transcriptomics and genetic ablation showed zebrafish macrophages are highly phagocytic and required for regeneration. Comparisons between zebrafish and mammalian macrophages identified transcription and immune response regulator (tcim) as an immune-enriched regenerative gene. Deletion of zebrafish tcim impairs phagocytosis and regeneration and activates a pro-inflammatory signature in leukocytes. Tcim expression in zebrafish and mouse macrophages establishes its conserved roles by …

Health Management Practices In Chronic Traumatic Brain Injury Rehabilitation: A Scoping Review Protocol, Davina Sharma, Shané J. Gill, Lizbeth Goodman, Amanda Rabinowitz, Louis N. Hunter, Reinhard Schaler, Kirby L. Wycoff

College of Health Professions Faculty Papers

INTRODUCTION: Traumatic brain injury is increasingly recognized as a chronic condition requiring long-term rehabilitation and coordinated care beyond the acute phase. Across Europe, substantial variation exists in healthcare system organization, funding structures, and service delivery models, which may influence access to rehabilitation and long-term functional outcomes for adults with chronic moderate-to-severe traumatic brain injury. The objective of this scoping review protocol is to systematically characterize systemic factors and management practices that shape rehabilitation access, continuity of care, and recovery outcomes across European healthcare systems. This review will map published evidence on health management practices influencing chronic traumatic brain injury rehabilitation …

Microglial Swell1 Deficiency Drives Male-Specific Seizure Vulnerability But Paradoxical Neuroprotection Through Impaired Phagocytosis, Abhijeet S Barath, Aastha Dheer, Laura Montier, Mekenzie M Peshoff, Emily Dale, Flavia Goche, Thanh Thanh Le Nguyen, Mastura Akter, Fangfang Qi, Dimitrios Kleidonas, Lauren Harris, Sarah A Jewanee, Anthony D Umpierre, Dale B Bosco, Koichiro Haruwaka, Rajan Sah, Long-Jun Wu, Rongzhuo Hua, Tejaswani Datla

The Brown Foundation: Institute of Molecular Medicine

The discovery of genes encoding the volume-regulated anion channel (VRAC) has enabled detailed exploration of its cell type-specific roles in the brain. LRRC8A (SWELL1) is the essential VRAC subunit. We observed seizure-induced, subunit-specific changes in microglial VRAC expression and investigated its function using conditional KO (cKO) of LRRC8A in microglia. SWELL1 cKO mice exhibited a male-specific increase in kainate-induced seizure severity, yet showed paradoxical neuroprotection against seizure-associated neuronal loss. Mechanistically, SWELL1 deletion led to a cell-autonomous reduction in microglial density and decreased release of VRAC-permeable neuroactive metabolites, including taurine, GABA, and glutamate in culture. Additionally, impaired phagocytic kinetics and reduced …

An Inf2-Dependent Actin-Mediated Step In Inositol 1,4,5-Trisphosphate Receptor Cluster Formation And Activity, Maite R. Zavala, Amrapali Ghosh, Suresh K. Joseph, Rajarshi Chakrabarti

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Intracellular calcium signaling plays a vital role in regulating various cellular processes including gene regulation, motility, metabolism, and cell death. Inositol 1,4,5-trisphosphate receptors (IP3Rs) on the endoplasmic reticulum (ER) are a major cation channel that regulates stimulus-induced calcium release from the ER. While several molecular players regulate the activity of IP3R, its regulation by actin filaments was uncharacterized. Here, we show that actin filaments polymerized by the specific actin nucleator INF2 facilitate agonist-induced IP3R activity. Our results demonstrate that INF2-mediated actin filaments regulate the formation and/or stability of IP3R clusters on the ER that have been previously shown to be …

Toolkit For Multistate Disease Progression Simulation And Treatment Decision-Making Aid, Can Xie, Ruosha Li, Wael Saber, Jorge E Cortes, Nicholas J Short, Xuelin Huang

Faculty, Staff and Student Publications

Background: The optimal timing of a treatment within therapy lines can maximize its benefit while minimizing risks and side effects. Because patients differ in clinical and biological characteristics, personalized treatment planning can support physicians' decision-making. However, multistate disease progression complicates the comparison of treatment strategies, motivating the development of a user-friendly web tool for multistate disease progression simulation and treatment decision support. Microsimulation is a natural approach for comparing prespecified treatment-timing strategies, where it generates disease trajectories for a large number of virtual patients matched to an individual patient's observed data. In our framework, microsimulation is performed using a multistate …

Pruritus Associated With Systemic Sclerosis: A Systematic Review Of Treatment-Based Clinical Trials, Kiana Mortezaei, Rishika Pasula, Meryem Nursoy, Amit Syal, Ioannis Panayiotou, Geeta Kumari, Andreas Chatzitoffis, Pavle Milutinovic, Olajumoke O. Fadugba, Chris T. Derk

Student Papers, Posters & Projects

This paper aims to examine the latest research on treatments for itch (pruritus) in people with systemic sclerosis (SSc), identify areas where information is lacking, and propose suggestions for future studies.A comprehensive literature search was performed in PubMed and Scopus in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify studies evaluating therapeutic interventions for pruritus in SSc. Eligible studies included randomized controlled trials, cohort studies, and case series comprising a minimum of three patients. Data extraction encompassed study design, patient demographics, pruritus assessment instruments including validated and non-validated measures, and clinical outcomes. Studies …

Bottlebrush Polymer Conjugates For Enhanced Antisense Oligonucleotide Therapy In Myotonic Dystrophy Type 1, Yao Li, Gyu Seong Heo, Yongjian Liu, Et Al.

2020-Current year OA Pubs

Oligonucleotides are a promising class of genetic medicine for myotonic dystrophy type 1 (DM1), the most common adult-onset muscular dystrophy. However, poor muscle distribution of nucleic acid drugs following systemic administration has hindered drug development, and no curative treatment currently exists. DM1 pathology requires drug localization to the nucleus, where pathogenic mutant RNA is sequestered, posing additional challenges after cellular internalization regarding endosomal escape and nuclear uptake. Here, we show that a locked nucleic acid oligonucleotide targeting mutant CUG repeat RNA tracts, conjugated to a bottlebrush polymer, exhibits improved muscle distribution and potent correction of DM1-associated splicing dysregulation in a …

Where Evidence-Based Medicine Meets Ai: Promise, Pitfalls, And Practice, Sangil Lee, Joshua Davis, Ken Milne, Christina Shenvi, Lars K. Beattie, Martin Wegman, Laura Melville, Richard D. Shih, Bryan Kane

Department of Emergency Medicine Faculty Papers

No abstract provided.

A Scoping Review Of Preventive Interventions To Reduce Violence Against Women And Girls In The Islamic Republic Of Iran, Wahiba Abu-Ras, Leena Babiker Idris, Shahira Amin, Ashley Butler, Patricia J. Kelly, Basil H. Aboul-Enein

College of Nursing Faculty Papers & Presentations

In Iran, violence against women (VAWG) remains highly prevalent, with reported rates ranging from 22.9% to 66%, underscoring the need for effective, contextually grounded interventions.   This scoping review aimed to systematically identify, map, and critically appraise intervention strategies addressing VAWG in Iran.   Guided by PRISMA-ScR and the PICOS framework, comprehensive searches were conducted across nine databases from 2000 to September 2024. Eligible studies included intervention-based research conducted in Iran that reported outcomes related to violence reduction, psychological well-being, or empowerment. Thirteen studies met the inclusion criteria.   The included studies demonstrated heterogeneous designs, theoretical frameworks, and outcome measures. Four interventions targeted …

Chiari Malformation Type 1 Is Associated With A Smaller Fourth Ventricle Volume - A Multi-Cohort Replication Study, Jarod L Roland, Thanda Meehan, Alexandra Gabliani, Scott Marek, Nico Dosenbach, Joshua S Shimony, Nilay Jakati, Yi Li, Leo Sugrue, Jennifer M Strahle, Chenyang Lu, David D Limbrick, Gabe Haller

2020-Current year OA Pubs

Chiari Malformation Type 1 (CM1) is canonically defined by ectopic position of the cerebellar tonsils with additional anatomic variations described inconsistently. Effect on fourth ventricle volume is controversial with prior studies reporting disparate results and methodologically limited to single institution series that hinder generalizability. This limitation was addressed utilizing multiple data sources, longitudinal replication, and reproducible methods using both FreeSurfer and the deep learning-based DL+DiReCT tools for automated volumetrics. First, we analyzed a local retrospective clinical cohort of individuals with CM1 and controls. Using data from the Adolescent Brain Cognitive Development (ABCD) Study, we analyzed volumes at baseline then replicated …

Prmt5 As A Key Driver Of Stemness And Metastatic Potential In Triple-Negative Breast Cancer, Jae Jin Jeong, Mauli Maniar, Shahrzad Ghane, Sakshi Deshpande, Claire Ellis, Ashakumary Lakshmikuttyamma

College of Pharmacy Faculty Papers

Protein arginine methyltransferase 5 (PRMT5) mediates arginine methylation of a wide range of proteins and plays context-dependent oncogenic or tumor-suppressive roles. In cancer, PRMT5 represses several tumor suppressor genes, including E-cadherin, TP53BP1, ST7, PTEN, and RB (retinoblastoma). Elevated PRMT5 expression has been reported across multiple cancer types, notably triple-negative breast cancer (TNBC). In TNBC, high PRMT5 levels are associated with enhanced cancer stem cell self-renewal, increased tumor growth and metastasis, and reduced patient survival. Mechanistically, PRMT5 promotes breast cancer stem cell maintenance and proliferation through stabilization of the transcription factors KLF4 and KLF5. Disruption of the PRMT5-KLF4 axis results in …

Integration Of Intraoperative Data In Interpretable Machine Learning Models To Predict Postoperative Aki In Noncardiac Surgery Patients, Justin Do, Karan H. Shah, Melissa Xu, Andrew Hyunwoo Kim, Vivaswat Suresh, Nidhir Guggilla, Michael Li, Rishi Kothari

Department of Anesthesiology Faculty Papers

OBJECTIVES: We aimed to (1) quantify changes in discrimination when adding intraoperative data to preoperative data and (2) compare tabular machine learning with feature engineering against a time-aware LSTM-based model.

MATERIALS AND METHODS: Retrospective cohort of 46 204 adults undergoing 57 055 eligible noncardiac surgery in the INSPIRE database. We extracted 38 preoperative and 49 intraoperative variables; acute kidney injury (AKI) was defined by KDIGO serum creatinine criteria and modeled as stage 2/3 postoperative AKI. Models were trained on preoperative-only and combined pre- and intraoperative data. Intraoperative series were summarized using eight statistical features for tabular models or integrated directly …

Quality Improvement Project: Implementation Of The Patient Health Questionnaire-9 Modified For Teens, Hedy Gerber, Leah Buchko, Jennifer Van Winkle

All Faculty and Staff Scholarship

Background: Adolescent depression is a prevalent and significant public health concern, strongly linked to increased suicidality, poor health outcomes, impaired psychosocial functioning, and substantial societal costs. Although measurement‑based care using validated screening instruments is recommended by clinical practice guidelines, routine use of standardized depression screening tools remains limited in mental health settings.

Objective: The purpose of this quality improvement project was to assess the impact of implementing the Patient Health Questionnaire-9 modified for teens (PHQ-9M) in depression screening rates among adolescents aged 11-17 years at an outpatient mental health clinic in Southern Colorado.

Methods: A quantitative, quasi‑experimental pre- and post-intervention …

A Multilevel Analysis Of Hiv Care Outcomes Across Age, Race, And Housing Among United States Women Veterans, Giselle Day, Amber B Amspoker, Alan Z Sheinfil, Liang Chen, Emmanuel Guajardo, Maria E Fernandez, Cici Bauer, Irene Tamí-Maury, Jan Lindsay

Faculty, Staff and Students Publications

Background: Women veterans with HIV represent a growing, diverse population within the Veterans Health Administration (VHA). This study examined HIV care continuum outcomes among women veterans using a multilevel intersectional approach.

Methods: We conducted a retrospective analysis of 1154 women veterans with HIV in VHA care in fiscal year 2022, with outcomes assessed in fiscal year 2023. We applied Multilevel Analysis of Individual Heterogeneity and Discriminatory Accuracy (MAIHDA) to evaluate how combinations of social positions (age, race/ethnicity, housing status) were associated with HIV outcomes.

Results: MAIHDA models showed that younger age (< 45 years) and being unhoused were consistently associated with lower odds of care engagement and viral suppression than midlife (45-64) and older (65+) housed women veterans. Additionally, predicted probability analyses revealed distinct clustering patterns. Younger non-Hispanic White women consistently ranked among the lowest performing strata across all outcomes, while midlife and older Hispanic and non-Hispanic Black women veterans clustered among the highest. Variance Partition Coefficients from null models were modest (1.8-3.0%). Fully adjusted models showed no remaining between-stratum variance, suggesting that the included social positions explained the observed differences in our dataset.

Conclusions: These findings highlight disparities in HIV care …

The Transitional Liver Clinic: Study Protocol For A Stepped-Wedge Cluster Randomized Trial, Lindsay Yoder, Elliot B. Tapper, Richard S. Kalman, Mary Rinella, Nicole Bendin, Manisha Verma, Francis Pike, Naga Chalasani, Neha Nalumasu, Eric S. Orman

Einstein Health Papers

BACKGROUND: Patients with complications of advanced liver disease experience high rates of hospital readmission after discharge. Transitional care models have improved outcomes in other chronic conditions, but their efficacy in liver disease care remains uncertain. This randomized trial evaluates the effectiveness of a tailored transitional care model-the Transitional Liver Clinic (TLC)-in reducing readmissions, improving quality of life, and enhancing patient satisfaction for patients with advanced liver disease.

METHODS: This is a 45-month, stepped-wedge cluster randomized trial enrolling up to 1000 patients with advanced liver disease across 4 academic medical centers. Each site transitions from usual care to the TLC intervention …

Sirt1 And Ifi16 Cooperatively Regulate Hbv Replication Via Epigenetic Modulation And Innate Immune Activation, Zahra Zahid Piracha, Umar Saeed, Neelam Abid, Syed Shahan Gilani, Hafiz Ahmad Bilal Akhtar Chughtai, Areesha Wasti, Muhammad Waseem, Dilber Uzun Ozsahin, Andromeda M. Nauli, Surya M. Nauli

Pharmacy Faculty Articles and Research

Background

Hepatitis B virus (HBV) establishes persistent infection through the formation of a covalently closed circular DNA (cccDNA) minichromosome, which enables immune evasion and sustained viral replication. While SIRT1, IFI16, and STING are known to modulate antiviral pathways, their cooperative role in regulating HBV transcription and host immunity remains poorly defined.

Methods

We investigated the functional interplay between SIRT1, IFI16, and STING using confocal microscopy, chromatin immunoprecipitation (ChIP), gene silencing, and quantitative PCR in HBV-replicating cell models. Interactions with HBV cccDNA and effects on viral transcription and interferon-stimulated gene (ISG) expression were analyzed. Northern blotting and RT-qPCR were used to …

Using United States Medicare Program Claims To Identify Reliable Measures Of Low Value Services Influenced By Primary Care Physician Decisions, Chris Fleming, Dmitriy Poznyak, Rhea E. Powell, Claire Erba, Eunhae Shin, Rui Wang, Claire Burkhart, Arkadipta Ghosh, Eugene C. Rich

Division of Internal Medicine Faculty Papers & Presentations

BACKGROUND: Low-value services (LVS) are those that “… provide little to no benefit to patients….”¹ Among an existing set of 31 LVS are invasive procedures not typically performed by primary care physicians (PCPs), and other LVS that may be commonly provided by specialists. To facilitate research on the role of primary care physicians in low-value care, we sought to identify the reliability of two subsets of LVS measures that are more directly subject to PCPs’ decisions. We refer to these as primary care adjacent (“PCA”) LVS measures.

METHODS: Retrospective observational cohort study to identify which of a 31-item LVS …

Targeted Inhibition Of Atr Kinase Promotes Antitumor Immunity In Hnscc Through Enhanced Sting Activation And T Cell Function, Fabio Hb Da Costa, Mutsuki Kawabe, Tsung-You Tsai, Kento Okamoto, Mason D Bartels, Sofia Cortes, Ratna Veeramachaneni, Roberto Rangel, Mitchell J Frederick, Vlad C Sandulache, Andrew G Sikora, Jeffrey N Myers, Abdullah A Osman

Faculty, Staff and Students Publications

Objectives: Oral cavity head and neck squamous cell carcinoma (HNSCC) represents a major global health burden, with over 40,000 new cases annually in the United States and >500,000 worldwide. Despite advances in surgery, radiation therapy, chemotherapy, and immunotherapy, overall survival rates have remained largely stagnant over the past three decades, and over half of patients ultimately die from the disease. Although immune checkpoint inhibitors (ICIs) have improved outcomes for a subset of patients with recurrent or metastatic HNSCC, the majority gain limited benefit. Thus, novel therapeutic strategies that enhance responses to immunotherapy are urgently needed. The ATR-CHK1 signaling pathway has …

3d Em Uncovers Mitochondrial Network Remodeling In Residual Triple Negative Breast Cancer After Conventional Chemotherapy Treatments, Mariah J Berner, Heather K Beasley, Benjamin Rodriguez, Audra Lane, Steven W Wall, Andrea G Marshall, Zer Vue, Larry Vang, Mokryun L Baek, Mason Killion, Faben Zeleke, Bryanna Shao, Dominique Parker, Autumn Peterson, Julie Sterling Rhoades, Lacey E Dobrolecki, Amber Crabtree, Annet Kirabo, Sepiso K Masenga, Prasanna Katti, Prasanna Venkhatesh, Chandravanu Dash, Michael T Lewis, Antentor Hinton, Gloria V Echeverria

Faculty, Staff and Students Publications

Mitochondria are hubs of metabolism and signaling. We previously demonstrated the importance of mitochondrial structure and function in chemotherapy-refractory triple-negative breast cancer (TNBC). Herein, we present the first 3D analysis of mitochondrial networks in human tumor tissues. Using serial block face scanning electron microscopy, we reconstructed 3,750 mitochondria and 800 lipid droplets (LDs) in naive and residual tumors persisting after conventional chemotherapies in two orthotopic patient-derived xenografts (PDX). Chemotherapies administered as monotherapy or in combination produced residual tumors that harbored mitochondria with significantly increased areas, volumes, and perimeters. We observed substantial reduction of mitochondrial intratumor heterogeneity following all treatments. Further, …

Targeting Arginine Metabolism Overcomes Chemotherapy Resistance In Aggressive-Variant Prostate Cancers, Elavarasan Subramani, Patrick G Pilié, Rebecca Slack-Tidwell, Paul V Viscuse, Xianghong Kuang, Thirukumaran Kandasamy, Dominik Awad, Jenny J Han, Licai Huang, Christine B Peterson, Amado J Zurita, Sumit K Subudhi, Paul G Corn, Rama Soundararajan, Peter Shepherd, Badrajee Piyarathna, Vasanta Putluri, Nagireddy Putluri, Arun Sreekumar, Yuzhuo Wang, Amina Zoubeidi, Iqbal Mahmud, Sara A Martinez, Lin Tan, Philip L Lorenzi, Sreyashi Basu, Sonali Jindal, Padmanee Sharma, Christopher J Logothetis, Timothy C Thompson, Daniel E Frigo, Ana M Aparicio

Faculty, Staff and Students Publications

Aggressive-variant prostate cancers (AVPCs) respond poorly to anti-androgen therapy but show sensitivity to taxane-platinum chemotherapy, though outcomes remain poor. We conducted a phase 2 trial testing induction cabazitaxel plus carboplatin (CabCarb) followed by olaparib maintenance versus observation in men with AVPC. The primary endpoint of improved progression-free survival (PFS) was not met, likely due to the study being underpowered after 38.5% of patients experienced early progression (ChemoPD) prior to randomization. No genomic alterations predicted ChemoPD; however, transcriptomic analysis revealed the enrichment of metabolic pathways, including arginine metabolism, in ChemoPD tumors. These findings were supported by metabolomics data from preclinical models. …