Digital Commons Network^™

Task-Optimized Brain Parcellations Reveal Latent Functional Organization For Enhanced Connectivity-Based Neuroimaging Classification, Andrew Hannum, Mario A. Lopez

Computer Science: Faculty Scholarship

Brain parcellation schemes are fundamental to neuroimaging, yet general-purpose atlases may obscure the specific functional architecture relevant to a given cognitive task or clinical condition. This reflects a growing consensus that the “optimal” brain map is context-dependent. Here, we introduce a novel framework that validates this principle by generating task-optimized human brain parcellation maps directly from supervised learning objectives. Our method defines functional parcels by grouping brain regions based on the similarity of their contributions to a classifier's decision boundary for a specific goal (e.g., cognitive state decoding or clinical group separation). This approach prioritizes a region's discriminative role over …

Stakeholder Perspectives On Humanistic Implementation Of Computer Perception In Health Care: Qualitative Study, Kristin M Kostick-Quenet, Meghan E Hurley, Syed Ayaz, John D Herrington, Casey J Zampella, Julia Parish-Morris, Birkan Tunç, Gabriel Lázaro-Muñoz, Jennifer Blumenthal-Barby, Eric A Storch

Center for Medical Ethics and Health Policy Staff Publications

Background: Computer perception (CP) technologies-including digital phenotyping, affective computing, and related passive sensing approaches-offer unprecedented opportunities to personalize health care, especially mental health care, yet they also provoke concerns about privacy, bias, and the erosion of empathic, relationship-centered practice. At present, it remains elusive what stakeholders who design, deploy, and experience these tools in real-world settings perceive as the risks and benefits of CP technologies.

Objective: This study aims to explore key stakeholder perspectives on the potential benefits, risks, and concerns associated with integrating CP technologies into patient care. A better understanding of these concerns is crucial for responding to …

Pathogenesis Of Polyglutamine Diseases: Piecing Together A Complex Molecular Puzzle, Esmeralda Villavicencio Gonzalez, Huda Y Zoghbi

Duncan NRI Faculty and Staff Publications

Polyglutamine (polyQ) diseases, caused by a CAG repeat expansion encoding a glutamine tract in nine distinct proteins, present a complex molecular puzzle in which each piece contributes to neurodegeneration. While each of the causative proteins has a distinct function, the downstream consequences of polyQ toxicity are often similar, including protein accumulation, transcriptional dysregulation, somatic CAG repeat instability, disrupted energy homeostasis, compromised synaptic function, and selective neuronal death. This review summarizes emerging insights into how proteins with an expanded polyQ tract disrupt distinct cellular functions, and we examine a multitude of discoveries that are inspiring and reshaping novel therapeutic strategies.

Conclusions Are Not Supported By The Published Statistical Analysis Comment On López-Toledo Et Al Flaxseed Improves Glucose And Lipid Metabolism In Mexican Subjects With Type 2 Diabetes: A Parallel Randomized Clinical Trial, Robert W Spitz, Deependra K Thapa, Thirupathi Reddy Mokalla, Wasiuddin Najam, Andrew W Brown, David B Allison

Children’s Nutrition Research Center Staff Publications

López-Toledo et al [...].

A Prognostic Matrix Gene Expression Signature Defines Functional Glioblastoma Phenotypes And Niches, Monika Vishnoi, Zeynep Dereli, Zheng Yin, Elisabeth K Kong, Meric Kinali, Kisan Thapa, Ozgun Babur, Kyuson Yun, Nourhan Abdelfattah, Xubin Li, Behnaz Bozorgui, Mary C Farach-Carson, Robert C Rostomily, Anil Korkut

Faculty, Staff and Student Publications

Interactions among tumor, immune, and vascular niches play major roles in glioblastoma (GBM) malignancy and treatment responses. The composition and heterogeneity of extracellular core matrix proteins (CMPs) that mediate such interactions are not well understood. Here, we present an analysis of the clinical relevance of CMP expression in GBM at bulk, single-cell, and spatial anatomical resolution. We show that CMP enrichment is associated with worse patient survival, specific driver oncogenic alterations, mesenchymal state, pro-tumor immune infiltration, and immune checkpoint expression. Matrisome expression is enriched in vascular and leading edge/infiltrative niches that are known to harbor glioma stem cells. Finally, we …

Precision Targeting Of Sting: Challenges, Innovations, And Clinical Outlook For Cancer Therapy, Jiaqi Shi, Yingying Zhang, Na Zhao, Ekihiro Seki, Li Ma, Gordana Kocic, Xiaobo Li, Janoš Terzić, Tongsen Zheng

Faculty, Staff and Student Publications

The stimulator of interferon genes (STING) pathway plays a crucial role in immune responses and has emerged as a compelling target in cancer therapy. Despite promising preclinical studies, clinical trials of STING agonists have largely failed to deliver durable efficacy, with no agents progressing to phase III trials. This review examines the biological, pharmacological, and clinical barriers limiting STING pathway activation in cancer treatment. We discuss the inherent limitations of STING agonists as well as host-related resistance driven by tumor heterogeneity, immune suppression, and chronic STING activation. Mechanisms of acquired resistance, such as immune checkpoint upregulation and suppression of effector …

International Guidelines On The Diagnosis And Treatment Of Nut Carcinoma, Yu Zhang, Qi Zhang, Yue Hao, Jia Luo, Yingshi Piao, Wenxian Wang, Zhengbo Song, Ziming Li, Luka Brcic, Aijun Liu, Jinpu Yu, Yasuhiro Tsutani, Wenzhao Zhong, Wenfeng Fang, Zhijie Wang, Shengxiang Ren, Athanasios G Papavassiliou, Yongchang Zhang, Jingjing Liu, Shirong Zhang, Xiuyu Cai, Ayten Kayi Cangir, Anwen Liu, Wen Li, Filippo Lococo, Ping Zhan, Hongbing Liu, Tangfeng Lv, Liyun Miao, Lingfeng Min, Helmut Popper, Yu Chen, Jingping Yuan, Feng Wang, Zhansheng Jiang, Gen Lin, Long Huang, Xingxiang Pu, Rongbo Lin, Kalevi Kairemo, Weifeng Liu, Chuangzhou Rao, Dongqing Lv, Zongyang Yu, Ashrafian Leanne, Xiaoyan Li, Chuanhao Tang, Hifzur R Siddique, Chengzhi Zhou, Junping Zhang, Junli Xue, Vishal Shelat, Hui Guo, Qian Chu, Rui Meng, Fatemeh Ardeshir, Jingxun Wu, Rui Zhang, Jin Zhou, Robert A Kratzke, Zhengfei Zhu, Yongheng Li, Hong Qiu, Fan Xia, Fiorella Calabrese, Yang Xia, Alessandro Wasum Mariani, Yuanyuan Lu, Xiaofeng Chen, Mark A Klein, Rui Ge, Enyong Dai, Axel H Schönthal, Yu Han, Zhenying Guo, Jian Zhang, Yinghua Ji, Xianbin Liang, Hongmei Zhang, Xuelei Ma, Marco Chiappetta, Xuewen Liu, Francoise Galateau Salle, Yu Yao, Malgorzata Szolkowska, Weiwei Pan, Fei Pang, Fan Wu, Stefan B Watzka, Liping Wang, Youcai Zhu, Li Lin, Aparna Sharma, Jianfei Tu, Xinqing Lin, Jing Cai, Ling Xu, Jisheng Li, Xiaodong Jiao, Kainan Li, Marjorie G Zauderer, Jia Wei, Huijing Feng, Lin Wang, Yingying Du, Wang Yao, Elizabeth Dudnik, Xuefei Shi, Xiaomin Niu, Dongmei Yuan, Yanwen Yao, Jianhui Huang, Yue Feng, Yinbin Zhang, Binbin Song, Wenfeng Li, Jianfei Fu, Marina K Baine, Pingli Sun, Hong Wang, Mingxiang Ye, Dong Wang, Zhaofeng Wang, Jing Wu, Yunyun Yang, Yuan Fang, Zhen Wang, Bin Wan, Donglai Lv, Huafei Chen, Shengjie Yang, Jing Kang, Jiatao Zhang, Chao Zhang, Lin Shi, Yina Wang, Mohamed Emam Sobeih, Bihui Li, Bin Lian, Lili Mao, Zhang Zhang, Ke Wang, Zhongwu Li, Zhefeng Liu, Nong Yang, Lin Wu, Xiaobing Chen, Gu Jin, Miao Li, Guansong Wang, Thomas U Marron, Jiandong Wang, Sanjay Popat, Meiyu Fang, Yong Fang, Daniel Mansilla, Yuan Li, Xiaojia Wang, Jing Chen, Yiping Zhang, Xixu Zhu, Yi Shen, Shenglin Ma, Aaron S Mansfield, Biyun Wang, Lu Si, Anja C Roden, Bjørn H Grønberg, Yong Song, Geoffrey I Shapiro, Christopher A French, Yuanzhi Lu, Qian Wang, Chunwei Xu

Faculty, Staff and Student Publications

Nuclear protein in testis (NUT) carcinoma (NC) represents a rare, clinically aggressive cancer defined by pathognomonic NUT Midline Carcinoma Family Member 1 (NUTM1) gene fusions, with bromodomain and extraterminal domain (BET) protein 4 (BRD4)-NUTM1 being the predominant oncogenic driver. Since its description in 1991, gradual advances have clarified the pathologic mechanisms of NC and its diagnostic methods; however, NC treatment remains a significant challenge. Moreover, diagnostic and treatment approaches for this cancer require further validation and standardization. These guidelines were developed by the Chinese Alliance of Research for NC (ChARN) based on current evidence in …

A Systematic Literature Review Of Cvid Reveals Pervasive Detrimental Noninfectious Manifestations, G Michelle Ducasa, Rebecca A Marsh, Ali Mojebi, Hsi-En Ho, Charlotte Cunningham-Rundles, Lisa Forbes Satter, Elena W Y Hsieh, Sinisa Savic, Marta Dafne Cabañero-Navalón, Hector Balastegui-Martin, Joud Hajjar, Gulbu Uzel, Kevin S Thorneloe, Jocelyn R Farmer

Faculty, Staff and Students Publications

Noninfectious manifestations of common variable immunodeficiency (CVID) are not formally summarized. We performed a systematic literature review to generate a comprehensive reference for the field. Splenomegaly was the most reported manifestation across 53 publications, occurring in a median of 35.2% of patients. Frequently reported digestive system manifestations included diarrhea (median 27.8%; 21 publications), hepato(spleno)megaly (median, 21.0%; 19 publications), portal hypertension (median 21.0%; 3 publications), nodular lymphoid hyperplasia (median, 17.0%; 9 publications), and enteropathy (median, 16.0%; 34 publications). Other notable manifestations included interstitial lung disease (median, 8.7%; 32 publications) and autoimmune cytopenias (median 18.0%; 21 publications). Steroids and rituximab were the …

Neurodevelopmental Outcomes Following Hematopoietic Cell Transplantation For Patients With Severe Combined Immunodeficiency (Scid): A Pidtc Study, Virdette L Brumm, Sharon A Kidd, Brent R Logan, Farheen Chunara, Jennifer Heimall, Linda M Griffith, Donald B Kohn, Lauren Sanchez, Jeffrey J Bednarski, Caridad Martinez, Mark Vander Lugt, Neena Kapoor, Nicola Wright, Barbara Spitzer, Joseph H Oved, Sharat Chandra, Deepak Chellapandian, Christen L Ebens, Aleks Petrovic, Ahmad Rayes, Hilary L Haines, Hannah Lust, Hannah-Lise Tirado Schofield, Lauren Christopher, Lynnette L Harris, Lisa Forbes Satter, Lauri Burroughs, Christopher C Dvorak, Elie Haddad, Jennifer W Leiding, Rebecca A Marsh, Luigi D Notarangelo, Sung Yun Pai, Michael A Pulsipher, Jennifer M Puck, Morton J Cowan, Ami J Shah

Faculty, Staff and Students Publications

Hematopoietic cell transplantation (HCT) is a potentially curative treatment for severe combined immunodeficiency (SCID). Since the initiation of newborn screening (NBS), survival rates have improved significantly, but the impact of HCT upon neurodevelopment for patients with SCID requires more investigation. We performed a cross-sectional study of subjects with SCID in North America to assess the impact of NBS, transplant conditioning regimen, and genotype on neurodevelopmental outcomes after HCT. 69 subjects with SCID from 17 PIDTC centers (excluding those with ADA deficiency), ages 6-16 years, received comprehensive standardized neurodevelopmental testing of cognitive, behavioral, and emotional function. Compared with the normative population, …

Anti-Csf-1r Therapy With Combined Immuno-Chemotherapy Coordinate An Adaptive Immune Response To Eliminate Macrophage Enriched Triple Negative Breast Cancers, Diego A Pedroza, Xueying Yuan, Fengshuo Liu, Hilda L Chan, Christina Zhang, William Bowie, Alex J Smith, Sebastian J Calderon, Nadia Lieu, Weiguo Wu, Paul Porter, Poonam Sarkar, Na Zhao, Constanze V Oehler, Ondrej Peller, M Waleed Gaber, Qian Zhu, Charles M Perou, Xiang H-F Zhang, Jeffrey M Rosen

Faculty, Staff and Students Publications

Women diagnosed with metastatic triple negative breast cancer (mTNBC) have limited treatment options, are more prone to develop resistance and are associated with high mortality. A cold tumor immune microenvironment (TIME) characterized by low T cells and high tumor associated macrophages (TAMs) in mTNBC is associated with the failure of standard-of-care chemotherapy and immune checkpoint blockade (ICB) treatment. We demonstrate that the combination of immunomodulatory low-dose Cyclophosphamide (CTX) coupled with anti-CSF-1R antibody targeted therapy (SNDX-ms6352) and anti-PD-1 (ICB), was highly effective against aggressive metastatic Trp53 null TNBC transplantable syngeneic models that present with high macrophage infiltration. Mechanistically, CSF-1R inhibition along …

Machine Learning Models Predict Long Covid Outcomes Based On Baseline Clinical And Immunologic Factors, Naresh Doni Jayavelu, Hady Samaha, Sonia Tandon Wimalasena, Annmarie Hoch, Jeremy P Gygi, Gisela Gabernet, Al Ozonoff, Shanshan Liu, Carly E Milliren, Ofer Levy, Lindsey R Baden, Esther Melamed, Lauren I R Ehrlich, Grace A Mccomsey, Rafick P Sekaly, Charles B Cairns, Elias K Haddad, Joanna Schaenman, Albert C Shaw, David A Hafler, Ruth R Montgomery, David B Corry, Farrah Kheradmand, Mark A Atkinson, Scott C Brakenridge, Nelson I Agudelo Higuit, Jordan P Metcalf, Catherine L Hough, William B Messer, Bali Pulendran, Kari C Nadeau, Mark M Davis, Linda N Gen, Ana Fernandez Sesma, Viviana Simon, Florian Krammer, Monica Kraft, Chris Bime, Carolyn S Calfee, David J Erle, Charles R Langelier, Leying Guan, Holden T Maecker, Bjoern Peters, Steven H Kleinstein, Elaine F Reed, Alison D Augustine, Joann Diray-Arce, Patrice M Becker, Nadine Rouphael, Matthew C Altman

Faculty, Staff and Students Publications

Background: The post-acute sequelae of SARS-CoV-2 (PASC), also known as long COVID, remain a significant health issue that is incompletely understood. Predicting which acutely infected individuals will develop long COVID is challenging due to the absence of established biomarkers, clear disease mechanisms, or well-defined sub-phenotypes. Machine learning (ML) models may address this gap by leveraging clinical data to enhance diagnostic precision.

Methods: Clinical data, including antibody titers and viral load measurements collected at the time of hospital admission, are used to predict the likelihood of acute COVID-19 progressing to long COVID. Machine learning models are trained and evaluated for predictive …

A Probabilistic Modeling Analysis Of The Longitudinal Immune Response To Infection And Vaccination Across Demographic Groups And Pulmonary Symptoms, James O'Hanlon, Kaitlyn Sullivan, Lyndsey M. Muehling, Glenda Canderan, Jie Sun, Judith A. Woodfolk, Jeffrey M. Wilson, Rayanne A. Luke

Spora: A Journal of Biomathematics

Antibody and cytokine kinetics describe the dynamic response to immune events such as infection and vaccination. These dynamics are not fully understood, and mathematical characterization may help explain variability across demographic groups and pulmonary symptoms post-acute infection. We fit time-dependent probability models to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) data to obtain distributions of longitudinal antibody response and cytokine values. To assess differences between groups, an overlap metric is applied to the modeled response curves. Our antibody models suggest significant differences between male and female populations and demonstrate deficient antibody responses of less-healthy groups such as smokers. Our cytokine …

Circadian-Shaped Immune Variability Predicts Infection Outcome, Jonathan Lalsiamthara, Mariko Locke, Alejandro Aballay

Faculty, Staff and Student Publications

Disease risk and severity are influenced by genetics, epigenetics, and environmental factors. However, immune responses vary even among genetically similar or related individuals, shaped by inherited and noninherited factors. Using Caenorhabditis elegans, we found that pathogen susceptibility can be predicted by preinfection biomarkers. Individuals with high-basal expression of irg-5, an infection response gene regulated by the p38 mitogen-activated protein kinase-1 (PMK-1) pathway, were more susceptible to Pseudomonas aeruginosa infection. A genome-wide screen identified the myeloid ecotropic viral integration site-1 (MEIS) homeobox protein UNC-62 as a regulator of irg-5 expression, acting through PMK-1 and GATA binding erythroid-like transcription factor …

Reported Safety Practices Of Publicly Advertised Psychedelic Retreats, Amy L Mcguire, Logan Neitzke-Spruill, Jill O Robinson, Caroline S Beit, Nikita Singh, David S Mathai, Lynnette A Averill

Center for Medical Ethics and Health Policy Staff Publications

Importance: The availability of psychedelic retreats has grown to meet the demand for access to these substances. Despite centuries of use among Indigenous communities, psychedelics can pose serious risks for some users.

Objective: To determine safety precautions that retreat organizations that offer psychedelic substances currently use.

Design, setting, and participants: This qualitative study included structured interviews conducted by phone or email with representatives from 49 organizations publicly advertising psychedelic retreat offerings from July to October 2023. Organizations were eligible if they marketed their services in English, offered at least 1 psychedelic substance, and made contact information available online. Organizations were …

Cholesterol Efflux Protein, Abca1, Supports Anticancer Functions Of Myeloid Immune Cells, Shruti V Bendre, Yu Wang, Basel Hajyousif, Rajendra K C, Shounak G Bhogale, Dhanya Pradeep, Natalia Krawczynska, Claire P Schane, Erin Weisser, Avni Singh, Simon Han, Hannah Kim, Lara Kockaya, Anasuya Das Gupta, Adam T Nelczyk, Hashni Epa Vidana Gamage, Yifan Fei, Desirée Rodríguez-Casiano, Xingyu Guo, Haoyun Li, Ryan J Deaton, Fei Mo, Maria Sverdlov, Peter H Gann, Saurabh Sinha, Sahil Sahni, Kun Wang, Kevin Van Bortle, Emad Tajkorshid, Wendy A Woodward, Wonhwa Cho, Erik R Nelson

Faculty, Staff and Student Publications

Breast and other solid tumors respond poorly to immune therapy. Myeloid cells (MCs) such as macrophages contribute to resistance. Established clinical evidence links cholesterol to cancer outcomes, with MC function being regulated by cholesterol metabolism. We screened MC-expressed regulators of cholesterol homeostasis linked to survival and identified the cholesterol efflux protein ABCA1. ABCA1 activity increases anticancer functions of macrophages: enhancing tumor infiltration, decreasing angiogenic potential, reducing efferocytosis, and improving support of CD8+ T cell activity. Mechanistically, different AKT isoforms are involved, through both PI3K-dependent and PI3K-independent mechanisms. Highlighting the clinical relevance of our findings are correlations between ABCA1 in macrophages …

Nf2 Loss Malignantly Transforms Human Pancreatic Acinar Cells And Enhances Cell Fitness Under Environmental Stress, Yi Xu, Michael H Nipper, Angel A Dominguez, Chenhui He, Francis E Sharkey, Sajid Khan, Han Xu, Daohong Zhou, Lei Zheng, Yu Luan, Jun Liu, Pei Wang

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) occurs as a complex, multifaceted event driven by the interplay of tumor-permissive genetic mutations, the nature of the cellular origin, and microenvironmental stress. In this study, using primary human pancreatic acinar 3D organoids, we performed a CRISPR-KO screen targeting 199 potential tumor suppressors curated from clinical PDAC samples. Our data revealed significant enrichment of a list of candidate genes, with neurofibromatosis type 2 associated gene (NF2) emerging as the top target. Functional validation confirmed that loss of NF2 promoted the transition of PDAC to an invasive state, potentially through extracellular matrix modulation. NF2 inactivation …

Racial, Ethnic, And Socioeconomic Survival Disparities In Early-Onset Metastatic Colorectal Cancer, Jennifer S Wang, Benny Johnson, Caitlin C Murphy

Faculty, Staff and Student Publications

Importance: Rates of metastatic colorectal cancer (mCRC) are rising among young adults. Disparities by race and ethnicity and neighborhood-level socioeconomic status (SES) among this population are understudied.

Objective: To examine the association of race and ethnicity and neighborhood-level SES with mortality among a community-based sample of young adults with mCRC.

Design, setting, and participants: This cohort study used a large electronic health record-derived database of young adults with cancer treated at 280 community-based US clinics between 2013 and 2021. Eligible patients were young adults aged 18 to 49 years diagnosed with de novo or recurrent mCRC. Patients were followed up …

Public Support For Alcohol-Control Policies And Political Ideology In The Us, Joël Fokom Domgue, Robert Yu, Ernest Hawk, Sanjay Shete

Faculty, Staff and Student Publications

This cross-sectional study examines the role of US adults’ political affiliation, perception about alcohol use and cancer, and sociodemographic and behavioral factors in banning outdoor alcohol advertising and adding cancer warnings on alcohol containers.

Peroxisomal Integrity In Demyelination-Associated Microglia Enables Cellular Debris Clearance And Myelin Renewal In Mice, Joseph A Barnes-Vélez, Xiaohong Zhang, Yaren L Peña Señeriz, Kiersten A Scott, Yinglu Guan, Jian Hu

Faculty, Staff and Student Publications

Demyelination associated microglia (DMAM) orchestrate the regenerative response to demyelination by clearing myelin debris and promoting oligodendrocyte maturation. Peroxisomal metabolism has emerged as a candidate regulator of DMAMs, though the cell-intrinsic contribution in microglia remains undefined. Here we elucidate the role of peroxisome integrity in DMAMs, using cuprizone-mediated demyelination coupled with conditional KO of peroxisome biogenesis factor 5 (PEX5) in microglia. Absent demyelination, PEX5 conditional KO (PEX5cKO) had minimal impact on homeostatic microglia. However, during cuprizone-induced demyelination, the emergence of DMAMs unmasked a critical requirement for peroxisome integrity. At peak demyelination, PEX5cKO DMAMs exhibited increased lipid droplet burden and reduced …

Type Iv Secretion Systems: Reconciling Diversity Through A Unified Nomenclature, Peter J Christie, Gabriel Waksman, Ronnie Per-Arne Berntsson, Nicolas Soler, Nathalie Leblond-Bourget, Badreddine Douzi

Faculty, Staff and Student Publications

Type IV secretion systems (T4SS) are versatile nanomachines responsible for the transfer of DNA and proteins across cell envelopes. From their ancestral role in conjugation, these systems have diversified into a superfamily with functions ranging from horizontal gene transfer to the delivery of toxins to eukaryotic and prokaryotic hosts. Recent structural and functional studies have uncovered unexpected architectural variations not only among Gram-negative systems but also between Gram-negative and Gram-positive systems. Despite this diversity, a conserved set of core proteins is maintained across the superfamily. To facilitate cross-system comparisons, we propose in this review a unified nomenclature for conserved T4SS …

The Efficacy Of Cgrp Antagonists Versus Other Non-Migraine Specific Medications As Prophylactic Treatment For Episodic And Chronic Migraine, Lauryn C. Hutto

The PA Department Journal of Medical Science

Introduction: Migraines are a disabling neurological condition affecting 12-15% of the population. Migraines are characterized by a unilateral throbbing headache lasting between 4 and 72 hours, often accompanied by photophobia, phonophobia, nausea, or vomiting. Until the approval of the first CGRP antagonist, Erenumab, in May 2018, the prophylactic treatment for migraines relied on non-migraine-specific medications, such as antihypertensives and antiepileptics. Studies have been done to determine the efficacy and safety of the new medications, but few have directly compared them to older non-migraine-specific medications used for prevention. The purpose of this paper is to compare the efficacy of CGRP …

Efficacy And Safety Of Semaglutide In Adults Without Diabetes Who Are Overweight Or Obese, Rebecca Petty

The PA Department Journal of Medical Science

INTRODUCTION:

Obesity is associated with an increased risk of cardiovascular and metabolic disorders and contributes to the leading cause of death in the US — heart disease. Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) have recently emerged as a treatment option for obesity. The purpose of this clinical review is to evaluate the efficacy and safety of semaglutide in adults without diabetes who are overweight or obese.

METHODS:

PubMed was searched using a precise search strategy and the key terms “semaglutide,” “weight loss,” and “without diabetes.” Results were filtered and narrowed using specific inclusion and exclusion criteria. Four high-quality studies were …

Patients Requiring Mechanical Ventilation Reported To The North American Snakebite Registry, Joshua Unger, Spencer Greene

Gulf Coast Division GME Research Day 2026

No abstract provided.

Isolated Clonidine Ingestions In Pediatric Patients, Spencer Greene, Caleb King, Sharan Campleman

Gulf Coast Division GME Research Day 2026

No abstract provided.

Differential Sensitivity Of Leukocyte Populations To Staphylococcus Aureus Biofilm, Nichole D. Brandquist, Tammy Kielian

Journal Articles: Pathology and Microbiology

Staphylococcus aureus is a leading cause of prosthetic joint infection (PJI) typified by biofilm formation. Anti-inflammatory granulocytic myeloid-derived suppressor cells (G-MDSCs) represent the main leukocyte population in a mouse model of S. aureus PJI, followed by neutrophils (PMNs), and macrophages (Mφs), which is also seen during human PJI. Defining how each leukocyte population responds to S. aureus biofilm vs planktonic bacteria could have important implications for how S. aureus evades immune detection to facilitate biofilm persistence. This study compared the kinetics of leukocyte death and relationship to mitochondrial ROS (mtROS) production following exposure to planktonic S. aureus or biofilm. Mφs …

In Vitro Dihalobenzene Nephrotoxicity In Isolated Kidney Cells, Jana Ahmed Sherif

Theses, Dissertations and Capstones

Brominated and chlorinated benzenes are common industrial chemicals linked to kidney injury. This study evaluated the nephrotoxicity of several mono- and dihalogenated derivatives using isolated kidney cells from male Fischer 344 rats. LDH release and trypan blue exclusion were measured after 30- and 60-minute exposures to 0.25–1.0 mM to test compounds. Toxicity increased with increased concentration and longer times. Mixed-halogen bromobenzenes, particularly 1-bromo-4-chlorobenzene, showed one of the highest toxicity levels, while 1,4dichlorobenzene was the most toxic chlorobenzene. Antioxidants (glutathione, ascorbate, and αtocopherol) markedly reduced injury, indicating oxidative mechanisms play a role in toxicity. cytochromes P450 (CYP) inhibitors (piperonyl butoxide and …

Somatosensory Realignment Following Single And Dual Force-Field Adaptation, Dylan Zangakis, Aaron Wong, Amanda S. Therrien

Moss-Magee Rehabilitation Papers

Evidence that adaptive motor learning coincides with a realignment of somatosensory perception has led to hypotheses that a shared mechanism underlies both processes. This implies that these two phenomena should exhibit similar properties. However, studies of somatosensory realignment with visuomotor adaptation have shown mixed support, possibly due to a confounding coactivation of sensory prediction errors and multisensory integration. Although the former is thought to drive adaptation, both processes may contribute to somatosensory realignment. Here, we examined somatosensory realignment following force-field adaptation, which is not confounded by multisensory integration. Across two experiments, we tested whether somatosensory realignment mimics three canonical properties …

Investigation Of Genx Exposure To Pathways Associated With Colorectal Cancer Risk, Emily J. Ferguson

Theses and Dissertations--Toxicology and Cancer Biology

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants widely detected in drinking water and food sources, resulting in chronic human exposure. Among these compounds, hexafluoropropylene oxide dimer acid (HFPO-DA), commonly known as GenX, has been introduced as a short-chain replacement for legacy PFAS such as perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA). Although GenX is believed to be a safer alternative, emerging research suggests it can still affect human health.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer-related death in the United States, highlighting the need to better understand environmental …

The Role Of Bacteriophage In The Rgg1-Mediated Virulence Control Of Streptococcus Pyogenes, Yuan Tian

Dissertations and Theses

In Streptococcus pyogenes, bacteriophages and other horizontally transmissible elements (HTEs) comprise approximately 10% of the genome, and each clinical isolate carries a unique combination of these elements, contributing to genetic diversity, virulence, antibiotic resistance, and immune evasion. Previously, our laboratory identified binding sites of the transcriptional regulator Rgg1 in the clinical isolate NZ131 and demonstrated that Rgg1 influences genome-wide gene expression, including bacteriophage genes. In the clinical isolate SF370, the prophage SpyCIM1, positioned in the chromosome between the mutL and mutS genes, controls DNA mismatch repair through excision and reintegration into the chromosome. In the integrated form, the prophage displaces …

Inhibition Of Fatty Acid Synthase Enhances Therapeutic Efficacy And Delays Acquired Resistance To Braf-Targeted Therapy In Colorectal Cancer, Mariah E. Geisen, Elisane W. Tessmann, Courtney O. Kelson, Daheng He, Chi Wang, Abu Saleh Mosa Faisal, Ellen J. Beswick, Yasmine Baca, Stephanie Rock, Jill M. Kolesar, Yekaterina Y. Zaytseva

Toxicology and Cancer Biology Faculty Publications

The presence of BRAF ^V600E mutations is associated with poor prognosis in colorectal cancer (CRC). Although the FDA-approved combination of encorafenib and cetuximab provides clinical benefit in this population, only 22% of patients respond and most eventually develop resistance. This study investigated the mechanisms of resistance to PLX8394, a second-generation BRAF inhibitor. Using primary and established BRAF ^V600E CRC cells, we show that the development of resistance to PLX8394 results in cross-resistance of cells to encorafenib. Moreover, the acquired resistance is associated with increased proliferation, invasion, and upregulation of lipid metabolism, including increased expression of fatty acid synthase (FASN), a …