Digital Commons Network^™

Care, Control, And The Racial Regulation Of Black Women’S Reproduction In American Medicine, Rheya K. Wilk

Honors Thesis

Black women in the United States continue to experience disproportionately high rates of maternal mortality, negative reproductive healthcare experiences, and documented disparities in medical treatment. From slavery through the twenty-first century, American medicine has repeatedly positioned Black women’s reproduction as a site of regulation, rather than care, making medical mistrust among Black women a rational response to a long history of institutional conflict embedded in American medicine. Drawing on medical history and bioethical analysis, this thesis traces reproductive abuse across distinct, yet connected, eras. Beginning with antebellum gynecological experimentation on enslaved women, it demonstrates how racialized assumptions about pain and …

Progressive Cardiac Phenotypes And Reduced Reversibility From Long-Term Cugexp Rna Expression In A Dm1 Mouse Model, Rong-Chi Hu, Mohammadreza Tabary, Xander Ht Wehrens, Thomas A Cooper

Faculty, Staff and Students Publications

Myotonic dystrophy type 1 (DM1) is caused by an expanded CTG repeat in the DMPK gene, resulting in mutant transcripts that form expanded CUG (CUGexp) RNA foci and sequester muscleblind-like (MBNL) RNA-binding proteins. DM1 is multisystemic, with progressive worsening of disease manifestations in affected tissues. Disease progression is attributed to somatic expansion of the CTG repeats with age, resulting in production of CUGexp RNA with enhanced intrinsic toxicity due to increased MBNL sequestration. To determine the degree to which cardiac disease progression can occur independently of repeat expansion, we used a transgenic DM1 mouse model with inducible heart-specific expression of …

Inflammatory Markers In The Emergency Department And Ptsd Symptoms In The Aurora Study: A Longitudinal Cohort Study, Kristen Nishimi, Sarah Linnstaedt, Thomas Neylan, Lauren Mckibben, Liz Marie Albertorio-Sáez, Ying Zhao, Stacey House, Francesca Beaudoin, Xinming An, Jennifer Stevens, Gari Clifford, Tanja Jovanovic, Laura Germine, Scott Rauch, John Haran, Alan Storrow, Paul Musey, Phyllis Hendry, Sophia Sheikh, Brittany Punches, Robert Swor, Jose Pascual, Mark Seamon, Elizabeth M Datner, Claire Pearson, David Peak, Roland Merchant, Robert Domeier, Niels Rathlev, Brian O'Neil, Paulina Sergot, Leon Sanchez, Steven Bruce, Steven Harte, Ronald Kessler, Karestan Koenen, Kerry Ressler, Samuel Mclean, Aoife O'Donovan

Department of Emergency Medicine Faculty Papers

BACKGROUND: Systemic inflammation is hypothesized to contribute to post-traumatic stress disorder (PTSD) vulnerability. Few studies have examined inflammation shortly after trauma as a predictor of later PTSD symptoms. We examined whether inflammation from the emergency department (ED) post-trauma is associated with PTSD symptom severity over the following 6 months.

METHODS: Our sample included 742 AURORA participants, a longitudinal cohort of patients in 29 EDs across the United States after a traumatic stressor, followed up to 6 months. Plasma cytokines were assessed from a study blood draw in the ED: an inflammatory index (standardized sum of generally pro-inflammatory markers interleukin [IL]-6, …

Modalities Of Vision Restoration In Optic Neuropathies And Retinal Disease, Batsheva Rubin, Fabio Lavinsky, Rachel Cain, Ajay E. Kuriyan, Gadi Wollstein, Ronald Zambrano, Joel Schuman

Wills Eye Hospital Papers

Visual impairment affects over 250 million people globally and carries a significant psychosocial and economic burden. In recent years, rapid advancements in biomedical engineering and regenerative medicine have driven the development of innovative therapies aimed at restoring visual function. Here, we first provide an overview of the visual pathway, imaging modalities, and the psychosocial and economic burden of vision loss. Then we review four vision restoration approaches: gene and stem cell therapies, optogenetics, retinal prosthetic devices, and visual pathway electrical stimulation. For each therapeutic approach, the mechanism of action, clinical outcomes, adverse events, and current limitations are discussed. Stem cell …

Systemic Α₂-Agonist Use And Lower Hazard Of Glaucoma Compared With Β-Blockers: A Cohort Study, Ibrahim Abboud, Amin Z. Khudari, Abdelaziz Abdelaal, Amr Almobayed, Subhi J. Al'aref, Jonathan S. Myers, Richard K. Lee, Abdelrahman M. Elhusseiny

Wills Eye Hospital Papers

OBJECTIVE: Systemic antihypertensive medications may influence glaucoma-related outcomes through intraocular pressure-dependent and vascular mechanisms. While topical α₂-agonists are established glaucoma therapies, the association between systemic α₂-agonists and glaucoma hazard remains unexamined; we compared their hazard with systemic β-blockers in adults with hypertension.

METHODS AND ANALYSIS: We conducted a multicentre retrospective cohort study using deidentified electronic health records. Adults aged ≥40 years with hypertension and chronic exposure to systemic α₂-agonists or β-blockers were included. Patients with pre-existing ocular hypertension (OHT), primary open-angle glaucoma (POAG), concomitant comparator use, or inadequate ophthalmic follow-up were excluded. We balanced cohorts using propensity score matching (PSM) …

Genetic Analysis Of The X-Linked Adrenoleukodystrophy Gene Abcd1 In Drosophila Uncovers A Conserved Phenotype, Joshua Manor, Sharayu V Jangam, Hyung-Lok Chung, Pranjali Bhagwat, Jonathan C Andrews, Hillary Chester, Shu Kondo, Saurabh Srivastav, Juan Botas, Ann B Moser, Suzette M Huguenin, Michael F Wangler

Duncan NRI Faculty and Staff Publications

X-linked adrenoleukodystrophy (X-ALD) is a progressive neurodegenerative disorder caused by a loss-of-function (LOF) mutation in the ATP-binding cassette subfamily D member 1 (ABCD1) gene, leading to the accumulation of very long-chain fatty acids (VLCFAs). This disorder exhibits striking heterogeneity; some male patients develop an early childhood neuroinflammatory demyelination disorder, while other patients, including adult males and most affected female carriers, experience a chronic progressive myelopathy. Adrenocortical failure is observed in almost all male patients, with the age of onset varying, sometimes being the first diagnostic finding. The gene underlying this spectrum of disease encodes an ATP-binding cassette (ABC) transporter that …

Applying User-Centered Design To Develop A Culturally Sensitive, Low-Calorie Meal Plan For Enhancing Dietary Behavioral Control In Masld, Maya Balakrishnan, Paola Martinez, Brett Deng, Ivonne Arguelles, Crystal Arguelles, Terri L Fletcher, Natalia I Heredia, Myriam Ibarra, Anna Christine Rome

Faculty, Staff and Students Publications

Background: Dietary changes are essential for managing metabolic dysfunction-associated steatotic liver disease (MASLD), yet patients often face barriers related to knowledge, skills, cost, time, and cultural fit.

Aims: The purpose of this paper is to report a process for culturally tailoring a dietary intervention and its application to create a calorie-restricted meal plan for Mexican and Central American patients with MASLD. Guided by the Theory of Planned Behavior and user-centered design, we produced a culturally tailored seven-day structured meal plan aligned with dietary guidelines for MASLD and weight loss.

Methods: We conducted a three-phase, mixed-methods process among Mexican/Central American patients …

Beyond Traditional Emergency Medicine Residency Match Interviews: Behavioral Questions As Stress Tests For Resident Selection A Theory-Driven Micro-Assessment Framework For Detecting High-Value Traits, Alan Lucerna, James Lee, Robin Lahr, James Espinosa

Rowan-Virtua Research Day

Background: Traditional residency selection metrics incompletely capture behavioral traits essential for emergency medicine (EM) performance.

Objective: To propose a theory-driven framework using structured behavioral questions as stress tests to detect high-value traits.

Methods: Conceptual analysis of three standardized behavioral prompts assessing execution, systems thinking, and team orientation.

Results: Distinct response patterns align with observable domains associated with reliability, performance, and leadership.

Conclusion: Behavioral stress test questions offer a scalable, low-cost method to enhance residency selection processes.

Comparison Of Ecg Features, Cardiac Biomarkers, And Clinical Outcomes In Three Waves Of Hospitalized Covid-19 Pneumonia Patients With Cardiovascular Events, Yuchen Han, Jahnavi Sunkara, Tshura S Ali, Harideep Samanapally, Vidyulata Salunkhe, Fnu Deepti, Emma C. Huang, Justin J. Huang, Maiying Kong, Jiapeng Huang

The University of Louisville Journal of Respiratory Infections

Background

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a rapidly evolving virus that can severely impact the cardiovascular system. With new variants, it is important to characterize wave-specific (defined by dominant circulating variants) clinical changes.

Methods

A multi-center retrospective cohort study of patients hospitalized with SARS-CoV-2 community acquired pneumonia at eight adult acute-care hospitals in the city of Louisville, KY was conducted. Patients hospitalized with Coronavirus Disease 2019 (COVID-19) community acquired pneumonia who experienced a cardiovascular event between March 2020 and July 2022 were included in this analysis. Variant assignment was based on temporal prevalence rather than genomic confirmation, and …

Purine Metabolic Adaptation Protects The Endothelium From Disturbed Flow-Induced Dna Damage And Atherosclerosis, Qian Ma, Yongfeng Cai, Zhidan Zhang, Dingwei Zhao, Yuan Zhao, Peishan Xu, Tammy Lu, Wendy Zhang, Qiuhua Yang, Yaqi Zhou, Varadarajan Sudhahar, Tohru Fukai, Hanjoong Jo, Yiming Xu, Yuqing Huo

Faculty, Staff and Students Publications

Despite effective lipid-lowering therapies, atherosclerosis continues to be a leading cause of death, with considerable residual cardiovascular risk. Atherosclerotic lesions develop preferentially at arterial regions exposed to disturbed flow (d-flow), which induces genomic stress, endothelial injury, and barrier dysfunction. Hemodynamic forces are known to reprogram endothelial metabolism, but the role of de novo purine synthesis (DNPS), which supplies nucleotides for genome maintenance and whose terminal steps are catalyzed by the bifunctional enzyme ATIC, remains undefined in atherosclerosis. By integrating bulk and single-cell multiomics with in vitro flow systems and in vivo models, we show that d-flow upregulates DNPS and ATIC …

Emerging Near-Infrared Targeted Imaging Pharmaceutics For Ovarian Cancer, Angel J. Phillip, Annu Karithara, Subhash Chauhan, Murali Yallapu

School of Medicine Publications

Background: Accurate intraoperative identification of ovarian cancer is challenging, as standard techniques such as visual inspection, palpation, and histopathology often fail to detect microscopic disease. Residual tumor contributes to poor cytoreductive outcomes, high recurrence rates, and chemoresistance. Near-infrared (NIR) imaging using tumor-specific biomarkers has emerged as a promising approach to enhance intraoperative visualization and improve tumor margin delineation. Methods: A focused literature review was conducted using PubMed to identify preclinical and clinical studies evaluating NIR image-guided strategies in ovarian cancer. Studies involving tumor-targeted probes against folate receptor alpha, α3-integrin, mesothelin, and CA125 were included, with emphasis on probe design, delivery, …

Nuclear Export As A Therapeutic Vulnerability In Zfta-Rela Ependymoma, Siri M Ippagunta, Amir Arabzade, Srinidhi Varadharajan, Erik Emanus, Amanda Bland, Alisha Kardian, Nicholas Laboe, Hua Sun, Tuyu Zheng, Amelia Hancock, Mark Zhai, Emma Caesar, Maxwell Park, Wilda Orisme, Melissa Johnson, Brittany Rodgers, Gregory H Turner, Jeffrey Steinberg, Burgess Freeman, Martine F Roussel, Anang Shelat, Richard Kriwacki, Thomas E Merchant, Benjamin Deneen, Michael D Taylor, Sameer Agnihotri, Shondra Pruett-Miller, Jacob A Steele, Anoop Murthy Kavirayani, David W Ellison, Arzu Onar-Thomas, Giles Robinson, Stephen C Mack, Kelsey C Bertrand

Faculty, Staff and Students Publications

Background: Ependymoma (EPN) is the third most common pediatric brain tumor with no targeted therapies available to patients. In supratentorial ependymoma, the most frequent driver alteration is a gene fusion between ZFTA and RELA (denoted ZR), leads to constitutive localization of ZR in the nucleus. Because ZR is not currently druggable, we tested whether ZR expression leads to aberrant protein interactions that could represent therapeutic vulnerabilities.

Methods: Using CRISPR-Cas9 pooled screening, we identified many novel druggable ZR interacting proteins including XPO1, CARM1, SMARCA4, and CDK1. We focused on the nuclear export protein (XPO1), given the ability of most XPO1 inhibitors …

Enhancing The Diversity And Number Of Certified Registered Nurse Anesthetists: A Proposed Pipeline Program For Underrepresented Students, Alexis Lamoreaux

Doctor of Nursing Practice Scholarly Projects

The underrepresentation of minority groups in the Certified Registered Nurse Anesthetist (CRNA) profession impacts healthcare providers’ diversity and cultural competence. This Final Scholarly Project (FSP) proposes a pipeline program to increase diversity within the CRNA field by providing academic support, mentorship, and clinical exposure to students from underrepresented backgrounds. Given the shortage of anesthesia providers, especially in underserved areas, improving access to the CRNA profession for minority students is critical for enhancing patient outcomes. This FSP suggests establishing mentorship and skill development concepts through a 12-month structured program that targets minorities, first-generation college students, or those from rural backgrounds. The …

Tropomyosin-Related Kinase Receptor Type B Agonism In Geographic Atrophy-The Translational Challenges From Preclinical Data To A First-In-Human Trial, David Brown, Oliver Zeitz, Clare Bailey, Sunir J. Garg, Karl Csaky, James Talks, Sobha Sivaprasad, Peter M. Benz, Rolf Herrmann, Remko A. Bakker, Sebastian Bandholtz, Ankit Mittal, Qihong Huang, Serge Kosobokovs, Gudrun Simons, Andrea Giani, Jochen Huber, Martin Gliem

Wills Eye Hospital Papers

OBJECTIVE: To report results of the first-in-human trial of intravitreal tropomyosin-related kinase receptor type B (TrkB) agonist BI 754132 in participants with geographic atrophy (GA). To discuss BI 754132 clinical data in the context of the preclinical findings and their translation into human data.

DESIGN: An open-label, uncontrolled, nonrandomized phase I trial (NCT04002310) assessing the safety, tolerability, and pharmacokinetics of BI 754132 in participants with GA supported by preclinical data.

PARTICIPANTS: Participants with GA recruited between July 2019 and August 2022 in the United States and UK.

METHODS: Clinical trial comprising a single rising dose (SRD) part (n = 15) …

Metabolic Dysfunction And Metabolic Management In Episodic Migraine, Delora E. Denney, Michael J. Marmura

Department of Jefferson Headache Center Papers and Presentations

PURPOSE OF REVIEW: Evidence suggests a significant link between migraine and metabolic syndrome,, especially in those with chronic or refractory migraine. Weight loss and exercise may effectively prevent migraine. Here, we review the evidence behind exercise and weight loss as migraine treatments.

RECENT FINDINGS: While metabolic syndrome and pain have long had a known association, only recently have strong studies demonstrated a higher risk of developing metabolic syndrome in people with migraine. Additionally, other sequelae of metabolic syndrome, obesity, hypertension, hypercoagulability, and diabetes also interplay with migraine. New medications like GLP-1 agonists may be a potential treatment for migraine as …

Antibody-Drug Conjugates Beyond Her2 In Non-Small Cell Lung Cancer (Nsclc): Mechanisms, Emerging Targets, And Future Directions., Ahmed Ismail, Aakash Desai, George R Simon, Yanis Boumber

Oncology Articles

Antibody-drug conjugates (ADCs) are a rapidly evolving class of oncology therapeutics that enable precise delivery of potent cytotoxic agents to tumor cells while minimizing systemic toxicity. While HER2-targeted ADCs such as trastuzumab deruxtecan (T-DXd) in HER2-mutant, Datopotamab deruxtecan (Dato-Dxd) in EGFR-mutant, and telisotumumab vedotin (Teliso-V) in MET IHC 3+ expressing lung cancer have already established a clinical role in non-small cell lung cancer (NSCLC), multiple ADCs targeting alternative antigens, including additional TROP2 ADCs, HER3, MET, CEACAM5, B7-H3, Nectin-4, and others, are now in advanced clinical development. This review synthesizes the current evidence for non-HER2 ADCs in NSCLC, highlighting mechanisms of …

Personalized Treatment Of Chronic Tendinopathy Using Ultrasound And Neuroimmune Markers: A Narrative Review, Rohan Phadke, Samer Salman, Kirtan Patel, Jad Wardeh, Akhil Marupudi, Rahul Kumar, Arbaz A. Momin, Alireza Tavakkoli

Department of Neurosurgery Faculty Papers

Introduction: : Chronic tendinopathy affects approximately 30% of musculoskeletal consultations, yet treatment outcomes remain inconsistent despite numerous available interventions. This variability stems from the absence of validated frameworks to match individual patients to optimal treatments based on underlying pathophysiology. To synthesize current evidence on ultrasound imaging biomarkers, neuroimmune mechanisms, and interventional therapies in chronic tendinopathy, and propose a clinically applicable framework integrating ultrasound phenotyping with neuroimmune assessment to guide personalized treatment selection. Methods: A systematic literature search was conducted across PubMed, Scopus, and Web of Science through December 2025. Studies examining ultrasound/elastography imaging, neuroimmune mechanisms, or treatment interventions in chronic …

Morphological Assessment Of Stage Hh38 Of The Japanese Quail (Coturnix Japonica) Heart By Micro-Sonogram, Jaden Roe, Ashlyn Benavides, Michael B. Filla, Douglas C. Bittel, Whitney Shae, Geetha Haligheri, James E. O'Brien, Nataliya Kibiryeva

Manuscripts, Articles, Book Chapters and Other Papers

A challenge of studying mammalian cardiac embryogenesis is the limited ability to perform experimental manipulations in animal models. The avian embryo is widely accepted as a model for mammalian heart developmental studies. In this study, we establish the methodology and protocols for studying the Japanese quail (Coturnix japonica) heart at embryonic day 10 (HH38) using the FUJIFILM VisualSonics Vevo 3100 ultrasound system equipped with a MX550D small animal cardiology transducer. These protocols were designed to measure right ventricular wall thickness, pulmonary artery diameter, and the outflow velocities of the right ventricular outflow tract (RVOT) and the pulmonary artery …

Global Perspectives On Central Nervous System Drug Innovation: Achievements, Barriers, And Priorities For The Next Decade, Hiroyuki Uchida, Gabriella Gobbi, Joseph Zohar, Allan Young, Dan Rujescu, Ming-Chyi Huang, Suresh Sundram, Lukoye Atwoli, Jana Vukovic, Kazutaka Ikeda

Internal Medicine, East Africa

Background Over the past decade, neuropsychopharmacology has shifted from stagnation to momentum, with first-in-class mechanisms and biomarker-enabled trials spanning psychiatry and neurology.

Methods We narratively synthesized advances from 2013 to 2026 across central nervous system (CNS) discovery and development, including pivotal trials, regulatory actions, digital/real-world evidence, genetics, artificial intelligence (AI), and implementation/global-access themes that are endorsed by international societies.

Results Therapeutic gains include rapid-acting drugs for treatment-resistant depression (intranasal esketamine); psychedelic-assisted therapy for posttraumatic stress disorder and depression; neuroactive steroid γ-aminobutyric acid-A receptor positive allosteric modulators (brexanolone, zuranolone) for postpartum depression; non-dopaminergic muscarinic agonists (xanomeline–trospium) for schizophrenia; orexin receptor antagonists …

The Relationship Between Mc1r Gene Variants For Red Hair And Clinical Responses To Anesthesia, Analgesia, And Pain: A Systematic Review Of The Literature, Mary Clark Allen

The Eleanor Mann School of Nursing Undergraduate Honors Theses

Background: Genetic variations of the melanocortin-1 receptor (MC1R) are commonly associated with red hair and pale skin. Research has linked MC1R variants with alterations in anesthetic response, pain perception, opioid sensitivity, and pain-related fear. Existing literature presents inconclusive findings, highlighting the need for further investigation.

Purpose: This review aims to synthesize current evidence concerning the role of MC1R variants in altering physiologic responses.

Methods: A systematic literature review was conducted by accessing CINAHL, MEDLINE, and PubMed through the University of Arkansas Libraries OneSearch platform. After applying inclusion and exclusion criteria, a total of 20 peer-reviewed articles were extracted for review. …

Assessment Of Correctness, Content Omission, And Risk Of Harm In Large Language Model Responses To Ophthalmology Continuing Medical Education Questions, Jacqueline L. Chen, Amanda J. Lu, Rohan Verma, Li Wang, Douglas D. Koch, Allison J. Chen

SKMC Student Presentations and Publications

PURPOSE: To evaluate the accuracy and prose responses of 2 large language models (LLMs) to ophthalmology continuing medical education questions.

DESIGN: Question prompts and multiple choice (MC) answer options were input into the 2 LLMs, and responses were analyzed for accuracy and assessed for evidence of correctness, completeness, bias, and potential harm using a previously reported standardized rubric.

SUBJECTS: Basic and Clinical Science Course questions and MC answer options from the American Academy of Ophthalmology question bank were used as inputs into the 2 LLMs (ChatGPT-4 and Google Vertex's Gemini Pro 1.5).

METHODS: The MC responses were assessed for accuracy …

Exploring Bidirectionality In Global Health Partnerships: Perspectives From U.S. Pediatric Residency Programs, Anik Patel, Pauline Kamau, Justus Simba, Ashley Combs, Adelaide Barnes, Kathy Ferrer, Heather Haq, Duncan K Hau, Lee Morris, Brittany Murray, Amy Rule, Reena P Tam, Lisa Umphrey, Megan S Mchenry

Faculty, Staff and Students Publications

Introduction Despite growing interest, little guidance exists to re-evaluate global health partnerships (GHPs) through promoting bidirectionality. This study aims to understand the perspectives of United States (U.S.) pediatric global health (GH) faculty on institutional bidirectional practices to inform future discussions with international collaborators. Methods An internally, iteratively developed REDCap-based online survey (REDCap, Vanderbilt University, Nashville, TN), by our diverse author group, collected qualitative data from January 18 to February 20, 2023. Free-text responses were reviewed and coded inductively, with findings framed to generate themes for subsequent engagement with international partners. Results Of the 88 U.S. programs that identify as having …

Ixodid And Flea Infestations And Associated Bacteria On Two Sympatric Felid Species In South Texas, Allan T Showler, Hilary Swarts, Maya Murry, Alisa Nelson, Alexander R Kneubehl, Sarah M Gunter

Faculty, Staff and Students Publications

Ixodid ticks and fleas parasitize wild felids and can transmit pathogens of veterinary and public health concern. We identified ixodid and flea species collected from sympatric South Texas bobcats, L. rufus, and ocelots, L. pardalis. Greater diversities of ixodids were found on both felids than in previous reports, with seven species in three genera on L. rufus and six species in three genera on L. pardalis. We report first findings of tropical horse tick, Dermacentor nitens, on L. rufus in Texas, and Ixodes keiransi on both felids in Texas. Although false cayenne tick, Amblyomma tenellum, nymphs were the most abundant …

Mif-Cd74 Signaling Drives Immune Modulation In Medulloblastoma, Benjamin Draper, Zhen You, Dean Thompson, Xu Guo, Alaide Morcavallo, Diego Chillon Pino, Carlos Lorenzo Gido Nery, Sumana Shrestha, Chantelle E Bowers, Courtney Himsworth, Alberto Delaidelli, Bethany Remeniuk, Sonia Morlando, Brandon Wade, Freya Gordon, Yara Sanchez-Corrales, Bei Hopkins, Natalie Monteiro, Darren Locke, Miao Liu, Jacob Torrejon Diaz, Kevin Greenslade, Barbara Martins Da Costa, Karen Barker, Colin Kwok, Olumide Ogunbiyi, Anya Fletcher, Stacey Richardson, Carlos Custodia, Rafael Roque, Thomas Jackson, Regan Barfoot, Sergi Castellano, Rebecca M Hill, Olivier Saulnier, Thomas S Jacques, Michael D Taylor, Claudia C Faria, Olivier Ayrault, Poul H Sorensen, John Anderson, Louis Chesler, L Frank Huang, Steven C Clifford, Laura K Donovan

Faculty, Staff and Students Publications

Background: Relapsed medulloblastoma remains a significant therapeutic challenge as it is near universally fatal. The tumor microenvironment of medulloblastoma plays a critical role in tumor progression, influencing tumor growth, immune evasion, and therapeutic resistance. We hypothesized that defining tumor-immune interactions in diagnostic and relapsed medulloblastoma may uncover mechanisms of immune evasion and identify novel therapeutic targets.

Methods: We analyzed paired primary and recurrent RNA-sequencing data from 140 medulloblastoma patients to profile immune cell composition and validate spatial relationships within the TME. To identify key tumor-immune interactions, we developed a novel algorithm to detect receptor-ligand pairs using single-cell RNA-sequencing data. These …

Natural Maternal Immunity Protects Neonates From Escherichia Coli Sepsis., Raymond E. Diep, Ujjwal Adhikari, Kubra Gokce Tezel, Giang Pham, Allison R. Burrell, Mary A. Staat, Nguyen Thi Khanh Nhu, Minh-Duy Phan, Kate M. Peters, Mark A. Schembri, Scott H. Saunders, David B. Haslam, John J. Erickson, Susana Chavez-Bueno, Sing Sing Way

Manuscripts, Articles, Book Chapters and Other Papers

Escherichia coli is a leading cause of neonatal sepsis, with infection occurring in approximately one in every 1,000 live births. However, with E. coli colonization beginning soon after birth and defects in neonatal host defence maturation, an alternative consideration is why infection does not occur even more frequently. Here we show that newborn babies with E. coli sepsis have selectively reduced vertically transferred natural antibodies that recognize E. coli, mechanistically explaining their susceptibility to infection. Complementary preclinical studies show that preconceptual intestinal colonization with probiotic E. coli Nissle 1917 (EcN) primes anti-E. coli immunoglobulin G (IgG) antibodies with broad cross-reactivity …

Determining Zap-70 Signaling Pathways Mediated By Ccr7 In Tcr T Cell Activation, Vivian Torres

Open Access Theses & Dissertations

Activation of T lymphocytes is the main event that occurs in the adaptive immune response after engagement of the T cell receptor (TCR) with the peptide of the major histocompatibility complex (pMHC) molecules that are demonstrated by antigen presenting cells [1]. A key step in this process is the recruitment and activation of the zeta chain associated protein of 70 kDa (ZAP-70). ZAP-70 couples TCR engagement to downstream intracellular signaling pathways through phosphorylation of tyrosine residues within intracellular tyrosine activation motifs (ITAMs) [2]. Although there have been extensive studies on the signaling response through TCR activation, the regulatory influence of …

Spectral Characterization Of Colorectal Cancer Using Excitation-Scanning Hyperspectral Imaging, Natalie Hadad

Honors Theses

Colorectal cancer is one of the most common and deadly cancers worldwide, with a lifetime risk of approximately one in twenty-three for men and one in twenty-five for women. Although early detection significantly improves survival, current diagnostic approaches such as tissue biopsy are invasive, reliant on subjective interpretation, have extended turnaround times, and risk missing flat or depressed lesions that are more difficult to detect than raised polyps. These limitations highlight the need for objective, minimally invasive technologies capable of detecting early tissue changes. This study investigates excitation-scanning hyperspectral imaging (Ex-HSI) as a label-free optical approach for identifying colorectal cancer–associated …

Global Perspectives On Cns Drug Innovation: Achievements, Barriers, And Priorities For The Next Decade, Hiroyuk Uchida, Gabriella Gobbi, Joseph Zohar, Allan Young, Dan Rujescu, Ming-Chyi Huang, Suresh Sundram, Lukoye Atwoli, Jana Vukovic, Kazutaka Ikeda

Internal Medicine, East Africa

Background Over the past decade, neuropsychopharmacology has shifted from stagnation to momentum, with first-in-class mechanisms and biomarker-enabled trials spanning psychiatry and neurology.

Methods We narratively synthesized advances from 2013 to 2026 across central nervous system (CNS) discovery and development, including pivotal trials, regulatory actions, digital/real-world evidence, genetics, artificial intelligence (AI), and implementation/global-access themes that are endorsed by international societies.

Results Therapeutic gains include rapid-acting drugs for treatment-resistant depression (intranasal esketamine); psychedelic-assisted therapy for posttraumatic stress disorder and depression; neuroactive steroid γ-aminobutyric acid-A receptor positive allosteric modulators (brexanolone, zuranolone) for postpartum depression; non-dopaminergic muscarinic agonists (xanomeline–trospium) for schizophrenia; orexin receptor antagonists …

Diacylglycerol Kinase Eta As A Novel Target In Nras Mutant Melanoma, Haley P. Wilson, Casey D. Stefanski, Signe Caksa, Glenn L. Mersky, Scott D. Varney, Jelan I. Haj, Dan A. Erkes, Timothy J. Purwin, Vivian Chua, Andrew E. Aplin

Research outputs 2022 to 2026

NRAS mutations occur in 10%–30% of cutaneous melanomas and are associated with high tumor mutational burden. Mutant NRAS signaling drives aberrant cell growth and proliferation, in part, through activation of the RAF–MEK-ERK1/2 kinase pathway; however, targeted therapies to this pathway have limited effectiveness in patients with NRAS mutant melanoma. The role of other targetable signaling pathways in NRAS mutant melanoma is poorly characterized. Here, we demonstrated that one isoform of diacylglycerol kinase, diacylglycerol kinase eta (DGKη), a lipid signaling regulator, was highly expressed in NRAS mutant melanoma patient samples. Knockdown of DGKH in NRAS mutant melanoma cell lines resulted in …

Preclinical Animal Modeling To Investigate Redox-Mediated Molecular Dysfunction In Traumatic Brain Injury, Brandon Z. Mcdonald

Department of Agricultural and Biological Systems Engineering: Dissertations, Theses, and Student Research

Impacts associated with traumatic brain injury (TBI) induce a multitude of neurological morbidities mediated by a spread of biochemical dysfunction. Redox stress is a significant contributor to TBI pathophysiology and several redox stress markers have substantial evidence to support their role in diagnosing preclinical and clinical TBI. However, there is a critical need to verify their translational utility through correlations with behavioral, imaging, and molecular modalities. In chapter two, we examined the therapeutic efficacy of an antioxidant treatment (NPC3) using a controlled cortical impact (CCI) mouse model of TBI. NPC3 alleviated glial expression and reactivity while influencing the expression of …