Translational Medical Research Commons^™

An Observational Study Of The Effect Of Concomitant Levetiracetam On Apixaban Concentrations In A Hospital Cohort, Chazmyn Riley, Kevin Lam, Cristina Micale, Lynda Thomson, Douglas F. Stickle, Walter K. Kraft

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Despite the lack of evidence of a mechanism-based drug interaction, some professional organizations have advised caution coadministering apixaban and levetiracetam. Eligible patients taking apixaban with or without levetiracetam for any indication for at least 72 h were screened from the electronic medical records. Plasma samples from 77 patients were retrieved from salvaged clinical blood collections. Apixaban minimum and maximum concentrations (Cmin and Cmax) were compared using descriptive statistics in R. While the median Cmin and Cmax appear to be marginally elevated, there were no apparent differences relative to apixaban alone. These findings suggest no apparent interaction of levetiracetam and support …

E3 Ligase Rnf145 Regulates Airway Smooth Muscle Cell Proliferation Via The Pp2a-P70s6k Signaling Axis, Vijaya Kumar Gangipangi, Erin O. Curley, Deepak A. Deshpande, Pawan Sharma

Center for Translational Medicine Faculty Papers

Airway smooth muscle (ASM) is a key determinant of airway caliber and a major contributor to structural remodeling in obstructive lung diseases, including asthma and COPD. ASM proliferation is regulated by transcriptional and post-transcriptional mechanisms, including ubiquitin-dependent protein turnover mediated by E3 ubiquitin ligases. Here, we investigated the role of the RING-type E3 ligase RNF145 in mitogenic signaling and ASM cell proliferation. Human ASM cells were transfected with RNF145 shRNA or treated with the E3 ligase inhibitor SMER3, followed by stimulation with fetal bovine serum (FBS) or platelet-derived growth factor (PDGF). RNF145 knockdown or SMER3 treatment dose-dependently inhibited mitogen-induced ASM …

Slc Transporter-Mediated Functional Imaging In Cancer Diagnosis, Lumeng Zhang, Jun He

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Functional imaging has become an important approach for evaluating tumor physiology in vivo beyond morphologic assessment. Radiotracers used for cancer imaging are designed to mimic endogenous substrates or substrate analogues, and their accumulation can depend on membrane transport, intracellular metabolism, and clearance from normal tissues. Specifically, SLC transporters contribute to tracer uptake and signal formation, linking transporter activity with measurable imaging signals in cancer. While [18F]FDG PET/CT remains the most widely used example of transporter-associated metabolic imaging, SLC transporter-mediated imaging strategies have been developed to assess amino acid transport, sodium-dependent glucose uptake, redox metabolism, lactate exchange, nucleoside metabolism, choline metabolism, …

Decorin Promotes Nascent Proteoglycan Retention In Cartilage Matrix By Strengthening Collagen Ii-Aggrecan Integration, Thomas Li, Gabriela Canziani, Yuchen Liu, Neil Patel, Biao Han, Mingyue Fan, Annie Porter, Bryan Kwok, Chao Wang, Qing Li, David E. Birk, Renato V. Iozzo, Irwin M. Chaiken, X. Lucas Lu, Robert L. Mauck, Lin Han

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Cartilage extracellular matrix (ECM), a hydrated collagen II-aggrecan composite, undergoes dynamic turnover during both normal homeostasis and disease-associated remodeling. This study elucidates a crucial role for decorin in promoting the retention and stability of nascent aggrecan within this matrix. By applying bio-orthogonal click-labeling, we demonstrate that loss of decorin accelerates the release of nascent aggrecan under both physiological and inflammatory conditions, without affecting its preferential localization to the pericellular matrix. Conversely, supplementation with exogenous decorin mitigates inflammation-induced loss of nascent aggrecan, supporting its potential as a therapeutic target. At the molecular level, decorin exhibits strong binding affinity for aggrecan, and …

A Predictive Coding Account Of Spatial Working Memory Following Prophylactic Levetiracetam Administration Prior To Traumatic Brain Injury, Omeima Mutwali

Dissertations, Theses, and Capstone Projects

Traumatic brain injury (TBI) symptom prevention and remediation is an important area of research that would benefit vulnerable groups, including active-duty and veteran soldiers. These patients can sustain penetrative forces in fields of combat or in training, which result in focal lesions that trigger inflammatory and degenerative processes in the brain. Both primary and secondary injuries are associated with changes to cognition, behavior and affective state. This disease poses increased risk of epileptogenesis, as well. Given these outcomes, prior research has evaluated levetiracetam (LEV) as a prophylactic treatment for seizures, cognitive deficits and negative emotionality. LEV acts as a presynaptic …

Clonal Reshaping And Clinical Outcomes After Rechallenge In Ici-Associated Myocarditis: Integrated Single-Cell And Tcr Repertoire Analysis, Jian Zhang, Xiaozhen He, Yerui Zhang, Xianling Qian, Yu Song, Shilong Zhang, Zheng Li, Zhiming Wang, Bo Lu, Qingqing Cai, Leilei Cheng, Yan Wang

Center for Translational Medicine Faculty Papers

BACKGROUND: Immune checkpoint inhibitor-associated myocarditis (ICIAM) poses significant challenges for cancer immunotherapy, particularly regarding the safety and efficacy of immune checkpoint blockade (ICB) rechallenge.

METHODS: The present study analyzed 23 cases of ICIAM by integrating longitudinal clinical data with single-cell RNA sequencing and T-cell receptor profiling of peripheral blood mononuclear cells (PBMCs) obtained from three representative patients before and after ICB rechallenge. The single-cell cohort comprised two patients who experienced recurrent irAEs upon rechallenge and one patient who did not develop recurrent irAEs.

RESULTS: Among 12 patients (52%) who experienced recurrent irAEs upon rechallenge, myocarditis recurrence occurred in 8 cases, …

Acidic Extracellular Ph-Induced Pth Secretion In Male Mouse Parathyroids Is Ogr1-Dependent, Yanmei Yang, Mengcun Chen, Mingshu Cui, Elisabeth Lashbrooks, Bin Wang

Center for Translational Medicine Faculty Papers

The role of extracellular acidity in regulating PTH secretion in cultured mouse parathyroid glands (PTGs) has not been studied to date, largely because of the technical difficulty of isolating mouse PTGs. We hypothesized that acidic extracellular pH directly stimulates PTH secretion through activation of a proton-sensing receptor, specifically ovarian cancer G protein-coupled receptor 1 (OGR1, also known as GPR68). To test this, we developed a method to reliably identify and isolate PTGs from male mice by administering 5-aminolevulinic acid, which induced selective fluorescence in these glands. Using this model, we demonstrate that acidic extracellular pH significantly stimulates PTH secretion in …

Acidic Extracellular Ph-Induced Pth Secretion In Male Mouse Parathyroids Is Ogr1-Dependent, Yanmei Yang, Mengcun Chen, Mingshu Cui, Elisabeth Lashbrooks, Bin Wang

Center for Translational Medicine Faculty Papers

The role of extracellular acidity in regulating PTH secretion in cultured mouse parathyroid glands (PTGs) has not been studied to date, largely because of the technical difficulty of isolating mouse PTGs. We hypothesized that acidic extracellular pH directly stimulates PTH secretion through activation of a proton-sensing receptor, specifically ovarian cancer G protein-coupled receptor 1 (OGR1, also known as GPR68). To test this, we developed a method to reliably identify and isolate PTGs from male mice by administering 5-aminolevulinic acid, which induced selective fluorescence in these glands. Using this model, we demonstrate that acidic extracellular pH significantly stimulates PTH secretion in …

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

Center for Translational Medicine Faculty Papers

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

Imbalance In Wnt: Retinoic Acid Signaling Dysregulates Hox Gene Expression: Implications For Cancer Stem Cell Heterogeneity And Crc Patient Survival, Brian Osmond, Chi Zhang, Pascal K. Kataboh, Caroline O. B. Facey, Lynn M. Opdenaker, Bruce M. Boman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

How HOX transcription factors play a role in the stem cell (SC) origin of cancer is unclear. Our goal is to determine how dysregulation of HOX gene expression promotes colorectal cancer (CRC) development through aberrant SC regulatory mechanisms. We investigated retinoic acid (RA) and WNT signaling because they regulate HOX expression and both pathways are dysregulated in cancer. Previously, we reported WNT and RA pathways are functionally linked, and in CRC, APC mutation generates a WNT:RA imbalance leading to incomplete differentiation and SC overpopulation. We hypothesize that aberrant WNT- and RA-signaling dysregulates HOX expression that contributes to the SC origin …

Rhythms Of Hippocampal Function And Memory After Moderate Prenatal Alcohol Exposure, Lilliana May Sanchez

Psychology ETDs

Fetal Alcohol Spectrum Disorders involve morphologic and neurobiological abnormalities in offspring subjected to prenatal alcohol exposure. Although not as well studied as high exposure, moderate prenatal alcohol exposure represents the most common and undetected form in humans. While learning and memory deficits have been well characterized at the behavioral level in humans with Fetal Alcohol Spectrum Disorders and in animal models of moderate prenatal alcohol exposure, few studies have determined the circuit or systems level mechanisms of the behavioral deficits. A complete understanding of the neural bases of memory deficits after moderate prenatal alcohol exposure is needed to ultimately identify …

Multiple Interest Holder Perspectives Of The True Grit Sci Residential Program: A Mixed Methods Program Evaluation, Keara Mcnair

Seton Hall University Dissertations and Theses (ETDs)

Young adults with spinal cord injury (SCI) face significant challenges during the transition to adulthood, including barriers to independence, community participation, and psychosocial adjustment (Ingimarsdóttir et al., 2023; Zebracki et al., 2010). Current rehabilitation models in the United States prioritize short-term physical recovery and offer limited support for the developmental and contextual needs that shape long-term outcomes after SCI, particularly during transitions from inpatient rehabilitation to the community (Anderson et al., 2024; Bryden & Gran, 2024). Community-based programs may help address these gaps, though few have been rigorously evaluated using implementation science frameworks that attend to health equity, contextual influences, …

Type-1 Ryanodine Receptor Plays An Important Role In Cardiac Hypertrophy And Heart Failure By Increasing Type-2 Ryanodine Receptor-Mediated Calcium Release, Yong-Xiao Wang, Ed Wilson Santos, Sarahann Mistretta, Yuexing Yuan, Harold A. Singer, Shey-Shing Sheu, Yun-Min Zheng

Center for Translational Medicine Faculty Papers

Type-1 ryanodine receptor (RyR1) is essential for skeletal muscle contraction. This Ca²⁺ release channel is expressed in cardiac myocytes; however, its function remains elusive. Cardiac-specific RyR1 overexpression (OE) mice were generated under the cardiac-specific Myh6 promoter. Cardiac hypertrophy (CH), cardiac functions, and mechanistic changes in RyR1 OE and control (wildtype, WT) mice were assessed using hematoxylin and eosin staining, echocardiography, electrocardiogram, quantitative RT-PCR, Western blotting, [³H]-ryanodine binding assay, confocal microscope, ROS dye Amplex Red and 2′,7′-dichlorofluorescein diacetate. RyR1 OE mice had increased whole heart, left ventricular weight, and left ventricular wall thickness, but decreased cardiac output and …

The Effects Of Acute Exercise And Observation On Procedural Learning: Considerations Of Biological Sex, Madeline R. Gossett

Honors Theses

As memories are formed or learning progresses, neurons within the brain establish a strong connection in what is referred to as a “neural engram.” This neural engram can be strengthened or weakened by certain physiological factors. Dopamine, for example, is released during physical exercise or when positive reinforcement is incorporated (Greenwood, 2019). This is a neurotransmitter that leads to a stronger connection between neurons, which in turn leads to a stronger memory formed in the brain. These physiological relationships that contribute to cognition are still being discovered, so research in this area is ongoing (Guskjolen and Cembrowski, 2023).

Memory is …

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 …

Feeding The Future: Prenatal Dietary Effects On Offspring Neurodevelopment, Emma Whatley

Senior Honors Theses

This study examined the effects of prenatal Western (WD) and Mediterranean (MD) diets on offspring metabolic, cognitive, and neurobiological outcomes in a preclinical mouse model. Working and long-term memory performance, dendritic morphology, and gene expression were assessed using behavioural tests (CAL, YMRM, WM) and Golgi-Cox analyses. Behavioural effects were minimal, with female MD offspring showing improved memory performance under standard conditions. Metabolic findings showed effects on body weight and blood glucose. Dendritic morphology was largely unchanged; however, subtle, sex-specific differences were observed. Differential gene expression between MD and WD suggests a role for future environmental stressors. Prenatal diet affects molecular …

The Impact Of Increased Beef Intake On Cardiometabolic Health In Postmenopausal Women: A 16-Week Randomized Controlled Trial, Leen Samman

Biological Sciences Undergraduate Honors Theses

By 2030, it is projected that the number of post-menopausal women globally will reach 1.2 billion. Moreover, because of increases in life expectancy, women will spend a greater proportion of their later years at elevated risk of chronic disease associated with the hormonal changes of the menopausal transition. Dietary interventions, specifically high-protein diets have shown potential mitigating effects; however, most interventions have focused on total protein intake or protein supplements, not whole foods like lean beef. This randomized controlled trial aimed to assess the effects of daily lean beef consumption as part of a higher protein diet on cardiometabolic markers …

Ai×Life 2026: Advances In Computational Biology Across Scales For Life & Health Sciences, Suma Mohan S., Devika N. T., Pranavathiyani G.

Conference Proceedings

Book of Abstracts of the International Conference, AIxLife 2026: Advances in Computational Biology Across Scales for Life & Health Sciences, held on 17–18 April 2026, SASTRA Deemed to be University, Thanjavur, Tamil Nadu, INDIA 

About the Conference

Conventional computational biology laid the foundation for biological data analysis through statistical models, algorithms, and curated databases, enabling insights into genes, proteins, and pathways. Today, the integration of artificial intelligence, spanning machine learning, deep learning, and large language models (LLMs) is driving a transformative shift across biological scales, from atomic and molecular interactions to pathways, cellular systems, organisms, and populations.

AI-powered approaches …

Improving Functional Electrical Stimulation Prescription For Persons With Multiple Sclerosis: A Case Series, Kurt Jackson

Thomas C. Hunt Building a Research Community Day

Purpose: Despite a growing body of evidence supporting the use of functional electrical stimulation (FES) in persons with MS (PwMS), prescription remains a highly individualized process with no well-established guidelines for assessing the immediate or long-term effects to ensure maximum benefit.  The purpose of this case series was to assess the feasibility and benefits of using wearable sensors and video analysis to provide immediate feedback on gait performance, when using lower leg and thigh stimulation individually or in combination, to improve FES prescription.

Subjects: 3 adults with multiple sclerosis (MS) with varying levels of gait dysfunction.

Methods: During …

Nurse Driven Intervention To Address Cesarean Section Rates, Cavetta Tulloch-Lewis

Doctor of Nursing Practice (DNP) Translational and Clinical Research Projects

Abstract

Cesarean sections (C-sections) account for approximately one-third of births in the United States and remain the most common inpatient surgical procedure. Primary cesarean sections are a major contributor to rising rates, often leading to repeat cesareans in subsequent pregnancies. While medically necessary C-sections are lifesaving, their overuse in low-risk pregnancies is associated with increased maternal morbidity. Labor dystocia is one of the leading indications for primary cesarean delivery and may be mitigated through evidence-based, nurse-driven interventions such as maternal positioning and peanut ball utilization. Registered nurses are uniquely positioned to influence labor progression and promote vaginal birth through continuous …