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Towards A Unified Gating Scheme For The Cnbd Ion Channel Family, Jenna L Lin, Baron Chanda Jan 2026

Towards A Unified Gating Scheme For The Cnbd Ion Channel Family, Jenna L Lin, Baron Chanda

2020-Current year OA Pubs

Cyclic nucleotide-binding domain (CNBD) channels are critical components of numerous bioelectrical processes, including cardiac pacemaking, neuronal signaling, phototransduction in the eye, and stomatal regulation in plants. While members of this channel family share a conserved overall structure, they exhibit striking differences in voltage sensitivity. Hyperpolarization-activated cyclic nucleotide-gated channels are activated by membrane hyperpolarization, whereas ether-à-go-go channels open upon depolarization. Mutagenesis and chimeragenesis studies have revealed that some mutants display bipolar gating behavior-remaining closed at intermediate membrane potentials but capable of opening in response to both hyperpolarization and depolarization. Remarkably, in certain cases, just a few mutations are sufficient to reverse …


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 Jan 2026

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 …


Β2 And Β3a Regulatory Subunits Can Coassemble In The Same Bk Channels, Yu Zhou, Vivian Gonzalez-Perez, Xiao-Ming Xia, Gopal S Kallure, Sandipan Chowdhury, Christopher J Lingle Jan 2026

Β2 And Β3a Regulatory Subunits Can Coassemble In The Same Bk Channels, Yu Zhou, Vivian Gonzalez-Perez, Xiao-Ming Xia, Gopal S Kallure, Sandipan Chowdhury, Christopher J Lingle

2020-Current year OA Pubs

Ca2+- and voltage-activated BK-type K+ channels are influenced profoundly by associated regulatory subunits, including β subunits (Kcnmb1-4; β1-β4). Although overlap in expression of different BK β subunits occurs in native tissues, whether they can coassemble in the same channel complex is not known. We coexpress β2 and β3a subunits together with BK α and, through a combination of macroscopic and single-channel recordings, along with quantitative pull-down of tagged subunits, test whether coassembly can occur. We evaluate two models: (1) random mixing in which β2 and β3a subunits coassemble in the same channels, and (2) segregation in which β2 and β3a …


Micrornas In Prostate Cancer Liquid Biopsies: Early Detection, Prognosis, And Treatment Monitoring, Seyyed Mohammad Yaghoubi, Erfan Zare, Sina Jafari Dargahlou, Maryam Jafari, Mahdiye Azimi, Maedeh Khoshnazar, Solmaz Shirjang, Behzad Mansoori Jan 2026

Micrornas In Prostate Cancer Liquid Biopsies: Early Detection, Prognosis, And Treatment Monitoring, Seyyed Mohammad Yaghoubi, Erfan Zare, Sina Jafari Dargahlou, Maryam Jafari, Mahdiye Azimi, Maedeh Khoshnazar, Solmaz Shirjang, Behzad Mansoori

Student Papers, Posters & Projects

Prostate cancer (PCa) is a common malignancy in men worldwide, with incidence projected to rise in the coming years. Traditional screening and diagnostic methods, such as prostate-specific antigen (PSA) testing and biopsy, face limitations in specificity and invasiveness. Circulating microRNAs (miRNAs) have emerged as stable, non-invasive biomarkers obtainable via liquid biopsies (blood, urine, semen) that could transform PCa management. These small regulatory RNAs reflect underlying tumor biology and are detectable at early disease stages, enabling improved early detection when used alongside or in place of PSA. Distinct miRNA expression patterns correlate with tumor aggressiveness. For example, miR-141 and miR-375 are …


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 Jan 2026

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 …


Optimal Intervention Strategies In Age-Structured Sirvd Model: Epidemiological And Economic Analysis Of Covid-19 In Korea, Joon Chun, Melisa Hendrata Jan 2026

Optimal Intervention Strategies In Age-Structured Sirvd Model: Epidemiological And Economic Analysis Of Covid-19 In Korea, Joon Chun, Melisa Hendrata

Spora: A Journal of Biomathematics

This study employed an age-structured Susceptible-Infected-Recovered-Vaccinated-Deceased (SIRVD) model to design optimal COVID‑19 intervention strategies by integrating epidemiological dynamics with economic costs. Using empirical data from South Korea, we estimated transmission parameters and analyzed quarantine-based non-pharmaceutical interventions (NPIs) alongside targeted vaccination scenarios. Our results indicated that a stronger form of mild NPI (upper range of Level I), when combined with targeted vaccination that prioritized seniors, achieved substantial reductions in infection peaks and overall economic burden. These findings underscore the effectiveness of age-specific strategies in epidemic management and offer critical insights for policymakers seeking balanced, resource-efficient approaches.


Sheep Umbilical Cord Mesenchymal Stem Cells: Biological Characteristics, Ethical Considerations, And Translational Applications, Hasan M. Agha, Mohammed A. Abdalqader, Oh Chin Kin Michelle, Sabaa M. Agha, Jantson Hoh, Abdulmutalib Alabeed Allaq, Amjad Abdulhadi Mohammed, Muneer Mohammed Saleh Alsayadi Jan 2026

Sheep Umbilical Cord Mesenchymal Stem Cells: Biological Characteristics, Ethical Considerations, And Translational Applications, Hasan M. Agha, Mohammed A. Abdalqader, Oh Chin Kin Michelle, Sabaa M. Agha, Jantson Hoh, Abdulmutalib Alabeed Allaq, Amjad Abdulhadi Mohammed, Muneer Mohammed Saleh Alsayadi

AUIQ Complementary Biological System

Mesenchymal stem cells (MSCs) are widely used in regenerative medicine due to their self-renewal capacity, multilineage differentiation potential, and paracrine activity. Limitations associated with the sourcing and scalability of human MSCs have increased interest in xenogeneic alternatives, particularly sheep umbilical cord–derived MSCs (sUC-MSCs). These cells display high proliferative capacity, stable karyotypes, and a typical MSC immunophenotype (CD44, CD73, CD90, CD105), with low basal immunogenicity. sUC-MSCs exhibit osteogenic, chondrogenic, and adipogenic differentiation potential and secrete angiogenic and immunomodulatory factors, including VEGF, HGF, IGF-1, TGF-β, and IL-10. Owing to their biological similarities to human MSCs and accessibility from perinatal tissue, …


Circadian-Shaped Immune Variability Predicts Infection Outcome, Jonathan Lalsiamthara, Mariko Locke, Alejandro Aballay Jan 2026

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 …


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 Jan 2026

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 Jan 2026

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 …


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 Jan 2026

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 …


Impaired Complement Regulation Drives Chronic Lung Allograft Dysfunction After Lung Transplantation, Hrishikesh S. Kulkarni, Laneshia K. Tague, Fuyi Liao, Zhiyi Liu, Lorena Garnica, Nishanth R. Shankar, Xiaobo Wu, Dequan Zhou, Yan Tao, Victoria E. Davis, Cory T. Bernardt, Derek E. Byers, Chad A. Witt, Daniel Kreisel, John P. Atkinson, Andrew E. Gelman, Et Al. Jan 2026

Impaired Complement Regulation Drives Chronic Lung Allograft Dysfunction After Lung Transplantation, Hrishikesh S. Kulkarni, Laneshia K. Tague, Fuyi Liao, Zhiyi Liu, Lorena Garnica, Nishanth R. Shankar, Xiaobo Wu, Dequan Zhou, Yan Tao, Victoria E. Davis, Cory T. Bernardt, Derek E. Byers, Chad A. Witt, Daniel Kreisel, John P. Atkinson, Andrew E. Gelman, Et Al.

2020-Current year OA Pubs

A greater understanding of chronic lung allograft dysfunction (CLAD) pathobiology, the primary cause of death after lung transplantation (LTx), is needed to improve outcomes. The complement system links innate to adaptive immune responses and is activated early after lung transplantation to form C3 convertase, a critical enzyme that cleaves the central complement component C3. We hypothesized that LTx recipients with a genetic predisposition to enhanced complement activation have worse CLAD-free survival mediated through increased adaptive alloimmunity. We interrogated a known functional C3 polymorphism (C3 R102G) that increases complement activation through impaired C3 convertase inactivation in 2 independent LTx recipient cohorts. …


The Prophylactic Effect Of Aqueous Chamomile Extract On Nitrogen Dioxide Exposed Mice, Mariam Kbaysi, Ruzanna Petrosyan, Jamilah Borjac Jan 2026

The Prophylactic Effect Of Aqueous Chamomile Extract On Nitrogen Dioxide Exposed Mice, Mariam Kbaysi, Ruzanna Petrosyan, Jamilah Borjac

BAU Journal - Science and Technology

Nitrogen dioxide (NO₂) a gaseous air pollutant resulting from industrial activities. It has been associated to various diseases related to oxidative stress and inflammation, including cardiovascular and nervous system disorders. Chamomile is mainly recognized for its high content of antioxidant flavonoids and is extensively utilized in herbal medicine for treating several disorders. The aim of this study is to examen the protective effects of chamomile extract against NO₂-induced damage in female mice. Balb/c mice were divided into four groups: control, chamomile extract, NO2 derivatives, and NO2 derivatives combined with chamomile extract. Upon completion of the study, Blood was …


Comparing Autografts And Bioengineered Skin Equivalents In The Management Of Severe Burns, Madison Hill Jan 2026

Comparing Autografts And Bioengineered Skin Equivalents In The Management Of Severe Burns, Madison Hill

The PA Department Journal of Medical Science

INTRODUCTION: Severe burns are associated with high morbidity, mortality, and treatment costs, often requiring surgical intervention to restore the skin barrier and prevent complications like infection and hypothermia. Autologous skin grafting is the current gold standard for burn wound closure but may not be feasible in cases of large TBSA injuries with limited donor sites. Bioengineered skin equivalents, including acellular dermal substitutes and cell-based therapies, offer potential benefits in wound healing and scar quality while reducing donor site morbidity. This review evaluates the effectiveness of autografts compared to bioengineered skin equivalents in severe burn management, with a focus on healing …


Extracorporeal Shockwave Therapy For Plantar Fasciitis Pain Reduction, Nathan J. Lopez Jan 2026

Extracorporeal Shockwave Therapy For Plantar Fasciitis Pain Reduction, Nathan J. Lopez

The PA Department Journal of Medical Science

Introduction: Plantar fasciitis (PF), aka plantar heel pain (PHP), is a degenerative and debilitating musculoskeletal condition that is prevalent across various populations. There is some debate concerning the hierarchy of second-line treatment options. The purpose of this article is to compare the efficacy, as it relates to pain reduction, of extracorporeal shockwave therapy (ESWT) and other invasive, non-surgical interventions (injections, dry needling, etc.).

Methods: PubMed was searched using a specific search strategy with key terms "extracorporeal shockwave therapy" and "plantar fasciitis". Operators and filters were then applied to narrow results to 4 relevant and quality articles for review. …


Effects Of Angiotensin-Converting Enzyme Inhibitors And Angiotensin Receptor Blockers On Covid-19 Outcomes In Severely Ill Patients, Madison L. Edwards Jan 2026

Effects Of Angiotensin-Converting Enzyme Inhibitors And Angiotensin Receptor Blockers On Covid-19 Outcomes In Severely Ill Patients, Madison L. Edwards

The PA Department Journal of Medical Science

Introduction: Coronavirus disease 2019 (COVID-19) is a contagious disease caused by the virus SARS-CoV-2 and can cause debilitating illness in vulnerable patient populations. The purpose of this clinical review is to analyze the effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on the clinical course and severity in COVID-19 adult patients.

Methods: PubMed was searched with a specific search strategy using key terms “adult,” “COVID-19,” and “RAAS inhibiting medications.” Specific operators and filters narrowed the results to a total of five relevant, quality articles for review.

Results: Two articles were randomized controlled trials that directly compared the continuation of …


Implementing An Anxiety Management Bundle In Long-Term Nursing Facilities, Sundan G. Bryson Jan 2026

Implementing An Anxiety Management Bundle In Long-Term Nursing Facilities, Sundan G. Bryson

Doctor of Nursing Practice (DNP) Scholarly Projects - Archive

There is currently a gap in accurate screening and treatment of anxiety in Long-Term Care (LTC) nursing facilities. The question for this quality improvement project was: Will implementing interventions for long-term care residents aged 65 and older improve anxiety screening, non-pharmacological interventions, and mental health referrals by 10% compared to current practices? Interventions to enhance anxiety screening included the Geriatric Anxiety Scale-Long Term Care (GAS-LTC) tool to assess and score anxiety. In addition, a Non-Pharmacological Intervention (Non-PI) tool was created to evaluate interventions performed by facility staff. Referrals to the mental health care provider were submitted if a resident scored …


Programming Macrophage Phenotypes And Promoting Ischemic Heart Repair With Precision Immunomodulatory Therapy, Jing Zhang Jan 2026

Programming Macrophage Phenotypes And Promoting Ischemic Heart Repair With Precision Immunomodulatory Therapy, Jing Zhang

Dissertations and Theses

Despite significant advances in reperfusion and pharmacological therapies, effective strategies to modulate the post-infarction inflammatory response remain limited, leaving a critical gap in improving cardiac repair and long-term outcomes. Excessive or prolonged inflammation after myocardial infarction (MI) drives cardiac remodeling and fibrosis, impairing myocardial recovery and increasing the risk of heart failure (HF) or recurrent ischemic events. I hypothesize that appropriate immunomodulation after MI may reduce unwanted inflammation and improve heart function. Interleukin‑10 (IL‑10) is a pleiotropic immunomodulatory cytokine with therapeutic promise for limiting excessive inflammation and improving tissue repair in ischemic hearts. However, two translational barriers remain for applying …


The Impact Of Nurse-Led Distraction Techniques On Pain And Anxiety During Cancer Treatment In Pediatric Oncology Patients: Examining Virtual Reality And Play Therapy, Alexis Abalos Jan 2026

The Impact Of Nurse-Led Distraction Techniques On Pain And Anxiety During Cancer Treatment In Pediatric Oncology Patients: Examining Virtual Reality And Play Therapy, Alexis Abalos

Nursing | Senior Theses

Children undergoing cancer treatment often experience pain and anxiety during cancer treatment, including chemotherapeutic invasive procedures such as frequent port access or peripheral catheterization. Nurse-led distraction techniques, including virtual reality and play therapy, have emerged as promising non-pharmacologic interventions to reduce levels of pain and anxiety in pediatric oncology patients. This thesis analyzes existing data through a close examination of primary and secondary research articles that prove the effectiveness of virtual reality and play therapy on reducing pain, anxiety, and psychosocial distress in pediatric oncology patients receiving cancer treatment. Using the University of California, San Francisco (UCSF) Symptom Management Theory, …


A Flupirtine Benzyl Carbamate Improves Neurocognitive Deficits And Molecular Pathology In The Cln6nclf Mouse, Victoria Chaoul, Omar Shmoury, Ramy Alam, Sara Saab, Joelle Makoukji, Lynn Al Aridi, Nadine J. Makhoul, Jihane Soueid, Angelica V. Carmona, Princess Simeon, Paul C. Trippier, Rose-Mary Boustany Jan 2026

A Flupirtine Benzyl Carbamate Improves Neurocognitive Deficits And Molecular Pathology In The Cln6nclf Mouse, Victoria Chaoul, Omar Shmoury, Ramy Alam, Sara Saab, Joelle Makoukji, Lynn Al Aridi, Nadine J. Makhoul, Jihane Soueid, Angelica V. Carmona, Princess Simeon, Paul C. Trippier, Rose-Mary Boustany

Journal Articles: Pharmaceutical Sciences

Neuronal ceroid lipofuscinosis type 6 (CLN6) is a fatal, autosomal recessive neurodegenerative disorder characterized by cognitive/motor impairment, vision loss, as well as neuronal loss and gliosis in the brain, and premature death. Onset typically occurs in childhood. No approved pharmacological treatments exist that halt or reverse disease progression. A novel flupirtine benzyl carbamate was orally administered to male and female Cln6nclf mice from 4 to 28 weeks of age to evaluate its neuroprotective and antispastic effects. Drug treatment produced significant, sex-dependent phenotypic improvements. Treated mice of both sexes exhibited reduced hindlimb spasticity, but only treated males demonstrated diminution in …


Investigating Neonatal Sepsis: Anti-Infectives, Diagnostics And Guidelines Used In Health Systems Across Sub-Saharan Africa – The Insights Study, Jack Louis Stanley, David Hettle, Rachel Poffley, Larisse Bolton, Emelyne Gres, Isabel Coelho, Raana Hussain, Gildas Boris Hedible, Gwendoline Lilly Chimhini, Valeriane Leroy Jan 2026

Investigating Neonatal Sepsis: Anti-Infectives, Diagnostics And Guidelines Used In Health Systems Across Sub-Saharan Africa – The Insights Study, Jack Louis Stanley, David Hettle, Rachel Poffley, Larisse Bolton, Emelyne Gres, Isabel Coelho, Raana Hussain, Gildas Boris Hedible, Gwendoline Lilly Chimhini, Valeriane Leroy

Paediatrics and Child Health, East Africa

Background Sepsis is a leading cause of neonatal mortality in sub-Saharan Africa (SSA), where microbiological diagnostic capacity and antibiotic access are limited. High antimicrobial resistance (AMR) rates limit the effectiveness of current treatment guidelines, with concern that available antibiotics are rarely adequate treatment for neonatal sepsis in the region.

Methods A cross-sectional online survey was electronically distributed in English, French and Portuguese to neonatal clinicians across SSA between April and June 2025. Questions focused on the management of neonatal sepsis including diagnostic, antibiotic and guideline use. Responses were analysed descriptively and presented as percentages of the total number of responses. …


Evaluation Of Peptides And Peptide–Doxorubicin Conjugates Designed And Synthesized For Targeting Triple-Negative Breast Cancer Via Cell-Surface Receptors, Shih-Jing (Jane) Yao Jan 2026

Evaluation Of Peptides And Peptide–Doxorubicin Conjugates Designed And Synthesized For Targeting Triple-Negative Breast Cancer Via Cell-Surface Receptors, Shih-Jing (Jane) Yao

Pharmaceutical Sciences (PhD) Dissertations

A significant problem faced in oncology is the lack of chemotherapeutic agents that are tumor site-specific, resulting in reduced therapeutic efficacy and unintended infliction of harm to surrounding healthy tissues and cells that often lead to serious side effects. Current strategies being explored to circumvent this issue aim to refine delivery of  chemotherapeutic agents specifically to tumor sites, which may be achieved via conjugation of these agents to biomarker-specific ligands. This forms the foundation of ligand-targeted drug delivery. Among different breast cancers, treatment of the triple-negative breast cancer (TNBC) subtype has been particularly challenging, largely due to the absence of …


Amyloid Β-Cholesterol Interplay: Removal Of Cholesterol From The Membranes To Catalyze Aggregation And Amyloid Pathology, Rishiram Baral, Ruan Van Deventer, Yuri L. Lyubchenko Jan 2026

Amyloid Β-Cholesterol Interplay: Removal Of Cholesterol From The Membranes To Catalyze Aggregation And Amyloid Pathology, Rishiram Baral, Ruan Van Deventer, Yuri L. Lyubchenko

Journal Articles: Pharmaceutical Sciences

The interplay between the cholesterol metabolism and assembly of Aβ42 (the 42-residue form of the amyloid-β peptide) peptides in pathological aggregates is considered one of the major molecular mechanisms in the development of Alzheimer's disease (AD). Numerous in vitro studies led to the finding that high cholesterol levels in membranes accelerate the production of Aβ aggregates. The molecular mechanisms explaining how cholesterol localized inside the membrane bilayer catalyzes the assembly of Aβ aggregates above the membrane remain unknown. We addressed this problem by combining different AFM modalities, including imaging and force spectroscopy, with fluorescence spectroscopy. Our combined studies revealed that …


Compensatory Responses To Glaucoma Pathology In The Dorsolateral Geniculate Nucleus, Shaylah Mccool, Arnav Jain, Jennie C. Smith, Victoria L. Schaal, Gurudutt Pendyala, Sowmya V. Yelamanchili, Matthew J. Van Hook Jan 2026

Compensatory Responses To Glaucoma Pathology In The Dorsolateral Geniculate Nucleus, Shaylah Mccool, Arnav Jain, Jennie C. Smith, Victoria L. Schaal, Gurudutt Pendyala, Sowmya V. Yelamanchili, Matthew J. Van Hook

Journal Articles: Anesthesiology

Glaucoma disrupts the conveyance of retinal signals to visual regions of the brain such as the dorsolateral geniculate nucleus (dLGN) due to degeneration of retinal ganglion cells (RGCs) and their axons. Although plasticity during development allows altered visual experience to modulate dLGN synapses and excitability, evidence for experience-dependent dLGN plasticity in adults is limited. However, glaucoma might trigger compensatory plasticity in adult dLGN, thereby compensating for diminished RGC synaptic drive. Here, we tested this theory using aged DBA/2J mice, which develop high intraocular pressure and glaucoma. In brain slice recordings, we found that diminished RGC inputs could drive robust action …


Differential Sensitivity Of Leukocyte Populations To Staphylococcus Aureus Biofilm, Nichole D. Brandquist, Tammy Kielian Jan 2026

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 Jan 2026

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 …


Examining The Association Between Ddt Exposure And Parkinson’S Disease, Hodges Mccathern Jan 2026

Examining The Association Between Ddt Exposure And Parkinson’S Disease, Hodges Mccathern

Undergraduate Honors Theses

Dichlorodiphenyltrichloroethane, commonly known as DDT, was an organochlorine pesticide widely used in the mid-20th century. It is highly stable and resistant to degradation, leading to its long-term presence in the environment. This chemical bioaccumulates in ecosystems and in human tissue, particularly adipose tissue, raising concerns about chronic exposure. Emerging research links DDT exposure to adverse neurological outcomes, including increased risk for neurodegenerative disorders such as Parkinson’s Disease. Mechanistically, DDT and its metabolites may disrupt dopaminergic neurons, induce oxidative stress, and interfere with mitochondrial function, contributing to neurotoxicity. Understanding the environmental fate of DDT and its bioaccumulative properties is essential for …


The Association Between Personal Particulate Matter Exposures And Cognitive Function Among Stroke Patients, Kentucky, Usa, Nana Afua Ankomah Dei Jan 2026

The Association Between Personal Particulate Matter Exposures And Cognitive Function Among Stroke Patients, Kentucky, Usa, Nana Afua Ankomah Dei

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Stroke, a major cause of long-term disability and cognitive problems in the U.S., significantly affects people’s quality of life. Exposure to particulate matter (PM2.5) may result in systemic inflammation and oxidative stress, which can worsen the cognitive function of post-thrombectomy stroke patients. This project thus assessed the relationship between PM2.5 exposure and its effect on the cognitive function of post-thrombectomy stroke patients. Fifteen stroke patients (9 non-Appalachian and 6 Appalachian) undergone thrombectomy were recruited. Personal PM2.5 exposure was measured using wearable sensors for a week during the study period. Montreal Cognitive Assessment (MoCA) scores and covariates …


Advancing Menstrual Health And Hygiene In Rural Kenya: A Guideline Based Approach, Tessia R. Winnfield Jan 2026

Advancing Menstrual Health And Hygiene In Rural Kenya: A Guideline Based Approach, Tessia R. Winnfield

Doctor of Nursing Practice (DNP) Scholarly Projects - Archive

Objective: To develop an evidence-based clinical practice guideline for menstrual health management addressing menstrual education, teacher training, menstrual school absenteeism, male student engagement, pain management, and provision of menstrual kits with product options.

Design: This evidence-based practice guideline development project used the Agency of Healthcare Research and Quality (AHRQ) Framework and the Johns Hopkins Nursing Evidence-Based Practice Model (JHNEBP). I conducted a systematic literature review and a critical appraisal to identify best practices for menstrual hygiene interventions in rural communities.

Setting: The guideline development occurred within an academic Doctor of Nursing Practice program focused on rural communities.

Participants: Seven stakeholders …


Identifying Relevant Covariates In Rna-Seq Analysis By Pseudo-Variable Augmentation, Yet Nguyen, Dan Nettleton Jan 2026

Identifying Relevant Covariates In Rna-Seq Analysis By Pseudo-Variable Augmentation, Yet Nguyen, Dan Nettleton

Mathematics & Statistics Faculty Publications

RNA-sequencing (RNA-seq) technology allows for the identification of differentially expressed genes, which are genes whose mean transcript abundance levels vary across conditions. In practice, RNA-seq datasets often include covariates that are of primary interest in addition to a set of covariates that are subject to selection. Some of these covariates may be relevant to gene expression levels, while others may be irrelevant. Ignoring relevant covariates or attempting to adjust for the effect of irrelevant covariates can compromise the identification of differentially expressed genes. To address this issue, we propose a variable selection method that uses pseudo-variables to control the expected …