Digital Commons Network^™

Manuka Honey Modulates Oxidative Stress In Neuro2-A Cells Through Mitochondrial Regulation, Rachel Abramovici

Honors Undergraduate Theses

Manuka honey is known for its vital usage in wound healing, being an agonist towards fighting infections, and is an acting antioxidant [32]. Its main constituents are flavonoids and phenolic compounds, with methyl syringate (MSYR) being a major active ingredient. The specific compounds responsible for these antioxidant effects, particularly in the CNS, remain unclear. It is hypothesized that pre-treatment of mouse neuroblastoma cells with MSYR followed by hydrogen peroxide exposure will activate the AMPK/SIRT1/PGC-1a pathway, due to MSYR’s phenolic structure, and thus reduce oxidative stress and improve mitochondrial biogenesis. Hydrogen peroxide is a standard reactive oxygen species (ROS) treatment to …

Bodies Of Knowledge: The Accuracy Of Medical Anatomical Drawings From The 14th To The 18th Century, Marina G. Mitchell

Honors Undergraduate Theses

From the fourteenth to the eighteenth centuries, European anatomical illustration underwent major transformations in response to changing scientific methods, technologies, and visual conventions, reflecting critical transitions in anatomical history. Scientific evolution allowed these images to achieve increasing structural precision and internal detail, though they frequently diverged from anatomical forms as they are understood today. This study examines how anatomical inaccuracies across five centuries emerged not from ignorance, but from deliberate mediation between purpose, observation, pedagogy, artistic convention, and cultural ideology. Through close analysis of works in visual comparison to their modern counterparts, this thesis identifies specific deviations from the twenty-first …

Rac1 Gtpase Regulates The Scfβtrcp-Mediated Degradation Of Claspin And The Cellular Response Of Pancreatic Cancer Cells To Gamma Rays, Neha Chaudhary, Tabbatha N. Somers, Surinder K. Batra, Ying Yan, Michel M. Ouellette

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND/OBJECTIVES: Pancreatic ductal adenocarcinomas (PDACs) are lethal tumors exhibiting resistance to most cancer therapeutics, particularly DNA-damaging agents. The

METHODS: Western blot analyses were used to assess the impacts of Rac1 inhibition on the components of the ATR/Chk1 cascade.

RESULTS: Here, we show that Rac1 inhibition disrupts ATR/Chk1 signaling by promoting degradation of Claspin, a key component of the fork protection complex needed for the Ser345-phosphorylation of Chk1 by ATR. In PDACs and normal pancreatic ductal cells, Rac1 inhibition (via inhibitors or siRNA) decreased Claspin protein levels without affecting its mRNA, reflecting a >3-fold reduction in Claspin's half-life. Claspin contains a …

Pancreatic Cancer Detection Consortium Biomarker Bakeoff: A Phase Ii Blinded Biomarker Validation And Panel Discovery Study, Ann L. Oberg, William R. Bamlet, Grant Izmirlian, Seetharaman Balasenthil, Surinder K. Batra, Masataka Hayashi, Daniel S. Herman, Michael A. Hollingsworth, Maneesh Jain, Ann M. Killary, Brianna M. Krusen, Suyu Liu, Shounak Majumder, Gopalakrishnan Natarajan, Subrata Sen, Lynette M. Smith, Sudhir Srivastava, Brian M. Wolpin, Kenneth S. Zaret, Michael G. Goggins

Journal Articles: Biochemistry & Molecular Biology

PURPOSE: The Pancreatic Cancer Detection Consortium (PCDC) performed a blinded Early Detection Research Network-defined phase II biomarker bakeoff study of blood-based biomarker panels. The aims were to evaluate panel performance, to compare the panels' performance with that of cancer antigen 19-9 (CA19-9) alone, and to evaluate the performance of new combinations of the individual biomarkers.

EXPERIMENTAL DESIGN: Ten biomarkers representing eight biomarker panels and CA19-9 were evaluated using plasma, serum, and germline DNA from 140 stage I to IV pancreatic ductal adenocarcinoma (PDAC) cases and 140 controls from three tertiary care institutions, with controls frequency matched to cases on age …

Overcoming Radiation Resistance: Ferroptosis Induction To Sensitize Solid Tumors To Radiation Therapy, Joseph Carmicheal, Caden M. Fritson, Alexandra Seas, Heidi M. Vieira, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Radiation therapy (RT) is a mainstay of treatment for a myriad of cancers, often utilized for tumors that are unable to be resected, as well as an adjunct to surgery and chemotherapy. Unfortunately, many cancers are resistant to RT-induced damage and subsequent cell death. This has spurred the pursuit of novel radiation sensitizers that could potentiate the effects of this widely used and important treatment modality. Since its discovery as a regulated cell death mechanism in 2012, ferroptosis has been studied for its connection to cancer and other known oxidative pathways. With this, the interplay between RT and ferroptosis in …

35 Individuals With Huwe1-Related Neurodevelopmental Disorder And Suggested Clinical Evaluations, Mindy H. Li, Deziree L. Coleman, Kelsey Hogan, Danielle Luz, Lindsay Bhandari, Newell Belnap, Tiffany Busa, Charles Coutton, Klaus Dieterich, Svetlana Gorokhova, Clara Hildebrandt, Rachel Logan, Milena Mariani, Manuela Morleo, Vincenzo Nigro, John Pappas, Rachel Rabin, Kelly Schoch, Angelo Selicorni, Vandana Shashi, Rebecca Spillman, Jennifer Sullivan, Charlotte Tardy, Samantha A. Schrier Vergano, Brock Grill, Kristin Baranano

Department of Pediatrics Faculty Publications

HUWE1 (HECT, UBA, and WWE Domain Containing E3 Ubiquitin Protein Ligase1, OMIM 300697), located at Xp11.22, encodes a ubiquitin ligase that is highly conserved across species. Genetic variants in HUWE1 described in multiple independent studies cause X-linked intellectual disability, including in the patients identified by Juberg, Marsidi, and Brooks. This report describes 35 additional cases of individuals with variants in HUWE1 and suggested guidelines for clinical management. Our study includes several female cases, which have not been widely reported previously. Our findings confirm earlier reported clinical features including developmental delay, autism, hypotonia, short stature, and dysmorphic facial features as well …

Dysregulation Of Alternative Splicing Patterns In The Ovaries Of Reproductively Aged Mice, Adnan T. Alsamaraee, Vanessa L. Correll, Julius O. Nyalwidhe, Pavla Brachova, Nehemiah S. Alvarez

Department of Biomedical and Translational Sciences Faculty Publications

Female reproductive aging is characterized by progressive deterioration of ovarian function, yet the molecular mechanisms driving these changes remain incompletely understood. Here, we used long-read direct RNA-sequencing to map transcript isoform changes in mouse ovaries across reproductive age. Comparing young and aged mice after controlled gonadotropin stimulation, we identified widespread alternative splicing changes, including shifts in exon usage, splice site selection, and transcript boundaries. Aged ovaries exhibited increased isoform diversity, favoring distal start and end sites, and a significant rise in exon skipping and intron retention events. Many of these age-biased splicing events altered open reading frames, introduced premature stop …

Stat4-Dependent Regulation Of Neuroinflammation In Atherosclerosis, Natalie Stahr, Alina K. Moriarty, Shelby D. Ma, W. Coles Keeter, Woong-Ki Kim, Larry D. Sanford, Elena V. Galkina

Department of Biomedical and Translational Sciences Faculty Publications

Atherosclerosis is linked to an increased risk of cognitive decline, with chronic inflammation being a common feature of both pathologies. IL-12 activates STAT4 to regulate myeloid cell functions, and blockade of this pathway alleviates cognitive impairment in Alzheimer's models. However, the mechanisms connecting vascular pathology to neuroinflammation remain unclear. Here, we examine whether STAT4 functions as a common mediator of neuroinflammation in atherosclerosis. We demonstrate that LysM^Cre-specific STAT4 deficiency ameliorates deficits in long-term memory in low-density lipoprotein-deficient (Ldlr^-/-) mice fed a high-fat diet (HFD-C). STAT4 deficiency moderately reduces Ser199-phosphorylated Tau burden. Atherosclerosis alters brain immune …

Lipid And Foam Cell Accumulation As Novel Pathological Features Of Benign Prostatic Hyperplasia, Dita Julianingsih, Samara V. Silver, Thaissa Horne, Kasun Gunawardena, Savannah Ward, Alicia Malewska, Douglas Strand, Julius Nyalwidhe, Ilya Sobol, Petra Popovics

Department of Biomedical and Translational Sciences Faculty Publications

Background

Benign prostatic hyperplasia (BPH) encompasses a heterogeneous set of pathological processes that instigate lower urinary tract symptoms (LUTS). Using a mouse model of steroid hormone imbalance-induced lower urinary tract dysfunction, we identified luminal lipid-laden foamy macrophages, although their presence and contribution to human pathology have not yet been established. The objective of this study was to determine whether luminal macrophages are associated with human BPH and to assess how lipid accumulation relates to underlying pathological features and clinical parameters.

Methods

Whole-mount tissue sections from simple prostatectomy specimens and prostates from healthy donors were used to evaluate the association of …

The Structure Of The Native Cardiac Crossbridge In The Rigor State, Cristina M. Risi, Tyler Nguyen, Betty Belknap, Howard D. White, Jose R. Pinto, Prescott B. Chase, Vitold E. Galkin

Department of Biomedical and Translational Sciences Faculty Publications

Cardiac contraction is driven by double-headed myosin cycling on cardiac thin filaments, where troponin-tropomyosin regulates myosin access to actin. Prior high-resolution structural studies used a single-headed myosin bound to bare actin, thereby limiting insight into coordination between myosin heads and the influence of troponin-tropomyosin on actomyosin interactions. Here, we report a high-resolution structure of the native cardiac rigor cross-bridge formed by heavy meromyosin bound to the thin filament. We show that direct communication between the two bound heads, uneven interactions between the heads and tropomyosin, and spatial constraints imposed by troponin govern myosin placement along the thin filament. Additionally, the …

Prolonged Qt Interval In Hiv-1 Infected Humanized Mice Treated Chronically With Dolutegravir/Tenofovir Disoproxil Fumarate/Emtricitabine, Ali Namvaran, Julian V. Garcia, Mahendran Ramasamy, Kayla Nguyen, Farzaneh Tavakkoli Ghazani, Bryan T. Hackfort, Prasanta Dash, Reagan E. Fisher, Benson J. Edagwa, Santhi Gorantla, Keshoer R. Bidasee

Journal Articles: Cellular & Integrative Physiology

The REPRIEVE Trial recently reported high rates of sudden cardiac death (SCD) middle-aged people living with HIV-1 infection (PWH) using the WHO/NIH-recommended two nucleoside reverse transcriptase inhibitors (NRTIs)/one integrase strand inhibitor (INSTI) regimen to manage HIV-1 viremia. To date, clinically relevant animal models to delineate underlying causes for this remain limited. Here, we assessed if HIV-1-infected NOD.Cg-Prkdc^scidIl2rg^tm1Wjl/SzJ humanized mice (Hu-mice) treated with the WHO/NIH-recommended antiretroviral regimen, dolutegravir (DTG, INSTI)/tenofovir disoproxil fumarate (TDF, NRTIs)/emtricitabine (FTC, NRTIs), can recapitulate abnormalities in the ECG and subclinical structural heart disease that serve as harbingers of SCD in middle-aged PWH. …

Development Of A Practical Lu-177 Activity Calibration Protocol For Clinical Nuclear Medicine: Dosimetric Impact Analysis And Implementation Tools, Azam Almolaiki

Theses and Dissertations

Lutetium-177 (Lu-177) is widely used in radionuclide therapy, where accurate activity measurement prior to administration is essential for safe and effective treatment delivery. However, variability in dose calibrator response due to measurement conditions and source geometry remains a practical challenge in routine clinical settings. This study presents a practical clinical calibration strategy under real-world constraints for Lu-177 activity measurement using standard nuclear medicine instrumentation. A vial-based approach was implemented using a well-type ionization chamber (Capintec CRC-15R) to evaluate measurement repeatability, temporal stability, and geometry dependence. All measurements were performed under consistent conditions with appropriate decay correction applied using the physical …

Dupilumab In Chronic Rhinosinusitis Without Nasal Polyps: Randomized Phase 2 Trial (Orion), Stella E. Lee, Anju T. Peters, Philippe Gevaert, Joseph K. Han, Claus Bachert, Francisco Moreira Da Silva, Andrés Rosenblüt, Chih-Chi Hu, Jennifer Maloney, Paolo Caferra, Adrianna Michalak, Andrew P. Fontenot, Lacey B. Robinson, Neelam A. Phadke

Department of Otolaryngology (ENT) Faculty Publications

BACKGROUND: Chronic rhinosinusitis (CRS) is often driven by type 2 inflammation and is characterized by nasal obstruction/ discharge, facial pain/pressure, and/or reduced smell, either with or without nasal polyps (CRSwNP or CRSsNP).

OBJECTIVE: To test whether dupilumab improves radiographic features in CRSsNP. Methods: ORION (NCT04678856), a phase 2, randomized, multicenter, double blind, placebo-controlled study, assessed dupilumab efficacy and safety in adults with uncontrolled CRSsNP. Patients were randomized 1:1 to dupilumab or placebo for 24 to 52 weeks. Endpoints included changes from baseline at week 24 in Lund–Mackay computed tomography (LMK-CT) score (dupilumab only [primary] and vs placebo [secondary]), sinus Total …

Analyzing Early Medieval Perspectives Of Fetal Development, Nivedha Srinivasan

Honors Undergraduate Theses

This thesis examines early medieval perspectives of fetal development by analyzing two manuscripts: British Library, Cotton Tiberius A III and Leiden University, Vossianus lat. Q69. This study will investigate how knowledge of pregnancy was shared throughout England before the establishment of universities. Interest in medieval reproductive language has piqued in importance in recent years, especially due to modern legal debates surrounding reproductive rights. By examining descriptions of the nine months of fetal development in these two manuscripts, as well as in widely known earlier medical texts like Pliny’s Natural History and Vindicianus’ Gynaecia, this research explores how monastic writers in …

Studying Chronotypes And Their Role In Sleep And Mental Health: A Scoping Review, Evan Nguyen

Honors Undergraduate Theses

Sleep patterns remain a significant public health concern globally, impacting several aspects of life, including mental health. This scoping review examined how chronotype and circadian typology predict mental health, with sleep quality serving as a crucial mediator. While the importance of sleep is widely acknowledged, there is a lack of studies specifically investigating chronotype-aligned interventions to reduce psychological distress. To address the shortage, a comprehensive review of the peer-reviewed literature was conducted, identifying six papers for analysis. These studies mostly utilized cross-sectional designs to assess diverse global groups, including university students, healthcare workers, and military personnel. The results indicate that …

Post-Metabolites Of Two Commensal Bacteria Suppress Dna Damage In An Experimental Model Of Acid Reflux Disease, Maanya Pradeep

Honors Undergraduate Theses

Chronic heartburn or gastroesophageal reflux disease (GERD) affects approximately 25% of the US population [1]. Repeated bile acid exposure from the regurgitation of stomach contents leads to the production of reactive oxygen species (ROS), which can cause oxidative DNA damage and promote genomic instability [2]. Barrett’s esophagus (BE), which can develop as a response to chronic bile acid exposure, increases the risk of esophageal adenocarcinoma (EAC) by 30% to 125% [1].

There are more than 18,000 new cases of esophageal cancer in the United States each year, and while its incidence is relatively low compared to other cancers, its mortality …

The Role Of P2y1 And P2y2 Receptors In Human Neural Stem Cell Proliferation, Daria Sokolova

Honors Undergraduate Theses

Endogenous neural stem cells (NSCs) are located in specialized niches of the adult brain and play a vital role in both neurogenesis and neuronal repair. However, declines in NSC proliferation and metabolism associated with age and pathology make these cells less efficient at responding to neurodegenerative disease. Understanding signaling pathways that regulate NSC function is therefore essential for the understanding and development of treatments for these conditions. P2Y receptors are G-protein-coupled purinergic receptors that are activated by extracellular nucleotides and regulate cellular metabolism and proliferation. Among the eight known P2Y subtypes, P2Y1 and P2Y2 have been linked to neuronal signaling …

Cerebellar Motor And Non-Motor Contributions To Dystonia Pathophysiology And Treatment, Linda H Kim, Cheryl Brandenburg, Roy V Sillitoe

Duncan NRI Faculty and Staff Publications

Dystonia is a complex neurological disorder characterized by sustained or intermittent abnormal movements and/or postures. However, dystonia's non-motor symptoms, particularly the sleep disturbances, are critical yet underexplored concerns that affect all ages. Here, we synthesize current knowledge on the motor and non-motor domains of dystonia, emphasizing the functional interconnections and plasticity within cerebellar motor, cognitive, and sleep-associated circuits to motivate more comprehensive and effective treatments that improve overall quality of life.

Managing Multi-Drug Resistance: An Evolutionary Game Theory And Optimal Control Approach, Shukhrat Nasrulloev

Theses and Dissertations

Multi-drug resistance is an evolutionary process in which treatment eliminates sensitive cells, allowing resistant clones to dominate. This thesis investigates this process using a framework integrating population dynamics, evolutionary game theory, and optimal control theory. We develop a two-population logistic growth model describing competition between drug-sensitive and drug-resistant cells under treatment, construct dose-dependent payoff matrices and replicator dynamics to characterize evolutionary competition, and derive a critical drug level D_crit = (r_S - rR)/(dS - d_R) at which resistant cells gain a fitness advantage. An optimal control problem is formulated via Pontryagin's Maximum Principle to identify schedules …

Once-Weekly Navepegritide In Children With Achondroplasia: The Approach Randomized Clinical Trial, Ravi Savarirayan, Ciara Mcdonnell, Carlos A Bacino, Daniel G Hoernschemeyer, Janet M Legare, M Jennifer Abuzzahab, Paul L Hofman, Philippe M Campeau, Josep Maria De Bergua Domingo, Leanne M Ward, Kevin Smit, Alden Smith, Meng Mao, Michael S Ominsky, Lærke C Freiberg, Aimee D Shu, Hanne B Hove

Faculty, Staff and Students Publications

Importance: Historically considered a skeletal dysplasia characterized by disproportionate short stature, achondroplasia is a condition with multisystemic effects due to the widespread expression of the fibroblast growth factor receptor 3 variant throughout the body, impacting muscle, neurological function, cardiorespiratory health, and health-related quality of life.

Objective: To evaluate the efficacy, safety, and tolerability of once-weekly navepegritide, an investigational prodrug of C-type natriuretic peptide, while assessing benefits beyond growth that may have important implications for complications and health-related quality of life in children with achondroplasia.

Design, setting, and participants: Enrollment for this pivotal phase 2b, randomized, double-blind, placebo-controlled trial (APPROACH) was …

The Words Community Dwelling, Spanish-Preferring Mexican/Mexican American Adults Use To Talk About Alzheimer’S Disease And Genetic Testing: Implications For Education And Outreach, Jamie C Fong, Fatima I Chavez, Karla Silos, Mirna L Arroyo-Miranda, Gabriela Castro Castro, Mark E Kunik, Joshua M Shulman, Luis D Medina

Faculty, Staff and Students Publications

Introduction: Hispanic/Latino (H/L) adults are more likely than non-Hispanic White individuals to have Alzheimer's disease (AD), yet fewer than one in five H/L adults has apolipoprotein E (APOE) Ɛ4, underscoring gaps in understanding genetic risk across H/L heritage groups. H/L adults remain underrepresented in AD research that uses genetic data for participant stratification. To inform culturally appropriate educational materials for 16 million U.S. Spanish speakers, we identified culturally salient words Spanish-preferring H/L adults use to describe AD and genetic testing beyond APOE.

Methods: Community-residing, Spanish-preferring Mexican/Mexican American adults (n = 14) completed freelisting interviews, a method eliciting …

Amino Acids And Lean Mass Accretion In Preterm Neonates, Antonio C Ramos Dos Santos, Marta L Fiorotto, Teresa A Davis

Faculty, Staff and Students Publications

Purpose of review: This review evaluates recent evidence on how total protein and energy intake, amino acid composition, and nutrient delivery modality influence protein synthesis in preterm neonates, with the goal of informing nutritional strategies to support optimal lean mass accretion and growth.

Recent findings: Preterm neonates exhibit anabolic resistance to feeding due to impaired insulin and amino acid signaling in skeletal muscle. Enteral nutrition, especially fortified human milk, supports better lean mass accretion and neurodevelopment than parenteral nutrition. Intermittent bolus feeding and pulsatile leucine supplementation during continuous feeding further enhance mTORC1-dependent translation initiation signaling and protein synthesis efficiency in …

In Vivo Volumetric Visualization And Quantification Of Cumulus Expansion In Mice With Intravital Optical Coherence Tomography, Kohei Umezu, Frank J Brooks, Irina Larina

Faculty, Staff and Students Publications

Ovulation is preceded by a critical physiological process known as cumulus expansion, during which the cumulus cell layer surrounding the oocyte undergoes structural remodeling. Despite the recognized importance of this process for reproductive success, live quantitative imaging of cumulus expansion has not been previously achieved due to limitations of current imaging technologies for deeply located ovaries. In this study, we employed intravital optical coherence tomography for three-dimensional visualization of mouse follicles containing cumulus-oocyte complexes (COC) within the physiological context of the ovary, both ex vivo and in vivo. This method enabled time-lapse measurement of cumulus layer thickness and COC …

Astrocytic Sox9 Overexpression In Alzheimer’S Disease Mouse Models Promotes Aβ Plaque Phagocytosis And Preserves Cognitive Function, Dong-Joo Choi, Sanjana Murali, Wookbong Kwon, Junsung Woo, Eun-Ah Christine Song, Yeunjung Ko, Debosmita Sardar, Brittney Lozzi, Yi-Ting Cheng, Michael R Williamson, Teng-Wei Huang, Kaitlyn Sanchez, Joanna Jankowsky, Benjamin Deneen

Faculty, Staff and Students Publications

Astrocytes play essential roles in the brain, and their dysfunction is associated with nearly every form of neurological disease. Despite their ubiquity, knowledge of how astrocytes contribute to disease pathogenesis is incomplete; accordingly, harnessing their biology toward therapeutics remains a major challenge. Here we show that the transcription factor Sox9 plays a context-specific role in maintaining astrocyte function and circuit activity in the aging hippocampus and Alzheimer's disease (AD) models. We found that Sox9 overexpression in astrocytes in AD models clears existing amyloid beta (Aβ) plaques and preserves cognitive function. Mechanistically, Sox9 promotes the phagocytosis of Aβ plaques by astrocytes …

Predictors Of Inpatient Rn Turnover In Rural And Urban Vha Hospitals, Katherine G Bay, Chase S Eck, Melissa K Knox, Paras Mehta, Laura A Petersen

Faculty, Staff and Students Publications

Background: The rising demand for health care delivery and an aging workforce is of particular concern in rural areas, where health care access depends upon an adequate nursing workforce. To address this shortage and optimize care, it is essential to measure when registered nurses (RN) leave inpatient direct care positions (ie, inpatient RN turnover) and identify modifiable factors correlated with RN turnover.

Objectives: Apply a novel method for characterizing inpatient RN turnover to understand factors associated with variation in RNs leaving inpatient positions at rural and urban Veterans Health Administration (VHA) hospitals.

Project design: Retrospective cohort study.

Subjects: Direct care …

Duration Of Antimicrobial Therapy In Cardiovascular Implantable Electronic Device Associated Systemic Infections: A Retrospective Analysis, Emily Y Xiao, Patrick T Lynch, Sarwat Khalil, Derrick A Draeger, Alexandra M Lewis, Faiz M Baqai, Mihail G Chelu, M Rizwan Sohail

Faculty, Staff and Students Publications

Background: While the need for complete device removal is well-established for cardiovascular implantable electronic device (CIED) infections, there is insufficient evidence on the optimal duration of antimicrobial therapy.

Objectives: To examine how antimicrobial duration affects clinical outcomes of patients presenting with CIED-associated bacteremia and lead endocarditis.

Design: This is a retrospective cohort study conducted at a quaternary care hospital in Houston, TX, USA.

Methods: Patients who underwent device removal for a primary indication of bacteremia or lead endocarditis over a 10-year period were stratified by prescribed duration of antibiotics as ⩽2 weeks or >2 weeks post-extraction. Measured outcomes included all-cause …

Modulation Of Corneal Sensory Processing And Pain Responses By Dry Eye And Corneal Wounding, Ebru Yaman, Yangluowa Qu, Kaylin C Arpaia, Fairouz Elsaeidi, Uma Lakshmi Balakrishnan, Lance He, Henry Skrehot, Jehan Alam, Rui Chen, Mary Ann Stepp, Cintia S De Paiva, Stephen C Pflugfelder

Faculty, Staff and Students Publications

Background: Dry eye disease (DED) is a multifactorial disorder of the ocular surface in which tear film instability, epithelial barrier disruption, and neurosensory dysfunction contribute to symptom generation. Although several contributing factors have been identified, how different forms of ocular surface stress affect sensory pathways and behavioral responses remains unclear.

Purpose: This study aimed to evaluate corneal barrier function, sensory responses, and pain-related behaviors across acute and chronic dry eye and corneal injury models, and to assess stimulus-specific responses associated with TRPV1 and TRPM8 mediated pathways.

Methods: Female C57BL/6 J wild type and Mmp9KO mice were evaluated in acute desiccating …

Efficacy And Safety Of Pyrimidine Nucleos(T)Ide Therapy In Thymidine Kinase 2 Deficiency, Michio Hirano, Caterina Garone, Richard Haas, Carmen Paradas, Fernando Scaglia, Irene Rebollo Mesa, Carl Chiang, Anny-Odile Colson, Susan Vanmeter, Cristina Domínguez-González

Faculty, Staff and Students Publications

Thymidine kinase 2 deficiency (TK2d) (MIM 609560) is an ultra-rare, autosomal recessive mitochondrial myopathy caused by TK2 variants, leading to mitochondrial DNA depletion and/or multiple deletions. People with thymidine kinase 2 deficiency experience progressive myopathy, bulbar weakness and respiratory insufficiency, often losing the ability to walk, eat and breathe independently. Doxecitine and doxribtimine represents the first approved treatment for patients with thymidine kinase 2 deficiency with age of symptom onset ≤12 years by the US Food and Drug Administration and the European Medicines Agency; previously, disease management was limited to supportive care. We investigated the efficacy and safety of pyrimidine …

Test-Retest Apparent Diffusion Coefficient Reproducibility In Head And Neck Cancer Using A 15-T Mr-Linac, Brigid A Mcdonald, Dina El-Habashy, Renjie He, Sam Mulder, Sarah Mirbahaeddin, Abdallah S R Mohamed, Sara Ahmed, Yao Ding, Jihong Wang, Stephen Y Lai, Alex Dresner, John Christodouleas, Clifton D Fuller

Faculty, Staff and Student Publications

Purpose

To evaluate the reproducibility of apparent diffusion coefficient (ADC) measurements in head and neck squamous cell carcinoma (HNSCC) using a 1.5-T MR-linac (MRI-guided linear accelerator) system.

Materials and Methods

In this retrospective study, conducted between February 2021 and January 2024, patients with HNSCC lesions underwent echo-planar imaging diffusion-weighted MRI on a 1.5-T MR-linac system at two time points before the start of radiation therapy. Mean and median ADC values and volumes were measured for each lesion. Absolute and percent reproducibility coefficients (RCs) were calculated. Linear regression analyses and F tests were performed to determine whether the lesion volume or …

Multisite, Multiancestry Genome-Wide Association Study Meta-Analysis Of Functional Seizure Disorder In A Hospital Sample Of 675,680 Patients, Slavina B Goleva, Costin Leu, Yen-Chen Anne Feng, David Burstein, Sanan Venkatesh, Rebecca Birnbaum, Veera M Rajagopal, Peter Straub, Jakob Christensen, Jocelyn F Bautista, Robyn M Busch, Imad M Najm, Jakob Grove, Anders D Børglum, Georgios Voloudakis, Panos Roussos, Jordan Smoller, Dennis Lal, Lea K Davis

Faculty, Staff and Student Publications

Background: Functional seizures (FS) are paroxysmal episodes that phenotypically resemble epileptic seizures but are not associated with brain epileptiform discharges; they are also known as psychogenic nonepileptic seizures. The exact etiology and pathophysiology of FS is unknown; however, trauma and stress-related disorders are known risk factors.

Methods: We used a validated algorithm applied to electronic health records to identify individuals with FS in 6 international biobanks and hospital sites. We conducted a multisite FS genome-wide association study (GWAS) meta-analysis, including 10,910 FS cases (9040 predicted European ancestry [EA] and 1870 predicted African ancestry [AA]) and 664,500 (561,150 EA and 103,350 …