Digital Commons Network^™

Promises, Pitfalls, And Paths Forward For The Pediatric Research Equity Act., Alexa L. Pagano, Danielle J. Green, Jennifer Goldman, Anjali Deshmukh

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Since its enactment in 2003, the Pediatric Research Equity Act (PREA) has significantly increased the number of pediatric drug studies performed and expanded pediatric drug labeling. Despite these advancements, many drugs used in children still lack pediatric-specific US Food and Drug Administration (FDA) labeling, even when pediatric studies are required by law. Recent legislative changes strengthened the FDA's enforcement authority over PREA. As these changes are implemented, persistent gaps in pediatric drug development warrant examination. Addressing these gaps may help ensure that children are systematically included in clinical research and that medications used in children are supported by rigorous …

An Investigation Of Data Granularity In Rag Pipelines For Personalized Medicine, Paritosh Pandey

Master's Theses

Generative AI, exemplified by large language models like the OpenAI GPT and Meta LLaMA families, can produce diverse content in response to prompts. This capability offers a promising solution to challenges in precision medicine, which seeks to tailor treatments to individual clinical profiles but often struggles with data collection, cost, and privacy concerns. By generating realistic, privacy-preserving patient data, generative AI has the potential to transform patient-centric healthcare. With such motivation, this research develops a comprehensive Generative AI pipeline emphasizing data granularity for accurate prediction of personalized treatments. The pipeline features a central Large Language Model interacting with a Machine …

Neuropsychological Functioning And Coping Strategy Intervention Approaches In Youth With Posttraumatic Stress Disorder, Kalliopi Megari, Dimitra V. Katsarou, Georgios A. Kougioumtzis, Evangelos Mantsos, Maria Sofologi, Agathi Argyriadi, Alexandros Argyriadis, Efthymia Efthymiou

All Works

Background: Posttraumatic stress disorder (PTSD) in ages 3–18 is associated with disturbances in attention, working memory, processing speed, and executive control, as well as persistent difficulties in affect regulation. These neuropsychological vulnerabilities might interfere with learning, peer relationships, and the consolidation of age-appropriate developmental skills. Methods: We conducted a narrative review informed by a structured literature search in PubMed, Scopus, PsycINFO, Embase, EBSCOhost, Web of Science, and Google Scholar. English-language publications from 1990 to 2025 were considered if they examined (1) neuropsychological outcomes of trauma exposure or PTSD in youth and/or (2) interventions with potential to modify neurocognitive or affective …

A Rare Case Of Gastric Ascariasis, Sharon Pan, Kevin Yu, Blaine A Mathison, Yan Gao, Marc Roger Couturier, Salem Muayad, Violeta Chávez, Ranya Selim

Faculty, Staff and Student Publications

Background: Ascariasis, caused by the parasitic roundworm Ascaris lumbricoides, is one of the most common helminthic infections globally. Spread by contaminated soil through the fecal-oral route, A. lumbricoides typically infects the small intestine and has rarely been reported to infect the stomach.

Case summary: We describe an unusual case of a male in his 30s with a history of neuroendocrine tumor (NET) who immigrated from Colombia and who underwent esophagogastroduodenoscopy (EGD) and colonoscopy for further evaluation of abdominal pain. He was incidentally found to have a female Ascaris worm in his stomach that was retrieved during the EGD.

Conclusion: …

Dolutegravir Developmental Toxicity Is Mitigated By Magnesium And Folate In Zebrafish Embryos, Robert M Cabrera, Ahmed Mohamed, Ryoko Minowa, Katheryn A Neugebauer, Daniel A Gorelick

Faculty, Staff and Students Publications

Integrase strand transfer inhibitors have transformed human immunodeficiency virus (HIV) therapy, yet the widely prescribed drug dolutegravir (DTG) has been linked to developmental toxicity, and its teratogenic mechanism remains unclear. Here, we used zebrafish to dissect DTG toxicity during early vertebrate development. DTG exposure from 2-4 h post-fertilization (hpf) to 24 hpf produced high mortality and abnormal morphology. Co-treatment with folates partially restored normal morphology, whereas calcium had no effect. Strikingly, supplementation with magnesium (Mg) partially rescued DTG-exposed embryos, implicating Mg availability in protection. In competitive binding assays, Mg increased binding of folate to purified folate receptor (FOLR1) by 30% …

Associations Between Water Intake, Dietary Quality, And Beverage Consumption Among University Students, Mohammad A. Qazi

Electronic Theses, Projects, and Dissertations

Title: Associations Between Water Intake, Dietary Quality, and Beverage Consumption Among University Students

Background and Aims: Sugar-sweetened beverage (SSB) and ultra-processed food (UPF) consumption significantly contribute to chronic disease risk and is often more common in underserved and racially/ethnically diverse communities. Drinking water is a low-cost, calorie-free behavior that may support healthier beverage and dietary patterns. Previous studies show that increased daily water consumption positively correlates with better diet quality and is inversely correlated with SSB and UPF consumption. This study aims to examine whether (1) increased daily water intake is associated with self-reported diet quality and (2) self-reported hydration …

Validation Of The German Version Of The Movement Disorder Society Non-Motor Scale (Mds-Nms), Jonas Bendig, Anika Frank, Adrianna Lipska-Dieck, Kristof Wunderlich, David Geißler-Lösch, Isabel Wurster, Roswitha Kemmner, Kathrin Brockmann, Sheng Luo, Christopher G Goetz, Glenn T Stebbins, Pablo Martinez-Martin, Tiago A Mestre, Alvaro Sanchez-Ferro, Monica M Kurtis, Michelle H S Tosin, Roberta Balestrino, Chi-Ying R Lin, Carmen Gasca-Salas, Heinz Reichmann, Bjoern H Falkenburger

Faculty, Staff and Students Publications

No abstract provided.

A Smoking-Related Plasma Protein Score And Smoking-Related Cancer Risk And Mortality In The Atherosclerosis Risk In Communities Study, Meng Ru, Christopher Douville, Aghiles Guenoun, Hana Zahed, Christie M Ballantyne, Kenneth R Butler, Josef Coresh, David J Couper, Panagis Galiatsatos, Marc J Gunter, Ron C Hoogeveen, Mattias Johansson, Corinne E Joshu, P Martijn Kolijn, Christina M Lill, Jiayun Lu, Michael T Marrone, Giovanna Masala, David C Muller, Anna E Prizment, Raul Zamora-Ros, Nilanjan Chatterjee, Adrienne Tin, Elizabeth A Platz

Faculty, Staff and Students Publications

Background: Self-reported smoking may not fully capture individualized risk of smoking-related cancer, but circulating proteins may reflect biological consequences of smoking. Thus, we developed a score based on smoking-related proteins and evaluated its association with smoking-related cancer.

Methods: This prospective cohort study included 10 563 participants aged 47-70 years in the Atherosclerosis Risk in Communities study. Plasma proteins were measured using the SomaScan Platform (SomaLogic Operating Co, Inc). The score was constructed from proteins associated with current smoking, pack-years, or recent quitting identified by linear regression and elastic net regression. Cox regression was used to estimate adjusted hazard ratios and …

Plasma Proteins Associated With Psychosocial Factors And Heart Disease: The Jackson Heart Study, Sara N O'Brien, Madeline G Gillman, Michael D Green, Daniel E Cruz, James S Floyd, Susan Hankinson, Daniel H Katz, Xiaojuan Liu, Michelle C Odden, Bruce M Psaty, Alexander P Reiner, Jerome I Rotter, Stephen S Rich, Robert E Gerszten, Amil Shah, Mario Sims, Usman A Tahir, Lesley F Tinker, Alexis C Wood, Bing Yu, Anthony S Zannas, Laura M Raffield, Láshauntá M Glover

Faculty, Staff and Students Publications

Background: Knowledge of proteomic mechanisms explaining the link between psychosocial stress and cardiovascular disease is limited. This study aimed to (1) identify plasma proteins associated with psychosocial factors and (2) assess associational pathways between psychosocial factors, identified proteins, and incident cardiovascular disease events in a discovery cohort, JHS (Jackson Heart Study), and 2 replication cohorts, the CHS (Cardiovascular Health Study), and the MESA (Multi-Ethnic Study of Atherosclerosis).

Methods: JHS participants from exam 1 (2000-2004) with SomaScan 1.3k platform proteomics data were included (n=2143, mean age=55.3). Depressive symptoms and perceived stress scores were measured via the 20-item Center for Epidemiological Studies …

Stance And Gait Analysis Of Apollo Astronauts On The Moon, Faye Y Chiou-Tan, Conrad Li, Jason P Caffrey, Millard Reschke, Timothy R Macaulay

Faculty, Staff and Students Publications

Introduction/aim: As humans return to the Moon, safe efficient ambulation and fall prevention on the lunar surface are key concerns. The analysis of gait from archived Apollo mission video footage is now possible with pose estimation video analysis software. Thus, this study aims to retrospectively quantify parameters of Apollo astronauts' stance and gait on the Moon.

Methods: Publicly available National Aeronautics and Space Administration (NASA) footage of astronauts ambulating on the Lunar surface was examined using body pose analysis software. Goniometric lower limb joint/torso angles and width of base of stance and gait were derived. Gait cycle stance phase, swing …

The "Hallett Sign" Of Functional Jerky Movement Disorder, Jon Stone, Anthony E Lang, Joseph Jankovic, Michele Tinazzi, Barbara A Dworetzky, Alan Carson, Marina A J Tijssen

Faculty, Staff and Students Publications

No abstract provided.

Adhesion G Protein-Coupled Receptors, Tobias Langenhan, Garret R Anderson, Demet Araç, Gabriela Aust, Monserrat Avila-Zozaya, Sofie Morsing Bagger, Patrick Barth, Sandra Berndt, Stephen C Blacklow, Beatriz Blanco-Redondo, Antony A Boucard, James P Bridges, Lara-Sophie Brodmerkel, Kathleen M Caron, Yin Kwan Chung, Andrew N Dates, Virginea De Araujo Farias, Daniel Del Toro, Joseph G Duman, Felix B Engel, David M Favara, Caroline J Formstone, Chaoyu Fu, Alain Garcia De Las Bayonas, Anastasia Georgiadi, David E Gloriam, Randy A Hall, Jörg Hamann, Peter W Hildebrand, Cheng-Chih Hsiao, Bill X Huang, Jonathan A Javitch, Hee-Yong Kim, Robert J Kittel, Gunnar Kleinau, Richard Leduc, Ines Liebscher, Hsi-Hsien Lin, Joshua Linnert, Marie-Gabrielle Ludwig, David C Martinelli, Signe Mathiasen, Daniel Matúš, Mariam Melkumyan, Ana L Moreno-Salinas, Jan Mulder, Michael A Nash, Kasturi Pal, Daniel T Pederick, Nicole A Perry-Hauser, Xianhua Piao, Yu-Qi Ping, Dimitris G Placantonakis, Fabian Pohl, Simone Prömel, Mette M Rosenkilde, Laurent Sabbagh, Richard C Sando, Patrick Scheerer, Torsten Schöneberg, Elena Seiradake, Mareike Selcho, Florian Seufert, Abhishek K Singh, Georgios Skiniotis, Katja Spiess, Norbert Sträter, David Strutt, Thomas C Südhof, Jinpeng Sun, Gregory G Tall, Doreen Thor, Douglas G Tilley, Kimberley F Tolias, Mario Vallon, Erwin G Van Meir, Benoit Vanhollebeke, Giselle R Wiggin, Uwe Wolfrum, Jie Yan, Nathan A Zaidman, Yimin Zou, Nicole Scholz

Faculty, Staff and Students Publications

Adhesion G protein-coupled receptors (aGPCRs) constitute a structurally and functionally distinct group within the superfamily of GPCRs. In 2015, the International Union of Pharmacology invited the Adhesion GPCR Consortium to publish a comprehensive review about aGPCRs and establish a unified nomenclature. Since then, substantial progress has been made in delineating the biological roles, molecular architecture, biochemical properties, expression profiles, ligand repertoire, and activation and signaling strategies of aGPCRs. Commensurate with these advances, their relevance to human pathophysiology has become increasingly apparent. In a coordinated effort, the Adhesion GPCR Consortium has reviewed recent progress in this field and provides a comprehensive …

Adhesion G Protein-Coupled Receptors, Tobias Langenhan, Garret R Anderson, Demet Araç, Gabriela Aust, Monserrat Avila-Zozaya, Sofie Morsing Bagger, Patrick Barth, Sandra Berndt, Stephen C Blacklow, Beatriz Blanco-Redondo, Antony A Boucard, James P Bridges, Lara-Sophie Brodmerkel, Kathleen M Caron, Yin Kwan Chung, Andrew N Dates, Virginea De Araujo Farias, Daniel Del Toro, Joseph G Duman, Felix B Engel, David M Favara, Caroline J Formstone, Chaoyu Fu, Alain Garcia De Las Bayonas, Anastasia Georgiadi, David E Gloriam, Randy A Hall, Jörg Hamann, Peter W Hildebrand, Cheng-Chih Hsiao, Bill X Huang, Jonathan A Javitch, Hee-Yong Kim, Robert J Kittel, Gunnar Kleinau, Richard Leduc, Ines Liebscher, Hsi-Hsien Lin, Joshua Linnert, Marie-Gabrielle Ludwig, David C Martinelli, Signe Mathiasen, Daniel Matúš, Mariam Melkumyan, Ana L Moreno-Salinas, Jan Mulder, Michael A Nash, Kasturi Pal, Daniel T Pederick, Nicole A Perry-Hauser, Xianhua Piao, Yu-Qi Ping, Dimitris G Placantonakis, Fabian Pohl, Simone Prömel, Mette M Rosenkilde, Laurent Sabbagh, Richard C Sando, Patrick Scheerer, Torsten Schöneberg, Elena Seiradake, Mareike Selcho, Florian Seufert, Abhishek K Singh, Georgios Skiniotis, Katja Spiess, Norbert Sträter, David Strutt, Thomas C Südhof, Jinpeng Sun, Gregory G Tall, Doreen Thor, Douglas G Tilley, Kimberley F Tolias, Mario Vallon, Erwin G Van Meir, Benoit Vanhollebeke, Giselle R Wiggin, Uwe Wolfrum, Jie Yan, Nathan A Zaidman, Yimin Zou, Nicole Scholz

Faculty, Staff and Students Publications

Adhesion G protein-coupled receptors (aGPCRs) constitute a structurally and functionally distinct group within the superfamily of GPCRs. In 2015, the International Union of Pharmacology invited the Adhesion GPCR Consortium to publish a comprehensive review about aGPCRs and establish a unified nomenclature. Since then, substantial progress has been made in delineating the biological roles, molecular architecture, biochemical properties, expression profiles, ligand repertoire, and activation and signaling strategies of aGPCRs. Commensurate with these advances, their relevance to human pathophysiology has become increasingly apparent. In a coordinated effort, the Adhesion GPCR Consortium has reviewed recent progress in this field and provides a comprehensive …

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 …

Noncanonical Clock Regulators Control Stress Responses In Digestive Diseases, Dishu Zhou, Roberto E López-Valiente, Samer G Mattar, Dongyin Guan

Faculty, Staff and Students Publications

The digestive system is essential for nutrient absorption, processing, and waste elimination. The expression of many genes and physiological processes within this system exhibits a 24-h rhythmicity. However, modern lifestyle factors, such as jet lag, shift work, and irregular eating patterns, significantly disrupt these rhythms, triggering various stress responses and contributing to numerous digestive disorders. Here, we focus on emerging studies on noncanonical clock regulators involved in stress responses, integrate these novel findings into the established model of the core circadian clock, and highlight recent advances in the development of novel therapeutics targeting these 24-h regulators. In addition, we discuss …

High-Penetrance Rare Variants Underlying Familial Lung Cancer Risk: Insights From Genetic Epidemiology Of Lung Cancer Consortium, Yanhong Liu, Yafang Li, Jinyoung Byun, Vikram R Shaw, Claudio Pikielny, Bo Peng, Chao Cheng, Spiridon Tsavachidis, Xiangjun Xiao, Dakai Zhu, Younghun Han, Ivan P Gorlov, Olga Y Gorlova, Michael Cole, Colette R Gaba, Erin L Crawford, Kristen Purrington, Ellen L Goode, Ping Yang, James Mckay, John K Field, Geoffrey Liu, Rayjean J Hung, Jun Xia, Jiyeon Choi, Matthew B Schabath, Jaclyn Lopiccolo, David C Christiani, Joan Bailey-Wilson, Ann G Schwartz, James C Willey, Diptasri Mandal, Susan M Pinney, Christopher I Amos

Faculty, Staff and Students Publications

Introduction: Rare, deleterious germline variants are key contributors to inherited lung cancer (LC) risk. The Genetic Epidemiology of LC Consortium (GELCC) has curated valuable high-risk LC families and is uniquely positioned to uncover rare, high-penetrance variants underlying familial LC (FLC).

Methods: We performed whole-genome and exome sequencing on germline DNA from 120 high-risk LC families (177 FLC cases, 309 unaffected relatives). We prioritized rare (allele frequency < 1% in the genome aggregation database), potentially deleterious variants present in two or more FLC cases. These variants were then validated in 10,085 sporadic LC (SLC) cases and 612,970 controls.

Results: We identified 118 candidate variants, 28 of which were validated in SLC with strong statistical support. We discovered a novel pathogenic axis of three truncating variants in GALNT6, MUC4, and ERBB3 genes, which …

Single-Nuclei Transcriptomic Profiling Of Human Myocardium In Long-Chain 3-Hydroxyacyl-Coenzyme A Dehydrogenase Deficiency, Hanna J Tadros, Diwakar Turaga, Yi Zhao, Chang-Ru Tsai, Lalita Wadhwa, Debra L Kearney, Iki Adachi, Xiao Li, James F Martin

Faculty, Staff and Students Publications

No abstract provided.

A Covalent Allosteric Molecular Glue Suppresses Nrf2-Dependent Cancer Growth, Nilotpal Roy, Ilah Bok, Harit Panda, Dhaval P Bhatt, Emily M Wilkerson, Soma Saeidi, Paul Zolkind, Michael B Major, Et Al.

2020-Current year OA Pubs

UNLABELLED: The NRF2 transcription factor is constitutively active in cancer, in which it functions to maintain oxidative homeostasis and reprogram cellular metabolism. NRF2-active tumors exhibit NRF2 dependency and resistance to chemotherapy/radiotherapy (RT). In this study, we characterize VVD-065, a first-in-class NRF2 inhibitor that acts via an unprecedented allosteric molecular glue mechanism. In the absence of stress or mutation, NRF2 is rapidly degraded by the Kelch-like ECH-associated protein 1 (KEAP1)-cullin3 (CUL3) ubiquitin-ligase complex. VVD-065 specifically and covalently engages Cys151 on KEAP1, which in turn promotes KEAP1-CUL3 complex formation, leading to enhancement of NRF2 degradation. Previously reported Cys151-directed compounds decrease KEAP1-CUL3 interactions …

Risk Factors For The Development Of Food Allergy In Infants And Children: A Systematic Review And Meta-Analysis, Nazmul Islam, Alexandro W L Chu, Falana Sheriff, Farid Foroutan, Gordon H Guyatt, Romina Brignardello-Petersen, Paul Oykhman, Alfonso Iorio, Ariel Izcovich, Katherine M Morrison, Yetiani Roldan Benitez, Rachel J Couban, Dorota Borovsky, Yiming Zhang, Leonardo Ologundudu, Keerthana Pasumarthi, Syed Fahad Farooq, Kyle Tong, Wang-Choi Tang, Haseeb Faisal, Muhammad Faran Khalid, Mohammad Saad Asif, Shannon French, Susan Waserman, R Sharon Chinthrajah, Hugh A Sampson, S Shahzad Mustafa, Jay A Lieberman, Kirsi M Järvinen, Sally Bailey, Philippe Bégin, Scott H Sicherer, Jennifer Gerdts, Melanie Carver, Lynda Mitchell, Kelly Cleary, Matthew J Greenhawt, Julie Wang, Aikaterini Anagnostou, Marcus S Shaker, Anita Chandra-Puri, Patricia C Fulkerson, Robert A Wood, Derek K Chu

Faculty, Staff and Students Publications

Importance: The incidence and risk (predictive) factors for early life food allergy development remain uncertain.

Objective: To estimate the incidence and quantify risk factors for food allergy development.

Data sources: MEDLINE and Embase were systematically searched to January 1, 2025. Data were analyzed from June 1, 2025, to November 25, 2025.

Study selection: Incidence estimates included studies confirming food allergy via food challenge. Risk factor analyses included cohort, case-control, and cross-sectional studies in any language assessing children younger than 6 years using multivariable analyses.

Data extraction and synthesis: Paired reviewers independently extracted data. Random-effects meta-analyses pooled incidence and adjusted odds …

Derivation And Validation Of The Pediatric Community-Acquired Pneumonia Severity (Pedcaps) Score: A Prospective Cohort Study, Todd A Florin, Ron Reeder, Lilliam Ambroggio, Richard M Ruddy, Samir S Shah, Allison Cator, Matthew J Lipshaw, Geoffrey A Capraro, Laura F Sartori, Amy Y Cheng, Leah Tzimenatos, Patrick S Walsh, Claudia R Morris, Chris A Rees, Son H Mclaren, Tamar R Lubell, Chari D Larsen, Justin Moher, Eileen J Klein, Shubhada Hooli, Nathan Kuppermann

Faculty, Staff and Students Publications

Introduction: Community-acquired pneumonia (CAP) is a frequent and costly cause of pediatric emergency department (ED) visits and hospitalizations. Previous prognostic tools for CAP are limited by small samples, single-center or retrospective designs, lack of generalizability to ED settings, lack of biomarkers, or limited objective data. To overcome these limitations, we will derive and externally validate a prediction rule for pediatric CAP severity in a large, multicenter prospective cohort.

Methods: This is a prospective cohort study of children 3 months to 18 years old with CAP who present to EDs within the Pediatric Emergency Care Applied Research Network. Enrollment began 8/2023 …

Phenotypic Diversity And Outcomes In Pediatric Nmda Receptor Encephalitis: A 15-Year Retrospective Study From The Largest Children's Hospital In The United States, Alexander J Sandweiss, Timothy Erickson, Yike Jiang, Varun Kannan, Jonathan M Yarimi, Kristen S Fisher, Nikita Shukla, Tim Lotze, Eyal Muscal, Kristy O Murray

Faculty, Staff and Students Publications

Anti‐NMDAR encephalitis (NMDARE) is an autoantibody‐mediated disorder characterized by seizures, movement disorders, neurocognitive deficits, and psychosis, but the complete phenotypic heterogeneity, and outcomes are incompletely understood in children. This single‐center retrospective analysis of NMDARE at the largest pediatric hospital in the United States between 2009 and 2024 screened 115 patients diagnosed with NMDARE. 103 had sufficient clinical data available for analyses. Two‐thirds were Hispanic, disproportionate to the Houston metro area demographics, and Hispanic patients had a higher CSF white cell count and antibody titer. Approximately one‐half of the patients with idiopathic NMDARE presented with a focal cortical phenotype that localized …

Beyond The First Bout: Adaptations To Repeated Injuries Across Physiological And Pathological Conditions, Cory W. Baumann, Christopher P. Ingalls, Kazunori Nosaka, Jarrod A. Call

Research outputs 2022 to 2026

Skeletal muscle exhibits remarkable plasticity following injury, yet most research has focused on responses to a single bout of eccentric contractions. This review addresses adaptations to repeated eccentric contraction–induced injuries across physiological and pathological conditions, with emphasis on insights from preclinical rodent models. In healthy muscle, the repeated bout effect (RBE) reduces strength loss and accelerates recovery after subsequent bouts. However, these adaptations are highly condition dependent. Aging can attenuate the RBE, while dystrophic muscle remains vulnerable to repeated injury despite compensatory remodeling. Other factors, including but not limited to, chronic alcohol intake and malignant hyperthermia can influence these responses, …

Circulating Sphingomyelins Correlate With Plasma T-Tau In Cognitively Unimpaired Older Adults At Risk Of Developing Alzheimer's Disease, Tahmida Sharmin, James D. Doecke, Pratishtha Chatterjee, Steve Pedrini, Hamid R. Sohrabi, Nicholas J. Ashton, Henrik Zetterberg, Manohar L. Garg, Kaj Blennow, Ralph N. Martins

Research outputs 2022 to 2026

Alterations in plasma sphingomyelin (SM) levels have been reported in Alzheimer's disease (AD), pointing to disturbances in lipid metabolism that may contribute to disease pathogenesis. Neuronal damage in early AD triggers tau release into central and peripheral systems. Despite influence from peripheral contributions, alterations in plasma total-tau (T-tau) remain valuable in indicating AD-related neurodegeneration. Investigating relationships between SM metabolism and tau release during preclinical AD may uncover important biochemical processes and support advancing early non-invasive detection and treatment approaches. This cross-sectional study investigated cognitively unimpaired (CU) older adults from the KARVIAH cohort, grouped by cortical amyloid-β (Aβ) status through positron …

A High-Throughput Assay For Monitoring And Quantifying Amyloid-Β Accumulation And Clearance In Alzheimer's Disease Cell Models, Ajish Ariyath, Fraulein Denise Arigo, Anna Fyfe, W. M.A.D.Binosha Fernando, Ralph Martins, Prashant Bharadwaj

Research outputs 2022 to 2026

Amyloidogenic proteins, such as amyloid-β (Aβ), self-assemble into cross-β fibrils whose accumulation is central to Alzheimer's disease (AD). Measuring Aβ aggregation and clearance in living cells remains challenging using current cell-based assays, which are often low-throughput or not suited for real-time monitoring. This study aimed to (1) develop a robust, quantitative, and scalable fluorescence-based assay using Amytracker to monitor Aβ accumulation and clearance in an Aβ-producing neuronal cell model, and (2) validate its utility for mechanistic studies and therapeutic screening. We established a plate-based fluorescence assay using Amytracker in MC65 neuronal AD model expressing the Amyloid precursor protein C-terminal fragment …

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 …

Characterizing Metabolic Flux Of Plant Secondary Metabolites From Diverse Animal-Source Foods To Humans, Muhammad Ahsin

All Graduate Theses and Dissertations, Fall 2023 to Present

There is a popular saying: “You are what you eat.” But does this also mean, “You are what your food eats”? This dissertation explores that question by examining how farming practices shape the nutritional quality of meat—and what, if anything, those differences mean for the people who consume it. While modern livestock production and nutrition research often emphasize protein and fat, this work tests the idea that animals function as biological mediators, linking soil and plant conditions to human diets through the chemical composition of meat and milk. To evaluate this hypothesis, we tracked health-relevant plant compounds— phytonutrients—across the soil–plant–animal–human …

The Rodent Electronic Nicotine Delivery System (Rends): Effects Of Age On Self-Administration Of Inhaled Nicotine In Female Rats, Daniel Santos Da Silva

All Graduate Theses and Dissertations, Fall 2023 to Present

Smoking tobacco is the leading avoidable cause of death and drives many health problems. Nicotine, the main chemical in tobacco products, keeps people using it. This study used the Rat Electronic Nicotine Delivery System (RENDS), an inexpensive and freely shared, to examine e-cigarette use in adolescent and adult female rats by exploring four phases of nicotine delivered and not delivered to understand use patterns among ages. Our study found that both adolescent and adult female rats chose to inhale nicotine when given the opportunity, showing drug-seeking behavior. Overall, nicotine use was similar between ages. These results could help inform therapies, …

Food-Form Delivery Of Spore-Forming Probiotics As An Alternative To Gavage In Animal Models, Aubreyona Faith Migliori Skalka

All Graduate Theses and Dissertations, Fall 2023 to Present

Western dietary patterns are characterized by nutrient-poor, calorie-rich diets and have been linked to poor health outcomes and gut inflammation phenotypes. Probiotics are often taken to support gut health, but many beneficial bacteria do not survive transport through the digestive system to produce any effect. Spore-forming bacteria, such as Bacillus coagulans, are more resilient due to their hardy outer coat which aids in survival through many obstacles encountered in the gastrointestinal tract, including acidic stomach conditions. In research studies, probiotics are usually given to mice through a procedure called oral gavage, where a tube is used to deliver the …

Interplay Between Genetic Ancestry, Self-Reported Race And Ethnicity, And Clinical Factors In Pediatric Acute Lymphoblastic Leukemia: A Redial Consortium Report, Pragati Kore, Jennifer M Geris, Maria Leon-Camarena, Maria I Castellanos, Olga A Taylor, Veronica Garcia-Morales, Austin L Brown, Pagna Sok, Jeremy M Schraw, Van Huynh, Kathleen F Ludwig, Laura J Klesse, Sandi L Pruitt, Amy E Hughes, Kevin Tien, Kenneth M Heym, Timothy Griffin, Rodrigo Erana, Juan Carlos Bernini, Maria M Gramatges, Elizabeth G Atkinson, Philip J Lupo, Michael E Scheurer, Karen R Rabin

Faculty, Staff and Students Publications

Background: Pediatric acute lymphoblastic leukemia (ALL) is the most common cancer in children, and its incidence and outcomes vary by race and ethnicity.

Methods: The Reducing Ethnic Disparities in Acute Leukemia (REDIAL) Consortium has assembled a cohort of patients < 25 years at diagnosis to examine genetic and neighborhood-level factors influencing ALL. As the cohort is ongoing, for this report, we examined sociodemographic and cytogenetic factors that might be associated with ALL outcome disparities.

Results: Among 2,512 patients diagnosed between 2005 and 2020, we observed distinct patterns of genetic ancestry and residential characteristics across self-reported race and ethnicity. Latino children, who comprised 55.3% of the cohort, had a mean Amerindigenous ancestry proportion of 50.9%, whereas non-Latino White children exhibited a predominantly European ancestry (mean = 78%). Neighborhood-level analysis revealed significant socioeconomic and geographic differences by …

Protecting Minors From Medical Malpractice Act: Implications For Otolaryngology-Head & Neck Surgery, Shiven Sharma, Margo K Mckenna, Julina Ongkasuwan, Michael J Brenner

Faculty, Staff and Students Publications

No abstract provided.