Digital Commons Network^™

Trem2 Depletion In Pancreatic Cancer Elicits Pathogenic Inflammation And Accelerates Tumor Progression Via Enriching Il-1Β+ Macrophages, Daowei Yang, Xinlei Sun, Hua Wang, Ignacio I Wistuba, Huamin Wang, Yang Chen

Faculty, Staff and Student Publications

Background & aims: Pancreatic ductal adenocarcinoma (PDAC) has a complex tumor microenvironment enriched with tumor-associated macrophages. Triggering receptor expressed on myeloid cells 2 (TREM2) is highly expressed by a subset of macrophages in PDAC. However, the functional role of TREM2 in PDAC progression remains elusive.

Methods: We generated a novel transgenic mouse model (KPPC;Trem2-/-) that enables the genetic depletion of TREM2 in the context of spontaneous PDAC development. Single-cell RNA-sequencing analysis was used to identify changes in the tumor immune microenvironment on TREM2 depletion. We evaluated the impacts of TREM2 depletion on the tumor immune microenvironment to elucidate the functions …

A Plain Language Summary Of Polaris: A Study To Look At Different Doses Of Encorafenib Plus Binimetinib For People With Braf V600-Mutant Melanoma With Brain Metastasis, Alexander M Menzies, Georgina V Long, Amiee Kohn, Hussein Tawbi, Jeffrey Webe, Grant A Mcarthur, Yanina Pfluger, Karl Lewis, Katy K Tsai, Omid Hamid, Hans Prenen, Luis Fein, Erjian Wang, Carolin Guenzel, Fan Zhang, Joseph F Kleh, Alessandra Di Pietro, Michael A Davies

Faculty, Staff and Student Publications

What is this summary about?People with a type of melanoma called advanced or metastatic BRAF V600- mutant melanoma, with a change in the BRAF gene, that has spread to the brain have poor outcomes.Current treatments include encorafenib (BRAFTOVI®) and binimetinib (MEKTOVI®). The POLARIS clinical study looked at whether increasing the encorafenib dose would make treatment more effective, with similar side effects, in these patients.The first part of the study, known as the safety lead-in, looked at the side effects of a high dose of encorafenib together with binimetinib. This was followed by a phase 2 part to …

The Potential Benefit Of Encorafenib Plus Cetuximab With Chemotherapy Compared With Standard Of Care In People With Braf V600e-Mutant Metastatic Colorectal Cancer In The Breakwater Study: A Plain Language Summary, Scott Kopetz, Takayuki Yoshino, Eric Van Cutsem, Cathy Eng, Tae Won Kim, Jayesh Desai, Rona Yaeger, Timothy S Maughan, Elena Beyzarov, Xiaoxi Zhang, Graham Ferrier, Xiaosong Zhang, Josep Tabernero

Faculty, Staff and Student Publications

No abstract provided.

Comparing Stroke Risk Factors Among Sexual Minority Groups In Texas, Brittany Krenek, Samuel Tundealao, Jennifer E S Beauchamp, Sean I Savitz, Irene Tamí-Maury

Faculty, Staff and Student Publications

Background: Knowledge gaps remain on stroke risk and disparities between sexual minority (SM) subgroups. In this study, stroke risk between SM subgroups, specifically gay/bisexual men and lesbian/bisexual women (G/BM and L/BW), was assessed.

Method: Data were collected in June 2022 using a bilingual (English and Spanish) cross-sectional paper-and-pen survey distributed among 183 SM individuals attending the 2022 Houston Pride Parade and Festival, as well as across Texas via phone call or online format. Relevant sociodemographic and stroke risk factors were compared between G/BM and L/BW using chi-square (or Fisher's exact, when appropriate) and two-sample t-tests. Sexual orientation was used to …

Advancing The Development Of Trip13 Inhibitors: A High-Throughput Screening Approach, Rae M Sammons, Soma Ghosh, Lacin Yapindi, Eun Jeong Cho, Faye M Johnson

Faculty, Staff and Student Publications

TRIP13, a promising target for cancer therapy, has been identified as a key regulator of the mitotic checkpoint. Overexpression of TRIP13 is associated with poor clinical outcomes in various cancers. Inhibition of TRIP13 has the potential to address therapeutic challenges in cancer, particularly in therapy-resistant and Rb-deficient cancers. Despite the potential therapeutic benefits of TRIP13 inhibition, the development of TRIP13 inhibitors has been hindered by the lack of a robust high-throughput screening (HTS) assay. We developed a luminescence-based biochemical assay for TRIP13 activity to address this challenge using the ADP-Glo detection system. This assay offers high sensitivity, low background signal, …

Aapm Task Group No 249b-Essentials And Guidelines For Clinical Medical Physics Residency Training Programs, Jonathon A Nye, Joseph P Dugas, William D Erwin, David P Gierga, Darryl G Kaurin, Ho-Ling Anthony Liu, Alphonso W Magri, Lynn N Rill, Leah K Schubert, Beth A Schueler, Irina Vergalasova, John Vetter, Brian D Wichman, Amy Shu-Jung Yu, Dandan Zheng

Faculty, Staff and Student Publications

The establishment of guidelines and curriculum standards for medical physics residency training is a critical component of setting expectations and competencies for the profession. Since the last publication of these standards, residency training has become integrated into the eligibility criteria for most medical physics certification bodies. The rapid growth of medical physics requires periodic review of the curriculum to remove outdated approaches, update established knowledge, and add emerging technologies. The goal of this document is to provide a reference standard for residency training program directors, training mentors, and residents to guide creation and/or optimization of their program's curriculum. The document …

Nlrp3 Inflammasome Activation Expands The Immunosuppressive Myeloid Stroma And Antagonizes The Therapeutic Benefit Of Sting Activation In Glioblastoma, Spencer T Lea, Chao-Hsien Chen, Jun Wei, Ivana William, Inés Lopez Del Castillo

Faculty, Staff and Student Publications

Glioblastoma (GBM) is the most common and deadly primary brain malignancy and is clinically refractory to immunotherapy. Active NLRP3 inflammasome signaling and IL-1β secretion have been observed in GBM, and NLRP3-driven myeloid-derived suppressor cell (MDSC) recruitment can mediate cancer immune evasion. Agonists of the cytosolic double-stranded DNA-sensing stimulator of IFN gene (STING) pathway can mediate proinflammatory conversion of cancer MDSCs; however, secretion of the NLRP3 products IL-1β and IL-18 has also been observed in certain myeloid populations following STING activation. In this study, we aimed to determine both the potential mechanistic synergy between STING and NLRP3 agonists, and the effects …

Multicancer Early Detection Tests At A Crossroads: Commercial Availability Ahead Of Definitive Evidence, Carmen E Guerra, Jennifer Keating Litton, Carolina E Viswanath, A Mark Fendrick

Faculty, Staff and Student Publications

Multicancer early detection tests (MCEDs), sometimes referred to as liquid biopsies, are tests that can screen for multiple cancers by analyzing blood, urine, and other bodily fluids for biomarkers released by cancer cells. These tests have the potential to change the cancer screening paradigm if they are shown to reduce cancer mortality. However, it is not yet known whether MCEDs reduce mortality. Randomized controlled trials, the gold standard for evaluating cancer screening programs, are currently evaluating the effectiveness of MCEDs. However, because cancer-specific and all-cause mortality are end points that can take years to reach, trials are being designed with …

An Enzyme-Linked Immunosorbent Assay (Elisa)-Based Activity Assay For Amp-Activated Protein Kinase (Ampk), Trezze P Nguyen, Shangze Lyu, Yang Liu

Faculty, Staff and Student Publications

AMP-activated protein kinase (AMPK) is the master regulator of cellular and organismal energy homeostasis, playing an essential role in modulating metabolism and other cellular processes. Substantial efforts have been made to develop pharmacological modulators of AMPK activity due to their therapeutic potential against various diseases. Measuring AMPK activity in vitro is a fundamental step for testing AMPK activators and inhibitors. Here, we report an enzyme-linked immunosorbent assay (ELISA)-based AMPK activity assay with simple steps and high sensitivity. This assay offers a robust, in-house alternative to the traditional radioactive methods and other approaches that rely on specialized reagents or commercial kits.

Cross-Institutional Dental Electronic Health Record Entity Extraction Via Generative Artificial Intelligence And Synthetic Notes, Xiaoqian Jiang, Muhammad F Walji, Oluwabunmi Tokede

Faculty, Staff and Student Publications

Background: While most health-care providers now use electronic health records (EHRs) to document clinical care, many still treat them as digital versions of paper records. As a result, documentation often remains unstructured, with free-text entries in progress notes. This limits the potential for secondary use and analysis, as machine-learning and data analysis algorithms are more effective with structured data.

Objective: This study aims to use advanced artificial intelligence (AI) and natural language processing (NLP) techniques to improve diagnostic information extraction from clinical notes in a periodontal use case. By automating this process, the study seeks to reduce missing data in …

Baseline Predictors Of Responders To Auricular Point Acupressure In Chronic Low Back Pain, Claudia M Campbell, Johannes Thrul, Xinran Huang, Paul Christo, Constance M Johnson

Faculty, Staff and Student Publications

Background: Chronic low back pain (cLBP) is a major cause of disability, with varied patient responses to treatments. Auricular point acupressure (APA) has shown potential as a non-pharmacological intervention, but individual responses may differ significantly.

Objective: This study aimed to determine the predictability of baseline characteristics, including functional disability, symptom severity, and treatment expectancy, on clinically significant responses to APA in reducing pain and improving function.

Methods: A secondary analysis was performed using data from a randomized controlled trial with 263 cLBP patients. Participants were randomly assigned to targeted APA (T-APA), non-targeted APA (NT-APA), or to a control group. APA …

Bile Acid Regulation Of Xenobiotic Nuclear Receptors On The Expressions Of Orosomucoids In The Liver, Ji Ho Suh, Inyoung Cheon, Hyun-Jung Jung, Sung Ho Lee, Mi Jeong Heo, Matthew Deberge, Clavia Ruth Wooton-Kee, Kang Ho Kim

Children’s Nutrition Research Center Staff Publications

The constitutive androstane receptor (CAR) and pregnane X receptor (PXR) are xenobiotic nuclear receptors activated by various xenobiotics, drugs, hormones, and bile acids (BAs). Upon activation, these nuclear receptors play critical roles in regulating systemic energy homeostasis. However, precise mechanisms through which CAR and PXR influence systemic metabolism remain incompletely understood. Here, we investigated the impact of CAR and PXR on the liver-secreted hormone (i.e., hepatokine) expressions in response to BA stress such as cholic acid (CA) feeding. Our analysis revealed that several BA-activated genes, including the well-known CAR/PXR target, aldo-keto reductase family 1, member B7 (Akr1b7 …

The Ethnobotany And Pharmacology Of Medicinal Plants For Caribbean Women’S Health, Ella Thomas Vardeman

Dissertations, Theses, and Capstone Projects

Approximately 55% of the world’s population lives in cities, and the United Nations estimates that this number will rise to 68% by 2050. Urban ethnobotany, the study of people’s traditional knowledge and use of plants in cities, is increasingly important as people adapt their cultural traditions to changing environments. In New York City (NYC), there have been several urban ethnobotany investigations in collaboration with Caribbean immigrant groups. However, there has yet to be an ethnobotanical survey that documents and botanically authenticates the medicinal plants used in the Haitian community. Previous collaborative research with women from the Caribbean in NYC has …

Environmental Enrichment Reduces Cue-Induced Reinstatement Of Heroin-Seeking Following Prolonged Use And Reverses Region-Specific Heroin-Induced Neuroadaptations, Apoorva Vashisht

Dissertations, Theses, and Capstone Projects

Background: Relapse remains the greatest barrier to long-term recovery and the consequential rising overdose-related mortality in heroin use disorder (HUD). Currently available behavioral and pharmacological interventions fail to extend their benefits beyond the duration of the treatment. Additionally, opioid agonist-based medications accompany harmful neurobiological risks and propensity to promote further drug-seeking post-treatment. We have shown that environmental enrichment (EE), as a therapeutic strategy applied after drug intravenous-self administration (IVSA), can effectively facilitate abstinence and reduce reinstatement of drug-seeking in animal models of drug abuse. Moreover, dopamine receptors like D1 and D3, and mu-opioid (MO) receptors are well known for their …

Disturbance And Diversity: Lichens In Changing Landscapes, Laura Boggess

Dissertations, Theses, and Capstone Projects

Disturbance is a fundamental ecological force that shapes biodiversity, community composition, and ecosystem function. Human-driven disturbances—such as habitat fragmentation, deforestation, and air pollution—are increasing worldwide, altering ecosystems at unprecedented rates. While ecological research has illuminated many effects of disturbance, significant knowledge gaps remain for underappreciated but ecologically vital organisms, such as lichens. Lichens are obligate symbioses between at least one fungus and one alga or cyanobacterium. As such, they are sensitive bioindicators of environmental change, offering unique insights into ecosystem health due to their responses to stressors such as poor air quality, habitat fragmentation, and deforestation. Yet, their responses to …

Understanding How Genetic Mutations Induce Oligodendrocyte Progenitors To Become Cancer Cells, Dennis Huang

Dissertations, Theses, and Capstone Projects

Gliomas are the most devastating adult brain tumors characterized by poor survival rate and limited options for treatment. Previous studies have shown that they are very heterogeneous and can be further sub-classified based on their transcriptional signature and the presence of specific mutations. One such subtype, is the “proneural glioma”, which is characterized by the enrichment in oligodendrocyte progenitor cell (OPC) transcripts and mutations in genes encoding for the tumor suppressor P53 (Trp53) and for Platelet Derived Grow Factor (PDGF) signaling. Since OPCs are the most abundant proliferative population in the adult brain, in this …

Fda Approves Lecanemab-Irmb Maintenance Dosing For Early Alzheimer’S Disease Treatment, Jordyn Linfield, Giang Nguyen, Ashley Jacob, Andrew Johnson, Maria Nguyen, Sara Ha, Joshua Honaker, Samantha Mccord, Kelly Kroustos

Pharmacy and Wellness Review

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder and is associated with progressive and irreversible cognitive decline that begins with memory lapses leading to physical and functional impairment. The conventional therapies that have been used for the treatment from Alzheimer's Disease include acetylcholinesterase inhibitors and memantine, but additional therapy options are being developed. Lecanemab, brand name Lequembi, is currently a Food and Drug Administration (FDA) approved humanized monoclonal antibody for the treatment of Alzheimer’s disease and indicated for mild cognitive impairment (MCI) or mild dementia. While there is impactful aid for treatment, lecanemab has three significant adverse reactions, which …

The Role Of Excitatory Neuromodulation In Managing Variability Of Neural System Output, Omar Itani

Dissertations

Neural systems can generate consistent outputs across a population despite substantial variability in the underlying components of individuals. This dissertation aims to identify mechanisms through which neuromodulation influences the relationship between parametric and output variability in neural systems. Through a combination of theoretical analysis, computational modeling, and data-driven approaches, the research addresses how excitatory neuromodulation can shape population-level activity variability and identifies key patterns that govern the production of consistent neural population output despite underlying parameter variability.

The theoretical foundation is established by considering how excitatory neuromodulation affects population variability in simplified neuronal models. Two fundamental patterns of variability reduction …

Cohabitation At Threshold: Carpenter House Reimagined For Multispecies Living, Zhixiao Yang

Masters Theses

With the rapid growth of the human population, we are encroaching further into wildlife habitats, particularly those surrounding urban environments. This accelerating urbanization leads to biodiversity loss, the degradation of ecological services essential to human health and well-being, and a diminishing connection between city dwellers and the natural world.

Today, urban planners, architects, economists, and other advocates for the future of humanity and the health of the planet are actively questioning how we might build greener, more resilient cities. While much of the focus has been on large-scale interventions — such as the use of sustainable materials, the creation of …

Covered In Snow, Katelynn M. Rogers

Masters Theses

Covered in Snow is a photographic exploration into the ripple effect of maternal loss and environmental decay in my hometown of Canton, Ohio. In the wake of a miscarriage, the woods I had grown up within began calling to me, urging me to return. Unbeknownst to me, a series of accidental deaths of women had been happening throughout these trees my entire life, their stories only coming to the surface as I looked to the trees for solace. This series of inexplicable deaths in the woods I so desperately loved began to alter my relationship to the trees, a distrust …

Field Journal: The Excluded Middle, Carrie E. Kouts

Masters Theses

What does it look like to engage with organisms and landscapes at the periphery of anthropocentric value structures? How does one break the internalized myth that the “built” environment is excluded from the natural world? When does a hyper-mobile and hyper-commodified society confront the exponential crisis of animal death? Within this series of journal entries, field notes, collection observations, weird prose, and sensory musings, one will find questions on the nature of being human and the complex narratives of care we encounter in a world shared with more-than-humans. Each handwritten vignette and photograph from daily life weaves a non-linear and …

Gamified Gait Rehabilitation Via Real-Time Biofeedback And Adaptive Hip-Exoskeleton Control, Mariya Huzaifa Tohfafarosh

Theses

Gait impairments arise from systemic diseases, age-related degeneration, musculoskeletal dysfunctions, or neurological conditions. While traditional rehabilitation can be effective, they often face challenges such as high costs, inaccessibility, and low patient engagement. To address these challenges, my work introduces a virtual reality-based rehabilitation (VRBR) system, integrating real-time motion and electromyographic (EMG) muscle activation feedback with a gamified virtual environment for enhanced adaptability and engagement. The system includes a custom-designed hip-exoskeleton that provides adaptive spring-like assistance or resistance, supporting both mobility-impaired users and strength training. Assistance levels can be tuned to match the user's progress. Additionally, a custom pressure insole was …

Neuroinflammation In The Ventral Tegmental Area Of Chronically Stressed Rats, Marie M. Hafez

Honors Projects

Chronic stress has been associated with maladaptive behaviors in both human and animal research models, but the underlying mechanisms are unclear. In this research study, we sought to define whether stress induces neural inflammation in the ventral tegmental area, the brain region primarily responsible for regulating reward consumption, learning, memory, and addictive behaviors through moderating dopamine release in other brain areas. To do this, male Sprague-Dawley rats were subjected to a chronic intermittent stress paradigm that included stressors such as wet bedding, delayed feedings, social isolation, strobe lights, and forced swims. Following the chronic stress intervention, brain sections were collected …

Analytical Approaches For Identification Of Essential Genomes Of Plasmodium Knowlesi And Babesia Divergens, Sida Ye

Graduate Doctoral Dissertations

Apicomplexa constitute a large phylum of single-celled, obligate intracellular protozoan parasites. Notably, Plasmodium spp. and Babesia spp. are apicomplexan parasites that infect red blood cells. Plasmodium species are the causative agent of malaria and are transmitted by Anopheles mosquitoes, affecting large human populations, whereas Babesia spp., transmitted through the bite of Ixodes ticks cause babesiosis.

In this dissertation, we investigate the essential genome of these parasites using high-throughput transposon mutagenesis. Identifying the essential genome is key to finding new drug targets and understanding resistance mechanisms, a crucial pursuit given the rising resistance to frontline antimalarial drugs and the challenges …

Pulped Landscapes, Allison P. Abrams

Masters Theses

Large corporations control intensive and extractive industrial land use practices through acts of dumping, capping, and neglect. The abandonment of industrial sites is increasing as well as the environmental consequences of such actions. How can impacted communities proactively engage in remediation processes while post-industrial sites sit in limbo?

With the former Foley Cellulose Plant in Perry, Florida (closed in 2023) as a case study, this thesis researches and speculates on potentials of phytoremediation experimentation and harvesting of plant fibers on contaminated soils. The site is a pulped landscape: land directly impacted by intensive, large corporation-led pulp production practices that is …

Genetic Factors Of Campylobacter Jejuni Required For Its Interactions With Free-Living Amoeba, Deepti Pranay Samarth, Asim Z. Abbasi, Young Min Kwon

Poultry Science Faculty Publications and Presentations

Acanthamoeba, a free-living amoeba ubiquitous in environmental water, has been considered as the environmental reservoir of certain bacterial pathogens, including Campylobacter jejuni, an intracellular human pathogen causing self-limiting gastroenteritis. Acanthamoeba-C. jejuni interaction mechanisms may help clarify how the otherwise fastidious bacterium C. jejuni survives in environmental waters. In this study, we constructed single deletion mutants of C. jejuni strain 81-176 for the 10 selected genes (motAB, ciaB, kpsE, virB11, cheY, flaAB, cstII, docB, sodB, and cadF) previously shown to be important for the interaction (invasion and intracellular survival) of C. jejuni with mammalian hosts. We used a modified gentamicin protection …

Anti-Viral Cd8 Central Memory Veto Cells As A New Platform For Car T Cell Therapy, Wei-Hsin Liu, Anat Globerson Levin, Assaf Lask, Galit Horn, Tova Waks, Irit Milman Krentsis, Xiaohua Su, Maksim Mamonkin, Richard E Champlin, Yair Reisner, Esther Bachar Lustig

Faculty, Staff and Student Publications

Central memory CD8 T cells exhibit marked veto activity enhancing engraftment in several mouse models of T cell-depleted bone marrow (TDBM) allografting. Graft-versus-host disease (GVHD) can be prevented by stimulation of mouse or human memory CD8 T cells against their cognate antigens under cytokine deprivation, in the early phase of culture followed by further expansion with IL21, IL15, and IL7. Thus, human anti-viral CD8 central memory veto T cells generated from CMV and EBV-positive donors are currently evaluated in a clinical trial at MD Anderson Cancer Centre (MDACC). Results in 15 patients indicate a low risk of GVHD. Considering that …

Development Of A Novel Biomarker Platform For Profiling Key Protein-Protein Interactions To Predict The Efficacy Of Bh3-Mimetic Drugs, Andrew J Kinloch, Faiyaz Rahman, Bahriye Karakas, Muhammad Shahid, Bora Lim, James A Walker, Walter D Fairlie, Kevin R Kelly, Michael H Cardone

Faculty, Staff and Student Publications

One of the hallmarks of cancer cells is their failure to respond to the cellular mechanism of apoptosis. The B-cell lymphoma 2 (BCL-2) family of proteins regulate apoptosis. Their ability to do so can be measured using several methods that in turn anticipate the fate of the cancer cell in response to apoptosis-inducing treatment. These assays ultimately identify the readiness of the cancer cell to undergo apoptosis, which is referred to as the mitochondrial priming state. These metrics, however, have been challenging to implement in the clinic.

Diversity And Activity Of Ground-Dwelling Spiders (Araneae) In Four Sub-Communities In A Degraded Oak Woodland At The Chicago Botanic Garden, Cook County, Illinois, James F. Steffen, Michael L. Draney

The Great Lakes Entomologist

Ground-dwelling spiders were sampled using pitfall traps over a twelve-month period from four sub-communities within a 40-ha oak woodland complex in northern Cook County, Illinois. Mesic and dry mesic oak woodland, mesic upland forest, buckthorn dominated mesic oak savanna and a mesic woodland control, where no restoration management is planned, were sampled. Fifty-five species within 44 genera and 18 families were trapped. The results suggest negative correlations between non-native spider abundance and spider species richness. Also, phenology of the various species indicates that a year-round inventory is necessary to adequately sample ground-dwelling spider assemblages. Possibilities of using Bathyphantes concolor (Wider) …

The Native And Introduced Bark And Ambrosia Beetles Of Michigan (Coleoptera: Curculionidae, Scolytinae), Anthony I. Cognato, Nicolas Barc, Michael Philip, Robert Mech, Aaron D. Smith, Eric Galbraith, Andrew J. Storer, Lawrence R. Kirkendall

The Great Lakes Entomologist

Our knowledge of the biogeography of Scolytinae of eastern temperate North America is very patchy. We used data from hand collecting, trapped material (from 65 of 83 counties), and museum collections, supplemented by literature records, to compile a list comprising 107 bark beetle species in 45 genera for Michigan, a state with an especially rich diversity of woody plants. We provide detailed collection data documenting 32 species not previously catalogued for Michigan, 23 of which are new state records; the genera Trypophloeus and Trischidias are reported from Michigan for the first time. Fifteen Michigan scolytines are not native to North …