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Cord Blood Treatment For Children With Cerebral Palsy: Individual Participant Data Meta-Analysis, Megan Finch-Edmondson, Madison C B Paton, Annabel Webb, Mahmoud Reza Ashrafi, Remy K Blatch-Williams, Charles S Cox, Kylie Crompton, Alexandra R Griffin, Minyoung Kim, Steven Kosmach, Joanne Kurtzberg, Masoumeh Nouri, Mi Ri Suh, Jessica Sun, Morteza Zarrabi, Iona Novak

The Brown Foundation: Institute of Molecular Medicine

Context: Umbilical cord blood (UCB) is a novel treatment for cerebral palsy (CP), with trials indicating UCB can improve gross motor function. However, heterogeneity has limited the ability to interpret findings.

Objective: Assess the safety and efficacy of UCB for improving gross motor function in children with CP, including exploring cell dose effect and responder subgroups.

Data sources: Individual participant data from published reports and registered trials identified via systematic searches.

Study selection: Studies administering UCB to individuals with CP collecting Gross Motor Function Measure (GMFM) scores.

Data extraction: A 1-stage individual participant data meta-analysis was conducted in R to …

Pediatric Predictive Artificial Intelligence Implemented In Clinical Practice From 2010 To 2021: A Systematic Review, Swaminathan Kandaswamy, Lindsey A Knake, Adam C Dziorny, Sean M Hernandez, Allison B Mccoy, Lauren M Hess, Evan Orenstein, Mia S White, Eric S Kirkendall, Matthew J Molloy, Philip A Hagedorn, Naveen Muthu, Avinash Murugan, Jonathan M Beus, Mark Mai, Brooke Luo, Juan D Chaparro

Faculty, Staff and Students Publications

To review pediatric artificial intelligence (AI) implementation studies from 2010 to 2021 and analyze reported performance measures.We searched PubMed/Medline, Embase CINHAL, Cochrane Library CENTRAL, IEEE, and Web of Science with controlled vocabulary. Inclusion criteria: AI intervention in a pediatric clinical setting that learns from data (i.e., data-driven, as opposed to rule-based) and takes actions to make patient-specific recommendations; published between 01/2010 and 10/2021; must have agency (AI must provide guidance that affects clinical care, not merely running in the background). We extracted study characteristics, target users, implementation setting, time span, and performance measures.Of 126 articles reviewed as full text, 17 …

Editorial: The Journal Of Pediatric Psychology Remains Committed To Advancing Pediatric Psychology Science, Avani C Modi, Kurt A Freeman, Cecelia Valrie, Marisa E Hilliard, Eleanor R Mackey, Katie A Devine, Susan Wood

Faculty, Staff and Students Publications

No abstract provided.

Produce Prescription Policy Project For The Securement Of A Grant To Address Food Insecurity For Low-Income Type Ii Diabetic Patients, Isabel D. Garcia-Gallegos

Doctor of Nursing Practice Final Project Abstract

PURPOSE

This policy-focused Doctor of Nursing Practice (DNP) quality improvement (QI) project aims to secure grant funding through the Gus Schumacher Nutrition Incentive Program (GusNIP) to implement a produce prescription program at a community clinic in Texas. The program targets low-income adults (18-65 years) with type II diabetes who experience food insecurity and are affected by Medicaid non-expansion.

BACKGROUND

Texas’ decision not to expand Medicaid has exacerbated food insecurity among low-income residents, particularly those managing type II diabetes. This decision creates a healthcare policy gap that this project aims to address with a food-as-medicine program.

METHODOLOGY

Using the Plan-Do-Study-Act (PDSA) …

Ascl2 Positive Tumor Cells Modulate The Response Of Metastatic Colorectal Cancer To Mapk-Targeting Therapy, Oscar Eduardo Villarreal

Dissertations and Theses (Open Access)

Colorectal cancer (CRC) is the second leading cause of cancer related deaths with nearly a quarter of patients presenting with metastatic disease at the time of their diagnosis. Therapeutic management of metastatic CRC continues to be a major challenge due to therapy resistance and disease heterogeneity. Due to its central role in tumorigenesis, CRC is commonly treated with MAPK pathway inhibitors (MAPKi). However, clinical trials repeatedly demonstrates that durability of benefit is short-lived in many patients. While genomic mechanisms of acquired resistance have been described, they explain a minority of patients, and further research is needed to determine the underlying …

Eepd1 Evolved A Unique Dna Clamping Dimer Protecting Reversed Replication Forks, Runze Shen

Dissertations and Theses (Open Access)

Exonuclease/endonuclease/phosphatase (EEP)-fold hydrolases are canonically monomeric phosphodiesterases exemplified by APE1, DNase I, and TDP2 nucleases. While EEP superfamily domain-containing protein 1 (EEPD1) acts in DNA stress responses, its proposed nuclease activities are enigmatic. Here, we integrate hybrid structural methods, evolution, biochemistry, cancer genomics, molecular and cell biology to define EEPD1’s structure, assembly, and function at stalled DNA replication fork intermediates. Combined results show that EEPD1 surprisingly requires both the unique EEP domain dimer and distinctive tandem Helix-hairpin-Helix [(HhH)₂] domains to clamp double-stranded(ds) DNA at reversed DNA replication forks for fork protection. X-ray scattering, crystal, and cryo-EM structures unveil …

Innovative Methods For The Design And Analysis Of Phase Ii Clinical Trials, Feng Tian

Dissertations and Theses (Open Access)

Drug development has become increasingly time-consuming, costly, and risky in recent years. There is significant potential for improving clinical trial designs, particularly for phase II trials, which play a critical role in the drug development process. Innovative methods are especially necessary for addressing key challenges in phase II trials in terms of dose-ranging study, patient population selection, and decentralized clinical trials (DCTs). This dissertation presents a comprehensive set of methodologies that address these critical issues with three projects. The first project introduces a Bayesian adaptive dose-ranging design that integrates both efficacy and toxicity data to evaluate each dose comprehensively. The …

Identification Of Mitochondrial Defects And Metabolic Consequences In Lynch Syndrome-Related Endometrial Cancer, Mikayla Bowen

Dissertations and Theses (Open Access)

Lynch syndrome (LS), defined by mutations in DNA mismatch repair genes including MSH2, carries a 60% lifetime risk of developing endometrial cancer (EC). Mismatch repair deficiency (MMRd) causes hypermutability, which is assumed to be the main driver of LS-related EC development. However, incomplete penetrance of EC development in women with LS suggests that other modulators are at play. The broad hypothesis of this dissertation is that MMRd causes consequences beyond hypermutability to impact LS-related EC development. Recent studies utilizing our lab’s Msh2-deficient mouse model for LS-EC revealed mitochondrial dysfunction in EC pathogenesis. This new insight led to the …

Dual-Criterion Dose Finding Designs For Phase I Clinical Trials, Yunlong Yang

Dissertations and Theses (Open Access)

The primary objective of Phase I oncology trials is to assess the safety and tolerability of novel therapeutics. Conventional dose escalation methods identify the maximum tolerated dose (MTD) based on dose-limiting toxicity (DLT). However, as cancer therapies have evolved from chemotherapy to targeted therapies, these traditional methods have become problematic. Many targeted therapies rarely produce DLT and are administered over multiple cycles, potentially resulting in the accumulation of lower-grade toxicities, which can lead to intolerance, such as dose reduction or interruption. To address this issue, we proposed dual-criterion designs that find the MTD based on both DLT and non-DLT-caused intolerance. …

Immune Landscape Of Early Liver Metastatic Lesions In A Novel Immunocompetent Murine Colorectal Cancer Metastasis Model, Alaa Mohamed

Dissertations and Theses (Open Access)

Colorectal cancer minimal residual disease (MRD) represents a major clinical problem for colorectal cancer patients, with failure rates of surgery and adjuvant chemotherapy between 5% to 40% depending on stage of disease. In our study, we simulated MRD using genetically engineered organoids with precise somatic editing of APC and TP53, creating a murine model that mimics human liver metastatic colorectal cancer. By implementing a meticulously timed experimental metastatic model, we could detect microscopic tumor lesions. Through genomic and transcriptomic analyses, we pinpointed the importance of macrophages, particularly those expressing high levels of CSF1R, in these microscopic metastatic focal lesions. We …

Unraveling Epigenetic Mechanisms That Regulate Breast Cancer Lung Metastatic Relapse By Rewiring The Immune Microenvironment, Jayanta Mondal

Dissertations and Theses (Open Access)

Metastasis accounts for >90% of cancer-related deaths and thwarting metastasis is widely considered to be the “Holy Grail” of cancer treatment. Breast cancer is the most common cause of cancer-related death among women and is characterized by its proclivity to spread to distant secondary organs like the lungs, and the brain. These disseminated tumor cells lie dormant at the secondary site and can undergo metastatic relapse. Epigenetic alterations are a predominant hallmark of cancer, however, its role in facilitating reawakening of dormant cancer cells and the subsequent metastatic relapse remains to be elucidated. To address this gap of knowledge, we …

Impact Of Tumor Cell Expressed Cd38 On Metastasis And Immune Evasion In Breast Cancer, Tanvi Visal

Dissertations and Theses (Open Access)

Triple-negative breast cancer (TNBC) is a highly metastatic breast cancer subtype. The epithelial-to-mesenchymal transition (EMT) of cancer cells is a key feature of the metastatic cascade and is not a binary process but often generates malignant cells with both epithelial (E) and mesenchymal (M) traits known as hybrid EM cells. Recent studies highlight the enhanced metastatic potential of the hybrid EM cells. However, molecular insights and targetable vulnerabilities within hybrid EM remain elusive. We discovered that hybrid EM murine tumors are enriched in CD38, an immunesuppressive molecule associated with worse clinical outcomes in liquid malignancies but relatively understudied in solid …

Evaluating Cancer Rates, Cancer Types, And Variant Hotspots Between Different Races And Ethnicities In Individuals With Li-Fraumeni Syndrome, Hillary Esplen

Dissertations and Theses (Open Access)

Li Fraumeni Syndrome (LFS) is a cancer predisposition syndrome that increases the risk for numerous cancer types in both children and adults. In the general population, incidence rates for various cancer types differ among races and ethnicities. Although a few germline TP53 pathogenic/likely pathogenic (P/LP) variants in those with LFS have been studied and associated with specific populations, such as the South and Southeast Brazil founder variant, p.Arg337His, there still lacks research on the variable expressivity of cancers within the LFS population based on specific variant, race and/or ethnicity. This study aims to describe the specific TP53 germline variants, the …

Relationship Between Processing Body Formation, Epithelial-To-Mesenchymal Transition, And Invasion In Lung Adenocarcinoma, Amanda Warner

Dissertations and Theses (Open Access)

Lung cancer is the leading cause of cancer-related deaths in the United States, largely due to its ability to metastasize. Epithelial-to-mesenchymal transition (EMT) is a process that enhances the ability of cells to lose their cell-cell contacts, invade, and enter the blood stream which are essential during metastasis. Many transcriptional gene programs are altered during EMT such as activation of mesenchymal transcription factors, like ZEB1, and enhanced response to the TGFβ1 cytokine. In oncogenic contexts, TGFβ1 enhances the formation of processing-bodies (P-bodies) where P-body proteins are required for invasion in multiple cancerous cell lines. P-bodies are a type of ribonucleoprotein …

Rod Photoreceptor Regeneration In A Zebrafish Model With Retinitis Pigmentosa, Eyad Shihabeddin

Dissertations and Theses (Open Access)

A cellular hallmark of inherited retinal degenerative diseases is progressive loss of photoreceptors until one is completely blind. Unlike mammalian models, Zebrafish have the ability to naturally regenerate their neurons after injury or disease is detected. We have generated a zebrafish model with the most common autosomal dominant form of the inherited retinal degenerative disease known as Retinitis Pigmentosa. We utilize immunohistochemistry, single-cell RNA sequencing, several analysis tools, behavioral assays and oligonucleotides to characterize our zebrafish model and identify the transcription factors necessary for rod photoreceptor regeneration. We show that our zebrafish model has continuous degeneration and regeneration of rod …

Automated Radiotherapy Treatment Planning For Breast Cancer: A Robust To Ol For Global Deployment, Hana Baroudi

Dissertations and Theses (Open Access)

Breast cancer incidence continues to rise worldwide, particularly in low- and middle-income countries, where limitations in resources already constrain access to timely care. Radiotherapy is a cornerstone of breast cancer management, proven to significantly lower both recurrence and mortality. However, a growing shortage of radiation staff worldwide threatens the prompt delivery of these treatments.This thesis proposes an automated solution to address the limited accessibility of radiotherapy planning in breast cancer management by developing an end-to-end automated treatment planning model and evaluating its performance and limitations across diverse patient populations.

An automated contouring model was trained using data from 104 whole-breast …

Exploring Veto Activity: Dnam-1-Cd155 Axis In Overcoming Nk Cell-Mediated Allo-Rejection And Applications For Car-T Cell Therapy, Wei-Hsin Liu

Dissertations and Theses (Open Access)

As Miller et al. defined veto activity, it enables cells to target host cytotoxic T lymphocyte (CTL) precursors specific to veto cells' antigens, selectively eliminating anti- donor T cell clones without inducing rejection. By leveraging this unique immune property, two key research aims were proposed: “Exploration of the Impact of Veto Activity on Natural Killer (NK) Cell-Mediated Allo-rejection” and “Development of Off-the- shelf Chimeric Antigen Receptor (CAR)-T Therapy: Engineering Anti-Viral Veto CD8+ T Cells”. As demonstrated in our previous research, in a murine model with mild conditioning, anti-third-party central memory CD8+ veto T cells (veto Tcm) can prevent T cell- …

The Gut Microbiome As A Novel Approach For Reversing Long-Term Inflammation And Accelerated Aging Across The Lifespan, Janelle M. Korf

Dissertations and Theses (Open Access)

Introduction: Neonatal hypoxic-ischemic encephalopathy (HIE) arises from disrupted perinatal cerebral oxygenation and perfusion. It is a leading global cause of infant death and disability which disproportionally affects males. Like adult stroke, HIE initiates a rapid influx of inflammatory cells across the blood brain barrier and a loss of microglial homeostasis. Persistent peripheral inflammation in children with a history of HIE is recognized but its ramifications, including accelerated aging, are poorly understood. As this coincides with critical stages of brain development, interventions started months or years post-injury may still improve survivors’ quality of life. One promising intervention is to manipulate the …

Development Of Lineal Energy Spectrum-Based Biological Effects Models For Protons, Joseph M. Decunha, Fada Guan, David Grosshans, Zhongxing Liao, Dragan Mirkovic, Oleg Vassiliev, Radhe Mohan

Dissertations and Theses (Open Access)

In this dissertation, methods are developed and described to allow for the rapid calculation of microdosimetric spectra (specifically, lineal energy) for protons. SuperTrack, a GPU-accelerated tool for calculation of microdosimetric spectra was developed and is capable of computing lineal energy spectra up to 5000x faster than using Geant4 directly. Proton lineal energy spectra generated by SuperTrack are indistinguishable from those generated by Geant4. With SuperTrack, large libraries of lineal energy spectra for monoenergetic protons spanning 0-300 MeV have been developed. The proton lineal energy spectra calculated by SuperTrack have been compared to experimental measurements made by a tissue equivalent proportional …

Novel Statistical Methods For Mediation Analysis With High-Dimensional Omics Mediators, Zhichao Xu

Dissertations and Theses (Open Access)

Mediation analysis is a widely used statistical method for examining how molecular traits, such as gene or protein expression, act as intermediaries linking an exposure to a health outcome. For example, it can help explain how smoking affects disease risk through molecular changes. The rapid progress in high-throughput omics profiling technologies and large-scale epidemiology consortia, such as the Trans-Omics for Precision Medicine (TOPMed) program from the National Heart, Lung and Blood Institute (NHLBI) and UK Biobank, now has resulted in an extensive accumulation of genomic data for biomedical research and analysis. At the same time, it poses significant methodological challenges, …

Overcoming Resistance To Cdk4/6-Targeted Therapy Using Jak2/Stat3 Inhibitor In Triple-Negative Breast Cancer, Chuling Zhuang

Dissertations and Theses (Open Access)

Breast cancer is the most common type of cancer diagnosed in women, with nearly 30% of cases becoming metastatic accounting for over 90% of breast cancer-related deaths. Among different breast cancer subtypes, triple-negative breast cancer (TNBC) has the worst prognosis and the highest propensity to metastasize. However, TNBC patients have limited treatment options due to their lack of actionable drug targets while therapeutic resistances result in high rates of recurrence and metastasis. Cyclin-dependent kinase 4 and 6 (CDK4/6) are major cell cycle regulators that control G1 to S phase transition and aberrant hyperactivation of the CDK4/6 pathway results in uncontrolled …

Combined Inhibition Of Lysine-Specific Demethylase 1 And Kinase Signaling As A Preclinical Treatment Strategy In Glioblastoma, Lea Stitzlein

Dissertations and Theses (Open Access)

Glioblastoma is the most common primary malignant brain tumor in adults, with limited treatment options resulting in a poor prognosis. Lysine-specific demethylase 1 (LSD1) is overexpressed in glioblastoma and contributes to tumor growth and treatment resistance. Inhibitors of LSD1 have shown preclinical promise but have had limited clinical development for glioblastoma. Given the frequent kinase pathway alterations in glioblastoma, the interplay between LSD1 inhibition and kinase signaling pathways was investigated to identify vulnerabilities that could be exploited through rationally designed combination therapies. We hypothesized that LSD1 inhibitors would activate kinase signaling pathways, such as MAPK, and the addition of kinase …

Impact Of Personal And Family History Of Huntington's Disease On The Decision And Ability To Obtain Life, Long-Term Care, And Disability Insurance, Karli Livingston

Dissertations and Theses (Open Access)

Huntington’s disease (HD) is an inherited, neurodegenerative condition characterized by a clinical triad of motor, cognitive, and psychiatric symptoms. Individuals diagnosed with HD manifest characteristic symptoms of the disease including motor and cognitive changes, and they may or may not have undergone genetic testing to confirm the diagnosis. Individuals at-risk for HD are those who have not yet undergone genetic testing for HD, but have a first- or second- degree relative diagnosed with the disease. Genetic testing for HD is categorized into two forms: predictive and confirmatory. However, many individuals choose not to pursue testing due to a fear of …

The Influence Of Scientific, Genetic, And Health Literacy On Carrier Screening Decision-Making, Brenna D. Albracht

Dissertations and Theses (Open Access)

For those wishing to assess their reproductive risks and make informed decisions in their reproductive planning, carrier screening for autosomal recessive and X-linked conditions, as well as cell-free DNA (cfDNA) screening for aneuploidy, are recommended during pregnancy. Despite similarities in purpose, sample requirements, insurance coverage, and safety, a lower percentage of individuals elect carrier screening than cfDNA screening, suggesting there may be a disconnect in what patients perceive as valuable information for their pregnancy. Previous studies have attempted to explain the factors associated with carrier screening uptake or decline; however, no models have yet accounted for a patient’s literacy level …

Achieving The Practice-Based Competencies: Are More Than 50 Cases Needed?, Farren Lopez

Dissertations and Theses (Open Access)

Genetic counseling graduate programs are required to provide didactic coursework and fieldwork experiences to foster development of the practice-based competencies (PBCs) in trainees. Currently, every graduating trainee must log a minimum of 50 participatory encounters to demonstrate readiness for entry-level practice of the PBCs. Previous studies have noted that many trainees exceed the 50-case standard, raising the question of whether this minimum satisfies the training needs of every student. To assess the perceived number of encounters needed for graduates to independently perform the PBCs, a survey was administered to 2023 and 2024 graduates of North American genetic counseling training programs. …

Role Of Mir-4732-3p In Breast Cancer Brain Metastasis And Brain Metastatic Tumor Microenvironment, Munazza Samar Khan

Dissertations and Theses (Open Access)

In this study, we aimed to identify microRNAs (miRNAs) that may play important roles in breast cancer brain metastasis (BCBM). To this end, we conducted miRNA-sequencing of extracellular vesicles isolated from the serum samples of 6 BCBM patients and 8 Stage I/II/III breast cancer patients, and identified 49 circulating miRNAs that were upregulated in BCBM patients compared to Stage I/II/III breast cancer. Upon further analysis, we identified miR-4732-3p to be upregulated in brain-tropic triple-negative breast cancer (TNBC) cell lines, compared to parental lines. MiR-4732-3p overexpression increased metastatic properties of TNBC cells, including proliferation, migration, invasion, and maintenance of a mesenchymal …

"Magic Computer In The Sky" - Participant Perspectives On Control And The Genetic Counseling Admissions Match, Jessica Clark

Dissertations and Theses (Open Access)

Since the 2018 admissions cycle, genetic counseling graduate programs in North America have utilized the Genetic Counseling Admissions Match (GCAM), a Match algorithm to place applicants. While a study prior to implementation found that most students were uninterested in a Match due to concerns of control, there has been no investigation into matched applicants’ experiences since its inception. A mixed-methods study explored the experiences and perceptions of control of genetic counselors and genetic counseling (GC) students who entered a program following the GCAM. An anonymous survey documenting GCAM experience and a validated measure for locus of control (LOC) was disseminated …

Exploring The Immunologic Consequences Of Atrx Deficiency In Glioma, Benjamin Whitfield

Dissertations and Theses (Open Access)

ATRX is a key chromatin regulator that is frequently mutated across multiple cancer types. One of the most common ATRX-mutated tumor types is the adult-type glioma, IDH-mutant, Astrocytoma. It is known that ATRX mutation leads to increases in DNA damage, replication stress, and global epigenetic regulation at a cell level; however, less is known about the impact of ATRX mutation on immune signaling. Furthermore, little is known about the interaction of ATRX loss with gain-of-function mutations in IDH. In this paper we set out to explore the impact of ATRX loss on immune signaling in gliomas, both in the context …

Investigating Prefrontal Cortex Neuronal Signatures Of Opioid-Induced Risk-Taking Behavior, Cana Quave

Dissertations and Theses (Open Access)

Opioid use disorder occurs alongside impaired risk-related decision-making, but the underlying neural correlates are unclear. We developed an approach-avoidance conflict task using a modified conditioned place preference procedure to study neural signals of risky opioid seeking in the prefrontal cortex, a region implicated in executive decision-making. Following morphine conditioned place preference, rats underwent a conflict test in which fear-inducing cat odor was introduced in the previously drug-paired side of the apparatus. While the saline-exposed control group avoided cat odor, the morphine group included two subsets of rats that either maintained a preference for the paired side despite the presence of …

Stat3, Nf-Κb, And Estrogen Receptor Beta: The Balance Of Inflammation In K-Ras Mutant Lung Adenocarcinoma, Michael J. Clowers

Dissertations and Theses (Open Access)

K-ras mutant lung adenocarcinoma (KM-LUAD) is a difficult-to-treat cancer subtype in which chronic inflammation pervades the tumor immune microenvironment (TIME). Pro-inflammatory pathways dampen the response to treatments, including immune checkpoint inhibitors, necessitating therapies that target this inflammatory signaling network in the TIME. This network is underpinned by interaction and coordination of two inflammatory pathways: signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa B (NF-κB). The balance of these transcription factors determines the degree of anti- vs. pro-tumor immunity, and a skewing towards STAT3 is known to promote tumor development and a pro-tumor TIME. It is also …