Translational Medical Research Commons^™

The Neuroadvocacy Toolkit: A Knowledge Translation Strategy To Strengthen Food Fortification Policies To Prevent Neural Tube Defects In Latin American Countries. A Mixed-Method Study, Kemel A. Ghotme

Doctor of Philosophy in Translational Health Sciences Dissertations

Background. Neural tube defects are one of the leading congenital malformations that affect children in Latin America and worldwide, leading to pregnancy terminations, morbidity, mortality, and long-term disability. The most cost-effective and equitable way to prevent them is by implementing public health policies for food fortification with folic acid. However, a lack of knowledge translation strategies partly accounts for the incomplete enactment, enforcement, and scaling-up of mandatory fortification. There is no evidence in the scientific literature of studies attempting to identify the factors contributing to the development and implementation of knowledge translation strategies aiming to influence policymakers’ decisions regarding mandatory …

An Entosis-Like Process Induces Mitotic Disruption In Pals1 Microcephaly Pathogenesis, Noelle A Sterling, Jun Young Park, Raehee Park, Seo-Hee Cho, Seonhee Kim

Center for Translational Medicine Faculty Papers

Entosis is cell cannibalism utilized by tumor cells to engulf live neighboring cells for pro- or anti-tumorigenic purposes. It is unknown whether this extraordinary cellular event can be pathogenic in other diseases such as microcephaly, a condition characterized by a smaller than normal brain at birth. We find that mice mutant for the human microcephaly-causing gene Pals1, which exhibit diminished cortices due to massive cell death, also exhibit nuclei enveloped by plasma membranes inside of dividing cells. These cell-in-cell (CIC) structures represent a dynamic process accompanied by lengthened mitosis and cytokinesis abnormalities. As shown in tumor cells, ROCK inhibition completely …

Research Annual Report Fy2023, Children's Mercy Kansas City

Research Annual Reports

Annual report of the research at Children's Mercy Kansas City in Kansas City MO, a pediatric medical center.

Moving Toward And Accessing Adult-Oriented Rehabilitation Therapy Services For Adults With Lifelong Disabilities: A Tale Of Three Studies, Catherine Gohrband

Theses and Dissertations--Rehabilitation Sciences

The aim of this dissertation was to explore how adults with a Lifelong Disability (LLD) access and experience rehabilitation therapy services across their lives. Many LLD diagnoses such as cerebral palsy and spina bifida are considered non-progressive; however, there are common challenges that occur as people with LLD become adults, including increased pain, fatigue, and functional loss. Literature addressing the needs of people with LLD to access adult-oriented medical providers has focused primarily on medical transitions, which have described the processes for pediatric patients moving to adult-oriented settings from pediatric settings. Few studies have addressed the rehabilitation therapy needs of …

Developing Ecologically Valid Clinical Tools For Persons With Tbi: Understanding The Role And Impact Of Distractions, Deanna Pinnow

Theses and Dissertations--Rehabilitation Sciences

There is a critical need for the development of ecologically valid clinical tools to assess real-life cognitive functioning in persons impacted by traumatic brain injury (TBI). Chronic cognitive impairments that are exacerbated by distractions are one of the core factors contributing to poor home and community re-integration post injury. Simulation-based digital platforms (i.e., virtual reality, augmented reality, and mixed reality) have become potential solutions for eliciting real-world cognitive performance in clinical settings. Yet, there is a paucity of research investigating the role and impact of distractions on cognition. As a result, there is no clear framework of measuring distractions to …

Mitochondria As Causes Of And Therapeutic Targets In Chronic Post-Sepsis Skeletal Muscle Weakness, Meagan Scott Kingren

Theses and Dissertations--Pharmacology and Nutritional Sciences

Sepsis, or the organ damage that ensues after the body fails to properly contain a local infection, is the leading cause of in-patient hospitalization in the United States. Advances in critical care medicine over the last 20 years have enabled most sepsis patients to survive the life-threatening dysregulated immune response. However, a majority of survivors report chronic weakness and fatigue years after sepsis, and the cause of this weakness remains largely unknown. This dissertation work focused first on elucidating the major causes of post-sepsis muscle weakness (Aim 1). This aim involved a time-course study to determine when muscle weakness was …

Assessment Of The Interplay Between Regional Β-Amyloid Burden And White Matter Hyperintensities On Cognition And Default Mode Network In Clinically Normal Older Participants, Doaa G. Ali

Theses and Dissertations--Clinical and Translational Science

Objective: Alzheimer’s disease (AD) and subcortical vascular dementia are considered the most common pathologic contributors to dementia in the aging population. Both frequently coexist in over 80% of community dwelling adults with dementia. The neuropathological development of AD arguably begins with β-amyloid (Aβ) deposition in the brain. This series of studies aims to test the hypothesis that early focal regional amyloid deposition in the brain is associated with cognitive performance in specific cognitive domain scores in preclinical AD (pAD) (study1). Since mixed dementia is widely recognized as the norm rather than the exception, the second study aimed to explore the …

Relative Adrenal Insufficiency In Sepsis, Dan Hao

Theses and Dissertations--Pharmacology and Nutritional Sciences

Sepsis is a leading cause of death in children. Glucocorticoid (GC) therapy had been strongly recommended for the pediatric sepsis (grade 1A). However, the recommendation was changed to grade 2C in 2020 due to weak evidence. Relative adrenal insufficiency (RAI) is a condition characterized by impaired inducible glucocorticoid (iGC) production in response to stress. It develops in 32.8% of pediatric septic patients. Unfortunately, little is known about the pathogenesis of RAI in pediatric sepsis, and whether GC therapy should be based on the status of RAI is controversial. In this study, we utilized 21-day-old SF1CreSRBI^fl/fl mice as the first …

Alzheimer’S Disease Genetics And Short-Chain Fatty Acid Treatment In Studies Of The Murine Gut Microbiome, Diana Zajac

Theses and Dissertations--Physiology

Elucidating the relationship of the gut microbiome in Alzheimer's Disease (AD) risk and pathogenesis is an area of intense interest. Since 60 to 80% of AD risk is related to genetics and APOE alleles represent the most impactful genetic risk factors for AD, their mechanism(s) of action are under intense scrutiny.

First, I conducted a study on APOE targeted replacement mice to investigate the impact of APOE alleles on the murine gut microbiome. The relative abundance of bacteria from the family Ruminococacceae and related genera increased with APOE2 status. The relative abundance of the class Erysipelotrichia increased with APOE4 status, …

Sodium Hyaluronate Based Drug Delivery To The Outer And Inner Ear, Emma Barrett-Catton

Graduate Student Theses, Dissertations, & Professional Papers

We have developed two projects using sodium hyaluronate (HA)-based systems for drug delivery to the ear. First, we investigated an HA-based hydrogel for use as a single use antibiotic treatment for otitis externa. Otitis externa, also known as outer ear infection, is a frequent affliction in both humans and animals. The most prevalent treatment for otitis externa is ear drops, but it is difficult to adhere properly to this treatment, causing poor patient compliance and the potential for complications. As a result, we have developed an HA-based hydrogel for use as a single application treatment for otitis externa to increase …

Efficient Federated Kinship Relationship Identification, Xinyue Wang, Leonard Dervishi, Wentao Li, Xiaoqian Jiang, Erman Ayday, Jaideep Vaidya

Faculty, Staff and Student Publications

Kinship relationship estimation plays a significant role in today's genome studies. Since genetic data are mostly stored and protected in different silos, retrieving the desirable kinship relationships across federated data warehouses is a non-trivial problem. The ability to identify and connect related individuals is important for both research and clinical applications. In this work, we propose a new privacy-preserving kinship relationship estimation framework: Incremental Update Kinship Identification (INK). The proposed framework includes three key components that allow us to control the balance between privacy and accuracy (of kinship estimation): an incremental process coupled with the use of auxiliary information and …

Sensitive Data Detection With High-Throughput Machine Learning Models In Electrical Health Records, Kai Zhang, Xiaoqian Jiang

Faculty, Staff and Student Publications

In the era of big data, there is an increasing need for healthcare providers, communities, and researchers to share data and collaborate to improve health outcomes, generate valuable insights, and advance research. The Health Insurance Portability and Accountability Act of 1996 (HIPAA) is a federal law designed to protect sensitive health information by defining regulations for protected health information (PHI). However, it does not provide efficient tools for detecting or removing PHI before data sharing. One of the challenges in this area of research is the heterogeneous nature of PHI fields in data across different parties. This variability makes rule-based …

Large Language Models For Healthcare Data Augmentation: An Example On Patient-Trial Matching, Jiayi Yuan, Ruixiang Tang, Xiaoqian Jiang, Xia Hu

Faculty, Staff and Student Publications

The process of matching patients with suitable clinical trials is essential for advancing medical research and providing optimal care. However, current approaches face challenges such as data standardization, ethical considerations, and a lack of interoperability between Electronic Health Records (EHRs) and clinical trial criteria. In this paper, we explore the potential of large language models (LLMs) to address these challenges by leveraging their advanced natural language generation capabilities to improve compatibility between EHRs and clinical trial descriptions. We propose an innovative privacy-aware data augmentation approach for LLM-based patient-trial matching (LLM-PTM), which balances the benefits of LLMs while ensuring the security …

Formation Of Vasculogenic Mimicry: Role Of Melanoma Differentiation Associated Gene-9 In Human Melanoma, Jinkal Shah

Theses and Dissertations

Malignant melanoma (MM) is the most aggressive skin cancer and the most frequent skin disorder in Caucasians. MM is associated with aggressive and progressive disease states, leading to major cancer-related morbidity and mortality. Recent investigations identify an alternative pathway -vasculogenic mimicry (VM), which is considered a cancer hallmark that can independently facilitate tumor neovascularization by the formation of fluid-conducting and vascular endothelial cells. MM cells undergoing VM can dedifferentiate into numerous cellular phenotypes and acquire endothelial-like features, resulting in the formation of the de novo matrix-rich vascular-like networks, such as plasma and red blood cells. The co-generation of endothelial cells, …

Age-Associated Collagen Crosslinking And Its Role In Skeletal Muscle Regeneration, Lucas C. Olson

Theses and Dissertations

Advanced glycation end-products (AGEs) non-enzymatically accumulate on skeletal muscle collagen in old age via the Maillard reaction, causing an increase in intramuscular collagen and a stiffening of the muscle’s microenvironment. AGEs abrogate muscle regeneration through stiffening the muscle stem cell (MuSC) microenvironment and by binding to the receptor for advanced glycation end products (RAGE). Stiffer substrates promote MuSC proliferation at the expense of differentiation, and soluble AGEs are known to abrogate myogenic differentiation. Previously our group has demonstrated that decellularized muscle matrix (DMM), a type of extracellular matrix (ECM) scaffold extracted from skeletal muscle, encourages regeneration in a challenging rat …

N-Of-1 Trials: The Epitome Of Personalized Medicine?, Joyce P Samuel, Susan H Wootton, Jon E Tyson

Faculty, Staff and Student Publications

Observational studies are notoriously susceptible to bias, and parallel-group randomized trials are important to identify the best overall treatment for eligible patients. Yet, such trials can be expected to be a misleading indicator of the best treatment for some subgroups or individual patients. In selected circumstances, patients can be treated in n-of-1 trials to address the inherent heterogeneity of treatment response in clinical populations. Such trials help to accomplish the ultimate goal of all biomedical research, to optimize the care of individual patients.

Use Of Bioheat Modeling To Characterize And Optimize Implantable Medical Devices And Neuromodulation Technologies, Adantchede Louis Zannou

Dissertations and Theses

Medical device development includes prototyping, benchtop characterization, preclinical studies, and clinical trials. Understanding the limitations and potential adverse effects of medical devices prior to their administration in humans is a crucial first step. Optimizing medical devices is essential to employing technology and improving patients care. Computational modeling is widely adopted as a powerful tool to predict stimulation/recording parameter optimization, rapid electrode/device prototyping, investigating novel mechanism of action, and testing working principles of any medical devices. Many implantable neuromodulation technologies including Spinal Cord Stimulation (SCS), which provide substantial therapeutic benefit for patient population with lower back pain, produces heat via the …

Physical Activity Promotion, Assessment, And Engagement In Clinical Settings In The United States, Kristin A. Grogg

Graduate Theses, Dissertations, and Problem Reports (ETD)

Physical inactivity is an important contributor to morbidity and all-cause mortality and the 2018 Physical Activity Guidelines Advisory Committee recommended that physicians increase their role in physical activity assessment and promotion to combat physical inactivity and related comorbidities. Healthcare providers are increasingly called upon to initiate physical activity promotion with their patients to manage conditions like obesity, diabetes, and cardiovascular diseases. Still, recent reports indicate that less than half of primary care visits include some type of physical activity promotion. Although the National Physical Activity Plan includes some recommendations for clinicians and the healthcare sector on physical activity promotion, it …

Leveraging Cell-Substrate Adhesion And Cell Migratory Properties In Skeletal Muscle Constructs And Cancer Metastasis Assays, Lauren E. Mehanna

Theses and Dissertations--Chemical and Materials Engineering

Volumetric muscle loss (VML) remains one of the few skeletal muscle injuries without a reliable and repeatable treatment. In large volume muscle injuries, muscle fibers as well as the surrounding connective tissue are damaged, preventing therapeutic muscle stem cells, called myogenic progenitor cells (MPCs), from reaching the injury site and initiating repair. There is a clinical need to rapidly fabricate in vitro muscle tissue constructs that mimic the native tissue organization, with aligned myotubes, for insertion and integration at the patient’s injury site. In this dissertation, we utilize the MPC’s natural propensity to close gaps across an injury site to …

Role Of Histone Deacetylase (Hdac) In Epithelial To Mesenchymal Transition (Emt) In A Human Cholangiocyte Model Of Ischemic Cholangiopathy, Priyanshi Pragnesh Parikh

Theses and Dissertations

Organ transplants are a vital intervention for many diseases that result in end stage organ failure. Currently, the donation pool is not meeting the demands of the transplant list. Expanding this pool to include donation after cardiac death (DCD) is highly sought-after. However, the use of DCD livers can lead to increased odds of graft failure and ischemic cholangiopathy. The loss of epithelialization and fibrosis that occurs during ischemic cholangiopathy is characteristic of these cells undergoing epithelial-to-mesenchymal transition (EMT). The biological changes the cell experiences enhance migratory capacity, invasiveness, and increased resistance to apoptosis. Our earlier studies have shown differential …