Translational Medical Research Commons^™

What? Now A Respiratory Syncytial Virus Epidemic, Aya Allam, Steven B Lippmann

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Speech-Language Pathologists’ Perspectives On Evidence-Based Practice In The Healthcare Setting: A Qualitative Study, Rosalyn A. Davis M.S., M.A., Ccc-Slp, Shelley B. Brundage, Phd, Ccc-Slp, Matthew Garber Pt, Dsc, Joseph M. Bocchino Edd, Mba, Sarah M. Ginsberg Phd, Ccc-Slp

Doctor of Philosophy in Translational Health Sciences Dissertations

Background: Evidence-based practice (EBP) was introduced to the profession of speech-language pathology in 2004. However, the limited empirical and implementation literature on EBP in speech-language pathology suggests that the field lags behind other healthcare disciplines, including physical therapy, occupational therapy, and nursing. Additionally, the limited empirical literature on EBP in speech-language pathology identified a need to know how speech-language pathologists (SLPs) in healthcare 1) defined and described their use of EBP and 2) perceived barriers and facilitators to utilizing EBP in clinical practice. While in the clinical instructor role, SLPs are expected to integrate theoretical, evidence-based knowledge in their clinical …

Leveraging Bio-Inspired Molecules For Cancer Theranostics, Douglas S. Macpherson

Dissertations, Theses, and Capstone Projects

A variety of molecules can be radiolabeled and delivered to a cancer site for the purposes of diagnostics and therapy. Among the most promising of tumor targeting molecules are peptides and antibodies. These bio-inspired molecules can be designed and synthesized to target and respond to cancer cells based on the properties of those cells. Matrix metalloproteinase (MMP) enzymes are over-expressed by some metastatic cancers, in which they are responsible for the degradation and remodeling of the extracellular matrix. In recent years, MMPs have emerged as promising targets for enzyme-responsive diagnostic probes because oligopeptides can be designed to be selectively hydrolyzed …

Mst1-Mediated Phosphorylation Of Nur77 Improves The Endometrial Receptivity In Human And Mice, Xinyu Cai, Yue Jiang, Zhiwen Cao, Mei Zhang, Na Kong, Lina Yu, Yedong Tang, Shuangbo Kong, Wenbo Deng, Haibin Wang, Jianxin Sun, Lijun Ding, Ruiwei Jiang, Haixiang Sun, Guijun Yan

Center for Translational Medicine Faculty Papers

Background: Successful embryo implantation requires the attachment of a blastocyst to the receptive endometrial epithelium, which was disturbed in the women with recurrent implantation failure (RIF). Endometrial β3-integrin was the most important adhesion molecule contributing to endometrial receptivity in both humans and mice. Nur77 has been proven indispensable for fertility in mice, here we explore the role of Nur77 on embryo-epithelial adhesion and potential treatment to embryo implantation failure.

Methods: The expression and location of Mst1 and Nur77 in endometrium from fertile women and RIF patients were examined by IHC, qRT-PCR and Western blotting. In vitro kinase assay following with …

The Meaning Of Family-Derived Knowledge To Healthcare Providers Treating Children With Autism Spectrum Disorder, Brian Samsell

Doctor of Philosophy in Translational Health Sciences Dissertations

Background: Families receive guidance from healthcare providers on managing their children’s autism spectrum disorder (ASD); however, both parents and providers have reported that providers often have insufficient knowledge about ASD. Successfully managing ASD requires knowledge about both the real-world needs of families with children who have ASD and the ability to evaluate the real-world effectiveness of strategies designed to meet these needs. The incorporation by providers of knowledge that originated from the families of their pediatric patients with ASD, termed family-derived knowledge, could overcome this gap. This phenomenological study explored what family-derived knowledge means to healthcare providers treating children with …

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 …

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 …

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 …

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.

An Exploration Of The Link Between Vertebral Endplate Fracture, Velocity, And Health Of The Intervertebral Disc., John Mcmorran

Theses and Dissertations (Comprehensive)

The capacity for fractures to manifest in the growth cartilage of the adolescent human spine is well documented, but much of the knowledge available regarding such fractures remains retrospective and is largely composed of small case series made up of relatively few participants. In-vitro tissue testing has demonstrated that pressurization of the intervertebral disc’s nucleus pulposus significantly contributes to the generation of growth plate fractures. However, a comprehensive biomechanical investigation of the mechanical consequences for the intervertebral disc when exposed to ring apophyseal (growth plate) fractures at different velocities remains to be demonstrated.

The first two experiments of the present …

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 …

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 …

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 …

Cocaine Sensitizes The Cd4+ T Cells For Hiv Infection By Co-Stimulating Nfat And Ap-1, Adhikarimayum Lakhikumar Sharma, Dylan Shafer, Daniel Netting, Mudit Tyagi

Center for Translational Medicine Faculty Papers

The productive infection of HIV, which generates new viral progeny, depends on the activation status of the cell. In this study, we found cocaine exposure sensitizes partially active CD4+ T cells and makes them poised for productive HIV infection. We discovered that cocaine treatment enhances the metabolic state of the cells by co-stimulating several transcription factors, mainly NFAT and AP-1, the two transcription factors, which specifically play a crucial role in enhancing both HIV and the overall cellular gene expression in T cells. We found that cocaine-induced AP-1 works in tandem with NFAT to boost HIV transcription. The enhanced HIV …

Campaigners, Capitalizers, And Cooperators: A Typology Of Professional Identities Of Physician-Researchers Who Care For Patients While Recruiting Them To Industry-Sponsored Clinical Trials, Romiya Felecia Glover Barry

Doctor of Philosophy in Translational Health Sciences Dissertations

The critical phase for a successful clinical trial is timely accrual of research participants. Interventions to improve the outcome of recruiting activities have been developed to address the research structure of clinical trials, the administrative and design burdens of study protocols, the lack of awareness and acceptance of trials from patients and clinicians, and the insufficient research training for trial investigators. Engagement with potential clinical trial participants is lower than expected with a contributing factor being that investigators do not identify and approach all potential participants. The behaviors of physician-researchers responsible for recruiting and enrolling their patients into clinical trials …

Understanding The Contributions Of Hormonal Contraceptives And Cortisol Levels To Fear Learning In Women, Sahil Bardai

Symposium of Student Scholars

Women are twice as likely to be diagnosed with an anxiety disorder than men. Eighty-five percent of women in the US will use hormonal contraceptives at some point in their lifetime. Women who use hormonal contraceptives show heightened startle reactivity to a threatening stimulus. Previous results from our lab showed a significant increase in fear-potentiated startle (FPS) in women who were on hormonal contraceptives compared to women who were naturally cycling. These results stayed consistent throughout three acquisition trials. Others have shown that the use of OCPs (oral contraceptive pills) is related to the dysregulation of the HPA-axis and elevated …

Bioprosthetic Reoperative Aortic Valve Replacement In Patients Under 50, Aisha Kazeem

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Chan V, Lam BK, Rubens FD, et al. Long-term evaluation of biological versus mechanical prosthesis use at reoperative aortic valve replacement. J Thorac Cardiovasc Surg. 2012;144(1):146-151. https://doi.org/10.1016/j.jtcvs.2011.08.041

for a patient considering reoperative aortic valve replacement.