Translational Medical Research Commons^™

A Microfluidics-Based Approach For Isolation Of Antigen-Specific Cd8+ T Cells, Meredith Frank

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Cancer is a global epidemic: there are predicted to be 200 million new cases this year alone. Almost a quarter of all cancer-related deaths are caused by lung cancer, for which 5-year survival rates are just above 20%. 85% of lung cancer diagnoses are classified as non-small cell lung cancer (NSCLC) for which 5-year survival rates in metastatic disease are less than 10%. Early detection and targeted therapies have improved prognoses, yet relapse is still common among patients.

Immunotherapies that leverage tumor-specific CD8⁺ cytotoxic T cells have shown great promise for the treatment of NSCLC. However, although highly promising, …

Role Of Deep Learning Techniques In Non-Invasive Diagnosis Of Human Diseases., Hisham Abouelseoud Elsayem Abdeltawab

Electronic Theses and Dissertations

Machine learning, a sub-discipline in the domain of artificial intelligence, concentrates on algorithms able to learn and/or adapt their structure (e.g., parameters) based on a set of observed data. The adaptation is performed by optimizing over a cost function. Machine learning obtained a great attention in the biomedical community because it offers a promise for improving sensitivity and/or specificity of detection and diagnosis of diseases. It also can increase objectivity of the decision making, decrease the time and effort on health care professionals during the process of disease detection and diagnosis. The potential impact of machine learning is greater than …

Bhlhe40: Required For Tumor Microenvironment Remodeling And Immune Checkpoint Therapy Efficacy, Avery Salmon, Avery J. Salmon

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Advancements in immunotherapy treatments have become essential in the treatment of various cancers, such as those with high tumor burden like melanoma(Brahmer et al., 2012; Hodi et al., 2010). Immunotherapy, specifically immune checkpoint therapy (ICT) provides antagonist effect on specific immune checkpoints to control effector T cell functions(Pardoll, 2012). This therapy allows for the modulation of anti-tumor responses through the use of monoclonal antibodies, such as anti-CTLA-4 or anti-PD-1 that block the receptors from binding with their ligands, thus allowing for CD4⁺ and CD8⁺ T cell priming and activation(Wei et al., 2017). However, the required epigenetic and transcriptional …

Cell-Free Dna Sequencing In Multiple Myeloma, Russell Irwin

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Multiple myeloma (MM) is an incurable plasma cell dyscrasia. Recent advances in MM therapy, including CAR-T therapy, have increased survival and shown the value of assessing treatment response with great sensitivity, both in acute and long-term settings. Cell-free DNA, DNA fragments which are released into circulation as a part of normal cellular turnover, is a useful and dynamic biomarker in cancer patients due to the presence of circulating tumor DNA (ctDNA), which is readily identified using next generation sequencing. Here we report the analytical sensitivity, applicability, consistency, and prognostic ability of M5Seq, a novel hybrid capture panel designed for MM …

Development Of A Decellularized Hydrogel Composite And Its Application In A Novel Model Of Disc-Associated Low Back Pain In Female Sprague Dawley Rats, David Lillyman

Biological Systems Engineering--Dissertations, Theses, and Student Research

Chronic low back pain is a global socioeconomic crisis compounded by an absence of reliable, curative treatments. The predominant pathology associated with chronic low back pain is degeneration of intervertebral discs in the lumbar spine. During degeneration, nerves can sprout into the intervertebral disc tissue and be chronically subjected to inflammatory and mechanical stimuli, resulting in pain. Pain arising from the intervertebral disc, or disc-associated pain, is a complex, multi-faceted disorder which necessitates valid animal models to screen therapeutics and study pathomechanisms of pain.

While many research teams have created animal models of disc degeneration, the translation of these platforms …

Radiation Therapy For Older Women With Early Breast Cancer: An Unnecessary Hardship, Lauren E. Shawver

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report appraising:

Kunkler IH, Williams LJ, Jack WJ, Cameron DA, Dixon JM; PRIME II investigators. Breast-conserving surgery with or without irradiation in women aged 65 years or older with early breast cancer (PRIME II): a randomised controlled trial [published correction appears in Lancet Oncol. 2015 Mar;16(3):e105]. Lancet Oncol. 2015;16(3):266-273. https://doi.org/10.1016/S1470-2045(14)71221-5

for an older patient seeking treatment for Stage 1 Ductal Breast Carcinoma

Lisdexamfetamine Is An Effective Monotherapy For Moderate To Severe Binge Eating Disorder, Benjamin Young

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using

McElroy SL, Hudson J, Ferreira-Cornwell MC, Radewonuk J, Whitaker T, Gasior M. Lisdexamfetamine dimesylate for adults with moderate to severe binge eating disorder: Results of two pivotal phase 3 randomized controlled trials. Neuropsychopharmacology. 2016;41(5):1251-1260. https://doi.org/10.1038/npp.2015.275

for a young woman requesting a novel pharmacological intervention for a Binge Eating Disorder (BED).

Enhanced Recovery After Surgery (Eras) Protocols Decrease Length Of Hospital Stay And Maintain Functional Independence In Elderly Patients Undergoing Colorectal Surgery, Kristen Hawes

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using

Ostermann S, Morel P, Chalé JJ, et al. Randomized controlled trial of enhanced recovery program dedicated to elderly patients after colorectal surgery. Dis Colon Rectum. 2019;62(9):1105-1116. https://doi.org/10.1097/DCR.0000000000001442

for an elderly patient undergoing colorectal surgery.

What About Anosmia From Covid-19 ?, Sharanya S E Santhi, Sara Elnour, Steven B Lippmann

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Lost In Translation? Communicating Nutrition Science, Lindsay Yarabek Datlow

Doctor of Philosophy in Translational Health Sciences Dissertations

Diet is directly correlated with overall health; therefore, nutrition is a critical piece of the obesity-epidemic puzzle. The news media has become a primary source for nutrition information yet results from International Food Information Council surveys indicate that the majority of Americans view the nutrition news they read as inconsistent and confusing. Very recent inquiry provides empirical evidence that nutrition confusion could be fueled by media. Nutrition confusion has been causally linked to “nutrition backlash,” which is complete disregard for even the most strongly supported nutrition advice. Understanding how nutrition research is translated in the news media and the mechanisms …

Treating Cytokine Storm In Patients With Covid-19, Ahmed Abdelhaleem, Deekshitha Turaka, Shameera Shaik Masthan, Steven B Lippmann

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Antimicrobial Stewardship Meets Transitions Of Care: Defining Length Of Therapy For Community-Acquired Pneumonia (Cap), Christopher Whitman, Sarah E. Moore Pharmd, Matthew Song Pharmd, Bcidp, Brian C. Bohn Pharmd, Bcidp, Ashley M. Wilde

The University of Louisville Journal of Respiratory Infections

Introduction: Hospital-based antimicrobial stewardship efforts have traditionally focused on inpatient settings. Antibiotic prescribing at discharge is often an overlooked area of focus for antimicrobial stewardship programs. Discharge prescribing optimization is necessary to combat antibiotic overuse.

Methods: This was an observational, retrospective cohort study at a four–adult community hospital system. Four hundred adult patients admitted with community-acquired pneumonia and discharged with antibiotics were included. The primary outcome was overall (inpatient and discharge) antibiotic length of therapy. The secondary outcome was percentage of patients discharged on a fluoroquinolone who had not received one in the hospital. Descriptive statistics were utilized.

Results: The …

Covid-19 Case Complicated With Organizing Pneumonia And Pneumothorax: Correspondence, Hammad A. Bhatti, Minh Q. Ho

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Regulation Of Oxidative Phosphorylation Of Liver Mitochondria In Sepsis, Pierre Eyenga, Benjamin Rey, Lilia Eyenga, Shey-Shing Sheu

Center for Translational Medicine Faculty Papers

The link between liver dysfunction and decreased mitochondrial oxidative phosphorylation in sepsis has been clearly established in experimental models. Energy transduction is plastic: the efficiency of mitochondrial coupling collapses in the early stage of sepsis but is expected to increase during the recovery phases of sepsis. Among the mechanisms regulating the coupling efficiency of hepatic mitochondria, the slipping reactions at the cytochrome oxidase and ATP synthase seem to be a determining element, whereas other regulatory mechanisms such as those involving proton leakage across the mitochondrial membrane have not yet been formally proven in the context of sepsis. If the dysfunction …

Akt Inhibition In The Central Nervous System Induces Signaling Defects Resulting In Psychiatric Symptomatology, Apostolia-Maria Tsimberidou, Antonis Skliris, Alan Valentine, Jamie Shaw, Ursula Hering, Henry Hiep Vo, Tung On Chan, Roger S Armen, Jeffrey R Cottrell, Jen Q Pan, Philip N Tsichlis

Center for Translational Medicine Faculty Papers

Background: Changes in the expression and activity of the AKT oncogene play an important role in psychiatric disease. We present translational data assessing the role of AKT in psychiatric symptoms.

Methods: (1) We assessed the protein activity of an AKT3 mutant harboring a PH domain mutation (Q60H) detected in a patient with schizophrenia, the corresponding AKT1 mutant (Q61H), and wild-type AKT1 and AKT3 transduced in AKT-null mouse fibroblasts and modeled the Q61H mutation onto the crystal structure of the Akt1 PH domain. (2) We analyzed the results of earlier genome-wide association studies to determine the distribution of schizophrenia-associated single-nucleotide polymorphisms …

Covid-19, Vaccination, And Heart Transplantation, Forest W. Arnold

The University of Louisville Journal of Respiratory Infections

No abstract provided.

A Survey To Highlight Areas Of Focus For Patient Care In Settings Utilizing Medical Interpretation, Azayzel Deregis

Undergraduate Honors Theses

This thesis recounts my personal experience working as a volunteer medical interpreter for the Language and Culture Resource Center at East Tennessee State University. The result of my time spent volunteering as a medical interpreter, shadowing professional medical interpreters, and witnessing patient-provider interactions during interpreted sessions was an inspiration to study medical interpretation further and delve into the challenges faced by patients who require medical interpreters. During my time researching this topic, I found that the United States is severely lacking in Spanish medical interpreters—with some healthcare facilities employing no medical interpreters—even though the size of the Hispanic population is …

Adipose-Derived Stromal Vascular Fraction Therapy Improves Age-Related Adrenergic Mediated Microvascular Dysfunction And Increases Revascularization Potential Following Injury., Gabrielle Brown

Electronic Theses and Dissertations

The role of the microcirculation is to balance blood flow and oxygen delivery to meet local metabolic and oxygen demands. With advancing age, the health of the endothelium declines leading to improper augmentation of the microcirculation; decreasing vasoreactivity and angiogenic potential which can further increase the risk of ischemia. The multiple contributing factors that drive the decline in endothelial health with age make traditional pharmacological interventions challenging whereas cell-based therapies can exert multifactorial gains. Adipose-derived stromal vascular fraction (SVF) is an emerging therapeutic for its easily accessible, autologous, anti-inflammatory, and angiogenic properties. It is a heterogenous population comprised of leukocyte …

Development And Application Of 3d Kinematic Methodologies For Biomechanical Modelling In Adaptive Sports And Rehabilitation, Anne Marie Severyn

All Dissertations

Biomechanical analysis is widely used to assess human movement sciences, specifically using three-dimensional motion capture modelling. There are unprecedented opportunities to increase quantitative knowledge of rehabilitation and recreation for disadvantaged population groups. Specifically, 3D models and movement profiles for human gait analysis were generated with emphasis on post-stroke patients, with direct model translation to analyze equivalent measurements while horseback riding in use of the alternative form of rehabilitation, equine assisted activities and therapies (EAAT) or hippotherapy (HPOT). Significant improvements in gait symmetry and velocity were found within an inpatient rehabilitation setting for patients following a stroke, and the developed movement …

Hdac6 Inhibition Reverses Long-Term Doxorubicin-Induced Cognitive Dysfunction By Restoring Microglia Homeostasis, Blake Mcalpin

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

One in 8 women in the US will be diagnosed with breast cancer. Currently, doxorubicin is one of the most effective chemotherapies for breast cancer. Unfortunately, up to 60% of survivors report long-term chemotherapy-induced cognitive dysfunction (CICD) characterized by deficits in working memory, processing speed, and executive functioning. Currently, no interventions for CICD have been approved by the US Food and Drug Administration. I show here that a 14-day treatment with a blood-brain barrier permeable histone deacetylase 6 (HDAC6) inhibitor successfully reverses long-term CICD following a therapeutic doxorubicin dosing schedule in female mice, as assessed by the puzzle box test …