Medicine and Health Sciences Commons^™

Dissecting Tumor Heterogeneity In Lung Cancer, Aparna Padhye

Dissertations and Theses (Open Access)

Lung cancer is a heterogeneous disease composed of genetically and phenotypically distinct tumor cells as well as a heterogeneous microenvironment consisting of non-cancer cells and extracellular matrix. Constant interactions among these components ultimately leads to a complex tumor tissue that is ever evolving and poses a therapeutic challenge for sustained benefit. Strategies for targeting lung cancers are largely guided by the genetic alterations identified in the tumor specimens. However, in order to gain a better understanding of lung cancer progression and develop effective treatment modalities, studying tumor in context of its microenvironment is crucial. The first aim of this project …

Understanding The Role Of Arglu1 In Interferon Signaling Activation In Breast Cancer, Phuoc Nguyen

Dissertations and Theses (Open Access)

In the U.S., the highest number of new cancer cases belongs to breast cancer in women, and this cancer also bears the second-highest death rate in women. Despite significant progress in breast cancer treatment that has been made in the past several decades, innovative and efficient therapies are still needed to eradicate this deadly disease. Novel cancer immunotherapy with immune checkpoint blockade (ICB) could induce long-lasting responses and improve survival in hard-to-treat malignancies. Regrettably, only a fraction of breast cancer patients respond to this highly promising strategy. To improving ICB therapy in breast cancer treatment, IFN signaling induction is a …

Intranasal Hpv Peptide Vaccine Formulation Induces Potent Cytotoxic Cd8 T Cell Immunity For The Treatment Of Genital Hpv Tumors, Gloria Sierra

Dissertations and Theses (Open Access)

Human Papillomavirus (HPV) induced cancers continue to affect millions of women worldwide, with the five year survival rate hovering just under 60% in some demographics. Therefore there is an unmet need to develop effective, yet, easily administered therapies to treat established HPV genital lesions. Even though immune checkpoint therapy (ICT) is a promising treatment option in some HPV+ cancers, the high cost and associated toxicities are still major concerns for their widespread application. HPV cancers are textbook candidates for therapeutic vaccination intervention because they’re driven by the expression of viral oncoproteins E6 and E7, which serve as ideal tumor specific …

Identification And Targeting Of Downstream Ar-Camkk2-Mediated Mechanisms For The Treatment Of Advanced Prostate Cancer, Chenchu Lin

Dissertations and Theses (Open Access)

The androgen receptor (AR) is the primary driver of prostate cancer and, therefore, AR-regulated signaling events are essential for the development and progression of the disease. Despite their initial effectiveness, drugs targeting AR eventually fail as sustained inhibition of receptor activity remains a challenge. Previously, Ca²⁺/calmodulin-dependent protein kinase kinase 2 (CAMKK2) was identified as an essential downstream component of AR signaling in prostate cancer that correspondingly tracked with disease progression. While the importance of CAMKK2 in AR-mediated prostate cancer progression has been established, our understanding of the events downstream that promote the disease remains incomplete. Here, I elucidated …

Trim24 Promotes Mammary Tumor Development By Upregulating Metabolic Reducing Power, Shucheng Miao

Dissertations and Theses (Open Access)

Metabolic reprograming is an emerging hallmark of cancer cells. Changes in cellular metabolism can contribute to cancer cell survival and tumor progression. Tripartite motif-containing protein 24 (TRIM24) is an E3 ligase for p53, a nuclear receptor co-regulator, and a histone reader. Over expression of TRIM24 correlates with poor overall survival of breast cancer patients. Previously, our lab created a mouse model that conditionally over-expresses (COE) TRIM24 protein in mammary epithelia (Trim24^COE) and develops carcinosarcoma or metaplastic mammary tumors (70% of all Trim24^COE tumors), a rare and aggressive triple-negative subtype called metaplastic TNBC in humans (MpBC). RNA-sequencing …

Micrornas As A Therapeutic Target To Regulate Microglial Activation In Post­ Stroke Isolation In Aged Male Mice, Anik Banerjee

Dissertations and Theses (Open Access)

Introduction:

It is increasingly recognized that social Isolation (SI) leads to a wide array of behavioral and cognitive deficits. Isolation and loneliness are linked to all-cause mortality, as well as mortality from stroke and other vascular diseases. In addition, isolated or lonely individuals have significantly poorer cognitive and functional outcomes following stroke and have higher rates of stroke recurrence. These detrimental effects have also been recapitulated in animal models; animals isolated prior to, or at the time of stroke, have larger infarcts than pair-housed mice. However, the mechanisms mediating the effects of social factors on stroke recovery are unknown. An …

Investigating The Role Of Abro1 In Dna Damage-Induced Immune Response, Ahmed Emam

Dissertations and Theses (Open Access)

Genomic instability can be induced by various forms of genotoxic stress and it is a hallmark of human cancer that is associated with metastasis, therapeutic resistance, and poor prognosis. During replication stress, the replication fork stalls and forms a reversed fork which may be degraded by several DNA nucleases. At the stalled fork, genome stability is maintained by fork end protection and subsequent restart of the replication. Abro1 has been shown to play an important role in protecting the integrity of the stalled replication forks by inhibiting DNA2 nuclease. Deficiency of Abro1 leads to stalled replication fork degradation and genomic …

Advancement Of A 3d Computational Phantom And Its Age Scaling Methodologies For Retrospective Dose Reconstruction Studies, Aashish Gupta

Dissertations and Theses (Open Access)

We have used a 3D age-scalable computational phantom for over two decades for retrospective dose reconstruction studies of childhood cancer survivors (CCS) treated with 2D historic radiotherapy (RT). However, our phantom and its age scaling functions (ASF) must be updated so that it can be used in studies that include survivors treated with contemporary RT. We aimed to implement our phantom and its age scaling functions in DICOM format and determine the feasibility of applying our ASFs to accurately scale the whole-body CT-based anatomies.

In the implementation study, we developed Python scripts that model the phantom and ASFs in a …

The Role Of Ifitm3 In The Immune Response Of Brca-Deficient High Grade Serous Ovarian Carcinoma, Han Cun

Dissertations and Theses (Open Access)

Background: Prior studies showed that BRCA-deficient high grade serous ovarian carcinoma (HGSOC) had increased tumor infiltrating lymphocytes (TILs) compared to BRCA-wildtype (WT). To better understand the underlying immune mechanism in these tumors, a preliminary transcriptome analysis was performed on a set of microdissected HGSOC tumor specimens with BRCA1-mutation, BRCA2-mutation, or WT. This demonstrated an upregulation of IFITM3, an essential gene in modulating immune function. Based on these findings, we hypothesized that BRCA-deficient HGSOC have increased DNA damage leading to upregulation of IFITM3 and subsequent increase in antigen presentation and T-cell activation.

Methods: Following IRB approval, preliminary transcriptome analysis was performed …

Characterizing The Role Of Uchl5 In Metastatic Melanoma, Seenya Vincent

Dissertations and Theses (Open Access)

Metastatic melanoma is one of the most aggressive cancers. In recent years, the survival rate has improved with the introduction of immunotherapy. Our lab conducted an in vivo ORF screen to identify potential drivers of metastasis. UCHL5/UCH37 was identified as one of the top candidates. UCHL5 is a deubiquitinating enzyme and interacts with the 26S proteasome complex and the INO80 chromatin remodeling complex. While UCHL5 has been shown to be overexpressed in many cancers, it has not been well characterized in melanoma. We investigated the role of UCHL5 in metastatic melanoma in vitro through overexpressing and knocking down UCHL5 in …

Modulating Immunometabolism To Improve The Activity Of Car-Nk Cells Targeting Cd70 In Renal Cell Carcinoma, Hind Rafei

Dissertations and Theses (Open Access)

Despite the approval of several therapies for metastatic clear cell renal cell carcinoma (ccRCC), disease resistance and relapse are common, and therapies with novel mechanisms of action are urgently needed. Chimeric antigen receptor (CAR) T-cell therapy has shown remarkable responses in hematologic malignancies, but many obstacles hinder success in solid tumors including the paucity of highly specific targets and the hostility of the tumor microenvironment (TME). Moreover, the limitations of generating an autologous cell product, such as cost of manufacture, and the challenges of toxicity with CAR-T cells highlight the need to develop new cell therapy products that are at …

Investigation Of Trophon® 2 For High Level Disinfection Of Rigid Endorectal Mri Coils, Rebecca Ditusa

Dissertations and Theses (Open Access)

Clinical Magnetic Resonance Imaging is most widely known for anatomical images with good image resolution and superb soft-tissue contrast. However, changes tumor metabolism may precede changes in gross size of the tumor. Newer studies present the use of 13C in MR imaging to interrogate tumor metabolism. With this additional information, not only can the size and makeup of a tumor be obtained, but also information about its metabolic characteristics. An increase in glucose uptake and production of lactate in the presence of oxygen—aerobic glycolysis—identifies abnormal metabolism, and hence a potential increase in tumor aggressiveness. Traditional 1H MRI of the prostate …

Cancer In Louisiana: 2014-2018, Volume 36, Louisiana Tumor Registry, Lauren Maniscalco, Mei-Chin Hsieh, Christina Lefante, Yong Yi, Lisa Pareti, Brent Mumphrey, Mary Anne Lynch, Xiao-Cheng Wu, Quintrelé Jones, Tingting Li

Policy & Position Papers

Mission:

To collect and report complete, high-quality, and timely population-based cancer data in Louisiana to support cancer research, control, and prevention.

Vision:

To reduce suffering and death from cancer using information collected by the Louisiana Tumor Registry.

History:

Cancer registration in Louisiana began in 1947 at the Charity Hospital Tumor Registry in New Orleans. In 1974, as part of its Surveillance, Epidemiology and End Results (SEER) Program, the National Cancer Institute provided funds for a population-based cancer incidence and survival registry covering Jefferson, Orleans, and St. Bernard parishes. Five years later, the Louisiana Tumor Registry (LTR) was transferred to the …

Musculoskeletal Injuries In Us Air Force Security Forces, January 2009 To December 2018, Julia N Sundstrom, Bryant J Webber, George L Delclos, John R Herbold, David Gimeno Ruiz De Porras

Faculty, Staff and Student Publications

OBJECTIVE: to determine the incidence, types, and risk factors of musculoskeletal injuries in a military security forces population.

METHODS: Demographic and diagnostic data were retrieved on enlisted US Air Force security forces personnel who served on active duty between January 2009 and December 2018. Incidence rates and ratios were calculated using Poisson regression.

RESULTS: During 251,787 person-years of exposure, 62,489 personnel served on active duty. Of these, 40,771 (65.2%) were diagnosed with at least one musculoskeletal injury. The majority (60.1%) of the 164,078 unique musculoskeletal injuries were inflammation and pain secondary to overuse. After adjusting for other factors, women had …

Hypertrophic Cardiomyopathy Associated E22k Mutation In Myosin Regulatory Light Chain Decreases Calcium-Activated Tension And Stiffness And Reduces Myofilament Ca2+ Sensitivity, Jiajia Zhang, Li Wang, Katarzyna Kazmierczak, Hang Yun, Danuta Szczesna-Cordary, Masataka Kawai

Faculty, Staff and Student Publications

We investigated the mechanisms associated with E22K mutation in myosin regulatory light chain (RLC), found to cause hypertrophic cardiomyopathy (HCM) in humans and mice. Specifically, we characterized the mechanical profiles of papillary muscle fibers from transgenic mice expressing human ventricular RLC wild-type (Tg-WT) or E22K mutation (Tg-E22K). Because the two mouse models expressed different amounts of transgene, the B6SJL mouse line (NTg) was used as an additional control. Mechanical experiments were carried out on Ca

SUB-DISCIPLINE: Bioenergetics.

DATABASE: The data that support the findings of this study are available from the corresponding authors upon reasonable request.

ANIMAL PROTOCOL: BK20150353 (Soochow …

Genome-Wide Association Study Of Serum Metabolites In The African American Study Of Kidney Disease And Hypertension, Shengyuan Luo, Elena V Feofanova, Adrienne Tin, Sarah Tung, Eugene P Rhee, Josef Coresh, Dan E Arking, Aditya Surapaneni, Pascal Schlosser, Yong Li, Anna Köttgen, Bing Yu, Morgan E Grams

Faculty, Staff and Student Publications

The genome-wide association study (GWAS) is a powerful means to study genetic determinants of disease traits and generate insights into disease pathophysiology. to date, few GWAS of circulating metabolite levels have been performed in African Americans with chronic kidney disease. Hypothesizing that novel genetic-metabolite associations may be identified in a unique population of African Americans with a lower glomerular filtration rate (GFR), we conducted a GWAS of 652 serum metabolites in 619 participants (mean measured glomerular filtration rate 45 mL/min/1.73m

Management Of Peritonsillar Abscess Within A Local Emergency Department: A Quality Analysis Study., Briana K Ortega, Spencer Short, Bryan G. Kane Md, Robert M. Dedio Md

Department of Emergency Medicine

OBJECTIVE: Peritonsillar abscess (PTA) is the most common deep space infection of the head and neck, affecting thousands of people annually with high treatment costs. The purpose of this project was to determine how in-network emergency departments (EDs) adhere to generally accepted guidelines regarding diagnosis and management of potential PTAs.

METHODS: The authors performed a retrospective chart review to identify patients with PTA in five EDs in one year. Information pertaining to diagnostic tests, treatment, and airway status was also collected. Descriptive analysis was used to assess if EDs were consistent with generally accepted guidelines.

RESULTS: Six hundred twenty-one patient …

Nurses' Pandemic Lives: A Mixed-Methods Study Of Experiences During Covid-19., Kathleen Gray, Paulette Dorney, Lori Hoffman, Albert Crawford

College of Nursing Faculty Papers & Presentations

BACKGROUND: The US healthcare settings and staff have been stretched to capacity by the COVID-19 pandemic. While COVID-19 continues to threaten global healthcare delivery systems and populations, its impact on nursing has been profound.

OBJECTIVES: This study aimed to document nurses' immediate reactions, major stressors, effective measures to reduce stress, coping strategies, and motivators as they provided care during COVID-19.

DESIGN: Mixed-methods, cross sectional design. Participants responded to objective and open-ended questions on the COVID-19 Nurses' Survey.

PARTICIPANTS: The survey, was sent to nurses employed in health care settings during the pandemic; 110 nurses participated.

RESULTS: Immediate reactions of respondents …

Gemcitabine-Loaded Microbubble System For Ultrasound Imaging And Therapy., Lauren J. Delaney, John R. Eisenbrey, David Brown, Jonathan R Brody, Masaya Jimbo, Brian E Oeffinger, Maria Stanczak, Flemming Forsberg, Ji-Bin Liu, Margaret A Wheatley

Department of Radiology Faculty Papers

Ultrasound imaging presents many positive attributes, including safety, real-time imaging, universal accessibility, and cost. However, inherent difficulties in discrimination between soft tissues and tumors prompted development of stabilized microbubble contrast agents. This presents the opportunity to develop agents in which drug is entrapped in the microbubble shell. We describe preparation and characterization of theranostic poly(lactide) (PLA) and pegylated PLA (PEG-PLA) shelled microbubbles that entrap gemcitabine, a commonly used drug for pancreatic cancer (PDAC). Entrapping 6 wt% gemcitabine did not significantly affect drug activity, microbubble morphology, or ultrasound contrast activity compared with unmodified microbubbles. In vitro microbubble concentrations yielding ≥ 500nM …

Institutional Factors In General Surgery Resident Wellness And Burnout: Identification Via A Modified Delphi Technique, Darci C. Foote, Gurjit Sandhu, Kathryn Ziegler, James Lau

Conference Presentation Abstracts

Background: While there has been significant focus on individual and programmatic factors impacting general surgical residents wellbeing and burnout, the effect of the greater institutional macrocosm has not been well studied. Our work seeks to identify organizational factors that may be implicated in resident wellness. Summary of Work: Using a modified Delphi technique, a survey structured around six domains of the Maslach Burnout Theory (workload, control, reward, community, fairness, values) was distributed to wellness stakeholders at two institutions. Participants identified factors that may be implicated in resident wellness and burnout. Two subsequent multiple-choice survey iterations were distributed to stakeholders who …

Treatment And Outcomes Of Soft Tissue Sarcoma Of Groin, Hip And Thigh: A Retrospective Review From A Tertiary Care Hospital, Masood Umer, Javeria Saeed, Zaid Ahmed Shamsi, Muhammad Usman Tariq

Section of Orthopaedic Surgery

Objective: To study the frequency of the thigh, hip and groin soft tissue sarcomas and retrospectively analyse the management, treatment results, and outcomes of these uncommon malignant tumours, in a tertiary care hospital of the city of Karachi.
Methodology: Data of soft tissue tumours registered from 2017-2018 was retrieved during January 2019 to March 2019 from Aga Khan University Hospital, Karachi bone and soft tissue tumour registry. A retrospective review was performed and all soft tissue tumour cases treated with surgical intervention (with adjuvant /neoadjuvant therapy) or palliative intention were included.
Results: Total 119 cases of soft tissue tumours (STS) …

Active Travel For Children And Youth: Lessons From Active Routes To Schools North Carolina, Leah Ferguson

Electronic Theses and Dissertations

This Integrated Learning Experience (ILE) investigates literature regarding the impact of national Safe Routes to School (SRTS) programs and takes a deeper dive into the lessons that can be learned from North Carolina’s Active Routes to School (NC ARTS) programs through an analysis of data collected from 2007 to 2019. This report is focused on understanding the relationship between and among variables included in the Six Es of SRTS framework: Education, Engineering, Encouragement, Enforcement, Equity, and Evaluation. This investigation provides insight that extends understanding of parental comfort and engagement with these programs. A unique theoretical model was developed as were …

Endothelial Heat Shock Protein A12b And Yes-Associated Protein Cooperatively Promote Angiogenesis Following Myocardial Infarction, Min Fan

Electronic Theses and Dissertations

Heart failure after myocardial infarction (MI) remains the leading cause of mortality among all cardiovascular diseases globally. Angiogenesis plays a critical role in cardiac functional recovery after MI. Heat shock protein A12B (HSPA12B) is predominately expressed in endothelial cells and required for angiogenesis. Yes-associated protein (YAP) has been reported to promote tumor angiogenesis.

In the present study, we investigated the cooperative role of HSPA12B and YAP in angiogenesis following myocardial ischemic injury. Endothelial specific deficiency of HSPA12B (eHspa12b^-/-) or YAP (eYap^-/-) impairs angiogenesis and exacerbates cardiac dysfunction after MI, when compared with wild type …

Prevention Of Falls In Hospital: Audit Report From A Tertiary Care Hospital Of Pakistan, Anum Sadruddin Pidani, Tashfeen Ahmad, Nasreen Panjwani, Shahryar Noordin

Department of Surgery Docs

Objective: The study aims to assess the fall incidents in past 5 years and fall assessment practices at the Aga Khan University Hospital, Karachi.
Methods: We performed a single-center retrospective audit at Aga Khan University Hospital from October 2019 to December 2019. A list of all patients admitted to Aga Khan University Hospital under the Musculoskeletal and Sports Medicine Service Line was obtained using the Hospital Information Management System (HIMS) from Jan 2017 to June 2018. Data including fall assessment scores was collected retrospectively from medical record files.
Results: A total of 1499 patients were admitted during this time period, …

Prelimbic Prefrontal Cortical Encoding Of Reward Predictive Cues, Mitchell Spring, Karan R. Soni, Daniel S. Wheeler, Robert A. Wheeler

Biomedical Sciences Faculty Research and Publications

Animals appoint incentive value and learn to approach otherwise behaviorally inert stimuli if these stimuli come to predict the delivery of reward. Interestingly, this adaptive Pavlovian learning process has been implicated in behavioral control disorders, such as drug addiction. One brain region implicated in directing conditioned approach behavior is the prelimbic region of the prefrontal cortex. The present study employed in vivo electrophysiology in the prelimbic cortex to characterize the distribution of neural responses to the presence of a cue that had acquired incentive value after being associated with a primary reward. Male rats were trained in a Pavlovian autoshaping …

The Moderating Role Of Social Support In Stigma And Symptoms Of Anxiety And Depression, Taylor Phillips

Undergraduate Honors Theses

In this study, we examine the relationship between having a support system and the stigma individuals face with depression and anxiety symptoms. The aim of this study was to examine if having a support system acts as a buffer between perceived stigma and mental health symptoms. For this study, I conducted an online survey to measure symptoms of depression and anxiety, experiences with both perceived and internalized stigma, and social support. While 93 total participants engaged in the survey, only 52 fully completed the survey and passed two attention-check questions to ensure no invalid participation (e.g., BOTS) were present. In …

Distinct Progression Patterns Across Parkinson Disease Clinical Subtypes, Peter S Myers, Joshua J Jackson, Amber K Clover, Christina N Lessov-Schlaggar, Erin R Foster, Baijayanta Maiti, Joel S Perlmutter, Meghan C Campbell

Open Access Publications

OBJECTIVE: To examine specific symptom progression patterns and possible disease staging in Parkinson disease clinical subtypes.

METHODS: We recently identified Parkinson disease clinical subtypes based on comprehensive behavioral evaluations, "Motor Only," "Psychiatric & Motor," and "Cognitive & Motor," which differed in dementia and mortality rates. Parkinson disease participants ("Motor Only": n = 61, "Psychiatric & Motor": n = 17, "Cognitive & Motor": n = 70) and controls (n = 55) completed longitudinal, comprehensive motor, cognitive, and psychiatric evaluations (average follow-up = 4.6 years). Hierarchical linear modeling examined group differences in symptom progression. A three-way interaction among time, group, and symptom …

Mental Health Awareness Training Manual: For Faculty To Help Students, Ricardo Vega

Electronic Theses, Projects, and Dissertations

Mental health issues and stigma can affect students in many ways. The teacher-student relationship can be affected by the fear and inconsistent thoughts to be successful in college settings caused by mental health issues. First-generation college students face mental health issues due to support, education degree expectations, inhibition of uncertainty, and resources (Pascarella et al., 2004). This project is about providing communication strategies for faculty to help reduce stigma and provide students with resources to support their mental health.

The Effect Of Training Status On Adaptations To 11 Weeks Of Block Periodization Resistance Training, Alexander Wetmore

Electronic Theses and Dissertations

The primary purpose of this dissertation was to investigate the effect of training status on adaptations to resistance training. A secondary purpose of this dissertation was to investigate the relationship between subjective and objective forms of monitoring resistance training (RT). The benefits of RT are well understood but training status may be a major influence on training outcomes. Fifteen males of various training status were recruited for this study. Subjects completed 11 weeks of block periodization (BP) training. Subjects were tested for absolute strength (ABS) and relative strength (REL) in the barbell back squat, 0kg and 20kg static jumps (SJ) …

Athlete Monitoring Program In Division I Collegiate Female Soccer, Ai Ishida

Electronic Theses and Dissertations

The objectives of this dissertation include 1) to review athlete monitoring strategies and the physical performance demands of female soccer match-play and to provide practical application of athlete monitoring programs, 2) to examine individual and group relationship between training load (TL) and subjective recovery and stress state and neuromuscular performance, and 3) to investigate acute effects of match-play on neuromuscular and subjective recovery and stress state in National Collegiate Association Athlete (NCAA) division I collegiate female soccer. TL was assessed using 10Hz Global Navigation Satellite System units. Subjective recovery and stress state was measured using the Short Recovery and Stress …