Medicine and Health Sciences Commons^™

Genetic Evolution And Prognostic Determinants Of Pancreatic Cancer On Longitudinal Liquid Biopsies, Vincent Bernard

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) has one of the lowest 5-year survival rates amongst solid tumors. As early detection of PDAC is unusual and typically incidental, most patients present with locally advanced and metastatic disease where effective therapeutic strategies remain a significant unmet need. Specifically, surrogate biomarkers for tumor monitoring of PDAC may lead to improved elucidation of clinical actionability and prognostic potential. On the other hand, tumor tissue is rarely sampled in patients presenting with de novo or recurrent metastatic PDAC, apart from a fine needle aspiration or a core needle biopsy performed for diagnosis. This precludes the opportunity for …

Assembly And Display Of Surface Proteins In Actinomyces Oris, Sara Siegel

Dissertations and Theses (Open Access)

Bacteria are an integral part of human health and disease. In the human host, dental plaques form as a result of up to 700 individual bacterial species colonizing oral surfaces and forming a multispecies biofilm. These biofilms are the cause of prevalent human diseases such as dental caries, gingivitis, and periodontitis. The microbes present in the oral biofilm are highly spatially and temporally structured and require a primary colonizing species to adhere to host tissue. As an important primary colonizer of the oral biofilm, the actinobacterium Actinomyces oris utilizes cell wall anchored proteins and glycoconjugates to initiate adherence to host …

Investigating The Single Cell Heterogeneity And Physiological Impact Of Mistranslation, Christopher Evans

Dissertations and Theses (Open Access)

Bacterial populations grow clonal populations; however, individual cells have a variety of phenotypes. The physiological heterogeneity observed in populations has been attributed to variations in the processes of gene expression. For example, promoter expression has been shown to be heterogeneous within a population and contribute to increased stress tolerance in a subpopulation of cells. In comparison to transcription, the influence of translation on single cells is unclear. In this study, my collaborators and I have developed a dual-fluorescence reporter that allows us to measure the mistranslation rate in single cells in vivo. Using this reporter, we found that mistranslation …

Hypothalamic Circuits In The Control Of Feeding And Emotional Behaviors, Leandra Mangieri

Dissertations and Theses (Open Access)

Feeding results from the integration of both nutritional and affective states, and is guided by complex neural circuitry in the brain. The hypothalamus is a critical center controlling feeding and motivated behaviors. We found that targeted photostimulation of projections from the lateral hypothalamus (LH) to the paraventricular hypothalamus (PVH) in mice elicited voracious feeding and repetitive self-grooming behavior. GABA neurotransmission in the LH->PVH circuit mediated the evoked feeding behavior, and elicited behavioral approach, whereas glutamate release promoted repetitive self-grooming, which was stress-related in nature. Optogenetic inhibition of LH^GABA ->PVH circuit reduced feeding after fasting, whereas photostimulation abruptly …

The Role Of Tumor Suppressor Dear1 In The Acquisition Of Mammary Stem/Progenitor Cell Properties, Uyen Le

Dissertations and Theses (Open Access)

Breast cancer is the most commonly diagnosed cancer in women in America. Ductal carcinoma in situ (DCIS), one of the earliest pre-invasive forms of invasive ductal carcinoma (IDC), has a 30-50% risk of progressing to IDC. Understanding the mechanisms regulating progression from DCIS to IDC would help identify biomarkers to stratify patients at higher risk of progression or metastasis. Cumulative literature suggests the earliest phase of dissemination from the primary tumor is driven by the epithelial-mesenchymal transition (EMT) program. DEAR1 is a tumor suppressor gene which is mutated, undergoes loss of heterozygosity in breast cancer, and is downregulated in DCIS …

Involvement Of Gdap1 In The Regulation Of Mtorc1 Activity In A Drosophila Mliv Model, Kristen Clemons

Dissertations and Theses (Open Access)

The master regulator of metabolism and growth, mechanistic target of rapamycin complex 1 (mTORC1), is responsible for maintaining metabolic homeostasis by sensing nutrient and energy levels within the cell to promote or inhibit translation and autophagy accordingly. In the childhood neurodevelopmental disorder Mucolipidosis type IV (MLIV), mTORC1 activity is decreased. The underlying mechanism for reduced mTORC1 signaling in MLIV is poorly understood. The gene encoding ganglioside-induced differentiation associated protein 1 (GDAP1) is transcriptionally upregulated in MLIV. This project investigated the involvement of GDAP1 in MLIV disease pathology. Using the UAS/GAL4 system in an established MLIV Drosophila model, we …

A Compressed Sensing Approach To Detect Immobilized Nanoparticles Using Superparamagnetic Relaxometry, Sara Thrower

Dissertations and Theses (Open Access)

Superparamagnetic relaxometry (SPMR) is an emerging technology that leverages the unique properties of biologically targeted superparamagnetic iron oxide nanoparticles to detect cancer. The use of ultra-sensitive sensors enables SPMR to detect tumors ten times smaller than current imaging methods. Reconstructing the distribution of cancer-bound nanoparticles from SPMR measurements is challenging because the inverse problem is ill posed. Current methods of source reconstruction rely on prior knowledge of the number of clusters of bound nanoparticles and their approximate locations, which is not known in clinical applications. In this work, we present a novel reconstruction algorithm based on compressed sensing methods that …

Behavioral Insights Into Nociceptor Function: A Systematic Approach To Understanding Postsurgical And Neuropathic Pain Mechanisms In Rats, Max Odem

Dissertations and Theses (Open Access)

Postsurgical and neuropathic pain are each clinically common, and often associated with ongoing pain. Ongoing pain has been linked to ongoing activity (OA) in human C-fiber nociceptors. Preclinical studies using rodent neuropathic models have concentrated on allodynia driven by OA generated in non-nociceptive Aβ fibers, but little attention has been paid to postsurgical pain in sham controls or to C-fiber nociceptor OA promoting ongoing pain.

Operant assays that reveal negative motivational and cognitive aspects of voluntary pain-related behavior may be particularly sensitive to pain-related alterations. In the mechanical conflict (MC) test, rodents can freely choose to escape from a brightly …

Targeting Ph Domain Proteins For Cancer Therapy, Zhi Tan

Dissertations and Theses (Open Access)

Targeted therapy has been one of the most promising treatment options for cancer during the past decade. Discoveries of potent and selective small molecule inhibitors are critical to new and promising targeted therapy. Pleckstrin Homology (PH) domain proteins are one of the biggest protein families in the human proteome. However, no drugs have been achieved to the late development stages, let alone getting to the market. Thus, a deeper understanding of this protein family is required and there is an urgent need to develop novel small molecule compounds targeting these proteins.

Studies of PH domains began around two decades ago …

A Role For Epac1 And Epac2 In Nociceptor Hyperexcitability And Chronic Pain After Spinal Cord Injury, Samantha Berkey

Dissertations and Theses (Open Access)

Chronic pain is a major complaint of those living with spinal cord injury (SCI), affecting 65-80% of the SCI population, but the treatment options remain limited or non-existent. The cAMP sensor EPAC has previously been shown to play a key role in chronic inflammatory and neuropathic pain, though the contribution from each of its two main isoforms, EPAC1 and EPAC2, is unclear. Here I test the hypothesis that both EPAC1 and EPAC2 play a key role in the maintenance of persistent nociceptor hyperexcitability and chronic pain after SCI.

Using both a T9 SCI mouse model and a T10 SCI rat …

Adenylyl Cyclase Type 9: Regulation And Cardiac Function, Tanya A. Baldwin, Tanya A. Baldwin

Dissertations and Theses (Open Access)

Abnormalities in cardiac stress signaling underlie a number of cardiovascular diseases (e.g. arrhythmias and heart failure). Cardiac stress signaling pathways normally integrate signals from the sympathetic nervous system to promote efficient contraction and relaxation under stress. Sympathetic control through β-adrenergic stimulation is propagated by adenylyl cyclase (AC). AC synthesizes cyclic AMP (cAMP), an important second messenger that initiates signaling pathways to modulate physiological and pathophysiological functions of the heart, including the activation of PKA and subsequent phosphorylation of ion channels, contractile machinery, and stress response proteins that enhance cardiac function. Alterations of cAMP signaling occur in the failing heart and …

3d Scintillator Detector Quenching Characterization For Scanning Proton Beams, Fahed Alsanea

Dissertations and Theses (Open Access)

Proton pencil beam scanning is becoming the standard treatment delivery technique for proton therapy centers. Scanned proton pencil beams provide a highly conformal dose distribution. The complex dose distribution poses challenges for quality assurance measurements leading to sophisticated detector setups and time consuming measurements. Fast 3D measurements are therefore desirable to verify the complex dose distribution and to enable the utilization of the full potential of proton therapy. The overall objective of this project is to improve volumetric scintillators detectors to provide 3D measurements for applications for beam commissioning, quality assurance program, and patient-specific treatment delivery verification.

Detectors based on …

Integrative Bioinformatics Approaches To Elucidating Prostate Cancer Cell Heterogeneity, Plasticity, And Treatment Response, Hsueh-Ping Chao

Dissertations and Theses (Open Access)

Prostate cancer (PCa) is the most common non-cutaneous tumor in American men, and the second leading cause of cancer-related deaths. PCa-related deaths can be attributed to heterogeneous tumors containing metastatic and therapy-resistant cancer cells. Cancer stem cells (CSC) are an important contributor to this tumor heterogeneity, which are present in primary tumors and become enriched in castration resistant PCa (CRPC). Our lab has demonstrated that the prostate cancer stem cells (PCSCs) are enriched in the phenotypically undifferentiated PCa cell population that lacks the expression of differentiation marker prostate-specific antigen (PSA). Our work has also demonstrated that PCa cells manifest significant …

Investigation Of Novel Virulence Mechanisms In Candida Albicans, Elisa Marie Tafoya Vesely

Dissertations and Theses (Open Access)

Candida albicans is the most important fungal species associated with humans. Normally present in the human microbiome as a commensal colonizer, C. albicans is also the fourth most prevalent organism isolated from bloodstream infections in hospitals. Disseminated infections have an associated mortality rate of around 40%. The results of the work described in this dissertation cover the broad subject of C. albicans adaptation to the host and the mechanisms by which this organism is able to survive and cause infection through a variety of means. A key determinant in disease progression is interaction with innate immune cells, specifically macrophages and …

Il-1Α Blockade Reduces Immune Suppression In The Early Tumor Micro-Environment, Brenda Melendez

Dissertations and Theses (Open Access)

IL-1α Blockade Reduces Immune Suppression in the Early Tumor Micro-Environment

Brenda Melendez, B.S.

Advisory Professor: Gregory Lizee, PhD.

Immunotherapy against melanoma has shown great promise in the clinic for treating advanced-stage patients. However, a major barrier against effective T cell mediated cytotoxicity is immunosuppression in the tumor micro-environment. It has been described that tumors secrete pro-inflammatory cytokines capable of modulating immune responses that favors the growth of tumor cells. Specifically, IL-1 plays a critical role in myeloid cell recruitment and activation, which can in turn inhibit T cell activity in vivo. Moreover, IL-1 is also known to up-regulate immune inhibitory …

Heme Peroxidase Hpx-2 Protects Caenorhabditis Elegans From Pathogens, Yi Liu

Dissertations and Theses (Open Access)

Heme-containing peroxidases are important components of innate immunity. Many of them functionally associate with NADPH oxidase (NOX)/dual oxidase (DUOX) enzymes by using the hydrogen peroxide they generate in downstream reactions. In Caenorhabditis elegans, a ShkT-containing peroxidase, SKPO-1, and the dual oxidase, BLI-3, contribute to resistance against the human pathogen Enterococcus faecalis, likely functioning in conjunction with each other. However, the exact mechanism(s) by which peroxidases and NOX/DUOXs contribute to pathogen resistance remain unclear. Here, we demonstrated that another peroxidase, HPX-2 (Heme-PeroXidase 2), is required for resistance against some, but not all pathogens. Tissue specific …

Comparisons Between Movement Onset Identification Methods Used In Isometric Mid-Thigh Pull Test, Junshi Liu

Electronic Theses and Dissertations

This dissertation aimed to explore the usefulness of using force derivatives for onset detection in the isometric mid-thigh pull test. First, we examined applications of three differential calculus principles, first and second derivative, and curvature using visual detection as a reference under different baseline conditions. Second, we compared the best derivative method to a threshold-based method using visual detection as a reference. Results of our first investigation showed trivial differences between many differential calculus methods and visual detection. However, statistical differences exceeding a trivial effect was observed when instantaneous force and rate of force develop were examined. Through the first …

Dreadd Targeting Projections From The Nucleus Accumbens To The Ventral Pallidum With Nicotine Self-Administration, Amanda Smith

Electronic Theses and Dissertations

Projections from the Nucleus Accumbens (NAc) to the Ventral Pallidum (VP) play a critical role in motivation and reward. Rewards and reward-associated cues are thought to alter this pathway by suppressing GABA release to the VP, however, the role of the NAc to VP pathway has never been investigated with regard to nicotine self-administration. We hypothesized that increasing GABAergic signaling from the NAc to the VP would decrease the reinforcing effects of nicotine. To increase GABA release, CRE dependent DREADD was expressed in the NAc of male rats. Administration of low dose clozapine activated the DREADD receptor and showed a …

The Role Of Non-Neuronal Acetylcholine In Urogenital Chlamydial Infection, Jessica R. Lockhart

Electronic Theses and Dissertations

Chlamydia trachomatiscauses a bacterial sexually transmitted infection, Chlamydia, that is often chronic and casues reproductive complications in women. We hypothesized that Chlamydia infection increases local acetylcholine (ACh) production, which regulates the host’s inflammatory response to the infection. Female mice infected with C. muridarumwere sacrificed at days 3, 9, 15, and 21 post-infection, genital tract tissues harvested, and immunohistochemistry performed to enumerate ACh-producing cells. Infection increased the number of ACh-producing cells in cervical tissue at days 3,15, and 21 post-infection (pi), uterine tissue at day 3 and 9 pi, and ovarian tissue day 3, 15, and 21 pi. These …

Comprehensive Sequencing With Surface Tagmentation Based Technology, Kuan Feng

Biomedical Sciences ETDs

Next-generation sequencing technologies (NGS) have undergone extensive improvements since the invention of the 454 sequencing system in 2005. With tremendous progress in throughput, speed and a dramatic reduction in per-base cost, DNA sequencing is widely used in basic science as well as translational research. However, it is still a challenge to acquire a complete human genome. The long-range information is often missing due to the short length of NGS reads, which leaves many gaps in between scaffolds rather than an entire piece for each chromosome. Moreover, without the long-range information, haplotype-resolved genome sequencing and structural variant detection can be difficult, …

Establishing Benchmark Criteria For Single Chromosome Bacterial Genome Assembly, Timothy J. Krause

School of Biological Sciences: Dissertations, Theses, and Student Research

Adequate recommendations for the amount and types of sequencing data necessary to optimize the recovery of single chromosomes from bacterial sequencing projects do not exist. Broad estimates for coverage depths needed to recover complete bacterial genomes are present in the literature, but required sequencing depths across bacterial and archaeal phylogenies needed for high-quality assembly are not known. Additionally, correlations between genomic complexity and expected quality of assembly have not been properly defined. Furthermore, the capabilities of multiplexing (sequencing more than one sample simultaneously on one flow cell) with long-read sequencing platforms in order to recover complete bacterial chromosomes are poorly …

The Impact Of Transfer Shock In A Dental Hygiene Program At A Four-Year Health-Sciences University, Claire Sallee Tucker

Graduate Theses and Dissertations

In order for a student to be successful in dental hygiene education, the student must gain the required knowledge and skills necessary to perform as a hygienist and possess the ability to utilize critical thinking to apply these attributes while in the program and on the National Board of Dental Hygiene Examination (NBDHE) (Alzahrani, Thompson, & Bauman, 2007; Fried, Maxey, Battani, Gurenlian, Byrd, & Brunick, 2017). Dental hygiene students who attend a medical university have the option to take required pre-requisite courses at a community college or a four-year university. All dental hygiene students transfer from another institution and all …

Secure Smart Health With Privacy-Aware Aggregate Authentication And Access Control In Internet Of Things, Yinghui Zhang, Robert H. Deng, Gang Han, Dong Zheng

Research Collection School Of Computing and Information Systems

With the rapid technological advancements in the Internet of Things (IoT), wireless communication and cloud computing, smart health is expected to enable comprehensive and qualified healthcare services. It is important to ensure security and efficiency in smart health. However, existing smart health systems still have challenging issues, such as aggregate authentication, fine-grained access control and privacy protection. In this paper, we address these issues by introducing SSH, a Secure Smart Health system with privacy-aware aggregate authentication and access control in IoT. In SSH, privacy-aware aggregate authentication is enabled by an anonymous certificateless aggregate signature scheme, in which users' identity information …

Better Inpatient Health Quality At Lower Cost: Should I Participate In The Online Healthcare Community First?, Kai Luo, Qiu-Hong Wang, Hock Hai Teo, Xi Chen

Research Collection School Of Computing and Information Systems

As policy makers across the globe look to health information technology (HIT) as a meansof improving the efficiency of the healthcare systems, it has sparked significant interestin understanding how HIT might help achieve that. While researchers have examined anddocumented the efficiency-improving effect of various institution HITs (e.g., electronicclinic pathways and telemedicine), the impacts of consumer HITs such as onlinehealthcare communities have been generally overlooked. Utilizing two unique datasetsfrom both an online healthcare community and a general hospital, we study the impactof online healthcare community on offline inpatient care efficiency. Through rigorousanalysis, we find that communications between physicians and patients on …

Living With Artificial Intelligence – Developing A Theory On Trust In Health Chatbots, Weiyu Wang, Keng Siau

Research Collection School Of Computing and Information Systems

The current world is AI-filled and AI-fueled. Humans need to be able to live in harmony with AI. In this research, we aim to develop a theory on Trust between human and health chatbots. With the development of intelligent personal assistants, chatbots are becoming common and ubiquitous. Chatbots can behave as a conversational partner, complete information acquisition, and provide responses to inquiries. Chatbots have been widely used in the healthcare area, supporting physicians and assisting patients. The potential threats to privacy issues and the unpredictable performances of the chatbots hindered people’s trust and adoption of the new technology. This research-in-progress …

Validity Of A Wireless Inertia Measurement Device In Quantifying Performance In Vertical Jumping Tests, Nicholas G. Anagnost, Alexandra Lates, John P. Wagle, Christopher B. Taber

Exercise Science Faculty Publications

The use of technology in sport and fitness training has rapidly become a tool for both athletes and coaches in monitoring performance variables for optimizing training stimulus and recovery (Duking, Hotho, Holmberg, Fuss, & Sperlich, 2016; Peake, Kerr & Sullivan, 2018). Wireless fitness trackers, GPS and accelerometry devices are growing in popularity with the athletic population outside of the clinical setting due to their lower cost and ease of use compared to traditional clinical measurement tools (Dellaserra, Gao & Ransdell, 2014). With the increased popularity of these devices comes the necessity to understand and validate the information collected from them …

Spinal Infections: From Prevention To Cure, James Harrop

Department of Neurosurgery Faculty Papers

AOSpine North America (AOSNA) is honored to have the ability to present this focused issue on spinal infections. As we are all aware, spinal infections are a prevalent part of our daily treatment regimen as spine surgeons—whether these infections are in our elective practice or emergencies.

The Ecology Of Fecal Indicators, Dennis A. Gilfillan

Electronic Theses and Dissertations

Animal and human wastes introduce pathogens into rivers and streams, creating human health and economic burdens. While direct monitoring for pathogens is possible, it is impractical due to the sporadic distribution of pathogens, cost to identify, and health risks to laboratory workers. To overcome these issues, fecal indicator organisms are used to estimate the presence of pathogens. Although fecal indicators generally protect public health, they fall short in their utility because of difficulties in public health risk characterization, inconsistent correlations with pathogens, weak source identification, and their potential to persist in environments with no point sources of fecal pollution. This …

Successful Anesthetic Management Of Patient With Stiff Person Syndrome, Muhammad Sohaib, Sarfraz Siddiqui

Department of Anaesthesia

We herein describe the successful anesthetic management of a patient with stiff person syndrome undergoing right total hip replacement under spinal anesthesia. We also describe the problems associated with general anesthesia. The advantage of using regional anesthesia in these patients is the avoidance of muscle relaxants. The use of general anesthesia carries the risk of hypotonia in stiff person syndrome postoperatively due to enhancement of γ aminobutyric acid (GABA) action on synaptic transmission by drugs that have a γ GABA agonistic action.

A Learning Community Approach To Identifying Interventions In Health Systems To Reduce Colorectal Cancer Screening Disparities., Lillian C. Man, Melissa Dicarlo, Emily Lambert, Randa Sifri, Martha Romney, Linda Fleisher, Ronald Myers

Department of Medical Oncology Faculty Papers

Although colorectal cancer (CRC) screening in the United States has been increasing, screening rates are not optimal, and there are persistent disparities in CRC screening and mortality, particularly among minority patients. As most CRC screening takes place in primary care, health systems are well-positioned to address this important population health problem. However, most health systems have not actively engaged in identifying and implementing effective evidence-based intervention strategies that can raise CRC screening rates and reduce disparities. Drawing on the Collective Impact Model and the Interactive Systems Framework for Dissemination and Implementation, our project team applied a learning community strategy to …