Absolute Quantification And Identification Of Rna From Rna-Lipid Nanoparticles Using High Resolution Mass Spectrometry, Jason C. Funderburk

Theses and Dissertations

RNA therapeutics are a rising drug category with potential use for a range of conditions encompassing infectious diseases to therapies for cancer, diseases, and genetic disorders. RNA-lipid nanoparticles (RNA-LNPs) are the prominent delivery method for these therapeutics approved products include mRNA vaccines and polyneuropathy treatments. The emergency use authorizations and orphan drug status of current RNA-LNP drugs has allowed approval without finalization of the regulatory analytical procedures for quality monitoring. The objective of the study was to develop an LC-MS assay to simultaneously measure identity and concentration of two therapeutically relevant intact RNA constructs extracted from RNA-LNPs to enhance quality …

Magnetic Resonance Only Planning Validation Using Synthetic Ct By Mvision, Eric D. Brass Sr

Theses and Dissertations

Problems: Adaptive radiotherapy requires clinically practical methods for responding to patient-anatomy changes that occur between the original planning images and the day of treatment delivery. Registering a previously acquired computed tomography scan to a newly acquired magnetic resonance image can introduce cross-modality uncertainty and may delay replanning. This thesis evaluates whether synthetic computed tomography generated from same-day magnetic resonance imaging can reduce registration-related uncertainty while supporting rapid dose recalculation for fraction-level adaptation.

Procedure: Magnetic resonance imaging DICOM data were exported from the ViewRay MRIdian treatment planning system and uploaded to MVision for synthetic computed tomography generation. The synthetic computed tomography …

Use Of Transcranial Magnetic Stimulation As An Assessment Of Corticospinal Excitability In Individuals With Persistent Postural Perceptual Dizziness, Elizabeth Cornforth

Theses and Dissertations

Persistent postural-perceptual dizziness (PPPD) is a common, disabling, chronic vestibular disorder whereby individuals experience symptoms of non-vertiginous dizziness, unsteadiness, and sway or rocking that are present most hours of the day, most days of the week. Individuals with PPPD have been noted to have an increased burden of dizziness and reduced quality of life compared to other dizziness diagnoses. The cause of PPPD is not well understood which can lead to years of diagnostic testing, failed therapies, and poor symptom management. It is important to understand PPPD pathophysiology so that optimal treatment interventions can be developed for this disorder to …

Metabolic Syndrome Beyond Diagnostic Criteria: Population-Scale Integrative Metabolomics Characterization, Marwa Talal

Theses and Dissertations

Background: Metabolic syndrome (MetS) is a complex cluster of interrelated metabolic abnormalities associated with elevated cardiometabolic risk. While diagnosis is based on well-established five clinical criteria, these may overlook early or atypical metabolic alterations. Large-scale metabolomic profiling offers an opportunity to identify biochemical signatures of MetS beyond diagnostic bias and to evaluate their relative importance across different presentations of the syndrome.

Methods: Data from 117,147 UK Biobank participants were analyzed in a cross-sectional design. High-throughput NMR quantified 75 circulating metabolites, for. Univariate analyses, MetS subtype stratification, and elastic net models with SHAP interpretation were applied to assess feature …

Generating Synthetic Ct From Mri Data, Foysal Ahmed

Theses and Dissertations

Magnetic resonance imaging (MRI) provides excellent soft tissue contrast without ionizing radiation, making it a strong alternative to computed tomography (CT) in medical imaging workflows. However, CT remains essential for applications requiring electron density information, such as radiation therapy treatment planning. This study investigated the feasibility of generating synthetic CT (sCT) images from MRI using a deep learning-based U-Net architecture. A two-dimensional U-Net was trained on paired MRI-CT data from the SynthRAD 2025 dataset, consisting of 120 T1-weighted (T1W) and 60 T2-weighted (T2W) axial cases, including deformed CT (dCT) aligned to MRI. Model testing used an independent dataset of 30 …

The Dubr/Mir-210-5p/Retsat Axis In Cholesterol-Associated Steatohepatitis: Clinical Signatures And Molecular Mechanisms, Hana Mahmoud Abdelzaher

Theses and Dissertations

Metabolic-associated fatty liver disease (MAFLD) represents an increasing global health challenge, with cholesterol-associated steatohepatitis (CASH) emerging as a distinct pathological entity warranting investigation. While CASH demonstrates unique features compared to traditional triglyceride-driven steatohepatitis, its underlying molecular mechanisms remain poorly understood. This study investigates a novel regulatory axis involving DPPA2 Upstream Binding RNA (DUBR), miR-210-5p, and retinol saturase (RETSAT). 170 patient samples revealed progressive axis dysregulation in disease states, with RETSAT emerging as a highly accurate diagnostic marker (AUC=1.000). Using novel in vitro models of MASH and CASH, we demonstrated that miR-210-5p modulation significantly affects lipid accumulation and cellular phenotype, with …

Developing A Small Molecule To Inhibit Hsf1 Expression In Cancer And Evaluating Natural Genetic Variation In Small Molecule Toxicity., Michaela Kendal Foley

Theses and Dissertations

Each year cancer affects nearly 20 million people worldwide and genetic differences across populations can impact cancer onset and progression. Specifically, tumors with high levels of HSF1, the master regulator of the cytoprotective heat shock response (HSR), are correlated with poor patient outcomes in multiple cancers such as prostate, breast, and melanoma. Subsequently, the development of pharmacological inhibitors of HSF1 represents a promising strategy for anticancer therapeutics. Using a luciferase-based transcriptional reporter, two small molecule libraries were screened for inhibitors of HSF1 expression in human embryonic kidney cells, yielding ten compounds that decrease HSF1 expression. To identify if cancer lines …

Automated Treatment Planning Framework For Cervical Cancer In Brachytherapy, Suman Gautam

Theses and Dissertations

Brachytherapy (BT) is a critical treatment modality for cervical cancer that delivers ionizing radiation directly to the tumor using intracavitary (IC) and/or interstitial (IS) applicators. In high dose-rate (HDR) BT, a remote afterloader guides the radioactive source to specific dwell positions for defined durations, known as dwell times, allowing for a conformal dose to the tumor while minimizing exposure to surrounding organs at risk (OAR). However, due to the inherent nature of ionizing radiation, some dose to OARs is unavoidable, creating a fundamentally conflicting objective in treatment planning: maximizing tumor coverage while minimizing OAR dose. This characterizes the problem as …

Development Of A Physics-Informed Neural Network For Prediction Of Blood Flow, Marcello Vittorio Mattei Di Eugenio

Theses and Dissertations

Abstract—Objective: We propose a new neural network architecture that accepts point clouds and outputs 3D velocity profiles for aneurysm geometries. Methods: We generated a synthetic aneurysm 3D flow dataset using CFD and used it to train our model architecture and compare it with other popular architectures like U-net and PointNet. We incorporate tools for improving model performance such as incorporating a distance function, a physics-informed loss to enforce the law of mass conservation, and the Huber loss to learn patterns across heterogeneous velocity components of multiple dimensions. Results: The tools implemented together with our architecture achieved the best performance on …

Nanoformulations Of Essential Oils Extracted From Pistacia Lentiscus And Boswellia Sacra And Investigation Of Their Anticancer, Antimicrobial, And Antioxidant Activities., Obaydah Abd Alkader Alabrahim

Theses and Dissertations

Essential oils (EOs) obtained from natural sources have shown promising biological and therapeutical properties such as anticancer, antimicrobial, and antioxidant activities, attributing to their high content of a variety of bioactive components. However, EOs’ therapeutic properties are limited by their low stability, poor bioavailability, high volatility, and low targeting ability. Therefore, the encapsulation and nanoformulation of EOs can maximize their therapeutical efficiency and physicochemical properties while overcoming their undesirable side effects and drawbacks. EOs extracted from the resins of Pistacia Lentiscus var. Chia (P.oil) and Boswellia Sacra (B.oil) are two promising EOs that have shown great therapeutic potential. P.oil was …

Electrochemical Sensors And Biosensors Of Biomarkers And Therapeutic Agents Detection, Mahmoud Abdelhakem

Theses and Dissertations

Electrochemical sensing is a pioneering tool amongst all other sensing techniques even though it had been started in the early 20th century. Due to their cost efficacy, accuracy, and real-time measurement, electrochemical sensing has been utilized in a vast of biomedical applications in therapeutic drug monitoring and biomarker detection. This thesis work concerned the monitoring of three therapeutic agents in spiked plasma, urine, dosage form, and interstitial skin fluid with high specificity and accuracy. Two of our sensing platforms utilized nanomaterials for sensing (sensors) of Cilostazol and Velpatasvir utilizing α-MnO2-V2O5 (metal oxide nanorods) and NH2- MIL-53 (Aluminum-based metal organic frameworks), …

Combining Novel Direction Modulated Brachytherapy Tandem-And-Ovoids Applicators For Treatment Planning Of Multi-Institutional Cervical Cancer Cases: Removing Needles In Intracavitary-Interstitial Techniques, Sharmin Alam

Theses and Dissertations

Lack of standard guidelines for optimal needle insertion during high-dose-rate (HDR) intracavitary-interstitial (IC-IS) brachytherapy of the cervix means a sophisticated and technical skillset of inserting needles next to IC applicators must be developed to enhance plan quality. This study sought to evaluate the performance of two separate direction modulated brachytherapy (DMBT) tandem applicators used in conjunction with one set of novel DMBT ovoids, to effectively obviate the need for IS needles.

A cohort of 32 retrospective clinical HDR brachytherapy plans was re-planned with Varian’s BrachyVision^® treatment planning system, using VEGO^® inverse optimization algorithm, with dose heterogeneity accounted for …

Finding Biomarkers From Long-Non-Coding Rnas In Serum Of Patients With Non-Alcoholic Fatty Liver Disease, Nouran Yonis

Theses and Dissertations

Nonalcoholic fatty liver disease (NAFLD) is becoming a serious global public health problem as it is a highly prevalent condition, that begins as simple liver steatosis and develops into an inflammatory steatosis form known as non-alcoholic steatohepatitis (NASH). NAFLD has been linked with multiple comorbidities, which in certain cases predisposes to mortality secondary to extrahepatic neoplasms and coronary diseases. On the other hand, NASH leaves patients at risk of developing hepatocellular carcinoma (HCC). The incidence of NAFLD- based HCC is steadily increasing and is projected to surpass the incidence of HCC from viral origins. Long non-coding RNAs (lncRNAs) have been …

Theta Burst Brain Stimulation In Painful Diabetic Neuropathy Patients: Investigating Neural Mechanisms, Bhushan Thakkar

Theses and Dissertations

Chronic pain (CP) is a significant contributor to disability and disease burden globally. In 2019, approximately 50.2 million adults (20.4% of the US population) experienced chronic pain, contributing to $560-635 billion in direct medical costs. In addition, the worldwide prevalence of diabetes mellitus has reached epidemic proportions and is set to increase to 629 million by 2045. Almost 50% of patients with diabetes present with diabetic neuropathy (DN), and one in five patients with diabetes presents with painful DN (pDN) which is the most common cause of neuropathic pain (NP) in the US. Symptomatic treatment is the mainstay of management …

Plan Quality And Isotoxic Dose Escalation Investigation Using A 0.35t Mr-Linac System In Ablative 5-Fraction Stereotactic Magnetic Resonance-Guided Radiation Therapy (Mrgrt) For Primary Pancreatic Cancer, Robert Eric Hawranko

Theses and Dissertations

This study investigates plan quality generated by an MR-Linac (MRL) treatment planning system (TPS) for 5-fraction stereotactic body radiation therapy (SBRT) of primary pancreatic cancer (PCa). In addition, an isotoxic dose escalation was investigated with the MRL TPS based on the stereotactic MR-guided adaptive radiation therapy (SMART) trial constraints. A clinical workflow was developed for adaptive and non-adaptive treatments with the MRL, on which a time-driven activity-based costing (TDABC) analysis was performed to quantify clinical efficacy. Fifteen Pca patients previously treated with a conventional Linac were retrospectively re-planned for this study. Three plans were generated for each patient: using the …

Modeling Of Patient-Specific Periaortic Mechanics And Pulmonary Artery Hemodynamics Based On Phase-Contrast Magnetic Resonance Imaging Sequences., Johane H. Bracamonte

Theses and Dissertations

Inverse modeling in cardiovascular medicine is a collection of methodologies that can provide non-invasive patient-specific estimations of clinical risk factors using medical imaging as inputs. Its incorporation into clinical practice has the potential to improve diagnosis and treatment planning with low associated risks and costs.

Herein, three different phase contrast magnetic resonance imaging (MRI) modalities were implemented as input data, displacement encoding with stimulated echoes (DENSE MRI) applied, and time-resolved velocity encoding phase-contrast MRI, in 1D and 3D, applied to pulmonary artery (PA) hemodynamics.

A model to account for the effect of periaortic interactions due to static and dynamic structures …

Advancing Proper Dataset Partitioning And Classification Of Visual Search And The Vigilance Decrement Using Eeg Deep Learning Algorithms, Alexander J. Kamrud

Theses and Dissertations

Electroencephalography (EEG) classification of visual search and vigilance tasks has vast potential in its benefits. In future human-machine teaming systems, EEG could act as the tool for operator state assessment, enabling AI teammates to know when to assist the operator in these tasks, with the potential to lead to increased safety of operations, better training systems for our operators, and improved operational effectiveness. This research investigates deep learning methods which utilize EEG signals to classify the efficiency of an operator's search and to classify whether an operator is in a decrement during a vigilance type task, and investigates performing these …

Copper Sulfide Manganese Nanoparticles For Multimodality Imaging And Therapy, Ali S. Gawi Ermi

Theses and Dissertations

Abstract

COPPER SULFIDE MANGANESE NANOPARTICLES FOR MULTIMODALITY IMAGING AND THERAPY

By Ali S. Gawi Ermi, MSc

Inorganic nanoparticles (NPs) are compatible with metal-based multi-modality molecular imaging and targeted therapy. Copper sulfide nanoparticles (CuS NPs) are attractive photoacoustic and photothermal agents and are amenable to incorporation of radionuclides and paramagnetic elements to facilitate image-guided therapy. The aim of this work is to develop manganese (Mn)- doped CuS NP, intrinsically radiolabeled with radionuclides such as (Zirconium-89 (⁸⁹Zr), Copper-64/67 (^64/67Cu) and Manganese-52/55 (^52/55Mn)). This novel approach combines Photoacoustic (PA), Positron emission tomography (PET), Single-photon emission computed tomography …

A Deep Learning U-Net For Detecting And Segmenting Liver Tumors, Vidhya Cardozo

Theses and Dissertations

Visualization of liver tumors on simulation CT scans is challenging even with contrast-enhancement, due to the sensitivity of the contrast enhancement to the timing of the CT acquisition. Image registration to magnetic resonance imaging (MRI) can be helpful for delineation, but differences in patient position, liver shape and volume, and the lack of anatomical landmarks between the two image sets makes the task difficult. This study develops a U-Net based neural network for automated liver and tumor segmentation for purposes of radiotherapy treatment planning. Non-contrast simulation based abdominal CT axial scans of 52 patients with primary liver tumors were utilized. …

Nebulizer-Based Systems To Improve Pharmaceutical Aerosol Delivery To The Lungs, Benjamin M. Spence

Theses and Dissertations

Combining vibrating mesh nebulizers with additional new technologies leads to substantial improvements in pharmaceutical aerosol delivery to the lungs across therapeutic administration methods. In this dissertation, streamlined components, aerosol administration synchronization, and/or Excipient Enhanced Growth (EEG) technologies were utilized to develop and test several novel devices and aerosol delivery systems. The first focus of this work was to improve the poor delivery efficiency, e.g., 3.6% of nominal dose (Dugernier et al. 2017), of aerosolized medication administration to adult human subjects concurrent with high flow nasal cannula (HFNC) therapy, a form of continuous-flow non-invasive ventilation (NIV). The developed Low-Volume Mixer-Heater (LVMH) …

Live Cell Biomass Tracking For Basic, Translational, And Clinical Research, Graeme Murray

Theses and Dissertations

Single cell mass is tightly regulated throughout generations and the cell cycle, making it an important marker of cell health. Abnormal changes in cell size can be the first indication of dysfunction in response to environmental stimuli such as cytotoxic drugs. Described here is the further development of high-speed live cell interferometry (HSLCI) to concurrently measure the changes in single cell mass of thousands of cells over time. Critically, the high-throughput nature of HSLCI provides realistic pictures of tumor heterogeneity. This throughput enabled HSLCI to correctly predict in vivo carboplatin sensitivity of three triple negative breast cancer patient derived xenografts, …

Understanding Predictors Of Telemedicine Adoption Before, During, And After The Covid-19 Pandemic, Bradford S. Pierce

Theses and Dissertations

This study examined change in physicians’ use of telemedicine before, during, and expectations after the COVID-19 pandemic. It also examined the ability of personal and environmental variables to predict telemedicine adoption, and applied the theory of reasoned action and technology acceptance model to physicians’ adoption of telemedicine during the pandemic. A total of 230 licensed physicians currently practicing in the United States were recruited. Telemedicine accounted for 3.72% of physicians’ clinical work prior to the pandemic, 46.03% during the pandemic, and predicted 25.44% after the pandemic ends. Physicians within hospitals reported less telemedicine use during the pandemic (M = …

Pushing The Limits: Increasing The Speed And Specificity Of Sars-Cov-2 Testing, Grayson Way

Theses and Dissertations

The prevalence and spread of the current COVID-19 pandemic have highlighted the importance of continual improvements upon current microbiological testing methods. Rapid and accurate testing can help mitigate spread by improving on the time to quarantine and quarantine duration required. As of the writing of this thesis, COVID-19 has been responsible for more than 500,000 deaths in the United States of America, and greater than 2 million deaths globally. The work done in this thesis has shown improvements in the current SARS-CoV-2 testing methodology by reducing the time it takes for patient testing while maintaining accuracy and the sensitivity required …

Strengthening Mental Health Diagnostic Detection In Integrated Primary Care, Julia Brechbiel

Theses and Dissertations

Primary care behavioral health (PCBH) is crucial for providing mental health treatment to underserved, minority, and uninsured populations. There is a lack of knowledge about accurate mental health diagnoses at PCBH. Underdetection of mental health symptoms has the potential to worsen racial and socioeconomic disparities. Using an expert review process, I developed an abbreviated diagnostic clinical interview (ADCI) for integrated primary care. Next, patients (N = 82) completed the interview after attending PCBH appointments. According to the interview, 63.4% of participants met criteria for a diagnosis, while 64.7% received a diagnosis from their provider. A large portion of patients …

Mass Spectrometry Based Lipidomic Investigation Of Staphylococcus Aureus Lipid Metabolism And Characterization Of Lipase A, Naren Gajenthra Kumar

Theses and Dissertations

Staphylococcus aureus produces an arsenal of virulence factors and is adept at colonizing multiple hosts by employing specific processes to persist at different sites of infection. Infections caused by this pathogen range from self-limiting infections of the skin like folliculitis to life threatening and chronic conditions like infective endocarditis, non-healing diabetic foot ulcers and atopic dermatitis. As the field continues to expand its understanding of the mechanisms by which this pathogen rapidly develops resistance to new antibiotics, the underlying mechanisms that facilitates niche adaptation and host colonization among healthy individuals remain elusive.

Bacterial and host lipid metabolism presents and area …

Molecular And Behavioral Mechanisms Mediated Paclitaxel-Induced Changes In Affect-Like Behavior In Mice, Julia Meade

Theses and Dissertations

Paclitaxel and oxaliplatin are two chemotherapeutics that cause acute neurotoxicity and chemotherapy-induce peripheral neuropathy (CIPN) in 70-90% of cancer patients. Chemotherapy-induced sensory changes are correlated with depression and anxiety. We characterized the effects of these drugs on sensation and various mood-related behaviors in mice, to determine if changes in sensation are associated with depression-like behavior, to explore putative mechanisms of chemotherapy-induced depression-like behavior (Aim 1), and to develop a mouse model of chemotherapy-induced operant responding deficit (Aim 2). In Aim 1, we observed that a cumulative dose of 32 mg/kg paclitaxel induced mechanical hypersensitivity and transiently reduced preference for sucrose …

Development Of A Torque-Based Device For The Quantification Of Arm Rigidity In Patients With Parkinson’S Disease, Georgina O. Miller

Theses and Dissertations

Parkinsonian rigidity is caused by the inability of the muscles to relax and extend properly, due to reduced dopamine levels and often begins on one side of the body before spreading contralaterally. The current standard for determining joint rigidity in a clinical setting is a test completed by the clinician based on the feel of the relaxed wrist and elbow joints as they are passively flexed and extended and a series of ordinal rating scales, the Movement Disorder Society’s – Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Hoehn and Yahr Scale (H&Y), and Parkinson’s Disease Questionnaire-39 (PDQ-39). These methods are used …

Pharmacologic Profiling Of Novel Compounds Via Fluorometric Analyses Of Monoamine Transporter Responses, Ashkhan Hojati

Theses and Dissertations

In humans and other organisms, monoaminergic systems are crucial in neuronal function and behavior. The monoamine transporters (MATs), which can be found on the presynaptic plasma membrane of neurons in the central nervous system (CNS), are crucial in the regulation of neurotransmitter concentration in the synaptic cleft. As the duration and concentration of neurotransmitters in the cleft affect further downstream signaling responses, these proteins are important targets for both understanding neuronal physiology and compounds of interest. Multiple theories exist proponing the contribution of MATs to a variety of mental and neurological disorders, including depression. This theory establishes that depression is …

Metaproteomic Investigation Of The Vaginal Microbiome In Pregnancy, Zaneera Hassan

Theses and Dissertations

The development of early diagnostics and prevention strategies for preterm birth is an important global health challenge with the potential to impact over 15 million children annually, by improving health outcomes and reducing economic burden. Advances in microbial sequencing technology have opened the door to 16S rRNA gene survey, whole metagenomics, and whole transcriptomics, providing molecular evidence that the composition of the vaginal microbiome affects pregnancy outcomes in women, particularly those of African descent. A current gap in our molecular level understanding of the vaginal microbiome as it relates to healthy pregnancies is the metaproteome which comprises proteins from both …

Illumination Of The Golgi Apparatus Of Pathogenic And Nonpathogenic Naegleria Species, Tyler M. Poe

Theses and Dissertations

In this study, Naegleria fowleri, a pathogenic amoeba and the causative agent of Primary Amebic Meningoencephalitis (PAM), was utilized to determine the presence or absence of classically conserved Golgi molecules featured in the expression of a Golgi apparatus. Previous studies concluded no Golgi expression via light microscopy and transmission electron microscopy, but a recent report on Naegleria gruberi indicated the presence of dispersed Golgi tubules. Non-pathogenic species of the Naegleria genus such as Naegleria gruberi 30540 and Naegleria lovaniensis 30569 were utilized in Western immunoblot analysis compared to reduced whole-cell lysate proteins of two strains of N. fowleri and …