VictorJuiz/thesis huggingface dataset:
A Cross-Sectional Study of COVID-19 Knowledge, Attitudes, and Practices Among Black Communities in the Greater Toronto Area
Keywords: Black communities
Health behaviours

BackgroundAdherence to preventative health practices is tied to knowledge and attitudes. The COVID-19 knowledge, attitudes, and practices (KAPs) among Black communities has had limited testing in a Canadian context. ObjectivesTo explore the associations between health literacy, sociodemographic variables, and KAPs and test their hypothesized relationships. DesignCross-sectional survey. MethodsAn online questionnaire was completed by Black adults living in the Greater Toronto Area. Associations between KAPs, health literacy, and sociodemographic variables were assessed using descriptive tests. A multivariate logistic regression model was used to examine predictors of high preventative practices. ResultsOf the 169 respondents, most had high knowledge scores (80.5%), low attitudes (85.2%), and high COVID-19 preventative practices (82.2%). Hotspot status, working from home, and high health literacy were found to be independent predictors of high preventative practices. ConclusionThis study provides new knowledge that advances understanding of the COVID-19 KAPs of Black communities in a Canadian context.
Development of a Clinically Feasible Functional Electrical Stimulation System with Visual Feedback Training to Improve Standing Balance
Keywords: Closed-loop
Functional electrical stimulation
Rehabilitation
Standing balance
Visual-feedback training

Individuals with spinal-cord injuries (SCI) are at an increased risk of falling due to their impaired ability to maintain balance. Our research group has developed a closed-loop visual-feedback training (VFT) system coupled with functional electrical stimulation (FES) for rehabilitation of standing balance (FES+VFT system); however, clinical usage of this system is limited by its use of force plates, which are expensive, cumbersome, and not easily accessible. For my thesis project, I 1) evaluated the validity of alternative sensors to the force plate for assessing postural balance and 2) developed and evaluated an updated FES+VFT system which uses the best alternative determined for real-time postural feedback. A clinically feasible version of the FES+VFT using the depth camera was developed and tested with ten able-bodied participants. The results of this research contribute to a more accessible standing balance rehabilitation system for individuals with incomplete SCI.
You Shall Call Me Yahweh: The How and Why El Came to be Known as Yahweh (Exod 3:1-15)
Keywords: Ancient Israelite religion
El to Yahweh
Folklore and Orality
Moses
Rhetorical criticism
The God of the Fathers

You shall Call Me Yahweh: The How and Why El Came to be Known as Yahweh (Exod 3:1-15)MA -Near & Middle Eastern Civilizations 2023 Thandazani Mhlanga Department of Near and Middle Eastern Civilizations University of Toronto Moses’s encounter with Yahweh at Horeb and the corresponding exodus have arguably attracted academic debate for a longer period than most biblical passages. In this thesis, it is the author’s intent to conduct a nuanced rhetorical criticism of Exodus 3:1-15 that considers form criticism and the oral tradition undergirding the text. A new all-encompassing interpretive system is also suggested and utilized for the purposes of sharpening our interpretive precision and enhancing our sensitivity and comprehension of the text. Through this nuanced multi-layered critical approach, it becomes evident that the story of Moses’s encounter with El, the God of Your fathers, in Exodus 3:1-15, is an etiological myth of Yahweh as the innate character of El. Furthermore, the corresponding Sitz im Leben of this switch from El to Yahweh brings to light the often elusive and, consequently, ignored relationship between the story and the storyteller.
Bioengineering Vascularized Porcine Free Flaps by Perfusion-Decellularization and Recellularization
Keywords: Regenerative Medicine
Tissue Engineering
Translational Medicine

Large volume soft tissue defects greatly impact patient quality of life and function while suitable repair options remain a challenge. Engineered tissues using decellularization/recellularization techniques may be a potential solution to circumvent issues of donor site morbidity or tissue availability associated with conventional free flap reconstruction. We developed and optimized a protocol to decellularize four vascularized porcine flaps within a custom designed perfusion-bioreactor and characterized the resultant extracellular matrix (ECM) components using both qualitative and quantitative techniques. Following decellularization, we designed a perfusion-based recellularization strategy by seeding a co-culture of human umbilical vein endothelial cell (HUVEC) with mesenchymal stromal cells (MSC) onto a decellularized omentum and tensor fascia lata flap. Our methods demonstrated evidence of cell attachment with early evidence of a regenerated neo-endothelium. Altogether, our described methods to engineer vascularized flaps scaffolds may help to obtain an “off-the-shelf” tissue option for application in large soft tissue defect reconstruction.
Evaluating Serum Urate Monitoring amongst Older Adults with Gout Initiating Urate Lowering Therapy in Ontario, Canada
Keywords: Crystal Arthropathies
Gout
Health Services Research
Quality of Health Care
Rheumatology

Serum urate (SUA) monitoring plays an important role in gout management. This thesis examined whether older adults with gout received SUA monitoring after initiating urate lowering therapy (ULT). Among a population-based cohort of 44,438 gout patients who initiated ULT between 2010 and 2019, 64% had SUA testing within six months. SUA testing was lowest in 2010 (56%) and increased over time to 71% by 2019. Increasing patient age, rural residence, low socioeconomic status, male ULT prescriber, chronic obstructive pulmonary disease and prior cardiovascular event(s) were associated with lower odds of SUA testing. Patients with kidney disease, hypertension, diabetes, ULT prescribed by rheumatologists, at lower starting doses, in more recent years and who received concurrent colchicine/oral corticosteroids had higher odds of SUA testing. These findings suggest variations in care and the need to develop/disseminate Canadian clinical guidelines for gout management to reduce care variation and potentially improve gout clinical care.
Identifying Probiotics that Modulate Mitophagy in Models of Mitochondrial Dysfunction
Keywords: mitophagy
Parkin
Parkinson disease
probiotic

Disruption of mitophagy in neurons is linked to Parkinson’s disease (PD), which is a multifactorial neurodegenerative disorder that currently has no cure. The neuroprotective effect of probiotics has become an emerging field of study due to growing evidence of the link between the health of the GI tract and the CNS. In various animal models and clinical trials, probiotic supplementation led to the alleviation of PD-like symptoms, while the mechanism of function remains unknown. The aim of this thesis was to identify probiotics that can potentiate mitophagy under mitochondrial stress and determine the active component(s). Utilizing cellular assays and a Drosophila model of PD, I validated that the probiotics Saccharomyces boulardii CNCM-I-1079 and Lactococcus lactis R1058 can induce Parkin-dependent mitophagy under mitochondrial stress, and only probiotics with mitophagy modulating ability shown neuroprotective effects. I also demonstrated that the small molecule MI6C is an active component released by CNCM-I-1079 and R1058 that induces mitophagy.
Combined Physiotherapy and Deep Brain Stimulation to Improve Independent Community Mobility in Parkinson’s disease
Keywords: balance
deep brain stimulation
mobility
Parkinson's disease
physiotherapy
rehabilitation

Despite overall improvements in motor function, studies have reported that deep brain stimulation (DBS) alone may not increase community mobility and may be associated with balance and gait instability and increased rate of falling in individuals with Parkinson’s disease (PD). The overall objective of this study was to determine if DBS combined with physiotherapy is effective for improving safe, independent mobility in the community in individuals with PD compared to individuals receiving DBS only. This is a single-center, single-blind non-randomized controlled study, whereby individuals receiving DBS were allocated to receive either physiotherapy three times per week for eight weeks or no intervention (control group). The findings from this study suggest that physiotherapy combined with DBS may be effective in improving balance and gait functions and reducing near-falls in PD compared to individuals receiving DBS only. Studies involving larger sample sizes are needed to determine its effect on overall community mobility.
Development of a Delivery Platform for Protein-Based Regenerative and Reparative Cardiac Therapies
Keywords: Cardiac
Nanoparticles
Protein
Regenerative medicine

Cell-based therapies for heart failure have been investigated in the field of regenerative medicine, however recent discoveries have shown that cardiac progenitor-cell derived paracrine effects (the secretome) may be inducing endogenous repair, instead of an intrinsic benefit from the stem cells themselves. We hypothesize that polyurethane-based nanoparticles will enable the delivery of therapeutic components of neonatal cardiac progenitor cell secretomes (BMP-4 and Ang1-7) and will induce characteristics representative of repair in damaged heart tissue. Polyurethane-based nanoparticles with a diameter of 190 ± 2 nm (polydispersity index < 0.2) and a zeta potential of -40 ± 1 mV were generated through an emulsion inversion technique. Through optimization of the concentration, coating duration, and coating efficiency, BMP-4 and Ang1-7 were coated onto the surface of the nanoparticles. Treatment with the coated nanoparticles significantly reduced expression of senescence associated b-galactosidase, a marker for senescence which is an important contributor to heart failure. On-going future work will further investigate the biological function of the nanoparticles with their biological payload, characterize both the particle and the biomolecule stabilities, and investigate co-delivery of multiple biomolecules simultaneously, in both in vitro cardiac cell and in vivo heart tissue models.
Intrinsic Photophysical Properties of Gaseous Acriflavine Ions
Keywords: Acriflavine
Excited State
Gaseous Ions
Laser Induced Fluorescence
Mass Spectrometry
Photophysics

Fluorescence is a widely used analytical technique in several disciplines of science. In this work, mass-selected ions are trapped in a quadrupole mass spectrometer for laser-induced fluorescence, and the photophysical properties of the fluorophore acriflavine - including steady state emission and time-resolved fluorescence lifetime - are characterized in the gas phase to learn more about its intrinsic photophysics in the absence of solvent interactions. The steady state emission spectrum of gaseous acriflavine displays two peaks, which I attribute to emission from two excited electronic states, showing that Kasha’s Rule does not always hold for warm gaseous molecular ions. The effects of excitation wavelength and internalenergy on the measured emission spectrum are investigated to further understand the flow of energy in the excited state of the acridine scaffold. This work provides experimental data that can be used to improve our models and understanding of excited states, and energy flow among these states.
Effects of Antenatal Glucocorticoids on MiRNA Levels in the Prefrontal Cortex of the Newborn Guinea Pig
Keywords: developmental epigenetics
fetal programming
glucocorticoids
miRNA
prefrontal cortex
pregnancy

Antenatal corticosteroid (ACS) treatment in cases of preterm birth (<37 weeks of gestation) significantly decreases neonatal morbidity and mortality, as it replaces an important endogenous surge in glucocorticoids that occurs in late gestation. While there are minimal short-term risks of ACS treatment, studies have demonstrated long term behavioural and structural impacts of ACS treatment on adult offspring. The underlying mechanisms of these effects are still unclear. One potential explanation is modulation by epigenetic mechanisms, including miRNA. This project seeks to identify differences in miRNA expression patterns in the medial prefrontal cortex of postnatal day 1 female guinea pig offspring that had been exposed to a single course of ACS treatment. A miRNA microarray showed no significant differences between control and treated animals. This is an important finding as it helps us understand the role epigenetic factors play at different time points of development in the modulation of the programming effects of ACS treatment.
Self-Reported Medical Cannabis Use and Inflammatory Cytokines and Chemokines in Chronic Pain Patients
Keywords: cannabinoids
chronic pain
cytokines
immune system
inflammation
medical cannabis

This dissertation investigated the association between medical cannabis (MC) use and inflammatory immune markers among chronic pain (CP) patients. Validated questionnaires, self-reported effectiveness of MC, and patient blood samples were collected. Fifty-six patients (64% females) were included with dried cannabis (53%) and THC-dominant products (70%) most commonly consumed. Majority of patients (83- 96%) self-reported symptom relief and and 76% reported a significant decrease in analgesic medication usage (p = <0.001). Compared to males, females had lower concentrations of some pro-inflammatory cytokines, cortisol, and significantly lower eotaxin levels (p=0.04). The regression analysis indicated that female sex was associated with decreased eotaxin (p = <0.01) concentrations. Blood CBD levels were associated with lower VEGF (p=0.04) concentrations and THC-COOH was a factor related to decreased TNF-α (p=0.02) and IL-12p70 (p=0.03). These findings suggest cannabis improves CP symptoms, reduces analgesic consumption, and has a potential immunomodulatory effect associated with patient sex and product type.
Stream Fragmentation Affects Movement in a Wetland-specialist fish, Grass Pickerel, Esox americanus vermiculatus
Keywords: dispersal
fish movement
population ecology
stream ecology
wetlands

Animal movement is a fundamental process for organisms to maximize their fitness, yet it is often challenged by human activities and climate change. For species listed under the Species at Risk Act, like Grass Pickerel (Esox americanus vermiculatus)—a wetland specialist—, understanding their movement ecology can inform conservation strategies. To determine their movement ecology, passive integrated transponder (PIT) tag data for Grass Pickerel in a Niagara Peninsula watershed gathered by Fisheries and Oceans Canada from 2009 to 2013 were analyzed. Of the 2,007 tagged fish, only 16% made movements more than 500m, with a median and maximum movement distance of 1.89 km and 13.5 km respectively. Movements mostly originated from locations with high local abundance, and mobile fish were longer than stationary fish. Hence, while a long-distance dispersal ability exists in extant Grass Pickerel populations, the conditions of riverscapes in southern Ontario may prevent these dispersals from occurring.
Investigating the Interactions Between G Proteins and Estrogen Loss in the Mouse Skeletal System
Keywords: Bone
G proteins
Osteoporosis
Postmenopause

Postmenopausal osteoporosis is the most common bone disease, as estrogen deficiency is directly related to reductions in trabecular and cortical bone. In addition to sex steroids, G proteins play important roles in bone development and maintenance. We have previously developed two transgenic mouse models that have high levels of Gαs (Gs-Tg) or Gα11 (G11-Tg) in osteoblasts. Gs-Tg mice had increased bone, whereas G11-Tg mice had osteopenia. To investigate how variations in G protein signaling in osteoblasts impact postmenopausal bone health, we ovariectomized (ovx) Gs-Tg and G11-Tg mice at 4 months of age and examined their skeletal phenotypes 5 weeks post-surgery. The high bone turnover in Gs-Tg mice made them more susceptible to bone loss with ovx. Conversely, G11-Tg mice were protected from ovx-induced bone loss. This offers new insight into predicting postmenopausal bone health in individuals with high G protein levels, in addition to potentially elucidating therapeutic targets.
Study of 48-to-1 V Multi-inductor Hybrid Converters
Keywords: 48-to-1 V DC-DC converter
Multi-inductor Hybrid Converter

The 48 V DC bus is an intermediate power bus in all telecommunication systems. The traditional approach is to employ cascaded converters to step-down the supply voltage from 48 V to 5/12 V, and 5/12 V to 1 V at the point of load. This usually results in inefficient power conversion. To achieve high efficiency, this thesis is aimed to determine the best multi-inductor hybrid converter (MIHC) configuration, for a direct 48-to-1 V conversion, 90 A, 200 kHz application. The simulated 6-to-1 level is found to be the best topology. The gate drive loss and inductor conduction loss outweigh the benefits of the 8-to-1 level configuration. The 6-to-1 level MIHC is also verified experimentally to outperform the 2-to-1 topology in 48-to-1 V conversion with a peak efficiency of 90 % at 5 A, and 65% at 25 A. The 6-to-1 MIHC topology provides a good trade-off between circuit complexity and power conversion efficiency.
Real-Time Motion Compensation of Magnetic Resonance Thermometry and Adaptive Targeting Algorithms for Focused Ultrasound Controlled Hyperthermia in Sarcomas
Keywords: High Intensity Focused Ultrasound
Hyperthermia
Magnetic Resonance Thermometry
Motion Compensation
Sarcomas
Thermosensitive Drug Delivery

Sarcomas are the most common extracranial solid tumours in children and have poor prognoses due to resistance to conventional treatments. Magnetic resonance-guided high-intensity focused ultrasound (HIFU) can non-invasively administer localized hyperthermia which can improve the efficacy of chemotherapy, radiation, and immunotherapy in various cancers. One of the challenges preventing the widespread clinical adoption of MRgHIFU is that thermometry is prone to motion artifacts that corrupt data. The objective of this work is to optimize MRgHIFU-controlled hyperthermia by implementing motion compensation and adaptive tumour targeting algorithms. During targeted drug delivery in a murine sarcoma model, motion artifacts resulted in underheating of the tumour, leading to less drug being released. In preparation for translation, a motion compensation algorithm demonstrated powerful artifact removal during robot-controlled motion in a phantom on a clinical MRgHIFU system. An adaptive targeting algorithm was implemented to correct a mistargeted HIFU focus with high accuracy and precision in gelatin phantoms.
Designing Epitope-specific CDR-H3 Loops via Deep Learning
Keywords: Antibody
CDR-h3
deep learning
GAN

Antibodies are great therapeutic candidates because of their ability to recognize and bind disease-related antigens with high specificity and affinity. Such binding is driven by the interaction between a subset of residues in the antigen, which collectively form the epitope, and loops within the antibody that are known as complementarity-determining regions (CDRs). One CDR loop in particular, the CDR-H3 loop, has a high degree of sequence and structural diversity, allowing such binding to be diverse and specific. Currently, approaches for the design of CDR-H3 loops are not antigen-specific. Here, I developed a pipeline to design backbones and sidechains for CDR-H3 loops that target specific epitopes. To determine the Cα position of the backbone, a Generative adversarial network (GAN) was trained to predict a Cα distance matrix defining the structure of the loop and its relative position to antigen residues. The resulting distance matrices show a high degree of similarity to the ground truth matrices (median 1.2Å difference). Using these generated matrices, the 3D positions of all Cα atoms were recovered. The full backbone and sidechains were subsequently reconstructed using existing physics-based methods such as Rosetta, yielding antibodies that were predicted to bind to the specified epitopes. This novel method has the potential to surpass or supplement current antibody development methods and can have numerous applications in biomedical sciences.
Local Metabolism of Progesterone Regulates Cervical Remodelling and Timing of Labour Onset
Keywords: Cervical Ripening
Inflammation
Labour
Preterm Birth
Progesterone
Promegestone

Withdrawal of pro-gestational hormone progesterone (P4) is necessary for labour onset in human and rodents. In murine cervix P4 withdrawal is mediated by enzymes 5-alpha-reductase (Srd5a1) and 20-alpha-hydroxysteroid-dehydrogenase (20αHSD/Akr1c18). I hypothesize that 1) inflammation (physiologic or infection-induced) alters the levels of both enzymes in mouse cervix, impacting local P4-metabolism; 2) Selective Progesterone Receptor Modulator (SPRM), Promegestone (aka R5020), non-metabolizable by 20αHSD, can prevent preterm labour (PTL) in mice by maintaining P4 signaling. I found significant induction (p<0.01) of Srd5a1 and Akr1c18 mRNA and protein levels during infectious (Lipopolysaccharide (LPS)-induced) PTL in mice which was inhibited by prophylactic R5020 administration. Transcript levels of cervical ripening enzymes Adamts1 and Has2, as well as pro-inflammatory markers Il1b, Il6, Cxcl1, and Ccl2 were induced during PTL (p<0.05) and inhibited with R5020 pre-treatment (p<0.05). I concluded that prophylactic R5020 administration prevents LPS-induced inflammation and cervical ripening in mice, thus presenting a promising novel therapeutic for women at risk of preterm birth.
Development of a CRISPR Screen to Identify Molecular Regulators of Photoreceptor Intercellular Material Transfer
Keywords: cell communication
CRISPR
material transfer
photoreceptors
primary cells
retina

A widely investigated therapeutic strategy for retinal degeneration is transplantation to restore photoreceptor function. Recent studies suggest that vision rescue from photoreceptor transplantation is due to material transfer (MT) of cytoplasmic proteins from donor to host photoreceptors. However, the mechanisms of MT are largely unknown. Our lab has established an in vitro co-culture assay to track cell contact-dependent mitochondria transfer. Using this system, we designed and investigated a genomic CRISPR/Cas9 screening strategy for an unbiased, large-scale investigation of genes regulating MT in acceptor photoreceptors. We generated retinal explant derived CRISPR/Cas9 edited photoreceptors with the capacity to efficiently accept mitochondria in the co-culture assay. We optimized culture components to increase the feasibility of this challenging primary cell-based strategy. Our findings have advanced the development of an approach for discovery of mechanisms underlying photoreceptor MT. Further understanding of MT regulators can lead to therapeutic applications of MT for treatment of retinal diseases.