VictorJuiz/thesis huggingface dataset:
Prescribing Characteristics Associated with Return to Opioid use following Buprenorphine Treatment in Ontario

Buprenorphine is a first-line treatment for opioid use disorder (OUD), however, many clients choose to discontinue therapy. We used Cox proportional hazards modelling to understand which prescribing characteristics were associated with return to opioids within 18 months following buprenorphine taper among persons 18 years or older with OUD in Ontario. Among 5,774 individuals, 65.8% experienced at least one opioid-overdose, treatment re-entry, or return to prescription opioid use. Time to taper initiation >1 year vs. ≤1 year (aHR:0.69, 95% CI:0.48-0.997) and a lower average rate of taper (≤ 2 mg/month and >2 to ≤4 mg/month compared with >4 mg/month) (aHR:0.65, 95% CI:0.46-0.91; aHR:0.69, 95% CI:0.51-0.93) were associated with lower risk of opioid-overdose. A more stepped taper, with doses decreasing in ≤1.75% of days compared with >3.5% of days, was also associated with reduced risk of opioid-overdose (aHR:0.64, 95% CI:0.43-0.93). Findings highlight the risks associated with tapering buprenorphine and underscore the importance of careful treatment planning.

Keywords: buprenorphine
discontinuation
opioid
opioid agonist therapy
overdose
taper
Advisor: Gomes, Tara
White Matter Microstructure in Male and Female Children with Mild Traumatic Brain Injuries and Association with Processing Speed

As maturation of the brain microstructure and cognitive processes continue throughout development, there is risk of interference from mild traumatic brain injury (mTBI). This thesis used T1-weighted and diffusion magnetic resonance imaging (MRI) to investigate differences in white matter and cortical microstructure between children with a history of mTBI and children with no history of mTBI, and to investigate whether differences in brain microstructure are associated with performance on cognitive tests. Group comparisons between children with and without a history of mTBI revealed significant differences in deep and superficial white matter microstructure in females with mTBI. In addition, in females with mTBI, superficial white matter microstructure was associated with lower scores on the processing speed test. These findings suggest that mTBI in childhood may alter white matter development in females. This sex dependent effect on the brain may be associated with enhanced vulnerability to persistent symptoms after mTBI in females.

Keywords: Concussion
Magnetic Resonance Imaging
Mild Traumatic Brain Injury
Paediatric
Processing Speed
Restriction Spectrum Imaging
Advisor: Wheeler, Anne L
Ameis, Stephanie H
The Role of Leucine Rich Repeat Containing G Protein-coupled Receptor 5 Positive Stem Cells in Glucagon-like Peptide-2 Induced Intestinal Epithelial Proliferation

GLP-2-based therapy is currently used to treat patients with short bowel syndrome (SBS). Glucagon-like peptide-2 (GLP-2) released from the intestinal L cell stimulates growth of the intestinal epithelium. This thesis endeavored to determine which crypt cell GLP-2 acts on to induce its proliferative effect. It was hypothesized that GLP-2 induces leucine rich repeat containing G protein-coupled receptor 5 (Lgr5)+ crypt-base columnar (CBC) stem cell proliferation under pharmacologic and physiologic conditions. Lgr5-enhanced green fluorescent protein (eGFP) reporter mice were used to visualize stem cells and cell cycle progression was measured with 5-ethynyl-2′-deoxyuridine (EdU) and 5-bromo-2'-deoxyuridine (BrdU) labeling, Ki67 and phospho-histone 3 (pH3). It was found that acute pharmacologic GLP-2 treatment stimulates S-phase entry in CBC stem cells. Also, antagonism of endogenous GLP-2 reduces the proportion of CBC stem cells in S-phase. Together, these findings demonstrate a role for CBC stem cells in GLP-2 signaling and proliferation through S-phase induction.

Advisor: Brubaker, Patricia L
Integrative Taxonomy as a Tool for Conservation: Exploring Freshwater Fish Diversity of the Barra del Colorado Wildlife Refuge, Costa Rica

As global biodiversity declines, conservation efforts are important in megadiverse areas such as the Neotropics where biodiversity is especially imperiled. The accurate identification of species/specimens is critical to successful conservation plans. However, in groups such as freshwater fishes, conventional methods for species/specimen identification such as morphology, or molecular methodologies such as DNA barcoding, have documented challenges. Approaches that integrate multiple data sources are likely to provide the best species identifications. Here, I assess the diversity of freshwater fishes in the Barra del Colorado Wildlife Refuge, Costa Rica, and document 51 species. I use and compare multiple approaches to identify species. My results demonstrate that barcode-based identifications are comparable to field-based identifications despite known gaps in resources for field-based identifications and are inferior to identifications by experts using morphology. I conclude that an integrative approach to specimen identification is a critical facet of successful preservation of biodiversity.

Keywords: barcode
ichthyology
identification
morphology
neotropics
Advisor: Lovejoy , Nathan
An Improved Approach for Optogenetic Locomotion Control of Caenorhabditis Elegans

Animals have greatly inspired the development of robotics with their sophisticated bodies after the evolution of millions of years. By directly harnessing the intelligence of animals, the technical bottlenecks such as integration of actuation mechanism and energy source for untethered microrobot could be overcome. Our research group proposed an approach to develop a living soft microrobot by optogenetic locomotion control of Caenorhabditis elegans, called RoboWorm. This thesis work further improves the RoboWorm technology. Firstly, the applications of RoboWorm to support biophysical research of C. elegans are illustrated through a literature review. Secondly, the performance of RoboWorm has been significantly improved by generating a new transgenic strain of C. elegans, with a different approach to hijack the worm motor neurons. The third aspect is to improve the operation and enhance the user-friendliness of the RoboWorm system. Overall, this thesis improves the performance and demonstrates applications of the RoboWorm technology.

Keywords: Caenorhabditis Elegans
Living robot
Micro robot
Optogenetics
Soft robot
Advisor: Liu, Xinyu XL
Information-seeking Drug Professionals: Information Practices of Peer Harm Reduction Workers in Toronto

While a significant body of literature exists studying the effectiveness of peer-led harm reduction programming, a much smaller body of work examines peer harm reduction workers’ professional capacities, particularly outside of public health policy or social work fields. Using a Library and Information Sciences theoretical framework, the purpose of this study is to investigate the information practices of peer harm reduction workers, thereby centring the experiences of people who use drugs working in the harm reduction field. Eight peer harm reduction workers who live and work in Toronto were interviewed about their workplace experiences, professional development, and community engagement. Applying Lloyd’s writing about embodied information practice as a theoretical framework, the findings of this study conceptualize how harm reduction workers with lived experience develop their career identities and collaboratively create social and cultural norms in their workplaces.

Keywords: Community health
Harm Reduction
Library and Information Sciences
Peer Harm Reduction Workers
People who use drugs
Public health policy
Advisor: Shachak, Aviv
Furness, Colin
The Effects of Combined h[Gly2]Glucagon-Like Peptide-2 and Exendin-4 on Parameters Relevant to Short Bowel Syndrome

The intestinotrophic hormone, Glucagon-Like Peptide-2 mimetic h[Gly2]GLP2 is used to treat patients with Short Bowel Syndrome. GLP-1 mimetics including Exendin-4(Ex4) improve metabolism but are also intestinotrophic. Given this overlap, intestinal growth and permeability, body weight (BW), and gastric emptying (GE) were investigated in male and female C57/BL6mice following h[Gly2]GLP2 and Ex4 treatment, alone and in combination at “low”, “medium”, and “high” doses. Only the h[Gly2]GLP2 low dose/Ex4 high combination increased small intestinal (SI) weight compared to vehicle and both mono-agonists, via increases in SI length and villus height. This combination also abolished Ex4 induced reductions in BW and GE. However, h[Gly2]GLP2 induced reductions in intestinal permeability were abrogated by this combination.These findings suggest that adding GLP-1 mimetics to GLP-2-based therapy improves intestinal growth without detrimental effects on BW and GE, although antagonistic effect on intestinal permeability, as well as use in SBS models necessitate further studies

Advisor: Brubaker , Patricia
Evaluating Variation In Red Blood Cell Transfusion for Patients undergoing Elective Gastrointestinal Cancer Surgery

Understanding variation in transfusion practice among patients undergoing gastrointestinal cancer surgery will support efforts working towards responsible transfusion use. We performed a population-based study of patients who underwent elective gastrointestinal cancer resection between 2007 and 2019 to measure variation in transfusion use across surgeons and hospitals. Variation was explored using funnel plots and multilevel regression. Of 59,964 patients, 18.0% were transfused. Wide variation in transfusion use among surgeons and hospitals was observed. Patient characteristics explained 12.8% of the variation. After adjusting for patient case-mix, between-surgeon and between-hospital differences were responsible for 2.8% and 2.1% of the variation, respectively, translating to an approximately 30% difference in the odds of transfusion for two similar patients treated by distinct surgeons or hospitals, respectively. Although transfusion provision depends on patient factors, important variation across surgeons and hospitals creates opportunities to target modifiable processes of care to standardize perioperative transfusion practice.

Keywords: Blood transfusions
Practice variation
Surgical oncology
Advisor: Coburn, Natalie
Phenotypic Examination of CD9 Overexpression in White Adipose Tissue

Adipose precursor cells (APCs) are a key target population for obesity-related alterations due to their bipotential differentiation capacity. APCs are capable of differentiating into white adipocytes, contributing to the development of fat-storing cells (i.e., adipogenesis), or into fibroblasts, which can lead to white adipose tissue (WAT) fibrosis. Recently, CD9high PDGFRα+ APCs demonstrated greater fibrotic nature compared to their, adipogenic, CD9low counterparts. This suggests the involvement of a CD9-based mechanism in the differentiation of PDGFRα+ APCs. To elucidate the role of CD9 in APC fate determination, we created a cell-type-specific and drug inducible overexpression mouse model that increases CD9 expression in PDGFRα+ APCs. The goal of this project is to phenotypically characterize this model and examine the role of CD9 expression fate determination of PDGFRα+ APCs. Our findings suggest that CD9 overexpression in PDGFRα+ APCs promotes systemic dysglycemia and enhanced WAT fibrosis. Altogether our results implicate CD9 in APC fate determination.

Keywords: Adipose Tissue
Diabetes
Fibrosis
Obesity
Advisor: Sung, Hoon-Ki
Ethnic Differences in Cardiometabolic Risk: A Meta-analysis in Adults and a Cross-sectional Study in Children

Type 2 diabetes (T2D) manifests differently in adults of different ethnicities. Whether these differences arise as early as childhood remains narrowly explored. For Objective 1 of this thesis, two separate meta-analyses of prospective cohort studies were conducted using random effects models to investigate whether the associations between BMI, WC, and T2D risk differ across ethnic groups. For Objective 2, a cross-sectional analysis was conducted among 5,557 children (ages 3-11 years), and linear and multivariate regression models were used to estimate differences in continuous cardiometabolic risk (CMR) outcomes, including a CMR score, between European and non-European children. In Objective 1, the meta-analyses showed that Southeast Asians displayed the highest risk of T2D per unit increase in BMI and WC. In Objective 2, African and East Asian children were observed to have significantly lower CMR scores than European children, while South Asian children displayed higher levels of lipid markers than Europeans.

Keywords: Cardiometabolic risk
Ethnicity
Obesity
Type 2 diabetes
Advisor: Malik, Vasanti S
First Records of a Cribriform Plate in Non-avian Dinosauria, with Implications for Olfactory Evolution and Ecology

The study of internal cranial anatomy in dinosaurs has allowed for insights into aspects of their neurology and sensory evolution. We describe the novel aspects of the olfactory anatomy of two ankylosaurids: Anodontosaurus lambei and Dyoplosaurus acutosquameus. These specimens exhibit ossified cribriform plates, a plate of bone perforated by olfactory nerve bundles. These represent the first known occurrences of this feature in non-avian dinosaurs, and it is rarely seen in non-mammals. The pattern of perforation in ankylosaurs is more peripheral than in mammals but the density is similar. This enables us to use the framework of a previous study to estimate the number of functional olfactory receptor genes from the plate area. We also examine the potential application of “maximum olfactory windows” in other dinosaurs, where the olfactory nerve passes through ossified foramina (ceratopsids, hadrosaurids and tyrannosaurids). This research provides the first estimates of functional sensory genes in non-avian dinosaurs.

Keywords: Cribriform plate
Genomics
Olfaction
Olfactory anatomy
Sensory evolution
Advisor: Evans, David C
Pharmacogenetic Analysis of Antipsychotic Response in Schizophrenia

Antipsychotic (AP) medications are the best treatment option for schizophrenia (SCZ), but the inter-individual difference in treatment response is a serious concern. Previous studies have revealed a strong genetic component in AP efficacy, thus we aimed to identify genetic predictors for AP response. We examined the metabotropic glutamate receptor 3 (GRM3) gene variants for association with AP response, and observed that rs274621 was associated with better response. We also investigated the associations between the polymorphisms in alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit genes and clozapine (CLZ) response and found rs1461225 to be associated with negative symptom improvement. Lastly, we studied the complement component 4 (C4) gene in relation to SCZ clinical characteristics. We found nominal associations between C4 and SCZ clinical characteristics, as well as a strong sex-specific effect on C4 genotype distribution in SCZ. Our studies pointed to several potential biomarkers for AP response, but future replication studies are required.

Keywords: Antipsychotic
Pharmacogenetics
Schizophrenia
Advisor: Kennedy, James JLK
Deciphering Stem Cell from Apical Papilla - Macrophage Choreography in Inflammatory Environment using a Novel 3D Organoid

The aim of this study is twofold: (1) develop and characterize a 3D binary-cells tissue construct to study SCAP (stem-cell-from-apical-papilla) - MQ (macrophage) interaction, and (2) investigate the interactions and cell signaling mechanisms between SCAP-MQ under pro-inflammatory/anti-inflammatory environments in the organoid system. 3D (dimensional) image analysis and cytokine profiles were employed in this investigation. It was demonstrated that the SCAP self-organized as a cap-shaped organoid in the tissue construct. The pro-inflammatory/anti-inflammatory environments influenced SCAP-MQ interactions, resulting in altered cell volume, cell viability, cell morphology and structural organization in 3D tissue construct. The increased cytokine/chemokine profiles at the earlier phase of pro-inflammation, increased ratio of pSTAT6/pSTAT1 and decreased CD206/80 indicated a distinct polarization behavior in macrophages during repair. Conversely, equal ratio of pSTAT6/pSTAT1 and late increase of CD206/80 with amplified secretion of IL-1RA, IL-10 and TGF-1 in the anti-inflammatory environment directed alternative macrophage polarization, while promoting SCAP differentiation and tissue modeling.

Keywords: 3D cell culture
Cell interaction
Inflammation
Macrophage
Organoid
SCAP
Advisor: Kishen, Anil AK
Investigating Sex Differences In Fetal Antiretroviral Drug Disposition: The Role Of Membrane-associated Transporters and Metabolic Enzyme

Antiretroviral (ARV) therapy is effective in reducing risk of vertical HIV transmission during pregnancy, however, the fetal toxicity of ARVs remains poorly understood and existing literature often does not account for fetal sex. New evidence of sex-linked toxicities in ARV-exposed children suggests sex-differential drug disposition, which may be explained by differential expression of membrane-associated drug transporters and metabolic enzymes, which are known to vary with sex. We investigated the effect of fetal sex and ARV treatment on the expression of transporters, metabolic enzymes and other relevant proteins in a mouse model of antiretroviral therapy in pregnancy. We also measured fetal brain and amniotic fluid drug concentrations by LC-MS/MS and assessed correlations between transporter expression and ARV penetration. Both fetal sex and ARV exposure were observed to impact transporter expression in fetal brain and placenta, suggesting an important role for transporters in mediating sex-specific ARV disposition and in utero toxicity.

Keywords: Antiretroviral Drugs
Drug Transport
HIV
Placenta
Pregnancy
Sex Differences
Advisor: Bendayan, Reina
Computational Evaluation of a Hybrid Electrochemical Reduction-bioproduction System for the Conversion of Carbon Dioxide to Fuels and Chemicals

The electrochemical reduction of CO2 (eCO2R) can produce a number of one and two carbon (C1/C2) compounds that can serve as sustainable feedstocks for bioproduction processes. The presented research seeks to optimize the integration of these two technologies by evaluating a wide range of eCO2R product-bioproduct pairs. Specifically, the costs of production of the eCO2R system were evaluated for eight C1/C2 eCO2R products, and these costs were combined with metabolic modeling predictions to investigate the most economically feasible pairs when considering more than 1000 bioproduction options (20+ assimilation pathways and 50+ bioproducts). The results suggest that the aerobic bioconversion of C2 products or methanol to highly oxidized products provide the most economically viable option, followed by the anaerobic bioconversion of formate/hydrogen or carbon monoxide/hydrogen to more reduced products. Overall, this analysis highlights areas of interest for future studies, particularly when selecting substrate-product combinations on which to focus experimental efforts.

Keywords: Biofuels
Bioproduction
CO2 Conversion
Electrochemical Reduction
Metabolic Engineering
Metabolic Modeling
Advisor: Mahadevan, Radhakrishnan
Deep Mutational Scanning of Missense Variants of SERPINA1, a Gene Involved in Alpha-1 Antitrypsin Deficiency

Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder that occurs in about 1 in 2500 individuals. The gene responsible for this condition is SERPINA1, which encodes the alpha-1 antitrypsin protein. This protein is secreted from the liver, and its main function is to inhibit neutrophil elastase activity in the lungs, which if unregulated can lead to inflammation and changes in the extracellular matrix. One of the challenges associated with AATD is that it is often misdiagnosed as chronic obstructive pulmonary disorder or liver disease, and there is a 5-7 year gap between initial symptoms and diagnosis. Thus, there is a need for a proactive map for genetic counselors and physicians to diagnose this condition early. This project will employ deep mutational scanning, a methodology to classify all possible missense variants with a functional assay. The result is a variant effect map that may allow for improved proactive diagnosis of AATD.

Keywords: deep mutational scanning
genetics
genomics
high-throughput
multiplex analysis of variant effect
variant effect map
Advisor: Roth, Frederick P
Evaluating the Energy Consumption of Battery Electric Vehicles Under a Diverse and Changing Climate

Passenger vehicles contribute considerably to global energy consumption and greenhouse gas emissions. Battery electric vehicles (BEVs) are one form of climate change mitigation through their higher efficiency compared to internal combustion engine vehicles as well as their use of electricity, which has potential to be less carbon intensive than fossil fuels. However, passenger vehicle energy consumption is affected by operating conditions provided by weather and climate variability.This thesis presents a review of known relationships between climate variables and passenger vehicle energy consumption, with an emphasis on BEVs. The impacts of rising global temperatures on passenger vehicle energy consumption in North America is also estimated. Finally, the impacts of BEV charging on electricity demand and peak demand were estimated for the Greater Toronto and Hamilton Area while taking ambient temperature into account. The results illustrate the importance of taking climate and climate change into account when conducting BEV impact analyses.

Keywords: battery electric vehicles
climate change
electric grid
electric vehicle charging
passenger vehicles
power demand
Advisor: Posen, Daniel
Loss of Bat3 on T Cells Impairs Response to Viral Infection via Altered T cell-NK Cell Crosstalk

Factors regulating T cell and innate lymphoid cell (ILC) cross-talk ensure coordinated immune responses. Human leukocyte antigen-B-associated transcript 3 (Bat3) protects T cells from Tim-3-induced exhaustion and regulates human Natural Killer (NK) cells. Herein, we use Bat3flox/flox CD4-cre mice in the RIP-gp model to demonstrate that loss of Bat3 on T cells impairs CD8+ T cell-mediated tissue destruction and reduces CD4+ T cells proliferation, expression of activation markers, and TNF- and IFN- production. Furthermore, we show mice lacking T cell-expressed Bat3 have a CD49b+NK1.1+ ILC population that expresses high levels of Galectin-9 and IL-22, and expands following viral infection. Depletion of NK1.1+ cells or ILCs (Nfil3-/-) restores normal T cell activity in vivo, and T cell proliferation and activation marker expression is restored in Bat3flox/flox CD4-cre Nfil3-/- mice. Collectively, this thesis provides evidence that NK cell regulation of anti-viral T cell responses is influenced by T cell expression of Bat3.

Keywords: Bat3
LCMV
NK cell
regulation
RIP-gp
T cell
Advisor: Crome, Sarah
Development and Analysis of Phase Change Slurries for Geothermal Energy Systems

Geothermal energy provides continuous baseload power, in contrast to the intermittent and seasonal capacity of other renewables. Closed loop geothermal (CLG) systems harvest thermal energy using a continuously circulating working fluid and enable the use of novel fluids to enhance thermal energy recovery. In this thesis, phase change material (PCM) based slurries (PCS) are developed and assessed for their suitability as a CLG working fluid. PCS enable enhanced thermal storage by capturing energy in both sensible and latent heat. First, non-encapsulated and microencapsulated based PCS are assessed based on their stability, flow behaviour and thermal properties. The impacts of surfactants and sub-surface contaminants are assessed. Next, a deep analysis into the flow behaviour of these fluids is performed. PCS are optimized and found to be suitable for use over many cycles in a geothermal system. The key properties impacting PCS flow behaviour are demonstrated, enabling their optimization for flow-based applications.

Keywords: Emulsions
Geothermal energy
Phase change material
Phase change slurry
Rheology
Thermal energy storage
Advisor: Sinton, David