VictorJuiz/thesis huggingface dataset:
Metformin Alters the Neuroinflammatory Response of Mcroglia following Neonatal Stroke

Neonatal stroke is a devastating disorder with long-term consequences for children and caregivers. Microglia and astrocytes mediate the neuroinflammatory response after injury which can exacerbate damage. Metformin is an antidiabetic drug which has been shown to improve functional impairments and promote neural repair after neonatal brain injury. Herein, we investigated metformin's potential role in regulating the neuroinflammatory response after neonatal stroke. Stroke-injured mice showed brain region-specific microglia and astrocyte activation and metformin treatment after stroke was sufficient to reduce microglia activation, without affecting the astrocyte response. Given the correlation with reduced microglia activation and improved functional outcomes, we established a microglia ablation model using Plexxikon 5622. This resulted in significant microglia depletion without effects on astrocytes or motor behaviour. This study is the first to characterize the spatiotemporal aspects of the neuroinflammatory response after neonatal stroke and metformin treatment and establish a model of microglia ablation in neonatal mice.

Keywords: Ablation
Astrocytes
Metformin
Microglia
Neonatal stroke
Advisor: Morshead, Cindi
The Therapeutic Potential of HMGB1 Inhibition in the Development of Systemic Sclerosis-associated Pulmonary Arterial Hypertension

High mobility group box-1 (HMGB1), a danger-associated molecular pattern, is gaining recognition as a mediator of pulmonary arterial hypertension (PAH). Unfortunately, current studies fail to address therapeutic interventions for pulmonary arterial hypertension associated with systemic sclerosis (SSc-PAH), which is a devastating subset of PAH. Our understanding of this entity is hampered by the lack of a readily available, high-fidelity animal model. Herein, we sought to assess the Tight Skin mouse (Tsk), which possesses many features of SSc, as a model of SSc-PAH, and to test the effect of HMGB1 inhibition upon the development of pulmonary hypertension (PH) in this model.Our data provide the first description of the hypoxic Tsk model of SSc-PAH. Mechanistically, our results indicate a key role for HMGB1, released in response to cellular damage, in the pathogenesis of PH in this model, potentially acting upon the pulmonary artery adventitial fibroblast.

Keywords: fibroblast
HMGB1
pulmonary arterial hypertension
systemic sclerosis
Advisor: Goldenberg, Neil NG
The Genetic Basis of Natural Variation in Algal Neutral Lipid Accumulation

Neutral lipids are known to be involved in an algal adaptation to cold, light, and nutrient stress, but the extent of intraspecific variation and the mechanisms maintaining the variation in this economically important trait are unclear. I predict algal strains from different latitudes will vary in neutral lipid accumulation because many of the stressor associate with climate. Inducing neutral lipid accumulation using nitrogen (N) starvation in 26 natural isolates of Chlamydomonas reinhardtii revealed genetic variation but no latitudinal pattern in neutral lipid accumulation. A further experiment demonstrated latitudinal variation in neutral lipid accumulation induced by cold shock and light deprivation. By analyzing molecular evolution of 473 lipid-candidate genes, I inferred stronger purifying selection and higher rates of positive selection driving genetic divergence in the lipid-associated genes. From this, I suggest the possibility that neutral lipid accumulation is an adaptive trait in C. reinhardtii under positive selection.

Keywords: adaptation
Chlamydomonas reinhardtii
natural selection
neutral lipid
nitrogen starvation
population genetics
Advisor: Ness, Rob W
An Interactive Machine Learning Approach to Integrating Physician Expertise into Delirium Prediction Model Development

Delirium is an acute neurocognitive disorder which affects up to half of older hospitalized patients, leading to dementia, longer hospital stays, increased health costs, and death. While delirium can be prevented and treated, it is difficult to identify and predict. Within the GEMINI study, a detailed manual review of medical records has been conducted on nearly 4000 admissions at six hospitals in the Greater Toronto Area, of which approximately 25% have been labeled as having delirium. Using the data collected from this study, we develop machine learning (ML) models with, and without, expert knowledge. By comparison, physician expertise indeed improves delirium status prediction performance and the performance is found to be stable over time. Based on the experimental findings, we further discuss the potential value of using such interactive machine learning (iML) approaches in general healthcare ML applications. Overall, this thesis provides a new perspective on developing delirium prediction models.

Keywords: Healthcare
Machine Learning
Advisor: Chignell, Mark
Functional Neuroimaging Biomarkers of Anhedonia Response to Adjunct Aripiprazole Treatment for Major Depressive Disorder

Anhedonia is a common, yet often overlooked symptom of major depressive disorder (MDD). Currently, there are no approved treatments for this symptom. Aripiprazole, an adjunct treatment for MDD, may be a potential treatment. Aripiprazole increases activity of dopamine, the main neurotransmitter implicated in anhedonia. In the current study, the effectiveness of aripiprazole for treating anhedonia, and potential resting-state functional neuroimaging biomarkers of improvement in anhedonia after aripiprazole treatment, were explored. Eighty-six participants with MDD were treated with eight-weeks of aripiprazole. Aripiprazole was associated with a significant improvement in anhedonia symptoms. Increased functional connectivity between the salience and default mode networks; and between the nucleus accumbens and brain regions implicated in neural transmission predicted improvement in anhedonia. Therefore, aripiprazole may represent an effective treatment for anhedonia as part of MDD. Further, particular functional connectivity patterns in the brain may be able to identify who will or will not respond to aripiprazole.

Keywords: anhedonia
aripiprazole
biomarkers
depression
neuroimaging
precision medicine
Advisor: Kennedy, Sidney H.
Graph Learning Perspective on EEG-based Human Identification

EEG-based user identification is an emerging field in biometric systems. EEG signals promise more secure recognition technology than other biometric traits because EEG waves are more robust to forgery and replication. Two of the main challenges of EEG biometric systems are the sensibility to a number of electrodes and instability to different human conditions during recording. We address these two problems by considering brain regions' connections and observing EEG signals from a graph perspective.In this thesis, we explore graph learning as a new approach for extracting brain features. First, graph convolutional neural network benchmarks and their power for EEG-based identification are studied. Second, we have developed a novel graph variational auto-encoder (GVAE) for deriving EEG embeddings. This generative model learns graphs' stochastic probabilities with a low computational cost. We illustrate that GVAE features discriminate the EEG signals of different subjects with high accuracy for both small and large graphs.

Keywords: Biometrics
Electroencephalogram
Functional connectivity
Graph Convolutional Neural Network
Graph Learning
Graph Variational Auto Encoder
Advisor: Hatzinakos, Dimitrios DH
Optimization-based Tail Risk Hedging

This thesis presents a mixed risk-return optimization framework for selecting long put option positions to hedge the tail risk of investments. We formulate tractable optimization models by utilizing hypothetical portfolios that roll put options on a constant basis. Variance and sample Conditional Value-at-Risk (CVaR) are used as risk measures. Firstly, the tail risk hedging for a single asset such as the S 500 ETF is considered. Our proposed models are tested against the out-of-sample historical S 500 index values as well as the values of the index paired with long put options of varying strike prices. The optimized hedged portfolios could provide sufficient protection in market downturns while not losing significant returns in a longer investment horizon without explicitly predicting future market behavior. This is achieved by dynamically adjusting the positions of put options with different protection levels according to the market trends. Allocations to different put options are analyzed under various market trends and investor risk aversion levels. Then our framework is extended to multiple underlying assets and put options associated with them by constructing a hypothetical portfolio consisting of a combination of each put option and the associated underlying asset. The optimized strategies overcome traditional drawbacks associated with protective put strategies, as well as outperform the strategies of investing directly in the underlying assets and holding constant long positions in put options.

Advisor: Kwon, Roy
Harm Reduction Ethics in Crisis (Work): The Manifestation of Spiritual Pain in the Everyday Practice of Street Outreach Work

From the accounts of street outreach workers in Toronto, Ontario, this critical qualitative study reveals the disjuncture between a street outreach worker’s harm-reduction ethics and their crisis work. Semi-structured interviews were conducted with seven street outreach workers who self-identified as working from a harm reduction ethic. This study sought to situate the everyday experiences of street outreach workers who engage in crisis work within the often-invisible realm of organizational and environmental influences, such as program funding, restrictive health care policies and processes, and the criminalization of people who use drugs. Through the lens of spiritual pain and collective ethics, the findings explicate how workers come to accept, consent, and resist ethical tensions present in their practice of crisis work and create a discussion for the implications of spiritual pain on workplace sustainability. In doing so, the scholarship of workplace ethics, harm reduction, and street outreach work has been bridged.

Keywords: Collective Ethics
Harm Reduction
Organizational relations
Outreach work
Spiritual Pain
Advisor: Sawchuk, Peter
Mirchandani , Kiran
Investigating the Role of Adipocyte YAP in Glucose Homeostasis and Adipose Tissue Fibrosis

Adipose tissue is a dynamic metabolic organ that is essential for the regulation of whole-body glucose homeostasis. Adipose tissue hypertrophy with obesity is positively associated with glucose intolerance and insulin resistance underlying type 2 diabetes. Yes-associated protein 1 (YAP) is a transcription cofactor important in the Hippo signaling pathway. However, the role of YAP in adipose tissue and glucose homeostasis is unknown. We found that YAP protein levels increase in adipose tissue with weight gain and insulin resistance. On a high-fat diet (HFD), adipocyte-specific YAP knockout mice show improved glucose tolerance compared to controls. Additionally, loss of adipocyte YAP protects against obesity-induced adipose tissue fibrosis. Together, these data indicate that YAP increases in adipose tissue with weight gain and disruption of YAP in adipocytes improves glucose tolerance and decreases the development of fibrosis; suggesting that adipocyte YAP plays an important role in modulating glucose homeostasis under metabolic stress conditions.

Keywords: Adipose tissue
Fibrosis
Glucose metabolism
Insulin sensitivity
Obesity
YAP
Advisor: Luk, Cynthia T
Construction Techniques for Lowering Embodied GHGs: A Review of Prefabrication and 3D Printed Concrete Mix Designs

With ongoing global urbanization, the construction industry has been steering towards adopting automated construction techniques to enhance efficiency and quality in production with the expectation of lowering greenhouse emissions (GHGs). However, there is a limited understanding of the impacts of using these techniques on GHGs. This thesis investigates two such techniques, prefabrication and 3D printing. It assesses the embodied GHGs of prefabricated buildings and 3D printed concrete (3DPC) mixes and compares them with that of conventional counterparts. A meta-analysis of published life cycle assessment results from prefabricated buildings and a detailed analysis of published 3DPC mixes are undertaken in this research. The findings suggest more similarity in terms of embodied GHGs between prefabricated and conventional buildings than widely reported. Results also show that 3DPC mixes usually have higher emissions compared to cast-in-place concrete due to having higher cement contents, though they also have lower emissions per unit of strength.

Keywords: 3D printing
buildings
Greenhouse Gas emissions
life cycle assessment
prefabrication
uncertainty assessment
Advisor: Saxe, Shoshanna
Panesar, Daman
The Psychological Consequences of Social Media Uses

The psychological consequences of social media use have been controversial amongresearchers, partly due to the field’s reliance on global measures and cross-sectional methods. To address that, we ran two studies. In study 1, we develop a scale to measure the different functions of social media use. We ran a factor analysis and ended up with five factors for social media use. The scale was related to personality in predictable ways. In study 2, we used experience sampling to analyze the psychological consequences of Twitter use over time. We found that Twitter use was negatively related to well-being and that most of the variance was within-subjects. With the scale developed in study 1, we found that passive Twitter use was related to decreases in well-being, but active Twitter use was not. Increases in affective polarization were predicted by Twitter use, but the results were not robust.

Keywords: Online communities
Polarization
Social Media
Well-being
Advisor: Inzlicht, Michael
A City in Crisis: Tenant Displacement and the Fight for Housing During COVID-19 in Toronto

In March 2020, the novel coronavirus triggered a state of emergency around the world and in the city of Toronto, provoking the exacerbation and collision of multiple crises, one of them being the transnational crisis of housing. This thesis investigates the conflict between landlords and tenants in Toronto in the time of COVID-19 as a struggle over and against “accumulation by dispossession." From March 2020 onwards, thousands of racialized working-class tenants who lost income due to COVID-19 have fought to stay housed while landlords, particularly ‘financialized landlords’ who see housing as a commodity — a pure financial asset — have been set on evicting people who fell behind on rent. I explore how this moment of crisis has led to the dispossession and displacement of working-class, primarily racialized people, while also opening possibilities for insurgent practices, producing new spatialities and subjectivities as people fight collectively for their right to stay housed.

Advisor: Cowen, Deborah
Investigating the role of the RNA-binding protein CFIM-1 in the germline of Caenorhabditis elegans

The gene cfim-1 encodes a subunit of the heterotetrameric CFIm complex, which is part of the broader array of core cleavage and polyadenylation (CPA) factors responsible for maturation of pre-mRNAs. In this work, I uncover a novel function for cfim-1 in the germline of Caenorhabditis elegans. Ablation of cfim-1 results in a temperature-sensitive reduction in fecundity with associated morphological changes to the organization of germ cell nuclei. Further analyses imply that the CFIm complex might inhibit recruitment of other factors required for CPA events at 3′ UTRs in a site-selective manner, suggesting a novel regulatory mechanism. In concert, these results highlight how fine-tuning of regulating cleavage and polyadenylation events is crucial in post-embryonic development.

Keywords: Alternative polyadenylation
Caenorhabditis elegans
Developmental biology
Germline
Post-transcriptional gene regulation
Transcriptomics
Advisor: Derry, W. Brent
Characterization and Cognitive Rehabilitation Research in Progressive Multiple Sclerosis (MS)

The purpose of this thesis was two-fold: Study 1 aimed to extend known brain-behaviour relationships to the progressive multiple sclerosis (MS) population, specifically lateralization and regiospecificity with regard to hippocampus-dependent memory, and Study 2 aimed to quantitatively and qualitatively evaluate the feasibility and preliminary efficacy of a novel, online allocentric spatial navigation intervention for staving off memory decline in people with progressive MS. As expected, Study 1 found a significant positive correlation between a behavioural proxy for pattern separation and CA3 (r=0.794 p=0.003) and dentate gyrus (r=0.611 p=0.030). No compelling evidence of lateralization, nor subregion specificity for pattern completion was found (all ps > .05). Study 2 showed that the spatial navigation intervention is feasible, though with limited benefits generalizable to everyday life, warranting further investigation in a larger-scale RCT. Key limitations, implications and contributions to a growing field of research on memory impairment and cognitive rehabilitation strategies for progressive MS are discussed.

Keywords: Hippocampus
Memory
Multiple Sclerosis
Neurodegeneration
Rehabilitation
Telerehabilitation
Advisor: Green, Robin RG
An Electrochemical Study of Wood Biochar Monolith as Electrode in Electrical Double Layer Capacitor

The core reason for global climate change is greenhouse gas emissions from fossil fuel combustion. Among many efforts devoted to reducing the dependence on fossil fuels, a particular focus has been developing low-cost and high-performance energy storage devices. The electrical double-layer capacitor (EDLC) is deemed a candidate due to its fast-charging capability and long-cycling life. With sugar maple as the precursor, this study investigates the behavior of EDLC with thick (up to 3 mm) wood biochar monolith (WBM) electrodes, addressing three topics - 1. the effect of electrode thickness on the performance of WBM-EDLC; 2. the unideal rate capability; 3. the origin of discharge curvature in galvanic cycling (GC). Results revealed that the electrode capacitance increased with the decrease in electrode thickness. Furthermore, the rate capability depends strongly on the electronic resistance of WBM-EDLC. Finally, a bus-passenger model was proposed to illustrate the reasons for GC discharge curvature.

Advisor: Jia, Charles Q
Prehabilitation Prior to Surgery: A Scoping Review and Pilot Quality Improvement Project

Frailty and lack of physical fitness are risk factors for poor perioperative outcomes in vascular surgery patients and other surgical populations. Prehabilitation is a multimodal approach to improving patient fitness prior to surgery to promote better coping with the stressors of surgery. We conducted a scoping review to explore the current scope of literature regarding the effect of prehabilitation in surgical populations and to identify gaps in knowledge. We then conducted a pilot quality improvement project to improve the rate of referrals and attendance for prehabilitation prior to vascular surgery. Our review showed that there is a high degree of heterogeneity in the literature related to the effect of prehabilitation on perioperative outcomes and that future work is needed to identify the composition of an optimal prehabilitation program. Although less than our target value, the rate of referrals increased by over 30% from baseline and prehabilitation was well-received by patients.

Keywords: Perioperative outcomes
Prehabilitation
Preoperative rehabilitation
Quality improvement
Surgery
Vascular surgery
Advisor: Kayssi, Ahmed
Forbes , Thomas L
Towards Assembly of a Multi-layered Cardiac Ventricle In Vitro using Microfabricated Elastomers

Despite current efforts in organ-on-chip engineering to construct miniature cardiac models, they often lack many aspects of 3D physiology of the whole heart. This motivates the development of bioartificial left ventricle models that enable mimicking the myofiber orientation of the native ventricle. We describe here an approach relying on microfabricated elastomers that enables hierarchical assembly of 2D aligned cell sheets into a functional conical left ventricle. The width of the micro-grooves was optimized to direct majority of cells towards the grove direction. The scaffold was wrapped around a central mandrel to obtain a conical-shaped left ventricle model comparable in size to a G19 human left ventricle. Cardiomyocytes within the 3D left ventricle constructs showed a high viability in all layers after 7 days of perfusion cultivation around a hollow mandrel. This model was responding to electrical stimulation by synchronous contractions and calcium transients.

Keywords: cardiomyocyte
cardiovascular disease
engineered ventricle
left ventricle
microfabrication
tissue engineering
Advisor: Radisic, Milica M
Enhancing Physical Activity Discussions of Oncologists for People Living with and Beyond Cancer: Implementing a Webinar Training Module

Oncologists hold a unique position to facilitating physical activity (PA) behaviour change in cancer survivors as they are highly trusted. Despite improved PA participation following recommendations by oncologists, many oncologists do not regularly discuss PA with survivors. Oncologists experience low knowledge and confidence with PA discussions, thus there is a need for formal training, targeting these outcomes, to facilitate PA discussions. The purpose of this study was to assess the feasibility of a theory-based webinar for enhancing oncologists’ PA discussion practices. Oncologists and oncology residents/fellows (N=13) attended a single 35-minute or 60-minute webinar. Outcomes were assessed pre- and post- webinar. Results demonstrated the feasibility of both a 35-minute and 60-minute webinar for oncologists and oncology residents/fellows. However, there were advantages unique to the 60-minute group, with the inclusion of discussion activities, that further enhanced the webinar experience. Future interventions should target changes in PA discussion practices with formal training.

Keywords: Cancer
Clinical practices
Physical activity promotion
Advisor: Trinh, Linda
Assessing Surgical Teamwork Skills and their Relationship to Adverse Events Using OR Black Box ®

Surgical teamwork deficiencies are associated with poor clinical outcomes, but the separate influence of individual multidisciplinary team members remains unclear. This thesis aimed to identify the teamwork skills demonstrated by surgical team members and determine if they varied during intraoperative adverse events (IAEs). Seventy laparoscopic procedures were captured using OR Black Box®. Using framework analysis, videos were coded for ‘present’ (i.e., outwardly observed) and ‘absent’ (i.e., expected but not observed) teamwork skills. Trained surgeons identified IAEs. Across four roles (nurses, anesthesiologists, surgeons, and trainees) 3539 skills were observed. While coordination was the skill most present across all roles, aspects of coordination (e.g., check-backs) were often not present when expected. During the 41 IAEs, (versus no IAE), nurses, surgeons and trainees expressed significantly more backup behaviour, conflict management and psychological safety, respectively. Understanding the separate contributions of surgical roles on intraoperative performance provides needed detail to inform targeted interventions.

Keywords: black box
healthcare
operating room
surgery
teamwork
teamwork skills
Advisor: Trbovich, Patricia