VictorJuiz/thesis huggingface dataset:
The Impact of Disease Progression on Health-related Quality of Life Outcomes in Patients with Oligo-metastatic Disease post Stereotactic Body Radiotherapy
Keywords: HRQOL
Oligo-Metastatic
Radiotherapy
SBRT

AbstractIntroduction There is a paucity of published health-related quality of life (HRQOL) outcomes in patients receiving stereotactic body radiotherapy (SBRT) as a treatment option for oligo-metastatic disease (OMD). Methods 107 OMD patients who received SBRT in a phase II single arm research ethics board approved study were analyzed. The study hypothesized that a different HRQOL pattern of change from baseline exists in patients with disease progression by 12-months compared to those without progression by 12-months. Results A statistically significant (SS) decline in the mean Global Health QOL score (73 (SD 21.8) to 67.2 (SD 27.1), p=0.04) of the entire population at the 12-month follow-up from baseline was found, with no SS difference in the mean GHQOL change score between patients who progressed and did not progress (-0.8 vs -8.8, p=0.07). Conclusion Patients who progress by 12-months do not have a SS difference in mean GHQOL change score compared to non-progressors.
Intracellular Interactions of the Hedgehog-signalling Pathway Receptor, Patched-1
Keywords: Hedgehog-Signalling
Mass spec
Patched-1
Primary Cilia
Smoothened

The Hedgehog (Hh)-signalling pathway is an evolutionarily-conserved signalling cascade that upon dysregulation causes lethal defects and is implicated in various neoplasms. Organized in the primary cilia, the principal receptor for the Hh-pathway, Patched-1, in the absence of Hh-ligand indirectly inhibits the activities of a seven-pass transmembrane protein, Smoothened, subsequently altering the transcriptional effectors, the Glioma-associated homolog Proteins. The mechanisms that control the subcellular translocation of Ptch1 and Smo into the primary cilia is not well understood. To elucidate this mechanism, we developed and characterized a fusion mutant Ptch1 protein modified with a biotin-ligase BirA, that constitutively localizes to primary cilia and represses Hh-signalling. Using proximity-dependent biotinylation and MS, we identified approximately 200 ciliary factors related to cilium assembly, trafficking, regulation, and ciliopathies. Investigating the interactions of Ptch1 in the primary cilia provides an understanding of the regulatory role of the cilium on Hh-signalling, while helping to develop targeted gene therapy.
Investigating Adenosine-to-Inosine RNA Editing in Rett Syndrome Neurons
Keywords: A-to-I editing
MECP2
Neurodevelopmemt
Rett Syndrome
RNA editing
RNA-seq

Rett syndrome (RTT) is a neurodevelopmental disorder (NDD) caused by mutations in the methyl-CpG binding protein 2 (MECP2) gene. Loss of MECP2 impacts transcription, translation, and post-transcriptional mechanisms governing these processes. Adenosine-to-inosine (A-to-I) RNA editing by ADAR enzymes is one such post-transcriptional process altered in other NDDs, yet no current literature examines editing in RTT. Using RTT patient induced pluripotent stem cell (iPSC) derived neuronal RNA-seq datasets, I address this gap and show increased global and novel editing in RTT that is not recapitulated in adult Mecp2 KO mice. Human TRAP-seq editing analysis show editing sites overlapping RNA-binding protein (RBP) motifs and microRNA binding sites in the 3’UTR along with a depletion of ribosomal engagement in RTT. Underlying these changes is a trend towards increased cytoplasmic localization of the ADAR1 p110 isoform. Overall, this works provides novel insight into A-to-I RNA editing in RTT patients.
Hepatic PKC-δ and p38? MAPK Mediate Free Fatty Acid-induced Liver Fat Accumulation and Triglyceride Secretion
Keywords: free fatty acids
hepatosteatosis
NAFLD
obesity
p38
PKC

Elevated plasma free fatty acids (FFA) have been implicated in Non-alcoholic Fatty Liver Disease (NAFLD). While increased PKC-δ activity has been observed in FFA-induced insulin resistance, and its activation of p38? documented in hepatocytes treated with FFA, its role and mechanism in FFA-induced hepatic lipid metabolic dysregulation has not been studied in vivo. 12-14 weeks old liver-specific PKC-δ knockout (PKC-δKO) and p38? MAPK knockout (p38?KO) mice were infused intravenously with an oleate and palmitate mixture (2:1) for 48 hours. To confirm the mechanism of PKC-δ action, PKC-δ was overexpressed in WT and p38?KO mice. Both PKC-δKO and p38?KO mice were protected from FFA-induced hepatosteatosis and increased triglyceride secretion. Furthermore, we showed that unexpectedly, PKC-δ might not mediate FFA-induced hepatosteatosis via liver-specific p38? MAPK. These findings suggest that both PKC-δ and p38? inhibitors could be effective in treating NAFLD and mitigating the metabolic effects of elevated FFA observed in obese humans.
An Analysis of Anti-Asian Stereotypes and Racist "Tweets" Linked to the COVID-19 Pandemic
Keywords: Anti-Asian hate
COVID-19 pandemic
Social media
Twitter

The COVID-19 pandemic and the popularity of social media platforms have combined to increase expressions of stigma, discrimination, and racism against East Asian communities. The purpose of this study is to develop a better understanding of pandemic-related anti-Asian sentiment found on social media platforms. To achieve this goal, a total of 4,000 tweets were randomly selected from over 600 million tweets to analyze for emergent themes. Results reveal that there are five themes: blaming and assigning responsibility, reactivated historical stereotypes, oppressive government, political, and unspecified direct insult. One supplementary theme is identified to capture tweets with potentially stigmatizing content. Theoretical and practical implications are discussed.
A Segmented Gate Driver Design for SiC Power MOSFETs with Optimized Driving Pattern
Keywords: Automatic optimization
Ringing suppression
Segmented gate driver

An external gate resistance (RG) is often employed to limit the charging speed of the gate capacitance in power transistors to avoid unwanted ringing oscillation. Currently, one solution is to use segmented gate drivers during switching to dynamically adjust RG can minimize ringing while maintaining the fast-switching speed of the transistor. The timing for the dynamic RG pattern is critical to the device performance. Traditionally, this pattern is determined via a time-consuming trial-and-error process. This thesis proposes a method to automatically determine the timing intervals by monitoring the gate signal via a sensor to detect change in the slope of a particular waveform. Experimentally, an RG profile between 2.5 and 10 Ω can keep the gate undershoot under 1 V for a 20-0 V transition for a SiC power MOSFET (GR40MT33N). The ringing is suppressed to less than 5% of the applied gate voltage while maintaining a switching speed of 194 ns.
Oriko: A Simulator for Energy Harvesting Systems and Intermittent Computing
Keywords: Energy Harvesting
Microcontroller
Simulator
Solar

The Internet of Things (IoT) is a fast-expanding class of computing devices that have applications everywhere from health monitors to satellites. However, many IoT devices cannot rely on conventional methods of powering the device due to their generally small form-factor and need to operate wirelessly. Thus a new class of devices emerges, capable of harvesting energy from its environment instead of relying on wall power or large, heavy batteries.However, environmental conditions are unpredictable and often result in frequent power losses. Energy harvesting systems require special software, hardware, or both, to recover from unexpected shutdowns while maintaining program progress and correctness. This work introduces Oriko, a simulator that helps developers design systems to overcome the challenges of working with energy harvesting systems and showcases how to design for application specific optimization targets.
The Effects of Sodium-Glucose Co-transporter 2 Inhibition on Plasma and Urine Ketones in Type 1 Diabetes
Keywords: empagliflozin
ketone
SGLT2
type 1 diabetes

Background: Adjunctive-to-insulin SGLT2 inhibition (SGLT2i) in type 1 diabetes (T1D) has meaningful metabolic benefits but can increase risk of ketoacidosis. Knowledge gaps include understanding ketone metabolism with and without SGLT2i treatment in T1D, and whether ketoacidosis risk in females is physiological or behavioral.Methods: Metabolomic analysis of plasma and urine beta-hydroxybutyrate and acetoacetate from stored baseline and 8-week eu- and mild hyper-glycemic samples in the 40-person single-arm Adjunctive-To-Insulin Renal MechAnistic (ATIRMA) trial of empagliflozin. Results: A significantly greater production of ketones even during mild hyperglycemia compared to euglycemia was observed, but this was compensated by increased urinary excretion leading to similar plasma concentrations. However, SGLT2i attenuated this increased excretion, resulting in higher plasma concentrations, particularly in females. Conclusions: Even mild hyperglycemia is associated with greater ketone production, compensated by urinary excretion. SGLT2i further exaggerates excess production and impaired excretion especially in females, indicating physiological rather than behavioral risk for ketoacidosis.
Abundance Estimates for the Last Remaining Population of Blue Racer (Coluber constrictor foxii) in Canada
Keywords: Blue Racer
Conservation
Endangered Species
Mark-recapture
Population Estimate
Robust Design

Estimating the size of endangered populations is a critical component for species-specific conservation management. My study used capture-mark-recapture analyses to produce population size estimates for the endangered population of Blue Racer (Coluber constrictor foxii) in Canada. Over two years, racers were captured and implanted with passive integrated transponders on Pelee Island on 15 sampling occasions. The robust design was used to produce estimates of the current population's abundance, survival, and capture probabilities. I estimated racer abundance to be 122 (95% CI = 58-256) individuals at its lowest and 182 (95% CI = 118-281) individuals at its highest. Further analyses of historical and current data using POPAN and Peterson models suggested a potentially declining trend in abundance over the last twenty years. As this population continuously faces the threats of habitat loss and anthropogenic activities, I recommend that this Blue Racer population receive continued monitoring and conservation efforts.
Role of the mTOR Pathway and Autophagy in Mediating PARP Inhibitor Sensitivity in Small Cell Lung Cancer
Keywords: autophagy
metabolism
mTOR
NAD
PARP
small cell lung cancer

Small cell lung cancer (SCLC) is an aggressive form of lung cancer with a dismal 5-year survival rate of 7%. Despite initial response rates (70-80%) to DNA damaging agents, patient relapse accompanied with treatment resistance is inevitable. Poly (ADP)-ribose inhibitors (PARPi) are a novel therapy that has been evaluated for SCLC treatment and are in clinical trials. There is increasing interest in identifying targetable factors involved in PARPi sensitization for combinatorial therapeutic strategies. This study shows that the mTOR pathway mediates PARPi sensitivity in SCLC cells through CRISPR genetic screens. We hypothesized that the constitutive activation of mTORC1 suppresses pro-survival autophagy. We used functional genetic validation with shRNAs to knock down the TSC1/2 complex and observed significant sensitization of SCLC cells to PARPi. Our data support that pharmacologically inhibiting autophagy is synergistic with PARPi in SCLC cells, creating a novel avenue for developing combination therapies to improve overall survival for SCLC patients.
Teachers' Peacebuilding and Holistic Pedagogies in Secondary Alternative "Behavioural" Classrooms in Ontario
Keywords: at-risk
behavioural students
conflict resolution
dialogic pedagogy
holistic education
peacebuilding

In Ontario, some “behavioural” students (often members of marginalized groups) are placed in Educational and Community Partnership Program classes. ECPP’s intent is to transition students back into mainstream classrooms after meeting their needs for special care or rehabilitation. One programming directive is that ECPP students be taught social skills. Peacebuilding pedagogies are promising avenues through which teachers can do so, while building community and restoring students’ trust in the school system. Through literature review, interviews with four ECPP teachers, and analysis of policy documents, this thesis explores two questions: 1) What do purposively selected teachers of secondary “behavioural” alternative students know and do about teaching conflict resolution and peacebuilding skills (what does this mean to them, and how are they incorporating relevant pedagogies into their classrooms)? 2) What has helped and hindered these teachers’ efforts? The analysis of ECPP Program policy and practice concludes with recommendations for improving these environments.
Examining the Effectiveness of the CARD (Comfort, Ask, Relax, Distract) System on Improving Student Experiences during School-based Vaccination Clinics: Results of a Randomized Cluster Trial
Keywords: Fear
Needles
Pain
Pediatrics
Vaccines

Background: Needle fear and pain can be exacerbated in school-based vaccination clinics when students are unprepared and fear cues are not systematically minimized. The CARD system (Comfort, Ask, Relax, Distract) incorporates evidence-based strategies to mitigate fear and pain. We examined CARD’s effectiveness in reducing student fear, pain and related symptoms during school vaccinations. Methods: Randomized cluster trial in 40 Wellington-Dufferin-Guelph schools during fall 2019. Schools were randomly assigned (1:1) to CARD or control. Students reported fear, pain and dizziness scores. Nurses reported coping tools used and post-vaccination reactions. Results: 1424 of 1919 students across participating schools were vaccinated at school. Fear and pain were lower in CARD vs. control: OR 0.65 (95% CI 0.47-0.90) and OR 0.62 (95% CI 0.50-0.77), respectively. No CARD students fainted compared to 0.8% control (p=0.02). Dizziness or post-vaccination reactions did not differ. Coping tools were used more frequently in CARD schools. Discussion: CARD reduced stress-related symptoms during school-based vaccinations.
Anticoagulant Use in Older Patients Receiving Home Palliative Care: A Retrospective Cohort Study
Keywords: anticoagulants
deprescriptions
palliative care
terminal care

Objective: To describe the prevalence of anticoagulant use and identify predictive factors for anticoagulant discontinuation among home palliative care recipients in Ontario.Methodology: Linked administrative population-based healthcare databases were used to identify and study home palliative care recipients ≥66 years old in Ontario from 2010-2019. The prevalence of anticoagulant use was calculated. Multilevel models were used to study patient and provider factors associated with early anticoagulant discontinuation following initial home palliative care consultation. Results: 98,089 older adults initiated home palliative care from 2010-2018, among whom 15.5% were taking anticoagulants. By multilevel logistic regression, few patient or physician characteristics—and neither comorbidity nor indications for therapeutic anticoagulation—were associated with discontinuation. Mean discontinuation rates by physician quintile ranged from 7-49%. Conclusion: Among home palliative care recipients, anticoagulant use is common and discontinuation may relate largely to physician preference. Further study on the risks and benefits of anticoagulants in this population is warranted.
Identity Navigation and Understanding in Demographic Surveys
Keywords: Demographic Survey Design
Disability
Equity
Diversity
Inclusion
Access
First-generation
Identity
Race

This study is concerned with how undergraduate students in disciplines related to Science, Technology, Engineering, and Math (STEM) select responses when answering demographic surveys, especially in cases where they are unable to map their identity onto provided responses. Fifteen undergraduate STEM students at various stages of their degrees were interviewed, and three types of demographic survey responses were identified: (1) alignment, (2) misreporting, and (3) misalignment. Students’ responses to questions about race and ethnicity, racialization/person of colour identification, first-generation/first-in-the-family, and disability were especially likely to be influenced by tensions between their self-determined identity and an identity that is placed onto them by others. Based on the findings, an adaptation of Tourangeau et al.’s (2000) Components of Survey Response model is proposed. The findings have implications for furthering the understanding of the survey response process, how to ask sensitive questions, and limitations of current demographic survey questions.
Investigating the Effects of Near-Streamflow Regions on Temperate Region Lake Ice
Keywords: Hydrology
Ice
Ice safety
Lakes
Outflows
Streamflow

This study uses a combination of modeling and fieldwork to investigate the relationship between stream outflows and lake ice in Central Ontario, by focusing on Clear and MacDonald Lakes in Haliburton Forest and Wild Life Reserve. A network of waterproof temperature sensors (HOBO pendants and tidbits) were submerged 1 – 4 m below the water level, and Reconyx outdoor digital cameras were installed around the outflows at both lakes. Results indicate thinner or no ice, and an earlier spring ice-off closer to the outflow regions. Incorporating an additional heat flux in the lake ice model to represent the near-streamflow heat sources, 9.5 Wm-2 for 2017 – 2018, and 20.5 Wm-2 for the 2018 – 2019, led to more accurate simulations of the lake outflow regions. Overall, results show that the near-streamflow region ice is unsafe for recreation most of the winter season, highlighting the need for accurate ice information and awareness for users.
Fazli: Identity and Wisdom in a Pakistani Adult with Autism
Keywords: ASD
Autism
Identity
Pakisan
Quality of Life
Wisdom

This study explored life of Fazli, a highly successful adult with autism in Pakistan, and the role of wisdom and identity in his life, using a mixed-method case study analysis. Fazli is an assistant professor at a renowned university in Pakistan and is an international and regional self-advocate for autism since 2006. A pragmatic, pluralist, method that included thematic, biographical and Interpretative Phenomenological Analysis, and statistical analyses were used analyzing Fazli’s interviews, audio diaries and answers to self-report questionnaires about wisdom, identity and quality of life. As per McAdams’ narrative identity theory, his life narrative exhibited high levels of personal agency. Although Fazli exhibited many traits of wisdom including high cognitive abilities, reflectivity, mastery, affection and openness, and had better life outcomes compared to other autistic individuals, nevertheless, his quality of life is low. Stigma, lack of recognition and inequitable monetary benefits all contribute to his poor quality of life.
Accurate Hotspots Detection with Deep Convolutional Neural Network and Generative Adversarial Network Based Data Augmentation
Keywords: Deep Learning
Generative Adversarial Network
Hotspot Detection

The increasing demand for computational power is pushing the photolithography technology to its physical limit. As one of its crucial technical bottlenecks, the design issue of layout hotspots requires innovative solutions to minimize the necessity of conducting expensive lithography simulation experiments but remain extremely accurate. In addition to the sustained development of conventional hotspots detection, the recent implementation of convolutional neural networks (CNN) has shown high effectiveness in flexible pattern recognitions. However, limited by the industrial data availability, technical issues such as imbalanced learning and rare/new hotspot detection need to be navigated. In this thesis, we introduced a deep learning hotspots detection method with an improved CNN classifier and enhanced the learning effectiveness by augmenting the dataset with the generative adversarial network (GAN) based synthetic pattern generation. Experiment results show competitive performance compared to the existing works, but further development is required to connect with the current industrial processes.
A 10-year Review of Intraoral Salivary Gland Tumor Diagnoses: Diagnostic Challenges and Inter-observer Agreement
Keywords: intraoral minor salivary gland tumors
minor salivary gland tumors
oral medicine
oral pathology
salivary gland tumors

Background: Intraoral minor salivary gland tumors (IMSGT) are uncommon and present diagnostic challenges that affect treatment. Objectives: Determine clinical and pathological features of IMSGT associated with diagnostic challenges. Methods: We conducted a retrospective analysis of 248 IMSGT in an outpatient oral pathology service, (2010-2019). Cases were stratified into definitive, favored, or indeterminate diagnoses. We evaluated inter-observer agreement and concordance of biopsy diagnosis with surgical resection diagnosis. Results: There were 191 definitive diagnosis, 38 favored diagnosis, and 19 indeterminate. Younger patient, smaller tumor, and larger biopsy size were significantly associated with definitive diagnosis. Overall inter-observer agreement for 68 representative cases was moderate (Fleiss’ Kappa 0.575). Sixty-five biopsy cases matched with resection specimens showed good concordance (Cramer’s V test 0.76). Conclusion: Diagnostic challenges in IMSGT were infrequent and tended to involve tumors with overlapping histologic patterns. Younger patient age, smaller tumor size and larger biopsy were associated with a definitive diagnosis.
IOS: Inter-operator Scheduler for CNN Acceleration
Keywords: Inference
Inter-Operator
Latency
Neural Network
Optimization
Scheduler

To accelerate CNN inference, existing deep learning frameworks focus on optimizing intra-operator parallelization. However, a single operator can no longer fully utilize the available parallelism given the rapid advances in high-performance hardware, resulting in a large gap between the peak performance and the real performance. This performance gap is more severe under smaller batch sizes. In this work, we extensively study the parallelism between operators and propose Inter-Operator Scheduler (IOS) to automatically schedule multiple operators’ parallel execution through a novel dynamic programming algorithm. IOS consistently outperforms state-of-the-art libraries (e.g., TensorRT) by 1.1 to 1.5x on modern CNN benchmarks.
Injection of a Cell Lysate Derived from Wharton’s Jelly Perivascular Mesenchymal Stromal Cells for the Treatment of Inflammation in the Temporomandibular Joint
Keywords: Anti-Inflammatory
Arthritis
Mesenchymal
Rat-Model
Stem Cell
Temporomandibular Joint

The objective of this study was to investigate the anti-inflammatory effects of human neonatal mesenchymal stromal cells (MSCs) and their cell lysate (CL) derived from perivascular Wharton’s Jelly (WJ) in a rat model of carrageenan-induced inflammation of the temporomandibular joint (TMJ). Male Wistar rats were injected with carrageenan, 10% CL, 1% CL, 1% gamma-irradiated CL, or MSCs. Rats were sacrificed at 4, 48, and 72-hrs post-injection. Articular tissue and synovial aspirates were analyzed for myeloperoxidase (MPO) and tumor necrosis factor alpha (TNF-alpha) levels, and for leukocyte infiltration. 1% CL and MSC-treated TMJs demonstrated significantly lower concentrations of leukocytes 4-hrs post-Injection compared to controls. No significant differences in the concentrations of MPO and TNF-alpha were found between the treatment groups and controls. Overall, MSCs and the CL derived from perivascular WJ reduced leukocyte infiltration into the synovium, while moderating signs of TMJ inflammation histologically.