VictorJuiz/thesis huggingface dataset:
Analysis of Prognostic Germline Polymorphisms in Patients with Advanced Hepatocellular Carcinoma

Introduction: There is a need for more prognostic biomarkers to guide the treatment of advanced HCC. Methods: Our aim was to validate SNPs prognostic of outcome in advanced HCC from the literature, and to analyze exploratory SNPs chosen from evaluation of the HCC tumor immune microenvironment. Using a database of patients with HCC treated with sorafenib, blood samples were genotyped, clinical variables were retrospectively collected, and SNPs were analyzed for association with PFS and OS. Results: Literature review identified 7 SNPs in VEGF, eNOS, ANGPT2 and VEGFR2, however none were externally validated in our dataset. Of the 35 exploratory SNPs, the following were associated with PFS or OS: rs1024611, rs1800896, rs231775, and rs28362491. Conclusion: SNPs identified by literature review to be prognostic in sorafenib treated patients with advanced HCC were not validated in our dataset. Our findings suggest potentially important prognostic implications of SNPs in VEGFR2, CCL2, IL-10, CTLA-4 and NFKB1 that deserve further study.

Keywords: Hepatocellular carcinoma
SNP
Advisor: Liu, Geoffrey
Pharmacological Mechanisms of Transcranial Ultrasound for Human Motor Cortical Plasticity

Transcranial ultrasound stimulation (TUS) is a non-invasive brain stimulation technique, capable of immediate (“online”) inhibitory effects and prolonged (“offline”) excitatory effects on the human motor cortex. However, the in vivo mechanisms of action are unclear. By administering brain-active drugs with known mechanisms together with TUS, we aimed to determine the mechanisms of action of TUS. Nine healthy subjects participated in a within-subjects randomized, double-blind, cross-over study with five visits. At each visit, one of four study drugs (carbamazepine, nimodipine, lorazepam, dextromethorphan) or placebo was administered. Online inhibitory TUS effects on motor evoked potentials (MEPs) from transcranial magnetic stimulation were reduced following administration of lorazepam. Offline excitatory TUS effects on MEPs were reduced by all study drugs compared to placebo. The online inhibitory effect of TUS may involve GABAA receptors, but the effect may have been confounded by auditory activation. The finding from the offline study suggests that offline theta burst TUS inducessynaptic plasticity and is mediated by GABAA and NMDA receptors, and Ca2+/Na+ channels.

Advisor: Chen, Robert
Towards Optimal Steady State Control of Multi-terminal HVDC Systems

This thesis applies linear-convex optimal steady state (LC-OSS) control to a multi-terminal high voltage DC (MTDC) system connecting AC systems. LC-OSS control framework uses real-time feedback to regulate the output of an LTI system to the solution of a constrained convex optimization problem. We first show that the LC-OSS control framework recovers some of the existing MTDC controllers in the literature. Then, we propose a dynamic controller which drives the AC systems to collectively respond to power load variation while minimizing DC losses and maintaining DC line currents within acceptable limits. Finally, we evaluate the controller's performance in simulation and verify that it is able to drive an MTDC test system to a desired optimal operating point.

Advisor: Taylor, Josh
Simpson-Porco, John
The Association Between Kindergarten Teachers’ Facilitation of Playful and Didactic Learning Activities and Their Responsive Interactions with Students

Research findings show the invaluable role of responsive student-educator interactions in promoting high-quality early childhood education and fostering positive student outcomes. Despite their importance, responsive interactions occur variably in early childhood education classrooms, in part because they are impacted by numerous classroom variables including the curriculum. In recent years, many early childhood education programs have implemented play-based learning curriculums. To investigate the association between educators’ responsive interactions with students and their facilitation of different levels of developmentally appropriate learning activities, the present study examined 5-minute videotaped interactions between 42 kindergarten teachers and their students, collectively spanning teachers’ facilitation of free play, guided play, teacher-directed play, and didactic activities for learning. Videos were coded for quality of responsive interactions using the RIFL-Ed. Results indicated that the type of playful or didactic learning activity being facilitated may influence the quality of responsive student-educator interactions. Implications for researchers, policymakers, and educators are considered.

Keywords: didactic instruction
kindergarten
play-based learning
process quality
responsive interactions
responsivity
Advisor: Pyle, Angela
The Role of Exosomes in Spreading Pathology in Synucleinopathies

Parkinson’s disease, dementia with Lewy bodies and multiple system atrophy are neurodegenerative diseases classified as synucleinopathies due to the accumulation of misfolded and aggregated α-synuclein (α-syn). This misfolded α-syn is implicated in templating the misfolding of additional α-syn in a prion-like manner, contributing to the spread of synuclein pathology between brain regions. A purported mechanism of intercellular α-syn transmission is through small extracellular vesicles called exosomes which are comprised of a lipid bilayer enclosing proteins and nucleic acids. Here, we isolated and characterized exosomes from the brains of synucleinopathy-affected mice and intracerebrally inoculated healthy mice. We demonstrated that exosomes can induce progressive neurological dysfunction which correlates with the accumulation of insoluble and protease resistant α-syn inclusions. Furthermore, we measured peripheral blood α-syn to investigate its potential utility as a biomarker for aberrant α-syn. This work suggests that exosomes can transport α-syn across brain regions contributing to the progression of synucleinopathies.

Keywords: Neurodegeneration
Parkinson's disease
Synucleinopathy
Advisor: Tandon, Anurag
Impact of a Digital Counselling Program with an Integrated Social Support Network for Self-care on Mental Health in Chronic Kidney Disease and Chronic Heart Failure

ODYSSEE-vCHAT is a novel intervention combining digital counselling (ODYSSEE) with social network support (vCHAT) to increase self-care behaviours to improve patient prognosis and psychological well-being. The role of social support in digital self-care programs is understudied. The primary objective was to assess the impact of vCHAT engagement on mental health at 4 months using the Mental Component Summary (MCS) of the 36-Item Short-Form Survey. Secondary outcomes included the MCS subscales, the 9-Item Patient Health Questionnaire, the Revised 6-Item UCLA Loneliness Scale, and the ENRICHD Social Support Instrument. Greater engagement was associated with higher composite and Vitality and Role-Emotional MCS scores. Individuals with greater vCHAT usage were less likely to express depressive symptoms. This study demonstrated the therapeutic benefit of vCHAT on psychological well-being. It added to our understanding of digital health interventions aimed at optimizing patient health-related quality-of-life. These findings will support a large-scale randomized controlled trial.

Keywords: Chronic Heart Failure
Chronic Kidney Disease
Digital Health
Psychological Well-being
Quality of Life
Self-care Behaviours
Advisor: Nolan, Robert P
Temozolomide Chemoradiotherapy and Pneumocystis Pneumonia Prophylaxis

Background: Pneumocystis pneumonia (PCP) can occur in glioma patients receiving chemoradiotherapy. Health Canada recommends PCP prophylaxis during temozolomide chemoradiotherapy. Not all neuro-oncologists follow these recommendations. The research objective was to characterize the risk-versus-benefit balance of PCP prophylaxis during chemoradiotherapy. Methods: Using ICES data, the risk of PCP in temozolomide-treated glioma patients with or without antibiotics was evaluated. Secondary outcomes included mortality, hospitalizations, and myelosuppression. Results: Between 2005–2019 there were 3225 patients included in the cohort (648 received antibiotics). Eighteen patients developed PCP within 90 days of therapy. The propensity score–adjusted absolute risk reduction in PCP with antibiotics was 0.0035 (95% CI -0.0013–0.0083), number needed to treat:288. Neither overall survival nor hospitalization count differed between groups. The number needed to harm by causing grade 3/4 neutropenia was 39. Conclusion: In regions where PCP is rare, routine PCP prophylaxis should not be offered, since the harms may outweigh the benefits

Keywords: Glioma
ICES
Pneumocystis pneumonia
Temozolomide
Advisor: Chan, Kelvin KW
Skeleton-based Body Geometry Reconstruction from Sparse Image Sequences

In this thesis, we propose a point cloud fusion algorithm to reconstruct a 3D model of the human body from a sparse set of depth images. The challenges we address are threefold: (1) complex body geometry; (2) non-rigid motion; and (3) self-occlusions with little image overlap. We define an energy function with an internal skeleton model to track non-rigid body motion and a visual hull term to promote spatial consistency. Supplementary to our algorithm is a novel lightweight automatic measurement extraction method. To evaluate our fusion algorithm, we generate a synthetic dataset with controlled body motion. An ablation analysis on our synthetic dataset quantitatively demonstrates the effectiveness of skeleton tracking. Furthermore, we simulate joint estimation errors and demonstrate algorithm robustness to joint estimation. Comparisons are made with existing techniques of various complexity. Our algorithm uses fewer images while maintaining low reconstruction error, a crucial step towards accessible 3D scanning technology.

Keywords: Geometry processing
Image fusion
Motion estimation
Object tracking
Spatial computing
Surface reconstruction
Advisor: Kundur, Deepa
A New Method for Estimating Total Wing Area to Determine Flight Efficiency and Dispersal Ability in Birds

Dispersal is a fundamental process in evolution and ecology. Due to the predominant role of flight in bird movement, their flight morphology can be used to predict dispersal capabilities. Most predictors of flight efficiency require an estimate of the total wing area, but the existing methodologies for estimating wing areas are multi-stepped and prone to compounding error. Here, I validated a new method for estimating the total wing area that requires only two measurements from the folded wings of study skin specimens–wing length and secondary length–and an associated wingspan. I demonstrate that the new folded-wing method estimates total wing area with high precision across various species and wing shapes. With the folded-wing method, estimates of the total wing area can readily be obtained from thousands of specimens in ornithology collections to benefit studies of flight efficiency and dispersal in birds.

Keywords: aerodynamic efficiency
birds
folded-wing method
natal dispersal distance
spread-wing method
wing shape
Advisor: Claramunt, Santiago
YouTube for Museums: The Role of YouTube Content in Museum Education and Outreach

The production of original educational content by museums has a long history, and throughout it, these institutions have found reward in experimenting and adapting to new forms of technology. YouTube is the most recent stage in this history, and as with previous changes in distribution mediums, YouTube comes with its own infrastructure, features, and user culture that must be navigated to utilize the platform to best effect. Rather than directly transplanting approaches from legacy media like television and radio, YouTube should be approached on its own terms. Using the successful museum-based YouTube channel The Brain Scoop as a case study, this thesis undertakes a qualitative and quantitative analysis of the channel’s content and production approaches, and from these findings, a set of best practices are identified for institutions looking to produce their own content on the platform as an extension of their educational and outreach objectives.

Keywords: Education
Educational YouTube
Museum
Online
Social Media
YouTube
Advisor: Luka, MaryElizabeth
Cohen, Nicole S
Investigating The Role of Long Non-coding RNA MEG3 in Diabetic Tissue-Specific Angiogenic Responses

12.1% of Canada’s population is projected to be affected by type 2 diabetes by 2025. Diabetic patients suffer from micro- and macrovascular diseases that arise from aberrant angiogenesis, both deficient and excessive angiogenic vascular beds. LncRNA MEG3’s role in angiogenesis is conflicting in literature, the majority highlighting an antiangiogenic role, and has been investigated as a therapy in diabetic vascular diseases with excess angiogenesis exclusively. We investigated the role of MEG3 overexpression in a diabetic cell model with deficient angiogenesis and healthy cells. In vitro matrigel assays report impaired tubule formation with MEG3 overexpression in both cell types by disrupting Notch1 and VEGF signaling pathways. This study introduces new data to the potential mechanism of action of MEG3 and highlights the importance of direct-target delivery of MEG3 in therapeutic areas.

Advisor: Leong-Poi, Howard
When the Measure Affects the Outcome more than the Intervention: The Unexpected Effect of Object Differences on Alternate Uses Test (AUT) Scores

The alternate uses test (AUT) is a divergent thinking measure wherein participants are asked to produce creative uses for common objects. A study done during my undergraduate degree revealed a positive effect of conflict-processing on AUT scores. During my master’s degree, studies were conducted to expand on and replicate this effect, but were unsuccessful. Unexpectedly, there was an effect of AUT object on AUT scores, suggesting that a characteristic of the measure (i.e., the object chosen to produce uses for in the AUT) affected the outcome non-uniformly. This object effect is concerning for studies that rely on the AUT, as AUT objects are not chosen consistently across studies. Furthermore, many studies do not analyze object differences, which can be problematic if preventative measures are not taken. A study is proposed to address this concern by standardizing AUT object usage with objects that have non-significant differences in AUT scores.

Keywords: creativity
Advisor: Shu, Li
Enabling Formation Flying Microsatellite Missions through the Microspace Approach

The growth of the small-satellite industry has created numerous benefits for life on Earth. This growth has been aided by the development of spacecraft formation flying. The Space Flight Laboratory has become a leader in formation flight through the development of the DEFIANT platform. This thesis presents contributions made to two DEFIANT missions across three spacecraft development areas: thermal control, formation control, and spacecraft assembly. A thermal control system was designed to predict spacecraft orbital temperatures. Model validation was performed using thermal vacuum test and on orbit data. A maneuver-time-efficient formation control approach was developed to reduce the time spent maneuvering spacecraft to achieve formation requirements. The approach was compared to an existing fuel-optimal method used by the Laboratory. A candidate propulsion system for achieving formation requirements was tested, and validated in orbit. Finally, design and analysis was put into practice through the assembly of flight hardware.

Advisor: Zee, Robert E.
A Comparative Analysis of Orthognathic Surgical Stability between Fixed Appliances and Clear Aligner Orthodontic Therapy

The purpose of this study is to: (1) compare the incidence of skeletal relapse following Orthognathic Surgery between patients treated with conventional fixed appliances (CFA) versus clear aligner orthodontic therapy (CAT) and (2) to compare outcome measures of peri-operative morbidity and surgical performance including surgical blood loss, operative time and length of hospital stay between the two treatments groups. The primary objective was evaluated on lateral cephalograms obtained at two post-operative time periods to identify changes in skeletal position of the maxilla and mandible. The secondary objectives were investigated through a chart review. Statistical analysis with parametric methods did not reveal any statistically significant difference in skeletal relapse, peri-operative morbidity or surgical performance between patients treated with CFA or CAT. Furthermore, the overall degree of relapse was minimal and did not require re-operation. The study supports both CFA and CAT as viable treatment options in combined surgical-orthodontic therapy.

Keywords: Clear aligner
Dentistry
Fixed appliance
Invisalign
Orthodontic
Orthognathic Surgery
Advisor: Caminiti, Marco F
Probabilistic Object-level Change Detection for Mapping Semi-static Scenes

Maintaining an up-to-date map to reflect recent changes in the scene is essential for robot autonomy in warehouse environments where goods need to be transported around the facility. An accurate map is particularly important for repeated traversals by a robot operating in an environment over an extended period. Undetected changes may cause a deterioration in map quality, leading to poor localization, inefficient operations, and lost robots. Volumetric scene mapping representations, such as truncated signed distance functions (TSDFs), have quickly gained traction due to their real-time production of a dense and detailed map, though map updating in scenes that change over time remains a challenge. We introduce a novel probabilistic object state representation to track object pose changes in semi-static scenes. The representation jointly models a stationarity score and a TSDF change measure for each object. A Bayesian update rule that incorporates both geometric and semantic information is derived to achieve consistent online map maintenance. To extensively evaluate our approach alongside the state-of-the-art, we release a novel real-world dataset in a warehouse environment. We also evaluate on the public ToyCar dataset. Our method outperforms state-of-the-art methods on the reconstruction quality of semi-static environments. Next, the problem of robot localization in slowly changing environments is tackled, introducing a multi-hypothesis cost function to deal with scene ambiguity.

Advisor: Waslander, Steven
Exploration of the Phylogenetic Properties of the Na+ Leak Channel NALCN and its Accessory Subunits UNC-79, UNC-80, and FAM155A

The Na+ leak channel NALCN is a constitutively open channel that provides depolarizing offset currents that help establish the resting membrane potential of many excitable cell types, and is implicated numerous human diseases. Until recently, the ion-conducting properties of NALCN have remained enigmatic, for difficulties in expressing the functional channel in vitro. Indeed, successful in vitro expression of the human NALCN channel requires co-expression with its three accessory subunits, UNC-79, UNC-80, and Fam155a/Nlf-1. This thesis explores the core functional properties of the human NALCN channel. Additionally, it is shown that the homologous auxiliary subunits of NALCN from Trichoplax adhaerens can promote functional expression of the human NALCN channel in vitro, in lieu of the human subunits. Furthermore, voltage-gated calcium channel α2δ and β1b accessory subunits promote in vitro expression of the NALCN channel, which may a useful tool for enhancing expression of the NALCN channel protein for in vitro experimentation.

Keywords: Electrophysiology
Ion channel
NALCN
Sodium Leak Channel
Trichoplax Adhaerens
Advisor: Senatore, Adriano
Simulation-based Analysis of Points Systems in Accumulative and Independent Sports

The goal of a points system is to synthesize multiple individual performances to capture an athlete’s overall skill. However, a complicating feature of a points system is the loss of information that comes from collapsing the raw athlete performances (e.g., judges scores, run times, goals, etc.) into ranks prior to assigning points. Furthermore, there is evidence in existing points systems that show poorer performance when neglecting competition characteristics such as competition size, quality of athletes, and selective athlete participation. In this work, we develop an extensive simulation framework to model the processes of any multi-competitor sport with an accumulative points system. Using our framework, we propose a set of experiments to identify and quantify sources of error within a points system. Lastly, we apply our framework and suggest improvements to the existing points system in slopestyle snowboarding, governed by the Fédération Internationale de Ski (FIS).

Keywords: points systems
rating systems
simulation
sports
Advisor: Chan, Timothy C. Y.
Using Wearable Technology to Measure Response to Deep Brain Stimulation in Children with Dystonia

Introduction: Although dystonia is a common movement disorder in children, there are no objective means to quantify its severity. Aim: To evaluate actigraphy as a tool for the assessment of the motor and nonmotor manifestations of dystonia. Methods: Children with generalized dystonia and healthy controls were asked to wear the actigraphs for 14 consecutive days. Data on total sleep time (TST), physical activity patterns, and fractal regulation (FR) of the motor activity were extracted. Results: Eighteen children with dystonia and eleven healthy controls were included. The mean TST was comparable in both groups and was not correlated to Burke-Fahn-Marsden Dystonia Rating Scale-movement (BFMDRS-M). BFMDRS-M was positively correlated with time spent in sedentary activity. FR analysis in the dystonia group revealed more predictable motor fluctuations. No association was observed between the FR to BFMDRS. Conclusion: Actigraphy data are of limited utility as biomarkers of dystonia severity when benchmarked against currently available rating scales.

Advisor: Ibrahim, George GMI
Is Basal Forebrain Volume Loss Associated with Visual Hallucinations, Mild Cognitive Impairment, or Concomitant Symptomology in Advanced Parkinson’s Disease?

Visual hallucinations (VH) and mild cognitive impairment (MCI) are prevalent and often co-occur in Parkinson’s Disease (PD). Basal forebrain (BF) atrophy and difficulties with visuoperception and semantic fluency are associated with each symptom type separately however the association in people with comorbid symptoms is unknown. I conducted a chart review including MRI data in a group of advanced PD patients (n=296) with and without each VH and MCI. Two-way ANCOVAs were run on total and regional BF volumes using VH and MCI as independent variables, covarying dopaminergic medication. Cognitive profiles of MCI-VH versus MCI-noVH were also studied using Mann-Whitney U tests. Atrophy of the Ch4 BF region was associated with MCI-VH while Ch1-2 was associated with MCI regardless of VH status. People with both MCI and VH had poorer performance than individuals with MCI-noVH on object recognition tasks. Future research will examine other brain areas and confounds of other medications.

Keywords: basal forebrain
mild cognitive impairment
nucleus basalis of Meynert
Parkinson's disease
visual hallucinations
Advisor: Cohn, Melanie
Ruocco, Anthony C