VictorJuiz/thesis huggingface dataset:
Establishing a Major Depressive Disorder Patient to Neural Organoid Pipeline

Major Depressive Disorder (MDD) is a debilitating mood disorder and one of the leading causes of disability worldwide. Advancements in induced pluripotent stem cell (iPSC) technology offers the opportunity to study the complex genetic background of MDD patients in vitro. The aim of my project is to establish a pipeline for efficient reprogramming of iPSCs from MDD patients and consistent generation of neural organoids, a 3D model which recapitulates cellular and structural features of the human brain. We recruited a hospitalized cohort of MDD in-patients from St. Joseph’s Healthcare (McMaster, Hamilton, ON) and collected whole blood for reprogramming to iPSCs. Age, sex and demographically matched control iPSC lines were obtained. To generate iPSC-derived neural organoids, we developed an optimized protocol which includes dual SMAD inhibitor-guided neural induction, resulting in the proper development of neuroepithelial tissue and morphology through development. Through immunohistochemistry, neural organoids exhibit markers for neurons and astrocytes, and have rudimentary cortical cytoarchitecture. Profiling of neural proliferation in patient-derived and control neural organoids using Ki67 and BrdU co-immunostaining show no differences between groups. The work presented here lays the groundwork for vital future research in MDD involving disease phenotyping, drug discovery and personalized medicine.

Keywords: iPSC Reprogramming
iPSCs
Major Depressive Disorder
Neural Organoid
Organoids
Advisor: Singh, Karun K
The Dynamics of Ecology, Demography, Dispersal, Habitat Selection, and Life History in a Crayfish Cambarus bartonii Population in Ontario

A fundamental goal in ecology is to understand how organisms operate and organize in ecosystems. Yet, there is much to be gleaned about the underlying drivers of these ecological mechanisms. I used mark-recapture methodology to study a Cambarus bartonii population in Ontario. I examined ecology, demography, dispersal, habitat selection, their underlying drivers and temporal patterns, and their ecological implications for this population. I identified patterns encompassing capture frequency, size classes, length-weight relationships, life history, and population size estimates. I documented considerable crayfish dispersal within a short period of time, uncovered patterns relating dispersal and life-history traits, and habitat selection and its underlying processes, which helps our understanding of how organisms disperse and choose habitats. My research has implications for understanding population dynamics and resource selection in a changing world, given that crayfish are characterized as keystone species, and they are of particular concern as both invasive and endangered species globally.

Keywords: crayfish
dispersal
habitat selection
life history
population ecology
Advisor: Jackson, Donald
Pathogenesis of Fetal and Neonatal Alloimmune Thrombocytopenia: Role of Maternal Immune Response on Fetus Survival and Megakaryocytes

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a life-threatening disease whereby maternal antibodies target paternally-derived fetal platelet antigens, depleting platelets in fetuses/neonates. While the platelet precursors megakaryocytes share all the targeted antigens, whether/how megakaryocytes and platelet production are affected has not been investigated in FNAIT fetuses. Importantly, the incidence of miscarriage and fetus pathophysiology in anti-αIIb mediated FNAIT have not been fully elucidated. I hypothesized maternal antibodies decrease fetus megakaryocyte numbers and impair fetus survival in anti-αIIb mediated FNAIT. Using mouse models of FNAIT, I demonstrated that severe thrombocytopenia, bleeding diatheses, and fetus loss occurred, particularly at high titers of maternal anti-αIIb antibodies. Significantly decreased fetal liver to whole body weight ratios, accompanied with disrupted liver morphology, but no significant apoptosis/necrosis occurred in FNAIT fetuses. Megakaryocyte numbers were significantly decreased in FNAIT fetal liver. My findings indicate maternal anti-αΙIb antibodies diminish both platelet production and fetus survival in FNAIT.

Advisor: Ni, Heyu
Characterization of Myocardial Metabolism using a Novel Hybrid PET/MRI ProtocolCombining Fasting and Glucose Loading

Hybrid PET-MRI is a promising tool that can characterize both metabolic and structural information and has been used extensively in the context of myocardial infarction (MI). Novel therapies have focused on early myocardial regeneration in the acute to sub-acute phase of MI, when inflammation is present. To accurately characterize graft metabolism, myocardial glucose metabolism must be isolated from inflammatory activity. This thesis develops a framework that combines fasting and glucose loading fluorodeoxyglucose (FDG) PET protocols to image both viability and inflammation, and then evaluates the effect of pharmacological immunosuppression on inflammatory cell activity. Results show significant metabolic differences between fasting and glucose loading, and more significant changes when protocols are performed on separate days. Longitudinal characterization of inflammation in the scar zone decreased significantly after immunosuppressive treatment. This framework could be used to circumvent the common confounding issue of inflammation in cardiac FDG-PET imaging of myocardial metabolism.

Advisor: Lau, Angus
Wright, Graham H.
And the Jordan Will Flow as a River of Peace Over Us All: The Music of Ofra Haza in Cabaret

The music of Ofra Haza marked a turning point in Israeli history in that Mizrahi music began to overtake the popularity of the previously dominant Ashkenazi sound, largely influenced by Russian music. By putting the music of Ofra Haza in conversation with the story of Israeli history, the author of this thesis created a cabaret using Haza's music as a storytelling device. As a creative constraint, the Kabbalistic mysticism of Hebrew letters was invoked in order to provide a non-linear element of storytelling, as each song represented a letter of the name of Ofra Haza, as it is spelled in the original Hebrew.

Keywords: Cabaret
Israel
Judaism
Kabbalah
Music
Ofra Haza
Advisor: Each, Douglas
They Kiss: How Intimacy Directors Translate Intimate Stage Directions

How does an intimacy director approach, analyse and stage an intimate stage direction? This thesis puts the pedagogy of intimacy directors and the history of stage directions into conversation with the practical application of how intimate moments are staged in Canada. By interviewing 13 intimacy directors who work in the theatre industry in Canada, a deeper understanding and common themes of how they work with dramatic text emerges. As the role of intimacy director becomes more prevalent in theatre halls across the nation and the world, it is crucial to examine the affect they have in rehearsal halls, moment to moment, as well as the larger societal impact the practice is capable of.

Keywords: consent
intimacy
intimacy direction
intimacy director
intimate stage directions
stage directions
Advisor: Eacho, Douglas
Validity Assessment of a 3D Depth Sensor used in Movement Tracking Games for Children with Cerebral Palsy

In-person therapy can decrease motivation in children, and limit accessibility due to distance. Bootle Blast and Bootle Boot Camp are interactive video games that use a low-cost 3D depth sensor (Orbbec Persee+), with the goal to support conventional therapy for children with cerebral palsy. This study aims to validate the accuracy of the Orbbec Persee+ to support home-based rehabilitation games and its potential for providing correct feedback on the quality of movements. Joint data were collected from eight children and twenty adults as they participated in the games, using the Persee+ and a gold standard motion capture system for comparison. The joint coordinates and derived kinematic measurements resulted in good concurrent validity (Pearson’s r > 0.8) with good to excellent inter-rater-reliability (0.75 [0.53~0.88]) <〖ICC〗_3,1<0.99 [0.98~1.00]). The Persee+ and the rehabilitation games show potential for integration within a home-environment to provide clinicians with accurate changes in movement quality over time.

Keywords: Accuracy
Cerebral Palsy
Motion Capture
Movement
Sensor
Validation
Advisor: Biddiss, Elaine EB
Preventing Emissions of Volatile Organic Compounds from Water Bodies Using Buoyant Photocatalysts

This work highlights an emerging issue in environmental engineering: mitigating gaseous emissions from water bodies. Anthropological waters like oilsands tailings ponds are responsible for large gaseous fluxes. These include volatile organic compounds (VOCs) such as methane and secondary organic aerosol (SOA) precursors. While source control is the best mitigation technique to reduce future emissions, in-situ technologies for already-emitting waters are desired. Accordingly, application of buoyant photocatalysts (BPCs) to reduce VOC emissions from oil sands tailings ponds was investigated. The passive BPC technology forms a floating layer, slowing diffusion of VOCs from water to atmosphere, while oxidizing them in water via solar power. Under 2 days of mock sunlight, 89% of SOA precursor emissions were prevented, while oxidizing 84% of aqueous parent compounds in water. This project’s success provides pathways for further research such as BPC design, modeling, long-term studies, and application to other waters.

Keywords: Advanced Oxidation Processes
Air Quality Control
Aqueous Gas Emissions
Buoyant Photocatalysts
Oil Sands Tailings Ponds
Water Remediation
Advisor: Gu, Frank FXG
Investigating the Role of the LINC Complex on Skeletal Muscle Stem and Progenitor Cell Expansion

Muscle stem cells, or satellite cells (SCs), are required for skeletal muscle regeneration. Emery-Dreifuss muscular dystrophy (EDMD), a debilitating muscle disorder, is associated with LINC complex mutations, a series of nuclear envelope proteins, including Nesprins, connecting the cytoskeleton and nucleoskeleton. Despite being expressed in SCs, the LINC complex’s influence on SC fate during regeneration remains unclear. We generated transgenic mice with SC-specific LINC disruption and observed regeneration defects characterized by diminished myofibre diameter. In vitro studies suggested these defects were likely caused by inadequate SC progeny amplification and myogenic progression. EDMD patient-derived myoblasts with a Nesprin-1 mutation and primary human myoblasts with Nesprin-2 knockdown exhibited delayed proliferation and disrupted myogenic progression. LINC-disrupted EDMD myoblasts had altered cell cycle-related genes, including PAI-1, MYOD, and CCNA2, hinting toward potential proliferation-related molecular mechanisms. This study highlights the LINC complex’s role in myoblast proliferation and muscle regeneration, paving the groundwork for SC-targeting EDMD therapeutics.

Keywords: EDMD
LINC complex
Muscle stem cell
Regeneration
Advisor: Gilbert, Penney
Trauma Bay Re-Design: A User-Centred Approach

Trauma bays are chaotic places due to the frequent rotation of trauma team members from different disciplines and levels of training as well as urgency in providing required treatments. The suboptimal and ad-hoc design of trauma bays has led to staff dissatisfaction and potential safety and quality concerns at Sunnybrook Health Sciences Centre (SHSC). We apply various empirical frameworks with considerations from management science and participatory design to trauma bay re-design, with emphasis on active and iterative engagement from stakeholders and the application of user-centred design principles. Through observations, focus groups, and a tabletop prototyping workshop, we identified six main themes for improvement: labelling, visibility, item location, space utilization, flow, and communication. Focusing on these themes and with the use of human factors principles, we rendered a three-dimensional model of a future state trauma bay. We continue to improve this model through virtual reality tours with stakeholders and simulation scenarios. We discuss ongoing progress on the trauma bay re-design process occurring at SHSC.

Keywords: Design
Design Thinking
Trauma
Trauma Bay
Trauma Bay Design
User Centred Design
Advisor: Carter, Michael W
Investigating Endocannabinoid Metabolism in Cannabis Use Disorder: A PET Study Measuring Fatty Acid Amide Hydrolase During Cannabis Withdrawal

Abstract Introduction: Fatty acid amide hydrolase (FAAH) is low during overnight abstinence from cannabis. We investigated FAAH in cannabis users at overnight abstinence (T1); after 3-to-7-days of abstinence (T2). Methods: [11C]CURB scans were conducted at T1 (n = 13) and T2 (n = 10). Measures of craving, withdrawal, mood were collected. Primary analysis utilized Repeated Measures Analysis of Covariance (ANCOVA) across whole brain in 12 regions of interest (ROIs). Results: Two participants (n = 2) had levels of cannabigerol (CBG) at T2 suggesting failure to abstain. We found no main effect of time (n = 8), (F(1,6) = 2.840, p = 0.143); pairwise comparison suggested higher FAAH at T2 across ROIs (p = 0.09 – 0.23). Craving-expectancy correlated with changes in FAAH in amygdala (n = 8; r = 0.654, p = 0.040). Discussion: These data suggest nominal increases in brain FAAH at T2 in cannabis users. Future studies may assess longer abstinence.

Keywords: cannabis
neuropsychopharmacology
positron emission tomography
Advisor: Boileau, Isabelle
“If We’re Going to do Anything, We Have to Do It Ourselves” - The Case for Drug User Self-Management

This research project looks at the (self-)management strategies of drug users amidst the hostile socio-political environment manifested through 100 years of prohibition. This thesis focuses on Vancouver, B.C., Toronto, Ontario and various Canadian regions, analysing how current measures of policy enacted to address the worsening drug poisoning crisis have not been sufficient considering the crisis' death toll. An examination of strategies of drug user (self-)management is illustrated through a study of different strategies of drug user (self-)management, examining moments of drug user self-management that illustrate that drug users are not an ambivalent, apolitical group, but rather a highly radical, organised and effective political force that has forced drug policy forward for the last 30+ years. Further, this thesis will examine and interrogate literature surrounding limitations to harm reduction implementation, problematization procedures, and the current literature on self-management. This thesis works to legitimise and celebrate the revolutionary work of drug users throughout Canada.

Keywords: autogestion
drug poisoning crisis
drug user
drug user self-management
harm reduction
self-management
Advisor: Hackworth, Jason JH
Experimental Characterization of Bacterial Plant Pathogen Emergence

Plant pathogens pose a serious threat to worldwide crop yields and cause widespread food insecurity. Insertion of host resistance genes is a common strategy deployed to protect crops; however, this resistance can be overcome by pathogen evolution. My research aims to characterize the evolutionary trajectories that enable the bacterial plant pathogen Pseudomonas syringae to overcome host resistance barriers to cause disease. Specifically, we applied in planta experimental evolution to adapt an initially weak pathogenic strain of P. syringae to the model host Arabidopsis thaliana. We expected the emergence of P. syringae as a pathogen to depend on modulation of an immune-eliciting effector gene. We quantified bacterial growth during eleven infection cycles and performed phenotyping and sequencing of evolved lineages at the conclusion of the experiment. We found that PmaYM7930 evolved increased pathogenesis within only five infection cycles and that multiple lineages had lost a genomic island harbouring an immune-eliciting effector. These findings illustrate the speed with which novel pathogenic P. syringae strains can emerge on resistant hosts and stress the importance of development of more robust resistance engineering in crops.

Keywords: Arabidopsis thaliana
Bacterial virulence
Genomic island
Plant pathology
Pseudomonas syringae
Type III secreted effector
Advisor: Dillon, Marcus M.
Exploring the Effects of Microstructure on Electrochemical Passivation of Copper Coatings for Used Fuel Containers in Canada’s Nuclear Industry

This thesis investigates the influence of copper microstructure on electrochemical passivation performance, for the long-term storage of nuclear waste. The increasing global demand for nuclear power necessitates safe and reliable disposal strategies. The Canada-Deuterium-Uranium (CANDU) reactors and upcoming Small-Modular-Reactors (SMRs) contribute to a significant accumulation of used fuel bundles in Canada. To address this, the Nuclear Waste Management Organization (NWMO) proposes using Deep Geological Repositories (DGRs), where copper coatings on Used Fuel Containers (UFCs) are used for corrosion prevention. Through microstructural analysis and immersion tests under corrosive conditions, the corrosion performance of electrodeposited (ED(Py)-Cu), cold-sprayed (CS-AS-Cu), and oxygen-free electronic copper sheet (OFE-Cu) were compared. The passivating layer morphology was also examined under the influence of chloride and bicarbonate ions. The findings highlight the differences in corrosion behavior and passivation between different types of copper, emphasizing the importance of microstructure in designing effective corrosion prevention strategies for long-term nuclear waste storage.

Keywords: Cold-Sprayed
Copper
Corrosion
Electrodeposited
Microstructure
Nuclear
Advisor: Howe, Jane
The Impact of Particle Size in Cereal and Pulse Flours on Postprandial Glycemia and Appetite in Healthy Adults

The hypothesis that decreasing particle size of oat and pea flours increases postprandial glycemia and decreases appetite and food intake was tested in healthy adults. Experiment 1 examined the effects of consuming a serving of porridge prepared using 40g of coarse, whole, fine, or commercial oat flour. Experiment 2 investigated the impact of eating 45g of crackers made with 25% of coarse, whole, or fine pea flour compared to 100% wheat flour. Blood glucose, insulin, and subjective appetite were measured over 140min and energy intake was assessed at an ad libitum pizza meal. Coarse and whole flour treatments led to lower blood glucose and insulin response, but the coarser oat flours were less effective at suppressing appetite, although resulting in no differences in food intake. Larger particle sized flours can be used to develop low-glycemic value-added products with improved nutritional quality and acceptability.

Keywords: Appetite
Cereal grains
Food Intake
Food processing
Postprandial glycemia
Pulses
Advisor: Anderson, G. Harvey
Innovations in UV Disinfection for Rainwater Treatment: System Design, Disinfection Efficiency, Pathogen Detection and Solar (PV) Power

Harvested rainwater (HRW) is an alternative source of potable water used internationally to meet the world's growing water demand gaps. HRW has increased in popularity, with some resource-poor countries encouraging its use to increase water resilience. However, due to potentially poor microbial quality, disinfection may be required to make it suitable for consumption. While chlorine is a widely used and successful disinfectant, there is an aversion to its taste and smell, and households often need regular maintenance and technical awareness for proper disinfection year-round. Alternatively, UV treatment has emerged as a potential alternative, providing a chemical-free alternative to conventional disinfection methods for water treatment. This systematic review explored the use of UV disinfection for rainwater treatment, examining their past implementations and identifying the challenges encountered during their integration. This study employs a semi-qualitative approach to explore the relationship between the efficacy of UV disinfection and the factors shaping its performance. These factors include initial water quality, pretreatment stages, system specifications, and ongoing maintenance protocols. However, while analysis of that water quality determined that most of the UV systems installed had post-treatment concentrations of microbial indicators that met guideline values, a few studies had microbial concentrations exceeding the threshold. Additionally, there is inconsistent reporting of critical UV parameters, including ultraviolet transmittance (UVT) and operational UV dose. This disparity must be revised to provide a comprehensive overview of the influencing factors. Furthermore, a handful of UV systems encountered operational failures primarily due to deficient system management and inadequate maintenance practices. Consequently, this study advocates for establishing a minimum set of monitoring and reporting requisites for the UV system and water quality. This will give researchers and operators minimum reporting guidelines to monitor UV lamps' operation effectively.

Advisor: Hofmann, Ron
Interventions to mitigate antipsychotic associated weight gain using an algorithmic measurement-based integrated clinical pathway-a retrospective chart review study

Antipsychotics form an essential component in the treatment of several psychiatric disorders; they are, however, associated with weight gain and metabolic dysregulation resulting in significant psychological and physical challenges, leading to treatment non-adherence, poor quality of life, and increased cardiovascular morbidity. Several non-pharmacological and pharmacological interventions are available to mitigate antipsychotic-induced weight gain (AIWG). However, data on the utility of these interventions in real-world settings are limited. In this study, a retrospective chart review of patients attending the mental health and metabolism clinic that specializes in providing care for metabolic dysfunction in those with mental illness was conducted from 2016-2022. Charts of included patients were reviewed, and data pertaining to demographic, anthropometric and metabolic measures were collected and analyzed. The primary outcome measure was a change in weight at 3, 6, 9, and 12 months. A significant effect of the clinic on body weight over time was noted. The mean change in body weight was -1.54kg (SE:0.35, p<0.001), -1.79kg (SE:0.42, p<0.001), -3.5kg (SE:0.832, p<0.001) and -1.77kg (SE:0.77, p=0.35) at 3, 6, 9, and 12 months respectively. Initial evidence from our real-world clinical setting suggests that periodic monitoring and systematic administration of interventions are effective in reducing AIWG.

Keywords: Antipsychotics
Diabetes Mellitus
Integrated clinical pathway
metabolic syndrome
Obesity
Severe mental illness
Advisor: Agarwal, Mahavir Sri
Hahn, Margaret K
Determining the Role of GABA/Glycine Neurons of the Ventromedial Medulla in REM Sleep Behaviour Disorder and Cataplexy

Muscle atonia loss during REM sleep underlies REM sleep behaviour disorder (RBD) while muscle atonia intrusions into wakefulness underlies cataplexy. Basic science demonstrates that ventromedial medulla (vmM) GABA/glycine neurons innervate spinal motor neurons, are selectively active during REM sleep and cataplexy in human patients and animal models, and that degeneration is associated with RBD-like behaviours. Thus, it is hypothesized that these neurons generate atonia by inhibiting motor neurons and play a role in cataplexy. To test, vmM GABA/glycine neurons in narcoleptic mice were selectively lesioned, resulting in increased twitching and muscle tone in the neck but not masseter muscles during REM sleep. Mice demonstrated reduced cataplexy during wakefulness paired with increased muscle tone during remaining cataplexic episodes without affecting waking motor performance or waking muscle tone. Furthermore, narcoleptic mice exhibited deficits in waking motor performance alongside increased twitching behaviours in the neck muscle during REM sleep compared to non-narcoleptic counterparts.

Keywords: Cataplexy
Narcolepsy
RBD
REM Sleep
REM Sleep Behaviour Disorder
Advisor: Peever, John