VictorJuiz/thesis huggingface dataset:
Transrectal Ultrasound-guided Brachytherapy in Early Cervical Cancers – Utopia or an Upcoming Reality?

Rationale: Transrectal ultrasound (TRUS) allows for great soft tissue discrimination in the pelvis. This study investigates the role of TRUS in cervical cancer brachytherapy. Methods: FIGO IB cervical cancer patients treated with MR-guided intracavitary brachytherapy boost were enrolled in this study. TRUS images acquired in axial axis were used to define the High-risk Clinical Target Volume (CTVHR) and pelvic organs at risk (OARs) with and without the applicator in place and compared to contours performed in MR images. Results: CTVHR contours were smaller and thinner in TRUS images. No statistical difference was seen in CTVHR height or width. CTVHR and OARs inter-rater contouring agreement were similar between contours in MR and TRUS when applicators were not in situ. Significant image deterioration was noticed in TRUS images once the applicators were inserted. Conclusions: TRUS images allow for consistent CTVHR and OAR contours whenever brachytherapy applicators are not in place.

Keywords: Brachytherapy
Cervical Cancer
Ultrasound
Advisor: Wong, Shun
GAIA: An “eEcosystem” of Aggregated Information for Plant Biology

Currently, there is a plethora of scientific data available online through many different tools, databases, repositories, and websites, making it difficult for researchers to find the information for their prospective investigation. When the Multinational Arabidopsis Steering Committee (MASC) conducted a 2018 bioinformatics survey, they found that researchers have expressed a strong desire to have data centralized. Inspired by this request, the General Agricultural Intelligent Agent (GAIA) was created. Aggregating data for plant biology across many scientific resources, GAIA can create an executive summary that can either summarize a gene or gene product of interest or use Natural Language Processing (NLP) and machine reading (MR) to answer an inputted question. Built with modular design philosophy, GAIA is created with simplicity in mind for its code, allowing new developers to easily access, modify, and create new components for its UI and functionality. GAIA is currently available at https://bar.utoronto.ca/gaia.

Keywords: computational biology
data mining
data visualization
natural language processing
nlp
web development
Advisor: Provart, Nicholas J
Novel Chemical Tools for Protein Labelling and Photodynamic Therapy

Protocols to purify and fluorescently label proteins are typically lengthy and inefficient. We describe a novel method that enables the preparation of purified and labelled proteins in a matter of hours. Our protocol gives high yield of the desired protein product using minimal mutations, gives high specificity of labelling, and ease of orthogonal attachment of other fluorescent probes in later steps. Photodynamic therapy is a therapeutic modality used to treat a variety of cancers and bacterial infections. While it has found great clinical success, the treatment remains hindered in application due to side effects arising from low selectivity. We describe a new class of photosensitizers that improve the selectivity of photodynamic therapy through the use of molecular rotors. The proof-of-concept experiments shown here display the potential of molecular rotors as selective photosensitizing agents in photodynamic therapy to improve the outlook of treatment in the clinical setting.

Advisor: Beharry, Andrew
Gradinaru, Claudiu
Characterizing the Role of SYK in the Pathogenesis of Inflammatory Disease

Inflammatory diseases can be caused by monogenic inborn defects in immunity. Whole exome sequencing was performed on patients with severe inflammatory disease. Six patients were identified with variants located at varying positions of the SYK gene (S550Y, S550F, P342T, M450I, A353T). SYK codes for a 72 kDa non-receptor tyrosine kinase and plays an important role in both innate and adaptive immunity. Through functional studies, multiple SYK variants had significant hyperactivation of SYK and dysregulated downstream inflammatory target proteins, indicating a gain-of-function. Moreover, a potential drug (R406) was identified to potentially alleviate observed biochemical phenotypes. This study provides impetus for the use of personalized therapies in patients affected by gain-of-function SYK variants with the ultimate goal of applying it to the broader inflammatory disease population.

Advisor: Muise, Aleixo
The Roles of TrkA and p75NTR NGF Receptors in Corneal Wound Healing

The cornea, i.e., one of the most densely innervated structures in the body, is the window through which we see the world. The loss of corneal innervation through injury, diabetes, tumors, infections and even improper contact lens use leads to neurotrophic keratopathy (NK). NK is a degenerative corneal disease characterized by corneal epithelial breakdown, scarring, and permanent vision loss. The only non-invasive treatment option for NK is recombinant human nerve growth factor (rhNGF); however, the short half-life of exogenous neurotrophin-based therapies limits their efficacy. Accordingly, small molecule ligands have been developed for neurotrophin receptors with more favorable pharmacokinetics and stability, showing promising results for the treatment of several neurodegenerative conditions in recent years. In this study, we investigate the molecular mechanism of NK and the role of the NGF receptors Tropomyosin Receptor Kinase A (TrkA) and p75NTR (neurotrophin receptor) in corneal healing.

Keywords: Corneal nerves
Corneal wound healing
Neurotrophik Keratopathy
NGF
p75NTR
TrkA
Advisor: Borschel, Gregory
Gordon, Tessa
Optimization of Compiler-generated OpenCL CNN Kernels and Runtime for FPGAs

This work explores the viability of end-to-end convolutional neural network inference using OpenCL HLS kernels generated from TVM on Intel FPGAs. We explore layer-pipelined execution for small networks and time-multiplexed kernels for larger CNNs. Naively generated kernels do not produce efficient hardware. We propose a set of optimizations to increase parallelism, resource utilization, and more efficiently use memory bandwidth. They include loop unrolling, tiling, fusion, invariant code motion, cached writes, CL channels, autorun kernels, concurrent execution, and parameterized kernels. These optimizations improve performance up to a factor of 1150x over the naive baseline implementation generated by TVM. Compared to Keras/Tensorflow on a 56-core Xeon 8280, we observe performance improvements up to 4.57x and 1.4x over LeNet and MobileNet but has a slowdown at 0.43x for ResNet-18/34.

Keywords: Compiler
Convolutional neural networks
Deep learning
FPGA
Advisor: Abdelrahman, Tarek S
Tightly Integrated Multiomics-based Deep Tensor Survival Model for Time-to-event Prediction

Multi-omics cancer profiles provide essential signals for predicting cancer survival. It is challenging to reveal the complex patterns from integrating multiple types of genomic data and extract valuable information strongly associated with patients’ survival outcomes. We proposed an innovative algorithm for cancer survival prediction to integrate tensor factorization of multi-omics cancer data and deep learning-based survival analysis, named Deep Tensor Survival (DTS). We built a three-dimension (3D) tensor to integrate multi-genomics data and factorized it into 2D matrices of latent factors, which were fed into a neural net to extract hidden features for survival prediction through a Log-hazard survival model. We applied the algorithm to the breast cancer data, colon and rectal cancer data from The Cancer Genome Atlas (TCGA) program. We evaluated the goodness-of-fit using the concordance index (C-index) and Integrated Brier Score (IBS) and showed new algorithm outperforms conventional methods.

Advisor: Xu, Wei WX
Design and Evaluation of a Researcher Platform to Automate Development of Customized Cognitive Games

The Interactive Media Lab (IML) at the University of Toronto has developed a suite of serious games that can be used to administer psychological tasks. To move these games from laboratory to practical use, it was important to establish their scientific validity through validation studies with large samples. With an increasing demand for customized versions for various research studies, a development capacity bottleneck was reached. To find a long-term solution to this challenge, we create a researcher platform, enabling researchers to customize cognitive games for their research studies without the need for coding skills. This thesis describes the human-centred design process of the platform, which culminated in a ready-to-implement prototype, as well as the insights learned from two rounds of usability evaluation. As a novel experiment builder of serious games for psychological tasks, this platform provides insights on leveraging software tools to make online experimentation more efficient.

Keywords: Human Factors Engineering
Interaction Design
Product Management
Usability Evaluation
Advisor: Chignell, Mark
Design of an Affibody-modified Hydrogel for the Controlled Release of FGF2

Proteins have demonstrated immense potential as therapeutic agents in the treatment of ocular diseases as they possess high specificity and affinity for their targets; however, their short half-lives comprise a significant barrier to their clinical translation. To tackle this challenge, affinity-based hydrogels have been employed to tune protein release and prolong therapeutic residence time. In this thesis, we designed an affibody-modified hyaluronan (HA)-based hydrogel as a delivery vehicle for fibroblast growth factor 2 (FGF2). We identified a highly specific affibody binding partner with an intermediate affinity (3.8 x 10-8 M) for FGF2 using yeast surface display. Importantly, we demonstrated controlled release of FGF2 from the hydrogel vehicle by modulating the affibody to protein ratio and showed a stabilizing effect of the affibody on FGF2. Ultimately, this system serves as a versatile delivery platform amenable to any protein with the potential for distinct multi-species release profiles based on specific affinity interactions.

Keywords: Affibody
Affinity interactions
Fibroblast growth factor 2
Hyaluronan
Hydrogel
Protein delivery
Advisor: Shoichet, Molly
Identifying Barriers and Facilitators to the use of Renal Tumor Biopsy (RTB) in the Management of Small Renal Masses (SRMs) in Ontario and Potential Implementation Strategies to Promote its Widespread Adoption

Background: Renal tumor biopsy (RTB) has been shown to be a useful diagnostic tool, however, it remains underutilized in Canada. No previous study has explored the barriers/facilitators of RTB using interviews. Methods: Phase one comprised qualitative telephone interviews with Ontario Urologists to determine barriers/facilitators to the use of RTB in practice. Phase two entailed a modified Delphi process with a panel of experts to determine the most critical barriers/facilitators to address for ongoing work. Results: Four barriers/facilitators were determined to be the most appropriate to address for ongoing work to promote the adoption of RTB in Ontario and included: 1) need for disseminating current Canadian Urological Association guidelines; 2) need for new Canadian guidelines for RTB; 3) Radiologists’ RTB technical skill; 4) Colleagues promoting RTB. Conclusion: This study provides Ontario healthcare with a tool that identified the most appropriate barriers/facilitators, along with interventions, to promote the adoption of RTB.

Keywords: Implementation Science
Knowledge Translation
Modified Delphi Process
Qualitative Research
Renal Tumor Biopsy
Semi-structured Interview
Advisor: Finelli, Antonio
The Matriarch, the Marxist, and the Radical: The Suffragettes of 20th Century Egypt

Egyptian history is rich with the stories of various feminists, the different movements they led and joined, and their numerous objectives and outcomes. This paper focuses on the feminist activity of three women, Huda Sha’rawi, Inji Afflatun, and Doria Shafik, and their efforts to achieve political rights for women. It explores how these different women employed the tool of defensive feminism in their activism, and why tools like this are a necessity for female activists in neopatriarchal states.

Advisor: Hanssen, Jens
A Star Put It There: Theatre, Astronomy, and Finding Our Place

Western theatre has reflected millennia of our evolving awareness of humanity’s place in the universe, and the more we learn, the smaller—and less significant—we appear. Two case studies illustrate this interplay between theatrical expression and scientific inquiry through close reading and astronomical context. Michael Frayn’s Copenhagen grapples with ethical questions surrounding the work of influential quantum physicists Niels Bohr and Werner Heisenberg, while Maureen Hunter’s Transit of Venus provides a biographical exploration of 18th-century astronomy and personal fallout in the life of stargazer Guillaume Le Gentil. A companion piece to the project, a solo play titled A Star Put It There, offers an increasingly macroscopic contemplation of the cosmos and its existential implications. As science continues to seek new truths about our reality, a renewed humanism prompts celebration of the meanings we create for ourselves and each other, an outlook well-suited to the interpersonal immediacy of theatre.

Keywords: Astronomy
Existentialism
Philosophy
Science History
Theatre
Advisor: Schotzko, Nikki
Freeman, Barry
Patients' Experiences and Perceptions of the Symptom Screening with Targeted Early Palliative Care (STEP) Process

Symptom screening with Targeted Early Palliative care (STEP) is a novel intervention offering early palliative care to symptomatic patients with advanced cancer. A qualitative descriptive approach was taken to explore patients’ experiences and perceptions of the STEP process and to identify factors considered when deciding to accept or decline a palliative care clinic (PCC) referral. Fifteen patients completed interviews. Participants stated they believed symptom screening helped healthcare providers, but emphasized the additional importance of discussing their symptom scores. Some participants felt shocked/discouraged, and others comforted/supported at being offered a PCC referral; benefits of receiving a referral were noted. Common factors considered when deciding to accept or decline a referral were: perceived symptom burden, perceived need for additional support, and readiness to contemplate a terminal prognosis. This information is important to guide future implementations of STEP and to ensure that timely palliative care is provided to those in greatest need.

Keywords: cancer
palliative care
qualitative
symptom screening
Advisor: Zimmermann, Camilla
Universal Rate-Distortion-Perception Representations for Lossy Compression and Applications using Generative Models

In the context of lossy compression, Blau \ Michaeli \cite{blau2019rethinking} adopt a mathematical notion of perceptual quality and define the information rate-distortion-perception (RDP) function. We consider the notion of universal representations in which one fixes an encoder and varies the decoder to achieve a collection of distortion-perception constraints. We prove that the corresponding information-theoretic universal RDP function is operationally achievable in an approximate sense. Under MSE distortion, we show that the entire distortion-perception tradeoff for Gaussian sources is achieved by a single encoder asymptotically. We then characterize the achievable distortion-perception region for a fixed representation for arbitrary distributions. This motivates the study of practical constructions that are approximately universal, alleviating the need to design an encoder for each objective. We provide experiments on MNIST/SVHN suggesting that for image compression, the operational tradeoffs achieved by fixed-encoder machine learning models are comparable to their variable encoder counterparts.

Keywords: Deep Learning
Image Compression
Information Theory
Lossy Compression
Advisor: Khisti, Ashish
Characterizing a Novel Type II-C Anti-CRISPR, AcrIIC6

Phages are the most ubiquitous species on the planet, outnumbering bacteria ten-to-one in almost all environments. Consequently, phages exert an immense amount of pressure on bacteria to evolve defense mechanisms against phage predation. One mechanism is the adaptive immune response known as the CRISPR-Cas system. In response to the CRISPR-Cas adaptive immunity, phages have evolved small proteins called anti-CRISPRs that inhibit the CRISPR-Cas system. I characterized a novel type II-C anti-CRISPR, AcrIIC6, discovered in a prophage within Neisseria meningitidis and Pasteurella multocida. Through in vivo phage targeting, I determined that AcrIIC6Nme/Pmu inhibits Cas9 proteins that are closely related to Nme1Cas9. Furthermore, AcrIIC6Nme/Pmu only bound to sgRNA loaded Cas9 and did not affect sgRNA integrity or loading. Lastly, I showed that AcrIIC6Pmu prevents Cas9 from binding target DNA efficiently. This work shows a novel anti-CRISPR of the type II-C CRISPR-Cas system that binds to the binary Cas9:sgRNA complex and prevents Cas9 from binding DNA.

Advisor: Maxwell, Karen
Moraes, Trevor
New Perspectives on The Role of Lipid Anchoring on G-Protein Coupling and Activation in the Adenosine A2A-Gs Complex

The G protein in a G protein coupled-receptor (GPCR) plays an important role in activation of the coupled receptor via nucleotide exchange and release of its α-subunit (Gα) and βγ-subunits (Gβγ) to allow for downstream signaling. We use 1D 19F nuclear magnetic resonance (19F NMR) and 2D heteronuclear single quantum coherence spectroscopy (HSQC) to resolve the conformational states of the α-subunit of the stimulatory G protein (Gαs). Specific sites on Gαs provide an improved perspective on the allosteric response upon 19F-tagging. Gαs exhibits at least two distinct broad conformations; a coupled and uncoupled state, whose populations are dependent on the interplay between receptor, Gβγ, and nucleotide. Gαs can also be modified to be N-myristoylated, which is envisioned to create an enhancement of its association with receptor, membrane, Gβγ, and its function. Here, Gαs is N-myristoylated through an in vitro reaction with the enzyme, N-myristoyltransferase (NMT1) to attach a lipid anchor.

Keywords: Biochemistry
Conformational Selection
G protein
GPCR
Lipidation
Receptor
Advisor: Prosser, Scott R
Memory Dependence Prediction for Energy Constrained Devices

Historically, energy constrained devices (ECDs) have favored simple in-order pipelines over out-of-order (OoO) ones due to lower energy consumption. While prior research has focused on optimizing in-order compute architectures, not a lot of work exists on adapting OoO pipelines for ECDs. This thesis aims to help enable speculative execution and OoO processing to increase performance on such devices. Memory dependence prediction (MDP) is one such mechanism used for achieving these goals. This thesis leverages prior work and applies machine learning to uncover new MDP designs. A novel perceptron MDP is first developed that almost matches the performance of Store Sets, a state of the art MDP. The insights gained during the process lead to a much simpler one bit counter (OBC) technique suitable for use on low powered devices. The OBC MDP design matches the performance of Store Sets while saving 95% area and 96% energy.

Advisor: Enright Jerger, Natalie
Effects of Hyperoxia Exposure on the Polarization of Alveolar-like Macrophages in a Mouse Model of LPS-induced Lung Inflammation

Acute respiratory distress syndrome (ARDS) is a severe lung disease of high mortality (30-50%). Patients require lifesaving oxygen therapy, however hyperoxia can induce pulmonary inflammation and cellular damage. Although alveolar macrophages (AMs) are essential for lung immune homeostasis, they become compromised during inflammatory lung injury. Stem cell-derived alveolar-like macrophages (ALMs) are a prospective therapeutic for lung diseases like ARDS. Using in vitro and in vivo methods, I investigated the impacts of hyperoxia on ALMs during acute inflammation. ALMs retain their viability and antimicrobial abilities during moderate hyperoxia exposure in vitro. ALMs possess a hybrid M1/M2 phenotype that remained stable upon moderate hyperoxia exposure. After intratracheal delivery to mice, ALMs adopt further characteristics of primary AMs. Hyperoxia did not exacerbate phenotypic changes of ALMs caused by LPS-induced lung inflammation in mice. These results support the concept that ALMs may have potential benefit in human ARDS patients receiving conservative oxygen therapy.

Keywords: acute respiratory distress syndrome
alveolar like macrophage
alveolar macrophage
ARDS
inflammation
lung disease
Advisor: Post, Martin
Breast Cancer Patients’ Experiences While Transitioning to a Virtual Cardiovascular Rehabilitation Program during a Pandemic (COVID-19)

COVID-19 restricted access to onsite Cardiovascular Rehabilitation (CR) programs for patients with breast cancer (BC). Objectives: [1] compare BC survivors’ Physical Activity (PA) in onsite CR to virtual CR following the COVID-19 transition and compare to a matched cohort from prior to the pandemic (2018/2019). [2] explore experiences of transitioning to and engaging in virtual CR. Methodology: Quantitative analysis of CR PA data from pandemic (n=18) and 2018/2019 cohorts (n=18), and semi-structured focus group interviews with the pandemic cohort (n=9) in the context of the PRECEDE-PROCEED model. Results: No significant differences in mean but increased variation of activity duration, frequency, and MET-minutes were observed. Focus groups revealed women valued their CR experiences pre-COVID-19 and were anxious during the transition. BC patients recommended virtual programs increase comradery, technology, and professional guidance. Conclusion: PA experiences with a pandemic transition vary among BC survivors. Targeting individualized strategies and exercise prescriptions are important.

Keywords: Cancer rehabilitation
COVID-19
Exercise
Neoplasm
Qualitative research
Survivorship
Advisor: Thomas, Scott
Oh, Paul
Characterizing the Effects of First Trimester Human Umbilical Cord Perivascular Cell (FTM HUCPVC) Treatment on the Lungs using an α-PD-1/α-CTLA-4 Combination Immunotherapy Mouse Model

One category of immunotherapy that has revolutionized cancer treatments is immune checkpoint inhibitors (ICI). ICI block cancer-induced negative regulation of T cells, thereby allowing a response against tumor cells. Although ICI use has led to positive therapeutic benefits,there are negative off-target effects, known as immune-related adverse events (irAEs). One irAE is checkpoint inhibitor pneumonitis (CIP). The use of mesenchymal stem cells (MSC) as cell therapies has been widely studied for many regenerative medicines as well as immunomodulatory applications but has not been studied in the context of ICI-induced irAE. The aim of my thesis was to establish a small animal model of irAE and investigate the use of firsttrimester human umbilical cord perivascular cells (FTM HUCPVC), a young andpromising source of MSC, to mitigate ICI-induced lung damage. We hypothesized that the use of FTM HUCPVC can reduce lung damage caused by ICI in vivo.

Keywords: Immune Checkpoint Inhibitors
Immune Related Adverse Events
Immunomodulation
Immunotherapy
Pneumonitis
Umbilical Cord Stem Cells
Advisor: Librach, Clifford L