VictorJuiz/thesis huggingface dataset:
Medical Devices and the ManGo: Prototyping Low-cost, High-quality Medical and Laboratory Systems That Make Healthcare More Accessible
Keywords: Design
Fluidics
Medical System
Point-of-Care
Protein Manufacturing
Prototyping

The COVID-19 pandemic that ravaged the world in 2020 gave light to a lot of things, but mostimportantly it highlighted how access to healthcare remains an obstacle to many, particularly to those in resource-poor areas of the world. In this work, I describe my efforts in building medical and laboratory systems that help provide high-quality healthcare with low-cost resources. My main project is the development of a portable fluidic system which takes advantage of cell-free systems to significantly reduce the time and costs associated with protein manufacturing. Two versions of this fluidic system have been developed, both of which manufacture therapeutics and research tools quickly and at low-cost. A second system I developed is an economical incubator as a companion device to augment the functionality of a glucose meter interface for diagnostics.
A Morphological and Molecular Investigation into the Role of Ethylene in Cannabis sativa Sex Determination
Keywords: Cannabis sativa
ethylene
genetics
molecular biology
morphology
sex determination

Commercial Cannabis producers rely on harvesting unfertilized female flowers for their high cannabinoid levels, but presence of male pollen can lead to fertilization and yield losses. Although male plants can be genetically identified, there is no reliable way to identify female plants which spontaneously produce viable male flowers. Understanding of Cannabis sativa’s sex determination mechanisms is limited, but the phytohormone ethylene is known to promote female flower development. Phenotypic analysis confirmed C. sativa responds canonically to ethylene. Microscopy revealed unisexual C. sativa flower development diverges early through distinct morphological pathways and ethylene inhibition in female plants exposed an alternative male flower formation pathway. From these, a model for C. sativa sex determination regulated by ethylene is proposed, with support from differential gene expression analyses. Future studies are needed to identify causal genes regulating sex determination so male flower-producing plants can be identified by growers, and female-only strains can eventually be bred.
Hyperglycemia from Glucocorticoid Use for Prophylaxis of Chemotherapy-induced Nausea and Vomiting (CINV)
Keywords: chemotherapy-induced nausea and vomiting
colorectal cancer
dexamethasone
glucocorticoids
hyperglycemia
oncology

Chemotherapy-induced nausea and vomiting (CINV), a frequent adverse effect of chemotherapy, is debilitating and negatively impacts patients’ wellbeing. Despite the introduction of newer antiemetics, glucocorticoids continue to play a fundamental role in CINV prophylaxis. Hyperglycemia is a well-documented adverse effect of glucocorticoids, yet there is a limited systematic effort to assess its occurrence and develop strategies for its management in the oncology population. We sought to provide a better understanding of glucocorticoid-induced hyperglycemia (GIH) in the setting of CINV prevention by conducting a: (1) systematic review of the current literature; (2) retrospective chart review to ascertain current glucose monitoring practices; and (3) prospective observational study to assess the occurrence of GIH. There is a paucity of high quality evidence addressing GIH in this population. Current glucose monitoring practices do not adequately identify the magnitude of the issue in practice as GIH occurs more frequently than is documented.
Lens-less In-fiber Bragg Grating (FBG) Spectrometer and Femtosecond Laser Welding-based Packaging
Keywords: FBG
femtosecond laser
fiber
fiber welding
glass welding
laser processing

A femtosecond laser was applied to single-mode optical fiber to embed a periodic filament array. The filament-grating resulted in azimuthally narrowed radiation modes, while chirped grating design provided spectral focusing. This combination permitted lens-less all-fiber spectrometry, offering a high-resolution of 335 pm in the visible spectrum with a low-cost CCD camera. The diffraction efficiency was improved in two directions: increasing radiative scattering from high refractive index contrast in air-filled nanoholes and by scaling from one-dimensional (1D) to 2D designs of photonic grating structure in the core. The further objective centred on laser writing of strong pseudo-continuous weld seams for fiber-to-ferrule packaging. Parallel welding tracks were aligned azimuthally around the interface, bonding over 90% of the interface circumference. This hermetic-like welding avoided thermal degradation of FBG devices in the core. Femtosecond laser processing thus demonstrated a flexible means for optical fiber fabrication and packaging, enabling robust packaged FBG sensor for high temperature and strain environments.
Accelerated Long-term Forgetting in Parkinson's Disease and Healthy Aging
Keywords: Aging
Episodic Memory
Executive Function
Forgetting
Parkinson's Disease

Accelerated long-term forgetting (ALF) is characterized by rapid forgetting of long-term episodic memories over hours to weeks despite normal initial learning. Emerging evidence suggests ALF occurs in Parkinson’s Disease (PD) and healthy aging. However, the few ALF studies in these groups use paradigms with high reliance on executive functions which hinders the ability to determine whether these forgetting effects are indicative of hippocampally-based episodic memory and/or fronto-executive declines. Using two long-term item memory measures that minimize demands on executive functions, I hypothesized that PD and healthy older adult groups would show greater forgetting by three days than healthy controls and younger adults respectively. Preliminary results show no significant ALF effects in either group, which may reflect the current under-powered sample or that executive functioning mediated ALF in previous studies. Notwithstanding, this research will help elucidate the relationship between ALF, hippocampally-based memory processes and fronto-executive abilities in PD and healthy aging.
The Impact of Dentin Conditioning and Sealer Modification with Chitosan-hydroxyapatite Nanocomplexes on the Antibacterial and Mechanical Characteristics of Root Dentin
Keywords: Chitosan
Dentin
Nanocomplexes
Tricalcium silicate sealer

This study assessed the effectiveness of dentin-conditioning with chitosan-hydroxyapatite-precursor (CS-HA) nanocomplexes alone or associated with tricalcium silicate sealer (TCS/CS-HA) on mechanical and antibiofilm properties in root-dentin. TCS and TCS/CS-HA characterization was evaluated. Lower premolars treated with CS-HA dentin-conditioning and/or associated to TCS were used to determine fracture resistance. Enterococcus faecalis-infected roots were utilized for antibacterial analysis. SEM findings were described. Paired t-test was used to analyse flowability results. Findings from solubility, fracture and antibacterial assays were assessed by ANOVA-Tukey’s tests. TCS/CS-HA slightly reduced flowability but did not affect solubility (p>.05). TCS/CS-HA significantly enhanced hardness/elasticity (p
Exploring the Combinatorial Function of Proneural Genes Neurog1 and Neurog2 in Neocortical Development
Keywords: neocortex
Neurog1
Neurog2
neurogenesis
proneural
Split-Cre

Proneural genes encode basic-helix-loop-helix (bHLH) transcription factors (TF) that promote neural progenitor cell (NPC) differentiation in the developing nervous system. The proneural genes Neurog1 and Neurog2 are co-expressed in neocortical NPCs, yet our lab recently found that they are functionally divergent, despite their sequence similarity. The work presented in my thesis further explores the fate and function of Neurog1/Neurog2 double+ NPCs. I first showed using RNAscope that Neurog1 and Neurog2 are only co-expressed in early cortical NPCs, consistent with previous reports. I then used a novel Split-Cre lineage tracing approach, in which only NPCs co-expressing these two genes are induced to express a fluorescent reporter, to track the fate of Neurog1/Neurog2 double+ NPCs. I found that double+ NPCs give rise to intermediate neuronal progenitors (INPs) and neurons in all cortical layers. These findings provide further support for the progressive restriction model of laminar fate specification, which states that early NPCs give rise to all cortical layers, in part via INPs, while late-stage NPCs are restricted to upper-layer laminar fates. I then characterized the effects of specifically deleting only Neurog1/Neurog2 double+ NPCs, comparing to a global double knock-out (DKO) of Neurog1 and Neurog2. I found that by the end of the normal neurogenic period, in both Split-Cre;Rosa-diptheria toxin A (DTA) ‘deletor’ and Neurog1-/-;Neurog2-/- DKO cortices, NPC pools were precociously depleted. Taken together my work supports the importance of the cooperative actions of these two proneural genes to coordinately regulate the timing of cortical neurogenesis.
Exploration of Surface Properties of Engineered Sponges for Effective Marine Oil Spill Cleanup
Keywords: Adsorption
Crude Oil
Emulsions
Nanocomposites
Oil Spill Treatment

Removing emulsified oil from seawater is challenging. Superwetting foams developed using afacile dip coating technique have emerged as a promising approach. They allow for the manipulation of surface properties to remove free and emulsified oil from seawater. Herein, new surface engineered sponges have been developed to remove different crude oils from seawater. These coatings were developed to improve performance for different oils and understand the influence of different factors on oil removal efficacy: surface chemistry, surface roughness and electrostatic compatibility. The developed materials displayed over 99% removal efficacy for light, conventional, and heavy crude oil emulsified in water, across a wide range of environmental conditions, including pH, temperature, and salinity. This approach is simple, scalable, and economical with the potential to address large-scale marine oil spills. The insights provided can provide researchers an understanding of pivotal surface properties necessary to drive emulsified crude oil adsorption when developing future materials.
Prescribing Characteristics Associated with Return to Opioid use following Buprenorphine Treatment in Ontario
Keywords: buprenorphine
discontinuation
opioid
opioid agonist therapy
overdose
taper

Buprenorphine is a first-line treatment for opioid use disorder (OUD), however, many clients choose to discontinue therapy. We used Cox proportional hazards modelling to understand which prescribing characteristics were associated with return to opioids within 18 months following buprenorphine taper among persons 18 years or older with OUD in Ontario. Among 5,774 individuals, 65.8% experienced at least one opioid-overdose, treatment re-entry, or return to prescription opioid use. Time to taper initiation >1 year vs. ≤1 year (aHR:0.69, 95% CI:0.48-0.997) and a lower average rate of taper (≤ 2 mg/month and >2 to ≤4 mg/month compared with >4 mg/month) (aHR:0.65, 95% CI:0.46-0.91; aHR:0.69, 95% CI:0.51-0.93) were associated with lower risk of opioid-overdose. A more stepped taper, with doses decreasing in ≤1.75% of days compared with >3.5% of days, was also associated with reduced risk of opioid-overdose (aHR:0.64, 95% CI:0.43-0.93). Findings highlight the risks associated with tapering buprenorphine and underscore the importance of careful treatment planning.
White Matter Microstructure in Male and Female Children with Mild Traumatic Brain Injuries and Association with Processing Speed
Keywords: Concussion
Magnetic Resonance Imaging
Mild Traumatic Brain Injury
Paediatric
Processing Speed
Restriction Spectrum Imaging

As maturation of the brain microstructure and cognitive processes continue throughout development, there is risk of interference from mild traumatic brain injury (mTBI). This thesis used T1-weighted and diffusion magnetic resonance imaging (MRI) to investigate differences in white matter and cortical microstructure between children with a history of mTBI and children with no history of mTBI, and to investigate whether differences in brain microstructure are associated with performance on cognitive tests. Group comparisons between children with and without a history of mTBI revealed significant differences in deep and superficial white matter microstructure in females with mTBI. In addition, in females with mTBI, superficial white matter microstructure was associated with lower scores on the processing speed test. These findings suggest that mTBI in childhood may alter white matter development in females. This sex dependent effect on the brain may be associated with enhanced vulnerability to persistent symptoms after mTBI in females.
Integrative Taxonomy as a Tool for Conservation: Exploring Freshwater Fish Diversity of the Barra del Colorado Wildlife Refuge, Costa Rica
Keywords: barcode
ichthyology
identification
morphology
neotropics

As global biodiversity declines, conservation efforts are important in megadiverse areas such as the Neotropics where biodiversity is especially imperiled. The accurate identification of species/specimens is critical to successful conservation plans. However, in groups such as freshwater fishes, conventional methods for species/specimen identification such as morphology, or molecular methodologies such as DNA barcoding, have documented challenges. Approaches that integrate multiple data sources are likely to provide the best species identifications. Here, I assess the diversity of freshwater fishes in the Barra del Colorado Wildlife Refuge, Costa Rica, and document 51 species. I use and compare multiple approaches to identify species. My results demonstrate that barcode-based identifications are comparable to field-based identifications despite known gaps in resources for field-based identifications and are inferior to identifications by experts using morphology. I conclude that an integrative approach to specimen identification is a critical facet of successful preservation of biodiversity.
An Improved Approach for Optogenetic Locomotion Control of Caenorhabditis Elegans
Keywords: Caenorhabditis Elegans
Living robot
Micro robot
Optogenetics
Soft robot

Animals have greatly inspired the development of robotics with their sophisticated bodies after the evolution of millions of years. By directly harnessing the intelligence of animals, the technical bottlenecks such as integration of actuation mechanism and energy source for untethered microrobot could be overcome. Our research group proposed an approach to develop a living soft microrobot by optogenetic locomotion control of Caenorhabditis elegans, called RoboWorm. This thesis work further improves the RoboWorm technology. Firstly, the applications of RoboWorm to support biophysical research of C. elegans are illustrated through a literature review. Secondly, the performance of RoboWorm has been significantly improved by generating a new transgenic strain of C. elegans, with a different approach to hijack the worm motor neurons. The third aspect is to improve the operation and enhance the user-friendliness of the RoboWorm system. Overall, this thesis improves the performance and demonstrates applications of the RoboWorm technology.
Information-seeking Drug Professionals: Information Practices of Peer Harm Reduction Workers in Toronto
Keywords: Community health
Harm Reduction
Library and Information Sciences
Peer Harm Reduction Workers
People who use drugs
Public health policy

While a significant body of literature exists studying the effectiveness of peer-led harm reduction programming, a much smaller body of work examines peer harm reduction workers’ professional capacities, particularly outside of public health policy or social work fields. Using a Library and Information Sciences theoretical framework, the purpose of this study is to investigate the information practices of peer harm reduction workers, thereby centring the experiences of people who use drugs working in the harm reduction field. Eight peer harm reduction workers who live and work in Toronto were interviewed about their workplace experiences, professional development, and community engagement. Applying Lloyd’s writing about embodied information practice as a theoretical framework, the findings of this study conceptualize how harm reduction workers with lived experience develop their career identities and collaboratively create social and cultural norms in their workplaces.
Evaluating Variation In Red Blood Cell Transfusion for Patients undergoing Elective Gastrointestinal Cancer Surgery
Keywords: Blood transfusions
Practice variation
Surgical oncology

Understanding variation in transfusion practice among patients undergoing gastrointestinal cancer surgery will support efforts working towards responsible transfusion use. We performed a population-based study of patients who underwent elective gastrointestinal cancer resection between 2007 and 2019 to measure variation in transfusion use across surgeons and hospitals. Variation was explored using funnel plots and multilevel regression. Of 59,964 patients, 18.0% were transfused. Wide variation in transfusion use among surgeons and hospitals was observed. Patient characteristics explained 12.8% of the variation. After adjusting for patient case-mix, between-surgeon and between-hospital differences were responsible for 2.8% and 2.1% of the variation, respectively, translating to an approximately 30% difference in the odds of transfusion for two similar patients treated by distinct surgeons or hospitals, respectively. Although transfusion provision depends on patient factors, important variation across surgeons and hospitals creates opportunities to target modifiable processes of care to standardize perioperative transfusion practice.
Phenotypic Examination of CD9 Overexpression in White Adipose Tissue
Keywords: Adipose Tissue
Diabetes
Fibrosis
Obesity

Adipose precursor cells (APCs) are a key target population for obesity-related alterations due to their bipotential differentiation capacity. APCs are capable of differentiating into white adipocytes, contributing to the development of fat-storing cells (i.e., adipogenesis), or into fibroblasts, which can lead to white adipose tissue (WAT) fibrosis. Recently, CD9high PDGFRα+ APCs demonstrated greater fibrotic nature compared to their, adipogenic, CD9low counterparts. This suggests the involvement of a CD9-based mechanism in the differentiation of PDGFRα+ APCs. To elucidate the role of CD9 in APC fate determination, we created a cell-type-specific and drug inducible overexpression mouse model that increases CD9 expression in PDGFRα+ APCs. The goal of this project is to phenotypically characterize this model and examine the role of CD9 expression fate determination of PDGFRα+ APCs. Our findings suggest that CD9 overexpression in PDGFRα+ APCs promotes systemic dysglycemia and enhanced WAT fibrosis. Altogether our results implicate CD9 in APC fate determination.
Ethnic Differences in Cardiometabolic Risk: A Meta-analysis in Adults and a Cross-sectional Study in Children
Keywords: Cardiometabolic risk
Ethnicity
Obesity
Type 2 diabetes

Type 2 diabetes (T2D) manifests differently in adults of different ethnicities. Whether these differences arise as early as childhood remains narrowly explored. For Objective 1 of this thesis, two separate meta-analyses of prospective cohort studies were conducted using random effects models to investigate whether the associations between BMI, WC, and T2D risk differ across ethnic groups. For Objective 2, a cross-sectional analysis was conducted among 5,557 children (ages 3-11 years), and linear and multivariate regression models were used to estimate differences in continuous cardiometabolic risk (CMR) outcomes, including a CMR score, between European and non-European children. In Objective 1, the meta-analyses showed that Southeast Asians displayed the highest risk of T2D per unit increase in BMI and WC. In Objective 2, African and East Asian children were observed to have significantly lower CMR scores than European children, while South Asian children displayed higher levels of lipid markers than Europeans.
First Records of a Cribriform Plate in Non-avian Dinosauria, with Implications for Olfactory Evolution and Ecology
Keywords: Cribriform plate
Genomics
Olfaction
Olfactory anatomy
Sensory evolution

The study of internal cranial anatomy in dinosaurs has allowed for insights into aspects of their neurology and sensory evolution. We describe the novel aspects of the olfactory anatomy of two ankylosaurids: Anodontosaurus lambei and Dyoplosaurus acutosquameus. These specimens exhibit ossified cribriform plates, a plate of bone perforated by olfactory nerve bundles. These represent the first known occurrences of this feature in non-avian dinosaurs, and it is rarely seen in non-mammals. The pattern of perforation in ankylosaurs is more peripheral than in mammals but the density is similar. This enables us to use the framework of a previous study to estimate the number of functional olfactory receptor genes from the plate area. We also examine the potential application of “maximum olfactory windows” in other dinosaurs, where the olfactory nerve passes through ossified foramina (ceratopsids, hadrosaurids and tyrannosaurids). This research provides the first estimates of functional sensory genes in non-avian dinosaurs.
Pharmacogenetic Analysis of Antipsychotic Response in Schizophrenia
Keywords: Antipsychotic
Pharmacogenetics
Schizophrenia

Antipsychotic (AP) medications are the best treatment option for schizophrenia (SCZ), but the inter-individual difference in treatment response is a serious concern. Previous studies have revealed a strong genetic component in AP efficacy, thus we aimed to identify genetic predictors for AP response. We examined the metabotropic glutamate receptor 3 (GRM3) gene variants for association with AP response, and observed that rs274621 was associated with better response. We also investigated the associations between the polymorphisms in alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit genes and clozapine (CLZ) response and found rs1461225 to be associated with negative symptom improvement. Lastly, we studied the complement component 4 (C4) gene in relation to SCZ clinical characteristics. We found nominal associations between C4 and SCZ clinical characteristics, as well as a strong sex-specific effect on C4 genotype distribution in SCZ. Our studies pointed to several potential biomarkers for AP response, but future replication studies are required.
Deciphering Stem Cell from Apical Papilla - Macrophage Choreography in Inflammatory Environment using a Novel 3D Organoid
Keywords: 3D cell culture
Cell interaction
Inflammation
Macrophage
Organoid
SCAP

The aim of this study is twofold: (1) develop and characterize a 3D binary-cells tissue construct to study SCAP (stem-cell-from-apical-papilla) - MQ (macrophage) interaction, and (2) investigate the interactions and cell signaling mechanisms between SCAP-MQ under pro-inflammatory/anti-inflammatory environments in the organoid system. 3D (dimensional) image analysis and cytokine profiles were employed in this investigation. It was demonstrated that the SCAP self-organized as a cap-shaped organoid in the tissue construct. The pro-inflammatory/anti-inflammatory environments influenced SCAP-MQ interactions, resulting in altered cell volume, cell viability, cell morphology and structural organization in 3D tissue construct. The increased cytokine/chemokine profiles at the earlier phase of pro-inflammation, increased ratio of pSTAT6/pSTAT1 and decreased CD206/80 indicated a distinct polarization behavior in macrophages during repair. Conversely, equal ratio of pSTAT6/pSTAT1 and late increase of CD206/80 with amplified secretion of IL-1RA, IL-10 and TGF-1 in the anti-inflammatory environment directed alternative macrophage polarization, while promoting SCAP differentiation and tissue modeling.