VictorJuiz/thesis huggingface dataset:
Postprandial Dyslipidemia and Intestinal Dysfunction in Adolescents with Obesity and Insulin Resistance
Keywords: Adolescents
Dyslipidemia
GLP-1
Insulin Resistance
Obesity
Postprandial

Obesity and the metabolic syndrome are becoming increasingly prevalent in adolescents. Dyslipidemia, a key metabolic syndrome component, contributes to increased cardiovascular disease (CVD) risk. While traditionally measured in the fasting state, postprandial dyslipidemia independently predicts CVD risk. Postprandial gut peptides, glucagon-like peptide (GLP)-1 and GLP-2, as well as bile acids are secreted in response to fat ingestion and modulate intestinal dietary fat absorption and triglyceride-rich lipoprotein (TRL) output. Postprandial dyslipidemia and metabolic regulators have been seldom examined in adolescents, despite the early genesis of atherosclerosis. I hypothesized that postprandial GLP-1, GLP-2, and bile acids are impaired in adolescents with insulin resistance and obesity and associate with postprandial dyslipidemia. Normal weight adolescents and adolescents with obesity and varying degrees of insulin resistance underwent an oral fat tolerance test with blood collected up to 6 hours. The postprandial lipoprotein phenotype profile was determined using various assays, including nuclear magnetic resonance spectroscopy, to characterize lipoprotein particle number, size, lipid content, and apolipoprotiens. Adolescents with obesity and insulin resistance exhibited dyslipidemia, particularly reduced high-density lipoprotein particle size and exaggerated postprandial intestinally-derived large TRLs. Both total and active GLPs were quantified to estimate their secretion and biological activity, respectively. Postprandial secretion and activity of GLPs were blunted in adolescents with obesity and insulin resistance and inversely correlated with postprandial dyslipidemia. Conversely, fasting total GLPs positively correlated with postprandial dyslipidemia, suggesting a compensatory increase in fasting secretion. Postprandial total bile acids were diminished in adolescents with obesity. Further quantifying the postprandial bile acid pool composition by mass spectrometry revealed a specific reduction in postprandial lithocholic acid, a potent stimulator of GLP-1 secretion. In summary, postprandial GLP-1, GLP-2, and bile acids were blunted in response to a high-fat meal in adolescents with obesity and insulin resistance and may contribute to the development of postprandial dyslipidemia.
Delivery of Drug Combination Therapy in Polymeric Nanoparticles for Treatment of Breast Cancer
Keywords: Active Targeting
Breast Cancer
Combination Therapy
Dual Targeting
Nanoparticles
Paclitaxel

The development of resistance and the serious side effects associated with the commercial preparation of paclitaxel (PTX) necessitate the development of new PTX formulations that have a better safety profile. The use of synergistic drug combination therapies has emerged as one promising avenue towards reducing the toxicities associated with high doses of single agents while maintaining therapeutic efficacy. The molar ratios at which the drugs are administered have significant impact on their synergistic effects. In this thesis, for the first time, we provide a systematic assessment of the synergistic effects of PTX and everolimus (EVER) combination and define the optimal synergistic ratio. Polymeric nanoparticles represent an effective nanocarrier platform for the delivery of drug combinations to the tumor site at the optimal synergistic ratio, allowing for selective delivery and sparing normal tissues from exposure to their cargo and the toxicities that result. This thesis describes the design and characterization of a dual-targeted polymeric nanoparticle formulation based on poly(ethylene glycol)-b-poly(lactide-co-glycolide) (PEG-b-PLGA) co-encapsulating PTX and EVER at the optimal synergistic molar ratio (Dual-NPs). HER2 and EGFR-targeted antibody Fab fragments were conjugated to the surface of the NPs to enhance specific delivery and facilitate NP internalization in breast cancer co-overexpressing HER2 and EGFR. Dual-targeting of HER2 and EGFR resulted in a significant increase in the cellular uptake and cytotoxicity of the Dual-NPs in breast cancer cells relative to untargeted and HER2 mono-targeted NPs. Cellular uptake was dependent on the level of expression of HER2 and EGFR, confirming receptor-mediated internalization of the NPs. Limited in vivo stability is one of the main practical challenges in the application of polymeric NPs for the delivery of PTX to the tumor site. Importantly, Dual-NPs maintained their stability in mouse models which is a essential to exploit the EPR effect, leading to increased tumor accumulation and reduced toxicities. As a result, the levels of body weight loss were significantly reduced and neurotoxicity was overall reduced with Dual-NP treatment relative to the free-drug combination. In conclusion, Dual-NPs represent a promising tool for the delivery of PTX and EVER drug combination therapy to BC while reducing the toxicities of the drugs.
Clinical Performance of Lithium Disilicate Glass-Ceramic CAD/CAM Crowns Provided by Predoctoral Students at the University of Toronto
Keywords: CAD/CAM
Clinical survival
Glass ceramic
Lithium disilicate
Longevity

The clinical success of monolithic lithium disilicate glass-ceramic (LDGC) crowns manufactured with computer-aided design (CAD) / computer-aided manufacturing (CAM) technology provided by predoctoral students has not yet been investigated. The aims of this retrospective clinical study were to evaluate the clinical performance of monolithic posterior LDGC CAD/CAM (IPS e.max CAD, Ivoclar Vivadent) crowns fabricated with conventional and digital workflows provided by predoctoral students at the Faculty of Dentistry, University of Toronto. In addition, it assessed the effect of different patient and operator-related factors on their longevity. Furthermore, their clinical performance was compared to the metal-ceramic (MC) posterior crowns. Clinical assessment of the crowns and supporting periodontal structures was performed following the modified California Dental Association criteria. Intra-oral photographs, periapical and bitewing radiographs were taken for further assessment by two evaluators. In part 1 of this study, the clinical performance of 210 LDGC-CAD/CAM crowns fabricated with polyvinyl siloxane impressions for 6 years was evaluated. Crowns were milled in-house with CEREC Bluecam system using IPS e.max CAD blocks. Twenty-eight complications were observed (12-technical, 11-biological, and 5-esthetic). The 6-year survival and success rates were 93% and 86.4%, respectively. In part 2, the clinical performance of 40 chairside LDGC-CAD/CAM posterior crowns fabricated with digital impressions was evaluated. Impressions were taken with the Omnicam system and crowns were milled using a CEREC MC-XL machine. Three complications were observed (1-biological and 2-technical). The 4-year survival and success rates were 92.6% and 89.7%, respectively. In part 3, the clinical performance of 112 MC crowns for up to 10 years was evaluated. The 10-year survival and success rates were 87.1% and 81.0%%, respectively. Esthetic problems accounted for the majority of complications. In part 4, the clinical performance of LDGC-CAD/CAM was compared to MC crowns using split-mouth design for 6 years. Twelve complications were observed in the MC crown group (9-esthetic, 2-technical and 1-biological) in comparison to 2 complications in the LDGC-CAD/CAM crown group (1-technical and 1-esthetic). The 6-year survival rates for MC crowns and LDGC-CAD/CAM crowns were 90.8% and 96%, respectively, whereas, the success rates were 83.4% and 96%, respectively. LDGC-CAD/CAM crowns proved to be a predictable, reliable and viable alternative to the “gold standard” MC crowns.
Extended Intelligence and Mediated Reality Veillametrics in the Space, Time, Frequency, and Amplitude Domains
Keywords: augmented reality
mediated reality
sensing
sensors
sensory enhancement
veillametrics

Sensing is a key part of human life, and also plays a key role in technological systems. Technology and humans share a need to sense the physical world accurately and precisely, preferably with low error rates, low noise, high dynamic range, and high bandwidth. With the rise of surveillance (institutional sensing) and sousveillance (individual grassroots sensing) --- or more generally, veillance --- in the world around us, it is desired to enhance, control, measure, and understand the capacity-to-sense, in the context of extended intelligence, in order that this capacity-to-sense can benefit humanity. This thesis proposes new algorithms, circuits, and devices to extend the sensory capability of machines and humans. This includes sensory enhancement systems, user-interface devices that embody humanistic intelligence (HI) and a proposed new field of veillametrics. Veillametrics --- the measurement of sensing --- is a quantified approach to the sensing of sensing itself, introducing the new concept of “veillance flux.” Veillance flux is the quantified capacity-to-sense “emitted” from sensors, as that capacity-to-sense propagates through space, reflects, refracts and scatters. The mathematics and physics of veillance flux are introduced, along with measurement systems and visualizations of it. Sensory aid systems are further proposed, to expand sensory capability for machines and humans, in the spatial, temporal, frequency, and amplitude domains. A first application is cameras, where the capability to sense extreme-dynamic-range signals is improved by compositing together dynamic ranges from multiple sensors. A new concept called “coupled dynamic dynamic range” is introduced, where sensors themselves are controlled in a feedback loop, to expand their range of sensing. This work is then expanded to a wider class of sensor signals, including audio, high voltages, and seismic vibrations. This has led to newly-published concepts such as the amplitude-frequency transform, and harmonic range density functions. Novel user-interfaces and algorithms are introduced, to sense human input continuously over spatial-temporal-range domains, and provide tactile, audible and visual feedback to the user, for a tightly coupled interaction. Finally, space-time-frequency-amplitude domain signal processing is used to characterize sensing itself, using veillance flux, to help us understand, mediate, and augment the sensory capability of machines and humans.
Methods and Probes towards Time-resolved Multiparametric Imaging with Mass Cytometry
Keywords: Chemical biology
imaging mass cytometry
mass cytometry

Mass cytometry (MC) provides highly-multiparametric analysis of biological systems, with up to 45 parameters measurable per cell. Imaging mass cytometry (IMC) extends MC to account for spatial heterogeneity in biological samples by measuring 2-dimensional images of tissues with the same parametricity. Our lab previously developed tellurophene probes for cellular biochemistries of interest to be used with MC and IMC. Tellurium has seven commercially-available isotopes, allowing for synthesis of probe ‘isotopologues’: isotopically-enriched versions of a probe that are chemically identical but distinguishable by MC and IMC. Sequential labelling with isotopologous probe (SLIP) experiments analyzed by IMC are able to provide time-resolved images of a biochemical process of interest, and so represent a powerful method of quantifying biology with spatiotemporal resolution. This thesis details work towards new methods and new probes compatible with SLIP experiments, MC, and IMC. First, we use SLIP experiments to quantify the action of the drug metformin on tumour hypoxia. We found unexpectedly that metformin only transiently reduces the hypoxia found in solid tumours, and after 6~hours its effect disappears. This brings into question the mechanism by which metformin potentiates radiotherapy. Second, we detail the development of our next-generation hypoxia probe, Telox~3. The probe clears rapidly, making it compatible with SLIP experiments to study cycling tumour hypoxia over time: a complication in cancer known to promote metastasis and aggressive disease. Third, we present our tellurophene probe for protein synthesis, TePhe. The tellurophene ring is a faithful bioisostere of a phenyl ring, allowing TePhe to be incorporated into proteins in vitro and in vivo. Quantification of tellurium incorporation by MC and IMC reports on the rate of protein synthesis in the cells or tissue of interest. Finally, we discuss data processing strategies arising from the idiosyncrasies of tellurium. We remove xenon background signal, quantify transmission efficiency biases across the tellurium isotopes, and present a strategy for combining images from natural abundance tellurium experiments to improve signal-to-noise ratio. In conclusion, the work in this thesis has made progress towards a more complete toolkit for studying complex biology with spatiotemporal resolution.
The Socio-economic Organization of Votive Pottery Production at Abydos, Egypt in the New Kingdom: A Metric Analysis Study
Keywords: Ancient Egyptian Economy
Ceramic Metric Analysis
Craft Production
Egyptian Archaeology
Pottery Production

The present study examines the metric variability of beer jars used for the official temple cult and private votive activities at the Thutmosis III chapel in the North Abydos Votive Zone (NAVZ), and beer jars and votive dishes deposited at Umm el-Qa’ab as private offerings for the Abydos Festival. An understanding of the socio-economic organization of pottery connected to private cultic activities and the official temple cult helps address broader debates regarding the pervasiveness of state/administrative control over the ancient Egyptian economy and the degree to which individuals had autonomy to participate in economic activities. The socio-economic organization of pottery production and procurement are examined in the present studying using metric analysis, or the statistical analysis of measurements of vessel attributes (e.g., rim diameter, height, etc.) of an assemblage that inform on its relative degree of standardization. Several issues persist with the theoretical foundation, methodology, and research design of metric analysis. In an effort to contribute to scholarship that seeks to address these issues, the present study additionally conducts metric analysis of modern Egyptian pottery. To contextualize the results of the Abydos metric analysis, this study also examines the extant archaeological and textual evidence related to the socio-economic organization of pottery production in the New Kingdom. The results of the Abydos metric analysis study and the examination of textual and arcaheological evidence of New Kingdom pottery production suggests that rather than directly administered state-controlled pottery production, the demand for pottery used in temple and private ritual activities was met by networks of dispersed pottery workshops that were connected through social, economic, and work obligation relationships. Utlimately, this study shows that the organization of pottery production was distributed in ancient Egypt with both individuals and larger institutions (in this case temples) employing diverse strategies to produce and obtain pottery.
From Behind the Scenes to Under the Skin: The Social Bodily Experiences of Stressful, Gendered Work in Police Communicators
Keywords: Allostatic Load
Emotional Labour
Gender
Occupational Stress
Police Communicators

Gender and work are complex social determinants of health. Little is known about how they intersect to shape health inequities. Differences in the acute strains and chronic stressors of particular occupations are systematically related to other socially structured categories, such as gender. Physiological representations of social structures like gender can be discerned through acute and chronic stress responses at work. The body cumulatively records the complexity of the social world, like work, translating gendered work into health inequities. Police communications (911 call-takers/dispatchers) is a gendered, high-stress occupation that requires intense emotion work and persistent social interactions. Engaging in this type of high-stakes emotionally demanding work – that I hypothesize is embodied – has the potential to shape health along gendered divisions of labour. Allostatic Load (AL) – a framework used to assess physiological dysregulation due to prolonged secretion of stress hormones – represents a construct through which the material embodiment of social life can be demonstrated. Long-term dysregulation, however, is the accumulation of repeated short-term responses that have become dysfunctional. Thus, acute physiological responses and AL, as biological registrations of social life, are used to examine how gendered work shapes health. Eighty-one communicators were individually observed as they worked. Participants wore a heart-rate-variability (HRV) monitor and received take-home questionnaires and salivary cortisol kits. Blood and physiological markers were collected for AL scores. A subset of 25 acutely stressful events also occurred, after which, saliva samples were collected for cortisol and oxytocin responses. Results indicate gender plays a role in the relationship between emotional labour and AL. Furthermore, the experience of posttraumatic stress is associated with increased AL. During acutely stressful events, changes in cortisol, oxytocin, and HRV are evident. Central to social stress responses, these physiological changes are differentially predicted by gendered workplace stressors. Findings suggest that gender structures might influence health through conformity to norms and the associated stress these relational beliefs/acts provoke. Furthermore, associations between physiological and subjective stress also point to mechanisms through which cumulative exposures to stressful events might increase the risk of stress-related disorders. Implications for future research on this biological embedding of gendered social experiences are discussed.
Publication and Registration Bias in Randomized Clinical Trials
Keywords: Clinical Trials
Digital Health
Health Informatics
Publication Bias
Randomzied Controlled Trials
Trial Registry and Registration

The research literature has identified the impact of publication bias in randomized clinical trials (RCTs). The prospective registration of RCTs provides a means to mitigate publication bias by allowing researchers to explore a source of trial information, that may or may not be published. This thesis offers a critical appraisal of the compliance in prospective registration and results publication of RCTs. This thesis includes three studies. The first study evaluated the publication bias and prospective registration in digital health RCTs in ClinicalTrials.gov. To expand the scope of this study beyond a single trial registry, the second study examined the global prospective registration, the reporting of the trial registration number (TRN), and the publication rates of digital health RCTs registered in any of the World Health Organization (WHO) registries. To improve the external validity beyond the realm of digital health RCTs, the third study provided an empirical analysis of the prospective registration, the inclusion of TRN, and the selective registration bias in all RCTs registered in any of the WHO registries, and published in any PubMed-indexed journal in 2018, ten years after the adoption of the 7th revision of the Declaration of Helsinki (DoH). The overall results showed that (1) nearly one third of all digital health RCTs remain unpublished (27% and 34.5% in the first and second study respectively), (2) the compliance in prospective registration of RCTs remains low (29.3%, 38% and 41.7% in the first, second and third study respectively), and (3) the compliance in reporting the TRN in published RCTs was low (49%, 52% and 71.2% in the first, second and third study respectively), and (4) a new form of bias was detected “Selective Registration Bias”, with an increased (biased) tendency of the investigators to register a trial only when intending to publish the trial. The majority of RCTs (95.7% and 85.1% in the second and third study respectively), that were registered retrospectively, were registered within one year before submitting the RCT manuscript for journal publication. Addressed to editors, investigators and ethics committees, this thesis proposed several recommendations to inform the future development of best practices to mitigate the publication and registration bias in evidence-based medical research. This thesis proposed several recommendations to inform the future development of best practices to mitigate the publication and registration bias in evidence-based medical research.
In Situ Bioprinting of Planar Biomaterials and Tissues
Keywords: Bio fabrication
Bio printing
Microfluidics
Regenerative medicine
Skin Substitutes

The goal of regenerative medicine is the synthesis of replacement tissue by positioning vital cells in three-dimensional (3D) patterns representing the arrangement, characteristics and functionality of natural tissue. The largest organ in humans - skin - possesses a unique hierarchical structure, comprised of cell populations whose fate and functionality is governed by their position. In severe burn injuries, effective strategies that ensure prompt and effective wound closure are essential for survival. Acellular substitutes require grafting and thus cause additional wounds, while cellular substitutes need long culture times, typically 3 - 4 weeks. In this thesis, a handheld instrument is presented that enables bioprinting of architected planar biomaterials and tissues in an approach that is compatible with in vitro and in vivo applications. Enzymatically, ionically, or light polymerizable biopolymer solutions that may contain skin cells are spatially organized to geometries resembling the skin using a microfabricated printhead and deposited onto a target surface. Homogeneous and architected (i.e., bi-layered and stripe-patterned) sheets are consistently formed and characterized. Cell-laden tissues were studied in vitro. Proof-of-concept experiments in small (murine) and big animal (porcine) wound models demonstrate the compatibility of the approach with in vivo requirements. The presented strategy enables the formation of organized soft tissues in a one-step manner that does not require multi-axis printhead translation or manipulation of printed constructs. With macroscopic and microscopic target surface specificity, in situ bioprinting shows great promises as an alternative bio-fabrication method for making tissue substitutes on arbitrary surfaces.