NCube/papyrus huggingface dataset:
Impact du statut nutritionnel sur la qualité de vie des patients atteints de carcinomes épidermoïdes de la tête et du cou

Background: Head and neck cancer and the side effects related to its treatment predispose patients to malnutrition, which is an important cause of morbidity and mortality. However, uncertainties persist as to its impact on quality of life. Objective: The objective of this study is to evaluate the nutritional status of patients treated for head and neck squamous cell carcinoma and its impact on their quality of life at four months and one year after diagnosis. Methods: Data regarding nutritional status, as measured with BMI, weight loss, albumin and prealbumin, was collected before the beginning of treatment. Quality of life was evaluated prospectively, using the University of Washington Quality of Life Questionnaire, on three occasions: before the beginning of treatment, four months after diagnosis and one year later. A total of 155 patients treated for head and neck squamous cell carcinoma were reviewed from this prospective databank. Multiple linear regression was used for statistical analysis. Results: With adjustment for age, sex, cancer stage, type of treatment, comorbidities and pretreatment quality of life, a lower BMI is associated with a poorer overall quality of life at one year post-diagnosis (p=0,03). No association was demonstrated between the nutritional markers and quality of life at four months after diagnostic. Conclusion: Evaluation of nutritional status is an essential component in the care of head and neck cancer patients, as malnutrition is correlated with poorer long-term quality of life.

Keyphrases: nutritional status, quality of life, head and neck cancer, squamous cell carcinoma
Impact de l’ajout de glutathion à la nutrition parentérale sur la synthèse protéique chez le cochon d’Inde

Parenteral nutrition (PN) is essential for children with severe intestinal disorders. However, this mode of nutrition is associated with significant side effects. Peroxides contaminating PN limit the use of methionine as precursor of cysteine. Cysteine deficiency is suggested by a lowered level of glutathione, limiting the detoxification of peroxides, contributing even more to oxidative stress. Hypothesis: PN-induced cysteine deficiency leads to suboptimal protein synthesis, especially in growing children. Objective: To demonstrate in an animal model of PN, that glutathione supplementation (GSSG), used as pro-cysteine, facilitates protein synthesis and reduces oxidative stress. Methodology: One-month-old Guinea pigs were exclusively fed by PN+/- GSSG via a jugular catheter. A group of animals fed regular food served as controls. On the third day of PN, tritiated leucine was infused to evaluate protein synthesis. On the fifth day, haemoglobin, urea, glutathione in different organs and protein incorporation into the gastrocnemius muscle were determined. Results: Muscle protein incorporation of tritiated leucine was 57% higher in animals with PN + GSSG (p <0.05). The reduced plasma protein concentration in the PN group (p <0.01) was back to the controls by the addition of GSSG. The presence of GSSG in PN prevented the increase of oxidative stress markers observed in the PN group (p <0.01). Conclusion: In a growing individual, enriching PN with glutathione is a simple way to maintain protein synthesis and reduce oxidative stress by impeding cysteine deficiency.

Keyphrases: glutathion, cachexie, parenteral nutrition, glutathione, oxidative stress, protein synthesis, peroxide, pediatrics, cachexia
Effets de la greffe pulmonaire sur la densité minérale osseuse et l’anthropométrie des individus atteints de fibrose kystique

Post-lung transplant weight and bone mineral density (BMD) early changes have been well-documented, but little is known about mid- to long-term changes, particularly among cystic fibrosis (CF) recipients. Post-lung transplant weight and BMD trajectories have important clinical implications, as low BMD may increase the risk of fractures whereas weight gain is associated with increased cardiometabolic and mortality risk. This study aims to document post-lung transplant BMD and weight changes and assess their predictors. To achieve this goal, we retrospectively examined a cohort of 131 CF patients who underwent lung transplant between 2000 and 2015 at the Centre hospitalier de l’Université de Montréal. Bone parameters (BMD and serum calcium, phosphate, 25OHD, PTH, osteocalcin, C-telopeptides), anthropometric (height, weight and BMI) and clinical data (medications and supplements) were collected during the waiting period, at transplant, and at 6 months, 1 year, 2 years, 5 years and 10 years post-transplant. Absolute weight changes since transplant (kg) and annualized percentages BMD changes since pre-transplant were computed. Our results showed a gradual increase in weight up to 10 years post-transplant. Proportion of  underweight patients  decreased between initial evaluation (36.6 %), transplant (26.0 %) and post-transplant follow-up (21.4 %, 11.6 %, 10.3 % and 8.5 %,) except at 10 years post-transplant where it increased (18.2 %). While obesity was nonexistent during the waiting period, a small proportion of patients developed it after transplant (0.8 % to 3.0 %). The final regression models strongly predicted the variance of weight changes (kg) at 6 months, 1, 2 and 5 years (r2 > 98.3 %). Sex, BMI at transplant and BMI post-transplant were significant predictors of weight changes at all post-transplant timepoints. The length of hospital stay after transplant was also a predictor of weight changes at 6 months post-transplant. The loss of BMD occurring between pre-transplant and 6 months post-transplant was more pronounced at the femoral neck than the lumbar spine. However, this loss is transient as recovery of BMD is observed over the long term. Regression models modestly predicted the variance of annualized percentages BMD changes (1- and 5-year femoral neck: r2 = 27.5 and 47.7 %, 1 year lumbar spine: r2 = 28.3 %). A majority of underweight CF recipients reach normal weight after transplant. However, the excessive weight gain seen in a number of subjects may have health implications. After transplant, BMD of CF recipients increased progressively to reach pre-transplant values, but remained suboptimal in most cases, despite the use of bisphosphonates.

Keyphrases: os, cystic fibrosis, lung transplant, bone mineral density, bone, anthropometry, weight, BMI, cystic fibrosis bone disease
La fonction protectrice des acides gras oméga-3 dans la neuroinflammation et les comportements anxio-dépressifs induits par l’obésité et l’implication du récepteur GPR120

Introduction: Obesity can elicit cerebral inflammation, including in the nucleus accumbens (NAc), a brain region involved in the control of anxio-depressive behaviors. Omega-3 polyunsaturated fatty acids (n-3) reduce symptoms of major depression and may inhibit metabolic inflammation. GPR120 is a G-protein coupled receptor activated by n-3. Peripherally, GPR120 is involved in the resolution of inflammation within macrophages.  Hypothesis: N-3 supplementation improves anxio-depressive behaviors as well as metabolic and inflammatory parameters altered by diet-induced obesity through the involvement of GPR120. Objectives: To measure the effects of a chronic n-3 supplementation in a context of obesity on metabolic, behavioral and inflammatory parameters as well as to describe the anti-inflammatory effects of GPR120 microglial activation. Methods: In the first study, C57Bl/6 mice were submitted to a high-fat or control diet and then gavaged daily with fish oil or corn oil. Behavioral, metabolic, inflammatory markers, as well as neurolipids measurements were performed. In the second study, GPR120 expression was assessed in several brain cell types. Inflammatory markers expression was measured in mouse primary microglia cultures exposed to a pro-inflammatory agent, the lipopolysaccharide (LPS) and a GPR120 specific agonist (cpdA). Similar treatments were administered in vivo to study their impact on anxiety-like behaviors.  Results: Chronic n-3 supplementation improved anxiety-like behavior, exploratory deficit, glucose intolerance, and cerebral lipidomic modulations induced by a high-fat diet. We reported that the expression of GPR120 primarily in microglia and cpdA decreased the expression and secretion of pro-inflammatory markers induced by LPS in microglia. Treatment with cpdA in vivo also improved sickness behaviors demonstrated by the resolution of locomotor deficit caused by LPS. These results demonstrate the behavioral and anti-inflammatory benefits of n-3 in the context of obesity and suggest that GPR120 microglial activation mediates these effects.

Keyphrases: Neuroinflammation, GPR120, Omega-3 fatty acids, Obesity, Anxiodepressive behaviors
Alliance thérapeutique dans un cadre de surveillance communautaire (probation et libération conditionnelle) : implications et enjeux

Therapeutic alliance as a component of interventions efficiency is frequently read in literature. This project aims to question about this relationship applied to a context of care imposed such as community supervision (probation and conditional release). More specifically, it tends to assess the possibility to establish a positive work environment and relationship in consideration of this specific context. To that end, the relationship between the community agent and his client is explored and the benefits provided by a working alliance. Moreover, the links between different components are considered (therapeutic alliance, optimal conditions, professional attitudes, desistances from crime) to apprehend the concept of assisted desistance

Keyphrases: Therapeutic alliance, Conditional release, Assisted desistance
Comment étudier la complexité des séries télévisées? : vers une approche spatiale

How to study the specificity of television series building evolving, shapeshifting, open, fragmented narratives? Questioning the use of the notion of complexity within and beyond narratology, this article proposes to read television series through an interdisciplinary perspective focused on spatialization. Indeed, beyond textual analysis and in the absence of primary sources on the production side (sources that more often than not prove inaccessible), the television series scholar is bound to explore the intermediate space between representation and reception – a complex space frequently navigated by users, as shown by the circular model of participatory culture (Jenkins, 2013).

Keyphrases: Spatialization, Complexity, Participatory culture, Narrative
Récits sériels exploratoires

This contribution puts forward a spatial perspective to the study and analysis of television series. Starting from a pragmatic approach, that considers the television series as a process and an exploratory experience of a multidirectional diegetic space, the point of view that we adopt here combines aesthetic and narratological analysis and compares television series to fictional worlds. Through various examples of shows from the 1990s to today, this essay displays series as world-building experiences and tries to understand the mechanism of their immersive power in the long run. Working on spatial theories of film and media studies we conceive space as a world or a diegetic territory, in order to complete the existing methods for the analysis of television series that consider time as the main element of a serial narrative.

Keyphrases: Exploration narrative, Immersion, Expansion narrative, TV series, Space, Fictional worlds, Narrative exploration, Narrative expansion, Longevity, Titles, Pilot
Unjustly dismissing an alternative : a case of epistemic injustice among epistemic frameworks

The concept of epistemic injustice has become a useful tool for understanding some of the wrongs and harms that result from the interplay of identity and knowledge. However, this paper proposes that analysis of epistemic injustice needs to consider not only the level of individual or institutional epistemic transactions, but also the level of epistemic frameworks. Drawing on Gaile Pohlhaus Jr. and Rajeev Bhargava, I examine the Cuban health care system and the epistemic framework it is based on as a case study of how prejudice that leads to the dismissal, discrediting and marginalization of such an epistemic framework can be an epistemic injustice.

Keyphrases: Ethics, Economics, Epistemic injustice, Cuba, Health care, Epistemic frameworks, Philosophy
L’apprentissage des tons lexicaux à partir du signal acoustique de la parole chez les nourrissons âgés de 4 mois

In the first year of life, the newborn learns the phonetic categories of his native language, including the lexical tones. However, it is unclear how this perceptive reorganisation takes place from an acoustic input that is so variable. In a study of simulations by artificial neural networks, the dynamic of the acoustic signal would be effective to process this variability and categorize the lexical tones of Chinese Mandarin. This study explored the newborn ability to learn the tones in Mandarin, from the fundamental frequency (F0), but also from their movement, that is to say the velocity patterns of F0 (D1). Thirty-two francophone newborns 4 months of age were initially familiarized with tones by a continuum of stimuli comprising 10 steps, that varied on both F0 and D1. In the first condition, the continuum was going from rising tone to descending tone so that D1 was distributed in a bimodal distribution and F0 was distributed in a unimodal distribution. In the second condition, the continuum was going from low tone to high tone, with a bimodal distribution of F0 variations and unimodal variations of D1. During the test phase, the performances suggest that the infant can discriminate tones as early 4 months of age, as seen in previous studies, but seems too young to learn the categorization of tones from the patterns of distribution of acoustic indices. Further studies are needed to better understand the underlying mechanisms of phonetic categories acquisition.

Keyphrases: Speech perception, Perceptual reorganization, Distributional learning, Lexical tone, Infants
Impact d'une suralimentation prolongée et d'une supplémentation en polyphénols sur le profil d'activité physique et de sédentarité

Overfeeding has been a classical technique for investigating the mechanisms of body weight regulation in humans. The concept that changes in energy expenditure, sedentary time and physical activity parameters may play an important role in the regulation of energy balance has been the subject of many investigations, but our understanding remained incomplete. For example, no overfeeding study to date has measured both sedentary and physical activity profiles. This research project thus includes a global approach where seventeen sedentary and physical activity parameters were assessed before and following 31 days of overfeeding at 150% of daily energy expenditure. The diet consisted in snacks rich in fat and sucrose. Subjects were assessed in a free-living condition using accelerometers. Another novelty of this work is that we investigated if the use of 2g/day of a polyphenol supplementation (procyanidin, anthocyanin and resveratrol) obtained from red grapes can protect from overfeeding and how activity profile can be impacted by this supplementation. While time spent running and resting energy expenditure increased by 49.0% in the placebo group and 49.1% in the polyphenols group and 2.3% in the placebo group and 2.2% in the polyphenols group respectively over the course of the overfeeding protocol, there was no interraction of polyphenol supplementation and overfeeding on sedentary and physical activity parameters. Interestingly, the non-exercise activity thermogenesis index, linked to trampling, standing and walking decrease with overfeeding, suggesting adaptive changes in more subtle elements of none-volitional physical activities, such as fidgeting, spontaneous muscle contraction and maintaining posture when not recumbent. This observation must however be validated by a future investigation. Aside from these findings, few changes have been observed following polyphenol consumption and overfeeding.

Keyphrases: Overfeeding, Polyphenols, Physical activity, Energy expenditure, Sedentariness, Accelerometer, Snacking, Obesogenic environment
A multiscale framework for microbial evolution to identify the emergence of antibiotic resistance

Antimicrobial resistance is an emerging health crisis that threatens our ability to control bacterial infections. Advances in medical treatments depend on the ability to fight infections with antibiotics. Thus, there is a need to understand the mechanism surrounding the evolution of antibiotic resistance. Predicting the evolutionary trajectories to drug resistance remains a daunting task and is urgently needed. Currently, our aptitude to predict pathways in bacterial evolution to drug resistance is limited. It entails bridging several constraints on various levels of biological organization—from molecular properties of proteins to organismal fitness, to microbial population dynamics. In this memoir, I develop a new multi-scale framework for microbial evolution that integrates principally population genetics with biophysics. My model system is beta-lactamase that provides broad-spectrum resistance against beta-lactam antibiotics. First, I determine the fitness landscape of ß‐lactamase using deep mutational scanning, a novel tool to experimentally assay the fitness of around 5000 variants of beta-lactamase. Then, I integrate this experimental fitness landscape data into my computational model of microbial evolution to study the evolutionary pathways to drug resistance. In the first chapter, I develop a deterministic evolutionary model combining population dynamics and the biochemical effects of mutations to capture the effects of purifying selection under selection with ampicillin. Due to the limited information that a deterministic model can provide, in the second chapter, I build upon the initial model to develop a stochastic model of microbial evolution. This updated model aims to determine mutations that might be enriched during antibiotic treatment. I investigate the landscape of fitness cost against resistance level. I also investigate drug regimens to alleviate the rise of resistance. In the third chapter, I experimentally determine with DMS the fitness landscape of TEM-1 (Temoneira-1), a ß-lactamase enzyme, to study its resistance level and its dose-dependence for cefotaxime.

Keyphrases: Antibiotic resistance, Evolution, Fitness landscape, Evolutionary model, Deep mutational scanning, Fitness cost
Contrôle génétique de l’épissage alternatif dans le contexte de la réponse immunitaire innée

When triggered, the innate immune response initiates molecular changes in the cells that allow an appropriate defense to the detected threat. These changes will affect the transcription of immune related genes while other genes are turned off to efficiently let the organism fight the pathogen. Alternative splicing plays a major role in the fine-tuning of messenger RNA expression. Recent researches have shown that there were major shifts of RNA splicing following infection by two bacteria (Listeria monocytogenes and Salmonella typhimurium). This study aims to better define the role of inter-individual genetic variation on alternative splicing in the context of bacterial infection. We first defined a list of annotated alternative splicing events for which we could recover the proportion of exclusion and inclusion form (PSI-value). We used this phenotype as a proxy for isoform usage. Unlike researches focusing on the proportion of annotated transcripts, we could isolate certain types of events and analyze the processing of exon separately. A multiple linear regression approach was then used to map the psi-value on the genotyping data. We identified 1948 unique events significantly correlated to genotype (rpQTL) and hundreds that were specific to infected macrophages. In total, this set of events spanned 1 162 genes. These results show that the inclusion of certain exons is genetically controlled in macrophages and that some of this control only occurs in infected macrophages. We also showed that alternative-first-exon (AFE) seem to be the least affected by genotype while alternative-last-exon (ALE) and TandemUTR are the most affected. Further analysis of rpQTL SNP showed independence between eQTLs and rpQTLs. Overall our results propose that splicing-QTLs are an important force in gene regulation during the immune response.

Keyphrases: Genetic Variation, Splicing, Immune Response, Macrophages, QTL, RNA Processing
Prédiction et visualisation de la réactivité chimique des ARN. 
Proposition d’un modèle basé sur la réactivité : 
des cycles minimaux et des sous-structures composées de ces cycles

Measuring the chemical reactivity of a nucleotide within a sequence allows to infer the local conformation of a nucleotide most of the time. The simplest interpretation of the local conformation of a nucleotide is by the terms paired or non-paired. However, these two states do not fully explain the reactivity of nucleotides in chemical probing experiments. Currently, the RNA mapping database (RMDB) contains 136,892 sequences probed under different conditions, which provides us a relatively good data set to learn using machine learning algorithms. In my research project, I attempted to predict and understand the reactivity or non-reactivity of nucleotides of thousands of RNA obtained from RMDB. For this, I used two secondary structure RNA folding algorithms: MCFlashFold from Dr. François Major's laboratory and RNAsubopt from the Vienna package collection. The originality of my project is that it is based on two abstractions of the secondary structure called cycle and substructure.  In this thesis, I demonstrate that the majority of the discretized (high / low) reactivity values of nucleotides can be predicted, but not all. In fact, in the tested dataset, there are more predicted paired than predicted non-paired nucleotides that are reactive to 1m7. As I show here, this result can be improved by using minimum cycle instead of base pair. The newly developed interface, named RDV, allows to quickly and easily compare homolog nucleotides between RNA. (See: http://majsrv1.iric.ca:3000/RDV ).

Keyphrases: ARN, SHAPE, RMDB, RNA, Sub-structure, Secondary structure