NCube/papyrus huggingface dataset:
Synthèse et fonctionnalisation de borocyclopropanes et développement d’un procédé de synthèse de diazoalcanes non-stabilisés en utilisant la technologie en débit continu

This manuscript summarizes the work realized in the context of two major topics in Pr. Charette laboratory which are the synthesis and the functionalization of cyclopropane derivatives as well as the synthesis of diazo compounds and their utilization in subsequent reactions. The cyclopropane motif has been increasingly used in pharmaceuticals as well as in agrochemical compounds. Thereby, developments of new synthetic methodologies as well as functionalization of highly substituted cyclopropanes are relevant. To efficiently access highly substituted cyclopropanes, the development of a Simmons-Smith type borocyclopropanation using a zinc carbenoid bearing pinacol boronate function has been selected. Those borocyclopropanes can be engaged in subsequent reactions allowing the formation of new substituted cyclopropane derivatives from a common intermediate; thus creating structural diversity. Different series of borocyclopropanes coming from allylic ether and styrene derivatives have been synthesized. Nevertheless, borocyclopropanes derived from styrenes were obtained in lower yields as well as lower diastereoselectivities. Those last results have led to elaborate of a second generation of borocyclopropanation reaction, harnessing a UVA-light mediated photochemical process using continuous flow technology. This chemical process has allowed a significant improvement of yields for this transformation. Finally, the last part of this manuscript is dedicated to the development of a safe and easy access to non-stabilized diazoalkanes using continuous flow technology. This process is based on oxidation of unprotected hydrazones by an immobilized metallic oxidant in a glass column. Those diazoalkanes are directly consumed at the reactor output in subsequent reactions. Herein, the use of continuous flow technology is highly relevant by minimizing operator exposure to highly reactive as well as toxic materials such as diazo compounds.

Keyphrases: Simmons-Smith, Borocyclopropane, Simmons-Smith, Borocyclopropane, Zinc carbenoid, Photochemistry, Continuous flow, Diazo compound
À qui le crédit? Division du travail et du capital dans les collaborations de recherche

The function of scientific authorship is to assign credit and responsibility to researchers for their contribution to a piece of knowledge, thus enabling the existence of an economy of reputation economy in which researchers advance their careers by, among others, having their names associated to scientific work. This system relies on the existence of a historically clear link between authorship and contribution. However, this link is obscured by the increasingly high number of authors appearing in the bylines of scientific papers, by the fact that authorship can be given for diverse (sometimes very small) contributions, and by the subjectivity of authorship decisions. Thus, when an article is authored by several researchers, it becomes difficult to determine their respective contributions.  In certain research fields, researchers can be involved in the commercialization of research, and often patent their discoveries. Patents are thus another form of contribution which is valued in the evaluation of researchers. Unlike the heterogeneous and subjective authorship practices, inventorship is, because if its legal aspect, awarded using stricter criteria. It is reserved for individuals who designed and materialized the invention. In some cases, research may lead to both an article and a patent. The list of inventors can then, in theory, help identify the authors who have made an inventive contribution and thus provide a better understanding of the relationship between authorship and the nature of the individual researchers’ contribution to the work.  Our study compares the lists of authors and inventors of articles and patents reporting the same research. Specifically, we use linear regression to analyse the relationship between the characteristics of articles (discipline, potential impact, number of authors, interinstitutional collaboration) and the proportion of authors who also appear as inventors. In addition, we use logistic regression to determine to what extent the inventor status of authors can be predicted by their position in the byline of the paper, their role in the research, the nature of their contribution, their gender and their reputation. The results show that the average proportion of authors who are named inventors differs by discipline, is lower for research involving multiple institutions, and is higher when the article is published in a top Impact Factor journal. The results also show that the authors in the first and last positions of the byline are more often inventors than authors in other positions, that highly cited authors are more often inventors than authors with fewer citations, and that men are more often inventors than women.

Keyphrases: Collaboration, Scientific article, Patent, Authorship, Inventorship, Collaboration, Bibliometrics, Scientometrics, Scientific capital
Le papier voyageur : provenance, circulation et utilisation en Nouvelle-France au XVIIe siècle

From the 17th century until the Conquest by the British in 1759-1763, there were neither paper mills nor printing presses in New France. This meant that the paper used onsite by the Administration, the religious communities, the merchants, the notaries and the elite had to be imported. The doctoral research project covers the provenance, trade and use of paper in New France in the 17th century. As paper was not manufactured in the colony, it had to be imported. In order to answer the question of the provenance of this paper, a body of data is being created based on original 17th century documents from various archival collections located in public institutions such as Library and Archives Canada (LAC) and Bibliothèeque et Archives nationales du Québec (BAnQ) Québec and Montréal regional centres. We are also interested in religious communities’ archives such as Ursulines and Augustines in Quebec City, the Congrégation de Notre-Dame, the Jésuites and the Sulpiciens in Montréal as well as the archives of the Séminaire of Quebec City and the Baby collection from Université de Montréal, which one is used as a comparative sample. The idea of commercial routes for the exportation / importation of paper from Europe to North America in 17th century is a new research topic and to my knowledge, no other research has been conducted on the subject. Added to this, the state of commerce within Europe at that time where countries such as England, France, Germany, Holland and Spain (just to name a few) were in competition to control the Atlantic and the New World economy pose extra challenges for the researcher. Our research focus on writing paper exclusively. We examined and analyzed the following categories of manuscripts: seigneurial documents, letters regarding colonization, obligations, hiring contracts, notary minutes, commercial and financial transactions, judicial documents, and civil and military documents. I also looked at dictionaries, vocabularies, travelers’ diaries, maps, etc. The methodology used is a combination of three disciplines: the historical approach (comparison and discussion of sources), the archival approach (typology of documents) as well as elements from the information science approach (criteria of validation and reliability and method triangulation). Our research focus also on the commercial routes from the French paper mills to the Atlantic ports to supply the colonial administrators, religious communities and merchants with the paper they needed to perform their duties to better understand the metropolitan/colonial commercial ties through the study of paper exportation in the 17th century. Our last chapter study the materiality of paper as a medium containing internal information that contribute to make the medium a document in itself.

Keyphrases: paper, paper-maker, New France, 17th century, watermark, Library and Archives Canada (LAC), Papetier, Archives, Ursulines, Augustines, Congrégation de Notre-Dame, Jésuites, Sulpiciens
Caractérisation du microbiote tumoral influençant la réponse immunitaire et de son importance pronostique dans le cancer du sein

Many biological processes, including the establishment of a competent immune system, are dependent on the human-associated bacteria which constitute our microbiota. The bacterial species equilibrium is primordial since an imbalance is observed in several inflammatory diseases, including cancer. Such perturbations in the gut can even modulate the effectiveness of certain immunotherapies or chemotherapies. Recent studies also indicate that bacteria can be found inside solid human tumors, including in breast cancer.  We hypothesized that the presence of bacteria in tumors could play a role in the progression of breast cancer, with or without treatments. Our objectives were to optimize a bacterial quantification method by qPCR, to verify the presence of bacteria in tumors from a cohort of patients with breast cancer and to determine if our results could have a clinical significance.  Following the validation of the quantification technique, we have shown that bacterial equivalents are detectable in several tumor fragments from our cohort and are found at higher levels in the normal tissue adjacent to these tumors. We have also shown that the detection of bacteria in tumors is associated with an enhanced patient survival. Furthermore, this improvement of survival in the presence of bacteria preferably concerns grade III or Luminal HER2+ tumors.  We believe that a comprehensive study of the tumor microbiota and its associated anti-tumor immune response will help define new therapeutic targets and lead to improvements of current breast cancer treatments.

Keyphrases: Microbiote tumoral, E. coli, Validation technique, Breast cancer, Tumor microbiota, Bacterial infiltration, quantitative Polymerase Chain Reaction (qPCR), Bacterial quantification, 16S RNA gene, Technical validation, Clinical characteristics, Survival analysis
Mesure de l’activité de la lécithine : cholestérol acyltransférase (LCAT), une enzyme impliquée dans la biogenèse des HDL, par chromatographie liquide - spectrométrie de masse (LC-MS)

The lecithin: cholesterol acyltransferase (LCAT) is the only plasmatic enzyme capable of esterifying cholesterol molecules present in circulating plasma lipoproteins, a function critical for high-density lipoproteins (HDL) biogenesis and reverse cholesterol transport. Its activity is defined as the fractional esterification rate of free cholesterol of HDL molecules (FERHDL), which is a potential biomarker of cardiovascular risk. The cholesterol esterification reaction is initiated by the hydrolysis of a fatty acid esterified to a phosphatidylcholine molecule (PC) and its subsequent transfer on the hydroxyl group of free cholesterol, resulting in the synthesis of a cholesteryl ester (CE) and a lysophosphatidylcholine (LPC). The objective for this project was to make the proof of concept of a novel method of LCAT activity measurement by liquid chromatography – mass spectrometry (LC-MS), which allows simultaneous identification and quantification of each substrates and products of the LCAT reaction. With this method, FERhdl was measured as with the standard enzymatic method (reference method for measurements of free cholesterol), but changes in specific lipid species was also evaluated. For example, a couple LPC were good candidates as markers of LCAT activity, as their abundance was augmented by at least 40% after incubation of plasma. LCAT activity was also measured in human plasma spiked with different concentrations of recombinant human LCAT and the 4 and 8 μg/mL doses were enough to measure significant differences from the native plasma in 5 lipid species: LPC(16:0), (LPC(18:0), PC(14:0|18:2), PC(16:0|16:1) and PC(16:0|18:0) . Finally, LCAT activity analysis in human plasma samples from the Montreal Heart Institute’s Biobank (50 controls and 50 cases which had a coronary atherosclerotic disease) allowed us to study the modulation of lipids in a more heterogeneous samples than pooled plasma samples. Of these lipids, PC(34:3) was lowered more following incubation of plasma in cases than in controls, making it a candidate biomarker for LCAT activity. In conclusion, application of LC-MS to the study of LCAT gave us a better understanding of lipid changes during plasma activation and opens the way to biomarker discovery.

Keyphrases: HDL, LC-MS, Phospholipides, MCAS, Lecithin: cholesterol acyltransferase, Mass spectrometry, Cholesterol, Lipidomics, CVD
Étude descriptive sur les crises de colère chez les enfants autistes d’âge préscolaire

Autistic temper tantrums are a common challenging behavior that induces parental stress and day care exclusion, and are targeted by intensive behavioral interventions. However, few studies have investigated whether they are qualitatively and quantitatively different from those arising in other conditions occurring at the same age, and from which autism has to be distinguished. Tantrums’ frequency, duration, triggering factors, behavioral components, parental responses and parental perception of impact on functioning were collected. Correlations between tantrums’ and children's characteristics were also analyzed. Participants were 48 ASD preschoolers and 47 preschoolers with other neurodevelopmental conditions (mostly a language delay), aged from 2 to 5 years, and referred for a differential diagnosis. Results show that the ASD group had more frequent tantrums with no apparent trigger, had a higher proportion of tantrums triggered by expression problems, had a higher proportion of demands as a tantrum behavior, and their parents gave them what they wanted in higher proportion in response to tantrums. No other group differences in tantrum frequency, duration, impact, triggers, modulators and behaviors were found. Tantrums’ frequency was correlated to parental perceived impact in both groups. While these results have to be replicated in other outpatient children not referred for autism, they suggest that autism may not favor tantrums more than other childhood psychiatric conditions and that tantrums may not be a good clinical indicator to distinguish between autism and other neurodevelopmental disorders, but that communication may play a role in tantrums in autism. This study is also the first to include a detailed description of tantrums in a group of ASD children.

Keyphrases: Autism spectrum disorders, tantrums, temper tantrums, behavioral and emotional problems, preschoolers
Le contexte comme élément distinctif entre les intrusions normales et les intrusions anormales

Obsessive-compulsive disorder (OCD) is characterized by the presence of obsessions and/or compulsions. Historically, the content of obsessions was judged so similar to intrusions experienced by the general population that they were said to be undistinguishable. This brought the scientific community to postulate that the only difference between obsessions and intrusions lies in the way these thoughts are appraised. Another approach suggested that obsession arise from an overinvestment in the imagination and a distrust of the senses, a process called inferential confusion. Compatible with these two approaches, researchers have proposed that OCD would come from a self-vulnerability, particularly a feared self, a self someone fears being or becoming. Other than the content of obsessions, a few studies have found that obsessions occur without an environmental context justifying the obsession. This memoir proposes two studies investigating the context in which OCD related intrusions arise and associated psychological processes. The goal of the first study was to investigate the importance of context in naturally occurring intrusions in a university sample, while the second study manipulated the context of occurrence of obsessions through an experimental task to verify the importance of OCD specific psychological processes in the occurrence of out of context intrusions. For the first study, 248 university students had to name a recurring intrusion, what was the trigger of the intrusion and why it kept coming back. Participants also completed a questionnaire battery and clinicians classified intrusions given by participants on whether or not they were potentially indicative of OCD and if there were environmental proofs supporting the intrusion. Results showed that clinical judgment allowing to determine if an intrusion was relevant to OCD was strongly guided by the presence of an environmental context justifying the presence of the intrusion. Intrusions occurring without direct evidence were related to more obsessive beliefs, more inferential confusion and more self-vulnerability for people having theses thoughts. During the second study, 29 community participants had to complete a battery of questionnaire online, including an experimental task manipulating the presence of the context justifying the intrusion following a chain of event. Results showed that participants having more obsessive beliefs, more inferential confusion and more self-vulnerabilities reacted more strongly to scenarios who lacked direct justification for an intrusion. Despite reliance on a non-clinical population, theses studies show that the context of occurrence of intrusions is important in research for OCD. Other studies conducted on OCD suffering participants are needed to confirm these studies.

Keyphrases: TCC, obsessive-compulsive disorder, OCD, inferential confusion, obsessive beliefs, cognitive-behaviour therapy, CBT, inference based approach, context, egodystonicity
Impact de la mutation du gène LRPPRC sur la vulnérabilité induite par un stress inflammatoire et nutritionnel in vitro et sur la morphologie cérébrale ex vivo

Leigh syndrome French Canadian Type (LSFC) is a rare disease caused by mutations in the LRPPRC gene (leucine-rich pentatricopeptide repeat motif containing). LSFC is primarily characterized by a tissue-specific deficiency (brain and liver) in cytochrome c oxidase (COX) and potentially fatal crises of lactic acidosis. These crises, which cause the death of 80% of children affected before the age of 4, are triggered, among others, by infection or inflammation and nutritional overload. To date, no treatment exists to prevent these crises. This study aims to characterize the impact of an inflammatory and nutritional stress (SIN) on cell death and mitochondrial function in skin fibroblasts of patients with LSFC, as well as the cerebral morphology of mouse with a liver specific knockout of LRPPRC (HKO). We assume that the LRPPRC mutations: 1) Leads to increased SIN susceptibility, which is associated with mitochondrial dysfunction and increased cell death; 2) Exerts a cerebral impact in the HKO mouse. In vitro, mitochondrial function and cell death were evaluated 24 h after SIN exposure induced by tumor necrosis factor alpha (TNF-α) and palmitate. Membrane potential (ΔΨm), reactive oxygen species (ERO) production, calcium retention capacity (CRC) and cell respiration were measured in order to characterize mitochondrial function. The impact of omega-3 fatty acids (O3), anti-inflammatory compound, on cell death and mitochondrial function was also assessed. Ex vivo, the global, neuronal and astrocytic populations were evaluated in the brains of HKO and wild type (HWT) mice. Mitochondrial dysfunction associated with LRPPRC mutations make fibroblasts less able to respond to SIN. As a result, higher rates of cell death were observed in LSFC fibroblasts. Also, O3 fatty acids exert a beneficial effect when modulating cell death and ΔΨm. Finally, liver specific knockout of LRPPRC causes neuronal loss in the brainstem of HKO mice. Our study identified cellular mechanisms involved in the pathophysiology of LSFC. The potential therapeutic role of O3 fatty acids should be considered in future research regarding the disease.

Keyphrases: LRPPRC, mitochondries, palmitate, TNF-α, inflammation, nutrition, Lactic acidosis, mitochondria, fibroblasts, omega-3
L’allaitement dans la formation initiale des futurs professionnels de la santé du Québec : parvenir à un consensus sur les objectifs de formation initiale pour améliorer les compétences en allaitement

Although exclusive breastfeeding in the first six months is recommended nationally and internationally, mothers from the Province of Quebec do not reach this goal. Undergraduate programs in health present gaps - preventing future health professionals from acquiring the skills to promote, protect, and support the breastfeeding mothers beyond the birth of their child. A common competency framework in breastfeeding, which could be used in diverse programs of undergraduate training, is often recommended. This study aimed to obtain a consensus from experts in breastfeeding and experts in medical and health science education, who come from diverse health disciplines and from Quebec, on the minimal objectives across disciplines in breastfeeding to be acquired through the undergraduate training of future health professionals. A Delphi method was used to guide and assemble the opinion of a group of experts, through three rounds, toward a final consensus. Thirty-three participants examined a preliminary list of minimal cross-cutting objectives in breastfeeding to be acquired through the undergraduate training of future health professionals. After round one, 15 of 29 objectives were validated and considered relevant for the preclinical and clinical management competency of breastfeeding. During round two, consensus was obtained for an additional objective. No consensus was obtained for the 13 remaining objectives. This study is a preliminary step prior to the elaboration of a multidisciplinary breastfeeding competency framework for all health professionals called to support breastfeeding mothers. The study will allow for the improvement of breastfeeding training, and ultimately practice. It will encourage change in the attitude of health professionals in Quebec regarding breastfeeding, which will allow them to support more adequately and more sustainably breastfeeding mothers, for the well-being of the newborn children, their mothers and the society.

Keyphrases: Delphi, Breastfeeding, Transversal objectives, Undergraduate school