NCube/papyrus huggingface dataset:
Étude de l'endocytose du récepteur PD-1 dans les lymphocytes T humains

PD-1 (Programmed Cell death protein -1) is a co-inhibitory receptor expressed on the surface of activated T cells. It plays an important role in maintaining peripheral tolerance and protecting against autoimmune and inflammatory diseases. However, permanent expression of PD-1 and its ligands PD-L1/ PD-L2 (PD-Ls) disrupts the immune response against pathogens and tumor cells.       Immune checkpoint blockade (ICB) targeting the PD-1/PD-Ls axis has revolutionized the treatment of many cancers. Nivolumab (nivo) and pembrolizumab (pembro) are two anti-PD-1 monoclonal antibodies (mAb) that block the interaction between PD-1 and its ligands. They have shown promising results in the treatment of multiple types of cancers such as melanoma, non-small cell lung cancer, renal cell carcinoma, etc.       Surprisingly, despite the success of anti-PD-1 in cancer immunotherapy, no-one has defined the destiny of surface PD-1 following antibody binding. Therefore, the objective of my master thesis was to define the fate of surface PD-1 following antibody binding and whether different anti-PD-1 Abs in the clinic differ in their ability to induce PD-1 endocytosis.        The study of PD-1 endocytosis was performed on human T lymphocytes obtained from peripheral blood of healthy donors and activated with anti-CD3/anti-CD28 Ab or concanavalin A to express PD-1 receptor. Data analysis by flow cytometry showed that following anti-PD-1 Ab binding, 50% of PD-1 becomes endocytosed by 30min.       In addition, we found that the PD-1 receptor is internalised upon its engagement with nivo and pembro and that most of the receptor is endocytosed within 30 min. However, 32 to 50% of the receptors are resistant to endocytosis.       The comparative analysis of nivo and pembro has revealed a statistically significant difference (p=0.03) between the internalisation rate of the PD-1/nivo complex versus PD-1/pembro (46% versus 25% by 30min, respectively). Even at high concentrations of pembro, nivo induces better internalization of PD-1, suggesting that nivo could be more effective than pembro.    Our study showed for the first time that ICB involves not only in the blockade of PD-1/PD-Ls interaction, but also in the endocytosis of PD-1 receptors from the surface of human T-cells, which differs between nivolumab and pembrolizumab. These results could be exploited to increase the therapeutic potential of nivolumab and pembrolizumab in cancer treatment.  Keywords: PD-1 receptor, PD-1 ligands, T lymphocytes, Immune checkpoint blockade, Anti-PD1 antibodies, Nivolumab, Pembrolizumab, Endocytosis, Cancer

Keyphrases: Endocytose, Nivolumab, Pembrolizumab, PD-1 receptor, T lymphocyte, Immune checkpoint blockade, Anti-PD-1 antibodies
Les tests prénataux : enjeux éthiques et politiques liés à la poursuite de grossesse après détection d’aneuploïdie fœtale

This thesis examines the practice of prenatal screening and prenatal diagnosis (henceforth “prenatal testing”) from two angles. Firstly, following a brief introduction to provide context, I present a framework analysis of the factors that influenced the implementation of the Trisomy 21 Prenatal Screening Program of Québec (T21PSPQ). Using governmental literature, I demonstrate how a combination of political, ethical and social pressures led to the imperative of the T21PSPQ. I then present a scoping review of primary empirical qualitative research regarding the experiences of continuing a pregnancy affected by fetal aneuploidy, including trisomy 21. The main findings of this review suggest the ‘rhetoric’ of choice is not always demonstrated in cases where prospective parents bring to term a fetus diagnosed with aneuploidy. The results of this work are then discussed through the Foucauldian concept of biopolitics, where norms and normalization are the principal forms of social and political regulation. Finally, recommendations for research and practice are offered, mainly the need to document the lived experience of those participating in prenatal testing and to incorporate those findings into policy making and into education for health care professionals.

Keyphrases: Framework analysis, Scoping review, Down syndrome, Fetal aneuploidy, Lived experience, Pregnancy, Prenatal diagnosis, Prenatal screening, Prospective parent, Public policy, Reproductive autonomy, Trisomy 21
La signalisation BMP9 maintient l’intégrité endothéliale et prévient la perméabilité vasculaire rétinienne hyperglycémique

A quiescent retinal vascular endothelium is essential for the supply and maintenance of tissue homeostasis to ensure proper visual function. Chronic hyperglycemia in diabetes can lead to multiple complications related to several structural and functional changes in the endothelium, characterized by  unstable and hyperpermeable vessels resulting in an inadequately perfused retinal tissue. These alterations are encountered in the pathophysiology of diabetic macular edema (DME), which affects more than a quarter of diabetics. Inhibition of the vascular permeability factor VEGF-A has revolutionized the treatments of DME but is associated with non-negligible side effects related to their non-specific action combined with an incomplete understanding of the mechanisms regulating vascular permeability. Specific endothelial targeting aiming to recover quiescence and reducing hyperpermeability could provide new therapeutic tools for the treatment or prevention of DME. BMP9 (Bone morphogenetic protein 9), which is produced by the liver, is known as a vascular quiescence and stability factor as well as for its effects on glucose homeostasis. Since these aspects are poorly documented in a diabetic context, we investigated BMP9’s  capabilities on endothelium stabilization and its paracrine/autocrine effects on hepatic gluconeogenesis. In our studies, we found that the canonical  BMP9/Smad1,5,9 signaling, via its physiological Alk1 endothelium-specific receptor, was deficient in a murine model of diabetes, which exacerbates retinal endothelial hyperpermeability. In contrast, adenoviral overexpression of BMP9 recovers physiological permeability, which was primarily associated with the enhancement of interendothelial junctions by limiting the action of VEGF. In addition, we found that BMP9 improves glycemic control in diabetic mice by inhibition of hepatic gluconeogenesis via the non-canonical ALK3/FOXO1 pathway. Fundamentally, this work highlights new insights of the mechanisms governing endothelial permeability in a diabetic context, providing a therapeutic alternative against DME.  Regulation of retinal permeability by BMP9 occurs on several levels, indirectly, through glycemic control, and directly through the junctional solidification of the hyperglycemic retinal endothelial barrier, thus rehabilitating the quiescence and stability of the physiological endothelium.

Keyphrases: BMP9, VEGF, Diabetes, Hyperglycemia, Vascular permeability, Junctions, Macular edema, Macular edema
Le gayle dans la communauté queer et coloured de Cape Town : idéologies linguistiques, performances et identités

This thesis focuses on sociohistorical transformations of Gayle, a linguistic variety consisting of an often-improvised lexical repertoire superimposed upon either Afrikaans or English in South Africa. Based on six months of fieldwork in Cape Town, this thesis draws on rich (meta)linguistic data drawn from participant-observation, as well as individual and group interviews within the coloured community. I critique an 'anti-language' (Halliday 1976) perspective, wherein Gayle is seen as uniquely anchored to a closed community for which it serves as an exclusive, ingroup code. Rather, I suggest that Gayle is best understood when approached as the register of a community of practice (Eckert & McConnell-Ginet 2003). My interviews expose the historical and 'enregistered' association of Gayle with the racialized, gendered and sexualized ‘characterological figure’ (Agha 2007) of the effeminate coloured gay man or 'moffie'. This association serves as a backdrop to contemporary anxieties about the ways in which Gayle is mapped onto speakers’ social identities and perhaps shows the respondent’s consciousness that these formulations ‘erase’ (Irvine and Gal 2000) non-canonical users of Gayle. Moving beyond lexical description, I suggest overlaps between the semantic and pragmatic features of the variety, both strategically deployed to invoke evanescent characteristics and social attributes in interaction (cf. Butler 1990). Just as elements of the Gayle repertoire do not code for fixed semantic meanings – but are rather contingent, discursive achievements – Gayle does not 'code for' static social identities. Instead, it achieves group belonging in interaction through legitimate use and mutual comprehension of creative linguistic 'deviations' and 'subversions'

Keyphrases: Gayle, Sexuality and language, Speech register, Community of practice, Post-colonial linguistics, South Africa, Queer linguistics, Lavender linguistics
Legacies of the modern movement : intraurban freeways and the renewed role of heritage

This paper explores the changing definition of heritage in recent years and its potential application to aging automotive infrastructure in urban settings across the globe. The proposed new approach to heritage, unlike a conventional understanding of the term, which emphasizes aesthetic and historical attributes, acknowledges a wider range of values that a structure can possess. This range includes social and ecological values either existing or added through adaptation. This broader understanding of heritage reflects current discussions about a paradigm shift in heritage conservation, which is rooted principally in English scholar Graham Fairclough's writings and in UNESCO's Recommendation on the Historic Urban Landscape. These theoretical developments embrace a holistic view of heritage, with the totality of the inherited urban environment potentially exhibiting value. Based on these principles, the term “heritage” applies not only to that which is rare, old, or aesthetically pleasing, but also to that which is commonplace, recently built, and unappealing. This definition suggests that not only buildings and monuments but also infrastructure can constitute heritage, as it can be associated with a broad range of values. This concept is put to the test through three case studies of aging intraurban expressways in three dense urban environments: central Seoul (Korea), Seattle (USA), and São Paulo (Brazil). Through examining these cases, this thesis attempts to deduce the role of this new heritage perspective in dealing with aging automotive infrastructure in cities.

Keyphrases: Conservation, Infrastructure, Heritage, Values, Landscape, Historic Urban Landscape
Les expériences photographiques formatrices de Melvin Charney : contours et contributions d’un outil de la pensée en architecture

Architects and artists used photography as a tool for creating and analyzing architecture. This postulate is the basis of this thesis project whose general purpose is the contribution of photographic experiences in architectural thinking. Here, the notion of photographic experience is used in a sense comparable to the artistic experience defined by the philosopher John Dewey. Dewey understood the experience of an art as an educational tool to learn to think and develop a critical sense. Experience was for him a way to aesthetically approach the world and understand it outside a strictly scientific framework. If historians have already traced the history of photographic experiments of architects, including Mies van der Rohe, Le Corbusier and Stirling and, also, have identified the roles of photography in the construction of their respective architectural thinking, the origins of photographic experiments by renowned architect, artist and theorist Melvin Charney and their contributions in the progressive construction of his thought have not been clearly circumscribed. The specific purpose of this thesis is, consequently, to clarify the surrounding of Charney's photographic experiences and offer a broader understanding of their contributions in the history of his architectural thinking.  Charney's motifs and influences in his photographic experiments and reflections on photography were identified through an investigation into his personal archives held at the Canadian Center for Architecture and the analysis of the content of documents that he produced before and during his studies in architecture. In particular, ramifications in Charney's work of photographic experiments of Laszlo Moholy-Nagy, Erich Mendelsohn, James Stirling, Walker Evans and Edward Ruscha have been revealed. Finally, partly thanks to the contributions of his photographic experiences, Charney learned from the built environment and to think about the built environment. More specifically, this study demonstrates that working with photography Charney has learned to analyze what is already there to better understand the origin of built forms. Also, photography was for him a tool for the critical figuration of the built environment, for the re-evaluation of the bases of the architectural discipline and, moreover, for the critical teaching of architecture. More broadly, this thesis contributes to the knowledge of artistic production as a research strategy in the disciplines of architecture and environmental design and to the essential recognition of other experiences, between art and architecture, as catalyst of a critical architectural thinking.

Keyphrases: architecture, Melvin Charney, Photography, Built environment, Artistic experience, Architectural thinking, Critical thinking, Critical figuration, Visual approach
Le triage et le transfert de patients aux soins intensifs : une revue systématique des critères de sélection

Context: Intensive care bed unavailability negatively affects patients' outcomes. Strategies that reduce inefficient use of resources and reduce unavailability may increase quality and accessibility of critical care. As advocacy for regionalization of critical care resources increases, there is a need for agreed triage and transport criteria. However, outside of the trauma population, such agreed criteria and recommendations are lacking. Objective: We aimed to identify and appraise articles defining criteria used to prioritize or withhold a critical care admission. Methods: We undertook a systematic review according to PRISMA guidelines. Relevant articles were identified through searches of PubMed, Embase, Medline, EBM Reviews, CINAHL Complete from inception until November 8th, 2016. We also undertook searches through gray literature as well as a manual review of references. We then assessed the quality of identified articles through an appraisal scale we developed. Finally, we extracted and evaluated all criteria within the articles and grouped them by theme. Results: A total of 5818 abstracts were identified. After screening, we reviewed 416 articles in full and 129 articles met study criteria. These articles were mainly original research (34%), guidelines (26%) and reviews (21%). Amongst them, we identified 200 unique triage and transport criteria. Most articles were published in the United States (43%) and highlighted exclusion criteria (71%) rather than a prioritization mechanism (17%). Very few articles pertained to transport of critically ill patients (4%). We classified criteria as they related to one of four emerging themes: patient, condition, physician and context. The most commonly found triage criteria was patient preference followed by physician’s assessment that the patient was too well to benefit from ICU admission. Conclusion: A systematic review aimed at identifying triage and transport criteria used to prioritize or exclude certain patient populations under different settings helped to generate a list of 200 criteria classified within 4 themes. Despite its limitations, this study may help clinicians and decision makers devise local, regional or national ICU triage criteria. It also identifies gaps in knowledge where future clinical research yielding specific and measurable criteria tailored to clearly defined patient populations may help to decrease ICU triage variability.

Keyphrases: triage, transport, transfert, admission, transfer, criteria, critical care, ICU admission, health policy
Activité éducationnelle pour outiller les assistantes infirmières-chefs à stimuler le raisonnement clinique chez les infirmières en soutien à domicile

Context: The assistant head nurses in home support participate in the professional development of the nurses in their teams with a view to promoting their professional autonomy. They also play a role in respecting the quality and safety of patient care. On balance, they provide support to nurses in their areas. Note that home care represents a daily challenge for nurses: on the one hand, because of their complexity in terms of clientele and the variety of care offered; on the other hand, due to the precariousness of the nursing resources available. Complexification of care requires that home care nurses use more clinical reasoning, especially since a lack at this level can compromise patient safety and lead to poor clinical results. It is therefore important to promote the development of clinical reasoning for nurses in home care. The purpose of this internship was to develop and test, with assistant head nurses, an educational activity promoting the deployment of strategies to stimulate clinical reasoning among nurses in home care. Internship intervention: An educational activity made up of three workshops on strategies for stimulating clinical reasoning, including questioning and think aloud, as well as individual coaching sessions were given to nine assistant head nurses from the home care of an integrated health and social services center located in the Metropolitan Community of Montreal. This educational activity is inspired by active learning theories and best practice guidelines from the Registered Nurse of Ontario [RNAO] in 2012. Benefits of the internship: The results of this internship proved that the continuing education workshops on clinical reasoning were relevant for assistant head nurses. These allowed them to acquire new knowledge on how to stimulate clinical reasoning among the nurses on their teams. Coaching seems to have facilitated the transfer of this new knowledge into their practice. Finally, at the end of this educational activity, the assistant head nurses felt better equipped to stimulate clinical reasoning within their teams.

Keyphrases: Coaching, Think aloud, Assistant head nurse, Clinical reasoning, Coaching, Home support, Questioning, Think aloud
A pilot study on the Mirror Effect PLUS protocol : a
standardized and adapted facial rehabilitation for acute
Bell’s palsy

Combining early facial exercises with medication may help patients with acute Bell’s palsy recover significantly faster and better than patients treated with medication alone. To date, exercise therapy in acute Bell’s palsy consists mostly of transferring facial rehabilitation techniques that were developed for chronic Bell’s palsy, despite the differences between those stages. The aim of this pilot study was to estimate the efficacy of the Mirror Effect PLUS Protocol, the first facial rehabilitation protocol specifically designed for acute Bell’s palsy. Ten patients with acute moderate-to-severe, severe, and total Bell’s palsy were recruited and assigned randomly to the Mirror Effect PLUS Protocol group or the control group. Both groups received the recommended medications. In addition, patients in the rehabilitation group performed exercises that were completed using a computer that duplicated their healthy hemiface. Compared to controls, a greater number of patients in the Mirror Effect PLUS Protocol group presented better facial symmetry and greater satisfaction towards their facial function. There were no differences in recovery between the rehabilitation and control groups; however, for the subset of patients with severe palsy, the Mirror Effect PLUS Protocol improved and accelerated recovery. These preliminary results support the hypothesis that the Mirror Effect PLUS Protocol enhances the recovery of severe acute Bell’s palsy. However, replication of these results with larger samples is necessary. Additionally, the intervention’s precise mechanisms of action need to be investigated thoroughly to exclude the effect of spontaneous recovery

Keyphrases: Acute Bell’s palsy, Mirror effect, Facial rehabilitation, Recovery, Facial palsy, Facial expressions
Travailleurs.euses de la construction au Québec : le rôle du soutien social sur la relation entre la charge de travail et le conflit travail-famille

This study investigates the moderating effect of emotional and instrumental social support provided by supervisor, co-workers and spouses in the relationship between workload and work-family conflict (WFC) among a population of Quebec construction workers. It has already been established that workload determines WFC levels. The study findings contribute to current knowledge by understanding the effect of workload on WFC in a sector where it is highly typical. Social support is acknowledged as a resource that protects individuals from the harmful effects of work. The study also contributes to the literature in its desire to examine which of two types of social support – emotional or instrumental – is better able to mitigate the detrimental effect of workload on WFC. It also considers whether there is a differentiated impact when one of the individuals offering social support plays a leadership role. A total of 811 workers took part in this cross-sectional study and the results of multiple regression analyses confirmed that increased workload in turn increases WFC. However, the protective role of social support is not supported as a theory and the results of mediation analyses suggest instead that social support impacts WFC by reducing effect of workload, supervisor’s social support having the greatest indirect effect. Moreover, the comparison of ratios between indirect and total effect reveals that the effect of spouse’s social support on WFC goes more through a change in the perception of workload. This essay demonstrates the importance of considering emotional and instrumental social support given by supervisors, co-workers and spouses in reducing the adverse effects of workload on WFC.

Keyphrases: Construction, Work-family conflict, Workload, Social support, Construction, Industrial and organizational psychology