NCube/papyrus huggingface dataset:
The Effects of Neuroligin-2 Absence on Sleep Architecture and EEG Activity in Mice

Sleep disorders are comorbid with most psychiatric disorders, but the link between these is not well understood. Neuroligin-2 (NLGN2) is a cell adhesion molecule that plays roles in synapse formation and neurotransmission. Moreover, NLGN2 has been associated with schizophrenia, but its implication in sleep remains unexplored. In the present thesis, the effect of Nlgn2 knockout (KO) on sleep architecture and EEG activity in mice has been investigated. Two electroencephalography (EEG) electrodes were implanted above the right hemisphere in Nlgn2 KO mice and littermates to record EEG for four consecutive days. Vigilance states (wakefulness, rapid eye movement sleep [REM sleep], non-REM sleep [NREM sleep]) were identified on 4 sec epochs and vigilance state duration was calculated. Spectral analysis was performed on epochs without artifact using a Fast Fourier Transform. Nlgn2 KO mice showed more wakefulness and less NREM and REM sleep compared to wild-type (WT) mice. The changes in wakefulness and sleep durations originated from alterations during the 12h dark period because KO mice exhibited normal sleep/wakefulness duration during the 12h light period. The relative power spectra showed a significant genotype effect for fast frequencies (25-50Hz) during all vigilance states, with KO mice having less activity than littermates. The KO mice exhibited increased spectral activity at 2-5 Hz during NREM sleep. Moreover, abnormal burst of EEG activity was identified in the KO mice during wakefulness and REM sleep. These data suggest that NLGN2 participates in the regulation of sleep duration as well as EEG activity during wakefulness and sleep.

Keyphrases: Neuroligin-2, Vigilance States, Knockout, Sleep-Wake Architecture, Power Spectra, Electroencephalogram
Co-conception d'une intervention de télésanté pour les aînés utilisateurs d'aides techniques et leurs proches aidants : perceptions des détenteurs d’enjeux

Purpose: Providing care to older adults using assistive technology (AT) can be challenging for family caregivers. MOvIT-PLUS ™ is a telehealth intervention aiming to provide remote monitoring, support and training to older adults and their caregivers after AT procurement. Objectives: To inform its development, this study identified the needs of older AT users and family caregivers related to AT procurement, and explored stakeholders’ perceptions about the proposed intervention. Methods: Based on an iterative user-centred design approach, 30 semi-structured interviews were conducted with stakeholders about their experiences with AT procurement and their perceptions of a proposed intervention. A modified content analysis approach was used, with a mix of emerging and a priori concepts. Results: Participants viewed AT procurement as an ongoing cyclical process, with potential unmet needs at key moments before and after AT procurement. AT user-family caregiver dyads’ needs focused on information, access, person-context match, training and support with ATs. While participants felt there were accessibility, self-efficacy and efficiency benefits to the proposed intervention they also identified potential implementation and sustainability barriers. As stated by stakeholders, AT telehealth interventions dedicated to family caregivers should ensure systematic and tailored follow-up while integrating some form of human support. Conclusion: Our results will guide the prototype design of the proposed intervention towards a graded support approach, empowering AT users and family caregivers to resolve AT-related challenges.

Keyphrases: Aide technique, Assistive technology, Caregiver, Telehealth, Telerehabilitation, Aged, Aging, Disabled Persons, Information and communication technologies
Development of an Awake Behaving model for Laser Doppler Flowmetry in Mice

Whilst the brain only constitutes 2% of total body weight in humans, it exhibits the highest metabolic activity in the body, and as such is a highly vascularized organ.  In fact, regional blood supply within the brain is strictly modulated through a fundamental process termed neurovascular coupling (NVC), which couples local metabolic needs with cerebral blood flow [1, 2]. A wide array of optical imaging studies in rodents has enhanced our understanding of NVC under physiological and pathological conditions. Nevertheless, these studies have been performed either under anesthesia, or in the awake mouse using restraint to prevent head-motion during image acquisition. Both anesthetics and restraint-induced stress have been clearly shown to alter cerebral hemodynamics, thereby potentially interfering with the obtained results [3, 4]. Hence, it is essential to control for these factors during future research which investigates the neurovascular response. In the present study, we have developed a new apparatus for awake optical imaging, where the mouse is head-restraint whilst allowed to walk, run or rest on an inclined wheel. In addition, we have tested several habituation protocols, according to which the mouse was gradually trained to tolerate head-restraint, in order to minimize the stress experienced during imaging sessions. Lastly, we have, for the first time, sought to validate the efficiency of these habituation protocols in reducing stress, by measuring the evolution of plasma corticosterone levels throughout the study.  We noted that the mice had quickly adapted to running on the wheel, and that the overt signs of stress (struggling, vocalizations and urination) were clearly reduced within two habituation sessions. Nevertheless, corticosterone levels were not significantly reduced in habituated mice, relative to naïve mice that were restrained on the wheel without prior training (p > 0.05).  This project highlights the necessity for a quantitative measure of stress, as a reduction in observable behaviors such as agitation or struggling may be indicative not of lower stress, but rather, of behavioral despair. Further research is needed to determine whether head-fixation during optical imaging in mice can be achieved with lower stress levels, and if restraint-induced stress using our apparatus is associated with changes in the hemodynamic response.

Keyphrases: Anesthesia, Cerebral blood flow, Corticosterone, Mice, Neurovascular coupling, Optical imaging, Stress
Exploration of the Cerebral Dysfunctions Induced by Arterial Rigidity and/or the Overexpression of TGFβ in a Mouse Model

Introduction: Alzhemer’s disease (AD) and vascular dementia (VaD) is multifaceted with multiple cerebrovascular deficits and not limited to the amyloidβ (Aβ) pathology. Cerebral modifications include changes to vascular structure, which can be reproduced in transgenic mice overexpressing transforming growth factor β1 (TGFβ1), a cytokine found in increased quantities in brains of AD and VaD patients. The mouse model overexpressing TGFβ demonstrates a chronically compromised cerebral circulation, which may precipitate cognitive deficits if combined with other risk factors of cognitive decline, such as arterial rigidity. Objective: To determine whether arterial rigidity induced by calcification will provoke cerebrovascular dysfunctions in the TGFβ mouse and trigger cogitive deficits. Methodology: We tested whether arterial rigidity induced by calcification of the right carotid artery trigger deficits in memory and learning in mice overexpressing TGFβ1 and their wild type litermates in a set of young and a set of aged mice. Spatial memory and memory consolidation were studied via the Morris water maze (MWM) and novel object recognition (NOR) at 1-, 2- and 4-months followin surgery to induce arterial calcification. Results: No significant difference was observed between all groups in the NOR test or the spatial learning of MWM (1-, 2- and 4-months post-surgery). For the memory consolidation tests of the MWM, young TGF mice with calcification showed significance at 4-months post-surgery (p <0,05) while TGF mice without calcification failed to demonstrate cognitive deficits. Conclusion: These results suggest that arterial calcification and overexpression of TGFβ1 may act in a synergistic manner to trigger cognitive deficits. Therefore, these two pathways may constitute possible therapeutic targets for prevention of dementia. Keywords : TGFβ, arterial rigidity, dementia, Alzheimer, vascular dementia, Morris water maze, calcification, cerebral dysfunction, neurovascular unit

Keyphrases: TGF beta, behavioral testing, Morris Water Maze, Neurovascular coupling, Alzheimer's disease, Vascular dementia, Dementia, Neurovascular unit, Mouse model, Oxidative stress, Gliosis, Novel object recognition, Cerebral dysfunction, Calcification, Arterial rigidity, TGFβ, Alzheimer
The Effect of Resveratrol on the Hyperproliferation of Vascular Smooth Muscle Cells from Spontaneously Hypertensive Rats : Molecular Mechanisms

Vascular remodeling due to the hyperproliferation and hypertrophy of vascular smooth muscle cells (VSMCs) is central in the development of hypertension. VSMCs from spontaneously hypertensive rats (SHR) exhibit hyperproliferation and overexpression of cell cycle proteins. Resveratrol, a natural polyphenolic compound found in the skin of grapes, is implicated in several vasoprotective effects. Resveratrol has also been reported to attenuate angiotensin II-induced VSMCs proliferation. However, it was not elucidated if resveratrol could also inhibit the hyperproliferation of VSMCs from SHR. The present study was undertaken to investigate if resveratrol could attenuate the hyperproliferation of VSMCs and explore the underlying molecular mechanisms responsible for this effect. Methods: For this study, aortic VSMCs from 14-week-old SHR and Wistar-Kyoto (WKY) rats were used. The proliferation of VSMCs was determined by [3H] thymidine incorporation and the levels of proteins were determined by Western blotting techniques. Results: VSMCs from SHR exhibit a hyperproliferation which was attenuated by resveratrol. The overexpression of cyclin D1, cyclin E, cyclin dependent kinase 4 (CDK4), cyclin dependent kinase 2 (CDK2), phosphorylated retinoblastoma protein (pRb), Giα-3, Giα-2 proteins and enhanced phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) and AKT in VSMCs from SHR were attenuated by resveratrol. Furthermore, resveratrol also inhibited the increase of the superoxide anion, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, overexpression of NADPH oxidase 2 (NOX2)/NADPH oxidase 4 (NOX4) and P47phox proteins, and the increased phosphorylation of epidermal growth factor receptor (EGF-R), insulin-like growth factor 1 receptor (IGF-1R), and c-Src to control levels. These results suggest that resveratrol through the inhibition of reactive oxygen species (ROS) and ROS-mediated transactivation of growth factor receptors, c-Src, mitogen-activated protein kinases (MAPK)/Phosphoinositide-3 kinase (PI3K), attenuates the overexpression of Giα and cell cycle proteins and results in the attenuation of hyperproliferation of VSMCs from SHR.

Keyphrases: Hypertension, Resveratrol, VSMCs proliferation, Cell cycle proteins, MAPK, PI3K, Giα proteins, Oxidative stress, SHR, Growth factor receptors, c-Src
Metabolic Engineering to Improve Biohydrogen Production by Rhodobacter capsulatus JP91

Energy demand is increasing day by day, resulting in global attention towards alternative eco- friendly fuels. Biohydrogen is considered the most promising energy carrier to replace conventional fossil fuels because its production and combustion is not harmful to the environment. Biological hydrogen production is an alternative method for hydrogen production, by which hydrogen is produced under mild conditions, making it environmentally friendly. Photo- biological hydrogen production by purple non-sulfur photosynthetic bacteria is a promising process in which bacteria can capture light energy to drive H2 production with their N2ase system. Some metabolic pathways, such as CO2 fixation and PHB biosynthesis, compete with nitrogenase for electrons (reducing equivalents). Recently, in attempts to improve the yield of H2, metabolic engineering has been applied to increase electron flow to N2ase. The purpose of the present study was to improve the yield of photosynthetic H2 production by Rhodobacter capsulatus JP91 using a metabolic engineering approach. The hypothesis was that inactivation of PHB synthase (phbC) would block PHB biosynthesis, thus directing more electron flux towards nitrogenase to catalyze increased H2 production. In previous studies, PHB synthase mutants were developed in other photosynthetic bacteria, including R. sphearoides and Rhodopseudomonas palustris but not Rhodobacter capsulatus. In this study, a new doubly mutated R. capsulatus strain RS15 (hup‾, phbC‾), a derivative of R. capsulatus JP91 (hup‾) was created. The results show that the newly created strain, R. capsulatus RS15, could grow in different carbon and nitrogen sources. This mutant has a long lag phase. However, once it reached log phase, growth was similar to the parental strain. From hydrogen production studies, the new developed strain RS15 is able to convert acetate, lactate, and glucose to hydrogen. Acetate was shown to be the best carbon source for H2 production by RS15 but not for its growth. Overall, R. capsulatus RS15 (hup‾, phbC‾) seems to be a promising candidate for use in two - stage hybrid systems since the main dark fermentation effluents are acetate and butyrate. Such a process could potentially make biohydrogen production technology feasible on an industrial scale.

Keyphrases: R. capsulatus JP91, R. capsulatus RS15, Photofermentation, Polyhydroxy butyrate, PHB synthase, Biohydrogen production, Metabolic engineering, Purple none sulfur bacteria
Déterminants virologiques de la discordance entre la biopsie diagnostique du col et l’histologie finale au traitement

Introduction: A persistent infection by high-risk HPV can cause high-grade cervical lesions (HSIL).  Women diagnosed by biopsy-proven HSIL undergo treatment by conisation (LEEP). LEEP can confirm HSIL or may have normal/LSIL pathology on treatment histology. Those women were treated unnecessarily. This discrepancy can be attributed to spontaneous clearance of HSIL, or errors in initial pathology readings. Objectives: To investigate if virus-related variables are associated with normal/LSIL LEEP pathology after an HSIL biopsy (discrepancy). Methods: CoHIPP is a randomized trial conducted in 13 colposcopy centers across Canada, comparing follow-up strategies after HSIL treatment. Out of women in CoHIPP, we selected 355 cases of discrepancy and matched them with 355 controls. We conducted conditional univariate logistic regression and univariate analysis to assess the association between clinical variables and viral variables (genotype, viral load and polymorphism). Genotype was obtained by Hybrid Capture 2 and Linear Array, viral load by real time PCR and polymorphism by sequencing. Results: Cases and controls did not differ in terms of age and delay between diagnostic and treatment. The absence of HR-HPV at baseline (treatment) was significantly associated with an increased risk of discrepancy (OR: 23,60 95% CI: 9,83-74,03). The only HPV genotypes associated with the lowest risk of discrepancy were types 16, 31, 33 or 52. HPV 16 (compared to no HPV or low risk HPV) had the strongest association against discrepancy. Viral load and polymorphism analysis were not good predictors of discrepancy.  Discussion/Conclusions: Future research should investigate the use of generic HR-HPV testing pre-treatment to identity women with HSIL biopsy who could be safely followed-up instead of being treated.

Keyphrases: LEEP, Cervical conization, HPV, High-grade squamous intraepithelial lesion, LSIL, HSIL
Knee gait kinematics : describing a normal cohort

Introduction:  The gait cycle has been studied by many disciplines. Despite multiple studies, our current understanding of the gait cycle does not allow us to model femoro-tibial kinematics in a clinically relevant manner. The primary objective of our study was to characterize femoro-tibial kinematics in healthy subjects using the KneeKGTM apparatus.   Materials and methods: Ninety-five patients, fifty-two females and forty-three males, without any known musculoskeletal or lower limb pathology, were recruited to participate in our study. Each patient underwent a KneeKGTM examination. All patients completed the knee injury and osteoarthritis outcome score (KOOS) and the 12-item Short Form Health Survey (SF-12) questionnaires and had full-length weight bearing (FLWB) x-rays. Gait cycle kinematics were generated in the sagittal motion, transverse rotation, and the frontal plane and were compared between men and women and between the right and left knees of the same patient. The results obtained were also correlated with the anatomic variations found in patients, which were estimated by angles measured on the FLWB x-rays.  Results: When comparing men and women, significant differences were found in the sagittal motion and transverse rotation planes and in the entirety of the gait cycle in the frontal plane.  In the sagittal plane, women have greater amplitude of flexion than men during the mid-swing and terminal swing phase (0.002 ≤ p ≤ 0.05).  In the transverse plabe, more internal rotation of the knee is observed in women than in men during the entire swing phase (0.005 ≤ p ≤ 0.05). In the frontal plane, more abduction occured in women compared to men throughout the entire gait cycle (0.001 ≤ p ≤ 0.002). When comparing the right and left knees, significant differences were only found in the frontal plane during which the right knees were more in adduction than the left knees during the entire swing phase (0.005 ≤ p ≤ 0.04). No meaningful correlations could be made between radiographic hip-knee-ankle (HKA) ankle and abduction-adduction angles during the gait cycle (-0.40 ≤ r ≤ -0.42, p<0.001).   Discussion-conclusion: The results of our study contribute to better understanding the kinematics of the gait cycle and foster the notion that cohorts should be divided for gender to account for gait differences in the frontal plane. Furthermore, static alignment does not appear to correlate with dynamic alignment.

Keyphrases: knee, movement, KneeKG, gait, kinematics, normal
Dealing with heterogeneity in the prediction of clinical diagnosis

Computer assisted diagnosis has emerged as a popular area of research at the intersection of medical imaging and machine learning. Medical data are very heterogeneous in nature and therefore require careful attention when one wants to train prediction models. In this thesis, I explored two sources of heterogeneity, multisite aggregation and clinical label heterogeneity, in an application of magnetic resonance imaging to the diagnosis of Alzheimer’s disease. In the process, I learned about the feasibility of multisite data aggregation and how to leverage that heterogeneity in order to improve generalizability of prediction models. Part one of the document is a general context introduction to Alzheimer’s disease, magnetic resonance imaging, and machine learning challenges in medical imaging. In part two, I present my research through three articles (two published and one in preparation). Finally, part three provides a discussion of my contributions and hints to possible future developments. The first article shows that data aggregation across multiple acquisition sites incurs some loss, compared to single site analysis, that tends to diminish as the sample size increase. These results were obtained through semisynthetic Monte-Carlo simulations based on real data. The second article investigates the generalizability of prediction models with various cross-validation schemes. I showed that training and testing on the same batch of sites over-estimates the accuracy of the model, compared to testing on unseen sites. However, I also showed that training on a large number of sites improves the accuracy on unseen sites. The third article, on clinical label heterogeneity, proposes a new framework where we can identify a subgroup of individuals that share a homogeneous signature highly predictive of AD dementia. That signature could also be found in patients with mild symptoms, 90% of whom progressed to dementia within three years. The thesis thus makes new contributions to dealing with heterogeneity in medical diagnostic applications and proposes ways to leverage that heterogeneity to our benefit.

Keyphrases: Machine-learning, Alzheimer, Early prediction, Heterogeneity, Multisite aggregation, Multisite
Contributions à la fusion de segmentations et à l’interprétation sémantique d’images

This thesis is dedicated to study two complementary problems, namely the fusion of image segmentation and the semantic interpretation of images. Indeed, at first we propose a set of algorithmic tools to improve the final result of the operation of the fusion. Image segmentation is a common preprocessing step which aims to simplify the image representation into significant and spatially coherent regions (also known as segments or super-pixels) with similar attributes (such as coherent parts of objects or the background). To this end, we propose a new fusion method of segmentation in the sense of the Global consistency error (GCE) criterion. GCE is an interesting metric of perception that takes into account the multiscale nature of any segmentations of the image while measuring the extent to which one segmentation map can be viewed as a refinement of another segmentation. Secondly, we present two new approaches for merging multiple segmentations within the framework of multiple criteria based on a very important concept of combinatorial optimization ; the multi-objective optimization. Indeed, this method of resolution which aims to optimize several objectives concurrently has met with great success in many other fields. Thirdly, to better and automatically understand the various classes of a segmented image we propose an original and reliable approach based on an energy-based model which allows us to deduce the most likely classes by using a set of identically partitioned segmentations (in the sense of a certain criterion) extracted from a learning database (with pre-interpreted classes) and a set of semantic likelihood (energy) terms

Keyphrases: Fusion, Segmentation ensemble, Global consistency error (GCE), Penalized likelihood model, Multi-objective optimization, Decision making, Semantic image segmentation