1,721,123 research outputs found
Periventricular remyelination failure in multiple sclerosis: a substrate for neurodegeneration
No full textIn multiple sclerosis, spontaneous remyelination is generally incomplete and heterogenous across patients. A high heterogeneity in remyelination may also exist across lesions within the same individual, suggesting the presence of local factors interfering with myelin regeneration. In this study we explored in-vivo the regional distribution of myelin repair and investigated its relationship with neurodegeneration. We first took advantage of the myelin binding property of the amyloid radiotracer [11C]PiB to conduct a longitudinal [11C]PiB positron emission tomography study in an original cohort of 19 participants with a relapsing-remitting form of multiple sclerosis, followed-up over a period of 1-4 months. We then replicated our results on an independent cohort of 40 people with multiple sclerosis followed-up over one year with magnetization transfer imaging, an MRI metrics sensitive to myelin content. For each imaging method, voxel-wise maps of myelin content changes were generated according to modality-specific thresholds. We demonstrated a selective failure of remyelination in periventricular white matter lesions of people with multiple sclerosis in both cohorts. In both the original and the replication cohort, we estimated that the probability of demyelinated voxels to remyelinate over the follow-up increased significantly as a function of the distance from ventricular cerebro-spinal fluid. Enlarged choroid plexus, a recently discovered biomarker linked to neuroinflammation, was found to be associated with the periventricular failure of remyelination in the two cohorts (r=-0.79, p = 0.0018; r=-0.40, p = 0.045 respectively), suggesting a role of the brain-cerebrospinal fluid barrier in affecting myelin repair in surrounding tissues. In both cohorts, the failure of remyelination in periventricular white matter lesions was associated with lower thalamic volume (r = 0.86, p < 0.0001; r = 0.33; p = 0.069 respectively) an imaging marker of neurodegeneration. Interestingly, we also showed an association between the periventricular failure of remyelination and regional cortical atrophy that was mediated by the number of cortex-derived tracts passing through periventricular white matter lesions, especially in patients at the relapsing-remitting stage. Our findings demonstrate that lesion proximity to ventricles is associated with a failure of myelin repair and support the hypothesis that a selective periventricular remyelination failure in combination with the large number of tracts connecting periventricular lesions with cortical areas is a key mechanism contributing to cortical damage in multiple sclerosis
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Tracking Lesion Genesis and Lesional Myelin Dynamics in Multiple Sclerosisusing Deep Learning Approaches with Biomedical Insightsand Advanced Imaging
No full textLa sclérose en plaques (SEP) est une maladie inflammatoire chronique caractérisée par la présence de lésions démyélinisantes dans le système nerveux central. Notre projet de doctorat se concentre sur l'exploration de la genèse des lésions et de l'évolution du contenu en myéline, de la démyélinisation à la réparation, chez les personnes atteintes de SEP. Pour ce faire, nous utilisons des modalités d'imagerie avancées capables de quantifier spécifiquement le contenu en myéline et nous investiguons comment l'intelligence artificielle (IA), enrichie de connaissances biomédicales, peut aider à répondre à ces questions—d'abord au sein de cohortes de recherche, puis en traduisant ces découvertes dans la pratique clinique réelle. Les mécanismes à l'origine de la naissance de nouvelles lésions à un instant précis à un endroit donné restent incertaines. Dans notre première contribution originale (Schmidt, Soulier et al., 2022), nous avons cherché à détecter automatiquement de nouvelles lésions SEP dans un cadre clinique et avons participé au défi MICCAI MSSEG II (Commowick et al., 2022). En nous appuyant sur un algorithme de type U-net généré dans ce travail, nous l'avons ensuite appliqué dans notre deuxième contribution pour étudier la formation des lésions, en nous concentrant sur la relation entre la perfusion sanguine et la dynamique de la myéline. Dans un manuscrit non publié, nous avons ainsi montré que les pré-lésions présentent une hétérogénéité dans leurs profils de perfusion, qui persiste dans le temps et est corrélée au contenu en myéline et aux changements micro-structuraux, du stade pré-lésionnel au stade prélésionnel au stade lésionnel, et y compris sur le long terme. Après avoir identifié l'apparition de nouvelles lésions, nos troisième et quatrième contributions se sont concentrées sur l'étude de leur réparation. Comprendre la démyélinisation et la réparation ultérieure nécessite un accès fiable et quantitatif au contenu myélinique des lésions dans un cadre clinique. Dans notre troisième approche (Soulier, Hamzaoui et al., 2024), nous avons démontré la faisabilité de la traduction en cartographies myéliniques à partir de séquences d'Imagerie par Résonance Magnétique (IRM) clinique, en particulier T1 et FLAIR (Fluid Attenuated Inversion Recovery), en utilisant des réseaux génératifs antagonistes conditionnels, produisant des résultats comparables à ceux générés par l'imagerie myélinique par TEP (Tomographie par Émission de Positons). Enfin, dans notre quatrième contribution (non publiée), nous avons étendu cette preuve de concept pour montrer que diverses modalités d'imagerie de la myéline peuvent être synthétisées simultanément à partir de l'IRM clinique standard en utilisant des approches d'IA générative. Nous avons confirmé la spécificité biologique des cartes multimodales de myéline synthétiques générées et testé la fiabilité de notre estimation synthétique du contenu en myéline, ainsi que des indices de démyélinisation et de remyélinisation générés, en utilisant des ensembles de données de validation externes. In fine, nous avons démontré que les profils individuels de remyélinisation synthétiques obtenus étaient des prédicteurs significatifs et indépendants de la progression de la maladie dans une cohorte de vie réelle hospitalière, démontrant ainsi la valeur ajoutée de l'implémentation de métriques myéliniques pour la prédiction des trajectoires de handicap en pratique clinique, et potentiellement un nouveau biomarqueur pour les essais thérapeutiques anciens et futurs.Multiple sclerosis (MS) is a chronic inflammatory disease characterized by the presence of demyelinating lesions in the central nervous system. Our PhD project focuses on exploring the genesis of lesions and the subsequent evolution of myelin content, from demyelination to repair, in people with MS (pwMS). To achieve this, we utilize advanced imaging modalities capable of specifically quantifying myelin content and investigate how Artificial Intelligence (AI), enriched with biomedical priors, can help address these questions—first within research cohorts and then translating these findings to real-life clinical practice. The underlying reasons for the development of new lesions at specific time points remain unclear. In our first original contribution (Schmidt, Soulier et al., 2022), we aimed to detect automatically new MS lesions in a clinical setting, and participated to the MICCAI MSSEG II challenge (Commowick et al., 2022). Building on the U-net based algorithm generated in this work, we then applied it in our second contribution to study lesion formation, focusing on the relationship between blood perfusion and myelin dynamics. In an unpublished manuscript, we showed that prelesions exhibit heterogeneity in their perfusion profiles, which persists over time and correlates with myelin content and microstructural changes from the prelesional to the lesional stage on the long term. After identifying the onset of new lesions, our third and fourth contributions focused on studying their repair. Understanding demyelination and subsequent repair requires accurate access to myelin content in a clinical setting. In our third approach (Soulier, Hamzaoui et al., 2024), we demonstrated the feasibility of translating clinical Magnetic Resonance Imaging (MRI) sequences, particularly T1 and FLAIR (Fluid Attenuated Inversion Recovery), into myelin maps using conditional generative adversarial networks, producing results comparable to those generated by myelin Positron Emission Tomography imaging. Finally, in our fourth contribution (unpublished), we extended this proof of concept to show that various myelin imaging modalities can be synthesized simultaneously from standard clinical MRI using generative AI approaches. We confirmed the biological specificity of the multimodal synthetic myelin maps generated and tested the reliability of our synthetic myelin content estimation, as well as of the indices of demyelination and remyelination generated, using external validation datasets. Ultimately, we demonstrated that the individual synthetic remyelination profiles obtained were significant and independent predictors of disease progression in a real-life cohort, demonstrating the added value of implementing a myelinic metrics for the prediction of disability trajectories in clinical practice, and opening new perspectives for regenerative research in the field of multiple sclerosis
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Imaging the neurodegenerative component of a demyelinating disorder : multiple sclerosis
No full textLa sclérose en plaques (SEP) a longtemps été considérée comme une affection inflammatoire démyélinisante de la substance blanche. (SB) Hors, de nombreuses études ont démontré l’implication extensive de la substance grise (SG). La souffrance neuronale joue un rôle majeur dans la détérioration physique et cognitive des patients atteints de SEP. Le développement de nouvelles techniques d’imagerie capables de quantifier cette atteinte neuronale est devenu crucial. Grace à la tomographie par émission de positons (TEP) et au radiotraceur [11C]flumazenil ([11C]FMZ), antagoniste du récepteur central aux benzodiazépines, nous avons quantifié de façon non-invasive la souffrance neuronale de la SG chez des patients atteints de SEP à différents stades de la maladie. Une cohorte de 18 patients atteints de SEP a été comparée à 8 sujets sains. Les participants ont bénéficié d’une évaluation clinique, cognitive, et radiologique par TEP au [11C]FMZ et IRM. Les données TEP ont été évaluées par région d’intérêt et vertex-à- vertex. Des réductions significatives de l’activité TEP au [11C]FMZ ont été mises en évidence au sein de la SG corticale et sous-corticale des patients comparés aux contrôles. Ces changements étaient présents dès le stade rémittent de la maladie et corrélaient modérément avec la charge lésionnelle de la SB. L’activité TEP corticale était aussi associée à la performance cognitive des patients. Cette étude pilote est la première à quantifier in vivo la souffrance neuronale chez des patients atteints de SEP. Nos résultats permettent de proposer la TEP au [11C]FMZ comme marqueur spécifique et discriminant de l’atteinte neuronale de la SG dans la SEP.Multiple sclerosis (MS) has long been regarded as an inflammatory demyelinating disorder of the white matter. But post-mortem studies have recently shed light on the extensive involvement of the grey matter (GM). Neuronal damage, characterized by synaptic and dendritic loss as well as neuronal apoptosis, is thought to be a major substrate of physical and cognitive deterioration in MS patients. There is a crucial need for new imaging techniques able to specifically assess neuronal damage in MS. Using positron emission tomography (PET) with [11C]flumazenil ([11C]FMZ), an antagonist of the central benzodiazepine site located within the GABAA receptor, and a non-invasive quantification method, we measured and mapped neurodegenerative changes in the GM of patients with MS at distinct disease stages. A cohort of 18 MS patients was compared to 8 healthy controls and underwent neurological and cognitive evaluations, high-resolution dynamic [11C]FMZ PET imaging and brain MRI. PET data were evaluated using a region of interest and a surface-based approach. [11C]FMZ binding was significantly decreased in the cortical and subcortical GM of MS patients compared to controls. These changes were significant in both progressive and relapsing-remitting forms of the disease and correlated moderately with white matter lesion load. [11C]FMZ cortical binding was also associated with cognitive performance. This pilot study is the first to quantify in vivo the neurodegenerative changes occurring in MS. Our results show that PET with [11C]FMZ could be a promising and sensitive quantitative marker to assess and map the neuronal substrate of GM pathology in MS
- …
