Background

PROCEEDINGS A rich internet application for remote visualization and collaborative annotation of digital slides in histology and cytolog

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Du Désordre Conformationnel des Protéines Structurées et Intrinsèquement Désordonnées par Résonance Magnétique Nucléaire

Biological macromolecules are, by essence, dynamical systems. While the importance of this flexibility is nowadays well established, the accurate characterization of the conformational disorder of these systems remains an important challenge. Nuclear magnetic resonance spectroscopy is a unique tool to probe these motions at atomic level, through the analysis of spin relaxation or residual dipolar couplings. The latter allows all motions occurring at timescales faster than the millisecond to be investigated, including physiologically important timescales. The information presents in those couplings is interpreted here using mainly analytical approaches in order to quantify the amounts of dynamics present in folded protein, to determine the direction of those motions and to obtain structural information within this conformational disorder. These analytical approaches are complemented by numerical methods, that allowed the observation of phenomena from a different point of view or the investigation of other systems such as intrinsically disordered proteins. All of these studies demonstrate an important complementarity between structural order and conformational disorder.Les macromolécules biologiques sont, par essence, des systèmes dynamiques. Si l'importance de cette flexibilité est maintenant clairement établie, la caractérisation précise du désordre conformationnel de ces systèmes reste encore une question ouverte. La résonance magnétique nucléaire constitue un outil unique pour sonder ces mouvements au niveau atomique que ce soit par les études de relaxation de spin ou par l'analyse des couplages dipolaires résiduels. Ces derniers permettent d'étudier l'ensemble des mouvements ayant lieu à des échelles de temps plus rapide que la milliseconde, englobant ainsi les temps caractéristiques de nombreux mouvements physiologiquement importants. L'information contenue dans ces couplages résiduels est ici interprétée principalement grâce à des approches analytiques pour quantifier la dynamique présente dans des protéines repliées, déterminer l'orientation de ces mouvements et obtenir de l'information structurale au sein de ce désordre conformationnel. Ces approches analytiques sont complémentées par des méthodes numériques, permettant ainsi soit d'observer les phénomènes sous un autre angle, soit d'examiner d'autres systèmes tels que les protéines intrinsèquement désordonnées. L'ensemble de ces études laisse transparaître une importante complémentarité entre ordre structural et désordre conformationnel

Du Désordre Conformationnel des Protéines Structurées et Intrinsèquement Désordonnées par Résonance Magnétique Nucléaire

Biological macromolecules are, by essence, dynamical systems. While the importance of this flexibility is nowadays well established, the accurate characterization of the conformational disorder of these systems remains an important challenge. Nuclear magnetic resonance spectroscopy is a unique tool to probe these motions at atomic level, through the analysis of spin relaxation or residual dipolar couplings. The latter allows all motions occurring at timescales faster than the millisecond to be investigated, including physiologically important timescales. The information presents in those couplings is interpreted here using mainly analytical approaches in order to quantify the amounts of dynamics present in folded protein, to determine the direction of those motions and to obtain structural information within this conformational disorder. These analytical approaches are complemented by numerical methods, that allowed the observation of phenomena from a different point of view or the investigation of other systems such as intrinsically disordered proteins. All of these studies demonstrate an important complementarity between structural order and conformational disorder.Les macromolécules biologiques sont, par essence, des systèmes dynamiques. Si l'importance de cette flexibilité est maintenant clairement établie, la caractérisation précise du désordre conformationnel de ces systèmes reste encore une question ouverte. La résonance magnétique nucléaire constitue un outil unique pour sonder ces mouvements au niveau atomique que ce soit par les études de relaxation de spin ou par l'analyse des couplages dipolaires résiduels. Ces derniers permettent d'étudier l'ensemble des mouvements ayant lieu à des échelles de temps plus rapide que la milliseconde, englobant ainsi les temps caractéristiques de nombreux mouvements physiologiquement importants. L'information contenue dans ces couplages résiduels est ici interprétée principalement grâce à des approches analytiques pour quantifier la dynamique présente dans des protéines repliées, déterminer l'orientation de ces mouvements et obtenir de l'information structurale au sein de ce désordre conformationnel. Ces approches analytiques sont complémentées par des méthodes numériques, permettant ainsi soit d'observer les phénomènes sous un autre angle, soit d'examiner d'autres systèmes tels que les protéines intrinsèquement désordonnées. L'ensemble de ces études laisse transparaître une importante complémentarité entre ordre structural et désordre conformationnel

Investigating protein conformational energy landscapes and atomic resolution dynamics from NMR dipolar couplings: a review.

International audienc

Dynamic Descriptions of Highly Flexible Molecules from NMR Dipolar Couplings: Physical Basis and Limitations.

International audienceBiomolecules that control physiological function by changing their conformation play key roles in biology and remain poorly characterized. NMR dipolar couplings (DCs) depend intrinsically on both molecular shape and structural fluctuations, thereby providing the enticing prospect of tracking these conformational changes at atomic detail. Although this dual dependence has until now severely complicated analysis of DCs from highly dynamic systems, general approaches have recently been proposed that simplify interpretation of experimental DCs, by entirely eliminating molecular alignment from the analysis. Using simple and intuitive simulation of target ensembles, we investigate the impact of such approaches on the resulting descriptions of the conformational energy landscape. We find that ensemble descriptions of highly flexible systems derived from DCs without explicit consideration of the alignment properties of the constituent conformations can be compromised and inaccurate, despite exhibiting high correlation with experimental measurement

A rich internet application for remote visualization and collaborative annotation of digital slide images in histology and cytology

This work proposes a new web-based tool to ease collaborative projects in digital histology and cytology.WIST3 Cytomine 101707

Looking at dynamic mRNA-miRNA interactions by 19F-NMR spectroscopy

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