Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Mesure de l'équation d'état de l'énergie noire à l'aide de l'échantillon complet de supernovae SNLS

A significant open question of modern cosmology is explaining the accelerated expansion of the universe in late times. The discovery of this acceleration was made using supernova measurements, which continue to be the most significant probe with which to characterize this acceleration. This thesis concerns itself with presenting the final analysis of the Supernova Legacy Survey (SNLS) which will be published in 2015. We begin by presenting the theoretical foundations of modern cosmology, with special emphasis on the challenges presented by acceleration. We then introduce type Ia supernovae (SNIa) and motivate their use as probes of cosmic expansion. Afterwards, we give an overview of the SNLS experiment. We then move on to the technical aspects of the analysis that was carried out. We start by exploring the process of photometry, with which supernova measurements are made. Here we look at the newly implemented photometry method that avoids resampling images. We also explore simulations aimed at ensuring the method’s linearity up to less than 1 per mille. We then explain the calibration process associated with these measurements using field stars calibrated up to the 3.5 per mille level. Finally, we end with an in depth look at the cosmology analysis itself, which utilizes all the tools we have explored to extract cosmological parameters from the data. To estimate the constraining power of the SNLS experiment, we undertake a preliminary analysis of the data by constructing a Hubble diagram using 960 supernovae, of which 450 come from the SNLS. Combining this Hubble diagram with constraints from other cosmological probes leads to an uncertainty on the equation of state parameter of dark energy of 0.048, its most preciseconstraint to date.L’un des plus grands défis de la cosmologie moderne est d’expliquer l’accélération de l’expansion de l’univers dans son histoire récente. La découverte de cette accélération s’est faite grâce à des mesures de supernovae, ces dernières restant les sondes les plus puissantes pour charactériser cette accélération. Cette thèse vise à présenter l’analyse finale du Supernova Legacy Survey (SNLS) qui sera publiée en 2015. Nous commençons par présenter les fondements théoriques de la cosmologie moderne, en nous focalisant en particulier sur les défis théoriques que présente cette accélération. Nous introduisont ensuite les supernovae de type Ia (SNIa) et justifions leur usage en tant que sonde cosmologique. Par la suite, nous donnons un aperçu global de l’expérience SNLS. Nous abordons alors les aspects techniques de l’analyse. Nous commençons par l’exploration du processus de photométrie, utilisé pour la mesure des supernovae. Nous détaillons alors la nouvelle méthode de photométrie implémentée par SNLS qui évite le rééchantillonnage des images. Nous explorons aussi les simulations mise en œuvre dans le but de garantir la linéarité de la méthode au dessous de 1 pour mille. Nous explorons ensuite la procédure de calibration associée à ces mesures utilisant des étoiles de champ dont la précision de calibration atteint les 3.5 pour mille. Enfin, nous terminons avec une description détaillée de la mise en oeuvre de tous les outils présentés, afin d’extraire des paramètres cosmologiques des données. Afin d’estimer la capacité de SNLS à contraindre les paramètres cosmologiques, nous contruisons un diagramme de Hubble grâce à une analyse préliminaire des données incluant 960 supernovae, dont 450 provenant du SNLS. La combinaison de ce diagramme de Hubble avec des contraintes apportées d’autres sondes cosmologiques mène à une incertitude sur le paramètre de l’équation d’état de l’énergie noire de 0.048, la mesure la plus précise jusqu’à nos jours

Influence of agricultural fibers size on mechanical and insulating properties of innovative chitosan-based insulators

International audienceThis work is dealing with the use of miscanthus, recycled textile and rice husks as reinforcement for chitosan matrix to elaborate new insulating composites for building application. Insulating composites having thermal conductivity of 0.07–0.09 W.m−1.K−1 and density of 350–400 Kg.m−3 were manufactured by thermocompression. Different granulometry of miscanthus (0.2–0.5 cm and 1–2 cm) and rice husks (1–2 cm) have been used with and without textile to evaluate the effect of reinforcements particle size and nature on composites thermal and mechanical properties. Thermal conductivity and effusivity shows a linear behavior related to their increasing by raising up the reinforcement’s particle size. The highest mechanical properties in bending (modulus: 69–65 MPa; stress: 0.48–0.45 MPa) and compression (modulus: 36–26 MPa; stress: 0.65–0.56 MPa) were found for the formulations with small size miscanthus. Thus, the incorporation of small miscanthus particle size <1 mm leads to satisfying and promising results in terms of composites competing with the conventional insulating materials used nowadays

Correlations between genotype biochemical characteristics and mechanical properties of maize stem - polyethylene composites

International audienceThis study was devoted to identifying specific biochemical traits that may be addressed in maize breeding programs for improving lignocellulosic composition for biomass utilization in the composites. To this aim, six maize contrasted genotypes were cultivated, harvested and compared in term of their capability to reinforce a low-density polyethylene (LDPE) matrix. Stem biochemical composition and histological pattern of a given internode were evaluated to determine the traits that impacted the mechanical properties of the maize-LDPE composites. Across genotypes, maize stems with higher concentrations of total cell wall residue, lignin, p-coumaric acids and cellulose in conjunction with lower concentrations of ferulic acids and hemicellulose yielded better composite performances. This strong influence of hydroxycinnamic acids is a new finding. Cellulose is found to be the component dominating the mechanical properties of the fragments since the effects of cell wall residue and cellulose are following the same pattern towards composite properties. Contrary to expectations, the correlations between the histological structure of stems and the mechanical properties of the composites prepared with stem fragments is complex and cannot be interpreted in a simple manner. The two most contrasted genotypes in terms of mechanical performances (Cm484 and F2bm3) have the most contrasted biochemical and histological parameters