Construction of a network describing asparagine metabolism in plants and its application to the identification of genes affecting asparagine metabolism in wheat under drought and nutritional stress

© 2018 The Authors. A detailed network describing asparagine metabolism in plants was constructed using published data from Arabidopsis (Arabidopsis thaliana) maize (Zea mays), wheat (Triticum aestivum), pea (Pisum sativum), soybean (Glycine max), lupin (Lupus albus), and other species, including animals. Asparagine synthesis and degradation is a major part of amino acid and nitrogen metabolism in plants. The complexity of its metabolism, including limiting and regulatory factors, was represented in a logical sequence in a pathway diagram built using yED graph editor software. The network was used with a Unique Network Identification Pipeline in the analysis of data from 18 publicly available transcriptomic data studies. This identified links between genes involved in asparagine metabolism in wheat roots under drought stress, wheat leaves under drought stress, and wheat leaves under conditions of sulfur and nitrogen deficiency. The network represents a powerful aid for interpreting the interactions not only between the genes in the pathway but also among enzymes, metabolites and smaller molecules. It provides a concise, clear understanding of the complexity of asparagine metabolism that could aid the interpretation of data relating to wider amino acid metabolism and other metabolic processes.Biotechnology and Biological Sciences Research Council. Grant Number: BB/I020918/1; Designing Future Whea

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/)

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

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