Deep learning of chest X‑rays can predict mechanical ventilation outcome in ICU‑admitted COVID‑19 patients

The COVID-19 pandemic repeatedly overwhelms healthcare systems capacity and forced the development and implementation of triage guidelines in ICU for scarce resources (e.g. mechanical ventilation). These guidelines were often based on known risk factors for COVID-19. It is proposed that image data, specifically bedside computed X-ray (CXR), provide additional predictive information on mortality following mechanical ventilation that can be incorporated in the guidelines. Deep transfer learning was used to extract convolutional features from a systematically collected, multi-institutional dataset of COVID-19 ICU patients. A model predicting outcome of mechanical ventilation (remission or mortality) was trained on the extracted features and compared to a model based on known, aggregated risk factors. The model reached a 0.702 area under the curve (95% CI 0.707-0.694) at predicting mechanical ventilation outcome from pre-intubation CXRs, higher than the risk factor model. Combining imaging data and risk factors increased model performance to 0.743 AUC (95% CI 0.746-0.732). Additionally, a post-hoc analysis showed an increase performance on high-quality than low-quality CXRs, suggesting that using only high-quality images would result in an even stronger model

Piceatannol and resveratrol share inhibitory effects on hydrogen peroxide release, monoamine oxidase and lipogenic activities in adipose tissue, but differ in their antilipolytic properties

International audiencePiceatannol is a hydroxylated derivative of resveratrol. While both dietary polyphenols coexist in edible plants and fruits, and share equivalent concentrations in several wines, the influence of piceatannol on adiposity has been less studied than that of resveratrol. Though resveratrol is now recognized to limit fat deposition in various obesity models, the benefit of its dietary supplementation remains under debate regarding human obesity treatment or prevention. The research for more potent resveratrol analogs is therefore still undergoing. This prompted us to compare various effects of piceatannol and resveratrol directly on human adipose tissue (hAT). Hydrogen peroxide release was measured by Amplex Red-based fluorescence in subcutaneous hAT samples from obese patients. Interactions of stilbenes with human amine oxidases and quinone reductase were assessed by radiometric methods, computational docking and electron paramagnetic resonance. Influences on lipogenic and lipolytic activities were compared in mouse adipocytes. Resveratrol and piceatannol inhibited monoamine oxidase (MAO) with respective IC50 of 18.5 and 133.7 μM, but not semicarbazide-sensitive amine oxidase (SSAO) in hAT. For both stilbenes, the docking scores were better for MAO than for SSAO. Piceatannol and resveratrol similarly hampered hydrogen peroxide detection in assays with and without hAT, while they shared pro-oxidant activities when incubated with purified quinone reductase. They exhibited similar dose-dependent inhibition of adipocyte lipogenic activity. Only piceatannol inhibited basal and stimulated lipolysis when incubated at a dose ≥100 μM. Thus, piceatannol exerted on fat cells dose-dependent effects similar to those of resveratrol, except for a stronger antilipolytic action. In this regard, piceatannol should be useful in limiting the lipotoxicity related to obesity when ingested or administered alone - or might hamper the fat mobilization induced by resveratrol when simultaneously administered with it

USP19 Deubiquitinating Enzyme Supports Cell Proliferation by Stabilizing KPC1, a Ubiquitin Ligase for p27Kip1▿

p27Kip1 is a cyclin-dependent kinase inhibitor that regulates the G1/S transition. Increased degradation of p27Kip1 is associated with cellular transformation. Previous work demonstrated that the ubiquitin ligases KPC1/KPC2 and SCFSkp2 ubiquitinate p27Kip1 in G1 and early S, respectively. The regulation of these ligases remains unclear. We report here that the USP19 deubiquitinating enzyme interacts with and stabilizes KPC1, thereby modulating p27Kip1 levels and cell proliferation. Cells depleted of USP19 by RNA interference exhibited an inhibition of cell proliferation, progressing more slowly from G0/G1 to S phase, and accumulated p27Kip1. This increase in p27Kip1 was associated with normal levels of Skp2 but reduced levels of KPC1. The overexpression of KPC1 or the use of p27−/− cells inhibited significantly the growth defect observed upon USP19 depletion. KPC1 was ubiquitinated in vivo and stabilized by proteasome inhibitors and by overexpression of USP19, and it also coimmunoprecipitated with USP19. Our results identify USP19 as the first deubiquitinating enzyme that regulates the stability of a cyclin-dependent kinase inhibitor and demonstrate that progression through G1 to S phase is, like the metaphase-anaphase transition, controlled in a hierarchical, multilayered fashion

Exercising the Sleepy-ing Brain: Exercise, Sleep, and Sleep Loss on Memory

We examine the novel hypothesis that physical exercise and sleep have synergistic effects on memory. Exercise can trigger mechanisms that can create an optimal brain state during sleep to facilitate memory processing. The possibility that exercise could counteract the deleterious effects of sleep deprivation on memory by protecting neuroplasticity is also discussed