Importantly, the correlation between 14-3-3ε expression, PIs sensitivity and protein load was observed in primary MM cells from two independent datasets; and its lower expression was associated with poor outcome in MM patients receiving a bortezomib-based therapy. Altogether these observations suggest that 14-3-3ε is a predictor of clinical outcome and may serve as a potential target to modulate PIs sensitivity in MM. Copyright © 2020 American Society of Hematology.The interplay between life sciences and advancing technology drives a continuous cycle of chemical data growth; these data are most often stored in open or partially open databases. In parallel, many different types of algorithms are being developed to manipulate these chemical objects and associated bioactivity data. Virtual screening methods are among the most popular computational approaches in pharmaceutical research. Today, user-friendly web-based tools are available to help scientists perform virtual screening experiments. This article provides an overview of internet resources enabling and supporting chemical biology and early drug discovery with a main emphasis on web servers dedicated to virtual ligand screening and small-molecule docking. This survey first introduces some key concepts and then presents recent and easily accessible virtual screening and related target-fishing tools as well as briefly discusses case studies enabled by some of these web services. Notwithstanding further improvements, already available web-based tools not only contribute to the design of bioactive molecules and assist drug repositioning but also help to generate new ideas and explore different hypotheses in a timely fashion while contributing to teaching in the field of drug development. © The Author(s) 2020. Published by Oxford University Press.Thromboembolism complicates disorders caused by IgG-containing immune complexes (ICs), but the underlying mechanisms are incompletely understood. Prior evidence indicates that induction of tissue factor (TF) on monocytes, a pivotal step in the initiation, localization and propagation of coagulation by ICs, is mediated through Fc gamma receptor IIa (FcγRIIa), yet the involvement of other receptors has not been investigated in detail.  https://www.selleckchem.com/products/apcin.html  The neonatal Fc receptor (FcRn) that mediates IgG and albumin recycling also participates in cellular responses to IgG-containing ICs. Here we asked whether FcRn is also involved in the induction of TF-dependent factor Xa activity by IgG-ICs by THP-1 monocytic cells and human monocytes. Induction of factor Xa activity by ICs containing IgG antibodies to platelet factor 4 (PF4) involved in heparin-induced thrombocytopenia (HIT), b-2-glycoprotein-1 implicated in the antiphospholipid syndrome (APS), or red blood cells coated with anti-(α)-Rh(D) antibodies that mediate hemolysis in vivo were inhibited by a humanized monoclonal antibody (MoAb) that blocks IgG binding to human FcRn. IgG ICs that bind to FcγR and FcRn induced Factor Xa activity, whereas IgG-ICs with an Fc engineered to be unable to engage FcRn did not. Infusion of an α-FcRn MoAb prevented fibrin deposition following microvascular injury in a murine model of HIT in which human FcgRIIa is expressed as a transgene. These data implicate FcRn in TF-dependent FXa activity induced by soluble and cell-associated IgG-containing ICs. Antibodies to FcRn, now in clinical trials in warm autoimmune hemolytic anemic to lower IgG antibodies and IgG containing ICs may also reduce the risk of venous thromboembolism. Copyright © 2020 American Society of Hematology.OBJECTIVES Valve repair for aortic insufficiency (AI) requires a tailored surgical approach determined by the leaflet and aortic disease. In this study, we used a repair-oriented system for the classification of AI, and we elucidated long-term outcomes of aortic root reimplantation with this classification system. METHODS From 1999 to 2018, a total of 197 patients underwent elective reimplantation (mean age 52.7 ± 17.7 years; 80% male). The aortic valve was tricuspid in 143 patients, bicuspid in 51 patients and quadricuspid in 3 patients. A total of 93 patients had type I AI (aortic dilatation), 57 patients had type II AI (cusp prolapse) and 47 patients had type III AI (restrictive). In total, 104 of the 264 patients (39%) had more than 1 identified mechanism. RESULTS In-hospital mortality was 0.5% (1/197). Mid-term follow-up (mean follow-up duration 5.5 years) revealed a late mortality rate of 4.2% (9/197). Aortic valve reoperation was performed on 16 patients (8.0%). Rates of freedom from aortic valve replacement and freedom from aortic valve-related events at 10 years of follow-up were 87.0 ± 4.0% and 60.6 ± 6.0%, respectively; patients with type Ib AI (98.3 ± 1.7%; 80.7 ± 7.5%) had better outcomes than patients with type III AI (59.6 ± 15.6%; 42.2 ± 13.1%, P = 0.01). In patients with types II and III AI who had bicuspid aortic valves, rates of freedom from aortic valve-related events at 5 years of follow-up were 95.2 ± 4.7% and 71.7 ± 9.1%, respectively (P = 0.03). CONCLUSIONS This repair-oriented system for classifying AI could help to predict the durable aortic valve repair techniques. Patient selection according to the classification is particularly important for long-term durability. CLINICAL TRIAL REGISTRATION NUMBER B190050. © The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.AIMS Fifteen to thirty percentage of patients with severe aortic stenosis (AS) have preserved left ventricular ejection fraction (LVEF) and a discordant AS pattern at Doppler echocardiography, which is characterized by a small ( less then 1 cm2) aortic area and low mean aortic gradient ( less then 40 mmHg). The 'Randomized study for the Optimal Treatment of symptomatic patients with low-gradient severe Aortic Stenosis and preserved left ventricular ejection fraction' (ROTAS trial) aims at demonstrating the superiority of aortic valve replacement vs. a 'watchful waiting strategy' in symptomatic patients with low-gradient (LS), severe AS, and preserved LVEF, stratified according to indexed stroke volume, in terms of all-cause mortality or cardiovascular-related hospitalization during follow-up (FU). METHODS AND RESULTS The ROTAS trial will be a multicentre randomized non-blinded study involving 16 reference centres. AS severity will be confirmed by a multimodality approach (rest and stress echocardiography, calcium scoring, and cardiac magnetic resonance imaging for optimally characterize the population), which could provide important inputs to improve the pathophysiological understanding of this complex disease.