Torsade de Pointes (TdP), a rare but lethal ventricular arrhythmia, is a toxic side effect of many drugs. To assess TdP risk, safety regulatory guidelines require quantification of hERG channel block in vitro and QT interval prolongation in vivo for all new therapeutic compounds. Unfortunately, these have proven to be poor predictors of torsadogenic risk, and are likely to have prevented safe compounds from reaching clinical phases. While this has stimulated numerous efforts to define new paradigms for cardiac safety, none of the recently developed strategies accounts for patient conditions. In particular, despite being a well-established independent risk factor for TdP, female sex is vastly underrepresented in both basic research and clinical studies, and thus current TdP metrics are likely biased toward the male sex. Here, we apply statistical learning to synthetic data, generated by simulating drug effects on cardiac myocyte models capturing male and female electrophysiology, to develop new sex-specific classification frameworks for TdP risk. We show that (1) TdP classifiers require different features in females vs. males; (2) malebased classifiers perform more poorly when applied to female data; (3) female-based classifier performance is largely unaffected by acute effects of hormones (i.e., during various phases of the menstrual cycle). Notably, when predicting TdP risk of intermediate drugs on female simulated data, male-biased predictive models consistently underestimate TdP risk in women. Therefore, we conclude that pipelines for preclinical cardiotoxicity risk assessment should consider sex as a key variable to avoid potentially lifethreatening consequences for the female population..

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With the vigorous development of information and communication technology, mobile internet has undergone tremendous changes. How to achieve global coverage of the network has become the primary problem to be solved. GEO satellites and LEO satellites, as important components of the satellite–ground network, can offer service for hotspots or distant regions where ground-based base stations’ coverage is limited. Therefore, we build a satellite–ground network model, which transforms the satellite–ground network resource allocation problem into a matching issue between GEO satellites, LEO satellites, and users. A GEO satellite provides data backhaul for users, and a LEO satellite provides data transmission services according to users’ requests. It is important to consider the relationships between all entities and establish a distributed scheme, so we propose a three-sided cyclic matching algorithm. It is confirmed by a large number of simulation experiments that the method suggested in this research is better than the conventional algorithm in terms of average delay, satellite revenue, and number of users served.

Along with the continuous revolution of energy production and energy consumption structures, the information data of smart grids have exploded, and effective solutions are urgently needed to solve the problem of power devices resource scheduling and energy efficiency optimization. In this paper, we propose a fifth generation (5G) and satellite converged network architecture for power transmission and distribution scenarios, where power transmission and distribution devices (PDs) can choose to forward power data to a cloud server data center via ground networks or space-based networks for power grid regulation and control. We propose a Joint Device Association and Power Control Online Optimization (JDAPCOO) algorithm to maximize the long-term system energy efficiency while guaranteeing the minimum transmission rate requirement of PDs. Since the formulated issue is a mixed integer nonconvex optimization problem with high complexity, we decompose the original problem into two subproblems, i.e., device association and power control, which are solved using a genetic algorithm and improved simulated annealing algorithm, respectively. Numerical simulation results show that when the number of PDs is 50, the proposed algorithm can improve the system energy efficiency by 105%, 545.05% and 835.26%, respectively, compared with the equal power allocation algorithm, random power allocation algorithm and random device association algorithm.