Efficacy and safety of tocilizumab in the management of COVID-19: A systematic review and meta-analysis of observational studies

BackgroundThis systematic review and meta-analysis was aimed to evaluate the efficacy and safety of tocilizumab (TCZ) in treating severe coronavirus disease 2019 (COVID-19).MethodsThe electronic search was performed using PubMed, Scopus, CENTRAL, and Google scholar to identify the retrospective observational reports. The studies published from 01 January 2020 to 30th September 2020. Participants were hospitalized COVID-19 patients. Interventions included tocilizumab versus placebo/standard of care. The comparison will be between TCZ versus standard of care (SOC)/placebo. Inconsistency between the studies was evaluated with I2 and quality of the evidences were evaluated by Newcastle-Ottawa scale.ResultsBased on the inclusion criteria there were 24 retrospective studies involving 5686 subjects were included. The outcomes of the meta-analysis have revealed that the TCZ has reduced the mortality (M-H,RE-OR −0.11(−0.18 to −0.04) 95% CI, p =0.001, I2 =88%) and increased the incidences of super-infections (M-H, RE-OR 1.49(1.13 to 1.96) 95% CI, p=0.004, I2=47%). However, there is no significant difference in ICU admissions rate (M-H, RE-OR −0.06(−0.23 to 0.12), I2=93%), need of MV (M-H, RE-OR of 0.00(−0.06 to 0.07), I = 74%), LOS (IV −2.86(−0.91 to 3.38), I2=100%), LOS-ICU (IV: −3.93(−12.35 to 4.48), I2=100%), and incidences of pulmonary thrombosis (M-H, RE-OR 1.01 (0.45 to 2.26), I2=0%) compared to SOC/control.ConclusionBased on cumulative low to moderate certainty evidence shows that TCZ could reduce the risk of mortality in hospitalized patients. However, there is no statistically significant difference observed between the TCZ and SOC/control groups in other parameters.

An Improved SOC Control Strategy for Electric Vehicle Hybrid Energy Storage Systems

In this paper, we propose an optimized power distribution method for hybrid electric energy storage systems for electric vehicles (EVs). The hybrid energy storage system (HESS) uses two isolated soft-switching symmetrical half-bridge bidirectional converters connected to the battery and supercapacitor (SC) as a composite structure of the protection structure. The bidirectional converter can precisely control the charge and discharge of the SC and battery. Spiral wound SCs with mesoporous carbon electrodes are used as the energy storage units of EVs. Under the 1050 operating conditions of the EV driving cycle, the SC acts as a “peak load transfer” with a charge and discharge current of 2isc~3ibat. An improved energy allocation strategy under state of charge (SOC) control is proposed, that enables SC to charge and discharge with a peak current of approximately 4ibat. Compared with the pure battery mode, the acceleration performance of the EV is improved by approximately 50%, and the energy loss is reduced by approximately 69%. This strategy accommodates different types of load curves, and helps improve the energy utilization rate and reduce the battery aging effect.

Narrow Band State of Charge (SOC) Control Strategy for Hybrid Container Cranes

This paper evaluates possibility of using a new hybrid system based on variable speed diesel generator (VSDG), Li-ion battery bank and supercapacitor bank (SC) for a rubber tire gantry crane (RTGC) used in container terminals. Existing commercial hybrid systems face difficulties producing high efficiencies, higher life span, and lower initial investment cost due to inheriting characteristics of batteries and supercapacitors. In the proposed power system, a variable speed diesel generator act as the principal energy source, while a Li-ion battery bank and SC bank act as an energy storage system. The battery supports the diesel generator during steady demand and further, it absorbs a part of energy during regeneration. The energy management strategy, control the power flow from different sources while maintaining battery state of charge (SOC) level within a narrow band. Unlike most battery systems, this narrow band operation of battery system increases its life span while reducing capacity fade. The originality of this study can be emphasized from this narrow band SOC control technique. Simulation results for real operational load cycles are presented showing a stable system operating under defined current limits which can enhance lifetime of battery system and increase fuel saving by downsizing 400 kW constant speed diesel generator to 200 kW VSDG.

Single-Cell Reprogramming of Mouse Embryo Development Through a Critical Transition State

Our work dealing with the temporal development of the genome-expression profile in single-cell mouse early embryo indicated that reprogramming occurs via a critical transition state, where the critical-regulation pattern of the zygote state disappears. In this report, we unveil the detailed mechanism of how the dynamic interaction of thermodynamic states (critical states) enables the genome system to pass through the critical transition state to achieve genome reprogramming.Self-organized criticality (SOC) control of overall expression provides a snapshot of self-organization and explains the coexistence of critical states at a certain experimental time point. The time-development of self-organization is dynamically modulated by exchanges in expression flux between critical states through the cell nucleus milieu, where sequential global perturbations involving activation-inhibition of multiple critical states occur from the early state to the late 2-cell state. Two cyclic fluxes act as feedback flow and generate critical-state coherent oscillatory dynamics. Dynamic perturbation of these cyclic flows due to vivid activation of the ensemble of low-variance expression (sub-critical state) genes allows the genome system to overcome a transition state during reprogramming.Our findings imply that a universal mechanism of long-term global RNA oscillation underlies autonomous SOC control, and the critical gene ensemble at a critical point (CP) drives genome reprogramming. Unveiling the corresponding molecular players will be essential to understand single-cell reprogramming.