Evaluation of the efficacy and safety of intravenous remdesivir in adult patients with severe COVID-19: study protocol for a phase 3 randomized, double-blind, placebo-controlled, multicentre trial.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by a novel corinavirus (later named SARS-CoV-2 virus), was fistly reported in Wuhan, Hubei Province, China towards the end of 2019. Large-scale spread within China and internationally led the World Health Organization to declare a Public Health Emergency of International Concern on 30th January 2020. The clinical manifestations of COVID-19 virus infection include asymptomatic infection, mild upper respiratory symptoms, severe viral pneumonia with respiratory failure, and even death. There are no antivirals of proven clinical efficacy in coronavirus infections. Remdesivir (GS-5734), a nucleoside analogue, has inhibitory effects on animal and human highly pathogenic coronaviruses, including MERS-CoV and SARS-CoV, in in vitro and in vivo experiments. It is also inhibitory against the COVID-19 virus in vitro. The aim of this study is to assess the efficacy and safety of remdesivir in adult patients with severe COVID-19. METHODS: The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. This is a phase 3, randomized, double-blind, placebo-controlled, multicentre trial. Adults (≥ 18 years) with laboratory-confirmed COVID-19 virus infection, severe pneumonia signs or symptoms, and radiologically confirmed severe pneumonia are randomly assigned in a 2:1 ratio to intravenously administered remdesivir or placebo for 10 days. The primary endpoint is time to clinical improvement (censored at day 28), defined as the time (in days) from randomization of study treatment (remdesivir or placebo) until a decline of two categories on a six-category ordinal scale of clinical status (1 = discharged; 6 = death) or live discharge from hospital. One interim analysis for efficacy and futility will be conducted once half of the total number of events required has been observed. DISCUSSION: This is the first randomized, placebo-controlled trial in COVID-19. Enrolment began in sites in Wuhan, Hubei Province, China on 6th February 2020. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04257656. Registered on 6 February 2020

Cardiac Resynchronization Therapy in Patients with Mild Heart Failure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

# The Author(s) 2011. This article is published with open access at Springerlink.com Objective This review aims at updating the results of cardiac resynchronization therapy (CRT) in mild heart failure patients, and investigating whether CRT can prevent or reverse heart failure progression in an earlier stage. Methods Randomized controlled trials of CRT in patients with New York Heart Association (NYHA) Class I or II heart failure were identified. The effects of CRT on worsening heart failure hospitalization, all-cause mortality, and overall adverse events were meta-analyzed, and the effects of CRT on left ventricular (LV) were systematically reviewed and meta-analyzed. Results Eight studies were identified with a total of 4,302 patients. CRT was associated with a substantial improvement in LVend-systolic volume (WMD −39, 95%CI −41.56 to −36.45). CRT also had a marked effect in reducing new hospitalizations for worsening heart failure by 31 % (RR 0.69, 95%CI 0.60 to 0.79). In addition, CRTsignificantly decreased all-cause mortality by 21 % (RR 0.79, 95%CI 0.67 to 0.93). However, complications in patients with CRT increased by 74 % (RR 1.74, 95%CI 1.44 to 2.11). Conclusions This meta-analysis suggests that CRT could improve the prognosis in patients with mild heart failure and ventricular dyssynchrony, but these improvements are accompanied by more adverse events. Since most patients in the included trials had received ICD therapy, our analysis suggests that CRT could offer an additional benefit. Key words Heart failure. Cardiac resynchronization therapy. Meta-analysi

The CAFA challenge reports improved protein function prediction and new functional annotations for hundreds of genes through experimental screens

Background The Critical Assessment of Functional Annotation (CAFA) is an ongoing, global, community-driven effort to evaluate and improve the computational annotation of protein function. Results Here, we report on the results of the third CAFA challenge, CAFA3, that featured an expanded analysis over the previous CAFA rounds, both in terms of volume of data analyzed and the types of analysis performed. In a novel and major new development, computational predictions and assessment goals drove some of the experimental assays, resulting in new functional annotations for more than 1000 genes. Specifically, we performed experimental whole-genome mutation screening in Candida albicans and Pseudomonas aureginosa genomes, which provided us with genome-wide experimental data for genes associated with biofilm formation and motility. We further performed targeted assays on selected genes in Drosophila melanogaster, which we suspected of being involved in long-term memory. Conclusion We conclude that while predictions of the molecular function and biological process annotations have slightly improved over time, those of the cellular component have not. Term-centric prediction of experimental annotations remains equally challenging; although the performance of the top methods is significantly better than the expectations set by baseline methods in C. albicans and D. melanogaster, it leaves considerable room and need for improvement. Finally, we report that the CAFA community now involves a broad range of participants with expertise in bioinformatics, biological experimentation, biocuration, and bio-ontologies, working together to improve functional annotation, computational function prediction, and our ability to manage big data in the era of large experimental screens.Peer reviewe

The CAFA challenge reports improved protein function prediction and new functional annotations for hundreds of genes through experimental screens

BackgroundThe Critical Assessment of Functional Annotation (CAFA) is an ongoing, global, community-driven effort to evaluate and improve the computational annotation of protein function.ResultsHere, we report on the results of the third CAFA challenge, CAFA3, that featured an expanded analysis over the previous CAFA rounds, both in terms of volume of data analyzed and the types of analysis performed. In a novel and major new development, computational predictions and assessment goals drove some of the experimental assays, resulting in new functional annotations for more than 1000 genes. Specifically, we performed experimental whole-genome mutation screening in Candida albicans and Pseudomonas aureginosa genomes, which provided us with genome-wide experimental data for genes associated with biofilm formation and motility. We further performed targeted assays on selected genes in Drosophila melanogaster, which we suspected of being involved in long-term memory.ConclusionWe conclude that while predictions of the molecular function and biological process annotations have slightly improved over time, those of the cellular component have not. Term-centric prediction of experimental annotations remains equally challenging; although the performance of the top methods is significantly better than the expectations set by baseline methods in C. albicans and D. melanogaster, it leaves considerable room and need for improvement. Finally, we report that the CAFA community now involves a broad range of participants with expertise in bioinformatics, biological experimentation, biocuration, and bio-ontologies, working together to improve functional annotation, computational function prediction, and our ability to manage big data in the era of large experimental screens.</p

A Novel Energy-Saving Route Planning Algorithm for Marine Vehicles

Recently, the ship energy consumption issue has been in the spotlight. Meanwhile, new conventions and standards of ship energy conservation as well as ship emission reduction have been continuously introduced by the International Maritime Organization and governments around the world. Energy conservation is a crucial factor in ship route planning. This paper proposes an improved ant colony algorithm that can handle a complicated ocean current environment and find an optimal energy-saving path. Firstly, this paper focuses on both the path length and energy consumption. To reduce energy consumption, a comprehensive energy cost function is introduced by a conventional ant colony algorithm. In addition, this paper analyzes the influence of the ocean current speed and setting on a marine vehicle and establishes an improved ant colony algorithm model based on the influence of the ocean current. Finally, simulation tests are carried out in Lianyungang and its surrounding areas to test the energy consumption performance of the improved ant colony algorithm. The simulation result shows that the improved ant colony algorithm can significantly reduce the energy consumption by 3.326% compared with the traditional algorithm

Multidrug-resistant tuberculosis in middle ear: A case report

Background: Tuberculosis (TB) continues to be a common disease in developing countries, among which middle ear TB is rare. Furthermore, it is relatively difficult to make an early diagnosis and provide follow-up treatment for middle ear TB. So, it is necessary to report this case for reference and further discussion. Case presentation: We reported 1 case of multidrug-resistant tuberculosis otitis media. TB otitis media is rare in tuberculosis; multidrug-resistant TB otitis media is even more rare. Our paper analyzes the possible causes, imaging, molecular biology, pathology, and clinical manifestations of multidrug-resistant TB otitis media. Conclusion: PCR and DNA molecular biology techniques are highly recommended for the early diagnosis of multidrug-resistant TB otitis media. Early, effective anti-tuberculosis treatment is the guarantee for further recovery for patients with multidrug-resistant TB otitis media

Zn (II) Porphyrin Built-in D&ndash;A Covalent Organic Framework for Efficient Photocatalytic H2 Evolution

Covalent organic frameworks (COFs) with donor&ndash;acceptor (D&ndash;A) units are credible photocatalysts for their per-designed structure, inherent porosity, large surface area, splendid stability and so forth. Developing COFs with an excellent photocatalytic efficiency for hydrogen evolution is of a great significance in alleviating the energy crisis. Herein, a D&ndash;A type imine-linked crystalline Zn-Por-TT COF was fabricated successfully via the co-polymerization of electron-deficient Zinc (II) 5,10,15,20-tetrakis(para-aminophenyl) porphyrin (Zn-TAPP), and electron-rich thieno[3,2-b]thiophene-2,5-dicarbaldehyde (TT). Profiting from the D&ndash;A complex structure, the obtained Zn-Por-TT COF showcases an excellent photocatalytic activity with a hydrogen evolution rate of 8200 &mu;mol/g/h, while the Zn-TAPP monomer presents practically no capacity for the generation of hydrogen under identical conditions. In addition, the counterparts Por-TT COF and COF-366-Zn were employed to illustrate the enhancement of the photocatalytic performance by metal catalytic sites and D&ndash;A structures. In addition, the counterparts Por-TT COF and COF-366-Zn were employed to illustrate the enhancement of metal catalytic sites and D&ndash;A structures for the photocatalytic performance

MiR-210 regulates lung adenocarcinoma by targeting HIF-1α

Object: This study sought to elucidate the role of microRNA-210 (miR-210) in the occurrence and development of lung adenocarcinoma (LUAD). Methods: The levels of lncRNA miR-210HG and miR-210 in LUAD tissues and corresponding normal tissues were analyzed by real-time quantitative PCR. The expression of the anti-hypoxia factor hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) were measured by qRT-PCR and Western blot. The target of miR-210 on HIF-1α was confirmed using TCGA, Western blot and luciferase reporter assay. The regulatory role of miR-210 on HIF-1α and VEGF in LUAD was investigated. The correlation of genes with clinical prognosis was analyzed using bioinformatics methods. The effect of miR-210 on LUAD cells was verified through apoptosis assays. Results: The expression of miR-210 and miR-210HG was significantly higher in LUAD tissues than in normal tissues. The expression of hypoxia-related indicators HIF-1α and VEGF was also significantly higher in LUAD tissues. MiR-210 suppressed HIF-1α expression by targeting site 113 of HIF-1α, thereby affecting VEGF expression. Overexpression of miR-210 inhibited HIF-1 expression by targeting the 113 site of HIF-1, thereby affecting VEGF expression. Conversely, inhibition of miR-210 resulted in a significant increase in HIF-1α and VEGF expression in LUAD cells. In TCGA-LUAD cohorts, the expression of VEGF-c and VEGF-d genes in LUAD tissues was significantly lower than in normal tissues, while overall survival was worse in LUAD patients with high expression of HIF-1α, VEGF-c and VEGF-d. Apoptosis was significantly lower in H1650 cells after miR-210 inhibition. Conclusion: This study reveals that miR-210 exerts an inhibitory effect on VEGF expression by down-regulating HIF-1α expression in LUAD. Conversely, inhibition of miR-210 significantly reduced H1650 apoptosis and led to worse patient survival by upregulating HIF-1α and VEGF. These results suggest that miR-210 could serve as a potential therapeutic target for the treatment of LUAD

Brillouin Frequency Shift of Fiber Distributed Sensors Extracted from Noisy Signals by Quadratic Fitting

It is a basic task in Brillouin distributed fiber sensors to extract the peak frequency of the scattering spectrum, since the peak frequency shift gives information on the fiber temperature and strain changes. Because of high-level noise, quadratic fitting is often used in the data processing. Formulas of the dependence of the minimum detectable Brillouin frequency shift (BFS) on the signal-to-noise ratio (SNR) and frequency step have been presented in publications, but in different expressions. A detailed deduction of new formulas of BFS variance and its average is given in this paper, showing especially their dependences on the data range used in fitting, including its length and its center respective to the real spectral peak. The theoretical analyses are experimentally verified. It is shown that the center of the data range has a direct impact on the accuracy of the extracted BFS. We propose and demonstrate an iterative fitting method to mitigate such effects and improve the accuracy of BFS measurement. The different expressions of BFS variances presented in previous papers are explained and discussed

Combined Treatment of Cinobufotalin and Gefitinib Exhibits Potent Efficacy against Lung Cancer

This study aimed to evaluate the efficacy of cinobufotalin combined with gefitinib in the treatment of lung cancer. A549 cells were treated with gefitinib, cinobufotalin, or cinobufotalin plus gefitinib. MTT assay, annexin-V/PI staining and flow cytometry, TUNEL staining, DCFH-DA staining, Western blot, and real-time RT-PCR were performed to investigate the synergistic inhibitory effect of cinobufotalin combined with gefitinib on the growth of A549 cells. Results showed that cinobufotalin synergized with gefitinib displayed inhibited cell viability and enhanced apoptosis in the combination group. Cinobufotalin combined with gefitinib induced a significant enhancement in reactive oxygen species (ROS) production accompanied by cell cycle arrest in the S phase arrest, characterized by upregulation of p21 and downregulation of cyclin A, cyclin E, and CDK2. Besides, cinobufotalin plus gefitinib downregulated the levels of HGF and c-Met. In summary, cinobufotalin combined with gefitinib impedes viability and facilitates apoptosis of A549 cells, indicating that the combined therapy might be a new promising treatment for lung cancer patients who are resistant to gefitinib