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A large percentage of the global population is currently afflicted by metabolic diseases (MD), and the incidence is likely to double in the next decades. MD associated co-morbidities such as non-alcoholic fatty liver disease (NAFLD) and cardiomyopathy contribute significantly to impaired health. MD are complex, polygenic, with many genes involved in its aetiology. A popular approach to investigate genetic contributions to disease aetiology is biological network analysis. However, data dependence introduces a bias (noise, false positives, over-publication) in the outcome. While several approaches have been proposed to overcome these biases, many of them have constraints, including data integration issues, dependence on arbitrary parameters, database dependent outcomes, and computational complexity. Network topology is also a critical factor affecting the outcomes. Here, we propose a simple, parameter-free method, that takes into account database dependence and network topology, to identify central genes in the MD network. Among them, we infer novel candidates that have not yet been annotated as MD genes and show their relevance by highlighting their differential expression in public datasets and carefully examining the literature. The method contributes to uncovering connections in the MD mechanisms and highlights several candidates for in-depth study of their contribution to MD and its co-morbidities.Usability is key to achieve quality in software products. https://www.selleckchem.com/products/(-)-Epigallocatechin-gallate.html The client applications with a high score in usability might impact on the power consumption when they are run in a PC. For this reason, energy savings turn to be critical in green software systems. In this paper the relationship between the usability evaluations of the GUIs and the power consumption measurements of the main components of a PC were analysed. A set of 5 web-based personal health records (PHRs) were selected as a case study. The usability assessment was performed by an expert, employing the 14 principles of design by Alan Dix as heuristics. They were scored on a Likert scale after performing a collection of common tasks in the PHRs. At the same time, an equipment to measure the energy consumption of hard disk drive, graphics card, processor, monitor and power supply was used. Spearman's index was studied for the correlations between the usability assessments and the power consumption measurements. As a results, some weak relationships were found. A total of 5 usability heuristics were observed to may influence energy consumption when they were considered in the implementation of the PHRs. These heuristics were the following ones consistency, task migratability, observability, recoverability and responsiveness. Based on the results, the usability principles of design cannot always be related to lower energy consumption. Future research should focus on the tradeoffs between usability and power consumption of client applications when they are used in a computer.Caspase-11 is a pro-inflammatory enzyme that is stringently regulated during its expression and activation. As caspase-11 is not constitutively expressed in cells, it requires a priming step for its upregulation, which occurs following the stimulation of pathogen and cytokine receptors. Once expressed, caspase-11 activation is triggered by its interaction with lipopolysaccharide (LPS) from Gram-negative bacteria. Being an initiator caspase, activated caspase-11 functions primarily through its cleavage of key substrates. Gasdermin D (GSDMD) is the primary substrate of caspase-11, and the GSDMD cleavage fragment generated is responsible for the inflammatory form of cell death, pyroptosis, via its formation of pores in the plasma membrane. Thus, caspase-11 functions as an intracellular sensor for LPS and an immune effector. This review provides an overview of caspase-11-describing its structure and the transcriptional mechanisms that govern its expression, in addition to its activation, which is reported to be regulated by factors such as guanylate-binding proteins (GBPs), high mobility group box 1 (HMGB1) protein, and oxidized phospholipids. We also discuss the functional outcomes of caspase-11 activation, which include the non-canonical inflammasome, modulation of actin dynamics, and the initiation of blood coagulation, highlighting the importance of inflammatory caspase-11 during infection and disease.Oncolytic virotherapy (OVT) is a promising approach in cancer immunotherapy. Oncolytic viruses (OVs) could be applied in cancer immunotherapy without in-depth knowledge of tumor antigens. The capability of genetic modification makes OVs exciting therapeutic tools with a high potential for manipulation. Improving efficacy, employing immunostimulatory elements, changing the immunosuppressive tumor microenvironment (TME) to inflammatory TME, optimizing their delivery system, and increasing the safety are the main areas of OVs manipulations. Recently, the reciprocal interaction of OVs and TME has become a hot topic for investigators to enhance the efficacy of OVT with less off-target adverse events. Current investigations suggest that the main application of OVT is to provoke the antitumor immune response in the TME, which synergize the effects of other immunotherapies such as immune-checkpoint blockers and adoptive cell therapy. In this review, we focused on the effects of OVs on the TME and antitumor immune responses. Furthermore, OVT challenges, including its moderate efficiency, safety concerns, and delivery strategies, along with recent achievements to overcome challenges, are thoroughly discussed. Metabolic acidosis in patients with chronic kidney disease (CKD) is a common complication. A bicarbonate concentration in venous blood (V-HCO ) is a key index for diagnosis and treatment initiation. The aim of our study is to evaluate usability of acid-base balance parameters of in blood taken simultaneously from peripheral artery and the vein. A total of 49 patients (median age 66 years [interquartile range IQR 45-75]), with CKD stage G4 or G5 were enrolled in this cross-sectional study. All patients were qualified for arteriovenous fistula creation in pre-dialysis period. The samples were taken during surgery, directly after dissection, and evaluated in a point of care testing analyzer. The arteriovenous difference in bicarbonate levels (Δ-HCO ) was calculated. According to glomerular filtration rate (eGFR) the group was divided into Group A eGFR ≥ 10 mL/min/1.73 m ) and Group B eGFR < 10 mL/min/1.73 m ). In Group A Δ-HCO was significantly higher compared to Group B. No such differences were observed in the case of V-HCO .
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