Phylemon 2.0 is a new release of the suite of web tools for molecular evolution, phylogenetics, phylogenomics and hypotheses testing. It has been designed as a response to the increasing demand of ...molecular sequence analyses for experts and non-expert users. Phylemon 2.0 has several unique features that differentiates it from other similar web resources: (i) it offers an integrated environment that enables evolutionary analyses, format conversion, file storage and edition of results; (ii) it suggests further analyses, thereby guiding the users through the web server; and (iii) it allows users to design and save phylogenetic pipelines to be used over multiple genes (phylogenomics). Altogether, Phylemon 2.0 integrates a suite of 30 tools covering sequence alignment reconstruction and trimming; tree reconstruction, visualization and manipulation; and evolutionary hypotheses testing.
A numerical model was developed in order to predict the heat transfer process and pressure drop in a vertical helical coil heat exchanger (HCHE) located inside a fluid storage tank in which water is ...used as inner and outer fluid. Natural convection was considered as boundary condition for the HCHE outer surface. The model was validated with experimental data obtained from an own facility with two HCHEs tested under several operating conditions. The model developed was used to evaluate the main HCHE representative geometrical parameter's influence on the overall heat transfer coefficient and pressure drop. The results show that by increasing the tube diameter causes an increase of the Nusselt number and a larger heat transfer rate to pressure drop ratio is obtained.
•A numerical model for vertical helical coils inside storage tanks was developed.•The model was validated against experimental data.•The Nusselt number improves by increasing the outer tube diameter.•The heat transfer rate depends mainly on the inner area.
Single nucleotide variants (SNVs) are, together with copy number variation, the primary source of variation in the human genome and are associated with phenotypic variation such as altered response ...to drug treatment and susceptibility to disease. Linking structural effects of non-synonymous SNVs to functional outcomes is a major issue in structural bioinformatics. The SNPeffect database (http://snpeffect.switchlab.org) uses sequence- and structure-based bioinformatics tools to predict the effect of protein-coding SNVs on the structural phenotype of proteins. It integrates aggregation prediction (TANGO), amyloid prediction (WALTZ), chaperone-binding prediction (LIMBO) and protein stability analysis (FoldX) for structural phenotyping. Additionally, SNPeffect holds information on affected catalytic sites and a number of post-translational modifications. The database contains all known human protein variants from UniProt, but users can now also submit custom protein variants for a SNPeffect analysis, including automated structure modeling. The new meta-analysis application allows plotting correlations between phenotypic features for a user-selected set of variants.
The relation of antipsychotics with severe Coronavirus Disease 19 (COVID-19) outcomes is a matter of debate since the beginning of the pandemic. To date, controversial results have been published on ...this issue. We aimed to prove whether antipsychotics might exert adverse or protective effects against fatal outcomes derived from COVID-19. A population-based retrospective cohort study (January 2020 to November 2020) comprising inpatients (15,968 patients) who were at least 18 years old and had a laboratory-confirmed COVID-19 infection. Two sub-cohorts were delineated, comprising a total of 2536 inpatients: individuals who either had no prescription medication or were prescribed an antipsychotic within the 15 days preceding hospitalization. We conducted survival and odds ratio analyses to assess the association between antipsychotic use and mortality, reporting both unadjusted and covariate-adjusted results. We computed the average treatment effects, using the untreated group as the reference, and the average treatment effect on the treated, focusing solely on the antipsychotic-treated population. Among the eight antipsychotics found to be in use, only aripiprazole showed a significant decrease in the risk of death from COVID-19 adjusted odds ratio (OR) = 0.86; 95% CI, 0.79-0.93, multiple-testing adjusted p-value < 0.05. Importantly, these findings were consistent for both covariate-adjusted and unadjusted analyses. Aripiprazole has been shown to have a differentiated beneficial effect in protecting against fatal clinical outcome in COVID-19 infected individuals. We speculate that the differential effect of aripiprazole on controlling immunological pathways and inducible inflammatory enzymes, that are critical in COVID19 illness, may be associated with our findings herein.
Different neurodegenerative disorders often show similar lesions, such as the presence of amyloid plaques, TAU-neurotangles and synuclein inclusions. The genetically inherited forms are rare, so we ...wondered whether shared epigenetic aberrations, such as those affecting DNA methylation, might also exist. The studied samples were gray matter samples from the prefrontal cortex of control and neurodegenerative disease-associated cases. We performed the DNA methylation analyses of Alzheimer's disease, dementia with Lewy bodies, Parkinson's disease and Alzheimer-like neurodegenerative profile associated with Down's syndrome samples. The DNA methylation landscapes obtained show that neurodegenerative diseases share similar aberrant CpG methylation shifts targeting a defined gene set. Our findings suggest that neurodegenerative disorders might have similar pathogenetic mechanisms that subsequently evolve into different clinical entities. The identified aberrant DNA methylation changes can be used as biomarkers of the disorders and as potential new targets for the development of new therapies.
As a result of environmental problems related to global warming and depletion of the ozone layer caused by the use of synthetic refrigerants (CFC's, HCFC's and HFC's) experienced over the last ...decades, the return to the use of natural substances for refrigeration purposes, appears to be the best long-term alternative. In this paper, a cascade refrigeration system with CO2 and NH3 as working fluids in the low and high temperature stages, respectively, has been analysed. Results of COP and exergetic efficiency versus operating and design parameters have been obtained. In addition, an optimization study based on the optimum CO2 condensing temperature has been done. Results show that following both method's exergy analysis and energy optimization, an optimum value of condensing CO2 temperature is obtained. The compressor isentropic efficiency influence on the optimum system COP has been demonstrated. A methodology to obtain relevant diagrams and correlations to serve as a guideline for design and optimization of this type of systems has been developed and it is presented in the paper.
•Tightly calibrated 100-μm DEB-TACE is safe.•100-μm DEB-TACE biliary toxicity is similar to lipiodol-TACE toxicity.•Tightly calibrated 100-μm DEB-TACE local tumor response is better than bigger ...DEB.•Increasing the doxorubicin dose increase the complications rate of DEB-TACE.•Patient comorbidities are as important as tumor response for survival in HCC.
To assess the safety and tolerability of transarterial drug-eluting bead chemoembolisation (DEB-TACE) using tightly calibrated 100-μm microspheres in hepatocellular carcinoma (HCC).
This multicentre prospective study included 131 patients with a 2-year follow-up. All patients had Child-Pugh scores ≤ B7, a good performance status, and Barcelona Clinic Liver Cancer stage A or B. Beads were loaded with 50 mg of doxorubicin per millilitre. Overall, 223 nodules were treated (mean size: 27.6 mm, average number of nodules per patient: 1.7). Toxicity was assessed using Common Terminology Criteria for Adverse Events 4.03 and response according to the modified Response Evaluation Criteria in Solid Tumours. The primary endpoint was safety. Secondary endpoints included technical success, post-embolisation syndrome (PES), local tumour response, and 2-year survival.
A total of 214 DEB-TACE procedures were performed (mean per patient: 1.64), with a technical success rate of 97.6 % and a PES rate of 9.3 %. Major complications occurred in 6.8 % of patients and 4.1 % of procedures. There were no treatment-related deaths. Doxorubicin dose was an independent predictor of complications (p = 0.01). Four patients were lost to follow-up and 18 received liver transplants. Objective response rates were 74.6 %, 45.7 %, and 44.1 % at 6, 12, and 24 months, respectively. The cumulative 24-month overall survival rate was 55.96 %. Median survival was 22 months (interquartile range = 13–24). Co-morbidities and tumour response were independent predictors of survival (p = 0.0012 and 0.0052, respectively). Complications did not affect survival (p = 0.24).
DEB-TACE with tightly calibrated 100-μm beads is safe and not associated with increases in biliary toxicity or complications. Tumour response and survival are in the expected range for chemoembolisation therapy. (Clinical trials ID: NCT02670122).
Colorectal cancer (CRC) has the second-highest tumor incidence and is a leading cause of death by cancer. Nearly 20% of patients with CRC will have metastases at the time of diagnosis, and more than ...50% of patients with CRC develop metastatic disease during the course of their disease. A group of experts from the Spanish Society of Medical Oncology, the Spanish Association of Surgeons, the Spanish Society of Radiation Oncology, the Spanish Society of Vascular and Interventional Radiology, and the Spanish Society of Nuclear Medicine and Molecular Imaging met to discuss and provide a multidisciplinary consensus on the management of liver metastases in patients with CRC. The group defined the different scenarios in which the disease can present: fit or unfit patients with resectable liver metastases, patients with potential resectable liver metastases, and patients with unresectable liver metastases. Within each scenario, the different strategies and therapeutic approaches are discussed.
We present Babelomics, a complete suite of web tools for the functional analysis of groups of genes in high-throughput experiments, which includes the use of information on Gene Ontology terms, ...interpro motifs, KEGG pathways, Swiss-Prot keywords, analysis of predicted transcription factor binding sites, chromosomal positions and presence in tissues with determined histological characteristics, through five integrated modules: FatiGO (fast assignment and transference of information), FatiWise, transcription factor association test, GenomeGO and tissues mining tool, respectively. Additionally, another module, FatiScan, provides a new procedure that integrates biological information in combination with experimental results in order to find groups of genes with modest but coordinate significant differential behaviour. FatiScan is highly sensitive and is capable of finding significant asymmetries in the distribution of genes of common function across a list of ordered genes even if these asymmetries were not extreme. The strong multiple-testing nature of the contrasts made by the tools is taken into account. All the tools are integrated in the gene expression analysis package GEPAS. Babelomics is the natural evolution of our tool FatiGO (which analysed almost 22 000 experiments during the last year) to include more sources on information and new modes of using it. Babelomics can be found at http://www.babelomics.org.
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