Reactome pathway analysis: a high-performance in-memory approach

BACKGROUND: Reactome aims to provide bioinformatics tools for visualisation, interpretation and analysis of pathway knowledge to support basic research, genome analysis, modelling, systems biology and education. Pathway analysis methods have a broad range of applications in physiological and biomedical research; one of the main problems, from the analysis methods performance point of view, is the constantly increasing size of the data samples. RESULTS: Here, we present a new high-performance in-memory implementation of the well-established over-representation analysis method. To achieve the target, the over-representation analysis method is divided in four different steps and, for each of them, specific data structures are used to improve performance and minimise the memory footprint. The first step, finding out whether an identifier in the user’s sample corresponds to an entity in Reactome, is addressed using a radix tree as a lookup table. The second step, modelling the proteins, chemicals, their orthologous in other species and their composition in complexes and sets, is addressed with a graph. The third and fourth steps, that aggregate the results and calculate the statistics, are solved with a double-linked tree. CONCLUSION: Through the use of highly optimised, in-memory data structures and algorithms, Reactome has achieved a stable, high performance pathway analysis service, enabling the analysis of genome-wide datasets within seconds, allowing interactive exploration and analysis of high throughput data. The proposed pathway analysis approach is available in the Reactome production web site either via the AnalysisService for programmatic access or the user submission interface integrated into the PathwayBrowser. Reactome is an open data and open source project and all of its source code, including the one described here, is available in the AnalysisTools repository in the Reactome GitHub (https://github.com/reactome/)

Use of antibiotics by spanish dentists receiving postgraduate training in endodontics

The incidence of endodontic infections is high. The contribution of Endodontics to the global problem of antibiotic resistance could be significant. The ESE, together with the World Health Organization, are promoting the World Antibiotic Awareness Week (13-19 November 2017) to promote the appropriate use of systemic antibiotics in Endodontics. The objective of this study was to determine the prescription pattern of antibiotics in the treatment of endodontic infections of Spanish dentists attending specialization programs in Endodontics. Material and Methods: Dentists from five Spanish endodontic postgraduate programs were requested to answer a one-page questionnaire surveying about antibiotics indications. Seventy-three dentists were required to participate in this investigation, and 67 (91.2%) fulfilled satisfactorily the survey and were included in the study. Data were analyzed using descriptive statistics and chi square test. Results: The average duration of antibiotic therapy was 6.8±1.2 days. All respondents chose amoxicillin as first choice antibiotic in patients with no medical allergies, alone (40%) or associated to clavulanic acid (60%). The first drug of choice for penicillin allergic patients was clindamycin (72%). For cases of irreversible pulpitis, 22% of respondents prescribed antibiotics. For the scenario of a necrotic pulp, symptomatic apical periodontitis and no swelling, 37% prescribed antibiotics. A quarter of dentists prescribed antibiotics for necrotic pulps with asymptomatic apical periodontitis and a sinus tract. Conclusions: The results of this study show that postgraduate training in Endodontics provides greater awareness of the correct indications of antibiotics. Dentists who have received specialized training in Endodontics have a prescription pattern of antibiotics more adjusted to the guidelines recommended by international organizations and by scientific societies. Key words:Antibiotics, apical periodontitis, dental curriculum, endodontic infections, postgraduate endodontic training

Safety and immunogenicity of the protein-based PHH-1V compared to BNT162b2 as a heterologous SARS-CoV-2 booster vaccine in adults vaccinated against COVID-19 : a multicentre, randomised, double-blind, non-inferiority phase IIb trial

A SARS-CoV-2 protein-based heterodimer vaccine, PHH-1V, has been shown to be safe and well-tolerated in healthy young adults in a first-in-human, Phase I/IIa study dose-escalation trial. Here, we report the interim results of the Phase IIb HH-2, where the immunogenicity and safety of a heterologous booster with PHH-1V is assessed versus a homologous booster with BNT162b2 at 14, 28 and 98 days after vaccine administration. The HH-2 study is an ongoing multicentre, randomised, active-controlled, double-blind, non-inferiority Phase IIb trial, where participants 18 years or older who had received two doses of BNT162b2 were randomly assigned in a 2:1 ratio to receive a booster dose of vaccine-either heterologous (PHH-1V group) or homologous (BNT162b2 group)-in 10 centres in Spain. Eligible subjects were allocated to treatment stratified by age group (18-64 versus ≥65 years) with approximately 10% of the sample enrolled in the older age group. The primary endpoints were humoral immunogenicity measured by changes in levels of neutralizing antibodies (PBNA) against the ancestral Wuhan-Hu-1 strain after the PHH-1V or the BNT162b2 boost, and the safety and tolerability of PHH-1V as a boost. The secondary endpoints were to compare changes in levels of neutralizing antibodies against different variants of SARS-CoV-2 and the T-cell responses towards the SARS-CoV-2 spike glycoprotein peptides. The exploratory endpoint was to assess the number of subjects with SARS-CoV-2 infections ≥14 days after PHH-1V booster. This study is ongoing and is registered with , . From 15 November 2021, 782 adults were randomly assigned to PHH-1V (n = 522) or BNT162b2 (n = 260) boost vaccine groups. The geometric mean titre (GMT) ratio of neutralizing antibodies on days 14, 28 and 98, shown as BNT162b2 active control versus PHH-1V, was, respectively, 1.68 (p < 0.0001), 1.31 (p = 0.0007) and 0.86 (p = 0.40) for the ancestral Wuhan-Hu-1 strain; 0.62 (p < 0.0001), 0.65 (p < 0.0001) and 0.56 (p = 0.003) for the Beta variant; 1.01 (p = 0.92), 0.88 (p = 0.11) and 0.52 (p = 0.0003) for the Delta variant; and 0.59 (p ≤ 0.0001), 0.66 (p < 0.0001) and 0.57 (p = 0.0028) for the Omicron BA.1 variant. Additionally, PHH-1V as a booster dose induced a significant increase of CD4 + and CD8 + T-cells expressing IFN-γ on day 14. There were 458 participants who experienced at least one adverse event (89.3%) in the PHH-1V and 238 (94.4%) in the BNT162b2 group. The most frequent adverse events were injection site pain (79.7% and 89.3%), fatigue (27.5% and 42.1%) and headache (31.2 and 40.1%) for the PHH-1V and the BNT162b2 groups, respectively. A total of 52 COVID-19 cases occurred from day 14 post-vaccination (10.14%) for the PHH-1V group and 30 (11.90%) for the BNT162b2 group (p = 0.45), and none of the subjects developed severe COVID-19. Our interim results from the Phase IIb HH-2 trial show that PHH-1V as a heterologous booster vaccine, when compared to BNT162b2, although it does not reach a non-inferior neutralizing antibody response against the Wuhan-Hu-1 strain at days 14 and 28 after vaccination, it does so at day 98. PHH-1V as a heterologous booster elicits a superior neutralizing antibody response against the previous circulating Beta and the currently circulating Omicron BA.1 SARS-CoV-2 variants in all time points assessed, and for the Delta variant on day 98 as well. Moreover, the PHH-1V boost also induces a strong and balanced T-cell response. Concerning the safety profile, subjects in the PHH-1V group report significantly fewer adverse events than those in the BNT162b2 group, most of mild intensity, and both vaccine groups present comparable COVID-19 breakthrough cases, none of them severe. HIPRA SCIENTIFIC, S.L.U

Global transpiration data from sap flow measurements : the SAPFLUXNET database

Plant transpiration links physiological responses of vegetation to water supply and demand with hydrological, energy, and carbon budgets at the land-atmosphere interface. However, despite being the main land evaporative flux at the global scale, transpiration and its response to environmental drivers are currently not well constrained by observations. Here we introduce the first global compilation of whole-plant transpiration data from sap flow measurements (SAPFLUXNET, https://sapfluxnet.creaf.cat/, last access: 8 June 2021). We harmonized and quality-controlled individual datasets supplied by contributors worldwide in a semi-automatic data workflow implemented in the R programming language. Datasets include sub-daily time series of sap flow and hydrometeorological drivers for one or more growing seasons, as well as metadata on the stand characteristics, plant attributes, and technical details of the measurements. SAPFLUXNET contains 202 globally distributed datasets with sap flow time series for 2714 plants, mostly trees, of 174 species. SAPFLUXNET has a broad bioclimatic coverage, with woodland/shrubland and temperate forest biomes especially well represented (80 % of the datasets). The measurements cover a wide variety of stand structural characteristics and plant sizes. The datasets encompass the period between 1995 and 2018, with 50 % of the datasets being at least 3 years long. Accompanying radiation and vapour pressure deficit data are available for most of the datasets, while on-site soil water content is available for 56 % of the datasets. Many datasets contain data for species that make up 90 % or more of the total stand basal area, allowing the estimation of stand transpiration in diverse ecological settings. SAPFLUXNET adds to existing plant trait datasets, ecosystem flux networks, and remote sensing products to help increase our understanding of plant water use, plant responses to drought, and ecohydrological processes. SAPFLUXNET version 0.1.5 is freely available from the Zenodo repository (https://doi.org/10.5281/zenodo.3971689; Poyatos et al., 2020a). The "sapfluxnetr" R package - designed to access, visualize, and process SAPFLUXNET data - is available from CRAN.Peer reviewe

The Influence of Flow Regime on Ecological Quality, Bird Diversity, and Shellfish Fisheries in a Lowland Mediterranean River and Its Coastal Area

Designing environmental flows in lowland river sections and estuaries is a challenge for researchers and managers, given their complexity and their importance, both for nature conservation and economy. The Ebro River and its delta belong to a Mediterranean area with marked anthropogenic pressures. This study presents an assessment of the relationships between mean flows (discharges) computed at different time scales and (i) ecological quality based on fish populations in the lower Ebro, (ii) bird populations, and (iii) two shellfish fishery species of socioeconomic importance (prawn, or Penaeus kerathurus, and mantis shrimp, or Squilla mantis). Daily discharge data from 2000 to 2015 were used for analyses. Mean annual discharge was able to explain the variation in fish-based ecological quality, and model performance increased when aquatic vegetation was incorporated. Our results indicate that a good ecological status cannot be reached only through changes on discharge, and that habitat characteristics, such as the coverage of macrophytes, must be taken into account. In addition, among the different bird groups identified in our study area, predators were related to river discharge. This was likely due to its influence on available resources. Finally, prawn and mantis shrimp productivity were influenced up to a certain degree by discharge and physicochemical variables, as inputs from rivers constitute major sources of nutrients in oligotrophic environments such as the Mediterranean Sea. Such outcomes allowed revisiting the environmental flow regimes designed for the study area, which provides information for water management in this or in other similar Mediterranean zones

A new MPPT method for low-power solar energy harvesting

This paper describes a new maximum-power-pointtracking (MPPT) method focused on low-power (< 1 W) photovoltaic (PV) panels. The static and dynamic performance is theoretically analyzed, and design criteria are provided. A prototype was implemented with a 500-mW PV panel, a commercial boost converter, and low-power components for the MPPT controller. Laboratory measurements were performed to assess the effectiveness of the proposed method. Tracking efficiency was higher than 99.6%. The overall efficiency was higher than 92% for a PV panel power higher than 100 mW. This is, in part, feasible due to the low power consumption of the MPPT controller, which was kept lower than 350 μW. The time response of the tracking circuit was tested to be around 1 s. Field measurements showed energy gains higher than 10.3% with respect to a direct-coupled solution for an ambient temperature of 26 ◦C. Higher gains are expected for lower temperatures

GEGEINTOOL: A Computer-Based Tool for Automated Analysis of Gene-Gene Interactions in Large Epidemiological Studies in Cardiovascular Genomics

Current methods of data analysis of gene-gene interactions in complex diseases, after taking into account environmental factors using traditional approaches, are inefficient. High-throughput methods of analysis in large scale studies including thousands of subjects and hundreds of SNPs should be implemented. We developed an integrative computer tool, GEGEINTOOL (GEne- GEne INTeraction tOOL), for large-scale analysis of gene-gene interactions, in human studies of complex diseases including a large number of subjects, SNPs, as well as environmental factors. That resource uses standard statistical packages (SPSS, etc.) to build and fit the gene-gene interaction models by means of syntax scripts in predicting one or more continuous or dichotomic phenotypes. Codominant, dominant and recessive genetic interaction models including control for covariates are automatically created for each SNP in order to test the best model. From the standard outputs, GEGEINTOOL extracts a selected set of parameters (regression coefficients, p-values, adjusted means, etc.), and groups them in a single MS Excel Spreadsheet. The tool allows editing the set of filter parameters, filtering the selected results depending on p-values, as well as plotting the selected gene-gene interactions to check consistency. In conclusion, GEGEINTOOL is a useful and friendly tool for exploring and identifying gene-gene interactions in complex diseases

Treatment satisfaction with injectable disease-modifying therapies in patients with relapsing-remitting multiple sclerosis (the STICK study)

<div><p>Background</p><p>Treatment satisfaction in patients with relapsing-remitting multiple sclerosis (RRMS) may impact adherence and thus clinical outcomes. The objective of this study was to measure the satisfaction of patients with RRMS with injectable disease-modifying therapies (DMTs) and to evaluate the factors associated with treatment satisfaction.</p><p>Material and methods</p><p>In this observational retrospective study conducted in the neurology departments of 35 hospitals throughout Spain, demographic data, disease characteristics, and information on treatment with injectable DMTs were collected at a single scheduled visit. Treatment satisfaction was assessed using the Treatment Satisfaction Questionnaire for Medication (TSQM), version 1.4. Patients also answered complementary questions about the factors that might affect treatment satisfaction. The data collected were analyzed descriptively. A regression model was used to explore the factors associated with treatment satisfaction.</p><p>Results</p><p>The study included 445 patients (mean±SD age, 41±10.2 years; two-thirds women). The percentages treated with each DMT were Avonex 28.5%, Rebif 44 μg 24.5%, Copaxone 22.5%, Betaferon 13.0%, Rebif22 μg 8.3% and Extavia 3.1%. The mean±SD overall satisfaction according to the TSQM was 68.8±18.6 and the highest overall satisfaction was reported for Rebif 22 μg (72.4±20.3) and the lowest for Extavia (61.7±23.7). In the regression analysis, rehabilitation, interference with social life, pain on injection and number of MS treatments received were significantly associated with a decrease in overall TSMQ score. A small but significant negative correlation was found between EDSS scores and TSMQ scores (rho = –0.11, p = 0.02) and effectiveness (rho = –0.17, p<0.001). A perceived inconvenience of injections was reflected by the stated preference of 83% for once-daily oral treatment over other administration routes.</p><p>Conclusions</p><p>Patients on stable injectable DMT therapy were reasonably satisfied with their treatment. Our results suggest that the main source of dissatisfaction with the current treatment is the inconvenience of the administration regimen.</p></div

TSQM score-distributions.

<p>TSQM score-distributions.</p

Preference for routes of administration.

<p>Preference for routes of administration.</p