Functional Enrichment Analysis of Regulatory Elements

This work has been partially supported by FEDER/Junta de Andalucia-Consejeria de Economia y Conocimiento/(grant CV20-36723), grant PID2020-119032RB-I00, MCIN/AEI/10.13039/501100011033 and FEDER/Junta de Andalucia-Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades (Grant P20_00335).Statistical methods for enrichment analysis are important tools to extract biological information from omics experiments. Although these methods have been widely used for the analysis of gene and protein lists, the development of high-throughput technologies for regulatory elements demands dedicated statistical and bioinformatics tools. Here, we present a set of enrichment analysis methods for regulatory elements, including CpG sites, miRNAs, and transcription factors. Statistical significance is determined via a power weighting function for target genes and tested by theWallenius noncentral hypergeometric distribution model to avoid selection bias. These new methodologies have been applied to the analysis of a set of miRNAs associated with arrhythmia, showing the potential of this tool to extract biological information from a list of regulatory elements. These new methods are available in GeneCodis 4, a web tool able to perform singular and modular enrichment analysis that allows the integration of heterogeneous information.FEDER/Junta de Andalucia-Consejeria de Economia y Conocimiento CV20-36723MCIN/AEI PID2020-119032RB-I00FEDER/Junta de Andalucia-Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades P20_0033

The acute effect of match-play on hip range of motion and isometric strength in elite tennis players

Background: Groin injuries are some of the most common injuries tennis players suffer. Several factors (e.g., post-match decrease in hip adductor (ADD) strength) have been proposed as possible mechanisms for increasing the incidence of this type of injury. However, the risk factors of developing groin injuries after a tennis match have not yet been delineated. Objective: The aim of this study was to determine the effect of tennis match-play on isometric ADD and abductor (ABD) strength and passive hip range of motion (ROM). Methods: Twenty-six male tennis players (20.30 ± 4.98 years) took part in this study. Participants completed an evaluation of strength and flexibility hip measurements before and after a simulated tennis match. Dominant and non-dominant passive hip ROM, ADD and ABD isometric strength, and the ADD/ABD strength ratio were measured before and immediately post-match. A global positioning system (GPS) and a session rating of perceived exertion (RPE) were used to assess the locomotive demands and internal match load. Results: Isometric dominant ADD strength (17.8%, p ≤ 0.01) and ADD/ABD strength ratio (11.6%, p = 0.04) were lower post-match compared to the pre-match values. No between-limbs differences were observed for isometric ADD strength, ABD strength, and passive hip ROM tests. RPE showed an expected increase between pre- vs. post-match (pre- vs. post-warming-up, 3.42 ± 2.08 vs. 5.62 ± 2.29, p < 0.01). In addition, a significant relationship between ADD strength and the volume of tennis practice per week was found, stablishing that tennis players with lower volume of training per week suffered a reduction in ADD strength in their dominant limb after match-play (r = 0.420, p = 0.04). Conclusion: The assessment of ADD strength and the ADD/ABD strength ratio in the dominant limb may be considered a post-match tool that can be used to identify players who require rest and additional recovery strategies before competing again.SIThe authors received no funding for this work

Exploring allele specific methylation in drug dependence susceptibility

Drug dependence is a neuropsychiatric condition that involves genetic, epigenetic and environmental factors. Allele-specific methylation (ASM) is a common and stable epigenetic mechanism that involves genetic variants correlating with differential levels of methylation at CpG sites. We selected 182 single-nucleotide polymorphisms (SNPs) described to influence cis ASM in human brain regions to evaluate their possible contribution to drug dependence susceptibility. We performed a case-control association study in a discovery sample of 578 drug-dependent patients (including 428 cocaine-dependent subjects) and 656 controls from Spain, and then, we followed-up the significant associations in an independent sample of 1,119 cases (including 589 cocaine-dependent subjects) and 1,092 controls. In the discovery sample, we identified five nominal associations, one of them replicated in the follow-up sample (rs6020251). The pooled analysis revealed an association between drug dependence and rs6020251 but also rs11585570, both overcoming the Bonferroni correction for multiple testing. We performed the same analysis considering only cocaine-dependent patients and obtained similar results. The rs6020251 variant correlates with differential methylation levels of cg17974185 and lies in the first intron of the CTNNBL1 gene, in a genomic region with multiple histone marks related to enhancer and promoter regions in brain. Rs11585570 is an eQTL in brain and blood for the SCP2 and ECHDC2 genes and correlates with differential methylation of cg27535305 and cg13461509, located in the promoter regions of both genes. To conclude, using an approach that combines genetic and epigenetic data, we highlighted the CTNNBL1, SCP2 and ECHDC2 genes as potential contributors to drug dependence susceptibility

Comprehensive characterization of a novel, oncogenic and targetable SEPTIN6::ABL2 fusion in T-ALL

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Benchmarking of Whole Exome Sequencing and Ad Hoc Designed Panels for Genetic Testing of Hereditary Cancer

Next generation sequencing panels have been developed for hereditary cancer, although there is some debate about their cost-effectiveness compared to exome sequencing. The performance of two panels is compared to exome sequencing. Twenty-four patients were selected: ten with identified mutations (control set) and fourteen suspicious of hereditary cancer but with no mutation (discovery set). TruSight Cancer (94 genes) and a custom panel (122 genes) were assessed alongside exome sequencing. Eightythree genes were targeted by the two panels and exome sequencing. More than 99% of bases had a read depth of over 30x in the panels, whereas exome sequencing covered 94%. Variant calling with standard settings identified the 10 mutations in the control set, with the exception of MSH6 c.255dupC using TruSight Cancer. In the discovery set, 240 unique non-silent coding and canonic splice-site variants were identified in the panel genes, 7 of them putatively pathogenic (in ATM, BARD1, CHEK2, ERCC3, FANCL, FANCM, MSH2). The three approaches identified a similar number of variants in the shared genes. Exomes were more expensive than panels but provided additional data. In terms of cost and depth, panels are a suitable option for genetic diagnostics, although exomes also identify variants in non-targeted genes

Th1 and Th17 hypercytokinemia as early host response signature in severe pandemic influenza

Abstract Introduction Human host immune response following infection with the new variant of A/H1N1 pandemic influenza virus (nvH1N1) is poorly understood. We utilize here systemic cytokine and antibody levels in evaluating differences in early immune response in both mild and severe patients infected with nvH1N1. Methods We profiled 29 cytokines and chemokines and evaluated the haemagglutination inhibition activity as quantitative and qualitative measurements of host immune responses in serum obtained during the first five days after symptoms onset, in two cohorts of nvH1N1 infected patients. Severe patients required hospitalization (n = 20), due to respiratory insufficiency (10 of them were admitted to the intensive care unit), while mild patients had exclusively flu-like symptoms (n = 15). A group of healthy donors was included as control (n = 15). Differences in levels of mediators between groups were assessed by using the non parametric U-Mann Whitney test. Association between variables was determined by calculating the Spearman correlation coefficient. Viral load was performed in serum by using real-time PCR targeting the neuraminidase gene. Results Increased levels of innate-immunity mediators (IP-10, MCP-1, MIP-1β), and the absence of anti-nvH1N1 antibodies, characterized the early response to nvH1N1 infection in both hospitalized and mild patients. High systemic levels of type-II interferon (IFN-γ) and also of a group of mediators involved in the development of T-helper 17 (IL-8, IL-9, IL-17, IL-6) and T-helper 1 (TNF-α, IL-15, IL-12p70) responses were exclusively found in hospitalized patients. IL-15, IL-12p70, IL-6 constituted a hallmark of critical illness in our study. A significant inverse association was found between IL-6, IL-8 and PaO2 in critical patients. Conclusions While infection with the nvH1N1 induces a typical innate response in both mild and severe patients, severe disease with respiratory involvement is characterized by early secretion of Th17 and Th1 cytokines usually associated with cell mediated immunity but also commonly linked to the pathogenesis of autoimmune/inflammatory diseases. The exact role of Th1 and Th17 mediators in the evolution of nvH1N1 mild and severe disease merits further investigation as to the detrimental or beneficial role these cytokines play in severe illness

Fomento de la inserción laboral desde el aprendizaje servicio y emprendimiento social en los estudiantes del grado de trabajo social

Este proyecto ha seguido las principales líneas definidas en anteriores proyectos de innovación entre los que se encuentran: 1. El Proyecto de Innovación y Mejora de la Calidad Docente de la Convocatoria 2016/2017, con el nº 109, con el tema: “El impulso del emprendimiento como competencia transversal en los estudiantes del Grado de Trabajo Social”, premiado en la VII EDICIÓN de PREMIOS EMPRENDEDOR UNIVERSITARIO UCM, en la 4ª modalidad de Premio Innova docente. 2. El Proyecto de innovación y Mejora de la Calidad Docente de la Convocatoria 2017/2018, con el nº 54, con el tema: “ Red de Empleabilidad y Emprendimiento en los estudiantes del Grado de Trabajo Social” Se ha seguido investigando sobre el emprendimiento social como competencia transversal “iniciativa y espíritu emprendedor” en las asignaturas de: 1. Bases Teóricas del Trabajo Social, 2º Practicum (donde debe realizarse un Proyecto Social); 3. en el Trabajo Fin de Grado (TFG), ayudando a configurar el perfil profesional del alumnado, visualizando nuevas formas de dar respuesta a las necesidades de la población. En otras universidades españolas estos proyectos de innovación, son definidos en sus convocatorias como proyectos de investigación en innovación ya que la innovación conlleva un previo trabajo de investigación. Estas universidades reconocen la investigación que se realiza. En esta línea se encuentran universidades como la Universidad de Alicante, la Universidad Nacional de Educación a Distancia (UNED), la Universidad de Barcelona, etc., que definen la convocatoria como redes de investigación e innovación. Este reconocimiento y acreditación ha sido solicitado a la Universidad Complutense el 30 de Junio de 2016 por email. La existencia de emprendedores sociales como referentes históricos que vincularon su actividad universitaria con la innovación social y el progreso de la humanidad, justifican esta línea de trabajo. En este sentido se ha continuado con el Proyecto de Aprendizaje Servicio “UCM_MEDIMAYOR_ ALUMNI”, de formación en mediación a un grupo de mayores pertenecientes al Centro de Día Peñagrande del Ayuntamiento de Madrid. La responsabilidad social de la universidad, puede encontrase en esta función ya que se ha potenciado la adquisición de competencias profesionales a través de la colaboración en la sociedad Se ha continuado trabajando el fortalecimiento del emprendimiento social relacionado con el desarrollo social y humano, para la realización de una sociedad más equitativa y participativa desde distintas iniciativas que motiven la participación y la cooperación en esta sociedad desde sus instituciones. Entre los resultados obtenidos está la presentación a los estudiantes de buenas prácticas de emprendedores sociales y de estudiantes que han conseguido su inserción laboral, con el fin de incentivar la generación de nuevas experiencias en los estudiantes del Grado de Trabajo Social. Se destaca el hecho de que 12 estudiantes han terminado con un contrato de trabajo en su centro de practicas externas

The role of open abdomen in non-trauma patient : WSES Consensus Paper

The open abdomen (OA) is defined as intentional decision to leave the fascial edges of the abdomen un-approximated after laparotomy (laparostomy). The abdominal contents are potentially exposed and therefore must be protected with a temporary coverage, which is referred to as temporal abdominal closure (TAC). OA use remains widely debated with many specific details deserving detailed assessment and clarification. To date, in patients with intra-abdominal emergencies, the OA has not been formally endorsed for routine utilization; although, utilization is seemingly increasing. Therefore, the World Society of Emergency Surgery (WSES), Abdominal Compartment Society (WSACS) and the Donegal Research Academy united a worldwide group of experts in an international consensus conference to review and thereafter propose the basis for evidence-directed utilization of OA management in non-trauma emergency surgery and critically ill patients. In addition to utilization recommendations, questions with insufficient evidence urgently requiring future study were identified.Peer reviewe