Design of an Advanced Platform for Citizen Participation Committed to Ensuring Freedom of Speech

This paper presents a proposal for an advanced system of debate in an environment of digital democracy which overcomes the limitations of existing systems. We have been especially careful in applying security procedures in telematic systems, for they are to offer citizens the guarantees that society demands. New functional tools have been included to ensure user authentication and to permit anonymous participation where the system is unable to disclose or even to know the identity of system users. The platform prevents participation by non-entitled persons who do not belong to the authorized group from giving their opinion. Furthermore, this proposal allows for verifying the proper function of the system, free of tampering or fraud intended to alter the conclusions or outcomes of participation. All these tools guarantee important aspects of both a social and technical nature, most importantly: freedom of expression, equality and auditability

Validation of a questionnaire on emotional eating for use in cases of obesity : the Emotional Eater Questionnaire (EEQ)

Introduction: Emotions have a powerful effect on our choice of food and eating habits. It has been found that in some people there is relationship between eating, emotions and the increased energy intake. This relationship should be measurable to better understand how food is used to deal with certain mood states and how these emotions affect the effectiveness of weight loss programs. Objective: To develop and analyze the psychometric characteristics of a questionnaire on emotional eating for obesity easy to apply in clinical practice. Subjects and methods: A ten-item questionnaire called Emotional-Eater-Questionnaire (EEQ) was developed and administered to a total of 354 subjects (body mass index, 31 ± 5), aged 39 ± 12, who were subjected to a weight-reduction program. The questionnaire was specifically designed for obesity. Analysis of the internal structure, internal consistency, test-retest reliability and convergent validity with Mindful-Eater-Questionnaire (MEQ) were conducted. Results: After principal components analysis, the questionnaire was classified in three different dimensions that explained 60% of the total variance: Disinhibition, Type-of-food and Guilt. Internal consistency showed that Cronbach's alpha was 0.773 for the "Dishinibition" subscale, 0.656 for the "Type of food" subscale and 0.612 for the "Guilt" subscale. The test-retest stability was r =0.70. The data showed that the percentage of agreement between the EEQ and the MEQ was around 70% with a Kappa index of 0.40; P < 0.0001. Conclusion: We have presented a new questionnaire, which classifies individuals as a function of the relation between food intake and emotions. Such information will permit personalised treatments to be designed by drawing up early strategies from the very beginning of treatment programmesIntroducción: Las emociones tienen un poderoso efecto sobre la elección de alimentos y los hábitos alimentarios. Existe una relación entre comer, emociones y el aumento del aporte calórico. Esta relación debería ser medible para comprender mejor cómo utilizamos los alimentos en determinados estados de ánimo y cómo las emociones afectan a la eficacia de los programas de pérdida de peso. Objetivo: Desarrollar y analizar las características psicométricas de un cuestionario para identificar la ingesta emocional en la obesidad de fácil aplicación en la práctica clínica. Material y métodos: Se ha desarrollado y administrado un cuestionario de diez ítems llamado Cuestionario-de-Comedor-Emocional (CCE) a un total de 354 sujetos (Índice de Masa Corporal: 31 ± 5), (Edad: 39 ± 12 años), pertenecientes a un programa de reducción de peso. Se llevó a cabo un análisis de la estructura interna del cuestionario, de la consistencia interna, la fiabilidad testretest y la validez convergente con el Mindful-Eater- Questionnaire (MEQ). Resultados: El análisis de componentes principales del cuestionario encontró tres dimensiones diferentes que explicaban el 60% de la varianza: desinhibición, tipo de alimento y culpa. La consistencia interna mostró que el alfa de Cronbach fue de 0,773 para la subescala "Desinhibición", 0,656 para "Tipo de alimentos" y 0,612 para "culpa". La estabilidad test-retest fue de r = 0,70. Los datos mostraron que el porcentaje de acuerdo entre el CCE y MEQ era del 70% con un índice Kappa de 0,40, P < 0,0001. Conclusión: Hemos presentado un nuevo cuestionario, que clasifica a los individuos en función de la relación entre la ingesta de alimentos y las emociones. Esta información permitirá el diseño de tratamientos personalizados desde el inicio para la obesida

TRIB3 suppresses tumorigenesis by controlling mTORC2/AKT/FOXO signaling.

In a recent article, we found that Tribbles pseudokinase 3 (TRIB3) plays a tumor suppressor role and that this effect relies on the dysregulation of the phosphorylation of v-akt murine thymoma viral oncogene homolog (AKT) by the mammalian target of rapamycin complex 2 (mTORC2 complex), and the subsequent hyperphosphorylation and inactivation of the transcription factor Forkhead box O3 (FOXO3)

A school-based program implemented by community providers previously trained for the prevention of eating and weight-related problems in secondary-school adolescents : the MABIC study protocol

Background: The prevention of eating disorders and disordered eating are increasingly recognized as public health priorities. Challenges in this field included moving from efficacy to effectiveness and developing an integrated approach to the prevention of a broad spectrum of eating and weight-related problems. A previous efficacy trial indicated that a universal disordered eating prevention program, based on the social cognitive model, media literacy educational approach and cognitive dissonance theory, reduced risk factors for disordered eating, but it is unclear whether this program has effects under more real-world conditions. The main aim of this effectiveness trial protocol is to test whether this program has effects when incorporating an integrated approach to prevention and when previously-trained community providers implement the intervention. Methods/design: The research design involved a multi-center non-randomized controlled trial with baseline, post and 1-year follow-up measures. Six schools from the city of Sabadell (close to Barcelona) participated in the intervention group, and eleven schools from four towns neighboring Sabadell participated in the control group. A total of 174 girls and 180 boys in the intervention group, and 484 girls and 490 boys in the control group were registered in class lists prior to baseline. A total of 18 community providers, secondary-school class tutors, nurses from the Catalan Government's Health and School Program, and health promotion technicians from Sabadell City Council were trained and delivered the program. Shared risk factors of eating and weight-related problems were assessed as main measures. Discussion: It will be vital for progress in disordered eating prevention to conduct effectiveness trials, which test whether interventions are effective when delivered by community providers under ecologically valid conditions, as opposed to tightly controlled research trials. The MABIC project will provide new contributions in this transition from efficacy to effectiveness and new data about progress in the integrated approach to prevention. Pending the results, the effectiveness trial meets the effectiveness standards set down by the Society for Prevention Research. This study will provide new evidence to improve and enhance disordered eating prevention programs

Stratification and therapeutic potential of PML in metastatic breast cancer.

Patient stratification has been instrumental for the success of targeted therapies in breast cancer. However, the molecular basis of metastatic breast cancer and its therapeutic vulnerabilities remain poorly understood. Here we show that PML is a novel target in aggressive breast cancer. The acquisition of aggressiveness and metastatic features in breast tumours is accompanied by the elevated PML expression and enhanced sensitivity to its inhibition. Interestingly, we find that STAT3 is responsible, at least in part, for the transcriptional upregulation of PML in breast cancer. Moreover, PML targeting hampers breast cancer initiation and metastatic seeding. Mechanistically, this biological activity relies on the regulation of the stem cell gene SOX9 through interaction of PML with its promoter region. Altogether, we identify a novel pathway sustaining breast cancer aggressiveness that can be therapeutically exploited in combination with PML-based stratification.The work of A.C. is supported by the Ramón y Cajal award, the Basque Department of Industry, Tourism and Trade (Etortek), Health (2012111086) and Education (PI2012-03), Marie Curie (277043), Movember Foundation (GAP1), ISCIII (PI10/01484, PI13/00031), FERO (VIII Fellowship) and ERC (336343). N.M.-M. and P.A. are supported by the Spanish Association Against Cancer (AECC), AECC JP Vizcaya and Guipuzcoa, respectively. J.U. and F.S. are Juan de la Cierva Researchers (MINECO). L.A., A.A.-A. and L.V.-J. are supported by the Basque Government of education. M.L.-M.C. acknowledges SAF2014-54658-R and Asociación Española contra el Cancer. R.B. acknowledges Spanish MINECO (BFU2014-52282-P, Consolider BFU2014-57703-REDC), the Departments of Education and Industry of the Basque Government (PI2012/42) and the Bizkaia County. M.S., V.S. and J.B. acknowledge Banco Bilbao Vizcaya Argentaria (BBVA) Foundation (Tumour Biomarker Research Program). M.S. and J.B. are supported by NIH grant P30 CA008748. M.dM.V. is supported by the Institute of Health Carlos III (PI11/02251, PI14/01328) and Basque Government, Health Department (2014111145). A.M. is supported by ISCIII (CP10/00539, PI13/02277) and Marie Curie CIG 2012/712404. V.S. is supported by the SCIII (PI13/01714, CP14/00228), the FERO Foundation and the Catalan Agency AGAUR (2014 SGR 1331). R.R.G. research support is provided by the Spanish Ministry of Science and Innovation grant SAF2013-46196, BBVA Foundation, the Generalitat de Catalunya (2014 SGR 535), Institució Catalana de Recerca i Estudis Avançats, the Spanish Ministerio de Economia y Competitividad (MINECO) and FEDER funds (SAF2013-46196).This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ncomms1259

Transient Changes in Bacterioplankton Communities Induced by the Submarine Volcanic Eruption of El Hierro (Canary Islands)

Postprint4,411

Genomic Characterization of Host Factors Related to SARS-CoV-2 Infection in People with Dementia and Control Populations: The GR@ACE/DEGESCO Study

Emerging studies have suggested several chromosomal regions as potential host genetic factors involved in the susceptibility to SARS-CoV-2 infection and disease outcome. We nested a COVID-19 genome-wide association study using the GR@ACE/DEGESCO study, searching for susceptibility factors associated with COVID-19 disease. To this end, we compared 221 COVID-19 confirmed cases with 17,035 individuals in whom the COVID-19 disease status was unknown. Then, we performed a meta-analysis with the publicly available data from the COVID-19 Host Genetics Initiative. Because the APOE locus has been suggested as a potential modifier of COVID-19 disease, we added sensitivity analyses stratifying by dementia status or by disease severity. We confirmed the existence of the 3p21.31 region (LZTFL1, SLC6A20) implicated in the susceptibility to SARS-CoV-2 infection and TYK2 gene might be involved in COVID-19 severity. Nevertheless, no statistically significant association was observed in the COVID-19 fatal outcome or in the stratified analyses (dementia-only and non-dementia strata) for the APOE locus not supporting its involvement in SARS-CoV-2 pathobiology or COVID-19 prognosis

A crowdsourcing database for the copy-number variation of the spanish population

Background: Despite being a very common type of genetic variation, the distribution of copy-number variations (CNVs) in the population is still poorly understood. The knowledge of the genetic variability, especially at the level of the local population, is a critical factor for distinguishing pathogenic from non-pathogenic variation in the discovery of new disease variants. Results: Here, we present the SPAnish Copy Number Alterations Collaborative Server (SPACNACS), which currently contains copy number variation profiles obtained from more than 400 genomes and exomes of unrelated Spanish individuals. By means of a collaborative crowdsourcing effort whole genome and whole exome sequencing data, produced by local genomic projects and for other purposes, is continuously collected. Once checked both, the Spanish ancestry and the lack of kinship with other individuals in the SPACNACS, the CNVs are inferred for these sequences and they are used to populate the database. A web interface allows querying the database with different filters that include ICD10 upper categories. This allows discarding samples from the disease under study and obtaining pseudo-control CNV profiles from the local population. We also show here additional studies on the local impact of CNVs in some phenotypes and on pharmacogenomic variants. SPACNACS can be accessed at: http://csvs.clinbioinfosspa.es/spacnacs/. Conclusion: SPACNACS facilitates disease gene discovery by providing detailed information of the local variability of the population and exemplifies how to reuse genomic data produced for other purposes to build a local reference database.This work is supported by Grants PID2020-117979RB-I00 from the Spanish Ministry of Science and Innovation; by the Institute of Health Carlos III (project IMPaCT-Data, exp. IMP/00019, IMP/00009 and PI20/01305), co-funded by the European Union, European Regional Development Fund (ERDF, “A way to make Europe”)

Targeting of PI3K/AKT/mTOR pathway to inhibit T cell activation and prevent graft-versus-host disease development

Producción CientíficaBackground: Graft-versus-host disease (GvHD) remains the major obstacle to successful allogeneic hematopoietic stem cell transplantation, despite of the immunosuppressive regimens administered to control T cell alloreactivity. PI3K/AKT/mTOR pathway is crucial in T cell activation and function and, therefore, represents an attractive therapeutic target to prevent GvHD development. Recently, numerous PI3K inhibitors have been developed for cancer therapy. However, few studies have explored their immunosuppressive effect. Methods: The effects of a selective PI3K inhibitor (BKM120) and a dual PI3K/mTOR inhibitor (BEZ235) on human T cell proliferation, expression of activation-related molecules, and phosphorylation of PI3K/AKT/mTOR pathway proteins were analyzed. Besides, the ability of BEZ235 to prevent GvHD development in mice was evaluated. Results: Simultaneous inhibition of PI3K and mTOR was efficient at lower concentrations than PI3K specific targeting. Importantly, BEZ235 prevented naïve T cell activation and induced tolerance of alloreactive T cells, while maintaining an adequate response against cytomegalovirus, more efficiently than BKM120. Finally, BEZ235 treatment significantly improved the survival and decreased the GvHD development in mice. Conclusions: These results support the use of PI3K inhibitors to control T cell responses and show the potential utility of the dual PI3K/mTOR inhibitor BEZ235 in GvHD prophylaxis.Asociación Española Contra el Cáncer (Proyecto AIOA110296BLAN).Gerencia Regional de Salud de Castilla y León (Proyecto GRS 726/A13