97 research outputs found

    Impact of COVID-19 on the Health of the General and More Vulnerable Population and Its Determinants: Health Care and Social Survey–ESSOC, Study Protocol

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    This manuscript describes the rationale and protocol of a real-world data (RWD) study entitled Health Care and Social Survey (ESSOC, Encuesta Sanitaria y Social). The study’s objective is to determine the magnitude, characteristics, and evolution of the COVID-19 impact on overall health as well as the socioeconomic, psychosocial, behavioural, occupational, environmental, and clinical determinants of both the general and more vulnerable population. The study integrates observational data collected through a survey using a probabilistic, overlapping panel design, and data from clinical, epidemiological, demographic, and environmental registries. The data will be analysed using advanced statistical, sampling, and machine learning techniques. The study is based on several measurements obtained from three random samples of the Andalusian (Spain) population: general population aged 16 years and over, residents in disadvantaged areas, and people over the age of 55. Given the current characteristics of this pandemic and its future repercussions, this project will generate relevant information on a regular basis, commencing from the beginning of the State of Alarm. It will also establish institutional alliances of great social value, explore and apply powerful and novel methodologies, and produce large, integrated, high-quality and open-access databases. The information described here will be vital for health systems in order to design tailor-made interventions aimed at improving the health care, health, and quality of life of the populations most affected by the COVID-19 pandemic.Andalusian Institute of Statistics and Cartography (IECA)Andalusian School of Public Health (EASP)SUPERA COVID-19 Fund of Santander Universities (SAUN)Conference of Spanish University Rectors (CRUE, Conferencia de Rectores de Universidades EspañolasSpanish National Research Council (CSIC, Consejo Superior de Investigaciones Científicas)COVID-19 Competitive Grant Program from Pfizer Global Medical GrantsIMAG–Maria de Maeztu grantMinisterio de Ciencia e Innovación, Spai

    TRANSWESD: inferring cellular networks with transitive reduction

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    Motivation: Distinguishing direct from indirect influences is a central issue in reverse engineering of biological networks because it facilitates detection and removal of false positive edges. Transitive reduction is one approach for eliminating edges reflecting indirect effects but its use in reconstructing cyclic interaction graphs with true redundant structures is problematic

    Characterization of endogenous Kv1.3 channel isoforms in T cells

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    Producción CientíficaVoltage-dependent potassium channel Kv1.3 plays a key role on T-cell activation; however, lack of reliable antibodies has prevented its accurate detection under endogenous circumstances. To overcome this limitation, we created a Jurkat T-cell line with endogenous Kv1.3 channel tagged, to determine the expression, location, and changes upon activation of the native Kv1.3 channels. CRISPR-Cas9 technique was used to insert a Flag-Myc peptide at the C terminus of the KCNA3 gene. Basal or activated channel expression was studied using western blot analysis and imaging techniques. We identified two isoforms of Kv1.3 other than the canonical channel (54 KDa) differing on their N terminus: a longer isoform (70 KDa) and a truncated isoform (43 KDa). All three isoforms were upregulated after T-cell activation. We focused on the functional characterization of the truncated isoform (short form, SF), because it has not been previously described and could be present in the available Kv1.3−/− mice models. Overexpression of SF in HEK cells elicited small amplitude Kv1.3-like currents, which, contrary to canonical Kv1.3, did not induce HEK proliferation. To explore the role of endogenous SF isoform in a native system, we generated both a knockout Jurkat clone and a clone expressing only the SF isoform. Although the canonical isoform (long form) localizes mainly at the plasma membrane, SF remains intracellular, accumulating perinuclearly. Accordingly, SF Jurkat cells did not show Kv1.3 currents and exhibited depolarized resting membrane potential (VM), decreased Ca2+ influx, and a reduction in the [Ca2+]i increase upon stimulation. Functional characterization of these Kv1.3 channel isoforms showed their differential contribution to signaling pathways involved in formation of the immunological synapse. We conclude that alternative translation initiation generates at least three endogenous Kv1.3 channel isoforms in T cells that exhibit different functional roles. For some of these functions, Kv1.3 proteins do not need to form functional plasma membrane channels.Ministerio de Economía y Competitividad (grant PID 2020‐118517RB‐I00)Junta de Castilla y León (grants VA172P20) and (CLU-2019-02)Funds from Institut Curie, INSERM,Agence Nationale de la Recherche RetroTact (ANR‐20CE15‐0009‐01,ANR‐10‐IDEX‐0001‐02 PSL*, and ANR‐11‐LABX‐0043)Fondation pour la Recherche Médicale FRM (EQU202003010280

    Perspectivas actuales de las fuentes del Derecho

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    Presentación / Rafael de Asís Roig. - Fuentes del Derecho y comunidad civil / Dionisio Llamazares Fernández. - Las fuentes del derecho y su problemática actual / Antonio Enrique Pérez Luño. - Fuentes del Derecho y sociedad civil : la participación de ésta en la creación normativa, desde la perspectiva del ordenamiento jurídico internacional / Montserrat Abad Castelos. - La tutela de la libertad religiosa en la Unión Europea y su incidencia en el ordenamiento interno español / Adoración Castro Jover. - Sistema normativo de la Unión Europea (naturaleza de las fuentes) / Carlos Moreiro González. - La incidencia de la Unión Europea en el sistema interno de fuentes de los Estados miembros / Ana Garriga Domínguez. - Las fuentes del Derecho Islámico / Mario Losano. - Multiculturalidad, Derecho islámico y ordenamiento secular; los supuestos de la poligamia y el repudio / Agustín Motilla de la Calle. - Interculturalidad y fuentes del Derecho : algunas reflexiones desde el Derecho Internacional / Carlos Fernández Liesa . - La definitiva secularización de la legislación sobre la interrupción del embarazo en España / Daniel Capodiferro Cubero. - Interculturalidade e Fontes do Direito. - A ética da racionalidade do outro como princípio e critério objetivo na análise da interculturalidade e sua relação quanto à legitimação das fontes do direito / Artur César de Souza. - El papel de los nuevos movimientos sociales en la regulación jurídica de la globalización / Jose Antonio García Saez. - Relaciones entre ordenamientos jurídicos en el ámbito de la Unión Europea / Cristina Hermida del LLano. - La incidencia «interesada» de la Directiva 2003/86/CE en la última reforma de la Ley de extranjería española / Encarnación La Spina. - La lex mercatoria : una excepción a la legitimidad del orden jurídico-político moderno / Francisco López Ruiz. - Un paralelismo entre las teorías de los principios y la jurisprudencia de conceptos: la ruptura del puente entre las fuentes del Derecho y la sociedad civil / Luis Lloredo Alix. - La configuración de un derecho cultural sobre lo religioso como una propuesta para la plena integración de las personas de origen musulman residentes en Europa / Andrés Murcia González. - Sobre algunas concepciones de la jurisprudencia en la cultura jurídica norteamericana / Oscar Pérez de la Fuent

    Big Data en Educación III: recomendaciones personalizadas de actuación ante estudiantes en riesgo de abandono

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    En este proyecto se elaboran un conjunto de recomendaciones personalizadas para guiar la actuación del profesor con estudiantes que hayan sido detectados en riesgo de abandono de una asignatura o de la titulación en general. Con carácter previo, se desarrollan métodos estadísticos que permitan la detección del riesgo de abandono de un estudiante

    El reto en la docencia de la igualdad ante la diversidad

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    El proyecto presenta iniciativas llevadas a cabo por el equipo investigador encaminadas a incorporar las perspectivas de género y discapacidad en la docencia. Del mismo modo, se señalan algunas actividades incorporadas a la docencia de la asignatura "Políticas Públicas" que se imparte en varias titulaciones, con el objetivo de favorecer la impartición de esta materia en inglés

    Risk factors and outcome of COVID-19 in patients with hematological malignancies

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    Background: Prognostic factors of poor outcome in patients with hematological malignancies and COVID-19 are poorly defned. Patients and methods: This was a Spanish transplant group and cell therapy (GETH) multicenter retrospective observational study, which included a large cohort of blood cancer patients with laboratory-confrmed SARS-CoV-2 infection through PCR assays from March 1st 2020 to May 15th 2020. Results: We included 367 pediatric and adult patients with hematological malignancies, including recipients of autologous (ASCT) (n=58) or allogeneic stem cell transplantation (allo-SCT) (n=65) from 41 hospitals in Spain. Median age of patients was 64 years (range 1-93.8). Recipients of ASCT and allo-SCT showed lower mortality rates (17% and 18%, respectively) compared to non-SCT patients (31%) (p=0.02). Prognostic factors identifed for day 45 overall mortality (OM) by logistic regression multivariate analysis included age>70 years [odds ratio (OR) 2.1, 95% con‑ fdence interval (CI) 1.2-3.8, p=0.011]; uncontrolled hematological malignancy (OR 2.9, 95% CI 1.6-5.2, p20 mg/dL (OR 3.3, 95% CI 1.7-6.4, p<0.0001). In multivariate analysis of 216 patients with very severe COVID-19, treatment with azithromycin or low dose corticosteroids was associated with lower OM (OR 0.42, 95% CI 0.2-0.89 and OR 0.31, 95% CI 0.11-0.87, respectively, p=0.02) whereas the use of hidroxycloroquine did not show signifcant improvement in OM (OR 0.64, 95% CI 0.37-1.1, P=0.1). Conclusions: In most patients with hematological malignancies COVID-19 mortality was directly driven by older age, disease status, performance status, as well as by immune (neutropenia) parameters and level of infammation (high CRP). Use of azithromycin and low dose corticosteroids may be of value in very severe COVID-19

    Inferring causal molecular networks: empirical assessment through a community-based effort.

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    It remains unclear whether causal, rather than merely correlational, relationships in molecular networks can be inferred in complex biological settings. Here we describe the HPN-DREAM network inference challenge, which focused on learning causal influences in signaling networks. We used phosphoprotein data from cancer cell lines as well as in silico data from a nonlinear dynamical model. Using the phosphoprotein data, we scored more than 2,000 networks submitted by challenge participants. The networks spanned 32 biological contexts and were scored in terms of causal validity with respect to unseen interventional data. A number of approaches were effective, and incorporating known biology was generally advantageous. Additional sub-challenges considered time-course prediction and visualization. Our results suggest that learning causal relationships may be feasible in complex settings such as disease states. Furthermore, our scoring approach provides a practical way to empirically assess inferred molecular networks in a causal sense
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