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Abstract Background The immune system has a central role in preventing carcinogenesis. Alteration of systemic immune cell levels may increase cancer risk. However, the extent to which common genetic variation influences blood traits and cancer risk remains largely undetermined. Here, we identify pleiotropic variants and predict their underlying molecular and cellular alterations. Methods Multivariate Cox regression was used to evaluate associations between blood traits and cancer diagnosis in cases in the UK Biobank. Shared genetic variants were identified from the summary statistics of the genome-wide association studies of 27 blood traits and 27 cancer types and subtypes, applying the conditional/conjunctional false-discovery rate approach. Analysis of genomic positions, expression quantitative trait loci, enhancers, regulatory marks, functionally defined gene sets, and bulk- and single-cell expression profiles predicted the biological impact of pleiotropic variants. Plasma small RNAs were sequenced to assess association with cancer diagnosis. Results The study identified 4093 common genetic variants, involving 1248 gene loci, that contributed to blood–cancer pleiotropism. Genomic hotspots of pleiotropism include chromosomal regions 5p15-TERT and 6p21-HLA. Genes whose products are involved in regulating telomere length are found to be enriched in pleiotropic variants. Pleiotropic gene candidates are frequently linked to transcriptional programs that regulate hematopoiesis and define progenitor cell states of immune system development. Perturbation of the myeloid lineage is indicated by pleiotropic associations with defined master regulators and cell alterations. Eosinophil count is inversely associated with cancer risk. A high frequency of pleiotropic associations is also centered on the regulation of small noncoding Y-RNAs. Predicted pleiotropic Y-RNAs show specific regulatory marks and are overabundant in the normal tissue and blood of cancer patients. Analysis of plasma small RNAs in women who developed breast cancer indicates there is an overabundance of Y-RNA preceding neoplasm diagnosis. Conclusions This study reveals extensive pleiotropism between blood traits and cancer risk. Pleiotropism is linked to factors and processes involved in hematopoietic development and immune system function, including components of the major histocompatibility complexes, and regulators of telomere length and myeloid lineage. Deregulation of Y-RNAs is also associated with pleiotropism. Overexpression of these elements might indicate increased cancer risk.

Las tecnologías digitales (TD) están transformando la educación, exigiendo a los docentes desarrollar competencias digitales. La madurez digital de las instituciones educativas es cada vez más importante con la integración de las TD en las estrategias y prácticas docentes. El objetivo del estudio es definir acciones e identificar ámbitos de actuación para mejorar la Competencia Digital Docente (CDD) y avanzar hacia la madurez digital. La revisión está basada en el modelo PRISMA entre 2017 y enero 2023. Las bases de datos utilizadas son WoS, Scopus y ERIC. Después de aplicar los criterios, la muestra es de 25 artículos. Las siete líneas de acción para mejorar la CDD son la formación, la autoeficacia, la evaluación, la integración de la Competencia Digital (CD), el asesoramiento, la reflexión y la integración en el currículo. Para avanzar en la madurez digital se distinguen cuatro ámbitos a tener en cuenta: CD del alumnado, CDD, gestión de recursos e infraestructura y gestión del centro educativo.

Las últimas excavaciones realizadas en la parte baja del Turó de Peralada han puesto al descubierto dos nuevas viviendas del Ibérico Pleno y Tardío que modifican la interpretación que se tenía actualmente del hábitat doméstico de este período en el yacimiento. Por esta razón, con base en estas nuevas evidencias y su posterior abandono intencionado a mediados del siglo I a. C. por la irrupción del mundo romano, se evidencian importantes cambios en el Turó de Peralada de los cuales hasta ahora se tenían muy pocos datos.

Background & Aims: Porto-sinusoidal vascular disorder (PSVD) encompasses a group of liver diseases with vascular abnormalities that can cause portal hypertension in the absence of cirrhosis. The new diagnostic criteria allow for coexistence with other liver diseases, however its relationship with chronic hepatitis B (CHB) remains unclear. This study aimed to assess HBV prevalence in a PSVD cohort and evaluate its clinical impact. Methods: This retrospective study was conducted on patients with PSVD at Hospital Clínic Barcelona. HBV serology was evaluated, and patients were categorized into HBV chronic infection, past infection, or no HBV exposure. Clinical characteristics and outcomes were compared. Results: We included 155 patients with PSVD. Prevalence of CHB and past HBV infection in patients with PSVD was higher than in the general population (5.8% vs. 0.5%, p

Background & Aims: Spontaneous portosystemic shunts (SPSS) develop frequently in cirrhosis. Changes over time and the effect of aetiological interventions on SPSS are unknown, so we aimed to explore the effect of these variables on SPSS evolution. Methods: Patients with cirrhosis from the Baveno VI-SPSS cohort were selected provided a follow-up abdominal CT or MRI scan was available. Clinical and laboratory data were collected at baseline and follow-up. Imaging tests were reviewed to evaluate changes in the presence and size of SPSS (large (L)-SPSS was ≥8 mm) over time. Regarding alcohol- or HCV-related cirrhosis, two populations were defined: cured patients (abstinent from alcohol or successful HCV therapy), and non-cured patients. Results: A total of 617 patients were included. At baseline SPSS distribution was 22% L-SPSS, 30% small (S)-SPSS, and 48% without (W)-SPSS. During follow-up (median follow-up of 63 months), SPSS distribution worsened: L-SPSS 26%, S-SPSS 32%, and W-SPSS 42% (p

The surgically induced remission of liver disease represents a model to investigate the signalling processes that trigger the development of nonalcoholic steatohepatitis with the aim of identifying novel therapeutic targets. We recruited patients with severe obesity with or without nonalcoholic steatohepatitis and obtained liver and plasma samples before and after laparoscopic sleeve gastrectomy for immunoblotting, immunocytochemical, metabolomic, transcriptomic and epigenetic analyses. Functional studies were performed in HepG2 cells and primary hepatocytes. Surgery was associated with a decrease in the inflammatory response and revealed the role of mitogen-activated protein kinases. Nonalcoholic steatohepatitis was associated with an increased glutaminolysis-induced production of α-ketoglutarate and the hyperactivation of mammalian target of rapamycin complex 1. These changes were crucial for adenosine monophosphate-activated protein kinase/mammalian target of rapamycin-driven pathways that modulated hepatocyte survival by coordinating apoptosis and autophagy and affected methylation-related epigenomic remodelling enzymes. Hepatic transcriptome signatures and differentially methylated genomic regions distinguished patients with and without steatohepatitis. Our results suggest that the increased glutaminolysis-induced α-ketoglutarate production and the mammalian target of rapamycin complex 1 dysregulation play a crucial role in the inefficient adaptive responses leading to steatohepatitis in obesity.

Aunque reciente en nuestra disciplina, la arqueología de las zonas de alta montaña poco a poco va consolidándose, generando corpus empíricos y procedimientos que en muchas ocasiones constituyen sus señas de identidad. Por encima de la diversidad de equipos y programas de investigación, algunos aspectos tienden a presentarse de forma recurrente. Uno es un cierto interés por las secuencias de larga duración. Otro lo constituye la mirada hacia un espacio amplio, que va mucho más allá del asentamiento. Este interés por el territorio o el paisaje, que en ocasiones se prefigura como un verdadero objeto de estudio, conlleva cambios en el diseño metodológico de la investigación. En este trabajo pretendemos recoger los ya casi veinte años de experiencia del Grupo de Arqueología de la Alta Montaña (GAAM) de la UAB y el CSIC para presentar una breve reflexión teórica sobre un aspecto que, a nuestro entender, es central en nuestra disciplina. La arqueología, en cuanto ciencia social, aborda una existencia humana colectiva que ocurre tanto en el tiempo como en el espacio. Por diversos motivos, la arqueología en áreas de alta montaña ha sido especialmente proclive a incorporar elementos metodológicos para tratar con el espacio también como instancia social. Quizás ha llegado el momento de empezar a evaluar los puntos fuertes de estas propuestas y tratar de identificar aquellas cuestiones que merecen mayor atención. En la parte final del artículo ilustramos, con un caso empírico, la pertinencia de la reflexión teórica planteada.

Background & Aims: Whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a risk factor for splanchnic vein thrombosis (SVT) is unknown. This study aims to assess the impact of SARS-CoV-2 infection on the presentation and prognosis of recent SVT and to identify specific characteristics of SARS-CoV-2-associated SVT. Methods: This is a retrospective study collecting health-related data of 27 patients presenting with recent SVT in the context of SARS-CoV-2 infection in 12 Vascular Liver Disease Group (VALDIG) centres and in comparison with 494 patients with recent SVT before the SARS-CoV-2 pandemic. Results: Twenty-one patients with SARS-CoV-2 had portal vein thrombosis with or without thrombosis of another splanchnic vein, two had superior mesenteric vein thrombosis, one had splenic vein thrombosis, and three had hepatic vein thrombosis. Diagnosis of SVT was made 10 days (95% CI 0–24 days) after the diagnosis of SARS-CoV-2 infection. Fever (52 vs. 15%; p

The effect of hyaluronan-mediated motility receptor (HMMR) expression in BRCA1-associated breast cancer risk remains unknown. Here, HMMR overexpression induces the activation of cGAS-STING and non-canonical NF-κB signalling, instigating an immune permissive environment for breast cancer development.