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Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association meta-analysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGGoverall) was 3.31% (SE = 0.0038). We found no genome-wide significant SNPs for AGGoverall. The gene-based analysis returned three significant genes: ST3GAL3 (P = 1.6E-06), PCDH7 (P = 2.0E-06), and IPO13 (P = 2.5E-06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (rg) among rater-specific assessment of AGG ranged from rg = 0.46 between self- and teacher-assessment to rg = 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rgs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range [Formula: see text]: 0.19-1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (rg = ~-0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range [Formula: see text]: 0.46-0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.

Resume: Introducción: Las ataxias (AT) y paraparesias espásticas hereditarias (PEH) son síndromes neurodegenerativos raros. Nos proponemos conocer la prevalencia de las AT y PEH en España en 2019. Pacientes y métodos: Estudio transversal, multicéntrico, descriptivo y retrospectivo de los pacientes con AT y PEH, desde marzo de 2018 a diciembre de 2019 en toda España. Resultados: Se obtuvo información de 1933 pacientes procedentes de 11 Comunidades Autónomas, de 47 neurólogos o genetistas. Edad media: 53,64 años ± 20,51 desviación estándar (DE); 938 varones (48,5%), 995 mujeres (51,5%). En 920 pacientes (47,6%) no se conoce el defecto genético. Por patologías, 1.371 pacientes (70,9%) diagnosticados de AT, 562 diagnosticados de PEH (29,1%). La prevalencia estimada de AT es 5,48/100.000 habitantes, y la de PEH es 2,24 casos/100.000 habitantes. La AT dominante más frecuente es la SCA3. La AT recesiva más frecuente es la ataxia de Friedreich (FRDA). La PEH dominante más frecuente es la SPG4, y la PEH recesiva más frecuente es la SPG7. Conclusiones: La prevalencia estimada de AT y PEH en nuestra serie es de 7,73 casos/100.000 habitantes. Estas frecuencias son similares a las del resto del mundo. En el 47,6% no se ha conseguido un diagnóstico genético. A pesar de las limitaciones, este estudio puede contribuir a estimar los recursos, visibilizar estas enfermedades, detectar las mutaciones más frecuentes para hacer los screenings por comunidades, y favorecer los ensayos clínicos. Abstract: Introduction: Ataxia and hereditary spastic paraplegia are rare neurodegenerative syndromes. We aimed to determine the prevalence of these disorders in Spain in 2019. Patients and methods: We conducted a cross-sectional, multicentre, retrospective, descriptive study of patients with ataxia and hereditary spastic paraplegia in Spain between March 2018 and December 2019. Results: We gathered data from a total of 1933 patients from 11 autonomous communities, provided by 47 neurologists or geneticists. Mean (SD) age in our sample was 53.64 (20.51) years; 938 patients were men (48.5%) and 995 were women (51.5%). The genetic defect was unidentified in 920 patients (47.6%). A total of 1371 patients (70.9%) had ataxia and 562 (29.1%) had hereditary spastic paraplegia. Prevalence rates for ataxia and hereditary spastic paraplegia were estimated at 5.48 and 2.24 cases per 100 000 population, respectively. The most frequent type of dominant ataxia in our sample was SCA3, and the most frequent recessive ataxia was Friedreich ataxia. The most frequent type of dominant hereditary spastic paraplegia in our sample was SPG4, and the most frequent recessive type was SPG7. Conclusions: In our sample, the estimated prevalence of ataxia and hereditary spastic paraplegia was 7.73 cases per 100 000 population. This rate is similar to those reported for other countries. Genetic diagnosis was not available in 47.6% of cases. Despite these limitations, our study provides useful data for estimating the necessary healthcare resources for these patients, raising awareness of these diseases, determining the most frequent causal mutations for local screening programmes, and promoting the development of clinical trials.

Introduction: Ataxia and hereditary spastic paraplegia are rare neurodegenerative syndromes. We aimed to determine the prevalence of these disorders in Spain in 2019. Patients and methods: We conducted a cross-sectional, multicentre, retrospective, descriptive study of patients with ataxia and hereditary spastic paraplegia in Spain between March 2018 and December 2019. Results: We gathered data from a total of 1933 patients from 11 autonomous communities, provided by 47 neurologists or geneticists. Mean (SD) age in our sample was 53.64 (20.51) years; 938 patients were men (48.5%) and 995 were women (51.5%). The genetic defect was unidentified in 920 patients (47.6%). A total of 1371 patients (70.9%) had ataxia and 562 (29.1%) had hereditary spastic paraplegia. Prevalence rates for ataxia and hereditary spastic paraplegia were estimated at 5.48 and 2.24 cases per 100 000 population, respectively. The most frequent type of dominant ataxia in our sample was SCA3, and the most frequent recessive ataxia was Friedreich ataxia. The most frequent type of dominant hereditary spastic paraplegia in our sample was SPG4, and the most frequent recessive type was SPG7. Conclusions: In our sample, the estimated prevalence of ataxia and hereditary spastic paraplegia was 7.73 cases per 100 000 population. This rate is similar to those reported for other countries. Genetic diagnosis was not available in 47.6% of cases. Despite these limitations, our study provides useful data for estimating the necessary healthcare resources for these patients, raising awareness of these diseases, determining the most frequent causal mutations for local screening programmes, and promoting the development of clinical trials. Resumen: Introducción: Las ataxias (AT) y paraparesias espásticas hereditarias (PEH) son síndromes neurodegenerativos raros. Nos proponemos conocer la prevalencia de las AT y PEH (APEH) en España en 2019. Pacientes y métodos: Estudio transversal, multicéntrico, descriptivo y retrospectivo de los pacientes con AT y PEH, desde Marzo de 2018 a Diciembre de 2019 en toda España. Resultados: Se obtuvo información de 1.933 pacientes procedentes de 11 Comunidades Autónomas, de 47 neurólogos o genetistas. Edad media: 53,64 años ± 20,51 desviación estándar (DE); 938 varones (48,5%), 995 mujeres (51,1%). En 920 pacientes (47,6%) no se conoce el defecto genético. Por patologías, 1.371 pacientes (70,9%) diagnosticados de AT, 562 diagnosticados de PEH (29,1%). La prevalencia estimada de AT es 5,48/100.000 habitantes, y la de PEH es 2,24 casos/100.000 habitantes. La AT dominante más frecuente es la SCA3. La AT recesiva más frecuente es la ataxia de Friedreich (FRDA). La PEH dominante más frecuente es la SPG4, y la PEH recesiva más frecuente es la SPG7. Conclusiones: La prevalencia estimada de APEH en nuestra serie es de 7,73 casos/100.000 habitantes. Estas frecuencias son similares a las del resto del mundo. En el 47,6% no se ha conseguido un diagnóstico genético. A pesar de las limitaciones, este estudio puede contribuir a estimar los recursos, visibilizar estas enfermedades, detectar las mutaciones más frecuentes para hacer los screenings por comunidades, y favorecer los ensayos clínicos.

Abstract Background The activation of dendritic cells (DCs) is pivotal for generating antigen-specific T-cell responses to eradicate tumor cells. Hence, immunotherapies targeting this interplay are especially intriguing. Moreover, it is of interest to modulate the tumor microenvironment (TME), as this harsh milieu often impairs adaptive immune responses. Oncolytic viral therapy presents an opportunity to overcome the immunosuppression in tumors by destroying tumor cells and thereby releasing antigens and immunostimulatory factors. These effects can be further amplified by the introduction of transgenes expressed by the virus. Methods Lokon oncolytic adenoviruses (LOAd) belong to a platform of chimeric serotype Ad5/35 viruses that have their replication restricted to tumor cells, but the expression of transgenes is permitted in all infected cells. LOAd732 is a novel oncolytic adenovirus that expresses three essential immunostimulatory transgenes: trimerized membrane-bound CD40L, 4-1BBL and IL-2. Transgene expression was determined with flow cytometry and ELISA and the oncolytic function was evaluated with viability assays and xenograft models. The activation profiles of DCs were investigated in co-cultures with tumor cells or in an autologous antigen-specific T cell model by flow cytometry and multiplex proteomic analysis. Statistical differences were analyzed with Kruskal–Wallis test followed by Dunn’s multiple comparison test. Results All three transgenes were expressed in infected melanoma cells and DCs and transgene expression did not impair the oncolytic activity in tumor cells. DCs were matured post LOAd732 infection and expressed a multitude of co-stimulatory molecules and pro-inflammatory cytokines crucial for T-cell responses. Furthermore, these DCs were capable of expanding and stimulating antigen-specific T cells in addition to natural killer (NK) cells. Strikingly, the addition of immunosuppressive cytokines TGF-β1 and IL-10 did not affect the ability of LOAd732-matured DCs to expand antigen-specific T cells and these cells retained an enhanced activation profile. Conclusions LOAd732 is a novel immunostimulatory gene therapy based on an oncolytic adenovirus that expresses three transgenes, which are essential for mediating an anti-tumor immune response by activating DCs and stimulating T and NK cells even under imunosuppressive conditions commonly present in the TME. These qualities make LOAd732 an appealing new immunotherapy approach.

Telephysiotherapy has emerged as a vital solution for delivering remote healthcare, particularly in response to global challenges such as the COVID-19 pandemic. This study seeks to enhance telephysiotherapy by developing a system capable of accurately classifying physiotherapeutic exercises using PoseNet, a state-of-the-art pose estimation model. A dataset was collected from 49 participants (35 males, 14 females) performing seven distinct exercises, with twelve anatomical landmarks then extracted using the Google MediaPipe library. Each landmark was represented by four features, which were used for classification. The core challenge addressed in this research involves ensuring accurate and real-time exercise classification across diverse body morphologies and exercise types. Several tree-based classifiers, including Random Forest, Extra Tree Classifier, XGBoost, LightGBM, and Hist Gradient Boosting, were employed. Furthermore, two novel ensemble models called RandomLightHist Fusion and StackedXLightRF are proposed to enhance classification accuracy. The RandomLightHist Fusion model achieved superior accuracy of 99.6%, demonstrating the system’s robustness and effectiveness. This innovation offers a practical solution for providing real-time feedback in telephysiotherapy, with potential to improve patient outcomes through accurate monitoring and assessment of exercise performance.

Physiotherapy plays a crucial role in the rehabilitation of damaged or defective organs due to injuries or illnesses, often requiring long-term supervision by a physiotherapist in clinical settings or at home. AI-based support systems have been developed to enhance the precision and effectiveness of physiotherapy, particularly during the COVID-19 pandemic. These systems, which include game-based or tele-rehabilitation monitoring using camera-based optical systems like Vicon and Microsoft Kinect, face challenges such as privacy concerns, occlusion, and sensitivity to environmental light. Non-optical sensor alternatives, such as Inertial Movement Units (IMUs), Wi-Fi, ultrasound sensors, and ultrawide band (UWB) radar, have emerged to address these issues. Although IMUs are portable and cost-effective, they suffer from disadvantages like drift over time, limited range, and susceptibility to magnetic interference. In this study, a single UWB radar was utilized to recognize five therapeutic exercises related to the upper limb, performed by 34 male volunteers in a real environment. A novel feature fusion approach was developed to extract distinguishing features for these exercises. Various machine learning methods were applied, with the EnsembleRRGraBoost ensemble method achieving the highest recognition accuracy of 99.45%. The performance of the EnsembleRRGraBoost model was further validated using five-fold cross-validation, maintaining its high accuracy.

The orderings of atoms in bimetallic 1.6–2.1 nm-large CuCo nanoparticles, important as catalytic and magnetic materials, were studied using a combination of DFT calculations with a topological approach. The structure and magnetism of Cu50Co151, Cu101Co100, Cu151Co50, and Cu303Co102 nanoparticles; their resistance to disintegrating into separate Cu and Co species; as well as the exposed surface sites, were quantified and analyzed, showing a clear preference for Cu atoms to occupy surface positions while the Co atoms tended to form a compact cluster in the interior of the nanoparticles. The surface segregation of Co atoms that are encapsulated by less-active Cu atoms, induced by the adsorption of CO molecules, was already enabled at a low coverage of adsorbed CO, providing the energy required to displace the entire compact Co species inside the Cu matrices due to a notable adsorption preference of CO for the Co sites over the Cu ones. The calculated adsorption energies and vibrational frequencies of adsorbed CO should be helpful indicators for experimentally monitoring the nature of the surface sites of CuCo nanoparticles, especially in the case of active Co surface sites emerging in the presence of CO.

El proceso de construcción de género es un proceso intra- e interindividual que se desarrolla como consecuencia de un proceso de interacción constante del sujeto con su contexto social y cultural, en el que se adquieren creencias y actitudes sobre lo que es típico de hombres y mujeres. El presente estudio, desarrollado en Melilla, ciudad española multicultural situada al norte de África, analiza los estereotipos de género basados en esas creencias culturales de adolescentes, teniendo en cuenta el sexo y su procedencia cultural. Para esto, se ha seleccionado una muestra de 1837 estudiantes de 1.º y 3.º de Educación Secundaria Obligatoria (eso) y 1.º de bachillerato, a los que se les solicitó contestar un cuestionario elaborado ad hoc para esta investigación. Los resultados, después de la aplicación de la prueba t y el análisis multivariado de covarianza, indican que los chicos tienen más arraigados los estereotipos de género que las chicas, y en ambos casos es elevada su interiorización. Además, la procedencia cultural influye en la consolidación de estas creencias de género como consecuencia de los estilos de crianza y valores culturales en los que se han socializado.

We report the case of a 24-year-old male presenting with obstructive renal failure, characterised by imaging evidence of a cystic lesion contingent upon the seminal vesicle and concurrent renal agenesis. Initial management involved urinary diversion, followed by outpatient monitoring and subsequent recurrence. Subsequent diagnostic assessments led to the identification of Zinner's syndrome, accompanied by retroperitoneal fibrosis. We present the clinical course, diagnostic methodology and the efficacious implementation of medical-surgical therapeutic interventions, yielding favourable outcomes.

Human Papillomavirus (HPV) prophylactic vaccination has proven effective in preventing new infections, but it does not treat existing HPV infections or associated diseases. Hence, there is still an important reservoir of HPV in adults, as vaccination programs are mainly focused on young women. The primary objective of this non-randomized, open-label trial is to evaluate if a 3-dose regimen of Gardasil-9 in HPV16/18-positive women could reduce the infective capacity of their body fluids. We aim to assess if vaccine-induced antibodies could neutralize virions present in the mucosa, thus preventing the release of infective particles and HPV transmission to sexual partners. As our main endpoint, the E1^E4-HaCaT model will be used to assess the infectivity rate of cervical, anal and oral samples, obtained from women before and after vaccination. HPV DNA positivity, virion production, seroconversion, and the presence of antibodies in the exudates, will be evaluated to attribute infectivity reduction to vaccination. Our study will recruit two different cohorts (RIFT-HPV1 and RIFT-HPV2) of non-vaccinated adult women. RIFT-HPV1 will include subjects with an HPV16/18 positive cervical test and no apparent cervical lesions or cervical lesions eligible for conservative treatment. RIFT-HPV2 will include subjects with an HPV16/18 positive anal test and no apparent anal lesions or anal lesions eligible for conservative treatment, as well as women with an HPV16/18 positive cervical test and HPV-associated vulvar lesions. Subjects complying with inclusion criteria for both cohorts will be recruited to the main cohort, RIFT-HPV1. Three doses of Gardasil-9 will be administered intramuscularly at visit 1 (0 months), visit 2 (2 months) and visit 3 (6 months). Even though prophylactic HPV vaccines would not eliminate a pre-existing infection, our results will determine if HPV vaccination could be considered as a new complementary strategy to prevent HPV-associated diseases by reducing viral spread. Trial registration: https://clinicaltrials.gov/ct2/show/NCT05334706.