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BACKGROUND: Dilated cardiomyopathy (DCM) is one of the most common causes of heart failure. Multiple identified mutations in nexilin (NEXN) have been suggested to be linked with severe DCM. However, the exact association between multiple mutations of Nexn and DCM remains unclear. Moreover, it is critical for the development of precise and effective therapeutics in treatments of DCM. RESULTS: In our study, Nexn global knockout mice and mice carrying human equivalent G645del mutation are studied using functional gene rescue assays. AAV-mediated gene delivery is conducted through systemic intravenous injections at the neonatal stage. Heart tissues are analyzed by immunoblots, and functions are assessed by echocardiography. Here, we identify functional components of Nexilin and demonstrate that exogenous introduction could rescue the cardiac function and extend the lifespan of Nexn knockout mouse models. Similar therapeutic effects are also obtained in G645del mice, providing a promising intervention for future clinical therapeutics. CONCLUSIONS: In summary, we demonstrated that a single injection of AAV-Nexn was capable to restore the functions of cardiomyocytes and extended the lifespan of Nexn knockout and G645del mice. Our study represented a long-term gene replacement therapy for DCM that potentially covers all forms of loss-of-function mutations in NEXN.

Introduction: The main objective of this research was to analyze the relationship between Emotional Intelligence (EI) and victimization and aggression through social networks in adolescents. Bullying causes situations of conflict between students and teachers, being currently a phenomenon of great importance in the socio-educational environment requiring special attention, where EI acts as a protective mechanism against such situations, which differs in relation to gender and socio-family environment. Method: A cross-sectional, descriptive, and ex post facto study was carried out. The sample consisted of 126 students between 15 and 17 years of age, 51.6% male and 48.4% female; differentiations are established according to this as part of the study method. The instruments used were the Bar-On Emotional Intelligence Inventory, the School Victimization Scale, and the Scale of aggressions through cell phones and the Internet (CYB-AG), using IBM SPSS software for statistical analysis. Results: The results obtained confirmed that the subjects who had suffered bullying or cyberbullying had a slightly lower level of EI and that, although traditionally the relationship between bully-bullied was emphasized, there are more factors that affect these cases with gender. Given that a higher score in EI is presented in the case of the female gender than in the male gender, being more significant in the stress management dimension. Discussion or Conclusion: The school and the family must work together to prevent peer violence, because it has serious consequences on those who suffer it. School bullying not only influences to a great extent the EI of the victims, but also bullying is determined by the low EI of the aggressors, certainly in relation to the management of stress.

This paper reports an exploratory, descriptive study on the emotions of content and language-integrated learning preservice teachers. The study, carried out in a Spanish university, aimed at analysing the internship experience of 19 preservice teachers in the context of a master's degree in bilingual education (Spanish-English) for primary and secondary school teachers to determine the emotions experienced and the causative factors. The participants completed a questionnaire which showed that positive emotions were more frequent than negative ones. The variable causing such feelings included the subject taught, the sex of the teaching staff, previous experience, attitudes of educational centre tutors, and the students themselves. Therefore, the study highlights the affective dimension of teaching content and language-integrated learning.

The use of technology in education has modified teaching and learning processes. New concepts such as science, technology, engineering and mathematics (STEM) are changing traditional learning. The purpose of STEM education is to prepare students for university engineering courses and higher technical education. The main aim of the study reported on here was to understand the influence of a STEM-based teaching process in different socio-educational dimensions. This was done by comparing the results achieved with a traditional expository teaching process with different groups of students. A quasi-experimental design was applied. A sample of 231 Spanish students from the first year of secondary education (ESO) was chosen. The results show that the STEM approach was significant in all the dimensions of study and, according to teachers, was more influential for student motivation and grades. The results also show that the STEM teaching approach was significant in all the dimensions of study. These dimensions are motivation; teacher-student, student-content and student-student interactions; autonomy; collaboration; depth of content; resolution of problems; class time, student ratings; and teacher ratings. According to teachers, the strongest influence was on the students' motivation and qualifications.

OBJECTIVE: To evaluate self-rated health and to identify its relationship with functional capacity, objective measures of muscle strength, and mobility in a sample of community-dwelling elderly adults. METHOD: A cross-sectional, population-based study using data from the "Fragility Study on Brazilian Elderly" (Fibra) electronic database, carried out between 2008 and 2009, in which 2,558 community-dwelling elderly were recruited. The dependent variable was self-rated health compared with peers of the same age, among the elderly. The odd ratios were adjusted for sociodemographic and health variables and were estimated through multinomial logistic regression. The analyses were carried out using the program Stata 14.0. RESULTS: The average age of the elderly participants was 72.3 years old (SD ± 5.5) and 65.6% of them were women. When comparing with someone of the same age, 70.2% of the participants rated their health as better than the other's; 23.4% of them rated it as equal, and 6.4% of the elderly rated it as worse. The adjusted regression model showed that the odd ratios were more important when rating health as worse among the elderly participants who were dependent on instrumental activities (OR = 2.19; 95%CI 1.22–3.92) and had weaker grip strength (OR = 0.96; 95%CI 0.93–0.99). Better health rating showed a statistically significant difference related to speed gait (OR = 0.88; 95%CI 0.81–0.94). CONCLUSION: We found associations between the self-rated health and instrumental activities of daily living, gait velocity, and grip strength. These results reinforce functionality as an important health predictor and broaden self-rated health approachs including social comparison criteria.

Abstract The dataset presents a 43 year-long reanalysis of pollen seasons for three major allergenic genera of trees in Europe: alder (Alnus), birch (Betula), and olive (Olea). Driven by the meteorological reanalysis ERA5, the atmospheric composition model SILAM predicted the flowering period and calculated the Europe-wide dispersion pattern of pollen for the years 1980–2022. The model applied an extended 4-dimensional variational data assimilation of in-situ observations of aerobiological networks in 34 European countries to reproduce the inter-annual variability and trends of pollen production and distribution. The control variable of the assimilation procedure was the total pollen release during each flowering season, implemented as an annual correction factor to the mean pollen production. The dataset was designed as an input to studies on climate-induced and anthropogenically driven changes in the European vegetation, biodiversity monitoring, bioaerosol modelling and assessment, as well as, in combination with intra-seasonal observations, for health-related applications.

Abstract Biochar application to soil is a potential climate change mitigation strategy. In addition to long-term sequestration of the carbon content of the biochar itself, its application may reduce the emissions of other greenhouse gases (GHGs) from the soil. However, the reported effects of biochar application on soil GHG fluxes exhibit inconsistent results. Prediction of such effects is an important gap that needs to be addressed in biochar research. In this study, rule-based machine learning models were developed based on rough-set theory. Data from the literature were used to generate the rules for predicting the effects of biochar application on soil GHG (CO2, N2O, and CH4) fluxes. Four rule-based models for CO2 fluxes, two rule-based models for N2O fluxes, and three rule-based models for CH4 fluxes were developed. The validity of these models was assessed based on both statistical measures and mechanistic plausibility. The final rule-based models can guide the prediction of changes in soil GHG fluxes due to biochar application, and thus serve as a decision-support tool to maximize the benefits of biochar application as a negative emission technology (NET). In particular, mechanistically plausible rules were identified that predict triggers for GHG fluxes that can offset carbon sequestration gains. This knowledge allows biochar application to be calibrated to local conditions for maximum efficacy. Graphical Abstract

Amyloidosis is defined as a rare group of 30 protein-folding diseases characterized by the extracellular deposition of a specific soluble precursor protein that aggregates in the form of insoluble fibrils. The gastrointestinal tract (GI) is a common site for amyloid deposits: Among patients with systemic amyloidosis, at least 70% present with gastrointestinal deposition. Rarely, the deposition is exclusively localized in this area, leading to various gastrointestinal symptoms (bleeding, weight loss, etc.). In this case report, we present a rare and unusual form of localized gastrointestinal amyloidosis, diagnosed after a post-mortem examination of an 83-year-old woman who died due to septic shock resulting from post-colonoscopy iatrogenic perforation of the sigma, in a suspected medical liability case. Morphological examination revealed AL amyloid deposits within the muscular wall of the submucosal vessels of the rectum, which caused increased friability of the vessels and ischemic changes in the intestinal mucosa. A renal cell carcinoma (RCC) was found, which might be related to amyloid deposits, as reported by the literature. Amyloid deposits are an unknown and unpredictable pathological substrate that increase the risk of iatrogenic perforation. Analysis of the medical documentation did not reveal any censurable conduct in terms of prescribing the procedure, technical execution, or subsequent management of the patient following the perforation. GI amyloidosis should be part of the risk stratification of patients with rectal bleeding and gastrointestinal symptoms, and awareness is essential to guide subsequent diagnostic and therapeutic approaches and investigate underlying causes.

Abstract Background Respiratory syncytial virus (RSV) is associated with substantial morbidity among infants. This study modelled the potential public health and economic impact of nirsevimab, a long-acting monoclonal antibody, as an immunoprophylactic strategy for all infants in Spain in their first RSV season. Methods A static decision-analytic model of the Spanish birth cohort during its first RSV season was developed to estimate the impact of nirsevimab on RSV-related health events and costs versus the standard of practice (SoP). Spain-specific costs and epidemiological data were used as model inputs. Modelled outcomes included RSV-related outpatient visits, emerging room (ER) visits, hospitalisations – including pediatric intensive care unit (PICU) admission, mechanical ventilation, and inpatient mortality. Results Under the current SoP, RSV caused 151,741 primary care visits, 38,798 ER visits, 12,889 hospitalisations, 1,412 PICU admissions, and 16 deaths over a single season, representing a cost of €71.8 million from a healthcare payer perspective. Universal immunisation of all infants with nirsevimab was expected to prevent 97,157 primary care visits (64.0% reduction), 24,789 ER visits (63.9%), 8,185 hospitalisations (63.5%), 869 PICU admissions (61.5%), and 9 inpatient deaths (52.6%), saving €47.8 million (62.4%) in healthcare costs. Conclusions These results suggest that immunisation with nirsevimab of all infants experiencing their first RSV season in Spain is likely to prevent thousands of RSV-related health events and save considerable costs versus the current SoP.

Current challenges in early identification of autism spectrum disorder lead to significant delays in starting interventions, thereby compromising outcomes. Digital tools can potentially address this barrier as they are accessible, can measure autism-relevant phenotypes and can be administered in children's natural environments by non-specialists. The purpose of this systematic review is to identify and characterise potentially scalable digital tools for direct assessment of autism spectrum disorder risk in early childhood. In total, 51,953 titles, 6884 abstracts and 567 full-text articles from four databases were screened using predefined criteria. Of these, 38 met inclusion criteria. Tasks are presented on both portable and non-portable technologies, typically by researchers in laboratory or clinic settings. Gamified tasks, virtual-reality platforms and automated analysis of video or audio recordings of children's behaviours and speech are used to assess autism spectrum disorder risk. Tasks tapping social communication/interaction and motor domains most reliably discriminate between autism spectrum disorder and typically developing groups. Digital tools employing objective data collection and analysis methods hold immense potential for early identification of autism spectrum disorder risk. Next steps should be to further validate these tools, evaluate their generalisability outside laboratory or clinic settings, and standardise derived measures across tasks. Furthermore, stakeholders from underserved communities should be involved in the research and development process.

A diagnosis of autism typically depends on clinical assessments by highly trained professionals. This high resource demand poses a challenge in low-resource settings. Digital assessment of neurodevelopmental symptoms by non-specialists provides a potential avenue to address this challenge. This cross-sectional case-control field study establishes proof of principle for such a digital assessment. We developed and tested an app, START, that can be administered by non-specialists to assess autism phenotypic domains (social, sensory, motor) through child performance and parent reports. N = 131 children (2-7 years old; 48 autistic, 43 intellectually disabled and 40 non-autistic typically developing) from low-resource settings in Delhi-NCR, India were assessed using START in home settings by non-specialist health workers. The two groups of children with neurodevelopmental disorders manifested lower social preference, greater sensory interest and lower fine-motor accuracy compared to their typically developing counterparts. Parent report further distinguished autistic from non-autistic children. Machine-learning analysis combining all START-derived measures demonstrated 78% classification accuracy for the three groups. Qualitative analysis of the interviews with health workers and families of the participants demonstrated high acceptability and feasibility of the app. These results provide feasibility, acceptability and proof of principle for START, and demonstrate the potential of a scalable, mobile tool for assessing neurodevelopmental conditions in low-resource settings.

The attitude of the teaching staff is positioned as a fundamental aspect for the development of good training practices. These good practices are essential when applied within an innovative techno-pedagogical methodology: augmented reality in education. The objectives of this study are to analyze the development of good teaching practices with augmented reality and to discover the factors that influence their quality. A descriptive and correlational design has been carried out. A total of 1490 Spanish Secondary Education teachers have participated. The instrument used was the adaptation to the Spanish context of the questionnaire of the Attitude Scale of Augmented Reality Applications. The results reveal that teachers show a positive attitude towards the use of augmented reality. As for the aspects that influence the good attitude of teachers are age, the number of devices teachers use, the time they dedicate to technological resources and teaching experience. However, ICT training is what determines a direct influence on the attitude of teachers, as well as satisfaction with reliability.

Aging, often considered a result of random cellular damage, can be accurately estimated using DNA methylation profiles, the foundation of pan-tissue epigenetic clocks. Here, we demonstrate the development of universal pan-mammalian clocks, using 11,754 methylation arrays from our Mammalian Methylation Consortium, which encompass 59 tissue types across 185 mammalian species. These predictive models estimate mammalian tissue age with high accuracy (r > 0.96). Age deviations correlate with human mortality risk, mouse somatotropic axis mutations and caloric restriction. We identified specific cytosines with methylation levels that change with age across numerous species. These sites, highly enriched in polycomb repressive complex 2-binding locations, are near genes implicated in mammalian development, cancer, obesity and longevity. Our findings offer new evidence suggesting that aging is evolutionarily conserved and intertwined with developmental processes across all mammals.