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Expansion of a single repetitive DNA sequence, termed a tandem repeat (TR), is known to cause more than 50 diseases1,2. However, repeat expansions are often not explored beyond neurological and neurodegenerative disorders. In some cancers, mutations accumulate in short tracts of TRs, a phenomenon termed microsatellite instability; however, larger repeat expansions have not been systematically analysed in cancer3–8. Here we identified TR expansions in 2,622 cancer genomes spanning 29 cancer types. In seven cancer types, we found 160 recurrent repeat expansions (rREs), most of which (155/160) were subtype specific. We found that rREs were non-uniformly distributed in the genome with enrichment near candidate cis-regulatory elements, suggesting a potential role in gene regulation. One rRE, a GAAA-repeat expansion, located near a regulatory element in the first intron of UGT2B7 was detected in 34% of renal cell carcinoma samples and was validated by long-read DNA sequencing. Moreover, in preliminary experiments, treating cells that harbour this rRE with a GAAA-targeting molecule led to a dose-dependent decrease in cell proliferation. Overall, our results suggest that rREs may be an important but unexplored source of genetic variation in human cancer, and we provide a comprehensive catalogue for further study.

During activation, T cells undergo extensive gene expression changes that shape the properties of cells to exert their effector function. Understanding the regulation of this process could help explain how genetic variants predispose to immune diseases. Here, we mapped genetic effects on gene expression (expression quantitative trait loci (eQTLs)) using single-cell transcriptomics. We profiled 655,349 CD4+ T cells, capturing transcriptional states of unstimulated cells and three time points of cell activation in 119 healthy individuals. This identified 38 cell clusters, including transient clusters that were only present at individual time points of activation. We found 6,407 genes whose expression was correlated with genetic variation, of which 2,265 (35%) were dynamically regulated during activation. Furthermore, 127 genes were regulated by variants associated with immune-mediated diseases, with significant enrichment for dynamic effects. Our results emphasize the importance of studying context-specific gene expression regulation and provide insights into the mechanisms underlying genetic susceptibility to immune-mediated diseases.

Objective: The aim of this study was to investigate the association and correlation between patient-reported outcomes associated with xerostomia and salivary flow in polymedicated patients. Subjects and Methods: A cross-sectional study was conducted. Unstimulated (UWS) and stimulated (SWS) salivary flows were collected. Xerostomia was assessed by a question and the use of Xerostomia Inventory (XI). Oral Health-related quality of life was assessed using the Oral Health Impact Profile-14 (OHIP-14). Results: 218 patients were included. 51.8% suffered from xerostomia and 38.1% and 27.5% suffered from UWS and SWS hyposalivation, respectively. Patients with xerostomia, UWS and SWS hyposalivation scored significantly higher on the XI questionnaire than patients without these disorders. However, only patients with xerostomia and UWS hyposalivation were observed to score significantly higher on the OHIP-14 than patients without these alterations. A significant positive correlation was observed between XI and OHIP-14. Significant negative correlations were observed between XI and UWS, and XI and SWS. OHIP-14 was negatively correlated with both salivary flows, but this correlation was only significant between OHIP-14 and UWS flow. Conclusions: Questionnaire XI scores are higher in patients with xerostomia and reduced UWS and SWS flows. However, OHIP-14 is increased in patients with xerostomia and reduced UWS flow. Clinical Relevance: The XI reflects changes in xerostomia and salivary flow so it could be a good questionnaire to assess drug-associated xerostomia in future research studies. However, the OHIP-14 reflects changes in xerostomia level and UWS flow but is not as reliable for assessing changes in SWS flow. Clinical Relevance: The XI reflects changes in xerostomia and salivary flow so it could be a good questionnaire to assess drug-associated xerostomia in future research studies. However, the OHIP-14 reflects changes in xerostomia level and UWS flow but is not as reliable for assessing changes in SWS flow. Trial Registration: None

The annual risks of colonization, skin infection, bloodstream infection (BSI), and disease burden from exposures to antibiotic-resistant and susceptible Staphylococcus aureus (S. aureus) were estimated using quantitative microbial risk assessment (QMRA). We estimated the probability of nasal colonization after immersion in wastewater (WW) or greywater (GW) treated across a range of treatment alternatives and subsequent infection. Horizontal gene transfer was incorporated into the treatment model but had little effect on the predicted risk. The cumulative annual probability of infection (resulting from self-inoculation) was most sensitive to the treatment log(10) reduction value (LRV), S. aureus concentration, and the newly calculated morbidity ratios and was below the health benchmark of 10(−4) infections per person per year (ppy) given a treatment LRV of roughly 3.0. The predicted annual disability-adjusted life years (DALYs), which were dominated by BSI, were below the health benchmark of 10(−6) DALYs ppy for resistant and susceptible S. aureus, given LRVs of 4.5 and 3.5, respectively. Thus, the estimated infection risks and disease burdens resulting from nasal colonization are below the relevant health benchmarks for risk-based, nonpotable, or potable reuse systems but possibly above for immersion in minimally treated GW or WW. Strain-specific data to characterize dose–response and concentration in WW are needed to substantiate the QMRA.

Pediatric renal tumors account for 3%-11% of childhood cancers, the most common of which is Wilms tumor or nephroblastoma. Epidemiology plays a key role in cancer prevention and control by describing the distribution of cancer and discovering risk factors for cancer. Large pediatric research consortium trials have led to a clearer understanding of pediatric renal tumors, identification of risk factors, and development of more risk-adapted therapies. These therapies have improved event-free and overall survival for children. However, several challenges remain and not all children have benefited from the improved outcomes. In this article, we review the global epidemiology of pediatric renal tumors, including key consortium and global studies. We identify current knowledge gaps and challenges facing both high and low middle-incomes countries.

Expansion of a single repetitive DNA sequence, termed a tandem repeat (TR), is known to cause more than 50 diseases. However, repeat expansions are often not explored beyond neurological and neurodegenerative disorders. In some cancers, mutations accumulate in short tracts of TRs (STRs), a phenomenon termed microsatellite instability (MSI); however larger repeat expansions have not been systematically analyzed in cancer. Here, we identified TR expansions in 2,622 cancer genomes, spanning 29 cancer types. In 7 cancer types, we found 160 recurrent repeat expansions (rREs); most of these (155/160) were subtype specific. We found that rREs were non-uniformly distributed in the genome with an enrichment near candidate cis-regulatory elements, suggesting a role in gene regulation. One rRE located near a regulatory element in the first intron of UGT2B7 was detected in 34% of renal cell carcinoma samples and was validated by long-read DNA sequencing. Moreover, targeting cells harboring this rRE with a rationally designed, sequence-specific DNA binder led to a dose-dependent decrease in cell proliferation. Overall, our results demonstrate that rREs are an important but unexplored source of genetic variation in human cancers, and we provide a comprehensive catalog for further study.

To make an effective transition towards a circular economy, we must have the responsibility and active participation of all the stakeholders involved, including customers. In this work, we seek to develop an agent-based model to describe and analyze an environmental awareness system in a population, whose behavior is based on an indicator that can change by agent’s interaction and modify its consumption habits. The model is described using the ODD + D protocol, and we use Netlogo software for coding. After model validation process, its results are analyzed to understand how can environmental awareness level, consumption habits and social skills of each individual influence on the average environmental awareness level of a heterogeneous population, which makes simple the identification of emerging behaviors and the forecasting of the potentially recyclable waste according to the quality in the separation at source.

El presente estudio relaciona la inteligencia emocional y el burnout en una muestra de 294 docentes de genero femenino de educación inicial en Ayacucho, de 23 a 65 años (Medad = 40). Se utilizó la Escala de Inteligencia Emocional (WLEIS) y el Cuestionario de Burnout del Profesorado Revisado (CBP-R). Los resultados reportaron que existen correlaciones negativas entre el burnout y el uso (rnúcleo del burnout = -.38; rfalta de realización = -.33; p < .01), regulación (rnúcleo del burnout = -.28; rfalta de realización = -.26; p < .01), valoración de las propias emociones (rburnout nucleus = -.25 rfalta de realización = -.21; p < .01). Por otro parte, al comparar la inteligencia emocional y el burnout con la situación laboral, se determinó que las docentes nombradas se sienten realizadas (U= 8328, z = -2.35, p = .02, RP= .42), usan sus propias emociones (U = 8417, z = -2.23, p = .03, RP= .42) y valoran sus emociones (U = 8330.50, z = -2.35, p = .02, RP= .42), a diferencia de las contratadas. En relación con los estudios de segunda especialidad y diplomados, las docentes que poseen dicha formación usan sus propias emociones (U = 8615, z = -2.33, p = .02, RP= .42), a diferencia de aquellas que no cuentan con dichos estudios. Finalmente, las maestras con auxiliar en el aula usan las propias emociones (U = 7942, z = -3.33, p = .00, RP= .39), valoran sus emociones (U = 8870.5, z = -2.01, p = .04, RP= .43) y se sienten realizadas (U = 8686, z = -2.27, p = .02, RP= .42) a diferencia de aquellas que no cuentan con auxiliar.

During activation, T cells undergo extensive changes in gene expression which shape the properties of cells to exert their effector function. Therefore, understanding the genetic regulation of gene expression during T cell activation provides essential insights into how genetic variants influence the response to infections and immune diseases. We generated a single-cell map of expression quantitative trait loci (eQTL) across a T cell activation time-course. We profiled 655,349 CD4+ naive and memory T cells, capturing transcriptional states of unstimulated cells and three time points of cell activation in 119 healthy individuals. We identified 38 cell clusters, including stable clusters such as central and effector memory T cells and transient clusters that were only present at individual time points of activation, such as interferon-responding cells. We mapped eQTLs using a T cell activation trajectory and identified 6,407 eQTL genes, of which a third (2,265 genes) were dynamically regulated during T cell activation. We integrated this information with GWAS variants for immune-mediated diseases and observed 127 colocalizations, with significant enrichment in dynamic eQTLs. Immune disease loci colocalized with genes that are involved in the regulation of T cell activation, and genes with similar functions tended to be perturbed in the same direction by disease risk alleles. Our results emphasize the importance of mapping context-specific gene expression regulation, provide insights into the mechanisms of genetic susceptibility of immune diseases, and help prioritize new therapeutic targets.

During activation, T cells undergo extensive gene expression changes that shape the properties of cells to exert their effector function. Understanding the regulation of this process could help explain how genetic variants predispose to immune diseases. Here, we mapped genetic effects on gene expression (expression quantitative trait loci (eQTLs)) using single-cell transcriptomics. We profiled 655,349 CD4

Coronavirus disease (COVID-19) is caused by SARS-CoV-2 and represents the causative agent of a potentially fatal disease that is of great global public health concern. COVID-19 is a respiratory disease produced by the coronavirus family. The World Health Organization declared the disease a pandemic on 11 March 2020. Podiatrists are in a peculiar situation regarding the COVID-19 pandemic: that of a health professional aspect and the singularity that most of them practise as self-employed workers. The aim of the study is to evaluate in a group of podiatrists, working at a national level, their knowledge, perception and degree of anxiety related to the COVID-19 pandemic via the use of a questionnaire specifically developed to this end in the initial phase of the pandemic. We employed a transversal descriptive study with 302 participants, with a purposive sampling technique. The degree of perception and knowledge of the podiatrists about COVID-19 was analysed as well as the cognitive impact of the situation of confinement. The results showed that the podiatrists perceive this situation as serious at the economic and health level, that they have a thorough knowledge of the disease and that they are in a moderate to severe percentile of anxiety. Additionally, 76.2% cancelled their usual work. The COVID-19 pandemic is negatively perceived by this group of podiatrists at the personal, professional, health and economic level, with even a state of anxiety being produced.

Background: Retirement is a final life stage characterized by the ceasing of work and the loss of a routine, social relations, role, status, accomplishments, and aspirations, etc. Many times it is accompanied by negative feelings and can provoke di erent psychoemotional reactions such as depression, among others. The aim of this study is to analyze the prevalence of depression, as well as its psychoeducational approach in retirees. Methods: A paired systematic review with meta-analysis was conducted in di erent databases—Medline, Scopus, CUIDEN, CINAHL, LILACS and PsycINFO. Original studies were included in English, Spanish and French that were published in the last 10 years, and which approached depression in retirees. Results: A total of 11 articles were selected after applying inclusion and exclusion criteria. The mean value of the prevalence levels of depression in retirees obtained in the meta-analysis was 28%. Depression is more frequent in retirees, with mandatory retirement, retirement due to illness, and anticipated retirement presenting higher levels of this disease. The health role in the psychoeducational approach is highlighted in 41.6% (n = 5). Conclusions: With almost one-third of retirees su ering from depression, it is necessary to implement prevention and early detection measures to approach a public health problem.

The prevalence of burnout in midwives has been briefly studied. Given the negative effects of burnout syndrome in the physical and mental health, and also related to the quality of care provided, rates of absenteeism and sick leave; identifying related factors for the syndrome are needed. The aim was to determine the prevalence, levels, and factors related to the burnout syndrome, measured with the Copenhagen Burnout Inventory in midwives. A systematic review and meta-analysis were selected from CINAHL, LILACS, ProQuest, PsycINFO, PubMed, SciELO, and Scopus databases, with the search equation “burnout AND (midwife OR midwives OR nurses midwives)”. Fourteen articles were found with a total of 8959 midwives. Most of the studies showed moderate levels of personal burnout. The prevalence obtained was 50% (95% CI = 38–63) for personal burnout; 40% (95% CI = 32–49) for work-related burnout; and 10% (95% CI = 7–13) for client-related burnout. Midwives’ age, less experience, and living alone constitute the main related factors, as well as, the scarcity of resources, work environment, and the care model used. Most midwives present personal and work-related burnout, which indicates a high risk of developing burnout. Personal factors and working conditions should be taken into account when assessing burnout risk profiles of midwives.

Palliative care nurses are exposed to hard situations, death, and duel feelings in their daily practice. These, and other work stressors, can favor burnout development. Thus, it is important to analyze the prevalence and risk factors of burnout in palliative care nurses and estimate its prevalence. A systematic review and meta-analysis was done with quantitative primary studies. n = 15 studies were included with n = 6 studies including information for the meta-analysis. The meta-analytic prevalence estimation of emotional exhaustion was 24% (95% CI 16–34%), for depersonalization was 30% (95% CI 18–44%) and for low personal accomplishment was 28% with a sample of n = 693 palliative care nurses. The main variables related with burnout are occupational variables followed by psychological variables. Some interventions to improve working conditions of palliative care nurses should be implemented to reduce burnout.

Bullying affects thousands of teenagers worldwide and has devastating consequences. Various studies suggest that the personality of teenagers is a risk profile for bullying. The aim of this study was to analyse the relationship between the personality of teenagers aged 14 to 16 years from three education centres located in the province of Seville (Spain) and bullying in any of its victim or aggressor roles. A multi-centre cross-sectional observational descriptive study was conducted in three education centres in the province of Seville (Spain). The sample consisted of 93 students. In order to measure the two main variables, the Bull-S test was used for bullying, and the EPQ-J questionnaire was used for personality traits. A descriptive and correlation analysis was performed between variables. The results showed that 14% (n = 13) of the sample were detected as victims and another 14% (n = 13) were detected as aggressors. Statistically significant differences were found between neuroticism (p = 0.044, Phi = 0.615), sincerity (p = 0.016, V de Cramer = 0.474), and anti-social behaviour (p = 0.007, Phi = 0.620) with the variables victim/aggressor. Bullies are typically males who score high on neuroticism and anti-social behaviour, with a tendency towards social dissimulation.

Studying for a university degree can be very demanding, as students must cope with a variety of academic, social and personal challenges. If these demands persist, and if there are insufficient resources with which to address them, they will eventually provoke stress. When stress is present for long periods of time, it can lead to academic burnout syndrome, the signs of which are emotional exhaustion, depersonalisation and inadequate personal accomplishment. This paper considers certain sociodemographic factors (age, sex, children, marital status, employment status, degree subject, faculty, academic year) in the identification of a risk profile of developing burnout syndrome. This study is cross-sectional, associative and ex post facto. The Maslach Burnout Inventory-Student Survey was administered to 445 students in the University of Granada. According to the risk profile obtained, first-year male students in Primary Education and Social Education courses are at risk of developing burnout syndrome., This research was funded by the Excellence Research Project P11HUM-77771 (Junta de Andalucía, Spain), the Instituto de las Culturas de la Ciudad Autónoma de Melilla and the University of Granada.