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Abstract Background The relative contribution of the different components of mechanical power to mortality is a subject of debate and has not been studied in COVID-19. The aim of this study is to evaluate both the total and the relative impact of each of the components of mechanical power on mortality in a well-characterized cohort of patients with COVID-19-induced acute respiratory failure undergoing invasive mechanical ventilation. This is a secondary analysis of the CIBERESUCICOVID project, a multicenter observational cohort study including fifty Spanish intensive care units that included COVID-19 mechanically ventilated patients between February 2020 and December 2021. We examined the association between mechanical power and its components (elastic static, elastic dynamic, total elastic and resistive power) with 90-day mortality after adjusting for confounders in seven hundred ninety-nine patients with COVID-19-induced respiratory failure undergoing invasive mechanical ventilation. Results At the initiation of mechanical ventilation, the PaO2/FiO2 ratio was 106 (78; 150), ventilatory ratio was 1.69 (1.40; 2.05), and respiratory system compliance was 35.7 (29.2; 44.5) ml/cmH2O. Mechanical power at the initiation of mechanical ventilation was 24.3 (18.9; 29.6) J/min, showing no significant changes after three days. In multivariable regression analyses, mechanical power and its components were not associated with 90-day mortality at the start of mechanical ventilation. After three days, total elastic and elastic static power were associated with higher 90-day mortality, but this relationship was also found for positive end-expiratory pressure. Conclusions Neither mechanical power nor its components were independently associated with mortality in COVID-19-induced acute respiratory failure at the start of MV. Nevertheless, after three days, static elastic power and total elastic power were associated with lower odds of survival. Positive end-expiratory pressure and plateau pressure, however, captured this risk in a similar manner.

Background: Virtual mindfulness may be helpful for individuals with intellectual disabilities in the context of COVID-related disruptions of in-person programming, such as Special Olympics (SO). This study examined the feasibility of a virtual mindfulness intervention for SO athletes and their caregivers. Method: SO athletes (n = 44) and their caregivers (n = 29) participated in a 6-week adapted virtual mindfulness intervention. Athletes completed mindfulness and well-being questionnaires prior to, immediately following, and 3-months post-intervention. Caregivers completed questionnaires assessing their own stress, mindfulness, and well-being, as well as athlete mental health. Exit interviews were conducted immediately following the intervention. Results: The intervention was feasible in terms of demand, implementation, acceptability, and limited testing efficacy. There were significant improvements in athlete well-being and mental health, and caregiver stress and mindfulness post-intervention. Conclusions: Adapted virtual mindfulness groups may be an effective intervention in improving the well-being of adults with intellectual disabilities and their caregivers.

Objetivo: compreender como ocorre a assistência à saúde no âmbito da Atenção Básica na perspectiva dos pacientes oncológicos em cuidados paliativos e seus familiares. Métodos: estudo descritivo-exploratório, de abordagem qualitativa, realizado com pacientes diagnosticados com câncer em cuidados paliativos e seus familiares. A coleta de dados ocorreu entre setembro e novembro de 2023, a partir de entrevistas abertas, guiadas por instrumento semiestruturado. O áudio gravado foi transcrito na íntegra e, posteriormente, analisado a partir da Análise de Conteúdo. Resultados: foram identificadas duas categorias temáticas: “Cuidados em saúde dispensados pela Atenção Básica” e “Satisfação com o atendimento apesar dos entraves percebidos”. A assistência em saúde envolveu encaminhamentos a especialistas, apoio no diagnóstico inicial e tratamento de consequências físicas da doença. Apesar dos entraves vivenciados, como demora e falta de capacitação profissional, os participantes perceberam a assistência como satisfatória. Conclusão: os cuidados paliativos não estão presentes na rotina da Atenção Básica, o que, em certa medida, pode ser reflexo da necessidade de preparo profissional.

Recommender systems in educational contexts have proven to be effective in identifying learning resources that fit the interests and needs of learners. Their usage has been of special interest in online self-learning scenarios to increase student retention and improve the learning experience. In this article, we present the design of a hybrid course recommendation system for an online learning platform. The proposed hybrid system articulates the recommendation carried out by collaborative and content-based filter strategies. For the collaborative filtering recommender, we address the challenge of recommending meaningful content with limited information from users by using rating estimation strategies from a log system (Google Analytics). Our approach posits strategies to mine logs and generates effective ratings through the counting and temporal analysis of sessions. We evaluate different rating penalty strategies and compare the use of per-user metrics for rating estimation. For the content-based recommender, we compare different text embeddings that range from well-known topic models (LSA and LDA) to more recent multilingual contextual embeddings pre-trained on large-scale unlabelled corpora. The results show that the best model in terms of P@5 was the Collaborative filtering recommendation model with a value of 0.4, i.e., two out of five courses recommended could be of the user's interest. This result is satisfactory considering that our models were trained from ratings inferred from implicit user data. The content-based strategies did not yield significant results, however, these strategies help to mitigate the cold start problem and validate the use of a combined hybrid strategy.

Diffuse midline gliomas (DMG), including diffuse intrinsic pontine gliomas (DIPGs), are the most lethal of childhood cancers. Palliative radiotherapy is the only established treatment, with median patient survival of 9-11 months. ONC201 is a DRD2 antagonist and ClpP agonist that has shown preclinical and emerging clinical efficacy in DMG. However, further work is needed to identify the mechanisms of response of DIPGs to ONC201 treatment and to determine whether recurring genomic features influence response. Using a systems-biological approach, we showed that ONC201 elicits potent agonism of the mitochondrial protease ClpP to drive proteolysis of electron transport chain and tricarboxylic acid cycle proteins. DIPGs harboring PIK3CA-mutations showed increased sensitivity to ONC201, while those harboring TP53-mutations were more resistant. Metabolic adaptation and reduced sensitivity to ONC201 was promoted by redox-activated PI3K/Akt signaling, which could be counteracted using the brain penetrant PI3K/Akt inhibitor, paxalisib. Together, these discoveries coupled with the powerful anti-DIPG/DMG pharmacokinetic and pharmacodynamic properties of ONC201 and paxalisib have provided the rationale for the ongoing DIPG/DMG phase II combination clinical trial NCT05009992.

Entrevista a la escritora Yuliana Ortiz Ruano sobre su novela Fiebre de carnaval (2022)

Terpenoids are valued chemicals in the pharmaceutical, biotechnological, cosmetic, and biomedical industries. Biosynthesis of these chemicals relies on polymerization of Isopentenyl di-phosphate (IPP) and/or dimethylallyl diphosphate (DMAPP) monomers, which plants synthesize using a cytosolic mevalonic acid (MVA) pathway and a plastidic methyleritritol-4-phosphate (MEP) pathway. Circadian regulation affects MVA and MEP pathway activity at three levels: substrate availability, gene expression of pathway enzymes, and utilization of IPP and DMAPP for synthesizing complex terpenoids. There is a gap in understanding the interplay between the circadian rhythm and the dynamics and regulation of the two pathways. In this paper we create a mathematical model of the MVA and MEP pathways in plants that incorporates the effects of circadian rhythms. We then used the model to investigate how annual and latitudinal variations in circadian rhythm affect IPP and DMAPP biosynthesis. We found that, despite significant fluctuations in daylight hours, the amplitude of oscillations in IPP and DMAPP concentrations remains stable, highlighting the robustness of the system. We also examined the impact of removing circadian regulation from different parts of the model on its dynamic behavior. We found that regulation of pathway substrate availability alone results in higher sensitivity to daylight changes, while gene expression regulation alone leads to less robust IPP/DMAPP concentration oscillations. Our results suggest that the combined circadian regulation of substrate availability, gene expression, and product utilization, along with MVA- and MEP-specific regulatory loops, create an optimal operating regime. This regime maintains pathway flux closely coupled to demand and stable across a wide range of daylight hours, balancing the dynamic behavior of the pathways and ensuring robustness in response to cellular demand for IPP/DMAPP.

The main objective is to analyse gas flow dynamics in a Convergent-Divergent (CD) nozzle and predict its behaviour under various conditions. The model assumes adiabatic, impermeable walls with bidimensional, compressible, steady, subsonic, and turbulent flow. Conservation equations for mass, energy, and momentum form the basis of the mathematical model, which is solved using Reynolds-Averaged Navier-Stokes turbulent models including Standard k-e, Realizable k-e, Standard k-?, and Shear-Stress Transport k-?. Evaluation of these models across different Nozzle Pressure Ratios (NPR) shows that Shear-Stress Transport k-? correlates best with experimental data on static pressure. Three ANSYS products: DesignModeler, Meshing, and Fluent, are used for numerical simulation. The methodology reliably predicts phenomena such as flow separation, Mach disc formation, and nozzle exit regime, crucial for safe and efficient system operation.

This study addresses gender inequality in rural areas, focusing on the structural and socio-cultural constraints faced by women, despite the increasing feminisation of agriculture. The research question posed is: what are the leadership experiences of rural women in the cocoa production chain in Tibú, Norte de Santander, Colombia? The objective is to unveil the leadership experiences of rural women in the cocoa production chain in Tibú, Norte de Santander, Colombia. Using a qualitative and interpretative approach and a case study design, the experiences of ten women cocoa producers were analysed. The coding technique was based on theoretical material, generating two subcategories and the respective theoretical codes. The subcategories are associativity and time use. The findings reveal barriers such as shyness or fear of rejection, low participation in community groups, limited education, decision-making restrictions, unpaid work overload, lack of leisure time, and gender-based violence, factors that perpetuate poverty and hinder their community leadership. However, it highlights how women’s leadership and associativity positively impact sustainable agriculture and community cohesion. Although public policies recognise their key role, their implementation remains insufficient. This study highlights the need for comprehensive strategies that overcome inequalities and promote inclusive rural development.

Rural women in the agricultural sector face greater challenges than men in accessing productive resources and equitably participating in agrifood value chains. This article highlights the empowerment experiences of rural women involved in the cocoa production chain in Sardinata, Norte de Santander, Colombia. A qualitative methodology was used, employing an inductive, interpretative approach and a case-study design. Interviews were conducted with 10 female cocoa producers from Sardinata. The coding process, grounded in theoretical material, generated five subcategories with corresponding theoretical codes, leading to the emergence of a new subcategory. The narratives revealed that women continue to face inequality in participation, decision-making and autonomy, which are reinforced by gender roles and stereotypes. Despite their involvement in agricultural production, they are often overburdened with unpaid caregiving duties. Land ownership, control and access to productive resources remain largely male-dominated. In addition, gender-based violence and patriarchal expectations continue to be significant barriers. The study underscores the fact that women’s empowerment and improved access to resources enhance their participation in decision-making, boost productivity and contribute to the economic and social development of their communities.

Global food insecurity and environmental degradation highlight the urgent need for more sustainable agricultural solutions. Plant synthetic biology emerges as a promising yet risky avenue to develop such solutions. While synthetic biology offers the potential for enhanced crop traits, it also entails risks of extensive environmental damage. This review highlights the complexities and risks associated with plant synthetic biology, while presenting the potential of multiscale mathematical modeling to assess and mitigate those risks effectively. Despite its potential, applying multiscale mathematical models in plants remains underutilized. Here, we advocate for integrating technological advancements in agricultural data analysis to develop a comprehensive understanding of crops across biological scales. By reviewing common modeling approaches and methodologies applicable to plants, the paper establishes a foundation for creating and utilizing integrated multiscale mathematical models. Through modeling techniques such as parameter estimation, bifurcation analysis, and sensitivity analysis, researchers can identify mutational targets and anticipate pleiotropic effects, thereby enhancing the safety of genetically engineered species. To demonstrate the potential of this approach, ongoing efforts are highlighted to develop an integrated multiscale mathematical model for maize (Zea mays L.), engineered through synthetic biology to enhance resilience against Striga (Striga spp.) and drought.

It is well known that road safety is a major problem in cities, resulting in a large number of accidents with significant injuries and loss of life. Much of this problem occurs when vehicles interact with pedestrians. To try to minimize this problem to a large extent, a combined system using resins and a photoluminescent additive was proposed. To confirm the goodness of this material, a characterisation was carried out covering luminance, vibroacoustic and mechanical properties and a study of its photogrammetry under real conditions of use. A luminance of 68 mcd/m2 at 20 min was confirmed, which would allow, by a wide margin, a pedestrian crossing to be observed in a vehicle more than 100 m away. The acoustic vibration test confirmed that the proposed system would provide a very efficient audible warning to pedestrians and would reduce the average vehicle speed by about 37 % overall, while in cases where vehicles have to stop for pedestrians, this reduction would be about 28 %. With the mechanical characterisation, it was possible to determine a vertical displacement of always less than 2 mm in vehicles with a wheel load of 12.5 kN, reaching a compressive and tensile strength of more than 56 MPa. The results obtained confirm a potential reduction in mortality of close to 110 %, and injuries by approximately 55 %, as a consequence of the reduction in vehicle speed. In addition, improved night-time visibility of pedestrian crossings would reduce deaths by 35 % and injuries by 26 %, while in the most favourable situations, these values would be 14 % and 10 % for deaths and injuries respectively. All this confirms the great advantage of the system for improving road safety in urban environments.

Single-cell transcriptomics has emerged as the preferred tool to define cell identity through the analysis of gene expression signatures. However, there are limited studies that have comprehensively compared the performance of different scRNAseq systems in complex tissues. Here, we present a systematic comparison of two well-established high throughput 3′-scRNAseq platforms: 10× Chromium and BD Rhapsody, using tumours that present high cell diversity. Our experimental design includes both fresh and artificially damaged samples from the same tumours, which also provides a comparable dataset to examine their performance under challenging conditions. The performance metrics used in this study consist of gene sensitivity, mitochondrial content, reproducibility, clustering capabilities, cell type representation and ambient RNA contamination. These analyses showed that BD Rhapsody and 10× Chromium have similar gene sensitivity, while BD Rhapsody has the highest mitochondrial content. Interestingly, we found cell type detection biases between platforms, including a lower proportion of endothelial and myofibroblast cells in BD Rhapsody and lower gene sensitivity in granulocytes for 10× Chromium. Moreover, the source of the ambient noise was different between plate-based and droplet-based platforms. In conclusion, our reported platform differential performance should be considered for the selection of the scRNAseq method during the study experimental designs.

Background This study aims to examine, through artificial intelligence, specifically machine learning, the emotional impact generated by disclosures about mental health on social media. In contrast to previous research, which primarily focused on identifying psychopathologies, our study investigates the emotional response to mental health-related content on Instagram, particularly content created by influencers/celebrities. This platform, especially favored by the youth, is the stage where these influencers exert significant social impact, and where their analysis holds strong relevance. Analyzing mental health with machine learning techniques on Instagram is unprecedented, as all existing research has primarily focused on Twitter. Methods This research involves creating a new corpus labelled with responses to mental health posts made by influencers/celebrities on Instagram, categorized by emotions such as love/admiration, anger/contempt/mockery, gratitude, identification/empathy, and sadness. The study is complemented by modelling a set of machine learning algorithms to efficiently detect the emotions arising when faced with these mental health disclosures on Instagram, using the previous corpus. Results Results have shown that machine learning algorithms can effectively detect such emotional responses. Traditional techniques, such as Random Forest, showed decent performance with low computational loads (around 50%), while deep learning and Bidirectional Encoder Representation from Transformers (BERT) algorithms achieved very good results. In particular, the BERT models reached accuracy levels between 86–90%, and the deep learning model achieved 72% accuracy. These results are satisfactory, considering that predicting emotions, especially in social networks, is challenging due to factors such as the subjectivity of emotion interpretation, the variability of emotions between individuals, and the interpretation of emotions in different cultures and communities. Discussion This cross-cutting research between mental health and artificial intelligence allows us to understand the emotional impact generated by mental health content on social networks, especially content generated by influential celebrities among young people. The application of machine learning allows us to understand the emotional reactions of society to messages related to mental health, which is highly innovative and socially relevant given the importance of the phenomenon in societies. In fact, the proposed algorithms’ high accuracy (86–90%) in social contexts like mental health, where detecting negative emotions is crucial, presents a promising research avenue. Achieving such levels of accuracy is highly valuable due to the significant implications of false positives or false negatives in this social context.

Abstract Background The optimal treatment approach for low‐risk prostate cancer (LRPC) remains controversial. While active surveillance is an increasingly popular option, definitive local treatments, including radical prostatectomy (RP), external beam radiotherapy (EBRT), and prostate seed implantation (PSI), are also commonly used. This study aimed to evaluate the survival outcomes of patients with LRPC using a large patient population from the National Cancer Database (NCDB). Methods We analyzed data from 195,452 patients diagnosed with LRPC between 2004 and 2015 using the NCDB. Patients were classified based on their treatment modalities, including RP, EBRT, PSI, or no local treatment (NLT). Only patients with Charlson–Deyo comorbidity scores of 0 or 1 were included to ensure comparability. Propensity score analysis was used to balance the treatment groups, and the accelerated failure time model was used to analyze the survival rates of the treatment groups. Results After a median follow‐up of 70.8 months, 24,545 deaths occurred, resulting in an all‐cause mortality rate of 13%. RP demonstrated a survival benefit compared with NLT, particularly in patients younger than 74 years of age. In contrast, radiation treatments (EBRT and PSI) did not improve survival in the younger age groups, except for patients older than 70 years for EBRT and older than 65 years for PSI. Notably, EBRT in patients younger than 65 years was associated with inferior outcomes. Conclusion This study highlights the differences in survival outcomes among LRPC treatment modalities. RP was associated with improved survival compared to NLT, especially in younger patients. In contrast, EBRT and PSI showed survival benefits primarily in the older age groups. NLT is a reasonable choice, particularly in younger patients when RP is not chosen. These findings emphasize the importance of individualized treatment decisions for LRPC management.

Objetivo: apresentar o protocolo de uma revisão sistemática que buscará sintetizar as melhores evidências qualitativas disponíveis sobre as repercussões do processo migratório transfronteiriço na vida familiar. Critérios de Inclusão: estudos qualitativos e interpretativos que se baseiam nas experiências das pessoas e famílias afetadas pelo processo migratório transfronteiriço internacional. Método: revisão sistemática com metassíntese. Os documentos serão identificados no primeiro semestre de 2024, nas bases de dados: PUBMED/Medline; LILACS; PsycInfo; SCOPUS; CINAHL e Social Science Citation Index. Também serão consultadas bases de literatura cinzenta. Após identificação e elegibilidade, os estudos serão avaliados quanto à qualidade metodológica e as informações pertinentes serão sistematicamente registradas e analisadas. ABSTRACT Objective: to present the protocol of a systematic review that will seek to synthesize the best qualitative evidence available on the repercussions of the cross-border migration process on family life. Inclusion criteria: qualitative and interpretative studies based on the experiences of people and families affected by the international cross-border migration process. Method: systematic review with meta-synthesis. The documents will be identified in the first half of 2024, in the following databases: PUBMED/Medline; LILACS; PsycInfo; SCOPUS; CINAHL and Social Sciences Citation Index. Gray literature databases will also be consulted. Once identified and made eligible, the studies will be evaluated regarding their methodological quality and all relevant information will be systematically recorded and analyzed.

The early postnatal period is a sensitive time window that is characterized by several neurodevelopmental processes that define neuronal architecture and function later in life. Here, we examined in young adult mice, using an auditory fear conditioning paradigm, whether stress during the early postnatal period 1) impacts fear acquisition and memory consolidation in male and female mice; 2) alters the fear responsiveness to corticosterone and 3) whether effects of early-life stress (ELS) can be prevented by treating mice with a glucocorticoid (GR) antagonist at adolescence. Male and female mice were exposed to a limited nesting and bedding model of ELS from postnatal day (PND) 2–9 and injected i.p with RU38486 (RU486) at adolescent age (PND 28–30). At two months of age, mice were trained in the fear conditioning (FC) paradigm (with and without post training administration of corticosterone - CORT) and freezing behavior during fear acquisition and contextual and auditory memory retrieval was scored. We observed that ELS impaired fear acquisition specifically in male mice and reduced both contextual and auditory memory retrieval in male and female mice. Acute post-training administration of CORT increased freezing levels during auditory memory retrieval in female mice but reduced freezing levels during the tone presentation in particular in control males. Treatment with RU486 prevented ELS-effects in acquisition in male mice and in females during auditory memory retrieval. In conclusion, this study highlights the long-lasting consequences of early-life stress on fear memory processing and further illustrates 1) the potential of a glucocorticoid antagonist intervention during adolescence to mitigate these effects and 2) the partial modulation of the auditory retrieval upon post training administration of CORT, with all these effects being sex-dependent.

ABSTRACT The annual meeting for the Intermountain Branch was held in April 2024 on the campus of Brigham Young University. There were 127 branch members from Utah, Idaho, and Nevada who attended the meeting and were composed of undergraduate students, graduate or medical students, and faculty. This report highlights the diversity of, and the emerging trends in, the research conducted by American Society for Microbiology members in the Intermountain Branch.

La investigación planteó como objetivo determinar la efectividad entre las infiltraciones articulares con plasma rico en plaquetas vs proloterapia con solución hipertónica de dextrosa al 50% + anestésico local: lidocaína al 1%, como estrategia para el manejo del dolor en pacientes con Osteoartrosis de rodilla, Instituto Autónomo Hospital Universitario de Los Andes, enero 2022 a marzo 2023. Método: estudio clínico experimental tipo ensayo terapéutico con dos grupos de estudio. Muestra de 74 casos que cumplieron con los criterios de inclusión, divididos en dos grupos, PRP (30 casos) y PRL (44 casos). Resultados: femenino (67,7%), edad (62,03 ± 11,016 años), IMC normal (43,5%), sobrepeso (37,1%) y obesidad (19,4%). 67,7% indicó alguna comorbilidad, siendo las más frecuentes HTA (50,0%). 77,9% asistieron a fisioterapia. 87,8% se encontraron según la escala de Kellgren y Lawrence en artrosis grado I a III y 12,2% grado IV. Se determinó p

Background: Stigma toward child and adolescent mental health problems among parents has been understudied, despite its importance. Method: Sociodemographic variables, stigma associated with mental health problems in childhood and adolescence, myths about suicide, familiarity with mental health, and seeking professional help were assessed in a cross-sectional study in a Spanish sample (N = 268). Descriptive analyses, mean difference and regression models were carried out. Results: The results reveal medium levels of stigma, the presence of myths about suicide and average familiarity with mental health. Mothers and a higher level of education, showed lower levels of stigma and fewer myths about suicide. A regression model explains the 44% of the variance with myths about suicide, stigma and familiarity with mental health as predictors of seeking professional help attitudes. Conclusions: Stigma, myths surrounding suicide, and parental unfamiliarity with mental health may act as barriers to appropriate diagnosis and treatment. Practical implications and recommendations are discussed.

Objectives: to examine the nature and context of discriminatory experiences among adolescents in Spain. Methods: A mixed study of discourse content analysis in 1000 randomly selected Spanish adolescents aged 12 to 16 years stratified by age, gender and territorial distribution. Data were analyzed to identify perpetrators, actions, and locations of discrimination. Results: Overall, 66% of adolescents reported witnessing or experiencing discrimination, primarily manifested through teasing, insults, and harassment. Peers were identified as the main perpetrators (73.9%), with schools being the primary context (69.4%) where discrimination occurs. Discrimination often lacked clear reasons (27.78%), but ethnicity (23.83%) and physical appearance (22.51%) were the most common factors, followed by gender (5.99%) or academic/ability issues (5.99%) or having an illness or developmental disorder (5.41%). Conclusions: Discrimination among adolescents is frequent, with racism and rejection of minority groups as the main causes. The findings underscore the need for interventions to address discriminatory behaviors in schools and broader society, with implications for adolescent well-being and mental health.