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Abstract Background Most children with developmental disabilities (DD) live in low- and middle-income countries, but access to services is limited, impacting their ability to thrive. Pilot study findings of the World Health Organization’s Caregiver Skills Training (WHO CST) intervention, which equips caregivers with strategies to facilitate learning and adaptive behaviours in children with DD, are promising but evidence from an appropriately powered trial delivered by non-specialist facilitators is lacking. This study will investigate the effectiveness and the resource impacts and costs and consequences of the WHO CST intervention in four sites in rural and urban Kenya and Ethiopia. Methods This is a 2-arm multi-site hybrid type-1 effectiveness implementation cluster randomised controlled superiority trial. After baseline assessments (T0) are completed by participants in clusters comprising 7 to 10 caregiver-child dyads, the clusters will be randomised to either the WHO CST intervention arm or a waitlist enhanced care as usual control arm. Further assessments will be completed at endpoint (T1, 18 ± 2 weeks after randomisation) and follow-up (T2, 44 ± 2 weeks after randomisation). The intervention comprises three individualised home visits and nine group sessions with trained non-specialist facilitators. Participants in the control arm will receive the intervention after completing follow-up assessments. We aim to recruit 544 child-caregiver dyads, evenly distributed across the two arms and countries. The co-primary outcomes are the child-focused Child Behavior Checklist (assessing emotional and behavioural problems) and the caregiver-focused Pediatric Quality of Life Inventory (assessing caregiver quality of life), both assessed at endpoint. Secondary outcome measures comprise the two co-primary outcomes at follow-up and ten additional outcome measures at endpoint, assessing stigma-based experiences, depressive symptoms, household food insecurity, child disciplinary strategies and beliefs, CST knowledge and skill competencies, caregiver and child quality of life, social support, and children’s communication modes and functions. After quantitative follow-up assessments are completed, a mixed-methods evaluation approach will be used to investigate implementation processes and acceptability, feasibility, and potential sustainability of the intervention. Discussion The study’s findings will provide evidence of the effectiveness and resource impacts and costs and consequences of a non-specialist-delivered intervention in under-resourced contexts in one low-income and one middle-income country in East Africa. Findings will inform future research, intervention, and policy efforts to support children with DD and their families in under-resourced majority world contexts. Trial registration Pan African Clinical Trial Registry PACTR202310908063134. Registered on October 16, 2023.

Abstract Background The purpose of scientific production is to synthesize and capture research for eventual publication. In Peru, scientific production at the undergraduate level is relatively limited. The purpose of this study was to identify the factors associated with scientific production conditions among dental students from the Peruvian capital. Methods This cross-sectional and analytical study evaluated 338 dental students from the Peruvian capital using a questionnaire composed of 15 questions on conditions for scientific production. Pearson’s chi-square test and Fisher’s exact test were used for bivariate analysis. To evaluate the influential variables, the adjusted Poisson regression model with robust variance using the adjusted prevalence ratio (APR) was employed. The significance level was p

On December 14, 2021, an earthquake with a magnitude of 7.4 originated from the Flores Sea, impacting Kalaotoa Island in Indonesia, resulting in significant structural damage. Macroseismic observations at the site classified that there were 120 buildings slightly damaged, 108 buildings moderately damaged, and 201 buildings heavily damaged. The shakemap shows that Kalaotoa Island experienced VI-VII MMI shaking. The results of the field survey showed many indications of subsidence as many fractures were found in Kalaotoa Island. This study employed Differential Interferometry Synthetic Aperture Radar (DInSAR) to quantify land subsidence and uplift in Kalaotoa Island before and after the earthquake. Sentinel-1A satellite radar data from December 2 and December 14, 2021, were analyzed. The results revealed subsidence of up to 12 cm in Garaupa Raya Village and uplift of up to ±10 cm in Lembang Mate’ne Village. Approximately 50.50% of Kalaotoa Island experienced subsidence (39.4 km²), primarily in Garaupa Village (18.85 km²), while 49.02% of the island experienced uplift (38.2 km²), mostly in Lembang Mate’ne Village (19.03 km²). This spatial analysis underscores the efficacy of DInSAR in detecting and mapping surface deformation, offering critical insights for earthquake preparedness, mitigation efforts for impacted landscape topography, stability soils, structure of ecosystems, and infrastructure resilience.

Abstract Background Defective mitochondria and aberrant brain mitochondrial bioenergetics are consistent features in syndromic intellectual disability disorders, such as Rett syndrome (RTT), a rare neurologic disorder that severely affects mainly females carrying mutations in the X-linked MECP2 gene. A pool of CB1 cannabinoid receptors (CB1R), the primary receptor subtype of the endocannabinoid system in the brain, is located on brain mitochondrial membranes (mtCB1R), where it can locally regulate energy production, synaptic transmission and memory abilities through the inhibition of the intra-mitochondrial protein kinase A (mtPKA). In the present study, we asked whether an overactive mtCB1R-mtPKA signaling might underlie the brain mitochondrial alterations in RTT and whether its modulation by systemic administration of the CB1R inverse agonist rimonabant might improve bioenergetics and cognitive defects in mice modeling RTT. Methods Rimonabant (0.3 mg/kg/day, intraperitoneal injections) was administered daily to symptomatic female mice carrying a truncating mutation of the Mecp2 gene and its effects on brain mitochondria functionality, systemic oxidative status, and memory function were assessed. Results mtCB1R is overexpressed in the RTT mouse brain. Subchronic treatment with rimonabant normalizes mtCB1R expression in RTT mouse brains, boosts mtPKA signaling, and restores the defective brain mitochondrial bioenergetics, abnormal peripheral redox homeostasis, and impaired cognitive abilities in RTT mice. Limitations The lack of selectivity of the rimonabant treatment towards mtCB1R does not allow us to exclude that the beneficial effects exerted by the treatment in the RTT mouse model may be ascribed more broadly to the modulation of CB1R activity and distribution among intracellular compartments, rather than to a selective effect on mtCB1R-mediated signaling. The low sample size of few experiments is a further limitation that has been addressed replicating the main findings under different experimental conditions. Conclusions The present data identify mtCB1R overexpression as a novel molecular alteration in the RTT mouse brain that may underlie defective brain mitochondrial bioenergetics and cognitive dysfunction.

The European Commission has identified the role of Living Labs and Citizen Science as needed tools for the process of citizen-centric knowledge valorisation. Backed by the Memorandum of Understanding (MoU) between the European Citizen Science Association (ECSA) and the European Network of Living Labs (ENoLL) signed in 2023, this workshop seeked to bridge these two worlds for mutual benefit and increased societal impact. During the workshop, we (1) introduced the features of Living Labs; (2) co-created practical examples on how Citizen Science and Living Labs can provide joint contributions in support of green, social and digital transitions; and (3) started to identify action items where the ECSA and ENoLL communities join forces to empower citizens to become true change makers. Although providing important first insights, the workshop revealed a need to develop a better understanding of the relationships and possible mutual benefits between Citizen Science and Living Labs. Next steps include a follow up mirror workshop at Open Living Lab Days conference 2024.

This paper presents the Scalability Toolkit developed in 2021–2023 within the “Mutual Learning Exercise on Citizen Science Initiatives – Policy and Practice” to provide a theoretical and methodological framework to support the scaling of CS projects and initiatives responsibly and inclusively.The Toolkit is made of three components: i) a multidimensional qualitative definition of scalability, ii) an operational scalability matrix composed of four models (scaling up, out, deep and down) and two approaches (top-down and bottom-up), and iii) eight action areas for policy making.Building on this work, further research as well as a cultural mind shift is needed to urther develop value-driven scalability models in CS according to more qualitative and ethical dimensions, the specific logic of CS projects as well as their domain and context dependency.

Abstract Even during the third wave of the COVID-19 pandemic health professionals were facing mental health challenges. The aim of this study was to examine the mental health of doctors, nurses and other professional groups in Europe and to identify differences between the professional groups. We conducted a cross-sectional online survey in 8 European countries. We asked for demographic data, whether the participants were exposed to COVID-19 at work, for main information sources about the pandemic, the Depression Anxiety Stress Scales (DASS-21), and major stressors. A MANCOVA was carried out to find predictors of mental health among health care professionals. The sample (N = 1398) consisted of 237 physicians, 459 nurses, and 351 other healthcare professionals and 351 non-medical professionals with no direct involvement in patient care. The mean mental health of all groups was affected to a mild degree. Major predictors for depression and anxiety were the profession group with higher scores especially in the group of the nurses and working directly with COVID-patients. In the third wave of the COVID-19 pandemic, the psychological burden on health professionals has remained high, with being nurse and working directly with COVID19 patients being particular risk factors for mental distress. We found as a main result that nurses scored significantly higher on depression and anxiety than practitioners.

This work presents the first ecosystem accounts for Marine-Based Tourism (MBT) in Italy. We develop a methodological approach to connect biophysical and economic information required to fill ecosystem accounting supply and use tables. Coherent with the System of Environmental Economic Accounting – Ecosystem Accounting (SEEA EA) framework, this approach starts by estimating the extent and the condition of marine ecosystems, showing the urgency in improving the availability, organisation and accessibility of biophysical data. This work provides valuable insights into understanding MBT from an ecosystem accounting perspective. We focus on the Posidonia oceanica and its role in the MBT sector in Italy, providing a physical quantification of such contribution and converting this flow into monetary terms. Our findings show that such habitat significantly contributes to the tourism sector, resulting in exchange values of MBT of €6 million in 2019 and €3.7 million in 2021.

[Objetivo] Verificar el cumplimiento de los niveles de exposición a SO2 y H2S, de los guardaparques del Parque Nacional Volcán Poás, tomando como referencia la norma internacional OSHA. [Metodología] Se estudió la concentración del SO2 desde setiembre 2018, hasta diciembre 2019 y para el H2S de febrero 2019, hasta diciembre 2019, haciendo uso de equipos de detección portátiles MultiRae. Los puntos de muestreo se colocaron en la casa de guardaparques, la caseta de entrada, el centro de visitantes y el mirador. El nivel de riesgo químico se determinó considerando: la salud de los trabajadores, el tiempo de exposición, el equipo de seguridad, las capacitaciones y los valores de TWA y STEL obtenidos. [Resultados] El valor más alto de la concentración de SO2 fue de 16,0 ppm, se registró en el centro de visitantes, y para el de H2S fue de 45 ppm (casa de guardaparques). La concentración promedio de los gases estuvo cercana al límite de detección para ambos gases, sugiriendo que los gases, en general, no se dirigen hacia las zonas de visitación. Ningún puesto de medición superó los 2 ppm para el SO2 en 8 horas (TWA). Sin embargo, en el centro de visitantes y en el mirador para visitantes, se superó los 5 ppm de SO2 en 15 minutos (STEL), con concentraciones de 10,1 ppm y 7,4 ppm, respectivamente. [Conclusiones] Se obtuvieron niveles bajos de riesgo químico, para ambos gases, en los puntos muestreados, a excepción del punto del centro de visitantes, donde el nivel de riesgo fue medio.

Los aldehídos son compuestos presentes en la atmósfera que se forman por la degradación fotoquímica de otros compuestos orgánicos en la tropósfera, estos pueden ser emitidos por fuentes naturales o antropogénicas. [Objetivo] En el presente trabajo se implementó un método analítico para la cuantificación de muestras de aldehídos en matrices como aire y agua de lluvia. [Metodología] El muestreo y el análisis de los aldehídos utilizó la metodología TO-11 de la Agencia de Protección Ambiental de los Estados Unidos (EPA). El muestreo se realizó mediante el uso de cartuchos de adsorción recubiertos con una disolución de 2,4-DNFH, formando una hidrazona con los aldehídos presentes en el agua de lluvia y en el aire. Estos fueron analizados mediante un cromatógrafo de líquido acoplado a un detector UV-Visible (HPLC-UV/Vis). Para la validación de la técnica de análisis y la calidad analítica de los resultados se determinaron: linealidad, sensibilidad, límites de cuantificación, límites de detección, repetibilidad, reproducibilidad y porcentaje de recuperación. En el caso de la repetibilidad, se utilizó la comparación del coeficiente de variación de Horwitz con los porcentajes de desviación estándar relativo (% DER) de las muestras. [Resultados] Los límites de detección obtenidos oscilan entre 0,18 μg/m3 para el acetaldehído y 3,20 μg/m3 en el caso de la acroleína, mientras que los límites de cuantificación están entre 0,62 μg/m3 para el acetaldehído y 4,70 μg/m3 para el heptanal; datos que garantizan la calidad analítica del método. [Conclusiones] En general, el método de análisis para los aldehídos mostró una buena correlación lineal, con valores de R2 igual o mayores a 0,9991 para cada curva de calibración, y valores de porcentajes de desvío relativo menores al 2,25 %, lo cual indica una buena precisión en el análisis.

Abstract Background Neural stem and progenitor cells (NSPCs) from extra-neural origin represent a valuable tool for autologous cell therapy and research in neurogenesis. Identification of proneurogenic biomolecules on NSPCs would improve the success of cell therapies for neurodegenerative diseases. Preliminary data suggested that follicle-stimulating hormone (FSH) might act in this fashion. This study was aimed to elucidate whether FSH promotes development, self-renewal, and is proneurogenic on neurospheres (NS) derived from sheep ovarian cortical cells (OCCs). Two culture strategies were carried out: (a) long-term, 21-days NS culture (control vs. FSH group) with NS morphometric evaluation, gene expression analyses of stemness and lineage markers, and immunolocalization of NSPCs antigens; (b) NS assay to demonstrate FSH actions on self-renewal and differentiation capacity of NS cultured with one of three defined media: M1: positive control with EGF/FGF2; M2: control; and M3: M2 supplemented with FSH. Results In long-term cultures, FSH increased NS diameters with respect to control group (302.90 ± 25.20 μm vs. 183.20 ± 7.63 on day 9, respectively), upregulated nestin (days 15/21), Sox2 (day 21) and Pax6 (days 15/21) and increased the percentages of cells immunolocalizing these proteins. During NS assays, FSH stimulated NSCPs proliferation, and self-renewal, increasing NS diameters during the two expansion periods and the expression of the neuron precursor transcript DCX during the second one. In the FSH-group there were more frequent cell-bridges among neighbouring NS. Conclusions FSH is a proneurogenic hormone that promotes OCC-NSPCs self-renewal and NS development. Future studies will be necessary to support the proneurogenic actions of FSH and its potential use in basic and applied research related to cell therapy.

ABSTRACT Introduction and objectives: Functional assessment of coronary stenosis severity with the piezo-electric sensor pressure wire has shown a discrepancy of up to 20% between hyperemic and nonhyperemic indexes. No data are available with fiber-optic pressure wires. The aim of this study was to evaluate the incidence and factors related to the diagnostic discordance between these indexes with a fiber-optic pressure wire. Secondary aims were to assess diagnostic reproducibility in 2 consecutive measurements of fractional flow reserve (FFR) and diastolic pressure ratio (dPR) and evaluate the drift rate. Methods: We conducted a prospective, observational multicenter study in patients undergoing functional assessment with a fiber-optic pressure wire. We took 2 consecutive measurements of the dPR (cutoff point 0.89) and FFR (cut-off point 0.80) in each lesion analyzed. The diagnostic correlation between 2 measurements with the same technique and between the 2 techniques (dPR and FFR) was assessed. Clinical and angiographic factors associated with discordance (FFR−/dPR+ and FFR+/dPR−) between the 2 techniques were analyzed. Results: We included 428 cases of stenosis (361 patients). Diagnostic reproducibility was 95.8% for the dPR, with a correlation coefficient between the 2 measurements (dPR1 and dPR2) of 0.974 (P 60%. The drift rate was 5.7%. Conclusions: Although FFR and dPR measurements with a fiber-optic pressure wire have excellent reproducibility and a low drift rate, the discordance rate remains similar to those in previous studies with a piezo-electric pressure wire. FFR−/dPR+ discordance is associated with intracoronary adenosine and hypertension. FFR+/dPR− discordance is related to age < 75 years old and stenosis > 60%.

RESUMEN Introducción y objetivos: La valoración funcional de las estenosis coronarias con guías de presión de sensor piezoeléctrico ha mostrado hasta un 20% de discordancia entre los índices hiperémico y no hiperémico. No hay datos disponibles con guía de presión de sensor óptico. El objetivo del estudio es evaluar la incidencia y los factores relacionados con la discordancia diagnóstica entre estos índices con guía de presión de sensor óptico. Como objetivos secundarios se evaluó la reproducibilidad diagnóstica en dos determinaciones consecutivas de la reserva fraccional de flujo (RFF) y la diastolic pressure ratio (dPR). También se evaluó la tasa de drift. Métodos: Estudio observacional, prospectivo, multicéntrico, en pacientes a quienes se realiza una valoración funcional con guía de presión de sensor óptico. Se hicieron dos mediciones consecutivas de dPR (umbral 0,89) y RFF (umbral 0,80) en cada lesión analizada. Se valoró la correlación diagnóstica entre dos mediciones con la misma técnica y entre ambas técnicas (dPR y RFF). Se analizaron factores clínicos y angiográficos asociados a la discordancia (RFF−/dPR+ y RFF+/dPR−) entre ambas técnicas. Resultados: Se incluyeron 428 estenosis (361 pacientes). La reproducibilidad diagnóstica fue del 95,8% para dPR, con un coeficiente de correlación entre ambas mediciones (dPR1 y dPR2) de 0,974 (p < 0,0001). Para RFF la reproducibilidad diagnóstica fue del 94,9%, con un coeficiente de correlación (RFF1 y RFF2) de 0,942 (p < 0,0001). La discordancia diagnóstica fue del 18,2% (RFF+/dPR− 8,2% y RFF−/dPR+ 10%). Entre las variables analizadas, en el análisis multivariado, la hipertensión arterial y la administración intracoronaria de adenosina se asociaron de manera significativa con la discordancia RFF−/dPR+. Solo la edad < 75 años y la estenosis > 60% se asociaron de manera significativa con la discordancia RFF+/dPR−. La tasa de drift fue del 5,7%. Conclusiones: Aunque las mediciones de RFF y dPR con guía de presión de sensor óptico tienen una excelente reproducibilidad y una baja incidencia de drift, la tasa de discordancia permanece similar a la de estudios previos con guía de presión de sensor piezoeléctrico. La adenosina intracoronaria y la hipertensión arterial se asocian con la discordancia RFF−/dPR+. La edad < 75 años y la estenosis > 60% se asocian a discordancia RFF+/dPR−.

Este documento se centra en determinar el consumo cultural de teatro, productos audiovisuales, televisión y museos durante el confinamiento por Covid-19 en Colombia. Estos descriptivos y tendencias de consumo se desarrollan y estiman a partir de SPSS versión 25, en donde se realizó reducción de dimensiones por medio de análisis factorial exploratorio para el consumo cultural resultado de la Encuesta de Consumo Cultural (ECC) de 2020, realizada por el Departamento Administrativo Nacional de Estadística (DANE); cuyos resultados permiten reconocer a la televisión como el canal por el que más consumen contenido las personas (73,7 %) en el país. Entre otros resultados, las edades de mayor consumo cultural están entre los menores de edad y de los 18 hasta los 32 años, los cuales representan el 52,6 %. Esto ratifica que debe darse un mayor apoyo a las tecnologías de información y virtualización, que involucren con mayor contundencia las necesidades de contenido para estas edades y posibiliten que aumenten el acceso y uso de diferentes formas de consumo de cultura.

Abstract Background Using next-generation sequencing technologies, scientists can sequence complex microbial communities directly from the environment. Significant insights into the structure, diversity, and ecology of microbial communities have resulted from the study of metagenomics. The assembly of reads into longer contigs, which are then binned into groups of contigs that correspond to different species in the metagenomic sample, is a crucial step in the analysis of metagenomics. It is necessary to organize these contigs into operational taxonomic units (OTUs) for further taxonomic profiling and functional analysis. For binning, which is synonymous with the clustering of OTUs, the tetra-nucleotide frequency (TNF) is typically utilized as a compositional feature for each OTU. Results In this paper, we present AFIT, a new l-mer statistic vector for each contig, and AFITBin, a novel method for metagenomic binning based on AFIT and a matrix factorization method. To evaluate the performance of the AFIT vector, the t-SNE algorithm is used to compare species clustering based on AFIT and TNF information. In addition, the efficacy of AFITBin is demonstrated on both simulated and real datasets in comparison to state-of-the-art binning methods such as MetaBAT 2, MaxBin 2.0, CONCOT, MetaCon, SolidBin, BusyBee Web, and MetaBinner. To further analyze the performance of the purposed AFIT vector, we compare the barcodes of the AFIT vector and the TNF vector. Conclusion The results demonstrate that AFITBin shows superior performance in taxonomic identification compared to existing methods, leveraging the AFIT vector for improved results in metagenomic binning. This approach holds promise for advancing the analysis of metagenomic data, providing more reliable insights into microbial community composition and function. Availability A python package is available at: https://github.com/SayehSobhani/AFITBin .

Abstract Background Early childhood caries (ECC) is a global public health challenge that requires innovation, infrastructure, and health system influences to bolster initiatives for its management and control. The aim of this scoping review was to investigate the published evidence on the association between ECC and the targets of the Sustainable Development Goal 9 (SDG9) concerned with industry, innovation, and infrastructure development. Methods The scoping review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. A search was conducted in PubMed, Web of Science, and Scopus between July and August 2023 using a search strategy related to the promotion of resilient infrastructure, sustainable industries, scientific research and innovation, access to the internet and ECC. Only English language publications were included. Studies that solely examined ECC without reference to the SDG9 targets were excluded. Results The search yielded 933 studies for review. After screening for the eligibility and removing duplicates, 916 unique articles remained for further screening. However, none of the identified studies provided data on the association between resilient infrastructure, sustainable industries, scientific research and innovation, access to the internet and ECC. Conclusion There were no primary studies that assessed the association between ECC and SDG9, even though the plausibility of a potential relationship exists. Future studies are needed to generate evidence on the link between ECC and SDG9 as this link may contribute to the reduction in the proportion of children with untreated ECC.

This study focuses on the application of activated carbon obtained from cocoa shells for wastewater treatment. The methodology covered the preparation of activated car-bon through collection, drying, carbonization, and chemical activation, followed by the characterization of the wastewater, its treatment through filtration, adsorption, and the final evaluation of the quality of the treated water. Trihalomethanes (THM), metabi-sulfite, and residual free chlorine were determined in the treated water before and after using activated charcoal. The results indicate a 31.2% reduction in THM levels with considerable decreases in metabisulfite and residual free chlorine concentrations. These findings suggest that cocoa shell-activated carbon is effective in removing common contaminants and more specialized compounds. The study highlights the im-portance of using sustainable materials in wastewater treatment, promoting more effi-cient and environmentally responsible practices.

Biogeography has as a central theme, which is the study of geographic ranges of species that are determined by evolutionary history, abiotic factors, and biotic interactions. Understanding the influence of biotic interactions on geographic ranges is a topic that has been little explored, especially in a way that compares species that vary in intensity of interaction. Here, we assessed interaction intensity as a determinant of geographic range overlap between ant-following birds and army ants in Mexico and Central America. We hypothesized that the intensity of the interaction between army ants and ant-following birds, obligate or facultative, predicts the overlap of geographic ranges of interacting species, as well as the extension of geographic ranges. We generated species distribution models with MAXENT and estimated the percentage of overlap between two species of army ants and 10 species of ant-following birds. Contrary to our predictions, Bayesian regression models found no support for an estimated higher range overlap for obligate ant-following birds and army ants, or wider geographic ranges for facultative ant-following bird species. However, our results suggested trends for higher percentages of range overlap between obligate ant-following birds and army ants, and for geographic ranges of facultative ant-following birds extending to areas without the presence of army ants. Our research encourages further exploration of the biogeography of biotic interactions as part of a quantitative gradient of intensities and not as qualitative categories, integrating spatial and temporal variation in the intensity of interaction.

Abstract The domestication process in grapevines has facilitated the fixation of desired traits. Nowadays, vegetative propagation through cuttings enables easier preservation of these genotypes compared to sexual reproduction. Nonetheless, even with vegetative propagation, various phenotypes are often present within the same vineyard due to the accumulation of somatic mutations. These mutations are not the sole factors influencing phenotype. Alongside somatic variations, epigenetic variation has been proposed as a pivotal player in regulating phenotypic variability acquired during domestication. The emergence of these epialleles might have significantly influenced grapevine domestication over time. This study aims to investigate the impact of domestication on methylation patterns in cultivated grapevines. Reduced-representation bisulfite sequencing was conducted on 18 cultivated and wild accessions. Results revealed that cultivated grapevines exhibited higher methylation levels than their wild counterparts. Differential Methylation Analysis between wild and cultivated grapevines identified a total of 9955 differentially methylated cytosines, of which 78% were hypermethylated in cultivated grapevines. Functional analysis shows that core methylated genes (consistently methylated in both wild and cultivated accessions) are associated with stress response and terpenoid/isoprenoid metabolic processes. Meanwhile, genes with differential methylation are linked to protein targeting to the peroxisome, ethylene regulation, histone modifications, and defense response. Collectively, our results highlight the significant roles that epialleles may have played throughout the domestication history of grapevines.

Since 2017, targeted therapies combined with conventional intensive chemotherapy have started to improve outcome of patients with acute myeloid leukemia (AML). However, even before these innovations outcomes with intensive chemotherapy have improved, which has not yet been extensively studied. Thus, we used a large pan-European multicenter dataset of the HARMONY Alliance to evaluate treatment-time dependent outcomes over two decades. In 5359 AML patients, we compared the impact of intensive induction therapy on outcome over four consecutive 5-year calendar periods from 1997 to 2016. During that time, the 5- year survival of AML patients improved significantly, also across different genetic risk groups. In particular, the 60-day mortality rate has dropped from 13.0% to 4.7% over time. The independent effect of calendar periods on outcome was confirmed in multivariate models. Improvements were documented both for patients

Food safety is a shared responsibility of all actors along the food supply chain. Changes in the primary production system can affect food safety hazards along the supply chain. This highlights the need for a framework that enables primary producers (i.e., farmers) to assess the potential food safety hazards and, if needed, to apply control measures. This paper presents a generic food safety assessment (GFSA) framework that has been developed based on Hazard Analysis and Critical Control Point (HACCP). The proposed framework was applied to a case study, i.e., the transition from sole cropping of oats to intercropping of oats with lupins. The application of the GFSA framework enabled the evaluation of potential changes in food safety hazards from this transition and the establishment of appropriate control measures. In addition, GFSA users can employ the results to support decision-making process. Our case study showed that implementing GFSA can be challenging for smallholder or individual farmers and may need coordinated action. Finally, effective and transparent communication is critical for managing food safety along the food supply chain, including when changes are implemented in primary production.

IntroductionValidations of previously detected quantitative trait loci (QTLs) to assess their reliability are crucial before implementing breeding programs. The objective of this study was to determine the reliability and practical usefulness of previously reported QTLs for resistance to stem tunneling by the Mediterranean stem borer (MSB) and yield. These authors used approximately 600 recombinant inbred lines (RILs) from a multiparent advanced generation intercross (MAGIC) population to map QTL using a genome-wide association study (GWAS) approach.MethodsWe identified RILs situated at the extremes of resistance and yield distributions within the whole MAGIC, and those QTLs were evaluated per se and crossed to a tester (A638) using lattice designs. In each set, a significant single-nucleotide polymorphism (SNP) was considered validated if (1) the same SNP was associated with the trait with a p-value < 0.02, or (2) within a ±2-Mbp interval, an SNP associated with the trait exhibited a p-value < 0.02 and demonstrated linkage disequilibrium (r2 > 0.2) with the SNPs previously reported.Results and discussionThe novel QTL validation approach was implemented using improved experimental designs that led to higher heritability estimates for both traits compared to those estimated with the whole MAGIC population. The procedure used allowed us to jointly validate several QTL and to ascertain their possible contribution to hybrid improvement. Specifically, nearly three-quarters of the QTLs for tunnel length were confirmed. Notably, QTLs located in the genomic region 6.05–6.07 were consistently validated across different sets and have been previously linked to resistance against stalk tunneling in various mapping populations. For grain yield, approximately 10 out of 16 QTLs were validated. The validation rate for yield was lower than for tunnel length, likely due to the influence of dominance and/or epistatic effects. Overall, 9 out of 21 QTLs for tunnel length and 6 out of 17 QTLs for grain yield identified in our previous research were validated across both validation sets, indicating a moderate genetic correlation between per se and testcross performance of inbred lines. These findings offer insights into the reliability of QTL and genomic predictions, both derived from assessments conducted on the entire MAGIC population. Genomic predictions for tunnel length based on inbred line evaluations could be useful to develop more resistant hybrids; meanwhile, genomic prediction for yield could only be valid in a homozygous background.

Background Cognitive assessment and the early detection of cognitive impairments have been enhanced by the use of remote digital solutions. The Brain on Track® is one of these digital solutions used in clinical practice for online screening and monitoring of cognitive functioning. Objectives This study aimed to explore the validity and reliability of the Brain on Track® computerized test on a tablet device in adults. Methods A community sample of 54 young adults, 51 middle-aged adults, and 50 older adults were invited to attend in two assessment sessions. The first session included data collection on sociodemographic data, user digital literacy, Brain on Track® on the computer and on the tablet device, and usability from the user and moderator perspective. The second session included the Montreal Cognitive Assessment Questionnaire (MoCA) and a second completion of the Brain on Track® on tablet to assess the criterion validity and test–retest reliability. Hypothesis testing was used to assess construct validity. Results A weak to moderate correlation was found between the Brain on Track® tablet score and the MoCA. The ICC was 0.72, 0.84, and 0.79, and Cronbach's alpha was 0.84, 0.83, and 0.89 in young adults, middle-aged adults, and older adults, respectively. Conclusions This study suggested that the Brain on Track® administered using a tablet device has criterion validity, particularly in middle-aged and older adults, and internal consistency and test–retest reliability in adults of any age group.

Objectives: This study aimed to characterize Aeromonas veronii CTe-01 focusing on its resistance to heavy metal and antibiotics. Methods: A. veronii CTe-01 was characterized using standard microbiological and molecular techniques. Antibiotic susceptibility and heavy metal resistance were tested per standard protocols. Genomic analysis, including plasmid characterization, was conducted in silico. Results: A. veronii CTe-01 showed resistance to various heavy metals and antibiotics. Multiple resistance genes were identified, including those for beta-lactamases, heavy metal resistance, and type III secretion system components. The bacterium carries a 9 kb plasmid with repA/repB replication genes, parA/parB partitioning genes, and a type II toxin-antitoxin system for stability. Conclusions: A. veronii CTe-01 is a genetic reservoir for antibiotic resistance, heavy metal resistance genes, and virulence factors. The study offers insights into its dual role as a pathogen and heavy metal remediator in aquatic environments.

Este artigo examina criticamente a teoria de Gilles Lipovetsky sobre o indivíduo hipermoderno, abordando diversas facetas do individualismo contemporâneo. Analisa a noção de individualismo, o dualismo no individualismo hipermoderno e suas tendências contraditórias, o individualismo selvagem e seu vínculo com o narcisismo. Discute o conceito de hiperindividualismo e a "indiferença pura" característica do indivíduo hipermoderno. Explora o impacto da mídia, a aniquilação da sociabilidade e dos valores morais pelo individualismo exacerbado e a necessidade de uma educação que contraponha a permissividade. O artigo oferece uma perspectiva crítica sobre as implicações sociais e culturais dessa forma extrema de individualismo.

ABSTRACT Background: Pathophysiological mechanisms of rheumatoid arthritis arise because of a proinflammatory environment, generated by the interaction of autoreactive lymphocytes and proinflammatory mediators. Current strategies to mitigate the progression of the disease produce adverse effects, so there is a need for new therapeutic strategies and molecular targets to treat this disease. In this context, evidence suggests that scorpion venoms could modulate the immune response and some important cellular mechanisms of pharmacological interest. To evaluate the immunomodulatory effect of the venom of Tityus sp. (a possible new species close to Tityus metuendus) peripheral blood mononuclear cells of women diagnosed with RA were compared to cells of a control group. Methods: A case-control study was conducted with a sample of 10 women with a confirmed diagnosis of RA and controls matched by sex and age. The cytotoxicity of the venom was evaluated to find sublethal concentrations of the venom, and subsequently, their immunomodulatory capacity in terms of percentage of proliferation, cell activation, and cytokines production. Results: the venom of Tityus sp. produced a decrease in the percentage of proliferation in the CD3+, CD3+CD4+, and CD3+CD8+ cell subpopulations of RA patients and healthy controls, at concentrations of 252 and 126 µg/mL. However, the venom did not induce significant differences in the percentage of cell activation markers. The venom caused a decrease in IL-10 at a concentration of 252 µg/mL compared to untreated cells from patients and controls. The remaining cytokines did not show significant differences. Conclusion: the venom of Tityus sp. is a potential source of molecules with immunomodulatory ability in CD4 and CD8 T lymphocytes. This result directs venom characterization studies to identify pharmacological targets with immunomodulatory capacity in T lymphocytes to enhance research in the treatment of autoimmune disorders such as RA.

CXCR4 is a ubiquitously expressed chemokine receptor that regulates leukocyte trafficking and arrest in both homeostatic and pathological states. It also participates in organogenesis, HIV-1 infection, and tumor development. Despite the potential therapeutic benefit of CXCR4 antagonists, only one, plerixafor (AMD3100), which blocks the ligand-binding site, has reached the clinic. Recent advances in imaging and biophysical techniques have provided a richer understanding of the membrane organization and dynamics of this receptor. Activation of CXCR4 by CXCL12 reduces the number of CXCR4 monomers/dimers at the cell membrane and increases the formation of large nanoclusters, which are largely immobile and are required for correct cell orientation to chemoattractant gradients. Mechanistically, CXCR4 activation involves a structural motif defined by residues in TMV and TMVI. Using this structural motif as a template, we performed in silico molecular modeling followed by in vitro screening of a small compound library to identify negative allosteric modulators of CXCR4 that do not affect CXCL12 binding. We identified AGR1.137, a small molecule that abolishes CXCL12-mediated receptor nanoclustering and dynamics and blocks the ability of cells to sense CXCL12 gradients both in vitro and in vivo while preserving ligand binding and receptor internalization.

Abstract This cluster randomised clinical trial carried out in 20 primary care centres in Barcelona was aimed at assessing the effect of a continuous intervention focused on C-reactive protein (CRP) rapid testing and training in enhanced communication skills (ECS) on antibiotic consumption for adults with acute cough due to lower respiratory tract infection (LRTI). The interventions consisted of general practitioners and nurses’ use of CRP point-of-care and training in ECS separately and combined, and usual care. The primary outcomes were antibiotic consumption and variation of the quality-adjusted life years during a 6-week follow-up. The difference in the overall antibiotic prescribing between the winter seasons before and after the intervention was calculated. The sample size calculated could not be reached due to the COVID-19 outbreak. A total of 233 patients were recruited. Compared to the usual care group (56.7%) antibiotic consumption among patients assigned to professionals in the ECS group was significantly lower (33.9%, adjusted odds ratio [aOR] 0.38, 95% CI 0.15–0.94, p = 0.037), whereas patients assigned to CRP consumed 43.8% of antibiotics (aOR 0.70, 95% CI 0.29–1.68, p = 0.429) and 38.4% in the combined intervention group (aOR 0.45, 95% CI, 0.17–1.21; p = 0.112). The overall antibiotic prescribing rates in the centres receiving training were lower after the intervention compared to those assigned to usual care, with significant reductions in β-lactam rates. Patient recovery was similar in all groups. Despite the limited power due to the low number of patients included, we observed that continuous training achieved reductions in antibiotic consumption.

El objetivo de esta investigación es hacer una revisión sistemática de las causas de deserción en Educación Superior. Recopilando la información por medio de una revisión documental por los diferentes autores consultados para esta investigación. Con la finalidad de identificar las causas de la deserción escolar, en la Universidad. Dicha revisión se llevó a cabo en un periodo del 2010 al 2020 con las palabras claves de deserción escolar, rezago, reprobación y rendimiento académico. Las bases de datos consultadas fueron SciELO, repositorio nacional cti.mx, Eric, Redalyc, dialnet, google académico, donde se utilizaron palabras claves en tesauros, afines a cada uno de los conceptos a investigar. Se realizaron búsquedas en inglés y español, en las áreas de psicología, educación y ciencias sociales. El enfoque metodológico es de tipo cualitativo descriptivo. Dando como resultado 15 artículos que muestran la relación de cada uno de los conceptos antes mencionados con deserción, de un total de 35 artículos seleccionados de las bases de datos consultadas que mostraban información referente a dichas problemáticas. Algunas de las causas de la deserción de los jóvenes universitarios se han basado en el modelo de supervivencia, dando a conocer que la deserción va en relación a la licenciatura en la cual se está cursando. También se identificaron variables pedagógicas, en varias de estas investigaciones concluyeron que el primer año universitario es el más complejo para estos jóvenes, de allí la importancia de las tutorías, también existen otras causas de importancia como son origen social, género, etnia, nacionalidad o la situación familiar. En conclusión, se puede decir que la Institución de Educación Superior debe de estar involucrada en cada uno de estos procesos.

Aim and Background: This research aimed to compare the effectiveness of dialectical behavior therapy and analytical cognitive psychotherapy in reducing the psychological symptoms of people with borderline personality disorder. Methods and Materials: This research is an applied research based on the goal. Based on the collection and type of data, it was quantitative and cross-sectional in terms of time. In addition, it was a semi-experimental research design in the form of pre-test-post-test with a control group. The statistical sample of the research was 45 people in a non-random way. They were chosen voluntarily. Multivariate covariance analysis was used in quantitative data and SPSS version 26 statistical program was used. Findings: The research findings indicated that the scores for Borderline Personality Inventory (BPI) and Self-harm Thoughts and Behaviors (STB) were higher for individuals who underwent Cognitive Analytic Therapy (CAT) compared to those who underwent Dialectical Behavior Therapy (DBT). Conclusions: The results of the present study suggest that the Cognitive Analytic approach is more effective than Dialectical Behavior Therapy. Overall, it can be concluded that Cognitive Analytic Psychotherapy, by improving interpersonal relationships, emotional regulation, and self-concept in individuals with Borderline Personality Disorder, helps in reducing impulsive, unplanned, and thoughtless behaviors through a proper patient-therapist relationship, thereby improving the social functioning of these patients.

Recently, new travel options such as micromobility and shared transport systems have been introduced in many urban areas in Spain, which are intended to increase the sustainability and accessibility of cities. The Covid-19 pandemic has boost the use of these new individual travel modes.In this conference paper, travel behavior and wellbeing of users of this new urban solutions compared to traditional transport modes are analyzed.Face-to-face and online surveys were carried out during the Summer of 2021 in Valencia (Spain) to collect information regarding travel behavior and wellbeing. Participants were habitual users of all urban travel modes, including those who also used motosharing, carsharing or private e-scooters. Satisfaction with Travel Scale (STS) is used to explore subjective wellbeing of users of new and traditional transport modes.Results show that current users of motosharing and private e-scooters were former users of public transport, while users of carsharing used to utilize more car and motosharing before. On the other hand, active transport is associated with higher satisfaction compared to new urban modes, while they provide more satisfaction than urban public transport. Received: 16 November 2023Accepted: 10 March 2024 Published: 27 March 2024

This Special Issue of TeMA - Journal of Land Use, Mobility and Environment proposes to delve into the concept of transition applied to urban and territorial systems with the aim of verifying the state of the art in scientific as well as in technical sector, also considering the effects of Covid-19pandemic crisis (Angiello, 2021). What is urgent is the need to change both social behaviors and the use of primary resources (water, energy and soil) which is claimed by technicians and scholars as the only solution to face environmental challenges affecting nowadays cities. These challenges and the linked risks are so relevant that an in-depth change in the operative actions as well as in the theoretical approaches has become mandatory, in order to avoid negative and disruptive effects. with this Special Issue we intended to draw the attention of technicians and scholars to the theme of urban transition which from many quarters seems to prefer the "ecological dimension" to pursue sustainability objectives. The eleven contributions received, while maintaining the underlying theme of the main theme, propose differentiated perspectives of sustainable transition which can be divided into three groups: • Methodologies and cognitive tools for urban transition • Urban policies and driver elements of the urban transition • Possible projects and applications for urban transition The contributions of the first group propose analysis methodologies oriented to the knowledge of the changes affecting cities, they try to identify adaptation solutions suitable for these changes. In particular, the aspects relating to the vulnerability of cities to the effects of climate change, the need to develop adequate tools to support informed decision-making processes, to define territorial planning tools capable of integrating the transition through the construction of a system of clear rules. The contributions of the second group focus on the analysis of the effects deriving from climate change, highlighting the urgency of integrating adaptation and mitigation actions within the process of defining land use policies at different scales. Aspects relating to the framework of European "green" policies are explored in depth, as well as the need for integration between urban planning and environmental assessment tools, and the search for appropriate methods and tools to improve the adaptation and resilience capacity of urban systems to the need to define approaches based on a holistic and systemic vision for the knowledge of urban phenomena at different scales. The contributions of the third group allow for the building of a first cognitive framework related to research projects and/or urban planning practices aimed at identifying interventions to improve the conditions of urban sustainability, with particular attention to "fragile" territories (lagoon areas, internal areas, coastal areas). Aspects related to the feasibility of creating zero energy emission urban districts as well as the definition of actions for the protection of urban ecosystems are always explored in depth with a view to tracing practicable and sustainable trajectories of change.

Abstract Abnormal trinucleotide repeat expansions alter protein conformation causing malfunction and contribute to a significant number of incurable human diseases. Scarce structural insights available on disease-related homorepeat expansions hinder the design of effective therapeutics. Here, we present the dynamic structure of human PHOX2B C-terminal fragment, which contains the longest polyalanine segment known in mammals. The major α-helical conformation of the polyalanine tract is solely extended by polyalanine expansions in PHOX2B, which are responsible for most congenital central hypoventilation syndrome cases. However, polyalanine expansions in PHOX2B additionally promote nascent homorepeat conformations that trigger length-dependent phase transitions into solid condensates that capture wild-type PHOX2B. Remarkably, HSP70 and HSP90 chaperones specifically seize PHOX2B alternative conformations preventing phase transitions. The precise observation of emerging polymorphs in expanded PHOX2B postulates unbalanced phase transitions as distinct pathophysiological mechanisms in homorepeat expansion diseases, paving the way towards the search of therapeutics modulating biomolecular condensates in central hypoventilation syndrome.

Chagas disease, caused by the parasite Trypanosoma cruzi, affects over 6 million people, mainly in Latin America. Two different clinical phases, acute and chronic, are recognised. Currently, 2 anti-parasitic drugs are available to treat the disease (nifurtimox and benznidazole), but diagnostic methods require of a relatively complex infrastructure and trained personnel, limiting its widespread use in endemic areas, and the access of patients to treatment. New diagnostic methods, such as rapid tests (RDTs) to diagnose chronic Chagas disease, or loop-mediated isothermal amplification (LAMP), to detect acute infections, represent valuable alternatives, but the parasite's remarkable genetic diversity might make its implementation difficult. Furthermore, determining the efficacy of Chagas disease treatment is complicated, given the slow reversion of serological anti-T. cruzi antibody reactivity, which may even take decades to occur. New biomarkers to evaluate early therapeutic efficacy, as well as diagnostic tests able to detect the wide variety of circulating genotypes, are therefore, urgently required. To carry out studies that address these needs, high-quality and traceable samples from T. cruzi-infected individuals with different geographical backgrounds, along with associated clinical and epidemiological data, are necessary. This work describes the framework for the creation of such repositories, following standardised and uniform protocols, and considering the ethical, technical, and logistic aspects of the process. The manual can be adapted according to the resources of each laboratory, to guarantee that samples are obtained in a reproducible way, favouring the exchange of data among different work groups, and their generalizable evaluation and analysis. The main objective of this is to accelerate the development of new diagnostic methods and the identification of biomarkers for Chagas disease.

The development of new biomaterials for musculoskeletal tissue repair is currently an important branch in biomedicine research. The approach presented here is centered around the development of a prototypic synthetic glycerogel scaffold for bone regeneration, which simultaneously features therapeutic activity. The main novelty of this work lies in the combination of an open meso and macroporous nanocrystalline cellulose (NCC)-based glycerogel with a fully biocompatible microporous bioMOF system (CaSyr-1) composed of calcium ions and syringic acid. The bioMOF framework is further impregnated with a third bioactive component, i.e., ibuprofen (ibu), to generate a multifold bioactive system. The integrated CaSyr-1(ibu) serves as a reservoir for bioactive compounds delivery, while the NCC scaffold is the proposed matrix for cell ingrowth, proliferation and differentiation. The measured drug delivery profiles, studied in a phosphate-buffered saline solution at 310 K, indicate that the bioactive components are released concurrently with bioMOF dissolution after ca. 30 min following a pseudo-first-order kinetic model. Furthermore, according to the semi-empirical Korsmeyer-Peppas kinetic model, this release is governed by a case-II mechanism, suggesting that the molecular transport is influenced by the relaxation of the NCC matrix. Preliminary in vitro results denote that the initial high concentration of glycerol in the NCC scaffold can be toxic in direct contact with human osteoblasts (HObs). However, when the excess of glycerol is diluted in the system (after the second day of the experiment), the direct and indirect assays confirm full biocompatibility and suitability for HOb proliferation.

Abstract A major current challenge related to invasions is the absence of a comprehensive theoretical basis for preventing the introduction of alien species and controlling their populations. By using a macroecological framework, we aim to examine patterns of symbiotic species diversity across native and invasive hosts to understand the mechanisms underlying the host–parasite system stability. The symbiotic communities of seven gammarid species, two native and five invasive, were analyzed at 16 fresh and brackish water sites along the Baltic coast of Poland. We investigated the influence of four factors—locality, habitat, host species, and host origin—on diversity patterns and assessed their relative contribution to diversity variation. Our results indicate that all factors are crucial in determining the composition and abundance of symbiotic communities in gammarids. Among these factors, locality and host species apparently have a greater influence on symbiotic communities than habitat conditions and host origin. Comparative analysis of diversity indexes of symbiotic organisms from native and invasive hosts showed that the richer communities of native gammarids were paradoxically less diverse. We assume that these rich and uneven symbiotic communities keep the host–parasite system of native gammarids in equilibrium. Highly dominant symbiotic species with a high load per host individual may stabilize the growth of the host population. Symbiotic communities of the invasive host exhibited lower species richness but displayed a relatively even distribution of species with moderate loads per individual, resulting in a scarcity of heavily infected gammarids within the population. Thus, the survival rate of invasive gammarids is expected to be relatively high, facilitating their population growth and further spread. We conclude that complex communities of native gammarids constructed from many symbiotic species may prevent host populations from undergoing explosive growth, while such mechanisms may be completely or partially reduced in invasive hosts.

In this research, several SO2 removal alternatives were evaluated for the treatment of gaseous effluents generated by the "Carlos Manuel de Céspedes" power plant in Cienfuegos to be use in gaseous stream to Ulva lettuce intensive culture. A low-cost sensor was used to monitor the gas concentration during the proposed methods. The sensor was previously calibrated and a linear regression model with a coefficient of determination of 0,9926 was obtained. The alternatives evaluated were adsorption with activated carbon, absorption with calcium hydroxide and absorption with seawater. The removal was evaluated at three levels SO2 concentration. In addition, the parameters pH, salinity and alkalinity were determined to a seawater sample from the Bay of Cienfuegos and with which the experiments were carried out. The values obtained were 8,17±0,003; 26,50±0,10 ups and 171,67±1,03 mg/L respectively, which confirms its good performance for gas removal. The three methods studied showed satisfactory results for SO2 removal. The seawater absorption experiment was the most efficient alternative, achieving the lowest final concentrations in the shortest time.

Assessing air quality's impact on human health involves monitoring pollutant concentrations such as NO2, O3, CO, SO2, and particulate matter. While high-income countries rely on expensive reference instruments, low-income nations face technological limitations. This study explores the potential of low-cost scientific devices as a viable solution for these regions. The research focuses on evaluating the reliability of low-cost NO2 sensors and consistency across five identical sensors. Calibration tests in controlled settings reveal a linear model with high coefficients of determination, contrasting with lower coefficients observed during field tests. Variability in intercepts and slopes is evident across time and campaign contexts. Time series analysis using low-cost NO2 sensors showed that many of the tall peaks atop a fluctuating baseline correlates with peaks identified by reference instruments. Additionally, NO gas sensors are also able to identify pollution peaks in monitoring campaigns. Therefore, such affordable sensors provide valuable insights into pollutant concentration trends, offering indicative magnitude information. However, improving calibration and reliability of these sensors necessitates further research.

Non-cystic fibrosis bronchiectasis, a condition that remains relatively underrecognized, has garnered increasing research focus in recent years. This scientific interest has catalyzed advancements in diagnostic methodologies, enabling comprehensive clinical and molecular profiling. Such progress facilitates the development of personalized treatment strategies, marking a significant step toward precision medicine for these patients.Bronchiectasis poses significant diagnostic challenges in both clinical settings and research studies. While computed tomography (CT) remains the gold standard for diagnosis, novel alternatives are emerging. These include artificial intelligence-powered algorithms, ultra-low dose chest CT, and magnetic resonance imaging (MRI) techniques, all of which are becoming recognized as feasible diagnostic tools.The precision medicine paradigm calls for refined characterization of bronchiectasis patients by analyzing their inflammatory and molecular profiles. Research into the underlying mechanisms of inflammation and the evaluation of biomarkers such as neutrophil elastase, mucins, and antimicrobial peptides have led to the identification of distinct patient endotypes. These endotypes present variable clinical outcomes, necessitating tailored therapeutic interventions. Among these, eosinophilic bronchiectasis is notable for its prevalence and specific prognostic factors, calling for careful consideration of treatable traits.A deeper understanding of the microbiome's influence on the pathogenesis and progression of bronchiectasis has inspired a holistic approach, which considers the multibiome as an interconnected microbial network rather than treating pathogens as solitary entities. Interactome analysis therefore becomes a vital tool for pinpointing alterations during both stable phases and exacerbations.This array of innovative approaches has revolutionized the personalization of treatments, incorporating therapies such as inhaled mannitol or ARINA-1, brensocatib for anti-inflammatory purposes, and inhaled corticosteroids specifically for patients with eosinophilic bronchiectasis. Resumen: Las bronquiectasias no fibrosis quística han atraído una creciente atención en investigación. Este interés científico ha catalizado avances en las metodologías de diagnóstico, permitiendo realizar perfiles clínicos y moleculares integrales. Este progreso facilita el desarrollo de estrategias de tratamiento personalizadas y marca un paso significativo hacia la medicina de precisión.Desde el punto de vista diagnóstico, las bronquiectasias plantean desafíos importantes en entornos clínicos y de investigación. Si bien la TC es el gold standard, están surgiendo nuevas alternativas. Entre ellas, algoritmos de inteligencia artificial, TC de tórax de dosis ultrabajas y técnicas de resonancia magnética.La medicina de precisión aboga por la caracterización de pacientes mediante análisis de perfiles inflamatorios y moleculares. Las investigaciones sobre mecanismos subyacentes de inflamación y la evaluación de biomarcadores como la elastasa de neutrófilos, mucinas y péptidos antimicrobianos, han llevado a la identificación de endotipos de pacientes. Estos endotipos exhiben resultados clínicos variables, requiriendo intervenciones terapéuticas personalizadas. La bronquiectasia eosinofílica destaca por su prevalencia y factores pronósticos específicos, exigiendo consideración de los rasgos tratables.Una comprensión profunda de la influencia del microbioma en la patogénesis y progresión de las bronquiectasias inspira un enfoque holístico. Considera el multibioma como una red microbiana interconectada, no entidades solitarias. El análisis del interactoma se convierte en una herramienta vital para identificar alteraciones durante fases estables y exacerbaciones.Este conjunto de enfoques innovadores revoluciona la personalización de los tratamientos, incorporando terapias como manitol inhalado o ARINA-1, brensocatib con fines antiinflamatorios y corticosteroides inhalados específicos para pacientes con bronquiectasias eosinofílicas.

Introduction: Organ motion (OM) and volumetric changes pose challenges in radiotherapy (RT) for locally advanced cervical cancer (LACC). Magnetic Resonance-guided Radiotherapy (MRgRT) combines improved MRI contrast with adaptive RT plans for daily anatomical changes. Our goal was to analyze cervico-uterine structure (CUS) changes during RT to develop strategies for managing OM. Materials and methods: LACC patients received chemoradiation by MRIdian system with a simultaneous integrated boost (SIB) protocol. Prescription doses of 55–50.6 Gy at PTV1 and 45–39.6 Gy at PTV2 were given in 22 and 25 fractions. Daily MRI scans were co-registered with planning scans and CUS changes were assessed.Six PTVs were created by adding 0.5, 0.7, 1, 1.3, 1.5, and 2 cm margins to the CUS, based on the simulation MRI. Adequate margins were determined to include 95 % of the CUSs throughout the entire treatment in 95 % of patients. Results: Analysis of 15 LACC patients and 372 MR scans showed a 31 % median CUS volume decrease. Asymmetric margins of 2 cm cranially, 0.5 cm caudally, 1.5 cm posteriorly, 2 cm anteriorly, and 1.5 cm on both sides were optimal for PTV, adapting to CUS variations. Post-14th fraction, smaller margins of 0.7 cm cranially, 0.5 cm caudally, 1.3 cm posteriorly, 1.3 cm anteriorly, and 1.3 cm on both sides sufficed. Conclusion: CUS mobility varies during RT, suggesting reduced PTV margins after the third week. MRgRT with adaptive strategies optimizes dose delivery, emphasizing the importance of streamlined IGRT with reduced PTV margins using a tailored MRgRT workflow with hybrid MRI-guided systems.

Abstract Given the multitude of challenges Earth is facing, sustainability science is of key importance to our continued existence. Evolution is the fundamental biological process underlying the origin of all biodiversity. This phylogenetic diversity fosters the resilience of ecosystems to environmental change, and provides numerous resources to society, and options for the future. Genetic diversity within species is also key to the ability of populations to evolve and adapt to environmental change. Yet, the value of evolutionary processes and the consequences of their impairment have not generally been considered in sustainability research. We argue that biological evolution is important for sustainability and that the concepts, theory, data, and methodological approaches used in evolutionary biology can, in crucial ways, contribute to achieving the UN Sustainable Development Goals (SDGs). We discuss how evolutionary principles are relevant to understanding, maintaining, and improving Nature Contributions to People (NCP) and how they contribute to the SDGs. We highlight specific applications of evolution, evolutionary theory, and evolutionary biology's diverse toolbox, grouped into four major routes through which evolution and evolutionary insights can impact sustainability. We argue that information on both within‐species evolutionary potential and among‐species phylogenetic diversity is necessary to predict population, community, and ecosystem responses to global change and to make informed decisions on sustainable production, health, and well‐being. We provide examples of how evolutionary insights and the tools developed by evolutionary biology can not only inspire and enhance progress on the trajectory to sustainability, but also highlight some obstacles that hitherto seem to have impeded an efficient uptake of evolutionary insights in sustainability research and actions to sustain SDGs. We call for enhanced collaboration between sustainability science and evolutionary biology to understand how integrating these disciplines can help achieve the sustainable future envisioned by the UN SDGs.

BackgroundRecent studies have shown positive, though small, clinical effects of digital smoking cessation (SC) interventions for cancer survivors. However, research on associations among participant characteristics, intervention engagement, and outcomes is limited. ObjectiveThis study aimed to explore the predictors and moderators of engagement and outcome of MyCourse-Quit Smoking (in Dutch: “MijnKoers-Stoppen met Roken”), a digital minimally guided intervention for cancer survivors. MethodsA secondary analysis of data from the randomized controlled trial was performed. The number of cigarettes smoked in the past 7 days at 6-month follow-up was the primary outcome measure. We analyzed interactions among participant characteristics (11 variables), intervention engagement (3 variables), and outcome using robust linear (mixed) modeling. ResultsIn total, 165 participants were included in this study. Female participants accessed the intervention less often than male participants (B=–11.12; P=.004). A higher Alcohol Use Disorders Identification Test score at baseline was associated with a significantly higher number of logins (B=1.10; P

IntroductionCervical cancer is a public health problem in our country and worldwide. Less than 25% of cases are diagnosed in the early stages, where survival is more remarkable than 90% at five years. Here, we review surgical treatment in the early stages of cervical cancer.MethodologyA literature review was carried out in the MEDLINE database. The search was mainly limited to the English language, with priority given to systematic reviews with or without meta-analysis and randomized studies. However, only retrospective or observational evidence was found for some topics.ResultsThe standard treatment for early-stage cervical cancer is hysterectomy, and its radical nature will depend on the tumor size, lymphovascular permeation, and tumor-specific prognostic factors. Furthermore, the type of surgery (hysterectomy or trachelectomy) will rely on the patient’s desire to preserve fertility. Nodal evaluation is indicated as part of the treatment from stage IAI with PLV. However, the sentinel lymph node is more relevant in the treatment. The incidental finding of cervical cancer after a hysterectomy requires a multidisciplinary evaluation to determine the therapeutic approach. Less radical surgery has been described as oncologically safe in low-risk groups.ConclusionSurgical treatment in its early stages has evolved in recent decades, making it more individualized and seeking less morbidity in patients without compromising their survival.

Summary: Beliefs—attitudes toward some state of the environment—guide action selection and should be robust to variability but sensitive to meaningful change. Beliefs about volatility (expectation of change) are associated with paranoia in humans, but the brain regions responsible for volatility beliefs remain unknown. The orbitofrontal cortex (OFC) is central to adaptive behavior, whereas the magnocellular mediodorsal thalamus (MDmc) is essential for arbitrating between perceptions and action policies. We assessed belief updating in a three-choice probabilistic reversal learning task following excitotoxic lesions of the MDmc (n = 3) or OFC (n = 3) and compared performance with that of unoperated monkeys (n = 14). Computational analyses indicated a double dissociation: MDmc, but not OFC, lesions were associated with erratic switching behavior and heightened volatility belief (as in paranoia in humans), whereas OFC, but not MDmc, lesions were associated with increased lose-stay behavior and reward learning rates. Given the consilience across species and models, these results have implications for understanding paranoia.

This study discusses the importance of minimal residual disease (MRD) detection in acute myeloid leukemia (AML) patients using liquid biopsy and next-generation sequencing (NGS). AML prognosis is based on various factors, including genetic alterations. NGS has revealed the molecular complexity of AML and helped refine risk stratification and personalized therapies. The long-term survival rates for AML patients are low, and MRD assessment is crucial in predicting prognosis. Currently, the most common methods for MRD detection are flow cytometry and quantitative PCR, but NGS is being incorporated into clinical practice due to its ability to detect genomic aberrations in the majority of AML patients. Typically, bone marrow samples are used for MRD assessment, but using peripheral blood samples or liquid biopsies would be less invasive. Leukemia originates in the bone marrow, along with the cfDNA obtained from peripheral blood. This study aimed to assess the utility of cell-free DNA (cfDNA) from peripheral blood samples for MRD detection in AML patients. A cohort of 20 AML patients was analyzed using NGS, and a correlation between MRD assessment by cfDNA and circulating tumor cells (CTCs) in paired samples was observed. Furthermore, a higher tumor signal was detected in cfDNA compared to CTCs, indicating greater sensitivity. Challenges for the application of liquid biopsy in MRD assessment were discussed, including the selection of appropriate markers and the sensitivity of certain markers. This study emphasizes the potential of liquid biopsy using cfDNA for MRD detection in AML patients and highlights the need for further research in this area.

Carbon monoxide (CO), a gaseous signaling molecule, has shown promise in preventing body weight gain and metabolic dysfunction induced by high fat diet (HFD), but the mechanisms underlying these effects are largely unknown. An essential component in response to HFD is the gut microbiome, which is significantly altered during obesity and represents a target for developing new therapeutic interventions to fight metabolic diseases. Here, we show that CO delivered to the gut by oral administration with a CO-releasing molecule (CORM-401) accumulates in faeces and enriches a variety of microbial species that were perturbed by a HFD regimen. Notably, Akkermansia muciniphila, which exerts salutary metabolic effects in mice and humans, was strongly depleted by HFD but was the most abundant gut species detected after CORM-401 treatment. Analysis of bacterial transcripts revealed a restoration of microbial functional activity, with partial or full recovery of the Krebs cycle, β-oxidation, respiratory chain and glycolysis. Mice treated with CORM-401 exhibited normalization of several plasma and fecal metabolites that were disrupted by HFD and are dependent on Akkermansia muciniphila's metabolic activity, including indoles and tryptophan derivatives. Finally, CORM-401 treatment led to an improvement in gut morphology as well as reduction of inflammatory markers in colon and cecum and restoration of metabolic profiles in these tissues. Our findings provide therapeutic insights on the efficacy of CO as a potential prebiotic to combat obesity, identifying the gut microbiota as a crucial target for CO-mediated pharmacological activities against metabolic disorders.

Water-soluble Carbon Quantum Dots (CQDs) featured with blue fluorescence were prepared by electrochemical synthesis at room temperature using carbon electrodes as a carbon source and encapsulated in liposomes of DMPC (1,2-dimyristoyl-sn‑glycero-3-phosphocholine) in a single quick step. The system liposome-CQDs was characterized by UV–vis absorption spectroscopy, fluorescence microscopy, scanning electron microscopy, Fourier transform infrared spectroscopy and epifluorescence microscopy. Electrochemical studies, such as cyclic voltammetry and impedance, have corroborated that electrosynthesis occurs at a voltage of -300 mV to form the hybrid system. The analysis includes the evaluation of variables with effect on the synthetic process of CQDs: voltage and reaction time. The results revealed that liposomes labeled with the CQDs are suitable for optical characterization by conventional and epifluorescence microscopies. In summary, this research involved the synthesis of water-soluble CQDs and their encapsulation in phospholipid vesicles in one pot, their characterization using various analytical techniques, the investigation of crucial synthesis variables, and particularly for visualization purposes in microscopy. Due to the rapidity and simplicity of the synthesis method, this work could have potential applications in analytical chemistry, biology, materials science, and related fields.