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Alterations in the tumor suppressor genes (TSGs) RB1, PTEN, and TP53 are associated with treatment resistance, worse survival, and aggressive variants of prostate cancer (AVPC). We previously developed and validated a signature reflecting low TSG expression (TSGlow) that was associated with poor outcomes in patients with metastatic hormone-sensitive prostate cancer (mHSPC) treated with androgen deprivation therapy (ADT) ± docetaxel. The aim of this multicenter retrospective study was to validate the TSGlow signature in patients with mHSPC treated with ADT and an androgen receptor pathway inhibitor (ARPI) and to explore clinical characteristics at progression according to TSG status. TSG mRNA expression in formalin-fixed, paraffin-embedded samples was assessed via nCounter. Correlation of expression levels with castration-resistant prostate cancer–free survival (CRPC-FS; primary endpoint) and overall survival (OS) was investigated via Kaplan-Meier and multivariate Cox analyses. Of the 137 patients included, 77.4% had de novo stage IV cancer and 44.5% had high-risk disease. TSGlow (16.8%) was correlated with visceral metastases (p = 0.013), high-risk disease (p = 0.038), higher Gleason score (p = 0.026), shorter CRPC-FS (hazard ratio 1.9; p = 0.046) and higher AVPC frequency (p = 0.01). Our results confirm that a TSGlow signature is an adverse prognostic factor and is associated with AVPC development in patients with mHSPC treated with ADT + ARPI. Further prospective validation is needed to define specific therapeutic strategies for these patients. Patient summary: We looked at outcomes for patients with metastatic hormone-sensitive prostate cancer treated with hormone therapies. We found that patients with low expression of two out of three tumor suppressor genes (TP53, RB1, PTEN) had worse clinical outcomes and had aggressive variants of prostate cancer. Measuring the expression of these genes in early-stage prostate cancer could help in finding better treatments for these patients.

Abstract Objective To develop a domain-specific large language model (LLM) for LI-RADS v2018 categorization of hepatic observations based on free-text descriptions extracted from MRI reports. Material and methods This retrospective study included 291 small liver observations, divided into training (n = 141), validation (n = 30), and test (n = 120) datasets. Of these, 120 were fictitious, and 171 were extracted from 175 MRI reports from a single institution. The algorithm’s performance was compared to two independent radiologists and one hepatologist in a human replacement scenario, and considering two combined strategies (double reading with arbitration and triage). Agreement on LI-RADS category and dichotomic malignancy (LR-4, LR-5, and LR-M) were estimated using linear-weighted κ statistics and Cohen’s κ, respectively. Sensitivity and specificity for LR-5 were calculated. The consensus agreement of three other radiologists served as the ground truth. Results The model showed moderate agreement against the ground truth for both LI-RADS categorization (κ = 0.54 [95% CI: 0.42–0.65]) and the dichotomized approach (κ = 0.58 [95% CI: 0.42–0.73]). Sensitivity and specificity for LR-5 were 0.76 (95% CI: 0.69–0.86) and 0.96 (95% CI: 0.91–1.00), respectively. When the chatbot was used as a triage tool, performance improved for LI-RADS categorization (κ = 0.86/0.87 for the two independent radiologists and κ = 0.76 for the hepatologist), dichotomized malignancy (κ = 0.94/0.91 and κ = 0.87) and LR-5 identification (1.00/0.98 and 0.85 sensitivity, 0.96/0.92 and 0.92 specificity), with no statistical significance compared to the human readers’ individual performance. Through this strategy, the workload decreased by 45%. Conclusion LI-RADS v2018 categorization from unlabelled MRI reports is feasible using our LLM, and it enhances the efficiency of data curation. Critical relevance statement Our proof-of-concept study provides novel insights into the potential applications of LLMs, offering a real-world example of how these tools could be integrated into a local workflow to optimize data curation for research purposes. Key Points Automatic LI-RADS categorization from free-text reports would be beneficial to workflow and data mining. LiverAI, a GPT-4-based model, supported various strategies improving data curation efficiency by up to 60%. LLMs can integrate into workflows, significantly reducing radiologists’ workload. Graphical Abstract

Abstract In citrus, the synthetic auxin 3,5,6-trichloro-2-pyridyloxyacetic acid (3,5,6-TPA), applied as a foliar spray at a concentration of 15 mg l− 1 during physiological fruitlet abscission, caused additional fruitlet drop and reduced the number of fruits reaching maturity. The effect was much more pronounced at full physiological abscission than after. In this study, this thinning effect was successfully exploited for the first time in sour orange trees grown in an urban environment, reducing harvesting costs by up to almost 40%. This effect is mediated by the leaves, which alter their photosynthetic activity. Our results show a reduction of carbon fixation and sucrose synthesis in the leaf, by 3,5,6-TPA repression of the RbcS, SUS1 and SUSA genes, its transport to the fruit, as shown by the reduced expression of the sucrose transporter genes SUT3 and SUT4, and its hydrolysis in the fruit, mainly by repression of the SUS1 gene expression. Genes involved in auxin homeostasis in the fruit, TRN2 and PIN1, were also repressed. The coordinated repression of all these genes is consistent with the decrease in the fruit cell division rate, as shown by the repression of CYCA1-1 gene, leading to the production of ethylene, which ultimately induces fruitlet abscission.

Background: Collaborative Online International Learning (COIL) involves international online activities that allow the support of transversal competencies in diverse and multicultural environments without moving from home. This paper presents the learning experiences and satisfaction of undergraduate nursing students at the University of Girona (Spain) from a COIL activity involving clinical simulation in collaboration with the University of Coventry (United Kingdom). Methods: Qualitative study of content analysis. Twelve students from each of the two universities participated in the data collection process using reflective diaries. Results: The data analysis highlighted five topics related to the COIL activity involving clinical simulation: (a) initial attitudes towards the COIL activity; (b) main learning through the COIL activity; (c) positive aspects of the COIL activity; (d) weaknesses of the COIL activity and proposals for improvement; and (e) overall evaluation of the COIL activity. Conclusions: The main learning outcomes referred to by students were the relationships between transversal competencies and the skills for life, language skills, cultural skills, and more specific skills related to clinical standards. The students were most satisfied with the teaching activities and specified positive aspects and weaknesses that will add value to future versions of the activities.

Abstract We propose to use atoms and molecules as quantum sensors of axion-mediated monopole-dipole forces. We show that electron spin precession experiments using atomic and molecular beams are well-suited for axion searches thanks to the presence of co-magnetometer states and single-shot temporal resolution. Experimental strategies to detect axion gradients from localised sources and the earth are presented, taking ACME III as a prototype example. Other possibilities including atomic beams, and laser-cooled atoms and molecules are discussed.

This review focuses on the intricate water relationships between internal and external tissues in growing fruits within the framework of the epidermal growth control hypothesis. It considers the components of water potential, including turgor pressure and osmotic potential of both internal and external tissues, taking into account factors such as fruit growth rate, sugar accumulation, cell wall metabolism, and climacteric. It also examines the effects of environmental conditions, genetic factors, and physiological influences in modifying water relations. By emphasizing the significance of skin tissue water potential components as indicators of growth stress, the review underlines their importance for a comprehensive understanding of water relations and associated physiological disorders in growing fruit.

Background: The role of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) validated with video-assisted mediastinoscopic lymphadenectomy (VAMLA) for mediastinal restaging of patients with non-small cell lung cancer (NSCLC) after induction therapy has never been described. Objective: To report on our experience in this clinical setting. Design: Retrospective analysis of a prospectively built database. Methods: Patients with stage IIIA (N2) NSCLC who underwent EBUS-TBNA for mediastinal restaging after induction therapy were included. The sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and diagnostic accuracy of EBUS-TBNA and VAMLA for mediastinal restaging were calculated. The number of patients needed to undergo confirmatory VAMLA (NNT) after a negative EBUS-TBNA for mediastinal restaging to avoid a case of pathologic (p) N2 disease after resection was also calculated. Results: Forty-six patients underwent EBUS-TBNA which was positive in 12 patients and negative in 34. Patients with a negative EBUS-TBNA underwent VAMLA which was positive in seven cases. Of the other 27 patients with a negative VAMLA, 26 underwent resection that did not show N2 disease. The sensitivity, specificity, NPV, PPV, and diagnostic accuracy of EBUS-TBNA for restaging were 63.1%, 100%, 79.4%, 100%, and 84.7%, respectively. The sensitivity, specificity, NPV, PPV, and diagnostic accuracy of confirmatory VAMLA after EBUS-TBNA was 100%. The NNT confirmatory VAMLA after a negative EBUS-TBNA to avoid a case of pN2 disease at resection was five patients. Conclusion: EBUS-TBNA must remain as the first-choice test for invasive mediastinal restaging. However, the results of our study in terms of sensitivity and NPV, even considering the small size of our population, suggest that negative results of EBUS-TBNA should be interpreted with caution and surgical exploration of the mediastinum (specially VAMLA, if available) should be considered in these patients.

The subject "Social Responsibility" is designed to instil a commitment to Sustainable Development Goals among future professionals. The social practicum of the subject consists of 50 hours of service at associations attending the most vulnerable. The aim of this study is to analyse the meaning of this practicum on the lives of alumni who are now working professions. A phenomenological qualitative study was conducted with the participation of 20 people who met the inclusion criteria. The sample was collected using convenience and snowball sampling. The average age was 32 and 60% of the participants were women. Data analysis was carried out in line with Giorgi's (1997) proposal and according to COREQ (2007) guidelines to ensure the quality of the study. The participants indicated that the practicum was a very significant experience in their lives, in which they discovered values such as empathy, justice and respect. They also developed greater social awareness, especially their sensitivity towards the vulnerable or those with disabilities, while also helping them to be more open-minded towards other realities and, in general, to mature. Finally, the participants noted that they learned to regard their profession as a service to society.

Abstract Background and Objectives Direct-acting antivirals (DAAs) offer a high rate of hepatitis C virus (HCV) eradication. However, concerns on the risk of cancer after HCV eradication remain. Our study aimed at quantifying the incidence of cancer in patients treated with anti-HCV therapies in Catalonia (Spain) and their matched controls. Methods This was a population-based study using real-world data from the public healthcare system of Catalonia between 2012 and 2016. Propensity score matching was performed in patients with HCV infection treated with interferon-based therapy (IFN), sequential IFN and DAA (IFN+DAA), and DAA only (DAA) with concurrent controls. We estimated the annual incidence of overall cancer, hepatocellular carcinoma, and non-liver cancer of HCV-treated patients and their corresponding rate ratios. Results The study included 11,656 HCV-treated patients and 49,545 controls. We found statistically significant increases in the rate of overall cancer for IFN+DAA-treated (rate ratio [RR] 1.77, 95% confidence interval [CI] 1.27–2.46) and DAA-treated patients (RR 1.90, 95% CI 1.66–2.19) and in the rate of HCC for IFN-treated (RR 1.50, 95% CI 1.02–2.22), IFN+DAA-treated (RR 3.89, 95% CI 2.26–6.69), and DAA-treated patients (RR 6.45, 95% CI 4.90–8.49) compared with their corresponding controls. Moreover, DAA-treated patients with cirrhosis showed an increased rate of overall cancer versus those without cirrhosis (RR 1.92, 95% CI 1.51–2.44). Conclusions Results showed that overall cancer and hepatocellular carcinoma incidence in Catalonia was significantly higher among HCV-treated patients compared with matched non-HCV-infected controls, and risks were higher in patients with cirrhosis. An increased awareness of the potential occurrence of uncommon malignant events and monitoring after HCV eradication therapy may benefit patients.

Background: The risk of hepatocarcinoma in HCV cirrhotic patient responders after treatment with DAAs decrease, but HCC still occurs. A correlation between specific miRNAs and the development of hepatocarcinoma have been highlighted. Aim: To investigate miRNA expression in HCV-infected cirrhotic patients treated with DAAs, regarding whether or not they developed HCC at follow-up. Methods: A total of 73 outpatients with HCV-related cirrhosis treated with DAAs were enrolled, 28 of which had HCC. Samples were collected at the start and at the end of treatment. In the screening phase, 172 miRNAs were analyzed at baseline. Differentially expressed miRNAs were validated in the entire cohort. Results: In the validation phase, at baseline and in patients treated for 12 weeks, miR-28-5p was confirmed to be more highly expressed in the HCC group compared to the non-HCC group. In all of the patients treated for 12 weeks, at end of the treatment we found a significant downregulation in miR-132-3p, miR-133b-3p, miR-221-3p and miR-324-3p. In the HCC group, miR-28-5p was significantly downregulated after DAA therapy as well as in HCC patients treated for 24 weeks. Conclusion: In the HCC group, miR28-5p was differently expressed both at baseline and at the end of therapy with DAAs. This difference in expression should suggest its involvement in HCC development.

Substantial evidence supports the idea that engaged workers reach high performance levels. Nevertheless, most research does not take into account that job performance is multidimensional. The current study aimed to investigate the relationship between work engagement and performance (task performance, contextual performance, counterproductive work behaviors, and adaptive performance) and determine whether work engagement provides incremental validity over the Big Five personality traits in the prediction of performance. A questionaire with the variables of interest was filled in by 365 workers. Regression analyses revealed that work engagement plays a role in all dimensions of job performance. Results also revealed the differential functioning of work engagement dimensions, with vigor as the main predictor of task performance and the second predictor of adaptive performance, even when considering personality. High absorption decreases task performance but increases contextual performance, while dedication mediates between personality (i.e., agreeableness and extraversion) and CWB.

Este artículo busca analizar si las estrategias de interactividad implementadas por universidades de América Latina, Europa y Estados Unidos en sus redes sociales influyen en el grado de participación de los usuarios. Se realizó un análisis de contenido de 90.241 publicaciones en perfiles institucionales de X/Twitter, Facebook y LinkedIn de 70 universidades. Los resultados muestran que las instituciones latinoamericanas no tienen una estrategia de interactividad notoriamente diferente de las europeas y estadounidenses. Las tasas de interacción logradas son muy bajas en relación con otros sectores y aquellas recomendadas por expertos. La estrategia de interactividad de las universidades no es lo suficientemente adecuada, pues el enfoque de comunicación de las publicaciones es altamente informativo en todas las redes sociales y los recursos de comunicación son principalmente expositivos, aunque cada vez se combinan más con recursos interactivos. Esta investigación propone un marco para medir y evaluar la estrategia de interactividad de las organizaciones en las redes sociales, identificando y analizando sus dimensiones clave.

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Neuronal apoptosis is a mechanism used to clear the cells of oxidative stress or DNA damage and refine the final number of neurons for a functional neuronal circuit. The tumor suppressor protein p53 is a key regulator of the cell cycle and serves as a checkpoint for eliminating neurons with high DNA damage, hyperproliferative signals or cellular stress. During development, p53 is largely expressed in progenitor cells. In the adult brain, p53 expression is restricted to the neurogenic niches where it regulates cell proliferation and self-renewal. To investigate the functional consequences of p53 deletion in the cortex and hippocampus, we generated a conditional mutant mouse (p53-cKO) in which p53 is deleted from pallial progenitors and their derivatives. Surprisingly, we did not find any significant change in the number of neurons in the mutant cortex or CA region of the hippocampus compared with control mice. However, p53-cKO mice exhibit more proliferative cells in the subgranular zone of the dentate gyrus and more granule cells in the granular cell layer. Glutamatergic synapses in the CA3 region are more numerous in p53-cKO mice compared with control littermates, which correlates with overexcitability and higher epileptic susceptibility in the mutant mice.

La UE se enfrenta a cambios demográficos, sociales y estructurales sin precedentes que exigen la adopción de políticas concretas para garantizar que el envejecimiento general de la población vaya acompañado de una correcta atención a la satisfacción de las necesidades sociales, asistenciales y sanitarias de las personas mayores y de sus familias. El artículo explora la contribución del Derecho de la UE en aspectos como el mercado de trabajo y el envejecimiento activo; la protección social y económica de las personas mayores; la lucha contra la discriminación por razón de edad o la garantía de acceso a los servicios y la brecha digital.

Background: Aging populations are driving a shift in emphasis toward enhancing chronic disease care, reflected in Catalonia’s regional plan which prioritizes standardized nursing care plans in primary care settings. To achieve this, the ARES-AP program was established with a focus on harmonizing standards and supporting routine nursing clinical decision-making. This study evaluates nurses’ perceptions of ARES-AP’s standardized care plans for chronic diseases. Methods: A mixed-methods approach based on an ad hoc questionnaire (n = 141) and a focus group (n = 14) was used. Quantitative data were statistically analysed, setting significance at p < 0.05. Qualitative data were explored via content analysis. Results: ARES-AP training was assessed positively. The resources for motivational interviewing and care plans for the most prevalent chronic diseases were rated very positively. This study identified key factors influencing program implementation, including facilitators such as structured information and nursing autonomy, barriers such as resistance to change, motivators such as managerial support, and suggested improvements such as technological improvements and time management strategies. Conclusions: This study identifies areas for improvement in implementing standardized nursing care plans, including additional time, motivation, enhanced IT infrastructure, and collaboration among primary care professionals. It enhances understanding of these plans in primary care, especially in managing chronic diseases in aging populations. Further research should assess the program’s long-term impact on chronic patients. This study was not registered.

Abstract Miniaturised optical spectrometers are attractive due to their small footprint, low weight, robustness and stability even in harsh environments such as space or industrial facilities. We report on a stationary-wave integrated Fourier-transform spectrometer featuring a measured optical bandwidth of 325 nm and a theoretical spectral resolution of 1.2 nm. We fabricate and test on lithium niobate-on-insulator to take full advantage of the platform, namely electro-optic modulation, broad transparency range and the low optical loss achieved thanks to matured fabrication techniques. We use the electro-optic effect and develop innovative layouts to overcome the undersampling limitations and improve the spectral resolution, thus providing a framework to enhance the performance of all devices sharing the same working principle. With our work, we add another important element to the portfolio of integrated lithium-niobate optical devices as our spectrometer can be combined with multiple other building blocks to realise functional, monolithic and compact photonic integrated circuits.

Abstract This paper introduces the design of a reconfigurable transmitarray operating within the D-band frequency range (110–170 GHz). The transmitarray unit cell is composed of three metal layers and two quartz dielectric substrates. It achieves a 1-bit phase shift resolution through the alternating states of two innovative switches integrated into the active transmitting patch of the unit cell. To address the challenge of miniaturization in the D-band, compact switches compatible with the proposed unit cell dimensions are introduced. These switches are constructed using phase change materials (PCM) that change between amorphous and crystalline states when exposed to heat. The paper includes a full-wave simulation of the unit cell, demonstrating an insertion loss below 1.5 dB across a wide frequency band of 27%. Additionally, a 10 $$\times $$ × 10 elements transmitarray is synthesized using a numerical tool and its theoretical results are compared to full-wave electromagnetic simulations for validation purposes. The results indicate that by incorporating the proposed switches into the unit cell, the transmitarray achieves promising reconfiguration capabilities within the D-band. Moreover, the paper presents the architecture of a command line designed to bias the PCM switches. Notably, this command line represents a novel approach, as it enables individual biasing of each PCM switch using direct current (DC). The influence of these command lines on the transmitarray’s performance is thoroughly investigated. Although there is a compromise in the 1-dB gain bandwidth, the overall behavior of the transmitarray remains encouraging.

Abstract Background Several studies have reported the effect of rhythmic auditory stimulation (RAS) on functional ambulation in stroke patients, yet no systematic overview has yet been published. This study aims to synthesize the available evidence describing changes in stroke patients after RAS intervention for functional ambulation and the use of walking assistive devices, and to find out if the effect of RAS and music-based RAS differs depending on the lesioned area. Methods The PubMed, PEDro, Cochrane Central Register of Controlled Trials, Web of Science, Scopus and CINAHL electronic databases were searched for reports evaluating the effect of RAS on walking in stroke patients, applying the PICOS criteria for the inclusion of studies. Results Twenty one articles were included (948 stroke survivors). Most studies were of good methodological quality according to the PEDro scale, but they had a high risk of bias. The most consistent finding was that RAS improves walking and balance parameters in stroke patients in all phases compared to baseline and versus control groups with conventional treatment. Functional ambulation and the use of walking assistive devices were inconsistently reported. Several studies also suggest that RAS may be as good as other complementary therapies (horse-riding and visual cueing). Conclusions Despite the beneficial effects of RAS, the question remains as to whether it is better than other complementary therapies. Given the heterogeneity of the interventions, the interventions in control groups, the varied durations, and the different outcome measures, we suggest that care should be taken in interpreting and generalizing findings. PROSPERO Registration CRD42021277940.

Microtubules play a central role in cytoskeletal changes during neuronal development and maintenance. Microtubule dynamics is essential to polarity and shape transitions underlying neural cell division, differentiation, motility, and maturation. Kinesin superfamily protein 2A is a member of human kinesin 13 gene family of proteins that depolymerize and destabilize microtubules. In dividing cells, kinesin superfamily protein 2A is involved in mitotic progression, spindle assembly, and chromosome segregation. In postmitotic neurons, it is required for axon/dendrite specification and extension, neuronal migration, connectivity, and survival. Humans with kinesin superfamily protein 2A mutations suffer from a variety of malformations of cortical development, epilepsy, autism spectrum disorder, and neurodegeneration. In this review, we discuss how kinesin superfamily protein 2A regulates neuronal development and function, and how its deregulation causes neurodevelopmental and neurological disorders.

Background: Kidney transplantation is the therapy of choice for patients with advanced chronic kidney disease; however, predicting graft outcomes remains a significant challenge. Early identification of reliable biomarkers could enhance post-transplant management and improve long-term outcomes. This study aimed to identify metabolomic biomarkers within the first week after kidney transplantation that predict renal function at six months. Methods: We conducted a prospective study involving 50 adult patients who received deceased donor kidney transplants. Plasma samples collected one week after transplant were analyzed using liquid chromatography–mass spectrometry in a semi-targeted metabolomic approach. A Partial Least Squares-Discriminant Analysis (PLS-DA) model identified metabolites associated with serum creatinine > 1.5 mg/dL at six months. Metabolites were selected based on a Variable Importance in Projection (VIP) score > 1.5, which was used to optimize model performance. Results: The PLS-DA model demonstrated strong predictive performance with an area under the curve (AUC) of 0.958. The metabolites negatively associated with serum creatinine > 1.5 mg/dL were 3-methylindole, guaiacol, histidine, 3-indolepropionic acid, and α-lipoic acid. Conversely, the metabolites positively associated with worse kidney graft outcomes included homocarnosine, 5-methylcytosine, xanthosine, choline, phenylalanine, kynurenic acid, and L-kynurenine. Conclusions: Early metabolomic profiling after transplantation shows promise in predicting renal function. Identifying metabolites with antioxidant and anti-inflammatory properties, as well as those that are harmful and could be targeted therapeutically, underscores their potential clinical significance. The link between several metabolites and the tryptophan pathway suggests that further specific evaluation of this pathway is warranted. These biomarkers can enhance patient management and graft survival.

Background and aimsMetabolic dysfunction-associated steatohepatitis (MASH) is a significant health concern with limited treatment options. AXL, a receptor tyrosine kinase activated by the GAS6 ligand, promotes MASH through activation of hepatic stellate cells and inflammatory macrophages. This study identified cell subsets affected by MASH progression and the effect of AXL inhibition.MethodsMice were fed chow or different fat-enriched diets to induce MASH, and small molecule AXL kinase inhibition with bemcentinib was evaluated. Gene expression was measured by qPCR. Time-of-flight mass cytometry (CyTOF) used single cells from dissociated livers, acquired on the Fluidigm Helios, and cell populations were studied using machine learning.ResultsIn mice fed different fat-enriched diets, liver steatosis alone was insufficient to elevate plasma soluble AXL (sAXL) levels. However, in conjunction with inflammation, sAXL increases, serving as an early indicator of steatohepatitis progression. Bemcentinib, an AXL inhibitor, effectively reduced proinflammatory responses in MASH models, even before fibrosis appearance. Utilizing CyTOF analysis, we detected a decreased population of Kupffer cells during MASH while promoting infiltration of monocytes/macrophages and CD8+ T cells. Bemcentinib partially restored Kupffer cells, reduced pDCs and GzmB− NK cells, and increased GzmB+CD8+ T cells and LSECs. Additionally, AXL inhibition enhanced a subtype of GzmB+CD8+ tissue-resident memory T cells characterized by CX3CR1 expression. Furthermore, bemcentinib altered the transcriptomic landscape associated with MASH progression, particularly in TLR signaling and inflammatory response, exhibiting differential cytokine expression in the plasma, consistent with liver repair and decreased inflammation.ConclusionOur findings highlight sAXL as a biomarker for monitoring MASH progression and demonstrate that AXL targeting shifted liver macrophages and CD8+ T-cell subsets away from an inflammatory phenotype toward fibrotic resolution and organ healing, presenting a promising strategy for MASH treatment.

Abstract This study provides a global analysis of the relationship between drought metrics obtained from several climatic, hydrologic and ecological variables in a climate change framework using CMIP6 model data. A comprehensive analysis of the evolution of drought severity on a global scale is carried out for the historical experiment (1850–2014) and for future simulations under a high emissions scenario (SSP5‐8.5). This study focuses on comparing trends in the magnitude and duration of drought events according to different standardized indices over the world land‐surface area. The spatial and temporal relationship between the different drought indices on a global scale was also evaluated. Overall, there is a fairly large consensus among models and drought metrics in pointing to drought increase in southern North America, Central America, the Amazon region, the Mediterranean, southern Africa and southern Australia. Our results show important spatial differences in drought projections, which are highly dependent on the drought metric employed. While a strong relationship between climatic indices was evident, climatic and ecological drought metrics showed less dependency over both space and time. Importantly, our study demonstrates uncertainties in future projections of drought trends and their interannual variability related to the relationship among indices, stressing the importance of coherent climatic, hydrological and plant physiological patterns when analyzing CMIP6 model simulations of droughts under a warming climate scenario.

Abstract Primary liver cancer arises either from hepatocytic or biliary lineage cells, giving rise to hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICCA). Combined hepatocellular- cholangiocarcinomas (cHCC-CCA) exhibit equivocal or mixed features of both, causing diagnostic uncertainty and difficulty in determining proper management. Here, we perform a comprehensive deep learning-based phenotyping of multiple cohorts of patients. We show that deep learning can reproduce the diagnosis of HCC vs. CCA with a high performance. We analyze a series of 405 cHCC-CCA patients and demonstrate that the model can reclassify the tumors as HCC or ICCA, and that the predictions are consistent with clinical outcomes, genetic alterations and in situ spatial gene expression profiling. This type of approach could improve treatment decisions and ultimately clinical outcome for patients with rare and biphenotypic cancers such as cHCC-CCA.

Abstract Drought monitoring systems are real‐time information systems focused on drought severity data. They are useful for determining the drought onset and development and defining the spatial extent of drought at any time. Effective drought monitoring requires databases with high spatial and temporal resolution and large spatial and temporal coverage. Recent reanalysis datasets meet these requirements and offer an excellent alternative to observational data. In addition, reanalysis data allow better quantification of some variables that affect drought severity and are more seldom observed. This study presents a global drought dataset and a monitoring system based on the Standardized Precipitation Evapotranspiration Index (SPEI) and ERA5 reanalysis data. Computation of the atmospheric evaporative demand for the SPEI follows the FAO‐56 Penman‐Monteith equation. The system is updated weekly, providing near real‐time information at a 0.5° spatial resolution and global coverage. It also contains a historical dataset with the values of the SPEI at different time scales since January 1979. The drought monitoring system includes the assessment of drought severity for dominant crop‐growing areas. A comparison between SPEI computed from the ERA5 and CRU datasets shows generally good spatial and temporal agreement, albeit with some important differences originating mainly from the different spatial patterns of SPEI anomalies, as well as from employing long‐term climate trends for different regions worldwide. The results show that the ERA5 dataset offers robust results and supports its use for drought monitoring. The new system and dataset are publicly available at the link https://global‐drought‐crops.csic.es/.

The development of intelligent transportation systems (ITS), vehicular ad hoc networks (VANETs), and autonomous driving (AD) has progressed rapidly in recent years, driven by artificial intelligence (AI), the internet of things (IoT), and their integration with dedicated short-range communications (DSRC) systems and fifth-generation (5G) networks. This has led to improved mobility conditions in different road propagation environments: urban, suburban, rural, and highway. The use of these communication technologies has enabled drivers and pedestrians to be more aware of the need to improve their behavior and decision making in adverse traffic conditions by sharing information from cameras, radars, and sensors widely deployed in vehicles and road infrastructure. However, wireless data transmission in VANETs is affected by the specific conditions of the propagation environment, weather, terrain, traffic density, and frequency bands used. In this paper, we characterize the path loss based on the extensive measurement campaign carrier out in vehicular environments at 700 MHz and 5.9 GHz under realistic road traffic conditions. From a linear dual-slope path loss propagation model, the results of the path loss exponents and the standard deviations of the shadowing are reported. This study focused on three different environments, i.e., urban with high traffic density (U-HD), urban with moderate/low traffic density (U-LD), and suburban (SU). The results presented here can be easily incorporated into VANET simulators to develop, evaluate, and validate new protocols and system architecture configurations under more realistic propagation conditions.

Oral health is crucial for the overall well-being and quality of life, and nurses play a significant role in promoting it. This study assessed the oral health knowledge of fourth-grade nursing degree students. Seventy-two students completed a questionnaire covering sociodemographic variables, oral health-related factors, knowledge about oral health, and perceptions of its importance and learning experiences. The results showed that 83.3% of students attended regular dental check-ups for preventive purposes, and 55.6% had visited a dentist during the last year. Most of the students reported experiencing cavities (66.7%) and undergoing orthodontic treatment (54.2%). The average knowledge score in oral health was 6.4 out of 10, and students recognized the importance of oral health in the nursing role. However, their knowledge acquired during their nursing degree scored relatively low, being 2.5 out of 5. Notably, students who valued problem-based learning achieved higher knowledge scores (p < 0.05). Overall, fourth-grade nursing students demonstrated a moderate level of oral health knowledge. Improving oral health education within nursing curricula, particularly through problem-based learning, is essential to enhance their preparedness in addressing oral health issues effectively. This study was not registered.

Abstract Motivation Quantitative descriptions of multi-cellular structures from optical microscopy imaging are prime to understand the variety of three-dimensional (3D) shapes in living organisms. Experimental models of vertebrates, invertebrates and plants, such as zebrafish, killifish, Drosophila or Marchantia, mainly comprise multilayer tissues, and even if microscopes can reach the needed depth, their geometry hinders the selection and subsequent analysis of the optical volumes of interest. Computational tools to “peel” tissues by removing specific layers and reducing 3D volume into planar images, can critically improve visualization and analysis. Results We developed VolumePeeler, a versatile FIJI plugin for virtual 3D “peeling” of image stacks. The plugin implements spherical and spline surface projections. We applied VolumePeeler to perform peeling in 3D images of spherical embryos, as well as non-spherical tissue layers. The produced images improve the 3D volume visualization and enable analysis and quantification of geometrically challenging microscopy datasets. Availability ImageJ/FIJI software, source code, examples, and tutorials are openly available in https://cimt.uchile.cl/mcerda

Dentro del paradigma de construcciones interrogativas polares del español, las interrogativas marcadas con qué empleadas en el español de México (¿Qué Julia llamó?, ¿qué Julia no llamó?, ¿qué no Julia llamó?) no han sido estudiadas hasta ahora. Este artículo analiza el significado no proposicional de estas construcciones a partir de la propuesta teórica de Sudo (2013). Se muestra que los dos sesgos propuestos, sesgo epistémico y sesgo evidencial, son necesarios para el análisis de estas interrogativas polares, pero no son suficientes para capturar las diferencias entre las dos interrogativas polares negativas. El artículo propone que estas construcciones difieren en el grado de su sesgo epistémico: ambas requieren una creencia positiva, pero con diferente grado de certeza.

Para la gestión de los asuntos diocesanos, el obispo ha contado desde antiguo con clérigos que le han auxiliado en dicha tarea. A pesar de no ser absolutamente idéntica la organización de las distintas diócesis, si podemos encontrar muchos elementos comunes a todas ellas. Este artículo pretende hacer un breve recorrido por la historia de las diócesis españolas para comprobar cuál era su organización interna, desde la Baja Edad Media hasta 1851 en que se impuso una normativa común única para todos los obispados sujetos al gobierno español.

Universities must confront social challenges and prepare their students to be future socially responsible professionals. This research considers social responsibility in depth and examines how it can be promoted among university students. Specifically, it analyses whether prosocial behaviour and moral values are predictor variables, and to study whether moral values are a mediator variable between prosocial behaviour and university student social responsibility. Non-probabilistic convenience sampling was used in a Spanish university (N = 193; 115 females; Mage = 19). Three scales were applied: the University Student Social Responsibility scale, the Prosocial Tendencies Measures scale and the Importance of Personal and Professional Values scale. The results of the regression models showed that prosocial behaviour and moral values both contributed significantly to the model (F (2,196) = 41.979; p < .001), predicting 30.2% of university student social responsibility. In the mediation model, total effects between the variables were observed, as was an indirect effect of prosocial behaviour on social responsibility mediated by moral values (β = .07; t = 3.80; p < .001). This suggests that university programmes that seek to help the community and enable people to discover values will more effectively be able to develop social responsibility.

Having experienced stress during sensitive periods of brain development strongly influences how individuals cope with later stress. Some are prone to develop anxiety or depression, while others appear resilient. The as-yet-unknown mechanisms underlying these differences may lie in how genes and environmental stress interact to shape the circuits that control emotions. Here, we investigated the role of the habenulo-interpeduncular system (HIPS), a critical node in reward circuits, in early stress-induced anxiety in mice. We found that habenular and IPN components characterized by the expression of Otx2 are synaptically connected and particularly sensitive to chronic stress (CS) during the peripubertal period. Stress-induced peripubertal activation of this HIPS subcircuit elicits both HIPS hypersensitivity to later stress and susceptibility to develop anxiety. We also show that HIPS silencing through conditional Otx2 knockout counteracts these effects of stress. Together, these results demonstrate that a genetic factor, Otx2, and stress interact during the peripubertal period to shape the stress sensitivity of the HIPS, which is shown to be a key modulator of susceptibility or resilience to develop anxiety.

BackgroundInformal caregivers are essential figures that deal with the effects of dependence in the elderly. However, they suffer from poorer health-related quality of life, particularly regarding mental health. Social support is crucial, but this was suspended or dramatically reduced during the Covid-19 pandemic. Salutogenesis theory explores the contributing factors for the promotion and maintenance of health. Considering all these, we offered caregivers the opportunity to join a participatory project aimed at creating communication spaces where they could share experiences, think together about potential solutions, and explore which salutogenic actions they used in their daily basis and how they had changed during Covid-19 restrictions.MethodsWe used a qualitative methodology with a socio-constructivist and phenomenological approach and purposive sampling. We organized two focus groups consisting of online semi-structured discussions with seven participants in total. Conversations were videotaped and transcribed and we conducted content thematic analyses using the NVivo software.ResultsCaregiving in our setting are primarily women with high levels of education that do not always feel comfortable with this load because it interferes with their personal and professional lives. The pandemic increased caregivers feelings of loneliness, resignation, and burden, directly affecting their mental health. Furthermore, the disappearance of prevention programs and the difficulties to access healthcare services produced negative consequences on the already fragile elderly and their family caregivers.ConclusionThe pandemic and its restrictions exacerbated the problematics affecting informal caregivers. Although these people are aware of their situation and have valued knowledge of how to improve their health, they cannot always put it into practice. We call policymakers to reframe interventions aimed at caregivers by introducing the voice of the community in the planning and to rethink the management of vulnerable people and their carers in other potential health crises.

BackgroundGlioblastoma is one of the most aggressive primary brain tumors, with a poor outcome despite multimodal treatment. Methylation of the MGMT promoter, which predicts the response to temozolomide, is a well-established prognostic marker for glioblastoma. However, a difference in survival can still be detected within the MGMT methylated group, with some patients exhibiting a shorter survival than others, emphasizing the need for additional predictive factors.MethodsWe analyzed DIAPH3 expression in glioblastoma samples from the cancer genome atlas (TCGA). We also retrospectively analyzed one hundred seventeen histological glioblastomas from patients operated on at Saint-Luc University Hospital between May 2013 and August 2019. We analyzed the DIAPH3 expression, explored the relationship between mRNA levels and Patient’s survival after the surgical resection. Finally, we assessed the methylation pattern of the DIAPH3 promoter using a targeted deep bisulfite sequencing approach.ResultsWe found that 36% and 1% of the TCGA glioblastoma samples exhibit copy number alterations and mutations in DIAPH3, respectively. We scrutinized the expression of DIAPH3 at single cell level and detected an overlap with MKI67 expression in glioblastoma proliferating cells, including neural progenitor-like, oligodendrocyte progenitor-like and astrocyte-like states. We quantitatively analyzed DIAPH3 expression in our cohort and uncovered a positive correlation between DIAPH3 mRNA level and patient’s survival. The effect of DIAPH3 was prominent in MGMT-methylated glioblastoma. Finally, we report that the expression of DIAPH3 is at least partially regulated by the methylation of three CpG sites in the promoter region.ConclusionWe propose that combining the DIAPH3 expression with MGMT methylation could offer a better prediction of survival and more adapted postsurgical treatment for patients with MGMT-methylated glioblastoma.

BackgroundPositive mental health (PMH) is a construct used to define and evaluate health from a positive perspective. Healthcare professionals in the emergency ambulance service are more likely to experience mental health disorders than the overall population. The demographic and occupational variables and Sense of Coherence (SOC) can act as predictors of PMH and can serve as protective elements against stress and demanding situations in the work environment.ObjectiveThis study aimed to evaluate PMH and its relationship with demographic and occupational variables and determine if SOC is a predictive variable for PMH in health professionals working in the emergency ambulance service.MethodsA descriptive, cross-sectional, and correlational study was conducted with a sample of 406 healthcare professionals from the emergency ambulance service in eight health regions of Catalonia, Spain. The following variables were analyzed: Age, biological sex, household members, dependents family members, professional category, type of contract, job satisfaction and sense of collaboration with other institutions. The following assessment instruments were used: Positive Mental Health Questionnaire and Sense of Coherence scale.ResultsHigh scores were obtained in Positive Mental Health (PMH). Study participants who reported feeling completely satisfied in their work also showed a significant relationship with all PMH factors: greater satisfaction with their personal life, in their helpful prosocial attitude toward others, in their capability to deal effectively with stress and navigate conflict scenarios, in their ability to solve problems and self-realization, greater empathy and ability to understand the feelings of others, greater ability to establish interpersonal relationships. Comprehensibility, as a dimension of SOC, was identified as a predictor for some factors of PMH: a greater personal satisfaction, self-control, autonomy, interpersonal skills and total PMHQ. More than 43% of positive mental health in health professionals is explained by higher Meaningfulness and Comprehensibility values of the SOC, the absence of dependent family members and having a non-graduate background.ConclusionHealthcare workers in the emergency ambulance service had high PMH. Meaningfulness (ME) and Comprehensibility (C), dimensions of SOC, were identified as model predictors of greater PMH, showing higher scores in most of PMH factors. To enhance SOC as a mental health promotion measure, resilience programs should be implemented to help professionals develop skills to face and overcome adverse situations. Educating in stress management thought networks are key elements to strengthen SOC. Managers in emergency medical services play a key role in transforming healthcare work environments to promote positive outcomes in the mental health of their healthcare workers.

En este artículo se presenta una investigación llevada a cabo, como un estudio de caso, con una secuencia didáctica de gramática titulada Nom o verb? (¿Nombre o verbo?), basada en el modelo Egramint. La secuencia pretende iniciar en la noción de verbo a un grupo de alumnos de 3.º de Educación Primaria y se articula mediante el contraste de los sintagmas nominales y las oraciones, con el fin de promover la reflexión metalingüística. Se presenta la secuencia didáctica y se ofrece una exploración preliminar de los resultados tras la implementación en el aula, relacionados con la enseñanza y el aprendizaje del verbo. Estos permiten realizar algunas consideraciones: atender a las formas lingüísticas desde la complejidad del uso contribuye a la mejora del uso lingüístico; el contraste interlingüístico incide en la conceptualización gramatical, y los alumnos recurren a la situación discursiva para fundamentar sus afirmaciones sobre nociones gramaticales y requieren metalenguaje para compartir sus reflexiones.

La alfabetización académica de los estudiantes universitarios es un largo camino que requiere de intervenciones didácticas en las distintas disciplinas. Este estudio plantea la creación de comunidades discursivas de socialización de la lectura académica entre iguales mediante la realización de videorreseñas. La intervención se realizó durante cuatro cursos académicos (entre 2017 y 2021) con estudiantes del Grado de Maestro/a de Educación Primaria (373) y del Máster de Profesorado de Secundaria (118) de la Universitat de València. El análisis de las videorreseñas se centra en la posición del lector (en nuestro caso, el futuro docente) como mediador. Tras la revisión de diferentes propuestas de análisis de este género audiovisual y la visualización del corpus (416 videorreseñas), se delimitaron cuatro categorías de análisis: selección de contenidos, criterios de recomendación, presentación de la lectura y de su autor y construcción del discurso. El análisis cualitativo realizado permitió diferenciar dos grandes tipos: videorreseñas reproductivas y críticas, caracterizadas en este trabajo. Los resultados muestran dos elementos clave: la apropiación de la situación retórica creada por el género de la videorreseña y la experiencia lectora. La adopción de una visión crítica no solo requiere de profundidad en el conocimiento disciplinar, sino que obliga a desarrollar recursos lingüísticos más complejos.

Les tecnologies digitals formen part de la nostra vida quotidiana de forma extensiva des de fa més d’una dècada. Tot i que l’accés material a la tecnologia s’ha anat popularitzant, part de la població es troba, encara, en risc d’exclusió digital. Davant d’aquest pretext, aquest article descriu els fonaments i les accions del Laboratori d’Innovació Social Digital (LISD) de la Universitat de Vic - Universitat Central de Catalunya (Uvic-UCC), el qual aposta pel desenvolupament de pràctiques digitals inclusives i, a través de la investigació-acció, acompanya processos de millora digital i social amb i per a la comunitat, concretament de la població jove. La metodologia utilitzada pretén reconèixer les necessitats sociodigitals del territori i treballar, juntament amb la comunitat, en la construcció d’accions de millora des d’una perspectiva pedagògica. En aquesta línia i fins ara, el LISD ha treballat en quatre accions per al desenvolupament de les competències digitals de la població jove, especialment aquella més vulnerable, i l’intercanvi de coneixements entre persones de contextos diversos. Els resultats evidencien que cal orientar la funció del LISD cap a la implementació d’accions sistèmiques contextuals vinculades a facilitar l’accés i l’ús de les tecnologies, així com al desenvolupament de les competències digitals amb la població del municipi.

Sweet syndrome is a neutrophilic dermatosis associated with multiple disorders. This retrospective case-series study of patients with Sweet syndrome in a tertiary hospital in Spain from 2001 to 2021, explores clinicopathological characteristics of Sweet syndrome and variables associated with malignancy, presence of autoinflammatory disorders and differences between histological subtypes. A total of 93 patients were identified: 30% idiopathic, 34% malignancy-associated, 29% reactive to infections or drug-associated, and 6% with an autoimmune/inflammatory condition. Acute myeloid leukaemia was the most common malignancy (16/93) followed by myelodysplastic syndrome (7/93). Patients with acute myeloid leukaemia presented isolated flares, marked cytopaenia and rapid response to treatment, whereas myelodysplastic syndrome followed a chronic-recurrent course. The most frequent associated medications and inflammatory disorders were filgrastim and hydroxyurea (n = 2); and inflammatory bowel disease (n = 4). In addition, 3 patients were diagnosed with VEXAS syndrome. Male sex (p = 0.006), fever (p = 0.034), increased erythrocyte sedimentation rate (p