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Introducción. Es imprescindible insertar a la familia en los programas de prevención e intervención del acoso. Por otra parte, las últimas investigaciones destacan la relevancia de analizar los factores que influyen en la perpetración del ciberacoso. Sin embargo, la investigación sobre la influencia de las variables sociofamiliares en los ciberagresores es limitada. Junto a ello, consideramos importante tener en cuenta las etapas de desarrollo en la adolescencia, ya que las relaciones familiares con los hijos se van modificando a lo largo de este periodo. El objetivo de este estudio ha sido analizar la influencia del apoyo social familiar, del clima familiar y de las emociones placenteras hacia el ciberacoso en los comportamientos de ciberagresión, incluyendo como variable de análisis la implicación en la cibervictimización, a través de las etapas de desarrollo de la adolescencia. Metodología. La muestra de estudio fue de 1029 adolescentes (26.9% adolescentes tempranos, 49.1% en la adolescencia media y un 24.0% en la adolescencia tardía). Los datos fueron recogidos empleando cuestionarios estandarizados de las variables de estudio. Resultados. Los resultados obtenidos señalan que en todas las etapas de la adolescencia la cibervictimización (temprana: OR= 1.94, IC= 1.15, 3.26; media: OR= 1.61, IC= 1.30, 1.61; tardía: OR= 1.15, IC= 1.02, 1.29) y las emociones placenteras hacia el ciberacoso (temprana: OR= 1.44, IC= 1.03, 2.02; media: OR= 1.40, IC= 1.09, 1.81; tardía OR= 1.44, IC= 1.03, 2.02) incrementan la probabilidad de ser ciberacosador. En la adolescencia temprana la cohesión familiar protege de ser ciberagresor (OR= 0.01, IC= 0.03. 0.16) y en la adolescencia media experimentar conflictos familiares actúan como factor de riesgo de ser ciberacosador (OR= 3.10, IC= 1.71, 5.59). Discusión. Los resultados coinciden con otros estudios que confirman la influencia de la familia como agente social relevante para la intervención en el ciberacoso. Nuestro trabajo aporta como aspecto novedoso la relevancia de esas variables atendiendo al periodo evolutivo de la adolescencia. Muestran el peso de la cohesión en la adolescencia temprana y de los conflictos durante la adolescencia media. Respecto a las emociones placenteras ante el ciberacoso, de forma similar a investigaciones previas, aparecen con significación como factor de riesgo del comportamiento de ciberagresión durante todo el periodo de la adolescencia. Conclusiones. Las conclusiones del trabajo pueden guiar a los profesionales del trabajo social para realizar un acercamiento preventivo del ciberacoso desde las familias. Desde un clima familiar positivo, manteniendo la familia como unidad, con una elevada cohesión durante la adolescencia temprana y una resolución de conflictos positiva en la adolescencia media, los trabajadores sociales pueden actuar en la prevención e intervención del comportamiento de ciberagresión.

Abstract Glioblastoma (GB) is a devastating tumor of the central nervous system characterized by a poor prognosis. One of the best-established predictive biomarker in IDH-wildtype GB is O6-methylguanine-DNA methyltransferase (MGMT) methylation (mMGMT), which is associated with improved treatment response and survival. However, current efforts to monitor GB patients through mMGMT detection have proven unsuccessful. Small extracellular vesicles (sEVs) hold potential as a key element that could revolutionize clinical practice by offering new possibilities for liquid biopsy. This study aimed to determine the utility of sEV-based liquid biopsy as a predictive biomarker and disease monitoring tool in patients with IDH-wildtype GB. Our findings show consistent results with tissue-based analysis, achieving a remarkable sensitivity of 85.7% for detecting mMGMT in liquid biopsy, the highest reported to date. Moreover, we suggested that liquid biopsy assessment of sEV-DNA could be a powerful tool for monitoring disease progression in IDH-wildtype GB patients. This study highlights the critical significance of overcoming molecular underdetection, which can lead to missed treatment opportunities and misdiagnoses, possibly resulting in ineffective therapies. The outcomes of our research significantly contribute to the field of sEV-DNA-based liquid biopsy, providing valuable insights into tumor tissue heterogeneity and establishing it as a promising tool for detecting GB biomarkers. These results have substantial implications for advancing predictive and therapeutic approaches in the context of GB and warrant further exploration and validation in clinical settings.

Abstract Background Type 2 diabetes mellitus (T2DM) is recognized an independent risk factor for chronic kidney disease (CKD). The precise contribution and differential response to treatment strategies to reduce kidney dysfunction, depending on whether obesity is present alongside T2DM or not, remain to be fully clarified. Our objective was to improve our understanding of how obesity contributes to kidney function in patients with T2DM and coronary heart disease (CHD), who are highly predisposed to CKD, to assign the most effective dietary approach to preserve kidney function. Methods 1002 patients with CHD and estimated glomerular filtration rate (eGFR)≥30 ml/min/1.73m2, were randomized to consume a Mediterranean diet (35% fat, 22% MUFA, 55% carbohydrates). Patients were classified into four groups according to the presence of T2DM and/or obesity at baseline: Non-Obesity/Non-T2DM, Obesity/Non-T2DM, Non-Obesity/T2DM and Obesity/T2DM. We evaluated kidney function using serum creatinine-based estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (uACR) before and after 5-years of dietary intervention. Results Patients with Obesity/T2DM had the lowest baseline eGFR and the highest baseline uACR compared to non-diabetics (p

Suicide is a serious public health problem, with a global mortality rate of 1.4% of all deaths worldwide and the leading cause of unnatural death in Spain. Clinical simulation has proven to be a beneficial tool in training nursing students. Such experiences allow them to develop cognitive and affective skills that are fundamental for the detection of warning signs and the use of interventions in cases of people who want to take their own lives. Working in a mental health environment can be difficult for nursing students; therefore, the purpose of this study was to explore the perceptions of nursing students on the approach, management, and intervention of suicidal crisis through clinical mental health simulation. Methods: qualitative descriptive phenomenological study through focus groups and reflective narratives in a sample of 45 students. A thematic analysis was performed using ATLAS-ti. Results: After the analysis, three themes were obtained: (a) management and handling of emotions, (b) identification of suicide motives, and (c) intervention in suicidal crisis. Discussion: Clinical simulation in mental health allows students to exercise clinical judgment reasoning, detect warning signs for a better treatment approach, and provide tools for effective intervention and management of patient care. The results of this study indicate that nursing students face challenges in approaching mental health clinical simulation due to a lack of prior exposure.

Abstract Background Telomere Length (TL), a marker of cellular aging, holds promise as a biomarker to elucidate the molecular mechanism of diabetes. This study aimed to investigate whether shorter telomeres are associated with a higher risk of type 2 diabetes mellitus (T2DM) incidence in patients with coronary heart disease; and to determine whether the most suitable dietary patterns, particularly a Mediterranean diet or a low-fat diet, can mitigate the development of diabetes in these patients after a follow-up period of five years. Methods The CORonary Diet Intervention with Olive oil and cardiovascular PREVention study (CORDIOPREV study) was a single-centre, randomised clinical trial done at the Reina Sofia University Hospital in Córdoba, Spain. Patients with established coronary heart disease (aged 20–75 years) were randomly assigned in a 1:1 ratio by the Andalusian School of Public Health to receive two healthy diets. Clinical investigators were masked to treatment assignment; participants were not. Quantitative-PCR was used to assess TL measurements. Findings 1002 patients (59.5 ± 8.7 years and 82.5% men) were enrolled into Mediterranean diet (n = 502) or a low-fat diet (n = 500) groups. In this analysis, we included all 462 patients who did not have T2DM at baseline. Among them, 107 patients developed T2DM after a median of 60 months. Cox regression analyses showed that patients at risk of short telomeres (TL

Abstract Post-COVID-19 interstitial lung disease (ILD) is a new entity that frequently causes pulmonary fibrosis and can become chronic. We performed a single-center parallel-group open-label pilot randomized clinical trial to investigate the efficacy and safety of cyclosporine A (CsA) in the development of ILD in the medium term among patients hospitalized with COVID-19 pneumonia. Patients were randomized 1:1 to receive CsA plus standard of care or standard of care alone. The primary composite outcome was the percentage of patients without ILD 3 months after diagnosis of pneumonia and not requiring invasive mechanical ventilation (IMV) (response without requiring IMV). The key secondary composite outcomes were the percentage of patients who achieve a response requiring IMV or irrespective of the need for IMV, and adverse events. A total of 33 patients received at least one dose of CsA plus standard of care (n = 17) or standard of care alone (n = 16). No differences were found between the groups in the percentage of patients who achieved a response without requiring IMV or a response requiring IMV. A higher percentage of patients achieved a response irrespective of the need for IMV in the CsA plus standard of care group although the RR was almost significant 2.833 (95% CI, 0.908–8.840; p = 0.057). No differences were found between the groups for adverse events. In hospitalized patients with COVID-19 pneumonia, we were unable to demonstrate that CsA achieved a significant effect in preventing the development of ILD. (EU Clinical Trials Register; EudraCT Number: 2020-002123-11; registration date: 08/05/2020).

Raúl Navarro, Elisa Larrañaga, Santiago Yubero, Beatriz Víllora Department of Psychology, University of Castilla-La Mancha, Cuenca, SpainCorrespondence: Raúl Navarro; Beatriz Víllora, Email raul.navarro@uclm.es; beatriz.villora@uclm.esIntroduction: Preschool aggression, a significant concern, requires an in-depth examination beyond individual factors. This study explored the link between individual characteristics, immediate social environment variables, and the likelihood of preschoolers being nominated as aggressors or victims. The novelty of the study lies in its comprehensive longitudinal examination, using a multi-informant approach, of how family dynamics, peer relations, teacher-child interactions, and community factors are related to preschool aggression within the context of Bronfenbrenner’s ecological system theory.Methods: Data was collected at two points, four months apart, to investigate the interplay among sociodemographic, individual, family, and school factors and subsequent child aggression. The study included 394 children (184 girls, 210 boys), aged 3 to 6 years (M = 4.36, SD = 0.87). Caregivers completed questionnaires on socioeconomic status, community relationships, children’s emotional regulation, and family functioning. Teachers rated closeness with each child, while children nominated liked and disliked peers, as well as those exhibiting aggressive or victimized behaviour.Results: Logistic regression models revealed stronger associations between peer aggression and victimization and individual factors over microsystems. Surprisingly, community cohesion showed a robust positive link with an increased likelihood of children being nominated as victims, challenging the assumption that positive parenting practices and strong community cohesion always leads to positive outcomes for individuals.Discussion: The study advances theoretical understanding by examining how factors within preschoolers’ microsystems influence aggressive behaviors, contributing to more holistic models for addressing preschool aggression and victimization in schools. The findings highlight the significance of targeted interventions, emphasizing early identification of aggression or victimization signs and customized programs for social and emotional skill development. Addressing parental stress and interparental conflict is crucial. Additionally, community-based initiatives, like strengthening support networks, play a pivotal role in fostering healthier social dynamics among preschoolers.Keywords: peer aggression, peer victimization, preschool, microsystem, community cohesion

Coenzyme Q10 (CoQ) is a ubiquitous lipid with different biological functions. In blood, there is a close relationship between CoQ status and cholesterol, which strongly supports the study of both molecules simultaneously. The objective of this study was to evaluate plasma CoQ, lipoprotein concentrations and CoQ/Chol ratio in a cohort of paediatric patients with different types of dyslipidaemias. A total of 60 paediatric patients were recruited (age range: 7 months–18 years), including 52 with different types of hypercholesterolemia, 2 with isolated hypertriglyceridemia and 6 with hypobetalipoproteinemia. Plasma CoQ was analysed by HPLC with electrochemical detection, and lipoprotein and cholesterol concentrations by standard automated methods. The lowest CoQ values were detected in patients with hypobetalipoproteinemia and in two cases of liver cirrhosis. Mean CoQ values were significantly higher in hypercholesterolemic patients compared to controls (average values 1.07 µmol/L and 0.63 µmol/L) while the CoQ/cholesterol ratio did not show differences (170 vs. 163, respectively). Mean CoQ values were significantly lower in the group of patients with hypobetalipoproteinemia compared to controls (mean CoQ values of 0.22 µmol/L vs. 0.63 µmol/L, respectively), while those of CoQ/cholesterol did not show differences. Pearson’s correlation test showed a positive correlation between the CoQ and cholesterol values (r = 0.565, p < 0.001) and between the CoQ and the LDL cholesterol values (r = 0.610, p < 0.001). Our results suggest that it is advisable to analyse plasma CoQ and cholesterol concentrations in patients with hypobetalipoproteinemia and hypercholesterolemia associated with liver damage.

The development of immune checkpoint inhibitors (ICIs) has changed the therapeutic paradigm of lung cancer (LC), becoming the standard of treatment for previously untreated advanced non-small cell lung cancer (NSCLC) without actionable mutations. It has allowed the achievement of durable responses and resulted in significant survival benefits. However, not all patients respond; hence, molecular biomarkers are needed to help us predict which patients will respond. With this objective, a prospective observational study was designed, including a cohort of 55 patients with NSCLC who received ICIs. We studied whether biomarkers such as TCRβ and specific cytokines involved in the regulation of T cell activity were related to the immunotherapy response. In the survival analysis, it was found that patients with higher TCRβ clonality, lower TCRβ evenness, higher TCRβ Shannon diversity and lower TCRβ convergence had higher overall survival (OS) and progression-free survival (PFS). However, no statistically significant association was observed. Regarding cytokines, those patients with higher levels of IL-2 and IL-15 presented statistically significantly shorter OS and PFS, respectively. In fact, in the multivariable analysis, the high IL-15 level increased the risk of death by three times. Although the sample size was small and more studies are needed to confirm our results, our study reveals promising markers of responses to ICIs.

Water utilities are facing significant challenges, such as supplying, with less water resources, more and more water due to population growth, amid the current scenario of climate change. In this context, urban water systems represent a crucial component of global public infrastructure for water utilities, with municipalities entrusted with the responsibility of managing and enhancing them for both current and future generations. The main challenge arises when these infrastructures inevitably age and deteriorate, significantly increasing water losses. Since it is unrealistic and unnecessary to rehabilitate and/or replace all pipes in an existing water distribution system, this manuscript is focused on identifying the independent key parameters which can be used to detect reinforced concrete pipe deterioration. To this end, the variables that affect mechanical properties are narrowed down, and the most significant factors crucial for pipe failure are identified. In this process, reinforced concrete pipe samples were collected to characterize them based on a set of potential key parameters. All potential key parameters were analyzed, with the objectives of identifying which key parameters were significant for the model and determining the interactions among them. All data were stored in a dataset which was used to generate a predictive model to estimate average concrete strength and pipe condition assessment versus independent key parameters. The predictive model, utilizing a design of experiments (DoE) and based on the analysis of variance (ANOVA), could estimate the average concrete strength with an accuracy of around 90%, and the external porosity was found to be the main factor. On the other hand, it was also possible to estimate a range of porosity values for the purpose of maintaining the reinforced concrete pipe in optimal condition.

Transduction of producer cells during lentiviral vector (LVV) production causes the loss of 70–90% of viable particles. This process is called retro-transduction and it is a consequence of the interaction between the LVV envelope protein, VSV-G, and the LDL receptor located on the producer cell membrane, allowing lentiviral vector transduction. Avoiding retro-transduction in LVV manufacturing is crucial to improve net production and, therefore, the efficiency of the production process. Here, we describe a method for quantifying the transduction of producer cells and three different strategies that, focused on the interaction between VSV-G and the LDLR, aim to reduce retro-transduction.

Previous research shows that classmates supporting victims' defence is fundamental to combat bullying. To find a suitable response for the bullying problem, we must bear in mind how all the victim's classmates respond and what variables can determine their helping behaviour. Moral disengagement has been demonstrated to be a factor that explains behaviour when faced with bullying. Emotions have also been shown to be relevant for bullying behaviour. This research aimed to gain knowledge of how adolescents behave when faced with bullying and to analyse how their behaviour relates to moral disengagement and both positive and negative emotions, specifically supportive behaviour for victims. In the present study 1029 students participated, all of whom came from Secondary Education, Training Cycles and Higher Secondary Education Stages in Spain. The regression analysis confirmed that being male increased the likelihood of performing active and passive behaviours. Conversely, being female involved displaying more proactive behaviours. Feeling positive/pleasant emotions about bullying increased active behaviour. Feeling negative/unpleasant emotions about bullying increased behaviour in the proactive behavior group. Adolescents should be aware that stopping bullying is their personal responsibility, which depends on their behaviour with the victim. Interventions must aim to reduce moral disengagement and positive emotions about bullying by increasing negative emotions about such behaviour.

IntroductionUniversity education is looking for innovative ways to enrich the teaching-learning process.MethodsThis study aims to describe and compare two gamified experiences: an educational Escape Room and a digital goose board game with Genially. The design of this research follows a quantitative correlational methodology. A total of 135 university students in the first year of the Bachelor’s Degree in Primary Education participated in the study.ResultsData were collected using the Gamified Game Experience Scale (GAMEX). The results of contrasting means for the game dimensions between both gamified experiences reveal a significant variability (p < 0.01) in favor of the Escape Room in fun, absorption, creative thinking, activation and mastery. On the other hand, the absence of negative affect was significant (p < 0.05) in favor of the digital board game.DiscussionIt could be said that the educational Escape Room manifests itself as a powerful resource for learning. However, it can induce a high level of stress, generating discomfort, hostility and frustration in students, so its implementation is not free of negative effects. These findings provide additional empirical evidence that could guide the design of gamified experiences in the Higher Education environment.

A reliable determination of equivalent black carbon (eBC) mass concentrations derived from filter absorption photometers (FAPs) measurements depends on the appropriate quantification of the mass absorption cross-section (MAC) for converting the absorption coefficient (babs) to eBC. This study investigates the spatial–temporal variability of the MAC obtained from simultaneous elemental carbon (EC) and babs measurements performed at 22 sites. We compared different methodologies for retrieving eBC integrating different options for calculating MAC including: locally derived, median value calculated from 22 sites, and site-specific rolling MAC. The eBC concentrations that underwent correction using these methods were identified as LeBC (local MAC), MeBC (median MAC), and ReBC (Rolling MAC) respectively. Pronounced differences (up to more than 50 %) were observed between eBC as directly provided by FAPs (NeBC; Nominal instrumental MAC) and ReBC due to the differences observed between the experimental and nominal MAC values. The median MAC was 7.8 ± 3.4 m2 g-1 from 12 aethalometers at 880 nm, and 10.6 ± 4.7 m2 g-1 from 10 MAAPs at 637 nm. The experimental MAC showed significant site and seasonal dependencies, with heterogeneous patterns between summer and winter in different regions. In addition, long-term trend analysis revealed statistically significant (s.s.) decreasing trends in EC. Interestingly, we showed that the corresponding corrected eBC trends are not independent of the way eBC is calculated due to the variability of MAC. NeBC and EC decreasing trends were consistent at sites with no significant trend in experimental MAC. Conversely, where MAC showed s.s. trend, the NeBC and EC trends were not consistent while ReBC concentration followed the same pattern as EC. These results underscore the importance of accounting for MAC variations when deriving eBC measurements from FAPs and emphasize the necessity of incorporating EC observations to constrain the uncertainty associated with eBC.

Pancreatic neuroendocrine tumors (PanNETs) comprise a heterogeneous group of tumors with growing incidence. Recent molecular analyses provided a precise picture of their genomic and epigenomic landscape. Splicing dysregulation is increasingly regarded as a novel cancer hallmark influencing key tumor features. We have previously demonstrated that splicing machinery is markedly dysregulated in PanNETs. Here, we aimed to elucidate the molecular and functional implications of CUGBP ELAV-like family member 4 (CELF4), one of the most altered splicing factors in PanNETs. CELF4 expression was determined in 20 PanNETs, comparing tumor and non-tumoral adjacent tissue. An RNA sequencing (RNA-seq) dataset was analyzed to explore CELF4-linked interrelations among clinical features, gene expression, and splicing events. Two PanNET cell lines were employed to assess CELF4 function in vitro and in vivo. PanNETs display markedly upregulated CELF4 expression, which is closely associated with malignancy features, altered expression of key tumor players, and distinct splicing event profiles. Modulation of CELF4 influenced proliferation in vitro and reduced in vivo xenograft tumor growth. Interestingly, functional assays and RNA-seq analysis revealed that CELF4 silencing altered mTOR signaling pathway, enhancing the effect of everolimus. We demonstrate that CELF4 is dysregulated in PanNETs, where it influences tumor development and aggressiveness, likely by modulating the mTOR pathway, suggesting its potential as therapeutic target.

The infrapatellar branch of the saphenous nerve (SN) is a widely described anatomic and functional structure; however, its relevance in daily clinical practice is underestimated. All surgical procedures performed on the anteromedial aspect of the knee are associated with a risk of iatrogenic injury to this nerve, including knee arthroscopy, knee arthroplasty, tibial nailing, etc. We present the case of a saphenous nerve neuroma after treatment with radiofrequency thermal ablation due to a knee pain problem. After conducting an anaesthetic suppression test, we decided to perform a denervation of the medial saphenous nerve in Hunter’s canal. We performed surgery on the anteromedial aspect of the knee. The distal end of the medial SN was coagulated with a bipolar scalpel. The proximal end of the nerve was released proximally, and a termino-lateral suture was made at the free end of the nerve after creating an epineural window to inhibit its growth. A double crush was produced proximally to the suture site to create a grade II-III axonal injury. Autologous plasma rich in growth factors (PRGF) was used to reduce potential post-surgical adhesions and to stimulate regeneration of the surgical lesions. One year after surgery, the patient was living a completely normal life.

Abstract Background Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a rare inherited skin disease caused by variants in the COL7A1 gene, coding for type VII collagen (C7), an important component of anchoring fibrils in the basement membrane of the epidermis. RDEB patients suffer from skin fragility starting with blister formation and evolving into chronic wounds, inflammation and skin fibrosis, with a high risk of developing aggressive skin carcinomas. Restricted therapeutic options are limited by the lack of in vitro models of defective wound healing in RDEB patients. Results In order to explore a more efficient, non-invasive in vitro model for RDEB studies, we obtained patient fibroblasts derived from discarded dressings) and examined their phenotypic features compared with fibroblasts derived from non-injured skin of RDEB and healthy-donor skin biopsies. Our results demonstrate that fibroblasts derived from RDEB chronic wounds (RDEB-CW) displayed characteristics of senescent cells, increased myofibroblast differentiation, and augmented levels of TGF-β1 signaling components compared to fibroblasts derived from RDEB acute wounds and unaffected RDEB skin as well as skin from healthy-donors. Furthermore, RDEB-CW fibroblasts exhibited an increased pattern of inflammatory cytokine secretion (IL-1β and IL-6) when compared with RDEB and control fibroblasts. Interestingly, these aberrant patterns were found specifically in RDEB-CW fibroblasts independent of the culturing method, since fibroblasts obtained from dressing of acute wounds displayed a phenotype more similar to fibroblasts obtained from RDEB normal skin biopsies. Conclusions Our results show that in vitro cultured RDEB-CW fibroblasts maintain distinctive cellular and molecular characteristics resembling the inflammatory and fibrotic microenvironment observed in RDEB patients’ chronic wounds. This work describes a novel, non-invasive and painless strategy to obtain human fibroblasts chronically subjected to an inflammatory and fibrotic environment, supporting their use as an accessible model for in vitro studies of RDEB wound healing pathogenesis. As such, this approach is well suited to testing new therapeutic strategies under controlled laboratory conditions.

Phenotype prediction is at the center of many questions in biology. Prediction is often achieved by determining statistical associations between genetic and phenotypic variation, ignoring the exact processes that cause the phenotype. Here, we present a framework based on genome-scale metabolic reconstructions to reveal the mechanisms behind the associations. We calculated a polygenic score (PGS) that identifies a set of enzymes as predictors of growth, the phenotype. This set arises from the synergy of the functional mode of metabolism in a particular setting and its evolutionary history, and is suitable to infer the phenotype across a variety of conditions. We also find that there is optimal genetic variation for predictability and demonstrate how the linear PGS can still explain phenotypes generated by the underlying nonlinear biochemistry. Therefore, the explicit model interprets the black box statistical associations of the genotype-to-phenotype map and helps to discover what limits the prediction in metabolism.

This study aims to determine the extent and manner in which the notion of death is provided for in laws regulating school curricula in Spain and the Spanish Autonomous Regions, and to identify any differences and similarities among the Regions. To this end a documentary survey of current legislation, curricular regulations and educational provision for learner diversity was conducted from a quantitative and qualitative, analytical and comparative perspective. 19 expert-selected terms relevant to death education were subjected to study. The main findings were: (a) death is present at all stages of education, but not in a planned and deliberate pattern; (b) comparison of results from the various Autonomous Regions of Spain reveals a range of different sensitivities regarding the issue. The study investigates an aspect of the curriculum that is of interest to an international audience.

In Spain, irrigated agriculture is the most water-intensive sector, consuming around of 80% of water resources. Moreover, irrigation water distribution systems are the infrastructure by which one-third of water resource losses take place. Monitoring and controlling operations in irrigation canals are essential for mitigating leakages and water waste in operational actions. On the other hand, energy consumption by agriculture is around 5% of usage in developed countries and even higher in undeveloped countries. Although it is a small part of the total energy supply for a country, energy waste reduces the competitiveness of the agriculture sector, which continually reduces profit margins in an economic sector with very low profit margins already. The tool developed in this paper aims to increase the efficiency of water and energy management in the agricultural sector and is included in an overall control diagram for scheduled irrigation management. This tool, the optimal pumping flow (OPF algorithm), optimizes the pumping flow from the irrigation canal to the irrigation reservoir in terms of water level at the canal and reservoir, crop flow demand, system constraints, and energy prices. Regarding the results, the OPF algorithm can calculate the optimum pumping operations, being able to optimize water resource usage and energy expenses by ensuring that the water level at reservoirs remains within a specified range and that pump flow never exceeds a threshold. Further, it allows for the management of pump operations outside of peak hours. On the other hand, the OPF algorithm is also integrated into the overall control diagram in a second test. Here, the OPF algorithm collaborates with a control canal algorithm such as the GoRoSo algorithm to optimize canal gates and pump operations, respectively. In this scenario, OPF reduces cumulative energy expenses by 58% compared to the scenario where the pump station operates only when the reservoir water level is below a certain threshold.

Immune checkpoint inhibitors have been proposed as the standard treatment for different stages of non-small-cell lung cancer in multiple indications. Not all patients benefit from these treatments, however, and certain patients develop immune-related adverse events. Although the search for predictors of response to these drugs is a major field of research, these issues have yet to be resolved. It has been postulated that microbiota could play a relevant role in conditioning the response to cancer treatments; however, the human factor of intestinal permeability also needs to be considered as it is closely related to the regulation of host–microbiota interaction. In this article, we analyzed the possible relationship between the response to immune checkpoint inhibitors and the onset of immune-related adverse events, gut microbiota status, and intestinal membrane permeability. In a pioneering step, we also measured short-chain fatty acid content in feces. Although the correlation analyses failed to identify predictive biomarkers, even when all variables were integrated, our patients’ microbial gut ecosystems were rich and diverse, and the intestinal barrier’s integrity was preserved. These results add new knowledge on the composition of microbiota and its correlation with barrier permeability and short-chain fatty acids and suggest that more studies are required before these potential biomarkers can be incorporated into the clinical management of patients via immune checkpoint inhibitor treatment.

In order to evaluate whether telomere maintenance is associated with type 2 diabetes remission, newly diagnosed type 2 diabetes patients without glucose-lowering treatment (183 out of 1002) from the CORDIOPREV study (NCT00924937) were randomized to consume a Mediterranean or low-fat diet. Patients were classified as Responders, those who reverted from type 2 diabetes during the 5 years of dietary intervention (n = 69), and Non-Responders, who did not achieve diabetes remission by the end of the follow-up period (n = 104). We found no differences in diabetes remission between the two diets, and we determined telomere length (TL) by measuring qPCR, telomerase activity using the TRAP assay, and direct redox balance based on the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSH) via colorimetric assay. Responders exhibited higher baseline TL in comparison with Non-Responders (p = 0.040), and a higher TL at baseline significantly predicted a higher probability of type 2 diabetes remission (OR 2.13; 95% CI, 1.03 to 4.41). After the dietary intervention, Non-Responders showed significant telomere shortening (−0.19, 95% CI −0.32 to 0.57; p = 0.005). Telomere shortening was significantly pronounced in type 2 diabetes patients with a worse profile of insulin resistance and/or beta-cell functionality: high hepatic insulin resistance fasting, a high disposition index (−0.35; 95% CI, −0.54 to −0.16; p < 0.001), and a low disposition index (−0.25; 95% CI, −0.47 to −0.01; p = 0.037). In addition, changes in TL were correlated to the GSH/GSSG ratio. Responders also showed increased telomerase activity compared with baseline (p = 0.048), from 0.16 (95% CI, 0.08 to 0.23) to 0.28 (95% CI, 0.15 to 0.40), with a more marked increase after the dietary intervention compared with Non-Responders (+0.07; 95% CI, −0.06–0.20; p = 0.049). To conclude, telomere maintenance may play a key role in the molecular mechanisms underlying type 2 diabetes remission in newly diagnosed patients. However, further larger-scale prospective studies are necessary to corroborate our findings.

Research on the characteristics shown by children who cyberbully others is scarce. The objective of this research is to know the variables that predict the involvement of youngsters in cyberbullying perpetration. The current study examined the relation between socio-cognitive and emotional variables and cyberbullying perpetration. It examined the cyberbullies' beliefs about moral disengagement towards cyberbullying. It tested also the social support and emotional reactions to cyberbullying with the aim of understanding their association with cyberbullying perpetration. A number of 1,062 teenagers (54% girls) between 12 and 19 years old (M = 15.20, SD = 1.91), from six public secondary schools in Castilla-La Mancha (Spain), participated in the study. Results suggest that students who engage in cyberbullying perpetration have higher levels of cyberbullying victimization and bullying aggression when compared with their peers who do not engage in cyberbullying. The findings show that socio-cognitive and emotional variables are important to understand individual differences in engagement in cyberbullying. Result of regressions indicated that perpetration of cyberbullying was positively associated with cyberbullying victimization, bullying aggression, moral disengagement towards cyberbullying, social support and satisfaction expression. In contrast, perpetration of cyberbullying was not associated with negative emotions. Gender and age did not play a significant role in the prediction on perpetration of cyberbullying. Future research should continue to examine predictive factors associated with cyberbullying perpetration.

The poly(ADP-ribose) polymerase inhibitor (PARPi) rucaparib is approved as maintenance therapy for patients with platinum-sensitive recurrent high-grade ovarian cancer (HGOC). The efficacy and safety of rucaparib after PARPi therapy are largely unknown; therefore, we analyzed outcomes in the subgroup of PARPi-pretreated patients from Spanish hospitals participating in the Rucaparib Access Program. This post hoc subgroup analysis explored baseline characteristics, treatment exposure, safety, effectiveness, and subsequent therapy among women receiving rucaparib 600 mg twice daily after at least one prior PARPi for HGOC. Of 14 women eligible for the analysis, 11 (79%) had tumors harboring BRCA1/2 mutations. Patients had received a median of 5 (range 3–8) treatment lines before rucaparib. Twelve patients (86%) had previously received olaparib and two (14%) niraparib; 12 patients received rucaparib as treatment for platinum-resistant HGOC, one as treatment for platinum-sensitive HGOC, and one as maintenance therapy. Progression-free survival was 0.2–9.1 months. One of seven patients assessable for response by RECIST achieved stable disease. Adverse events occurred in 11 patients (79%; grade 3 in 29%), leading to treatment interruption in eight patients (57%), dose reduction in six (43%), but treatment discontinuation in only one (7%). No new safety signals were observed. This is one of the first reported series of real-world data on rucaparib after prior PARPi for HGOC. In this heavily pretreated population, rucaparib demonstrated meaningful activity in some patients and tolerability consistent with previous prospective trials. Future investigation should focus on identifying patients who may benefit from rucaparib after prior PARPi exposure.

Abstract Background: Rucaparib is a poly(ADP-ribose) polymerase inhibitor approved in Europe as maintenance therapy for recurrent platinum-sensitive (Pt-S) ovarian cancer (OC). The Rucaparib Access Programme (RAP) was designed to provide early access to rucaparib for the above-mentioned indication, as well as for patients with BRCA-mutated Pt-S or platinum-resistant (Pt-R) OC and no therapeutic alternatives. Methods: In this observational, retrospective study we analysed the efficacy and safety of rucaparib within the RAP in Spain. Hospitals associated with the Spanish Ovarian Cancer Research Group (GEICO) recruited patients with high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer treated with rucaparib 600 mg twice daily as maintenance or treatment (Pt-S/Pt-R) in the RAP. Baseline characteristics, efficacy, and safety data were collected. Results: Between July 2020 and February 2021, 51 patients treated in 22 hospitals in the RAP were included in the study. Eighteen patients with a median of 3 (range, 1–6) prior treatment lines received rucaparib as maintenance; median progression-free survival (PFS) for this group was 9.1 months (95% confidence interval [CI], 4.2–11.6 months). Among 33 patients (median 5 [range, 1–9] prior treatment lines) who received rucaparib as treatment, 7 and 26 patients had Pt-S and Pt-R disease, respectively. Median PFS was 10.6 months (95% CI, 2.5 months-not reached) in the Pt-S group and 2.2 months (95% CI, 1.1–3.2 months) in the Pt-R group. Grade ≥ 3 treatment-emergent adverse events were reported in 39% of all patients, the most common being anaemia (12% and 15% in the maintenance and treatment groups, respectively). At data cut-off, 5 patients remained on treatment. Conclusion Efficacy results in these heavily pre-treated patients were similar to those from previous trials. The safety profile of rucaparib in real life was predictable and manageable.

The optimization of genetically engineered biological constructs is a key step to deliver high-impact biotechnological applications. The use of high-throughput DNA assembly methods allows the construction of enough genotypic variants to successfully cover the target design space. This, however, entails extra workload for researchers during the screening stage of candidate variants. Despite the existence of commercial colony pickers, their high price excludes small research laboratories and budget-adjusted institutions from accessing such extensive screening capability. In this work we present COPICK, a technical solution to automatize colony picking in an open-source liquid handler Opentrons OT-2. COPICK relies on a mounted camera to capture images of regular Petri dishes and detect microbial colonies for automated screening. COPICK’s software can then automatically select the best colonies according to different criteria (size, color and fluorescence) and execute a protocol to pick them for further analysis. Benchmark tests performed for E. coli and P. putida colonies delivers a raw picking performance over pickable colonies of 82% with an accuracy of 73.4% at an estimated rate of 240 colonies/h. These results validate the utility of COPICK, and highlight the importance of ongoing technical improvements in open-source laboratory equipment to support smaller research teams.

Background: This study aimed to explore the association between a verbal learning task that evaluates the potential mutual dependency between memory and executive functions (i.e., the Test of Memory Strategies, TMS) and cerebrospinal fluid (CSF) Alzheimer’s Disease (AD) biomarkers. Methods: A sample of 47 mild cognitive impairment (MCI) participants from Poland and Spain were classified according to the Erlangen Score Diagnostic Algorithm (ESA) into CSF- (n = 16) and CSF+ (n = 31) groups. Correlation analyses between TMS word-list conditions and CSF biomarkers were conducted. Additionally, an analysis of covariance was performed to define the effect on ESA classification in the sample, using as a covariable the country of origin of the participants. Results: Significant associations between the TMS-3 condition and Aβ42, t-tau, and p-tau were observed for the whole sample. In addition, the CSF- participants obtained higher cognitive performance in TMS-3 compared to the CSF+ group. This outcome persisted if the groups were based on Aβ42 scores, but not t-tau or p-tau values. Conclusions: These findings could indicate that poor performance on verbal learning tests may be affected by executive dysfunctions. Therefore, future intervention plans focused on training executive functions would be of interest to improve the ability of MCI patients to encode and organize information.

It is important to study the impact of social media on mental health and well-being, as most young people use social media. Research has provided evidence of the link between social media and mental health, identifying vulnerability variables, risk factors, comorbidity, and predictors of deterioration or improvement. However, there is still very little qualitative insight into young people’s experiences and perceptions of social media and its impact on their subjective well-being. This study consists of a systematic review of the literature and a narrative synthesis of scientific articles published between 2013 and 2023 and indexed in the most important scientific databases in our field of knowledge. The SALSA protocol for systematic reviews of scientific literature was followed. We worked on a final sample of 25 articles, all of which were qualitative in methodology. From the content analysis, we extracted five thematic categories that describe and explore in depth the complex impact of social networks on adolescents’ well-being. The interactions between positive and negative effects, as well as the links with protective or vulnerability factors, are presented with the aim of constructing as complete a knowledge framework as possible. The paper concludes with useful implications for educational interventions.

Background. The risk of herpes zoster reactivation is increased in immunocompromised patients, especially in those with immune-mediated inflammatory diseases (IMIDs) on Janus kinase inhibitor (JAKi) treatment. The recombinant subunit herpes zoster vaccine (RZV) is a non-live vaccine, recently approved for this subgroup of patients, which shows high rates of vaccine effectiveness, with few adverse effects reported in clinical trials. Purpose. The aim of this real-world study was to determine the immunogenicity and safety of RZV in IMID patients on JAKi treatment. Methods. The increase in the concentration of anti-gE antibody for varicella zoster virus post-vaccination, compared to the pre-vaccination concentration, was analyzed to test the humoral immune response. Adverse effects after the first and second vaccine doses were registered. Results. In total, 49 patients were analyzed, and a fourfold increase in antibody concentration was achieved in almost 40% of subjects, with only one serious local adverse effect. Discussion. The resulting immunogenicity was lower than that observed in clinical trials, probably due to the presence of immune disease and immunosuppressive treatment, and to the fact that this was a real-world study. No differences in response according to age, previous virus zoster reactivation, or concomitant treatments were found. Conclusions. RZV was well tolerated and reached the immune response objective in 40% of patients. These results reinforce the importance of including RZV vaccination for immunosuppressed patients. Real-world studies regarding vaccine effectiveness are still needed in order to gain a full understanding of the response to RZV in this group of patients.