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Resumen: Antecedentes y objetivo: La enfermedad renal crónica (ERC) se asocia a una elevada morbilidad, carga y consumo de recursos, y constituye un importante desafío para los sistemas sanitarios. El objetivo de este trabajo fue analizar los modelos asistenciales de atención a estos pacientes y consensuar los factores clave que deben implementarse para un modelo óptimo de atención en la ERC, a través de una visión multidisciplinar e integradora. Materiales y métodos: Se conformó un panel multidisciplinar de profesionales con experiencia en el ámbito de la ERC, integrado por un comité asesor (CA) de 15 expertos y un panel adicional de 44 también especialistas. Se identificaron los retos y las áreas de mejora a lo largo de todo el proceso asistencial, a través de la revisión de la evidencia científica y entrevistas individuales al CA. Se consensuaron los factores clave para un modelo óptimo de atención en la ERC que fueron valorados utilizando la metodología de consenso RAND Corporation y Universidad de California en Los Ángeles (RAND/UCLA) (Delphi adaptado), valorando su adecuación y necesidad. Resultados: Se identificaron 38 factores clave para un modelo óptimo de atención al paciente con ERC, estructurados en cuatro retos: 1) desarrollo de modelos de gestión de la ERC y aumento de la visibilidad de la enfermedad, 2) prevención, optimización del cribado, diagnóstico precoz y registro de la ERC en todos los niveles asistenciales, 3) seguimiento integral, multidisciplinar y coordinado, asegurando la optimización terapéutica y la continuidad asistencial, y 4) refuerzo de la formación en ERC a los profesionales sanitarios y pacientes. Un total de 35 factores clave fueron valorados por el panel como adecuados y claramente necesarios, y de estos, 14 fueron considerados altamente prioritarios. Conclusiones: Existe un consenso sobre la necesidad de priorizar la atención de la ERC tanto a nivel institucional como social, avanzando hacia modelos óptimos de atención en ERC basados en la prevención y detección precoz de la enfermedad, así como en el seguimiento integral y coordinado de los pacientes y la formación y concienciación a todos los niveles. Los factores clave identificados constituyen una hoja de ruta implantable en las distintas comunidades autónomas (CCAA) que puede contribuir a una mejora significativa en la atención a estos pacientes. Abstract: Background and Purpose: Chronic kidney disease (CKD) is associated with high morbidity, burden, and resource utilization, and represents a major challenge for healthcare systems. The purpose of this study was to analyse the care patterns for these patients and to reach a consensus on the key factors that should be implemented for an optimal care model in CKD, through a multidisciplinary and integrative vision. Materials and Methods: A multidisciplinary panel of professionals with experience in the field of CKD was formed, composed of an advisory committee of 15 experts and an additional panel of 44 experts. Challenges and areas for improvement across the continuum of care were identified through review of scientific evidence and individual interviews with the advisory committee. Key factors for an optimal model of care in CKD were agreed and assessed using the Rand/UCLA consensus methodology (adapted Delphi), evaluating their appropriateness and necessity. Results: 38 key factors were identified for an optimal CKD patient care model, organised into four challenges: 1) Development of CKD management models and increased visibility of the disease, 2) Prevention, optimisation of screening, early diagnosis and registration of CKD at all levels of care, 3) Comprehensive, multidisciplinary and coordinated monitoring, ensuring therapeutic optimisation and continuity of care, and 4) Reinforcement of CKD training for health care professionals and patients. 35 key factors were assessed by the panel as adequate and clearly necessary, and of these, 14 were considered highly imperative. Conclusions: There is consensus on the need to prioritise CKD care at both institutional and societal levels, moving towards optimal models of CKD care based on prevention and early detection of the disease, as well as comprehensive and coordinated patient monitoring and training and awareness-raising at all levels. The key factors identified constitute a roadmap that can be implemented in the different Autonomous Communities and contribute to a significant improvement in the patient's care.

Abstract Regional citrate anticoagulation use in intermittent hemodialysis is limited by the increased risk of metabolic complications due to faster solute exchanges than with continuous renal replacement therapies. Several simplifications have been proposed. The objective of this study was to validate a mathematical model of hemodialysis anticoagulated with citrate that was then used to evaluate different prescription scenarios on anticoagulant effectiveness (free calcium concentration in dialysis filter) and calcium balance. A study was conducted in hemodialyzed patients with a citrate infusion into the arterial line and a 1.25 mmol/L calcium dialysate. Calcium and citrate concentrations were measured upstream and downstream of the citrate infusion site and in the venous line. The values measured in the venous lines were compared with those predicted by the model using Bland and Altman diagrams. The model was then used with 22 patients to make simulations. The model can predict the concentration of free calcium, bound to citrate or albumin, accurately. Irrespective of the prescription scenario a decrease in free calcium below 0.4 mmol/L was obtained only in a fraction of the dialysis filter. A zero or slightly negative calcium balance was observed, and should be taken into account in case of prolonged use.

We report a case of a 44-year-old male patient, who presented to the University Hospital of Salzburg, Austria with abdominal pain, persistent jaundice, and lack of appetite. Radiological work-up (CT, MRI, PET/CT) indicated a suspicious mass of the uncinate process of the pancreatic head with adjacent infiltration and regional lymphadenopathy. The differential diagnosis was between primary pancreatic cancer and focal autoimmune pancreatitis. Further laparoscopic biopsies from multiple areas, showed only fibrous scarring processes, with no malignancy. Treatment with steroids didn't give any benefits. After multiple follow-up CTs and MRs within 6 months—additional biopsies were done, which eventually demonstrated adenocarcinoma. Evidently the cancer diagnosis was much delayed and the patient started receiving chemotherapy, but radical surgery was not possible. Multiple articles and case reports can be found in the literature, that are reviewing the fact that pancreatic inflammatory processes are mimicking pancreatic tumor, but not many articles or case reports are available in the literature, where neoplastic processes are misinterpreted as inflammatory and incorrectly proven with histological examination. One of the main reasons for improper diagnosis is the desmoplastic reaction around the pancreatic malignancy. Another important aspect is the acceptance of histological diagnosis as conclusive, where no opposing arguments are specified, based on radiological criteria.

Abstract Introduction Seizures are common reasons to call an ambulance, and this study aims to analyze the burden of seizures in the prehospital setting based on incidence, hospital admission rate, and costs. Methods This was a population-based, cross-sectional analysis of prehospital emergency medical services (EMS) data on suspected seizure cases from the federal state of Hesse, Germany, in 2019. Results A total of 6534 suspected seizure cases were identified, of which most were those with a known seizure disorder. Incidence rate for epilepsy-related seizures (ES; pediatric epilepsy, first seizure [1stS], seizure with known seizure disorder [SEPI]) was 205.7 per 100,000 inhabitants and incidence rate for pediatric febrile seizures (PFS) was 36.7 per 100,000 inhabitants, corresponding to 171,275 ES and 28,500 PFS (99.3%

Abstract Machine learning-based jet classifiers are able to achieve impressive tagging performance in a variety of applications in high-energy and nuclear physics. However, it remains unclear in many cases which aspects of jets give rise to this discriminating power, and whether jet observables that are tractable in perturbative QCD such as those obeying infrared-collinear (IRC) safety serve as sufficient inputs. In this article, we introduce a new classifier, Jet Flow Networks (JFNs), in an effort to address the question of whether IRC unsafe information provides additional discriminating power in jet classification. JFNs are permutation-invariant neural networks (deep sets) that take as input the kinematic information of reconstructed subjets. The subjet radius and a cut on the subjet’s transverse momenta serve as tunable hyperparameters enabling a controllable sensitivity to soft emissions and nonperturbative effects. We demonstrate the performance of JFNs for quark vs. gluon and Z vs. QCD jet tagging. For small subjet radii and transverse momentum cuts, the performance of JFNs is equivalent to the IRC-unsafe Particle Flow Networks (PFNs), demonstrating that infrared-collinear unsafe information is not necessary to achieve strong discrimination for both cases. As the subjet radius is increased, the performance of the JFNs remains essentially unchanged until physical thresholds that we identify are crossed. For relatively large subjet radii, we show that the JFNs may offer an increased model independence with a modest tradeoff in performance compared to classifiers that use the full particle information of the jet. These results shed new light on how machines learn patterns in high-energy physics data.

Abstract Studying human fetal lungs can inform how developmental defects and disease states alter the function of the lungs. Here, we sequenced >150,000 single cells from 19 healthy human pseudoglandular fetal lung tissues ranging between gestational weeks 10–19. We capture dynamic developmental trajectories from progenitor cells that express abundant levels of the cystic fibrosis conductance transmembrane regulator (CFTR). These cells give rise to multiple specialized epithelial cell types. Combined with spatial transcriptomics, we show temporal regulation of key signalling pathways that may drive the temporal and spatial emergence of specialized epithelial cells including ciliated and pulmonary neuroendocrine cells. Finally, we show that human pluripotent stem cell-derived fetal lung models contain CFTR-expressing progenitor cells that capture similar lineage developmental trajectories as identified in the native tissue. Overall, this study provides a comprehensive single-cell atlas of the developing human lung, outlining the temporal and spatial complexities of cell lineage development and benchmarks fetal lung cultures from human pluripotent stem cell differentiations to similar developmental window.

Abstract Epileptogenesis is the process by which a normal brain becomes hyperexcitable and capable of generating spontaneous recurrent seizures. The extensive dysregulation of gene expression associated with epileptogenesis is shaped, in part, by microRNAs (miRNAs) – short, non-coding RNAs that negatively regulate protein levels. Functional miRNA-mediated regulation can, however, be difficult to elucidate due to the complexity of miRNA-mRNA interactions. Here, we integrated miRNA and mRNA expression profiles sampled over multiple time-points during and after epileptogenesis in rats, and applied bi-clustering and Bayesian modelling to construct temporal miRNA-mRNA-mRNA interaction networks. Network analysis and enrichment of network inference with sequence- and human disease-specific information identified key regulatory miRNAs with the strongest influence on the mRNA landscape, and miRNA-mRNA interactions closely associated with epileptogenesis and subsequent epilepsy. Our findings underscore the complexity of miRNA-mRNA regulation, can be used to prioritise miRNA targets in specific systems, and offer insights into key regulatory processes in epileptogenesis with therapeutic potential for further investigation.

Abstract Mass spectrometry has revolutionized cell signaling research by vastly simplifying the analysis of many thousands of phosphorylation sites in the human proteome. Defining the cellular response to perturbations is crucial for further illuminating the functionality of the phosphoproteome. Here we describe µPhos (‘microPhos’), an accessible phosphoproteomics platform that permits phosphopeptide enrichment from 96-well cell culture and small tissue amounts in 90% selectivity, and excellent quantitative reproducibility. Employing highly sensitive trapped ion mobility mass spectrometry, we quantify ~17,000 Class I phosphosites in a human cancer cell line using 20 µg starting material, and confidently localize ~6200 phosphosites from 1 µg. This depth covers key signaling pathways, rendering sample-limited applications and perturbation experiments with hundreds of samples viable. We employ µPhos to study drug- and time-dependent response signatures in a leukemia cell line, and by quantifying 30,000 Class I phosphosites in the mouse brain we reveal distinct spatial kinase activities in subregions of the hippocampal formation.

Abstract Background Seed retention is the basic prerequisite for seed harvest. However, only little breeding progress has been achieved for this trait in the major forage grasses. The aim of this study was to evaluate the potential of plant genetic resources of the important fodder grasses Festuca pratensis Huds. and Lolium perenne L. as source for seed retention in the breeding process. Furthermore, the morphology of the abscission zone, where shattering occurs, was studied on the cell tissue level in different developmental stages of contrasting accessions. Results 150 and 286 accessions of Festuca pratensis and Lolium perenne were screened for seed retention, respectively. Contrasting accessions were selected to be tested in a second year. We found a great variation in seed retention in Festuca pratensis and Lolium perenne, ranging from 13 to 71% (average: 35%) and 12 to 94% (average: 49%), respectively, in the first year. Seed retention was generally lower in the second year. Cultivars were within the accessions with highest seed retention in Festuca pratensis, but had lower seed retention than ecotypes in Lolium perenne. Field-shattered seeds had a lower thousand grain weight than retained seeds. Cell layers of the abscission zone appeared already in early seed stages and were nested within each other in accessions with high seed retention, while there were two to three superimposed layers in accessions with low seed retention. Conclusions Plant genetic resources of Lolium perenne might be a valuable source for breeding varieties with high seed retention. However, simultaneous selection for high seed weight is necessary for developing successful commercial cultivars.

Abstract Repetitive mild traumatic brain injuries (rmTBI) sustained within a window of vulnerability can result in long term cognitive deficits, depression, and eventual neurodegeneration associated with tau pathology, amyloid beta (Aβ) plaques, gliosis, and neuronal and functional loss. However, a comprehensive study relating acute changes in immune signaling and glial reactivity to neuronal changes and pathological markers after single and repetitive mTBIs is currently lacking. In the current study, we addressed the question of how repeated injuries affect the brain neuroimmune response in the acute phase of injury (

An underrepresentation of women in executive positions has persisted for decades. This paper aims to analyze the financial impact of women in executive positions in German companies by examining the economic value added and exploring the effects of Environmental, Social, and Governance (ESG) factors and female supervisory board members on female board members. The results indicate that in the 200 largest German companies, the share of female executives increased between 2018 and 2022. Regardless of industry, female executives started at very low levels at around 4% in 2018; in 2022, this figure reached around 11%. Thereby, the financial sector showed the highest share of female executives at around 14% in 2022, and the industrial sector at around 9%. A closer look reveals that large companies have higher shares of female executives than smaller companies. Large companies show an average of 17% compared to small ones, and in 2022, only 8%. There is a positive correlation between the share of female supervisory board members and female executives, arguing that female supervisory board members seem to hire more female executives. Companies with more female executives tend to have lower ESG controversy scores, and companies with more female executives, measured by the economic value added, perform better financially than companies with few or no women. Companies with female executives show about 2 percentage points higher economic value added than those with the lowest share of females (no or few female executives). Thus, it seems that female executives matter and make a difference in companies.

Abstract Objective Self‐management interventions may enhance health‐related quality of life (HRQoL) in epilepsy. However, several barriers often impair their implementation in the real world. Digital interventions may help to overcome some of these barriers. Considering this, the Helpilepsy Plus Prototype was developed as a prototype smartphone‐delivered self‐care treatment program for adults with epilepsy. Methods The 12‐week Helpilepsy Plus Prototype was evaluated through a randomized controlled feasibility trial with a waiting‐list control (WLC) group. Outcome measurement at baseline and at 12 weeks assessed adherence to the prototype intervention and changes in epilepsy‐related outcomes. The primary endpoint was patient autonomy measured with EASE, and secondary endpoints included HRQoL measured with QOLIE‐31, health literacy measured with HLQ, anxiety, and depression symptoms measured with HADS. Semi‐structured interviews were conducted with a heterogeneous sample of participants to assess user‐friendliness and usefulness. The prototype program was delivered through the Neuroventis Platform (Neuroventis, BV, Overijse, Belgium), a certified medical device (under EU/MDD Class I, and EU/MDR grace period). Results Ninety‐two patients were included (46 in the intervention group, 46 in WLC). Most participants (63%, 58/92 women, median age 30 years) had pharmacoresistant epilepsy (61%, 56/92). Only 22% of participants (10/46) in the intervention group completed at least half of all intervention sessions. No significant differences between the intervention group and WLC were observed. Although there was a larger proportion of patients in the intervention group with meaningful improvements in HRQoL compared to WLC (19/46 versus 11/46), the difference was not significant (p = 0.119). Qualitative feedback showed that participants would appreciate more personalization, such as adaptation of the content to their current epilepsy knowledge level, a more interactive interface, shorter text sections, and interaction through reminders and notifications. Significance Digital interventions should allow sufficient scope for personalization and interaction to increase patient engagement and enable benefits from self‐care apps. Feedback loops allow the participatory development of tailored interventions. Plain Language Summary In this study, we investigated the effectiveness of an app‐based self‐help intervention. Study participants were either randomly assigned to a group that had access to the app or a group that received access to the app after the end of the study. Although a larger proportion of participants in the intervention group showed a relevant improvement in quality of life, the difference between the two groups was not statistically significant. Less than one‐fifth of participants in the intervention group attended at least half of all intervention sessions; patient feedback showed that patients required more personalization and interactive options.

The idea of exporting dispatchable solar electricity from the North African region to Europe is still the subject of several bilateral meetings, workshops, and conferences, despite doubts and previous failures with the Desertec concept. Given that each North African country has its own privacy policy, energy strategy, and distinct approach to the concept of renewable energy exports, while the potential of renewable energy sources varies from country to country, it would be very helpful to assess the potential and export opportunities of each country. In this respect, this paper focuses on the potential of Algeria. Several key factors that can make Algeria an attractive place to supply Europe with dispatchable solar electricity have been identified and discussed. The factors have been identified from the European perspective and can be used to analyze the potentials of neighboring countries. The barriers that could impede the export of dispatchable solar electricity from Algeria to Europe have also been identified. Based on certain given criteria, the paper provides some scenarios of possible solar electricity import corridors from Algeria to Europe. This work is timely as the Algerian government has expressed interest in exporting its surplus electricity to Europe and is studying an electricity interconnection project with Italy.

Abstract Background Depending on the underlying etiology and epilepsy type, the burden of disease for patients with seizures can vary significantly. This analysis aimed to compare direct and indirect costs and quality of life (QoL) among adults with tuberous sclerosis complex (TSC) related with epilepsy, idiopathic generalized epilepsy (IGE), and focal epilepsy (FE) in Germany. Methods Questionnaire responses from 92 patients with TSC and epilepsy were matched by age and gender, with responses from 92 patients with IGE and 92 patients with FE collected in independent studies. Comparisons were made across the main QoL components, direct costs (patient visits, medication usage, medical equipment, diagnostic procedures, ancillary treatments, and transport costs), indirect costs (employment, reduced working hours, missed days), and care level costs. Results Across all three cohorts, mean total direct costs (TSC: €7602 [median €2620]; IGE: €1919 [median €446], P

Abstract Amphiphysin 2 (BIN1) is a membrane and actin remodeling protein mutated in congenital and adult centronuclear myopathies. Here, we report an unexpected function of this N-BAR domain protein BIN1 in filopodia formation. We demonstrated that BIN1 expression is necessary and sufficient to induce filopodia formation. BIN1 is present at the base of forming filopodia and all along filopodia, where it colocalizes with F-actin. We identify that BIN1-mediated filopodia formation requires IRSp53, which allows its localization at negatively-curved membrane topologies. Our results show that BIN1 bundles actin in vitro. Finally, we identify that BIN1 regulates the membrane-to-cortex architecture and functions as a molecular platform to recruit actin-binding proteins, dynamin and ezrin, to promote filopodia formation.