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Non-cell autonomous autophagy in amyotrophic lateral sclerosis: A new promising target?
No full textAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative non-cell-autonomous disease with no cure, thus research is intensely focused on identifying pharmacological targets. Several studies aimed to clarify the pathogenic mechanisms and involvement in various cell types. A crucial factor in ALS is autophagy, which plays a key role in degrading intracellular protein aggregates. The connection between ALS and autophagy is reinforced by the fact that several genes mutated in ALS are linked to fundamental aspects of autophagy. The blockage of the autophagic flux was observed in ALS motor neurons, where it occurs earlier than in glia. However, the inconsistent effects of autophagy modulators in preclinical and clinical studies indicate the need for a deeper understanding of the role of autophagy in other cell types, such as astrocytes, microglia, and oligodendrocytes. Astrocytes and microglia are significantly impacted by autophagy dysregulation, contributing to neurodegeneration in both mouse and human-derived models. Autophagy is overactivated early in the disease, even before symptoms appear. This overactivation is influenced by the timing and specific tissue involved. It can alter cells' immunophenotype, favouring proinflammatory responses and affecting the cellular environment and autophagy in the surrounding cells. In contrast, oligodendrocytes show mild autophagic alterations. Additionally, sex hormones may affect proper autophagy function and ALS progression. The lack of information on how sex influences autophagy in glia highlights the need for more nuanced investigation into this mechanism. Future research should focus on these aspects, paving the way for personalised pharmacological approaches that consider the roles of cell types, time of intervention, and sex
Public value integration into performance management systems: Insights from universities
No full textEnhanced crop calibration for SWAT+: evaluating water, sediment and nutrient impacts across ten European catchments
No full textThis study proposes a new workflow for crop growth evaluation and yield calibration in the Soil and Water Assessment Tool Plus (SWAT+) model and evaluates its impact on simulated hydrological and biogeochemical processes. The workflow was applied for ten small agricultural catchments in Europe. A detailed demonstration is provided for the German catchment, Schwarzer Schöps. The workflow proved effective across all catchments, improving yield calibration from an initial R2 of 0.5–0.84. The results show that evapotranspiration and soil moisture were only moderately affected by crop calibration in three catchments (Belgium, Czech Republic and Norway) and negligibly changed in the remaining ones. Sediment and nutrient balance were affected more strongly: sediment, nitrogen and phosphorus loss change reached 82 % (Norway), 16 % and 20 % (Czech Republic), respectively. The proposed workflow is a valuable tool for improving the accuracy of SWAT + simulations and can be used to support decision-making in environmental management
Two‐tier screening approach for liver fibrosis stratification in outpatients with type 2 diabetes mellitus: A multicenter cross‐sectional study
No full textBackground: To examine the prevalence and severity of metabolic dysfunction-associated steatotic liver disease (MASLD) in outpatients with type 2 diabetes mellitus (T2DM), and to assess the effectiveness of the EASL-EASD-EASO algorithm for liver fibrosis screening. Methods: We retrospectively enrolled 1203 Italian older outpatients with T2DM who underwent vibration-controlled transient elastography (VCTE) with liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) assessment. MASLD was defined as CAP ≥248 dB/m. Significant liver fibrosis was defined as LSM ≥8 kPa, compensated advanced chronic liver disease (cACLD) as LSM ≥10 kPa, and clinically significant portal hypertension (CSPH) as LSM ≥25 kPa or LSM ≥20 kPa and platelet count <150 000/mm3. FIB-4 index was calculated in all participants. Results: The prevalence rates of MASLD, significant liver fibrosis, cACLD, and CSPH were 71.3%, 21.1%, 11.7% and 1.7%, respectively. A 2-tier screening strategy for liver fibrosis using the FIB-4 index and VCTE showed that among patients with a normal FIB-4 index, 629 (83.3%) had LSM <8 kPa and 126 (16.7%) had LSM≥8 kPa. Sensitivity, specificity, NPV, and PPV of the FIB-4 index for detecting LSM≥8 kPa were 50.4%, 66.3%, 83.3% and 28.6%, respectively. Increased body weight (adjusted-OR 3.34, 95%CI 1.75–6.39) and elevated ALT levels (adjusted-OR 1.54, 95%CI 1.01–2.36) were the strongest predictors of significant liver fibrosis. Conclusions: MASLD and significant liver fibrosis are common in older patients with T2DM. Fibrosis risk stratification using FIB-4, followed by VCTE, is a good strategy in real-world settings. However, relying solely on FIB-4 may fail to identify some patients with advanced disease, particularly those with increased body weight and elevated serum aminotransferase levels
Advancements in Superconducting Magnet Design for Hadron Therapy: Design, Construction Readiness, and Assembly Challenges of a Curved CCT Magnet in the HITRIplus Project
No full textA detailed overview of the ultimate magnet design developed within Work Package 8 of the collaborative European project HITRIplus is presented. Focused on the development of superconducting magnets for ion therapy synchrotron and gantry systems, the study introduces an innovative approach utilizing a curved Canted Cosine Theta layout magnet based on Nb Ti superconductor. The design targets a central magnetic field strength of 4 T, an 80 mm aperture, and a maximum ramp rate of 0.4 T/s, while addressing the challenge of a tight 1.65 m bending radius. This paper highlights the latest advancements in magnetic and mechanical designs, as well as the construction and assembly procedures for the curved former. The rope cable conductor utilizes a 2×7 layout, optimizing current density distribution with a 1.5 kA current per rope. Key advancements include magnetic and mechanical design improvements, construction readiness, and a detailed comparison of assembly procedures with and without an iron yoke. The vertically split iron yoke design manages thermal contraction through innovative approaches, including tapered iron laminations and aluminium clamps. Alu minium bronze is selected for the curved former, with machining and validation tests highlighting its suitability. Additionally, the paper explores field quality analysis before and after magnet energization, addressing geometric yoke optimization to enhance field uniformity. Progress in conductor development, winding, and wax impregnation tests, and assembly trials are presented, with a focus on ensuring robustness and field accuracy in both yoke-inclusive and yoke-free configurations
Creativity and AI
No full textWe investigate whether AI systems outperform humans in creative tasks that vary in their degree of “openness.” To this end, we generated creative responses using three versions of ChatGPT and recruited 738 participants to blindly evaluate six creative answers randomly drawn from three pools—comprising 160 responses each—generated by both humans and AI. This process yielded 4,428 individual evaluations. Our results show that, regardless of the GPT version employed, human-generated responses achieve significantly and substantially higher average scores than machine-generated responses in open tasks. Conversely, AI-generated responses outperform human ones in closed tasks. Furthermore, we estimate that human imagination accounts for between 22% and 45% of the creative score in open tasks
The School Anxiety Scale – Teacher Repo-TR): Adaptation and Validation in Italian
No full textThe School Anxiety Scale - Teacher Report (SAS-TR) assesses children's anxiety from the teacher's perspective. Originally developed in English and subsequently validated in Spanish and Iranian populations, a validated Italian version is still lacking. The current study aimed to translate, adapt and validate the SAS-TR into Italian. The SAS-TR was translated from English into Italian following 5 stages of cross-cultural adaptation and was assessed for face and content validity by five primary school teachers. A sample of 66 teachers completed the SAS-TR in a community sample of 201 children aged 6-11 years. Exploratory and confirmatory factor analysis were performed. To investigate the concurrent validity, teachers also completed the Strengths and Difficulties Questionnaire-Teacher (SDQ-T). After four weeks, the teachers re-provided ratings on the SAS-TR to assess test-retest reliability. SAS-TR ratings for the same children provided by permanent teachers (who have ≥ 10 teaching hours in classroom) and specialist teachers (who have < 10 teaching hours in classroom) were compared. Exploratory and confirmatory factor analysis confirmed the two-factor structure and the goodness fit of the scale, excluding item 12. The Italian SAS-TR exhibited strong face and content validity (mean = 3.71 ± 0.57), excellent internal consistency (α = 0.902) and almost perfect test-retest reliability over 4-weeks (ICC = 0.829). Additionally, moderate and statistically significant correlations between SAS-TR and SDQ-T "Emotional symptoms" subscale (ρs = 0.62) supported concurrent validity. Finally, permanent teachers reported higher levels of anxiety symptoms compared to specialist teachers (p < 0.05). Overall, the Italian version of SAS-TR demonstrates adequate psychometric properties, suggesting its suitability for assessing anxiety symptoms in children aged 6-11 by teachers
Elexacaftor-tezacaftor-ivacaftor and cystic fibrosis liver disease: A turning point that calls for cautious optimism
No full textPlatelet count, fibrinogen and ROTEM® parameters predict deep vein thrombosis in elderly patients with femoral fracture
No full textBackground: Deep vein thrombosis (DVT) is a frequent complication in elderly patients undergoing surgery for proximal femoral fractures. Identifying early coagulation and viscoelastic changes may help to personalize thromboprophylaxis strategies. This study evaluated the temporal evolution of coagulation and ROTEM parameters and explored whether baseline values and early changes could predict the development of asymptomatic DVT. Methods: We conducted a prospective observational study including patients ≥ 80 years undergoing surgical repair of proximal femoral fractures. Conventional coagulation tests and ROTEM were performed at admission (T0) and on postoperative day 3 (T3). Compression ultrasonography was used to screen for DVT on day 5 (T5). Longitudinal changes were assessed with linear mixed-effects models. Results: Among 40 enrolled patients, 7 (17.5%) developed asymptomatic DVT. Platelet count was consistently higher in DVT patients (baseline: 275.0 ± 47.1 vs 186.5 ± 54.9 × 109/L; p < 0.001). ROTEM revealed increased EXTEM maximum clot firmness (67.6 ± 1.7 vs 62.2 ± 5.7 mm; p = 0.024) and shorter clot formation time (92.0 ± 9.3 vs 116.1 ± 32.0 s; p = 0.041). Fibrinogen levels diverged over time: while baseline values were comparable, DVT patients showed progressive increases (+ 43.7 mg/dL/day) versus reductions in non-DVT patients (-9.5 mg/dL/day), yielding significant differences at T3 (525.3 ± 177.0 vs 372.1 ± 177.8 mg/dL; p = 0.015). FIBTEM-MCF did not differ between groups. A baseline platelet count ≥ 277 × 109/L predicted DVT with 71% sensitivity and 97% specificity (AUC 0.896). Conclusion: In elderly patients with femoral fractures, asymptomatic DVT was associated with elevated baseline platelet counts, enhanced clot firmness, and progressive fibrinogen elevation over time. These findings suggest multifaceted hypercoagulable abnormalities with temporal monitoring potentially superior to single-timepoint assessments for DVT prediction