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Comprehensive Analysis of the Melanoma DNA Methylome Identifies LY75 Methylation as an Independent Marker Predicting Poor Clinical Outcome
No full textAccurate risk assessment of local recurrences or metastases is essential for melanoma treatment, but current clinical parameters are suboptimal. Therefore, we conducted a comprehensive DNA methylation analysis to identify prognostic markers that could improve risk prediction in patients with melanoma. We integrated methyl-binding domain sequencing, RNA sequencing, Infinium HumanMethylation450 analyses, and The Cancer Genome Atlas data to identify potential prognostic DNA methylation markers. Validation was performed using methylation-specific PCR in 2 independent melanoma cohorts as well as an in silico validation using The Cancer Genome Atlas data. Cox proportional hazards models and backward stepwise elimination determined the prognostic value of candidate markers. LY75 promoter methylation, Breslow thickness, and metastatic disease at diagnosis were significant independent predictors of recurrence-free survival. LY75 promoter methylation was also found to be an independent predictor of metastatic disease development in patients with localized stage I/II melanoma specifically. This association was confirmed in a second validation cohort and The Cancer Genome Atlas melanoma dataset. LY75 promoter methylation identifies patients at high risk of recurrences or metastases, independent of conventional prognostic parameters. This marker could help refine patient selection for sentinel node biopsies, imaging, (neo)adjuvant treatment, and closer monitoring, ultimately leading to improved clinical outcomes.</p
ToF-SIMS spectra of gallic acid, ellagic acid, castalin, and quercetin in positive polarity
No full textInitially used for fermentation or storage, oak wood barrels were found to enhance the organoleptic properties of spirits. Over time, wood extractives like ellagitannins and aromatic precursors have been linked to the quality of the spirits. ToF-SIMS being an ionization technique produces intense fragmentation patterns that are not fully understood, and reference spectra are required to analyze wood samples confidently. Here, positive polarity ToF-SIMS reference spectra of important oak wood compounds are involved in spirit maturation, using a Bi-3(+) primary ion species, are presented
"Look at Yourself":Teachers' Reflective Practices Toward Enjoyment in Primary School Physical Education
No full textBackground Enjoyment is key in primary school physical education (PE), yet ensuring enjoyable PE experiences for all children is challenging. Reflection may help teachers improve lesson quality and foster PE enjoyment.Methods This cross-sectional study explored Dutch primary school teachers' perspectives on enjoyable PE and reflective practices. An online questionnaire was completed by 173 teachers (70.5% PE specialists, 29.5% generalists) who teach at least one PE lesson per week. Teacher type differences were analyzed using Chi-square tests, Mann-Whitney U tests, and logistic regressions.Results Perspectives on reflective practices were similar among teacher types. Generalists reported more teacher- and policy-related barriers to providing enjoyable PE, while specialists cited child-related challenges. Most teachers reflected internally, with limited use of written reflection or feedback from children and colleagues. Specialists used professional networks and peer feedback more. Time constraints and low prioritization were key barriers to reflection.Implications for School Health Policy Schools should allocate time and promote reflection tools. Generalists could benefit from coaching and targeted professional development. For specialists, teacher education might foster reflective practices using video and child feedback to improve child outcomes like PE enjoyment.Conclusions Tailored strategies are needed to strengthen reflection and improve PE quality to foster children's PE enjoyment
Achter gesloten deuren:Over de vergoedbaarheid van gemist voordeel bij een niet-aangevangen exploitatie
No full textIn de planschade- en nadeelcompensatiepraktijk rijst regelmatig de vraag of gemist voordeel uit een op de peildatum nog niet-aangevangen exploitatie – zogenaamde fictieve exploitatieschade – voor vergoeding in aanmerking komt. De bestuursrechter hanteert als hoofdregel dat dit niet wordt vergoed, maar erkent inmiddels enkele uitzonderingen. Dit artikel brengt het juridisch kader omtrent fictieve exploitatieschade in kaart
Managing the Transition to a Circular Urban Waste Management System
No full textTransition to a circular urban waste management system is a complex, incremental process involving systemic change. Transition studies have focused on identifying actions and plans to support this radical shift, with governance and control of the process primarily following the transition management approach. Transition management encompasses strategic, tactical, operational, and reflexive activities that are designed to guide, manage, and lead the process of systemic change. In the Netherlands, managing the transition towards a circular urban waste management system has become a priority for cities seeking to address environmental and economic challenges associated with traditional linear waste management practices. This chapter examines the principles of transition management in the context of transforming urban waste management system into a circular and more resilient system. It explores the different types of governance activities involved in this process and investigates how existing capabilities can be leveraged to support the transition toward circular urban waste management practices. Ultimately, by reviewing the current practices of circular urban waste management in the Netherlands, this chapter aims to provide insights to inform policy and practice in managing the transition process, both at the national and international levels
DTW-Align: Bridging the Modality Gap in End-to-End Speech Translation with Dynamic Time Warping Alignment
No full textEnd-to-End Speech Translation (E2E-ST) is the task of translating source speech directly into target text bypassing the intermediate transcription step. The representation discrepancy between the speech and text modalities has motivated research on what is known as bridging the modality gap. State-of-the-art methods addressed this by aligning speech and text representations on the word or token level. Unfortunately, this requires an alignment tool that is not available for all languages. Although this issue has been addressed by aligning speech and text embeddings using nearest-neighbor similarity search, it does not lead to accurate alignments. In this work, we adapt Dynamic Time Warping (DTW) for aligning speech and text embeddings during training. Our experiments demonstrate the effectiveness of our method in bridging the modality gap in E2E-ST. Compared to previous work, our method produces more accurate alignments and achieves comparable E2E-ST results while being significantly faster. Furthermore, our method outperforms previous work in low resource settings on 5 out of 6 language directions
Effects of pharmacist care on hospitalizations in heart failure across outpatient and inpatient settings:A systematic review and meta-analysis
No full textAims Heart failure (HF) is major cause of unplanned (re)hospitalizations, especially in high-risk patients such as those recently discharged or those with worsening HF. Hospital-affiliated or clinic-based pharmacists, though underutilized, may help reduce this burden. This systematic review and meta-analysis assessed their impact on all-cause and HF hospitalizations.Methods A systematic literature search using PUBMED and EMBASE and conducted according to PRISMA guidelines identified randomized controlled trials published up to November 2024. Eligible studies evaluated the effects of pharmacy interventions on hospitalizations and mortality among patients with HF. Studies with community pharmacy- or home-based interventions were excluded. Study quality was appraised using the Cochrane risk-of-bias tool. Random-effects models were applied to derive odds ratios (OR), with heterogeneity assessed using the I2 statistic and Cochrane's Q test.Results Eleven studies were included, involving 3576 patients and a variety of pharmacist interventions. Pharmacists significantly reduced the odds of all-cause hospitalizations compared to usual care (3472 patients, 927 events; OR 0.67, 95% confidence interval [CI]: 0.49-0.92, P = 0.0119). For HF hospitalizations (3442 patients, 504 events), similar results were retrieved (OR 0.64, 95% CI: 0.48-0.87, P = 0.0038). Heterogeneity was moderate for both analyses. Sensitivity analyses supported the robustness of these two analyses. Subgroup analyses indicated greater effectiveness in outpatient settings and when extended interventions were provided.Conclusions Across inpatient and outpatient settings, pharmacist interventions in HF significantly reduced all-cause as well as HF hospitalizations. Our findings highlight the importance of integrating pharmacists into multidisciplinary teams to improve HF management for in- and outpatients
Fully personalized contrast injection optimized for weight and tube voltage in low-dose high-pitch coronary CT angiography
No full textBackground: To evaluate the performance of a fully individualized, weight- and tube voltage-tailored contrast media injection protocol (MINDS-CAD) for high-pitch coronary CT angiography (CCTA). Methods: This IRB-approved, single-center study included 112 patients undergoing clinically indicated CCTA using third-generation dual-source CT. Fifty-six patients were scanned with the MINDS-CAD protocol, which adapts contrast delivery rate (DR, range: 1.7-9.7 mL/s) and contrast volume (CV, range: 23-97 mL) based on body weight and automatic tube voltage selection, creating 56 pairs of CV and DR and uses high-pitch scanning. Fifty-six matched controls underwent CCTA with an institutional standard protocol (retrospective spiral scan, CV, range: 50-80 mL; DR, range: 3.2-5.0 mL/s). Objective image quality was assessed via coronary artery attenuation (HU) in proximal and distal segments. Subjective image quality was graded on a four-point scale (4: excellent), and multiple linear regression was used to identify predictors of coronary attenuation. Dose-length-product (DLP) was compared between cohorts. Results: Groups were matched for age, BMI, and heart rate (all p > 0.05); over 60 % were obese (BMI >= 30 kg/m(2)). Coronary attenuation was higher with MINDS-CAD (391.1 +/- 88.1 HU vs. 305.6 +/- 103.1 HU, p < 0.001). Subjective quality was superior (4 [IQR: 3-4] vs. 3 [IQR: 3-3], p < 0.001), with fewer poor-quality scans (Likert 1, 3.5 % vs. 8.8 %) in the MINDS-CAD cohort. In the standard group, BMI and tube voltage predicted attenuation (beta = -7.998 and -2.864; p < 0.001), whereas in the MINDS-CAD group, neither was predictive (p = 0.411). Most importantly, MINDS-CAD achieved superior image quality in a matched cohort while considerably lowering radiation dose (90 +/- 50 mG center dot cm vs 576 +/- 386 mG center dot cm, p < 0.001). Conclusion: A fully individualized, weight- and tube voltage-tailored contrast protocol achieved more consistent coronary attenuation and superior image quality. These results, demonstrated in a predominantly obese cohort, highlight the robustness of the protocol and provide a framework for reliable low-dose, high-pitch CCTA across challenging patient populations
Pros and cons of different dietary patterns for the treatment of metabolic dysfunction-associated steatotic liver disease
No full textMetabolic dysfunction-associated steatotic liver disease (MASLD) is becoming the most prevalent hepatic disorder, affecting up to 33 % of the global population. An altered lifestyle, characterized by extended physical inactivity and increased consumption of highly caloric food, often low in nutritional value, is recognised as one of the main contributing factors for MASLD. Cornerstone for MASLD treatment is a healthy lifestyle, starting from diet. However, the most appropriate dietary pattern for the treatment of MASLD remains a subject of debate. The aims of this narrative review are therefore to explore the mechanisms through which nutrition influences MASLD pathogenesis and to evaluate different dietary patterns for MASLD treatment, highlighting their advantages and limitations. Multiple dietary patterns-including the Mediterranean Diet (MD), the Dietary Approaches to Stop Hypertension (DASH), the Low-Carb Diet (LCD), the Ketogenic Diet (specifically the Very Low-Calorie Ketogenic Diet, VLCKD), the Low-Fat Diet (LFD), Vegetarian Diets (VDs), and Intermittent Fasting (IF)-are reviewed, with a focus on their efficacy on MASLD and the ameliorating of the associated cardiometabolic risks factors (CMRF)
Symptom over- and underreporting are relatively stable behavioral opposites in forensic patients and undergraduates
No full textThe phenomena of symptom overreporting, underreporting, and inattentive responding have often been linked to traits using cross-sectional designs. The preliminary question - the temporal stability of these phenomena - has remained largely unexamined. We conducted a test-retest study in forensic inpatients and students (all ns >= 64), who twice - across a six- to ten-week interval - completed stand-alone measures of symptom overreporting, symptom underreporting, inattentive responding, and Big Five personality domains. Symptom overreporting rates were similar in patients and students (+5 %). The same was true for symptom underreporting in patients (+15-20 %) and students (+5-10 %), whereas inattentive responding was non-trivial in patients (+15 %), but low in students (+0-5 %). In both groups, symptom overreporting and underreporting were relatively stable behavioral opposites. Trait scores of those who engaged in symptom overreporting and underreporting deviated +0.75 SD from those who passed all validity indices, and in a patterned rather than arbitrary way. The shared variance may reflect a common underlying mechanism. In patients, borderline personality disorder was linked to symptom overreporting, whereas narcissistic personality disorder was associated with symptom underreporting. Overall, our findings suggest that both traits and contextual factors shape how accurately people report their symptoms