University of Groningen

The mean overall satisfaction score from parents was 7.5 out of 10 (with 1 being the lowest and 10 the highest possible score). DiscussionWhile overall satisfaction was high, experiences varied, and less than half of parents achieved their goal at the end of the treatment.Some parents primarily sought guidance rather than complete dryness.A lack of dialogue about goals or treatment options may leave needs (like guidance) unmet and lead to unnecessary care (e.g.treatment for total dryness). ConclusionParents' experiences overall are positive, but can vary widely, affected by their goals and expectations.These findings highlight the importance of discussing expectations to improve outcomes and reduce healthcare use.

Achieving efficient and stable hydrogen evolution reaction (HER) with earth-abundant electrocatalysts is pivotal for boosting the efficiency of alkaline water electrolysis. Here, we report an oxygen vacancy (O v )-rich Cu₂O/NiO heterostructure, which triggers a peculiar interfacial charge transfer from NiO to Cu₂O, creating catalytically active Ni³⁺–Cu 0/+ dual sites to synergistically promote water dissociation and hydrogen adsorption. The Cu₂O/NiO heterostructure exhibits a low overpotential of 19.7 mV at 10 mA cm⁻² with Tafel slope of 36 mV dec⁻¹, outperforming most of the reported catalysts. The anion exchange membrane (AEM) electrolyzer equipped Cu₂O/NiO electrode enables 1.78 V to reach 1 A cm⁻² for more than 200 hours of continuous operation. A thorough characterization study involving HRTEM/XPS/EPR/XANES and DFT calculation exemplifies the interfacial charge transfer dynamics in Cu₂O/NiO heterostructure and its HER catalytic mechanism, offering a new paradigm for rational design of noble metal-free HER electrocatalysts for practical AEM water electrolysis. • Interfacial charge transfer from NiO to Cu₂O in oxygen vacancy-rich Cu₂O/NiO • Catalytically active Ni³⁺–Cu 0/+ dual sites promote HER • 19.7 mV overpotential at 10 mA cm⁻² with 36 mVdec⁻¹ Tafel slopes were obtained • HRTEM/XPS/EPR/XANES and DFT exemplified interfacial charge transfer in Cu₂O/NiO

Fc receptor-like (FCRL) proteins constitute a receptor family that displays overlapping yet distinct features compared to classical Fc receptors. In a healthy immune system, FCRL proteins play a role in promoting and regulating the immune response through their immunoreceptor tyrosine-based motifs. FCRL proteins are expressed mainly by B cells, suggesting a primary role in B-cell responses. For several autoimmune diseases, studies have shown that particularly FCRL4, which binds to dimeric IgA, and FCRL5, which binds to IgG, may have a role in disease pathology and prognosis. These proteins and their transcripts are often enriched in blood and/or affected tissue of patients with a systemic or organ-specific autoimmune disease like rheumatoid arthritis, Sjögren's disease, systemic lupus erythematous, Graves' disease or myasthenia gravis. The expression of FCRL4 and FCRL5 appears to be disease- and context-specific, and influenced by the tissue microenvironment. Yet, the functions of FCRL proteins are still incompletely understood, and more mechanistic studies are necessary to unravel the contribution of FCRL4 and FCRL5 to pathogenic B-cell responses occurring in autoimmune diseases.

Medication reconciliation (MR) in the emergency department (ED) is essential to ensure medication safety, especially for patients admitted to the hospital. However, performing MR for all ED patients, including those discharged, can be inefficient. To optimize prioritization, an artificial intelligence (AI)-powered hospital admission prediction dashboard was introduced. The primary aim of this study was to evaluate the effect of an artificial intelligence (AI) powered hospital admission prediction dashboard on the proportion of patients admitted to the hospital with an MR performed in the ED. The secondary aim was to assess its effect on the proportion of patients discharged from the ED with an MR. This retrospective before-after study was conducted at Hospital Group Twente and included ED visits between March 15 and December 31 in both 2023 and 2024. In the pre-intervention period, MR was strived for any patient, including patients discharged directly from the ED (i.e. potentially unnecessary MR as the risk for errors is low) and for admitted patients (i.e. correct MR). In 2024, the post-intervention period, a set of Extreme Gradient Boosting (XGBoost) models was trained on historical data (2015-2022) and integrated into a real-time dashboard to prioritize patients with the highest admission probability to perform MR. Primary outcome was the proportion of patients with correct MR. Secondary outcome was the proportion of patients with a potentially unnecessary MR. Chi-square test was used to compare proportions before and after implementation of the dashboard. The study included 25,505 ED visits. Pre-intervention 12,743 ED visits were included with 5,252 MRs performed. Post-intervention 12,762 ED visits were included with 4,882 MRs. After implementing the dashboard, the proportion of patients with correct MR increased from 86.4 to 89.0% (p = 0.0002), and the proportion of patients with potentially unnecessary MR decreased from 17.9 to 12.6% (p < 0.0001). The AI-powered hospital admission prediction dashboard improved the prioritization of MR in the ED. The proportion of patients with potentially unnecessary MR remains substantial and requires further improvement.

• Mutational scanning indicates more processing sites in K2 than initially recognized. • Insights into precursor processing help to predict the mature toxin structure. • Single mutations can enhance killer toxin function and change target specificity. • Yeast killer toxins are part of structural families despite low sequence identity. Yeast killer toxins (YKTs) are antimicrobial proteins secreted by yeast with potential applications ranging from food preservation to therapeutic agents in human health. However, the practical use of many YKTs is limited by specific pH requirements, low temperature stability, low production yields, and narrow target specificity. While protein engineering could potentially overcome these challenges, progress is hindered by a lack of detailed knowledge about sequence-function relationships and structural data for these often multi-step processed proteins. In this study, we focused on the YKT K2, encoded by the M2 satellite dsRNA in Saccharomyces cerevisiae . Using alanine scanning mutagenesis of the full open reading frame and structure predictions combined with molecular dynamics simulations, we generated a comprehensive sequence-structure–function map, refined the model for the proteolytic processing of the K2 precursor, and predicted the mature toxin structure. Our findings also demonstrate that K2 can be engineered toward enhanced toxicity and altered target specificity through single-site mutations. Furthermore, we identified structural homology between K2 and other killer toxins, including the SMK toxin from the yeast Millerozyma farinosa . Our cost-effective workflow provides a platform to broadly map YKT sequence-structure–function relationships.

Weed management is a key to the adoption of conservation agriculture practices in Sub-Saharan Africa. This study assessed the effect of conservation agriculture practices, strip-tillage and direct mulch-based cropping system on weed emergence, biomass and community structure in cotton-based cropping systems in northern Benin. The experiment was conducted in 2023 and 2024 using a randomized complete block design with three replications under three cropping systems: conventional tillage, strip tillage (cotton in biannual rotation with maize-cowpea intercropping over strip tillage) and direct mulch-based cropping system (cotton in three-season rotation with maize and Stylosanthes guianensis intercropping and sorghum and soybean intercropping over direct mulch-based cropping system). Weed emergence and species were inventoried at seven-day intervals starting from the first rainfall triggering their germination. Weed biomass was measured at each weeding. Conservation agriculture systems significantly reduced weed emergence compared to conventional tillage. The reductions were 15 % (cotton) and 46 % (maize) under strip tillage, and 33 % (cotton) and 56 % (maize) under direct mulch-based cropping system. Weed biomass increased significantly under the strip tillage system, i.e. by 40 % in cotton plots and by 41 % in maize plots. Crop yields were not significantly affected by systems. Weed community structure was shaped by the interaction between the cropping system and seasons, with distinct indicator species associated with cropping systems. These findings demonstrate that conservation agriculture practices can reduce weed emergence and alter weed community structure without compromising yield performance. This is the first study to characterize weed management under conservation agriculture in Sub-Saharan African cotton-based cropping systems. • Conservation agriculture reduced weed emergence and biomass in a cotton-based system. • Strip-tillage reduced weed emergence but increased biomass compared to conventional tillage. • Tillage, intercropping and mulching influenced weed community structure. • No-/strip tillage led to greater dicots weed emergence in a cotton-based system. • There is no significant difference of cotton and maize yields between three systems.

RET fusions appear in 1%-2% of non-small cell lung cancers (NSCLCs). The results from the ARROW study (ClinicalTrials.gov identifier: NCT03037385) supported US Food and Drug Administration approval of pralsetinib, an oral selective RET inhibitor, for metastatic RET-altered NSCLC and RET fusion-positive thyroid cancers. ARROW was a phase I/II open-label study of pralsetinib 400 mg once daily in RET fusion-positive NSCLCs. Coprimary end points were overall response rate (ORR) and safety. Key secondary end points included duration of response, progression-free survival, and overall survival (OS). At data lock (May 20, 2024), 281 patients initiated pralsetinib (median treatment duration, 15.0 months). ORR (measurable disease patients; n = 259) was 78% (95% CI, 69 to 86) for treatment-naïve patients and 63% (95% CI, 54 to 71) for prior platinum-based chemotherapy patients. Median OS was 44.3 months (95% CI, 30.9 to 53.1), 50.1 months (95% CI, 28.3 to not reached) in treatment-naïve patients, and 39.7 months (95% CI, 27.8 to 53.2) in prior platinum patients. Common grade ≥3 treatment-related adverse events were anemia (21%), hypertension (15%), and decreased neutrophils (13%). Three treatment-related deaths occurred (pneumonia, n = 2; interstitial lung disease and rhabdomyolysis, n = 1 each). Safety was consistent with previous ARROW reports; no hypersensitivity was reported in patients receiving prior immunotherapies. Pralsetinib produced robust, durable responses with manageable safety in treatment-naïve and previously treated patients with RET fusion-positive NSCLCs, confirming previous findings with longer follow-up.