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John Wallingford and colleagues combine proteomics, in vivo imaging and genetic analyses to identify a new ciliopathy-associated protein module, which they call CPLANE. They show that CPLANE proteins, which include Fuzzy, Inturned and Wdpcp, interact with Jbts17 at basal bodies, where they act to recruit a specific subset of intraflagellar transport proteins. Cilia use microtubule-based intraflagellar transport (IFT) to organize intercellular signaling. Ciliopathies are a spectrum of human diseases resulting from defects in cilia structure or function. The mechanisms regulating the assembly of ciliary multiprotein complexes and the transport of these complexes to the base of cilia remain largely unknown. Combining proteomics, in vivo imaging and genetic analysis of proteins linked to planar cell polarity (Inturned, Fuzzy and Wdpcp), we identified and characterized a new genetic module, which we term CPLANE (ciliogenesis and planar polarity effector), and an extensive associated protein network. CPLANE proteins physically and functionally interact with the poorly understood ciliopathy-associated protein Jbts17 at basal bodies, where they act to recruit a specific subset of IFT-A proteins. In the absence of CPLANE, defective IFT-A particles enter the axoneme and IFT-B trafficking is severely perturbed. Accordingly, mutation of CPLANE genes elicits specific ciliopathy phenotypes in mouse models and is associated with ciliopathies in human patients.

Background/Objectives: The effect of fusidic acid on oral bacteria, especially on Gram- negative periodontopathogenic species, has not yet been investigated. This in vitro study aimed to analyze the antibacterial effect of fusidic acid alone and as an active component in electrospun poly(L-lactide-co-D/L-lactide) fiber fleeces. Methods: Minimal inhibitory concentrations (MIC) of fusidic acid and metronidazole (control) were determined for various oral bacteria. Eluates were collected from electrospun poly(L-lactide-co-D/L-lactide) fiber fleeces loaded with 10 and 20 wt% fusidic acid over a period of 28 d. Antibacterial activity was analyzed by means of a microdilution assay. Cytotoxicity was observed toward human gingival fibroblasts (HGFs). Results: All tested Gram-positive and Gram-negative oral bacteria were susceptible to fusidic acid. The lowest MIC was observed for Porphyromonas gingivalis (MIC < 0.062 µg/mL). Compared to the antibacterial activity of metronidazole, that of Porphyromonas gingivalis was suppressed by significant lower fusidic acid concentrations (p < 0.01). The eluates obtained from electrospun poly(L-lactide-co-D/L-lactide) fiber fleeces inhibited the growth of P. gingivalis, S. aureus, A. viscosus, and A. neslundii over a course of 28 days. The largest inhibition zones were detected for Porphyromonas gingivalis in case of the 20 wt% concentrations. The eluates were not cytotoxic toward HGFs. Conclusions: It was shown that fusidic acid has significant antibacterial potential. The results of the present investigation suggest that fusidic acid alone or delivered by electrospun fiber fleeces might be attractive for controlling oral pathogenic bacteria.

IntroductionFamilial hypercholesterolaemia (FH) is a frequent (1:300) autosomal dominantly inherited condition which causes premature (women <60 years, men <55 years) cardio–cerebrovascular disease (CVD). Early detection and initiation of treatment can prevent the development of CVD and premature death. Our pilot study aims to investigate the prevalence of FH, the feasibility and efficacy of a screening based on a capillary blood test performed during a school medicine visit in primary school children.Methods and analysisIn this cross-sectional study, all children (n=3200) between 7 and 12 years, attending primary school in the city of Luxembourg and invited for their mandatory medical school examinations between 2021 and 2023 are invited to participate. A study nurse performs a capillary blood test to analyse the lipid profile. Families receive the result including an interpretation and invitation to seek medical advice if indicated. If FH is confirmed, a reverse cascade screening in that family will be proposed. The child will receive standard care. Primary outcome is the occurrence of confirmed FH in the study population. Secondary outcomes include the percentage of children screened, percentage of children with abnormal lipid values, percentage of families screened and percentage of families with additionally identified members suffering from hypercholesterolaemia. A health economic analysis will be performed.Ethics and disseminationEthics approval (reference number 202108/01) has been obtained from the National Research Ethics Committee (CNER (Luxembourg)) and was authorised by the ministry of health in Luxembourg. Families receive written information with an informed consent form. Participation requires an informed consent form signed by the parents. The results will be disseminated in peer-reviewed publications, conference presentations and by public media to the general public.Trial registration numberNCT05271305.

Background Air pollution may induce or reinforce nasal inflammation regardless of allergy status. There is limited direct clinical evidence informing the treatment of airborne pollution-related rhinitis. Objective To assess the effectiveness of intranasal budesonide in adults with self-reported rhinitis symptoms triggered/worsened by airborne pollution. Methods Adults in northern China with self-reported rhinitis symptoms triggered or worsened by airborne pollution were randomized to budesonide 256 µg/day or placebo for 10 days in pollution season (October 2019 to February 2020). The primary endpoint was the mean change from baseline in 24-h reflective total nasal symptom score (rTNSS) averaged over 10 days. The secondary endpoints were subject-assessed Global Impression of Change (SGIC), mean change from baseline in individual nasal symptom severity, and mean change from baseline in individual non-nasal symptoms of cough and postnasal drip severity. One-sided P  < 0.0125 was considered statistically significant. Results After an interruption by COVID-19, an interim analysis showed that the study could be ended for efficacy with n = 206 participants (103/group) since the primary efficacy endpoint demonstrated significant results. The final efficacy results showed that the 10-day-averaged rTNSS change in the budesonide group was greater than with placebo (− 2.20 vs − 1.72, P  = 0.0107). Budesonide also significantly improved 10-day-averaged itching/sneezing change (− 0.75 vs − 0.51, P  = 0.0009). Results for SGIC and all other individual symptoms did not show significant differences between the two groups. Conclusions Intranasal budesonide 256 µg once daily improved the total nasal symptoms and itching/sneezing over 10 days in adults with rhinitis triggered/worsened by airborne pollution.

The toxicity of Loxosceles spider venom has been attributed to a rare enzyme, sphingomyelinase D, which transforms sphingomyelin to ceramide-1-phosphate. The bases of its inflammatory and dermonecrotic activity, however, remain unclear. In this work the effects of ceramide-1-phosphate on model membranes were studied both by in situ generation of this lipid using a recombinant sphingomyelinase D from the spider Loxosceles laeta and by pre-mixing it with sphingomyelin and cholesterol. The systems of choice were large unilamellar vesicles for bulk studies (enzyme kinetics, fluorescence spectroscopy and dynamic light scattering) and giant unilamellar vesicles for fluorescence microscopy examination using a variety of fluorescent probes. The influence of membrane lateral structure on the kinetics of enzyme activity and the consequences of enzyme activity on the structure of target membranes containing sphingomyelin were examined. The findings indicate that: 1) ceramide-1-phosphate (particularly lauroyl ceramide-1-phosphate) can be incorporated into sphingomyelin bilayers in a concentration-dependent manner and generates coexistence of liquid disordered/solid ordered domains, 2) the activity of sphingomyelinase D is clearly influenced by the supramolecular organization of its substrate in membranes and, 3) in situ ceramide-1-phosphate generation by enzymatic activity profoundly alters the lateral structure and morphology of the target membranes.

Dropout rates in higher education remain high, particularly during students’ early semesters. Universities have become increasingly diverse, offering a broader range of degree programs. However, this diversity also brings challenges, particularly in transitioning from school to university. In Germany, up to 47% of dropouts occur within the first two semesters, with higher rates among male students, first-generation students, and those with a migration background. Academic difficulties, especially exam failure and perceived high-performance demands, are among the leading causes of dropout.This dissertation presents the design and evaluation of a course recommendation system aimed at supporting students at risk of dropping out. The system’s design is based on significant performance differences between students who dropped out and those who graduated, identified through data exploration from three undergraduate programs. Early involvement of students in the development process helped shape a transparent and interpretable recommendation system that is accessible to all students.The system uses an explainable nearest neighbors algorithm to recommend courses based on the academic performance of similar, successful students. Two success criteria are considered: (1) graduation and (2) passing a minimum number of courses in a semester. The second criterion enables earlier feedback on success and allows the system to adapt more quickly to curriculum changes.The system’s potential impact was comprehensively evaluated using historical data and multiple metrics, including overlap quality with passed courses, the number of recommended courses, and the change in predicted dropout risk. A key finding is that the number of recommended courses dynamically adapts to students’ academic performance, helping to prevent overload for at-risk students. The system also tends to recommend courses for at-risk students that are easier to pass, increasing their chances of passing and progressing academically. Course recommendations were more aligned with the courses passed by successful graduates, confirming the system’s potential to support academic success.A user study with 100 students further validated the system’s perceived explanation and recommendation quality. The results showed that students generally understand the explanations, although no clear preference emerged between list- and set-based presentation formats.This work contributes to the fields of Educational Data Mining and Learning Analytics by demonstrating how personalized course recommendations can support students at risk of dropping out while ensuring that successful students are not negatively affected. The findings highlight the importance of explainability and flexibility in course recommendation systems and provide insights for future research and practical implementation.

Background Osteoarthritis (OA) is a major cause of chronic pain. Non-steroidal anti-inflammatory drugs (NSAIDs) are analgesics commonly used for musculoskeletal pain; however, NSAIDs can increase the risk of certain adverse events, such as gastrointestinal bleeding, edema, heart failure, and hypertension. Objective The objective of this study was to characterize existing comorbidities among patients with OA. For patients with OA with and without a coexisting medical condition of interest (CMCOI), we estimated the prevalence of prescribing and dispensing NSAIDs pre-OA and post-OA diagnosis. Methods Data from three large administrative claims databases were used to construct an OA retrospective cohort. Databases leveraged were IBM MarketScan Medicare Supplemental Database (MDCR), IBM MarketScan Commercial Database (CCAE), and Optum’s de-identified Clinformatics ® Data Mart Database (Optum CDM). The OA study population was defined to be those patients who had an OA diagnosis from an inpatient or outpatient visit with at least 365 days of prior observation time in the database during January 2000 through May 2021. Asthma, cardiovascular disorders, renal impairment, and gastrointestinal bleeding risks were the CMCOI of interest. Patients with OA were then classified as having or not having evidence of a CMCOI. For both groups, NSAID dispensing patterns pre-OA and post-OA diagnosis were identified. Descriptive analysis was performed within the Observational Health Data Sciences and Informatics framework. Results In each database, the proportion of the OA population with at least one CMCOI was nearly 50% or more (48.0% CCAE; 74.4% MDCR; 68.6% Optum CDM). Cardiovascular disease was the most commonly observed CMCOI in each database, and in two databases, nearly one in four patients with OA had two or more CMCOI (23.2% MDCR; 22.6% Optum CDM). Among the OA population with CMCOI, NSAID utilization post-OA diagnosis ranged from 33.0 to 46.2%. Following diagnosis of OA, an increase in the prescribing and dispensing of NSAIDs was observed in all databases, regardless of patient CMCOI presence. Conclusions This study provides real-world evidence of the pattern of prescribing and dispensing of NSAIDs among patients with OA with and without CMCOI, which indicates that at least half of patients with OA in the USA have a coexisting condition. These conditions may increase the risk of side effects commonly associated with NSAIDs. Yet, at least 32% of these patients were prescribed and dispensed NSAIDs. These data support the importance of shared decision making between healthcare professionals and patients when considering NSAIDs for the treatment of OA in patients with NSAID-relevant coexisting medical conditions.

This paper deals with the characterization of the properties of wood fibres leather shavings composite board by using the near infrared spectroscopy (NIRS) and multivariate data analysis. In this study fibreboards were manufactured with different leather amounts by using spruce fibres, as well as vegetable and mineral tanned leather shavings (wet white and wet blue). The NIR spectroscopy was used to analyse the raw materials as well as the wood leather fibreboards. Moreover, the physical and mechanical features of the wood leather composite fibreboards were determined to characterize their properties for the further data analysis. The NIR spectra were analysed by univariate and multivariate methods using the Principal Component Analysis (PCA) and the Partial Least Squares Regression (PLSR) method. These results demonstrate the potential of FT-NIR spectroscopy to estimate the physical and mechanical properties (e.g., bending strength). This phenomenon provides a possibility for quality assurance systems by using the NIRS.

Many of current bio-based materials are not fully or partly used for material utilization, as the composition of their raw materials and/or possible applications are unknown. This study deals with the analysis of the wood extractives from three different tissue of larch wood: Sapwood mainly from outer part of the log, and sound knotwood as well as dead knotwood. The extractions were performed with an accelerated solvent extractor (ASE) using hexane and acetone/water. The obtained extracts were analyzed by gas chromatography coupled to mass spectrometry (GC-MS). Three various vibrational spectroscopy (FT-RAMAN, FT-IR and FT-NIR) methods reflect the information from the extracts to the chemical composition of the types of wood before the extraction processes. Multivariate data analysis of the spectra was used to obtain a better insight into possible classification methods. Taxifolin and kaempferol were found in larger amount in sound knotwood samples compared to larch wood with high percentage of sapwood and dead knotwood samples. While the extractions of dead knotwood samples yielded more larixol and resin acids than the other larch wood samples used. Based on the chemical composition, three lead compounds were defined for the classification of the different wood raw materials. The vibrational spectroscopy methods were applied to show their potential for a possible distinction of the three types of larch wood tissue. This new insight into the different larch wood extracts will help in the current efforts to use more environmentally friendly raw materials for innovative applications. The connection between the raw materials and extraction yields of the target values is important to transform the results from the laboratory to industry and consumer applications.