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Hearing loss drives region-specific amyloid accumulation along the auditory pathway in female 5xFAD mice
Real-world incidence of G3-G4 adverse events with enfortumab vedotin in patients with advanced urothelial carcinoma (ARON-2EV study)
Abstract Enfortumab vedotin (EV) is an antibody–drug conjugate targeting Nectin-4 and is approved for patients with advanced urothelial carcinoma (UC) who have progressed after platinum-based chemotherapy and immune checkpoint inhibitors. While clinical trials have demonstrated manageable safety profiles, real-world toxicity data remain limited. We conducted a multi-center retrospective study of consecutive patients with locally advanced or metastatic UC treated with EV between January 2022 and April 2025. Demographic, clinical, and treatment-related data were extracted from electronic medical records. Primary endpoints included incidence of G3-G4 AEs, dose reductions, and discontinuations. A total of 770 patients were included; 195 patients (25%) reported G3-G4 AEs. The most common G3-G4 AEs were dermatologic (10%), neuropathy (9%) and diarrhea (7%). Seventy-four patients (10%) discontinued EV due to G3-G4 AEs. Both the median OS (21.3 months vs 16.1 months, p = 0.010) and PFS (8.2 months vs 6.8 months, p = 0.012) were significantly longer in patients who started EV therapy at standard dose versus at reduced dose. In conclusion, this real-world cohort showed that EV demonstrated a toxicity profile broadly consistent with clinical trial data, though rates of dose modification were substantial. Enhanced monitoring and early toxicity management may optimize treatment continuity in advanced UC patients.
Identification of palmitoylation-related diagnostic biomarkers in dilated cardiomyopathy through multi-omics integration and experimental validation
Systemic influences of dietary NAD+ supplementation relevant to the search for ocular hypertensive therapies for glaucoma
Abstract Dietary nicotinamide (NAM) is neuroprotective in rodent models of glaucoma. With dietary delivery, additional systemic influences of NAM are possible, prompting us to test for influences on non-neuronal phenotypes relevant to glaucoma. Test cohorts of mice on high-fat diets differed by NAM content (control, “CON-diet”; 2,000 mg/kg/day supplementation, “NAM-diet”) and by ocular treatments inducing various levels of ocular hypertension (Naïve; Ad5-Empty; Ad5-ATF4). Masked observers assessed intraocular pressure (IOP), body weight, and slit-lamp appearance. Naïve and Ad5-Empty cohorts were analyzed for gut microbiome composition. Regardless of diet, Naïve cohorts maintained consistent IOP. On CON-diet, the Ad5-ATF4 and Ad5-Empty cohorts developed IOP elevation. Based on results from a linear mixed-effects model evaluating the effects of diet and ocular treatment on IOP, NAM-diet lowered IOP in only the Ad5-Empty cohort. NAM-diet also prevented weight gain associated with a high-fat diet. NAM-diet was linked to altered alpha and beta diversity of the gut microbiome, including changes to a butyrate-producing genus, Faecalibaculum . Among the systemic influences resulting from dietary NAM consumption, NAM’s ability to affect both neuroprotection and IOP would be favorable for glaucoma therapy. The possibility of dietary NAM influencing body weight and microbiome composition in humans warrants additional investigation.
Efficacy of an anonymous, preventive, personalized online counselling to improve shift workers’ sleep quality: a randomized controlled trial
Abstract Shift work is associated with an increased risk of sleep disorders, yet tailored prevention and treatment programs remain rare and understudied. Cognitive behavioral therapy for insomnia is the first-line treatment for insomnia in the general population. We thus developed an anonymous online counselling service based on cognitive behavioral principles, adapted it to shift workers’ needs, and evaluated it in a sample of German shift workers from various industries. This prospective, randomized, controlled superiority trial compares two parallel groups: an intervention group that received four personalized counselling messages and completed four weekly sleep diaries, and a waiting-list control-group that completed sleep diaries only during the four-week waiting period. In the Intention to Treat sample ( n = 66), significant improvements were observed in both groups for the primary outcome, sleep efficiency, and for the secondary outcomes, symptoms of insomnia and depression. Daytime sleepiness did not improve in either group. However, improvements were not significantly greater in the treatment than in the control group. We can thus not demonstrate superiority of the counselling intervention over the control condition, where repeated sleep diary completion and study participation may themselves have had therapeutic effects. Limitations regarding time frame and sample size, as well as implications for research and practice are discussed. Trial registration: The study was registered with the German Clinical Trials Register DRKS under the trial ID DRKS00017777 ( https://drks.de/search/en/trial/DRKS00017777 ). Date of registration: 14.01.2020. This study was registered during the early stages of data collection. Of the 27 participants in the final sample, the first four had initiated data collection at the date of registration. No complete data sets were available at that time.
SEM-based parallel and serial mediation linking instructor technology integration competence to academic performance in AI-supported online learning
Functionalised MWCNT@CoCuMoO4 electrocatalytic nanocomposite for metronidazole sensing and water splitting reaction applications
Superimposed effects on strata movement during co-mining of stacked coal seam and bauxite in coal-measures
Design and analysis of a compact multi-band flexible metasurface with low-loss characteristics for S, C, and X-band applications
Abstract In this study, the focus is on developing a compact, multi-band, and flexible metasurface (MS) with low-loss characteristics for microwave applications. Recently, there has been a strong need to explore MS designs that can efficiently operate across multiple resonance bands while maintaining a compact size and low loss for advanced performance in ever-increasing microwave technology. The unit cell configuration of the MS is designed using three split-ring resonators (SRRs) interconnected with a spiral notch to achieve multi-resonance characteristics with low loss. The miniaturization of the proposed MS is achieved through inductive loading, which is enabled by extending the metallic strip length within the unit cell. Increasing the metal length increases the effective inductance-to-capacitance ratio (L/C), resulting not only in greater compactness but also lower loss. Despite its compact size and low loss, the numerical simulation results reveal that the proposed SRR-MS unit cell exhibits hexa-resonance frequencies at 2.7 GHz (S-band), 4.22 GHz, 6.25 GHz (C-band), 8.27 GHz, 9.65 GHz, and 10.95 GHz (X-band), respectively. The proposed MS exhibits six distinct $$\epsilon$$ -negative (ENG) regions and one $$\mu$$ -negative (MNG) region across the S, C, and X microwave frequency bands with high refractive index (HRI) properties near all six resonances. Importantly, the low-loss behavior is maintained across all six resonance frequencies of the MS. Additionally, the MS is designed on a single-sided flexible dielectric substrate, and its performance characteristics remain stable to some extent under bending and twisting.
Intelligent university timetabling: a reinforcement learning enhanced Particle Swarm Optimization framework
Uncertainty-aware FMEA-MCDM prioritization of wind turbine drivetrain failure modes
Knowledge, attitudes, and practices of hand hygiene and the prevalence of pathogenic bacteria on the hands of primary school children in Ho Municipality
Circadian phase and diet shape feeding responses to arcuate cholinergic neuron activation
Synergistic regulation of anthocyanin synthesis in soybean sprouts under blue light by GmMYB306 and GmMYB114
Therapeutic potential of date seed (Phoenix dactylifera) powder against human breast cancer: integrated computational and experimental analyses
A prospective study for validating an automated AI-based system for detecting age-related macular degeneration in clinical settings
Abstract Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. Early detection is essential for implementing preventative measures that can slow or stop the progression of late AMD. This study evaluates the performance of an AI-based system designed to detect referable AMD, defined as more than early AMD (mteAMD), in adults over 50 who have not been previously diagnosed. Using color fundus photographs, we recruited 845 subjects from three primary care and three general ophthalmology clinics in New York City. Non-dilated images of both eyes were taken, and for validation, dilated images were reviewed by three ophthalmologists who classified the cases as no AMD, early, intermediate, or late AMD. The system’s performance was assessed on both a per-patient and per-eye basis, comparing its results to expert gradings using metrics such as AUC, sensitivity, specificity, positive predictive value, and negative predictive value. For identifying mteAMD at the subject level, the AI system achieved an AUC of 0.92, with a sensitivity of 90.27% and specificity of 83.36%, demonstrating its strong potential for early diagnosis and screening of AMD in real-world clinical settings.
Perception of oral hygiene during orthodontic treatment: an eye-tracking and cross-sectional study
Abstract The objective of this study was to analyze visual perception of patients undergoing orthodontic treatment with multi-bracket appliances (MBA), and examine differences in oral hygiene perception among adolescents, their guardians, and dental students. The lay person group included 56 participants (28 adolescents and guardians), while the expert group consisted of 30 dentistry students. Both groups evaluated randomized intraoral frontal photographs of adolescents with MBA, taken with or without a plaque disclosing agent. Using eye-tracking methods, eye movements were recorded during the evaluation. Significant differences in visual path length and oral hygiene evaluation were found. The expert group evaluated oral hygiene most accurately, with parents being stricter and adolescents more lenient. The expert group’s visual path was significantly shorter than the lay person group’s. Use of a plaque disclosing agent improved the accuracy of oral hygiene evaluation ( p < 0.001). A correlation was observed between oral hygiene behavior and evaluation. In conclusion, dental students provided the most accurate oral hygiene evaluations. Parents were stricter, and adolescents were more lenient. Among adolescents, longer brushing time was weakly associated with more accurate evaluations, and plaque disclosing agents enhanced evaluation accuracy.
Conformational changes in insulin receptor illuminated by live-cell linear dichroism imaging and a FLIP biosensor
Abstract Insulin receptor (IR) is a tyrosine kinase involved in vital cellular signaling processes related to glucose metabolism and cell growth. Detailed understanding of molecular mechanisms of IR signaling is important for improved treatments of diabetes and related disorders. Although many aspects of IR signaling have over the past years been elucidated, much of the available information comes from studies made in vitro, using protein preparations. However, observations performed directly in living cells, tissues and organisms are needed for proper understanding of IR signaling. To address this need, we decided to investigate GP2(1)-eGFP-CD59, a recently identified FLIP biosensor of IR conformation that takes advantage of the powerful yet underutilized technique of linear dichroism fluorescence microscopy. Our approach allowed us to detect, in living cells, changes in the IR ectodomain in response to IR agonists and inhibitors. Surprisingly, we observed rearrangements in the ectodomain even upon administering an IR kinase inhibitor. Our findings suggest that the state of the intracellular kinase domain plays a role in the stability/conformation of the ectodomain, and urge caution in using solely the ectodomain in structural studies. Furthermore, our results open doors to sensitive imaging of various aspects of IR function in living cells, tissues, and ultimately whole organisms, under conditions close to natural.