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Abstract Epitranscriptomic RNA modifications are crucial for the maintenance of glioma stem cells (GSCs), the most malignant cells in glioblastoma (GBM). 3-methylcytosine (m3C) is a new epitranscriptomic mark on RNAs and METTL8 represents an m3C writer that is dysregulated in cancer. Although METTL8 has an established function in mitochondrial tRNA (mt-tRNA) m3C modification, alternative splicing of METTL8 can also generate isoforms that localize to the nucleolus where they may regulate R-loop formation. The molecular basis for METTL8 dysregulation in GBM, and which METTL8 isoform(s) may influence GBM cell fate and malignancy remain elusive. Here, we investigated the role of METTL8 in regulating GBM stemness and tumorigenicity. In GSC, METTL8 is exclusively localized to the mitochondrial matrix where it installs m3C on mt-tRNAThr/Ser(UCN) for mitochondrial translation and respiration. High expression of METTL8 in GBM is attributed to histone variant H2AZ-mediated chromatin accessibility of HIF1α and portends inferior glioma patient outcome. METTL8 depletion impairs the ability of GSC to self-renew and differentiate, thus retarding tumor growth in an intracranial GBM xenograft model. Interestingly, METTL8 depletion decreases protein levels of HIF1α, which serves as a transcription factor for several receptor tyrosine kinase (RTK) genes, in GSC. Accordingly, METTL8 loss inactivates the RTK/Akt axis leading to heightened sensitivity to Akt inhibitor treatment. These mechanistic findings, along with the intimate link between METTL8 levels and the HIF1α/RTK/Akt axis in glioma patients, guided us to propose a HIF1α/Akt inhibitor combination which potently compromises GSC proliferation/self-renewal in vitro. Thus, METTL8 represents a new GBM dependency that is therapeutically targetable.

Objectives With the sudden global shift to online learning modalities, this study aimed to understand the unique challenges and experiences of emergency remote teaching (ERT) in nursing education. Methods We conducted a comprehensive online international cross-sectional survey to capture the current state and firsthand experiences of ERT in the nursing discipline. Our analytical methods included a combination of traditional statistical analysis, advanced natural language processing techniques, latent Dirichlet allocation using Python, and a thorough qualitative assessment of feedback from open-ended questions. Results We received responses from 328 nursing educators from 18 different countries. The data revealed generally positive satisfaction levels, strong technological self-efficacy, and significant support from their institutions. Notably, the characteristics of professors, such as age (p = 0.02) and position (p = 0.03), influenced satisfaction levels. The ERT experience varied significantly by country, as evidenced by satisfaction (p = 0.05), delivery (p = 0.001), teacher-student interaction (p = 0.04), and willingness to use ERT in the future (p = 0.04). However, concerns were raised about the depth of content, the transition to online delivery, teacher-student interaction, and the technology gap. Conclusions Our findings can help advance nursing education. Nevertheless, collaborative efforts from all stakeholders are essential to address current challenges, achieve digital equity, and develop a standardized curriculum for nursing education.

Background Cardiovascular disease is a leading cause of global death. Prospective population-based studies have found that changes in retinal microvasculature are associated with the development of coronary artery disease. Recently, artificial intelligence deep learning (DL) algorithms have been developed for the fully automated assessment of retinal vessel calibres.Methods In this study, we validate the association between retinal vessel calibres measured by a DL system (Singapore I Vessel Assessment) and incident myocardial infarction (MI) and assess its incremental performance in discriminating patients with and without MI when added to risk prediction models, using a large UK Biobank cohort.Results Retinal arteriolar narrowing was significantly associated with incident MI in both the age, gender and fellow calibre-adjusted (HR=1.67 (95% CI: 1.19 to 2.36)) and multivariable models (HR=1.64 (95% CI: 1.16 to 2.32)) adjusted for age, gender and other cardiovascular risk factors such as blood pressure, diabetes mellitus (DM) and cholesterol status. The area under the receiver operating characteristic curve increased from 0.738 to 0.745 (p=0.018) in the age–gender-adjusted model and from 0.782 to 0.787 (p=0.010) in the multivariable model. The continuous net reclassification improvements (NRIs) were significant in the age and gender-adjusted (NRI=21.56 (95% CI: 3.33 to 33.42)) and the multivariable models (NRI=18.35 (95% CI: 6.27 to 32.61)). In the subgroup analysis, similar associations between retinal arteriolar narrowing and incident MI were observed, particularly for men (HR=1.62 (95% CI: 1.07 to 2.46)), non-smokers (HR=1.65 (95% CI: 1.13 to 2.42)), patients without DM (HR=1.73 (95% CI: 1.19 to 2.51)) and hypertensive patients (HR=1.95 (95% CI: 1.30 to 2.93)) in the multivariable models.Conclusion Our results support DL-based retinal vessel measurements as markers of incident MI in a predominantly Caucasian population.

This research examined the relationship between social network site (SNS) intensity, SNS addiction, and the severity of obsessive-compulsive disorder (OCD), alongside its factors of obsession and compulsion. The overlap of SNS intensity and SNS addiction was controlled in the study to predict the measured severity of OCD. In this study, 204 Malaysian undergraduate students were recruited to complete the revised Facebook Intensity Scale, the revised Bergen Facebook Addiction Scale, and the self-report version of the Yale-Brown Obsessive-Compulsive Scale. The overlap of SNS intensity and SNS addiction was supported by their significant positive correlation. Furthermore, SNS addiction significantly correlated with the measured OCD and its corresponding factors. The hierarchical regression analysis revealed that the entry of SNS intensity enhanced the facilitative effect of SNS addiction on OCD and its factors. Therefore, the role of SNS intensity as a suppressor was supported. In the same regression model, SNS intensity predicted the severity of OCD and its compulsion subscale negatively. Implications and directions for future research were also discussed in this manuscript.

BackgroundAntimicrobial stewardship programs attempting to optimize antibiotic therapy and clinical outcomes mainly focus on inpatient and outpatient settings. The lack of antimicrobial stewardship program studies in the emergency department (ED) represents a gap in tackling the problem of antimicrobial resistance as EDs treat a substantial number of upper respiratory tract infection cases throughout the year. ObjectiveWe intend to implement two evidence-based interventions: (1) patient education and (2) providing physician feedback on their prescribing rates. We will incorporate evidence from a literature review and contextualizing the interventions based on findings from a local qualitative study. MethodsOur study uses a quasi-experimental design to evaluate the effects of interventions over time in the EDs of 4 public hospitals in Singapore. We will include an initial control period of 18 months. In the next 6 months, we will randomize 2 EDs to receive 1 intervention (ie, patient education) and the other 2 EDs to receive the alternative intervention (ie, physician feedback). All EDs will receive the second intervention in the subsequent 6 months on top of the ongoing intervention. Data will be collected for another 6 months to assess the persistence of the intervention effects. The information leaflets will be handed to patients at the EDs before they consult with the physician, while feedback to individual physicians by senior doctors is in the form of electronic text messages. The feedback will contain the physicians’ antibiotic prescribing rate compared with the departments’ overall antibiotic prescribing rate and a bite-size message on good antibiotic prescribing practices. ResultsWe will analyze the data using segmented regression with difference-in-difference estimation to account for concurrent cluster comparisons. ConclusionsOur proposed study assesses the effectiveness of evidence-based, context-specific interventions to optimize antibiotic prescribing in EDs. These interventions are aligned with Singapore’s national effort to tackle antimicrobial resistance and can be scaled up if successful. Trial RegistrationClinicalTrials.gov NCT05451863; https://clinicaltrials.gov/study/NCT05451836 International Registered Report Identifier (IRRID)DERR1-10.2196/50417

Objectives: This study aimed to establish reference values for fetal aortic isthmus blood flow velocity and associated indices during the first trimester, utilizing a novel ultrasonographic technique known as high-definition flow imaging (HDFI). Additionally, the correlation between Doppler profiles of aortic blood flow and key fetal parameters, including nuchal thickness (NT), crown-rump length (CRL), and fetal heartbeat (FHB), was investigated. Methods: A total of 262 fetuses were included in the analysis between December 2022 and December 2023. Utilizing 2D power Doppler ultrasound images, aortic blood flow parameters were assessed, including aortic peak systolic velocity (PS), aortic end-diastolic velocity (ED), aortic time average maximal velocity (TAMV), and various indices such as aortic systolic velocity/diastolic velocity (S/D), aortic pulsatile index (PI), aortic resistance index (RI), aortic isthmus flow velocity index (IFI), and aortic isthmic systolic index (ISI). Concurrently, fetal FHB, NT, and CRL were evaluated during early trimester Down syndrome screening. Results: Significant findings include a positive correlation between gestational age (GA) and PS (PS = 3.75 × (GA) − 15.4, r2 = 0.13, p < 0.01), ED (ED = 0.42 × (GA) − 0.61, r2 = 0.04, p < 0.01), PI (PI = 0.07 × (GA) + 1.03, r2 = 0.04, p < 0.01), and TAMV (TAMV = 1.23 × (GA) − 1.66, r2 = 0.08, p < 0.01). In contrast, aortic ISI demonstrated a significant decrease (ISI = −0.03 × (GA) + 0.57, r2 = 0.05, p < 0.05) with gestational age. No significant correlation was observed for aortic RI (p = 0.33), S/D (p = 0.39), and IFI (p = 0.29) with gestational age. Aortic PS exhibited positive correlations with NT (0.217, p = 0.001) and CRL (0.360, p = 0.000) but a negative correlation with FHB (−0.214, p = 0.001). Aortic PI demonstrated positive correlations with CRL (0.208, p = 0.001) and negative correlations with FHB (−0.176, p = 0.005). Aortic TAMV showed positive correlations with NT (0.233, p = 0.000) and CRL (0.290, p = 0.000) while exhibiting a negative correlation with FHB (−0.141, p = 0.026). Aortic ISI demonstrated negative correlations with NT (−0.128, p = 0.045) and CRL (−0.218, p = 0.001) but a positive correlation with FHB (0.163, p = 0.010). Conclusions: Power Doppler angiography with Doppler ultrasound demonstrates the ability to establish accurate reference values for fetal aortic blood flow during the first trimester of pregnancy. Notably, aortic PS, TAMV, and ISI exhibit significant correlations with NT, CRL, and FHB, with ISI appearing more relevant than IFI, PS, TAMV, and FHB. The utilization of HDFI technology proves advantageous in efficiently detecting the site of the aortic isthmus compared to traditional color Doppler mode in early second trimesters.

The identification of distinct charge transport features, deriving from nontrivial bulk band and surface states, has been a challenging subject in the field of topological systems. In topological Dirac and Weyl semimetals, nontrivial conical bands with Fermi-arc surface states give rise to negative longitudinal magnetoresistance due to chiral anomaly effect and unusual thickness dependent quantum oscillation from Weyl-orbit effect, which were demonstrated recently in experiments. In this work, we report the experimental observations of large nonlinear and nonreciprocal transport effects for both longitudinal and transverse channels in an untwinned Weyl metal of SrRuO_{3} thin film grown on a SrTiO_{3} substrate. From rigorous measurements with bias current applied along various directions with respect to the crystalline principal axes, the magnitude of nonlinear Hall signals from the transverse channel exhibits a simple sinα dependence at low temperatures, where α is the angle between bias current direction and orthorhombic [001]_{o}, reaching a maximum when current is along orthorhombic [11[over ¯]0]_{o}. On the contrary, the magnitude of nonlinear and nonreciprocal signals in the longitudinal channel attains a maximum for bias current along [001]_{o}, and it vanishes for bias current along [11[over ¯]0]_{o}. The observed α-dependent nonlinear and nonreciprocal signals in longitudinal and transverse channels reveal a magnetic Weyl phase with an effective Berry curvature dipole along [11[over ¯]0]_{o} from surface states, accompanied by 1D chiral edge modes along [001]_{o}.

Link prediction aims to predict the potential existence of links between two unconnected nodes within a network based on the known topological characteristics. Evaluation metrics are used to assess the effectiveness of algorithms in link prediction. The discriminating ability of these evaluation metrics is vitally important for accurately evaluating link prediction algorithms. In this study, we propose an artificial network model, based on which one can adjust a single parameter to monotonically and continuously turn the prediction accuracy of the specifically designed link prediction algorithm. Building upon this foundation, we show a framework to depict the effectiveness of evaluating metrics by focusing on their discriminating ability. Specifically, a quantitative comparison in the abilities of correctly discerning varying prediction accuracies was conducted encompassing nine evaluation metrics: Precision, Recall, F1-Measure, Matthews correlation coefficient, balanced precision, the area under the receiver operating characteristic curve (AUC), the area under the precision-recall curve (AUPR), normalized discounted cumulative gain (NDCG), and the area under the magnified receiver operating characteristic. The results indicate that the discriminating abilities of the three metrics, AUC, AUPR, and NDCG, are significantly higher than those of other metrics.

This article presents the findings of a study conducted in Singapore that examined the use of oral antivirals (OAVs) among older adults with COVID-19 in primary care during the Omicron waves. The study revealed that a small percentage of older adults received OAVs, with nirmatrelvir-ritonavir being the most commonly prescribed medication. The study also identified factors such as primary care characteristics and socioeconomic status (SES) indicators that influenced the likelihood of receiving OAVs. The authors emphasize the importance of addressing disparities in OAV access among older adults and socioeconomically disadvantaged groups. They recommend targeted efforts to improve access for individuals with lower SES. [Extracted from the article]