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SARS-CoV-2 NSP14 inhibitor exhibits potent antiviral activity and reverses NSP14-driven host modulation

Generalized Navier-Stokes model for ballistic and tomographic electrons

Association between obesity and psychological distress in the Chilean population during the COVID-19 pandemic: Social Wellbeing Survey 2021

The COVID-19 pandemic has exacerbated obesity and mental health problems, particularly anxiety and depression. Both conditions share common risk factors, suggesting a possible bidirectional relationship. This study analyses the association between obesity and psychological distress in the Chilean population during the pandemic. A secondary analysis of data from the 2021 Social Wellbeing Survey (n = 10395) was conducted using logistic regression models to examine the relationship between obesity and the presence of severe psychological distress. The prevalence of obesity and severe psychological distress was higher in women (31.85% and 7.66%) than in men (25.1% and 3.6%). Individuals with obesity had a higher risk of severe psychological distress OR 1.3 (95% CI 1.05–1.60), as did women OR 2.16 (95% CI 1.83–2.65). Conversely, individuals with severe psychological distress had a higher risk of obesity OR 1.4 (95% CI 1.19–1.71), as did women OR 1.4 (95% CI 1.26–1.51) and individuals couple/married OR 1.3 (95% CI 1.17–1.46). Additionally, higher educational levels are a protective factor for both obesity and severe psychological distress. A higher prevalence of obesity and psychological distress was observed in women and variations by age. Obesity and severe psychological distress behaved as mutual risk factors, suggesting a possible bidirectional relationship. These findings support the need for mental health interventions for at-risk groups.

Most long-lived contrails form within cirrus clouds with uncertain climate impact

Abstract Contrail-cirrus is considered the most important component of aviation-induced climate impact. However, a reliable assessment requires better understanding of their radiative effects. Analysis of seven years of humidity observations by instrumented passenger aircraft shows that conditions promoting long-lived contrails are fulfilled most often in regions already covered by subvisible or visible cirrus: ~90% over the Northern midlatitudes and almost 100% in the Southeast Asian subtropics, approximately equally distributed among visible and subvisible cirrus clouds. A conceptual analysis shows that subvisible cirrus and clear-sky cover ~10% of the cruise altitude over Northern midlatitudes ( < 2% in the subtropics) and contrails within these regions are expected to cause additional warming. However, most contrails in the thicker, visible cirrus, only slightly enhance the cirrus warming effect or possibly reverse it to cooling. Our results suggest that potential flight rerouting concepts for contrail avoidance need to consider cirrus cloud coverage in addition to ice-supersaturation.

Optimising bifacial dye-sensitized solar cells with graphene-enhanced TPT configuration photoanode for operational stability

Abstract Bifacial Dye-sensitized solar cells (bifacial DSSCs) are a promising low-cost and with promising light absorbance alternative to conventional DSSCs, known for their potential for transparency and customizability to be integrated into building-integrated photovoltaic (BIPV). This study explores enhancing efficiency and stability in bifacial DSSCs by integrating graphene into the bifacial configured photoanode. Graphene was incorporated into titanium dioxide ( $$\hbox {TiO}_2$$ ) photoanodes using a modified Ti-Nanoxide (T/sp) commercial paste, and powder type (P25) configurate as (T/sp-P25-T/sp) in tri-layer (identified optimal structure to maximizing bifacial light harvesting in our previous study) with Concentrations of 0.05%, 0.1%, and 0.2% graphene were tested. The structural, optical, and electrical properties of the materials were characterised using field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDS), Raman spectroscopy, ultraviolet-visible (UV-Vis) spectroscopy, Tauc plots, current-voltage (J-V) measurements, and electrochemical impedance spectroscopy (EIS). The incorporation of 0.1% graphene resulted in the highest initial power conversion efficiency (PCE) of 11.09% under combined front and back illumination at the 4th day of testing, indicating improved electron transport and stability. Over a period of ten days, the performance of these cells remained significantly superior compared to those with pure $$\hbox {TiO}_2$$ . These results highlight the potential of graphene-enhanced TPT-configured photoanodes for improving both the efficiency and durability of bifacial DSSCs, particularly in applications such as building-integrated photovoltaics.

Resampling methods for class imbalance in clinical prediction models: A scoping review protocol

Introduction Class imbalance—where clinically important “positive” cases make up less than 30% of the dataset—systematically reduces the sensitivity and fairness of medical prediction models. Although data-level techniques, such as random oversampling, random undersampling, SMOTE, and algorithm-level approaches like cost-sensitive learning, are widely used, the empirical evidence on when these corrections improve model performance remains scattered across different diseases and modelling frameworks. This protocol outlines a scoping systematic review with meta-regression that will map and quantitatively summarise 15 years of research on resampling strategies in imbalanced clinical datasets, addressing a key methodological gap in reliable medical AI. Methods and analysis We will search MEDLINE, EMBASE, Scopus, Web of Science Core Collection, and IEEE Xplore, along with grey literature sources (medRxiv, arXiv, bioRxiv) for primary studies (2009–31 Dec 2024) that apply at least one resampling or cost-sensitive strategy to binary clinical prediction tasks with a minority-class prevalence of less than 30%. There will be no language restrictions. Two reviewers will screen records, extract data using a piloted form, and document the process in a PRISMA flow diagram. A descriptive synthesis will catalogue the clinical domain, sample size, imbalance ratio, resampling strategy, model type, and performance metrics where 10 or more studies report compatible AUCs. A random-effects mixed-effects meta-regression (logit-transformed AUC) will be used to examine the effect of moderators, including imbalance ratio, resampling strategy, model family, and sample size. Small-study effects will be assessed with funnel plots, Egger’s test, trim-and-fill, and weight-function models; influence diagnostics and leave-one-out analyses will evaluate robustness. Since this is a methodological review, formal clinical risk-of-bias tools are optional; instead, design-level screening, influence diagnostics, and sensitivity analyses will enhance transparency. Discussion By combining a comprehensive conceptual framework with quantitative estimates, this review aims to determine when data-level versus algorithm-level balancing leads to genuine improvements in discrimination, calibration, and cost-sensitive metrics across various medical fields. The findings will help researchers select concise, evidence-based methods for addressing imbalance, inform journal and regulatory reporting standards, and identify research gaps such as the under-reporting of calibration and misclassification costs, which must be addressed before balanced models can be reliably trusted in clinical practice. Systematic review registration INPLASY202550026.

Complex de novo structural variants are an underestimated cause of rare disorders

Abstract Complex de novo structural variants (dnSVs) are crucial genetic factors in rare disorders, yet their prevalence and characteristics in rare disorders remain poorly understood. Here, we conduct a comprehensive analysis of whole-genome sequencing data of 12,568 families, including 13,698 offspring with rare diseases, obtained as part of the UK 100,000 Genomes Project. We identify 1,870 dnSVs, constituting the largest dnSV dataset reported to date. Complex dnSVs (n = 158; 8.4%) emerge as the third most common type of SV, following simple deletions and duplications. We classify 65% of these complex dnSVs into 11 subtypes. Among probands with dnSVs (n = 1,696), 9% exhibit exon-disrupting pathogenic dnSVs associated with the probands’ phenotype. Notably, 12% of exon-disrupting pathogenic dnSVs and 22% of de novo deletions or duplications previously identified by array-based or whole-exome sequencing methods are found to be complex dnSVs. We also find distinct genomic properties of de novo deletions depending on the parent of origin. This study highlights the importance of complex dnSVs in the cause of rare disorders and demonstrates the necessity of specific genomic analysis to avoid overlooking these variants.

Quantum resilient security framework for privacy preserving AI in Apple MM1 on device architecture

Designing interventions to scaffold emotional awareness, beliefs and action tendencies

I demonstrate – via a novel intervention comprising evaluation of emotional contrasting cases and expressive writing – improvements in emotional awareness, beliefs and action tendencies among lower secondary students ( N  = 71). Relative to their pre-intervention profiles, students were able to better identify and articulate emotions, as well as showcase a more nuanced understanding of both positive and negative emotions and their respective roles in learning. While the intervention successfully reduced avoidance behaviors towards unpleasant emotions and encouraged a more balanced appraisal of emotional experiences, it also highlighted certain limitations – for instance, students showed little change in their acceptance of unpleasant emotions, suggesting further support may be needed to fully utilize emotions as learning tools.

Harnessing microbial-derived metabolites in the urinary tract to prevent infection induced catheter encrustation

Abstract Proteus mirabilis is a predominant cause of catheter associated urinary tract infection (CAUTI), and a key virulence factor is its urease enzyme which can increase urine pH and form urinary stones, causing catheter blockage and facilitating bacteremia. The only FDA approved urease inhibitor, acetohydroxamic acid (AHA), has side effects that limit its clinical use, necessitating new approaches to target urease activity. We previously discovered that common urinary tract colonizers modulate P. mirabilis urease activity via secreted small molecules. In this study, we conduct a metabolomics analysis of six modulatory bacterial species to reveal urease-dampening metabolites. Of 31 candidate metabolites, seven reproducibly decrease P. mirabilis urease activity. All seven metabolites dampen urease activity in other urease-positive bacterial species, suggesting conserved targets. Six of the metabolites act via mixed inhibition of the urease enzyme. One metabolite, D-imidazole lactate, exhibits a non-competitive mechanism of urease inhibition along with antimicrobial activity and repression of the urease operon in P. mirabilis . Metabolite combinations with AHA demonstrate synergistic activity and prevent catheter encrustation in an in vitro model for CAUTI. Prophylactic use of urease dampening metabolites with AHA could improve the efficacy of antimicrobial treatment against catheter biofilms.

Variations in blood levels of the anti-fusogenic endogenous retroviral protein suppressyn are associated with fetal growth outcome in preeclampsia

Comparison of volumetric responses to different corticosteroid administration methods in IgG4-related ophthalmic disease

Purpose To analyze the clinical and volumetric responses to different corticosteroid administration methods for IgG4-related ophthalmic disease (IgG4-ROD). Methods The medical records of patients with bilateral lacrimal gland (LG) enlargement diagnosed with IgG4-ROD through unilateral LG biopsy between January 2011 and January 2022 were retrospectively reviewed. Clinical signs and the non-biopsied LG volume across three administration routes were compared: oral prednisolone (Pd), intravenous (IV) methylprednisolone (methylPd), and local triamcinolone (TA) injection. Radiological relapse was defined as the first instance of failure to satisfy the radiological response criteria, i.e., a post-treatment volume of <1.0 cm 3 or a post-treatment to pre-treatment volume ratio of <35%. Results Among the 28 patients, eight, ten, and ten received oral Pd, IV methylPd, and local TA injection, respectively. No significant differences were observed between the groups in terms of the baseline characteristics. Ophthalmic adverse effects were not observed in any patient. Kaplan–Meier survival analysis revealed that the 2-year radiological relapse-free survival in the IV methylPd group (80.0%) was higher than that in the oral Pd group (37.5%, p = 0.036) but comparable with that in the local TA group (100.0%, p = 0.886). The median post-treatment to pre-treatment volume ratio in the IV methylPd group (35.4%) was significantly lower than that in the oral Pd group (75.0%, p = 0.042) but comparable with that in the local TA injection group (38.5%, p = 0.321) one year after treatment. Conclusion Compared with oral Pd, IV methylPd yielded better and more sustained radiological responses in patients with LG-involving IgG4-ROD. Local TA injection was also an effective alternative treatment option.

Reading signatures of supermassive binary black holes in pulsar timing array observations

Abstract Constraining the origin of the nanohertz gravitational-wave background necessitates precise noise modelling to avoid parameter estimation biases. In this work, we find the inferred properties of the putative gravitational wave background in the second data release of the European Pulsar Timing Array to be in better agreement with theoretical expectations under the improved noise model. In particular, our improved noise models show consistency of the background’s strain spectral index with the value of  −2/3, favoring the population of supermassive black hole binaries as the origin of the background. Our results further suggest that the observed gravitational wave emission is the dominant source of the binary energy loss, with no evidence of environmental effects or eccentric orbits. At the reference gravitational wave frequency of yr −1 , we also find a lower power-law strain amplitude of the background than in previous data analyses. This mitigates some of the tensions of the strain amplitude with the expected number density and mass scale of binaries discussed in the literature. Our analysis demonstrates the importance of accurate modelling of radio pulsar pulse profile variations, hierarchical properties of noise across pulsars, as well as noise model averaging, when inferring properties of the gravitational wave background.

Prokaryotic co-occurrence patterns in diverse Indian mangrove ecosystems

In silico identification, high yielding isolation and in vitro validation of 6β-cinnamoyl-7β -hydroxyvouacapen – 5α - ol as a Wnt/β-catenin pathway targeted anti-cancer secondary metabolite of Caesalpinia pulcherrima

Wnt/β-catenin signaling pathway is frequently dysregulated in cancer stem cells (CSCs), a sub population of cancer cell mass that drives tumor proliferation, metastasis, recurrence, and chemoresistance. Despite its therapeutic significance, no clinically approved drugs specifically target this pathway. In the present study, secondary metabolites of the medicinal plant Caesalpinia pulcherrima was computationally screened by molecular docking, dynamics simulation and Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) based free energy calculations to identify potential inhibitors of β-catenin–Tcf/Lef interaction, a key downstream event essential for Wnt/β-catenin signaling. Diterpene metabolite 6β-Cinnamoyl-7β-hydroxyvouacapen-5α-ol (6βCHV) was identified as a potent inhibitor of the pathway along with four previously reported Wnt/β-catenin pathway inhibitors. To validate the results, bioactivity-guided isolation of major active compound was performed using NTERA-2 cells as a cancer stem cell (CSC) model. The isolated compound was spectroscopically characterized and confirmed to be 6βCHV. Anti-proliferative activity assays revealed that 6βCHV suppressed proliferation of breast cancer stem cells (bCSCs) (IC₅₀ = 49.18 µM), NTERA-2 cells (IC₅₀ = 8.92 µM), and highly Wnt-dependent cancer types, including gastric adenocarcinoma (IC₅₀ = 1.90 µM), hepatocellular carcinoma (IC₅₀ = 5.96 µM), and ovarian carcinoma (IC₅₀ = 7.66 µM). 6βCHV upregulated the tumor suppressor gene, p53 while downregulating Wnt target genes, Cyclin D1 and CD44 leading to apoptosis in bCSCs as confirmed by Caspase 3/7 activation. These findings establish 6βCHV as the principal anticancer compound in C. pulcherrima , exerting its effects, at least in part, through Wnt/β-catenin pathway inhibition.

Increasing temperatures affect thoracic muscle performance in Arctic bumblebees

Abstract Increasing temperature beyond a species’ optimum is a major threat to insect biodiversity, particularly in rapidly warming regions such as the Arctic. For cold-adapted pollinators, high temperatures can disrupt physiology and ecosystem services, threatening pollinator populations and plant reproduction. In bumblebees, increased temperature disrupts the physiology of the indirect flight muscles. However, these muscles, which generate the bee’s charismatic buzz, also facilitate key non-flight behaviours including communication, defence, and buzz-pollination, where temperature effects remain unexplored. Here, we assess the thermal performance of non-flight muscle function across 15 Arctic bumblebee species by measuring thorax vibrations during defensive buzzing behaviour. Thorax acceleration is found to peak at an air temperature of 25 °C, declining after this peak as a potential strategy to prevent overheating. Conversely, vibration frequency continues to increase with temperature, and is better explained by thorax temperature than air temperature. Surprisingly, there are no differences in thermal response across species, castes, or temperature habitat specialisations, indicating that non-flight vibrations are similarly susceptible to unfavourable temperatures across bumblebee species. If such findings translate to non-flight buzzing in other contexts, such as buzz-pollination, changes in buzzes have the potential to disrupt key plant-pollinator interactions.

Safety of ribavirin in cockatiels (Nymphicus hollandicus) – a preliminary study

Abstract Viral infections remain a major health concern in psittacine birds, with avian bornaviruses (ABV) causing proventricular dilatation disease (PDD), a chronic and often fatal condition. Ribavirin, a broad-spectrum antiviral drug widely used in human medicine, has shown in vitro (ABV) and in ovo (Newcastle disease virus) efficacy against some avian viruses, but its safety profile in birds is largely unknown. This study aimed to evaluate the safety of prolonged ribavirin administration in healthy cockatiels ( Nymphicus hollandicus ) aged approximately 6 months. The experiment consisted of experimental group (10 cockatiels) and negative control group (10 cockatiels). Ribavirin was administered to the experimental cockatiels according to the following protocol: orally (by gavage at dose 30 mg/kg body weight [BW]/day) two consecutive 28-day courses (course 1 & 2) separated and followed by 14-day recovery periods, then 15 mg/kg BW/day orally and 15 mg/kg BW/day intranasally for 28 days (course 3). The cockatiels were regularly weighed, clinically examined, and blood was collected for hematological and biochemical analyses. No clinical signs of adverse reactions were observed, neither during the therapy nor for 12 weeks after the therapy. BW changed significantly during the experiment, however without any link to ribavirin treatment. Only hematocrit decreased significantly after the ribavirin course 1. Our results indicate that ribavirin at 30 mg/kg BW, administered orally or in combination with intranasal dosing does not appear to cause apparent clinical or laboratory adverse reactions in cockatiels, except for potential alteration of hematocrit which is, however, too mild to be clinically meaningful. This provides an essential first step toward evaluating ribavirin as a therapeutic option for avian viral diseases.

Investigation of accessory navicular in local pre-adolescence children: A longitudinal study with 2-year follow-up—KID Locomo Study

Introduction The accessory navicular (AN) is an accessory ossicle located on the medial side of the navicular bone and is often associated with sports-related overuse injuries during adolescence. However, little is known about the natural history of AN. This study aimed to clarify the natural course of AN, including symptomatic cases, in children through a longitudinal epidemiological investigation. Methods Data from the KID Locomo Study, a prospective cohort study aimed at elucidating musculoskeletal disorders in childhood, were used. Of the 834 children recruited in the 2022 baseline survey, 66 children (109 feet) aged 11–13 years with AN were enrolled in this 2-year longitudinal analysis. The presence of AN was assessed using ultrasonography. Data on sex, age, height, weight, presence of pain at the AN site, laterality, flatfoot (based on footprint analysis), and participation in athletic clubs were collected. The natural history of AN, including painful presentations, was evaluated. Multivariable logistic regression analysis was performed to identify risk factors for non-fusion of the AN with the navicular bone. Results Among the 109 feet with AN at baseline, 38 (34.9%) demonstrated fusion with the navicular bone at the 2-year follow-up. Of the 21 feet with painful AN at baseline, pain had resolved in 15 (71.4%) after 2 years. Multivariable logistic regression analysis revealed that female sex (odds ratio: 3.00; 95% confidence interval: 1.26–7.45; p = 0.01) and higher body mass index (BMI) (odds ratio: 1.20; 95% confidence interval: 1.02–1.43; p = 0.02) were significant risk factors for non-fusion. Conclusions This study provides epidemiological data on the natural history of AN, including symptomatic cases, in children. To our knowledge, this is the first study to report the natural course of painful AN. These findings may offer fundamental insights into prevention and management strategies for painful AN in children.

Hypoxic-ischemic brain injury in neonatal mice sequentially recruits neutrophils with dichotomous phenotype and function

Abstract Neonatal encephalopathy caused by hypoxia-ischemia (HI) leads to a strong neutrophil infiltration. The long-held assumption that neutrophils act exclusively as tissue-damaging cells, is challenged by increasing evidence of a profound neutrophil heterogeneity. Here, we uncovered a pronounced phenotypical and functional diversification of neutrophils in neonatal mice depending on the disease stage. Neutrophil infiltration was biphasic, peaking 1 and 7 days after HI. Early brain-infiltrating neutrophils displayed a hyperactivated phenotype, whereas neutrophils at day 7 exhibited an angiogenic phenotype with high Siglec-F expression. Acute neutrophil depletion protected against neural cell death, associated with decreased hyperactivity in adolescent animals. Delayed neutrophil depletion impaired vascular and oligodendrocyte regeneration, resulting in exacerbated alterations of anxiety-related behavior and myelination deficits. These findings suggest a divergent function of neutrophils, with early neutrophils aggravating tissue damage and late neutrophils contributing to neurological recovery. The disease stage-dependent neutrophil diversification offers new possibilities to identify disease-stage-specific therapeutic targets.

A multivariate approach to identify association between peripheral blood DNA methylation and cerebrospinal fluid biomarkers of Alzheimer disease

Abstract DNA methylation has been shown to play a crucial role in many diseases, including Alzheimer’s disease (AD). Although many studies have correlated DNA methylation in blood samples with risk of clinical AD diagnosis, few have examined links with AD neuropathology. Using data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) study, we investigate the associations between peripheral blood DNA methylation and three AD-associated biomarkers in cerebrospinal fluid: amyloid- $$\beta$$ , phosphorylated tau-181, and total tau using an innovative multivariate approach. In our approach, we first adjusted the methylation values for covariates that have known wide-spread effects on methylation. We then developed and implemented a multivariate penalized model to find associations, jointly, between CSF biomarkers and sets of methylation residuals defined by regions around each gene. These penalized models then selected probes showing associations with one or more CSF biomarkers. We demonstrate, using both simulations and actual data, that our proposed multivariate approach is beneficial for detecting weak signals. We also provide complementary validation using data from the Canadian Longitudinal Study on Aging. Our multivariate strategy has the potential to increase feature selection accuracy among correlated predictors in epigenetic studies.