Search Results (52,845)

Background/Objectives: Seasonal waves of respiratory viruses—including SARS-CoV-2, influenza A virus (IAV), and respiratory syncytial virus (RSV)—continue to pose a global health burden and highlight the need for antiviral agents that are effective, safe, broadly active, affordable, and widely accessible. Current interventions are limited by the need for their early administration, the risk of resistance, their costs, and the restricted availability in large parts of the world. For certain natural products, such as European black elderberry (Sambucus nigra L.) fruit extract (ElderCraft^®; EC) and the seaweed-derived sulfated polymer iota-carrageenan (IC), antiviral activities against respiratory viruses, particularly IAV and SARS-CoV-2, have previously been shown. Here, we assessed the antiviral activity of IC and an anthocyanin-standardized EC extract against SARS-CoV-2, IAV, and RSV, either as monotherapy or in multiple-dose combinations. Methods: MDCKII cells were infected with IAV_PR8, human Calu-3 lung epithelial cells with the SARS-CoV-2 Omicron variant, and HEp-2 cells with RSV (A2 strain). Inhibitors were administered either by pre-incubation of cell-free virions prior to infection or, in separate time-of-addition experiments, during or post-infection. Viral replication was quantified by qRT-PCR or intracellular immunostaining. Cytotoxicity was evaluated using a neutral red uptake assay. Results: Most intriguingly, both EC and IC are able to neutralize virions derived from SARS-CoV-2, IAV, or RSV extracellularly in a dose-dependent manner. Notably, EC and IC alone exhibited strong anti-RSV activity, which was not reported previously. Most importantly, combined treatment with IC and EC caused a pronounced synergistic antiviral effect against the tested viruses, as confirmed by the Bliss independence model, without any detectable impact on cell viability. Finally, solutions prepared from matrix-standardized mono- or combi-lozenges, containing IC and/or EC in high or low doses, reproduced the antiviral and synergistic combination effects observed with the pure compounds. Conclusions: In summary, these findings support further development of EC and IC as a topically accessible, virion-neutralizing combination (e.g., lozenges) to provide additional protection against major respiratory viruses and potentially strengthen pandemic preparedness. Full article

Background: Cervicofacial actinomycosis is an uncommon chronic bacterial infection that can mimic neoplasia or granulomatous disease because of its infiltrative presentation. Diagnosis is often delayed, particularly in pregnant patients in whom imaging and invasive procedures may be limited. Case report: A 25-year-old woman at 14 weeks of gestation presented with a multiple-fistulized cervical mass. The lesion was initially diagnosed as a cutaneous furuncle in a private dermatology practice and treated with topical therapy, resulting in only transient improvement. Two weeks later, multiple fistulizations developed, prompting consultation in the emergency department. ENT assessment and ultrasound raised suspicion of cervical actinomycosis versus fistulized tuberculous lymphadenitis. Considering the pregnancy, drainage of the collection was performed under local anesthesia and empiric antibiotic therapy with amoxicilin-clavulanic acid was started. Microbiological confirmation of Actinomyces (Schaalia) georgiae led to infectious disease evaluation that established a long-term antibiotic therapy while monitoring fetal safety. Progressive clinical improvement was observed, with complete resolution after three months. The pregnancy progressed without complications and fetal morphology remained normal under therapy. Conclusions: This case illustrates the diagnostic complexity of cervicofacial actinomycosis caused by A. georgiae during pregnancy, representing the first such report in the current literature, and emphasizes the need for a multidisciplinary approach. Full article

The evaluation of biodiversity is an essential tool for conservation, management of natural resources, and assessment of ecosystem functioning. Choosing an appropriate and understandable diversity metric is critical to ultimately make better decisions and apply more sustainable resource management. However, biodiversity metrics are numerous, and care must be taken when using them. So, should one consider all these metrics to obtain the right information? If not, how should one choose? This paper aims to demonstrate the importance of understanding and selecting the appropriate diversity metrics to reach accurate conclusions. We simulated theoretical plant communities for which calculations of different biodiversity metrics were carried out to understand why and how to use them. We explored Richness, Evenness and Disparity components of biodiversity using both scales of diversity partitioning (i.e., alpha and beta diversity). In doing so, a decision tree is proposed to select diversity metrics according to user objectives. We also suggest an add-in term if alpha metrics are calculated with subsamples to better reflect biodiversity. Finally, we recommend that when dealing with ecosystem functioning or conservation concerns, species-dependent metrics should be used, as they reflect Disparity. However, there is a critical need to increase knowledge and data availability on species traits or phylogeny to be able to better analyze Disparity. Full article

Social determinants of health (SDoH) are non-medical factors shaped by the socioeconomic status of individuals or communities that influence the onset and progression of diseases and affect their outcomes. We have narratively analyzed the most important findings relating chronic kidney disease (CKD) and SDoH, evaluating the following items: (i) medical care and social determinants of health, (ii) socioeconomic risk for kidney disease at the individual level and (iii) socioeconomic risk for kidney disease at the population level. SDoH can be categorized by how they influence a person’s daily life. Individual factors include personal lifestyle choices such as smoking habits, alcohol consumption, and how a patient spends their non-working time. Community factors include structural elements such as average household income, educational attainment, employment rates, and the quality of the surrounding physical environment. Research consistently shows that a low socioeconomic status is a primary driver of poor clinical outcomes. While healthcare systems vary globally, the negative impact of socioeconomic deprivation on CKD patients remains a constant. Disadvantaged patients experience a faster loss of renal function, and there is a significantly higher incidence of cardiovascular events and mortality compared to those with financial stability. Financial hardship often leads to a “double burden,” where the struggle to afford care triggers a decline in both physical health and mental well-being. To improve patient care, it is essential to raise awareness among healthcare providers regarding the profound impact of these social factors. More precise data and thorough research are needed to fully understand these associations and develop targeted interventions. Full article

The Basel Accords refer to a series of international banking regulatory frameworks developed by the Basel Committee on Banking Supervision to strengthen the stability and resilience of the global banking system. Introduced as Basel I, Basel II, and Basel III, these accords establish minimum capital requirements, risk management standards, and supervisory principles for internationally active banks. Their primary purpose is to reduce the risk of bank failure, promote financial stability, and enhance consistency in banking regulation across jurisdictions. The Basel III framework and its 2017 Final Reforms represent the most advanced stage of this regulatory evolution, addressing weaknesses revealed by the global financial crisis and subsequent regulatory experience. Banking institutions play a central role in economic development, making their stability essential. The global financial crisis that began in 2007 exposed significant weaknesses in existing regulatory frameworks and led to the failure of several major banks, despite the earlier establishment of Basel I and Basel II by the Basel Committee on Banking Supervision. These shortcomings prompted the development of the Basel III framework as a direct response to the crisis. However, early criticisms of the initial Basel III Accord, particularly regarding variability in risk-weighted assets, reliance on internal models, and opportunities for regulatory arbitrage, led the Basel Committee to issue the Basel III Final Reforms in 2017, which represented a substantial upgrade to the post-crisis regulatory architecture. This study reviews the evolution of the Basel Accords; examines the key components of Basel I, Basel II, and Basel III; and analyses the enhancements introduced through the Basel III Final Reforms. It also considers the major arguments and criticisms surrounding these accords, highlighting the persistent challenges of achieving global regulatory consistency. Given the inability of earlier Basel frameworks to prevent bank failures and the fact that many jurisdictions have yet to fully implement the 2017 reforms, the paper underscores the need for ongoing evaluation of international banking regulation as national authorities adapt and refine their supervisory approaches to strengthen financial stability. Full article

Background: Subarachnoid hemorrhage (SAH) has high mortality and disability rates. The timely and precise assessment of SAH severity is of critical importance in predicting life-threatening complications. Several CT-based radiological grading systems have been proposed, but a comprehensive meta-analysis of their inter-rater reliability (IRR) has not been conducted. Methods: This study followed the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Two authors performed a systematic search of original articles in the PubMed database. Methodological quality of the studies was assessed using the Quality Appraisal of Reliability Studies (QAREL). Meta-analyses of Cohen’s kappa and intra-class correlation coefficient (ICC) were performed using R packages “metafor” and “meta”. Results: A systematic literature analysis was performed for twenty articles that met the inclusion criteria. The methodological quality was moderate in 14 of 20 studies; five studies were of low quality. Only eight articles were suitable for meta-analysis. Cohen’s kappa of the binarized Fisher scale was 0.85 (95% CI 0.70–0.93), though it was based on only two studies and 109 patients. The Hijdra scale had an ICC of 0.75 (95% CI 0.29–0.93). The original and modified Graeb scales proposed for the assessment of concomitant intra-ventricular hemorrhage demonstrated ICC of 0.83 (95% CI 0.59–0.94) and 0.93 (95% CI 0.84–0.97), respectively. For other scales, meta-analysis was not possible due to incomplete reporting or single evaluations. Conclusions: The current evidence on IRR of radiological grading scales for SAH is limited, emphasizing the need for further high-quality research to validate their reliability and clinical applicability. Full article

Background: Gut microbiome-derived metabolites, particularly short-chain fatty acids (SCFA) and tryptophan derivatives, are central mediators of the gut–brain axis. This ex vivo study assessed how nutritional interventions impact such metabolites during early life, a critical period for neurodevelopment. Methods: The effects of galacto-oligosaccharides (GOS), nutrient blends (vitamins, minerals and amino acids) and their combinations were evaluated in the gut microbiomes of infants (2–4 months, n = 6) and young children (2–3 years old, n = 6) using the ex vivo SIFR^® technology. Results: Baseline microbiome composition was age-dependent, with infants displaying lower α-diversity and greater interpersonal variability. After ex vivo incubation, nutrient blends increased the propionate/butyrate ratio and branched-chain fatty acids in young children and elevated several B-vitamins and amino acid-derived metabolites, including indole-3-carboxaldehyde, imidazoleacetic acid and pipecolinic acid. Combining nutrient blends with GOS exhibited potential synergistic effects on propionate (infants) and 2-hydroxyisocaproic acid (HICA, both age groups). GOS strongly stimulated Bifidobacteriaceae and increased metabolites linked to bifidobacterial metabolism like acetate, HICA, N-acetylated amino acids, aromatic lactic acids and acetylagmatine; in young children, butyrate and γ-aminobutyric acid (GABA) also increased. Conclusions: Combinations of GOS with nutrient blends impacted microbiome-derived metabolites associated with the gut–brain axis, with potential synergistic increases of metabolites with emerging roles in neurodevelopment, including GABA, acetylagmatine and HICA. Despite shared bifidogenic effects, differences between age groups indicate that microbiome maturity may influence responses to nutritional intervention. Future clinical studies are needed to determine whether these metabolite changes translate into neurodevelopmental benefits in vivo. Full article

Background and Objectives: The prioritization of intensive care unit (ICU) admission following surgery for cancer is controversial. There is an urgent need to develop an appropriate clinical predictive model to aid in making ICU admission decisions after surgery. Materials and Methods: Four model strategies were used to build post−operative ICU admission predictive models: SVM, Catboost, ANN, and KNN. Internal verification was used for model evaluation at a ratio of 7:3. The area under the curve (AUC) value, calibration plots, and decision curve analysis were employed to assess the performance and clinical usefulness of the model. Results: The ICU group of patients with cancer who underwent surgery showed better prognosis for disease−free survival (DFS, p = 0.0008) and overall survival (OS, p < 0.0001). Cox multivariate analyses validated that lower baseline RBC, LDH, and CRP; higher baseline ALB, LCR, and lower post−operative LDH; higher post−operative HCT and ApoA−I; and higher fluctuating MCH independently predicted better DFS and OS (all p < 0.05). The AUC of the Catboost model was superior to that of the other models in the training cohort and internal validation cohort. Calibration plot and decision curve analysis indicated that the Catboost model possessed the best performance, with higher clinical utility, compared with other models. Conclusions: ICU admission after surgery was associated with superior survival in patients with cancer. The cost−effective Catboost model has promising clinical application but requires further clinical evaluation. Unravelling the cellular and molecular foundation of ICU admission might enable the development of more practical life−support strategies. Full article

Background/Objectives: Women and girls, particularly in sub-Saharan Africa, face high risks for both HIV and unintended pregnancy. Inconsistent condom use underscores the need for new multipurpose prevention technologies (MPTs) that combine HIV pre-exposure prophylaxis (PrEP) and contraception. Long-acting (LA) injectables are especially promising. To this end, an LA cabotegravir (CAB)/medroxyprogesterone acetate (MPA) in situ-forming implant (ISFI) has been developed. We report pharmacokinetic (PK) modeling to characterize CAB and MPA disposition and absorption to support the development of the MPT ISFI. Methods: Female BALB/c mice received single intravenous (IV) or subcutaneous (SQ) bolus doses of CAB or MPA. Sparse plasma samples were collected (~3 mice/timepoint) for PK analysis by LC-MS/MS. Noncompartmental analysis assessed SQ bioavailability. Macroparameterized compartmental PK models were fit to IV data to derive unit impulse responses (UIRs) for each drug. Results: CAB and MPA exhibited 61% and 42% bioavailability, respectively. CAB IV PK was best described by a two-compartment model with macroconstant parameters: A = 16,621 ng/mL, α = 4.52 h⁻¹, B = 30,206 ng/mL, and β = 0.053 h⁻¹. MPA IV PK was also best described by a two-compartment model, with A = 2506 ng/mL, α = 10.5 h⁻¹, B = 439 ng/mL, and β = 0.65 h⁻¹. These values define the UIR for CAB and MPA. Conclusions: Our IV PK modeling framework fully characterizes CAB/MPA disposition in mouse, enabling downstream deconvolution-based estimation of absorption from controlled-release formulations. This provides a foundation for in vitro–in vivo correlation, facilitating preclinical evaluation of long-acting formulations such as ISFIs. Full article

This study evaluated how a partial substitution of pea protein isolate (PPI) with brewer’s spent grain (BSG) or barley rootlets (BRs) affects high-moisture meat analogues (HMMAs). PPI was substituted with 10% and 20% with BSG or BRs, respectively. Extrudates were produced on a co-rotating twin-screw extruder at maximum temperatures of 140 °C and 160 °C. Extrudates were assessed for colour, moisture, firmness and fibre morphology. Furthermore, the technofunctional and nutritional properties of the raw materials were determined. Extrudates with BSG produced the darkest colour, whereas PPI and BR formulations exhibited the lightest. A stronger reddish tint was observed at 160 °C, while the colour within the yellow–blue spectrum was largely temperature-independent. Firmness was generally higher at 160 °C, consistent with lower end-product moisture. Side stream addition lowered protein content and weakened fibre formation, with the effect most pronounced for BRs. Overall, formulation was the dominant factor influencing lightness, while temperature modestly increased redness and firmness. Preliminary sensory evaluation supported these trends. Extrudates produced at 140 °C were perceived as having a more fibrous structure. Higher substitution levels resulted in a weaker, more crumbly texture. With respect to the environmental assessment, a 20% replacement of PPI with BRs or BSG reduced overall environmental impacts by up to 19% and climate impacts by up to 16%. With regard to the novel food status, the EU Novel Food Status Catalogue classifies BSG as not novel, whereas BRs are not novel only when used in food supplements. Any other food uses, other than as, or in, food supplements, might considered to be novel and consequently might need to be authorised under the novel food regulation framework prior to market placement. Full article

The rapid integration of artificial intelligence (AI) into educational systems is transforming how student performance is analysed and how educational policies are informed by large-scale data. Within this context, machine learning techniques are increasingly used to identify patterns associated with academic success and educational inequality. However, the use of predictive algorithms in education also raises important questions regarding transparency, fairness, and potential algorithmic bias. This study examines the predictive performance and fairness implications of machine learning models used to identify academically resilient students using data from the Programme for International Student Assessment (PISA) 2022. The analysis is based on a dataset containing more than 600,000 student observations across multiple national education systems. Academic resilience is operationalised following the OECD framework, identifying students who belong to the lowest quartile of the socioeconomic status index (ESCS) within their country while simultaneously achieving mathematics performance in the top quartile (PV1MATH). A predictive framework incorporating six supervised learning algorithms—Logistic Regression, Random Forest, Gradient Boosting, XGBoost, LightGBM, and CatBoost—was implemented. The modelling pipeline includes data preprocessing, missing value imputation, class imbalance correction using SMOTE, and model evaluation through multiple classification metrics, including accuracy, F1-score, and the area under the ROC curve (AUC). In addition, fairness diagnostics are conducted to examine potential disparities in prediction outcomes across gender groups, while feature importance analysis and SHAP-based explanations are used to interpret the contribution of key predictors. The results indicate that ensemble-based models achieve the highest predictive performance, particularly those based on gradient boosting techniques. At the same time, the analysis reveals that socioeconomic status, migration background, and school repetition constitute the most influential predictors of academic resilience. Although gender displays relatively low predictive importance, measurable differences in positive prediction rates across gender groups suggest the presence of potential algorithmic disparities. These findings highlight the importance of integrating fairness evaluation, transparency, and interpretability into educational data science workflows. The study contributes to ongoing discussions on the responsible use of artificial intelligence in education by emphasising the need for governance frameworks capable of ensuring that algorithmic systems support equity-oriented educational policies. Full article

Intensive aquaculture induces severe environmental stress and disease susceptibility in Pacific white shrimp (Litopenaeus vannamei). Cannabidiol (CBD) offers significant potential as a bioactive stress-mitigating additive. This study evaluated the effects of dietary CBD supplementation (0, 10, 20, 40, and 80 mg/kg) on the growth, intestinal microecology, and stress tolerance of juvenile L. vannamei over an 8-week feeding trial, followed by a combined chronic ammonia and acute hypoxia challenge. Moderate CBD supplementation (10–40 mg/kg) significantly promoted growth, minimized feed conversion ratios, and enriched muscle eicosapentaenoic (EPA) and docosahexaenoic acids (DHA). Furthermore, CBD restructured the intestinal microbiota by suppressing opportunistic pathogens and enriching beneficial taxa. Under combined stress, moderate CBD prolonged the median lethal time (LT₅₀) by up-regulating hypoxia-inducible factor 1-alpha (hif-1α) and heat shock protein 70 (hsp70) transcription and boosting systemic antioxidant capacity to neutralize lipid peroxidation. Conversely, the highest dose (80 mg/kg) induced metabolic exhaustion and hepatopancreatic toxicity, evidenced by drastically elevated serum transaminases and diminished stress tolerance. Conclusively, dietary CBD exerts a classic biphasic effect in L. vannamei. Inclusion at 10–40 mg/kg safely promotes the best comprehensive effects on growth, immune homeostasis, and environmental resilience within the concentration range tested in this study, whereas excessive administration provokes severe metabolic burden, highlighting the critical need for strict dosage regulation. Full article

Estrogen deficiency is an established risk factor for menopausal brain dysfunctions in women. Urgent exploration of drugs is needed to improve estrogen deficiency-related brain dysfunctions without the side effects of estrogen supplements. Three-month-old rats had bilateral ovariectomy (OVX) performed and were treated with emodin (EMO, 80 mg/kg/day) and 17 β-estradiol (EST, 0.5 mg/kg/day). Brain functions were evaluated by cognition and emotion-related behavioral tests. Levels of glucagon-like peptide-1 (GLP-1) and estrogen in blood, mRNA levels of estrogen receptor (ER) α, ERβ, GLP-1 receptor (GLP-1R), proprotein convertase subtilisin/kexin type 1 (PCSK1) and proglucagon (proGCG) in intestinal segments, and brain ERα and GLP-1R levels were evaluated. Contractions of isolated intestinal segments were recorded. Additionally, an ERβ antagonist, PHTPP (200 μg/kg/day), was used to clarify the role of ERβ. EST and EMO significantly ameliorated cognition deficit and depressive behaviors in OVX rats, and reduced neuronal loss and synaptic abnormalities in the hippocampus and prefrontal cortex. The blood GLP-1 levels of sham operation rats (sham, 3.09 pg/mL), EMO-treated (2.57 pg/mL) and EST-treated OVX rats (2.64 pg/mL), were higher than that of OVX rats (1.03 pg/mL). EMO had no effect on the blood estrogen level. Furthermore, EMO up-regulated mRNA levels of ERβ in ileum, colon, and cerebral GLP-1R level, while EST increased mRNA levels of ERβ in colon and cerebral ERα level. In vitro intestinal segment spontaneous contraction tests revealed that EMO reduced contraction amplitudes in isolated intestinal segments from OVX rats, with the ileum and proximal colon showing greater sensitivity to EMO. The ileum and colon segments from OVX rats were less sensitive to EST as compared to those of normal rats. Upon PHTPP intervention, the up-regulated intestinal mRNA levels of ERβ, PCSK1, proGCG, blood GLP-1 level by EMO, and the beneficial effects of EMO in abnormal behaviors of OVX rats were significantly inhibited. Overall, it was found that EMO up-regulated blood GLP-1 level via intestinal Erβ-dependent mechanism and increased brain GLP-1R level, which may be involved in the neuroprotection of EMO in OVX animals. Full article

Background/Objectives: Hypothyroidism, including subclinical hypothyroidism, may affect mental health in children and adolescents through disturbances of neurotransmission and dysregulation of the hypothalamic–pituitary–thyroid and stress axes. Anxiety disorders are common in this population and frequently coexist with somatic symptoms overlapping those of hypothyroidism, complicating diagnosis and treatment. This study aimed to evaluate the association between levothyroxine treatment for hypothyroidism and the need for psychiatric interventions in children and adolescents with anxiety disorders. Methods: A retrospective cohort study was performed using data from the TriNetX global research network. Patients aged 5–18 years with diagnoses of hypothyroidism (ICD-10: E03) and anxiety disorders (ICD-10: F41) were included. Two propensity score–matched cohorts were analysed: patients treated with levothyroxine (n = 1861) and untreated patients (n = 1861). Outcomes included psychiatric hospitalisations, use of selective serotonin reuptake inhibitors and tricyclic-like antidepressants, frequency of psychiatric and psychotherapeutic consultations, and the occurrence of suicidal ideation and self-harm. Results: Levothyroxine treatment was associated with lower odds of SSRI use (OR = 0.58; p < 0.001), fewer psychiatric consultations (OR = 0.48; p < 0.001), and lower recorded use of psychotherapy (OR = 0.75; p = 0.029). Suicidal ideation and self-harm were recorded less frequently in the treated group (OR = 0.53; p = 0.001). No significant differences were observed in psychiatric hospitalisation rates. Use of tricyclic-like antidepressants was uncommon and did not differ significantly between groups. Conclusions: Among children and adolescents with comorbid anxiety disorders, levothyroxine treatment for hypothyroidism is associated with lower recorded utilization of certain psychiatric services and lower recorded rates of suicidal ideation and self-harm. Due to the retrospective design, causal inferences cannot be made, and the findings should be considered hypothesis-generating, requiring confirmation in prospective studies with standardised psychiatric outcome measures. Full article