Browse Articles

Antimalarial potential of curcumin derivatives evaluated through experimental and computational approaches

Development of PBAT films reinforced with SiC/g-C3N4 nanohybrids for enhanced biocompatibility and antibacterial performance

Delayed, transient, lateralized deficits in pattern separation and pattern completion after focal hippocampal irradiation in humans

Is price associated with the quality of medicines? Evidence from active pharmaceutical ingredient testing in Nigeria

Determining the quality of medicines remains a challenge, particularly in low- and middle-income countries, where regulatory oversight and enforcement vary, and resources and infrastructure for quality testing are often constrained. In these settings, price is often used as a proxy for higher-quality medicines, yet empirical evidence supporting this assumption remains scarce. We conducted a mystery shopper survey in over 1,200 retail pharmacies across urban and rural areas in the six geopolitical zones of Nigeria, purchasing one drug sample from a list of twenty branded medicines, including analgesics, antimalarials, antibiotics, antihypertensives, and multivitamins. A sub-sample of the purchased medicines (N = 246) was tested for quality, defined as passing a laboratory test using High-Performance Liquid Chromatography (HPLC) to measure the Active Pharmaceutical Ingredient (API) content of each medicine. Using probit regressions, we examined the extent to which price is associated with quality, controlling for observable pharmacy and drug sample characteristics. A 1% increase in price is associated with a 16.7 percentage point increase in the probability of passing the laboratory test, conditional on other factors. Receiver Operating Characteristic (ROC) analysis shows strong out-of-sample classification performance, with an Area Under the Curve (AUC) of 0.82 for the price-only model, indicating that price alone explains much of the variation in quality. Other results show that medicines organized by brand and displaying visible expiration dates may signal higher quality, while the presence of other observable characteristics (e.g., packaging, storage, display) shows more counterintuitive associations with drug quality in this context. Stratified analyses show that the association between price and quality is particularly strong for analgesics and antibiotics. These findings suggest that price appears to be a reliable signal of medicine quality, whereas other characteristics of pharmacies and drug samples provide weaker and less consistent indicators. This underscores the need for stronger regulatory oversight, greater market transparency, and targeted consumer education to promote safer access to quality medicines.

Correction: Informal care in different European care systems: Effects of caregiving on mental health over time

Development of a competition assay to assess the in vitro fitness of dengue virus serotypes using an optimized serotype-specific qRT-PCR

Background Comparing the in vitro fitness of dengue virus (DENV) isolates is a pivotal approach to assess the contribution of DENV strains’ replicative fitness to epidemiological contexts, including serotype replacements. Competition assays are the gold standard to compare the in vitro replicative fitness of viral strains. Implementing competition assays between DENV serotypes requires an experimental setup and an appropriate read-out to quantify the viral progeny of strains belonging to different serotypes. Methods In the current study, we optimized an existing serotyping qRT-PCR by adapting primer/probe design and multiplexing the serotype-specific qRT-PCR reactions, allowing to accurately detect and quantify all four DENV serotypes. We next developed an in vitro competition assay to compare the replicative fitness of two DENV serotypes in the human hepatic cell line HuH7. Findings The qRT-PCR was specific, and had a limit of detection below 7.52, 1.19, 3.48 and 1.36 genome copies/µL, an efficiency of 1.993, 1.975, 1.902, 1.898 and a linearity (R²) of 0.99975, 0.99975, 0.99850, 0.99965 for DENV-1, −2, −3 and −4, respectively. Challenge of this multiplex serotype-specific qRT-PCR on mixes of viral supernatants containing known concentrations of strains from two serotypes evidenced an accurate quantification of the amount of genome copies of each serotype. Quantification of the viral progeny of each serotype in the inoculum and the supernatant of competition assays using the serotype-specific multiplex qRT-PCR unveiled an enrichment of the supernatant in DENV-1 genome copies, uncovering the enhanced replicative fitness of this DENV-1 isolate. Conclusions This optimized qRT-PCR combined with a relevant cellular model allowed to accurately quantify the viral progeny of two DENV strains belonging to two different serotypes in a competition assay, allowing to determine which strain had a replicative advantage. This reliable experimental setup is adaptable to the comparative study of the replicative fitness of any DENV serotypes.

Development of a floxed Gabbr2 gene allows for widespread conditional disruption of GABBR2 and recapitulates the phenotype of germline Gabbr2 knockout mice

GABBR1 and GABBR2 are widely expressed in the brain and genetic inhibition of their function leads to neurologic dysfunction and premature death in mice. Given that GABBR1 and GABBR2 heterodimerize to form a functional receptor, global knockout of GABBR1 or GABBR2 results in a similar phenotype, characterized by spontaneous epileptiform activity, hyperlocomotor activity, hyperalgesia, impaired memory and premature death. Both GABBR1 and GABBR2 are expressed in a variety of tissues outside the nervous system and GABA-B receptors have been shown to heterodimerize with other class C GPCRs. However, the neurologic consequences of global GABBR1 or GABBR2 knockout mice have made it difficult to study the effects of loss of GABBR function in other organs. While a conditional knockout for GABBR1 is available, the Gabbr2 gene had not been “floxed”. Therefore, we used CRISPR to insert loxP sites into the Gabbr2 locus in mice. These mice are normal at baseline but when bred with mice expressing Cre-recombinase under the control of the ubiquitously expressed Actin gene promoter, Gabbr2 lox/lox mice recapitulate the phenotype of global GABBR2 knockout mice demonstrating alterations throughout the brain, including the cortex, hippocampus and cerebellum. We document abnormal neurological function, increased neuronal cell death, changes in neuronal architecture, and premature death. These mice should be useful tools to study cell type-specific loss of GABBR2 function in the brain and other organs.

Lifetime physical intimate partner violence (pIPV) among Mozambican women: Individual and contextual level factors driving its prevalence

Background Intimate partner violence (IPV) remains a significant public health issue in Mozambique. This study uses data from the 2022–2023 Mozambique Demographic and Health Survey (DHS) to examine the prevalence and sociodemographic determinants of Lifetime IPV among women. Specifically, this study focuses on physical IPV (pIPV), as measured in the Mozambique Demographic and Health Survey (DHS), which does not capture sexual or emotional violence. Methods A nationally representative sample of 4,813 women aged 15–49 was analyzed to assess the prevalence of Lifetime pIPV. Lifetime pIPV was defined as physical violence perpetrated by a current or former partner, by DHS definitions. Logistic regression models were used to identify individual- and contextual-level factors associated with Lifetime IPV. Results Nearly 1 in 4 women (21.92%) reported experiencing physical abuse from a current or former partner in their lifetime. Marital status emerged as a key individual-level determinant, with cohabitating and separated women being at significantly higher odds of experiencing pIPV compared to women who had never been in a union. Educational attainment and current employment were also associated with increased odds of pIPV. Similarly, women who justified physical abuse had higher odds of experiencing pIPV. Additionally, husbands/partners’ alcohol consumption was one of the strongest predictors, nearly tripling the odds of Lifetime pIPV. Finally, the effect modification between marital status and education showed that the effect of marital status on pIPV was further modified by women educational attainment. At the contextual level, provincial disparities were observed, with Cabo Delgado and Manica showing the highest pIPV prevalence, while Inhambane and Gaza had the lowest. Conclusion This study provides updated data on the prevalence of Lifetime pIPV in Mozambique and highlights key individual and contextual factors contributing to pIPV. The findings underscore the need for targeted interventions addressing socio-cultural norms, improving educational opportunities, mitigating male partner’s alcohol consumption, and implementing province-specific strategies to reduce pIPV and enhance women’s safety across Mozambique.

A multi-factor dynamic time series measure for stock correlation analysis

Existing similarity measures in stock correlation analysis often overlook the multidimensional nature of stock data and the dynamics of the time-lag effect (TLE) in phase differences. To address these limitations, this paper proposes a novel method, called Multi-Factor Dynamic Temporal Similarity Measure (MFDTSM). The method introduces an enhanced eXtreme Gradient Boosting (XGBoost) model based on Shapley Additive exPlanations (SHAP) to comprehensively evaluate the influence of stock factors. The proposed method effectively categorizes stocks and reveals the heterogeneity of factor influence by clustering the SHAP values of stock factors. Furthermore, MFDTSM is able to successfully quantify the dynamic rate of phase differences in TLE by constructing the cumulative distance matrix and analyzing the optimal alignment paths of time series data, thereby significantly improving the accuracy of the similarity measure. Empirical analysis is performed using 102 stocks from the communication and financial industries, including 12 key stock factors. The experimental results demonstrate that MFDTSM improves the accuracy of the analysis of industry correlation, linear correlation, and stock correlation pricing by 10%, 16%, and 5%, respectively, over existing methods, which highlight the efficiency and stability of MFDTSM in analyzing complex stock market dynamics.

A novel algorithm for model uncertainty reduction in trapezoidal fuzzy fault tree risk assessment

Intelligent risk assessment in complex systems increasingly relies on methods like trapezoidal fuzzy fault trees. However, conventional techniques often struggle with accurately calculating top-event probabilities and handling model uncertainty, which undermines the reliability of risk evaluations. To address this, we propose a novel algorithm that effectively reduces model uncertainty in trapezoidal fuzzy fault tree analysis. By leveraging the cut-set theorem and operating directly on trapezoidal fuzzy numbers without defuzzification, our approach preserves the completeness of fuzzy information throughout the calculation. The algorithm accommodates three common fault tree logics: OR-only, AND-only, and mixed OR/AND gates. In a case study on liquid ammonia leakage, the method achieved a 45.25% reduction in model uncertainty—surpassing existing approaches, which reached only 36.65%. Results showed 99.40% consistency with benchmark literature, affirming the algorithm’s accuracy. Additional analysis using OREDA field data demonstrated the method’s stability across different system structures and risk levels. To further verify robustness under input uncertainty, we conducted 60 perturbation tests on representative basic events with high, medium, and low failure probabilities. The algorithm exhibited exceptional stability, with output variations remaining below ±1% even under ±15% input perturbations, confirming its suitability for real-world applications where data uncertainties are common. This work offers a reliable and scalable solution for risk assessment in high-stakes industries such as nuclear energy and chemical processing.

Comparison of outcomes between minimally invasive percutaneous bunnell suture and traditional open modified Kessler technique for acute closed achilles tendon rupture: A single-center cohort study

Percutaneous Bunnell repair and open modified Kessler repair remain debated options for acute Achilles tendon rupture (AATR). We retrospectively compared a minimally invasive percutaneous Bunnell technique (Group A) with an open modified Kessler repair (Group B) within a standardized early functional rehabilitation (EFR) protocol at a single center. Fifty-five adults with closed AATR treated between January 2021 and December 2022 were analyzed (Group A, n = 25; Group B, n = 30). Between-group comparisons used Welch t tests for continuous variables and χ² or Fisher exact tests for categorical variables; American Orthopaedic Foot & Ankle Society (AOFAS) and Achilles Tendon Total Rupture Score (ATRS) were assessed at 12 and 24 weeks, with Holm adjustment applied within each scale. Compared with Group B, Group A had shorter operative time (56.6 ± 15.1 vs 68.2 ± 23.2 minutes; mean difference −11.6; 95% CI −22.05 to −1.15; P = 0.030), less intraoperative blood loss (28.4 ± 8.4 vs 74.7 ± 19.4 mL; −46.3; 95% CI −54.22 to −38.38; P < 0.001), and a shorter length of stay (4.8 ± 2.0 vs 6.6 ± 2.9 days; −1.8; 95% CI −3.13 to −0.47; P = 0.009). At 12 weeks, AOFAS favored Group A (+1.36; 95% CI + 0.19 to +2.53; P = 0.047) and ATRS also favored Group A (+1.73; 95% CI + 0.48 to +2.98; P = 0.008). At 24 weeks, AOFAS was not different (+0.51; 95% CI −0.49 to +1.51; P = 0.312), whereas ATRS remained higher in Group A (+2.17; 95% CI + 0.88 to +3.46; P = 0.003). Overall complications were 12.0% vs 26.7% (risk difference −14.7%; 95% CI −34.10 to +7.20; P = 0.310); no sural nerve injuries occurred. Within an EFR framework, percutaneous Bunnell repair provided superior perioperative efficiency with comparable safety and modest, sub-MCID functional advantages, supporting confirmation in larger prospective studies.

Correction: Targeted modulation of MMP9 and GRP78 via molecular interaction and in silico profiling of Curcuma caesia rhizome metabolites: A computational drug discovery approach for cancer therapy

A disproportionality analysis of FDA adverse event reporting system (FAERS) events for filgotinib

Background Although filgotinib, a selective Janus kinase 1 inhibitor, has been increasingly applied in the treatment of inflammatory diseases, its comprehensive safety profile remains insufficiently characterized. Using data from the FAERS database covering Q1 2014 to Q2 2024, this study attempts to analyze adverse event signals linked to filgotinib and provide guidance for the safe and sensible clinical usage of filgotinib. Methods From Q1 2014 to Q2 2024, information on adverse drug events (ADEs) associated with filgotinib was gathered. The reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) were among the signal detection methods that were employed for analysis following data normalization. Results Filgotinib was shown to be the main suspected medication in ADE reports, exposing 103 preferred terms (PTs) in 17 system organ classes (SOCs). Infections, gastrointestinal disorders, and musculoskeletal and connective tissue disorders were the most commonly reported adverse effects. Additionally, atrial fibrillation, alopecia, elevated serum creatinine, blood creatinine increased, pulmonary embolism, epididymitis, respiratory failure, and osteopenia were identified as potential disproportionate reporting signals for filgotinib, although these were not listed in the official drug label. Notable significant signals included large intestine erosion (ROR 2186.05, 95%CI (ROR) : 1015.94–4703.86, PRR 2176.18, 95%CI (PRR) : 1014.64–4667.42), mesenteric arterial occlusion (ROR 1832.17, 95%CI (ROR) : 897.68–3739.48, PRR 1822.71, 95%CI (PRR) : 896.17–3707.20), repetitive strain injury (ROR 1149.27, 95%CI (ROR) : 363.16–3637.01, PRR 1147.05, 95%CI (PRR) : 363.24–3622.15), oligoarthritis (ROR 755.02, 95%CI (ROR) : 310.74–1834.54, PRR 752.59, 95%CI (PRR) : 310.60–1823.51), and periostitis (ROR 676.03, 95%CI (ROR) : 319.36–1431.06, PRR 672.98, 95%CI (PRR) : 318.97–1419.87). The subgroup analysis identified obvious sex and age-specific trends in filgotinib-related adverse reactions, emphasizing a higher risk of renal disorders in females, a preponderance of gastrointestinal events in males, and age-dependent trends involving mesenteric occlusion, increased serum creatinine, and immunoglobulin reduction. Conclusion While filgotinib demonstrates therapeutic efficacy, it is associated with a range of potential adverse events, underscoring the need for vigilant clinical monitoring. Particular attention should be given to gastrointestinal, cardiovascular, respiratory, and metabolic complications.

A large-scale trial in Chennai, India shows effective reduction of Anopheles stephensi populations by the biolarvicide Natular

Biolarvicides present an environmentally safer alternative to chemical larvicides, demonstrating selectivity against target species. However, the available options for biolarvicide use in mosquito control remain limited. This study aimed to assess the effectiveness of three formulations of the biolarvicide Natular, namely the 20.6% Emulsifiable Concentrate (EC), 2.5% G30 granular, and 7.48% tablet (DT) for direct application, against Anopheles stephensi in large-scale field trials conducted in Chennai, India. When the 7.48% DT formulation was applied at a rate of 1 tablet per 200 L in overhead tanks with An. stephensi breeding sites, on an average, led to a > 90–100% reduction in An. stephensi larval and pupal density for a duration of 8–9 weeks in rainy, winter and summer seasons. Similarly, the 2.5% G30 formulation, at a concentration of 0.074 mg (AI)/L in overhead tanks, impressively suppressed An. stephensi larval and pupal density by 91–100% for 4–5 weeks in three seasons. The application of the 20.6% EC formulation at 0.073 mg (AI)/L in overhead tanks achieved a remarkable 100% reduction in larval and pupal density for 2 weeks in all seasons. The Natular 7.48% DT formulation is well-suited for An. stephensi larval control at 1 tablet per 200 L with an 8-week application interval. The 2.5% G30 formulation is recommended at 0.074 mg (AI)/L at 4-week intervals. Meanwhile, the 20.6% EC formulation can effectively control An. stephensi at 0.073 mg (AI)/L with fortnightly application intervals. These Natular formulations serve as potent biolarvicides, offering a valuable tool for An. stephensi control within the Integrated Vector Management (IVM) program.

Gender and mental health of adolescents: A conceptual framework developed in a Delphi study

Objective Adolescence is one of the most neglected developmental phases, yet there are few phases in the life course when gender socialisation is as intense. So far, no framework or theory exists that theoretically conceptualises gender norms, gender attitudes and mental health outcomes. To address this gap, we aim to develop a conceptual framework that illustrates the interplay of key constructs in the gendered pathways of health, using the Delphi technique. Methods We carried out a Delphi study enrolling an international panel of 21 experts from different disciplines, with 43% of the respondents completing all three survey rounds. We asked the experts to identify core constructs (first round), suggest operationalisations of the constructs (second round), and to hypothesise about their relationships (third round). Items were included, excluded or adapted according to experts’ feedback. A 70% threshold was used for consensus. Results The panelists consented on the following core constructs: gender norms (social environment), sex assigned at birth, gender attitudes, gender roles, competencies, and gender identity to the mental health of adolescents. They further consented on gender approaches, namely the intersectional, multidimensional and multilevel approach as well as the power relations lens. The operationalisation of the constructs in round two led to the inclusion of variables forming an intersectional lens and four social environment levels: the household, community, political and digital level. In round three, the experts formed 14 hypotheses about the relationships between the core constructs. Conclusion The derived conceptual framework links the interplay of six key constructs, four gender approaches and four social environment levels to adolescent mental health. Future research should validate and apply the hypothesised relationships between the constructs to disentangle the gendered pathways to (mental) health in adolescence.

Validation of the Rosenberg Self-Esteem Scale among the Iranian adult population: A cross-sectional study

Background Self-esteem refers to an individual’s overall sense of self-worth, which plays a crucial role in their well-being. One of the most commonly used instruments to measure this concept is the Rosenberg Self-Esteem Scale (RSES), which has been translated and psychometrically validated in numerous cultures and languages to date. Therefore, this study aimed to assess the psychometric properties of the Persian version of the RSES in the Iranian adult population. Methods This cross-sectional validation study was conducted following the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines in Shahroud city, northeastern Iran. A total of 533 adults from this city who spoke Persian and were literate were included in the study using convenience sampling. After translating and culturally adapting the RSES in accordance with World Health Organization (WHO) guidelines, face and content validity were assessed using both qualitative and quantitative methods. Additionally, construct validity was evaluated through exploratory and confirmatory factor analysis. Reliability was also determined by calculating Cronbach’s alpha coefficient, McDonald’s omega coefficient, composite reliability (CR), and intraclass correlation coefficient (ICC). Results The face and content validity of all items were confirmed through both qualitative and quantitative methods. Based on the results of the exploratory factor analysis using polychoric correlations and robust weighted least squares (WLSMV) estimation, the Persian version of this scale consists of two factors: (1) Positive self-esteem and (2) Negative self-esteem, which account for 59.1% of the total variance of the scale. All goodness-of-fit indices in the confirmatory factor analysis also supported this model (CMIN/ df  = 2.29, RMSEA = .049, CFI = .981). These two factors showed acceptable internal consistency and stability, as evidenced by Cronbach’s alpha coefficients (.828 and .801), McDonald’s omega coefficients (.833 and .810), composite reliabilities (.820 and .796), and intraclass correlation coefficients (.838 and .875). Conclusion The findings of the current study showed favorable psychometric properties of the Persian version of the RSES for measuring self-esteem in the Iranian adult population.

Lexical feature analysis of Chinese informed consent forms based on the information entropy methods: A paired study of minor and their guardian’ version

High-quality informed consent forms (ICFs) are crucial to facilitate effective communication between researchers and patients. However, the complex and specialized terminologies in ICFs often result in biased or late interpretations, thus hindering the ability to make decisions in line with their own will. Therefore, evaluating the readability of ICFs is an important task for Institutional Review Boards (IRBs) and regulatory agencies. This study proposes the use of information theory methods, including Shannon entropy and its extension—Rényi entropy ( α values = 0, 0.5, and 1.5), as a set of comparisons, to quantify the lexical characteristics of Chinese ICFs, for either minors or their guardians. The Shannon entropy and Rényi entropy values of minor-version ICFs were significantly lower than those of guardian-version ICFs. The Shannon entropy and Rényi entropy with α  = 1.5 of the ICFs for minors show no significant differences compared to those of the sixth-grade textbooks, while the Rényi entropy with both α  = 0 and 0.5 shows no significant differences compared to the ninth-grade textbooks. This study utilized information entropies to assess lexical features of ICFs, as a pilot study to validate the feasibility of implementing Shannon and Rényi entropies to evaluate readability in Chinese ICFs.

Editorial Note: Measurement and driving factors of carbon productivity in China’s provinces: From the perspective of embodied carbon emissions

Zinc ion increases the effectiveness of phosphorus in agricultural soils through microbial solubilization

Phosphorus (P) is a key limiting factor for crop growth in agroecosystems, where soil microorganisms and mineral ions are essential for P turnover and mobilization. However, it is unclear how mineral ions affect microbially-mediated phosphorus cycling. In this study, 15 soil samples were collected from a typical agricultural area in Southwest China with a complex mineral composition. Soil phosphorus levels, microbial phosphorus genes, and typical soil mineral ions were subsequently analyzed to determine the mechanism of soil mineral ions on phosphorus cycling. The results showed that Zn 2+ was the main driver of P mobilization in the soils, and its accumulation led to changes in the expression of two important phosphorus genes, gcd and phnW . Ecological clusters dominated by Actinobacteria and Proteobacteria, phyla that carry the gcd gene, directly contributed to P activation through mutualistic interactions. phnW encodes a phosphorylglycolide hydrolase enzyme involved in phosphate accumulation, and its transcription may enhance the soil available phosphorus (AP) content by promoting enzymatic carbon-phosphorus bond cleavage, a process influenced by microbes in the phyla Proteobacteria, Gemmatimonadetes, Actinobacteria, and Acidobacteria. Herein, our work provides a new perspective on the mechanism of P cycling and improve P effectiveness in agricultural soils.

Hybrid machine learning models for enhanced arrhythmia detection from ECG signals using autoencoder and convolution features

Automated arrhythmia detection from electrocardiogram (ECG) signals is crucial and important for the early treatment of cardiac disease (CD). In this investigation, eight machine-learning models have been developed to identify improved ECG arrhythmia detection using two standard datasets (MIT-BIH Arrhythmia and the ECG 5000). In the first phase, two types of feature extraction schemes (autoencoder) and (Convolution) are used to obtain relevant features from ECG samples and subsequently, eight ML models are successfully trained and tested to find various performance matrices through simulation-based experiments. Then, the TOPSIS and mRMR ranking schemes are used to rank the ML models and identify the three best-performing models recommended for real-time arrhythmia detection. In this study, it is observed that for the same number of input features, models based on autoencoder features offer enhanced performance compared to those based on convolutional features. It is generally observed that the top identified hybrid model, Autoencoder Features with Neural Network (AEFNN) on the MIT-BIH dataset, achieves an accuracy of 97.96% and on the ECG5000 dataset, the hybrid model achieves an accuracy of 99.20%. This proposed model can be utilized for the early detection of arrhythmia, particularly in large-scale healthcare screening programs, thereby aiding in timely diagnosis and intervention. In this study, two types of features are used to model development in future work. Other relevant important features can be extracted from ECG samples, and those features can be used to develop accurate models to identify Heart disease.