Browse Articles

Genetic surveillance of first- and second-line drug-resistant isolates of Mycobacterium tuberculosis in Peru

Tuberculosis (TB) remains a critical public health crisis in Peru, which bears the highest multidrug-resistant TB (MDR-TB) burden in the Americas. The objective of this study was to conduct a nationwide genetic surveillance of first- and second-line drug-resistant Mycobacterium tuberculosis isolates in Peru to characterize their structural and geographic distribution using a multilocus genotype approach. We analyzed 38,339 valid results from first- and second-line line probe assays (LPA 1L, GenoType MTBDR plus v2; and LPA 2L, GenoType MTBDR sl v2) routinely collected between 2019 and 2022 by the Peruvian National Institute of Health. First-line (G1) and second-line (G2) multilocus genotypes were generated by concatenating specific hybridization banding patterns across resistance-associated loci. Additionally, targeted next-generation sequencing was performed on a stratified proportional sample of 170 isolates exhibiting “inferred” resistance genotypes, defined by a missing wild-type signal without a corresponding mutant probe, to elucidate their underlying mutational profiles. Resistance genotypes were identified in 13.5% and 11.8% of LPA 1L and LPA 2L results, respectively. The genotypic landscape was highly concentrated: 13 dominant G1 genotypes and 19 dominant G2 genotypes accounted for over 85% of their respective resistant cohorts. Structurally, these dominant genotypes mainly carried globally successful, canonical mutations (e.g., katG S315T1, rpoB S450L). Geographically, dominant genotypes were heavily consolidated within the hyper-endemic central coastal axis (Lima, Callao, and Ica) and the Amazonian department of Ucayali, maintaining highly stable temporal frequencies. Conversely, heteroresistance and complex multi-mutational patterns were exclusively restricted to low-frequency rare and orphan genotypes. Targeted sequencing of inferred patterns successfully expanded the national catalog of resistance variants, identifying non-canonical determinants (e.g., inhA g-17t, gyrB T500N) and preventing false-positive resistance calls driven by synonymous mutations. This large-scale mapping demonstrates that Peru’s drug-resistant TB epidemic is characterized by the widespread consolidation of a restricted number of canonical multilocus genotypes. Integrating targeted sequencing with routine molecular screening is essential to resolve unclassified hybridization patterns and optimize epidemiological management in high-burden settings.

In-depth characterization of the CaV2.2-knockout mouse line

Abstract The voltage-gated calcium channel Ca V 2.2 is predominantly located in neuronal synapses, where it plays a role in pain signaling and neurotransmitter release. Furthermore, Ca V 2.2 is important during early central nervous system development, as it is subsequently replaced by other calcium channels. A number of mouse lines with disrupted Ca V 2.2 channels have been developed through the utilization of a gene-targeting vector. The Ca V 2.2-deficient mice primarily exhibited reduced anxiety-linked behavior and response to pain stimuli. In a previous study, we observed hyperactivity and seizures in Ca V 2.2-knockout mice. Given the absence of prior descriptions of these characteristics, an in-depth characterization was conducted. This characterization included longitudinal behavioral studies, as well as histological, proteomic, and metabolomic analyses. Irrespective of the frequency with which testing was conducted, a variety of behaviors were observed (e.g., hyperactivity and increased exploratory behavior) in comparison with wild-type mice. The frequency and severity of the performed tests demonstrated a positive correlation with the magnitude of the difference in molecular markers between Ca V 2.2-knockout and wild-type mice. Seizures were observed but were not common. These results suggest that the Ca V 2.2-knockout mouse lines are susceptible to repeated stress stimuli during experimental studies. The mice are characterized by hyperactivity, explorative behavior, and sometimes experience seizures.

Quantifying institutional gender inequality in contemporary visual art

A distributionally-robust bayesian adaptive EWMA chart for joint surveillance of lognormal process location and scale

Reliability surveillance of safety-critical systems often involves monitoring positively skewed characteristics, such as failure rates, repair times, or material degradation paths, which are robustly modeled by the lognormal distribution. We propose a Distributionally-Robust Bayesian Adaptive EWMA (DR-BAEWMA) framework for the joint surveillance of the log-scale mean and variance under practical model and information uncertainty. Decisively departing from standard Bayesian charts that assume a perfectly specified likelihood, our architecture integrates a distributional-robustification layer using Wasserstein ambiguity sets to protect online estimates against heavy-tailed contamination and misspecified sensor noise. Operating on the log scale, the method treats process health as a latent variable within a non-stationary state-space formulation, decoupling true signals from instrumentation noise via variance-inflation surrogates derived from distributionally robust optimization (DRO) duality results. Decision-theoretic point estimates under both symmetric squared-error loss (SELF) and asymmetric Linex loss (LLF) are incorporated to support risk-sensitive monitoring priorities integrated into the alarm thresholding. We present an adaptive sampling approach that minimizes a principled cost-delay objective to estimate the optimal inspection effort online in order to account for practical problems. Robust univariate and multivariate alarms are provided by a scalar Max statistic and a multivariate Mahalanobis intensity; control limits are obtained by nested Monte Carlo calibration to guarantee that the framework maintains its specified in-control average run length ( A R L 0 ) under ambiguity and variable information density. Extensive simulation across steady-state, polluted, and cross-distributional regimes demonstrates a significantly reduced worst-case detection time as compared to conventional Bayesian and frequentist EWMA approaches. An industrial semiconductor hard-bake case study is used to illustrate implementation, robustness diagnostics utilizing the information ratio, and the effectiveness of adaptive maintenance-on-demand bursts. For real-time monitoring in safety-critical engineering applications, the framework offers an operationally tractable and mathematically rigorous instrument.

Beyond the procedure: a game-theoretic analysis of multilevel determinants shaping doctor-patient engagement after angioplasty

Time to give hydration breaks the red card? What science says about keeping cool

Climatic reach of small-scale turbulence in the ocean interior

Horn trace element profiles of managed rhinoceros species and comparisons to matched livers and wild African rhinoceros horns

Rhino horn is composed of keratin which contains numerous minerals and metals that may provide insight into the species’ environment and health. Our goals were to identify horn trace elements that differ according to sex, species, and continent, and those that reflect liver loads. Samples from 82 horns representing (male.female): 25.16 black rhino, 13.16 white rhino, 6.3 greater one-horned (GOH) rhino, 0.1 Sumatran rhino, and 2.0 undetermined were analyzed for 14 trace elements: arsenic, barium, cadmium, chromium, cobalt, copper, iron, lead, manganese, mercury, molybdenum, selenium, thallium, and zinc. A subset of matched liver tissues (n = 21) also was analyzed for up to 12 of the elements. Horn trace element concentrations did not differ by sex ( p  ≥ 0.05), but several were impacted by species and continent. Copper concentrations in white rhino horn trended higher compared to those measured in black rhino horn ( p  = 0.051), whereas selenium and molybdenum concentrations were higher in black rhino horn compared to those in white rhino horn ( p  < 0.05), and cobalt was higher in black rhino horn compared to GOH rhino horn ( p  < 0.05). Horns from Africa (n = 7) were higher in arsenic and barium and lower in copper and zinc ( p  < 0.05) compared to those from the United States (n = 52). Both arsenic and selenium were positively correlated with matched liver tissue values; arsenic across all species (Spearman’s p  = 0.017, rho = 0.659) and selenium within black rhinos ( p  = 0.004, rho = 0.790). Rhino horn trace element concentrations differed by species, and preliminarily between continents, reflecting population trends in element status, but most were not significantly correlated to individual liver loads.

Identification of PDE10A binding ligands as potential therapeutics for the Parkinson’s disease through a computational approach

Author Correction: Mitochondrial adaptor TRAK2 activates and functionally links opposing kinesin and dynein motors

Association of systemic immune-inflammatory index with stress urinary incontinence in U.S. Adults: NHANES 2007–2016

Background The aim of this study is to explore the association between the systemic immune-inflammatory index (SII) and stress urinary incontinence (SUI). Methods We used information obtained from the National Health and Nutrition Examination Survey (NHANES) that was conducted between 2007 and 2016. The weighted multivariate logistic regression model was used in order to evaluate the relationship that exists between the SII index and the SUI measurement. In addition, a technique from the field of smooth curve fitting was used to investigate the linear connection that exists between these variables. In order to determine whether or not the SII index and SUI relationship remained stable across a variety of demographic strata, subgroup analyses were carried out. Results The research had a grand total of 20,849 individuals. After full adjustment for confounders, each 1-unit increase in log₁₀(SII) was associated with a 29.7% increase in the odds of SUI (OR=1.297, 95%CI 1.028–1.636, P = 0.032). Categorizing the SII index into quartiles revealed that even in the highest SII quartile, there remained a significant positive association with SUI when compared to the lowest quartile (OR =1.177, 95%CI 1.013–1.368, P  = 0.038). Furthermore, an augmented correlation between alcohol consumption and SUI was detected among drinkers compared to non-drinkers ( P  < 0.05). Conclusions Higher systemic inflammatory burden reflected by SII is statistically significantly associated with increased odds of SUI in the U.S. adult population, though the effect size is small; this association is particularly prominent in alcohol drinkers.

Simulation and experimental validation of spent nuclear fuel cask shields

The rise of computer chips — and the race to control them

Self-reconfiguring modular robotic boats

A multi-product, multi-period vaccine supply chain network planning with injection centers and storage conditions

This study develops a mixed-integer linear programming model for a multi-product, multi-period vaccine supply chain network that incorporates injection centers and heterogeneous storage conditions, including cold and ultra-cold refrigeration. The model captures key operational decisions such as distribution center location, vaccine allocation, and storage configuration under capacity and demand constraints, while ensuring no shortage at injection centers. To efficiently solve large-scale instances, a tailored genetic algorithm (GA) is proposed. The main achievements of this research are as follows. First, the proposed model provides an integrated framework that simultaneously considers multi-vaccine characteristics and storage requirements within a three-tier supply chain. Second, computational experiments demonstrate that the GA achieves high-quality solutions with very small optimality gaps compared to exact solutions obtained by GAMS for small and medium-sized problems. Third, the results show that while exact methods become computationally inefficient or infeasible for large-scale instances, the GA remains robust and capable of producing near-optimal solutions within reasonable computational time. Finally, sensitivity analysis confirms the consistency and validity of the model, showing that total cost increases logically with demand and cost parameters. These findings highlight the effectiveness and scalability of the proposed approach and demonstrate its applicability as a decision-support tool for policymakers and healthcare planners in managing complex vaccine distribution systems, particularly during large-scale public health emergencies.

Construction and empirical study of a safety risk assessment index system for sports venues based on regional disaster system theory

Universities are relying on AI-detection software to catch cheating. How well do the programs work?

Deep Learning Predicts Dissimilar DNA-DNA Binding and Engineers Hyperconnected Networks

Perceptions of plastic pollution among inland fishery stakeholders in a subtropical reservoir

Plastic pollution is becoming a serious problem in freshwater ecosystems, impacting the livelihoods of people who rely on inland fisheries. Although plastic waste is widely discussed around the world, limited research has explored how local fishery stakeholders perceive pollution, particularly in Southern Africa. As such, using semi-structured interviews, the current study assessed the awareness, concerns, and solution perspectives of three different stakeholder groups, i.e., commercial fishers (CF), recreational fishers (RF), and fishmongers (FM) around Nandoni Dam, a subtropical reservoir in Limpopo Province, South Africa. Thirty participants, i.e., 10 per stakeholder, were interviewed, and our results showed that 96.7% of all stakeholders were aware of plastic pollution, yet 86.7% had limited understanding of microplastics. Perceptions of the impacts of plastic pollution varied across groups, with visitors (CF = 60%; RF = 60%; FM = 66.7%) and local residents (CF = 20%; RF = 20%; FM = 11.1%) being linked as a source of plastic pollution around Nandoni Dam. Willingness to participate in reducing plastic pollution was high across stakeholders (CF = 90%; RF = 90%; FM = 70%), with the majority emphasising the need for local municipal involvement and community engagement during clean-up activities and awareness initiatives. These findings highlight the need for targeted environmental education, and enhanced community-municipal collaboration to improve awareness and support collective action against plastic pollution in inland fisheries. Strengthening these actions could promote sustainable fisheries management, protect inland waters, and improve the well-being of the people who rely on these waters for food, income, and daily activities.

Vibration control of a variable-size beam supported manipulator system based on nonlinear energy sink

Abstract This study addresses vibration control of a gradually varying-size beam supported manipulator system (VBSMS) under on-orbit assembly conditions, achieved by incorporating a nonlinear energy sink (NES) consisting of a cubic nonlinear spring in parallel with a linear spring. A dynamic model of the coupled system is developed, and the frequency and amplitude responses are obtained using the harmonic balance-alternating frequency/time (HB-AFT) method in conjunction with the arc-length continuation technique. A composite optimization objective is formulated, which considers both the suppression ratio of the maximum steady-state response and a supplementary indicator that evaluates the overall performance of the absorber by capturing the severity of the vibration amplification and the extent of the affected region. A parametric analysis was subsequently conducted, leading to the proposal of optimal design guidelines for the NES parameters. Focusing on the response amplitude over a selected frequency range, the analysis yields optimal design criteria that minimize the steady-state amplitude of the beam throughout the assembly process, thereby offering practical guidance for absorber design in VBSMS.