Search Results (56)

Background/Objectives: Streptococcus pyogenes (Group A Streptococcus, GAS) is a major human pathogen that causes a wide spectrum of diseases. While mild infections like pharyngitis and impetigo are common, severe and invasive infections, though less frequent, pose significant health risks, particularly in children. In recent years, the re-emergence of hypervirulent GAS strains has heightened global concern. Nowadays, the absence of universally accepted guidelines compels clinicians to rely on a combination of clinical judgment, microbiological data and available evidence to manage these infections effectively. Our aim was to assess the current management of invasive GAS (iGAS) infections in Italy and the variability in therapeutic and preventive approaches. Methods: A web-based current clinical practice survey about invasive and severe GAS infections was designed according to the Checklist for Reporting of Survey Studies (CROSS) methodology and circulated among the members of the Italian Society of Pediatric Infectious Diseases (SITIP). Results: The survey reveals that while many practices are commonly shared among clinicians, particularly regarding first-line therapies (penicillin or ceftriaxone depending on the infection site), significant uncertainties remain, particularly about the use of combined antibiotic regimens and supportive treatments. The use of combined antibiotic regimens was considered appropriate as first-line therapy for STSS, NF and brain abscesses. Clindamycin was the preferred agent for combination with beta-lactam for most infections, except for brain abscesses, where linezolid was favored. However, there was disagreement regarding the optimal timing for de-escalation to beta-lactam monotherapy. Responses varied widely concerning the indications and dosages for IVIG, as well as the use of corticosteroids. Conclusions: Addressing the burden of invasive GAS (iGAS) infections in children requires enhanced surveillance, early recognition, prompt treatment and preventive strategies. Further work to increase surveillance, e.g., developing national registries, and to standardize the management of the disease, e.g., developing country-specific guidelines, is essential to build solid evidence on the most effective approaches. Full article

Earthquakes remain among the most destructive natural hazards, causing severe loss of life and property in seismically active regions such as Nepal. Major events such as the 1934 Nepal–Bihar earthquake (M_w 8.2), the 2015 Gorkha earthquake (M_w 7.8), and the 2023 Jajarkot earthquake (M_L 6.4) have repeatedly exposed the vulnerability of Nepal’s built environment. In response, the Ready-to-Use Detailing (RUD) guideline (NBC 205:2024) was introduced to provide standardized structural detailing for low-rise reinforced concrete buildings without masonry infill, particularly for use in areas where access to professional engineering services is limited. This study was motivated by the need to critically assess the structural performance of buildings designed according to such rule-of-thumb detailing, which is widely applied through owner–builder practices. Nonlinear pushover analyses were carried out using finite element modelling for typical configurations on soil types C and D, under peak ground accelerations of 0.25 g, 0.30 g, 0.35 g, and 0.40 g. The response spectrum from NBC 105:2020 was adopted to determine performance points. The analysis focused on global response, capacity curves, storey drift, and hinge formation to evaluate structural resilience. The maximum story drift for the linear static analysis is found to be 0.56% and 0.86% for peak ground acceleration of 0.40 g, for both three and four-storied buildings. Also, from non-linear static analysis, it is found that almost all hinges formed in the beams and columns are in the Immediate Occupancy (IO) level. The findings suggest that the RUD guidelines are capable of providing adequate seismic performance for low-rise reinforced concrete buildings, given that the recommended material quality and construction standards are satisfied. Full article

This study addresses the critical need for region-specific ground motion selection methods in the Xi’an area by proposing a novel Peak Ground Acceleration (PGA)-based target spectrum, developed through the relationship between PGA and response spectrum attenuation. Based on the relationship between the peak ground acceleration (PGA) and the attenuation of the response spectrum, a PGA target spectrum applicable to the Xi’an area was studied. Using the PGA and code-specified Standard Spectrum as the target spectrum, earthquake records were selected and their amplitudes scaled by employing various methods, including fundamental period scaling, average spectral ratio scaling, equal spectral intensity scaling, minimum squared error scaling, and minimum moving average scaling. Based on the 70 ground motion records obtained from the five scaling methods applied to the two target spectra (grouped into 10 distinct sets), the dynamic time history analysis was conducted for a frame-core tube structure; the effects of different scaling methods and different target spectra were investigated on the dispersion of floor displacement, interstory drift ratio and interstory shear. The results show that the spectral value of the PGA target spectrum at the peak is 54% higher than that of the code-specified spectrum, while in the long-period range, the acceleration values of the PGA target spectrum are comparatively smaller, only about 50% of those of the code spectrum. For structural response, the code target spectrum is more conservative compared with the PGA target spectrum, and the minimum moving average method is the least sensitive to different target spectra. This work offers preliminary insights that may contribute to the optimization of ground motion selection in regionally tailored seismic design practices. Full article

Evaluating the spectral properties of cocoa beans based on their fermentation state (fermented, in a poor state, unfermented) is essential for ensuring their quality in the cocoa industry. This study examined the spectral response of beans in the range of 380 nm to 780 nm using the Konica-Minolta CS-2000 spectrophotometer comes from Dijon, France, a device designed to measure the spectrum of objects and sources in the visible range. Different spectral band selection methods have been applied to identify the most discriminating wavelengths for their classification. Several techniques were used: ANOVA, F-score, Lasso, Linear Discriminant Analysis (LDA), Mutual Information, and Partial Least Squares (PLS). A band selector voting process was implemented to determine standard wavelengths identified using the different methods. The selected spectral bands were then leveraged to train classification models, including Random Forest, SVM, and XGBoost. The results show that a restricted subset of wavelengths allows for effective class separation, thereby improving model performance. Among the approaches tested, ANOVA and F-score combined with Random Forest achieved an accuracy of 92.59%, while F-score and Mutual Information coupled with SVM and voting associated with SVM obtained an accuracy of 96.30%. These feature selection methods have effectively reduced dimensionality while maintaining high classification accuracy. These results open up promising prospects for the automation of quality control of cocoa beans, thus contributing to the optimization of industrial processes. Full article

Mycobacterium tuberculosis (Mtb) vaccines are designed to prevent infection, prevent reactivation of latent infection, and/or provide adjuvant therapy to standard TB treatment for active Mtb. Emerging vaccine technologies include reverse vaccinology, DNA and RNA vaccines, subunit vaccines, and multi-epitope vaccines. Currently, many different types of vaccine candidates are in clinical trials, though, to date, BCG remains the only approved Mtb vaccine. Mtb has a complex genome with numerous antigens, but not all are equally effective in eliciting immunity, so a critical challenge is the selection of antigens and epitopes that are most likely to induce a long-term, broad-spectrum protective immune response. Multi-epitope vaccines (MEVs) represent a new event horizon in vaccine development. Bioinformatic computer modeling is being used to maximize efficacy and minimalize adverse effects. Although no multi-epitope vaccines have proceeded to in vivo clinical trials, three candidate MEVs have made it through in silico tests. Multi-epitope vaccine candidate PP13138R, containing 13 HTL epitopes, 13 CTL epitopes, and 8 B cell epitopes in addition to both TLR2 and TLR4 agonists, aims to elicit a broad immune response that could address both active and latent Mtb infection. Similarly, immunoinformatic data were used to design and validate another MEV candidate based on the biomarker PE_PGRS17 with four B cell, nine HTL, and six CTL linked epitopes, with a griselimycin sequence as the adjuvant. A third novel prophylactic and therapeutic MEV was developed that targets Ag85A, AG85B, ESAT-6, and CFP-10 proteins with 12 CTL, 25 HTL, and 21 LBL epitopes with a CpG adjuvant. Full article

This study presents a comprehensive comparative analysis of a hospital located in Costa Rica, examining the performance of sliding pendulum isolators under different international seismic design standards. The standards considered in this research include the U.S. code ASCE/SEI 7-22 and various European standards, namely EN 15129, EN 1337, and EN 1998-1. The case study employs the Equivalent Linear Analysis method, as prescribed by Eurocode 8, alongside the Equivalent Lateral Force procedure from ASCE/SEI 7-22. The seismic action is defined using the acceleration response spectrum from the Costa Rican Seismic Code (CSCR-10, 2010). However, certain limitations must be acknowledged when applying the equivalent linear analysis approach. One key restriction is that the isolation system must be modeled with equivalent viscoelastic behavior, which is feasible for sliding pendulum isolators. Despite being a simplified method, this approach proves valuable in the initial selection and optimization of an isolation system, particularly for practitioners. It is recommended that this method be applied as a preliminary step before performing more advanced nonlinear analyses. After determining the optimized parameters for the friction pendulum system, the detailed design of the isolators will be conducted following the provisions of the selected international standards. This process includes verifying compliance with key performance requirements such as self-recentering capability, type testing procedures, deformation verification, and partial load verification on the concrete pedestal, where the isolators are assumed to be installed. These requirements ensure that the isolation system meets the necessary structural performance criteria, providing reliable seismic protection while adhering to international engineering best practices. Full article

Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability and a major genetic contributor to autism spectrum disorder. It is caused by a CGG trinucleotide repeat expansion in the FMR1 gene, resulting in gene silencing and the loss of FMRP, an RNA-binding protein essential for synaptic plasticity. This review covers over 80 years of FXS research, highlighting key milestones, clinical features, genetic and molecular mechanisms, the FXS mouse model, disrupted molecular pathways, and current therapeutic strategies. Additionally, we discuss recent advances including AI-driven combination therapies, CRISPR-based gene editing, and antisense oligonucleotides (ASOs) therapies. Despite these scientific breakthroughs, translating preclinical findings into effective clinical treatments remains challenging. Clinical trials have faced several difficulties, including patient heterogeneity, inconsistent outcome measures, and variable therapeutic responses. Standardized preclinical testing protocols and refined clinical trial designs are required to overcome these challenges. The development of FXS-specific biomarkers could also improve the precision of treatment assessments. Ultimately, future therapies will need to combine pharmacological and behavioral interventions tailored to individual needs. While significant challenges remain, ongoing research continues to offer hope for transformative breakthroughs that could significantly improve the quality of life for individuals with FXS and their families. Full article

Precise determination of structural elastic–plastic displacement and component states under rare earthquakes is crucial for structural design. This article proposes a quasi-elastic–plastic optimization method for reinforced concrete structures. First, an approximate formula for calculating the yield bending moment of shear walls is provided through analysis of 64 shear walls. Second, a quasi-elastic–plastic analysis method is proposed. Using the elastic response spectrum analysis, strain energy for each component is calculated, and stiffness reduction factors for walls, beams, and columns are derived based on the energy equivalence principle. Finally, combining the elastic response spectrum analysis and the quasi-elastic–plastic analysis, various constraint indicators at the elastic and elastic–plastic design stages are calculated, and structural size optimization is completed using the particle swarm optimization method. The feasibility of this method is validated with examples of a 15-story reinforced concrete frame structure and a 15-story frame–shear wall structure. The quasi-elastic–plastic optimization with the particle swarm optimization efficiently completes elastic–plastic optimization for reinforced concrete structures, determining section sizes that meet performance standards while reducing material usage. Full article

Antimicrobial peptides (AMPs) are a diverse group of small, naturally occurring molecules that orchestrate the innate immune response of various organisms, from microorganisms to humans. Characterized by their broad-spectrum activity against bacteria, fungi and viruses, AMPs are increasingly recognized for their potential as novel therapeutic agents in the face of rising antibiotic resistance. Here, we present several newly designed AMPs, one of which, DTN6, exerts significant activity against several organisms with MIC values as low as 0.5 µg/mL. The D-TN6 peptide influences both bacteria and yeasts. Scanning electron microscopy and transmission electron microscopy results showed that the bacterial membrane is affected by D-TN6, which is resistant to proteases and is effective against antibiotic-resistant pathogens with hemolytic activity and low toxicity. The D-TN6 peptide is effective in vivo against standard S. aureus strains in wounds. Thus, D-TN6 is a potent antibiotic candidate with a broad spectrum of activity. Overall, AMPs are a promising tool for the development of next-generation antimicrobial agents that could mitigate global health threats posed by multidrug-resistant pathogens. Full article

This research investigates the seismic behavior of rigid and flexible cylindrical steel tanks, focusing on tanks with an open top and fully anchored at the base. The primary objective is to evaluate the hydrodynamic pressures exerted by the fluid on the tank walls during seismic excitation. Three widely recognized design approaches—New Zealand NZSEE recommendations, European code UNI EN 1998-4:2006 (CEN, 2006), and American Water Works Association AWWA D100-05 standard (ANSI/AWWA, 2005)—were implemented and compared with high-definition finite element models and then validated against the experimental results. Nonlinear fluid–structure interaction (FSI) was modeled using an Arbitrary Lagrangian–Eulerian (ALE) formulation with the Navier–Stokes equations governing the fluid motion and material and geometric nonlinearities considered in the tank walls. Parametric analyses were conducted to investigate the impact of tank geometry, specifically height-to-radius and radius-to-thickness ratios, on seismic response, identifying a transition between rigid and flexible behavior. The study also examined the influence of seismic input using a set of ten displacement spectrum-compatible ground motions. The findings contribute to a better understanding of the seismic resilience of cylindrical steel tanks, offering valuable insights for improving design standards and safety in earthquake-prone regions where these systems may abound. Full article

To evaluate the seismic safety of components in a structure, an in-structure response spectrum (ISRS) must be obtained, and this also applies to seismically isolated structures. The main variables for designing seismic isolators are effective stiffness and effective damping, which can be given as the characteristic strength and secondary stiffness in seismic isolators for nonlinear behaviors. Many studies on the ISRS of isolated structures have been conducted to evaluate the effects of these two variables of isolators, but the effect of other variables related to the hysteresis curve of isolators also needs to be studied. This study focused on the effect of the initial stiffness of isolators on an ISRS because there were no clear criteria for determining the initial stiffness in isolator design standards, which has an effect on the ISRS that cannot be ignored. As a result, the initial stiffness contributed significantly to the ISRS not only at the natural frequency of the structure but also at low frequencies. An analysis was also performed in terms of the uncertainty of each variable. The sharpness of the yield point in the hysteresis curve was implemented using the Bouc–Wen model, and its impact was analyzed. In addition, the frequency content of the ISRS depending on the seismic intensity, which can considerably change the nonlinear hysteresis behavior, was examined. Through this study, although secondary stiffness and characteristic strength are the most important characteristics of seismic isolation design, it was confirmed that other variables also have a significant impact on the frequency content of an ISRS. Based on this study, the considerations when developing the ISRS of an isolated structure can be established. Full article

Background/Objectives: Autism Spectrum Disorder (ASD) are neurodevelopmental disorders marked by challenges in social interaction, communication, and repetitive behaviors. People with ASD may exhibit repetitive behaviors, unique ways of learning, and different ways of interacting with the world. The term “spectrum” reflects the wide variability in how ASD manifests in individuals, including differences in abilities, symptoms, and support needs, and conditions characterized by difficulties in social interactions, communication, restricted interests, and repetitive behaviors. Inflammation plays a crucial role in the pathophysiology, with increased pro-inflammatory cytokines in cerebrospinal fluid. Previous studies with transcranial magnetic stimulation have shown promising results, suggesting nervous system susceptibility to electromagnetic fields, with evidence indicating that extremely low-frequency electromagnetic field (ELF-EMF) treatment may modulate inflammatory responses through multiple pathways, including the reduction of pro-inflammatory cytokines like IL-6 and TNF-α, and the enhancement of anti-inflammatory mediators. Methods: This pilot study included 20 children (ages 2–13) with a confirmed diagnosis of ASD. A 15-week protocol involved ELF-EMF treatments using the SEQEX device, with specific day and night programs. Assessment was conducted through standardized pre- and post-treatment tests: Achenbach Child Behavior Checklist, Peabody Picture Vocabulary Test-4, Expressive One Word Picture Vocabulary Test-4, and Conner’s 3GI. Results: Statistically significant improvements were observed in receptive language (PPVT-4: from 74.07 to 90.40, p = 0.002) and expressive language (EOWPVT-4: from 84.17 to 90.50, p = 0.041). Notable reductions, with statistical significance, were found in externalizing problems across both age groups (1.5–5 years: p = 0.028; 6–18 years: p = 0.027), with particular improvement in attention and behavioral problems. The results were observed over a short period of 15 weeks, therefore excluding the possibility of coincidental age-related gains, that would typically occur during a normal developmental timeframe. Parent evaluations showed significant reduction in ASD symptoms, particularly in the 1.5–5 years group (p = 0.046). Conclusions: ELF-EMF treatment demonstrated a high safety profile and efficacy in mitigating ASD-related symptoms. The observed improvements suggest both direct effects on central and autonomic nervous systems and indirect effects through inflammatory response modulation. Further studies are needed to confirm these promising results through broader demographics and randomized control designs. Full article

This article introduces a robust metaverse forensic framework designed to facilitate the investigation of cybercrime within the dynamic and complex digital metaverse. In response to the growing potential for nefarious activities in this technological landscape, the framework is meticulously developed and aligned with international standardization, ensuring a comprehensive, reliable, and flexible approach to forensic investigations. Comprising seven distinct phases, including a crucial incident pre-response phase, the framework offers a detailed step-by-step guide that can be readily applied to any virtualized platform. Unlike previous studies that have primarily adapted the existing digital forensic methodologies, this proposed framework fills a critical research gap by providing a proactive and granular investigative process. The approach goes beyond mere adaptation, ensuring a comprehensive strategy that addresses the unique challenges posed by the metaverse environment. The seven phases cover a spectrum of forensic investigation, offering a thorough interpretation with careful consideration of real-life metaverse forensic scenarios. To validate its effectiveness, the proposed framework undergoes a rigorous evaluation against the appropriate ISO/IEC standards. Additionally, metaverse expert reviews, based on the task–technology fit theory, contribute valuable insights. The overall assessment confirms the framework’s adherence to forensic standards, making it a reliable guide for investigators navigating the complexities of cybercrime in the metaverse. This comprehensive metaverse forensic framework provides investigators with a detailed and adaptable tool to address a wide range of cybercrime incidents within the evolving virtualized landscape. Furthermore, its stepwise guidance ensures a thorough and reliable investigation process, offering significant contributions to proactive security measures in the face of emerging challenges in the metaverse. Full article

Autism spectrum disorder (ASD) is a neurological disease and lifelong condition. The treatment gap in ASD has led to growing interest in alternative therapies, particularly in phytocannabinoids, which are naturally present in Cannabis sativa. Studies indicate that treatment with cannabidiol (CBD)-rich cannabis may possess the potential to improve fundamental ASD symptoms as well as comorbid symptoms. This systematic review aims to assess the safety and efficacy of CBD-rich cannabis in alleviating the symptoms of ASD in both children and adults, addressing the treatment gap and growing interest in CBD as an alternative treatment. A comprehensive literature search was conducted in February 2024 using the PUBMED and Scopus databases while following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search focused on studies from 2020 onward involving human populations diagnosed with ASD and treated with CBD. Four studies met the inclusion criteria and were analyzed. The review included 353 participants with ASD from studies conducted in Israel, Turkey, and Brazil. The studies varied in design, sample size, dose, and treatment duration. Dosages of CBD were often combined with trace amounts of THC. Improvements were noted in behavioral symptoms, social responsiveness, and communication, but cognitive benefits were less consistent. Adverse effects ranged in severity. Mild effects such as somnolence and decreased appetite were common, while more concerning effects, including increased aggression, led to some cases of treatment discontinuation. CBD-rich cannabis shows promise in improving behavioral symptoms associated with ASD. However, variations in study designs, dosages, and outcome measures highlight the need for standardized assessment tools and further research to understand pharmacological interactions and optimize treatment protocols. Despite the mild adverse effects observed, larger, well-controlled trials are necessary to establish comprehensive safety and efficacy profiles. Full article

The development of a suitable set of input ground motions is crucial for dynamic time history analyses. The US Nuclear Regulatory Commission (NRC) requires that these motions generate response spectra closely matching the plant’s design spectrum. Additionally, the NRC recommends verifying the motions’ power spectral densities (PSDs) against a target function to ensure sufficient energy across all frequencies. Current NRC guidelines in Standard Review Plan (SRP) provide a general method for creating target PSDs for any design spectrum. However, this method does not explicitly consider the influence of strong motion duration on the relationship between PSD and response spectrum. This article proposes an improved approach that incorporates the expected strong motion duration into the target PSD generation process. The method first constructs a Fourier amplitude spectrum (FAS) compatible with both the design spectrum and the expected strong motion duration. Subsequently, a large set of synthetic motions based on this FAS is used to construct the target PSD function. It is shown that current target PSD functions tabulated in SRP 3.7.1 implicitly infer an expected strong motion duration of approximately 9 s. The proposed method can be used to construct target PSDs tailored to different strong motion durations. Full article