Search Results (221)

Background/Objectives: Norovirus is a major cause of acute gastroenteritis worldwide. Considering its highly infectious and transmissible nature, rapid and accurate diagnostic tools are of utmost importance for the effective control of outbreaks in the context of point-of-care testing (POCT). In this study, we developed a genogroup-specific multiplex reverse transcriptase loop-mediated isothermal amplification assay to detect the human norovirus genogroups I and II (GI and GII, respectively). Methods: For the comprehensive detection of clinically relevant genotypes, two sets of primers were incorporated into the assays targeting the RdRp-VP1 junction: one against GI.1 and GI.3, and the other for GII.2 and GII.4. Following optimization of the reaction variables, we standardized the reaction conditions at 65 °C with 6 mM MgSO₄, 1.4 mM dNTPs, 7.5 U WarmStart RTx Reverse Transcriptase, and Bst DNA polymerase at 8 U and 10 U for GI and GII, respectively. Amplification was monitored in real-time using a thermocycler platform to ensure precise quantification and detection. Finally, the assay was evaluated through portable isothermal detection device to test its feasibility in on-site settings. Results: Both assays detected the template down to 10²–10³ copies per reaction and showed high target selectivity, yielding no non-specific amplification across 39 enteric pathogens. These assays enabled prompt detection of GI within 10–12 min and of GII within 12–17 min after the reaction was initiated. Onsite validation reveals all template detection below 15 min, demonstrating its potential feasibility in point-of-care applications. Including the sample preparation time, test results were obtained in less than 1 h. Conclusions: This method is a rapid, reliable, and scalable solution for detecting human norovirus in POCT settings for both clinical diagnosis and public health surveillance. Full article

Amid the growing debate over how cryptocurrencies are reshaping global finance, this study explores the nexus between Bitcoin, Brent Crude Oil, Gold and the U.S. Dollar Index. We used a time-varying vector autoregressive (tvVAR) model to examine the connection among these four assets during the Trump (2017–2020) and Biden (2021–2024) governments. The 48-week return forecast of the Bitcoin–Gold correlation was also conducted by using the Bayesian Structural Time Series (BSTS) model. Results indicate that Bitcoin was the most volatile asset, while the U.S. Dollar remained the least volatile under both regimes. Under Trump, U.S. Dollar significantly influenced Oil and Bitcoin while Bitcoin and Gold were negatively linked to Oil and positively associated with U.S. Dollar. An inverse relationship between Bitcoin and Gold also emerged. Under Biden, Bitcoin, Gold, and U.S. Dollar all significantly affected Oil with Bitcoin showing a positive impact. Bitcoin and Gold remained negatively correlated though not significantly, and the Dollar maintained positive ties with both. Forecasts show a positive link between Bitcoin and Gold in the coming year. However, Bitcoin does not exhibit consistent characteristics of a safe-haven asset during the U.S. presidential transitions examined, largely due to its high volatility and unstable correlations with a traditional safe-haven asset, Gold. This study contributes to the understanding of shifting relationships between digital and traditional assets across political regimes. Full article

High-grade gliomas (HGGs, WHO grades 3–4) are highly aggressive, with a poor prognosis and treatment resistance. Immune evasion may contribute to their progression, but the role of cytotoxic T-lymphocyte immune evasion (CTLE) is not well-validated. This study analyzed the transcriptomic data of 525 patients from TCGA-GBM-HG_U133A. Two molecular subtypes were identified based on 182 CTLE-associated genes, with 238 differentially expressed genes between them. A prognostic model was developed, identifying BST2 and DIRAS3 as key risk factors, and validated in multiple cohorts. The subtypes had distinct immune profiles, with Cluster 2 showing higher immune infiltration but a poorer prognosis. The model had a good predictive performance. High-risk patients had upregulated BST2 and DIRAS3, linked to immunosuppression and shorter survival. Knockdown experiments confirmed their roles in GBM cell migration and invasion. Mechanistically, they promote immune evasion. BST2 and DIRAS3 could be therapeutic targets for HGG immunotherapy. Full article

Approximately 72% of older adults in residential care have dementia and present with different levels of functioning. People living with dementia (PLwD) may not always be facilitated to independently carry out activities of daily living (ADLs) in care, increasing the likelihood of excess disability. This study incorporated Behavioural Skills Training (BST) to train healthcare staff how to increase opportunities for independence for PLwD by using task analyses and least-to-most (L-M) prompting procedures during ADLs. Three healthcare staff, two female and one male (mean age = 42.67, SD = 16.82), participated in the intervention. The What Works Clearinghouse (WWC) Single-Case Design Technical Documentation guided the study’s design. A randomised single-case experimental (N-of-1) design was employed, using a multiple-baseline design (MBD) across participants (n = 3) for three separate ADLs. The dependent variable (DV) was the percentage of correct staff responses when implementing the L-M prompting procedure for each step during ADLs. Visual and statistical analyses demonstrated an increase in the correct use of a task analysis and L-M prompting for all three participants during the intervention compared to the baseline: for ADL1 (assistance to stand), effect sizes were d = 5.39, d = 9.38, and d = 6.79 for the three participants, respectively; for ADL2 (assistance with drinking), effect sizes were d = 3.27, d = 8.55, and d = 3.67; and for ADL3 (assistance to brush teeth), effect sizes were d = 5.99, d = 12.93, and d = 9.39. Maintenance data ranged from 70% to 100% correct responses at follow-up (mean = 93.11% SD = 7.85). Participants successfully generalised skills learned to two new ADLs (PLwD eating a meal and putting on a jumper). BST was demonstrated to be an effective training strategy to increase opportunities for independent responding for PLwD in care environments. The contingencies influencing staff behaviour require attention within the healthcare environment. Full article

Hereditary α-tryptasemia (HαT)—a genetic trait caused by increased α-tryptase-encoding typtase alpha/beta-1 (TPSAB1) copy number—is associated with adult mastocytosis. The primary objective was to assess the association between α-tryptase and pediatric mastocytosis. We also want to evaluate whether the KIT p.D816V mutation in peripheral blood leukocytes (PBLs) reliably predicts systemic mastocytosis (SM) in children. A prospective cohort of 68 children from a referral center in Slovenia with cutaneous mastocytosis (CM) underwent tryptase genotyping by droplet digital PCR and examination for KIT p.D816V in PBL using a sensitive PCR test. A significant majority of patients (57 of 68; [83.8%]) had at least one α-tryptase-encoding gene; none had HαT. 7 of the 68 (10.3%) who were positive for KIT p.D816V in PBL, one fulfilled diagnostic criteria for indolent SM, and another was diagnosed with monoclonal mast cell activation syndrome. One of those individuals had an increased basal serum tryptase (BST) level (14.5 ng/mL). We found a high presence of germline α-tryptase in children with CM, but not HαT. By employing sensitive examination for KIT p.D816V in PBL, in combination with clinical data and other examinations, our study suggests that KIT p.D816V in PBL may indicate systemic disease in children with CM. Full article

Adaptive Large Neighborhood Search (ALNS) represents a versatile and highly efficient optimization methodology that has demonstrated significant effectiveness in practical applications. This study introduces an enhanced ALNS approach integrated with Simulated Annealing (SA), termed IALNS-SA. The proposed algorithm incorporates supplementary destruction and repair operators within the ALNS framework to augment its robustness and generalization capacity. Additionally, it adopts the SA acceptance criterion to mitigate local optima entrapment. The research investigates the applicability of IALNS-SA to the Vehicle Routing Problem with Simultaneous Delivery and Pickup and Time Windows (VRPSDPTWs), a pivotal challenge in logistics optimization. Through comprehensive evaluation across 56 large-scale benchmark instances, the algorithm’s performance is systematically compared against four established methods: p-SA, DCS, VNS-BSTS, and DGWO. Empirical results indicate that IALNS-SA achieves superior performance relative to DGWO in 69.64% of cases, surpasses VNS-BSTS in 94.64% of instances, and consistently outperforms both p-SA and DCS. The obtained optimal solutions exhibit reduced total vehicle routing distances, thereby substantiating the operational feasibility and algorithmic efficacy of the proposed methodology. Full article

This study investigated the genetic diversity of Mycobacterium avium subsp. paratuberculosis (Map)—the causative agent of paratuberculosis—isolated from different host species in Germany. A total of 500 isolates from 243 cattle herds and 9 other host species originating from 13 federal states were genotyped. A multi-target approach was applied, comprising IS900-RFLP with BstEII and PstI digestion; MIRU-VNTR; and SSR1, SSR8, and SSR9 analysis. In total, 93 combined genotypes were identified, 84 in cattle and 21 in non-cattle isolates. Ninety genotypes were assigned to the C-type group, and three genotypes (three from sheep and one from cattle) were assigned to the S-type/subtype III group. Cluster analysis divided genotypes into subgroups similar to those shown for WGS-SNP-based phylogenetic trees. New genotypes were revealed, including INMV262–267 and a specific sequence at locus VNTR7. Five genotypes that were predominant in cattle were also detected in sheep, goats, and deer. The majority of genotypes [61%] were identified only once. Polyclonal infections were observed in individual animals and herds, and various potential Map transmission linkages were uncovered. This high genotype richness of Map reflects the long history of paratuberculosis in Germany and intensive nationwide animal movement and international trading activity. Full article

Effective teacher training is critical for improving student outcomes. Behavior Skills Training (BST), which consists of instruction, modeling, role play, and feedback, has been demonstrated to be effective for training teachers, staff, and peers to deliver a wide range of interventions to individuals with disabilities. This study examined the effects of using BST to train a teacher to implement a Universal Protocol treatment package. The Universal Protocol package included procedures for building rapport, identifying the potential triggers of challenging behavior, and making data-based decisions on the type and intensity of services required. A multiple-baseline design across school settings (e.g., reward, work, transition) demonstrated a functional relation of BST with the correct implementation of the Universal Protocol. Student problem behaviors appeared to be sensitive to teacher implementation of the Universal Protocol. Limitations and future directions are presented. Full article

Training people interested in implementing Applied Behavior Analysis (ABA) interventions to children with autism spectrum disorder (ASD) is important to promote skill gains. A recommended training package is called behavioral skills training (BST), which involves four components (didactic instruction, modeling, role-play, and performance feedback). Background/Objectives: The purpose was to assess the effects of BST on the accurate teaching of multiple skills via DTT by six psychology university students to a confederate and six children diagnosed with ASD. Generalization and maintenance assessments were conducted. Results: Through the research conditions, all university participants were able to teach ten different skills (sitting still, motor imitation, making requests, vocal imitation, receptive identification of non-verbal stimuli, making eye contact, following instructions, intraverbal, labeling, receptive identification of non-verbal stimuli by function, feature and class) with a high integrity level to the children. In addition, across four months after training, all participants maintained high teaching integrity levels while teaching skills to the children related to their individualized curriculum goals. Each child accumulated over 1000 correct responses across several sessions. The university participants rated their training with the highest possible score in a social validity assessment. Conclusions: BST successfully trained psychology university students to accurately teach multiple skills via DTT to children with ASD and involved long lasting effects. Limitations and new avenues for research were discussed. Full article

This review explores the mechanisms by which Human Immunodeficiency Virus type 1 (HIV-1) regulatory proteins manipulate host cellular pathways to promote viral replication and immune evasion. Key viral proteins, such as Nef, Vpu, Vif, Vpr, and Env, disrupt immune defenses by downregulating surface molecules such as CD4 (Cluster of Differentiation 4) and Major Histocompatibility Complex (MHC) class I, degrading antiviral enzymes like APOBEC3G (Apolipoprotein B mRNA editing catalytic polypeptide-3G) and SAMHD1 (Sterile Alpha Motif and Histidine Aspartate domain-containing protein 1), and counteracting restriction factors including BST-2 (Bone Marrow Stromal Antigen 2)/Tetherin and SERINC5 (Serin Incorporator 5). These interactions support viral persistence and contribute to the establishment of chronic infection. Emerging therapeutic strategies aim to disrupt these HIV-host interactions to restore innate antiviral responses and enhance immune clearance. Approaches such as stabilizing host restriction factors or blocking viral antagonists offer a promising alternative to conventional antiretroviral therapy. By targeting host-dependent pathways, these interventions may reduce drug resistance, tackle latent reservoirs, and provide a pathway toward sustained viral remission or functional cure. Full article

Adaptor protein (AP) complexes are critical components of the cellular membrane transport machinery. They mediate cargo selection during endocytosis and intracellular vesicular trafficking. Five AP complexes have been characterized (AP1-5), and together their roles extend to diverse cellular processes including the homeostasis of membranous organelles, membrane protein turnover, and immune responses. Human Immunodeficiency Virus type 1 (HIV-1) and other lentiviruses co-opt these complexes to support immune evasion and the assembly of maximally infectious particles. HIV-1 Nef interacts with AP1 and AP2 to manipulate intracellular trafficking and downregulate immune-related proteins such as CD4 and MHC-I. Vpu also co-opts AP1 and AP2, modulating the innate defense protein BST2 (Tetherin) and facilitating the release of virions from infected cells. The envelope glycoprotein (Env) hijacks AP complexes to reduce its expression at the cell surface and potentially support incorporation into virus particles. Some data suggest that Gag co-opts AP3 to drive assembly at intracellular compartments. In principle, targeting the molecular interfaces between HIV-1 proteins and AP complexes is a promising therapeutic approach. Blocking these interactions should impair HIV-1’s ability to produce infectious particles and evade immune defenses, leading to novel antivirals and facilitating a cure. Full article

Giardia duodenalis is a flagellated protozoan pathogen causing parasitic enteric disease outbreaks worldwide. Among detection methods, loop-mediated isothermal amplification (LAMP) has high selectivity and sensitivity, and the detection time is lower than that of conventional molecular methods. In this study, three published Giardia LAMP primer sets were tested and adapted to touchdown LAMP conditions. The measurement time, the volume of reagents, the effect of the denaturation step, different kinds of polymerases, and the presence or absence of betaine on the reaction were tested and evaluated. Based on the results of this study, the 66–60 °C range touchdown LAMP with the use of betaine, 90 °C denaturation step, Bst 2.0 WarmStart^® DNA Polymerase, and the primer set of Momoda et al. were the optimal conditions. We increased the analytical sensitivity of the LAMP reaction to 7.8- and 8-fold higher than the previously published methods for G. duodenalis assemblages A and B, with detection limits of 20 and 19.5 fg/assay, respectively, instead of 156 fg/assay. The detection time was less than 49 min for G. duodenalis assemblage A and less than 35 min for assemblage B, compared to the previously published 60 min. Our optimized LAMP protocol can be directly applied to improve Giardia LAMP tests in routine testing laboratories, could be implemented in standard diagnostic or environmental monitoring workflows, and can be used for the development of Giardia LAMP point-of-care devices or high-throughput systems. Full article

This paper captures a qualitative review of the regulatory prescribed stress tests for UK financial services designed by the Bank of England and the Prudential Regulation Authority (PRA)/Financial Conduct Authority (FCA) after the Global Financial Crisis. It presents a critical analysis of the use of stress testing as part of supervisory practices for UK banking institutions and insurance undertakings, commenting on their qualitative characteristics, after looking at the regulatory prescribed stress tests from three key categories: the macroeconomic scenarios for banks, denoted as the bank stress tests (BST), the insurance stress tests (IST), and the biennial exploratory scenarios (BES). In this study, five trends describing regulatory prescribed stress are identified: (1) the regulatory collaboration, (2) cross-industry stress tests, (3) exploratory scenarios, (4) reporting and disclosure requirements, and (5) the underlying modelling capabilities and tools. The associated challenges of (A) governance, (B) frequency, (C) individual disclosures, (D) data and modelling, and (E) capabilities and skillset from participating institutions underpinning these stresses are highlighted, shaping the policy recommendations for future exercises. These address the gaps identified from existing stress tests towards the effective prudential supervision of UK financial services, based on each scenario category, for improvements and advances to practices. Full article

Background/Objectives: Older adults with type 2 diabetes mellitus (T2DM) often experience impaired physical function and metabolic control. This study aimed to evaluate the effectiveness of a 12-week Pilates-based intervention on blood glucose concentration and physical function in this population. Methods: A randomized controlled trial was conducted with 104 older adults (mean age: 70.6 ± 3.15 years; 70.2% women), all diagnosed with T2DM. The participants were assigned to a control group (CG, n = 52) or a Pilates training group (PG, n = 52). The intervention included 24 Pilates sessions over 12 weeks (2 sessions/week, 60 min each). Outcomes were assessed pre- and post-intervention and included capillary blood glucose, handgrip strength, functional mobility (Timed Up and Go), balance (Berg Balance Scale), and flexibility (Chair Sit-and-Reach Test and Back Scratch Test). Results: Compared to the control group, the Pilates group showed statistically significant improvements in blood glucose levels (−4.06 mg/dL (p < 0.001; d = 0.68)), handgrip strength (+1.76 kg (p < 0.001; d = 0.48)), gait speed (p < 0.001; d = 0.53), balance (Berg score) (+2.37 points (p < 0.001; d = 0.66)), and flexibility (improvements in upper limbs (BST, d = 0.78–0.98) and lower limbs (CSRT, d = 1.07 right; d = 0.63 left)). Conclusions: A 12-week Pilates program led to significant improvements in glycemic control, muscular strength, gait speed, balance, and flexibility in older adults with T2DM. These findings support Pilates as a safe, effective, and adaptable non-pharmacological intervention to promote functional and metabolic health in this population. Full article

In this manuscript, strontium barium titanate (BST) ferroelectric memory film materials for applications in the feasibility of applying to non-volatile RAM devices were obtained and compared. Solutions were synthesized with a proportional ratio and through the deposition of BST films on titanium nitride/silicon substrates using the sol–gel method, using rapid thermal annealing for defect repair and re-crystallization processing. The crystallization structure and surface morphology of annealed and as-deposited BST films were obtained by XPS, XRD, and SEM measurements. Additionally, the ferroelectric and resistive switching properties for the memory window, the maximum capacitance, and the leakage current were examined for Al/BST/TiN and Cu/BST/TiN structure memory devices. In addition, the first-order reaction equation of the decay reaction behavior for the BST film RRAM devices in the reset state revealed that $r=0.19{[O^{2-}]}^1$. Finally, the Cu/BST/TiN and Al/BST/TiN structures of the ferroelectric BST films RRAM devices exhibited good memory window properties, bipolar switching properties, and non-volatile properties for applications in non-volatile memory devices. Full article