The interaction of helminth infections with type 2 diabetes (T2D) has been a major area of research in the past few years. This paper, therefore, focuses on the systematic review of the effects of helminthic infections on metabolism and immune regulation related to T2D, with mechanisms through which both direct and indirect effects are mediated. Specifically, the possible therapeutic role of helminths in T2D management, probably mediated through the modulation of host metabolic pathways and immune responses, is of special interest. This paper discusses the current possibilities for translating helminth therapy from basic laboratory research to clinical application, as well as existing and future challenges. Although preliminary studies suggest the potential for helminth therapy for T2D patients, their safety and efficacy still need to be confirmed by larger-scale clinical studies.

The hypersonic vehicle surfaces are subjected to intense thermal loads during atmospheric re-entry. Such conditions induce material ablation and structural deformation, potentially causing changes to aerodynamic configuration that critically endanger mission integrity. In this paper, a mathematical model of thermochemical non-equilibrium magnetohydrodynamics (MHD) at low magnetic Reynolds number is introduced to investigate the effects of MHD on the flow field. Variation of the magnetic pole angle (θ), the flow field profiles are quantitatively analysed, including gas component distributions and aerodynamic heating characteristics. Results indicate that the heat flux at the stagnation point initially decreases and then increases with θ increasing, reaching a minimum at θ = 60°. A portion of the heat flux from the blunt position is transferred to the shoulder (α between 30° and 60°). Notably, the shock standoff distance also shows a non-monotonic trend with θ increasing, peaking at θ = 30°, mirroring the effect of θ on the stagnation point heat flux. As θ increases, the component of the Lorentz force along the X-direction gradually increases, with its peak position corresponding to the shock standoff distance. The electrons and nitrogen atoms are primarily concentrated at the blunt nose, while nitric oxide and oxygen atoms are predominantly distributed along the vehicle wall. The dissociation region of the gas is influenced by the shock standoff distance, which increases as the shock standoff distance increases. At θ = 30°, the concentration of oxygen atoms, nitrogen atoms, nitric oxide molecules and electrons on the stagnation point line reaches its maximum. The present study provides a theoretical foundation for the application of MHD thermal protection methods on hypersonic vehicles.

Background: TERT promoter mutation (TPM) is an established biomarker in meningiomas associated with aberrant TERT expression and reduced progression-free survival (PFS). TERT expression, however, has also been observed even in tumours with wildtype TERT promoters (TP-WT). This study aimed to examine TERT expression and clinical outcomes in meningiomas. Methods: TERT expression, TPM status, and TERT promoter methylation of a multi-institutional cohort of meningiomas (n=1241) was assessed through nulk RNA sequencing (n=604), Sanger sequencing of the promoter (n=1095), and methylation profiling (n=1218). 380 Toronto meningiomas were used for discovery, and 861 external institution samples were compiled as a validation cohort. Results: Both TPMs and TERTpromoter methylation were associated with increased TERT expression and may represent independent mechanisms of TERT reactivation. TERT expression was detected in 30.4% of meningiomas that lacked TPMs, was associated with higher WHO grades, and corresponded to shorter PFS, independent of grade and even among TP-WT tumours. TERT expression was associated with a shorter PFS equivalent to those of TERT-negative meningiomas of one higher grade. Conclusions: Our findings highlight the prognostic significance of TERT expression in meningiomas, even in the absence of TPMs. Its presence may identify patients who may progress earlier and should be considered in risk stratification models.

Background: Meningiomas are the most common intracranial tumors. Radiotherapy (RT) serves as an adjunct following surgical resection; however, response varies. RTOG-0539 is a prospective, phase 2, trial that stratified patients risk groups based on clinical and pathological criteria, providing key benchmarks for RT outcomes. This is the first study that aims to characterize the molecular landscape of an RT clinical trial in meningiomas. Methods: Tissue from 100 patients was analyzed using DNA methylation, RNA sequencing, and whole-exome sequencing. Copy number variations and mutational profiles were assessed to determine associations with meningioma aggressiveness. Tumors were molecularly classified and pathway analyses were conducted to identify biological processes associated with RT response. Results: High-risk meningiomas exhibited cell cycle dysregulation and hypermetabolic pathway upregulation. 1p loss and 1q gain were more frequent in aggressive meningiomas, and NF2 and non-NF2 mutations co-occurred in some high-risk tumors. Molecular findings led to the reclassification of several cases, highlighting the limitations of histopathologic grading alone. Conclusions: This is the first study to comprehensively characterize the molecular landscape of any RT trial in meningioma, integrating multi-omic data to refine treatment stratification. Findings align with ongoing genomically driven meningioma clinical trials and underscore the need for prospective tissue banking to enhance biomarker-driven treatment strategies.

Background: The WHO grade of meningioma was updated in 2021 to include homozygous deletions of CDKN2A/B and TERT promotor mutations. Previous work including the recent cIMPACT-NOW statement have discussed the potential value of including chromosomal copy number alterations to help refine the current grading system. Methods: Chromosomal copy number profiles were inferred from from 1964 meningiomas using DNA methylation. Regularized Cox regresssion was used to identify CNAs independenly associated with post-surgical and post-RT PFS. Outcomes were stratified by WHO grade and novel CNAs to assess their potential value in WHO critiera. Results: Patients with WHO grade 1 tumours and chromosome 1p loss had similar outcomes to those with WHO grade 2 tumours (median PFS 5.83 [95% CI 4.36-Inf] vs 4.48 [4.09-5.18] years). Those with chromosome 1p loss and 1q gain had similar outcomes to those with WHO grade 3 cases regardless of initial grade (median PFS 2.23 [1.28-Inf] years WHO grade 1, 1.90 [1.23-2.25] years WHO grade 2, compared to 2.27 [1.68-3.05] years in WHO grade 3 cases overall). Conclusions: We advocate for chromosome 1p loss being added as a criterion for a CNS WHO grade of 2 meningioma and addition of 1q gain as a criterion for a CNS WHO grade of 3.

Background: Meningiomas exhibit considerable heterogeneity. We previously identified four distinct molecular groups (immunogenic, NF2-wildtype, hypermetabolic, proliferative) which address much of this heterogeneity. Despite their utility, the stochasticity of clustering methods and the requirement of multi-omics data limits the potential for classifying cases in the clinical setting. Methods: Using an international cohort of 1698 meningiomas, we constructed and validated a machine learning-based molecular classifier using DNA methylation alone. Original and newly-predicted molecular groups were compared using DNA methylation, RNA sequencing, whole exome sequencing, and clinical outcomes. Results: Group-specific outcomes in the validation cohort were nearly identical to those originally described, with median PFS of 7.4 (4.9-Inf) years in hypermetabolic tumors and 2.5 (2.3-5.3) years in proliferative tumors (not reached in the other groups). Predicted NF2-wildtype cases had no NF2 mutations, and 51.4% had others mutations previously described in this group. RNA pathway analysis revealed upregulation of immune-related pathways in the immunogenic group, metabolic pathways in the hypermetabolic group and cell-cycle programs in the proliferative group. Bulk deconvolution similarly revealed enrichment of macrophages in immunogenic tumours and neoplastic cells in hypermetabolic/proliferative tumours. Conclusions: Our DNA methylation-based classifier faithfully recapitulates the biology and outcomes of the original molecular groups allowing for their widespread clinical implementation.

Background: The combination of PARP inhibitor and immune checkpoint inhibitors have been proposed as a potentially synergistic combinatorial treatment in IDH mutant glioma, targeting dysregulated homologous recombination repair pathways. This study analyzed the cell-free DNA methylome of patients in a phase 2 trial using the PARP inhibitor Olaparib and the PD-1 inhibitor Durvalumab. Methods: Patients with recurrent high-grade IDH-mutant gliomas were enrolled in a phase II open-label study (NCT03991832). Serum was collected at baseline and monthly and cell-free methylated DNA immunoprecipitation and high-throughput sequencing (cfMeDIP-seq) was performed. Binomial GLMnet models were developed and model performance was assessed using validation set data. Results: 29 patients were enrolled between 2020–2023. Patients received olaparib 300mg twice daily and durvalumab 1500mg IV every 4 weeks. The overall response rate was 10% via RANO criteria. 144 plasma samples were profiled with cfMeDIP-seq along with 30 healthy controls. The enriched circulating tumour DNA methylome during response periods exhibited a highly specific signature, accurately discriminating response versus failure (AUC 0.98 ± 0.03). Additionally, samples that were taken while on treatment were able to be discriminated from samples off therapy (AUC 0.74 ± 0.11). Conclusions: The cell-free plasma DNA methylome exhibits highly specific signatures that enable accurate prediction of response to therapy.

Background: We’ve adopted a novel approach that combines cellular barcoding with CRISPR/Cas-9 technology and single-cell RNA sequencing known as continuous lineage tracing to track the development, treatment and inevitable recurrence of glioblastoma. Methods: Patient derived glioma initiating cell lines were engineered with expressed DNA barcodes with CRISPR/Cas-9 targets and engrafted into NOD scid-mice. Clonal and relationships are surmised through identification of expressed barcodes, and cells were characterized by their transcriptional profiles. Phylogenetic lineage trees are created using lineage reconstructive algorithms to define cell fitness and expansion. Results: Our work has revealed a significant amount of intra-clonal cell state heterogeneity, suggesting that tumour cells engage in phenotype switching prior to therapeutic intervention. Phylogenetic lineage trees allowed us to define a gene signature of cell fitness. GBMs exist along a transcriptional gradient between undifferentiated but “high-fit” cells and terminally differentiated, “low-fit” cells, lending further evidence that these tumours consist of pools of cells that are capable of recapitulating the tumour microenvironment after treatment. Conclusions: We have successfully engineered a set of glioma initiating tumours with a novel lineage tracing technique, creating a powerful tool for real-time tracing of tumour growth through the analysis of highly detailed singe-cell RNA sequencing data with associated clonal and phylogenetic relationships.

We conducted an analysis of a nationwide survey of US physician offices between 2016 and 2019 and calculated annualized prevalence rates of urinary tract infections (UTIs). During the 3-year study period, UTI was the most common infection in US physician offices, accounting for approximately 10 million annualized encounters.

With numerous applications of coilable masts in high-precision space application scenarios, there are also greater demands on the accuracy of their dynamic modelling and analysis. The modelling of hinges is a critical issue in the dynamic modelling of coilable masts, which significantly affects the accuracy of the dynamic response analysis. For coilable masts, the rotational effect is the most important problem in hinge modelling. However, few studies have focused on this topic. To address this problem, the concept of hinge equivalent rotational stiffness is proposed in this paper to describe the rotational effect of the coilable mast hinges. After that, a new coilable mast dynamic model containing the undetermined hinge equivalent rotational stiffness is introduced, and an identification method for the hinge equivalent rotational stiffness based on the hammer test is proposed. Finally, the dynamic modelling method is validated through an actual coilable mast example, and the analysis and test results show that the accuracy of the dynamic model established by the proposed method in this paper is greater than that of the traditional model.

A three-dimensional robust nonlinear cooperative guidance law is proposed to address the challenge of multiple missiles intercepting manoeuvering targets under stringent input constraints and thruster failure. The finite-time convergence theory is used to design a distributed nonlinear sliding mode guidance law, ensuring that the system converges in finite time, with the upper limit of convergence time related to the initial state. A nonlinear sliding surface is adopted to mitigate actuator saturation issues. Then, considering thruster failure, a robust cooperative guidance law is further introduced, ensuring mission completion through the reconstruction of the guidance law. The closed-loop system is proven to be stable using Lyapunov theory, and the influence of hyperparameters on the cooperative guidance law is analysed. Additionally, the results of numerical simulations and hardware-in-the-loop experiments demonstrate the effectiveness and robustness of the proposed algorithm in dealing with stringent input saturation and various disturbances.

Vaccines have revolutionised the field of medicine, eradicating and controlling many diseases. Recent pandemic vaccine successes have highlighted the accelerated pace of vaccine development and deployment. Leveraging this momentum, attention has shifted to cancer vaccines and personalised cancer vaccines, aimed at targeting individual tumour-specific abnormalities. The UK, now regarded for its vaccine capabilities, is an ideal nation for pioneering cancer vaccine trials. This article convened experts to share insights and approaches to navigate the challenges of cancer vaccine development with personalised or precision cancer vaccines, as well as fixed vaccines. Emphasising partnership and proactive strategies, this article outlines the ambition to harness national and local system capabilities in the UK; to work in collaboration with potential pharmaceutic partners; and to seize the opportunity to deliver the pace for rapid advances in cancer vaccine technology.

As avionics systems become increasingly complex, traditional fault prediction methods are no longer sufficient to meet modern demands. This paper introduces four advanced fault prediction methods for avionics components, utilising a multi-step prediction strategy combined with a stacking regressor. By selecting various standard regression models as base regressors, these base regressors are first trained on the original data, and their predictions are subsequently used as input features for training a meta-regressor. Additionally, the Tree-structured Parzen Estimator (TPE) algorithm is employed for hyperparameter optimisation. The experimental results demonstrate that the proposed stacking regression methods exhibit superior accuracy in fault prediction compared to traditional single-model approaches.

The objective of this study was to investigate the effects of different cockpit primary flight display (PFD) interface designs on pilot cognitive efficiency and cognitive load. This study designed five optimised PFD interfaces and conducted interface cognition experiments to assess cognitive responses across six different PFD interface designs, including the original design. It compared various subjective and objective metrics across different interface designs and evaluated the impact of each design factor on cognitive task performance. The experimental results show that the PFD interface in the original interface design performs better under different flight symbol designs, and the interface with 50% increase in font size performs better among interface designs with different font sizes with relatively lower cognitive load. This study provides experimental support and optimization suggestions for the optimal design of cockpit PFD interface, which can help improve pilots’ perception and operational capabilities, and thus enhance task performance efficiency and flight safety. Future research can investigate the effects of various design factors on the cognitive effects of the interface to enhance the ongoing improvement and optimisation of interface design.

In this paper, a brand-new adaptive fault-tolerant non-affine integrated guidance and control method based on reinforcement learning is proposed for a class of skid-to-turn (STT) missile. Firstly, considering the non-affine characteristics of the missile, a new non-affine integrated guidance and control (NAIGC) design model is constructed. For the NAIGC system, an adaptive expansion integral system is introduced to address the issue of challenging control brought on by the non-affine form of the control signal. Subsequently, the hyperbolic tangent function and adaptive boundary estimation are utilised to lessen the jitter due to disturbances in the control system and the deviation caused by actuator failures while taking into account the uncertainty in the NAIGC system. Importantly, actor-critic is introduced into the control framework, where the actor network aims to deal with the multiple uncertainties of the subsystem and generate the control input based on the critic results. Eventually, not only is the stability of the NAIGC closed-loop system demonstrated using Lyapunov theory, but also the validity and superiority of the method are verified by numerical simulations.

Aircraft ground taxiing contributes significantly to carbon emissions and engine wear. The electric towing tractor (ETT) addresses these issues by towing the aircraft to the runway end, thereby minimising ground taxiing. As the complexity of ETT towing operations increases, both the towing distance and time increase significantly, and the original method for estimating the number of ETTs is no longer applicable. Due to the substantial acquisition cost of ETT and the need to reduce waste while ensuring operational efficiency, this paper introduces for the first time an ETT quantity estimation model that combines simulation and vehicle scheduling models. The simulation model simulates the impact of ETT on apron operations, taxiing on taxiways and takeoffs and landings on runways. Key timing points for ETT usage by each aircraft are identified through simulation, forming the basis for determining the minimum number of vehicles required for airport operations using a hard-time window vehicle scheduling model. To ensure the validity of the model, simulation model verification is conducted. Furthermore, the study explores the influence of vehicle speed and airport scale on the required number of ETTs. The results demonstrate the effective representation of real-airport operations by the simulation model. ETT speed, airport runway and taxiway configurations, takeoff and landing frequencies and imbalances during peak periods all impact the required quantity of ETTs. A comprehensive approach considering these factors is necessary to determine the optimal number of ETTs.

This study presents observations of coherent modes (CMs) in a spherical tokamak using a microwave interferometer near the midplane. The CMs within the 30–60 kHz frequency range were observed during electron cyclotron resonance heating only, and the frequency of the CMs increased proportionally with the square root of the electron temperature near $R = 0.7m$. Generally, these modes displayed bursting and chirping signatures with strong density rise and fall. Their appearance indicated an increase in the intensity of hard x rays, suggesting a deterioration in energetic electron confinement. Furthermore, the effect of CMs on the intensity of energetic electron-driven whistler waves was observed. They decreased when CMs were present and gradually increased with the decrease in CM intensity. The CMs may influence the intensity of whistler waves by affecting the energetic electron confinement.