Search Results (543)

Background: Huntington’s disease (HD) causes progressive motor dysfunction, with chorea as its hallmark symptom. Vesicular monoamine transporter 2 (VMAT 2) inhibitors (tetrabenazine, deutetrabenazine, valbenazine) are established symptomatic therapies, while dopamine stabilizers (pridopidine, ordopidine) are emerging therapies, but their net benefit and safety remain uncertain. Methods: Seven databases were searched through May 2025 following PRISMA guidelines. Random effects meta-analyses calculated mean differences (MDs) for the Unified Huntington Disease Rating Scale total motor score (UHDRS TMS) and total maximal chorea score (TMC), plus risk ratios (RRs) for adverse events (AEs). Trial Sequential Analysis (TSA) applied a Lan DeMets O’Brien Fleming α spending function with 80% power. Results: Seven randomized trials (1431 participants) met inclusion criteria. VMAT 2 inhibitors significantly improved motor outcomes versus placebo (UHDRS TMS: MD −3.80, 95% CI −5.76 to −1.83; TMC: MD −3.05, 95% CI −3.84 to −2.26; both I² = 0%). Dopamine stabilizers produced no meaningful change (UHDRS TMS: MD −0.98, 95% CI −2.48 to 0.51; I² = 32%). Neither class increased total AEs (VMAT 2: RR 1.21, 95% CI 0.99 to 1.48; dopamine stabilizers: RR 1.05, 95% CI 0.92 to 1.20; both I² = 0%). TSA confirmed robust evidence for VMAT 2 benefits on TMC but indicated additional data are required to verify dopamine stabilizer effects on UHDRS TMS. Trial sequential analysis confirmed the reliability of VMAT2 for TMC; however, the sample size was insufficient to draw conclusions about the effects of dopamine stabilizers on UHDRS TMS or their safety outcomes, indicating that additional data are needed. Conclusions: VMAT-2 inhibitors may suggest potential improvements in motor symptoms in Huntington’s disease, while current evidence does not demonstrate a significant benefit of dopamine stabilizers. The safety profiles of both treatments appear generally comparable to placebo. Further rigorous and long-term studies are required to better establish their efficacy and safety. Full article

We investigate the key factors that shape the dynamic evolution of Day-Ahead spot prices of seven European interconnected electricity markets of the Core Capacity Calculation Region, Core CCR (Austria AT, Hungary HU, Slovenia SI, Romania RO), the Southeast CCR (Bulgaria BG, Greece GR) and the Greece-Italy CCR (GRIT CCR), with emphasis on price surges and discrepancies observed in SEE CCR markets, during the period 2022–2024. The high differences in the prices of the two groups have generated political reactions from the countries that ‘suffer’ from these price discrepancies. By applying Machine Learning (ML) approaches, as Markov Blanket (MB) and Local, causal structures learning (LCSL), we are able of ‘revealing’ the entire path of volatility spillover of both spot price and the Cross-Border Transfer Availabilities (CBTA) between the countries involved, from north to south, thus uncovering i.e., ‘lifting the blanket’, to discover the ‘true’ structure’ of the path of causalities, responsible for the price disparity. The above methods are supported by the ‘mainstream’ approach of computing the correlation of the spot price and CBTA’s volatility curves of all markets, to detect volatility spillover effects across markets. The main findings of this hybrid approach are (a) the volatility of some Core CCRs (AT, HU, RO) markets’ spot price and CBTAs with neighboring countries, ‘uncovered’ to be pivotal, operating as a ‘transmitter’ of volatility ‘disturbances’, over its entire connection and causal path from Core CCR to SEE CCR markets, partially contributing to their price surge, (b) reduced available capacity for cross-border trading of some Core and SEE CCRs (they have not satisfied the minimum 70% requirement margin available for cross-zonal trade, MACZT), combined with local weather and geopolitical conditions, could have exacerbated the impact of the Flow-based Market coupling method (FBMC) used in the Core CCRs, on the prices’ surge of SEE CCR’s countries, e.g., via induced non-intuitive flows. This phenomenon questions the efficiency and reliability of the European Target’s model (TM) in securing ‘homogeneous’ power prices across all interconnected markets, core and peripheral. Full article

Traffic-induced noise pollution is a significant environmental issue, driving the development of advanced noise-reducing pavement materials. Semi-dense graded asphalt mixtures (SDAMs) present a promising compromise, offering enhanced acoustic properties compared to conventional dense-graded asphalt mixtures while maintaining superior durability to porous asphalt mixtures. However, the mechanism underlying the relationship between the energy dissipation characteristics and noise reduction effects of such mixtures remains unclear, which limits further optimization of their noise reduction performance. This study designed and prepared semi-dense graded noise-reducing asphalt mixtures SMA-6 TM, SMA-10 TM, and SMA-13 TM (SMA TM represents noise-reducing SMA mixture) based on traditional dense-graded asphalt mixtures SMA-6, SMA-10, and SMA-13, and conducted tests for water stability, high-temperature performance (60 °C), and low-temperature performance (−10 °C). Subsequently, energy loss parameters such as loss factor and damping ratio were calculated through dynamic modulus tests to characterize their energy dissipation properties. The mechanism linking the energy dissipation characteristics of semi-dense graded asphalt mixtures to noise reduction was investigated. Finally, the noise reduction effect was further verified through a tire free fall test and a close-proximity (CPX) method. The indoor test results indicate that the semi-dense mixtures exhibited a trade-off in performance: their dynamic stability was 11.1–11.3% lower and low-temperature performance decreased by 4.2% (SMA-13 TM) to 14.1% (SMA-6 TM), with moisture stability remaining comparable. Conversely, they demonstrated superior damping, with consistently higher loss factors and damping ratios. All mixtures reached peak damping at 20 °C, and the loss factor showed a strong positive correlation (R² > 0.91) with energy dissipation. Field results from a test section showed that the optimized SMA-10 TM mixture yielded a significant tire–road noise reduction of 3–5 dB(A) relative to the SMA-13, while concurrently meeting key performance criteria for anti-water ability and durability. This study establishes a link between the energy dissipation in SDAM and their noise reduction efficacy. The findings provide a theoretical framework for optimizing mixture designs and support the wider application of SDAM as a practical noise mitigation solution. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing public health concern influenced by both genetic and metabolic factors. Polygenic risk scores (PRSs), which combine the effects of known single-nucleotide polymorphisms (SNPs), may improve early risk stratification. We conducted an observational study on 298 MASLD patients: 148 from a Hepatology Unit and 150 from a Bariatric Surgery Unit. Genotyping was performed for the PNPLA3, TM6SF2, MBOAT7, and GCKR variants. A PRS was calculated and used to stratify patients by genetic risk. Liver fibrosis was assessed using the FIB-4 index, and a subset also underwent transient elastography. Clinical, biochemical, and anthropometric data were analyzed across genetic strata. PRSs showed positive correlations with AST, ALT, and FIB-4, indicating increased liver injury and fibrosis risk with higher genetic burden. Transaminases increased significantly across PRS quartiles (p < 0.05), and individuals with PRS > 0.532 exhibited elevated AST, ALT, and borderline FIB-4. Variant-specific associations included PNPLA3 with increased AST and MBOAT7 with higher hepatic steatosis (CAP). Subgroup analyses revealed distinct genetic and phenotypic patterns between the two clinical cohorts. These findings support the additive role of genetic risk in MASLD progression and underscore the value of polygenic profiling for the early identification and personalized management of high-risk patients. Full article

Al-based intermetallic compounds possess excellent mechanical and thermal properties, making them promising candidates for high-temperature structural applications. In this study, the structural stability, mechanical properties, and electronic characteristics of Al₅TM (TM = Mo, Nb, Os, Re, Ru, Ta, Tc, Ti) intermetallic compounds were systematically investigated using first-principles calculations based on density functional theory. All alloys exhibit negative formation energy, indicating favorable thermodynamic stability. Elastic constant analysis shows that all compounds satisfy the Born stability criteria, confirming their mechanical stability. Among them, Al₅Mo (205.9 GPa), Al₅Nb (201.1 GPa), and Al₅Ta (204.1 GPa) exhibit relatively high Young’s moduli, while Al₅Os, Al₅Re, and Al₅Ru demonstrate large bulk moduli and good ductility. The high Debye temperatures of Al₅Mo (600.5 K) and Al₅Nb (606.7 K) suggest excellent thermal stability at elevated temperatures. Electronic structure analysis reveals that all alloys exhibit metallic behavior with no band gap near the Fermi level. The hybridization between TM-d and Al-3p orbitals enhances the covalent bonding between Al and TM atoms. This study provides theoretical guidance for the design and application of high-performance Al-based intermetallic compounds. Full article

A novel efficient method to evaluate time-periodic flows is applied to turbomachinery configurations in this paper (PSpTM). The technique reduces the overall computational cost of unsteady CFD calculations relative to conventional implicit approaches. The method is based on a pseudo-spectral definition of the time derivative rearranged in a time-marching fashion. The key advantage of this novel formulation compared with classical harmonic methods is that it requires minor modifications in the CFD solver structure. The method was implemented into an existing unstructured edge-based, second-order, compressible RANS solver. To benchmark the method, a well-established implicit time scheme based on a second-order backward implicit approach (BDF2) is used. Sample unsteady turbomachinery configurations are used to determine the accuracy and efficiency of the method. The accuracy of the solution is highly linked to the number of harmonics prescribed for the solution. An adequate level of accuracy was obtained while retaining a reduced number of harmonics, with approximately twice the number of harmonics of the unsteady perturbation. Notable savings in computational cost were observed when the PSpTM method was used with speed-up factors of between 2 and 10 with respect to the BDF2, depending on the case. However, the PSpTM method exhibits a poor periodic convergence rate, leaving room for further improvements in efficiency. However, even in its current form and with the current understanding, the method has a remarkable performance. Full article

The goal of this paper is to evaluate the life of HVDC extruded cables subjected to the extension of qualification test (EQT) load cycles, introduced by Cigrè Technical Brochure 852, as well as to compare the results thus obtained with those formerly obtained by the authors in the case of the prequalification test (PQT) load cycles. This goal has been achieved in the present investigation by properly modifying a previously developed procedure for the life and reliability estimation of HVDC cables—implemented in Matlab^TM environment—to make it applicable to EQT load cycles in addition to PQT and type test load cycles, which are already considered in the former version of the procedure. Considering a 500 kV DC-XLPE cable as the case study, the time-varying temperature profile and electric field profile within the cable insulation are calculated. Then, the fractions of life lost and the life of the cable at five locations within the insulation thickness are evaluated by means of a proper electrothermal life model. A comparison between the electric field distributions, fractions of life lost, and cable life under EQT and PQT is carried out. In this way, important features of the EQT compared to the PQT load cycles are singled out, and eventually, a new modified extension of qualification test (MEQT) is proposed as a feasible and meaningful compromise between the pros and cons of the EQT and PQT. Full article

Air stability caused by the H₂O/CO₂ reaction at the layered oxide NaTMO₂ surface is one of the main obstacles to commercializing sodium-ion batteries (SIBS). The H₂O and CO₂ adsorption properties on the (100) surface of sodium layered transition metal oxide NaTMO₂ (TM = Co, Ni, Mo, Nd) are calculated using the DFT method to study the surface air stability. This study showed that the material bulk phase (symmetry), surface site, element type, and surface termination are all (though not the only) important factors that affect the adsorption strength. Contrary to previous studies, the P phase is not always more air-stable than the O phase; our calculations showed that the NaNiO₂ O phase is more stable than the P phase. The calculated band center and occupation showed a direct relationship with the adsorption energy. The Na site adsorption for CO₂ and H₂O showed the same V-shape trend. However, the TM adsorption for CO₂ and H₂O showed a different trend. With an increased t₂g band center, CO₂ adsorption strength increases. There is no clear trend for H₂O adsorption. Our calculations showed that the electronic structure of the surface atomic of adsorption site plays a decisive role in CO₂ and H₂O adsorption strength. This study demonstrated an effective method for obtaining a stability parameter regarding the electronic structure, which can be used to screen the air-stable layered oxide sodium cathode in the future. Full article

Introduction: The multigene molecular testing of prostate cancer tissue after biopsy provides individualized information to guide further management. The utility of selective genetic testing for MRI-visible target versus systematic cancer in patients as well as during different time points of active surveillance (AS) is unknown. The objective of this study was to compare Prolaris^TM results of MRI-target cancers versus systematic cancers on prostate needle biopsy as well as both during consideration for initial AS candidacy and candidacy for remaining on AS. Methods: Our prospectively maintained institutional multiparametric (mp) MRI prostate cancer active surveillance database (2013–2024) was queried for patients that underwent Prolaris^TM genetic testing of positive biopsy cores. Baseline information for PSA, PSA density, and Prolaris^TM calculated data were collected. Information on the timing of the Prolaris testing, defined as during the initial cancer diagnostic biopsy or on a subsequent confirmatory biopsy was collected. SPSS v29.0 was used to compare the selective Prolaris^TM results of MRI-target cancers versus systematic cancers during different points of AS. Results: 264 patients with a Prolaris^TM test were identified, 86 with MRI-target and 178 on systematic cancers. 182 Prolaris^TM tests were sent on a diagnostic biopsy and 81 on a subsequent biopsy. Overall, MRI-target cancers had similar risk scores (3.23 vs. 3.14, p = 0.18). Prolaris^TM scores were higher for GG2 systematic than GG1 target cancers (3.40 vs. 3.18, p = 0.023). The GG2 systematic lesion cohort also had higher predicted the 10-year disease-specific mortality (DSM) (3.40% vs. 2.30%, p < 0.01) and 10-year metastasis risk (1.90% vs. 1.20%, p = 0.013), and more aggressive recommended treatment. Analyses of the Prolaris^TM results sent during a diagnostic biopsy yielded similar results. Finally, on an analysis of the Prolaris^TM results sent during subsequent biopsy, a systematic GG2 biopsy was noted to have a higher 10-year DSM and metastasis rate, but similar risk scores and treatment recommendations. Conclusions: Prolaris^TM tests can be sent at multiple time points of AS, and selectively for MRI-visible versus higher grade cancers. There is no consistent association between MRI-visible cancer and Prolaris risk profile. When utilizing multigene molecular testing in prostate cancer, each individual patient must be evaluated to decide the appropriate level of care. Full article

Membrane-based direct air capture of CO₂ (m-DAC) is a promising solution for atmospheric decarbonization. Despite growing interest, the impact of relative air humidity on the performance of m-DAC systems is often neglected in the literature. This study presents detailed parametric analyses that take into account humidity variability and several hypothetical scenarios regarding membrane selectivity toward water vapor. Specifically, cases were considered where the permeance of H₂O relative to CO₂ was assumed to be 0.5, 2, and 5 times higher, which allowed for a systematic assessment of the impact of relative humidity on process performance. The calculations were carried out both for membranes with assumed separation parameters and for the PolyActive^TM membrane, enabling a realistic evaluation of the influence of atmospheric conditions on the process. The results show that an increase in humidity in the analyzed range from 0 to 80% can lead to a rise in the energy intensity of the process by up to approximately 34%, and an increase in total power demand by around 29%. As humidity increases, key process parameters such as CO₂ purity in the permeate and recovery rate decrease. The water vapor content in the permeate in a single-stage membrane separation process can reach up to 60%. It is recommended to use gas drying systems and to develop membranes with low H₂O permeance in order to reduce the energy cost of the process. The potential location of m-DAC systems should preferably be in regions with low air humidity. The study highlights the necessity of considering local climate conditions and the need for further research on membrane selectivity. Full article

The present study focuses on the dynamics of trace metals (TM) in two European rivers, the Mosel and the Meuse. A deterministic description of hydro-sedimentary processes has been performed. The model used to describe pollutant transport and dilution at the watershed scale has been enhanced with the implementation of the MicMod sub-model. The objective of this study is to characterise the dynamics of TM in the water column and bed sediment. A multi-class grain size representation has been developed in MicMod. The dissolved and particulate TM phases have been calculated with specific partitioning coefficients associated with each suspended sediment (SS) class. The processes involved in TM fate have been calibrated in MicMod, including settling velocity, TM releases from the watershed (point and diffuse loads), etc. Following the calibration of the parameters involved in TM transport within the river ecosystem, the main goal is to describe TM dynamics using a pressure–impact relationship model. It was demonstrated that the description of at least one class of fine particles is necessary to obtain an adequate representation of TM concentrations. The focus of this study is low flow periods, which are characterised by the presence of fine particles. The objective is to gain a deeper understanding of the processes that control the transport of TM. This paper establishes consistent pressure–impact relationships between TM loads (urban, industrial, soils) from watersheds and concentrations in rivers. Full article

This study introduces a Self-Attention (SA) Generative Adversarial Network (GAN) framework that applies artificial intelligence techniques to microwave sensing for electromagnetic imaging. The approach involves illuminating anisotropic objects using Transverse Magnetic (TM) and Transverse Electric (TE) electromagnetic waves, while sensing antennas collecting the scattered field data. To simplify the training process, a Back Propagation Scheme (BPS) is employed initially to calculate the preliminary permittivity distribution, which is then fed into the GAN with SA for image reconstruction. The proposed GAN with SA offers superior performance and higher resolution compared with GAN, along with enhanced generalization capability. The methodology consists of two main steps. First, TM waves are used to estimate the initial permittivity distribution along the z-direction using BPS. Second, TE waves estimate the x- and y-direction permittivity distribution. The estimated permittivity values are used as inputs to train the GAN with SA. In our study, we add 5% and 20% noise to compare the performance of the GAN with and without SA. Numerical results indicate that the GAN with SA demonstrates higher efficiency and resolution, as well as better generalization capability. Our innovation lies in the successful reconstruction of various uniaxial objects using a generator integrated with a self-attention mechanism, achieving reduced computational time and real-time imaging. Full article

MXenes have emerged as promising candidates for energy storage and catalyst design. Through detailed density functional theory (DFT) calculations, we designed a series of new 2D composite MXene-based nanomaterials by covering excellent TM₃N₂ MXenes (TM = Nb, Ta, Mo, and W) with graphene or buckled silicene. Our findings demonstrate that this coating can lead to high catalytic activity for hydrogen evolution reactions (HER) in these composite MXene-based systems, with silicene exhibiting superior performance compared to graphene. The relevant carbon and silicon atoms in the coated materials serve as active sites for HER due to complex electron transfer processes. Additionally, doping N or P atoms into graphene/silicene, which have similar atomic radii, but larger electronegativity than C/Si atoms, can further enhance the HER activity of adjacent carbon or silicon atoms, thus endowing the composite systems with higher HER catalytic performance. Coupled with their high stability and metallic conductivity, all these composite systems show great potential as electrocatalysts for HER. These remarkable findings offer new strategies and valuable insights for designing non-precious and highly efficient MXene-based HER electrocatalysts. Full article

(1) Background: In order to conduct in vitro studies regarding muco-supported dentures, it is necessary to have a simulation model that simulates the oral mucosa, as it is the main influencing factor for their retention and stabilisation. The aim of this study is to perform tensile and wettability tests in three different elastomers to identify the best material for simulating the oral mucosa. (2) Methods: A tensile test was performed according to ISO 527-1 and a compressive test was performed according to ISO 604:2002, at a constant speed of 10 mm/min. The E-modulus was calculated. A wettability test was performed according to ISO 19403-2. Shore A hardness was measured according to ISO 868:2003. All values were compared with the oral mucosa data. (3) Results: Tensile E-modulus calculation revealed no significant difference between Molloplast^® B and EXA’lence^TM Light Body. The mean drop angle calculation revealed no significant difference between Ufi Gel^® SC and Molloplast^® B. The compression E-modulus showed significant differences for Ufi Gel^® SC and EXA’lence^TM Light Body, while Molloplast^® B showed no significant deviation. Ufi Gel^® SC has a similar Shore A hardness to the other materials. (4) Conclusions: Molloplast^® B and Ufi Gel^® SC are the most similar elastomers to the alveolar mucosa. Full article

Drilling long horizontal wells in naturally cracked/fractured unconventional shale gas/oil formations presents a huge challenge to the energy industry because of wellbore clogging complications that cause pipe sticking problems. This work proposes to use smooth catenary well trajectories to reduce drilling friction to mitigate these problems. A mathematical model was developed in this study for designing well trajectory profiles with a smooth transition from the kick-out point (KOP) to the catenary section. This model consists of closed-form equations for the radius of curvature and inclination angle in the catenary section. Using the radius of curvature at the top point of the catenary section to design the arc section below the KOP eliminates the trial-and-error procedure required for achieving the smooth transition between the two sections. The result of a field case study with Tuscaloosa Marine Shale (TMS) data shows that the drilling drag (hook load) can be reduced by 15% to 30% with the use of smooth catenary well trajectories to replace the conventional arc-type well trajectories. Model-calculated reduction in the hook load drops linearly with the horizontal borehole friction coefficient (clog indicator). The reduction increases non-linearly from 15% to 30% with drill collar weight increasing from 20 lb/ft to 92 lb/ft. Full article