Search Results (334)

Atherosclerotic cardiovascular disease treatment is being reevaluated, since a residual cardiovascular risk (RCR) persists even in patients who achieve optimal LDL-C values. Underlying causes are metabolic dysfunction, lipoprotein(a), inflammation, and triglyceride-rich lipoproteins and their remnants. Dietary treatment options like time-restricted eating (TRE) are becoming more widely acknowledged for their potential advantages in metabolic health and weight control, as a treatment of atherosclerosis expanding beyond LDL-C medication. Beyond weight loss, TRE (which restricts meals to a window of 6 to 8 h) appears as the most accessible treatment, and has been shown to improve blood pressure, lipid profiles, and glucose regulation through mechanisms like metabolic switching and circadian synchronization. We hypothesize, and will present our arguments, that a key mechanism underlying the cardiovascular and weight-related benefits of TRE is its impact on the circadian regulation of angiopoietin-like protein 4 (ANGPTL4) activity within adipose tissue. Additionally, lipolysis is accelerated by ANGPTL4 activation. TRE, via its actions on ANGPTL4, therefore not only inhibits adipose fatty acid uptake but stimulates their release as well. Additionally, TRE may increase intravascular very low-density lipoprotein (VLDL) catabolism by muscle due to the reduced exposure of lipoprotein lipase (LPL) to competing chylomicrons, known to slow the rate of VLDL catabolism. During the prolonged fasting, VLDL residence time is thus shortened, limiting the exposure to endothelium and hepatic lipases and thus reducing the amount of atherogenic remnant particles. Larger, longer-term randomized controlled studies in a variety of groups are required to further clarify TRE’s function in RCR prevention and therapy. As knowledge of triglyceride lipoprotein (TRL) metabolism expands, a comprehensive strategy for the management of RCR emerges, and a broader spectrum of LPL regulator-based therapeutics is created. Consequently, it is advisable to prioritize further research into the influence of TRE on LPL modulation via ANGPTL4 and ANGPTL8, which provides a natural, accessible, and low-cost alternative. Full article

This study investigates the transverse loads acting on high-speed train bogie frames under actual service conditions. To enable direct identification, the locating arms were instrumented as bending sensors and calibrated under realistic lateral-stop constraints, ensuring robustness of the measurement channels. Field tests were conducted on a CR400BF high-speed EMU over a 226 km route at six speed levels (260–390 km/h), with gyroscope and GPS signals employed to recognize typical operating conditions, including straights, curves, and switches (straight movement and diverging movements). The results show that the proposed recognition method achieves high accuracy, enabling rapid and effective identification and localization of typical operating conditions. Under switch conditions, the bogie frame transverse loads are characterized by low-frequency, large-amplitude fluctuations, with overall RMS levels being higher in diverging switches and straight-through depot switches. Curve parameters and speed levels exert significant influence on the amplitude of the transverse-load trend component. On curves with identical parameters, the trend-component amplitude exhibits a quadratic nonlinear relationship with train speed, decreasing first and then increasing in the opposite direction as speed rises. In mainline curves and straight sections, the RMS values of transverse loads on Axles 1 and 2 scale proportionally with speed level, with the leading axle in the direction of travel consistently producing higher transverse loads than the trailing axle. When load samples are balanced across both running directions, the transverse load spectra of Axles 1 and 2 at the same speed level show negligible differences, while the spectrum shape index increases proportionally with speed level. Full article

Brushless DC (BLDC) motors are commonly used in electric vehicles (EVs) because of their efficiency, small size and great torque-speed performance. These motors have a few benefits such as low maintenance, increased reliability and power density. Nevertheless, BLDC motors are highly nonlinear and their dynamics are very complicated, in particular, under changing load and supply conditions. The above features require the design of strong and adaptable control methods that can ensure performance over a broad spectrum of disturbances and uncertainties. In order to overcome these issues, this paper uses a Fractional-Order Proportional-Integral-Derivative (FOPID) controller that offers better control precision, better frequency response, and an extra degree of freedom in tuning by using non-integer order terms. Although it has the benefits, there are three primary drawbacks: (i) it is not real-time adaptable, (ii) it is hard to choose appropriate initial gain values, and (iii) it is sensitive to big disturbances and parameter changes. A new control framework is suggested to address these problems. First, a Reinforcement Learning (RL) approach based on Deep Deterministic Policy Gradient (DDPG) is presented to optimize the FOPID gains online so that the controller can adjust itself continuously to the variations in the system. Second, Snake Optimization (SO) algorithm is used in fine-tuning of the FOPID parameters at the initial stages to guarantee stable convergence. Lastly, cascade control structure is adopted, where FOPID controllers are used in the inner (current) and outer (speed) loops. This construction adds robustness to the system as a whole and minimizes the effect of disturbances on the performance. In addition, the cascade design also allows more coordinated and smooth control actions thus reducing stress on the power electronic switches, which reduces switching losses and the overall efficiency of the drive system. The suggested RL-enhanced cascade FOPID controller is verified by Hardware-in-the-Loop (HIL) testing, which shows better performance in the aspects of speed regulation, robustness, and adaptability to realistic conditions of operation in EV applications. Full article

Light is a powerful environmental factor with proven effects on human cognitive activity. This study investigated the effects of two types of light—LED with an enhanced long-wavelength spectrum and classic fluorescent—on concentration and attention of undergraduate students. Concentration was assessed through EEG, while attention was evaluated using d2 and TP psychometric tests. The experiment was carried out in a classroom equipped with both lighting systems, with each participant completing two testing sessions under different light conditions, separated by at least seven days to allow for washout. Results showed that during the first administration, LED lighting supported better performance across both EEG and psychometric measures compared to fluorescent light, suggesting enhanced concentration and attention. By the second administration, these differences were less evident, likely due to learning and task familiarization effects. Nonparametric ANOVA-type analyses further indicated that the effect of lighting on performance depended not only on the light type but also on the order of exposure, with students who switched from fluorescent to LED showing improvement, whereas the reverse sequence was associated with a decline. Overall, the findings suggest that LED lighting enriched in warm tones may positively influence attention and concentration, though results should be viewed as exploratory due to the small sample size. Full article

We present a single-slab metasurface that converts a normally incidental linearly polarized wave into either right- or left-handed circular polarization (RHCP/LHCP) through a simple ${90}^{\circ }$ mechanical rotation. Each unit cell comprises two L-shaped metallic resonators placed on the opposite faces of a low-permittivity substrate. Operating in transmission mode, the linear-to-circular (LTC) converter does not require any active electronic components. The geometry is optimized by using full-wave simulations to maximize the conversion up to 26% relative bandwidth with polarization conversion efficiency up to 65%, and insertion loss below 1.3 dB. Power balance analysis confirms low-loss, impedance-matched behavior. A scaled prototype fabricated from AWG-25 steel wires validates the model: experimental measurements closely reproduce the simulated bandwidth and demonstrate robust handedness switching. Because the resonance frequency depends primarily on resonator length and unit-cell pitch and thickness, the design can be retuned across the microwave spectrum through straightforward geometrical scaling. These results suggest that mechanical rotation could provide a simple and reliable alternative to electronic tuning in reconfigurable circular polarizers. Full article

The television white space (TVWS) spectrum presents a promising opportunity to extend wireless broadband access, particularly in rural, underserved, and hard-to-reach communities. To leverage this potential, low-power radio communication equipment must efficiently utilise the TVWS spectrum on a secondary basis while ensuring strict compliance with regulatory requirements to prevent harmful interference to primary services. This paper presents a comparative performance analysis of TVWS radio equipment from three original equipment manufacturers (OEMs). The equipment under test was identified to reflect each OEM, as follows: OEM 1 and OEM 2 from South Korea and OEM 3 from the USA. We evaluated their performance in two real-world field scenarios, namely outdoor short-distance and outdoor long-distance. The evaluation was based on the following key metrics: (i) spectrum utilisation efficiency (SUE), (ii) received signal strength (RSS), (iii) downlink throughput, and (iv) connectivity to the Geo-Location Spectrum Database (GLSD) in compliance with the South African TVWS regulatory framework. The overall preliminary experimental results indicate that in both scenarios, white space devices (WSDs) based on the Institute of Electrical and Electronics Engineers (IEEE) 802.11af Standard demonstrated better performance than those based on the 3rd Generation Partnership Project Long-Term Evolution-Advanced (3GPP LTE-A) Standard in terms of the SUE, downlink throughput, and RSS metrics. All WSDs under test demonstrated sufficient compliance with the regulatory requirement metric. Full article

Multidrug-resistant bacterial infections pose a severe global health threat, highlighting the urgent need for innovative therapeutic options beyond traditional antibiotics. Phage therapy, which employs bacteriophages to infect and eradicate pathogenic bacteria, specifically offers a promising solution. However, the lack of well-characterized therapeutic phages has limited their broader clinical use. A critical aspect of activating the lytic potential of dormant prophages involves the strategic manipulation of transcription factor binding sites (TFBS), which function as pivotal regulatory nodes governing the transition between lysogenic dormancy and lytic activation. Our platform utilizes advanced bioinformatics tools to accurately identify and analyze TFBS, facilitating the targeted redesign or replacement of these sites to disrupt host-mediated repression. By systematically simulating modifications of these regulatory ‘switches,’ our platform computationally predicts reduced repressor activity, suggesting the potential for prophage activation and bacterial cell lysis. This novel methodology not only broadens the spectrum of therapeutic bacteriophages but also establishes a basis for individualized phage-based therapies, presenting a robust strategy to address the escalating challenge of antibiotic-resistant infections. By enabling the precise identification and engineering of TFBS, our platform signifies a transformative advancement in phage biology, effectively bridging the divide between computational analysis and therapeutic application. Full article

Background/Objective: The overnight 1-mg dexamethasone suppression test (DST) represents the conventional/standard tool for endogenous hypercortisolemia screening, typically in relationship with adrenal and pituitary masses. Nevertheless, an associated spectrum of challenges and pitfalls is found in daily practice. This analysis aimed to evaluate: (I.) the diagnosis relevance of 1-mg DST in patients with adrenal incidentalomas (AIs) with/without mild autonomous cortisol secretion (MACS) exploring different cutoffs of the second-day plasma cortisol after dexamethasone administration (cs-DST) with respect to cardio-metabolic outcomes; (II.) the potential utility of adding other biomarkers to DST [plasma morning adrenocorticotropic hormone (ACTH), 24-h urinary free cortisol (UFC), late-night salivary cortisol (LNSC), dehydroepiandrosterone sulfate (DHEAS)]; and (III.) DST variability in time. Methods: This narrative analysis was based on searching full-text, English articles in PubMed (between January 2023 and April 2025) via using different term combinations: “dexamethasone suppression test” (n = 239), “diagnosis test for autonomous cortisol secretion” (n = 22), “diagnosis test for mild autonomous cortisol secretion” (n = 13) and “diagnosis test for Cushing Syndrome” (n = 61). We manually checked the title and abstract and finally included only the studies that provided hormonal testing results in adults with non-functional adenomas (NFAs) ± MACS. We excluded: reviews, meta-analyses, editorials, conference abstracts, case reports, and case series; non-human research; studies that did not provide clear criteria for distinguishing between Cushing syndrome and MACS; primary aldosteronism. Results: The sample-focused analysis (n = 13 studies) involved various designs: cross-sectional (n = 4), prospective (n = 1), retrospective (n = 7), and cohort (n = 1); a total of 4203 patients (female-to-male ratio = 1.45), mean age of 59.92 years. I. Cs-DST cutoffs varied among the studies (n = 6), specifically, 0.87, 0.9, 1.2, and 1.4 µg/dL in relationship with the cardio-metabolic outcomes. After adjusting for age (n = 1), only the prevalence of cardiovascular disease remained significantly higher in >0.9 µg/dL vs. ≤0.9 group (OR = 2.23). Multivariate analysis (n = 1) found cs-DST between 1.2 and 1.79 µg/dL was independently associated with hypertension (OR = 1.55, 95%CI: 1.08–2.23, p = 0.018), diabetes (OR = 1.60, 95%CI: 1.01–2.57, p = 0.045), and their combination (OR = 1.96, 95%CI:1.12–3.41, p = 0.018) after adjusting for age, gender, obesity, and dyslipidemia. A higher cs-DST was associated with a lower estimated glomerular filtration rate (eGFR), independently of traditional cardiovascular risk factors. Post-adrenalectomy eGFR improvement was more pronounced in younger individuals, those with lower eGFR before surgery, and with a longer post-operative follow-up. Cs-DST (n = 1) was strongly associated with AIs size and weakly associated with age, body mass index and eGFR. Cortisol level increased by 9% (95% CI: 6–11%) for each 10 mL/min/1.73 m² decrease in eGFR. A lower cs-DST was associated with a faster post-adrenalectomy function recovery; the co-diagnosis of diabetes reduced the likelihood of this recovery (OR = 24.55, p = 0.036). II. Additional biomarkers assays (n = 5) showed effectiveness only for lower DHEAS to pinpoint MACS amid AIs (n = 2, cutoffs of <49.31 µg/dL, respectively, <75 µg/dL), and lower ACTH (n = 1, <12.6 pmol/L). III. Longitudinal analysis of DST’s results (n = 3): 22% of NFAS switch to MACS after a median of 35.7 months (n = 1), respectively, 29% (n = 1) after 48.6 ± 12.5 months, 11.8% (n = 1) after 40.4 ± 51.17 months. A multifactorial model of prediction showed the lowest risk of switch (2.4%) in individuals < 50 years with unilateral tumor and cs-DST < 0.45 µg/dL. In the subgroup of subjects without cardio-metabolic comorbidities at presentation, 25.6% developed ≥1 comorbidities during surveillance. Conclusions: The importance of exploring the domain of AIs/NFAs/MACS relates to an increasing detection in aging population, hence, the importance of their optimum hormonal characterization and identifying/forestalling cardio-metabolic consequences. The spectrum of additional biomarkers in MACS (other than DST) remains heterogeneous and still controversial, noting the importance of their cost-effectiveness, and availability in daily practice. Cs-DST serves as an independent predictor of cardio-metabolic outcomes, kidney dysfunction, while adrenalectomy may correct them in both MACS and NFAs, especially in younger population. Moreover, it serves as a predictor of switching the NFA into MACS category during surveillance. Changing the hormonal behavior over time implies awareness, since it increases the overall disease burden. Full article

Background/Objectives: While complete loss-of-function (LoF) SPINK1 variants in the simple heterozygous state cause chronic pancreatitis, biallelic complete LoF variants result in a rare pediatric disorder termed severe infantile isolated exocrine pancreatic insufficiency (SIIEPI). To date, only two individuals with a null SPINK1 genotype have been reported—one homozygous for a whole-gene deletion and the other for an Alu insertion in the 3′ untranslated region. Here, we report the genetic basis of a third SIIEPI case, presenting in early infancy with severe exocrine pancreatic insufficiency and diffuse pancreatic lipomatosis. Methods: Targeted next-generation sequencing (NGS) was used to analyze the entire coding region and exon–intron boundaries of the SPINK1 gene. Copy number variant (CNV) analysis was performed with SeqNext, based on normalized amplicon coverage. Results: The proband harbored compound heterozygous complete LoF SPINK1 variants. One was the known NM_001379610.1:c.180_181del (p.(Cys61PhefsTer2)), inherited from the father. The second, initially detected as an exon 2 deletion and confirmed by quantitative fluorescent multiplex PCR (QFM-PCR), was further characterized by long-range PCR as a complex rearrangement comprising a 1185 bp deletion removing exon 2, a 118 bp templated insertion followed by a non-templated nucleotide, and an 8 bp deletion. The mutational signature is consistent with serial replication slippage or template switching involving translesion synthesis. This maternally inherited variant has not been previously reported. Conclusions: This study expands the mutational spectrum of SPINK1-related SIIEPI and suggests that this distinct pediatric disorder may be under recognized in clinical practice. Full article

To exploit the near-infrared (NIR) light of MoO₃, the MoVO_x mixed oxide was synthesized using a one-pot approach. The effects of different electrodes, V doping, and bias on the optoelectronic properties were investigated. The photoelectric responses to light sources with wavelengths of 405, 532, 650, 780, 808, 980, and 1064 nm were studied using both Au and carbon electrodes with 6B pencil drawings. The results demonstrate that the MoVO_x nanoblets exhibit photocurrent switching characteristics across the broadband region of the light spectrum. Even when zero bias was applied and the mixed oxide sample was stored at room temperature for over two years, a good photoelectric signal was still observed. This demonstrates that the MoVO_x nanoblets present an interface where interfacial charge transfer forms a strong built-in electric field, promoting photogenerated charge separation and transfer while suppressing photogenerated carrier recombination, and exhibiting self-powered characteristics. Interestingly, reducing the power of the typical excitation light sources resulted in a transition from positive to negative photocurrent features. This reflects the result of an imbalance between the concentration of material defects and the concentration of photogenerated electrons. The MoVO_x nanoblets not only enhance charge transport performance, but also significantly improve the exploitation of near-infrared light. Doping with V significantly improves the nanocomposites’ near-infrared (NIR) photoelectric sensitivity. This study demonstrates that heavily doping aliovalent ions during the in situ preparation of nanocomposites effectively enhances their photophysical properties. It provides a straightforward approach to narrowing the band gap of wide-bandgap oxides and effectively avoiding the recombination of photogenerated carriers. Full article

The effective integration of energy storage systems is paramount for the widespread deployment of renewable energy technologies. Selection of a specific storage system is typically dictated by the primary challenge it aims to mitigate, such as intermittency, grid stability, or power quality. The optimization of overall system efficiency and longevity is increasingly achieved through hybrid storage systems that integrate supercapacitors into their designs. This research introduces a novel circuital equivalent for a commercial supercapacitor, optimized for precise simulations within the frequency range of power electronics applications. A key distinction of this circuital equivalent lies in its rigorous foundation: its comprehensive characterization across a broad frequency spectrum, specifically from 0.01 Hz to 300 kHz, employing a commercial frequency response analyzer. This precise circuital representation offers substantial utility in simulation, analysis, and design of high-frequency circuits, particularly for switched-power converter design and control. It enables the anticipation of undesirable phenomena, such as significant voltage ripple and operational instability. This predictive capability is crucial for experimental preparation, facilitating the proactive integration of necessary filters and protective measures within sensing circuits, thereby underscoring its value prior to physical implementation. In addition, the developed circuital equivalent exhibits broad compatibility, allowing seamless implementation within commercial circuit simulators. Finally, the proposed methodology was illustrated with a commercial supercapacitor, but it can be applied to other supercapacitor types or manufacturers. Full article

The stable operation of micromachine systems relies on reliable power management, where DC-DC converters provide energy with high efficiency to extend operational endurance. However, these converters also constitute significant electromagnetic interference (EMI) sources that may interfere with the normal functioning of micro-electromechanical systems. This paper proposes a boost converter utilizing Pulse Width Modulation (PWM) with peak current mode control to address the EMI issues inherent in the switching operation of DC-DC converters. The converter incorporates a Hybrid Spread Spectrum (HSS) technique to effectively mitigate EMI noise. The HSS combines a 1.2 MHz pseudo-random spread spectrum with a 9.4 kHz triangular periodic spread spectrum. At a standard switching frequency of 2 MHz, the spread spectrum range is set to ±7.8%. Simulations conducted using a 0.5 μm Bipolar Complementary Metal-Oxide-Semiconductor Double-diffused Metal-Oxide-Semiconductor (BCD) process demonstrate that the HSS technique reduces EMI around the switching frequency by 12.29 dBμV, while the converter’s efficiency decreases by less than 1%. Full article

LEDs are readily controllable and demonstrate rapid switching capabilities. These attributes facilitate their efficient integration across a broad spectrum of applications. Indeed, their inherent versatility renders them ideally suited for diverse sectors, including consumer electronics, traffic signage, automotive technology, and architectural illumination. Furthermore, LEDs serve as effective light sources for applications in spectroscopy, agriculture, pest control, and wireless optical transmission. The capability to choice high-efficiency LED devices with a specified dominant wavelength renders them particularly well-suited for integration into underwater optical communication systems. In this paper, we present the state-of-the-art of Light-Emitting Diodes (LEDs) for use in underwater wireless optical communications (UOWC). In particular, we focus on the challenges posed by water turbidity and evaluate the optimal wavelengths for communication in coastal environments, especially in the presence of chlorophyll or suspended particulate matter. Given the growing development and applications of underwater optical communication, it is crucial that the topic becomes not only a subject of research but also part of the curricula in technical school and universities. To this end, we introduce a simple and cost-effective UOWC system designed for educational purposes. Some tests have been conducted to evaluate the system’s performance, and the results have been reported. Full article

Background/Objectives: Oncogenic KRAS drives ~30% of solid tumours, yet the only approved G12C-specific drugs benefit ≈ 13% of KRAS-mutant patients, leaving a major clinical gap. We sought mutation-agnostic natural ligands from Ziziphus lotus, whose stereochemically rich phenolics may overcome this limitation by occupying the SI/II (Switch I/Switch II) groove and locking KRAS in its inactive state. Methods: Phytochemical mining yielded five recurrent phenolics, such as (+)-catechin, hyperin, astragalin, eriodictyol, and the prenylated benzoate amorfrutin A, benchmarked against the covalent inhibitor sotorasib. An in silico cascade combined SI/II docking, multi-parameter ADME/T (Absorption, Distribution, Metabolism, Excretion, and Toxicity) filtering, and 100 ns explicit solvent molecular dynamics simulations. Pharmacokinetic modelling predicted oral absorption, Lipinski compliance, mutagenicity, and acute-toxicity class. Results: Hyperin and astragalin showed the strongest non-covalent affinities (−8.6 kcal mol⁻¹) by forging quadridentate hydrogen-bond networks that bridge the P-loop (Asp30/Glu31) to the α3-loop cleft (Asp119/Ala146). Catechin (−8.5 kcal mol⁻¹) balanced polar anchoring with entropic economy. ADME ranked amorfrutin A the highest for predicted oral absorption (93%) but highlighted lipophilic solubility limits; glycosylated flavonols breached Lipinski rules yet remained non-mutagenic with class-5 acute-toxicity liability. Molecular dynamics trajectories confirmed that hyperin clamps the SI/II groove, suppressing loop RMSF below 0.20 nm and maintaining backbone RMSD stability, whereas astragalin retains pocket residence with transient re-orientation. Conclusions: Hyperin emerges as a low-toxicity, mutation-agnostic scaffold that rigidifies inactive KRAS. Deglycosylation, nano-encapsulation, or soft fluorination could reconcile permeability with durable target engagement, advancing Z. lotus phenolics toward broad-spectrum KRAS therapeutics. Full article

Background/Objective: This study aimed to evaluate the effectiveness of very early oral transition in Enterobacterales bloodstream infections (E-BSIs), identify factors associated with it, compare the effectiveness of different oral options, and assess its economic and ecological benefits. Methods: Retrospective, observational cohort study including monomicrobial E-BSI in clinically stable adult patients by day 3 of bacteremia with oral antibiotic options. Transition to oral antibiotics by day 3 or earlier (early oral (EO) group) was compared to later transition or remaining on intravenous therapy (nEO group). Early oral transition-associated factors were analyzed. Oral high-dose beta-lactams (BLs) were compared to quinolones (QLs) or trimethoprim/sulfamethoxazole (TS). Economic and ecological costs were assessed. Results: Of 345 E-BSI, 163 (47.2%) were in the EO group, characterized by more urinary tract infections (UTIs) and shorter hospital stays. The nEO group had higher Charlson Comorbidity Index (CCI), extended-spectrum beta-lactamase (ESBL) production, greater source control need, and longer time to clinical stability. There were no significant differences in mortality and relapse. UTIs were associated with early oral transition (OR 2.02, IC 95% 1.18–3.48), while higher CCI (0.85, 0.77–0.95), source control need (0.39, 0.19–0.85), longer time to clinical stability (0.51, 0.39–0.66), and ESBL isolates (0.39, 0.19–0.80) hindered this practice. High-dose BLs and QL/TS were equally effective. Early oral transition resulted in 38.794 KgCO₂eq reduction and EUR 269,557.99 savings. Conclusions: Very early oral transition at day 3 or before in stable E-BSI patients is effective, eco-sustainable, and cost-effective; UTI is related with the early oral switch, while comorbidities, ESBL production, source control need, or longer time to clinical stability hinder this practice. Full article