Search Results (4,772)

Background/Objectives: MSS-CRC comprises a heterogeneous group of tumors generally considered “immune cold” due to limited neoantigen generation and T-cell exclusion or inactivation. Current evidence indicates that the composition of T and B immune cells within the tumor microenvironment represents a prognostically relevant factor, significantly associated with both tumor expression profiles and molecular subtypes. Methods: We conducted an exploratory analysis to identify prognostically relevant immune cell components in this group of tumors and to investigate corresponding differences in RNA-based bulk expression and high-resolution spatial transcriptomic profiles. Results: A total of 254 localized mismatch repair-proficient colorectal cancer cases were evaluated. Our findings revealed PD-L1 expression as a robust independent prognostic biomarker associated with favorable outcomes in this specific population. Bulk RNA expression analysis showed that PD-L1-negative tumors exhibited an expression profile consistent with abundant cancer-associated fibroblast infiltration, increased matrix stiffness, and impaired immune activation—features consistent with tumor progression and poorer clinical outcomes. In contrast, PD-L1-positive tumors displayed stromal programs enriched in immune activation and controlled remodeling, consistent with an immunologically active microenvironment. Spatial transcriptomics added an additional layer of evidence, revealing that epithelial to mesenchymal transition-related programs can dominate stromal niches in PD-L1-negative tumors, particularly within macrophage-enriched stromal regions. Conclusions: Our observations suggest an association between PD-L1 expression on immune cells and immune-activated versus mesenchymal-dominant states, potentially occurring within macrophage-enriched stromal niches. These results provide insight into the biological mechanisms underlying disease progression and highlight tumor-associated macrophages as a potential therapeutic target to overcome immune resistance, particularly in PD-L1-negative MSS-CRC tumors. Full article

This paper presents a 13 W Ku-band GaN HEMT MMIC power amplifier employing a coupled-line interstage stabilization technique for radar sensor front-end applications. High-efficiency and stable power amplification in the Ku-band is essential for radar sensing systems, where low-frequency instability and process sensitivity often limit multistage GaN amplifier performance. To address these challenges, a coupled-line interstage network is introduced instead of conventional series capacitors and parallel RC stabilization circuits. The proposed structure effectively suppresses low-frequency gain while maintaining RF performance and improving robustness against process variations due to its planar transmission-line implementation. The two-stage power amplifier was fabricated using a 0.25 μm commercial GaN HEMT MMIC process. For compact implementation, the coupled-line structure was realized in a meandered layout and verified through full electromagnetic simulations. Measured small-signal results show a gain (S21) of 18.6–21.6 dB, with input and output return losses (S11 and S22) of −3.3 to −10.2 dB and −4.4 to −7.2 dB, respectively, over 13.5–16 GHz. Large-signal measurements demonstrate a saturated output power of 40.7–41.5 dBm and a power-added efficiency of 21.3–28.1% across the same frequency range. The fabricated MMIC achieved stable operation without oscillation, validating the effectiveness of the proposed coupled-line stabilization approach for Ku-band radar sensor systems. Full article

Background/Objectives: Atopic dermatitis (AD)-related skin inflammation involves the release of cytokines and chemokines from keratinocytes; therefore, keratinocyte-based models are widely used to evaluate the anti-inflammatory potential of botanical extracts. This study examined the relationship between phytochemical profiles and anti-inflammatory potential of baobab fruit 30% and 70% ethanol extracts (BE-30 and BE-70, respectively) in a TNF-α/IFN-γ (TI)-stimulated HaCaT keratinocyte model. Methods: The anti-inflammatory effects of both extracts were evaluated by measuring cytokine and chemokine secretion in TI-stimulated HaCaT cells. Phytochemical characterization was performed using liquid chromatography–tandem mass spectrometry (LC–MS/MS) and targeted high-performance liquid chromatography (HPLC). Results: Both extracts were non-cytotoxic. TI-stimulation markedly increased interleukin (IL)-6, IL-8 and monocyte chemotactic protein (MCP)-1 secretion, while BE-30 and BE-70 significantly reduced all three mediators in a dose-dependent manner. At comparable doses, BE-70 exhibited greater inhibition than BE-30. BE-30 showed a non-monotonic IL-8 response at low concentrations, whereas BE-70 consistently reduced IL-8 in a dose-dependent manner. LC–MS/MS profiling revealed a polyphenol-rich composition, including flavonol glycosides and related phenolic compounds. HPLC confirmed the presence of four marker analytes (procyanidin B2, epicatechin, rutin and tiliroside), which were enriched in BE-70. The content of these four polyphenols was 1.94-fold higher in BE-70. Conclusions: Baobab fruit extracts exhibit anti-inflammatory activity associated with polyphenols. These findings suggest that they could be used as analytical standards and in dermatological applications. Full article

Background/Objectives: Alzheimer’s disease (AD) is an irreversible neurodegenerative disorder that imposes a profound burden on global public health. While resting-state functional magnetic resonance imaging (rs-fMRI)-based dynamic functional connectivity (dFC) analysis has demonstrated promise in capturing time-varying brain network abnormalities, existing deep learning methods suffer from three fundamental limitations: (1) an inability to model temporal dependencies across dynamic connectivity windows, (2) reliance on post hoc black-box explainability tools, and (3) misalignment between feature learning and classification objectives. Methods: To address these challenges, we propose MambaKAN, an end-to-end interpretable framework integrating a Variational Autoencoder (VAE), a Selective State Space Model (Mamba), and a Kolmogorov–Arnold Network (KAN). The VAE encodes each dFC snapshot into a compact latent representation, preserving nonlinear connectivity patterns. The Mamba encoder captures long-range temporal dynamics across the sequence of latent representations via input-selective state transitions. The KAN classifier provides intrinsic interpretability through learnable B-spline activation functions, enabling direct visualization of how latent features influence diagnostic decisions without post-hoc approximation. The entire pipeline is trained end-to-end with a joint loss function that aligns feature learning with classification. Results: Evaluated on the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset across five classification tasks (CN vs. AD, CN vs. EMCI, EMCI vs. LMCI, LMCI vs. AD, and four-class), MambaKAN achieves accuracies of 95.1%, 89.8%, 84.0%, 86.7%, and 70.5%, respectively, outperforming strong baselines including LSTM, Transformer, and MLP-based variants. Conclusions: Comprehensive ablation studies confirm the indispensable contribution of each module, and the three-layer interpretability analysis reveals key temporal patterns and brain regions associated with AD progression. Full article

Classifying power quality disturbances (PQDs) under strong noise conditions remains challenging for existing deep learning models. These models typically separate denoising from feature extraction, often rely on attention mechanisms that operate along only a single dimension, and tend to achieve high accuracy at the cost of high complexity, which limits their performance under low signal-to-noise ratio conditions and hinders practical deployment. To address these limitations, this paper proposes AD-PDAF-Net, which organically integrates three key mechanisms through a co-design strategy. Unlike conventional methods that depend on preprocessing, an adaptive soft thresholding denoising layer is embedded into a lightweight residual network to progressively suppress noise during feature extraction, thereby unifying denoising with feature learning. A parallel dual attention module independently refines features along the channel and temporal dimensions, then adaptively fuses them using learnable weights to capture both frequency domain and temporal characteristics of disturbances. The lightweight network entry replaces aggressive downsampling with small convolutions to preserve transient details, and a bidirectional long short-term memory network (BiLSTM) efficiently captures temporal dependencies. Evaluated on a dataset of 25 disturbance categories defined in IEEE Std 1159-2019, the model achieves a classification accuracy of 97.26% and a Kappa coefficient of 97.02% under 20 dB white Gaussian noise, along with an accuracy of 98.78% under mixed noise conditions. The model has only 0.36 million parameters and a computational cost of just 1.50 GFLOPS. Through this co-design, AD-PDAF-Net achieves both high noise robustness and high classification accuracy with minimal computational overhead, offering an effective solution for time series signal recognition in resource constrained environments. Full article

Maize biomass production and quality are influenced by numerous factors, including fertilization, soil characteristics, and climatic conditions. The aim of our study was to evaluate how different fertilization treatments ((1) Control, (2) farmyard manure (FYM), (3) FYM with added mineral nitrogen (FYM + N), and (4) FYM with added NPK mineral fertilizers (FYM + NPK)) affect the biomass yield and quality parameters (crude protein (CP), fiber content (FC), neutral detergent fiber (NDF), starch content (STR), organic matter digestibility (OMD), and neutral detergent fiber digestibility (DNDF)) of silage maize under various soil and climatic conditions in the Czech Republic (Caslav—degraded Chernozem, Ivanovice na Hané–Chernozem, Lukavec–Cambisol). The experiment was conducted from 2020 to 2023. Additionally, the study analyzed the effects of fertilization on soil chemical properties (pH, P, K, Ca, Mg, C, N). The highest average biomass yields were recorded in Ivanovice (23.8 t ha⁻¹, A), followed by Lukavec (19.7 t ha⁻¹, B) and Caslav (18.1 t ha⁻¹, B). Comparing fertilizer treatments, no significant differences were observed among FYM, FYM + N, and FYM + NPK; however, all three treatments significantly outperformed the Control at all sites. Conversely, fertilization did not affect the quality parameters. For silage maize, FYM represents the optimal fertilization strategy, providing yields and quality comparable to the combined application of mineral N, P, and K, which are more costly (in terms of purchase and application) and, under certain conditions, may negatively impact the environment. Nevertheless, the application of mineral fertilizers increased soil nutrient content, thereby improving conditions for subsequent crops. Full article

Background: We evaluated whether adding S100B to NSE improved discrimination or high-specificity rule-in of poor neurological outcome after out-of-hospital cardiac arrest (OHCA). Methods: In this single-center retrospective cohort study, comatose adult OHCA survivors treated with targeted temperature management had NSE and S100B measured at 0, 24, 48, and 72 h after return of spontaneous circulation. At each time point, we assessed NSE alone, S100B alone, and a logistic model combining both biomarkers in paired complete cases. Discrimination was assessed using the area under the receiver operating characteristic curve (AUC). Rule-in performance was evaluated using a timepoint-specific threshold that achieved 100% specificity in our cohort. Poor neurological outcome was defined as cerebral performance category 3–5 at 6 months. Results: Among 124 patients, 66 (53.2%) had poor outcomes. AUCs were similar between NSE alone and the combination across all time points (all p > 0.3). At 48 h, the combination ruled in 46/65 (70.8%) patients with poor outcome versus 36/65 (55.4%) with NSE alone, identifying 10 additional patients and a 15.4-percentage-point difference (95% confidence interval, −5.6 to 23.6). Conclusions: Adding S100B to NSE did not improve overall discrimination. The higher 48 h rule-in yield was estimated imprecisely and should be interpreted cautiously. Our findings require external validation before they can be translated to clinical settings. Full article

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by cholinergic dysfunction, amyloid-β aggregation, mitochondrial stress, and aberrant kinase activity. Carotenoids, naturally occurring pigments with antioxidant and neuroprotective properties, have emerged as promising candidates for AD intervention. In this study, we performed a systematic stepwise computational screening of a large carotenoid library (n = 1191) to identify multitarget candidates against AD–related proteins. The workflow consisted of predefined ADMET filtering (oral absorption > 90%, Caco-2 > 0.9, logBB > −1, and absence of major CYP inhibition and toxicity alerts), reducing the dataset to 61 compounds, followed by multi-target molecular docking against AChE, BChE, BACE-1, MAO-B, and GSK3-β. Compounds were ranked using an aggregated mean docking score across all five targets, and the top-performing candidate was subjected to detailed mechanistic analyses. Hopkinsiaxanthin emerged as the highest-ranked multitarget carotenoid and was further evaluated using frontier molecular orbital (FMO) analysis, pharmacophore modeling, 100 ns molecular dynamics (MD) simulations, MM/PBSA binding free energy calculations, and per-residue decomposition. Docking predicted favorable estimated binding affinities toward all targets. MD simulations confirmed stable receptor–ligand complexes with low RMSD values (0.278–0.285 nm). MM/PBSA analysis indicated favorable binding free energies, particularly for GSK3-β (−22.73 kcal/mol) and AChE (−21.50 kcal/mol). Per-residue decomposition identified key hotspot residues driving stabilization. Overall, this structured computational framework identifies Hopkinsiaxanthin as a promising multitarget scaffold and supports its prioritization for experimental validation in AD models. Full article

Background/Objectives: Our previous study demonstrated that while the third SARS-CoV-2 booster effectively enhanced immunity against the Delta subvariant, its protection declined over time. This study aimed to evaluate and compare the humoral and cellular immune responses, as well as reactogenicity, of the mRNA-1273 vaccine administered as a fourth booster in healthy Thai adults previously vaccinated with two doses of CoronaVac (CV) followed by a third dose of either AZD1222 (AZ) or BNT162b2 (BNT). Methods: Participants received a single 100 µg (0.5 mL) intramuscular dose of mRNA-1273. Blood samples were collected at baseline (D0), D14, D90, and D180 to assess anti-RBD IgG, conduct a surrogate virus neutralization test (sVNT) against the Delta and Omicron variants, and assess IFN-γ levels and reactogenicity. Results: Both 2CV/AZ- and 2CV/BNT-primed groups exhibited comparable local and systemic reactogenicity. The fourth mRNA-1273 dose markedly increased Delta variant inhibition within 14 days in both groups and remained at high levels at Days 90 and 180. sVNT inhibition against Omicron rose similarly in both groups at Day 14; it declined sharply by Days 90 and 180, with the 2CV/AZ-primed group showing significantly lower levels than the 2CV/BNT-primed group. Baseline anti-RBD IgG levels were lower in the 2CV/AZ group (p = 0.003) but surpassed those of the 2CV/BNT group by Day 14, with no significant differences at later time points. IFN-γ responses followed a similar pattern to anti-RBD IgG Conclusions: A heterologous fourth mRNA-1273 booster in both 2CV/AZ- and 2CV/BNT-primed groups effectively enhances B-cell and T-cell responses against SARS-CoV-2. However, emerging variants such as Omicron may still pose challenges. The trial was registered with the Thai Clinical Trials Registry: the name of the registry: “The comparison of immune response to the 4th dose booster with mRNA-1273 COVID-19 vaccine in individuals who had received 2 doses of CoronaVac and booster with ChAdOx-1 or BNT162b2 COVID-19 vaccine”, TCTR20220205002 on 5 February 2022. Full article

The natural and cultural components of the acoustic environment are a resource intrinsic to parks and protected areas and are critical to wildlife and the visitor experience. However, noise degrades the natural acoustic environment, and aircraft introduce spatially extensive noise into such environments. This study examined aircraft noise events at Great Smoky Mountains National Park, U.S., for different jet aircraft types categorized as “Light” (<20,000 pounds) and “Heavy” (>20,000 pounds). Detection distances were determined for these aircraft types by examining the active space of each aircraft’s noise events. The results of this study determined mean detection distances of 15.2 km for “Light” aircraft and 18.3 km for “Heavy” aircraft to the active space boundaries. Increased thrust or jet velocity from the higher mean altitude resulted in a larger active space. From a practical management perspective, to minimize noise impacts on the park’s natural and cultural resources, efforts should focus on “Heavy” aircraft because they produce greater thrust and frequently operate above GRSM. Using detection distances, managers could work with these aircraft operators or airports to reduce thrust and velocity when flying above protected areas and to discuss routing around noise-sensitive areas, especially with low-level overflights. Full article

Background: The steady increase in allergic diseases among children has coincided with increased global vaccination coverage and the expansion of routine childhood immunization programs. This has contributed to the widespread belief that there is a possible link between immunoprophylaxis and allergic diseases. However, a number of scientific studies have demonstrated the protective effect of early neonatal immunization on the development of nonspecific immunological protection against infections. This is believed to be due to a shift in the immune response from the Th2 type, traditionally predominant in newborns, to the Th1 type, which reduces the risk of developing allergic diseases. Methods: This prospective cohort study analyzed the medical records of 2279 children born between 2018 and 2022 to evaluate the impact of neonatal BCG-M and hepatitis B (HepB) vaccination on the incidence of atopic dermatitis (AD) by 36 months of age. Factors analyzed included family history of allergy, cesarean section, prematurity, delayed initiation of breastfeeding, maternal antibiotic use during pregnancy, and antibiotic use in the child during the first three years of life. Results: The cumulative incidence of AD by 36 months of age was 19.9%. Timely neonatal vaccination coverage was 76.2% for BCG-M and 69.2% for HepB; by 12 months of age, these rates increased to 90.2% and 88.5%, respectively. A full-term birth demonstrated a significant protective effect (OR 0.52; 95% CI 0.30–0.93). A positive family history of allergy was the strongest predictor of AD (OR 21.49; 95% CI 14.4–32.9). Cesarean section was also significantly associated with AD (OR 1.30; 95% CI 1.01–1.65). AD incidence was comparable between vaccinated (20.5%) and non-vaccinated (17.5%) children (chi-squared with Yates’ correction, p = 0.192), indicating no statistically significant overall impact of immunization on AD risk. Conclusions: The development of AD is primarily driven by hereditary predisposition and specific perinatal factors rather than by routine immunization. These findings confirm that neonatal BCG-M and HepB vaccination does not increase the risk of AD, providing a scientific basis to address vaccine hesitancy. Full article

This study details the design and development of an ultra-sensitive microwave sensor for non-invasive blood glucose monitoring, achieved by analyzing variations in the response of a split-ring resonator (SRR) through advanced engineering methodologies. There were three design phases in the development process. In the first phase, a standard SRR design was used. It had a resonant frequency of 2.975 GHz in S₂₁ and a sensitivity of only 0.0032 dB/(mg/dL). In the second phase, an interdigital capacitor (IDC) was added to the SRR structure. This made it work better and made it more sensitive, with a sensitivity of 0.015 dB/(mg/dL) at 4.1 GHz. The third phase was to use a fourth-order Moore fractal geometry to improve the resonance properties of the design a lot. From the obtained S₁₁, the maximum sensitivity was 0.042 dB/(mg/dL), which was a huge improvement in sensing efficiency compared to earlier designs. Several resonant frequencies were recorded between 4.84 and 7.56 GHz. The addition of the fractal structure made the electromagnetic field stronger in the resonant space and made the waves interact more with small changes in the biological medium, all without changing the sensor’s size (80 mm × 40 mm). These results show that fractal architecture is a promising way to create non-invasive, accurate, and easily integrated sensors in biological systems that can continuously measure blood glucose levels. Full article

Background/Objectives: Atopic dermatitis (AD) is associated with gut dysbiosis linked to early-life antibiotic use and Staphylococcus aureus colonization. Gum Arabic (GA), a prebiotic, may modulate this dysbiosis and influence AD-related microbial balance. This study evaluated whether GA could support AD-associated probiotics-Lactobacillus casei, Bifidobacterium bifidum, and Bifidobacterium infantis-under amoxicillin- or azithromycin-containing conditions, examined the response of S. aureus under the same screening conditions, and developed GA-phospholipid-based semisolid carriers for topical application. Methods: Probiotic strains were cultured with 1–5% GA in the presence and absence of antibiotics, and viable cell counts were assessed. Sixteen topical formulations containing propylene glycol or isopropyl myristate in a hydrogenated phosphatidylcholine base were prepared and screened for rheological properties and galactose release using in vitro release testing (IVRT) and HPLC-UV. Results: GA at 1–2% concentrations promoted probiotic growth in antibiotic-free conditions. GA preserved B. infantis viability under azithromycin exposure in this in vitro screening model. For S. aureus, numerical CFU differences were observed between antibiotic-only and GA-containing conditions; however, the present screening design was not intended to determine antibiotic interaction outcomes. Formulations F14 (2% GA + 7% IPM) and F15 (3% GA + 7% IPM) exhibited optimal spreadability. IVRT showed that 6 h cumulative galactose release varied by formulation (F6 > F10 > F14 > F15). Conclusions: GA demonstrated dose-dependent prebiotic activity and preserved B. infantis viability under azithromycin exposure in this in vitro screening model. For S. aureus, the observed CFU differences between antibiotic-only and GA-containing conditions should be considered exploratory only and do not allow for conclusions regarding interference with antibiotic efficacy. Optimized GA-HPC systems with suitable rheological and release characteristics represent promising candidates for further preclinical investigation. Full article

The Galileo High Accuracy Service (HAS) provides free-of-charge corrections for PPP through both the E6b signal and the internet. Currently, HAS targets a horizontal and vertical accuracy of 15 cm and 20 cm, respectively (68% confidence level) for static users. Although the service is not yet fully operational, it already delivers orbit and clock corrections, as well as satellite code biases. This paper evaluates the current performance of HAS, showing positioning errors below 5 cm in both horizontal and vertical components. However, the convergence time required to reach these accuracies remains relatively long. To address this limitation, ionospheric corrections were estimated from a European network of 34 stations and added to the processing. The results show a clear improvement in both accuracy and convergence time: horizontal and vertical errors were reduced by half, as well as the horizontal convergence time. To complete the HAS correction set, only satellite phase biases were missing. These were also generated using the same European network. Although no improvement was observed when including them, no degradation was found either. This suggests that, with further refinement, HAS could significantly benefit from phase biases and achieve even better positioning performance. Full article

The production and use of plastics have direct consequences on the environment, such as the greenhouse gas emissions (GHGs) they cause. Therefore, it is necessary to develop materials from renewable sources with a lower environmental impact to replace plastic. In this work, films with bioactive properties have been developed from cellulose nanofibers (CNFs) and natural phenolic compounds for food packaging applications. First, the optimization of the incorporation of three different natural phenolic compounds (tannic acid, p-coumaric acid, and acetosyringone) into nanocellulose was studied using a Box–Behnken design, with the phenols adsorbed by the nanocellulose as the output variable. Once the incorporation was optimized, films containing nanocellulose and phenolic compounds were produced and characterized. Tannic acid showed the best results with regard to the optical properties of the resulting films and achieved a complete blocking of UV-B radiation, as well as adding to nanocellulose antioxidant (4.32 mM TE/g film) and antibacterial capacity (log R of 6.6 ± 0.2 and 3.8 ± 0.1 for Staphylococcus aureus and Escherichia coli, respectively), making these films a promising material for use in contact with food as a packaging material, although more in-depth studies and measures are needed to make these films viable for use in food packaging. Full article