Search Results (740)

With the rapid proliferation of unmanned aerial vehicles (UAVs) and the associated rise in security concerns, there is a growing demand for robust detection and identification systems capable of operating reliably in complex electromagnetic environments. To address this challenge, this paper proposes a deep learning-based passive UAV detection and identification system leveraging radio frequency (RF) spectrograms. The system employs a high-resolution RF front-end comprising a multi-beam directional antenna and a wideband spectrum analyzer to scan the target airspace and capture UAV signals with enhanced spatial and spectral granularity. A YOLO-based detection module is then used to extract frequency hopping signal (FHS) regions from the spectrogram, which are subsequently classified by a convolutional neural network (CNN) to identify specific UAV models. Extensive measurements are carried out in both line-of-sight (LoS) and non-line-of-sight (NLoS) urban environments. The proposed system achieves over 96% accuracy in both detection and identification under LoS conditions. In NLoS conditions, it improves the identification accuracy by more than 15% compared with conventional full-spectrum CNN-based methods. These results validate the system’s robustness, real-time responsiveness, and strong practical applicability. Full article

Familial hypercholesterolemia (FH) is a common genetic disorder with a fairly constant worldwide prevalence of 1 case per 311 individuals worldwide. It is characterized by severe hypercholesterolemia from birth, early atherosclerosis and death from cardiovascular disease at a young age. Diagnosis and treatment from childhood are essential to reduce cardiovascular mortality. Many countries have developed a strategy of implementing pediatric screening, which has led to an increase in diagnoses. This paper evaluates the screening strategies implemented in different countries worldwide. First, we examined which schemes were preferred in various national contexts in Europe. Next, we evaluated the screening methods used in the US, Canada, Australia and Japan. Finally, we researched the screening strategies proposed in some low-resource countries, discovering the difficulties and limitations they face. We have highlighted a wide range of realities, from small-scale pilot studies to cutting-edge proposals. We have also emphasized that, while the topic is certainly of interest, it is burdened by multiple difficulties and unresolved questions. Full article

Background: Pulp canal calcification (PCC) poses a challenge for endodontic treatment, as it obscures the canal and increases the risk of complications. This study aimed to evaluate the accuracy of endodontic access cavity preparation using dynamic navigation (DN) and to compare it with the freehand (FH) technique in teeth with severe PCC. Materials and Methods: Sixty 3D printed maxillary central incisors with simulated severe PCC were divided into two groups and accessed either with a DN system or by the conventional FH technique. Accuracy was evaluated by comparing planned and performed access cavity trajectories on preoperative and postoperative CBCT scans. Preparation time and procedural errors were recorded. Normality was assessed with the Shapiro–Wilk test. The Mann–Whitney U test was used to compare continuous variables. The significance level was set at 0.05. Results: The DN group showed significantly lower apical point 3D deviation (1.25 vs. 1.96 mm, p = 0.001), apical point depth deviation (0.43 vs. 0.88 mm, p < 0.001), and angular deflection (1.93 vs. 5.71 degrees, p < 0.001) than the FH group. The DN group had fewer procedural errors. The endodontic access entry point deviation was comparable between both techniques (p = 0.395). The preparation time was significantly higher in the DN group (204 vs. 108.5 s, p < 0.001). Conclusions: DN significantly improves the accuracy of access cavity preparation in calcified canals compared to the FH approach, reducing the risk of complications. Therefore, DN can be a valuable tool for managing challenging endodontic cases. As guided endodontic access preparation can be more time-consuming, extended treatment appointments may be required. Full article

Cellular senescence is a state of irreversible growth arrest characterized by a pro-inflammatory phenotype, playing dual roles in development. In the fetal intestine, the regulation of senescent cells is critical for maintaining tissue homeostasis. Human breast milk (HBM), known for its rich composition of bioactive molecules, may play a role in modulating senescence, although its effects on senescent intestinal cells remain unexplored. This study investigated whether HBM selectively eliminates senescent cells in the FHs74Int fetal intestinal epithelial cell line. Senescence was assessed via β-galactosidase activity and expression of p16 and p21. The model cell line was treated with HBM, infant formula, and milk fractions, and outcomes included cell recovery, senescence markers, apoptosis, and mitochondrial potential. Total free fatty acids (FFA) were quantified and correlated with senolytic activity. HBM reduced senescent cell recovery without affecting non-senescent cells, correlating with decreased β-galactosidase activity, reduced phospho-p38 and γH2AX expression, mitochondrial depolarization, and caspase activation. Only the lipid fraction retained senolytic activity, which was associated with elevated FFA levels. Incubation of HBM at 37 °C increased FFA content and conferred senolytic activity. These findings are consistent with the idea that HBM exerts selective senolytic effects via FFA, revealing a novel mechanism by which breast milk could contribute to intestinal homeostasis. Full article

The increase in the incidence and antibiotic-resistant strains show a need for a broadly protective vaccine to prevent gonorrhea. OMVax has developed a combination vaccine based on native outer membrane vesicles (NOMVs) from two Neisseria meningitidis (Nm) and two Neisseria gonorrhoeae (Ng) strains. The strains had the acyl transferase LpxL1 knocked out to increase safety, and the reduction-modifiable protein was also knocked out in the Ng strains. Factor H binding protein (FHbp) mutants with reduced Factor H (FH) binding from Subfamilies A and B, respectively, were overexpressed in the Nm strains. The Ng strains individually expressed porin outer membrane protein B 1a (PorB.1a) or PorB.1b. Antibodies elicited by the Nm-Ng NOMV vaccine had SBA with a human complement against diverse Nm and Ng strains grown in the presence of Cytidine-5′-monophospho-N-acetylneuraminic acid (CMP-NANA), had no significant reduction in serum bactericidal activity (SBA) compared to the respective individual vaccines, inhibited the adhesion to human cervical and vaginal cells in five out of six Ng strains tested, and inhibited Nm and Ng colonization in a transgenic mouse model. In conclusion, the Nm-Ng NOMV vaccine has the potential to protect against disease and inhibit colonization by diverse Nm and Ng strains, which may be an advantage for controlling the disease through vaccination, particularly in the adolescent/young adult age group. Full article

Background: Fasciola hepatica causes important economic losses in ruminants with only pharmacological treatments currently available, which produces several secondary problems. Because of this, vaccines have become an interesting alternative. Leucine aminopeptidases (LAPs) are attractive vaccine targets against fasciolosis since they play essential roles in the parasite such as host invasion and nutrient acquisition. To characterize immune responses, we produced two recombinant F. hepatica LAPs (FhLAP1 and FhLAP2), formulated with ISCOM-matrices (IMXs) nanoparticles from Quillaja brasiliensis saponins. Methods: Forty female Corriedale sheep were assigned to four groups (n = 10): FhLAP1/IMX, FhLAP1/FhLAP2/IMX, IMX (control), and FhLAP1/Adj50 (Adjuvac 50). Animals received two subcutaneous immunizations at weeks 0 and 4 and were challenged orally with 200 metacercariae at week 6. Results: FhLAP1 and FhLAP1/FhLAP2 induced specific IgG responses, with the predominance of the IgG1 response. However, these responses were lower than those generated by FhLAP1 formulated with Adj50. A qPCR analysis revealed that FhLAP1/IMX stimulated a Th1-type response profile before the challenge, but this profile was not sustained after infection. The post-infection profile of FhLAP1/FhLAP2/IMX was more congruent with expected values despite not achieving a robust IFN-γ expression. No significant differences in the fluke burden were observed. Conclusions: Further research on the optimal antigen/adjuvant combination in ruminants is encouraged. For instance, a higher concentration of adjuvant in the formulation used in this work may enhance the strength and duration of the inflammatory response and improve protective immunity against fasciolosis. Full article

Background: To investigate if the sagittal inclinations of anterior occlusal plane (AOP) and posterior occlusal plane (POP) differ between skeletal classes II and III in the mixed dentition period. Methods: Retrospective analysis of cross-sectional lateral cephalometric radiograph data of 61 children with skeletal class II and 60 children with skeletal class III (average age 8.4 ± 1.5 years). We measured the inclinations of AOP and POP to the Frankfort horizontal (FH) and the sella-nasion line (SN). Angles FH–AOP, FH–POP, SN–AOP, and SN–POP were compared between both groups using model-based ANOVA F tests and quantile regressions. Results: The differences in means between the groups came to 1.3° ± 5.1 (FH–AOP), 1.8° ± 4.6 (FH–POP), 2.6° ± 5.3 (SN–AOP), and 5.5° ± 4.4 (SN–POP). In the ANOVA, angles SN–AOP, FH–POP, and SN–POP differed significantly between the groups (p = 0.041, p = 0.006, p < 0.001, respectively). Quantile regressions showed significant between-group differences for FH–AOP (lower quartile, p = 0.012), FH–POP (upper quartile, p = 0.006), SN–AOP (median, p = 0.004; upper quartile, p = 0.011), and SN–POP (all 3 quartiles, p < 0.001). Conclusions: Distinct occlusal plane inclinations of mixed dentitions represent diagnostic traits. Longitudinal and interventional data are needed if therapeutic flattening of mixed dentition AOP or POP is beneficial in treating skeletal class II, same as their steepening in skeletal class III. Our clinical hypothesis suggests alterations by approximately 3° (AOP) and 6° (POP) but requires further study and confirmation. Full article

Atherosclerosis as a multifactorial disease remains the first cause of death worldwide. Current oral lipid-lowering drugs (especially statins) reduce low-density lipoprotein cholesterol (LDLC) levels in the blood, but their clinical efficacy seems to be partially attributed to pleiotropic effects on different pathophysiologic factors of atherosclerosis extending beyond lipid-lowering properties such as anti-inflammatory, antithrombotic and antioxidative features. Novel drugs that interfere with proprotein convertase subtilisin/kexin type 9 (PCSK9) axis of LDL-C receptors (LDLRs) degradation, from the group of monoclonal antibodies (e.g., alirocumab, evolocumab) or small interfering RNA (siRNA), e.g., inclisiran, are effective in reducing LDLC as well. However, data depicting their antithrombotic and antiplatelet activity are scarce, whereas prothrombotic properties of PCSK9 are widely described. Thus, we performed a study to assess the effects of inclisiran on subclinical prothrombotic [fibrinogen, coagulation factor VIII (FVIII), plasminogen activator inhibitor-1 (PAI-1)] and platelet activation markers (platelet factor-4 (PF-4), soluble p-selectin (sCD62P)). Ten patients at high cardiovascular risk with concomitant heterozygous familial hypercholesterolemia (HeFH)—study group 1, and fourteen patients at very high cardiovascular risk without concomitant HeFH—study group 2, were recruited for the study. Lipid profile, subclinical prothrombotic and platelet activation markers were assessed at the beginning and after 3 months of therapy with inclisiran. During therapy, statistically significant reductions in both study groups were seen in total cholesterol levels (study group 1: from 287.6 ± 94.2 to 215.2 ± 89.1 (mg/dL), p = 0.022; study group 2: from 211.7 ± 52.7 to 147.6 ± 55.4 (mg/dL), p < 0.001) and LDL-c (study group 1: from 180.8 ± 73.3 to 114.7 ± 71.5 (mg/dL), p = 0.031; study group 2: from 129.6 ± 46.8 to 63.4 ± 43.6 (mg/dL), p < 0.001). Lipid profile changes were associated with significant decrease in the concentration of FVIII in both groups (study group 1: from 33.3 ± 22 to 22 ± 14.5 (ng/mL), p = 0.006; study group 2: from 37 ±16.9 to 29.3 ±16.4 (ng/mL), p = 0.002) and fibrinogen, but only in study group 2 (from 51.4 (33.2–72.7) to 42.6 (31.3–57.2) (µg/mL), p = 0.035). Among platelet activation markers, a significant decrease in PF-4 in study group 2 was noted (from 286 (272–295.5) to 272 (268–281.5) (ng/mL), p = 0.047). However, there were no statistically significant changes in PAI-1 and sCD62P throughout the study. In our study, inclisiran appeared to be an effective lipid-lowering drug in patients at high cardiovascular risk. Moreover, it was shown that beyond lipid-lowering properties, the drug may also partially affect thrombogenesis and platelet activation. Full article

As is typical of deep rock engineering, fault-controlled hydrothermal systems (FHS) have emerged as a highly promising solution for geothermal energy exploitation. The stability and thermal recovery performance of such systems are critical to their long-term efficiency and viability. In this study, we establish a coupled Thermo-Hydro-Mechanical (THM) model to investigate the mechanical response and thermal output of an FHS. The stability of the system is evaluated based on the evolution of the failure zone within the fault. Key findings include the following: (1) The pore pressure distribution between injection and production wells leads to an elliptical failure pattern in the fault, caused by the constraint exerted by the negative pore pressure zone around the production well on the positive pressure zone around the injection well along the well connectivity direction; (2) Reducing the injection flow rate by 50% can result in a 76% decrease in the thermal recovery efficiency. Meanwhile, reducing the number of reinjection sub-wells from seven to three can lead to a 95% reduction in the failure volume; and (3) Larger fault thickness diminishes both failure volume and thermal performance; specifically, increasing the fault thickness from 5 m to 30 m can result in an 89% reduction in the failure volume. The fault damage zone volume exhibits a sharp decrease as permeability rises from 2 × 10⁻¹² m² to 8 × 10⁻¹² m². This study provides scientific insights and practical guidelines for the design and stability assessment of FHS-based geothermal systems. Full article

The objective of this study was to investigate the epidemiology of Fasciola hepatica in Cervus elaphus kept in natural conditions in the Riaño Regional Hunting Reserve, north-west of Spain, where several species of domestic and wild animals coexist. One hundred red deer were examined and classified according to age, sex, and sampling season. After the necropsy of the animals, the liver was removed and inspected to obtain the adult parasites of F. hepatica. Faecal samples were collected and processed using the coprological sedimentation technique. The prevalence of this trematode by necropsy was 12%, with a low number of specimens per animal ($\overline{\mathrm{x}}$ = 2.7 ± 1.5; range 1–6). The young animals and the males had a higher prevalence than the adults and the females, finding statistically significant differences only according to the host age. Significant variations were also observed when considering the seasons of the year, with the highest number of infected animals in spring. The histopathological study revealed the presence of lesions compatible with a chronic fasciolosis similar to that found in domestic animals. The shedding of F. hepatica eggs was quite low in terms of prevalence (6%) and mean intensity of infection ($\overline{\mathrm{x}}$ = 27.3 ± 20.6, range 4–60 epg), being in young animals, in males, and in spring, where the greatest excretion of eggs was observed. These results suggest that the deer are suitable definitive hosts for F. hepatica in the northwest of the Iberian Peninsula, but they are unusual hosts. The serum samples were analysed using a native excretory/secretory antigen (FhES) and a 2.9 kDa recombinant protein (FhrAPS) used for diagnosis of early and current fasciolosis in livestock. A commercial kit for serodiagnosis of F. hepatica in sheep and cattle, based on a monoclonal antibody (BIO K 211), was also evaluated in red deer. The seroprevalence of seropositivity of F. hepatica by FhES-ELISA was 32%, by FhrAPS-ELISA 13%, and by BIO K 211, 9%. In the three serological tests, the seroprevalence obtained was higher in adult animals, in males, and in spring. In the three serological tests used to understand the epidemiology of F. hepatica in red deer, we have observed that the sensitivity was low, perhaps due to the use of an anti-bovine IgG1 as a conjugate, so in future immunodiagnostic tests, it would be more desirable to obtain an anti-deer IgG, probably achieving better results. Due to these results, it is essential to investigate other serological or molecular tests that allow us to know the real importance of F. hepatica in deer and other wild animals. The role of deer as a reservoir of this trematode does not appear to be very important. Full article

Background: Fumarate hydratase (FH) deficiency is a rare metabolic alteration in breast cancer that may drive tumor progression through angiogenic remodeling. However, its role in shaping the tumor microenvironment remains poorly defined, limiting our understanding of metabolism-driven angiogenesis and its therapeutic significance. Methods: We analyzed genomic and transcriptomic profiles from thousands of breast cancer samples, including the TCGA cohort, to identify FH mutations and copy number alterations. Differential expression, pathway enrichment, and weighted gene co-expression network analysis (WGCNA) were performed to characterize metabolic and signaling changes. Clinical relevance was examined in a triple-negative breast cancer patient with an FH mutation treated with bevacizumab. Results: FH alterations were enriched in larger, primary tumors and in older patients. FH-deficient tumors displayed metabolic reprogramming, with reduced oxidative phosphorylation and TCA cycle activity, accompanied by upregulation of angiogenesis, VEGF signaling, and epithelial–mesenchymal transition pathways. WGCNA identified 11 hub genes (including CDH5, CLDN5, VWF, and PECAM1) linked to a pro-angiogenic microenvironment. A clinical case illustrated a durable and exceptional response to bevacizumab-based therapy in an FH-mutant patient. Conclusions: FH deficiency promotes an angiogenic tumor microenvironment and may serve as a predictive biomarker for VEGF-targeted therapies. These findings underscore the therapeutic potential of exploiting metabolic vulnerabilities to inform precision oncology. Full article

This study aimed to evaluate how acidic and alkaline staining solutions affect the optical properties (mean color change, ΔE*), geometric characteristics (surface roughness, Ra), and bacterial adhesion of zirconia Ceramill Zolid PS computer-aided design/computer-aided manufacture (CAD/CAM) material after 21 days of immersion. Ninety-six zirconia CAD/CAM Ceramill Zolid multilayer PS specimens were prepared and allocated to eight groups based on the pH values of the immersion solutions; the acidic solutions included Mirinda Citrus, CodeRed, yerba mate tea, Saudi coffee, and Nescafe (A–E), and the alkaline solutions included artificial saliva, DZRT (tobacco-free nicotine pouches), and smokeless tobacco (F–H). The specimens were immersed for 21 days at 37 °C, with the solutions replaced every 12 h to ensure consistency. Color changes were measured using a VITA Easyshade V spectrophotometer, and Ra was evaluated via white-light interferometric microscopy. The bacterial adhesion of Streptococcus mutans was quantified by counting colony-forming units (CFUs, CFU/mm²). Statistical analyses included the Shapiro–Wilk test for normality, one-way ANOVA with Tukey’s HSD post hoc test for group comparisons, and paired t-tests, with significance set at <0.05. The recorded pH values of the staining materials ranged from acidic (Mirinda Citrus: 3.23) to alkaline (smokeless tobacco: 8.54). Smokeless tobacco caused the most unacceptable mean color change (ΔE* = 6.84), followed by DZRT (ΔE* = 6.46), whereas artificial saliva produced the least discoloration (ΔE* = 2.15), with statistically significant differences among the solutions (p < 0.001). The Ra measurements varied significantly (p < 0.001), with Nescafe demonstrating the lowest value (0.486 µm) and DZRT the highest (0.748 µm). S. mutans adhesion was the highest for CodeRed (546.75 CFU) and the lowest for smokeless tobacco (283.92 CFU), demonstrating significant variation across groups (ANOVA, p < 0.001). The acidic and alkaline solutions significantly altered the optical properties, Ra, and bacterial adhesion of zirconia Ceramill Zolid PS CAD/CAM, with acidic solutions leading to higher bacterial adhesion. Full article

This study examines the use of Filtered Historical Simulation (FHS) to estimate tail risk in cryptocurrency markets for the optimization of robustness in this area under model misspecification. An ARMA-GARCH model is employed on the daily returns on Binance Coin and Litecoin in order to compare the performance of classical and block bootstrap procedures in residual risk. Diagnostic tests indicate that standardized residuals are dependent, contrary to the independent and identically distributed (i.i.d.) assumption of conventional FHS. Comparing the block and ordinary bootstrapping approaches, we find that block bootstrap produces wider, more conservative confidence intervals, particularly in extreme tails (e.g., 0.1% and 99.9% percentiles). The findings suggest that block bootstrapping can be employed as a correction instrument in risk modeling where the standard volatility filters do not work. The article highlights the necessity to account for remaining dependencies and offers practical recommendations for more robust tail risk estimation during volatile markets. Full article

Background: Achilles tendon (AT) thickening reflects cumulative low-density lipoprotein cholesterol (LDL-C) exposure. The Japan Atherosclerosis Society (JAS) explicitly includes AT thickness as a diagnostic criterion for familial hypercholesterolemia (FH) in adults, whereas internationally, it is not a standard diagnostic measure. However, the clinical significance of AT thickening in pediatric populations remains unclear. Methods: We conducted a single-center, retrospective, observational study involving pediatric patients (11–18 years old) with suspected FH through standardized universal lipid screening across Kagawa Prefecture, Japan. Genetic testing confirmed FH through pathogenic variants in the LDLR, PCSK9, or APOB genes. The AT thickness was measured using a standardized ultrasonography protocol. We assessed associations between the FH status, cumulative LDL-C levels, and AT thickness. Results: In the pediatric patients, no significant difference in the AT thickness was observed between the FH and non-FH groups (median 4.4 vs. 4.5 mm; p = 0.570). Cumulative LDL-C was higher in the FH group, while no clear association between cumulative LDL-C and AT thickness was apparent in either group. Conclusions: In this single-center, retrospective study of pediatric patients identified through standardized universal lipid screening, no significant differences were found in AT thickness between FH and non-FH groups although cumulative LDL-C levels were higher in the FH group. Given methodological limitations (small sample size, selection bias, and residual confounding related to statin therapy and growth), these findings should be interpreted as exploratory rather than confirmatory. Regardless of genotype, early risk management may be warranted. Full article

Lipoprotein(a) [Lp(a)] has emerged as a significant independent risk factor for atherosclerotic cardiovascular disease (ASCVD). While plasma Lp(a) levels remain relatively stable throughout life, their clinical impact varies depending on age and concentration. This comprehensive review examines the age-dependent clinical relevance of Lp(a), from childhood through adulthood. In pediatric populations, elevated Lp(a) levels are associated with early indicators of vascular dysfunction and with conditions like familial hypercholesterolemia (FH). In adults, elevated Lp(a) is consistently linked to an increased risk of myocardial infarction (MI), stroke, and calcific aortic valve disease, particularly in those with additional cardiovascular risk factors. We also discuss emerging therapies targeting Lp(a) that may significantly alter long-term cardiovascular risk if implemented early. Understanding the lifelong implications of elevated Lp(a) highlights the need for age-specific strategies for screening, monitoring, and intervention. Future research should prioritize identifying high-risk pediatric populations, refining risk thresholds, and determining optimal timing for therapeutic initiation to improve long-term cardiovascular outcomes. Full article