Search Results (1,623)

Background/Objectives: Miscarriage is an increasingly common event worldwide arising from various factors, and identifying its etiology is important for planning and managing any future pregnancies. It is estimated that about half of early pregnancy loss cases are caused by genetic abnormalities, while a significantly lower rate is found in late pregnancy loss. Multiplex ligation-dependent probe amplification (MLPA) can detect small changes within a gene with precise breakpoints at the level of a single exon. The aim of our study was to identify the rate of copy number variations (CNVs) in spontaneous pregnancy loss samples after having previously tested them via quantitative fluorescence PCR (QF-PCR), with no abnormal findings. Methods: DNA was extracted from product-of-conception tissue samples, followed by the use of an MLPA kit for the detection of 31 microdeletion/microduplication syndromes (SALSA^® MLPA^® Probemix P245 Microdeletion Syndromes-1A, MRC-Holland, Amsterdam, The Netherlands). Results: A total of 11 (13.1%) out of the 84 successfully tested samples showed CNVs. Duplications accounted for 9.5% of the analyzed samples (eight cases), while heterozygous or hemizygous deletions were present in three cases (3.6%). Among all the detected CNVs, only three were certainly pathogenic (3.6%), with two deletions associated with DiGeorge-2 syndrome and Rett syndrome, respectively, and a 2q23.1 microduplication syndrome, all detected in early pregnancy loss samples. For the remaining cases, additional genetic tests (e.g., aCGH/SNP microarray) are required to establish CNV size and gene content and therefore their pathogenicity. Conclusions: MLPA assays seem to have limited value in detecting supplementary chromosomal abnormalities in miscarriages. Full article

Future $e^{+}{e}^{-}$ colliders are expected to play a fundamental role in measuring Standard Model (SM) parameters with unprecedented precision and in probing physics beyond the SM (BSM). This study investigates two-particle angular correlation distributions involving final-state SM charged hadrons. Unexpected correlation structures in these distributions is considered to be a hint for new physics perturbing the QCD partonic cascade and thereby modifying azimuthal and (pseudo)rapidity correlations. Using Pythia8 Monte Carlo generator and fast simulation, including selection cuts and detector effects, we study potential structures in the two-particle angular correlation function. We adopt the QCD-like Hidden Valley (HV) scenario as implemented in Pythia8 generator, with relatively light HV v-quarks (below about 100 GeV), to illustrate the potential of this method. Full article

We present Bayesian Binary Search (BBS), a novel framework that bridges statistical learning theory/probabilistic machine learning and binary search. BBS utilizes probabilistic methods to learn the underlying probability density of the search space. This learned distribution then informs a modified bisection strategy, where the split point is determined by probability density rather than the conventional midpoint. This learning process for search space density estimation can be achieved through various supervised probabilistic machine learning techniques (e.g., Gaussian Process Regression, Bayesian Neural Networks, and Quantile Regression) or unsupervised statistical learning algorithms (e.g., Gaussian Mixture Models, Kernel Density Estimation (KDE), and Maximum Likelihood Estimation (MLE)). Our results demonstrate substantial efficiency improvements using BBS on both synthetic data with diverse distributions and in a real-world scenario involving Bitcoin Lightning Network channel balance probing (3–6% efficiency gain), where BBS is currently in production. Full article

The study examined the effect of BIE eCoaching on the functional communication training (FCT) implementation skills of pre-service teachers (PTs) and the effect of FCT implemented by PTs on reducing problem behaviors and increasing communication skills of children with autism spectrum disorder (ASD). After the intervention, it was examined whether PTs and children with ASD maintained and generalized the acquired behaviors. Moreover, PTs answered a social validity form before and after the intervention. The methodology of this study involved single-subject research with a multiple-probe design between pairs of participants. The BIE eCoaching intervention was effective in children with ASD’s use, maintenance, and generalization of FCT. FCT was effective in reducing problem behaviors, increasing communication skills, and maintaining and generalizing these skills in children with ASD. Social validity findings showed that PTs’ perceptions of BIE eCoaching changed positively at the end of the intervention. Full article

Periodontitis is a chronic inflammatory disease caused by periodontopathic bacteria such as Porphyromonas gingivalis (P. gingivalis), which leads to alveolar bone destruction and systemic inflammation. Emerging evidence suggests that probiotics may mitigate periodontal pathology. To systematically evaluate the alleviative effects and mechanisms of different forms of probiotics, including live bacteria and postbiotics, on periodontitis, we first screened and identified Ligilactobacillus salivarius CCFM1332 (L. salivarius CCFM1332) through in vitro antibacterial and anti-biofilm activity assays. Subsequently, we investigated its therapeutic potential in a rat model of experimental periodontitis. The results demonstrated that both live L. salivarius CCFM1332 (PL) and its postbiotics (PP) significantly reduced the gingival index (GI) and probing depth (PD) in rats, while suppressing oral colonization of P. gingivalis. Serum pro-inflammatory cytokine levels were differentially modulated: the PL group exhibited reductions in interleukin-17A (IL-17A), interleukin-6 (IL-6), and interleukin-1β (IL-1β) by 39.31% (p < 0.01), 17.26% (p < 0.05), and 14.74% (p < 0.05), respectively, whereas the PP group showed decreases of 34.79% (p < 0.05), 29.85% (p < 0.01), and 19.74% (p < 0.05). Micro-computed tomography (Micro-CT) analysis demonstrated that compared to the periodontitis model group (PM), the PL group significantly reduced alveolar bone loss (ABL) by 30.1% (p < 0.05) and increased bone volume fraction (BV/TV) by 49.5% (p < 0.01). In contrast, while the PP group similarly decreased ABL by 32.7% (p < 0.05), it resulted in a 40.4% improvement in BV/TV (p > 0.05). Histological assessments via hematoxylin and eosin (H&E) and tartrate-resistant acid phosphatase (TRAP) staining confirmed that both the PL group and the PP group alleviated structural damage to alveolar bone-supporting tissues and reduced osteoclast-positive cell counts. This study suggests that live L. salivarius CCFM1332 and its postbiotics reduce alveolar bone resorption and attachment loss in rats through antibacterial and anti-inflammatory pathways, thereby alleviating periodontal inflammation in rats. Full article

Investigating biodiversity in remote and harsh environments, particularly in the Southern Ocean, remains costly and challenging through traditional sampling methods such as trawling. Environmental DNA (eDNA) sampling, which refers to sampling genetic material shed by organisms from environmental samples (e.g., water), provides a more cost-effective and sustainable alternative to traditional sampling approaches. To study the biogeographic patterns of two typical mesopelagic fishes, Antarctic lanternfish (Electrona antarctica) and Antarctic deep-sea smelt (Bathylagus antarcticus), in the Cosmonaut Sea in the Indian Ocean sector of the Southern Ocean, we conducted both eDNA and trawling sampling at a total of 86 stations in the Cosmonaut Sea during two cruises in 2021–2022. Two sets of species-specific primers and probes were developed for a quantitative eDNA analysis of two fish species. Both the eDNA and trawl results indicated that the two fish species are widely distributed in the Cosmonaut Sea, with no significant difference in eDNA concentration, biomass, or abundance between stations. Spatially, E. antarctica tended to be distributed in shallow waters, while B. antarcticus tended to be distributed in deep waters. Vertically, E. antarctica was more abundant above 500 m, while B. antarcticus had a wider range of habitat depths. The distribution patterns of both species were affected by nutrients, with E. antarctica additionally affected by chlorophyll, indicating that their distribution is primarily influenced by food resources. Our study provides broader insight into the biogeographic patterns of the two mesopelagic fishes in the remote Cosmonaut Sea, demonstrates the potential of combining eDNA with traditional methods to study biodiversity and ecosystem dynamics in the Southern Ocean and even at high latitudes, and contributes to future ecosystem research and biodiversity conservation in the region. Full article

We developed a mathematical model to examine the scattering of radiation by a periodic structure of circular and elliptical microcavities formed in a planar optical waveguide. The waveguide simulates the behaviour of a 62.5/125 µm multimode optical fibre. The calculations focused on the intensity distribution of scattered light with a wavelength of 1310 nm along the periodic structure, i.e., along the side surface of the waveguide, as a function of the microcavity dimensions and their spatial arrangement within the waveguide core. The optimal geometrical parameters of the microstructure, ensuring the most uniform light scattering, were identified. The model is valid for multimode optical fibres containing strictly periodic structures of microcavities with spherical or elliptical cross-sections that scatter laser radiation in all directions. One potential application of such fibres is as light sources in medical probes for surgical procedures requiring additional illumination and uniform irradiation of affected tissues. Furthermore, the findings of this study offer significant potential for the development of sensing elements for fibre-optic sensors. The findings of this study will facilitate the design of scattering structures with microcavities that ensure a highly uniform scattering pattern. Full article

Oncological hyperthermia (HT) is a medical technique aimed at heating a specific region of the human body containing a tumour. The heat makes the tumour cells more sensitive to the cytotoxic effects of radiotherapy and chemotherapy. Electromagnetic (EM) HT devices radiate a single-frequency EM field that induces a temperature increase in the treated region of the body. The typical radiative HT frequencies are between 60 and 150 MHz for deep HT applications, while 434 MHz and 915 MHz are used for superficial HT. The input EM power can reach up to 2000 W in deep HT and 250 W in superficial applications, and the E-field should be linearly polarized. This study proposes the development and use of E-field sensors to measure the distribution and evaluate the polarization of the E-field radiated by HT devices inside equivalent phantoms. This information is fundamental for the validation and assessment of HT systems. The sensor is constituted by three mutually orthogonal probes. Each probe is composed of a dipole, a diode, and a high-impedance transmission line. The fundamental difference in the operability of this sensor with respect to the standard E-field square-law detectors lies in the high-power values of the considered EM sources. Numerical analyses were performed to optimize the design of the E-field sensor in the whole radiative HT frequency range and to characterize the sensor behaviour at the power levels of HT. Then the sensor was realized, and measurements were carried out to evaluate the E-field radiated by commercial HT systems. The results show the suitability of the developed sensor to measure the E-field radiated by HT applicators. Additionally, in the measured devices, the linear polarization is evidenced. Accordingly, the work shows that in these devices, a single probe can be used to completely characterize the field distribution. Full article

The Very Long Baseline Interferometry Global Observing System (VGOS), a global network of stations equipped with small-diameter, fast-slewing antennas and broadband receivers, is primarily utilized for geodesy and astrometry. In China, the Shanghai and Urumqi VGOS stations have been developed to perform radio source observation regularly. However, these VGOS stations have not yet been used to observe Earth satellites or deep-space probes. In addition, suitable systems for processing VGOS satellite data are unavailable. In this study, we explored a data processing pipeline and method suitable for VGOS data observed in the dual linear polarization mode and applied to the differential observation of satellites. We present the VGOS observations of the Chang’e 5 lunar orbiter as a pilot experiment for VGOS observations of Earth satellites to verify our processing pipeline. The interferometric fringes were obtained by the cross-correlation of Chang’e 5 lunar orbiter signals. The data analysis yielded a median delay precision of 0.16 ns with 30 s single-channel integration and a baseline closure delay standard deviation of 0.14 ns. The developed data processing pipeline can serve as a foundation for future Earth-orbiting satellite observations, potentially supporting space-tie satellite missions aimed at constructing the terrestrial reference frame (TRF). Full article

DNA methylation, as a critical epigenetic modification, plays a central role in gene regulation and has emerged as a powerful biomarker for early disease diagnostics, particularly in cancer. Owing to the limitations of traditional bisulfite sequencing—such as high cost, complexity, and chemical degradation—electrochemical biosensors have gained substantial attention as promising alternatives. This review summarizes recent advancements in electrochemical platforms for bisulfite-free detection of DNA methylation, encompassing direct oxidation strategies, enzyme-assisted recognition (e.g., restriction endonucleases and methyltransferases), immunoaffinity-based methods, and a variety of signal amplification techniques such as rolling circle amplification and catalytic hairpin assembly. Additional approaches, including strand displacement, magnetic enrichment, and adsorption-based detection, are also discussed. These systems demonstrate exceptional sensitivity, often down to the attomolar or femtomolar level, as well as high selectivity, reproducibility, and suitability for real biological matrices. The integration of nanomaterials and redox-active probes further enhances analytical performance. Importantly, many of these biosensing platforms have been validated using clinical samples, reinforcing their translational relevance. The review concludes by outlining current challenges and future directions, emphasizing the potential of electrochemical biosensors as scalable, cost-effective, and minimally invasive tools for real-time epigenetic monitoring and early-stage disease diagnostics. Full article

Floridoside (2-O-D-glycerol-α-D-galactopyranoside) is a natural product typically found in red algae. It serves as the algae’s carbon reserve and is produced as a protective response against osmotic and heat stress. Both floridoside and its acylated derivatives have been associated with modulating redox homeostasis and inflammatory responses. Therefore, we aimed to evaluate whether the newly synthesized floridoside phosphotriesters (1b–1d, 1f–1h) and acylated floridoside derivative (1e) can modulate the oxidative burst in stimulated human neutrophils. Synthetic strategies included the glycosylation of the thioglycoside donor with glycerol derivatives, having NIS/TfOH as the promoter. Phosphorylation was achieved with POCl₃ in the presence of pyridine. The compounds were analysed for their cytotoxicity, with 1b and 1h being cytotoxic at 50 μM, while the others showed no cytotoxicity in the tested concentrations. The detection of the neutrophils’ oxidative burst was performed using multiple probes [luminol, aminophenyl fluorescein (APF), and Amplex Red (AR)] to evaluate reactive species levels. Compound 1e prevented the oxidative burst in activated human neutrophils (IC₅₀ = 83 ± 7 μM). All the other tested compounds were ineffective in inhibiting APF and AR oxidation under the present experimental conditions. These findings highlight the potential of floridoside-based derivatives as candidates for targeting inflammatory pathways. Full article

Bedaquiline is known to shorten the duration of therapy of tuberculosis but has limitations, e.g., poor solubility and adverse effects such as prolongation of the QT interval. In this study, bedaquiline was incorporated into an inherently targeted nanosystem for improved permeation of the drug, with ex vivo diffusion studies performed to investigate its penetration. The bedaquiline-loaded mannan–chitosan oligosaccharide lactate nanoparticles were prepared by a one-step ionic gelation probe sonication method. A PermeGear 7-in-line flow-through diffusion system was used for the ex vivo diffusion studies across porcine and human pericardia. Bedaquiline-loaded nanoparticles with a particle size and potential of 192.4 nm and 40.5 mV, respectively, were obtained. The drug-loaded mannan–chitosan nanoparticles had an encapsulation efficacy of 98.7% and drug loading of 0.6%. Diffusion data indicated a steady-state flux of 2.889 and 2.346 µg.cm⁻².min⁻¹ for porcine and human pericardia, respectively. The apparent permeability coefficients were calculated to be 2.66 × 10⁻⁴ cm.min⁻¹ and 2.16 × 10⁻⁴ cm.min⁻¹ for porcine and human pericardia, respectively. The lag phases were 52.72 min and 0 min for porcine and human pericardia, respectively. The drug permeation indicated a consistent and linear diffusion pattern across both porcine and human pericardia, additionally approving the porcine pericardium as a great comparable tissue to human tissue for pericardial studies. This study is the first to demonstrate ex vivo diffusion of bedaquiline-loaded, macrophage-targeted chitosan–mannan nanoparticles across both human and porcine pericardia, representing a novel platform for disease-targeted, localized treatment of TB pericarditis. Full article

(1) Background: Esthetic regenerative medicine is increasingly in demand for facial and neck rejuvenation due to its proven efficacy, safety profile, and minimal downtime. This study aimed to evaluate the role of standardized assessment tools in optimizing the outcomes of non-invasive regenerative esthetic technologies, both during the treatment course and in follow-up. (2) Methods: A literature review of the main articles published in peer-reviewed journals was conducted to identify high-quality studies addressing the use of validated esthetic scales and questionnaires (patient-reported outcomes) for evaluating the effectiveness of non-invasive regenerative treatments for the face and neck using accessible clinical tools such as photographs and 3D facial scanning. (3) Results: Clinician-reported outcomes (CROs) can be collected using standardized and reproducible photographic documentation and facial scans. The esthetic scales and classifications target both specific facial areas (e.g., upper third, perioral, periorbital) and overall skin appearance. Furthermore, advanced software allows overlay facial scan analysis and wrinkle mapping for precise quantification of improvements. In addition to objective CROs, patient-reported outcomes (PROs) offer essential insights into perceived esthetic changes, satisfaction, and emotional well-being, completing a multidimensional evaluation of treatment efficacy. (4) Conclusions: Standardized evaluation protocols based on accessible tools such as clinical photographs, 3D facial scans, and validated PRO questionnaires are essential for guiding effective, personalized regenerative treatments. Their integration into routine practice enhances clinical decision-making and patient satisfaction. While advanced tools like dermal probes may further refine assessments, they require specific expertise and resources and may be less practical for daily clinical use. Full article

This paper presents the design and validation of a novel specialized fixture device for machining inclined planes with barrel cutters on 3-axis CNC machine tools. Barrel milling, also known as Parabolic Performance Cutting (PPC), is extensively used on 5-axis machines to enhance the efficiency of machining complex surfaces. While significant research has focused on optimizing barrel milling for aspects such as surface roughness and cutting forces, implementing this technique on 3-axis machines poses a challenge due to limitations in tool orientation. To overcome this, an innovative adaptable device was designed, enabling precise workpiece orientation relative to the barrel cutter. To overcome this limitation, an adaptable device was designed that enables precise workpiece orientation relative to the barrel cutter. The device utilizes interchangeable locating elements for different cutter programming angles (such as 18°, 20°, and 42.5°), thereby ensuring correct workpiece positioning. Rigid workpiece clamping is provided by the device’s mechanism to maintain precise workpiece positioning during machining, and probing surfaces are integrated into the device to facilitate the definition of the coordinate system necessary for CNC machine programming. Device control was performed using a Hexagon RA-7312 3D measuring arm. Inspection results indicated minimal dimensional deviations (e.g., surface flatness between 0.002 mm and 0.012 mm) and high angular accuracy (e.g., angular non-closure of 0.006°). The designed device enables the effective and precise use of barrel cutters on 3-axis CNC machines, offering a previously unavailable practical and economical solution for cutting tool tests and cutting regime studies. Full article

Positron emission tomography (PET) imaging targeting glypican-3 (GPC3) holds promise for improving the detection and characterization of hepatocellular carcinoma (HCC). Preclinical and early clinical studies have largely utilized high-molecular-weight antibodies radiolabeled with isotopes such as ⁸⁹Zr and ¹²⁴I, demonstrating high affinity and tumor uptake but suffering from prolonged circulation times and suboptimal signal-to-background ratios. To address these limitations, interest has shifted toward low-molecular-weight vectors—synthetic peptides and small antibody fragments—labeled with shorter-lived radionuclides (e.g., ⁶⁸Ga and ¹⁸F) to enable rapid pharmacokinetics and same-day imaging protocols. Emerging platforms such as affibodies and aptamers offer further advantages in target affinity and reduced immunogenicity. However, clinical translation requires rigorous validation: larger, histologically confirmed cohorts, head-to-head comparison with CT/MRI, and correlation with hard clinical endpoints. Moreover, leveraging GPC3 expression as a biomarker could guarantee a deeper knowledge of tumor biology—differentiation grade and vascular invasion risk—and guide theranostic strategies. While β-emitters (⁹⁰Y, ¹⁷⁷Lu) have been explored for GPC3-directed therapy, their efficacy is influenced by oxygenation and cell-cycle status, whereas α-emitters (²²⁵Ac) may overcome these constraints, albeit with challenges in radionuclide selection and daughter nuclide management. Finally, dual-targeting probes combining GPC3 and prostate-specific membrane antigen (PSMA) have demonstrated superior uptake and retention in murine models, suggesting a versatile approach for future clinical diagnostics and therapy planning. Full article