Search Results (5,997)

Background/Objectives: The combination of hearing loss and visual impairment in a single patient strongly suggests a genetic aetiology. However, after conventional testing, a considerable proportion of deafblindness cases remain without a genetic diagnosis. The aim of this study was to address this diagnostic gap. Methods: We developed an enhanced exome strategy that uses a whole-exome backbone complemented by spike-in capture probes for (i) low-coverage coding segments and clinically validated, non-coding regions (including deep intronic splice-altering sites and untranslated exonic sequences) across 659 genes associated with hearing loss and/or visual impairment, and (ii) mitochondrial DNA. Results: With 66.6 million paired-end reads per sample, this methodology achieved coverage of at least 20 reads per base at 99.3% of target coding and non-coding positions of genes associated with deafness and/or blindness, as well as 98.8% of the whole exome. The enhanced exome approach correctly identified the genetic variants causative of deafness and/or blindness in 10 out of 10 cases with a previously known genetic cause, in 3 out of 10 additional cases that remained undiagnosed after extensive panel sequencing, and in 4 out of 4 cases that had not been genetically studied before. Comparison of the performance of two commercial bioinformatics platforms for enhanced exome interpretation revealed that eVAI consistently prioritised causative variants higher than, or as high as, VarSome Clinical, resulting in a tendency toward shorter interpretation times using the former. Both platforms offered the same diagnostic yield and both failed to correctly call one of the causative variants. Conclusions: In an era where many centres operate exome analysis through virtual panels, enhanced exome sequencing leverages the advantages of whole-exome and custom panel sequencing: it provides panel-like sensitivity for clinically actionable loci, while offering the flexibility to periodically reanalyse data and discover candidate genes. Full article

Ice accretion on aircraft, wind-turbine blades, power networks, civil infrastructure, and exposed sensors poses severe safety risks and economic costs. Passive icephobic surfaces mitigate icing by delaying heterogeneous nucleation, altering droplet impact/solidification and wetting transitions, and/or weakening the ice–substrate bond so that accreted ice sheds under modest aerodynamic, gravitational, or vibrational loads. This review synthesizes recent progress using a unified mechanism framework linking (i) nucleation and early freezing, (ii) droplet dynamics during impact or condensation/frosting, and (iii) ice accretion and removal governed by interfacial fracture. Smooth low-surface-energy coatings, textured (superhydrophobic) surfaces, slippery liquid-infused porous surfaces (SLIPS), and low-interfacial-toughness strategies are critically compared in terms of achievable performance ranges, failure modes, durability limits, fabrication scalability, and test-method dependence. Ice-adhesion measurement approaches (push-off, pull-off/tensile, centrifugal) are assessed and a minimum reporting checklist is provided to improve comparability. Case studies across aviation, wind energy, power infrastructure, sensors, and emerging civil-engineering coatings highlight that durability and scale-dependent failure modes remain the dominant barriers to durable, energy-free icing mitigation. The review concludes with priorities for eco-friendly chemistries, self-healing or renewable layers, standardized testing/reporting, and data-driven (machine learning-assisted) optimization to accelerate translation into durable passive ice-mitigation technologies. Full article

Background/Objectives: Individuals with diabetes often experience difficulties in the healing of their alveolar sockets. Furthermore, obesity is strongly associated with the development and progression of type 2 diabetes through complex metabolic and inflammatory mechanisms. The current study provides new insights into the use of Luteolin (LU) and/or chitosan vesicles (CHV) to accelerate bone regeneration, highlighting a biologically and clinically relevant approach that leverages implants as a clinical solution. Methods: Sixty rats were randomly categorized into five groups: Group I (negative control); Group II (positive control), diabetic and obese rats; Group III (LU-treated), diabetic and obese rats with an extraction socket loaded with LU; Group IV (CHV-treated), diabetic and obese rats with an extraction socket loaded with CHV; and Group V (LU-CHV), diabetic and obese rats with an extraction socket loaded with LU-CHV. After 2 and 6 weeks, rats’ mandibles underwent histological, histomorphometric, biochemical, and statistical analyses. Results: The results demonstrated significant differences among the experimental groups. The LU-CHV formulation showed superior therapeutic performance compared with free luteolin and the untreated control group. In vitro release studies revealed sustained, controlled release from LU-CHV, whereas free luteolin exhibited rapid drug release. Additionally, LU-CHV significantly enhanced biological activity, as evidenced by improved anti-inflammatory and/or therapeutic markers compared to the other groups. These findings indicate that encapsulation within chitosan vesicles improved drug stability, bioavailability, and overall therapeutic efficiency. Conclusions: LU-CHV demonstrated superior efficacy compared to free luteolin, highlighting the advantage of chitosan-based vesicular delivery systems. LU-CHV not only enhanced controlled drug release and therapeutic outcomes but also presents a promising platform that could significantly advance targeted drug delivery strategies in inflammatory and metabolic disorders. The findings suggest that LU-CHV represents a transformative approach in improving treatment effectiveness and patient outcomes. Full article

Computed Tomography (CT) is a widely used imaging modality that employs X-rays and computational reconstruction to visualize internal anatomy. Although higher radiation doses produce higher-quality images, they also increase long-term cancer risk, motivating the use of low-dose protocols. However, low-dose CT data inherently suffer from elevated Poisson–Gaussian noise, necessitating effective denoising strategies. In myocardial CT perfusion (CTP) imaging, this challenge is compounded by residual cardiac motion, which misaligns consecutive time points and impairs accurate estimation of perfusion maps for diagnosing coronary artery disease. Traditional approaches typically treat these two problems, noise and motion, separately, denoising the reconstructed images first or applying the registration first. Such serial pipelines often degrade clinically significant features; e.g., denoising may destroy structural details essential for registration, while motion correction can distort subtle intensity cues needed for noise modelling. To overcome these limitations, we propose a unified deep learning framework that performs noise suppression and motion correction jointly for low-dose myocardial CTP. The method integrates two complementary components through a parallel ensemble strategy: (i) a modified Fast and Flexible Denoising Network (FFDNet) that incorporates noise-level maps to mitigate blended noise effectively, and (ii) a CNN-based registration model, extended with Time Enhancement Curve (TEC) correction and 4D physiological consistency constraints to estimate temporally coherent and anatomically plausible motion fields. By combining their outputs without iterative dependencies, the proposed framework produces motion-corrected and denoised CTP sequences in a single unified processing step, thereby better preserving myocardial structure and perfusion dynamics than conventional serial pipelines. The model has been evaluated using both reference-based (MSE, PSNR, SSIM, PCC, Noise Variance, TRE) and no-reference (NIQE, FID, KID, AUC) image quality metrics, supplemented by expert human assessment. Results demonstrate that jointly learning noise characteristics and motion patterns enables restoration of low-dose CTP images while minimizing feature corruption, thereby advancing the clinical utility of low-dose myocardial CTP imaging. Full article

Late relapses are one of the most frustrating aspects of cancer treatment. They are frequently driven by dormant tumor cells and drug-tolerant persisters (DTPs) that survive therapy and later re-enter proliferation. Focal adhesion kinase (FAK) and the mechanosensitive transcriptional co-activators YAP/TAZ integrate extracellular matrix mechanics with intracellular stress signaling to coordinate survival, quiescence and reactivation. We propose that the key determinant is often not “FAK on/off”, but functional mode selection between (Mode I) kinase-dependent signaling bursts linked to adhesion remodeling and regrowth and (Mode II) kinase-independent scaffolding and non-canonical localization (including nuclear pools) that sustain a persistence architecture under stress. This Mode-Switch lens helps explain why ATP-competitive FAK inhibitors can suppress pY397-FAK-dependent outputs yet incompletely eradicate persister reservoirs and motivates strategies that remove FAK protein or disrupt persistence circuitry. We outline operational, pathology-compatible proxies for assigning dominant mode using composite readouts of pY397-FAK/total FAK, FAK localization, and YAP/TAZ/TEAD executor output. Finally, we discuss modality matching—kinase inhibition to suppress regrowth versus FAK degradation and/or YAP/TEAD blockade to dismantle persister reservoirs—as a testable framework for biomarker-stratified intervention in minimal residual disease. Full article

Modern agriculture faces increasing pressure to maintain productivity while reducing soil degradation, chemical inputs, and ecological footprint, making biologically based soil-improvement strategies highly relevant. This study examined whether microbial inoculation, combined with conservation tillage practices (loosening and no-tillage), can enhance soil physical quality during pea (Pisum sativum) cultivation in an agroecological market garden in Hungary. A 2 × 2 factorial field experiment was established, testing tillage (loosening vs. no-tillage) and microbial inoculation (with vs. without) in a randomized design with three replications per treatment (12 plots total). A single microbial application was performed prior to planting using a consortium of Rhizobium spp., Ensifer spp., Pseudomonas spp., and Bacillus spp. The research focused on (I) soil penetration resistance, (II) soil moisture dynamics, and (III) infiltration capacity, with most parameters measured before and after planting. Microbial inoculation significantly reduced penetration resistance under both tillage systems and influenced soil moisture behavior, indicating improved soil structure and water retention. Infiltration rate did not change significantly within the study period. Overall, the results demonstrate that microbial amendments can rapidly improve key soil physical properties, offering a practical, nature-based strategy for resilient, low-input farming systems. Full article

Cartilage is an important yet vulnerable tissue with limited self-healing capacity, where damage often progresses to joint degeneration, which eventually leads to severe osteoarthritis (OA). Current tissue engineering strategies focus on biocompatible scaffolds for cartilage regeneration, particularly amnion (or amniotic membrane), emerging as a promising biomaterial due to its wide availability, low immunogenicity, and naturally derived microenvironment that is advantageous for cartilage regeneration. This systematic review aims to evaluate the existing evidence on the efficacy of amnion as a tissue scaffolding material for cartilage regeneration in both preclinical and clinical studies. Using terms such as “cartilage damage”, “cartilage injuries”, “amnion” and “amniotic membrane”, 19 relevant studies were identified across three major databases (PubMed, Scopus and Web of Science) until 25 December 2025. All preclinical and clinical studies that utilized amnion for cartilage repair or as cartilage tissue engineering scaffolding materials were included. Evidence quality was assessed using the OHAT and MINORS risk of bias tool. This study is prospectively registered in the PROSPERO database under the ID 1178444. The findings consistently indicate that amniotic scaffolds, regardless of processing methods or cell seeding, yield favorable outcomes without adverse effects across different species. In vitro analysis revealed that treatment groups with amnion show better cell attachment, viability, and proliferation, and higher content of cartilage-related markers expressed by the seeded cells, either chondrocyte, bone marrow-derived mesenchymal stem cells (MSCs), adipose tissue-derived MSCs, placenta-derived MSCs, umbilical cord-derived MSCs, amniotic MSCs or amniotic epithelial cells. In in vivo and ex vivo studies, amnion-treated groups demonstrated improved quality of the treated cartilage, with better integration, as indicated by higher histological scores and the presence of type II collagen (COL-II). There was an inconsistency in the reporting of cartilage defect dimensions in the in vivo models across the different studies. Nevertheless, the outcome measurements were consistently reported with histological analysis, with or without International Cartilage Repair Society (ICRS) scoring and immunohistochemistry (IHC) analysis, across the studies. Clinically, most subjects show improvement in the Knee Injury and Osteoarthritis Outcome Score (KOOS) Sports and Recreation score and KOOS Quality of Life score, as well as reduced Visual Analogue Scale (VAS) average and maximum pain scores. In conclusion, preclinical and clinical studies support amnion as an ideal scaffold material for cartilage tissue engineering and regeneration. Future research should focus on optimizing and standardizing amnion scaffold preparation at a production scale to facilitate the translation of these positive outcomes into clinical applications. This study is funded by the Ministry of Higher Education Malaysia via Prototype Research Grant Scheme (PRGS/1/2021/SKK01/UM/02/1) and UM International Collaboration Grant—2023 SATU Joint Research Scheme Program: ST007-2024. Full article

During multi-layer commingled production of coalbed methane (CBM), fluid interference induced by interlayer pressure differences is a major constraint on productivity, representing a dynamic coupling process of reservoir pressure, temperature, and deformation. To elucidate this mechanism, we constructed a four-layer superimposed reservoir physical model using a self-developed large-scale true triaxial multi-field coupling test system, which reflects the geological conditions of the Eastern Yunnan and Western Guizhou region. We precisely regulated interlayer pressure differences and monitoring multi-physical parameters in real time to analyze the dynamic evolution of reservoir temperature, pressure, and deformation fields. The findings reveal that: (1) Increased interlayer pressure difference intensifies fluid interference in low-pressure reservoirs, causing abnormal pressure buildup. For example, when the pressure difference rose from 0.2 MPa to 0.6 MPa, the maximum pressure increase in Reservoir I grew from 1.03 MPa to 1.13 MPa. (2) The high-pressure reservoir (Reservoir IV) remained largely unaffected throughout production, with its temperature decline rate consistently correlated positively with pressure difference, indicating a distinct response behavior. (3) Reservoir deformation correlates positively with initial pressure. When the initial pressure of Reservoir II increased from 1.2 MPa to 1.6 MPa, its volumetric strain rose from 1.81‰ to 2.21‰, attributable to the combined effects of matrix shrinkage, elevated effective stress, and desorption-induced thermal cooling. This study demonstrates how interlayer pressure differences regulate the coupled evolution of reservoir pressure, temperature, and deformation, providing experimental evidence and theoretical support for identifying interference mechanisms and optimizing development strategies in CBM commingled production. Full article

Boron neutron capture therapy (BNCT) is a biologically targeted, high–linear energy transfer radiotherapy that selectively delivers cytotoxic α-particles to boron-loaded tumor cells and has re-emerged with the development of hospital-compatible accelerator neutron sources and improved boron carriers. We performed a structured literature review of PubMed, Embase, and the Cochrane Library through October 2025 to summarize the radiobiological rationale, boron delivery strategies, and clinical outcomes of BNCT in glioblastoma (GBM) and other high-grade central nervous system tumors. Eligible clinical and translational studies were screened independently, and data on patient populations, boron agents, neutron source technologies, dosimetry, survival, response, and toxicity were extracted. Contemporary series and phase II trials indicate that BNCT is technically feasible and generally well tolerated, with encouraging survival outcomes in selected newly diagnosed and recurrent GBM, meaningful activity in recurrent high-grade meningiomas, and acceptable safety in limited pediatric cohorts. Current practice relies primarily on second-generation carriers such as boronophenylalanine and sodium borocaptate, while third-generation molecular and nanocarrier platforms remain in preclinical development. Overall, BNCT represents a promising high-LET, pharmacologically targeted modality for heavily pretreated and radioresistant CNS tumors, and ongoing prospective studies are needed to define its comparative effectiveness and optimal integration into patient care. Full article

Aggressive behavior in Muscovy ducks (Cairna moschata) has become a predominant concern in intensive farming systems, leading to reduced animal welfare and production losses. To unravel the molecular mechanisms underlying this behavior, transcriptomic profiling was performed on the hypothalamus, a key regulatory hub for aggressive responses. A total of 120 healthy 60-day-old female Muscovy ducks were continuously monitored for 24 h/day over one month using Media Recorder 2.0 software. Based on instantaneous and continuous behavioral observations, the ducks were categorized into three groups: aggressor (Experimental group I, actively attacking conspecifics), victim (Experimental group II, receiving aggression), and non-aggressive (Control group, no aggressive interactions). Hypothalamic tissues were collected from each group (n = 4 per group) for Illumina HiSeq 2000 high-throughput transcriptome sequencing. Functional annotation and enrichment analysis of differentially expressed genes (DEGs) were performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, followed by quantitative real-time PCR (qRT-PCR) validation. GO analysis identified 626 DEGs in the aggressor group and 649 DEGs in the victim group compared to the control group, with 26 DEGs directly involved in aggressive behavior regulation. Integration of GO and KEGG annotations revealed 69 candidate genes associated with aggressive behavior, enriched in two GO terms (behavior [GO:0007610] and sensory perception of pain [GO:0019233]) and the ERBB signaling pathway (map04012). qRT-PCR validation of 14 randomly selected candidate genes (e.g., NPY, ERBB4, MAPK9, PRDM12) confirmed that their expression patterns were consistent with transcriptomic data, verifying the reliability of the sequencing results. These findings provide novel insights into the molecular genetic basis of aggressive behavior in Muscovy ducks and lay a foundation for developing targeted strategies to mitigate aggression in intensive farming systems. Full article

Paradoxical hypertrichosis is an adverse effect of photo-epilation, involving the induction of hair growth within treated or adjacent non-treated areas. Given the significant psychosocial burden associated with facial hair growth in women, effective adjunctive strategies to mitigate this phenomenon are required. Chymotrypsin and papain are bioactive proteolytic enzymes whose activity has been associated with structural alterations in hair follicle components. This study investigated the effect of combining Alexandrite laser with enzyme-assisted hair removal compared with laser alone on the occurrence of paradoxical hypertrichosis. The outcome was assessed by recording the number of laser pulses performed per treatment session. Fifty-nine adult Greek women with facial hirsutism were allocated into two groups: Group I (Laser + Enzymes, n = 30), treated with Alexandrite laser (755 nm) combined with iontophoretic delivery of aqueous chymotrypsin and papain solutions, and Group II (Laser, n = 29), treated with laser alone. After 10 sessions, the combined intervention resulted in a significantly greater change in laser pulse counts compared with laser alone (−18.53 ± 16.31 vs. +1.68 ± 9.61, p < 0.005). This finding suggests that adjunctive iontophoresis of bioactive proteolytic enzymes is associated with reduced laser pulse requirements, which may be considered in the clinical management of paradoxical hypertrichosis in women with facial hirsutism. Larger studies with extended follow-up are warranted. Full article

Copper oxide nanoparticles (CuONPs) have received considerable attention because of their wide range of applications, particularly in the development of antimicrobial materials for medical, environmental, and industrial purposes. However, conventional synthesis routes often involve the use of toxic chemicals and environmentally harmful conditions. To overcome these limitations, green synthesis strategies have been developed as sustainable alternatives through the use of natural reducing and stabilizing agents. In this study, Citrus sinensis leaf extract, which exhibits high antioxidant capacity, was investigated for green synthesis of CuONPs, followed by their subsequent incorporation into a chitosan polymeric matrix. The optimal synthesis conditions were achieved at a pH of 7.0 using copper(II) acetate monohydrate (Cu(CH₃COO)₂·H₂O) at a concentration of 10.0 g L⁻¹ and a calcination temperature of 300 °C. The resulting CuONPs exhibited a heterogeneous morphology, with average particle sizes ranging from 20 to 30 nm, and demonstrated satisfactory antimicrobial activity against Escherichia coli and Staphylococcus aureus. The incorporation of these NPs into chitosan yielded composite materials with enhanced antimicrobial performance, highlighting the added value of polymer–NP hybrid systems. Although these composite materials were not evaluated under realistic operational conditions, the optimized green protocol provides a robust methodological basis for future studies targeting water disinfection and other environmentally relevant technologies. Full article

Silica-supported zinc (II)–Schiff-base complexes were prepared through a simple and high-yield immobilization strategy and evaluated as heterogeneous catalysts for the ring-opening polymerization (ROP) of lactide. Silica gel and silica nanoparticles were employed as supports to assess the influence of support morphology and textural properties on catalytic performance. Comprehensive characterization by AAS, BET, SEM, and SEM–EDS confirmed effective anchoring of the Zn complexes, homogeneous metal distribution, and support-dependent textural modifications. The supported catalysts were active in the bulk ROP of racemic and enantiopure lactide, affording PLA with high conversions and moderate dispersities. Silica-gel-supported systems exhibited high and reproducible activity over a wide range of conditions, whereas catalysts supported on silica nanoparticles showed a stronger dependence on reaction time and ligand electronic effects, highlighting the key role of the support in modulating active site accessibility and chain growth. Microstructural and thermal analyses confirmed the formation of atactic PLA from rac-lactide and stereoregular PLLA from L-lactide. Overall, this study demonstrates that silica-supported zinc(II)–Schiff-base complexes constitute an effective and versatile heterogeneous platform for lactide ROP and underscore the importance of support properties in the rational design of sustainable catalysts for biodegradable polyester synthesis. Full article

Background: In the wake of the COVID-19 pandemic, the dietary landscapes of young adults have been profoundly reshaped. As social restrictions ease, the resurgence of dining out presents new behavioral shifts regarding health and safety. Objective: This study investigates the post-pandemic experiences of young adults in Hong Kong, focusing on the burgeoning phenomenon of eating out of home and its complex influence on eating habits and food hygiene consciousness. Methods: This qualitative study utilized a phenomenological approach to explore participants’ lived experiences. Semi-structured interviews were conducted with 12 young adults in Hong Kong to gather narratives regarding their dining practices. The data were analyzed using thematic analysis to identify recurring patterns associated with their return to public dining spaces. Results: Three core themes emerged: (i) confined palates: the remaking of the Hong Kong meal in the shadow of a pandemic; (ii) shared screen: mediating hunger from the home-as-hub; and (iii) watchful guard: the moralization of the meal amidst viral uncertainty. Conclusions: These findings dissect the critical, evolving relationship between contemporary consumption patterns and health maintenance. While the small size limits statistical generalizability, the study suggests that post-pandemic dining involves a modified reality of sustained hypervigilance. These insights offer a basis for developing sensitive and targeted public health strategies that resonate with the altered dietary realities of young adults in a post-pandemic world. Full article

Background: Annuloplasty ring sizing is critical for durable outcomes in surgical mitral valve repair (MVr). However, there is no clear consensus on optimal sizing strategies. Artificial intelligence (AI)-based imaging tools may help to reduce uncertainty in preoperative decision-making by providing objective, reproducible and reliable measurements. This study evaluated the predictive capability of a fully automated, computed tomography (CT)-based AI-driven tool for annuloplasty ring sizing in patients undergoing minimally invasive MVr (MI-MVr). Methods: A total of 71 consecutive patients undergoing MI-MVr for Carpentier type II mitral valve insufficiency during the study period were included. Preoperative CT scans were analyzed using a cloud-based, fully automated AI tool to quantify mitral valve geometric parameters. Correlations between AI-derived measurements and implanted ring sizes were assessed using the Pearson correlation test. Univariable and multivariable linear regression analyses were performed to identify independent predictors of ring size selection. Results: Several AI-derived parameters correlated significantly with implanted ring size, with the strongest correlations observed for commissural width (R = 0.693, p < 0.001) and mitral annular area (R = 0.693, p < 0.001). In multivariable regression analysis, these parameters were the strongest predictors of annuloplasty ring size (R² = 0.504, p < 0.001). Using this model, accurate annuloplasty ring sizing could be predicted in 78.8% of patients. There were no in-hospital mortality and residual mitral regurgitation at discharge. Conclusions: A fully automated, CT-based AI-driven tool demonstrated good accuracy for preoperative annuloplasty ring size prediction in MI-MVr and may have the potential to support surgical decision-making, reduce operator dependence, and improve reproducibility. Full article