Search Results (4,406)

Background: The interaction between human immunoglobulin G (IgG)1 Fc and the Fc gamma receptor (FcγR) IIIa/CD16a elicits protective immune responses. Antibody N-glycosylation stabilizes the FcγR-binding interface and is thus essential for interaction with wildtype IgG1 Fc. Furthermore, the N-glycan introduces substantial compositional and functional heterogeneity, with distinct glycoforms providing different affinities and discrete responses in vivo. Accordingly, various engineering endeavors to improve antibody binding strive to boost the therapeutic efficacy of monoclonal antibodies but do not directly address compositional heterogeneity. Objective: Here, we describe a previously unexplored approach to engineer IgG1 Fc. We eliminated carbohydrate heterogeneity by removing the N-glycan but stabilizing the FcγR-binding interface with disulfide bonds. Conclusions: These newly generated Fc domains served as a starting point for protein engineering through yeast surface display to enhance receptor-binding affinity. We recovered Fc variants from this approach that demonstrated FcγRIIIa binding affinities comparable to the starting sequence and thus serve as a proof-of-principle for this strategy. Full article

Background/Objectives: Vaccine hesitancy is a complex and growing phenomenon worldwide, posing a serious threat to public health achievement in disease control and prevention. This study aimed to assess willingness to uptake and factors linked to shifts between different categories of willingness and uptake regarding the COVID-19 and influenza vaccines. Methods: Prospective cohort study with a representative sample of 1400 individuals aged ≥60 years residing in mainland Portugal, randomly selected. Two telephone surveys were conducted: one at the start of the 2023/2024 vaccination campaign, assessing patients’ characteristics and willingness for vaccination (using an 11-point Likert scale), and another at the end, assessing vaccination status and reasons for uptake/non-uptake. Results: Shifts were observed among both acceptance and refusal groups—12.93% of the individuals within these categories shifted to an opposite decision. Hesitancy presents divergent attitudes: for the COVID-19 vaccine, 56.50% declined vaccination, while for the influenza vaccine, non-uptake was only 30.60%. Age, presence of chronic disease, level of education, household dimension, and previous uptake of booster doses are significantly associated with shifting attitudes, playing different roles for each category of willingness and uptake outcome. For the acceptance category, non-uptake relates to confidence factors. For hesitancy, non-uptake is mainly due to complacency. For refusal, the decision is influenced by all domains. Conclusions: Vaccine hesitancy remains an important public health concern in the Portuguese population and appears to differ between COVID-19 and influenza vaccination. Attitudes toward COVID-19 and influenza vaccines can vary in all directions over a short period. Acceptance does not guarantee uptake, and refusal can shift towards uptake. These findings highlight the importance of reinforcing public health strategies and interventions for uptake across a population, taking into consideration the specificities of each willingness group. Full article

Vegetation phenology is a sensitive indicator of climate change in China’s drylands (aridity index, AI < 0.65). However, accurate phenological monitoring remains challenging due to low signal-to-noise ratios, persistent soil background interference, and the scarcity of ground phenological sites. Existing global phenology products also perform poorly in hyper-arid and arid regions. This study developed an optimal phenology detection framework for China’s drylands by systematically evaluating various vegetation indices, noise-reduction techniques, fitting functions, and dynamic thresholds against ground observations, generating a dataset at 500-m resolution spanning 2001–2024. Specifically, we determined vegetation index thresholds to distinguish vegetated from non-vegetated pixels based on 453 field survey sites. Our results indicate that the Normalized Difference Phenology Index (NDPI) coupled with a 10% threshold and polynomial fitting provided the highest accuracy for Start of Season (SOS) (RMSE = 12.02 days). For End of Season (EOS), EVI2 combined with a 70% threshold and self-weighted double-logistic fitting yielded superior performance (RMSE = 19.89 days). Compared to the MODIS global phenology product (MCD12Q2), our dataset demonstrates significantly higher accuracy (higher R and lower RMSE) and broader spatial coverage, particularly in hyper-arid and arid regions. Spatiotemporal analysis reveals that SOS was earlier while EOS was later in more arid areas, potentially reflecting the opportunistic life strategies of ephemeral plants. Notably, a trend of delayed SOS was observed in these regions, which we potentially linked to the shifts in precipitation regimes under global change. This optimized framework and the resulting Chinese dryland phenology dataset provide a robust foundation for assessing ecosystem resilience and carbon cycle dynamics in water-limited environments. Full article

Background/Objectives: Prepubertal localized aggressive periodontitis/LPP is an extremely rare but extremely fast-progressing form of periodontal disease involving systemically healthy children, starting in primary and mixed dentition. Our aim is to synthesize the data (January 2014–April 2026) on LPP progression description in systemically healthy children aged 2–13 years; clinical and biological responses to available treatment strategies, focusing on disease progression pattern, treatment efficacy and factors influencing treatment outcomes; and correlating findings with a report of a 24-month follow-up of a female prepubertal Caucasian patient during the primary and early stages of mixed dentition. Methods: A total of 489 studies were found after deduplication for the selected period. Due to the eligibility criteria, 9 studies plus another 10 contextual publications were included. Additionally, a 24-month follow-up of a previous LPP case was correlated. Results: LPP displayed rapid tissular destruction in primary dentition with risks to transfers to mixed and permanent dentition. The systemic antibiotic treatment reduced tissue loss, enabling fast periodontal regeneration. LPP is rare but severe, with a continuous biological trajectory, and with the window of opportunity remaining when the first symptoms appear. A few months (4–6 months) delay in diagnosis leads to irreversible tooth loss even in young patients with high biological healing potential. Conclusions: Systemic antibiotic treatment is mandatory in LPP/C-MIP cases from the primary dentition phase but does not reset host susceptibility. The Amoxicillin/Augmentin–Metronidazole association is recommended, with caution regarding dosage (adverse reactions). Periodontal gains are radiologically and clinically proven, but rebounding is possible. Full article

Renal cell carcinoma (RCC) is one of the most common malignant tumors of the urinary system, with clear cell renal cell carcinoma (ccRCC) accounting for more than 75% of RCC cases and representing the primary cause of mortality in renal cancer patients. CDC6 exhibits oncogenic characteristics and plays a significant role in tumor grading and prognosis prediction. Analysis of The Cancer Genome Atlas (TCGA) data shows that the CDC6 gene is significantly overexpressed in 97.22% (70/72) of paired clinical samples in ccRCC tissues compared to adjacent normal tissues. Consistent with this, elevated CDC6 protein levels were observed across all four paired tumor tissues examined. Functional experiments further confirm that CDC6 expression levels directly influence cellular proliferation, as its knockdown suppresses cell viability by ~60% in CCK-8 assays (p < 0.001) and reduces EdU incorporation by ~50%. Mechanistically, in tumor tissues, CDC6 transcription is epigenetically regulated by histone acetylation and methylation, which in turn modulates downstream effectors, e.g., the exosome complex protein EXOSC5. Our findings indicate that in ccRCC, increased histone H3K4 trimethylation near the CDC6 transcriptional start site enhances its expression. The methyltransferase SETD1A may act as a potential upstream regulator mediating the transcriptional activation of CDC6, thereby driving tumor progression through the regulation of EXOSC5. We have further investigated the relationship between the CDC6-associated gene network and tumor development and clarified the diagnostic and prognostic relevance of the SETD1A–CDC6–EXOSC5 axis in ccRCC. The outcomes of this research are expected to provide novel insights into the pathogenesis of renal cell carcinoma and establish a theoretical foundation for new diagnostic strategies. Full article

Currently, more than half of Pyrenean high mountain lakes are occupied by fish as a result of historical introductions that date back centuries and which have accelerated during the last 70 years. In the southern slope of these mountains, the main fish that have been introduced are Brown trout (Salmo trutta), Brook trout (Salvelinus fontinalis), Rainbow trout (Oncorhynchus mykiss), and European minnow (Phoxinus sp). The specific impacts of the introduction of fish include, among others, the transformation of the ecosystem structure and trophic relationships, and the reduction and extirpation of native species. The project LIFE RESQUE ALPYR (LIFE20 NAT/ES/000369), started in 2022 and ending in 2026, includes among its main objectives the restoration of ten high mountain lakes with fish (trout or minnow) and the recovery of native species of European interest by the eradication of introduced fish. We planned and executed continuous and sustained campaigns to achieve the complete removal of fish. From 2022, we began with operations in seven objective lakes by means of several capture techniques, mainly gill nets for trout and a combination of gill nets, fyke-nets, and electrofishing for minnows. In 2024 and 2025, in three other lakes, chemical treatments with rotenone were carried out to achieve rapid eradication of fish. Currently, we have already achieved the complete removal of fish in four lakes, either with sustained capture or chemical treatments. In the other three lakes, this objective is also expected to be achieved in 2026, and only few individuals persist in actuality. In the other two lakes, the European minnow has been removed, and trout are now the focus of a two-stage strategy. In the remaining lake, we have only achieved a reduction in the European minnow (>50% reduction), with trout still remaining. We present, in detail, the methodologies applied and the results obtained. Full article

Accurate and reliable localization is a fundamental requirement for autonomous mobile robots operating in structured indoor environments. Adaptive Monte Carlo Localization (AMCL), widely used due to its probabilistic flexibility, suffers from performance degradation in challenging situations such as low-motion, sensor degradation, symmetry ambiguity, and abrupt position changes (kidnapped robot). This study proposes the Confidence-Gated Virtual Scan Motion AMCL (CG-VSM-AMCL) approach, which extends the standard AMCL structure with a selective and confidence-based posterior enhancement mechanism to overcome these limitations. The proposed method integrates beam partitioning, cluster-based dominance analysis, observability-aware gating, and recovery-driven adaptive particle injection components within a holistic architecture. The method was evaluated on a structured department map under seven representative scenarios: cold-start, low-motion, kidnapped robot recovery, odometry bias, scan dropout, world–model mismatch, and symmetry ambiguity. Experimental results demonstrate that the proposed approach systematically reduces localization error, false-lock rate, and convergence time compared to basic AMCL variants, and improves stability under challenging conditions. The significant improvements achieved, particularly in low-motion and symmetry-containing environments, reveal that selectively activated correction strategies can substantially increase localization robustness without altering the fundamental probabilistic structure of AMCL. Full article

This paper presents a comprehensive numerical investigation into the transient thermo-structural response of axial bellows during start-up and shutdown cycles in long-distance heating pipelines. Using ANSYS-based transient thermal–structural coupling finite element analysis under the pure linear elasticity and constant internal pressure, the spatio-temporal evolution mechanisms of temperature fields, axial deformation, and equivalent stress are systematically analyzed. The results demonstrate the highly synchronized evolution between temperature and deformation fields, with maximum axial deformation and equivalent stress consistently concentrated at the convolution root and transition arcs. Under steady-state high-temperature conditions (130 °C), the maximum equivalent stress reaches 332.78 MPa. However, after complete cooling and unloading, minimal residual deformation (≤0.001 mm) and residual stress (8.86 MPa) are observed, satisfying the pressure vessel shakedown criteria and confirming the inherent self-limiting nature of thermal secondary stresses. A specific decoupling phenomenon is revealed during the high-temperature steady-state holding period, where the deformation stabilizes while the stress undergoes secondary redistribution. The comparative analysis of different temperature change rates indicates that the fast start-up/shutdown (0.55 °C/s) induces severe transient temperature gradients, causing a nearly 50% increase in the maximum equivalent stress compared to the slow start-up/shutdown (0.275 °C/s). This study provides theoretical foundations for the service safety assessment of axial bellows and recommends gradual heating/cooling operation strategies (≤0.3 °C/s) to mitigate structural thermal shock risks. Full article

Money laundering remains a critical challenge for financial systems because of the complex, hidden, and interlinked nature of illicit financial transaction networks. Understanding how these networks respond to targeted disruption is essential for exposing structural vulnerabilities and refining existing anti-money laundering (AML) prevention and intervention strategies. This study involves a social network analysis (SNA)-based resilience framework to evaluate the robustness of financial transaction networks through targeted node removal. In this approach, a network is represented as a directed graph, where nodes correspond to accounts and edges represent transactions. Centrality measures (i.e., degree, closeness, betweenness and pagerank), which capture local influence, global reach, and control over information flow, are applied to identify the most influential nodes. Network resilience is assessed by analyzing the variation in the size of the Largest Connected Component (LCC) under progressive node removal. An adaptive LCC-based resilience strategy is used, starting with large batches of nodes and gradually moving to smaller ones until the LCC drops below 50% of its original size, allowing for a more detailed analysis near the fragmentation threshold. The findings reveal that Betweenness centrality is the most effective metric in disrupting network connectivity under targeted attack scenarios, both outflow- and inflow-based analyses. Specifically, targeting only the top 2% of nodes by Betweenness centrality collapses the network’s core, reducing the Largest Connected Component (LCC) to 60% of its original size. In contrast, random attack strategy exhibit limited impact on overall network resilience compared to targeted approaches. Our findings provide actionable AML insights, showing that resilience-driven targeting of structurally critical accounts can effectively fragment money laundering networks and support more focused interdiction strategies. Full article

Metabolic dysfunction–associated steatotic liver disease (MASLD) is now the most common chronic liver disorder worldwide. Once started with hepatic steatosis, it can progress to metabolic dysfunction–associated steaohepatitis (MASH), cirrhosis, and even hepatocellular carcinoma. Insulin resistance is a major driver of hepatic lipogenesis in this disease context. Gut barrier dysfunction also contributes to the progression to MASH by allowing bacterial lipopolysaccharide (LPS) to breach into the hepatic tissues. Amphibian skin secretion peptides (ASSPs) are therefore of particular interest, given their combined metabolic and antimicrobial activities. Some ASSPs enhance glucose-stimulated insulin secretion and GLP-1 release, whereas others attenuate LPS-driven inflammatory signaling. This review introduces these ASSPs with a focus on their insulinotropic/incretinotropic and immunomodulatory activities. Also, in the latter part, pharmaceutical strategies to improve blood circulation time and structural stability would be discussed. Full article

Cryptomeria japonica (Japanese cedar) is extensively planted as windbreaks in Jeju, Korea, producing highly allergenic pollen that significantly affects local populations. This study analyzed 10-year trends of airborne C. japonica pollen concentrations and their relationship with meteorological factors in Jeju to provide essential data for allergy management and climate adaptation strategies. Daily airborne pollen sampling was conducted using Burkard traps from 2015 to 2024 at a monitoring site in Jeju. Meteorological data, including temperature, wind speed, relative humidity, precipitation, solar radiation, and cloud amount, were obtained from the Korea Meteorological Administration. Temporal trends were analyzed using linear regression and the Mann–Kendall test, while correlations between pollen parameters and meteorological variables were calculated using Spearman’s correlation coefficients. Over the 10-year period, annual pollen integral (APIn) and peak concentrations showed statistically significant increasing trends. Pollen season start dates demonstrated a tendency toward earlier occurrence. Season onset was strongly negatively correlated with pre-season temperatures in January and February. January solar radiation showed positive correlations with both season end and period duration. C. japonica pollen concentrations in Jeju demonstrate significant increasing trends with earlier seasonal onset, primarily driven by pre-season warming in January and February. These changes may lead to prolonged allergen exposure periods, necessitating enhanced public health preparedness and adaptation of clinical management strategies for allergic populations. Full article

Pediatric drug therapy remains fundamentally challenged by profound interindividual variability driven by dynamic development, genetic, and environmental factors. Although dosing strategies based on age, body weight, or body surface area remain important starting points in pediatric pharmacotherapy, they may not fully capture ontogeny-dependent variability in drug disposition and response. Consequently, clinically relevant differences in efficacy and toxicity may still occur among children receiving similar weight-adjusted doses. Pharmacogenomics offers a promising framework for individualized therapy; however, its clinical translation in pediatrics is limited by developmental variability in gene expression and enzyme activity. Emerging evidence highlights the pivotal role of epigenetic regulation, including DNA methylation, histone modifications, and microRNAs, in modulating pharmacogenetic expression across developmental stages, thereby reshaping drug response trajectories. Concurrently, advances in artificial intelligence and next-generation sequencing enable integration of multidimensional datasets, facilitating predictive modeling of drug efficacy and toxicity. This narrative review provides a comprehensive synthesis of developmental pharmacology, pharmacogenomics, and epigenetic mechanisms, while critically evaluating current translational gaps and implementation challenges. Importantly, it proposes an integrative precision framework that incorporates genetic, epigenetic, and computational insights to optimize pediatric pharmacotherapy. By bridging mechanistic biology with emerging digital health technologies, this work advances a paradigm shift from empirical prescribing toward predictive, adaptive, and individualized therapeutic strategies. The proposed approach holds significant potential to enhance clinical outcomes, minimize adverse effects, and accelerate the realization of precision medicine in pediatric populations. Full article

The biological treatment risk associated with wastewater containing the novel pigment intermediate N,N′-(1,4-phenylene)bis(acetoacetamide) has not been previously characterized. This study systematically evaluated the tolerance and performance of a laboratory-scale anaerobic–anoxic–oxic (AAO) system subjected to progressively increasing loadings of high-concentration (COD > 10,000 mg·L⁻¹) wastewater. During a 39-day trial, the influent proportion was incrementally increased from 0.57% to 52.14% without system collapse. Complete microbial adaptation required approximately seven days. The anaerobic unit exhibited the highest sensitivity to shock loads, followed by the oxic unit, while the anoxic unit remained stable. GC-MS analysis confirmed the degradation of complex organic intermediates throughout the treatment stages, and TEST-based predictions indicated that the effluent exhibited lower predicted toxicity than the influent. Notably, cessation of mother liquor addition resulted in system self-recovery, further demonstrating robust shock resistance. This study provides the first experimental evidence of (i) unit-specific shock sensitivity (anaerobic > oxic > anoxic), (ii) a quantified adaptation period of approximately seven days, (iii) an operational threshold of 52.14% mother liquor without causing system collapse, and (iv) self-recovery following load cessation in an AAO system treating wastewater containing N,N′-(1,4-phenylene)bis(acetoacetamide). These findings extend previous AAO toxicity studies on industrial wastewater and present a practical, cost-effective mitigation strategy for full-scale applications. Full article

Background/Objectives: Papua New Guinea has a population of over 10 million, with its public cardiac surgical service provided by only one tertiary center. Despite the climbing burden of ischemic heart disease, no CABG operation has been performed before 2025 due to limited local surgical capacity. An international collaboration was planned in order to launch a CABG program in the country. Methods: Three cases were shortlisted after a multidisciplinary team discussion. A team-based “On-the-job” mentoring strategy was employed to facilitate skill transfer. The operation was carried out in a “twinning” fashion, with each role of the surgical team being taken up by “a pair”—the trainer (visiting team) and the learner (local team). The trainer demonstrated key skills and tips in the first case, and the “pair” switched positions in the following cases to maximize hands-on learning. The last case was performed entirely by the local team. Results: Three patients underwent CABG operations in this pilot program. A total of 2.33 grafts/case were performed on average, with no 30-day mortality. There were no major complications except for one patient developing right middle cerebral artery infarct on postoperative day 5. The patient was discharged one month later after achieving functional recovery and was started on anticoagulation therapy. Conclusions: International collaborations with strategic planning can play a critical role in starting new cardiac surgical programs in low–middle-income countries, with acceptable surgical outcomes. History has been made with the first-ever CABG operation successfully performed in Papua New Guinea. The journey ahead to sustain local cardiac surgical capacity and to provide safe and accessible cardiac surgical care for the country remains challenging. Full article

This paper presents a comparative analysis of three workspace discretization strategies, Cartesian, cylindrical and spherical, integrated into a graph-based path planning application developed in Python and connected to RoboDK. The study starts from the observation that the workspace of an articulated industrial robot is not naturally aligned with a uniform Cartesian partitioning, and this aspect can influence the internal structure of the graph and the planning effort. For the initial analysis, the three discretizations were tested for the same start-goal pair and for resolutions ranging from 1500 mm to 600 mm. All three variants led to the same validated route, with a length of 3292.215 mm, which shows that the main differences did not occur at the level of the final geometric solution, but at the level of the internal structure of the graph. On average, the spherical discretization generated the most compact graph, with 101.7 nodes and 256.4 edges, compared to 277.3 nodes and 724.9 edges for the Cartesian discretization. The average planning time was also shorter for the spherical discretization, 0.0069 s, compared to 0.0150 s for the Cartesian discretization and 0.0127 s for the cylindrical discretization. At the 600 mm resolution, the spherical discretization used approximately 63% fewer nodes and 66% fewer edges than the Cartesian discretization, while retaining a larger number of candidate routes. The evaluation was then extended by 180 additional trials, performed on two scenarios and on several start-goal pairs. Of these, 151 led to valid routes, corresponding to an overall success rate of 83.9%. The results show that the spatial representation influences the graph size, connectivity, planning time and length of validated routes. However, additional tests also show that these effects depend on the scenario and the criterion analyzed. The spherical discretization produced the most compact graphs, but did not lead in all cases to the shortest routes or the highest success rate. Therefore, the contribution of the paper consists in a controlled comparative evaluation of the influence of the spatial representation on a graph-based planning pipeline, not in demonstrating the universal superiority of a single discretization. Full article