Search Results (2,073)

Background. Preoperative risk stratification of pancreatic neuroendocrine tumors (PNETs) is constrained by the unavailability of histologic grade before resection. We hypothesized that a panel of biologically informed CT-radiomic signatures, combined with patient-level Δ-radiomics referenced to the contralateral pancreas, would support preoperative discrimination of progression and grade in a two-center pilot cohort. Methods. Forty-four patients with histologically confirmed PNET who underwent contrast-enhanced preoperative CT and surgical resection at two academic centers were analyzed. Lesion and contralateral non-tumor-bearing pancreatic parenchyma regions of interest were revised in 3D Slicer by a board-certified pancreatic surgeon and verified intraoperatively against surgical pathology. PyRadiomics v3.0 features were extracted with IBSI-concordant settings. Parametric ComBat batch correction was applied across the two centers (biological-covariate balance verified beforehand), and Δ-radiomic features (lesion combat–pancreas combat) were computed for the 106 intensity/texture primitives. We constructed a panel of biology-informed hybrid signatures partitioned into a preoperative lesion-only family (Family A; seven signatures) and a preoperative Δ-radiomic family (Family B; three signatures). Candidate features were filtered through correlation clustering, baseline-adjusted likelihood-ratio testing with Benjamini–Hochberg FDR control, and 100-bootstrap stability selection. Three predictor blocks were compared per target with three classifiers each (Logistic Regression, Random Forest, Gradient Boosting): M0 (five-variable clinical baseline), MA (M0 + Family A), and MB (M0 + Family B). Discrimination was reported as AUC with bootstrap 95% CI; calibration was assessed using the Brier score and TRIPOD-recommended calibration intercept and slope; and cross-center generalization was evaluated with leave-one-center-out (LOCO) cross-validation. Univariable Cox regression with bootstrap and permutation inference was used for progression-free survival (PFS). Results. The cohort had 16 progression events and eight deaths (median follow-up was 38 months, IQR 14–59). Prespecified clinical–radiomic and Δ-radiomic signatures were associated with progression-free survival, including B2 = ΔBusyness × Ki-67 (HR 0.38, 95% CI 0.19–0.76, p = 0.006). For progression prediction, the Δ-radiomic model achieved the strongest discrimination, with a nested cross-validation AUC of 0.85 and leave-one-center-out AUC of 0.87. For higher-grade disease, radiomic models also demonstrated high discrimination, with AUCs up to 0.93. Conclusions. Radiomics-derived shape and texture features, especially when combined with clinical markers, may noninvasively identify aggressive PNET phenotypes and support preoperative risk stratification. Prospective validation in larger multicenter cohorts is warranted. Full article

Background: Microsatellite instability (MSI) is an important biomarker for the diagnosis of Lynch syndrome and for guiding immunotherapy in various solid tumors. Droplet digital PCR (ddPCR) has emerged as a highly sensitive method for detecting MSI, particularly in circulating tumor DNA (ctDNA). This study aimed to evaluate the analytical and clinical performance of a ddPCR assay using three MSI markers (BAT-26, ACVR2A, and DEFB105A/B) in colorectal, gastric, and endometrial cancers. Methods: Formalin-fixed paraffin-embedded (FFPE) samples from 190 patients (83 colorectal, 44 gastric, and 63 endometrial cancers) and 21 plasma samples from patients with metastatic solid tumors were analyzed. MSI status determined by ddPCR was compared with conventional PCR using a pentaplex panel and immunohistochemistry (IHC). Analytical performance, including limit of blank (LoB) and limit of detection (LoD), was evaluated using cell line DNA, and clinical cut-offs were established using receiver operating characteristic analysis. Results: The ddPCR assay demonstrated high analytical sensitivity, with LoD values of 0.075% for BAT-26, 0.1% for ACVR2A, and 0.025% for DEFB105A/B. Using optimized clinical cut-offs, the concordance rate between ddPCR and conventional PCR assays was 98.4% in tissue samples. Marker performance varied by cancer type, with reduced sensitivity observed in endometrial cancer. In plasma samples, MSI-H was detected in 1 of 21 cases (4.8%), and the overall concordance rate with tissue-based MSI status was 94.7%. Conclusions: The ddPCR assay demonstrated high concordance with conventional MSI testing methods and showed potential as a sensitive tool for MSI detection in both tissue and plasma samples. However, optimization of marker panels and establishment of sample-type-specific clinical cut-offs are required, particularly for ctDNA-based analysis. Further large-scale studies are needed to validate the clinical utility of ddPCR for MSI detection and monitoring. Full article

Background/Objectives: The increasing use of pea protein in plant-based foods raises concerns about IgE-mediated reactions, particularly in individuals sensitized to peanut. Knowledge on clinically relevant pea allergens and the impact of heat processing remains limited. This study investigated how thermal treatment affects the IgE binding and functional allergenicity of pea proteins in children with a confirmed pea allergy, with or without a concomitant peanut allergy. Methods: Serum from 11 patients was analyzed using SDS-PAGE, Western blotting, and an indirect basophil activation test (iBAT). Results: All patients showed IgE binding to Pis s 1 and PA2a/b in raw pea extract, with variable sensitization to Pis s 2 and mitogenic lectin. Heating (120 °C, 5 min) markedly reduced IgE binding and eliminated detectable IgE to Legumin S and ML. Despite this reduction, basophil sensitivity did not decrease; in several patients, EC50 values significantly decreased, indicating increased basophil responsiveness to heated pea. Patients with IgE profiles dominated by Pis s 1 and PA2a/b were most likely to show enhanced basophil activation after heating. Conclusions: These findings demonstrate that heat-stable vicilin subunits and albumins can maintain functional allergenicity despite reduced IgE recognition, underscoring the need for diagnostic approaches that incorporate processed food allergens. Full article

Intrusion detection system (IDS) research relies on accurately labeled network traffic datasets; however, label quality in IDS datasets is seldom audited prior to modeling. Many publicly available IDS datasets assign ground-truth labels based on capture filenames or temporal session windows rather than per-flow inspection, a practice referred to as file-level labeling. This study identifies and corrects a systematic mislabeling instance in SDN-MG25, a CICFlowMeter-based dataset for software-defined networking (SDN)-enabled microgrid intrusion detection. IP composition analysis, which cross-references each attack-labeled flow with the documented attacker IP address, reveals that the BackgroundAttackTraffic (BAT) class, comprising 3167 flows (79.5% of all attack labels), contains no attacker-originated traffic. All BAT flows involve legitimate microgrid hosts communicating with external services during the attack capture window. Correcting this labeling error increases binary detection F1 from 0.578 to $0.956\pm 0.005$, an improvement of $+0.378$ that is 4.2 times greater than the best single modeling improvement (threshold tuning, $+0.090$). Furthermore, Confident Learning, a state-of-the-art automated label-noise detector, recovers only 8.4% of mislabeled BAT flows (recall $=0.084$, precision $=0.247$), indicating that domain-knowledge audits are essential for detecting systematic, class-level mislabeling that statistical methods cannot identify. The end-to-end pipeline Macro F1 improves from 0.749 to 0.862 after label correction. IP composition analysis is proposed as a mandatory prerequisite for IDS dataset evaluation, and a reproducible two-stage pipeline with feature-tier ablation for session confound diagnosis is provided. Full article

Background/Objectives: Shenfu Decoction (SFD) is a traditional Chinese herbal formula composed of Panax ginseng and Aconitum carmichaelii that can revive and counteract shock. However, how SFD can mitigate hypothermia caused by seawater immersion is poorly understood. Methods: Three commonly used ratios of SFD (Panax ginseng:Aconitum carmichaelii = 1:1, 1:2, 2:1) were prepared, and their chemical properties were analyzed with UPLC-Q-TOF-MS. A rat model of hypothermia caused by seawater immersion at 15 °C was utilized. Survival analysis was used to evaluate the prophylactic effect of single intragastric administration of SFD with different ratios and doses on the survival time of rats, and to identify the optimal intervention conditions. Network pharmacology analysis based on the absorbed constituents of SFD was performed to preliminarily predict the underlying mechanisms, which were subsequently validated using RT-PCR, Western blotting, ELISA, and H&E staining. Results: SFD contained 54 compounds, including ginsenosides and aconitine alkaloids, whose relative concentrations varied across different ratios of SFD. Animal studies showed that pretreatment of SFD (1:1) administered at a dose of 1.35 g/kg was very effective in increasing rats’ survival time in hypothermia and slowed down core body temperature decline. Based on the 28 plasma-absorbed compounds of SFD, network pharmacology identified 503 targets, enriched in cAMP and MAPK signaling pathways. SFD (1:1, 1.35 g/kg) resulted in larger lipid droplets in brown adipose tissue (BAT) and enhanced the respiratory metabolic rate in seawater-immersion-induced hypothermia rats. Furthermore, its thermogenic effect is likely associated with the upregulation of uncoupling protein 1 (UCP1) via activating p38 MAPK/PGC1α/PPARγ and NE-(β3-AR)-cAMP-PKA pathways. Conclusions: The results of this study demonstrate that a single prophylactic administration of the traditional Chinese medicine formula SFD prior to cold seawater exposure significantly prolongs the survival time of rats. This effect is associated with the upregulation of UCP1 and the subsequent enhancement of thermogenesis in BAT. These findings highlight the great potential of SFD as a promising intervention for the management of hypothermia. Full article

The exceptional longevity of bats challenges classical theories of inflammaging and suggests an alternative that improved resilience in responding to pathogens and cellular damage can increase longevity. Accordingly, we have developed the Core Longevity State Vector (CLSV-6) to characterize an expanded explanation for inflammaging that can be predictive of successful aging and used to develop potential strategies for successful aging. Despite high metabolic rates and persistent viral exposure, many bat species have much longer lifespans than would be predicted for mammals of their size. The increased longevity of many bat species is achieved through damage tolerance, regulated inflammasome activity, constitutive basal antiviral defenses, enhanced autophagy–mitophagy, and efficient resolution of inflammation, rather than through heightened inflammatory immunity. The CLSV-6 is introduced as a multidimensional immunotype framework integrating six conserved mechanisms that link bat immunity to bat longevity and to human healthy aging: (1) damage tolerance, (2) autophagy–mitophagy, (3) proteostasis (management of degraded proteins), (4) basal immune readiness without activation, (5) inflammasome regulation, and (6) inflammatory resolution capacity. Together, these mechanisms enable a robust antiviral defense when needed without chronic inflammation. Notably, centenarians converge toward this bat-like configuration. Studies suggest that centenarians often preserve more functional NK cells, better macrophage regulation, and improved anti-inflammatory control, with both bats and humans exhibiting reduced activation of the NLRP3 inflammasome, resulting in greater immune resilience. Building on this framework, functional foods—including polyphenols, fermented foods, and herbal extracts—are proposed as practical strategies to shift human immunity toward bat-like, CLSV-6 immunotype by enhancing cellular quality control, regulating inflammasome activity, strengthening basal antiviral readiness, and supporting inflammatory resolution, thereby redirecting longevity strategies from immune stimulation toward damage containment and repair. This review reframes longevity as an emergent property of integrated immune damage management and provides a mechanistic roadmap for nutritional interventions to engineer healthier human aging inspired by bat immunity. Full article

The poly(A) tail has long been known to play a central role in mRNA stability, storage, and translational competence, making it a potential key regulator during hypometabolic states. During seasonal torpor, hibernating mammals must frequently enter these hypometabolic states to survive. In this study, we examined protein abundance changes in key enzymes involved in poly(A) tail synthesis, binding, and removal during torpor in the brown adipose tissue of the 13-lined ground squirrel, Ictidomys tridecemlineatus, using immunoblots. BAT during late torpor exhibited significantly reduced abundance of the catalytic cleavage enzyme CPSF73, but increased abundance of poly(A) polymerase PAPOLA. In contrast, poly(A)-binding proteins and major complex subunits of deadenylases, including CCR4-Not, exhibited no significant changes. Furthermore, despite unchanged levels of the translation initiation factor eIF4E, the phosphorylated variant of 4E-BP1, a potent inhibitor of the initiation factor when hypophosphorylated, was significantly reduced during late torpor. Overall, constrained mRNA maturation, preserved transcript stability, and reversible translational inhibition suggest that an important role exists for poly(A) tail regulatory machinery in hypometabolic survival throughout the torpid state. Full article

Constant light (LL) exposure is an established environmental risk factor for metabolic diseases, in which the whitening of brown adipose tissue (BAT) plays a critical role. This study aimed to elucidate the molecular mechanisms through which cordycepin counteracts LL-induced BAT whitening and improves metabolic function. We established an LL-exposed mouse model and employed an integrative approach combining pharmacological, metabolic, molecular, and computational (docking) assays to define cordycepin’s effects and targets. Cordycepin treatment significantly improved cold tolerance and attenuated BAT whitening in LL mice. Mechanistically, cordycepin directly bound to and enhanced the activity of the NAD⁺-dependent deacetylase SIRT1. This activation mitigated LL-induced impairments in mitochondrial biogenesis, dynamics, and autophagy. Furthermore, SIRT1 activation rebalanced fatty acid metabolism by downregulating CD36 and upregulating CPT1, thereby restoring the coupling of fatty acid uptake to oxidation. All beneficial effects of cordycepin were abolished by the selective SIRT1 inhibitor EX-527. In summary, our work provides strong evidence that cordycepin directly interacts with SIRT1 and enhances its deacetylase activity, thereby restoring mitochondrial function and fatty acid oxidative homeostasis in BAT to counteract constant LL-induced metabolic dysfunction. These findings position cordycepin as a promising natural compound targeting the SIRT1 pathway for metabolic disorders. Full article

Nipah virus (NiV) is an animal-borne RNA virus of the genus Henipavirus that poses a significant global health threat. This threat is driven by the virus’s high mortality rate, its capacity to cause epidemics, and the lack of licensed therapeutic interventions or vaccines. Since its initial identification during the 1998–1999 outbreak in Malaysia and Singapore, recurrent episodes have occurred primarily in Bangladesh and India, with mortality rates frequently exceeding 70%. Fruit bats of the genus Pteropus serve as the biological host for the virus. Transmission to humans occurs via contact with infected wildlife, consumption of contaminated products, such as freshly harvested date palm sap, or direct person-to-person exposure. Other modes of transmission, such as transplacentally or via breast milk, are still under investigation. The clinical presentation of NiV infection varies widely, from mild flu-like symptoms to life-threatening respiratory disease and acute encephalitis. It frequently attacks the nervous system, which can lead to coma, permanent neurological damage, or relapsing encephalitis. The virus enters host cells via ephrin-B2/B3 receptors, enabling systemic dissemination and infiltration of the central nervous system. Diagnosis relies primarily on RT-PCR and serological assays, and virus isolation requires high-containment laboratories. Management remains largely supportive, as no approved antiviral therapy exists. Experimental agents, such as remdesivir, favipiravir, and monoclonal antibodies such as m102.4, have shown promise in preclinical studies. Multiple vaccine platforms—including subunit, viral vector, mRNA, and nanoparticle-based approaches—are under development, though none is yet licensed for human use. Strengthened surveillance, infection control measures, and continued research are essential to mitigate the threat posed by this emerging pathogen. This review summarizes current knowledge on NiV, including its virology, epidemiology, pathogenesis, transmission, and recent progress in therapeutic and vaccine development. Full article

Globba bicolor Gagnep., an ornamental ginger of cultural importance in Thailand’s “Tak Bat Dok Mai” festival, faces conservation challenges due to climate change and slow natural propagation. Limited understanding of its cultivation and chemical composition further constrains sustainable utilization. This study provides the first integrated investigation of micropropagation using rhizome-derived explants under various combinations of exogenous hormones, acclimatization strategies, and comparative phytochemical profiling between wild and in vitro-propagated plants. An optimized clonal regeneration system was established from plantlets, with Murashige and Skoog (MS) medium containing 2.0 mg/L 6-benzylaminopurine (BA) and 0.5 mg/L 1-naphthaleneacetic acid (NAA), yielding the highest multiplication (9.10 shoots/explant and 12.40 roots/explant) after eight weeks of cultivation. During acclimatization, sand substrate proved superior, facilitating a 90% survival rate and enhanced physiological vigor. Comparative analysis revealed that while wild plants possessed significantly higher total phenolic (TPC) and total flavonoid (TFC) contents and antioxidant activities (DPPH, ABTS, and FRAP) than their in vitro counterparts, both sources maintained a rich diversity of chemical constituents. HPLC analysis identified cinnamic acid, rutin, and quercetin as major metabolites, while GC–MS detected 90 volatile compounds, with β-caryophyllene and β-pinene as predominant constituents. Notably, rhizomes of wild plants exhibited particularly high-value detections. To provide a rapid and non-destructive approach for linking chemical composition with antioxidant activity, FTIR-based chemometric models were applied, demonstrating high predictive accuracy (R²–cv = 0.9712–0.9862). These results provide a scientific foundation for the conservation and sustainable commercial utilization of G. bicolor as a potential source of bioactive natural products. Full article

The recent SARS-CoV-2 pandemic—which had significant worldwide health, economic, and other effects—indicated the need to monitor zoonotic viruses with pandemic potential. The aim of this review is to assess bat-borne viruses as a potential pandemic risk, with a particular focus on Europe. The presence and activity of bats, as well as diseases emerging in humans in various regions of the world, point to their importance in the context of a possible outbreak of future epidemics. The rate of genetic change observed among viruses requires constant scrutiny on all continents, including Europe. Bats are a considerable source of many zoonotic viruses, including coronaviruses, filoviruses and paramyxoviruses. Among viruses associated with bats, RNA viruses are the dominant ones, characterized by high pathogenicity and often leading to interspecies transmission. The majority (about 80%) of RNA viruses were identified in bats from three families: Vespertilionidae, Rhinolophidae and Pteropodidae. Understanding how viruses are transmitted in the environment and the role of reservoir organisms and intermediate hosts is crucial to determining the level of epidemic risk. This review discuses viruses identified in bats globally, with a special focus on Europe, and evaluates their potential to cause epidemics. Full article

The Yellow Sea is an important offshore area in China, and the accurate prediction of its seawater temperature is of great significance for marine environmental monitoring and climate adaptation management. However, existing research on predicting the three-dimensional (3D) temperature field in the Yellow Sea is scarce and insufficiently accurate. This study proposes a TCN-U-Net++ fusion model to reconstruct the Yellow Sea temperature field using remote sensing satellite data and SODA reanalysis data, while considering the influence of a series of factors, including wind (USSW and VSSW), absolute bathymetric data (BAT), sea surface height anomaly (SSHA), latitude (LAT), longitude (LON), solar radiation (SR), surface runoff (SRO), and precipitation (P). The results show that the model can accurately capture the temporal and spatial distribution characteristics of the temperature field in the Yellow Sea. The results indicate that the deviations from SODA are generally within 2 °C, with errors being approximately 45% lower than those of other models, while the prediction errors relative to Argo and voyage observations are mostly within 1 °C, further demonstrating the accuracy and robustness of the proposed model. In addition, the predictions of the Yellow Sea Cold Water Mass (CWM) are highly consistent with SODA in terms of their evolution and key characteristic parameters. Specifically, the maximum deviation in core temperature is only 0.3 °C, and the difference in its spatial extent is less than 1%. The results demonstrate that TCN-U-Net++ effectively enhances the accuracy of 3D sea temperature prediction in the Yellow Sea, providing technical support for temperature monitoring, ecological early warning, and climate change research. Full article

Traditional approaches for identifying bearing defects in metro traction systems often suffer from low diagnostic efficiency and accuracy. To address this, we propose an information fusion approach using the Bat Algorithm-Optimized Variational Mode Decomposition (BA-VMD) and the Self-Attention Convolutional Neural Network (SA-CNN). Vibration and acoustic emission signals are denoised via BA-VMD to optimize decomposition, followed by a diagnosis model utilizing attention-based fusion and SA-CNN to enhance key feature extraction. Experiments on subway traction motor bearings under varying operating conditions demonstrate the method’s efficacy. Results indicate that BA-VMD achieves a signal-to-noise ratio of 6.791, which is 1.595 higher than that of EMD (5.196). Furthermore, the SA-CNN model achieves an average diagnostic accuracy of 98.6%, significantly outperforming MLP (93.57%) and SVM (90.90%). These findings confirm that the proposed framework ensures accurate and stable bearing fault detection in highly variable operating conditions. Full article

In Cambodia, farmers construct artificial household bat roosts to collect and sell guano as fertilizer. We investigated farming practices and attendant spillover risks using (1) surveys on guano production; (2) an estimation of bat population size and species present using carcasses, visual identification, and audio recordings; (3) surveys of guano-producing and neighboring households on water, sanitation, and hygiene practices; and (4) the testing of guano and household food, water, and surfaces for coronaviruses using RT-qPCR. Bat roosts are constructed using dried palm leaves with coconut tree and/or steel/concrete supports. Roosting areas ranged from 42 to 327 m², bat abundance varied from 0 to 11,187, guano production was between 5 and 120 kg/week, guano yields were from 0.15 to 0.4 kg/m²/week, and farmers earned USD ~100–200/household/month. Higher guano production in the peak (normally wet) season was associated with greater bat abundance (p = 0.016). The lesser Asiatic yellow house bat (Scotophilus kuhlii) was the only bat species identified. Roosts were <20 m from guano-producing households. Neighbors and households’ hygiene risks included not having handwashing stations and not covering food in storage/while drying. Coronaviruses (Alphacoronaviruses or Infectious Bronchitis Virus) were detected in 14.6%, 17.3%, 2.9%, 1.4%, and 0.0% of guano, urine, household surface, food, and water samples, respectively. While guano farming offers economic benefits, spillover risks exist. Safe guano collection and storage, handwashing, and food covering in guano-producing communities are necessary to mitigate spillover risks. Full article

Bats are recognized reservoirs for a vast array of viral diversity, including members of the Hepadnaviridae family. Within a One Health framework, genomic surveillance of these animals is fundamental to understanding viral diversity and the potential risks of zoonotic spillover in high-density human population areas. This study describes the detection of a bat hepadnavirus through agnostic viral metagenomics in samples from passive surveillance collected in urban and peri-urban areas in Brazil. Sequencing was performed using the Oxford Nanopore Technologies (MinION) platform, and the bioinformatics pipeline involved de novo assembly and taxonomic identification against viral databases. We identified several contigs with similarity to the Tent-making bat hepatitis B virus (TBHBV) in a single liver sample. The largest contig (3182 bp) represents the complete genome, exhibiting a nucleotide identity of 80.93% with the original reference isolate. Our findings document the circulation of this viral lineage in a new epidemiological setting (the Brazilian urban interface), underscoring the importance of continuous surveillance to monitor the evolution and geographic distribution of bat orthohepadnaviruses and their relevance to public health. Full article