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Efficacy and safety assessment of gelatin hemostatic matrix in a burr hole neurosurgical beagle model
Abstract Absorbable topical hemostatic agents are indispensable for managing excessive bleeding during neurosurgical and emergency procedures, significantly reducing the risk of serious complications. In the current study, we evaluated the hemostatic efficacy of two commercialized hemostatic agents, SURGIFLO (Ethicon, Johnson & Johnson, USA) and Borayerflo (Jiangxi Borayer Biotechnology Ltd, China), in a cerebral hemorrhage model using Beagle dogs. As a result, both SURGIFLO and Borayerflo achieved 100% hemostasis within 5 min of treatment, with no statistically significant differences observed between the two groups. Additionally, blood test results, including fibrinogen (FIB) level, thrombin time (TT), prothrombin time (PT), International Normalized Ratio (INR), and activated partial thromboplastin time (APTT), demonstrated that both SURGIFLO and Borayerflo matrices exhibited excellent blood compatibility and did not interfere with fibrinogen’s role in coagulation. Furthermore, toxicity test results indicated that no adverse reactions were observed post-operatively, confirming the safety of both SURGIFLO and Borayerflo. Consequently, the study validates the comparable safety and efficacy of the Borayerflo to SURGIFLO in terms of preclinical hemostatic efficacy and safety, making it a potential alternative product as a suitable absorbable topical hemostatic agent in the market.
Lycopene inhibits ER stress and apoptosis while modulating PI3K/AKT and enhancing antioxidant and anti-apoptotic proteins
Acute kidney injury (AKI) is a critical clinical syndrome with limited therapeutic options. This study investigated the renoprotective effects of lycopene, a potent antioxidant, in both in vivo and in vitro AKI models. In a murine cecal ligation and puncture (CLP)-induced sepsis-AKI model, pretreatment with lycopene (10, 20, 40 mg/kg) dose-dependently ameliorated renal histopathological damage (HE staining) and restored serum biomarkers (AST, ALT, BUN, CREA). Mechanistically, lycopene suppressed oxidative stress and apoptosis by downregulating the PI3K/Akt axis: it significantly reversed the CLP-induced upregulating of p-PI3K and p-Akt, and the pro-apoptotic proteins (Bax, Cleaved Caspase-3), while increasing Nrf 2 and SOD1. Consistent results were observed in LPS- and H₂O₂-induced cellular AKI models, where lycopene attenuated cell death and restored redox homeostasis in a dose-dependent manner. Immunofluorescence assays further validated these trends. Crucially, PI3K siRNA or cDNA transfection experiments confirmed that lycopene’s antioxidant and anti-apoptotic effects were PI3K-dependent. Our findings highlight lycopene as a promising therapeutic agent for AKI, acting via PI3K/Akt-mediated activation of Nrf 2 to counteract oxidative damage and apoptosis. This study provides novel insights into the molecular mechanisms underlying lycopene’s renoprotection and supports its potential clinical translation for sepsis or oxidative stress-associated AKI.
Phylodynamic analysis reveals disparate transmission dynamics of Mycobacterium tuberculosis complex lineages in Botswana
Abstract Tuberculosis epidemics have traditionally been conceptualized as arising from a single uniform pathogen. However, Mycobacterium tuberculosis complex (Mtbc), the pathogen causing tuberculosis in humans, encompasses multiple lineages exhibiting genetic and phenotypic diversity that may be responsible for heterogeneity in tuberculosis transmission. We analysed a population-based dataset of 1,354 Mtbc whole-genome sequences collected over four years in Botswana, a country with high HIV and tuberculosis burden. We identified Lineage 4 (L4) as the most prevalent (87.4%), followed by L1 (6.4%), L2 (5.3%), and L3 (0.9%). Within L4, multiple sublineages were identified, with L4.3.4 being the predominant sublineage. Phylodynamic analysis revealed that L4.3.4 expanded steadily from the late 1800s to early 2000s. Conversely, L1, L4.4, and L4.3.2 showed population trajectories closely aligned with the HIV epidemic. Meanwhile, L2 saw rapid expansion throughout most of the 20th century but declined sharply in the early 1990s. Additionally, pairwise genome comparison of Mtbc highlighted differences in clustering proportions due to recent transmission at the sublineage level. These findings emphasize the diverse transmission dynamics of strains of different Mtbc lineages and highlight the potential for phylodynamic analysis of routine sequences to refine our understanding of lineage-specific behaviors.
Centriflaken: An automated data analysis pipeline for assembly and in silico analyses of foodborne pathogens from metagenomic samples
Rapid and comprehensive analysis of metagenomic data from samples associated with foodborne outbreaks is of critical importance in food safety. Equally important is the need for automated analysis pipelines that allow the rapid and effective construction of metagenomic assembled genomes (MAGs) to enable bacterial source-tracking from metagenomic data. Here, we present centriflaken, an automated precision metagenomics pipeline for detecting and characterizing Shiga toxin-producing Escherichia coli (STEC) from metagenomic data. centriflaken streamlines the process of generating metagenome-assembled genomes (MAGs) and conducting in silico analyses of STECs, significantly reducing the time and manual effort required for comprehensive pathogen profiling. centriflaken was validated using Oxford Nanopore long-read sequencing data from agricultural water enrichments, successfully reproducing results from our previous study that involved multiple manual bioinformatics steps (Maguire et al., 2021). The tool’s efficacy was further demonstrated through its application to ZymoBIOMICS microbial community standards and 21 additional irrigation water samples, completing STEC precision metagenomics analyses in less than 7 hours per sample. centriflaken’s versatility allows for the analysis of user-defined taxa beyond STEC, including other foodborne pathogens like Listeria monocytogenes or Salmonella . The pipeline generates comprehensive summary plots and tables, accessible through a MultiQC HTML report. Designed for portability, centriflaken packages all software dependencies within containers and virtual environments. This open-source tool is available on GitHub under the MIT license ( https://github.com/CFSAN-Biostatistics/centriflaken ), offering a powerful resource for rapid, automated pathogen detection and characterization in food safety applications.
A baseline study of interpretable machine learning using GC-MS breath VOCs for classifying asthma, bronchiectasis, and COPD
Abstract Accurate differentiation among asthma, bronchiectasis, and chronic obstructive pulmonary disease (COPD) remains a critical challenge due to overlapping clinical symptoms and limitations of conventional diagnostic tools. This study establishes a transparent, reproducible baseline using gas chromatography-mass spectrometry (GC-MS) data derived from exhaled breath to classify asthma, bronchiectasis, and COPD. Using a publicly available clinical dataset comprising 121 breath samples and 76 shared volatile organic compounds (VOCs), we evaluated seven supervised classifiers under nested cross-validation. Among the classifiers, XGBoost achieved the highest performance, with a mean accuracy of 95.83% and macro-averaged AUC of 0.998. To enhance clinical interpretability, we applied Shapley Additive exPlanations (SHAP) to identify the most influential VOCs for each disease class. This analysis revealed several candidate biomarkers with disease-specific or cross-disease relevance, such as 2-pentylfuran and hexadecane. This integrative approach demonstrates the potential of breathomics combined with explainable AI as a scalable and non-invasive tool for respiratory disease classification and biomarker discovery. By providing this reproducible baseline, our work offers a reference point for future methodological advances and clinical validation using breathomics data.
Functional beverage development from traditional Thai polyherbal tonic: Antioxidant-rich microcapsules and comprehensive sub-chronic toxicity assessment
This study aimed to optimize microencapsulation conditions for Phy-Blica-O (PBO), a traditional Thai polyherbal tonic, and to assess the safety of its consumer-accepted herbal tea formulation, Phy-Blica-D (PBD). PBO decoction and its phenolic-rich extract were spray-dried at different inlet temperatures (140°C, 180°C) and maltodextrin-gum Arabic ratios. Encapsulation efficiency was highest at 140°C with maltodextrin alone, while antioxidant activity was greatest in microcapsules prepared at 180°C with a 6:4 maltodextrin to gum Arabic ratio, as shown by DPPH, ABTS, and FRAP assays. PBD demonstrated strong in vitro antioxidant activities and was subsequently assessed in a 90-day subchronic toxicity study in Wistar rats. No treatment-related mortality, clinical abnormalities, organ toxicity, or hematological or biochemical disruptions were seen at doses up to 300 mg/kg/day, indicating a NOAEL above this level. These findings suggest that optimized PBO microcapsules and the PBD tea blend are safe, antioxidant-rich functional ingredients with strong potential for commercialization in complementary and integrative medicine.
Behavioural and electrophysiological correlates of sensory attenuation in the somatosensory and auditory modality within a virtual reality setup
Abstract Sensory attenuation is the phenomenon that self-produced stimulations are suppressed compared to externally generated ones, both at the subjective and electrophysiological level. Despite the extensive literature on this phenomenon, it remains unclear whether electrophysiological attenuations are consistent across senses and whether they do reflect subjective attenuations of perceived intensity for self-produced sensations. Therefore, the aim of the present study is twofold: first we aimed to collect behavioural and electrophysiological measures of sensory attenuation in a controlled virtual reality setup, both in the auditory and somatosensory domain. Secondly, we correlated behavioural and electrophysiological indices of sensory attenuation to formally test whether the suppression for potentials evoked by self-generated stimulations reflects the sensory suppression revealed by behavioural measures. A total of 28 participants were included to compare the intensity of a first stimulation, which was self-generated or externally administered, to a second stimulation, which was administered at rest with varying intensity. The stimulations could be either electrical pulses at the fingertip or auditory clicks. Participants were also required to undergo a control task in which no stimulation was administered. The behavioural results indicate a reduced perceived intensity for self-produced compared to externally administered stimuli for the auditory domain. In contrast, no such difference was observed for the somatosensory domain. EEG results revealed suppression of the P2 for the auditory modality and the P200 in the somatosensory modality. Furthermore, a positive correlation between the P2 suppression and subjective intensity attenuation was found for the auditory modality. Together, our results suggest that electrophysiological suppression at mid-latency components reflect the perceived subjective attenuation of self-produced stimulation. This relationship, however, might be dependent on the sensory domain.
Dynamic growth risk of incidentally detected gallbladder polyps–A retrospective, single-center analysis
Background Size of gallbladder polyps (GP) is considered as a relevant risk factor for neoplastic polyps. However, the definitive impact is an ongoing debate. Current German and European guidelines recommend surveillance for GP > 6 mm and cholecystectomy for GP > 10 mm over a period of two to five years. We aimed to analyze the dynamic growth of gallbladder polyps. Methods Patients at Hanover Medical School who underwent sonography from 2001 to 2020 were retrospectively evaluated for growth rate (GR) of detected GP independent of the underlying primary disease. Only patients with at least one follow-up as well as accurate GP size data were included in the study. Results A number of 253 patients with GP were eligible. Median follow-up was 66 months (24–209 months). Median GR was −0.3 mm/year (IQR 0.79). A subgroup analysis (polyp size 6–10 mm) showed a positive GR in 20.3% of the cases with a median GR of 0.09 mm/year (IQR 0.17). Of note, in 46% of the patients GP were not detectable at follow-up exam. Overall, two patients reached the indication for cholecystectomy (0.8%), whereas only a single patient developed histologically confirmed gallbladder cancer (0.4%). Logistic regression analysis did not reveal any risk factors associated with GP growth. Conclusion The majority of GP, which should be monitored within the current follow-up strategy, are no longer detectable sonographically over time or show a decreasing growth behavior. Only a minority shows a very slow positive GR and only a minority of patients develop malignancy.
Integrated single-cell and machine learning analysis identifies PMAIP1 as a novel biomarker for predicting prognosis and immunotherapy response in colorectal cancer
Assessing community pharmacists’ responses to pregnancy-related nausea and vomiting: A national simulated patient study in Jordan
Background and aim Nausea and vomiting of pregnancy (NVP) is the most common medical condition of gestation, affecting up to 90% of women and significantly impacting their quality of life. Community pharmacists (CPs) are often the first point of contact for these women, yet there is a lack of objective data on their practice quality in Jordan. This study aimed to conduct the first national, simulated patient study to assess objectively the assessment, management, counseling, satisfaction and predictors of appropriate practice among Jordanian community CPs when managing NVP. Materials and methods A national, cross-sectional study using a simulated patient methodology was conducted in 380 community pharmacies, selected via proportionate stratified random sampling. Two validated scenarios (mild NVP and severe NVP with red flags) were used. A validated structured data collection form documented CPs ‘ assessment, management, counseling, and patient satisfaction. Multivariable logistic regression was used to identify independent predictors of “Appropriate Practice.” All data were analysed using SPSS (V28.0). Results A significant gap between guideline-recommended care and actual practice was evident, particularly in high-risk situations. While most CPs (84.2%) initiated symptom inquiry, crucial assessment of red flags in the severe NVP scenario was dangerously low (e.g., inquiry about dehydration, 21.1%). This assessment failure translated directly to practice: only 56.8% of CPs correctly referred the high-risk patient, while 43.2% inappropriately sold an over-the-counter medication, delaying necessary medical care. Counseling on medication safety was consistently poor, with only 29.9% of CPs discussing potential side effects. Despite these clinical deficiencies, the overall patient satisfaction was high, appearing to be driven more by interpersonal skills than clinical accuracy. Multivariable analysis revealed that appropriate practice was independently predicted by prior maternal health training (aOR = 3.48, p < 0.001) and being a female pharmacist (aOR = 2.01, p = 0.009). Conversely, a high pharmacy workload was a significant independent barrier, reducing the odds of providing appropriate care by 50% (aOR = 0.50, p = 0.018). Conclusion Jordanian community CPs are a critical but currently underperforming resource in maternal care. The prevalent gaps in clinical assessment and referral for severe NVP represent a significant patient safety risk. A one-size-fits-all approach to quality improvement is unlikely to succeed. Instead, a dual-pronged strategy is essential: (1) national professional pharmacy bodies must mandate targeted continuing professional development in maternal health, focusing on risk assessment and referral protocols; and (2) health policymakers and community pharmacy owners must address systemic barriers, particularly the detrimental impact of high workload on the delivery of safe and effective patient care.
Implementing electronic informed consent in rare disease genomics
Abstract In rare disease research, sharing of individual health data is essential for advancing diagnostics and therapies, requiring robust and ethically sound informed consent processes. Within the Genomic Medicine Sweden Rare Diseases (GMS-RD) multicenter study, an electronic informed consent (eConsent) platform was developed to support data sharing, facilitate participation and enable research engagement. Tailored to the complex consent needs of rare disease contexts, the platform was piloted at three Genomic Medicine Centers in Sweden. A total of 2244 individuals were invited in the clinical routine cohort, with an overall eConsent rate of 18.6%. Uptake was highest among adult singletons (27.8%) and lowest in trios (14.3%). In contrast, the Undiagnosed Diseases Network (UDN) Sweden cohort achieved a 94% consent rate, attributed to targeted communication and active patient organization involvement. Key challenges included technical accessibility limitations, digital literacy deficits, comprehension and language barriers, and the burden of multi-step processes, especially for families. Findings underscore the need to improve usability, strengthen communication, and implement flexible consent management over time. eConsent can broaden participation in genomic research and promote responsible data sharing. However, in rare diseases contexts, it must be designed with inclusivity, clarity, and adaptability to meet the diverse participant needs.
Correction: Determination of nutritional sufficiency ranges for pomelo (Citrus grandis Osbeck) grown on alluvial soils using DRIS
Miniaturised wideband metasurface polarisation converter with high angular stability
Construction of an intelligent screening model for allergic rhinitis based on routine blood tests
The incidence of allergic rhinitis (AR) has been increasing annually, severely impacting patients’ quality of life and increasing socioeconomic burdens. The limitations of current diagnostic methods have made the development of efficient, low-cost early screening tools urgent. Based on routine blood test data, this study employed an ensemble hard voting strategy, a comprehensive filtering strategy, an embedding strategy, and a packing strategy to select 16 highly correlated features with a frequency of at least two occurrences as model inputs. Subsequently, the top three machine learning algorithms (K-nearest neighbor, logistic regression, random forest, decision tree, and support vector machine) were selected based on the area under the curve (AUC) metric as the base classifiers. An intelligent early screening model for AR was constructed using an ensemble soft voting strategy. This model demonstrated superior performance, achieving an AUC of 0.862, significantly outperforming any single algorithm. Furthermore, the external validation accuracy was 73.91%. These results demonstrate that combining an ensemble voting strategy with machine learning methods can effectively construct an early screening model for AR based on routine blood test parameters without adding additional burden to patients, providing a new approach to improving diagnosis and treatment in primary care settings.
Multi-function multi-level grid tied inverter based on a new combined logic-analog controller with capacitors balancing ability
Correction: Reconciliation and evolution of Penicillium rubens genome-scale metabolic networks–What about specialised metabolism?
Saffron as a natural modulator of reverse cholesterol transport genes in atherosclerotic rabbits, with molecular docking insights
Treatment outcomes of paul versus ahmed glaucoma implants
Objectives To compare the outcomes of Paul (PGI) and Ahmed glaucoma implants (AGI) in patients with complex glaucoma. Methods 64 patients undergoing PGI and 40 patients undergoing AGI were included in this study. Intraocular pressure (IOP), the number of IOP-lowering eye drops, and complications were evaluated during an 18-month follow-up. Results At 18 months, follow-up was completed by 26 patients (65.0%) in the AGI group and 45 patients (70.3%) in the PGI group. IOP was significantly reduced 18 months following PGI (12.3 ± 4.0 vs. 28.0 ± 9.3 mmHg, p < 0.001) and AGI (15.6 ± 5.2 vs. 30.7 ± 8.9 mmHg, p < 0.001) compared to preoperatively. The PGI achieved significantly lower IOP compared to the AGI group (p = 0.042). Similarly, the use of IOP-lowering eye drops decreased significantly at 18 months in the PGI (0.5 ± 0.8, p < 0.001) and AGI (1.3 ± 1.0, p < 0.001) groups, from baseline values of 3.3 ± 1.3 in PGI and 3.5 ± 1.3 in AGI. The number of IOP-lowering eye drops was significantly lower in the PGI than in the AGI group at both 12 (p = 0.031) and 18 months (p = 0.018). At the 18-month follow-up, qualified success rates for target pressures ≤18 mmHg were higher after PGI than AGI (IOP ≤ 18 mmHg: 66.6% vs. 84.2%, p = 0.017, ≤ 15 mmHg: 46.3% vs. 64.8%, p = 0.049, ≤ 12 mmHg: 24.9% vs. 43.0%, p = 0.047). There was no significant difference in the complication rates between PGI and AGI. Conclusion Both PGI and AGI effectively reduced IOP and the number of IOP-lowering eye drops over an 18-month follow-up period. The PGI demonstrated significantly greater reductions in IOP and IOP-lowering eye drops than AGI at 18 months. The safety profiles of PGI and AGI were comparable.
Permeability evolution and modeling analysis of anisotropic coal under different stress paths
WBA: Word Boundary Attention for Chinese Named Entity Recognition
Chinese words often exhibit a parallel structural relationship within sentences, while individual characters are sequentially connected. To capture this structural distinction, we extract the head and tail positions of characters within words and incorporate them into a relative positional encoding scheme. Building upon this design, we introduce Word Boundary Attention (WBA), a mechanism that assigns dynamic attention weights to characters and enhances their representations with contextual information derived from the word lattice. By explicitly modeling word boundaries, WBA effectively suppresses noise, improves word recognition, and leverages richer lexicon-based context during training. Extensive experiments across multiple datasets demonstrate that WBA consistently outperforms existing approaches, achieving, for instance, a 2.51% improvement over the base model on the Weibo dataset with YJ lexicon encoding. Furthermore, visualizations of the learned attention weights reveal the interactive relationships between words and characters, providing interpretable insights into the process of word discovery. The source code of the proposed method is publicly available at https://github.com/na978292231/WBA/tree/main/WBA4NER-main .