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Genomic analysis of high pathogenicity avian influenza viruses from Antarctica reveals multiple introductions from South America
Enhancing intrusion detection in encrypted DoH traffic through a robust ensemble learning framework
The DNS over HTTPS (DoH) protocol enhances user privacy by encrypting DNS queries and responses within HTTPS. However, this encryption enables attackers to tunnel malicious traffic through covert DoH channels and make detection difficult for network security and enterprises. In this study, we propose a stacked ensemble approach that employs four sequential base learners’ — two Long Short-Term Memory (LSTM) and two Gated Recurrent Unit (GRU) neural networks as base classifier networks with varied hyperparameters and XGBoost (eXtreme Gradient Boosting) as the meta-learner. An XGBoost model trained on out-of-fold predictions generated by base learners supported through stratified 5-fold cross validation. We also applied Recursive Feature Elimination (RFE) with XGBoost for cross-validated feature selection and decreased high-dimensional feature spaces from 29 to 13 and 20 features on the CIRA-CIC-DoHBrw-2020 and DoH-Tunnel-Traffic-HKD datasets respectively. The proposed framework was evaluated on the CIRA-CIC-DoHBrw-2020 and DoH-Tunnel-Traffic-HKD datasets achieved 0.9996 recall, 0.9999 F1-score and 1.0000 AUC-PR on CIC-DoH dataset and 0.9998 recall, 0.9999 F1-score, and 1.0000 for both AUC-ROC and AUC-PR on HKD-DoH dataset. The proposed model outperforms all individual base classifiers, evaluated ML models, and existing state-of-the-art approaches. The proposed XGBoost meta-model needs only 1.26 seconds for training and 0.129 seconds for inference on HKD-DoH dataset, thus making the proposed framework both highly accurate and computationally efficient for real-world intrusion detection in encrypted DoH traffic.The preprocessed data and the source code supporting the findings of this study are available at: https://github.com/soreettihussein/Stacked-ensemble-meta-learning-IDS-for-DoH-network-traffic/tree/main .
From the Literature
Protein coacervation-driven active forces power protocell dynamics
Plasma gelsolin as a potential biomarker for intrauterine inflammation in pregnant women with preterm premature rupture of membranes: A pilot study
Background Gelsolin is an actin-binding protein, the blood levels of which decrease in response to inflammation and tissue injury. However, the dynamics of gelsolin during pregnancy and its relationship with intrauterine inflammation remain unclear. In cases of preterm premature rupture of membranes, conventional indicators such as white blood cell (WBC) count and C-reactive protein (CRP) have known limitations, and reliable biomarkers for predicting intrauterine inflammation are limited. In this study, we investigated changes in plasma gelsolin concentrations during pregnancy and evaluated their association with intrauterine inflammation in patients with preterm premature rupture of membranes. Methods In this pilot study, plasma gelsolin concentrations were measured by enzyme-linked immunosorbent assay in healthy pregnant women and in patients with preterm premature rupture of membranes. In healthy pregnancies, samples from the first, second, and third trimesters were analyzed. In cases with preterm premature rupture of membranes, serial measurements were performed from the time of membrane rupture to delivery. Correlation analyses with inflammatory markers (C-reactive protein and white blood cell) were conducted. Additionally, immunohistochemical staining for gelsolin was performed on placental tissues from chorioamnionitis cases and controls to compare expression levels and distribution patterns. Results In healthy pregnant women, plasma gelsolin levels significantly decreased as pregnancy progressed. In cases with preterm premature rupture of membranes, plasma gelsolin levels showed a significant negative correlation with C-reactive protein and tended to decrease over time following membrane rupture. Immunohistochemical staining revealed a trend toward an increased number of gelsolin-positive cells in the chorionic membrane of chorioamnionitis cases. Conclusion Plasma gelsolin decreases with the progression of pregnancy and intrauterine inflammation and may particularly reflect the progression of intrauterine inflammation in cases of preterm premature rupture of membrane. Gelsolin has the potential to serve as a novel biomarker for detecting inflammatory conditions that are not readily identified by conventional markers.
Apolipoprotein D, a Novel Ligand for CD36, Is Essential for Blood–Brain Barrier Integrity
BACKGROUND: The disruption of the blood–brain barrier (BBB) is a central pathogenic event in many central nervous system disorders. However, the mechanisms regulating BBB function remain incompletely understood, and effective treatments are lacking. Brain mural cells differ significantly from their peripheral counterparts, a distinction likely critical for maintaining BBB integrity. METHODS: We combined proteomic profiling of human brain vs peripheral mural cells with multiple ischemic stroke models (global apolipoprotein D [ApoD] knockout, mural cell–specific ApoD knockout, and adeno-associated virus–mediated ApoD overexpression) to evaluate the role of ApoD in BBB integrity. Mechanistic studies (co-immunoprecipitation, binding assays, including surface plasmon resonance, bio-layer interferometry, cross-linking mass spectrometry, and CD36 loss-of-function approaches, both in vitro and in vivo) were performed to determine how ApoD interacts with CD36 and inhibits its signaling. Finally, we assessed the effect of ApoD glycosylation on CD36 binding and tested therapeutic delivery of hypoglycosylated ApoD in stroke. RESULTS: Our study has shown an increased expression of ApoD in mural cells after ischemic stroke. We found that mural cell–derived ApoD functions as an inhibitory ligand of endothelial CD36, suppressing pathological endothelial proliferation, preserving BBB integrity, and promoting neurological recovery. Additionally, overexpression of ApoD in mural cells improved BBB integrity and enhanced functional recovery in ApoD -null mice. Mechanistically, ApoD competes with long-chain fatty acids for CD36 binding and directly attenuates downstream CD36 signaling. Furthermore, we reveal that peripheral hyperglycosylated ApoD (hyperglyco-ApoD) showed minimal effect on BBB integrity maintenance, whereas hypoglycosylation of ApoD enhances its binding affinity to CD36, amplifying its therapeutic efficacy. Exogenous administration of hypoglyco-ApoD via vein injection profoundly inhibited BBB disruption and improved neural function, especially in aging stroke. CONCLUSIONS: Our work identifies a previously unrecognized paracrine mechanism in which mural cell–derived ApoD directly engages endothelial CD36 to restrain pathological endothelial proliferation, thereby preserving BBB integrity and promoting neurological recovery after stroke. These findings further suggest that hypoglycosylated ApoD, with its higher CD36-binding affinity, merits investigation as a potential strategy to enhance BBB repair in central nervous system disorders.
Electrically modulated plasmonic metasurfaces for light communication
Ecological speciation in allopatry is rooted in older divergence
Mapping the role of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptors in chronic kidney disease: A scoping review protocol
Chronic kidney disease (CKD) is increasingly recognized as a global public health concern, impacting about 800 million people worldwide. Despite having different CKD etiologies, apoptosis, inflammation and fibrosis are the central mechanisms of pathogenesis. Tumor necrosis factor (TNF)- related apoptosis-inducing ligand (TRAIL) is a critical regulator of these mechanisms, suggesting a prominent role in pathogenesis and progression of CKD. Therefore, systematic mapping of the available evidence is pivotal in identifying the exact role of TRAIL and its receptors in CKD. The proposed scoping review will be conducted in line with Arksey and O’Malley’s methodological framework and the Joanna Briggs Institute (JBI) reviewer’s manual. Accordingly, the review will be guided by the five-stage approach, namely (1) identify the research question; (2) identify relevant studies; (3) select studies; (4) chart the data; and (5) collate, summarize, and report the results. Eligibility criteria and search strategies will be formulated based on population, concept, and context (PCC) strategy. Articles published up to January 2026 will be searched using electronic databases (PubMed/ MEDLINE, Science Direct, Scopus, CINAHL, EMBASE, Web of Science and Cochrane Library) and clinical trial registries (ClinicalTrials.gov and WHO ICTRP). Reference lists of relevant reviews retrieved from Google Scholar will also be screened for grey literature. A formal quality appraisal of the selected studies will be conducted using the mixed-method appraisal tool (MMAT version 2018). The reporting will be done following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for the Scoping Reviews checklist. The literature search is expected to commence in March 2026, followed by study selection and data extraction by April 2026. Data synthesis will be completed by June 2026. The review protocol is registered at Open Science Framework (OSF) under https://doi.org/10.17605/OSF.IO/AENBX .
Wearable-Derived Training Load and Coronary Atherosclerosis in Middle-Aged and Older Athletes and Physically Active Controls: A New Perspective From the Master@Heart Study
BACKGROUND: Middle-aged and older endurance athletes have increased prevalence of coronary artery disease (CAD) on coronary computed tomography angiography compared with healthy controls, despite similarly low cardiovascular risk. Previous studies relied on self-reported data to quantify training load (TL), which poorly correlates with objective wearable-derived TL and may bias outcomes. The effect of objective TL on CAD risk remains unknown. METHODS: In this observational, cross-sectional analysis of the Master@Heart study, 222 men (median age, 54 [49–59] years) were included: 77 lifelong athletes, 98 late-onset athletes, and 47 controls. TL was assessed using objective wearable-derived training duration and intensity (12 consecutive months), as well as self-reported training measures. Coronary computed tomography angiography–derived CAD prevalence was compared across TL quartiles (Q) using a global unadjusted chi-square test and logistic regression, adjusted for cardiovascular risk factors and years of endurance exercise, to estimate odds ratios between Q4 and Q1. In addition, adjusted logistic regression models were fitted with continuous TL, using smoothing splines to capture potential nonlinear associations. RESULTS: Across quartiles of objective Edwards training impulse (training duration × heart rate–weighted intensity), unadjusted global differences were observed for ≥1 plaque ( P <0.001), coronary artery calcification (CAC)>0 ( P =0.002), and CAC>100 ( P =0.012). Q4 participants had significantly higher adjusted odds of ≥1 plaque (odds ratio, 5.85; 95% CI, 2.33–14.71), CAC>0 (odds ratio, 5.03; 95% CI, 2.04–12.35), and CAC>100 (odds ratio, 3.50; 95% CI, 1.22–10.00) versus Q1. Similar associations were found for objective training duration, whereas no clear associations were observed for relative time spent in high-intensity zones. In continuous analyses, Edwards training impulse and objective training duration showed significant positive associations with ≥1 plaque and CAC>100 ( P <0.05), whereas self-reported training duration was only significantly associated with CAC>100 ( P <0.05). Metabolic equivalent of task-minutes per week based on self-reported TL was not associated with CAD ( P >0.05). CONCLUSIONS: High training duration (hours/week), particularly when combined with cumulative high-intensity TL (Edwards training impulse), was independently associated with increased prevalence of subclinical CAD in middle-aged and older athletes and physically active controls. Exercise intensity alone, in the absence of high duration, was not clearly linked to CAD. These findings underscore the potential of objectively measured TL for understanding associations with subclinical CAD in endurance athletes. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03711539.
Modelling synaptic dysfunction in childhood dementia using human iPSC-derived cortical networks
Loss of ABC transporters, White, Brown, and Scarlet, prevents increase in mitotic divisions of germline stem cells in response to mating in Drosophila melanogaster
The replenishment of specialized cells depends on the activity of stem cells. Recent advances in stem cell research have shown that the germline stem cells (GSCs) in Drosophila melanogaster can increase their mitotic activity in response to mating. Here, we show that this ability to respond to mating is eliminated if the males are mutant for either of the ABC transporters, White (W), Brown (Bw) or Scarlet (St), which are known for their role in eye pigmentation and amine production. However, reducing the expression of w specifically from the germline cells also caused a failure to increase GSC mitotic activity upon mating, suggesting that w is required intrinsically in the stem cells. The w gene is a common genetic background for genetic experiments and frequently used as a control. Our findings underline the importance of careful experimental design and control choice.
Letter by Liu and Li Regarding Article, “Ponatinib, But Not the New Abl-Kinase Inhibitor Asciminib, Activates Platelets, Leukocytes, and Endothelial Cell TNF Signaling to Induce Atherosclerotic Plaque Inflammation, Myocardial Infarction, and Stroke”
Ponatinib inhibits LCK and PI3K signaling and promotes CD8+ T stem cell memory cell development
The low-density lipoprotein receptor LDLR mediates cellular entry of nonenveloped hepatitis A virus
Hepatitis A virus (HAV) is an unusual picornavirus with two types of extracellular virions: nonenveloped particles (nHAV) shed in feces and quasi-enveloped particles (eHAV) circulating in blood. Both enter cells by clathrin-dependent endocytic pathways merging in late endolysosomes with capsid binding to ganglioside receptors. Phosphatidylserine receptors facilitate eHAV endocytosis, but no protein receptor has been identified for nHAV. Here, we show low-density lipoprotein receptor (LDLR) is such a receptor. LDLR knockout did not alter viral attachment to cells, but restricted cellular uptake of nHAV (not eHAV). Soluble LDLR ectodomain blocked nHAV entry, as did antibody to LDLR. Recombinant LDLR-related protein-associated protein 1, a pan-LDLR family chaperone, also inhibited nHAV entry, including residual entry into knockout cells, suggesting other LDLR family members may similarly facilitate endocytosis. Reconstituting full-length LDLR expression restored nHAV entry in knockout cells, whereas LDLR mutants lacking LA repeats 4 to 7 or the EGF-like/propeller domain did not. ELISAs confirmed LDLR binds nHAV, optimally above pH7, without destabilizing the capsid. A 1.7Å resolution cryoelectron microscopy (cryo-EM) structure revealed LDLR interacts with VP1 at the fivefold vertex of the capsid. Extreme blurring of the LDLR density prevented detailed identification of LDLR interactions, and suggested binding does not follow particle symmetry, being either flexible or to multiple LDLR regions. Additional cryo-EM studies show ganglioside GD1a binds to a similar region of the capsid. Collectively, these data reveal the LDLR to be an important entry factor, shuttling nHAV from the extracellular environment to endolysosomes where it is likely released at low pH to bind gangliosides.
Comparative evaluation of immunoserological detection of F-actin antibodies
Autoantibody detection remains essential in diagnosing autoimmune liver diseases (AILD), particularly autoimmune hepatitis (AIH), in which smooth muscle antibodies (SMA) targeting filamentous actin (F-actin) are commonly observed. This study assessed the concordance between immunofluorescence testing (IFT), the gold standard for SMA detection, and a commercially available F-actin ELISA in a real-world clinical setting. During the three-months study period, 244 samples were sent to our laboratory for autoantibody testing; 241 were included in the study. SMA IFT on rodent stomach, kidney and liver sections identified 104 positive cases, with ELISA-detected F-actin antibody levels being significantly higher in these cases. F-actin ELISA concentrations significantly increased with higher SMA IFT titer. Concordance between the ELISA (using manufacturer-recommended cut-offs of 20 and 30 units) and IFT depended on the SMA staining pattern. Only slight agreement was found between positive kidney SMA staining patterns and ELISA concentration. Stomach SMA staining showed moderate agreement (Cohen’s kappa = 0.49) and a subgroup analysis revealed better agreement in autoimmune disease cases, particularly AIH. An optimized ELISA cut-off of 27.6 units improved agreement slightly (Cohen’s kappa = 0.55). The results suggest that, although there is a certain level of concordance between the ELISA and stomach SMA IFT, the F-actin ELISA does not reliably predict SMA IFT staining. These findings underscore the importance of method validation and context-specific interpretation when implementing ELISA-based autoantibody screening in routine diagnostics.
Correction to: Abstract 4367615: The Cardiovascular Paradox of Gout Prophylaxis: A Systematic Review and Meta-analysis
Respiration as a dynamic modulator of sensory sampling
Abstract Respiration dynamically modulates sensory perception by orchestrating transient states of the brain and the body. Using simultaneous recordings of high-density magneto- encephalography (MEG), respiration, and pupillometry, we show that human perceptual sensitivity to near-threshold visual stimuli was enhanced during inspiration, coinciding with respiration-modulated increases in arousal neuromodulation and cortical excitability. Participants adapted their breathing patterns to align with predictable stimulus onset, and this adaptive respiratory alignment correlated with improved performance. We further reveal that respiration-modulated changes in alpha and beta oscillations reflect distinct shifts in sensory and motor excitability, respectively. Crucially, respiration-resolved multivariate Granger causality analyses demonstrate that the breathing rhythm systematically shapes directed information flow within a widespread interoceptive network. This respiration-brain coupling was flexibly adjusted based on stimulus predictability, highlighting a mechanism for active sensing which integrates internal bodily rhythms with external sensory demands to optimise perception.
Workload perception and job satisfaction among Lebanese practicing dietitians: A cross-sectional study by employment location
Objective Workload perception and job satisfaction are fundamental components of human resource management. While these factors have been studied across healthcare professionals worldwide, research on this topic, specifically among dietitians, is lacking in Lebanon. This study aims (1) to assess the perceived workload and job satisfaction levels among Lebanese practicing dietitians and (2) to explore its associations with sociodemographic characteristics and employment location (Lebanon only vs Lebanon and abroad). Methods This cross-sectional study included 138 Lebanese dietitians, using a structured questionnaire covering sociodemographic status, workload perception (NASA-TLX) and job satisfaction (Spector’s job satisfaction survey). Scores were expressed as percentages, categorized into six groups, and stratified by employment location. Descriptive statistics, independent t-test and multiple linear regression models were used. Results The total job satisfaction score (JSS) was significantly associated with middle-aged groups ranging from 31 to 40 years old (p = 0.003), with 16–20 years of experience (p = 0.001), having a higher education level (p = 0.01) and greater income (p < 0.0001). Middle age was significantly associated with being satisfied with payment (p = 0.0001) and the nature of the work (p < 0.0001). When stratified by employment location, dietitians practicing in Lebanon and abroad reported significantly higher satisfaction in several facets compared with those practicing in Lebanon only (p < 0.05), while communication and fringe benefits did not differ significantly. The total median workload score was 62.8% indicating a slightly high perception of workload among the target participants. Conclusion Lebanese dietitians reported slight overall job satisfaction, higher among those aged 31–40 years, with 16–20 years of experience, higher education, greater income. Dietitians practicing in Lebanon and abroad reported higher satisfaction across several facets than those practicing in Lebanon only. Perceived workload was slightly high, with no significant difference in total workload by employment location, although differences emerged across specific workload dimensions. This highlights the need for strategies addressing workload management, early-career mentorship, and stress management to support dietitians’ career satisfaction.