Browse Articles

Dynamics of botnet propagation model in complex networks considering hybrid method for botnet detection

In this paper, a dynamic epidemic model of botnet attack propagation in scale-free networks is introduced based on the epidemic model. The proposed attack propagation model is based on the Susceptible-Exposure-Infected-Improved-Vaccinated-Recovery (SEIRVS) epidemic model. Here, an Intrusion Detection System (IDS) for botnet attack detection is also presented. This method is based on a combination of machine learning and metaheuristic algorithms, the Golden Ratio Optimization (GRO) algorithm, Bat Algorithm (BA), and K-Nearest Neighbor (KNN) algorithms named (GRO-BA-K-NN), which includes three steps: 1) preprocessing, 2) GRO feature selection 3) attack detection using BA-K-NN. The proposed IDS, using the three datasets BOT-IOT, UNSW-NB15, and NLS-KDD, and the dynamic behavior of the proposed model, is evaluated using the metric of the initial production ratio; evaluating the dynamic behavior of the model can be used to predict whether the infection spreads or stops. The evaluation results show that the epidemic model reduces the density of infected nodes and stops the spread of infection compared to other existing models. The simulation results show that the proposed IDS was able to detect attacks with accuracy (0.938, 0.931, and 0.928) and also reduced the false negative and false positive rates.

Olfactory Receptor Activation Reduces Platelet Reactivity and Arterial Thrombosis Through Actin Cytoskeleton Remodeling

BACKGROUND: Despite antiplatelet therapy, some patients remain at high ischemic risk because of drug nonresponsiveness or high residual platelet reactivity. We aimed to target an orphan platelet GPCR (G protein–coupled receptor) from the OR (olfactory receptor) family as a novel antithrombotic strategy. METHODS: Using an engineered reporter cell line expressing human OR2L13 , an orphan GPCR implicated in limiting platelet reactivity, we conducted a high-throughput screen of 8000 nonodorant bioactive compounds with counterscreen validation. Subsequent studies assessed platelet function in healthy subjects and patients with coronary artery and peripheral artery disease. Phospho-proteomics revealed key signaling pathways, whereas ex vivo and in vivo studies evaluated the impact of a lead compound on platelet signaling, biomechanics, and thrombosis in both arterial and venous vasculature. RESULTS: We identified 6 OR2L13 (olfactory receptor family 2 subfamily L member 13)-specific agonists that suppressed platelet aggregation and α-granule exocytosis through multiple receptors, suggesting a shared downstream mediator. The lead agonist (CCF0054500) phosphorylated platelet HSP27 (heat shock protein 27), disrupting the actin cytoskeleton and reducing clot retraction (clot area, 70.6 versus 5.2; P <0.0001), an effect reversed by HSP27 inhibition. In a murine arterial injury model, CCF0054500 decreased platelet accumulation by 88.9% ( P <0.0003) without affecting fibrin generation or hemostasis. In a myocardial infarction model with high residual platelet reactivity, CCF0054500 lowered platelet reactivity ( P <0.0001) and improved left ventricular function ( P =0.007). CONCLUSIONS: We describe and characterize the first nonolfactory probe for the purpose of inhibiting platelet activation and thrombosis through downstream HSP27 in a comprehensive investigation using a first-of-its-kind platelet inhibitor targeting an orphan platelet GPCR.

Stochastic analysis of compact stars under composite polytropes

Abstract The study of dense matter has been greatly advanced by progress in theoretical high-energy simulations and modern observational astronomy. Neutron stars serve as natural laboratories for probing matter under extreme density and strong gravitational fields. While polytropic equations of state are widely employed, conventional models based on a single polytropic index cannot adequately represent the stratified, layered nature of realistic compact-star interiors. To address this limitation, we develop a composite relativistic polytropic model in which the polytropic index varies smoothly with radius. By coupling the Einstein field equations with a generalized composite polytropic equation of state, we derive the composite Tolman–Oppenheimer–Volkoff (CTOV) system. The resulting nonlinear equations are solved using a Monte Carlo-based numerical integration method, which efficiently handles stiffness while enabling probabilistic exploration of the parameter space and natural uncertainty quantification. Our results demonstrate that increasing the relativistic parameter σ significantly reduces both the Emden function and the enclosed mass function, producing more compact stellar configurations. Sharper core–envelope transitions (ε = 0.01) yield systematically higher compactness than smoother transitions (ε = 0.03). The derived mass–radius relations reproduce the observed diversity of neutron stars, successfully matching both low-mass, large-radius systems such as PSR J0030 + 0451 and high-mass compact pulsars such as PSR J1614–2230. Importantly, the maximum-mass analysis shows that stiff composite configurations (n c = 1, n e = 2, x c = 0.7) can support gravitational masses up to M max ≈ 3.47 M $$_{ \odot }$$ for ε = 0.01 and M max ≈ 2.71 M $$_{ \odot }$$ for ε = 0.03, with corresponding minimum radii in the range R min ≈ 10.6–13.2 km, consistent with current observational constraints. These findings confirm that composite polytropes provide a flexible, physically motivated framework for modeling stratified compact stars and for constraining the dense-matter equation of state.

Type I hair cells of striolar and central zones in vestibular organs are essential for head stability and postural control

The vestibular system of the inner ear provides head motion and orientation information required for maintaining balance and spatial orientation. Each of the five vestibular sensory organs contains type I and type II hair cells (HCs). Type I HCs are particularly notable for their evolutionary adaptability and unique calyceal synapses, in which the vestibular afferent nerve ending envelopes the HC body. In vitro studies indicate that calyceal synapses can transduce signals from HCs to afferents via nonquantal transmission, a mechanism proposed to be faster than conventional bouton synaptic transmission. In specialized regions of vestibular organs—striolae and central zones—many afferents form calyces that encase multiple type I HC bodies, suggesting that nonquantal transmission could be especially important in these regions. Consistently, striolar/central zone afferents are thought to preferentially mediate rapid and high-frequency stimulations. However, the direct consequences of selectively losing these HCs remain unknown. Here, we investigated the role of type I HCs within striolar/central zones by genetically ablating these cells. Reduction of type I HCs in these regions led to a loss of calyces and a compensatory increase in striolar type II HCs. These mutants exhibit reduced vestibular-evoked potentials, a response driven predominantly by striolar activity. In contrast, the vestibulo-ocular reflex, which is thought not to require striolar/central zone function, remained intact. Furthermore, loss of striolar/central zone-specific type I HCs causes head tremor in pups and abnormal head motion in adults, indicating that these HCs are essential for mediating head stability and postural control.

Determining the Physiological Threshold for Angina (ORBITA-FIRE): A Double-Blind, Randomized, Placebo-Controlled Study

BACKGROUND: In stable coronary artery disease, the primary goal of percutaneous coronary intervention (PCI) is symptom relief. Fractional flow reserve (FFR) and nonhyperemic pressure ratios such as resting full-cycle ratio (RFR) are used to guide revascularization. Although these indices correlate with myocardial ischemia, they have never been validated against the onset of angina. The physiological thresholds for angina, FFR angina and RFR angina , at rest and during exercise remain undefined. METHODS: ORBITA-FIRE (Finding the Invasive Threshold for Symptom Relief in Exertional Angina) was a multicenter, double-blind, randomized, placebo-controlled study in patients with stable angina and single-vessel coronary artery disease. After imaging-guided PCI, an in-stent balloon was incrementally inflated until angina occurred at rest. This angina threshold was verified against placebo inflation, and corresponding FFR angina and RFR angina values were recorded at symptom onset. The protocol was repeated during low- and high-intensity exercise to assess changes in angina thresholds with increasing cardiac workload. RESULTS: Sixty-five patients were enrolled (mean age, 63.9±8.7 years; 74% male; 69% hypertensive; 23% diabetic; 91% with Canadian Cardiovascular Society class II–III angina). Median pre-PCI FFR was 0.59 (interquartile range [IQR], 0.46–0.70) and RFR was 0.61 (IQR, 0.40–0.82). Median FFR angina at rest was 0.29 (IQR, 0.23–0.35), increasing to 0.38 (IQR, 0.30–0.48) during low-intensity exercise and 0.45 (IQR, 0.36–0.55) during high-intensity exercise. RFR angina similarly increased from 0.22 (IQR, 0.16–0.30) at rest to 0.26 (IQR, 0.18–0.36) and 0.32 (IQR, 0.23–0.46) during low- and high-intensity exercise. All thresholds were significantly lower than clinical diagnostic cut points ( P <0.001). Lower FFR angina and RFR angina thresholds were associated with greater symptom reproducibility across rest, low- and high-intensity exercise conditions (FFR angina : P =0.008, P <0.001, P <0.001, respectively; RFR angina : P =0.015, P <0.001, P =0.002, respectively). Lower angina thresholds across all conditions predicted higher baseline angina burden and greater symptom relief with PCI (probability of interaction >0.999). CONCLUSIONS: Physiological thresholds for angina, FFR angina and RFR angina , are highly individualized, vary with cardiac workload, and are consistently lower than the universal ischemia-based thresholds used to guide revascularization. These findings support integrating personalized, symptom-linked physiology to refine patient selection and to improve symptomatic response to PCI.

Isolation and evaluation of candidate plant-protecting bacteria from rice seedlings asymptomatic to Burkholderia glumae infection

From bedside to bench: A multimodal approach uncovering the molecular basis of the <i>MYBPC1</i> -linked Myotrem myopathy

Myotrem is an untreatable, early-onset, congenital myopathy characterized by hypotonia, muscle weakness, skeletal deformities, dysmorphia, respiratory insufficiency, and myogenic tremor (V. Shashi et al., Hum Mutat , 2019 and J. Stavusis et al., Ann. Neurol. , 2019). It is associated with dominant variants in the pivotal M-domain of slow-skeletal Myosin Binding Protein-C (sMyBP-C) that modulates the dynamic binding to myosin and actin filaments and thereby crossbridge formation and kinetics. Herein, we report a nonmissense Myotrem variant, c.795_803dup p.(Leu266_Arg268dup), referred to as LKR-duplication. Our comprehensive studies, integrating clinical findings with biophysical, structural, and computational approaches, uncover the previously unreported structure and properties of the slow-skeletal M-domain, while elucidating the impact of the LKR-duplication. We show that the LKR-duplication stabilizes local helicity but alters global domain dynamics, leading to increased myosin binding, while impairing myosin-ATPase activity and crossbridge cycling. Critically, we pinpoint the specific amino acid residues facilitating the M-domain/myosin interaction and demonstrate that the LKR-duplicated residues not only directly contribute to myosin binding but also enhance the myosin interacting capability of neighboring and distant residues. Our multimodal approach sheds light on aspects of the pathobiology of the slow-skeletal M-domain—the Myotrem hotspot—by unveiling underlying pathogenic etiologies thereby paving the way for the development of targeted treatments.

Response by Moura-Ferreira et al Regarding Article, “Prognostic Value of Exercise Right Ventricular–Pulmonary Arterial Coupling in Primary Mitral Regurgitation”

Integrated surveillance for lymphatic filariasis and other infectious diseases with a nationwide non-communicable disease STEPwise survey in the small Pacific Island Nation of Niue, 2025

Canadian wildfires are losing their climate-cooling influence from postfire snow albedo

The 2023 Canadian fire season was record-breaking in terms of burned area and carbon emissions. Here, we present estimates of the regional climate-cooling effect from postfire surface albedo changes, which have historically partially offset the warming influence of fire emissions by wildfires. We estimate that the 2023 fires generated a time-integrated climate cooling of –3.41 W m −2 of burned area (95% CI: −4.39 to −2.43) over a 70-y period. We show that the climate-cooling impact has weakened on average by 29% since the 1960s due to changes in snow cover and duration. Collectively, this result implies that modern-day boreal fires are on average twice as likely to result in a net climate-warming influence.

Numerical evidence of contrasting hydrodynamic responses of concave and convex breakwaters

Control of lipid metabolism in chondrocytes is critical for skeletal growth

Chondrodysplasia is a genetic disorder characterized by impaired cartilage development and bone growth. Dysregulation of the endoplasmic reticulum (ER) stress is associated with chondrodysplasia. Here, we demonstrate a critical role for the ER stress regulator PPP1R15B in chondrocyte development. PPP1R15B is a protein phosphatase that constitutively represses eIF2α phosphorylation to attenuate global protein translation in response to stress. Remarkably, deletion of Ppp1r15b in Prx1 + skeletal progenitors ( Ppp1r15b Prx1 ) impairs chondrogenesis, resulting in a disorganized growth plate, reduced trabecular bone, and shortened long bones in mice. Similarly, inducible deletion of Ppp1r15b in Col2 + chondroprogenitors ( Ppp1r15b Col2 ) leads to abnormal cartilage development and bone growth. Remarkably, no skeletal phenotype is observed in mice lacking Ppp1r15b in committed Osx + osteoprogenitors ( Ppp1r15b Osx ) and Dmp1 + mature osteoblasts and osteocytes ( Ppp1r15b Dmp1 ), indicating that its role is limited to regulation of chondrogenesis, not osteogenic differentiation. Mechanistically, PPP1R15B deletion increases eIF2α phosphorylation, which in turn enhances lipogenic gene expression by suppressing leptin expression. This effect was reversed in Ppp1r15b Prx1 mice by reconstitution with wild-type PPP1R15B, but not with a mutant form incapable of eIF2α dephosphorylation. Exogenous expression of leptin also reversed skeletal abnormalities in these mice. Collectively, these findings reveal a critical role for PPP1R15B in cartilage development through its regulation of lipid metabolism.

Salicylic acid and silicon cross talk influence physiological and biochemical attributes of sorghum under salinity stress

Bilingualism predicts executive function resilience after COVID-19 in aging

Bilingualism has been associated with enhanced executive functions (EFs), particularly attentional control, and may confer protection against cognitive decline in older age. At the same time, the COVID-19 pandemic has emerged as a factor negatively affecting EF in older adults. Bilingualism might offer resilience against these COVID-related cognitive declines, especially in late adulthood, by bolstering cognitive reserve. The present study collected data from 312 community-dwelling individuals spanning the adult lifespan (aged 18 to 80) to address two goals. Goal 1 was to identify a latent structure linking bilingualism and EF across the adult lifespan, using a continuous multivariate approach to help resolve controversies in the literature. Goal 2 was to determine whether bilingualism can protect against post-COVID EF decline in the most vulnerable older age group. We used partial least squares correlation (PLSC) analysis to extract latent relationships between multiple bilingual experience measures (and relevant covariates) and a battery of EF task outcomes. Results revealed that individuals with greater bilingual experience (earlier L2 age of acquisition and greater L2 proficiency) showed a multivariate association with executive function measures, with the most consistent behavioral expression observed in task-switching performance. Earlier L2 AoA was most robustly associated with better nonverbal task-switching performance among older adults reporting a history of COVID, even when modeling COVID burden continuously (i.e., number of infections and recency of last infection). These findings demonstrate that bilingual experience contributes to resilience in attentional control under flexible task-switching demands in older adults even in the context of COVID-19.

Immunological effects of subcutaneous and sublingual immunotherapy in house dust mite-allergic adults: a nine-month prospective pilot study

Abstract House dust mite (HDM) allergy contributes to allergic rhinitis and asthma worldwide. Allergen-specific immunotherapy (AIT) is the only disease-modifying treatment, with immunoglobulin G4 (IgG4) and regulatory T cells (Tregs) mediating immune tolerance. Comparative immunological effects of subcutaneous (SCIT) versus sublingual (SLIT) therapy remain underexplored. To evaluate immunological changes induced by SCIT and SLIT and their association with clinical improvement in HDM-allergic patients. In this prospective cohort, 43 adults with HDM-sensitized allergic patients received SCIT (n = 22) or SLIT (n = 21) for nine months. Clinical outcomes were assessed using the Asthma Control Test (ACT) and Rhinitis Control Assessment Test (RCAT). Serum IgG4 and total IgE were measured by ELISA and electrochemiluminescence, respectively, and CD4⁺CD25⁺FoxP3⁺ Tregs were analyzed by flow cytometry. Responders were defined as patients achieving ≥ 20% improvement in ACT or RCAT. Wilcoxon signed-rank, Mann–Whitney U, and Spearman correlation tests were used. AIT increased IgG4 (320 → 920 ng/mL; p  &lt; 0.001) and Tregs (3.4% → 6.3%; p  &lt; 0.001), with a non-significant decrease in IgE. Responders had higher IgG4 and Tregs and lower IgE than non-responders. SCIT elicited higher IgG4 levels (median 1035 vs 705 ng/mL) and a trend toward greater Treg expansion compared with SLIT, although clinical improvement was similar between groups. IgG4 correlated with ACT ( p  &lt; 0.001) and RCAT (p = 0.002), and Tregs correlated positively with IgG4 (p = 0.003) and inversely with IgE (p = 0.010). Both SCIT and SLIT improve clinical outcomes in HDM-allergic patients via total IgG4 elevation and Treg expansion. SCIT may induce stronger systemic immunological responses, supporting the use of these biomarkers for early monitoring and personalized therapy. These findings should be interpreted within the context of a pilot study with a relatively small sample size.

Did Stora Karlsö wolves reach the island naturally or by boat?

Beyond structural MRI: combined diffusion metric improve delineation of epileptogenic tissue in focal cortical dysplasia

Abstract Accurate delineation of the epileptogenic zone in focal cortical dysplasia (FCD) remains challenging, as structural MRI often underestimates the extent of dysplastic tissue. Diffusion MRI can probe microstructural alterations, yet individual diffusion models provide limited sensitivity and clinical interpretability. We prospectively studied 19 patients with histologically confirmed FCD who underwent presurgical evaluation, surgical resection, and postsurgical MRI. Fourteen diffusion metrics derived from complementary diffusion models were integrated using logistic regression to generate a single combined diffusion metric (CDM). Spatial correspondence among structural MRI, resected tissue, perilesional cortex, and contralateral homologues was assessed using Dice similarity and ROC analyses. Histological cellularity and multimodal imaging data were used for biological validation. Individual diffusion metrics identified microstructural abnormalities within MRI-visible lesions, including reduced anisotropy, lower fibre density, and increased isotropic diffusion. Integration into the CDM improved discrimination between lesional and healthy tissue ( p  &lt; 0.03), detected abnormalities extending beyond radiological borders, and showed spatial concordance with FDG-PET hypometabolism and epileptiform activity in 90% of patients. CDM-guided delineation increased agreement with resected regions and reduced unresected perilesional volume. CDM provides a biologically grounded and clinically interpretable representation of epileptogenic tissue in FCD, refining presurgical mapping beyond conventional MRI and potentially improving surgical targeting.

miR-146a is a pleiotropic regulator of motor neuron degeneration

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting motor neurons. Here, we have profiled motor neuron microRNAs (miRNAs) during motor neuron degeneration in vivo to gain a better understanding of ALS pathophysiology. We demonstrate that one miRNA, miR-146a, is downregulated in diseased motor neurons despite upregulation in bulk tissue. Genetic deletion of miR-146a significantly extended survival in SOD1 G93A mice with heterozygous animals demonstrating the largest benefit. A corresponding reduction in spinal cord gliosis but not motor neuron loss was observed. Finally, we observed that a proportion of miR-146a knockout animals develop spontaneous paralysis, motor neuron loss and chronic neuroinflammation with advanced age. Together these findings demonstrate that a single miRNA influences multiple aspects of motor neuron disease and highlights the complex role for neuroinflammation in ALS pathogenesis.

AdaptiveFrequencyNet: a long-term time series forecasting approach based on learnable frequency decomposition and cross-scale attention fusion

Resetting population mobility responses under repeated nonpharmaceutical interventions: Implications for hypothesized pandemic fatigue

Nonpharmaceutical interventions (NPIs) are essential for controlling infectious diseases during prevaccine periods, yet their success hinges on sustained population behavioral responses to restrictions. This study investigates how mobility responses to tiered restriction systems evolved over time during COVID-19 in six geographical regions across Europe, North America, Africa, and South America. Using daily mobility data and linear-mixed models, we characterized three temporal dimensions shaping these responses: cumulative exposure to restrictions, time spent under a given tier, and repeated reintroduction of the same tier. Time spent under a given tier caused the most rapid attenuation of mobility reduction, producing effects within days that cumulative exposure, required months of restrictions to achieve. Iterative application of shorter NPIs, interspersed with temporary relaxation, was associated with a restoration of mobility responses when restrictions were reintroduced, mitigating attenuation and sometimes even strengthening responses. These patterns are consistent with mechanisms discussed under the umbrella of pandemic fatigue, whereby temporary relaxation may provide psychological relief and a sense of regained autonomy that can renew public willingness to respond to restrictions when reintroduced, while remaining compatible with behavioral adjustment and structural constraints. However, they are also compatible with alternative explanations, including behavioral adaptation, structural constraints on mobility, or evolving interpretations of restrictions. These findings emphasize the dual benefits of short, strategic NPIs for epidemic control and public resilience, offering actionable insights for designing more sustainable pandemic interventions.