Browse Articles
Discover research articles across all indexed journals
Author Correction: A mechanical ratchet drives unilateral cytokinesis
AhR inhibition promotes axon regeneration via a stress–growth switch
AI driven Hybrid CNN transformer model for early detection and severity assessment of diabetic retinopathy
Abstract As the major cause of sight impairment in working age adults is diabetic retinopathy (DR) which requires timely and proper diagnosis to avoid the irreversible vision loss. Traditional retinal fundus image based manual diagnosis is time consuming, subjective, and requires highly skilled ophthalmologists, and therefore is not scalable in resource constrained environments. Automated DR grading systems are essential to overcome this issue especially in underserved areas. Although Convolutional Neural Networks (CNNs) are suitable in capturing the fine grained local features namely Microaneurysms and exudates, they are incapable of considering the global retinal context, which is required to accurately grade the severity. Transformer models, on the other hand, are more effective in capturing long range dependencies, at the cost of low spatial resolution. To address these shortcomings, this research suggests Fusion Net a hybrid DL model that combines a CNN branch that extracts local features in the form of GoogLeNet with a Vision Transformer (ViT) branch that captures global context. This is a dual stream architecture that combines complementary embeddings to categorize DR into five ordinal levels of severity. The model has been trained on a mixed dataset of APTOS 2019 and Messidor-2 and tested on three datasets that are not used during training. Fusion Net had overall accuracy percent of 98.85, AUC-ROC of 0.981 and weighted F1-score percent of 97.62. It was also highly sensitive in detecting early stage DR and balanced in all the severity levels. The thorough ablation experiments, ordinal assessment scales, and feature map confirms the strength and clarity of the suggested framework. The findings indicate that Fusion Net is an effective, explainable, and computationally efficient system to use in grading automated DR with a high chance of implementation into clinical practice and tele-ophthalmology systems.
Biaxial strength under fatigue of 4YSZ: Surface treatment and resin cement viscosity effects
This study aimed to investigate the effect of different surface treatments combined with high- or low-viscosity resin cements on the biaxial flexural strength of 4YSZ ceramics. Discs of 4YSZ (IPS e.max ZirCAD MT, Ivoclar AG; 15 mm diameter, 1.2 mm thickness) were prepared, subjected to CAD/CAM milling simulation using #220 silicon carbide papers, and divided into 10 groups according to two factors: “Surface Treatment” – Control (CTRL, no treatment); air abrasion with 45 µm (AB45) or 110 µm (AB110) alumina oxide particles; and glaze either followed (GLZ + HF) or not (GLZ) by 10% hydrofluoric acid; and “Resin Cement Viscosity” – High (H) or Low (L). The discs were treated, luted with resin cement, and subjected to two monotonic tests (n = 2) to determine fatigue parameters, followed by biaxial fatigue testing (n = 15; piston-on-three-balls; 20 Hz; 10,000 cycles; initial stress: 75 MPa; increments of 25 MPa). Topography, fractography, and surface roughness analyses were also performed. Surface treatment significantly influenced fatigue performance (p < 0.05, F = 60.25), whereas resin cement viscosity and its interaction with surface treatment did not show significant effects (p > 0.05, F = 0.86; p > 0.05, F = 0.07). The GLZ groups exhibited the highest flexural strength (H/L-GLZ: 382–396 MPa), followed by intermediate values in CTRL (H/L-CTRL: 285–288 MPa), AB45 (H/L-AB45: 310–315 MPa), and GLZ + HF (H/L: 273–280 MPa), while AB110 groups presented the lowest strength (H/L: 205–210 MPa). Surface roughness was lower for GLZ (Ra: 1.44 µm) and GLZ + HF (Ra: 1.38 µm) compared to AB45 (Ra: 1.83 µm) and AB110 (Ra: 1.69 µm). GLZ produced smooth and homogeneous surfaces, GLZ + HF led to areas partially exposed by acid, and AB110 caused more pronounced surface defects than AB45. Hence, the GLZ treatment offered superior fatigue performance; AB45 and GLZ + HF showed behavior similar to CTRL, whereas AB110 impaired mechanical performance. Resin cement viscosity had no significant influence on fatigue strength
Clusterin maintains hemostatic equilibrium by stabilizing VWF multimers in plasma
Abstract The coagulation-anticoagulation balance is tightly regulated by endothelial-derived factors, which have not been clearly defined. Here, we report that clusterin, a component of Weibel-Palade bodies (WPBs), plays a crucial role in maintaining hemostatic equilibrium by stabilizing von Willebrand factor (VWF) multimers in plasma. Clusterin was identified by proteomic analysis as a component of the endothelial secretome under both chemical and physical conditions and demonstrated as a WPB component via immunostaining and cotransfection assays. Notably, a significant reduction of clusterin protein level was observed in plasma from patients with type 2A von Willebrand disease. Furthermore, loss of clusterin in mice led to hemorrhagic diathesis and impaired thrombosis, accompanied by reduced high molecular weight (HMW) VWF levels. These defects were rescued by exogenous clusterin administration, underscoring its therapeutic potential. Mechanistically, clusterin binds to the D4N domain of VWF, which competitively inhibits ADAMTS13-mediated proteolysis under shear stress, and thereby preserves HMW VWF multimers essential for hemostasis. This study redefines WPBs as hubs for regulatory proteins and establishes clusterin as a key modulator of VWF multimer quality, offering a paradigm shift in targeting coagulation dysfunction through multimer stabilization rather than protein replacement. Our findings bridge a critical gap in understanding endothelial-driven coagulation homeostasis and suggest a potential therapeutic strategy targeting VWF multimer quality for bleeding disorder diseases.
Improving airport security with IoT-powered deep learning methods for threat detection and intelligent recommendation systems
Abstract This study introduces a novel framework that integrates deep learning algorithms, intelligent recommendation systems, and Internet-of-things (IoT) devices to improve airport security. Surveillance cameras are used by the system to identify potentially dangerous activities, such leaving luggage unattended. By analyzing interactions and movement patterns, anomalies can be found, and security staff can receive notifications. To improve security measures based on historical data and current information, it makes use of recommendation systems. This integrated approach reduces false alerts, improves operating efficiency, and strengthens security safeguards. Case studies and simulations confirm the framework’s effectiveness. Interestingly, transfer learning using MVCNN architecture detected threats in test data that had never been seen before with an accuracy of above 95%. Additionally, the suggested ISODI approach outperformed Decision Tree and K-Nearest Neighbors in identifying anomalies associated with aircraft delays, with an accuracy of 0.99. These results show how the framework can raise airport security requirements. Notwithstanding the beneficial developments of this paradigm, more investigation is necessary to identify the best use case for it in the security systems in place today and to handle any privacy issues that may arise. To handle the complexities of various airport environments, practical systems would require extensive testing and adaptability.
UAV-based RGB and multispectral mango leaf disease detection with benchmarking of YOLOv5 to YOLOv10 and SeqOpt-optimised YOLOv8 for real-time edge deployment
The article presents a real-time mango leaf disease detection framework with embedded edge deployment, using UAV-based multispectral imaging combined with optimised deep learning models. A custom dataset of 6,334 high-resolution RGB and multispectral images representing four common diseases was collected under natural orchard conditions using MAPIR RGB and multispectral OCN cameras mounted on a UAV. A controlled benchmarking of YOLOv5-YOLOv10 architectures was performed under identical training configurations. Although YOLOv10 achieved the highest detection accuracy, YOLOv8 offered a more favourable balance between detection performance and deployment efficiency on edge devices. To further enhance robustness and deployment suitability, the proposed SeqOpt method was applied to YOLOv8, improving the F1-score by 9.7%, mAP@50 by 8.6%, and mAP@50–95 by 21.7% compared to YOLOv10 trained under identical conditions on the multispectral validation data. In addition, on the Raspberry Pi 5 using ONNX inference, latency and energy consumption were reduced by up to 25% compared to the SGD-only YOLOv8 baseline. On the NVIDIA Jetson Orin Nano, the PyTorch model achieved 72 ms per-image inference latency, demonstrating near real-time capability. Overall, the proposed pipeline outperforms single-optimiser YOLOv8 (SGD-only and AdamW-only) and YOLOv10 baselines in detection accuracy and deployment efficiency, making it suitable for practical precision agriculture applications.
High-dimensional spatiotemporal single-cell atlas and 3D imaging of the bone marrow microenvironment during CML progression
Abstract The bone marrow microenvironment (BMME) is essential for hematopoiesis and immunity, yet spatiotemporal single-cell analysis during leukemogenesis remains challenging. We characterized the BMME in femurs from wild-type and chronic myeloid leukemia (CML) mice at 7, 14, and 21 days after induction by highly multiplexed and 3-dimensional (3D) microscopy. Using a 54-marker codetection by indexing panel, we profiled 2 033 725 cells in 55 regions of interest and identified 41 cell types. During CML progression, we observed myeloid and progenitor cell expansion, increased programmed death ligand 1–positive leukemic cells, programmed death 1 (PD-1) upregulation on CD4+ and CD8+ T cells, and a profound loss of B cells, plasma cells, and bone cells. Advanced CML exhibited a striking expansion of immature, pericyte-deficient vasculature that disrupted vascular niches and impaired hematopoietic stem/progenitor cell positioning. Spatial mapping revealed leukemia-specific cellular neighborhoods enriched in PD-1+CD8+ T cells, suggesting localized immune exhaustion. Early CML showed increased contacts between plasmacytoid dendritic cells and megakaryocytes (MKs), whereas advanced CML featured heightened MK emperipolesis of nonleukemic granulocytes. MKs were morphologically irregular in CML mice and patient bone marrow biopsies. In contrast, in mice with acute myeloid leukemia, vasculature and MKs were reduced, whereas the remaining MKs retained normal morphology. Laser-capture microdissected MKs from patients with newly diagnosed CML had reduced cytoskeleton gene expression, which was reversed in advanced cases treated with tyrosine kinase inhibitors. 3D imaging revealed vascular disorganization and depleted MKs in the diaphysis, underscoring region-specific pathology. Together, this study provides a spatiotemporal single-cell atlas of the BMME during leukemic progression, showing how leukemic cells reprogram it to support their expansion and immune evasion.
Nitzschia excavata sp. nov. (Bacillariaceae), a new diatom species from a post-mining reservoir revealed by morphology, molecular phylogeny, and metabarcoding-based biogeography
COVID-19 pandemic-related stress and substance use behaviors among people with HIV – a mixed method analysis
Background Stress and financial concerns due to the COVID-19 pandemic are well documented, with mixed evidence regarding their relationship with substance use. This mixed-methods study describes the prevalence of pandemic-related stress and financial worry, and their association with changes in substance use among people with HIV with a history of injection drug use in Russia. Methods We conducted a secondary analysis of survey and qualitative data collected from two trials between May 2020 and July 2021. We used multivariable logistic regression to assess associations between pandemic-related stress and financial worry, and reported changes in illicit opioids (primary), cigarettes (secondary), and alcohol (exploratory) use. The outcome was defined as any change (increase, decrease, or stopping) in substance use. A thematic analysis of semi-structured interviews explored experiences of stress and substance use during the pandemic. Results and conclusions Among 132 survey participants, 52% reported high pandemic financial worry and 31% reported high pandemic stress. Overall, 22% reported changes in opioid use (20% decrease, 2% increase), 21% in cigarette smoking (18% decrease, 3% increase), and 15% in alcohol use (9% decrease, 6% increase). High stress was associated with reporting any change in opioid use due to the pandemic (AOR 2.98; 95%CI: 1.20, 7.40; p = 0.02). Financial worry showed a similar but imprecise association (AOR 2.45; 95%CI: 0.96, 6.21; p = 0.06). No associations were observed for cigarette or alcohol use. Qualitative findings indicated that pandemic-related stressors and disruptions in drug access may have been linked to substance use patterns for some participants, although changes in use were not a dominant theme. Most participants did not report changes in substance use; among those who did, changes were primarily decreases. Pandemic-related stress was associated with opioid use change, though direction varied. These findings suggest that stress-related responses are context-specific and may not uniformly lead to increased substance use among PWH.
Structural basis of HPA-1a alloimmunization in FNAIT and allosteric regulation of integrin conformation
Abstract Fetal and neonatal alloimmune thrombocytopenia (FNAIT) can be caused by maternal immunoglobulin G alloantibodies against the human platelet antigen 1a (HPA-1a), a Leu33Pro polymorphism at the plexin-semaphorin-integrin (PSI) domain of the β3 subunit shared by integrins αIIbβ3 and αVβ3. Although serologic detection of anti–HPA-1a alloantibodies has long aided FNAIT diagnosis, the disease remains a major clinical challenge due to unpredictable severe outcomes, particularly intracranial hemorrhage and fetal loss. To define the molecular basis of HPA-1a immunogenicity and antibody pathogenicity, we determined crystal structures of the HPA-1a antigen bound to Fabs from 4 anti–HPA-1a monoclonal antibodies, including 3 clinically relevant maternal alloantibodies (26.4, D-204, and M-204) and 1 murine antibody (SZ21). The structures reveal that all antibodies recognize an HPA-1a epitope centered on Leu33, spanning both PSI and integrin-epidermal growth factor (I-EGF) 1 domains of β3 integrin. Variations in antibody-binding interfaces account for differential affinities to both αIIbβ3 and αVβ3, whereas distinct binding orientations determine whether antibody engagement stabilizes the bent inactive β3 conformation. Functional assays demonstrated antibody-dependent inhibition of αIIbβ3-mediated platelet aggregation, thrombus formation, and clot retraction, as well as αVβ3-mediated endothelial adhesion and spreading. These results establish the structural framework of HPA-1a alloantigenicity, explain the conformational selectivity of anti–HPA-1a antibodies, and elucidate how they block integrin activation. The findings provide mechanistic insight into FNAIT pathogenesis and suggest that antibody heterogeneity in affinity and function may contribute to clinical variability. Furthermore, these findings demonstrate antibody-mediated stabilization of the PSI/I-EGF1 domain as a potential strategy for allosteric modulation of integrin structure and function.
An eye tracking examination of fantasy television’s immediate influence on children’s executive functions
In vitro dissolution and release kinetics of multisource ciprofloxacin 500 mg tablets in West Gondar, Ethiopia: Implications for interchangeability and regulatory oversight
Background In vitro dissolution is a critical quality control test in pharmaceutical development, used to measure the rate and extent at which an active pharmaceutical ingredient (API) is released from solid dosage forms, such as tablets, into solution under standardized conditions. It serves as a predictive tool for in vivo drug behavior, providing insights into drug release mechanisms and ensuring the development of robust, effective, and consistent products. Despite its importance, data on dissolution performance remain limited for certain drugs. As a rapid, reliable, and cost-effective method to estimate drug absorption, this study focused on evaluating the dissolution profiles of different brands of ciprofloxacin 500 mg tablets and applying kinetic modeling to support regulatory decision-making. Methods Twenty samples of ciprofloxacin 500 mg tablets were collected from retail outlets in six selected sites of the West Gondar Zone including Humera, Mai Kadra, Metema, Gendawuha, Kokit, and Midregenet towns between January and July 2022. The samples were obtained from purposively selected outlets using prescription papers issued by the University of Gondar Comprehensive Hospital, following a mystery shopper approach in line with WHO (2015) strategies. All collected samples were transported to the Ethiopian Food and Drug Authority (EFDA) laboratory and conducted as per USP specification. The amount of ciprofloxacin released was quantified using UV-Vis spectrophotometry at 276 nm. While the onset of pharmacological action was not directly measured, the Mean Dissolution Time (MDT) values suggested differences in release rates, which may influence the onset of action in vivo were considered. Dissolution profiles were evaluated using both model-independent parameters (difference factor f₁, similarity factor f₂, dissolution efficiency, and mean dissolution time) and model-dependent kinetics. Results were presented in tables, figures, and narrative form. Results All of the included tablet brands complied with single-point dissolution study test, as their Active Pharmaceutical Ingredient release were greater than 80% within the specified 30 minutes time frame according to USP standards. Only 4 brands (21.05%) met the f1/f2 similarity criteria. However, fifteen brands (78.95%) were not interchangeable with the comparator, as the difference factors (f1) were greater than 15% and the similarity factor (f2) were less than 50%. The mean dissolution time values ranged between 1.02 and 7.16 minutes, and the results showed that four of the twenty brands (4/20) exhibited the fastest dissolution rate and onset of action. The evaluated brands followed the Korsmeyer-Peppas and Weibull curve approach (the highest coefficient of determination) for the release of drug substances from the dosage forms. Conclusion The study reveals that while all tested ciprofloxacin 500 mg tablet brands complied with USP single-point dissolution criteria, only 21.05% met the similarity factor (f₂) and difference factor (f₁) standards for interchangeability with the comparator product. Significant variability in dissolution profiles among brands raises concerns regarding bioequivalence and potential implications for therapeutic efficacy and antimicrobial resistance. These findings underline the necessity for enhanced regulatory oversight, including routine dissolution profiling and, where appropriate, in vivo bioequivalence studies to ensure the quality and interchangeability of multisource ciprofloxacin products in Ethiopia and similar settings.
Nonmyeloablative conditioning combined with the anti-CD117 antibody briquilimab in older adults with high-risk AML and MDS
Abstract Briquilimab is a monoclonal antibody inhibiting stem cell factor (SCF) binding to CD117 (c-Kit). Based on preclinical data demonstrating the antibody clears hematopoietic stem and progenitor cells (HSPC) and myeloid malignant cells, we conducted a phase 1 trial examining briquilimab plus nonmyeloablative fludarabine (Flu) and total body irradiation (TBI) as conditioning for older adults with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) undergoing matched donor allogeneic hematopoietic cell transplantation (HCT). Briquilimab was infused 10 to 14 days before transplant day (TD) 0; Flu 30 mg/m2 and TBI 2 to 3 Gy were administered on TD −4 to −2 and TD0, respectively. Graft-versus-host disease prophylaxis consisted of tacrolimus, sirolimus, and mycophenolate mofetil. Thirty-two patients enrolled (n = 13 AML in complete remission [CR]; n = 3 AML in relapse; n = 16 MDS). Median age was 70 years, and most had detectable measurable residual disease (MRD) at screening. There were no briquilimab infusion reactions, dose-limiting toxicities, or primary graft failure events; briquilimab clearance was predictable across patients. Among the AML in CR cohort, 1-year event-free survival (EFS) was 69.2%; 1-year overall survival (OS) was 75%. Among the MDS cohort, 1-year EFS was 53.8%; 1-year OS was 76.4%. One of 3 patients with AML in relapse experienced a transient response. Marrow samples obtained before and after briquilimab and before Flu/TBI demonstrated AML/MDS HSPC depletion (mean, 62.4% ± 22.7%) with resultant threefold increase in serum SCF. In summary, we demonstrate the feasibility, safety, and proof of concept of CD117 targeting with briquilimab as HCT conditioning for AML/MDS. The trial was registered at www.clinicaltrials.gov as NCT04429191.
An ultra-wideband Vivaldi antenna development for brain microwave imaging
Editorial Note: Re-use of laboratory utensils reduces CO2 equivalent footprint and running costs
CSNK1E as a key to unlocking drug persistence in DLBCL
CO2 leakage alters bacterial community structure and metabolic function of soybean rhizosphere in the Ordos Basin
Validating hip- and wrist-ActiGraph accelerometer cut-points for physical activity intensities in people living with coronary heart disease
People with coronary heart disease (CHD) are encouraged to meet the public health moderate-to-vigorous aerobic physical activity (MVPA) guidelines for secondary prevention of cardiovascular disease. However, no accelerometer aerobic intensity cut-points are currently available to classify MVPA in this population. This study aimed to establish absolute and relative aerobic physical activity intensity accelerometer cut-points in people with CHD and compare the new with existing cut-points in an international cohort. Eighty-six participants with CHD performed a resting-metabolic-rate (RMR) assessment, activities-of-daily-living (ADLs) and a peak treadmill test with mixed-chamber gas analysis while wearing two ActiGraph GT3X accelerometers (hip and wrist). The average RMR was 2.8 ml.kg -1 .min -1 , 20% less than the commonly used 1 Metabolic Equivalent of Task (3.5 ml.kg -1 .min -1 ). The study sample was randomly split into a training and independent validation set (2:1) allowing for cross validation. In the training set, there were significant positive correlations between accelerometer counts.min -1 (y-axis, vector-magnitude (VM)) and intensity (relative and absolute) across both accelerometer hip- and wrist-placements for all activities (p < 0.001). Using Generalized Estimating Equation modelling, there was a strong linear relationship between accelerometer counts and absolute intensity for hip-placement (R 2 = 0.62–0.71), and weaker relationships for hip relative intensity (R 2 = 0.40–0.47) and wrist-placement (R 2 = 0.09–0.25). In the validation set, Bland-Altman plots found that the mean differences between predicted and actual absolute and relative intensity measures were negligible for all accelerometer counts.min -1 (y-axis, VM) and placements (hip, wrist), although the dispersion of the differences (95% limits of agreement) were wide. Hip VM counts.min -1 cut-points were found to best identify absolute and relative MVPA. In the international comparison (n = 176), participants completed significantly more MVPA using the new cut-points (p < 0.001). Thus, accelerometer cut-points developed in healthy individuals appear to under-estimate physical activity intensity in this population and cut-points specific to people with CHD should be used. Australian New Zealand Clinical Trials Registry: ACTRN12623000605695.