Browse Articles

Micronucleus quantification from whole-slide haematology images using AI serves as a translatable pharmacodynamic biomarker for DNA damage response inhibitors

Abstract Micronuclei are widely recognised biomarkers of genomic instability and DNA damage, making their accurate quantification essential for understanding the pharmacodynamic properties of chemotherapeutic agents and inhibitors of the DNA damage response (DDR). Here, we report the development and validation of a novel assay for the automated detection and quantification of micronuclei within circulating red blood cells (RBC) from peripheral blood smears. We integrate recent advances in whole-slide imaging (WSI) technologies and supervised deep-learning algorithms to quantify micronuclei in over 100,000 RBCs from a single image. We demonstrate that this approach achieves strong analytical concordance with flow cytometry (Pearson’s r = 0.926, P < 0.0001) while offering distinct advantages. Additionally, using May-Grünwald Giemsa dyes we show that deep-learning algorithms can stratify red blood cells into both mature erythrocytes and immature reticulocytes from WSIs. Critically, we establish that micronuclei-positive red blood cell (MN + -RBC) frequency correlates with anti-tumor efficacy in BRCA1 -deficient xenograft models following exposure to PARP inhibitors and demonstrates dose-dependent pharmacodynamic (PD) responses. Furthermore, we show that whole-slide imaging offers several advantages over widely used flow cytometry approaches, including the identification of cells with multiple micronuclei and the ability to quantify morphological features associated with detrimental pre-analytical conditions. These findings position automated WSI-based micronucleus quantification as a scalable, minimally invasive PD biomarker requiring only 5 μl of blood that enables longitudinal monitoring of DDR inhibitor therapies.

Green synthesis and characterization of Annona squamosa seed chemical constituents derived silver nanoparticles against Tuta absoluta (Meyrick, 1917) larvae, non-target effect, and confirmed through molecular docking

Two-stage-method-based calculation and analysis of the deformation of the existing subway tunnel caused by the diagonal crossing of the new tunnel

Abstract This study presents a theoretical analysis of the deformation induced in an existing curved subway tunnel by a new shield tunnel crossing diagonally beneath it. A refined two-stage method is developed to address this engineering problem. In the first stage, the additional stress on the existing tunnel is calculated using Mindlin’s solution. In the second stage, the existing tunnel is modeled as an Euler–Bernoulli beam on a Pasternak foundation, explicitly incorporating the effects of tunnel curvature and a stress reduction factor for the grout-reinforced zone. The proposed method is validated against monitoring data from a case study of the Zhengzhou Metro, showing good agreement. A systematic parametric analysis investigates the influence of key factors: the clearance and intersection angle between tunnels, the curvature radius of the existing tunnel, the length of the grouted section, and Poisson’s ratio of the grouted soil. Results demonstrate that the crossing angle and grouting length are the most significant parameters affecting deformation, whereas the existing tunnel’s curvature and the grout’s Poisson’s ratio have a negligible impact.

Racialized vulnerability and socioeconomic determinants of health among Afghan refugees in Pakistan

Development and characterization of an inducible Tensin1 deficient transgenic murine model

Abstract Tensin1 (TNS1) is a key component of focal and fibrillar adhesions, mediating fibrillogenesis, as well as the transduction of mechanical cues and adhesive signaling. To enable further TNS1 characterization, we have developed a novel transgenic mouse that allows for temporally controlled and lineage specific knockout of TNS1. We found no differentially observed effects of TNS1 knockout on mouse health, breeding capacity, or vital organ histopathology. In contrast, RNA sequencing analysis identified 171 differentially expressed genes with Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrating differential expression in osteoclast differentiation and a number of pathways involved in host immune response. Furthermore, STRING pathway analysis showed differential regulation of genes involved in B-cell and myeloid-related signaling pathways, a number of which were validated by reverse transcription-quantitative polymerase chain reaction (RT qPCR). Loss of TNS1 in THP-1 monocyte/macrophage cell line resulted in impaired migration and phagocytosis. We also observed a trend toward increased detection of lymphocytes in the bronchoalveolar lavage within days following TNS1 knockout. This study provides a novel understanding of the phenotypic and genotypic changes that occur following knockout of TNS1 that may lead to subsequent understanding of its role in disease.

Cascaded regulatory network composed of small RNAs involves in the symbiosis of Panax notoginseng and fungus Acremonium sp. D212

Transportation-oriented isolated type energy interaction converter for vehicle-to-vehicle

Integrative ensemble learning framework for forecasting controlled drug release based on Raman spectral signatures

Abstract Modeling drug-release kinetics from polysaccharide-coated oral controlled-release formulations remains challenging due to nonlinear diffusion–dissolution behavior, complex polymer–drug interactions, and the limited interpretability of conventional machine-learning approaches. In this study, we develop and validate a predictive framework for targeted colonic delivery of 5-aminosalicylic acid (5-ASA) from polysaccharide-coated solid oral dosage forms using Raman spectroscopy–derived molecular fingerprints and time-resolved dissolution data. The dataset comprises 155 formulation samples, each characterized by more than 1,500 Raman spectral features, categorical formulation variables (polysaccharide type and release medium), and drug-release measurements at 2, 8, and 24 h collected under simulated physiological conditions. A dual-optimizer, dual-ensemble learning strategy is introduced, integrating the Puma Optimizer Algorithm (POA) and Black-Winged Kite Algorithm (BWKA) within a Damsphere Weighted Ensemble (DWE) of XGBoost regression and AdaBoost models. The complementary exploration–exploitation dynamics of the two optimizers enhance convergence stability and generalization, yielding strong predictive performance under five-fold cross-validation (RMSE = 0.038; R 2 = 0.991). Feature-level analysis based on F-statistics highlights release time, dissolution medium, and chemically meaningful Raman bands as dominant predictors, consistent with diffusion- and erosion-controlled release mechanisms in polysaccharide-coated systems. From a pharmaceutical perspective, the proposed framework reduces experimental burden while maintaining mechanistic interpretability, supporting Quality by Design (QbD) and green pharmaceutics principles. Owing to its modular architecture, the approach is readily extensible to other polymer-based oral controlled-release formulations and spectroscopic modalities.

SARS-CoV-2 nucleocapsid protein-specific monoclonal antibodies as tools for studying its antigenic structure and interaction with host cells

Abstract Diagnostics and prevention of COVID-19 are essential for controlling the spread of the virus and reducing mortality rates. As SARS-CoV-2 surface proteins are susceptible to mutations, the nucleocapsid protein (NP) with its highly conserved gene sequence is an attractive target for studying virus-host interactions. NP plays a key role in the coronavirus life cycle, modulating viral RNA packaging, transcription, and assembly. In addition, its abundant expression during infection makes it a valuable diagnostic marker. NP is involved in modulating the host’s innate immunity; however, the cellular mechanisms of its pathogenicity are not yet fully understood. This study developed and characterized murine monoclonal antibodies (MAbs) specific to the SARS-CoV-2 NP to investigate its antigenic regions and utilize the MAbs in virus-detecting systems or cellular NP blocking assays. The MAbs showed cross-reactivity with Omicron NP, recognizing epitopes within functionally active domains. They also identified NP in SARS-CoV-2-infected cells, supporting their feasibility in future immunoassays. Additionally, the ability to inhibit NP-cell interaction was assessed, with MAbs 4B3, 7F10, 16D9, and 18A8 found to reduce NP internalization. Overall, this study provides well-characterized tools for investigating SARS-CoV-2 antigenicity and pathogenicity and demonstrates the functional potential of the generated MAbs in studying NP-mediated host cell interactions.

Investigating distributed generator high penetration in improving technical, emission and economic constraints of distribution network

Assessment of lipid mediators in the urine of patients with Lyme disease, tick-borne encephalitis and human granulocytic anaplasmosis

Religiosity spirituality and nonreligious spiritual practices linked to anxiety and depressive symptoms

Topographic modulation of soil functional indicators in shaded coffee agroforestry systems: a multivariate and network-based approach

Immunophenotypic skewing of B cells toward IgD⁻CD27⁻IgG⁺ subtype and metabolic attenuation in colorectal cancer

Abstract Colorectal cancer (CRC) is the third most prevalent cancer and understanding its tumor microenvironment (TME) is crucial for the development of innovative therapies. Despite the presence of B cells in CRC infiltrate, their clinical significance is poorly understood. In this study, we observed an enrichment of double-negative (DN) B cells, a subset lacking surface IgD and CD27, in CRC biopsies. Typically underrepresented in physiological conditions, DN B cells expand in certain chronic infections, autoimmune diseases, and cancers. Within this subpopulation, low CD21 expression—a phenotypic hallmark of exhaustion—was observed. Consistently, DN B cells displayed low metabolic activity. Accordingly, total B cells infiltrating CRC tissues showed a diminished capacity to differentiate into antibody-secreting cells (ASCs) upon stimulation. In the murine setting, CRC organoids decreased the frequency of ASCs in co-cultured B cells and induced metabolic dysfunction, marked by altered glucose and fatty acid uptake and dysregulated expression of key metabolic proteins. Moreover, B cells displayed reduced glycolysis and mitochondrial respiration, despite increased mitochondrial dependence. This study provides evidence for DN B cell accumulation within CRC infiltrate and metabolic reprogramming of B cells, suggesting that targeting B cell metabolism may represent a promising strategy to potentiate anti-tumor immune responses.

Exploring the optimal follow-up time for resectable colorectal cancer patients: a multicenter, five-year longitudinal cohort study

Functional connectivity in infants’ visual cortex and its links to motion processing and autism

Abstract In a previously published study, we found atypical visual cortical laterality patterns during global motion perception in 5-month-old infants who showed high levels of autistic symptoms in toddlerhood. Here, using data from a separate experiment within the same recording session, we examined whether these results could reflect altered visual cortical functional connectivity in theta, alpha, and gamma rhythms. We assessed this in a sample of 5-month- old infants ( n  = 59; 39 elevated familial likelihood of autism) by means of electroencephalography (EEG) when they were watching videos showing social and non-social scenes. Gamma connectivity between midline and far-lateral visual cortex when viewing social scenes was linked to both later autism symptoms and global motion visual cortical laterality we reported in the previous study. This may indicate a shared integrative mechanism underlying social perception and global motion processing. Further, we found that higher midline-to-lateral theta connectivity in the visual cortex when perceiving non-social scenes in infancy was strongly associated with having more autistic symptoms at follow up, but uncorrelated with concurrent motion perception. Our study points to atypical functional connectivity in the visual cortex as a potential early marker of autistic symptoms and highlights a probable link between motion processing and social perception.

Low power reprogrammable DNA basecaller with an efficient HMM accelerator for real time nanopore sequencing

Analyzing sustainable cotton production in Türkiye through the water energy carbon nexus framework

Human values and physical activity before and during COVID-19 restrictions in Hungary

Abstract Physical inactivity is a major public health challenge in Hungary. Drawing on Schwartz’s Theory of Basic Human Values, we exploit a natural experiment created by temporary population-wide restrictions to examine how value orientations relate to physical activity across contrasting contexts. In a nationally representative survey of 1,031 adults, respondents reported frequency of structured exercise training (SET) and light daily physical activity (LDPA) for the period before the restrictions and during them. Generalized ordered logistic models linked activity categories to self-transcendence, conservation, openness to change, and self-enhancement, controlling for sociodemographic and health factors. Self-transcendence predicted higher participation in both SET and LDPA under usual conditions; during restrictions, its association with SET attenuated, whereas the link with LDPA remained robust. Conservation values consistently predicted lower SET, with avoidance intensifying under constraints; associations with LDPA were weaker. Openness to change and self-enhancement showed no independent effects after adjustment. Age, gender, education, self-rated health, BMI, smoking and alcohol use were associated with activity. Findings indicate that values shape activity differently depending on context: self-transcendence is associated with greater persistence in daily activity, whereas conservation corresponds to declines in structured exercise. Aligning interventions with motivational profiles may improve adherence when opportunities to be active are disrupted.

Synthesis of the porous Co–N-doped carbon catalysts as a durable cathode for zinc–air battery

Abstract Due to the exceptional ORR catalytic activity and stability, cobalt and nitrogen-doped carbon (Co–N–C) catalysts are regarded as highly promising candidates for cathode catalysts in zinc–air batteries. However, it remains a challenge to expose more stable and more efficient active sites. Therefore, this work focuses on the design and preparation of Co–N–C catalysts with a robust and porous structure. The results revealed that the robust and porous structure could be easily achieved by the template (SiO 2 )-assisted hydrothermal method. Moreover, the Co-900-50 catalyst has the highest half-wave potential, and the Co-900-100 catalyst has the highest limiting current density. Both individuals are chosen for further examination regarding their potential use in zinc–air batteries. The battery with Co-900-100 catalyst demonstrated exceptional stability across the current densities (5–20 mA cm − 2 ). Specifically, the voltage rose by 0.04 V following a 100 h discharge at a rate of 5 mA cm − 2 , while the discharge voltage remained nearly constant at 1.24 V throughout 300 charge/discharge cycles at 5 mA cm − 2 .