Search Results (3,402)

Accurate identification of Alzheimer’s disease (AD)-related cellular characteristics from microscopy images is essential for understanding neurodegenerative mechanisms at the cellular level. While most computational approaches focus on macroscopic neuroimaging modalities, cell type classification from microscopy remains relatively underexplored. In this study, we propose a hybrid vision transformer–convolutional neural network (ViT–CNN) framework that integrates DeiT-Small and EfficientNet-B7 to classify three AD-related cell types—astrocytes, cortical neurons, and SH-SY5Y neuroblastoma cells—from phase-contrast microscopy images. We perform a comparative evaluation against conventional CNN architectures (DenseNet, ResNet, InceptionNet, and MobileNet) and prompt-based multimodal vision–language models (GPT-5, GPT-4o, and Gemini 2.5-Flash) using zero-shot, few-shot, and chain-of-thought prompting. Experiments conducted with stratified fivefold cross-validation show that the proposed hybrid model achieves a test accuracy of 61.03% and a macro F1 score of 61.85, outperforming standalone CNN baselines and prompt-only LLM approaches under data-limited conditions. These results suggest that combining convolutional inductive biases with transformer-based global context modeling can improve generalization for cellular microscopy classification. While constrained by dataset size and scope, this work serves as a proof of concept and highlights promising directions for future research in domain-specific pretraining, multimodal data integration, and explainable AI for AD-related cellular analysis. Full article

Cardiovascular disease (CVD) persists as the leading cause of global mortality, with adult mammalian hearts exhibiting limited regenerative capacity. Although cardiomyocytes (CMs) can re-enter the cell cycle and undergo DNA synthesis in response to injury, they fail to complete mitosis and cytokinesis, resulting in a functional blockade of productive proliferation following ischemic or aging-related injury. Reactive oxygen species (ROS) exhibit a context-dependent duality in cardiac regeneration: while maintaining redox homeostasis and supporting developmental signaling at physiological concentrations, pathological ROS accumulation exacerbates myocardial decline by inducing DNA damage response (DDR)-mediated cell cycle arrest at G2/M phase, along with structural and functional impairments. This review examines the mechanisms of ROS generation—from its cellular origins to its molecular drivers—in ischemic heart disease, and explores the modulation of regenerative signaling by oxidative stress. We further critically assess emerging therapeutic interventions targeting ROS-mediated myocardial regeneration. By delineating the functional roles of ROS in cardiac injury and repair, this review provides a mechanistic and translational framework for developing redox-based therapies aimed at promoting cardiomyocyte proliferation and myocardial regeneration after ischemic injury. Full article

Receptive endometrium (RE) is essential for mammalian embryo implantation. The establishment of RE is a complex and precise dynamic process regulated by various cytokines, including non-coding RNAs (miRNAs, lncRNAs, and circRNAs). We identified candidate miR-26b-3p and circRNA3890 from our previous endometrial non-coding RNA sequencing data. CircRNA3890 adsorbs miR-26b-3p and inhibits its activity. Mouse double minute 4 (MDM4) is a target gene of miR-26b-3p, and circRNA3890 up-regulates the expression level of MDM4 by inhibiting the activity of miR-26b-3p in dairy goat endometrial epithelial cells (gEECs) in vitro. circRNA3890/miR-26b-3p/MDM4 could promote the proliferation of gEECs through the p53 signaling pathway. MiR-26b-3p could regulate the expression levels of vascular endothelial growth factor A (VEGFA) and leukemia inhibitory factor (LIF) through MDM4 in gEECs, which contributes to the development of endometrial receptivity. Furthermore, the results showed that miR-26b-3p significantly promoted the development of RE and embryo implantation. These findings demonstrate that circRNA3890 targets and adsorbs miR-26b-3p to relieve MDM4 inhibition and promotes EEC proliferation through the p53 signaling pathway. They reveal the regulatory effect of miR-26b-3p on receptive endometrial development and embryo implantation in vitro and in vivo. Full article

Electroluminescence (EL) imaging is widely used for non-destructive inspection of photovoltaic (PV) cells; however, the low contrast of grayscale EL images limits the performance of automated defect detection methods. This manuscript proposes a defect-aware EL image classification framework that enhances defect visibility through local contrast enhancement and physically motivated RGB false-color mapping. Instead of simple channel replication, grayscale intensities are segmented into defect-related ranges and encoded to emphasize cracks, inactive regions, healthy silicon emission, and conductive pathways. The approach is evaluated on the public ELPV benchmark dataset proposing ResNet–50, EfficientNet–B0, and EfficientNet–B3 architectures at two input resolutions. The proposed representation consistently improves defect discrimination and achieves a maximum classification accuracy, outperforming previously reported CNN-based results on the same dataset. Notably, comparable accuracy is obtained at lower resolution, significantly reducing computational cost and inference time, which supports deployment with cheaper sensors and faster inspection pipelines. Class imbalance is addressed using focal loss, class weighting, and threshold calibration without artificial resampling, preserving realistic operating conditions. The results confirm that combining defect-aware RGB representation with resolution-efficient learning provides an accurate and computationally practical solution for EL-based PV defect detection. Full article

Tyrosine kinase inhibitors (TKIs) added to chemotherapy have improved outcomes of adult patients with Philadelphia-positive B-cell acute lymphoblastic leukemia (Ph+ B-ALL). These improvements initially led to a larger proportion of patients realizing allogeneic stem cell transplantation (alloSCT), long considered essential for cure, but there has been a re-evaluation of alloSCT. At Princess Margaret Hospital (PM), adult patients with Ph+ B-ALL have been treated with a pediatric-inspired chemotherapy protocol with mostly imatinib. In the last two decades, we have witnessed many iterative changes in our approach. Here, we examine the outcomes of all Ph+ B-ALL patients treated at our institution from 2001 to 2019. During this time, there were two major protocol changes—omission of asparaginase in 2009 and discontinuation of routine referral for first complete remission (CR1) alloSCT from the early 2010s. Median follow-up was 41.13 months (range, 0.46–228.79). In total, 141 patients (91.56%) achieved CR1. Patient outcomes improved iteratively, with the best results seen in the final (2016–2019) cohort: no asparaginase, no routine alloSCT referral in CR1; 4-year overall survival (OS) and relapse-free survival (RFS) were 87.0% and 69.3%, respectively. The long-term OS in this patient group retained statistical significance in the multivariable analysis (p = 0.0176) when BCR::ABL1 molecular measurable residual disease (MRD) was considered. Full article

Obesity is associated with numerous pathological processes in the body, including inflammation, oxidative stress, and consequently, mitochondrial dysfunction. In recent years, research in anti-obesity therapy has also focused on the function of adipocytes and the inhibition of adipogenesis. In this study, we investigated the effect of the well-known flavonoid quercetin on mitochondrial function, apoptosis and differentiation of human preadipocytes. The Chub-S7 cell line model was used in the in vitro studies. Mitochondrial function was measured by oxygen consumption rates, intracellular ATP content, mitochondrial membrane potential, apoptosis assay (Annexin-5, caspase-9 activity), and ROS generation. Chub-S7 cell differentiation was assessed by Oil Red O staining. The results showed that the quercetin inhibited differentiation of human Chub-S7 preadipocytes and reduced fat accumulation in lipid droplets. Additionally, quercetin influenced mitochondrial biogenesis and mitochondrial uncoupling by changes in mitochondrial respiratory states and also increased mitochondrial membrane potential. Quercetin decreased routine respiration, R/E and netROUTINE control ratio. Our results demonstrate that quercetin is a dietary component that may modulate mitochondrial bioenergetics and inhibit adipogenesis. If these results were confirmed in in vivo studies, quercetin could be considered a factor used to prevent obesity. Full article

Multiple myeloma (MM) is characterised by the clonal expansion of plasma cells in the bone marrow followed by end-organ damage. Despite a significant increase in the five-year survival rate in recent years, MM is still considered an incurable disease as patients will repeatedly relapse and develop resistance to standard-of-care therapies. A central theme for the personalization of MM therapy is understanding the biological mechanisms of drug resistance and identifying clinically relevant biomarkers of therapeutic response. Highly effective protocols for the enrichment of phosphorylated peptides followed by high-resolution mass spectrometry makes possible the quantitation of thousands of site-specific phosphorylation events, principally on serine, threonine or tyrosine residues. In this study, phosphoproteomic analysis of 20 MM patient cell lysates was performed, stratified based on their ex vivo drug response profiles to Bortezomib and Lenalidomide, two of the most foundational therapeutic agents in the management of MM. In this study, patients who are highly sensitive to these drugs show increased phosphorylation of proteins concerned with translation and RNA processing including the spliceosome, RNA transport and RNA binding pathways, while highly resistant patients demonstrated an increased phosphorylation of proteins involved with tight junctions, the Rap1 signalling pathway and the phosphatidylinositol signalling system. This study has established a phosphoproteomic dataset displaying unique phosphorylation signatures associated with drug sensitivity in MM patient plasma cells. The identification of phosphorylation signatures associated with drug resistance provides the foundation for further exploration of these mechanisms and associated signalling pathways to further characterise drug resistance mechanisms in MM and identify promising biomarkers of therapeutic response and targets for drug re-sensitization in MM. Full article

Diabetic foot ulcers (DFUs) are wounds characterized by chronic inflammation and elevated oxidative stress that delay tissue regeneration and render them susceptible to infection, thereby complicating healing. Therefore, treating DFUs effectively is often challenging and requires a combined approach that integrates anti-inflammatory, antioxidant, and antibacterial effects. Curcumin, a widely studied natural compound, has shown promise in wound healing by modulating inflammation, oxidative stress, and infections. However, its bioavailability, absorption, and solubility issues limit its clinical applications. To overcome these limitations, curcumin has been incorporated into nanosystems, such as hydrogels, nanofibers, nanoparticles, vesicles, and micelles, thereby improving its delivery and enabling efficient local administration. Among these nanosystems, those formulated with chitosan are of particular interest due to chitosan’s intrinsic wound-healing properties. For that reason, this review comprehensively analyzes the literature on the therapeutic mechanisms of the chitosan–curcumin system for diabetic wound closure and compares them with those of free curcumin. The results show that this system exerts anti-inflammatory, antioxidant, and antimicrobial effects through specific mechanisms, including macrophage polarization, modulation of oxidative stress, and alteration of bacterial cell walls. In addition, significant improvements are observed in key healing processes, including cell migration, fibroblast proliferation, collagen deposition, and re-epithelialization. It should be noted that chitosan not only promotes curcumin release but also contributes to its therapeutic effect through its inherent antimicrobial and hemostatic properties, reinforcing its potential as a comprehensive strategy for the treatment of DFUs. Full article

Background: Host cell proteins (HCPs) are process-related impurities that must be monitored in biopharmaceutical products due to their potential impact on product quality and patient safety. Targeted LC–MS/MS approaches such as multiple reaction monitoring (MRM) enable protein-specific HCP quantification but are difficult to apply in highly multiplexed assays because of retention time (RT) variability across complex bioprocess matrices. Methods: Here, we show that conventional RT-scheduled MRM workflows lack transferability when applied to heterogeneous drug substances and process intermediates. Using a targeted assay comprising 240 peptides corresponding to 97 CHO-derived HCPs, RT shifts of several minutes resulted in truncated chromatographic peaks and peptide signal loss, even when wide scheduling windows were used. To overcome this limitation, a scout-triggered MRM (st-MRM) acquisition strategy based on event-driven monitoring was implemented. Results: This approach enabled robust peptide detection across diverse matrices within a single injection, without method re-optimization. Absolute quantification using stable isotope-labeled peptides spanned six orders of magnitude, with HCPs quantified down to 2.9 ppm in purified drug substances. Conclusion: Overall, st-MRM improves the robustness and transferability of highly multiplexed targeted proteomics workflows for HCP analysis. Full article

Histopathological image analysis remains the cornerstone of cancer diagnosis; however, manual assessment is challenged by stain variability, differences in imaging magnification, and complex morphological patterns. The proposed multi-pretrained deep learning fusion (MPDLF) approach combines two widely used CNN architectures: ResNet50, which captures deeper semantic representations, and VGG16, which extracts fine-grained details. This work differs from previous fusion studies by providing a controlled evaluation of early, intermediate, and late fusion for integrating two pretrained CNN backbones (ResNet50 and VGG16) under single-modality histopathology constraints. To isolate the fusion effect, identical training settings are used across three public H&E datasets. Early fusion achieved the best test performance for the two primary tasks reported here: breast cancer binary classification (accuracy = 0.9070, 95% CI: 0.8742–0.9404; AUC = 0.9707, 95% CI: 0.9541–0.9844) and renal clear cell carcinoma (RCCC) five-class grading (accuracy = 0.8792, 95% CI: 0.8529–0.9041; AUC (OvR, macro) = 0.9895, 95% CI: 0.9859–0.9927). Future work will extend these experiments to additional magnification levels (100×, 200×, and 400×) for breast cancer histopathology images and explore advanced hybrid fusion strategies across different histopathology datasets. Full article

The kynurenine pathway (KP) is the primary route of tryptophan metabolism and a key interface linking immune activation, metabolic state, and neurochemical signaling. Although KP biomarkers are widely studied in psychiatric disorders, their interpretation remains inconsistent, in part due to biological context and compartmentalization. In this narrative review, we integrate evidence across peripheral and central systems to clarify how age, sex hormones, metabolic health, inflammation, and behavioral factors systematically bias KP flux and shape biomarker readouts. We re-examine the interpretation of the kynurenine/tryptophan ratio in light of differential IDO1 and TDO2 regulation, blood–brain barrier constraints, and cell-specific downstream metabolism that governs neuroprotective and neurotoxic outputs. We further synthesize clinical evidence linking KP alterations to symptom severity, cognitive dysfunction, treatment resistance, and suicidality, highlighting quinolinic acid as a mechanistic node connecting immune activation to glutamatergic dysregulation. Together, this framework reframes the kynurenine pathway not as a static biomarker of disease, but as a context-sensitive metabolic system with direct implications for study design, risk stratification, and personalized approaches in psychiatry. Full article

Organoid technology has transformed experimental virology by offering physiologically relevant 3D human models that bridge the gap between conventional 2D cell cultures and complex in vivo systems. Derived from pluripotent or adult stem cells, organoids self-organize into multicellular structures that recapitulate native tissue architecture and function, enabling more accurate modeling of host–virus interactions and disease mechanisms. This review outlines the evolution and application of organoid-based systems across neural, intestinal, hepatic, pulmonary, and renal tissues for studying a broad range of human viruses that remain a public health burden. These models can reproduce viral tropism, immune signaling, and host variability, offering new molecular insights into infection dynamics. Integration with single-cell transcriptomics, CRISPR editing, and antiviral screening has expanded the translational utility of organoids, establishing them as a powerful platform for antiviral discovery, vaccine testing, and precision medicine. Full article

This study presents an analysis of selected approaches to transforming the Polish power system towards a net-zero greenhouse gas (GHG) emission economy by 2060. The generation-side system models primarily comprise renewable energy sources (RES), supported by nuclear power plants. Two system balancing scenarios were examined: Model G, based on biomethane-fired gas turbines and electrolysers utilising surplus energy; and Model H, which relies primarily on reversible fuel cells (RFCs) operating in a Power-to-Power configuration. Both models were considered under two demographic projections for Poland in 2060: maintaining the current population level (100%) and a decline to 71%. Simulations were performed with an hourly time step over a nine-year period, starting from 2060, using weather data from 2015 to 2023. The total electricity demand in the analysed scenarios ranges from 352 to 542 TWh/year, representing 2.1–3.2 times the current level. The proposed systems include 64 GW of onshore wind capacity, 33 GW of offshore wind, 136 GW of PV, 10 GW of nuclear generation, and extensive storage systems for electricity, heat, and gases (biomethane and hydrogen). In Model G, biomethane and hydrogen storage play a crucial role, requiring storage capacities of 5.8–7.5 billion Nm³ for biomethane and 6.2–7.0 billion Nm³ for hydrogen. In Model H, long-term storage relies on hydrogen reservoirs (approximately 12.5 billion Nm³) integrated with RFC units. The results demonstrate that the choice of architecture dictates the scale and technical requirements of the storage infrastructure. Notably, hydrogen serves as an effective energy storage medium, enabling the elimination of peak gas turbines from the system. Consequently, biomethane resources can be redirected to support the decarbonisation of other sectors of the economy. Full article

Class I myosins form an abundant group of single-headed motor proteins that interact with actin and membrane phospholipids and are employed in a variety of cell processes like cell shape remodeling, motility and invasion, exocytosis, and endocytosis. The large number of class members and their uneven distribution in human cells and tissues complicate their study. Furthermore, this hinders the assessment of their biomarker potential and mechanistic role in oncogenesis and other diseases. Despite the emerging data on their mutations and altered abundance in a number of tumors and other diseases, most studies examine class I myosins individually or in groups of several proteins. Thus, the question of their redundancy and possible functional substitution is ignored. In this work, we simultaneously assess all eight human MYO1 genes on cell lines of different origins by RNA-seq re-analysis. We also report a qPCR system for human myosin I screening and test it on a set of 35 continuous cell lines widely used in biomedicine and fundamental research. These data clarify the restricted expression patterns of MYO1 genes in various human cell types and allow to assess the pattern specific of haematopoietic cell lines. Full article

Background: Cryptococcal meningitis (CM) remains a leading cause of mortality among people with advanced HIV disease (AHD) in sub-Saharan Africa. Current guidelines recommend induction therapy with amphotericin B and flucytosine, typically administered in an inpatient setting due to concerns over severe clinical presentation and drug-related toxicities. This requirement poses a significant burden on resource-limited health systems. We evaluated the real-world outcomes of a fully outpatient model for CM therapy in Maputo, Mozambique. Methods: A longitudinal retrospective cohort study was conducted at the Centro de Referência de Alto-Maé (CRAM), a specialized AHD outpatient clinic. We included 83 PLWH with laboratory-confirmed CM treated between October 2020 and December 2024. The primary outcome was hospitalization-free survival (HFS) within the first 10 weeks of treatment. Secondary outcomes included the frequency and severity of adverse drug reactions (ADRs), analysed by tracking haemoglobin (Hgb), potassium (K+), and creatinine (Creat) levels on days 1, 3, and 7 of induction therapy, and retention in care (RIC) at 6, 12, and 24 months. Statistical analyses included Kaplan–Meier survival estimates and paired t-tests. Results: The median age was 37 years (IQR: 27–42), 63.9% were male, and the median CD4 count was 62 cells/µL (IQR: 27–105). Most patients (95.2%) were symptomatic at presentation, and 56.6% had concurrent tuberculosis. For the 52 patients who completed the full induction protocol at CRAM, the HFS rate at 10 weeks was 84.6% (44/52), with an overall survival of 90.4% (47/52). ADR analysis (n = 52) showed a predictable pattern of mild, manageable toxicity: a significant decline in Hgb (11.2 ± 1.8 to 10.6 ± 2.0 g/dL, p < 0.001) and K+ (4.27 ± 0.66 to 3.86 ± 0.78 mmol/L, p = 0.008), and a transient increase in Creat (0.83 ± 0.42 to 1.13 ± 0.64 mg/dL, p = 0.001) from day 1 to day 3, with stabilization or a trend toward recovery by day 7. No significant differences in ADRs were found between single-dose (47%) and multiple-dose (53%) L-AmB regimens. RIC for the entire cohort (n = 83) was high at 81.9% at 6 months, declining to 74.0% at 12 months and 70.4% at 24 months. Conclusions: An ambulatory model for CM therapy is feasible and effective in a resource-limited setting, demonstrating high hospitalization-free survival, manageable and reversible adverse drug reactions, and excellent medium-term retention in care. These findings suggest potential benefits and provide support for re-evaluating the standard of inpatient care. They indicate that integrating outpatient CM management into advanced HIV disease (AHD) care packages could help alleviate health system burdens and may contribute to improved patient outcomes. Full article