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A metabolomic study for determination of certain urinary metabolomes, 1-methyladenosine (1-MA), 1-methylguanosine (1-MG), and 8-hydroxy-2′ deoxyguanosine (8-OHdG) in urine specimens of breast cancer patients. The accuracy of these metabolites and their combined score with cancer antigen 15-3 (CA15-3) was developed to improve the early detection of breast cancer. This study recruited 52 healthy individuals, 47 benign breast tumors, and 167 malignant breast tumor patients. Urine samples were handled to adjust the creatinine concentrations to 8 mg/dL (0.7 mmol/L) and analyzed using GC–MS to detect and quantify the selected urinary metabolomes in urine samples of all participants. The accuracy of individual urinary metabolomes and their combination with CA15-3 were evaluated using multivariate statistical analysis. The cutoff value of CA15-3 was 32.5 U/mL. Cutoff values of 1-MA, 1-MG, and 8-OHdG were 2.19, 2.1, and 7.3 µmol/mmol creatinine, respectively. The concentrations of 1-MA, 1-MG, and 8-OHdG were significantly higher in breast cancer patients, especially in the early-stage. The combination of three urinary metabolomes with CA15-3 improves the diagnostic sensitivity of breast cancer. For the combined score, the area under the curve (AUC) value of combined score ranged from 0.820 to 0.950, with high accuracy, ranged from 77.0 to 95.5%. The most significant AUC (0.973), sensitivity (90.1%), selectivity (94.0%) was recorded at comparing the healthy control with the early-stage of malignant breast cancer. In conclusion, the combination of three urinary metabolomes with serum CA15-3 improves the diagnostic sensitivity of breast cancer.

The goal of the current study is to determine the effect of THIEVES strategy on ESP university students' reading comprehension and inquiry learning skills. It was assumed that students received training on THIEVES strategy would perform better on reading comprehension and inquiry learning skills than their counterparts in the control group. The tools -designed by the researchers- that were used for reaching statistical results included: (reading skills checklist, inquiry learning skills checklist, reading comprehension test and inquiry learning test). Findings showed that THIEVES strategy made a significant difference in enhancing reading comprehension and inquiry learning skills of the experimental group.

Repeated pancreatic insults and inflammation can lead to the development of pancreatitis. In this study, the therapeutic potential of a nano-formulated metformin drug with chitosan (Cs-Met NPs) and/or low doses of γ-irradiation (IR) was evaluated against acute pancreatitis (AP) induced by L-arginine in an animal model. Thirty adult Wistar rats were randomly divided into five groups: normal control, L-arginine-treated (AP), AP + IR, AP + Cs-Met NPs, and AP + IR + Cs-Met NPs. Histopathological examination of the pancreas was performed, and biochemical parameters including serum amylase and lipase levels, random blood glucose (RBS), plasma insulin levels, insulin-like growth factor 1 (IGF-1), tumor necrosis factor-alpha (TNF-α), interleukins (IL-6, IL-8, IL-10), and C-reactive protein (CRP) were measured. L-arginine treatment significantly elevated serum amylase and lipase levels, as well as IL-6, IL-8, TNF-α, RBS, and CRP levels. It also substantially decreased IL-10, insulin, and IGF-1 levels. Microscopic examination revealed loss of pancreatic lobular architecture, marked fibrosis, acinar cell degeneration, inflammation, and edema. Administration of Cs-Met NPs and/or low-dose γ-irradiation markedly improved both the biochemical parameters and histopathological features.Conclusion: Nano-formulated metformin and/or low-dose γ-irradiation demonstrated significant therapeutic effects in a rat model of L-arginine-induced acute pancreatitis.

The prognostic value of determining mRNA levels of two markers for regulatory T cells, IL-10 and FoxP3, in lymph nodes (LNs) and primary tumors of colon cancer (CC) patients receiving curative surgery was investigated. mRNA levels were determined by real-time qRT-PCR in 370 LNs from 120 CC patients representing all four TNM stages, 66 primary tumors, 30 normal colon tissue samples and appropriate cell lines. Protein expression was analyzed by immunohistochemistry. Patients were followed for 12 years. High levels of IL-10 mRNA in LNs were associated with poor prognosis with shorter mean survival time of 10 and 32 months ( = 0.001 and = 0.004) at 5- and 12-year follow-up with hazard ratios of 12.4 and 6.3, respectively. No association between IL-10 level and prognosis was seen in the primary tumor. High levels of FoxP3 mRNA were associated with good prognosis, both in LNs and primary tumor. The difference in survival time was, however, small. Analysis of IL-10 mRNA in combination with LGR6 or CXCL17 mRNA in LNs generated patients with different risk of recurrence - low-, high- and very high risk. Immunohistochemistry identified IL-10 and FoxP3 positive cells located at the outer rim of tumor aggregates. Level determinations of IL-10 mRNA in LNs are useful for prediction of outcome for CC patients after curative surgery. Low levels indicate that the patients do not require further treatment, while IL-10 in combination with LGR6 or CXCL17 can be used to identify patients at very high risk of recurrence.

Hepatic fibrosis is a progressive disease with serious clinical complications that arise from abnormal propagation and activation of multiple inflammatory pathways. Nilotinib is an oral tyrosine kinase inhibitor with antifibrotic activity. Mesenchymal stem cells (MSCs) are blank cells and can differentiate into specific cell types. They have the potential to repair and regenerate cells. MSCs have a special paracrine fashion where they produce special exosomes, microvesicles, and cytokines like IL-6, transforming growth factor-beta (TGF-β), and HGF as well as hepatic stellate cell suppressors. This paracrine fashion can decrease collagen deposition, enhance antifibrotic, anti-inflammatory, and angiogenic activity in vitro and in vivo. In our study, the rat’s hepatic stellate cells (HSCs) in addition to different normal cell lines were treated with Nilotinib alone and in combination with liver mesenchymal stem cells conditioned medium (LMSCs-CM) for 24 h. Mono and combined therapy antifibrotic and cytotoxicity effects were evaluated using different parameters including α-SMA, cytochrome c, P53 expression, collagen deposition, DNA content, oxidative stress parameters, cell viability, and apoptosis by flow cytometry analysis. Our results showed that Nilotinib and LMSCs-CM in combination had a significantly potent antifibrotic and anti-inflammatory effect on activated hepatic stellate cells than Nilotinib alone; otherwise, this combination showed the best safety with minimal cytotoxicity on different normal cell lines.

Liver fibrosis is the excessive extracellular matrix accumulation of proteins, such as collagen, which follows the chronic liver diseases. Advanced liver fibrosis leads to cirrhosis and liver failure. Nilotinib is a second-generation tyrosine kinase inhibitor, which showed antifibrotic efficacy. Stem cell therapy still has some limitations such as oncogenesis, unexpected differentiation, and ethical consideration. Stem cells secrete cytokines and growth factors that showed paracrine-mediated antifibrotic and anti-inflammatory effects in vivo and in vitro. Thus, stem cell-conditioned medium (SC-CM), which contains the secretory proteins of stem cells, may have an antifibrotic role. This study was carried out to examine the antifibrotic effect of Nilotinib and stem cell exosomes on CCl4-induced liver fibrosis in rats. Male Wistar rats were injected intraperitoneally with CCl4 twice a week for 9 weeks and given daily treatments of Nilotinib (20 mg/kg), stem cell exosomes (0.5 ml/rat), and the combination treatment of Nilotinib and stem cell exosomes during the last 5 weeks of CCl4 intoxication. Liver fibrosis and also antifibrotic efficacy of the treatments were estimated with liver function tests, oxidative stress parameters, apoptotic parameters, histopathological examination, and hydroxyproline contents. Results showed that the combination of Nilotinib and stem cell-conditioned media had more antifibrotic effects than each one alone (P value < 0.001).

The current study examined the effect of using Nearpod with a guided reading strategy on primary pupils’ reading comprehension skills and motivation. I designed three tools to accomplish the research, including a reading skills checklist, a reading test, and a reading motivation scale. The results confirmed that the regular technique used in teaching is not as significant as using Nearpod with a guided reading strategy. The experimental group of pupils outperformed their counterparts in the control group in the reading comprehension test and reading motivation scale. Using Nearpod with guided reading improved reading comprehension skills and motivation.

The main purpose of this study was to determine the impact of sheltered instruction observation protocol on student teachers’ teaching skills and self-efficacy. Questions formulated to achieve the purpose of the study focused on. (1) Determining the teaching skills necessary for the EFL student teachers. (2) Finding out differences in both EFL student teachers’ teaching performance observation checklist experimental and control group. (3) Finding out differences in both EFL student teachers’ self-efficacy scale of experimental and control group. Twenty two EFL student teachers constituted the sample for this study and two instruments-designed by the researchers- were used for data collection. Results indicated that students of experimental group outperformed their counterparts of control group in EFL teaching performance. The effect of sheltered instruction observation protocol model on student teachers teaching skills and self-efficacy was profound and significant. Sheltered instruction observation protocol model was very motivating for student teachers and gave them opportunities to make decisions and be creative.

Background: Na+/K+ ATPase enzyme is essential for nerve cell membrane integrity, and reduction in its activity, probably due to ATP1A1 gene polymorphisms, is related to diabetic neuropathy progression. Therefore, the goal of the existent study is to evaluate the Na+/K+ ATPase activity in type 2 diabetes mellitus (T2DM) Egyptian patients with or without neuropathy, search for polymorphism(s) in the highly polymorphic region of ATP1A1 gene, exon 2, and study its (their) associations with T2DM with and without neuropathy. Materials and Methods: A total number of 150 individuals were subclassified into healthy controls (n = 30), T2DM without complications (n = 60), and T2DM with neuropathy (n = 60). Results: The biochemical results exhibited a significant reduction in fasting C-Peptide and activity of Na+/K+ ATPase in T2DM patients with neuropathy followed by T2DM without complication in comparison with healthy controls. ATP1A1 exon2 was amplified by polymerase chain reaction (PCR) then digested by the PstI restriction enzyme, and the obtained data from restriction fragment length polymorphism-PCR and sequencing revealed the existence of a novel synonymous G94A single nucleotide polymorphism (SNP) at nucleotide 27 in exon 2 of ATP1A1 gene (rs1060366). Diabetic groups had only allele A, while the control group had G allele. Interestingly, individuals carrying AA genotype had a significantly lower Na+/K+ ATPase, C-peptide, and higher glycosylated hemoglobin (HBA1c %) than those having GG genotype, suggesting a possible association for this SNP, and this developed phenomenon of not only T2DM but also diabetic neuropathy. Conclusion: Thus, allele A of G94A SNP (rs1060366) could be a risk allele for diabetes susceptibility among Egyptian patients.

White blood cells (WBCs) play a crucial role in the immune system, protecting the body from infections and foreign invaders. Abnormalities in WBCs can be indicative of various conditions, including leukemia. WBCs classification is pivotal for diagnosing hematological disorders. This study advances automated WBCs analysis through an 8-class classification framework encompassing rare but clinically critical subtypes: neutrophils, eosinophils, basophils, lymphocytes, monocytes, immature granulocytes (IGs), erythroblasts, and platelets. Leveraging a dataset of 17,092 CellaVision DM96-generated images standardized for clinical relevance, we implement rigorous preprocessing (normalization, resizing) and dynamic augmentation (rotations, flips) to enhance robustness. Six architectures are evaluated: ResNet50, InceptionV3, EfficientNetB3, MobileNetV3, Swin Transformer, and a custom convolutional neural network (CNN). ResNet50 emerged as the top performer 98.83% accuracy, followed by InceptionV3 98.77% and Swin Transformer 98.71%, demonstrating the efficacy of transfer learning and transformer-based attention mechanisms. Class-weighted loss mitigated dataset imbalance, achieving > 0.98 F1-scores for 6/8 classes. Computational efficiency analysis revealed MobileNetV3 as optimal for deployment (3.43 ms/inference). The study addresses key challenges—class imbalance, model interpretability via Gradient-weighted Class Activation Mapping (Grad-CAM) visualizations—and validates improved diagnostic precision over prior work. By integrating clinically critical subtypes and state-of-the-art architectures, it provides a robust tool for medical education and practice, enabling early detection of leukemia, sepsis, and myelodysplastic syndromes. This study can enhance the training of medical students and doctors, equipping them with better tools for diagnosis and decision-making. Furthermore, the ability to classify a broader range of WBCs types could lead to more accurate and early diagnoses of diseases, ultimately improving patient care.