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Quinolones are broad-spectrum synthetic antibacterial drugs first obtained during the synthesis of chloroquine. Nalidixic acid, the prototype of quinolones, first became available for clinical consumption in 1962 and was used mainly for urinary tract infections caused by Escherichia coli and other pathogenic Gram-negative bacteria. Recently, significant work has been carried out to synthesize novel quinolone analogues with enhanced activity and potential usage for the treatment of different bacterial diseases. These novel analogues are made by substitution at different sites—the variation at the C-6 and C-8 positions gives more effective drugs. Substitution of a fluorine atom at the C-6 position produces fluroquinolones, which account for a large proportion of the quinolones in clinical use. Among others, substitution of piperazine or methylpiperazine, pyrrolidinyl and piperidinyl rings also yields effective analogues. A total of twenty six analogues are reported in this review. The targets of quinolones are two bacterial enzymes of the class II topoisomerase family, namely gyrase and topoisomerase IV. Quinolones increase the concentration of drug-enzyme-DNA cleavage complexes and convert them into cellular toxins; as a result they are bactericidal. High bioavailability, relative low toxicity and favorable pharmacokinetics have resulted in the clinical success of fluoroquinolones and quinolones. Due to these superior properties, quinolones have been extensively utilized and this increased usage has resulted in some quinolone-resistant bacterial strains. Bacteria become resistant to quinolones by three mechanisms: (1) mutation in the target site (gyrase and/or topoisomerase IV) of quinolones; (2) plasmid-mediated resistance; and (3) chromosome-mediated quinolone resistance. In plasmid-mediated resistance, the efflux of quinolones is increased along with a decrease in the interaction of the drug with gyrase (topoisomerase IV). In the case of chromosome-mediated quinolone resistance, there is a decrease in the influx of the drug into the cell.

Abstract The study aimed at identifying the level of performance of the teaching staff at the Yemeni University of Science and Technology through the students point of view on a number of teaching competencies. For this purpose, the researchers developed a questionnaire composed of 22 items, distributed to 6 teaching competencies which are: teaching, feedback, academic support, class management, learning resources, and personal development. The total number of the students participating in the evaluation is 6591, representing all the specialties and levels and the number of teachers being evaluated was 102, 88 male and 14 female. Results reveal no significant differences among the teachers mean scores that can be attributed to either qualification or gender at α =0.05. The researchers recommend setting plans necessary to training the teaching staff with regard to teaching, evaluation, academic support, class management, and personal development. They also recommend giving teachers feedback on their evaluation. They replicating the same study considering other variables.

Breast cancer, a widespread and life-threatening disease, necessitates precise diagnostic tools for improved patient outcomes. Tumor-Infiltrating Lymphocytes (TILs), reflective of the immune response against cancer cells, are pivotal in understanding breast cancer behavior. However, inter-observer variability in TILs scoring methods poses challenges to reliable assessments. This study introduces a novel and interpretable proof-of-principle framework comprising two innovative inter-observer agreement measures. The first method, Boundary-Weighted Fleiss' Kappa (BWFK), addresses tissue segmentation predictions, focusing on mitigating disagreements along tissue boundaries. BWFK enhances the accuracy of stromal segmentation, providing a nuanced assessment of inter-observer agreement. The second proposed method, the Distance Based Cell Agreement Algorithm (DBCAA), eliminates the need for ground truth annotations in cell detection predictions. This innovative approach offers versatility across histopathological analyses, overcoming data availability challenges. Both methods were applied to assess inter-observer agreement using a clinical image dataset consisting of 25 images of invasive ductal breast carcinoma tissue, each annotated by four pathologists, serving as a proof-of-principle. Experimental investigations demonstrated that the BWFK method yielded gains of up to 32% compared to the standard Fleiss' Kappa model. Furthermore, a procedure for conducting clinical validations of artificial intelligence (AI) based cell detection methods was elucidated. Thoroughly validated on a clinical dataset, the framework contributes to standardized, reliable, and interpretable inter-observer agreement assessments. This study is the first examination of inter-observer agreements in stromal segmentation and lymphocyte detection for the TILs scoring problem. The study emphasizes the potential impact of these measures in advancing histopathological image analysis, fostering consensus in TILs scoring, and ultimately improving breast cancer diagnostics and treatment planning. The source code and implementation guide for this study are accessible on our GitHub page, and the full clinical dataset is available for academic and research purposes on Kaggle. [ABSTRACT FROM AUTHOR]

In this study, we used a three-dimensional airway "organ tissue equivalent" (OTE) model at an air-liquid interface (ALI) to mimic human airways. We investigated the effects of three viruses (Influenza A virus (IAV), Human metapneumovirus (MPV), and Parainfluenza virus type 3 (PIV3) on this model, incorporating various control conditions for data integrity. Our primary objective was to assess gene expression using the NanoString platform in OTE models infected with these viruses at 24- and 72-hour intervals, focusing on 773 specific genes. To enhance the comprehensiveness of our analysis, we introduced a novel algorithm, namely MAS (Magnitude-Altitude Score). This innovative approach uniquely combines biological significance, as indicated by fold changes in gene expression, with statistical rigor, as represented by adjusted p-values. By incorporating both dimensions, MAS ensures that the genes identified as differentially expressed are not mere statistical artifacts but hold genuine biological relevance, providing a more holistic understanding of the airway tissue response to viral infections. Our results unveiled distinct patterns of gene expression in response to viral infections. At 24 hours post-IAV infection, a robust interferon-stimulated gene (ISG) response was evident, marked by the upregulation of key genes including IFIT2, RSAD2, IFIT3, IFNL1, IFIT1, IFNB1, ISG15, OAS2, OASL, and MX1, collectively highlighting a formidable antiviral defense. MPV infection at the same time point displayed a dual innate and adaptive immune response, with highly expressed ISGs, immune cell recruitment signaled by CXCL10, and early adaptive immune engagement indicated by TXK and CD79A. In contrast, PIV3 infection at 24 hours triggered a transcriptional response dominated by ISGs, active immune cell recruitment through CXCL10, and inflammation modulation through OSM. The picture evolved at 72 hours post-infection. For IAV, ISGs and immune responses persisted, suggesting a sustained impact. MPV infection at this time point showed a shift towards IL17A and genes related to cellular signaling and immune responses, indicating adaptation to the viral challenge over time. In the case of PIV3, the transcriptional response remained interferon-centric, indicating a mature antiviral state. Our analysis underscored the pivotal role of ISGs across all infections and time points, emphasizing their universal significance in antiviral defense. Temporal shifts in gene expression indicative of adaptation and fine-tuning of the immune response. Additionally, the identification of shared and unique genes unveiled host-specific responses to specific pathogens. IAV exerted a sustained impact on genes from the initial 24 hours, while PIV3 displayed a delayed yet substantial genomic response, suggestive of a gradual and nuanced strategy. [ABSTRACT FROM AUTHOR]