AITeQ: a machine learning framework for Alzheimer's prediction using a distinctive five-gene signature.

Neurodegenerative diseases, such as Alzheimer's disease, pose a significant global health challenge with their complex etiology and elusive biomarkers. In this study, we developed the Alzheimer's Identification Tool (AITeQ) using ribonucleic acid-sequencing (RNA-seq), a machine learning (ML) model based on an optimized ensemble algorithm for the identification of Alzheimer's from RNA-seq data. Analysis of RNA-seq data from several studies identified 87 differentially expressed genes. This was followed by a ML protocol involving feature selection, model training, performance evaluation, and hyperparameter tuning. The feature selection process undertaken in this study, employing a combination of four different methodologies, culminated in the identification of a compact yet impactful set of five genes. Twelve diverse ML models were trained and tested using these five genes (CNKSR1, EPHA2, CLSPN, OLFML3, and TARBP1). Performance metrics, including precision, recall, F1 score, accuracy, Matthew's correlation coefficient, and receiver operating characteristic area under the curve were assessed for the finally selected model. Overall, the ensemble model consisting of logistic regression, naive Bayes classifier, and support vector machine with optimized hyperparameters was identified as the best and was used to develop AITeQ. AITeQ is available at: https://github.com/ishtiaque-ahammad/AITeQ.

A meta-analysis of bulk RNA-seq datasets identifies potential biomarkers and repurposable therapeutics against Alzheimer's disease.

Alzheimer's disease (AD) poses a major challenge due to its impact on the elderly population and the lack of effective early diagnosis and treatment options. In an effort to address this issue, a study focused on identifying potential biomarkers and therapeutic agents for AD was carried out. Using RNA-Seq data from AD patients and healthy individuals, 12 differentially expressed genes (DEGs) were identified, with 9 expressing upregulation (ISG15, HRNR, MTATP8P1, MTCO3P12, DTHD1, DCX, ST8SIA2, NNAT, and PCDH11Y) and 3 expressing downregulation (LTF, XIST, and TTR). Among them, TTR exhibited the lowest gene expression profile. Interestingly, functional analysis tied TTR to amyloid fiber formation and neutrophil degranulation through enrichment analysis. These findings suggested the potential of TTR as a diagnostic biomarker for AD. Additionally, druggability analysis revealed that the FDA-approved drug Levothyroxine might be effective against the Transthyretin protein encoded by the TTR gene. Molecular docking and dynamics simulation studies of Levothyroxine and Transthyretin suggested that this drug could be repurposed to treat AD. However, additional studies using in vitro and in vivo models are necessary before these findings can be applied in clinical applications.

Prevalence of inappropriate antibiotic doses among pediatric patients of inpatient, outpatient, and emergency care units in Bangladesh: A cross-sectional study.

The heterogeneous pediatric populations, their physiological differences, along with the necessity of performing additional dose calculation, make the pediatric population more vulnerable to the incidences of inappropriate antibiotic doses. This study was conducted to examine and evaluate the appropriateness of antibiotic doses. A cross-sectional study with a quantitative approach was conducted in three hospitals located in Savar from January 06, 2021 to October 17, 2022. This study had used a convenient sampling method to collect 405 filled prescription orders from heterogeneous pediatric patients prescribed by physicians from emergency, inpatient, and outpatient care units of various clinical settings. The Harriet Lane Handbook was used as reference to investigate inappropriate doses of antibiotics. Subsequently, all analyses were conducted using the RStudio 1.3.959 software. Binary logistic regression was used to assess the risk of inappropriate antibiotic prescription in pediatrics. The overall prevalence of inappropriate antibiotic dosing in pediatrics was 335 out of 545 (61.5%). Overdosing (36.3%) and oral antibiotic prescriptions (64%) were more common than underdosing (20.4%) and parenteral antibiotics (36%). The majority (230 out of 405, 56.8%) of pediatric patients had prescriptions with inappropriate antibiotic doses, with prevalence rates of 33.8% for inpatients, 86.7% for outpatients, and 50% for emergency pediatrics. The results also indicated that pediatric patients in outdoor and emergency care units, infants, toddlers, and early childhood, those prescribed two antibiotics simultaneously, and those receiving parenteral antibiotics, were less likely to have inappropriate antibiotic dosages in their prescriptions. This study demonstrated that about one out of every two prescriptions had inappropriate antibiotic doses; in particular, prescriptions containing only one antibiotic exhibited a substantial proportion of inappropriate antibiotic doses. Inappropriate antibiotic doses may result in therapeutic failure, patient harm, and antibiotic resistance. Good clinical pharmacy practice and careful adherence to pediatric dosing standards may minimize inappropriate antibiotic doses.

An integrated comparative genomics, subtractive proteomics and immunoinformatics framework for the rational design of a Pan-Salmonella multi-epitope vaccine.

Salmonella infections pose a significant global public health concern due to the substantial expenses associated with monitoring, preventing, and treating the infection. In this study, we explored the core proteome of Salmonella to design a multi-epitope vaccine through Subtractive Proteomics and immunoinformatics approaches. A total of 2395 core proteins were curated from 30 different isolates of Salmonella (strain NZ CP014051 was taken as reference). Utilizing the subtractive proteomics approach on the Salmonella core proteome, Curlin major subunit A (CsgA) was selected as the vaccine candidate. csgA is a conserved gene that is related to biofilm formation. Immunodominant B and T cell epitopes from CsgA were predicted using numerous immunoinformatics tools. T lymphocyte epitopes had adequate population coverage and their corresponding MHC alleles showed significant binding scores after peptide-protein based molecular docking. Afterward, a multi-epitope vaccine was constructed with peptide linkers and Human Beta Defensin-2 (as an adjuvant). The vaccine could be highly antigenic, non-toxic, non-allergic, and have suitable physicochemical properties. Additionally, Molecular Dynamics Simulation and Immune Simulation demonstrated that the vaccine can bind with Toll Like Receptor 4 and elicit a robust immune response. Using in vitro, in vivo, and clinical trials, our findings could yield a Pan-Salmonella vaccine that might provide protection against various Salmonella species.

Subtractive genomics study of Xanthomonas oryzae pv. Oryzae reveals repurposable drug candidate for the treatment of bacterial leaf blight in rice.

BACKGROUND: Xanthomonas oryzae pv. oryzae is a plant pathogen responsible for causing one of the most severe bacterial diseases in rice, known as bacterial leaf blight that poses a major threat to global rice production. Even though several experimental compounds and chemical agents have been tested against X. oryzae pv. oryzae, still no approved drug is available. In this study, a subtractive genomic approach was used to identify potential therapeutic targets and repurposible drug candidates that could control of bacterial leaf blight in rice plants. RESULTS: The entire proteome of the pathogen underwent an extensive filtering process which involved removal of the paralogous proteins, rice homologs, non-essential proteins. Out of the 4382 proteins present in Xoo proteome, five hub proteins such as dnaA, dnaN, recJ, ruvA, and recR were identified for the druggability analysis. This analysis led to the identification of dnaN-encoded Beta sliding clamp protein as a potential therapeutic target and one experimental drug named [(5R)-5-(2,3-dibromo-5-ethoxy-4hydroxybenzyl)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid that can be repurposed against it. Molecular docking and 100 ns long molecular dynamics simulation suggested that the drug can form stable complexes with the target protein over time. CONCLUSION: Findings from our study indicated that the proposed drug showed potential effectiveness against bacterial leaf blight in rice caused by X. oryzae pv. oryzae. It is essential to keep in consideration that the procedure for developing novel drugs can be challenging and complicated. Even the most promising results from in silico studies should be validated through further in vitro and in vivo investigation before approval.

Knowledge, attitudes, and practices regarding antibiotic use in Bangladesh: Findings from a cross-sectional study.

BACKGROUND: Escalating antibiotic resistance presents a notable worldwide dilemma, pointing a large involvement of general population. The objective of this study was to assess knowledge, attitudes, and practices regarding the utilization of antibiotics among Bangladeshi residents. METHODS: A cross-sectional study, conducted from January 01 to April 25, 2022, included 1,947 Bangladeshi adults with a history of antibiotic use, via online surveys and face-to-face interviews using a pretested semi-structured questionnaire. Descriptive statistics, Chi-square tests, and multivariate linear regression models were employed. RESULTS: Mean scores for knowledge, attitudes, and practices were 6.59±1.20, 8.34±1.19, and 12.74±2.59, with correct rates of 73.22%, 92.67%, and 57.91%. Positive predictors for knowledge included being unmarried (ß = 0.10, p = 0.001), higher education (College: ß = 0.09, p = 0.025; Bachelor: ß = 0.22, p<0.001; Master or above: ß = 0.14, p<0.001), various professions (student: ß = 0.57, p<0.001; housewife: ß = 0.33, p<0.001; employee: ß = 0.53, p<0.001; businessman: ß = 0.31, p<0.001; unemployed: ß = 0.15, p<0.001), and residing in semi-urban (ß = 0.32, p<0.001) or urban areas (ß = 0.15, p<0.001). Positive predictors for attitudes included being married (ß = 0.18, p<0.001), specific professions (student: ß = 1.06, p<0.001; housewife: ß = 0.33, p<0.001; employee: ß = 0.86, p<0.001; businessman: ß = 0.37, p<0.001; unemployed: ß = 0.47, p<0.001), higher SES (Lower-middle: ß = 0.22, p<0.001; Middle: ß = 0.26, p<0.001), and residing in semi-urban areas (ß = 0.18, p<0.001); negative predictors included higher education (College: ß = -0.12, p = 0.001; Master or above: ß = -0.09, p = 0.008) and being rich (ß = -0.13, p<0.001). Positive predictors for practices included being married (ß = 0.18, p<0.001), specific professions (student: ß = 0.32, p<0.001; employee: ß = 0.43, p<0.001; businessman: ß = 10, p = 0.034; unemployed: ß = 0.11, p = 0.009), and higher SES (Lower-middle: ß = 0.14, p = 0.009; Middle: ß = 0.38, p<0.001; Higher-middle: ß = 0.15, p = 0.008); negative predictors included higher education (College: ß = -0.21, p<0.001), being rich (ß = -0.12, p<0.001), residing in semi-urban (ß = -0.14, p<0.001) or urban areas (ß = -0.16, p<0.001). CONCLUSIONS: Participants exhibited adequate knowledge and positive attitudes but lagged behind in proper practice of antibiotic use. Proper initiatives should be tailored to enhance prudent antibiotic use and mitigate the risk of antimicrobial resistance.

Identification of repurposable drug targets in Mycoplasma pneumoniae using subtractive genomics, molecular docking and dynamics simulation.

Mycoplasma pneumoniae is a significant causative agent of community-acquired pneumonia, causing acute inflammation in the upper and lower respiratory tract as well as extrapulmonary syndromes. In particular, the elderly and infants are at greater risk of developing severe, life-threatening pneumonia caused by M. pneumoniae. Yet, the global increase in antimicrobial resistance against antibiotics for the treatment of M. pneumoniae infection highlights the urgent need to explore novel drug targets. To this end, bioinformatics approaches, such as subtractive genomics, can be employed to identify specific metabolic pathways and essential proteins unique to the pathogen that could be potential targets for new drugs. In this study, we implemented a subtractive genomics approach to identify 61 metabolic pathways and 42 essential proteins that are unique to M. pneumoniae. A subsequent screening in the DrugBank database revealed three druggable proteins with similarity to FDA-approved small-molecule drugs, and finally, the compound CHEBI:97093 was identified as a promising novel putative drug target. These findings can provide crucial insights for the development of highly effective drugs that selectively inhibit the pathogen-specific metabolic pathways, leading to better management and treatment of M. pneumoniae infections.