Exome sequencing in Nigerian children with early-onset epilepsy syndromes.

Objective: Nigeria, along with other Sub-Saharan African countries, bears the highest burden of epilepsy worldwide. This high prevalence is attributed to a combination of factors, including a significant incidence of infectious diseases, perinatal complications, and genetic etiologies. Genetic testing is rarely available and is not typically included in the routine diagnostic work-up for individuals with infantile and childhood epilepsy syndromes in these regions.

Employing Hexahydroquinolines as CDPK4 Inhibitors to Combat Malaria Transmission: An Advanced Computational Approach.

Background: Existing antimalarial drugs primarily target blood-stage parasites, but there is a need for transmission-blocking drugs to combat malaria effectively. Calcium-dependent Protein Kinase 4 (CDPK4) is a promising target for such drugs. This study employed advanced in silico analyses of hexahydroquinolines (HHQ) derivatives to identify CDPK4 inhibitors capable of disrupting malaria transmission.

studies of benzothiazole derivatives as potential inhibitors of and trehalase.

Introduction: In malaria management, insecticides play a crucial role in targeting disease vectors. Benzothiazole derivatives have also been reported to possess insecticidal properties, among several other properties they exhibit. The female Anopheles mosquito is responsible for transmitting the malaria parasite when infected.

Combination of computational techniques and RNAi reveal targets in Anopheles gambiae for malaria vector control.

Increasing reports of insecticide resistance continue to hamper the gains of vector control strategies in curbing malaria transmission. This makes identifying new insecticide targets or alternative vector control strategies necessary. CLassifier of Essentiality AcRoss EukaRyote (CLEARER), a leave-one-organism-out cross-validation machine learning classifier for essential genes, was used to predict essential genes in Anopheles gambiae and selected predicted genes experimentally validated.

Correction: Heuristic-enabled active machine learning: A case study of predicting essential developmental stage and immune response genes in Drosophila melanogaster.

[This corrects the article DOI: 10.1371/journal.pone.

In Silico Design of Potential Small-Molecule Antibiotic Adjuvants against Ortho Acetyl Sulphydrylase Synthase to Address Antimicrobial Resistance.

The inhibition of -acetyl sulphydrylase synthase isoforms has been reported to represent a promising approach for the development of antibiotic adjuvants. This occurs via the organism developing an unpaired oxidative stress response, causing a reduction in antibiotic resistance in vegetative and swarm cell populations. This consequently increases the effectiveness of conventional antibiotics at lower doses.

Computational Studies on 6-Pyruvoyl Tetrahydropterin Synthase (6-PTPS) of .

6-Pyruvoyl tetrahydropterin synthase (6-PTPS) is a lyase involved in the synthesis of tetrahydrobiopterin. In species where dihydroneopterin aldolase (DHNA) is absent, it acts in the folate biosynthetic pathway necessary for the growth and survival of the parasite. The 6-pyruvoyl tetrahydropterin synthase of (PTPS) has been identified as a potential antimalarial drug target.

Structure-based design, and development of amidinyl, amidoximyl and hydroxamic acid based organic molecules as novel antimalarial drug candidates.

Malaria remains a significant global health concern causing numerous fatalities and the emergence of antimalarial drug resistance highlights the urgent need for novel therapeutic options with innovative mechanisms of action and targets. This study aimed to design potential inhibitors of 6-pyruvoyltetrahydropterin synthase (PTPS), synthesize them, and experimentally validate their efficacy as antimalarial agents. A structure-based approach was employed to design a series of novel derivatives, including amidinyl, amidoximyl and hydroxamic acid analogs (, , , and ), with a focus on their ability to bind to the Zn present in the active site of PTPS.

Impact of congenital heart disease on mortality and other associated outcomes in children hospitalised for acute asthma exacerbation.

Background: Acute asthma exacerbation is one of the most common reasons for paediatric emergency room visits and hospital admissions in the United States of America.

Objective: To assess the impact of CHD on outcomes of children hospitalised for acute asthma exacerbation.

Methods: Children primarily admitted for acute asthma exacerbation were sampled from 2006, 2009, 2012, and 2016 kid inpatient database of the Healthcare Cost and Utilization Project using ICD codes.

A deep population reference panel of tandem repeat variation.

Tandem repeats (TRs) represent one of the largest sources of genetic variation in humans and are implicated in a range of phenotypes. Here we present a deep characterization of TR variation based on high coverage whole genome sequencing from 3550 diverse individuals from the 1000 Genomes Project and H3Africa cohorts. We develop a method, EnsembleTR, to integrate genotypes from four separate methods resulting in high-quality genotypes at more than 1.

Temporal trends and regional variation of heart transplantation in children with intellectual and developmental disabilities.

Background: Historically, intellectual and developmental disability (IDD) has been considered an important factor in choosing potential recipients of organ transplants among many transplant centers. This study evaluated the temporal changes at the national and regional levels in the proportion of heart transplantation in children with IDD.

Methods: Children younger than 19 years in the United Network for Organ Sharing (UNOS) database who received heart transplants from 2010 to 2021 were included in this study.

Synthesis, and antimicrobial efficacy of substituted arylidene-based quinazolin-4(3)-one motifs.

Quinazolin-4(3)-one derivatives have attracted considerable attention in the pharmacological profiling of therapeutic drug targets. The present article reveals the development of arylidene-based quinazolin-4(3)-one motifs as potential antimicrobial drug candidates. The synthetic pathway was initiated through thermal cyclization of acetic anhydride on anthranilic acid to produce 2-methyl-4H-3,1-benzoxazan-4-one 1, which (upon condensation with hydrazine hydrate) gave 3-amino-2-methylquinazolin-4(3)-one 2.

Personalizing medicine in Africa: current state, progress and challenges.

Personalized medicine has been identified as a powerful tool for addressing the myriad of health issues facing different health systems globally. Although recent studies have expanded our understanding of how different factors such as genetics and the environment play significant roles in affecting the health of individuals, there are still several other issues affecting their translation into personalizing health interventions globally. Since African populations have demonstrated huge genetic diversity, there is a significant need to apply the concepts of personalized medicine to overcome various African-specific health challenges.

A Descriptive Analysis of Febrile Seizure Hospitalizations in Children with Congenital Heart Disease in the United States.

Background: Febrile seizure (FS) is the most common convulsive disorder in children. This study analyzed the national proportion of congenital heart disease (CHD) and hospital resource utilization among children admitted for FSs in the U.S.

Mathematical modeling of malaria transmission dynamics in humans with mobility and control states.

Malaria importation is one of the hypothetical drivers of malaria transmission dynamics across the globe. Several studies on malaria importation focused on the effect of the use of conventional malaria control strategies as approved by the World Health Organization (WHO) on malaria transmission dynamics but did not capture the effect of the use of traditional malaria control strategies by vigilant humans. In order to handle the aforementioned situation, a novel system of Ordinary Differential Equations (ODEs) was developed comprising the human and the malaria vector compartments.

Heuristic-enabled active machine learning: A case study of predicting essential developmental stage and immune response genes in Drosophila melanogaster.

Computational prediction of absolute essential genes using machine learning has gained wide attention in recent years. However, essential genes are mostly conditional and not absolute. Experimental techniques provide a reliable approach of identifying conditionally essential genes; however, experimental methods are laborious, time and resource consuming, hence computational techniques have been used to complement the experimental methods.

Polygenic Risk Score in African populations: progress and challenges.

Polygenic Risk Score (PRS) analysis is a method that predicts the genetic risk of an individual towards targeted traits. Even when there are no significant markers, it gives evidence of a genetic effect beyond the results of Genome-Wide Association Studies (GWAS). Moreover, it selects  single nucleotide polymorphisms (SNPs) that  contribute to the disease with low effect size  making it more precise at individual level risk prediction.

Association of Adverse Childhood Experiences with Heart Conditions in Children: Insight from the 2019-2020 National Survey of Children's Health.

Unlabelled: Adverse Childhood Experiences (ACEs) have been associated with a higher risk of developing cardiovascular diseases and premature mortality in adults.

Objectives: We evaluated the associations between ACEs and heart diseases among children in the United States.

Methods: Data on children ages 0 to 17 years reported by parents/guardians to have current heart conditions were analyzed.

A deep population reference panel of tandem repeat variation.

Tandem repeats (TRs) represent one of the largest sources of genetic variation in humans and are implicated in a range of phenotypes. Here we present a deep characterization of TR variation based on high coverage whole genome sequencing from 3,550 diverse individuals from the 1000 Genomes Project and H3Africa cohorts. We develop a method, EnsembleTR, to integrate genotypes from four separate methods resulting in high-quality genotypes at more than 1.

Pharmacophore-Aided Virtual Screening and Molecular Dynamics Simulation Identifies TrkB Agonists for Treatment of -Deficiency Disorders.

Therapeutic intervention in cyclin-dependent kinase-like 5 (CDKL5) deficiency disorders (CDDs) has remained a concern over the years. Recent advances into the mechanistic interplay of signalling pathways has revealed the role of deficient tropomyosin receptor kinase B (TrkB)/phospholipase C γ1 signalling cascade in CDD. Novel findings showed that in vivo administration of a TrkB agonist, 7,8-dihydroxyflavone (7,8-DHF), resulted in a remarkable reversal in the molecular pathologic mechanisms underlying CDD.

Chemistry and Pharmacological diversity of Benzothiazepine - Excellent pathway to drug discovery.

In this era of sporadic advancement in science and technology, a substantial amount of intervention is being set in motion to reduce health-related diseases. Discoveries from researchers have pinpointed the usefulness of heterocyclic compounds, amongst which benzothiazepine (BTZ) derivatives have been synthesized for their various pharmacological activities. This also contributes to their undeniable application in therapeutic medicine for the development of efficacious drugs.

Structure-based pharmacophore modeling, virtual screening, and molecular dynamics simulation studies for identification of 5-aminolevulinate synthase inhibitors.

() 5-aminolevulinic acid synthase (5-ALAS) is an essential enzyme with high selectivity during liver stage development, signifying its potential as a prophylactic antimalarial drug target. The aim of this study was to identify important potential lead compounds which can serve as inhibitors of 5-ALAS using pharmacophore modeling, virtual screening, qualitative structural assessment, ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) evaluation and molecular dynamics simulation. The best model of the tertiary structure of 5-ALAS was obtained using MolProbity, while the following databases were explored for the pharmacophore-based virtual screening: CHEMBL, ChemDiv, ChemSpace, MCULE, MCULE-ULTIMATE, MolPort, NCI Open Chemical Repository, LabNetwork and ZINC databases.

Structure Prediction, Molecular Docking, and Dynamic Simulation of AP2-I Transcription Factor.

Apicomplexan Apetala 2 Invasion (AP2-I) transcription factor (TF) is a protein that regulates the expression of a subset of gene families involved in red blood cell (RBC) invasion. Inhibiting AP2-I TF with small molecules represents a potential new antimalarial therapeutic target to combat drug resistance, which this study aims to achieve. The 3D model structure of AP2-I was predicted using ROBETTA prediction tool and was validated using Save server 6.

Recent advances in functionalized quinoline scaffolds and hybrids-Exceptional pharmacophore in therapeutic medicine.

Quinoline is one of the most common nitrogen-containing heterocycles owing to its fascinating pharmacological properties and synthetic value in organic and pharmaceutical chemistry. Functionalization of this moiety at different positions has allowed for varying pharmacological activities of its derivative. Several publications over the last few decades have specified various methods of synthesis.