Class imbalance is a known issue in classification tasks that can lead to predictive bias toward dominant classes. This paper introduces a novel straightforward Bayesian framework that adjusts posterior probabilities to counteract the bias introduced by imbalanced data sets. Instead of relying on the mean posterior distribution of class probabilities, we propose a method that scales the posterior probability of each class according to their representation in the training data.
View Article and Find Full Text PDFBackground: Despite the outstanding measles vaccine coverage (MVC) in Eritrea, sporadic outbreaks are not uncommon. Therefore, understanding the incidence of laboratory-confirmed measles virus cases, related factors, and spatial inequalities in testing and surveillance remains crucial. In this analysis, we evaluated the incidence and spatiotemporal distribution of measles in Eritrea.
View Article and Find Full Text PDFCardiotoxicity is one of the leading causes of compound attrition during drug development. Most screening platforms aim at detecting acute cardio-electrophysiological changes and drug-induced chronic functional alterations are often not studied in the early stage of drug development. Therefore, we developed an assay using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) that evaluates both drug-induced acute and delayed electrophysiological and cytotoxic effects of reference compounds with clinically known cardiac outcomes.
View Article and Find Full Text PDFDrug-induced seizure liability is a significant safety issue and the basis for attrition in drug development. Occurrence in late development results in increased costs, human risk, and delayed market availability of novel therapeutics. Therefore, there is an urgent need for biologically relevant, in vitro high-throughput screening assays (HTS) to predict potential risks for drug-induced seizure early in drug discovery.
View Article and Find Full Text PDFEarly identification of cardiac risk is essential for reducing late-stage attrition in drug development. We adapted the previously published cardiac hazard risk-scoring system using a calcium transient assay in human stem cell-derived CMs for the identification of cardiac risks recorded from the new hiPSC-CM line and investigated its predictivity and translational value based on the screening of a large number of reference and proprietary compounds. Evaluation of 55 reference drugs provided the translation of various pharmacological effects into a single hazard label (no, low, high, or very high hazard) using a Ca-sensitive fluorescent dye assay recorded by -by FDSS/µCell Functional Drug Screening System (Hamamatsu on hiPSC-CM line (FCDI iCell Cardiomyocytes).
View Article and Find Full Text PDFEritrea is an East African multiethnic country with an intermediate endemicity for hepatitis B. Our aim was to establish the most prevalent genotypes of hepatitis B virus (HBV) among patients with liver disease. A total of 293 Eritrean patients with liver disease who were hepatitis B surface antigen (HBsAg) positive were enrolled.
View Article and Find Full Text PDFBackground: Understanding the natural history of chronic hepatitis B (CHB) virus infection is important for determining optimal management and predicting prognosis in patients. The aim of this study was to determine the prevalence of different phases of CHB infection among Eritrean patients and to identify the proportion of patients who are eligible for treatment according to the latest American Association for the Study of Liver Diseases (AASLD) guidelines.
Methods: This cross-sectional study enrolled 293 CHB patients (213 males and 80 females) between Jan 2017 and Feb 2019.
Background: Globally, sixty-two percent of cerebrovascular disease and forty-nine percent of ischemic heart disease are attributable to increased blood pressure. Half of the patients with stroke and heart disease were due to hypertension.
Objective: This study aimed to identify prevalence of hypertension and its associated factors in Gimbi town, Ethiopia.
The blood-brain barrier (BBB) is often a limiting factor for getting drugs in the brain. Bypassing the BBB by intranasal (IN), or also called nose to brain (NTB), route is an interesting and frequently investigated concept for brain drug delivery. However, despite the body of evidence for IN drug delivery in literature over the last decades, reproducibility and interpretation of animal data remain challenging.
View Article and Find Full Text PDFAcetaminophen, a nonmutagenic compound as previously concluded from bacteria, in vitro mammalian cell, and in vivo transgenic rat assays, presented a good profile as a nonmutagenic reference compound for use in the international multilaboratory Pig-a assay validation. Acetaminophen was administered at 250, 500, 1,000, and 2,000 mg·kg ·day to male Sprague Dawley rats once daily in 3 studies (3 days, 2 weeks, and 1 month with a 1-month recovery group). The 3-Day and 1-Month Studies included assessments of the micronucleus endpoint in peripheral blood erythrocytes and the comet endpoint in liver cells and peripheral blood cells in addition to the Pig-a assay; appropriate positive controls were included for each assay.
View Article and Find Full Text PDFThe goal of this research consortium including Janssen, MSD, Ncardia, FNCR/LBR, and Health and Environmental Sciences Institute (HESI) was to evaluate the utility of an additional in vitro assay technology to detect potential drug-induced long QT and torsade de pointes (TdP) risk by monitoring cytosolic free Ca2+ transients in human stem-cell-derived cardiomyocytes (hSC-CMs). The potential proarrhythmic risks of the 28 comprehensive in vitro proarrhythmia assay (CiPA) drugs linked to low, intermediate, and high clinical TdP risk were evaluated in a blinded manner using Ca2+-sensitive fluorescent dye assay recorded from a kinetic plate reader system (Hamamatsu FDSS/µCell and FDSS7000) in 2D cultures of 2 commercially available hSC-CM lines (Cor.4U and CDI iCell Cardiomyocytes) at 3 different test sites.
View Article and Find Full Text PDFAs the Ethiopian health system faced critical resource constraints, wise use of the available health resources is a priority agenda. Therefore, our study aimed to assess technical efficiency of maternal and reproductive health services in public hospitals of Oromia regional state, Ethiopia. Two-stage data envelopment analysis was performed among 14 hospitals with input orientation and variable returns to scale assumptions.
View Article and Find Full Text PDFBackground: The fact that the majority of patients come late creates management difficulties as these first hours are important to avoid secondary insults to the brain and preserve the ischemic penumbra. Although thrombolytic treatments are currently not available in our hospital, significant delays during the prehospital or in-hospital phases of care create management difficulties and would make such advanced treatments impossible in the future in Ethiopia.
Methods: Prospective observational study was carried at stroke unit of Jimma University Medical Center for 4 consecutive months from March 10 to July 10, 2017.
Flubendazole (FBZ) is highly efficacious against filarial nematodes after parenteral administration and presents a promising macrofilaricidal drug candidate for the elimination of onchocerciasis and other filariae. In the present study the efficacy of a newly developed bioavailable amorphous solid dispersion (ASD) oral formulation of FBZ was investigated in the Litomosoides sigmodontis jird model. FBZ was administered to chronically infected, microfilariae-positive jirds by single (40mg/kg), repeated (2, 6 or 15mg/kg for 5 or 10 days) oral (OR) doses or single subcutaneous (SC) injections (2 or 10mg/kg).
View Article and Find Full Text PDFRiver blindness and lymphatic filariasis are two filarial diseases that globally affect millions of people mostly in impoverished countries. Current mass drug administration programs rely on drugs that primarily target the microfilariae, which are released from adult female worms. The female worms can live for several years, releasing millions of microfilariae throughout the course of infection.
View Article and Find Full Text PDFThe Onchocerca ochengi adult implant and Brugia malayi microfilariemic Severe-Combined Immunodeficient (SCID) mouse models are validated screens to measure macrofilaricidal and microfilaricidal activities of candidate onchocerciasis drugs. The purpose of this study was to assess whether 5 daily sub-cutaneous (s.c.
View Article and Find Full Text PDFHepatocellular carcinoma is a major cause of cancer death worldwide, accounting for over half a million deaths per year. Its incidence varies with geographic locations and the type of etiologic factors. In Ethiopia, unidentified causes of liver disease are of sizeable proportion.
View Article and Find Full Text PDFHuman induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as a promising cardiac safety platform, demonstrated by numerous validation studies using drugs with known cardiac adverse effects in humans. However, the challenge remains to implement hiPSC-CMs into cardiac de-risking of new chemical entities (NCEs) during preclinical drug development. Here, we used the calcium transient screening assay in hiPSC-CMs to develop a hazard score system for cardiac electrical liabilities.
View Article and Find Full Text PDFBackground/aims: There have been numerous efforts to reduce mother-to-child transmission (MTCT) of hepatitis B virus (HBV) with antiviral agents during pregnancy. However, there are limited data regarding the outcomes of pregnant women after delivery. This study was performed to evaluate the efficacy of antiviral agents in preventing MTCT of HBV and maternal long-term outcomes.
View Article and Find Full Text PDFThe present study shows that small non-territorial terminal-phase males of the rusty parrotfish Scarus ferrugineus are reproductively active and are comparable with initial-phase males in behaviour, rates of participation during group-spawning and success in streaking into pair spawning. Large territorial terminal-phase males defend contiguous territories for several hours during the morning where they pair spawn with initial-phase females.
View Article and Find Full Text PDFThe latent Markov (LM) model is a popular method for identifying distinct unobserved states and transitions between these states over time in longitudinally observed responses. The bootstrap likelihood-ratio (BLR) test yields the most rigorous test for determining the number of latent states, yet little is known about power analysis for this test. Power could be computed as the proportion of the bootstrap p values (PBP) for which the null hypothesis is rejected.
View Article and Find Full Text PDFBackground: Mixed findings in biobehavioral research on heart disease may partly be attributed to age-related differences in the prognostic value of psychological distress. This study sought to test the hypothesis that Type D (distressed) personality contributes to an increased mortality risk following implantable cardioverter defibrillator (ICD) treatment in younger patients but not in older patients.
Methods: The Type D Scale (DS14) was used to assess general psychological distress in 455 younger (≤70 y, m = 59.
Background: The patient assessment of chronic illness care (PACIC) is a promising instrument to evaluate the chronic care experiences of patients, yet additional validation is needed to improve its usefulness.
Methods: A total of 1941 patients with diabetes completed the questionnaire. Reliability coefficients and factor analyses were used to psychometrically test the PACIC and PACIC+ (i.