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In recent years, human dihydroorotate dehydrogenase inhibitors have been associated with acute myelogenous leukemia as well as studied as potent host targeting antivirals. Starting from MEDS433 (IC50 1.2 nM), we kept improving the structure-activity relationship of this class of compounds characterized by 2-hydroxypyrazolo[1,5-a]pyridine scaffold. Using an in silico/crystallography supported desig
The assessment of remediation on metal-polluted soils is usually focused on total and/or bioavailable metal content. However, these chemical variables do not provide direct information about reductions in heavy metals pressure on soil microorganisms. We propose the use of bacterial communities to evaluate the efficiency of three remediation techniques: crushed mussel shell (CMS) and pine bark (PB)
Appropriate evaluation and experimental design are fundamental for empirical sciences, particularly in data-driven fields. Due to the successes in computational modeling of languages, for instance, research outcomes are having an increasingly immediate impact on end users. As the gap in adoption by end users decreases, the need increases to ensure that tools and models developed by the research co
Importance: The nature of the genetic relationship between major depression and bipolar disorder remains unclear and might be clarified by considering disorders outside of the mood spectrum. Objective: To better understand the relationship between genetic liabilities for major depression (MD) and bipolar disorder (BD). Design, Setting, and Participants: A cohort study was conducted with data for i
High-sensitivity cardiac troponin assays have become the gold standard for diagnosing acute and chronic myocardial injury. The detection of troponin levels beyond the 99th percentile is included in the fourth universal definition of myocardial infarction, specifically recommending the use of sex-specific thresholds. Measurable concentrations below the proposed diagnostic thresholds have been shown
INTRODUCTION: Remote consultations help reduce contact between people and prevent cross-contamination. Little is known about the changes in consultation in European rural primary care during the SARS-CoV-2 (COVID-19) pandemic. The purpose of this mixed-methods cross-sectional study was to find out more about the effects of the pandemic on changes in patient consultations in European rural primary
Several machine learning models have been formulated for protein classification based on an important prerequisite for industrial usage, thermostability, and described herein a classification model for a specific enzyme; serine protease. For building the classifier, 283 thermophilic and 200 mesophilic bacterial genomes were mined for their respective serine protease sequences. Features were extrac
Background: Urosepsis is a life-threatening condition that needs to be addressed without delay. Two critical issues in its management are: (1) Appropriate empirical antibiotic therapy, considering the patients general condition, comorbidity, and the pathogen expected; and (2) Timing of imaging to identify obstruction requiring decompression. Objectives: To identify risk factors associated with 30-
In this paper, we present several possible anomaly free implementations of the Branco-Grimus-Lavoura (BGL) model with two Higgs doublets and one singlet scalar. The model also includes three generations of massive neutrinos that get their mass via a type-I seesaw mechanism. A particular anomaly free realization, which we dub νBGL-1 scenario, is subjected to an extensive phenomenological analysis,
The Thomas-Reiche-Kuhn sum rule is used to form an effective potential that is added to the time-dependent configuration-interaction singles (TDCIS) equations of motion in velocity gauge. The purpose of the effective potential is to include virtual coupling from singles to doubles, which is required for size-consistent velocity-gauge TDCIS results. The proposed method is compared to length-gauge T
Scarce water resources present a major hindrance to ensuring food security. Crop water productivity (WP), embraced as one of the Sustainable Development Goals (SDGs), is playing an integral role in the performance-based evaluation of agricultural systems and securing sustainable food production. This study aims at developing a cloud-based model within the Google Earth Engine (GEE) based on Landsat
Shelterbelts (or windbreaks) can effectively improve the microclimate and soil conditions of adjacent farmland and thus increase crop yield. However, the individual contribution of these two factors to yield changes is still unclear since the short-term effect from the microclimate and the accumulated effect from the soil jointly affect crop yield. The latter (soil effect) is supposed to remain af
A new genus of Neotropical Satyrinae butterflies, Viloriodes Pyrcz & Espeland gen. n. is described in the Pedaliodes Butler complex comprising 11–13 genera and more than 400 species. Support for the new genus is provided by a phylogenetic analysis based on target enrichment (TE) data including 618 nuclear loci with a total of 248,940 nucleotides, and the mitochondrial gene cytochrome oxidase s
Current visual text analysis approaches rely on sophisticated processing pipelines. Each step of such a pipeline potentially amplifies any uncertainties from the previous step. To ensure the comprehensibil- ity and interoperability of the results, it is of paramount importance to clearly communicate the uncertainty not only of the output but also within the pipeline. In this paper, we characte
Nonlinear group delay signals with frequency-varying characteristics are common in a wide variety of fields, for instance, structural health monitoring and fault diagnosis. For such applications, the signal is composed of multiple modes, where each mode may overlap in the frequency-domain. The resulting decomposition and forming of time-frequency representations of the nonlinear group delay modes
Background: Bone Scan Index (BSI) derived from 2D whole-body bone scans is considered an imaging biomarker of bone metastases burden carrying prognostic information. Sodium fluoride (NaF) PET/CT is more sensitive than bone scan in detecting bone changes due to metastases. We aimed to develop a semi-quantitative PET index similar to the BSI for NaF PET/CT imaging and to study its relationship to BS
In myocardial ischemia, melatonin confers antiarrhythmic action, but its electrocardiographic expression is unclear. We aimed to evaluate the effects of melatonin treatment on electrocardiogram (ECG) parameters reflecting major arrhythmogenic factors and to test the association of these parameters with ventricular fibrillation (VF) incidence. Myocardial ischemia was induced by 40 min coronary arte
Many patients with outlet obstruction secondary to prostatic enlargement have lower urinary tract symptoms (LUTSs) and an increased frequency of micturition. The standard treatment is transurethral resection of the prostate (TURP), which alleviates obstruction and symptoms. However, after TURP, 20–40 percent of patients continue to experience LUTSs. The aim of the present study in rats was to iden
