An open repository of real-time COVID-19 indicators Reinhart, Alex; Brooks, Logan; Jahja, Maria ...
Proceedings of the National Academy of Sciences - PNAS,
12/2021, Letnik:
118, Številka:
51
Journal Article
Recenzirano
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The COVID-19 pandemic presented enormous data challenges in the United States. Policy makers, epidemiological modelers, and health researchers all require up-to-date data on the pandemic and relevant ...public behavior, ideally at fine spatial and temporal resolution. The COVIDcast API is our attempt to fill this need: Operational since April 2020, it provides open access to both traditional public health surveillance signals (cases, deaths, and hospitalizations) and many auxiliary indicators of COVID-19 activity, such as signals extracted from deidentified medical claims data, massive online surveys, cell phone mobility data, and internet search trends. These are available at a fine geographic resolution (mostly at the county level) and are updated daily. The COVIDcast API also tracks all revisions to historical data, allowing modelers to account for the frequent revisions and backfill that are common for many public health data sources. All of the data are available in a common format through the API and accompanying R and Python software packages. This paper describes the data sources and signals, and provides examples demonstrating that the auxiliary signals in the COVIDcast API present information relevant to tracking COVID activity, augmenting traditional public health reporting and empowering research and decision-making.
Today, early characterization of drug properties by the Biopharmaceutics Classification System (BCS) has attracted significant attention in pharmaceutical discovery and development. In this ...direction, the present report provides a systematic study of the development of a BCS-based provisional classification (PBC) for a set of 322 oral drugs. This classification, based on the revised aqueous solubility and the apparent permeability across Caco-2 cell monolayers, displays a high correlation (overall 76%) with the provisional BCS classification published by World Health Organization (WHO). Current database contains 91 (28.3%) PBC class I drugs, 76 (23.6%) class II drugs, 97 (31.1%) class III drugs, and 58 (18.0%) class IV drugs. Other approaches for provisional classification of drugs have been surveyed. The use of a calculated polar surface area with a labetalol value as a high permeable cutoff limit and aqueous solubility higher than 0.1 mg/mL could be used as alternative criteria for provisionally classifying BCS permeability and solubility in early drug discovery. To develop QSPR models that allow screening PBC and BCS classes of new molecular entities (NMEs), 18 statistical linear and nonlinear models have been constructed based on 803 0-2D Dragon and 126 Volsurf+ molecular descriptors to classify the PBC solubility and permeability. The voting consensus model of solubility (VoteS) showed a high accuracy of 88.7% in training and 92.3% in the test set. Likewise, for the permeability model (VoteP), accuracy was 85.3% in training and 96.9% in the test set. A combination of VoteS and VoteP appropriately predicts the PBC class of drugs (overall 73% with class I precision of 77.2%). This consensus system predicts an external set of 57 WHO BCS classified drugs with 87.5% of accuracy. Interestingly, computational assignments of the PBC class reasonably correspond to the Biopharmaceutics Drug Disposition Classification System (BDDCS) allocations of drugs (accuracy of 63.3–69.8%). A screening assay has been simulated using a large data set of compounds in different drug development phases (1, 2, 3, and launched) and NMEs. Distributions of PBC forecasts illustrate the current status in drug discovery and development. It is anticipated that a combination of the QSPR approach and well-validated in vitro experimentations could offer the best estimation of BCS for NMEs in the early stages of drug discovery.
In silico prediction of antileishmanial activity using quantitative structure–activity relationship (QSAR) models has been developed on limited and small datasets. Nowadays, the availability of large ...and diverse high-throughput screening data provides an opportunity to the scientific community to model this activity from the chemical structure. In this study, we present the first KNIME automated workflow to modeling a large, diverse, and highly imbalanced dataset of compounds with antileishmanial activity. Because the data is strongly biased toward inactive compounds, a novel strategy was implemented based on the selection of different balanced training sets and a further consensus model using single decision trees as the base model and three criteria for output combinations. The decision tree consensus was adopted after comparing its classification performance to consensuses built upon Gaussian-Naı̈ve-Bayes, Support-Vector-Machine, Random-Forest, Gradient-Boost, and Multi-Layer-Perceptron base models. All these consensuses were rigorously validated using internal and external test validation sets and were compared against each other using Friedman and Bonferroni–Dunn statistics. For the retained decision tree-based consensus model, which covers 100% of the chemical space of the dataset and with the lowest consensus level, the overall accuracy statistics for test and external sets were between 71 and 74% and 71 and 76%, respectively, while for a reduced chemical space (21%) and with an incremental consensus level, the accuracy statistics were substantially improved with values for the test and external sets between 86 and 92% and 88 and 92%, respectively. These results highlight the relevance of the consensus model to prioritize a relatively small set of active compounds with high prediction sensitivity using the Incremental Consensus at high level values or to predict as many compounds as possible, lowering the level of Incremental Consensus. Finally, the workflow developed eliminates human bias, improves the procedure reproducibility, and allows other researchers to reproduce our design and use it in their own QSAR problems.
The heterogeneity of the Caco-2 cell line and differences in experimental protocols for permeability assessment using this cell-based method have resulted in the high variability of Caco-2 ...permeability measurements. These problems have limited the generation of large datasets to develop accurate and applicable regression models. This study presents a QSPR approach developed on the KNIME analytical platform and based on a structurally diverse dataset of over 4900 molecules. Interpretable models were obtained using random forest supervised recursive algorithms for data cleaning and feature selection. The development of a conditional consensus model based on regional and global regression random forest produced models with RMSE values between 0.43–0.51 for all validation sets. The potential applicability of the model as a surrogate for the in vitro Caco-2 assay was demonstrated through blind prediction of 32 drugs recommended by the International Council for the Harmonization of Technical Requirements for Pharmaceuticals (ICH) for validation of in vitro permeability methods. The model was validated for the preliminary estimation of the BCS/BDDCS class. The KNIME workflow developed to automate new drug prediction is freely available. The results suggest that this automated prediction platform is a reliable tool for identifying the most promising compounds with high intestinal permeability during the early stages of drug discovery.
In the last century, there has been more than enough research that proved the association of high lipid and glucose levels with cardiovascular disease, thus establishing the current well-known ...traditional cardiovascular risk factors such as dyslipidemia, diabetes, and metabolic syndrome. Hence, these cardiovascular risk factors are target therapy for glucose and lipid-lowering agents to prevent adverse cardiovascular events. However, despite controlling the lipid and glucose levels, some studies demonstrated the subclinical atherosclerosis suggesting that these cardiovascular risk factors alone cannot account for the entire atherosclerosis burden. In the last years, large-scale clinical trials demonstrated the operation of the inflammatory pathway in atherosclerotic cardiovascular disease (ASCVD) by the immune system, both the innate (neutrophils, macrophages) and adaptive (T cell and other lymphocytes) limbs, contribute to atherosclerosis and atherothrombosis. In this regard, some studies that use antiinflammatory therapy targeting the immune system by modulating or blocking interleukins, also known as anti-cytokine therapy, have been shown to reduce the risk of adverse cardiovascular events in patients with previous coronary artery disease. In this regard, the U.S. Food and Drug Administration (FDA) approved the use of colchicine 0.5 mg once daily for reducing cardiovascular events in patients who have established ASCVD and high residual systemic inflammation. Therefore, measuring the systemic inflammation can improve the cardiovascular risk assessment and identify the subsets of patients that will benefit from anti-cytokine therapy after diagnosis of ASCVD or after myocardial revascularization.
The interaction between climate change and biological invasions is a global conservation challenge with major consequences for invasive species management. However, our understanding of this ...interaction has substantial knowledge gaps; this is particularly relevant for invasive snakes on islands because they can be a serious threat to island ecosystems. Here we evaluated the potential influence of climate change on the distribution of invasive snakes on islands, using the invasion of the California kingsnake (Lampropeltis californiae) in Gran Canaria. We analysed the potential distribution of L. californiae under current and future climatic conditions in the Canary Islands, with the underlying hypothesis that the archipelago might be suitable for the species under these climate scenarios. Our results indicate that the Canary Islands are currently highly suitable for the invasive snake, with increased suitability under the climate change scenarios tested here. This study supports the idea that invasive reptiles represent a substantial threat to near-tropical regions, and builds on previous studies suggesting that the menace of invasive reptiles may persist or even be exacerbated by climate change. We suggest future research should continue to fill the knowledge gap regarding invasive reptiles, in particular snakes, to clarify their potential future impacts on global biodiversity.
•We used the invasion of Lampropeltis californiae to contribute to filling knowledge gaps regarding invasive species and climate change synergy.•Most of the archipelago is currently suitable to host the invasive snake, and future climatic conditions are likely to foster its expansion.•Climate change may aggravate the impact of invasive snakes on islands.
ObjectiveThe main objective of the present study was to compare the use of four-dimensional (4D) flow MRI with the habitual sequence (two-dimensional phase-contrast (2DPC) MRI) for the assessment of ...aortic regurgitation (AR) in the clinical routine.MethodsThis was a retrospective, observational cohort study of patients with varying grades of AR. For the purposes of the present study, we selected all the cases with a regurgitant fraction (RF)>5% as determined by 2DPC MRI (n=34). In all cases, both sequences (2DPC and 4D flow MRI) were acquired in a single session to ensure comparability. We compared the results of the two techniques by evaluating forward flow, regurgitant flow and regurgitation fraction. Then, the patients were divided into subgroups to determine if these factors had any influence on the measurements: aortic diameter (≤ vs >38 mm), valve anatomy (tricuspid vs bicuspid/quadricuspid), stenosis (gradient ≥15 vs <15) and region of interest location (aortic valve vs sinotubular junction).ResultsNo statistically significant differences were observed between the two techniques with Pearson’s correlation coefficients (r) of forward flow (r=0.826/p value<0001), regurgitant flow (r=0.866/p value<0001) and RF (r=0.761/p value<0001).ConclusionsThe findings of this study confirm the value of 4D flow MRI for grading AR in clinical practice with an excellent correlation with the standard technique (2DPC MRI).
Anatomy of the cardiac conduction system Padala, Santosh K.; Cabrera, José‐Angel; Ellenbogen, Kenneth A.
Pacing and clinical electrophysiology,
January 2021, Letnik:
44, Številka:
1
Journal Article
Recenzirano
The specialized cardiomyocytes that constitute the conduction system in the human heart, initiate the electric impulse and result in rhythmic and synchronized contraction of the atria and ventricles. ...Although the atrioventricular (AV) conduction axis was described more than a century ago by Sunao Tawara, the anatomic pathway for propagation of impulse from atria to the ventricles has been a topic of debate for years. Over the past 2 decades, there has been a resurgence of conduction system pacing (CSP) by implanting pacing leads in the His bundle region in lieu of chronic right ventricular pacing that is associated with worse clinical outcomes. The inherent limitations of implanting the leads in the His bundle region has led to the emergence of left bundle branch area pacing in the past 3 years as an alternative strategy for CSP. The clinical experience from performing CSP has helped electrophysiologists gain deeper insight into the anatomy and physiology of cardiac conduction system. This review details the anatomy of the cardiac conduction system, and highlights some of the recently published articles that aid in better understanding of the AV conduction axis and its variations, the knowledge of which is critical for CSP. The remarkable evolution in technology has led to visualization of the cardiac conduction system using noninvasive, nondestructive high‐resolution contrast‐enhanced micro‐computed tomography imaging that may aid in future CSP. We also discuss from anatomical perspective, the differences seen clinically with His bundle pacing and left bundle branch area pacing.
Introducción: Las piezas dentarias luego de tratamiento de endodoncia aumentan su susceptibilidad a la fractura, lo que está asociado, principalmente, con la pérdida de la estructura dental. ...Objetivo: Evaluar in vitro, la resistencia a la fractura de premolares superiores con tratamientos de endodoncia mediante acceso tradicional, conservador y conservador Ninja, con restauración provisoria y final. Métodos: Estudio prospectivo de diseño experimental longitudinal con 42 premolares superiores donados, separados en 3 grupos según el tipo de acceso de endodoncia a aplicarse y luego cada uno en dos subgrupos según el tipo de restauración, y un grupo control, al cual no se le realiza endodoncia. Luego de realizar el tratamiento y la restauración, se evaluó la resistencia a la fractura mediante carga compresiva oblicua (45°), en una máquina de carga universal. Las cargas requeridas para la fractura se registraron en newtons y fueron comparadas estadísticamente. Resultados: Las piezas tratadas mediante acceso conservador Ninja con restauración provisoria y final, requirieron una carga promedio para la fractura de 513,45 N y 638,13 N, respectivamente. Fuerzas significativamente mayores a las resistencias ofrecidas por los otros tratamientos con p < 0,05. Asimismo, no hubo diferencias significativas en las resistencias ofrecidas, entre los casos de acceso conservador y acceso tradicional, ni al comparar los tipos de restauración aplicados con p > 0,05. Conclusiones: En la endodoncia in vitro, el diseño del acceso a la cavidad, tipo conservador Ninja, afectó significativamente la resistencia a la fractura de los premolares superiores, adquiriendo un comportamiento biomecánico similar al de las piezas control.
Bentonite is a claystone formed by a complex mineralogical mixture, composed of montmorillonite, illite, and accessory minerals like quartz, cristobalite, feldspars, carbonates, and minor amounts of ...iron oxy-hydroxides. Bentonite presents complexity at various scales: (1): a single mineral may present different chemical composition within the same quarry (e.g., feldspars solid solutions); (2): montmorillonite presents variability in the cation-exchange distribution while illite may be presented as mixed-layer with smectite sheets; and (3): hardness and crystal size are larger in accessory minerals than in clay minerals, preventing uniform grinding of bentonite. The FEBEX bentonite used is originally from Almería (Spain), and it is a predominantly calcium, magnesium, and sodium bentonite. This Spanish FEBEX bentonite has been hydrothermally altered at laboratory scale for 7–14 years. A thermal gradient was generated by heating a disk of pressed iron powder, simulating the metal waste canister, in contact with the compacted bentonite sample. Hydration was forced from the opposite direction. XRD recorded patterns were very similar. In order to minimize the bias of XRD semi-quantitative determination methods, Rietveld refinement was performed using BGMN software and different structural models. Confidence in the quantification of the main phases allows us to convincingly detect other subtle changes such as the presence of calcite in the hydration front, right at the interface between the saturated and unsaturated bentonite, or the presence of goethite, and not hematite, in the saturated bentonite, near the source of hydration. Smectite component was 72 ± 3% and the refinement was consistent with the presence of ~10% illite, comparable with previous characterizations.
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