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Due to the large amount of chemical substances on the market, fast and reproducible screening is essential to prioritize chemicals for further evaluation according to highest concern. We here evaluate the performance of structural similarity models that are developed to identify potential substances of very high concern (SVHC) based on structural similarity to known SVHCs. These models were developed following a systematic analysis of the performance of 112 different similarity measures for varying SVHC-subgroups. The final models consist of the best combinations of fingerprint, similarity coefficient and similarity threshold, and suggested a high predictive performance (≥80%) on an internal dataset consisting of SVHC and non-SVHC substances. However, the application performance on an external dataset was not evaluated. Here, we evaluated the application performance of the developed similarity models with a 'pseudo-external assessment' on a set of substances (n = 60-100 for the varying SVHC-subgroups) that weexpert opinions. For the PBT/vPvB model, particularly false positive substances were identified, indicating the necessity of outcome interpretation. The developed similarity models are made available as a freely-accessible online tool. In general, the structural similarity models showed great potential for screening and prioritization purposes. The models proved to be effective in identifying groups of substances of potential concern, and could be used to identify follow-up directions for substances of potential concern.Quantitative whole-body autoradiography (QWBA) is largely used to evaluate tissue distribution of small molecule drugs. In QWBA, radioactivity is measured as the intensity obtained from the autoradiogram. It is known that lower intensity per a region of interest (ROI) or smaller size of ROI increases the variability of intensity. In fact, as some tissues are very small (e.g., the choroidea), ensuring reliability on the intensity for measuring radioactivity in these tissues is difficult in case of under- or over-estimation of radioactivity concentration owing to their variation of low radioactivity intensity of ROI. We thus analyzed the relationships between the size, intensity, and precision of ROI to determine the statistically significant lower limit of quantification (LLOQ) in very small tissues. To investigate the difference in correlation between the radiation source (commercial planar radiation standard [com-ST] and self-made radiation standard [self-ST] consisting of radioactive compounds and matrices), apparatus, or setting environment of the apparatus, correlation analysis was conducted under various conditions. Our results revealed that LLOQ can be calculated by simply using the correlation equation because a common relationship was observed between self-ST, which is used in QWBA, and com-ST. This methodology was thus considered valuable for ensuring LLOQ determination in QWBA.
Diabetes self-care requires support to empower patients to improve self-monitoring and maintain the necessary self-care behaviors. We aimed to identify features of a mobile-based application as a technology-based device for self-care of people living with T2DM.
This study was conducted in two main phases in 2020. In the first phase, a literature review study was performed to identify the data elements and technical features of the T2DM self-care application. In the second phase, using the information obtained from the review of similar articles, a questionnaire was designed to validate identified requirements. The statistical population of the present study consisted of 22 endocrinologists and metabolic specialists.
Identification of 55 data elements and technical features for mobile-based self-care application for people with T2DM, and according to the statistical population, 15data elements for demographic requirements, 16 data elements for clinical requirements, and 17 features for the technical capability of this app were selected.
Blood sugar monitoring, exercise, nutrition, weight monitoring, and educational capabilities were the most highlighted technical features of the T2DM self-care application. Software designers can use these requirements to design a self-care app for people with type-2 diabetes that can help manage and improve patients' health status.
Blood sugar monitoring, exercise, nutrition, weight monitoring, and educational capabilities were the most highlighted technical features of the T2DM self-care application. Software designers can use these requirements to design a self-care app for people with type-2 diabetes that can help manage and improve patients' health status.
Circulating uric acid levels were associated with insulin resistance, but the causality is unclear. We aimed to investigate the association between plasma uric acid and insulin resistance in newly diagnosed type 2 diabetes (T2D).
We enrolled 1,938 patients who underwent a 75-g oral glucose tolerance test. Insulin resistance was estimated based on the homeostatic model assessment index (HOMA2-IR) and the Matsuda index. Uric acid was measured in fasting plasma by uricase-peroxidase method. INF195 We genotyped single nucleotide polymorphisms (SNPs) that were recently identified as top hits in genome-wide association studies of uric acid levels. A weighted genetic risk score (wGRS) was calculated based on the associations between selected SNPs and uric acid levels.
The adjusted β coefficients for Ln-transformed Matsuda index and HOMA2-IR per 1mg/dL uric acid increment were -0.070 (95%CI -0.089, -0.052) and 0.057 (95%CI 0.039, 0.075). These associations were more pronounced among women than men. In Mendelian randomization analysis, the wGRS raised uric acid by 0.225mg/dL (95%CI 0.138, 0.312) per SD increase of the score. However, no association was observed between the wGRS and insulin resistance indices whether in men or women.
Elevated plasma uric acid was associated with higher risk of insulin resistance, along with observation of gender difference in such association. However, our study does not support a causal role of plasma uric acid on insulin resistance among newly diagnosed T2D patients.
Elevated plasma uric acid was associated with higher risk of insulin resistance, along with observation of gender difference in such association. However, our study does not support a causal role of plasma uric acid on insulin resistance among newly diagnosed T2D patients.
Read More: https://www.selleckchem.com/products/inf195.html
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