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Background Pain is a common symptom in pediatric inflammatory bowel disease (IBD) and is associated with poor health outcomes, yet additional knowledge about the psychosocial correlates of pain is needed to optimize clinical care. The purpose of this study is to systematically review the psychosocial factors associated with pain and pain impact in youth diagnosed with IBD within a developmentally informed framework. Methods Manual and electronic searches yielded 2641 references. Two authors conducted screening (98% agreement), and data extraction was performed in duplicate. Average study quality was rated using the National Institutes of Health Quality Assessment Tool. Results Ten studies (N = 763 patients; N = 563 Crohn disease, N = 200 ulcerative/ indeterminate colitis) met the inclusion criteria. Findings showed consistent evidence that higher levels of child depression symptoms and child pain catastrophizing were associated with significantly greater pain and pain impact (magnitude of association ranged from small to large across studies). Greater pain and pain impact were also associated with higher levels of child anxiety symptoms, child pain threat, child pain worry, and parent pain catastrophizing. Within the included studies, female sex and disease severity were both significantly associated with pain and pain impact. Study quality was moderate on average. Conclusions There is evidence that child psychosocial factors are associated with pain and pain impact in pediatric IBD; more studies are needed to examine parent- and family-level psychosocial factors. Youth with IBD should be routinely screened for pain severity, pain impact, and psychosocial risk factors such as anxiety/depression.Methotrexate (MTX) is an efficient chemotherapeutic and immunosuppressant drug, but the hepatotoxicity of MTX limits its clinical use. Naringin (Nar) is a flavonoid derived from Citrus paradise, and has been shown to possess several pharmacological activities, including free-radical scavenging and antioxidant properties. In the present study, we first tested the possible protective effects of multiple doses of Nar against MTX-induced acute hepatotoxicity in rats, and then we investigated the growth inhibition and apoptotic effects of MTX and/or Nar against the HepG2 hepatocarcinoma cell line. Our in vivo results showed that Nar significantly reduced MTX-induced increases in serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and total bilirubin levels. Nar also reduced MTX-induced oxidative stress by significantly reducing liver malondialdehyde (MDA) and nitric oxide (NO) content and increasing superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione (GSH). In addition, Nar significantly counteracted MTX-induced increases in hepatic interleukin-6 and tumor necrosis factor-α (TNF-α). Further, Nar greatly protected hepatocyte ultrastructure against MTX-induced injury. In contrast, in vitro MTX and/or Nar treatment of HepG2 cells for 48 h exhibited a cytotoxic effect and induced apoptosis in a dose-dependent manner mediated by a significant increase in the Bax/Bcl-2 protein expression ratio. Noticeably, Nar potentiated the MTX effect on the Bax/Bcl-2 ratio. In conclusion, Nar decreased MTX-induced functional and ultrastructural liver damage in a tumor-free animal model. Also, our data introduce MTX and Nar as promising antiproliferative agents with a distinctive mode of action, inducing apoptosis in HepG2 tumor cells through activation of Bax and down-regulation of Bcl-2 protein expression.Objective As COVID-19 started its rapid emergence and gradually transformed into an unprecedented pandemic, the need for having a knowledge repository for the disease became crucial. To address this issue, a new COVID-19 machine readable dataset known as COVID-19 Open Research Dataset (CORD-19) has been released. Based on this, our objective was to build a computable co-occurrence network embeddings to assist association detection amongst COVID-19 related biomedical entities. Materials and methods Leveraging a Linked Data version of CORD-19 (i.e., CORD-19-on-FHIR), we first utilized SPARQL to extract co-occurrences among chemicals, diseases, genes, and mutations and build a co-occurrence network. We then trained the representation of the derived co-occurrence network using node2vec with four edge embeddings operations (L1, L2, Average, and Hadamard). https://www.selleckchem.com/products/cx-5461.html Six algorithms (Decision Tree, Linear Regression, Support Vector Machine, Random Forest, Naive Bayes, and Multi-layer Perceptron) were applied to evaluate performance on link prediction. An unsupervised learning strategy was also developed incorporating the t-SNE and DBSCAN algorithms for case studies. Results Random Forest classifier showed the best performance on link prediction across different network embeddings. For edge embeddings generated using the Average operation, Random Forest achieved the optimal average precision of 0.97 and F1 score of 0.90. For unsupervised learning, 63 clusters were formed with silhouette score of 0.128. Significant associations were detected for five coronavirus infectious diseases in their corresponding subgroups. Conclusion In this study, we constructed COVID-19-centered co-occurrence network embeddings. Results indicated that the generated embeddings were able to extract significant associations for COVID-19 and coronavirus infectious diseases.Amidines are a preeminent group of organic compounds having wide applications in various industries. Here, we have developed a simple one-step reaction protocol for the facile synthesis of N-arylamidines catalysed by calcium bis(hexamethyldisilazide) [CaN(SiMe3)22(THF)2]. The amidine synthesis was readily achieved from organic nitriles and amines which provided a broad substrate scope ranging from electron-withdrawing to electron-donating substitutions as well as heterocyclic substitution. The reaction was carried out in a solvent-free medium under ambient conditions. The nucleophilic addition of aromatic amines to aryl nitriles led to good to excellent yields of the corresponding amidines. The reactivity of the amidines was further examined and the respective urea derivatives were achieved in excellent yields. The plausible mechanism involves the generation of an active calcium amido pre-catalyst that helps in the activation of nitriles in the reaction course.
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