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  • Roberson Frederiksen posted an update 2 days, 8 hours ago

    CIViCpy enables users to query CIViC content as dynamic objects in Python. We assess the viability of CIViCpy as a tool for advancing individualized patient care by using it to systematically match CIViC evidence to observed variants in patient cancer samples. RESULTS We used CIViCpy to evaluate variants from 59,437 sequenced tumors of the American Association for Cancer Research Project GENIE data set. We demonstrate that CIViCpy enables annotation of > 1,200 variants per second, resulting in precise variant matches to CIViC level A (professional guideline) or B (clinical trial) evidence for 38.6% of tumors. CONCLUSION The clinical interpretation of genomic variants in cancers requires high-throughput tools for interoperability and analysis of variant interpretation knowledge. These needs are met by CIViCpy, a software development kit for downstream applications and rapid analysis. CIViCpy is fully documented, open-source, and available free online.PURPOSE To construct a multi-institutional radiomic model that supports upfront prediction of progression-free survival (PFS) and recurrence pattern (RP) in patients diagnosed with glioblastoma multiforme (GBM) at the time of initial diagnosis. PATIENTS AND METHODS We retrospectively identified data for patients with newly diagnosed GBM from two institutions (institution 1, n = 65; institution 2, n = 15) who underwent gross total resection followed by standard adjuvant chemoradiation therapy, with pathologically confirmed recurrence, sufficient follow-up magnetic resonance imaging (MRI) scans to reliably determine PFS, and available presurgical multiparametric MRI (MP-MRI). The advanced software suite Cancer Imaging Phenomics Toolkit (CaPTk) was leveraged to analyze standard clinical brain MP-MRI scans. A rich set of imaging features was extracted from the MP-MRI scans acquired before the initial resection and was integrated into two distinct imaging signatures for predicting mean shorter or longer PFS and neaccessibility to advanced computational algorithms for deriving imaging signatures predictive of clinical outcome and could similarly be used for a variety of radiomic and radiogenomic analyses.Background Obesity is present in 17% of US youth, age 2-19 years, but the extent to which obesity in childhood is associated with higher BMI and fat mass in middle age is unclear. In this study, links between childhood body size and BMI and body composition at age ∼50 were assessed. Methods Child Health and Development Studies participants, born between 1960 and 1963 in Alameda County, and still living in California, from whom anthropometric data were collected at age 5, 9-11, and/or 15-17 years were followed-up at age ∼50 for anthropometric outcomes (251 women; 249 men). Linear regression analyses assessed whether overweight (85th to less then 95th BMI percentile) or obesity (≥95th BMI percentile) at age 5 were associated with BMI, fat mass index (FMI), and lean mass index (LMI) at age ∼50. NSC 27223 chemical structure Results At age 50, participants with obesity at age 5 had BMI scores that were 6.51 units higher [95% confidence interval (CI) = 3.67-9.35] than participants who were normal weight at age 5; FMI and LMI scores were 4.15 (95% CI = 1.98-6.32) and 2.36 (95% CI = 1.45-3.26) units higher, respectively. However, obesity experienced at age 5 had only a modest positive predictive value for predicting the presence of obesity at age 50 (67%), whereas obesity present at age 15-17 had a higher positive predictive value (86%). Conclusions The experience of obesity at age 5 for members of this birth cohort was associated with significantly higher BMI, FMI, and LMI at age ∼50.Cancer, still in the limelight due to its dreadful nature, shows overexpression of multiple signaling macromolecules leading to failure of many chemotherapeutic agents and acquired resistance to chemotherapy. These factors highlight the significance of shifting toward targeted therapy in cancer research. Recently, ERKs (ERK1 and 2) have been established as a promising target for the management of various types of solid tumors, due to their aberrant involvement in cell growth and progression. Several ERKs inhibitors have reached clinical trials for the management of cancer and their derivatives are being continuously reported with noteworthy anticancer effect. This review highlights the recent reports on various chemical classes involved in the development of ERKs inhibitors along with their in vitro and in vivo activity and structure-activity relationship profile.Background – The optimal timing of catheter ablation for atrial fibrillation (AF) in reference to the time of diagnosis is unknown. We sought to assess the impact of the duration between first diagnosis of AF and ablation, or diagnosis-to-ablation time (DAT), on AF recurrence following catheter ablation. Methods – We conducted a systematic electronic search for observational studies reporting the outcomes associated with catheter ablation for atrial fibrillation stratified by diagnosis-to-ablation time. The primary meta-analysis using a random effects model assessed AF recurrence stratified by DAT ≤ 1 year versus = 1 year. A secondary analysis assessed outcomes stratified by DAT ≤ 3 years versus = 3 years. Results – Of the 632 screened studies, 6 studies met inclusion criteria for a total of 4,950 participants undergoing AF ablation for symptomatic AF. A shorter DAT ≤ 1 year was associated with a lower relative risk (RR) of AF recurrence compared to DAT = 1 year (RR 0.73; 95% confidence interval (CI) 0.65 to 0.82, p less then 0.001). Heterogeneity was moderate (I2=51%). When excluding the one study consisting of only persistent AF patients, the heterogeneity improved substantially (I2=0%, Cochran’s Q p=0.55) with a similar estimate of effect (RR 0.78; 95% CI 0.71 to 0.85, p less then 0.001). Conclusions – Duration between time of first AF diagnosis and AF ablation is associated with an increased likelihood of ablation procedural success. Additional study is required to confirm these results and to explore implementation of earlier catheter AF ablation and patient outcomes within the current AF care pathway.

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