Daphnia magna transcriptome by RNA-Seq across 12 environmental stressors

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Conditional analyses of recurrence and progression in patients with TaG1 non-muscle-invasive bladder cancer.

OBJECTIVE To determine conditional recurrence-free survival (RFS) and progression-free survival (PFS) and improve decision-making toward surveillance protocols and scheduling. Furthermore, evaluating the evolution of predictors for disease recurrence over time, because TaG1 non-muscle-invasive bladder cancer harbors a risk of disease recurrence and progression. MATERIAL AND METHODS The retrospective multicenter design study includes 1,245 TaG1 bladder cancer patients with median follow-up of 62.7 (interquartile range: 34.3-91.1) months. Conditional RFS and PFS estimates were calculated using the Kaplan-Meier method. Multivariable Cox regression model was calculated proportional for the prediction of recurrence and progression (covariables: age, tumor size, multiple tumors, prior recurrence, and immediate postoperative instillation of chemotherapy). RESULTS After 3 months without event, the conditional RFS and PFS (to ≥pT2) rates for 5 additional years without event were 57.5% and 93.4%, respectively. Given a 1-, 2-, 3-, and 5-year survival, the conditional RFS rates for 5 additional years without event improved by +9.8 (67.3%), +5.2 (72.5%), +6.5 (79.0%), +2.0 (81.0%), and +1.0% (82.0%), respectively. In contrast, the 5-year conditional PFS rates were more or less stable with 94.3% after 1 year to 94.1% after 5 years. Multivariable analyses showed decreasing impact of risk parameters on RFS estimates over time. Based on these findings, we suggest a risk stratification to individualize follow-up for intermediate risk TaG1. Main limitation was the retrospective design. CONCLUSIONS Conditional-survival analyses demonstrates that the patient risk profile changes over time. RFS rates rise with increasing survival whereas PFS rates were stable. The impact of prognostic features decreases over time. Our findings can be used for patient counseling and planning of personalized follow-up

Daphnia magna transcriptome by RNA-Seq across 12 environmental stressors.

Scientific Data 3:160030 doi:10.1038/sdata.2016.30 (2016); Published 10 May 2016; Updated 31 Jan 2017 The original version of this Data Descriptor contained a typographical error in the spelling of the author Douglas B. Rusch, which was incorrectly given as Douglas Rush. This has now been corrected in the PDF and HTML versions of the Data Descriptor

Daphnia magna transcriptome by RNA-Seq across 12 environmental stressors

The full exploration of gene-environment interactions requires model organisms with well-characterized ecological interactions in their natural environment, manipulability in the laboratory and genomic tools. The waterflea Daphnia magna is an established ecological and toxicological model species, central to the food webs of freshwater lentic habitats and sentinel for water quality. Its tractability and cyclic parthenogenetic life-cycle are ideal to investigate links between genes and the environment. Capitalizing on this unique model system, the STRESSFLEA consortium generated a comprehensive RNA-Seq data set by exposing two inbred genotypes of D. magna and a recombinant cross of these genotypes to a range of environmental perturbations. Gene models were constructed from the transcriptome data and mapped onto the draft genome of D. magna using EvidentialGene. The transcriptome data generated here, together with the available draft genome sequence of D. magna and a high-density genetic map will be a key asset for future investigations in environmental genomics.status: publishe

Long-term outcomes and genetic predictors of response to metastasis-directed therapy versus observation in oligometastatic prostate cancer : analysis of STOMP and ORIOLE trials

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. The initial STOMP and ORIOLE trial reports suggested that metastasis-directed therapy (MDT) in oligometastatic castration-sensitive prostate cancer (omCSPC) was associated with improved treatment outcomes. Here, we present long-term outcomes of MDT in omCSPC by pooling STOMP and ORIOLE and assess the ability of a high-risk mutational signature to risk stratify outcomes after MDT. The primary end point was progression-free survival (PFS) calculated using the Kaplan-Meier method. High-risk mutations were defined as pathogenic somatic mutations within ATM, BRCA1/2, Rb1, or TP53. The median follow-up for the whole group was 52.5 months. Median PFS was prolonged with MDT compared with observation (pooled hazard ratio [HR], 0.44; 95% CI, 0.29 to 0.66; P value < .001), with the largest benefit of MDT in patients with a high-risk mutation (HR high-risk, 0.05; HR no high-risk, 0.42; P value for interaction: .12). Within the MDT cohort, the PFS was 13.4 months in those without a high-risk mutation, compared with 7.5 months in those with a high-risk mutation (HR, 0.53; 95% CI, 0.25 to 1.11; P = .09). Long-term outcomes from the only two randomized trials in omCSPC suggest a sustained clinical benefit to MDT over observation. A high-risk mutational signature may help risk stratify treatment outcomes after MDT