Biology subjects

Turner, D.

Publications and source records attributed to Turner, D..

5 recordsLinked to original sources

bioRxiv2018

Evaluation of the NCCN guidelines using the RIGHT Statement and AGREE II instrument: a cross-sectional review.

IntroductionRobust, clearly reported clinical practice guidelines (CPGs) are essential for evidence-based clinical practice. The Reporting Items for practice Guidelines in HealThcare (RIGHT) statement and Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument were published to improve the methodological and reporting quality in healthcare CPGs.\n\nMethodsWe applied the RIGHT statement checklist and AGREE II instrument to 48 National Comprehensive Cancer Network (NCCN) guidelines. Our primary objective was to assess the adherence to RIGHT and AGREE II items. Since neither RIGHT nor AGREE-II can judge the clinical usefulness of a guideline, our study is designed to only focus on the methodological and reporting quality of each guideline.\n\nResultsThe NCCN guidelines demonstrated notable strengths and weaknesses. For example, RIGHT statement items 19 (conflicts of interest), 7b (description of subgroups), and 13a (clear, precise recommendations) were fully reported in all guidelines. However, the guidelines inconsistently incorporated patient values and preferences and cost, nor did they consistently describe the method for assessing the quality and certainty of evidence. Regarding the AGREE II instrument, the NCCN guidelines scored highly on the domains 4 (clear, precise recommendations) and 6 (handling of conflicts of interest), but lowest on domain 2 (inclusion of all relevant stakeholders).\n\nConclusionsIn this investigation we found that NCCN CPGs demonstrate key strengths and weaknesses with respect to the reporting of key items essential to CPGs. We recommend the continued use of NCCN guidelines and adherence to the RIGHT and AGREE II items. Doing so serves to improve the evidence delivered to healthcare providers, thus potentially improving patient care.

epidemiology↗

bioRxiv2018

Treatment-Specific Composition of Gut Microbiota Is Associated with Disease Remission in a Pediatric Crohn’s Disease Cohort

BackgroundThe beneficial effects of antibiotics in Crohns disease (CD) depend in part on the gut microbiota but are inadequately understood. We investigated the impact of metronidazole (MET) and metronidazole plus azithromycin (MET+AZ) on the microbiota in pediatric CD, and the use of microbiota features as classifiers or predictors of disease remission.\n\nMethods16S rRNA-based microbiota profiling was performed on stool samples from 67 patients in a multinational, randomized, controlled, longitudinal, 12-week trial of MET vs. MET+AZ in children with mild to moderate CD. Profiles were analyzed together with disease activity, and then used to construct Random Forest models to classify remission or predict treatment response.\n\nResultsBoth MET and MET+AZ significantly decreased diversity of the microbiota and caused large treatment-specific shifts in microbiota structure at week 4. Disease remission was associated with a treatment-specific microbiota configuration. Random Forest models constructed from microbiota profiles pre- and during antibiotic treatment with metronidazole accurately classified disease remission in this treatment group (AUC of 0.879, 95% CI 0.683, 0.9877; sensitivity 0.7778; specificity 1.000, P < 0.001). A Random Forest model trained on preantibiotic microbiota profiles predicted disease remission at week 4 with modest accuracy (AUC of 0.8, P = 0.24).\n\nConclusionsMET and MET+AZ antibiotic regimens in pediatric CD lead to distinct gut microbiota structures at remission. It may be possible to classify and predict remission based in part on microbiota profiles, but larger cohorts will be needed to realize this goal.\n\nSummaryWe investigated the impact of metronidazole and metronidazole plus azithromycin on the gut microbiota in pediatric Crohns disease. Disease remission was associated with a treatment-specific microbiota configuration, and could be predicted based on pre-antibiotic microbiota profiles.

microbiology↗

bioRxiv2018

Convergent evolution of psilocybin biosynthesis by psychedelic mushrooms

Psilocybin is a psychoactive compound with clinical applications produced by dozens of mushroom species1. There has been a longstanding interest in psilocybin research with regard to treatment for addiction2, depression3, and end-of-life suffering4. However, until recently very little was known about psilocybin biosynthesis and its ecological role. Here we confirm and refine recent findings5 about the genes underpinning psilocybin biosynthesis, discover that there is more than one psilocybin biosynthesis cluster in mushrooms, and we provide the first data directly addressing psilocybins ecological role. By analysing independent genome assemblies for the hallucinogenic mushrooms Psilocybe cyanescens and Pluteus salicinus we recapture the recently discovered psilocybin biosynthesis cluster5,6 and show that a transcription factor previously implicated in its regulation is actually not part of the cluster. Further, we show that the mushroom Inocybe corydalina produces psilocybin but does not contain the established biosynthetic cluster, and we present an alternative cluster. Finally, a meta-transcriptome analysis of wild-collected mushrooms provides evidence for intra-mushroom insect gene expression of flies whose larvae grow inside Psilocybe cyanescens. These larvae were successfully reared into adults. Our results show that psilocybin does not confer complete protection against insect mycophagy, and the hypothesis that it is produced as an adaptive defense compound may need to be reconsidered.

evolutionary biology↗

bioRxiv2017

Juicebox.js provides a cloud-based visualization system for Hi-C data

Contact mapping experiments such as Hi-C explore how genomes fold in 3D. Here, we introduce Juicebox.js, a cloud-based web application for exploring the resulting datasets. Like the original Juicebox application, Juicebox.js allows users to zoom in and out of such datasets using an interface similar to Google Earth. Furthermore, Juicebox.js encodes the exact state of the browser in a shareable URL. Creating a public browser for a new Hi-C dataset does not require coding and can be accomplished in under a minute.

bioinformatics↗

bioRxiv2017

Gastruloids develop the three body axes in the absence of extraembryonic tissues and spatially localised signalling

Establishment of the three body axes is a critical step during animal development. In mammals, genetic studies have shown that a combination of precisely deployed signals from extraembryonic tissues position the anteroposterior axis (AP) within the embryo and lead to the emergence of the dorsoventral (DV) and left-right (LR) axes. We have used Gastruloids, embryonic organoids, as a model system to understand this process and find that they are able to develop AP, DV and LR axes as well as to undergo axial elongation in a manner that mirror embryos. The Gastruloids can be grown for 160 hours and form derivatives from ectoderm, mesoderm and endoderm. We focus on the AP axis and show that in the Gastruloids this axis is registered in the expression of T/Bra at one pole that corresponds to the tip of the elongation. We find that localisation of T/Bra expression depends on the combined activities of Wnt/{beta}-Catenin and Nodal/Smad2,3 signalling, and that BMP signalling is dispensable for this process. Furthermore, AP axis specification occurs in the absence of both extraembryonic tissues and of localised sources of signalling. Our experiments show that Nodal, together with Wnt/{beta}-Catenin signalling, is essential for the expression of T/Bra but that Wnt signalling has a separable activity in the elongation of the axis. The results lead us to suggest that, in the embryo, the role of the extraembryonic tissues might not be to induce the axes but to bias an intrinsic ability of the embryo to break its initial symmetry and organise its axes.\n\nOne sentence summaryCulture of aggregates of defined number of Embryonic Stem cells leads to self-organised embryo-like structures which, in the absence of localised signalling from extra embryonic tissues and under the autonomous influence of Wnt and Nodal signalling, develop the three main axes of the body.

developmental biology↗