WikiPathways: building research communities on biological pathways.

Here, we describe the development of WikiPathways (http://www.wikipathways.org), a public wiki for pathway curation, since it was first published in 2008. New features are discussed, as well as developments in the community of contributors. New features include a zoomable pathway viewer, support for pathway ontology annotations, the ability to mark pathways as private for a limited time and the availability of stable hyperlinks to pathways and the elements therein. WikiPathways content is freely available in a variety of formats such as the BioPAX standard, and the content is increasingly adopted by external databases and tools, including Wikipedia. A recent development is the use of WikiPathways as a staging ground for centrally curated databases such as Reactome. WikiPathways is seeing steady growth in the number of users, page views and edits for each pathway. To assess whether the community curation experiment can be considered successful, here we analyze the relation between use and contribution, which gives results in line with other wiki projects. The novel use of pathway pages as supplementary material to publications, as well as the addition of tailored content for research domains, is expected to stimulate growth further

Pharmacokinetics of vibunazole (Bay n7133) administered orally to healthy subjects

Contains fulltext : 4447.pdf (publisher's version ) (Open Access

Evaluation of robustly optimised intensity modulated proton therapy for nasopharyngeal carcinoma

BACKGROUND AND PURPOSE: To evaluate the dosimetric changes occurring over the treatment course for nasopharyngeal carcinoma (NPC) patients treated with robustly optimised intensity modulated proton therapy (IMPT). MATERIALS AND METHODS: 25 NPC patients were treated to two dose levels (CTV1: 70Gy, CTV2: 54.25Gy) with robustly optimised IMPT plans. Robustness evaluation was performed over 28 error scenarios using voxel-wise minimum distributions to assess target coverage and voxel-wise maximum distributions to assess possible hotspots and critical organ doses. Daily CBCT was used for positioning and weekly repeat CTs (rCT) were taken, on which the plan dose was recalculated and robustly evaluated. Deformable image registration was used to warp and accumulate the nominal, voxel-wise minimum and maximum rCT dose distributions. Changes to target coverage, critical organ and normal tissue dose between the accumulated and planned doses were investigated. RESULTS: 2 patients required a plan adaptation due to reduced target coverage. The D98% in the accumulated voxel-wise minimum distribution was higher than planned for CTV1 in 24/25 patients and for CTV2 in 20/25 patients. Maximum doses to the critical organs remained acceptable in all patients. Other normal tissue doses showed some variation as a result of soft tissue deformations and weight change. Normal tissue complication probabilities for grade ≥2 dysphagia and grade ≥2 xerostomia remained similar to planned values. CONCLUSION: Robustly optimised IMPT plans, in combination with volumetric verification imaging and adaptive planning, provided robust target coverage and acceptable OAR dose variation in our NPC cohort when accumulated over longitudinal data

Stereotactic large-core needle breast biopsy: analysis of pain and discomfort related to the biopsy procedure

The purpose of this study was to determine the significance of variables such as duration of the procedure, type of breast tissue, number of passes, depth of the biopsies, underlying pathology, the operator performing the procedure, and their effect on women’s perception of pain and discomfort during stereotactic large-core needle breast biopsy. One hundred and fifty consecutive patients with a non-palpable suspicious mammographic lesions were included. Between three and nine 14-gauge breast passes were taken using a prone stereotactic table. Following the biopsy procedure, patients were asked to complete a questionnaire. There was no discomfort in lying on the prone table. There is no relation between type of breast lesion and pain, underlying pathology and pain and performing operator and pain. The type of breast tissue is correlated with pain experienced from biopsy (P = 0.0001). We found out that patients with dense breast tissue complain of more pain from biopsy than patients with more involution of breast tissue. The depth of the biopsy correlates with pain from biopsy (P = 0.0028). Deep lesions are more painful than superficial ones. There is a correlation between the number of passes and pain in the neck (P = 0.0188) and shoulder (P = 0.0366). The duration of the procedure is correlated with pain experienced in the neck (P = 0.0116) but not with pain experienced from biopsy

Answering biological questions: querying a systems biology database for nutrigenomics

The requirement of systems biology for connecting different levels of biological research leads directly to a need for integrating vast amounts of diverse information in general and of omics data in particular. The nutritional phenotype database addresses this challenge for nutrigenomics. A particularly urgent objective in coping with the data avalanche is making biologically meaningful information accessible to the researcher. This contribution describes how we intend to meet this objective with the nutritional phenotype database. We outline relevant parts of the system architecture, describe the kinds of data managed by it, and show how the system can support retrieval of biologically meaningful information by means of ontologies, full-text queries, and structured queries. Our contribution points out critical points, describes several technical hurdles. It demonstrates how pathway analysis can improve queries and comparisons for nutrition studies. Finally, three directions for future research are given

Process‐informed subsampling improves subseasonal rainfall forecasts in Central America

Subseasonal rainfall forecast skill is critical to support preparedness for hydrometeorological extremes. We assess how a process-informed evaluation, which subsamples forecasting model members based on their ability to represent potential predictors of rainfall, can improve monthly rainfall forecasts within Central America in the following month, using Costa Rica and Guatemala as test cases. We generate a constrained ensemble mean by subsampling 130 members from five dynamic forecasting models in the C3S multimodel ensemble based on their representation of both (a) zonal wind direction and (b) Pacific and Atlantic sea surface temperatures (SSTs), at the time of initialization. Our results show in multiple months and locations increased mean squared error skill by 0.4 and improved detection rates of rainfall extremes. This method is transferrable to other regions driven by slowly-changing processes. Process-informed subsampling is successful because it identifies members that fail to represent the entire rainfall distribution when wind/SST error increases

Nonstationary weather and water extremes: a review of methods for their detection, attribution, and management

Hydroclimatic extremes such as intense rainfall, floods, droughts, heatwaves, and wind or storms have devastating effects each year. One of the key challenges for society is understanding how these extremes are evolving and likely to unfold beyond their historical distributions under the influence of multiple drivers such as changes in climate, land cover, and other human factors. Methods for analysing hydroclimatic extremes have advanced considerably in recent decades. Here we provide a review of the drivers, metrics, and methods for the detection, attribution, management, and projection of nonstationary hydroclimatic extremes. We discuss issues and uncertainty associated with these approaches (e.g. arising from insufficient record length, spurious nonstationarities, or incomplete representation of nonstationary sources in modelling frameworks), examine empirical and simulation-based frameworks for analysis of nonstationary extremes, and identify gaps for future research