A novel pathway to detect muscle-invasive bladder cancer based on integrated clinical features and VI-RADS score on MRI: results of a prospective multicenter study

Purpose To determine the clinical, pathological, and radiological features, including the Vesical Imaging-Reporting and Data System (VI-RADS) score, independently correlating with muscle-invasive bladder cancer (BCa), in a multicentric national setting. Method and Materials Patients with BCa suspicion were offered magnetic resonance imaging (MRI) before trans-urethral resection of bladder tumor (TURBT). According to VI-RADS, a cutoff of >= 3 or >= 4 was assumed to define muscle-invasive bladder cancer (MIBC). Trans-urethral resection of the tumor (TURBT) and/or cystectomy reports were compared with preoperative VI-RADS scores to assess accuracy of MRI for discriminating between non-muscle-invasive versus MIBC. Performance was assessed by ROC curve analysis. Two univariable and multivariable logistic regression models were implemented including clinical, pathological, radiological data, and VI-RADS categories to determine the variables with an independent effect on MIBC. Results A final cohort of 139 patients was enrolled (median age 70 [IQR: 64, 76.5]). MRI showed sensitivity, specificity, PPV, NPV, and accuracy for MIBC diagnosis ranging from 83-93%, 80-92%, 67-81%, 93-96%, and 84-89% for the more experienced readers. The area under the curve (AUC) was 0.95 (0.91-0.99). In the multivariable logistic regression model, the VI-RADS score, using both a cutoff of 3 and 4 (P < .0001), hematuria (P = .007), tumor size (P = .013), and concomitant hydronephrosis (P = .027) were the variables correlating with a bladder cancer staged as >= T2. The inter-reader agreement was substantial (k = 0.814). Conclusions VI-RADS assessment scoring proved to be an independent predictor of muscle-invasiveness, which might implicate a shift toward a more aggressive selection approach of patients' at high risk of MIBC, according to a novel proposed predictive pathway

MRI-targeted or standard biopsy for prostate-cancer diagnosis

Background Multiparametric magnetic resonance imaging (MRI), with or without targeted biopsy, is an alternative to standard transrectal ultrasonography-guided biopsy for prostate-cancer detection in men with a raised prostate-specific antigen level who have not undergone biopsy. However, comparative evidence is limited. Methods In a multicenter, randomized, noninferiority trial, we assigned men with a clinical suspicion of prostate cancer who had not undergone biopsy previously to undergo MRI, with or without targeted biopsy, or standard transrectal ultrasonography-guided biopsy. Men in the MRI-targeted biopsy group underwent a targeted biopsy (without standard biopsy cores) if the MRI was suggestive of prostate cancer; men whose MRI results were not suggestive of prostate cancer were not offered biopsy. Standard biopsy was a 10-to-12-core, transrectal ultrasonography-guided biopsy. The primary outcome was the proportion of men who received a diagnosis of clinically significant cancer. Secondary outcomes included the proportion of men who received a diagnosis of clinically insignificant cancer. Results A total of 500 men underwent randomization. In the MRI-targeted biopsy group, 71 of 252 men (28%) had MRI results that were not suggestive of prostate cancer, so they did not undergo biopsy. Clinically significant cancer was detected in 95 men (38%) in the MRI-targeted biopsy group, as compared with 64 of 248 (26%) in the standard-biopsy group (adjusted difference, 12 percentage points; 95% confidence interval [CI], 4 to 20; P=0.005). MRI, with or without targeted biopsy, was noninferior to standard biopsy, and the 95% confidence interval indicated the superiority of this strategy over standard biopsy. Fewer men in the MRI-targeted biopsy group than in the standard-biopsy group received a diagnosis of clinically insignificant cancer (adjusted difference, -13 percentage points; 95% CI, -19 to -7; P<0.001). Conclusions The use of risk assessment with MRI before biopsy and MRI-targeted biopsy was superior to standard transrectal ultrasonography-guided biopsy in men at clinical risk for prostate cancer who had not undergone biopsy previously. (Funded by the National Institute for Health Research and the European Association of Urology Research Foundation; PRECISION ClinicalTrials.gov number, NCT02380027 .)

MINT, the molecular interaction database: 2009 update

MINT (http://mint.bio.uniroma2.it/mint) is a public repository for molecular interactions reported in peer-reviewed journals. Since its last report, MINT has grown considerably in size and evolved in scope to meet the requirements of its users. The main changes include a more precise definition of the curation policy and the development of an enhanced and user-friendly interface to facilitate the analysis of the ever-growing interaction dataset. MINT has adopted the PSI-MI standards for the annotation and for the representation of molecular interactions and is a member of the IMEx consortium

The MIntAct project—IntAct as a common curation platform for 11 molecular interaction databases

IntAct (freely available at http://www.ebi.ac.uk/intact) is an open-source, open data molecular interaction database populated by data either curated from the literature or from direct data depositions. IntAct has developed a sophisticated web-based curation tool, capable of supporting both IMEx- and MIMIx-level curation. This tool is now utilized by multiple additional curation teams, all of whom annotate data directly into the IntAct database. Members of the IntAct team supply appropriate levels of training, perform quality control on entries and take responsibility for long-term data maintenance. Recently, the MINT and IntAct databases decided to merge their separate efforts to make optimal use of limited developer resources and maximize the curation output. All data manually curated by the MINT curators have been moved into the IntAct database at EMBL-EBI and are merged with the existing IntAct dataset. Both IntAct and MINT are active contributors to the IMEx consortium (http://www.imexconsortium.org

The Protein-Protein Interaction tasks of BioCreative III: classification/ranking of articles and linking bio-ontology concepts to full text

BACKGROUND: Determining usefulness of biomedical text mining systems requires realistic task definition and data selection criteria without artificial constraints, measuring performance aspects that go beyond traditional metrics. The BioCreative III Protein-Protein Interaction (PPI) tasks were motivated by such considerations, trying to address aspects including how the end user would oversee the generated output, for instance by providing ranked results, textual evidence for human interpretation or measuring time savings by using automated systems. Detecting articles describing complex biological events like PPIs was addressed in the Article Classification Task (ACT), where participants were asked to implement tools for detecting PPI-describing abstracts. Therefore the BCIII-ACT corpus was provided, which includes a training, development and test set of over 12,000 PPI relevant and non-relevant PubMed abstracts labeled manually by domain experts and recording also the human classification times. The Interaction Method Task (IMT) went beyond abstracts and required mining for associations between more than 3,500 full text articles and interaction detection method ontology concepts that had been applied to detect the PPIs reported in them.RESULTS:A total of 11 teams participated in at least one of the two PPI tasks (10 in ACT and 8 in the IMT) and a total of 62 persons were involved either as participants or in preparing data sets/evaluating these tasks. Per task, each team was allowed to submit five runs offline and another five online via the BioCreative Meta-Server. From the 52 runs submitted for the ACT, the highest Matthew's Correlation Coefficient (MCC) score measured was 0.55 at an accuracy of 89 and the best AUC iP/R was 68. Most ACT teams explored machine learning methods, some of them also used lexical resources like MeSH terms, PSI-MI concepts or particular lists of verbs and nouns, some integrated NER approaches. For the IMT, a total of 42 runs were evaluated by comparing systems against manually generated annotations done by curators from the BioGRID and MINT databases. The highest AUC iP/R achieved by any run was 53, the best MCC score 0.55. In case of competitive systems with an acceptable recall (above 35) the macro-averaged precision ranged between 50 and 80, with a maximum F-Score of 55. CONCLUSIONS: The results of the ACT task of BioCreative III indicate that classification of large unbalanced article collections reflecting the real class imbalance is still challenging. Nevertheless, text-mining tools that report ranked lists of relevant articles for manual selection can potentially reduce the time needed to identify half of the relevant articles to less than 1/4 of the time when compared to unranked results. Detecting associations between full text articles and interaction detection method PSI-MI terms (IMT) is more difficult than might be anticipated. This is due to the variability of method term mentions, errors resulting from pre-processing of articles provided as PDF files, and the heterogeneity and different granularity of method term concepts encountered in the ontology. However, combining the sophisticated techniques developed by the participants with supporting evidence strings derived from the articles for human interpretation could result in practical modules for biological annotation workflows

SIGNOR: a new SIGnaling network open resource

Standardization and analysis of large datasets have played, in recent decades, a key role in many fields of knowledge including biology. Biological information, starting from the sequence of a protein to its function, are increasingly being analyzed and made accessible to the scientific community through the use of web-services and databases. In particular the protein-protein interaction network has proved a crucial resource to promote the advancement of systems biology and facilitate the understanding of events occurring in biological systems. Despite the many insights we gained from the analysis of this information, currently available interactomes have several shortcomings. One of the most important limitations is the lack of information on protein regulation and on the direction of the information flow that from the sense of a stimulus leads to the cellular response. In addition, in the available picture, information about the participation of other important biological entities (e.g., small molecule, transcription factors and genes) is still missing. To this purpose, in recent years, different signalling resources have been created, with the aim of capturing all the signal transduction information reported in the scientific literature, organizing it in a structured format and offering it to the community in a user friendly way. Our group decided to create a new resource to "fill the gap" between protein-protein interactions and signalling networks and at the same time, to provide researchers with a tool to support experimental approaches based on multi-parametric analysis of cell systems. SIGNOR (http://signor.uniroma2.it), the Signalling Network Open Resource is a new database-centered application specifically designed to facilitate the storage and analysis of directed molecular interaction and regulation. An ongoing curation effort aims at making SIGNOR a prominent resource in the biological community by offering a comprehensive network of experimentally validated functional relationships between signalling proteins that can be used as an a priori model for optimization strategies. At the time of writing, the core of SIGNOR is a collection of approximately 7400 manually-annotated logic relationships between proteins and other biological entities that participate in signal transduction. Each relationship is linked to the literature reporting the experimental evidence and is assigned a score. These numbers are expected to increase thanks to the manual annotation of further publications carried out by our expert curators. Scientists from various branches of biology may find SIGNOR a precious resource to foster their own research

Exploiting Publicly Available Biological and Biochemical Information for the Discovery of Novel Short Linear Motifs

The function of proteins is often mediated by short linear segments of their amino acid sequence, called Short Linear Motifs or SLiMs, the identification of which can provide important information about a protein function. However, the short length of the motifs and their variable degree of conservation makes their identification hard since it is difficult to correctly estimate the statistical significance of their occurrence. Consequently, only a small fraction of them have been discovered so far. We describe here an approach for the discovery of SLiMs based on their occurrence in evolutionarily unrelated proteins belonging to the same biological, signalling or metabolic pathway and give specific examples of its effectiveness in both rediscovering known motifs and in discovering novel ones. An automatic implementation of the procedure, available for download, allows significant motifs to be identified, automatically annotated with functional, evolutionary and structural information and organized in a database that can be inspected and queried. An instance of the database populated with pre-computed data on seven organisms is accessible through a publicly available server and we believe it constitutes by itself a useful resource for the life sciences (http://www.biocomputing.it/modipath)

Screening in von Hippel-Lindau disease: Concurrent pheochromocytomas, paragangliomas and spinal hemangioblastomas revealed by helical-CT, MIBG scintigraphy and MRI in an asymptomatic patient

Early detection of visceral as well as neurological abnormalities in von Hippel-Lindau (VHL) disease is highly recommended and usually accomplished by a combination of radiological and nuclear medicine techniques. We report a case of an asymptomatic 30-year-old male with VHL disease who was found to have concurrent bilateral pheochromocytomas, a carotid body tumor, sacral para-gangliomas and spinal hemangioblastomas during a screening performed by contrast-enhanced helical computed tomography, 131I-metaiodobenzylguanidine scintigraphy and magnetic resonance imaging. Despite their common embriogenetic origin from the neural crest, the concurrence of pheochromocytomas and para-gangliomas in VHL disease is rare. Although frequently asymptomatic, the occurrence of spinal hemangioblastomas in the clinical context of the screening has not been previously reported