An organoid biobank for childhood kidney cancers that captures disease and tissue heterogeneity

Kidney tumours are among the most common solid tumours in children, comprising distinct subtypes differing in many aspects, including cell-of-origin, genetics, and pathology. Pre-clinical cell models capturing the disease heterogeneity are currently lacking. Here, we describe the first paediatric cancer organoid biobank. It contains tumour and matching normal kidney organoids from over 50 children with different subtypes of kidney cancer, including Wilms tumours, malignant rhabdoid tumours, renal cell carcinomas, and congenital mesoblastic nephromas. Paediatric kidney tumour organoids retain key properties of native tumours, useful for revealing patient-specific drug sensitivities. Using single cell RNA-sequencing and high resolution 3D imaging, we further demonstrate that organoid cultures derived from Wilms tumours consist of multiple different cell types, including epithelial, stromal and blastemal-like cells. Our organoid biobank captures the heterogeneity of paediatric kidney tumours, providing a representative collection of well-characterised models for basic cancer research, drug-screening and personalised medicine

MassNet: a functional annotation service for protein mass spectrometry data.

Although mass spectrometry has been frequently used to identify proteins, there are no web servers that provide comprehensive functional annotation of those identified proteins. It is necessary to provide such web service due to a rapid increase in the data. We, therefore, introduce MassNet, which provides (i) physico-chemical analysis information, (ii) KEGG pathway assignment (iii) Gene Ontology mapping and (iv) proteinprotein interaction (PPI) prediction for the data from MASCOT, Prospector and Profound. MassNet provides the prediction information for PPIs using both 3D structural interaction and experimental interaction deposited in PSIMAP, BIND, DIP, HPRD, IntAct, MINT, CYGD and BioGrid. The web service is freely available at http://massnet.kr or http://sequenceome.kobic.re.kr/MassNet/close4

Systematic review of methods used in meta-analyses where a primary outcome is an adverse or unintended event

addresses: Peninsula College of Medicine and Dentistry, St Luke's Campus, University of Exeter, Exeter, UK. [email protected]: PMCID: PMC3528446types: Journal Article; Research Support, Non-U.S. Gov't© 2012 Warren et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Adverse consequences of medical interventions are a source of concern, but clinical trials may lack power to detect elevated rates of such events, while observational studies have inherent limitations. Meta-analysis allows the combination of individual studies, which can increase power and provide stronger evidence relating to adverse events. However, meta-analysis of adverse events has associated methodological challenges. The aim of this study was to systematically identify and review the methodology used in meta-analyses where a primary outcome is an adverse or unintended event, following a therapeutic intervention

The expanded human disease network combining protein–protein interaction information

The human disease network (HDN) has become a powerful tool for revealing disease–disease associations. Some studies have shown that genes that share similar or same disease phenotypes tend to encode proteins that interact with each other. Therefore, protein–protein interactions (PPIs) may help us to further understand the relationships between diseases with overlapping clinical phenotypes. In this study, we constructed the expanded HDN (eHDN) by combining disease gene information with PPI information, and analyzed its topological features and functional properties. We found that the network is hierarchical and, most diseases are connected to only a few diseases, whereas a small part of diseases are linked to many different diseases. Diseases in a specific disease class tend to cluster together, and genes associated with the same disease are functionally related. Comparing the eHDN with the original HDN (oHDN, constructed using disease gene information) revealed high consistency over all topological and functional properties. This, to some extent, indicates that our eHDN is reliable. In the eHDN, we found some new associations among diseases resulting from the shared genes interacting with disease genes. The new eHDN will provide a valuable reference for clinicians and medical researchers

Computer and psychotherapy – do they fit? Review of the state of development of internet-based and blended interventions in psychotherapy

Die Verbreitung moderner Medien wirkt sich zunehmend auf psychologische Behandlungsangebote aus. Während die empirische Basis internetbasierter Interventionen zur Behandlung häufiger psychischer Beeinträchtigungen wächst und ihre Anwendung in der Regelversorgung gegenwärtig international erprobt wird, bestehen zusätzliche Bestrebungen, das gewonnene Knowhow mit konventioneller Psychotherapie zu kombinieren. Die daraus entstehende Behandlungsform der „gemischten Psychotherapie“ („blended therapy“) hat das deklarierte Ziel, das Beste aus beiden Welten zu vereinen. Nach einer einleitenden Begriffsbestimmung gibt die vorliegende Übersichtsarbeit Einblick in die Inhalte und die Bestandteile internetbasierter sowie gemischter Interventionen. Der aktuelle Forschungsstand wird skizziert und vor dem Hintergrund der praktischen Anwendbarkeit durch eine Zusammenschau quantitativer und qualitativer Studien dargelegt. Besonderes Augenmerk gilt der Rolle der therapeutischen Unterstützung und der Beschaffenheit der therapeutischen Allianz bei internetbasierten Interventionen sowie den Stärken und Schwächen beider Behandlungsstrategien. Ziel ist es, sowohl die Entwicklung als auch das Potenzial beider Forschungsrichtungen plausibel und realistisch darzustellen und in eine strategische Versorgungsperspektive zu setzen.Modern media have an increasing impact on psychological health services. While the empirical foundation of internet-based interventions for frequently occurring mental disorders grows and their effectiveness is investigated in routine care trials, efforts also exist to transfer the knowledge gained to classical psychotherapy. The resulting treatment format “blended therapy” aims to combine the best of both worlds. After an introductory definition of both terms this overview describes the contents and components of internet-based and blended interventions. Summarizing the current state of research with an emphasis on feasibility, selected quantitative and qualitative articles are presented. The article depicts the development, application and potential of both interventional strategies and focuses on the role of therapist support as well as on the nature of the therapeutic alliance. Strengths and weaknesses of each intervention are addressed and integrated into a strategic perspective