MADNet: microarray database network web server

MADNet is a user-friendly data mining and visualization tool for rapid analysis of diverse high-throughput biological data such as microarray, phage display or even metagenome experiments. It presents biological information in the context of metabolic and signalling pathways, transcription factors and drug targets through minimal user input, consisting only of the file with the experimental data. These data are integrated with information stored in various biological databases such as NCBI nucleotide and protein databases, metabolic and signalling pathway databases (KEGG), transcription regulation (TRANSFAC©) and drug target database (DrugBank). MADNet is freely available for academic use at http://www.bioinfo.hr/madnet

Osteocyte transcriptome mapping identifies a molecular landscape controlling skeletal homeostasis and susceptibility to skeletal disease.

Osteocytes are master regulators of the skeleton. We mapped the transcriptome of osteocytes from different skeletal sites, across age and sexes in mice to reveal genes and molecular programs that control this complex cellular-network. We define an osteocyte transcriptome signature of 1239 genes that distinguishes osteocytes from other cells. 77% have no previously known role in the skeleton and are enriched for genes regulating neuronal network formation, suggesting this programme is important in osteocyte communication. We evaluated 19 skeletal parameters in 733 knockout mouse lines and reveal 26 osteocyte transcriptome signature genes that control bone structure and function. We showed osteocyte transcriptome signature genes are enriched for human orthologs that cause monogenic skeletal disorders (P = 2.4 × 10-22) and are associated with the polygenic diseases osteoporosis (P = 1.8 × 10-13) and osteoarthritis (P = 1.6 × 10-7). Thus, we reveal the molecular landscape that regulates osteocyte network formation and function and establish the importance of osteocytes in human skeletal disease

The vertical hip fracture – a treatment challenge. A cohort study with an up to 9 year follow-up of 137 consecutive hips treated with sliding hip screw and antirotation screw

<p>Abstract</p> <p>Background</p> <p>Femoral neck fractures with a vertical orientation have been associated with an increased risk for failure as they are both axial and rotational unstable and experience increased shear forces compared to the conventional and more horizontally oriented femoral neck fractures. The purpose of this study was to analyse outcome and risk factors for reoperation of these uncommon fractures.</p> <p>Methods</p> <p>A cohort study with a consecutive series of 137 hips suffering from a vertical hip fracture, treated with one method: a sliding hips screw with plate and an antirotation screw. Median follow-up time was 4.8 years. Reoperation data was validated against the National Board of Health and Welfare’s national registry using the unique Swedish personal identification number.</p> <p>Results</p> <p>The total reoperation rate was 18%. After multivariable Logistic regression analysis adjusting for possible confounding factors there was an increased risk for reoperation for displaced fractures (22%) compared to undisplaced fractures (3%), and for fractures with poor implant position (38%) compared to fractures with adequate implant position (15%).</p> <p>Conclusions</p> <p>The reoperation rate was high, and special attention should be given to achieve an appropriate position of the implant.</p

A single-cell and spatially resolved atlas of human breast cancers

Breast cancers are complex cellular ecosystems where heterotypic interactions play central roles in disease progression and response to therapy. However, our knowledge of their cellular composition and organization is limited. Here we present a single-cell and spatially resolved transcriptomics analysis of human breast cancers. We developed a single-cell method of intrinsic subtype classification (SCSubtype) to reveal recurrent neoplastic cell heterogeneity. Immunophenotyping using cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) provides high-resolution immune profiles, including new PD-L1/PD-L2+ macrophage populations associated with clinical outcome. Mesenchymal cells displayed diverse functions and cell-surface protein expression through differentiation within three major lineages. Stromal-immune niches were spatially organized in tumors, offering insights into antitumor immune regulation. Using single-cell signatures, we deconvoluted large breast cancer cohorts to stratify them into nine clusters, termed ‘ecotypes’, with unique cellular compositions and clinical outcomes. This study provides a comprehensive transcriptional atlas of the cellular architecture of breast cancer

Osteocyte transcriptome mapping identifies a molecular landscape controlling skeletal homeostasis and susceptibility to skeletal disease

Osteocytes are master regulators of the skeleton. We mapped the transcriptome of osteocytes from different skeletal sites, across age and sexes in mice to reveal genes and molecular programs that control this complex cellular-network. We define an osteocyte transcriptome signature of 1239 genes that distinguishes osteocytes from other cells. 77% have no previously known role in the skeleton and are enriched for genes regulating neuronal network formation, suggesting this programme is important in osteocyte communication. We evaluated 19 skeletal parameters in 733 knockout mouse lines and reveal 26 osteocyte transcriptome signature genes that control bone structure and function. We showed osteocyte transcriptome signature genes are enriched for human orthologs that cause monogenic skeletal disorders (P = 2.4 × 10−22) and are associated with the polygenic diseases osteoporosis (P = 1.8 × 10−13) and osteoarthritis (P = 1.6 × 10−7). Thus, we reveal the molecular landscape that regulates osteocyte network formation and function and establish the importance of osteocytes in human skeletal disease