Tuberculosis diagnosis and treatment practices of private physicians in Karachi, Pakistan

In a densely populated urban area of Karachi, Pakistan, a questionnaire survey was made of the knowledge and practices of 120 private general practitioners about the diagnosis and treatment of tuberculosis (TB). The majority knew that cough, fever and weight loss were the main symptoms of TB, but less than half knew that blood in sputum, poor appetite and chest pain were associated with the disease. Only 58.3% of physicians used sputum microscopy for diagnosing TB and 35.0% used it as a follow-up test. Only 41.7% treated TB patients themselves, the remaining referring their patients to specialists. Around 73.3% of the doctors were aware of the 4 first-line anti-TB drugs. Efforts to improve the knowledge of private practitioners, and strategies to enhance public-private collaboration forTB control in urban areas are urgently required

Supporting systematic reviews using LDA-based document representations

BACKGROUND: Identifying relevant studies for inclusion in a systematic review (i.e. screening) is a complex, laborious and expensive task. Recently, a number of studies has shown that the use of machine learning and text mining methods to automatically identify relevant studies has the potential to drastically decrease the workload involved in the screening phase. The vast majority of these machine learning methods exploit the same underlying principle, i.e. a study is modelled as a bag-of-words (BOW). METHODS: We explore the use of topic modelling methods to derive a more informative representation of studies. We apply Latent Dirichlet allocation (LDA), an unsupervised topic modelling approach, to automatically identify topics in a collection of studies. We then represent each study as a distribution of LDA topics. Additionally, we enrich topics derived using LDA with multi-word terms identified by using an automatic term recognition (ATR) tool. For evaluation purposes, we carry out automatic identification of relevant studies using support vector machine (SVM)-based classifiers that employ both our novel topic-based representation and the BOW representation. RESULTS: Our results show that the SVM classifier is able to identify a greater number of relevant studies when using the LDA representation than the BOW representation. These observations hold for two systematic reviews of the clinical domain and three reviews of the social science domain. CONCLUSIONS: A topic-based feature representation of documents outperforms the BOW representation when applied to the task of automatic citation screening. The proposed term-enriched topics are more informative and less ambiguous to systematic reviewers. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13643-015-0117-0) contains supplementary material, which is available to authorized users

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment