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

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

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

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

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

Lower lid entropion secondary to treatment with alpha-1a receptor antagonist: a case report

<p>Abstract</p> <p>Introduction</p> <p>The use of alpha-1a receptor antagonists (tamsulosin) is widely accepted in the treatment of benign prostatic hypertrophy (BPH). It has previously been implicated as a causative agent in intra-operative floppy iris syndrome due to its effects on the smooth muscle. We report a case of lower lid entropion that may be related to a patient commencing treatment of tamsulosin.</p> <p>Case presentation</p> <p>A 74-year-old Caucasian man was started on alpha 1-a receptor antagonist (Tamsulosin) treatment for benign prostatic hypertrophy. Eight days later, he presented to the ophthalmology unit with a right lower lid entropion which was successfully treated surgically with a Weiss procedure.</p> <p>Conclusion</p> <p>We report a case of lower lid entropion that may be secondary to the recent use of an alpha-1a blocker (tamsulosin). This can be explained by considering the effect of autonomic blockade on alpha-1 receptors in the Muller's muscle on a patient that may already have an anatomical predisposition to entropion formation due to a further reduction in muscle tone.</p

Survey of epidemiological of parasitic and bacterial infection in cultured fishes of Khouzestan Province

In this study which was carried out in khouzestan province, 1914 Pieces (1160 Pieces silver carp, Hypophthalmychthys molitrix; 498 Pieces common carp, cyprinus carpio; 172 Pieces Grass carp, ctenophryngodon idella and 84 Pieces Big head, Arysthychthys nobilis) from different parts of the province were examined. In three year period, 1378 to 1381, fish samples from four stations were transferred a live to the lab. Water samples also were taken and tested for some of the physicochemical factors. From a total of 1914 fish examined, 1190 showed parasitic infestation and bacterial infections (62.2%). Infestation study, infestation with these parasites have been found: Ichthophthirius, cryptobia, Trichodina, Costia, Hexamita, Dactylogyrus, Gyrodactylus, Lernea, Bothrio cephalus, Diplostomum and Capillaria. Also some species of Aeromonas, staphylococcus, Moraxella, Pectobacterium, Flavobacterium, Citrobacteria, pasteurella, Psedomonas and Alcaligenese were identified in the samples, which normally occur in Water, but in some conditions (High pH, temperature and ammonia) could cause disease and lesions specially in gills. Infestation with dactylogyrus and Gyrodactylus was found in all four kind of fishes with different infestation rate. But the highest infestation rate with dactylogyrus was in silver carp (55.2%) and lowest in common carp (14.6%). The highest infestation rate with gyrodactylus was in grass carp (42.4%) and lowest in common carp (10.6%). Ich, Bothrio cephalus and capillalia were found only in common carp and grass carp. Infestation with adult lernea and copepodid stage of lernea had greater percentage in the gills and derm of grass carp. The data showed infestation with this parasites (especially protozoans and lernea) and bacterial infection had occurred in all seasons especially in C area

Effects of Artemia parthenogenetica culturing on socioeconomic development of the eastern marginal lands, Qom Salt Lake

Saltwater resources with Artemia (Brine shrimp) are the important ecosystems in Semi-arid Areas. That can play an important role in sustaining the economic and social system. Alternatively, will ensure that economic and social issues with of continuity and sustainability of these ecosystems resident. This study carried out "Effects of Artemia parthenogenetica culturing on socio-economic development of the eastern marginal lands, Qom Salt Lake" that was ordered by Qom province general directorate of fisheries during the 2012-2013. According to previous studies, despite the potential of human resources and Social conditions for the development of economic activities, factors such as the low groundwater and drying the salt lake , lack of fresh water in the region, environmental problems , successive droughts, prioritize and rationalize water use in agriculture, Artemia cyst harvest or Artemia culture has made virtually impossible with the current situation and has deprived the tools to make investments for the construction of earthen ponds and exploitation of native Artemia in the eastern margin of the Qom lake . Also, due to the occurrence of the Lake in the national park and privacy protection and Prohibited areas of environmental protection organization, it seems unlikely that this organization grant approval agreement required for any exploitation