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

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

Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

Summary Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (TP53, ATRX, RB1) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types

Comparing thigh muscle cross-sectional area and squat strength among national class Olympic weightlifters, power lifters, and bodybuilders

Few studies have compared anthropometric characteristics among national class athletes from different resistance training disciplines, such as Olympic Weightlifting (OL), Power Lifting (PL), and Bodybuilding (BB). Objective: The purpose of the current study was to determine if significant differences exist in the relationship between thigh muscle cross-sectional area and back squat strength among national class athletes from the sports of OL, PL, and BB. Methods: Fifteen national class athletes were assessed for back squat strength, mid-thigh circumference, and mid-thigh skinfold from which total thigh cross-sectional was estimated. A series of One-Way ANOVAs and Pearson Product Moment Correlations were used to compare groups and assess the relationship between variables. Results: The OL (200.18 + 25.16kg) and PL (205.45 + 17.28kg) groups were significantly stronger than the BB (160 + 16.80 kg; p \u3c 0.05) group. However, mid-thigh skinfold thickness (p = 0.36), mid-thigh circumference (p = 0.87), and estimated thigh cross-sectional area (p = 0.34) were not significantly different between groups. Thigh muscle cross-sectional area was weakly correlated to back squat strength in the OL (r = .42) and PL (r = .12) groups, but moderately correlated in the BB (r = .70) group. Conclusion: Thigh cross-sectional area was of relatively minor importance in determining back squat strength for the OL and PL groups, despite these groups being significantly stronger than the BB group. Specific training protocols will elicit different outcomes with regard to muscular hypertrophy that may or may not contribute to a functional increase in back squat strength

Does Probe Positioning and Pressure Effect the Reliability of M-wave Max?

Appropriate assessment of nerve function is vital to establish the outcomes of neuromuscular excitability, muscle activation, and the standardization of electromyographic data. Further, the determination of this measure has clinical relevance in the diagnosis of nerve disorders. However, factors such as probe orientation and pressure may lead to inconsistencies in the accurate assessment of nerve function. PURPOSE: The purpose of this study was to determine the interrater reliability of varying probe orientations and pressures on the maximal m-wave (M-wavemax). METHODS: Fourteen females and ten males (age: 20.9 ± 2.2yrs) underwent electrical stimulation to the median nerve and M-wavemax was recorded in the abductor pollicis brevis. Two raters administered five conditions on separate visits to evaluate the effects of varying probe orientations and pressures on the M-wavemax response. Measures included a 1) parallel (PAR) probe nerve orientation with a pressure of 4-6 N; 2) PAR probe nerve stimulation with a pressure of 9-11 N; 3) perpendicular (PERP) nerve orientation with a pressure of 9-11 N, 4) stimulation disc electrodes in the PAR and 5) PERP direction. The intraclass correlation coefficient (ICC) was calculated for interrater reliability. The reliability of two raters was assessed using a two-way mixed model (ICC[2,1]). RESULTS: Regarding the PERP orientation, there was moderate reliability for the 9-11 N and stimulation disc electrodes (ICC(2,1) = 0.57, p = 0.003, M = 14.77, SE = 5.02; ICC(2,1) = 0.65, p = 0.211, M = 14.88, SE = 4.30; respectively). Similarly, in the PAR orientation, there was moderate reliability for the 9-11 N and stimulation patches (ICC(2,1) = 0.53, p = 0.952, M = 14.20, SE = 5.02; ICC (2,1) = 0.56, p = 0.889, M = 14.52, SE = 5.13; respectively). Lastly, in the PAR orientation, there was poor reliability for 4-6 N (ICC(2,1) = 0.33, p = 0.821, M = 13.61, SE = 5.99). CONCLUSION: The poor and moderate reliability indicate varying levels of consistency between the measurements acquired. This is meaningful in clinical applications because measurement reliability is crucial in the effectiveness of diagnosis and treatment. These findings suggest appropriate standardization should be emphasized to increase reliability in common peripheral nerve stimulation

PLANO DE SUCESSÃO: UM ESTUDO DE CASO EM UMA EMPRESA FAMILIAR DE MÍDIA EXTERIOR

Objetivou-se com este estudo, compreender e descrever como se desenvolve um plano de sucessão familiar para uma empresa de mídia exterior que se encontra na sua primeira geração. Para isto, foi realizado um estudo de caso na empresa Color Painéis em Londrina-PR, bem como, a revisão bibliográfica acerca das características e conceitos ligados ao âmbito das empresas familiares quanto ao processo sucessório e os planos de sucessão. Esta pesquisa qualitativa, com natureza descritiva e exploratória se deu a partir da inexistência de estudos relacionados ao tema nesse tipo de negócio, além da necessidade de um plano de sucessão por parte do fundador da empresa. Os resultados da pesquisa revelam que o plano de sucessão que melhor se adéqua às características da empresa analisada é o do autor Oliveira (2006), visto suas etapas claras, em especial, as análises acerca do tratamento de possíveis conflitos característicos das empresas familiares, e a possibilidade de se escolher o perfil do sucessor conforme a missão, visão, valores e objetivos da empresa.

PLANO DE SUCESSÃO: UM ESTUDO DE CASO EM UMA EMPRESA FAMILIAR DE MÍDIA EXTERIOR

Objetivou-se com este estudo, compreender e descrever como se desenvolve um plano de sucessão familiar para uma empresa de mídia exterior que se encontra na sua primeira geração. Para isto, foi realizado um estudo de caso na empresa Color Painéis em Londrina-PR, bem como, a revisão bibliográfica acerca das características e conceitos ligados ao âmbito das empresas familiares quanto ao processo sucessório e os planos de sucessão. Esta pesquisa qualitativa, com natureza descritiva e exploratória se deu a partir da inexistência de estudos relacionados ao tema nesse tipo de negócio, além da necessidade de um plano de sucessão por parte do fundador da empresa. Os resultados da pesquisa revelam que o plano de sucessão que melhor se adéqua às características da empresa analisada é o do autor Oliveira (2006), visto suas etapas claras, em especial, as análises acerca do tratamento de possíveis conflitos característicos das empresas familiares, e a possibilidade de se escolher o perfil do sucessor conforme a missão, visão, valores e objetivos da empresa.