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

Protocol for collection and separation of bone marrow mononuclear cells in Chlorocebus aethiops

Abstract: Chlorocebus aethiops is a species of non-human primate frequently used in biomedical research. Some research involves this species as an experimental model for various diseases and possible treatment with stem cells. The bone marrow is one of the main sources of these cells and provides easy access. The aim of this study was to standardize the protocol of collection and separation of bone marrow in C. aethiops. Ten animals were submitted to puncture of bone marrow with access to the iliac crest and cell separation by density gradient. The bone marrow of C. aethiops had an average of 97% viability. From the results achieved, we can conclude that C. aethiops is an excellent model to obtain and isolate mononuclear cells from bone marrow, fostering several studies in the field of cell therapy

Combination of inoculation methods of Azospirilum brasilense with broadcasting of nitrogen fertilizer increases corn yield

Nitrogen (N) is the most limiting nutrient for corn production. Thereby, the goal of the paper was to evaluate inoculation methods of Azospirillum brasilense in order to partially supply N required by the crop. The experiment was carried out in Guarapuava, PR, Brasil, in 2011/2012 growing season. Randomized blocks with factorial 3 inoculation methods (seed treatment, planting furrow and non-inoculated control) x 5 doses of nitrogen (0, 75, 150, 225 and 300kg ha-1) x 8 replications was used as the experimental design. Leaf are index, foliar nitrogen content, total chlorophyll, grains per ear and yield were evaluated. There was significant interaction between inoculation methods and nitrogen fertilization to leaf area index, but not for yield. Inoculation with the diazotrophic bacteria provided yield increase of 702kg ha-1 for inoculation in seeding furrow and 432kg ha-1 for inoculation in seed treatment compared to the control, but both treatments did not differ between each other. Furthermore, total chlorophyll, grains per ear and yield were positively affected, with quadratic response, by the nitrogen fertilization in broadcastin

Reparative cell therapy for the heart: critical internal appraisal of the field in response to recent controversies

The concept that cell-based repair of myocardial injury might be possible was introduced almost two decades ago; however, the field of cardiovascular reparative medicine has been criticized as translation to clinically effective approaches has been slow. The recent retraction of a series of papers has further impacted perception of this area of research. As researchers, clinicians, and teachers in this field, we felt it incumbent to critically appraise the current state of cardiac cell repair, determine what can be learned from past mistakes, and formulate best practices for future work. This special communication summarizes an introspective assessment of what has fallen short, how to prevent similar issues, and how the field might best move forward in the service of science and patients.Cardiolog

Soil uses in the sugarcane fallow period to improve chemical and physical properties of two latosols (oxisols)

Sugarcane production should be integrated with crop diversification with a view to competitive and sustainable results in economic, social and environmental aspects. The purpose of this study was to assess the influence of different soil uses during the sugarcane fallow period on the chemical and physical properties of eutroferric Red Latosol - LVef (Oxisol) and Acric Latosol - LVw (Acric Oxisol), in Jaboticabal, São Paulo State, Brazil (21º14'05'' S, 48º17'09'' W, 600 m asl). A randomized block design was used with five replications and four treatments, consisting of different soil uses (crops) in the sugarcane fallow period: soybean only, soybean/fallow/soybean, soybean/millet/soybean, and soybean/sunn hemp/soybean. After two soybean crops, the LVef chemical properties remained at intermediate to high levels; while those of the LVw, classified as intermediate to high in the beginning, increased to high levels. Thus, the different soil uses during the sugarcane fallow period allowed the maintenance of LVef fertility levels and the improvement of those of the LVw. Two soybean crops increased macroporosity in the 0.0-0.1 m layer of the LVef; reduced soil aggregates in the 0.0-0.1 and 0.1-0.2 m layers of both soils, and reduced aggregate stability in these two layers of the LVw. Planting pearl millet or sunn hemp between the two soybean growing seasons promoted the formation of larger soil aggregates in the surface layer (0.0-0.1 m) of the LVw

Adubação nitrogenada para milho com o uso de plantas de cobertura e modos de aplicação de calcário

O sistema plantio direto (SPD) é uma realidade na região dos Cerrados, mas alguns questionamentos persistem nesse tipo de manejo como o modo de realização da calagem e a dose de nitrogênio (N) a ser adotada em cultura comercial, em relação às culturas precedentes. Desse modo, objetivou-se avaliar modos de aplicar o calcário na implantação do SPD e o efeito de culturas de cobertura precedentes sobre a necessidade de adubação nitrogenada da cultura do milho, durante diferentes anos agrícolas. O delineamento experimental utilizado foi de blocos casualizados, em esquema fatorial 5 x 2 (modos de aplicação do calcário x culturas de cobertura) e posterior divisão em três subparcelas, referentes às doses de N (0, 90 e 180 kg ha-1). Foram avaliados quatro modos de aplicação de calcário: incorporado a 0-0,2 m, em out./2001; dose total em superfície aplicada, em out./2001; aplicação de 1/2 da dose, em out./2001, e 1/2, em ago./2002, na superfície; e aplicação de 1/3 da dose recomendada, em mar./2001, + 1/3, em out./2001, e 1/3, em ago./2002, também em superfície. Além de um tratamento testemunha (sem calcário) e duas culturas de cobertura, crotalária e milheto. Os diferentes modos de calagem não alteraram a produtividade de grãos de milho. O cultivo de milho após crotalária apresentou melhor desempenho e menor demanda de adubação nitrogenada, quando comparado ao cultivado após milheto.The no-tillage (NT) management is widely used in the Cerrado region, but some questions remain unanswered, for example about the need of liming and adequate nitrogen rates for commercial crops when preceded by cover crops. Our objective was to evaluate the effect of precedent cover crops on the maize demand for nitrogen fertilization and forms of liming preceding the adoption of no-tillage management (NT) in different growing seasons. The experiment was arranged in a randomized block factorial design 5 x 2 (liming forms x cover crops) and later divided into three subplots representing the N rates (0, 90 and 180 kg ha-1). Four liming forms were evaluated: lime rate incorporated in the 0 - 0.2 m soil layer in Oct/2001; total dose applied on the surface in Oct/2001; 1/2 amount applied in Oct/2001 and 1/2 in Aug/2002 on the surface; and 1/3 of the recommended dose applied in Mar/2001 + 1/3 in Oct/2001 + 1/3 in Aug/2002, all on the soil surface; plus a control treatment (no lime) and two cover crops (sunn hemp and millet). Maize grain yield was not affected by the different liming forms. Sunn hemp proved more efficient than millet as cover crop preceding maize.Universidade Federal de Mato Grosso do Sul (UFMS)Universidade Estadual Paulista (Unesp) Departamento de Fitotecnia, Sócio-Economia e Tecnologia de AlimentosUnesp AgronomiaUSP Centro de Energia Nuclear na Agricultura - CENA CiênciasUniversidade Estadual Paulista (Unesp) Departamento de Fitotecnia, Sócio-Economia e Tecnologia de AlimentosUnesp Agronomi

Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy