158 research outputs found

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

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    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

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

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    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

    Hypoxic Pulmonary Vasoconstriction in Humans:Tale or Myth

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    Hypoxic Pulmonary vasoconstriction (HPV) describes the physiological adaptive process of lungs to preserves systemic oxygenation. It has clinical implications in the development of pulmonary hypertension which impacts on outcomes of patients undergoing cardiothoracic surgery. This review examines both acute and chronic hypoxic vasoconstriction focusing on the distinct clinical implications and highlights the role of calcium and mitochondria in acute versus the role of reactive oxygen species and Rho GTPases in chronic HPV. Furthermore it identifies gaps of knowledge and need for further research in humans to clearly define this phenomenon and the underlying mechanism

    Search for heavy resonances decaying into a Z or W boson and a Higgs boson in final states with leptons and b-jets in 139 fb−1 of pp collisions at s√ = 13 TeV with the ATLAS detector

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    This article presents a search for new resonances decaying into a Z or W boson and a 125 GeV Higgs boson h, and it targets the ÎœÎœÂŻÂŻÂŻbbÂŻÂŻ, ℓ+ℓ−bbÂŻÂŻ, or ℓ±ΜbbÂŻÂŻ final states, where ℓ = e or ÎŒ, in proton-proton collisions at s√ = 13 TeV. The data used correspond to a total integrated luminosity of 139 fb−1 collected by the ATLAS detector during Run 2 of the LHC at CERN. The search is conducted by examining the reconstructed invariant or transverse mass distributions of Zh or Wh candidates for evidence of a localised excess in the mass range from 220 GeV to 5 TeV. No significant excess is observed and 95% confidence-level upper limits between 1.3 pb and 0.3 fb are placed on the production cross section times branching fraction of neutral and charged spin-1 resonances and CP-odd scalar bosons. These limits are converted into constraints on the parameter space of the Heavy Vector Triplet model and the two-Higgs-doublet model

    Search for boosted diphoton resonances in the 10 to 70 GeV mass range using 138 fb−1 of 13 TeV pp collisions with the ATLAS detector

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    A search for diphoton resonances in the mass range between 10 and 70 GeV with the ATLAS experiment at the Large Hadron Collider (LHC) is presented. The analysis is based on pp collision data corresponding to an integrated luminosity of 138 fb−1 at a centre-of-mass energy of 13 TeV recorded from 2015 to 2018. Previous searches for diphoton resonances at the LHC have explored masses down to 65 GeV, finding no evidence of new particles. This search exploits the particular kinematics of events with pairs of closely spaced photons reconstructed in the detector, allowing examination of invariant masses down to 10 GeV. The presented strategy covers a region previously unexplored at hadron colliders because of the experimental challenges of recording low-energy photons and estimating the backgrounds. No significant excess is observed and the reported limits provide the strongest bound on promptly decaying axion-like particles coupling to gluons and photons for masses between 10 and 70 GeV

    Evidence for the charge asymmetry in pp → tt¯ production at s√ = 13 TeV with the ATLAS detector

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    Inclusive and differential measurements of the top–antitop (ttÂŻ) charge asymmetry AttÂŻC and the leptonic asymmetry Aℓℓ¯C are presented in proton–proton collisions at s√ = 13 TeV recorded by the ATLAS experiment at the CERN Large Hadron Collider. The measurement uses the complete Run 2 dataset, corresponding to an integrated luminosity of 139 fb−1, combines data in the single-lepton and dilepton channels, and employs reconstruction techniques adapted to both the resolved and boosted topologies. A Bayesian unfolding procedure is performed to correct for detector resolution and acceptance effects. The combined inclusive ttÂŻ charge asymmetry is measured to be AttÂŻC = 0.0068 ± 0.0015, which differs from zero by 4.7 standard deviations. Differential measurements are performed as a function of the invariant mass, transverse momentum and longitudinal boost of the ttÂŻ system. Both the inclusive and differential measurements are found to be compatible with the Standard Model predictions, at next-to-next-to-leading order in quantum chromodynamics perturbation theory with next-to-leading-order electroweak corrections. The measurements are interpreted in the framework of the Standard Model effective field theory, placing competitive bounds on several Wilson coefficients

    Search for third-generation vector-like leptons in pp collisions at s√ = 13 TeV with the ATLAS detector

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    A search for vector-like leptons in multilepton (two, three, or four-or-more electrons plus muons) final states with zero or more hadronic τ-lepton decays is presented. The search is performed using a dataset corresponding to an integrated luminosity of 139 fb−1 of proton-proton collisions at a centre-of-mass energy of 13 TeV recorded by the ATLAS detector at the LHC. To maximize the separation of signal and background, a machine-learning classifier is used. No excess of events is observed beyond the Standard Model expectation. Using a doublet vector-like lepton model, vector-like leptons coupling to third-generation Standard Model leptons are excluded in the mass range from 130 GeV to 900 GeV at the 95% confidence level, while the highest excluded mass is expected to be 970 GeV

    Measurements of Zγ+jets differential cross sections in pp collisions at s√ = 13 TeV with the ATLAS detector

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    Differential cross-section measurements of Zγ production in association with hadronic jets are presented, using the full 139 fb−1 dataset of s√ = 13 TeV proton–proton collisions collected by the ATLAS detector during Run 2 of the LHC. Distributions are measured using events in which the Z boson decays leptonically and the photon is usually radiated from an initial-state quark. Measurements are made in both one and two observables, including those sensitive to the hard scattering in the event and others which probe additional soft and collinear radiation. Different Standard Model predictions, from both parton-shower Monte Carlo simulation and fixed-order QCD calculations, are compared with the measurements. In general, good agreement is observed between data and predictions from MATRIX and MiNNLOPS, as well as next-to-leading-order predictions from MADGRAPH5_AMC@NLO and SHERPA

    A search for new resonances in multiple final states with a high transverse momentum Z boson in s√ = 13 TeV pp collisions with the ATLAS detector

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    A generic search for resonances is performed with events containing a Z boson with transverse momentum greater than 100 GeV, decaying into e+e− or ÎŒ+Ό−. The analysed data collected with the ATLAS detector in proton-proton collisions at a centre-of-mass energy of 13 TeV at the Large Hadron Collider correspond to an integrated luminosity of 139 fb−1. Two invariant mass distributions are examined for a localised excess relative to the expected Standard Model background in six independent event categories (and their inclusive sum) to increase the sensitivity. No significant excess is observed. Exclusion limits at 95% confidence level are derived for two cases: a model-independent interpretation of Gaussian-shaped resonances with the mass width between 3% and 10% of the resonance mass, and a specific heavy vector triplet model with the decay mode Wâ€Č → ZW → ℓℓqq

    Measurement of the Higgs boson mass in the H → ZZ⁎ → 4ℓ decay channel using 139 fb−1 of √s = 13 TeV pp collisions recorded by the ATLAS detector at the LHC

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    The mass of the Higgs boson is measured in the H → Z Z∗ → 4 decay channel. The analysis uses proton– proton collision data from the Large Hadron Collider at a centre-of-mass energy of 13 TeV recorded by the ATLAS detector between 2015 and 2018, corresponding to an integrated luminosity of 139 fb−1. The measured value of the Higgs boson mass is 124.99 ± 0.18(stat.) ± 0.04(syst.) GeV. In final states with muons, this measurement benefits from an improved momentum-scale calibration relative to that adopted in previous publications. The measurement also employs an analytic model that takes into account the invariant-mass resolution of the four-lepton system on a per-event basis and the output of a deep neural network discriminating signal from background events. This measurement is combined with the corresponding measurement using 7 and 8 TeV pp collision data, resulting in a Higgs boson mass of 124.94 ± 0.17(stat.) ± 0.03(syst.) GeV
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