Gene expression patterns unveil a new level of molecular heterogeneity in colorectal cancer.

The recognition that colorectal cancer (CRC) is a heterogeneous disease in terms of clinical behaviour and response to therapy translates into an urgent need for robust molecular disease subclassifiers that can explain this heterogeneity beyond current parameters (MSI, KRAS, BRAF). Attempts to fill this gap are emerging. The Cancer Genome Atlas (TGCA) reported two main CRC groups, based on the incidence and spectrum of mutated genes, and another paper reported an EMT expression signature defined subgroup. We performed a prior free analysis of CRC heterogeneity on 1113 CRC gene expression profiles and confronted our findings to established molecular determinants and clinical, histopathological and survival data. Unsupervised clustering based on gene modules allowed us to distinguish at least five different gene expression CRC subtypes, which we call surface crypt-like, lower crypt-like, CIMP-H-like, mesenchymal and mixed. A gene set enrichment analysis combined with literature search of gene module members identified distinct biological motifs in different subtypes. The subtypes, which were not derived based on outcome, nonetheless showed differences in prognosis. Known gene copy number variations and mutations in key cancer-associated genes differed between subtypes, but the subtypes provided molecular information beyond that contained in these variables. Morphological features significantly differed between subtypes. The objective existence of the subtypes and their clinical and molecular characteristics were validated in an independent set of 720 CRC expression profiles. Our subtypes provide a novel perspective on the heterogeneity of CRC. The proposed subtypes should be further explored retrospectively on existing clinical trial datasets and, when sufficiently robust, be prospectively assessed for clinical relevance in terms of prognosis and treatment response predictive capacity. Original microarray data were uploaded to the ArrayExpress database (http://www.ebi.ac.uk/arrayexpress/) under Accession Nos E-MTAB-990 and E-MTAB-1026. © 2013 Swiss Institute of Bioinformatics. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland

Histological and immunohistochemical features of medullary breast cancer

Disputes take place among many scientists about the position of MC in the classification of breast cancer. Some say that this kind of tumor is a sign of invasive ductal carcinoma (IDC). Instead, most of modern researchers distinguish MC of the breast as a separate nosological unit. Primarily there were selected 20 cases of MC and 10 cases of IDC (as control group). The immunohistochemical study revealed the presence of ER, PR, HER2/neo, p53, Ki-67, MMP1 and E-cadherin receptors. In the study of receptor status of tumors it was observed that 100% of MC cases were estrogen-, progesterone- and HER2/neu negative. The status of tumors on receptor p53 and Ki-67 was as follows: p53+ status had 80% and Ki-67+ had 85% of tissues of MC. In 75% of cases MC cells expressed marker of adhesion and in 100% of cases cells were receptor-negative for expression of MMP1. The data of the study show that the invasive ductal carcinoma and medullary carcinoma are completely independent and different types of malignancy in the breast. The favorable behavior of medullary cancer is associated with expression of E-cadherin receptors, which are essentially adhesion factor and absence of MMP1 which are factors of metastatic potential of the tumor

Search for supersymmetry in final states with missing transverse momentum and three or more b-jets in 139 fb−1^{-1} of proton–proton collisions at s=13\sqrt{s} = 13 TeV with the ATLAS detector

International audienceA search for supersymmetry involving the pair production of gluinos decaying via off-shell third-generation squarks into the lightest neutralino $(\tilde{\chi }^0_1)$ is reported. It exploits LHC proton–proton collision data at a centre-of-mass energy $\sqrt{s} = 13$ TeV with an integrated luminosity of 139 fb$^{-1}$ collected with the ATLAS detector from 2015 to 2018. The search uses events containing large missing transverse momentum, up to one electron or muon, and several energetic jets, at least three of which must be identified as containing b-hadrons. Both a simple kinematic event selection and an event selection based upon a deep neural-network are used. No significant excess above the predicted background is found. In simplified models involving the pair production of gluinos that decay via off-shell top (bottom) squarks, gluino masses less than 2.44 TeV (2.35 TeV) are excluded at 95% CL for a massless $\tilde{\chi }^0_1.$ Limits are also set on the gluino mass in models with variable branching ratios for gluino decays to $b\bar{b}\tilde{\chi }^0_1,t\bar{t}\tilde{\chi }^0_1$ and $t\bar{b}\tilde{\chi }^-_1/\bar{t}b\tilde{\chi }^+_1.

Search for pair production of third-generation leptoquarks decaying into a bottom quark and a τ\tau -lepton with the ATLAS detector

International audienceA search for pair-produced scalar or vector leptoquarks decaying into a b-quark and a $\tau$-lepton is presented using the full LHC Run 2 (2015–2018) data sample of 139 fb$^{-1}$ collected with the ATLAS detector in proton–proton collisions at a centre-of-mass energy of $\sqrt{s} =13$ TeV. Events in which at least one $\tau$-lepton decays hadronically are considered, and multivariate discriminants are used to extract the signals. No significant deviations from the Standard Model expectation are observed and 95% confidence-level upper limits on the production cross-section are derived as a function of leptoquark mass and branching ratio $\mathcal {B}$ into a $\tau$-lepton and b-quark. For scalar leptoquarks, masses below 1460 GeV are excluded assuming $\mathcal {B}=100$%, while for vector leptoquarks the corresponding limit is 1650 GeV (1910 GeV) in the minimal-coupling (Yang–Mills) scenario

Luminosity determination in pppp collisions at s=13\sqrt{s}=13 TeV using the ATLAS detector at the LHC

The luminosity determination for the ATLAS detector at the LHC during Run 2 is presented, with $pp$ collisions at $\sqrt{s}=13$ TeV. The absolute luminosity scale is determined using van der Meer beam separation scans during dedicated running periods in each year, and extrapolated to the physics data-taking regime using complementary measurements from several luminosity-sensitive detectors. The total uncertainties in the integrated luminosities for each individual year of data-taking range from 0.9% to 1.1%, and are partially correlated between years. After standard data-quality selections, the full Run 2 $pp$ data sample corresponds to an integrated luminosity of $140.1\pm 1.2$ fb$^{-1}$, i.e. an uncertainty of 0.83%. A dedicated sample of low-pileup data recorded in 2017-18 for precision Standard Model physics measurements is analysed separately, and has an integrated luminosity of $338.1\pm 3.1$ pb$^{-1}$.The luminosity determination for the ATLAS detector at the LHC during Run 2 is presented, with pp collisions at a centre-of-mass energy $\sqrt{s}=13$ TeV. The absolute luminosity scale is determined using van der Meer beam separation scans during dedicated running periods in each year, and extrapolated to the physics data-taking regime using complementary measurements from several luminosity-sensitive detectors. The total uncertainties in the integrated luminosity for each individual year of data-taking range from 0.9% to 1.1%, and are partially correlated between years. After standard data-quality selections, the full Run 2 pp data sample corresponds to an integrated luminosity of $140.1\pm 1.2$ $\hbox {fb}^{-1}$, i.e. an uncertainty of 0.83%. A dedicated sample of low-pileup data recorded in 2017–2018 for precision Standard Model physics measurements is analysed separately, and has an integrated luminosity of $338.1\pm 3.1$ $\hbox {pb}^{-1}$.The luminosity determination for the ATLAS detector at the LHC during Run 2 is presented, with $pp$ collisions at $\sqrt{s}=13$ TeV. The absolute luminosity scale is determined using van der Meer beam separation scans during dedicated running periods in each year, and extrapolated to the physics data-taking regime using complementary measurements from several luminosity-sensitive detectors. The total uncertainties in the integrated luminosities for each individual year of data-taking range from 0.9% to 1.1%, and are partially correlated between years. After standard data-quality selections, the full Run 2 $pp$ data sample corresponds to an integrated luminosity of $140.1\pm 1.2$ fb$^{-1}$, i.e. an uncertainty of 0.83%. A dedicated sample of low-pileup data recorded in 2017-18 for precision Standard Model physics measurements is analysed separately, and has an integrated luminosity of $338.1\pm 3.1$ pb$^{-1}$

Exclusive dielectron production in ultraperipheral Pb+Pb collisions at sNN \sqrt{s_{\textrm{NN}}} = 5.02 TeV with ATLAS

International audienceExclusive production of dielectron pairs, γγ → e$^{+}$e$^{−}$, is studied using ${\mathcal{L}}_{\textrm{int}}$ = 1.72 nb$^{−1}$ of data from ultraperipheral collisions of lead nuclei at $\sqrt{s_{\textrm{NN}}}$ = 5.02 TeV recorded by the ATLAS detector at the LHC. The process of interest proceeds via photon–photon interactions in the strong electromagnetic fields of relativistic lead nuclei. Dielectron production is measured in the fiducial region defined by following requirements: electron transverse momentum ${p}_{\textrm{T}}^e$> 2.5 GeV, absolute electron pseudorapidity |η$^{e}$| 5 GeV, and dielectron transverse momentum ${p}_{\textrm{T}}^{ee}$< 2 GeV. Differential cross-sections are measured as a function of m$_{ee}$, average ${p}_{\textrm{T}}^e$, absolute dielectron rapidity |y$_{ee}$|, and scattering angle in the dielectron rest frame, |cos θ$^{*}$|, in the inclusive sample, and also with a requirement of no activity in the forward direction. The total integrated fiducial cross-section is measured to be $215\pm 1{\left(\textrm{stat}.\right)}_{-20}^{+23}\left(\textrm{syst}.\right)\pm 4\left(\textrm{lumi}.\right)$μb. Within experimental uncertainties the measured integrated cross-section is in good agreement with the QED predictions from the Monte Carlo programs Starlight and SuperChic, confirming the broad features of the initial photon fluxes. The differential cross-sections show systematic differences from these predictions which are more pronounced at high |y$_{ee}$| and |cos θ$^{*}$| values.[graphic not available: see fulltext

Search for pair-produced scalar and vector leptoquarks decaying into third-generation quarks and first- or second-generation leptons in pp collisions with the ATLAS detector

International audienceA search for pair-produced scalar and vector leptoquarks decaying into quarks and leptons of different generations is presented. It uses the full LHC Run 2 (2015–2018) data set of 139 fb$^{−1}$ collected with the ATLAS detector in proton–proton collisions at a centre-of-mass energy of $\sqrt{s}$ = 13 TeV. Scalar leptoquarks with charge −(1/3)e as well as scalar and vector leptoquarks with charge +(2/3)e are considered. All possible decays of the pair-produced leptoquarks into quarks of the third generation (t, b) and charged or neutral leptons of the first or second generation (e, μ, ν) with exactly one electron or muon in the final state are investigated. No significant deviations from the Standard Model expectation are observed. Upper limits on the production cross-section are provided for eight models as a function of the leptoquark mass and the branching ratio of the leptoquark into the charged or neutral lepton. In addition, lower limits on the leptoquark masses are derived for all models across a range of branching ratios. Two of these models have the goal of providing an explanation for the recent B-anomalies. In both models, a vector leptoquark decays into charged and neutral leptons of the second generation with a similar branching fraction. Lower limits of 1980 GeV and 1710 GeV are set on the leptoquark mass for these two models.[graphic not available: see fulltext

Measurement of single top-quark production in the s-channel in proton–proton collisions at s \sqrt{s} = 13 TeV with the ATLAS detector

International audienceA measurement of single top-quark production in the s-channel is performed in proton–proton collisions at a centre-of-mass energy of 13 TeV with the ATLAS detector at the CERN Large Hadron Collider. The dataset corresponds to an integrated luminosity of 139 fb$^{−1}$. The analysis is performed on events with an electron or muon, missing transverse momentum and exactly two b-tagged jets in the final state. A discriminant based on matrix element calculations is used to separate single-top-quark s-channel events from the main background contributions, which are top-quark pair production and W-boson production in association with jets. The observed (expected) signal significance over the background-only hypothesis is 3.3 (3.9) standard deviations, and the measured cross-section is $\sigma ={8.2}_{-2.9}^{+3.5}$ pb, consistent with the Standard Model prediction of ${\sigma}^{\textrm{SM}}={10.32}_{-0.36}^{+0.40}$ pb.[graphic not available: see fulltext

Search for pair production of third-generation leptoquarks decaying into a bottom quark and a τ\tau-lepton with the ATLAS detector

A search for pair-produced scalar or vector leptoquarks decaying into a $b$-quark and a $\tau$-lepton is presented using the full LHC Run 2 (2015-2018) data sample of 139 fb$^{-1}$ collected with the ATLAS detector in proton-proton collisions at a centre-of-mass energy of $\sqrt{s}=13$ TeV. Events in which at least one $\tau$-lepton decays hadronically are considered, and multivariate discriminants are used to extract the signals. No significant deviations from the Standard Model expectation are observed and 95% confidence-level upper limits on the production cross-section are derived as a function of leptoquark mass and branching ratio into the $\tau$-lepton. For scalar leptoquarks, masses below 1490 GeV are excluded assuming a 100% branching ratio, while for vector leptoquarks the corresponding limit is 1690 GeV (1960 GeV) in the minimal-coupling (Yang-Mills) scenario.A search for pair-produced scalar or vector leptoquarks decaying into a $b$-quark and a $\tau$-lepton is presented using the full LHC Run 2 (2015-2018) data sample of 139 fb$^{-1}$ collected with the ATLAS detector in proton-proton collisions at a centre-of-mass energy of $\sqrt{s}=13$ TeV. Events in which at least one $\tau$-lepton decays hadronically are considered, and multivariate discriminants are used to extract the signals. No significant deviations from the Standard Model expectation are observed and 95% confidence-level upper limits on the production cross-section are derived as a function of leptoquark mass and branching ratio into the $\tau$-lepton. For scalar leptoquarks, masses below 1490 GeV are excluded assuming a 100% branching ratio, while for vector leptoquarks the corresponding limit is 1690 GeV (1960 GeV) in the minimal-coupling (Yang-Mills) scenario

Measurement of the total cross section and ρ\rho -parameter from elastic scattering in pp collisions at s=13\sqrt{s}=13 TeV with the ATLAS detector

International audienceIn a special run of the LHC with $\beta ^{\star } = 2.5$ km, proton–proton elastic-scattering events were recorded at $\sqrt{s} = 13$ TeV with an integrated luminosity of 340~\upmu {\text {b}}^{-1} using the ALFA subdetector of ATLAS in 2016. The elastic cross section was measured differentially in the Mandelstam t variable in the range from $-t = 2.5 \cdot 10^{-4}$ GeV$^{2}$ to $-t = 0.46$ GeV$^{2}$ using 6.9 million elastic-scattering candidates. This paper presents measurements of the total cross section $\sigma _{\text {tot}}$, parameters of the nuclear slope, and the $\rho$-parameter defined as the ratio of the real part to the imaginary part of the elastic-scattering amplitude in the limit $t \rightarrow 0$. These parameters are determined from a fit to the differential elastic cross section using the optical theorem and different parameterizations of the t-dependence. The results for $\sigma _{\text {tot}}$ and $\rho$ are $\begin{aligned} \sigma _{\text {tot}}(pp\rightarrow X) = 104.7 \pm 1.1 \; \text{ mb },\quad \rho = 0.098 \pm 0.011 . \end{aligned}$The uncertainty in $\sigma _{\text {tot}}$ is dominated by the luminosity measurement, and in $\rho$ by imperfect knowledge of the detector alignment and by modelling of the nuclear amplitude