Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170.

We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER(+) or ER(-)) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER(-) tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.352

Search for new physics in multijet events with at least one photon and large missing transverse momentum in proton-proton collisions at 13 TeV

A search for new physics in final states consisting of at least one photon, multiple jets, and large missing transverse momentum is presented, using proton-proton collision events at a center-of-mass energy of 13 TeV. The data correspond to an integrated luminosity of 137 fb−1, recorded by the CMS experiment at the CERN LHC from 2016 to 2018. The events are divided into mutually exclusive bins characterized by the missing transverse momentum, the number of jets, the number of b-tagged jets, and jets consistent with the presence of hadronically decaying W, Z, or Higgs bosons. The observed data are found to be consistent with the prediction from standard model processes. The results are interpreted in the context of simplified models of pair production of supersymmetric particles via strong and electroweak interactions. Depending on the details of the signal models, gluinos and squarks of masses up to 2.35 and 1.43 TeV, respectively, and electroweakinos of masses up to 1.23 TeV are excluded at 95% confidence level

Observation of the Rare Decay of the η Meson to Four Muons

A search for the rare η→μ+μ−μ+μ− double-Dalitz decay is performed using a sample of proton-proton collisions, collected by the CMS experiment at the CERN LHC with high-rate muon triggers during 2017 and 2018 and corresponding to an integrated luminosity of 101  fb−1. A signal having a statistical significance well in excess of 5 standard deviations is observed. Using the η→μ+μ− decay as normalization, the branching fraction B(η→μ+μ−μ+μ−)=[5.0±0.8(stat)±0.7(syst)±0.7(B2μ)]×10−9 is measured, where the last term is the uncertainty in the normalization channel branching fraction. This work achieves an improved precision of over 5 orders of magnitude compared to previous results, leading to the first measurement of this branching fraction, which is found to agree with theoretical predictions

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Search for Scalar Leptoquarks Produced via τ-Lepton-Quark Scattering in pppp Collisions at s=13TeV\sqrt{s}=13 TeV

The first search for scalar leptoquarks produced in τ-lepton–quark collisions is presented. It is based on a set of proton-proton collision data recorded with the CMS detector at the LHC at a center-of-mass energy of 13 TeV corresponding to an integrated luminosity of 138  fb$^{−1}$. The reconstructed final state consists of a jet, significant missing transverse momentum, and a τ lepton reconstructed through its hadronic or leptonic decays. Limits are set on the product of the leptoquark production cross section and branching fraction and interpreted as exclusions in the plane of the leptoquark mass and the leptoquark-τ-quark coupling strength

Measurements of inclusive and differential cross sections for the Higgs boson production and decay to four-leptons in proton-proton collisions at s \sqrt{s} = 13 TeV

Measurements of the inclusive and differential fiducial cross sections for the Higgs boson production in the H → ZZ → 4ℓ (ℓ = e, μ) decay channel are presented. The results are obtained from the analysis of proton-proton collision data recorded by the CMS experiment at the CERN LHC at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 138 fb−1. The measured inclusive fiducial cross section is 2.73 ± 0.26 fb, in agreement with the standard model expectation of 2.86 ± 0.1 fb. Differential cross sections are measured as a function of several kinematic observables sensitive to the Higgs boson production and decay to four leptons. A set of double-differential measurements is also performed, yielding a comprehensive characterization of the four leptons final state. Constraints on the Higgs boson trilinear coupling and on the bottom and charm quark coupling modifiers are derived from its transverse momentum distribution. All results are consistent with theoretical predictions from the standard model

Performance of the local reconstruction algorithms for the CMS hadron calorimeter with Run 2 data

A description is presented of the algorithms used to reconstruct energy deposited in the CMS hadron calorimeter during Run 2 (2015–2018) of the LHC. During Run 2, the characteristic bunch-crossing spacing for proton-proton collisions was 25 ns, which resulted in overlapping signals from adjacent crossings. The energy corresponding to a particular bunch crossing of interest is estimated using the known pulse shapes of energy depositions in the calorimeter, which are measured as functions of both energy and time. A variety of algorithms were developed to mitigate the effects of adjacent bunch crossings on local energy reconstruction in the hadron calorimeter in Run 2, and their performance is compared

First measurement of the top quark pair production cross section in proton-proton collisions at s \sqrt{s} = 13.6 TeV

The first measurement of the top quark pair (tt¯) production cross section in proton-proton collisions at s√ = 13.6 TeV is presented. Data recorded with the CMS detector at the CERN LHC in Summer 2022, corresponding to an integrated luminosity of 1.21 fb−1, are analyzed. Events are selected with one or two charged leptons (electrons or muons) and additional jets. A maximum likelihood fit is performed in event categories defined by the number and flavors of the leptons, the number of jets, and the number of jets identified as originating from b quarks. An inclusive tt¯ production cross section of 881 ± 23 (stat + syst) ± 20 (lumi) pb is measured, in agreement with the standard model prediction of 924+32−40 pb