Enhancement of red blood cell transfusion compatibility using CRISPR‐mediated erythroblast gene editing

Regular blood transfusion is the cornerstone of care for patients with red blood cell (RBC) disorders such as thalassaemia or sickle-cell disease. With repeated transfusion, alloimmunisation often occurs due to incompatibility at the level of minor blood group antigens. We use CRISPR-mediated genome editing of an immortalised human erythroblast cell line (BEL-A) to generate multiple enucleation competent cell lines deficient in individual blood groups. Edits are combined to generate a single cell line deficient in multiple antigens responsible for the most common transfusion incompatibilities: ABO (Bombay phenotype), Rh (Rhnull), Kell (K0), Duffy (Fynull), GPB (S−s−U−). These cells can be differentiated to generate deformable reticulocytes, illustrating the capacity for coexistence of multiple rare blood group antigen null phenotypes. This study provides the first proof-of-principle demonstration of combinatorial CRISPR-mediated blood group gene editing to generate customisable or multi-compatible RBCs for diagnostic reagents or recipients with complicated matching requirements

Effective Treatment of Erythema Nodosum Leprosum with Thalidomide Is Associated with Immune Stimulation

The immunomodulatory drug thalidomide is the treatment of choice for erythema nodosum leprosum (ENL), an inflammatory cutaneous and systemic complication of multibacillary leprosy. To elucidate the mechanism of action of thalidomide in this syndrome, we prospectively investigated 20 patients with ENL who were treated with thalidomide for 21 days. All patients responded to treatment, with the majority of them having complete resolution of cutaneous lesions within 7 days. This response was associated with a marked but transient increase in ex vivo mitogen-induced expression of interleukin (IL)-2 and interferon-γ by CD4+ and CD8+ T cells that was observed on treatment day 7, but these returned to pretreatment levels by day 21. Plasma tumor necrosis factor-α levels were not high at baseline, and they increased modestly during treatment. Plasma levels of IL-12 increased steadily during thalidomide treatment. Hence, the therapeutic effect of thalidomide in ENL appears to be associated with transient immune stimulation, which suggests that the drug may promote an active immunoregulatory respons

Search for CPCP violation in D0^0→\to KS0^0_\mathrm{S}KS0^0_\mathrm{S} decays in proton-proton collisions at s\sqrt{s} = 13 TeV

International audienceA search is reported for charge-parity D$^0$$\to$ K$^0_\mathrm{S}$K$^0_\mathrm{S}$$CP$ violation in D$^0$$\to$ K$^0_\mathrm{S}$K$^0_\mathrm{S}$ decays, using data collected in proton-proton collisions at $\sqrt{s}$ = 13 TeV recorded by the CMS experiment in 2018. The analysis uses a dedicated data set that corresponds to an integrated luminosity of 41.6 fb$^{-1}$, which consists of about 10 billion events containing a pair of ẖadrons, nearly all of which decay to charm hadrons. The flavor of the neutral D meson is determined by the pion charge in the reconstructed decays D$^{*+}$$\to$ D$^0\pi^+$ and D$^{*-}$$\to$ D$^0\pi^-$. The D$^0$$\to$ K$^0_\mathrm{S}$K$^0_\mathrm{S}$$CP$ asymmetry in D$^0$$\to$ K$^0_\mathrm{S}$K$^0_\mathrm{S}$ is measured to be $A_{CP}$( K$^0_\mathrm{S}$K$^0_\mathrm{S}$) = (6.2 $\pm$ 3.0 $\pm$ 0.2 $\pm$ 0.8)%, where the three uncertainties represent the statistical uncertainty, the systematic uncertainty, and the uncertainty in the measurement of the D$^0$ $\to$ K$^0_\mathrm{S}$K$^0_\mathrm{S}$ $CP$ asymmetry in the D$^0$ $\to$ K$^0_\mathrm{S}\pi^+\pi^-$ decay. This is the first D$^0$ $\to$ K$^0_\mathrm{S}$K$^0_\mathrm{S}$ $CP$ asymmetry measurement by CMS in the charm sector as well as the first to utilize a fully hadronic final state

The CMS Statistical Analysis and Combination Tool: COMBINE

International audienceThis paper describes the COMBINE software package used for statistical analyses by the CMS Collaboration. The package, originally designed to perform searches for a Higgs boson and the combined analysis of those searches, has evolved to become the statistical analysis tool presently used in the majority of measurements and searches performed by the CMS Collaboration. It is not specific to the CMS experiment, and this paper is intended to serve as a reference for users outside of the CMS Collaboration, providing an outline of the most salient features and capabilities. Readers are provided with the possibility to run COMBINE and reproduce examples provided in this paper using a publicly available container image. Since the package is constantly evolving to meet the demands of ever-increasing data sets and analysis sophistication, this paper cannot cover all details of COMBINE. However, the online documentation referenced within this paper provides an up-to-date and complete user guide

Dark sector searches with the CMS experiment

Astrophysical observations provide compelling evidence for gravitationally interacting dark matter in the universe that cannot be explained by the standard model of particle physics. The extraordinary amount of data from the CERN LHC presents a unique opportunity to shed light on the nature of dark matter at unprecedented collision energies. This Report comprehensively reviews the most recent searches with the CMS experiment for particles and interactions belonging to a dark sector and for dark-sector mediators. Models with invisible massive particles are probed by searches for signatures of missing transverse momentum recoiling against visible standard model particles. Searches for mediators are also conducted via fully visible final states. The results of these searches are compared with those obtained from direct-detection experiments. Searches for alternative scenarios predicting more complex dark sectors with multiple new particles and new forces are also presented. Many of these models include long-lived particles, which could manifest themselves with striking unconventional signatures with relatively small amounts of background. Searches for such particles are discussed and their impact on dark-sector scenarios is evaluated. Many results and interpretations have been newly obtained for this Report.Astrophysical observations provide compelling evidence for gravitationally interacting dark matter in the universe that cannot be explained by the standard model of particle physics. The extraordinary amount of data from the CERN LHC presents a unique opportunity to shed light on the nature of dark matter at unprecedented collision energies. This Report comprehensively reviews the most recent searches with the CMS experiment for particles and interactions belonging to a dark sector and for dark-sector mediators. Models with invisible massive particles are probed by searches for signatures of missing transverse momentum recoiling against visible standard model particles. Searches for mediators are also conducted via fully visible final states. The results of these searches are compared with those obtained from direct-detection experiments. Searches for alternative scenarios predicting more complex dark sectors with multiple new particles and new forces are also presented. Many of these models include long-lived particles, which could manifest themselves with striking unconventional signatures with relatively small amounts of background. Searches for such particles are discussed and their impact on dark-sector scenarios is evaluated. Many results and interpretations have been newly obtained for this Report

Search for a resonance decaying to a W boson and a photon in proton-proton collisions at s= \sqrt{s} = 13 TeV using leptonic W boson decays

A search for a new charged particle X with mass between 0.3 and 2.0 TeV decaying to a W boson and a photon is presented, using proton-proton collision data at a center-of-mass energy of 13 TeV, collected by the CMS experiment and corresponding to an integrated luminosity of 138 fb$^{-1}$. Particle X has electric charge $\pm$1 and is assumed to have spin 0. The search is performed using the electron and muon decays of the W boson. No significant excess above the predicted background is observed. The upper limit at 95% confidence level on the product of the production cross section of the X and its branching fraction to a W boson and a photon is found to be 94 (137) fb for a 0.3 TeV resonance and 0.75 (0.81) fb for a 2.0 TeV resonance, for an X width-to-mass ratio of 0.01% (5%). This search presents the most stringent constraints to date on the existence of such resonances across the probed mass range. A statistical combination with an earlier study based on the hadronic decay mode of the W boson is also performed, and the upper limit at 95% confidence level for a 2.0 TeV resonance is reduced to 0.50 (0.63) fb for an X width-to-mass ratio of 0.01% (5%).A search for a new charged particle X with mass between 0.3 and 2.0 TeV decaying to a W boson and a photon is presented, using proton-proton collision data at a center-of-mass energy of 13 TeV, collected by the CMS experiment and corresponding to an integrated luminosity of 138 fb$^{-1}$. Particle X has electric charge $\pm$1 and is assumed to have spin 0. The search is performed using the electron and muon decays of the W boson. No significant excess above the predicted background is observed. The upper limit at 95% confidence level on the product of the production cross section of the X and its branching fraction to a W boson and a photon is found to be 94 (137) fb for a 0.3 TeV resonance and 0.75 (0.81) fb for a 2.0 TeV resonance, for an X width-to-mass ratio of 0.01% (5%). This search presents the most stringent constraints to date on the existence of such resonances across the probed mass range. A statistical combination with an earlier study based on the hadronic decay mode of the W boson is also performed, and the upper limit at 95% confidence level for a 2.0 TeV resonance is reduced to 0.50 (0.63) fb for an X width-to-mass ratio of 0.01% (5%)

Search for CP violation in D0→KS0KS0 \mathrm{D^0}\to\mathrm{K^0_S}\mathrm{K^0_S} decays in proton-proton collisions at s= \sqrt{s} = 13 TeV

A search is reported for charge-parity CP violation in $\mathrm{D^0}\to\mathrm{K^0_S}\mathrm{K^0_S}$ decays, using data collected in proton-proton collisions at $\sqrt{s} =$ 13 TeV recorded by the CMS experiment in 2018. The analysis uses a dedicated data set that corresponds to an integrated luminosity of 41.6 fb$^{-1}$, which consists of about 10 billion events containing a pair of b hadrons, nearly all of which decay to charm hadrons. The flavor of the neutral $\mathrm{D}$ meson is determined by the pion charge in the reconstructed decays $\mathrm{D}^{*+}\to\mathrm{D^0}\pi^{+}$ and $\mathrm{D}^{*-}\to\overline{\mathrm{D}}^{0}\pi^{-}$. The CP asymmetry in $\mathrm{D^0}\to\mathrm{K^0_S}\mathrm{K^0_S}$ is measured to be $A_{CP}(\mathrm{K^0_S}\mathrm{K^0_S}) =$ (6.2 $\pm$ 3.0 $\pm$ 0.2 $\pm$ 0.8)%, where the three uncertainties represent the statistical uncertainty, the systematic uncertainty, and the uncertainty in the measurement of the CP asymmetry in the $\mathrm{D^0}\to\mathrm{K^0_S}\pi^{+}\pi^{-}$ decay. This is the first CP asymmetry measurement by CMS in the charm sector as well as the first to utilize a fully hadronic final state.A search is reported for charge-parity D$^0$$\to$ K$^0_\mathrm{S}$K$^0_\mathrm{S}$$CP$ violation in D$^0$$\to$ K$^0_\mathrm{S}$K$^0_\mathrm{S}$ decays, using data collected in proton-proton collisions at $\sqrt{s}$ = 13 TeV recorded by the CMS experiment in 2018. The analysis uses a dedicated data set that corresponds to an integrated luminosity of 41.6 fb$^{-1}$, which consists of about 10 billion events containing a pair of ẖadrons, nearly all of which decay to charm hadrons. The flavor of the neutral D meson is determined by the pion charge in the reconstructed decays D$^{*+}$$\to$ D$^0\pi^+$ and D$^{*-}$$\to$ D$^0\pi^-$. The D$^0$$\to$ K$^0_\mathrm{S}$K$^0_\mathrm{S}$$CP$ asymmetry in D$^0$$\to$ K$^0_\mathrm{S}$K$^0_\mathrm{S}$ is measured to be $A_{CP}$( K$^0_\mathrm{S}$K$^0_\mathrm{S}$) = (6.2 $\pm$ 3.0 $\pm$ 0.2 $\pm$ 0.8)%, where the three uncertainties represent the statistical uncertainty, the systematic uncertainty, and the uncertainty in the measurement of the D$^0$ $\to$ K$^0_\mathrm{S}$K$^0_\mathrm{S}$ $CP$ asymmetry in the D$^0$ $\to$ K$^0_\mathrm{S}\pi^+\pi^-$ decay. This is the first D$^0$ $\to$ K$^0_\mathrm{S}$K$^0_\mathrm{S}$ $CP$ asymmetry measurement by CMS in the charm sector as well as the first to utilize a fully hadronic final state

Search for baryon number violation in top quark production and decay using proton-proton collisions at s= \sqrt{s} = 13 TeV

A search is presented for baryon number violating interactions in top quark production and decay. The analysis uses data from proton-proton collisions at a center-of-mass energy of 13 TeV, collected with the CMS detector at the LHC with an integrated luminosity of 138 fb$^{-1}$. Candidate events are selected by requiring two oppositely-charged leptons (electrons or muons) and exactly one jet identified as originating from a bottom quark. Multivariate discriminants are used to separate the signal from the background. No significant deviation from the standard model prediction is observed. Upper limits are placed on the strength of baryon number violating couplings. For the first time the production of single top quarks via baryon number violating interactions is studied. This allows the search to set the most stringent constraints to date on the branching fraction of the top quark decay to a lepton, an up-type quark (u or c), and a down-type quark (d, s, or b). The results improve the previous bounds by three to six orders of magnitude based on the fermion flavor combination of the baryon number violating interactions.A search is presented for baryon number violating interactions in top quark production and decay. The analysis uses data from proton-proton collisions at a center-of-mass energy of 13 TeV, collected with the CMS detector at the LHC with an integrated luminosity of 138 fb$^{-1}$. Candidate events are selected by requiring two oppositely-charged leptons (electrons or muons) and exactly one jet identified as originating from a bottom quark. Multivariate discriminants are used to separate the signal from the background. No significant deviation from the standard model prediction is observed. Upper limits are placed on the strength of baryon number violating couplings. For the first time the production of single top quarks via baryon number violating interactions is studied. This allows the search to set the most stringent constraints to date on the branching fraction of the top quark decay to a lepton, an up-type quark (u or c), and a down-type quark (d, s, or b). The results improve the previous bounds by three to six orders of magnitude based on the fermion flavor combination of the baryon number violating interactions

Measurement of inclusive and differential cross sections for W+^{+}W−^{-} production in proton-proton collisions at s= \sqrt{s} = 13.6 TeV

Measurements at $\sqrt{s}=$ 13.6 TeV of the opposite-sign W boson pair production cross section in proton-proton collisions are presented. The data used in this study were collected with the CMS detector at the CERN LHC in 2022, and correspond to an integrated luminosity of 34.8 fb$^{-1}$. Events are selected by requiring one electron and one muon of opposite charge. A maximum likelihood fit is performed on signal- and background-enriched data categories defined by the flavour and charge of the leptons, the number of jets, and number of jets originating from b quarks. An inclusive W$^{+}$W$^{-}$ production cross section of 125.7 $\pm$ 5.6 pb is measured, in agreement with standard model predictions. Cross sections are also reported in a fiducial region close to that of the detector acceptance, both inclusively and differentially, as a function of the jet multiplicity in the event. For first time in proton-proton collisions, WW events with at least two reconstructed jets are studied and compared with recent theoretical predictions.Measurements at $\sqrt{s}$ = 13.6 TeV of the opposite-sign W boson pair production cross section in proton-proton collisions are presented. The data used in this study were collected with the CMS detector at the CERN LHC in 2022, and correspond to an integrated luminosity of 34.8 fb$^{-1}$. Events are selected by requiring one electron and one muon of opposite charge. A maximum likelihood fit is performed on signal- and background-enriched data categories defined by the flavour and charge of the leptons, the number of jets, and number of jets originating from b quarks. An inclusive W$^+$W$^-$ production cross section of 125.7 $\pm$ 5.6 pb is measured, in agreement with standard model predictions. Cross sections are also reported in a fiducial region close to that of the detector acceptance, both inclusively and differentially, as a function of the jet multiplicity in the event. For first time in proton-proton collisions, WW events with at least two reconstructed jets are studied and compared with recent theoretical predictions