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B cell depletion by the anti-CD20 antibody ocrelizumab is effective in relapsing-remitting (RR) and primary progressive (PP) multiple sclerosis (MS). We investigated immunological changes in peripheral blood of a real-world MS cohort after 6 and 12 months of ocrelizumab. All RRMS and most PPMS patients (15/20) showed treatment response. Ocrelizumab not only reduced CD20+ B cells, but also numbers of CD20+ T cells. Absolute numbers of monocytes, dendritic cells and CD8+ T cells were increased, while CD56hi natural killer cells were reduced after ocrelizumab. The residual B cell population shifted towards transitional and activated, IgA+ switched memory B cells, double negative B cells, and antibody-secreting cells. Delaying the treatment interval by 2-3 months increased mean B cell frequencies and enhanced naive B cell repopulation. Ocrelizumab reduced plasma levels of interleukin(IL)-12p70 and interferon(IFN)-α2. These findings will contribute to understanding ineffective treatment responses, dealing with life-threatening infections and further unravelling MS pathogenesis.
Assuntos
Anticorpos Monoclonais Humanizados , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Humanos , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Linfócitos T CD8-Positivos , Fatores Imunológicos/uso terapêutico , Interleucina-12 , Sistema ImunitárioRESUMO
A search for dark matter in events with a displaced nonresonant muon pair and missing transverse momentum is presented. The analysis is performed using an integrated luminosity of 138 fb^{-1} of proton-proton (pp) collision data at a center-of-mass energy of 13 TeV produced by the LHC in 2016-2018. No significant excess over the predicted backgrounds is observed. Upper limits are set on the product of the inelastic dark matter production cross section σ(ppâA^{'}âχ_{1}χ_{2}) and the decay branching fraction B(χ_{2}âχ_{1}µ^{+}µ^{-}), where A^{'} is a dark photon and χ_{1} and χ_{2} are states in the dark sector with near mass degeneracy. This is the first dedicated collider search for inelastic dark matter.
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The observation of WWγ production in proton-proton collisions at a center-of-mass energy of 13 TeV with an integrated luminosity of 138 fb^{-1} is presented. The observed (expected) significance is 5.6 (5.1) standard deviations. Events are selected by requiring exactly two leptons (one electron and one muon) of opposite charge, moderate missing transverse momentum, and a photon. The measured fiducial cross section for WWγ is 5.9±0.8(stat)±0.8(syst)±0.7(modeling) fb, in agreement with the next-to-leading order quantum chromodynamics prediction. The analysis is extended with a search for the associated production of the Higgs boson and a photon, which is generated by a coupling of the Higgs boson to light quarks. The result is used to constrain the Higgs boson couplings to light quarks.
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A search is reported for near-threshold structures in the J/ψJ/ψ invariant mass spectrum produced in proton-proton collisions at sqrt[s]=13 TeV from data collected by the CMS experiment, corresponding to an integrated luminosity of 135 fb^{-1}. Three structures are found, and a model with quantum interference among these structures provides a good description of the data. A new structure is observed with a local significance above 5 standard deviations at a mass of 6638_{-38}^{+43}(stat)_{-31}^{+16}(syst) MeV. Another structure with even higher significance is found at a mass of 6847_{-28}^{+44}(stat)_{-20}^{+48}(syst) MeV, which is consistent with the X(6900) resonance reported by the LHCb experiment and confirmed by the ATLAS experiment. Evidence for another new structure, with a local significance of 4.7 standard deviations, is found at a mass of 7134_{-25}^{+48}(stat)_{-15}^{+41}(syst) MeV. Results are also reported for a model without interference, which does not fit the data as well and shows mass shifts up to 150 MeV relative to the model with interference.
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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.
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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 3 to 6 orders of magnitude based on the fermion flavor combination of the baryon number violating interactions.
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The first search for singly produced narrow resonances decaying to three well-separated hadronic jets is presented. The search uses proton-proton collision data corresponding to an integrated luminosity of 138 fb^{-1} at sqrt[s]=13 TeV, collected at the CERN LHC. No significant deviations from the background predictions are observed between 1.75 and 9.00 TeV. The results provide the first mass limits on a right-handed boson Z_{R} decaying to three gluons and on an excited quark decaying via a vector boson to three quarks, as well as updated limits on a Kaluza-Klein gluon decaying via a radion to three gluons.
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The production of Ï(2S) and Ï(3S) mesons in lead-lead (Pb-Pb) and proton-proton (pp) collisions is studied in their dimuon decay channel using the CMS detector at the LHC. The Ï(3S) meson is observed for the first time in Pb-Pb collisions, with a significance above 5 standard deviations. The ratios of yields measured in Pb-Pb and pp collisions are reported for both the Ï(2S) and Ï(3S) mesons, as functions of transverse momentum and Pb-Pb collision centrality. These ratios, when appropriately scaled, are significantly less than unity, indicating a suppression of Ï yields in Pb-Pb collisions. This suppression increases from peripheral to central Pb-Pb collisions. Furthermore, the suppression is stronger for Ï(3S) mesons compared to Ï(2S) mesons, extending the pattern of sequential suppression of quarkonium states in nuclear collisions previously seen for the J/ψ, ψ(2S), Ï(1S), and Ï(2S) mesons.
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The first search exploiting the vector boson fusion process to probe heavy Majorana neutrinos and the Weinberg operator at the LHC is presented. The search is performed in the same-sign dimuon final state using a proton-proton collision dataset recorded at sqrt[s]=13 TeV, collected with the CMS detector and corresponding to a total integrated luminosity of 138 fb^{-1}. The results are found to agree with the predictions of the standard model. For heavy Majorana neutrinos, constraints on the squared mixing element between the muon and the heavy neutrino are derived in the heavy neutrino mass range 50 GeV-25 TeV; for masses above 650 GeV these are the most stringent constraints from searches at the LHC to date. A first test of the Weinberg operator at colliders provides an observed upper limit at 95% confidence level on the effective µµ Majorana neutrino mass of 10.8 GeV.
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We present an observation of photon-photon production of τ lepton pairs in ultraperipheral lead-lead collisions. The measurement is based on a data sample with an integrated luminosity of 404 µb^{-1} collected by the CMS experiment at a center-of-mass energy per nucleon pair of sqrt[s_{NN}]=5.02 TeV. The γγâτ^{+}τ^{-} process is observed for τ^{+}τ^{-} events with a muon and three charged hadrons in the final state. The measured fiducial cross section is σ(γγâτ^{+}τ^{-})=4.8±0.6(stat)±0.5(syst) µb, where the second (third) term corresponds to the statistical (systematic) uncertainty in σ(γγâτ^{+}τ^{-}) in agreement with leading-order QED predictions. Using σ(γγâτ^{+}τ^{-}), we estimate a model-dependent value of the anomalous magnetic moment of the τ lepton of a_{τ}=0.001_{-0.089}^{+0.055}.
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We present the first direct search for exotic Higgs boson decays HâAA, Aâγγ in events with two photonlike objects. The hypothetical particle A is a low-mass spin-0 particle decaying promptly to a merged diphoton reconstructed as a single photonlike object. We analyze the data collected by the CMS experiment at sqrt[s]=13 TeV corresponding to an integrated luminosity of 136 fb^{-1}. No excess above the estimated background is found. We set upper limits on the branching fraction B(HâAAâ4γ) of (0.9-3.3)×10^{-3} at 95% confidence level for masses of A in the range 0.1-1.2 GeV.
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The first observation of the production of W^{±}W^{±} bosons from double parton scattering processes using same-sign electron-muon and dimuon events in proton-proton collisions is reported. The data sample corresponds to an integrated luminosity of 138 fb^{-1} recorded at a center-of-mass energy of 13 TeV using the CMS detector at the CERN LHC. Multivariate discriminants are used to distinguish the signal process from the main backgrounds. A binned maximum likelihood fit is performed to extract the signal cross section. The measured cross section for production of same-sign W bosons decaying leptonically is 80.7±11.2(stat) _{-8.6}^{+9.5}(syst)±12.1(model) fb, whereas the measured fiducial cross section is 6.28±0.81(stat)±0.69(syst)±0.37(model) fb. The observed significance of the signal is 6.2 standard deviations above the background-only hypothesis.
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A search for the rare ηâµ^{+}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 ηâµ^{+}µ^{-} decay as normalization, the branching fraction B(ηâµ^{+}µ^{-}µ^{+}µ^{-})=[5.0±0.8(stat)±0.7(syst)±0.7(B_{2µ})]×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.
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The dependence of the ratio between the B_{s}^{0} and B^{+} hadron production fractions, f_{s}/f_{u}, on the transverse momentum (p_{T}) and rapidity of the B mesons is studied using the decay channels B_{s}^{0}âJ/ψÏ and B^{+}âJ/ψK^{+}. The analysis uses a data sample of proton-proton collisions at a center-of-mass energy of 13 TeV, collected by the CMS experiment in 2018 and corresponding to an integrated luminosity of 61.6 fb^{-1}. The f_{s}/f_{u} ratio is observed to depend on the B p_{T} and to be consistent with becoming asymptotically constant at large p_{T}. No rapidity dependence is observed. The ratio of the B^{0} to B^{+} meson production fractions, f_{d}/f_{u}, is also measured, for the first time in proton-proton collisions, using the B^{0}âJ/ψK^{*0} decay channel. The result is found to be within 1 standard deviation of unity and independent of p_{T} and rapidity, as expected from isospin invariance.
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A search for the standard model (SM) Higgs boson (H) produced with transverse momentum (p_{T}) greater than 450 GeV and decaying to a charm quark-antiquark (cc[over ¯]) pair is presented. The search is performed using proton-proton collision data collected at sqrt[s]=13 TeV by the CMS experiment at the LHC, corresponding to an integrated luminosity of 138 fb^{-1}. Boosted Hâcc[over ¯] decay products are reconstructed as a single large-radius jet and identified using a deep neural network charm tagging technique. The method is validated by measuring the Zâcc[over ¯] decay process, which is observed in association with jets at high p_{T} for the first time with a signal strength of 1.00_{-0.14}^{+0.17}(syst)±0.08(theo)±0.06(stat), defined as the ratio of the observed process rate to the SM expectation. The observed (expected) upper limit on σ(H)B(Hâcc[over ¯]) is set at 47 (39) times the SM prediction at 95% confidence level.
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A search for nonresonant Higgs boson (H) pair production via gluon and vector boson (V) fusion is performed in the four-bottom-quark final state, using proton-proton collision data at 13 TeV corresponding to 138 fb^{-1} collected by the CMS experiment at the LHC. The analysis targets Lorentz-boosted H pairs identified using a graph neural network. It constrains the strengths relative to the standard model of the H self-coupling and the quartic VVHH couplings, κ_{2V}, excluding κ_{2V}=0 for the first time, with a significance of 6.3 standard deviations when other H couplings are fixed to their standard model values.
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A search for the standard model Higgs boson decaying to a charm quark-antiquark pair, Hâcc[over ¯], produced in association with a leptonically decaying V (W or Z) boson is presented. The search is performed with proton-proton collisions at sqrt[s]=13 TeV collected by the CMS experiment, corresponding to an integrated luminosity of 138 fb^{-1}. Novel charm jet identification and analysis methods using machine learning techniques are employed. The analysis is validated by searching for Zâcc[over ¯] in VZ events, leading to its first observation at a hadron collider with a significance of 5.7 standard deviations. The observed (expected) upper limit on σ(VH)B(Hâcc[over ¯]) is 0.94 (0.50_{-0.15}^{+0.22})pb at 95% confidence level (C.L.), corresponding to 14 (7.6_{-2.3}^{+3.4}) times the standard model prediction. For the Higgs-charm Yukawa coupling modifier, κ_{c}, the observed (expected) 95% C.L. interval is 1.1<|κ_{c}|<5.5 (|κ_{c}|<3.4), the most stringent constraint to date.
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The structure of nucleons is multidimensional and depends on the transverse momenta, spatial geometry, and polarization of the constituent partons. Such a structure can be studied using high-energy photons produced in ultraperipheral heavy-ion collisions. The first measurement of the azimuthal angular correlations of exclusively produced events with two jets in photon-lead interactions at large momentum transfer is presented, a process that is considered to be sensitive to the underlying nuclear gluon polarization. This study uses a data sample of ultraperipheral lead-lead collisions at sqrt[s_{NN}]=5.02 TeV, corresponding to an integrated luminosity of 0.38 nb^{-1}, collected with the CMS experiment at the LHC. The measured second harmonic of the correlation between the sum and difference of the two jet transverse momentum vectors is found to be positive, and rising, as the dijet transverse momentum increases. A well-tuned model that has been successful at describing a wide range of proton scattering data from the HERA experiments fails to describe the observed correlations, suggesting the presence of gluon polarization effects.
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Quasireal photons exchanged in relativistic heavy ion interactions are powerful probes of the gluonic structure of nuclei. The coherent J/ψ photoproduction cross section in ultraperipheral lead-lead collisions is measured as a function of photon-nucleus center-of-mass energies per nucleon (W_{γN}^{Pb}) over a wide range of 40
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A search for pairs of Higgs bosons produced via gluon and vector boson fusion is presented, focusing on the four b quark final state. The data sample consists of proton-proton collisions at a center-of-mass energy of 13 TeV, collected with the CMS detector at the LHC, and corresponds to an integrated luminosity of 138 fb^{-1}. No deviation from the background-only hypothesis is observed. A 95% confidence level upper limit on the Higgs boson pair production cross section is observed at 3.9 times the standard model prediction for an expected value of 7.8. Constraints are also set on the modifiers of the Higgs field self-coupling, κ_{λ}, and of the coupling of two Higgs bosons to two vector bosons, κ_{2 V}. The observed (expected) allowed intervals at the 95% confidence level are -2.3<κ_{λ}<9.4 (-5.0<κ_{λ}<12.0) and -0.1<κ_{2 V}<2.2 (-0.4<κ_{2 V}<2.5). These are the most stringent observed constraints to date on the HH production cross section and on the κ_{2 V } coupling.