949 research outputs found

    Case Report: Successful Treatment of a Child With COVID-19 Reinfection-Induced Fulminant Myocarditis by Cytokine-Adsorbing oXiris® Hemofilter Continuous Veno-Venous Hemofiltration and Extracorporeal Membrane Oxygenation

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    BACKGROUND: Indirect cardiomyocyte damage-related hyperinflammatory response is one of the key mechanisms in COVID-19-induced fulminant myocarditis. In addition to the clinical benefit of using cytokines absorption hemofiltration, the effectiveness of instituting veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support for cardiac compromise has been reported. However, current literature enunciates a paucity of available data on the effectiveness of these novel modalities. CASE PRESENTATION: We reported a 9-year-old boy with recurrent COVID-19 infection-causing fulminant myocarditis, who was treated successfully by using novel modalities of CONCLUSION: We conclude that the novel highly-absorptive hemofilter CVVH and VA-ECMO may be effective treatment modalities in managing SARS-CoV-2-induced fulminant myocarditis. Our report highlights the need for further well-designed investigations to confirm this extrapolation

    SETD2 Loss and ATR Inhibition Synergize to Promote cGAS Signaling and Immunotherapy Response in Renal Cell Carcinoma

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    PURPOSE: Immune checkpoint blockade (ICB) demonstrates durable clinical benefits in a minority of patients with renal cell carcinoma (RCC). We aimed to identify the molecular features that determine the response and develop approaches to enhance it. EXPERIMENTAL DESIGN: We investigated the effects of SET domain-containing protein 2 (SETD2) loss on the DNA damage response pathway, the cytosolic DNA-sensing pathway, the tumor immune microenvironment, and the response to ataxia telangiectasia and rad3-related (ATR) and checkpoint inhibition in RCC. RESULTS: ATR inhibition activated the cyclic GMP-AMP synthase (cGAS)-interferon regulatory factor 3 (IRF3)-dependent cytosolic DNA-sensing pathway, resulting in the concurrent expression of inflammatory cytokines and immune checkpoints. Among the common RCC genotypes, SETD2 loss is associated with preferential ATR activation and sensitizes cells to ATR inhibition. SETD2 knockdown promoted the cytosolic DNA-sensing pathway in response to ATR inhibition. Treatment with the ATR inhibitor VE822 concurrently upregulated immune cell infiltration and immune checkpoint expression in Setd2 knockdown Renca tumors, providing a rationale for ATR inhibition plus ICB combination therapy. Setd2-deficient Renca tumors demonstrated greater vulnerability to ICB monotherapy or combination therapy with VE822 than Setd2-proficient tumors. Moreover, SETD2 mutations were associated with a higher response rate and prolonged overall survival in patients with ICB-treated RCC but not in patients with non-ICB-treated RCC. CONCLUSIONS: SETD2 loss and ATR inhibition synergize to promote cGAS signaling and enhance immune cell infiltration, providing a mechanistic rationale for the combination of ATR and checkpoint inhibition in patients with RCC with SETD2 mutations

    Microtubules gate tau condensation to spatially regulate microtubule functions.

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    Tau is an abundant microtubule-associated protein in neurons. Tau aggregation into insoluble fibrils is a hallmark of Alzheimer's disease and other types of dementia1, yet the physiological state of tau molecules within cells remains unclear. Using single-molecule imaging, we directly observe that the microtubule lattice regulates reversible tau self-association, leading to localized, dynamic condensation of tau molecules on the microtubule surface. Tau condensates form selectively permissible barriers, spatially regulating the activity of microtubule-severing enzymes and the movement of molecular motors through their boundaries. We propose that reversible self-association of tau molecules, gated by the microtubule lattice, is an important mechanism of the biological functions of tau, and that oligomerization of tau is a common property shared between the physiological and disease-associated forms of the molecule

    Measurements of differential cross sections of Z/gamma*+jets+X events in proton anti-proton collisions at sqrt{s}=1.96 TeV

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    We present cross section measurements for Z/gamma*+jets+X production, differential in the transverse momenta of the three leading jets. The data sample was collected with the D0 detector at the Fermilab Tevatron proton anti-proton collider at a center-of-mass energy of 1.96 TeV and corresponds to an integrated luminosity of 1 fb-1. Leading and next-to-leading order perturbative QCD predictions are compared with the measurements, and agreement is found within the theoretical and experimental uncertainties. We also make comparisons with the predictions of four event generators. Two parton-shower-based generators show significant shape and normalization differences with respect to the data. In contrast, two generators combining tree-level matrix elements with a parton shower give a reasonable description of the the shapes observed in data, but the predicted normalizations show significant differences with respect to the data, reflecting large scale uncertainties. For specific choices of scales, the normalizations for either generator can be made to agree with the measurements.Comment: Published in PLB. 11 pages, 3 figure

    Measurement of the t-channel single top quark production cross section

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    The D0 collaboration reports direct evidence for electroweak production of single top quarks through the t-channel exchange of a virtual W boson. This is the first analysis to isolate an individual single top quark production channel. We select events containing an isolated electron or muon, missing transverse energy, and two, three or four jets from 2.3 fb^-1 of ppbar collisions at the Fermilab Tevatron Collider. One or two of the jets are identified as containing a b hadron. We combine three multivariate techniques optimized for the t-channel process to measure the t- and s-channel cross sections simultaneously. We measure cross sections of 3.14 +0.94 -0.80 pb for the t-channel and 1.05 +-0.81 pb for the s-channel. The measured t-channel result is found to have a significance of 4.8 standard deviations and is consistent with the standard model prediction.Comment: 7 pages, 6 figure

    Dependence of the ttˉt\bar{t} production cross section on the transverse momentum of the top quark

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    We present a measurement of the differential cross section for ttˉt\bar{t} events produced in ppˉp\bar{p} collisions at s=1.96\sqrt{s}=1.96 TeV as a function of the transverse momentum (pTp_T) of the top quark. The selected events contain a high-pTp_T lepton (\ell), four or more jets, and a large imbalance in pTp_T, and correspond to 1 fb1{}^{-1} of integrated luminosity recorded with the D0 detector. Each event must have at least one candidate for a bb jet. Objects in the event are associated through a constrained kinematic fit to the ttˉWbWbˉνbqqˉbˉt\bar{t}\to WbW\bar{b} \to \ell\nu b q\bar{q}'\bar{b} process. Results from next-to-leading-order perturbative QCD calculations agree with the measured differential cross section. Comparisons are also provided to predictions from Monte Carlo event generators using QCD calculations at different levels of precision.Comment: 8 pages, 6 figures, 4 tables, updated to reflect the published versio

    Double parton interactions in photon+3 jet events in ppbar collisions sqrt{s}=1.96 TeV

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    We have used a sample of photon+3 jets events collected by the D0 experiment with an integrated luminosity of about 1 fb^-1 to determine the fraction of events with double parton scattering (f_DP) in a single ppbar collision at sqrt{s}=1.96 TeV. The DP fraction and effective cross section (sigma_eff), a process-independent scale parameter related to the parton density inside the nucleon, are measured in three intervals of the second (ordered in pT) jet transverse momentum pT_jet2 within the range 15 < pT_jet2 < 30 GeV. In this range, f_DP varies between 0.23 < f_DP < 0.47, while sigma_eff has the average value sigma_eff_ave = 16.4 +- 0.3(stat) +- 2.3(syst) mb.Comment: 15 pages, 13 figure

    Measurement of trilinear gauge boson couplings from WW + WZ to lnu jj events in pp-bar collisions at sqrt{s}=1.96 TeV

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    We present a direct measurement of trilinear gauge boson couplings at gammaWW and ZWW vertices in WW and WZ events produced in pp-bar collisions at sqrt{s}=1.96 TeV. We consider events with one electron or muon, missing transverse energy, and at least two jets. The data were collected using the D0 detector and correspond to 1.1/fb of integrated luminosity. Considering two different relations between the couplings at the gammaWW and ZWW vertices, we measure these couplings at 68% C.L. to be kappa_{gamma}=1.07^{+0.26}_{-0.29}, lambda =0.00^{+0.06}_{-0.06} and g_{1}^{Z}=1.04^{+0.09}_{-0.09} in a scenario respecting SU(2)_L x U(1)_Y gauge symmetry and kappa =1.04^{+0.11}_{-0.11} and lambda=0.00^{+0.06}_{-0.06} in an "equal couplings" scenario.Comment: 14 pages, 7 figures, published in Phys. Rev. D, updated to published versio

    Measurement of the W boson mass

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    We present a measurement of the W boson mass in W -> ev decays using 1 fb^-1 of data collected with the D0 detector during Run II of the Fermilab Tevatron collider. With a sample of 499830 W -> ev candidate events, we measure M_W = 80.401 +- 0.043 GeV. This is the most precise measurement from a single experiment.Comment: As published in PR
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