218 research outputs found

    Anti-erbB2 treatment induces cardiotoxicity by interfering with cell survival pathways

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    INTRODUCTION: Cardiac dysfunction is among the serious side effects of therapy with recombinant humanized anti-erbB2 monoclonal antibody. The antibody blocks ErbB-2, a receptor tyrosine kinase and co-receptor for other members of the ErbB and epidermal growth factor families, which is over-expressed on the surface of many malignant cells. ErbB-2 and its ligands neuregulin and ErbB-3/ErbB-4 are involved in survival and growth of cardiomyocytes in both postnatal and adult hearts, and therefore the drug may interrupt the correct functioning of the ErbB-2 pathway. METHODS: The effect of the rat-anti-erbB2 monoclonal antibody B-10 was studied in spontaneously beating primary myocyte cultures from rat neonatal hearts. Gene expression was determined by RT-PCR (reverse transcription polymerase chain reaction) and by rat stress-specific microarray analysis, protein levels by Western blot, cell contractility by video motion analysis, calcium transients by the FURA fluorescent method, and apoptosis using the TUNEL (terminal uridine nick-end labelling) assay. RESULTS: B-10 treatment induces significant changes in expression of 24 out of 207 stress genes analyzed using the microarray technique. Protein levels of ErbB-2, ErbB-3, ErbB-4 and neuregulin decreased after 1 day. However, both transcription and protein levels of ErbB-4 and gp130 increased several fold. Calreticulin and calsequestrin were overexpressed after three days, inducing a decrease in calcium transients, thereby influencing cell contractility. Apoptosis was induced in 20% cells after 24 hours. CONCLUSION: Blocking ErbB-2 in cultured rat cardiomyocytes leads to changes that may influence the cell cycle and affects genes involved in heart functions. B-10 inhibits pro-survival pathways and reduces cellular contractility. Thus, it is conceivable that this process may impair the stress response of the heart

    Point-of-Care Technologies for Precision Cardiovascular Care and Clinical Research

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    Point-of-care technologies (POC or POCT) are enabling innovative cardiovascular diagnostics that promise to improve patient care across diverse clinical settings. The National Heart, Lung, and Blood Institute convened a working group to discuss POCT in cardiovascular medicine. The multidisciplinary working group, which included clinicians, scientists, engineers, device manufacturers, regulatory officials, and program staff, reviewed the state of the POCT field; discussed opportunities for POCT to improve cardiovascular care, realize the promise of precision medicine, and advance the clinical research enterprise; and identified barriers facing translation and integration of POCT with existing clinical systems. A POCT development roadmap emerged to guide multidisciplinary teams of biomarker scientists, technologists, health care providers, and clinical trialists as they: 1) formulate needs assessments; 2) define device design specifications; 3) develop component technologies and integrated systems; 4) perform iterative pilot testing; and 5) conduct rigorous prospective clinical testing to ensure that POCT solutions have substantial effects on cardiovascular care

    Amplitude analysis of the Λb0→pK−γ decay

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    The resonant structure of the radiative decay Λb0→pK−γ in the region of proton-kaon invariant-mass up to 2.5 GeV/c2 is studied using proton-proton collision data recorded at centre-of-mass energies of 7, 8, and 13 TeV collected with the LHCb detector, corresponding to a total integrated luminosity of 9 fb−1. Results are given in terms of fit and interference fractions between the different components contributing to this final state. Only Λ resonances decaying to pK− are found to be relevant, where the largest contributions stem from the Λ(1520), Λ(1600), Λ(1800), and Λ(1890) states

    Studies of η\eta and ηâ€Č\eta' production in pppp and ppPb collisions

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    The production of η\eta and ηâ€Č\eta' mesons is studied in proton-proton and proton-lead collisions collected with the LHCb detector. Proton-proton collisions are studied at center-of-mass energies of 5.025.02 and 13 TeV13~{\rm TeV}, and proton-lead collisions are studied at a center-of-mass energy per nucleon of 8.16 TeV8.16~{\rm TeV}. The studies are performed in center-of-mass rapidity regions 2.5<yc.m.<3.52.5<y_{\rm c.m.}<3.5 (forward rapidity) and −4.0<yc.m.<−3.0-4.0<y_{\rm c.m.}<-3.0 (backward rapidity) defined relative to the proton beam direction. The η\eta and ηâ€Č\eta' production cross sections are measured differentially as a function of transverse momentum for 1.5<pT<10 GeV1.5<p_{\rm T}<10~{\rm GeV} and 3<pT<10 GeV3<p_{\rm T}<10~{\rm GeV}, respectively. The differential cross sections are used to calculate nuclear modification factors. The nuclear modification factors for η\eta and ηâ€Č\eta' mesons agree at both forward and backward rapidity, showing no significant evidence of mass dependence. The differential cross sections of η\eta mesons are also used to calculate η/π0\eta/\pi^0 cross section ratios, which show evidence of a deviation from the world average. These studies offer new constraints on mass-dependent nuclear effects in heavy-ion collisions, as well as η\eta and ηâ€Č\eta' meson fragmentation.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/Publications/p/LHCb-PAPER-2023-030.html (LHCb public pages

    Observation of Cabibbo-suppressed two-body hadronic decays and precision mass measurement of the Ωc0\Omega_{c}^{0} baryon

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    The first observation of the singly Cabibbo-suppressed Ωc0→Ω−K+\Omega_{c}^{0}\to\Omega^{-}K^{+} and Ωc0→Ξ−π+\Omega_{c}^{0}\to\Xi^{-}\pi^{+} decays is reported, using proton-proton collision data at a centre-of-mass energy of 13 TeV13\,{\rm TeV}, corresponding to an integrated luminosity of 5.4 fb−15.4\,{\rm fb}^{-1}, collected with the LHCb detector between 2016 and 2018. The branching fraction ratios are measured to be B(Ωc0→Ω−K+)B(Ωc0→Ω−π+)=0.0608±0.0051(stat)±0.0040(syst)\frac{\mathcal{B}(\Omega_{c}^{0}\to\Omega^{-}K^{+})}{\mathcal{B}(\Omega_{c}^{0}\to\Omega^{-}\pi^{+})}=0.0608\pm0.0051({\rm stat})\pm 0.0040({\rm syst}), B(Ωc0→Ξ−π+)B(Ωc0→Ω−π+)=0.1581±0.0087(stat)±0.0043(syst)±0.0016(ext)\frac{\mathcal{B}(\Omega_{c}^{0}\to\Xi^{-}\pi^{+})}{\mathcal{B}(\Omega_{c}^{0}\to\Omega^{-}\pi^{+})}=0.1581\pm0.0087({\rm stat})\pm0.0043({\rm syst})\pm0.0016({\rm ext}). In addition, using the Ωc0→Ω−π+\Omega_{c}^{0}\to\Omega^{-}\pi^{+} decay channel, the Ωc0\Omega_{c}^{0} baryon mass is measured to be M(Ωc0)=2695.28±0.07(stat)±0.27(syst)±0.30(ext) MeV/c2M(\Omega_{c}^{0})=2695.28\pm0.07({\rm stat})\pm0.27({\rm syst})\pm0.30({\rm ext})\,{\rm MeV}/c^{2}, improving the precision of the previous world average by a factor of four.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-011.html (LHCb public pages

    Search for CP\textit{CP} violation in the phase space of D0→KS0K±π∓D^{0} \rightarrow K_{S}^{0} K^{\pm} \pi^{\mp} decays with the energy test

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    A search for CP\textit{CP} violation in D0→KS0K+π−D^{0} \rightarrow K_{S}^{0} K^{+} \pi^{-} and D0→KS0K−π+D^{0} \rightarrow K_{S}^{0} K^{-} \pi^{+} decays is reported. The search is performed using an unbinned model-independent method known as the energy test that probes local CP\textit{CP} violation in the phase space of the decays. The data analysed correspond to an integrated luminosity of 5.4 5.4~fb−1^{-1} collected in proton-proton collisions by the LHCb experiment at a centre-of-mass energy of s=13\sqrt{s}=13~TeV, amounting to approximately 950000 and 620000 signal candidates for the D0→KS0K−π+D^{0} \rightarrow K_{S}^{0} K^{-} \pi^{+} and D0→KS0K+π−D^{0} \rightarrow K_{S}^{0} K^{+} \pi^{-} modes, respectively. The method is validated using D0→K−π+π−π+D^{0} \rightarrow K^{-} \pi^{+} \pi^{-} \pi^{+} and D0→KS0π+π−D^{0} \rightarrow K_{S}^{0} \pi^{+} \pi^{-} decays, where CP\textit{CP}-violating effects are expected to be negligible, and using background-enhanced regions of the signal decays. The results are consistent with CP\textit{CP} symmetry in both the D0→KS0K−π+D^{0} \rightarrow K_{S}^{0} K^{-} \pi^{+} and the D0→KS0K+π−D^{0} \rightarrow K_{S}^{0} K^{+} \pi^{-} decays, with pp-values for the hypothesis of no CP\textit{CP} violation of 70% and 66%, respectively.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-019.html (LHCb public pages

    Fraction of χc\chi_c decays in prompt J/ψJ/\psi production measured in pPb collisions at sNN=8.16\sqrt{s_{NN}}=8.16 TeV

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    The fraction of χc1\chi_{c1} and χc2\chi_{c2} decays in the prompt J/ψJ/\psi yield, Fχc=σχc→J/ψ/σJ/ψF_{\chi c}=\sigma_{\chi_c \to J/\psi}/\sigma_{J/\psi}, is measured by the LHCb detector in pPb collisions at sNN=8.16\sqrt{s_{NN}}=8.16 TeV. The study covers the forward (1.5<y∗<4.01.5<y^*<4.0) and backward (−5.0<y∗<−2.5-5.0<y^*<-2.5) rapidity regions, where y∗y^* is the J/ψJ/\psi rapidity in the nucleon-nucleon center-of-mass system. Forward and backward rapidity samples correspond to integrated luminosities of 13.6 ±\pm 0.3 nb−1^{-1} and 20.8 ±\pm 0.5 nb−1^{-1}, respectively. The result is presented as a function of the J/ψJ/\psi transverse momentum pT,J/ψp_{T,J/\psi} in the range 1<pT,J/ψ<20<p_{T, J/\psi}<20 GeV/cc. The FχcF_{\chi c} fraction at forward rapidity is compatible with the LHCb measurement performed in pppp collisions at s=7\sqrt{s}=7 TeV, whereas the result at backward rapidity is 2.4 σ\sigma larger than in the forward region for 1<pT,J/ψ<31<p_{T, J/\psi}<3 GeV/cc. The increase of FχcF_{\chi c} at low pT,J/ψp_{T, J/\psi} at backward rapidity is compatible with the suppression of the ψ\psi(2S) contribution to the prompt J/ψJ/\psi yield. The lack of in-medium dissociation of χc\chi_c states observed in this study sets an upper limit of 180 MeV on the free energy available in these pPb collisions to dissociate or inhibit charmonium state formation.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-028.html (LHCb public pages

    Observation of strangeness enhancement with charmed mesons in high-multiplicity pPbp\mathrm{Pb} collisions at sNN=8.16 \sqrt {s_{\mathrm{NN}}}=8.16\,TeV

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    The production of prompt Ds+D^+_{s} and D+D^+ mesons is measured by the LHCb experiment in proton-lead (pPbp\mathrm{Pb}) collisions in both the forward (1.5<y∗<4.01.5<y^*<4.0) and backward (−5.0<y∗<−2.5-5.0<y^*<-2.5) rapidity regions at a nucleon-nucleon center-of-mass energy of sNN=8.16 \sqrt {s_{\mathrm{NN}}}=8.16\,TeV. The nuclear modification factors of both Ds+D^+_{s} and D+D^+ mesons are determined as a function of transverse momentum, pTp_{\mathrm{T}}, and rapidity. In addition, the Ds+D^+_{s} to D+D^+ cross-section ratio is measured as a function of the charged particle multiplicity in the event. An enhanced Ds+D^+_{s} to D+D^+ production in high-multiplicity events is observed for the whole measured pTp_{\mathrm{T}} range, in particular at low pTp_{\mathrm{T}} and backward rapidity, where the significance exceeds six standard deviations. This constitutes the first observation of strangeness enhancement in charm quark hadronization in high-multiplicity pPbp\mathrm{Pb} collisions. The results are also qualitatively consistent with the presence of quark coalescence as an additional charm quark hadronization mechanism in high-multiplicity proton-lead collisions.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-021.html (LHCb public pages

    Enhanced production of Λb0\Lambda_{b}^{0} baryons in high-multiplicity pppp collisions at s=13\sqrt{s} = 13 TeV

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    The production rate of Λb0\Lambda_{b}^{0} baryons relative to B0B^{0} mesons in pppp collisions at a center-of-mass energy s=13\sqrt{s} = 13 TeV is measured by the LHCb experiment. The ratio of Λb0\Lambda_{b}^{0} to B0B^{0} production cross-sections shows a significant dependence on both the transverse momentum and the measured charged-particle multiplicity. At low multiplicity, the ratio measured at LHCb is consistent with the value measured in e+e−e^{+}e^{-} collisions, and increases by a factor of ∌2\sim2 with increasing multiplicity. At relatively low transverse momentum, the ratio of Λb0\Lambda_{b}^{0} to B0B^{0} cross-sections is higher than what is measured in e+e−e^{+}e^{-} collisions, but converges with the e+e−e^{+}e^{-} ratio as the momentum increases. These results imply that the evolution of heavy bb quarks into final-state hadrons is influenced by the density of the hadronic environment produced in the collision. Comparisons with a statistical hadronization model and implications for the mechanisms enforcing quark confinement are discussed.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-027.html (LHCb public pages
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