Sublayer- and cell-type-specific neurodegenerative transcriptional trajectories in hippocampal sclerosis

Altres ajuts: Fundación Tatiana Pérez de Guzman el Bueno; SynCogDis Network (SAF2014-52624-REDT, SAF2017-90664-REDT); Human Frontiers Science Program (HFSP RGP0022/2013); Fondo Europeo de Desarrollo Regional (FEDER).Hippocampal sclerosis, the major neuropathological hallmark of temporal lobe epilepsy, is characterized by different patterns of neuronal loss. The mechanisms of cell-type-specific vulnerability and their progression and histopathological classification remain controversial. Using single-cell electrophysiology in vivo and immediate-early gene expression, we reveal that superficial CA1 pyramidal neurons are overactive in epileptic rodents. Bulk tissue and single-nucleus expression profiling disclose sublayer-specific transcriptomic signatures and robust microglial pro-inflammatory responses. Transcripts regulating neuronal processes such as voltage channels, synaptic signaling, and cell adhesion are deregulated differently by epilepsy across sublayers, whereas neurodegenerative signatures primarily involve superficial cells. Pseudotime analysis of gene expression in single nuclei and in situ validation reveal separated trajectories from health to epilepsy across cell types and identify a subset of superficial cells undergoing a later stage in neurodegeneration. Our findings indicate that sublayer- and cell-type-specific changes associated with selective CA1 neuronal damage contribute to progression of hippocampal sclerosis

Factors associated with lesion detection in colonoscopy among different indications

Background and objective: Different factors may influence colonoscopy performance measures. We aimed to analyze procedure- and endoscopist-related factors associated with detection of colorectal lesions and whether these factors have a similar influence in the context of different colonoscopy indications: positive fecal immunochemical test (+FIT) and post-polypectomy surveillance colonoscopies. Methods: This multicenter cross-sectional study included adults aged 40-80 years. Endoscopists (N = 96) who had performed ≥50 examinations were assessed for physician-related factors. Adenoma detection rate (ADR), adenomas per colonoscopy rate (APCR), advanced ADR, serrated polyp detection (SDR), and serrated polyps per colonoscopy rate (SPPCR) were calculated. Results: We included 12,932 procedures, with 4810 carried out after a positive FIT and 1967 for surveillance. Of the 96 endoscopists evaluated, 43.8% were women, and the mean age was 41.9 years. The ADR, advanced ADR, and SDR were 39.7%, 17.7%, and 12.8%, respectively. Adenoma detection rate was higher in colonoscopies after a +FIT (50.3%) with a more than doubled advanced ADR compared to non-FIT procedures (27.6% vs. 13.0%) and similar results in serrated lesions (14.7% vs. 13.5%). Among all the detection indicators analyzed, withdrawal time was the only factor independently related to improvement (p < 0.001). Regarding FIT-positive and surveillance procedures, for both indications, withdrawal time was also the only factor associated with a higher detection of adenomas and serrated polyps (p < 0.001). Endoscopist-related factors (i.e., weekly hours dedicated to endoscopy, annual colonoscopy volume and lifetime number of colonoscopies performed) had also impact on lesion detection (APCR, advanced ADR and SPPCR). Conclusions: Withdrawal time was the factor most commonly associated with improved detection of colonic lesions globally and in endoscopies for + FIT and post-polypectomy surveillance. Physician-related factors may help to address strategies to support training and service provision. Our results can be used for establishing future benchmarking and quality improvement in different colonoscopy indications

Measurement of the mass and lifetime of the Ωb−\Omega_b^- baryon

A proton-proton collision data sample, corresponding to an integrated luminosity of 3 fb$^{-1}$ collected by LHCb at $\sqrt{s}=7$ and 8 TeV, is used to reconstruct $63\pm9$ $\Omega_b^-\to\Omega_c^0\pi^-$, $\Omega_c^0\to pK^-K^-\pi^+$ decays. Using the $\Xi_b^-\to\Xi_c^0\pi^-$, $\Xi_c^0\to pK^-K^-\pi^+$ decay mode for calibration, the lifetime ratio and absolute lifetime of the $\Omega_b^-$ baryon are measured to be \begin{align*} \frac{\tau_{\Omega_b^-}}{\tau_{\Xi_b^-}} &= 1.11\pm0.16\pm0.03, \\ \tau_{\Omega_b^-} &= 1.78\pm0.26\pm0.05\pm0.06~{\rm ps}, \end{align*} where the uncertainties are statistical, systematic and from the calibration mode (for $\tau_{\Omega_b^-}$ only). A measurement is also made of the mass difference, $m_{\Omega_b^-}-m_{\Xi_b^-}$, and the corresponding $\Omega_b^-$ mass, which yields \begin{align*} m_{\Omega_b^-}-m_{\Xi_b^-} &= 247.4\pm3.2\pm0.5~{\rm MeV}/c^2, \\ m_{\Omega_b^-} &= 6045.1\pm3.2\pm 0.5\pm0.6~{\rm MeV}/c^2. \end{align*} These results are consistent with previous measurements.Comment: 11 pages, 5 figures, All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-008.htm

Constraints on the unitarity triangle angle γ\gamma from Dalitz plot analysis of B0→DK+π−B^0 \to D K^+ \pi^- decays

The first study is presented of CP violation with an amplitude analysis of the Dalitz plot of $B^0 \to D K^+ \pi^-$ decays, with $D \to K^+ \pi^-$, $K^+ K^-$ and $\pi^+ \pi^-$. The analysis is based on a data sample corresponding to $3.0\,{\rm fb}^{-1}$ of $pp$ collisions collected with the LHCb detector. No significant CP violation effect is seen, and constraints are placed on the angle $\gamma$ of the unitarity triangle formed from elements of the Cabibbo-Kobayashi-Maskawa quark mixing matrix. Hadronic parameters associated with the $B^0 \to D K^*(892)^0$ decay are determined for the first time. These measurements can be used to improve the sensitivity to $\gamma$ of existing and future studies of the $B^0 \to D K^*(892)^0$ decay.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-059.html; updated to correct figure 9 (numerical results unchanged

Observation of the Bs0→J/ψϕϕB_s^0 \rightarrow J/\psi \phi \phi decay

The $B_s^0 \rightarrow J/\psi \phi \phi$ decay is observed in $pp$ collision data corresponding to an integrated luminosity of 3 fb$^{-1}$ recorded by the LHCb detector at centre-of-mass energies of 7 TeV and 8 TeV. This is the first observation of this decay channel, with a statistical significance of 15 standard deviations. The mass of the $B_s^0$ meson is measured to be $5367.08\,\pm \,0.38\,\pm\, 0.15$ MeV/c$^2$. The branching fraction ratio $\mathcal{B}(B_s^0 \rightarrow J/\psi \phi \phi)/\mathcal{B}(B_s^0 \rightarrow J/\psi \phi)$ is measured to be 0.0115\,\pm\, 0.0012\, ^{+0.0005}_{-0.0009}. In both cases, the first uncertainty is statistical and the second is systematic. No evidence for non-resonant $B_s^0 \rightarrow J/\psi \phi K^+ K^-$ or $B_s^0 \rightarrow J/\psi K^+ K^- K^+ K^-$ decays is found.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-033.htm

A new algorithm for identifying the flavour of Bs0B_s^0 mesons at LHCb

A new algorithm for the determination of the initial flavour of $B_s^0$ mesons is presented. The algorithm is based on two neural networks and exploits the $b$ hadron production mechanism at a hadron collider. The first network is trained to select charged kaons produced in association with the $B_s^0$ meson. The second network combines the kaon charges to assign the $B_s^0$ flavour and estimates the probability of a wrong assignment. The algorithm is calibrated using data corresponding to an integrated luminosity of 3 fb$^{-1}$ collected by the LHCb experiment in proton-proton collisions at 7 and 8 TeV centre-of-mass energies. The calibration is performed in two ways: by resolving the $B_s^0$-$\bar{B}_s^0$ flavour oscillations in $B_s^0 \to D_s^- \pi^+$ decays, and by analysing flavour-specific $B_{s 2}^{*}(5840)^0 \to B^+ K^-$ decays. The tagging power measured in $B_s^0 \to D_s^- \pi^+$ decays is found to be $(1.80 \pm 0.19({\rm stat}) \pm 0.18({\rm syst}))$\%, which is an improvement of about 50\% compared to a similar algorithm previously used in the LHCb experiment.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-056.htm

Search for hidden-sector bosons in B0 ⁣→K∗0μ+μ−B^0 \!\to K^{*0}\mu^+\mu^- decays

A search is presented for hidden-sector bosons, $\chi$, produced in the decay ${B^0\!\to K^*(892)^0\chi}$, with $K^*(892)^0\!\to K^{+}\pi^{-}$ and $\chi\!\to\mu^+\mu^-$. The search is performed using $pp$-collision data corresponding to 3.0 fb$^{-1}$ collected with the LHCb detector. No significant signal is observed in the accessible mass range $214 \leq m({\chi}) \leq 4350$ MeV, and upper limits are placed on the branching fraction product $\mathcal{B}(B^0\!\to K^*(892)^0\chi)\times\mathcal{B}(\chi\!\to\mu^+\mu^-)$ as a function of the mass and lifetime of the $\chi$ boson. These limits are of the order of $10^{-9}$ for $\chi$ lifetimes less than 100 ps over most of the $m(\chi)$ range, and place the most stringent constraints to date on many theories that predict the existence of additional low-mass bosons.Comment: All figures and tables, along with supplementary material, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-036.htm

Measurement of the Bs0→J/ψηB_{s}^{0} \rightarrow J/\psi \eta lifetime

Using a data set corresponding to an integrated luminosity of $3 fb^{-1}$, collected by the LHCb experiment in $pp$ collisions at centre-of-mass energies of 7 and 8 TeV, the effective lifetime in the $B^0_s \rightarrow J/\psi \eta$ decay mode, $\tau_{\textrm{eff}}$, is measured to be $\tau_{\textrm{eff}} = 1.479 \pm 0.034~\textrm{(stat)} \pm 0.011 ~\textrm{(syst)}$ ps. Assuming $CP$ conservation, $\tau_{\textrm{eff}}$ corresponds to the lifetime of the light $B_s^0$ mass eigenstate. This is the first measurement of the effective lifetime in this decay mode.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-017.htm

Search for the rare decays B0→J/ψγB^{0}\to J/\psi \gamma and Bs0→J/ψγB^{0}_{s} \to J/\psi \gamma

A search for the rare decay of a $B^{0}$ or $B^{0}_{s}$ meson into the final state $J/\psi\gamma$ is performed, using data collected by the LHCb experiment in $pp$ collisions at $\sqrt{s}=7$ and $8$ TeV, corresponding to an integrated luminosity of 3 fb$^{-1}$. The observed number of signal candidates is consistent with a background-only hypothesis. Branching fraction values larger than $1.7\times 10^{-6}$ for the $B^{0}\to J/\psi\gamma$ decay mode are excluded at 90% confidence level. For the $B^{0}_{s}\to J/\psi\gamma$ decay mode, branching fraction values larger than $7.4\times 10^{-6}$ are excluded at 90% confidence level, this is the first branching fraction limit for this decay.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-044.htm