Predictive model of pheochromocytoma based on the imaging features of the adrenal tumours

The purpose of our study was to develop a predictive model to rule out pheochromocytoma among adrenal tumours, based on unenhanced computed tomography (CT) and/or magnetic resonance imaging (MRI) features. We performed a retrospective multicentre study of 1131 patients presenting with adrenal lesions including 163 subjects with histological confirmation of pheochromocytoma (PHEO), and 968 patients showing no clinical suspicion of pheochromocytoma in whom plasma and/or urinary metanephrines and/or catecholamines were within reference ranges (non-PHEO). We found that tumour size was significantly larger in PHEO than non-PHEO lesions (44.3 +/- 33.2 versus 20.6 +/- 9.2 mm respectively; P < 0.001). Mean unenhanced CT attenuation was higher in PHEO (52.4 +/- 43.1 versus 4.7 +/- 17.9HU; P < 0.001). High lipid content in CT was more frequent among non-PHEO (83.6% versus 3.8% respectively; P < 0.001); and this feature alone had 83.6% sensitivity and 96.2% specificity to rule out pheochromocytoma with an area under the receiver operating characteristics curve (AUC-ROC) of 0.899. The combination of high lipid content and tumour size improved the diagnostic accuracy (AUC-ROC 0.961, sensitivity 88.1% and specificity 92.3%). The probability of having a pheochromocytoma was 0.1% for adrenal lesions smaller than 20 mm showing high lipid content in CT. Ninety percent of non-PHEO presented loss of signal in the out of phase MRI sequence compared to 39.0% of PHEO (P < 0.001), but the specificity of this feature for the diagnosis of non-PHEO lesions low. In conclusion, our study suggests that sparing biochemical screening for pheochromocytoma might be reasonable in patients with adrenal lesions smaller than 20 mm showing high lipid content in the CT scan, if there are no typical signs and symptoms of pheochromocytoma

Diets containing sea cucumber (Isostichopus badionotus) meals are hypocholesterolemic in young rats

Peer reviewedPublisher PD

Structural and Functional Insights into Endoglin Ligand Recognition and Binding

Endoglin, a type I membrane glycoprotein expressed as a disulfide-linked homodimer on human vascular endothelial cells, is a component of the transforming growth factor (TGF)-β receptor complex and is implicated in a dominant vascular dysplasia known as hereditary hemorrhagic telangiectasia as well as in preeclampsia. It interacts with the type I TGF-β signaling receptor activin receptor-like kinase (ALK)1 and modulates cellular responses to Bone Morphogenetic Protein (BMP)-9 and BMP-10. Structurally, besides carrying a zona pellucida (ZP) domain, endoglin contains at its N-terminal extracellular region a domain of unknown function and without homology to any other known protein, therefore called the orphan domain (OD). In this study, we have determined the recognition and binding ability of full length ALK1, endoglin and constructs encompassing the OD to BMP-9 using combined methods, consisting of surface plasmon resonance and cellular assays. ALK1 and endoglin ectodomains bind, independently of their glycosylation state and without cooperativity, to different sites of BMP-9. The OD comprising residues 22 to 337 was identified among the present constructs as the minimal active endoglin domain needed for partner recognition. These studies also pinpointed to Cys350 as being responsible for the dimerization of endoglin. In contrast to the complete endoglin ectodomain, the OD is a monomer and its small angle X-ray scattering characterization revealed a compact conformation in solution into which a de novo model was fitted

Translation without eIF2 Promoted by Poliovirus 2A Protease

Poliovirus RNA utilizes eIF2 for the initiation of translation in cell free systems. Remarkably, we now describe that poliovirus translation takes place at late times of infection when eIF2 is inactivated by phosphorylation. By contrast, translation directed by poliovirus RNA is blocked when eIF2 is inactivated at earlier times. Thus, poliovirus RNA translation exhibits a dual mechanism for the initiation of protein synthesis as regards to the requirement for eIF2. Analysis of individual poliovirus non-structural proteins indicates that the presence of 2Apro alone is sufficient to provide eIF2 independence for IRES-driven translation. This effect is not observed with a 2Apro variant unable to cleave eIF4G. The level of 2Apro synthesized in culture cells is crucial for obtaining eIF2 independence. Expression of the N-or C-terminus fragments of eIF4G did not stimulate IRES-driven translation, nor provide eIF2 independence, consistent with the idea that the presence of 2Apro at high concentrations is necessary. The finding that 2Apro provides eIF2-independent translation opens a new and unsuspected area of research in the field of picornavirus protein synthesis

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Studies of η\eta and η′\eta' production in pppp and ppPb collisions

The production of $\eta$ and $\eta'$ 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 $5.02$ and $13~{\rm TeV}$, and proton-lead collisions are studied at a center-of-mass energy per nucleon of $8.16~{\rm TeV}$. The studies are performed in center-of-mass rapidity regions $2.5<y_{\rm c.m.}<3.5$ (forward rapidity) and $-4.0<y_{\rm c.m.}<-3.0$ (backward rapidity) defined relative to the proton beam direction. The $\eta$ and $\eta'$ production cross sections are measured differentially as a function of transverse momentum for $1.5<p_{\rm T}<10~{\rm GeV}$ and $3<p_{\rm T}<10~{\rm GeV}$, respectively. The differential cross sections are used to calculate nuclear modification factors. The nuclear modification factors for $\eta$ and $\eta'$ mesons agree at both forward and backward rapidity, showing no significant evidence of mass dependence. The differential cross sections of $\eta$ mesons are also used to calculate $\eta/\pi^0$ 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 $\eta$ and $\eta'$ 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

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

The fraction of $\chi_{c1}$ and $\chi_{c2}$ decays in the prompt $J/\psi$ yield, $F_{\chi c}=\sigma_{\chi_c \to J/\psi}/\sigma_{J/\psi}$, is measured by the LHCb detector in pPb collisions at $\sqrt{s_{NN}}=8.16$ TeV. The study covers the forward ($1.5<y^*<4.0$) and backward ($-5.0<y^*<-2.5$) rapidity regions, where $y^*$ is the $J/\psi$ 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$^{-1}$ and 20.8 $\pm$ 0.5 nb$^{-1}$, respectively. The result is presented as a function of the $J/\psi$ transverse momentum $p_{T,J/\psi}$ in the range 1$<p_{T, J/\psi}<20$ GeV/$c$. The $F_{\chi c}$ fraction at forward rapidity is compatible with the LHCb measurement performed in $pp$ collisions at $\sqrt{s}=7$ TeV, whereas the result at backward rapidity is 2.4 $\sigma$ larger than in the forward region for $1<p_{T, J/\psi}<3$ GeV/$c$. The increase of $F_{\chi c}$ at low $p_{T, J/\psi}$ at backward rapidity is compatible with the suppression of the $\psi$(2S) contribution to the prompt $J/\psi$ yield. The lack of in-medium dissociation of $\chi_c$ 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

Measurement of lepton universality parameters in B+→K+ℓ+ℓ−B^+\to K^+\ell^+\ell^- and B0→K∗0ℓ+ℓ−B^0\to K^{*0}\ell^+\ell^- decays

A simultaneous analysis of the $B^+\to K^+\ell^+\ell^-$ and $B^0\to K^{*0}\ell^+\ell^-$ decays is performed to test muon-electron universality in two ranges of the square of the dilepton invariant mass, $q^2$. The measurement uses a sample of beauty meson decays produced in proton-proton collisions collected with the LHCb detector between 2011 and 2018, corresponding to an integrated luminosity of $9$ $\text{fb}^{-1}$. A sequence of multivariate selections and strict particle identification requirements produce a higher signal purity and a better statistical sensitivity per unit luminosity than previous LHCb lepton universality tests using the same decay modes. Residual backgrounds due to misidentified hadronic decays are studied using data and included in the fit model. Each of the four lepton universality measurements reported is either the first in the given $q^2$ interval or supersedes previous LHCb measurements. The results are compatible with the predictions of the Standard Model.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-045.html (LHCb public pages

Helium identification with LHCb

The identification of helium nuclei at LHCb is achieved using a method based on measurements of ionisation losses in the silicon sensors and timing measurements in the Outer Tracker drift tubes. The background from photon conversions is reduced using the RICH detectors and an isolation requirement. The method is developed using $pp$ collision data at $\sqrt{s}=13\,{\rm TeV}$ recorded by the LHCb experiment in the years 2016 to 2018, corresponding to an integrated luminosity of $5.5\,{\rm fb}^{-1}$. A total of around $10^5$ helium and antihelium candidates are identified with negligible background contamination. The helium identification efficiency is estimated to be approximately $50\%$ with a corresponding background rejection rate of up to $\mathcal O(10^{12})$. These results demonstrate the feasibility of a rich programme of measurements of QCD and astrophysics interest involving light nuclei.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-DP-2023-002.html (LHCb public pages

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

The production rate of $\Lambda_{b}^{0}$ baryons relative to $B^{0}$ mesons in $pp$ collisions at a center-of-mass energy $\sqrt{s} = 13$ TeV is measured by the LHCb experiment. The ratio of $\Lambda_{b}^{0}$ to $B^{0}$ 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 $e^{+}e^{-}$ collisions, and increases by a factor of $\sim2$ with increasing multiplicity. At relatively low transverse momentum, the ratio of $\Lambda_{b}^{0}$ to $B^{0}$ cross-sections is higher than what is measured in $e^{+}e^{-}$ collisions, but converges with the $e^{+}e^{-}$ ratio as the momentum increases. These results imply that the evolution of heavy $b$ 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