Microfluidic vessel-on-chip platform for investigation of cellular defects in venous malformations and responses to various shear stress and flow conditions.

A novel microfluidic platform was designed to study the cellular architecture of endothelial cells (ECs) in an environment replicating the 3D organization and flow of blood vessels. In particular, the platform was constructed to investigate EC defects in slow-flow venous malformations (VMs) under varying shear stress and flow conditions. The platform featured a standard microtiter plate footprint containing 32 microfluidic units capable of replicating wall shear stress (WSS) in normal veins and enabling precise control of shear stress and flow directionality without the need for complex pumping systems.

Identification of cell type-specific cell-penetrating peptides through in vivo phage display leveraged by next generation sequencing.

Vascular anomalies (VA) refer to abnormal blood or lymphatic vessel architecture, most often as a result of dysregulated growth. Venous malformations (VM), a subgroup of VAs, are triggered by activating mutations in the Angiopoietin/TIE2-PI3K/AKT/mTOR signaling pathway with TIE2 L914F (gene name TEK) being one of the most frequent mutations in patients with VMs. Although systemic targeting of the overactivated pathway is possible, it would be a therapeutic advantage to restrict treatment to only the affected lesions.

Search for Time-Dependent CP Violation in D^{0}→π^{+}π^{-}π^{0} Decays.

A measurement of time-dependent CP violation in D^{0}→π^{+}π^{-}π^{0} decays using a pp collision data sample collected by the LHCb experiment in 2012 and from 2015 to 2018, corresponding to an integrated luminosity of 7.7  fb^{-1}, is presented. The initial flavor of each D^{0} candidate is determined from the charge of the pion produced in the D^{*}(2010)^{+}→D^{0}π^{+} decay.

Spatial Machine Learning for Exploring the Variability in Low Height-For-Age From Socioeconomic, Agroecological, and Climate Features in the Northern Province of Rwanda.

Childhood stunting is a serious public health concern in Rwanda. Although stunting causes have been documented, we still lack a more in-depth understanding of their local factors at a more detailed geographic level. We cross-sectionally examined 615 height-for-age prevalence observations in the Northern Province of Rwanda, linked with their related covariates, to explore the spatial heterogeneity in the low height-for-age prevalence by fitting linear and non-linear spatial regression models and explainable machine learning.

Sustained meningeal lymphatic vessel atrophy or expansion does not alter Alzheimer's disease-related amyloid pathology.

Discovery of meningeal lymphatic vessels (LVs) in the dura mater, also known as dural LVs (dLVs) that depend on vascular endothelial growth factor C expression, has raised interest in their possible involvement in Alzheimer's disease (AD). Here we find that in the APdE9 and 5xFAD mouse models of AD, dural amyloid-β (Aβ) is confined to blood vessels and dLV morphology or function is not altered. The induction of sustained dLV atrophy or hyperplasia in the AD mice by blocking or overexpressing vascular endothelial growth factor C, impaired or improved, respectively, macromolecular cerebrospinal fluid (CSF) drainage to cervical lymph nodes.

Modification of χ_{c1}(3872) and ψ(2S) Production in pPb Collisions at sqrt[s_{NN}]=8.16 TeV.

The LHCb Collaboration measures production of the exotic hadron χ_{c1}(3872) in proton-nucleus collisions for the first time. Comparison with the charmonium state ψ(2S) suggests that the exotic χ_{c1}(3872) experiences different dynamics in the nuclear medium than conventional hadrons, and comparison with data from proton-proton collisions indicates that the presence of the nucleus may modify χ_{c1}(3872) production rates. This is the first measurement of the nuclear modification factor of an exotic hadron.

Loss-of-function mutations of the TIE1 receptor tyrosine kinase cause late-onset primary lymphedema.

Primary lymphedema (PL), characterized by tissue swelling, fat accumulation, and fibrosis, results from defects in lymphatic vessels or valves caused by mutations in genes involved in development, maturation, and function of the lymphatic vascular system. Pathogenic variants in various genes have been identified in about 30% of PL cases. By screening of a cohort of 755 individuals with PL, we identified two TIE1 (tyrosine kinase with immunoglobulin- and epidermal growth factor-like domains 1) missense variants and one truncating variant, all predicted to be pathogenic by bioinformatic algorithms.

Human iPSC and CRISPR targeted gene knock-in strategy for studying the somatic TIE2 mutation in endothelial cells.

Induced pluripotent stem cell (iPSC) derived endothelial cells (iECs) have emerged as a promising tool for studying vascular biology and providing a platform for modelling various vascular diseases, including those with genetic origins. Currently, primary ECs are the main source for disease modelling in this field. However, they are difficult to edit and have a limited lifespan.

Contribution of VEGF-B-Induced Endocardial Endothelial Cell Lineage in Physiological Versus Pathological Cardiac Hypertrophy.

Background: Preclinical studies have shown the therapeutic potential of VEGF-B (vascular endothelial growth factor B) in revascularization of the ischemic myocardium, but the associated cardiac hypertrophy and adverse side effects remain a concern. To understand the importance of endothelial proliferation and migration for the beneficial versus adverse effects of VEGF-B in the heart, we explored the cardiac effects of autocrine versus paracrine VEGF-B expression in transgenic and gene-transduced mice.

Methods: We used single-cell RNA sequencing to compare cardiac endothelial gene expression in VEGF-B transgenic mouse models.

Amplitude Analysis of the B^{0}→K^{*0}μ^{+}μ^{-} Decay.

An amplitude analysis of the B^{0}→K^{*0}μ^{+}μ^{-} decay is presented using a dataset corresponding to an integrated luminosity of 4.7  fb^{-1} of pp collision data collected with the LHCb experiment. For the first time, the coefficients associated to short-distance physics effects, sensitive to processes beyond the standard model, are extracted directly from the data through a q^{2}-unbinned amplitude analysis, where q^{2} is the μ^{+}μ^{-} invariant mass squared.

Fraction of χ_{c} Decays in Prompt J/ψ Production Measured in pPb Collisions at sqrt[s_{NN}]=8.16 TeV.

The fraction of χ_{c1} and χ_{c2} decays in the prompt J/ψ yield, F_{χ_{c}→J/ψ}=σ_{χ_{c}→J/ψ}/σ_{J/ψ}, is measured by the LHCb detector in pPb collisions at sqrt[s_{NN}]=8.16  TeV. The study covers the forward (1.

Observation of Cabibbo-Suppressed Two-Body Hadronic Decays and Precision Mass Measurement of the Ω_{c}^{0} Baryon.

The first observation of the singly Cabibbo-suppressed Ω_{c}^{0}→Ω^{-}K^{+} and Ω_{c}^{0}→Ξ^{-}π^{+} decays is reported, using proton-proton collision data at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 5.4  fb^{-1}, collected with the LHCb detector between 2016 and 2018. The branching fraction ratios are measured to be B(Ω_{c}^{0}→Ω^{-}K^{+})/B(Ω_{c}^{0}→Ω^{-}π^{+})=[6.

Enhanced Production of Λ_{b}^{0} Baryons in High-Multiplicity pp Collisions at sqrt[s]=13 TeV.

The production rate of Λ_{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 Λ_{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 ∼2 with increasing multiplicity.

Improved Measurement of CP Violation Parameters in B_{s}^{0}→J/ψK^{+}K^{-} Decays in the Vicinity of the ϕ(1020) Resonance.

The decay-time-dependent CP asymmetry in B_{s}^{0}→J/ψ(→μ^{+}μ^{-})K^{+}K^{-} decays is measured using proton-proton collision data, corresponding to an integrated luminosity of 6  fb^{-1}, collected with the LHCb detector at a center-of-mass energy of 13 TeV. Using a sample of approximately 349 000 B_{s}^{0} signal decays with an invariant K^{+}K^{-} mass in the vicinity of the ϕ(1020) resonance, the CP-violating phase ϕ_{s} is measured, along with the difference in decay widths of the light and heavy mass eigenstates of the B_{s}^{0}-B[over ¯]_{s}^{0} system, ΔΓ_{s}, and the difference of the average B_{s}^{0} and B^{0} meson decay widths, Γ_{s}-Γ_{d}. The values obtained are ϕ_{s}=-0.

Blood pressure lowering enhances cerebrospinal fluid efflux to the systemic circulation primarily via the lymphatic vasculature.

Background: Inside the incompressible cranium, the volume of cerebrospinal fluid is directly linked to blood volume: a change in either will induce a compensatory change in the other. Vasodilatory lowering of blood pressure has been shown to result in an increase of intracranial pressure, which, in normal circumstances should return to equilibrium by increased fluid efflux. In this study, we investigated the effect of blood pressure lowering on fluorescent cerebrospinal fluid tracer absorption into the systemic blood circulation.

Synchronous functional magnetic resonance eye imaging, video ophthalmoscopy, and eye surface imaging reveal the human brain and eye pulsation mechanisms.

The eye possesses a paravascular solute transport pathway that is driven by physiological pulsations, resembling the brain glymphatic pathway. We developed synchronous multimodal imaging tools aimed at measuring the driving pulsations of the human eye, using an eye-tracking functional eye camera (FEC) compatible with magnetic resonance imaging (MRI) for measuring eye surface pulsations. Special optics enabled integration of the FEC with MRI-compatible video ophthalmoscopy (MRcVO) for simultaneous retinal imaging along with functional eye MRI imaging (fMREye) of the BOLD (blood oxygen level dependent) contrast.

Measurement of CP Violation in B^{0}→ψ(→ℓ^{+}ℓ^{-})K_{S}^{0}(→π^{+}π^{-}) Decays.

A measurement of time-dependent CP violation in the decays of B^{0} and B[over ¯]^{0} mesons to the final states J/ψ(→μ^{+}μ^{-})K_{S}^{0}, ψ(2S)(→μ^{+}μ^{-})K_{S}^{0} and J/ψ(→e^{+}e^{-})K_{S}^{0} with K_{S}^{0}→π^{+}π^{-} is presented. The data correspond to an integrated luminosity of 6  fb^{-1} collected at a center-of-mass energy of sqrt[s]=13  TeV with the LHCb detector. The CP-violation parameters are measured to be S_{ψK_{S}^{0}}=0.

Precision Measurement of CP Violation in the Penguin-Mediated Decay B_{s}^{0}→ϕϕ.

A flavor-tagged time-dependent angular analysis of the decay B_{s}^{0}→ϕϕ is performed using pp collision data collected by the LHCb experiment at the center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 6  fb^{-1}. The CP-violating phase and direct CP-violation parameter are measured to be ϕ_{s}^{ss[over ¯]s}=-0.042±0.

Observation of New Baryons in the Ξ_{b}^{-}π^{+}π^{-} and Ξ_{b}^{0}π^{+}π^{-} Systems.

The first observation and study of two new baryonic structures in the final state Ξ_{b}^{0}π^{+}π^{-} and the confirmation of the Ξ_{b}(6100)^{-} state in the Ξ_{b}^{-}π^{+}π^{-} decay mode are reported using proton-proton collision data collected by the LHCb experiment, corresponding to an integrated luminosity of 9  fb^{-1}. In addition, the properties of the known Ξ_{b}^{*0}, Ξ_{b}^{'-} and Ξ_{b}^{*-} resonances are measured with improved precision. The new decay mode of the Ξ_{b}^{0} baryon to the Ξ_{c}^{+} π^{-} π^{+} π^{-} final state is observed and exploited for the first time in these measurements.

Tyrosine-protein kinase Yes controls endothelial junctional plasticity and barrier integrity by regulating VE-cadherin phosphorylation and endocytosis.

Vascular endothelial (VE)-cadherin in endothelial adherens junctions is an essential component of the vascular barrier, critical for tissue homeostasis and implicated in diseases such as cancer and retinopathies. Inhibitors of Src cytoplasmic tyrosine kinase have been applied to suppress VE-cadherin tyrosine phosphorylation and prevent excessive leakage, edema and high interstitial pressure. Here we show that the Src-related Yes tyrosine kinase, rather than Src, is localized at endothelial cell (EC) junctions where it becomes activated in a flow-dependent manner.

Measurement of the Λ_{b}^{0}→Λ(1520)μ^{+}μ^{-} Differential Branching Fraction.

The branching fraction of the rare decay Λ_{b}^{0}→Λ(1520)μ^{+}μ^{-} is measured for the first time, in the squared dimuon mass intervals q^{2}, excluding the J/ψ and ψ(2S) regions. The data sample analyzed was collected by the LHCb experiment at center-of-mass energies of 7, 8, and 13 TeV, corresponding to a total integrated luminosity of 9  fb^{-1}. The result in the highest q^{2} interval, q^{2}>15.

Evidence of a J/ψK_{S}^{0} Structure in B^{0}→J/ψϕK_{S}^{0} Decays.

An amplitude analysis of B^{0}→J/ψϕK_{S}^{0} decays is performed using proton-proton collision data, corresponding to an integrated luminosity of 9  fb^{-1}, collected with the LHCb detector at center-of-mass energies of 7, 8, and 13 TeV. Evidence with a significance of 4.0 standard deviations of a structure in the J/ψK_{S}^{0} system, named T_{ψs1}^{θ}(4000)^{0}, is seen, with its mass and width measured to be 3991_{-10}^{+12} _{-17}^{+9}  MeV/c^{2} and 105_{-25}^{+29} _{-23}^{+17}  MeV, respectively, where the first uncertainty is statistical and the second systematic.