Microneedles (MNs) are a prospective system in cancer immunotherapy to overcome barriers regarding proper antigen delivery and presentation. This study aims at identifying the potential of MNs for the delivery of Peptide-coated Conditionally Replicating Adenoviruses (PeptiCRAd), whereby peptides enhance the immunogenic properties of adenoviruses presenting tumor associated antigens. The combination of PeptiCRAd with MNs containing polyvinylpyrrolidone and sucrose was tested for the preservation of structure, induction of immune response, and tumor eradication.
View Article and Find Full Text PDFSeptiCyte RAPID is a transcriptional host response assay that discriminates between sepsis and non-infectious systemic inflammation (SIRS) with a one-hour turnaround time. The overall performance of this test in a cohort of 419 patients has recently been described [Balk et al., J Clin Med 2024, 13, 1194].
View Article and Find Full Text PDFA 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.
View Article and Find Full Text PDFestablishes within host cells by inducing anti-apoptotic Bcl-2 family proteins, triggering necrosis, inflammation, and fibrosis. Here, we demonstrate that navitoclax, an orally bioavailable, small-molecule Bcl-2 inhibitor, significantly improves pulmonary tuberculosis (TB) treatments as a host-directed therapy. Addition of navitoclax to standard TB treatments at human equipotent dosing in mouse models of TB, inhibits Bcl-2 expression, leading to improved bacterial clearance, reduced tissue damage / fibrosis and decreased extrapulmonary bacterial dissemination.
View Article and Find Full Text PDFUnlabelled: The pathogenesis of COVID-19 is associated with a hyperinflammatory immune response. Monocytes and macrophages play a central role in this hyperinflammatory response to SARS-CoV-2. NLRP3 inflammasome activation has been observed in monocytes of patients with COVID-19, but the mechanism and consequences of inflammasome activation require further investigation.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
August 2024
Size-dependent phagocytosis is a well-characterized phenomenon in monocytes and macrophages. However, this size effect for preferential gene delivery to these important cell targets has not been fully exploited because commonly adopted stabilization methods for electrostatically complexed nucleic acid nanoparticles, such as PEGylation and charge repulsion, typically arrest the vehicle size below 200 nm. Here, we bridge the technical gap in scalable synthesis of larger submicron gene delivery vehicles by electrostatic self-assembly of charged nanoparticles, facilitated by a polymer structurally designed to modulate internanoparticle Coulombic and van der Waals forces.
View Article and Find Full Text PDFAlveolar macrophages (AMs) act as gatekeepers of the lung's immune responses, serving essential roles in recognizing and eliminating pathogens. The transcription factor (TF) early growth response 2 (EGR2) has been recently described as required for mature AMs in mice; however, its mechanisms of action have not been explored. Here, we identified EGR2 as an epigenomic regulator and likely direct proximal transcriptional activator in AMs using epigenomic approaches (RNA sequencing, ATAC sequencing, and CUT&RUN).
View Article and Find Full Text PDFThe 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.
View Article and Find Full Text PDFAnim Reprod Sci
October 2024
Biosecurity is a major concern in the global pig production. The separation in time of semen collection, processing and insemination in the pig farm is a few days for chilled semen but it can be indefinite when using cryopreserved semen. Field fertility results of boar cryopreserved semen are close to chilled semen, which makes it a valuable resource for the establishment of semen genebanks, long-distance semen trade, and the implementation of other technologies such as the sex-sorted semen.
View Article and Find Full Text PDFAn 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.
View Article and Find Full Text PDFCancer immunotherapy requires a specific antitumor CD8 T cell-driven immune response; however, upon genetic and epigenetic alterations of the antigen processing and presenting components, cancer cells escape the CD8 T cell recognition. As a result, poorly immunogenic tumors are refractory to conventional immunotherapy. In this context, the use of viral cancer vaccines in combination with hypomethylating agents represents a promising strategy to prevent cancer from escaping immune system recognition.
View Article and Find Full Text PDFMasses in the parapharyngeal area are rare and often due to infectious phenomena arising from the oral cavity or pharynx which lead to abscess formation. Less frequently, the lesion can be neoplastic. Tumours of the parapharyngeal space are rare, accounting for less than 1% of all head and neck neoplasms.
View Article and Find Full Text PDFThe 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.
View Article and Find Full Text PDFBackground: Cancer immunotherapy relies on using the immune system to recognize and eradicate cancer cells. Adaptive immunity, which consists of mainly antigen-specific cytotoxic T cells, plays a pivotal role in controlling cancer progression. However, innate immunity is a necessary component of the cancer immune response to support an immunomodulatory state, enabling T-cell immunosurveillance.
View Article and Find Full Text PDFThe 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.
View Article and Find Full Text PDFThe 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.
View Article and Find Full Text PDFOver the past few decades, a growing body of evidence has emerged regarding the positive impact of boardgames in promoting life skills and well-being in various settings including health, education, and military schooling. However, the use of boardgames with inmates for cultural and educational purposes is still an unexplored and fragmented area of research. Incorporating boardgames into correctional settings can be a complex challenge for correctional stakeholders who seek to identify innovative tools to enhance inmate education and promote integration into society after incarceration.
View Article and Find Full Text PDFInformation on the dynamics and decline/persistence of antibody titres is important in vaccine development. A recent vaccine trial in malaria-exposed, healthy African adults and children living in a malaria hyperendemic and seasonal area (Ouagadougou, Burkina Faso) was the first study in which BK-SE36/CpG was administered to different age groups. In 5- to 10-year-old children, the risk of malaria infection was markedly lower in the BK-SE36/CpG arm compared to the control arm.
View Article and Find Full Text PDFThe 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.
View Article and Find Full Text PDFA 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.
View Article and Find Full Text PDFA 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.
View Article and Find Full Text PDFThe 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.
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