Cancer-associated Fibroblasts (CAFs) have emerged as critical regulators of anti-tumour immunity, with both beneficial and detrimental properties that remain poorly characterised. To investigate this, we performed single-cell and spatial transcriptomic analysis, comparing head & neck squamous cell carcinoma (HNSCC) subgroups, which although heterogenous, can be considered broadly immune-hot and immune-cold (human papillomavirus [HPV]+ve and HPV-ve tumours respectively). This identified six fibroblast subpopulations, including two with immunomodulatory gene expression profiles (IL-11 + inflammatory [i]CAF and CCL19 + fibroblastic reticular cell [FRC]-like).
View Article and Find Full Text PDFA search for the exclusive hadronic decays W^{±}→π^{±}γ, W^{±}→K^{±}γ, and W^{±}→ρ^{±}γ is performed using up to 140 fb^{-1} of proton-proton collisions recorded with the ATLAS detector at a center-of-mass energy of sqrt[s]=13 TeV. If observed, these rare processes would provide a unique test bench for the quantum chromodynamics factorization formalism used to calculate cross sections at colliders. Additionally, at future colliders, these decays could offer a new way to measure the W boson mass through fully reconstructed decay products.
View Article and Find Full Text PDFBackground: The impact of nucleos(t)ide analogues on intrahepatic viral burden and immune microenvironment in patients with chronic hepatitis B (CHB) is not clear.
Objective: We aimed to characterise the effects of tenofovir disoproxil fumarate (TDF) on intrahepatic viral burden and the liver immune microenvironment in patients with CHB.
Design: Core liver biopsies were collected at baseline and year 3 from patients with CHB with minimally raised serum alanine aminotransferase in a double-blind placebo-controlled trial (NCT01522625).
The human microbiome emerges as a promising reservoir for diagnostic markers and therapeutics. Since host-associated microbiomes at various body sites differ and diseases do not occur in isolation, a comprehensive analysis strategy highlighting the full potential of microbiomes should include diverse specimen types and various diseases. To ensure robust data quality and comparability across specimen types and diseases, we employ standardized protocols to generate sequencing data from 1931 prospectively collected specimens, including from saliva, plaque, skin, throat, eye, and stool, with an average sequencing depth of 5.
View Article and Find Full Text PDFThe main bottleneck in training a robust tumor segmentation algorithm for non-small cell lung cancer (NSCLC) on H&E is generating sufficient ground truth annotations. Various approaches for generating tumor labels to train a tumor segmentation model was explored. A large dataset of low-cost low-accuracy panCK-based annotations was used to pre-train the model and determine the minimum required size of the expensive but highly accurate pathologist annotations dataset.
View Article and Find Full Text PDFStatistical combinations of searches for charginos and neutralinos using various decay channels are performed using 139 fb^{-1} of pp collision data at sqrt[s]=13 TeV with the ATLAS detector at the Large Hadron Collider. Searches targeting pure-wino chargino pair production, pure-wino chargino-neutralino production, or Higgsino production decaying via standard model W, Z, or h bosons are combined to extend the mass reach to the produced supersymmetric particles by 30-100 GeV. The depth of the sensitivity of the original searches is also improved by the combinations, lowering the 95% C.
View Article and Find Full Text PDFPurpose: Human trophoblast cell surface antigen 2 (Trop-2) is a protein highly expressed in urothelial cancer (UC). Sacituzumab govitecan (SG) is a Trop-2-directed antibody drug conjugate with a hydrolysable linker and a potent SN-38 payload. This study explored Trop-2 expression in tumors treated with SG in cohorts 1 to 3 (C1-3) from the TROPHY-U-01 study and evaluated whether efficacy was associated with Trop-2 expression.
View Article and Find Full Text PDFSao Paulo Med J
July 2024
Background: Brazilian medical schools equitably divide their medical education assessments into five content areas: internal medicine, surgery, pediatrics, obstetrics and gynecology, and public health. However, this division does not follow international patterns and may threaten the examinations' reliability and validity.
Objective: To assess the reliability indices of the content areas of serial, cross-institutional progress test examinations.
Angular correlations between heavy quarks provide a unique probe of the quark-gluon plasma created in ultrarelativistic heavy-ion collisions. Results are presented of a measurement of the azimuthal angle correlations between muons originating from semileptonic decays of heavy quarks produced in 5.02 TeV Pb+Pb and pp collisions at the LHC.
View Article and Find Full Text PDFCapsid assembly mediated by hepatitis B virus (HBV) core protein (HBc) is an essential part of the HBV replication cycle, which is the target for different classes of capsid assembly modulators (CAMs). While both CAM-A ("aberrant") and CAM-E ("empty") disrupt nucleocapsid assembly and reduce extracellular HBV DNA, CAM-As can also reduce extracellular HBV surface antigen (HBsAg) by triggering apoptosis of HBV-infected cells in preclinical mouse models. However, there have not been substantial HBsAg declines in chronic hepatitis B (CHB) patients treated with CAM-As to date.
View Article and Find Full Text PDFThis Letter presents the first study of Higgs boson production in association with a vector boson (V=W or Z) in the fully hadronic qqbb final state using data recorded by the ATLAS detector at the LHC in proton-proton collisions at sqrt[s]=13 TeV and corresponding to an integrated luminosity of 137 fb^{-1}. The vector bosons and Higgs bosons are each reconstructed as large-radius jets and tagged using jet substructure techniques. Dedicated tagging algorithms exploiting b-tagging properties are used to identify jets consistent with Higgs bosons decaying into bb[over ¯].
View Article and Find Full Text PDFQuantum cascade lasers (QCLs) are ubiquitous mid-infrared sources owing to their flexible designs and compact footprints. Manufacturing multiwavelength QCL chips with high power levels and good beam quality is highly desirable for many applications. In this study, we demonstrate an λ ∼ 4.
View Article and Find Full Text PDFATLAS measured the centrality dependence of the dijet yield using 165 nb^{-1} of p+Pb data collected at sqrt[s_{NN}]=8.16 TeV in 2016. The event centrality, which reflects the p+Pb impact parameter, is characterized by the total transverse energy registered in the Pb-going side of the forward calorimeter.
View Article and Find Full Text PDFIn chronic inflammation, regulatory immune cells, such as regulatory T cells and myeloid-derived suppressor cells, can develop. Local signals in the inflamed tissue, such as cytokines and eicosanoids, but also contact-dependent signals, can promote myeloid-derived suppressor cell development. In the liver, hepatic stellate cells may provide such signals via the expression of CD44.
View Article and Find Full Text PDFThis Letter reports the observation of WZγ production and a measurement of its cross section using 140.1±1.2 fb^{-1} of proton-proton collision data recorded at a center-of-mass energy of 13 TeV by the ATLAS detector at the Large Hadron Collider.
View Article and Find Full Text PDFThe first evidence for the Higgs boson decay to a Z boson and a photon is presented, with a statistical significance of 3.4 standard deviations. The result is derived from a combined analysis of the searches performed by the ATLAS and CMS Collaborations with proton-proton collision datasets collected at the CERN Large Hadron Collider (LHC) from 2015 to 2018.
View Article and Find Full Text PDFAims: Treatment options for advanced urothelial carcinoma (aUC) rapidly evolved: besides immunomodulative therapeutic options and inhibitors targeting Fibroblast growth factor receptor (FGFR) alterations, two new antibody-drug conjugates (ADC), sacituzumab govitecan (SG) and enfortumab vedotin (EV), have been approved. However, little is known about the associations of specific aUC properties and the surface target expression of TROP2 and NECTIN-4. Our aim was to characterize associations of TACSTD2/TROP2 and NECTIN-4/NECTIN-4 protein and gene expression with morphomolecular and clinicopathological characteristics of aUC in two large independent cohorts.
View Article and Find Full Text PDFA search for events with a dark photon produced in association with a dark Higgs boson via rare decays of the standard model Z boson is presented, using 139 fb^{-1} of sqrt[s]=13 TeV proton-proton collision data recorded by the ATLAS detector at the Large Hadron Collider. The dark boson decays into a pair of dark photons, and at least two of the three dark photons must each decay into a pair of electrons or muons, resulting in at least two same-flavor opposite-charge lepton pairs in the final state. The data are found to be consistent with the background prediction, and upper limits are set on the dark photon's coupling to the dark Higgs boson times the kinetic mixing between the standard model photon and the dark photon, α_{D}ϵ^{2}, in the dark photon mass range of [5, 40] GeV except for the ϒ mass window [8.
View Article and Find Full Text PDFA measurement of the mass of the Higgs boson combining the H→ZZ^{*}→4ℓ and H→γγ decay channels is presented. The result is based on 140 fb^{-1} of proton-proton collision data collected by the ATLAS detector during LHC run 2 at a center-of-mass energy of 13 TeV combined with the run 1 ATLAS mass measurement, performed at center-of-mass energies of 7 and 8 TeV, yielding a Higgs boson mass of 125.11±0.
View Article and Find Full Text PDF