Enhancing immune response and survival in hepatocellular carcinoma with novel oncolytic Jurona virus and immune checkpoint blockade.

Members of the genus including Jurona virus (JURV) have emerged as promising immunotherapeutic agents, characterized by their tumor selectivity, fast kinetics, low seroprevalence, and minimal toxicity in humans. Here, we demonstrate that the administration of JURV leads to tumor regression in both hepatocellular carcinoma (HCC) xenograft and syngeneic models. Furthermore, our findings indicate that combining JURV and anti-PD-1 therapy reduced tumor burden and improved survival rates over JURV or anti-PD-1 alone in an orthotopic HCC model.

Disentangling Sources of Momentum Fluctuations in Xe+Xe and Pb+Pb Collisions with the ATLAS Detector.

High-energy nuclear collisions create a quark-gluon plasma, whose initial condition and subsequent expansion vary from event to event, impacting the distribution of the eventwise average transverse momentum [P([p_{T}])]. Disentangling the contributions from fluctuations in the nuclear overlap size (geometrical component) and other sources at a fixed size (intrinsic component) remains a challenge. This problem is addressed by measuring the mean, variance, and skewness of P([p_{T}]) in ^{208}Pb+^{208}Pb and ^{129}Xe+^{129}Xe collisions at sqrt[s_{NN}]=5.

Circulating Galectin-3: A Prognostic Biomarker in Hepatocellular Carcinoma.

Introduction: Galectin-3 plays critical roles in the adhesion, proliferation, and differentiation of tumor cells. Recent data have suggested that galectin-3 plays a role in the development of hepatocellular carcinoma (HCC); however, its prognostic value has not been validated. The aim of our study was to evaluate the clinical and prognostic value of galectin-3 in patients with HCC.

Fluorescence Lifetime Imaging Enables In vivo Quantification of PD-L1 Expression and Inter-tumoral Heterogeneity.

Patient selection for cancer immunotherapy requires precise, quantitative readouts of biomarker expression in intact tumors that can be reliably compared across multiple subjects over time. The current clinical standard biomarker for assessing immunotherapy response is programmed death-ligand-1 (PD-L1) expression, typically quantified using immunohistochemistry. This method, however, only provides snapshots of PD-L1 expression status in microscopic regions of ex vivo specimens.

Combination CXCR4 and PD1 blockade enhances intratumoral dendritic cell activation and immune responses against hepatocellular carcinoma.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of unresectable hepatocellular carcinoma (HCC), but their impressive efficacy is seen in just a fraction of patients. One key mechanism of immunotherapy resistance is the paucity of dendritic cells (DCs) in liver malignancies. Here, we tested combination blockade of programmed death receptor 1 (PD1) and CXCR4, a receptor for CXCL12, a pleiotropic factor that mediates immunosuppression in tumors.

Search for the Exclusive W Boson Hadronic Decays W^{±}→π^{±}γ, W^{±}→K^{±}γ and W^{±}→ρ^{±}γ with the ATLAS Detector.

A 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.

A Novel Liver Cancer-Selective Histone Deacetylase Inhibitor Is Effective against Hepatocellular Carcinoma and Induces Durable Responses with Immunotherapy.

Hepatocellular carcinoma (HCC) progression is facilitated by gene-silencing chromatin histone hypoacetylation due to histone deacetylase (HDAC) activation. However, inhibiting HDACs-an effective treatment for lymphomas-has shown limited success in solid tumors. We report the discovery of a class of HDAC inhibitors (HDACi) that demonstrates exquisite selective cytotoxicity against human HCC cells.

Combination of Searches for Higgs Boson Pair Production in pp Collisions at sqrt[s]=13 TeV with the ATLAS Detector.

This Letter presents results from a combination of searches for Higgs boson pair production using 126-140  fb^{-1} of proton-proton collision data at sqrt[s]=13  TeV recorded with the ATLAS detector. At 95% confidence level (CL), the upper limit on the production rate is 2.9 times the standard model (SM) prediction, with an expected limit of 2.

Studies of the Energy Dependence of Diboson Polarization Fractions and the Radiation-Amplitude-Zero Effect in WZ Production with the ATLAS Detector.

This Letter presents the first study of the energy dependence of diboson polarization fractions in WZ→ℓνℓ^{'}ℓ^{'}(ℓ,ℓ^{'}=e,μ) production. The dataset used corresponds to an integrated luminosity of 140  fb^{-1} of proton-proton collisions at a center-of-mass energy of 13 TeV recorded by the ATLAS detector. Two fiducial regions with an enhanced presence of events featuring two longitudinally polarized bosons are defined.

PEARL: A Phase Ib/II Biomarker Study of Adding Radiation Therapy to Pembrolizumab Before Neoadjuvant Chemotherapy in Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer.

Purpose: To assess safety and immune biomarkers after preoperative radiation therapy (RT) and anti-PD1 therapy in breast cancer.

Materials And Methods: A phase I/IIb trial of pembrolizumab with RT was conducted in patients with triple-negative breast cancer (TNBC) and hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer. All received pembrolizumab followed by a second cycle + RT (anti-PD1/RT) of 24 Gy/three daily fractions delivered to the breast tumor and then neoadjuvant chemotherapy (NAC).

Translational modeling-based evidence for enhanced efficacy of standard-of-care drugs in combination with anti-microRNA-155 in non-small-cell lung cancer.

Background: Elevated microRNA-155 (miR-155) expression in non-small-cell lung cancer (NSCLC) promotes cisplatin resistance and negatively impacts treatment outcomes. However, miR-155 can also boost anti-tumor immunity by suppressing PD-L1 expression. Therapeutic targeting of miR-155 through its antagonist, anti-miR-155, has proven challenging due to its dual molecular effects.

Statistical Combination of ATLAS Run 2 Searches for Charginos and Neutralinos at the LHC.

Statistical 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.

Phosphine versus Carbene Metal Interactions: Bond Energies.

A variety of different ground-state structures of carbene and phosphine groups 1 and 2 cationic, group 11 cationic, and group 10 neutral complexes were studied using density functional theory (DFT) and correlated molecular orbital theory (CCSD(T)) methods. Geometries of complexes with phosphines were studied and compared to available experimental data. Among the three analyzed phosphine ligands, PH, PMe, and PPh, PH was found to have noticeably smaller ligand binding energies (LBEs, Δ).

Combination of Searches for Resonant Higgs Boson Pair Production Using pp Collisions at sqrt[s]=13 TeV with the ATLAS Detector.

A combination of searches for a new resonance decaying into a Higgs boson pair is presented, using up to 139  fb^{-1} of pp collision data at sqrt[s]=13  TeV recorded with the ATLAS detector at the LHC. The combination includes searches performed in three decay channels: bb[over ¯]bb[over ¯], bb[over ¯]τ^{+}τ^{-}, and bb[over ¯]γγ. No excess above the expected Standard Model background is observed and upper limits are set at the 95% confidence level on the production cross section of Higgs boson pairs originating from the decay of a narrow scalar resonance with mass in the range 251 GeV-5 TeV.

Search for Nearly Mass-Degenerate Higgsinos Using Low-Momentum Mildly Displaced Tracks in pp Collisions at sqrt[s]=13 TeV with the ATLAS Detector.

Higgsinos with masses near the electroweak scale can solve the hierarchy problem and provide a dark matter candidate, while detecting them at the LHC remains challenging if their mass splitting is O(1  GeV). This Letter presents a novel search for nearly mass-degenerate Higgsinos in events with an energetic jet, missing transverse momentum, and a low-momentum track with a significant transverse impact parameter using 140  fb^{-1} of proton-proton collision data at sqrt[s]=13  TeV collected by the ATLAS experiment. For the first time since LEP, a range of mass splittings between the lightest charged and neutral Higgsinos from 0.

Azimuthal Angle Correlations of Muons Produced via Heavy-Flavor Decays in 5.02 TeV Pb+Pb and pp Collisions with the ATLAS Detector.

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.