Integrating IL-12 mRNA nanotechnology with SBRT eliminates T cell exhaustion in preclinical models of pancreatic cancer.

Pronounced T cell exhaustion characterizes immunosuppressive tumors, with the tumor microenvironment (TME) employing multiple mechanisms to elicit this suppression. Traditional immunotherapies, such as immune checkpoint blockade, often fail due to their focus primarily on T cells. To overcome this, we utilized a proinflammatory cytokine, interleukin (IL)-12, that re-wires the immunosuppressive TME by inducing T cell effector function while also repolarizing immunosuppressive myeloid cells.

The Lactate Receptor GPR81 is a Mechanism of Leukemia-Associated Macrophage Polarization in the Bone Marrow Microenvironment.

Interactions between acute myeloid leukemia (AML) and the bone marrow microenvironment (BMME) are critical to leukemia progression and chemoresistance. Altered metabolite levels in the tumor microenvironment contribute to immunosuppression in solid tumors, while this has not been studied yet in the leukemic BMME. Metabolomics of AML patient bone marrow serum detected elevated metabolites, including lactate, compared to age- and sex-matched controls.

Observation of Medium-Induced Yield Enhancement and Acoplanarity Broadening of Low-p_{T} Jets from Measurements in pp and Central Pb-Pb Collisions at sqrt[s_{NN}]=5.02 TeV.

The ALICE Collaboration reports the measurement of semi-inclusive distributions of charged-particle jets recoiling from a high transverse momentum (high p_{T}) hadron trigger in proton-proton and central Pb-Pb collisions at sqrt[s_{NN}]=5.02  TeV. A data-driven statistical method is used to mitigate the large uncorrelated background in central Pb-Pb collisions.

Photoproduction of K^{+}K^{-} Pairs in Ultraperipheral Collisions.

K^{+}K^{-} pairs may be produced in photonuclear collisions, either from the decays of photoproduced ϕ(1020) mesons or directly as nonresonant K^{+}K^{-} pairs. Measurements of K^{+}K^{-} photoproduction probe the couplings between the ϕ(1020) and charged kaons with photons and nuclear targets. The kaon-proton scattering occurs at energies far above those available elsewhere.

Continuities and change in alcohol policy at the global level: a documentary analysis of the 2010 Global Strategy for Reducing the Harmful Use of Alcohol and the Global Alcohol Action Plan 2022-2030.

Background: There are only two major statements which define alcohol policy development at the global level. There has not been any comparative analysis of the details of these key texts, published in 2010 and 2022 respectively, including how far they constitute similar or evolving approaches to alcohol harm.

Methods: Preparatory data collection involved examination of documents associated with the final policy statements.

Are we moving into a new era for alcohol policy globally? An analysis of the Global Alcohol Action Plan 2022-30.

The Global Alcohol Action Plan 2022-30 (GAAP) represents an important milestone in policy implementation at the global level on alcohol and health. There has, however, been little attention paid to the GAAP in the research literature. With a focus on the alcohol industry, this analysis examines the content of, and prospects for, the GAAP.

The confluence of legacy, corporate social responsibility, and public health: The case of Migros and alcohol-free retailing in Switzerland.

Background: Alcohol policy studies have traditionally focused on formal policymaking processes. Retail cooperatives, however, have rarely been studied as sites of public health interventions. Migros, a cooperatively owned chain of supermarkets in Switzerland, has long forbidden alcohol sales in its supermarkets.

ψ(2S) Suppression in Pb-Pb Collisions at the LHC.

The production of the ψ(2S) charmonium state was measured with ALICE in Pb-Pb collisions at sqrt[s_{NN}]=5.02  TeV, in the dimuon decay channel. A significant signal was observed for the first time at LHC energies down to zero transverse momentum, at forward rapidity (2.

Local Delivery of SBRT and IL12 by mRNA Technology Overcomes Immunosuppressive Barriers to Eliminate Pancreatic Cancer.

Unlabelled: The immunosuppressive milieu in pancreatic cancer (PC) is a significant hurdle to treatments, resulting in survival statistics that have barely changed in 5 decades. Here we present a combination treatment consisting of stereotactic body radiation therapy (SBRT) and IL-12 mRNA lipid nanoparticles delivered directly to pancreatic murine tumors. This treatment was effective against primary and metastatic models, achieving cures in both settings.

Measurement of the Lifetime and Λ Separation Energy of _{Λ}^{3}H.

The most precise measurements to date of the _{Λ}^{3}H lifetime τ and Λ separation energy B_{Λ} are obtained using the data sample of Pb-Pb collisions at sqrt[s_{NN}]=5.02  TeV collected by ALICE at the LHC. The _{Λ}^{3}H is reconstructed via its charged two-body mesonic decay channel (_{Λ}^{3}H→^{3}He+π^{-} and the charge-conjugate process).

Enhanced Deuteron Coalescence Probability in Jets.

The transverse-momentum (p_{T}) spectra and coalescence parameters B_{2} of (anti)deuterons are measured in p-p collisions at sqrt[s]=13  TeV for the first time in and out of jets. In this measurement, the direction of the leading particle with the highest p_{T} in the event (p_{T}^{lead}>5  GeV/c) is used as an approximation for the jet axis. The event is consequently divided into three azimuthal regions, and the jet signal is obtained as the difference between the toward region, that contains jet fragmentation products in addition to the underlying event (UE), and the transverse region, which is dominated by the UE.

Measurement of the J/ψ Polarization with Respect to the Event Plane in Pb-Pb Collisions at the LHC.

We study the polarization of inclusive J/ψ produced in Pb-Pb collisions at sqrt[s_{NN}]=5.02  TeV at the LHC in the dimuon channel, via the measurement of the angular distribution of its decay products. We perform the study in the rapidity region 2.

Relevance of Host Cell Surface Glycan Structure for Cell Specificity of Influenza A Viruses.

Influenza A viruses (IAVs) initiate infection via binding of the viral hemagglutinin (HA) to sialylated glycans on host cells. HA's receptor specificity towards individual glycans is well studied and clearly critical for virus infection, but the contribution of the highly heterogeneous and complex glycocalyx to virus-cell adhesion remains elusive. Here, we use two complementary methods, glycan arrays and single-virus force spectroscopy (SVFS), to compare influenza virus receptor specificity with virus binding to live cells.

New insights into the responder/nonresponder divide in rectal cancer: Damage-induced Type I IFNs dictate treatment efficacy and can be targeted to enhance radiotherapy.

Rectal cancer ranks as the second leading cause of cancer-related deaths. Neoadjuvant therapy for rectal cancer patients often results in individuals that respond well to therapy and those that respond poorly, requiring life-altering excision surgery. It is inadequately understood what dictates this responder/nonresponder divide.

Evolution of the major alcohol companies key global policy vehicle through the prism of tax records 2011-19.

Background: Important insights have been generated into the nature of the activities of the International Center for Alcohol Policies (ICAP). Its successor, the International Alliance for Responsible Drinking (IARD) is less well understood. This study aims to rectify evidence limitations on the political activities of the alcohol industry at the global level.

CD73 and PD-L1 dual blockade amplifies antitumor efficacy of SBRT in murine PDAC models.

Background: Stereotactic body radiotherapy (SBRT) induces immunogenic cell death, leading to subsequent antitumor immune response that is in part counterbalanced by activation of immune evasive processes, for example, upregulation of programmed cell death-ligand 1 (PD-L1) and adenosine generating enzyme, CD73. CD73 is upregulated in pancreatic ductal adenocarcinoma (PDAC) compared with normal pancreatic tissue and high expression of CD73 in PDACs is associated with increased tumor size, advanced stage, lymph node involvement, metastasis, PD-L1 expression and poor prognosis. Therefore, we hypothesized that blockade of both CD73 and PD-L1 in combination with SBRT might improve antitumor efficacy in an orthotopic murine PDAC model.

Harnessing the Immunological Effects of Radiation to Improve Immunotherapies in Cancer.

Ionizing radiation (IR) is used to treat 50% of cancers. While the cytotoxic effects related to DNA damage with IR have been known since the early 20th century, the role of the immune system in the treatment response is still yet to be fully determined. IR can induce immunogenic cell death (ICD), which activates innate and adaptive immunity against the cancer.