Outcomes of an Emergency Department opioid alternatives Program implemented within a safety-net hospital system.

Background: The ongoing opioid epidemic in the United States has reinforced the need to provide multimodal and non-opioid pain management interventions. The PAMI-ED ALT program employed a multifaceted approach in the Emergency Department (ED) developing electronic health record (EHR) pain management order panels and discharge panels, as well as educating patients, clinicians, and ED staff on opioid alternatives, including non-pharmacologic interventions. The primary objective of this analysis was to compare changes in opioid and non-opioid analgesic administrations and prescribing in ED patients with select pain conditions (renal colic, headache, low back, and non-low back musculoskeletal pain) before and after implementation of PAMI ED-ALT.

Multiomic molecular patterns of lipid dysregulation in a subphenotype of sepsis with higher shock incidence and mortality.

Background: Lipids play a critical role in defense against sepsis. We sought to investigate gene expression and lipidomic patterns of lipid dysregulation in sepsis.

Methods: Data from four adult sepsis studies were analyzed and findings were investigated in two external datasets.

Impact of isotype on the mechanism of action of agonist anti-OX40 antibodies in cancer: implications for therapeutic combinations.

Background: OX40 has been widely studied as a target for immunotherapy with agonist antibodies taken forward into clinical trials for cancer where they are yet to show substantial efficacy. Here, we investigated potential mechanisms of action of anti-mouse (m) OX40 and anti-human (h) OX40 antibodies, including a clinically relevant monoclonal antibody (mAb) (GSK3174998) and evaluated how isotype can alter those mechanisms with the aim to develop improved antibodies for use in rational combination treatments for cancer.

Methods: Anti-mOX40 and anti-hOX40 mAbs were evaluated in a number of in vivo models, including an OT-I adoptive transfer immunization model in hOX40 knock-in (KI) mice and syngeneic tumor models.

Early Physician Gestalt Versus Usual Screening Tools for the Prediction of Sepsis in Critically Ill Emergency Patients.

Study Objective: Compare physician gestalt to existing screening tools for identifying sepsis in the initial minutes of presentation when time-sensitive treatments must be initiated.

Methods: This prospective observational study conducted with consecutive encounter sampling took place in the emergency department (ED) of an academic, urban, safety net hospital between September 2020 and May 2022. The study population included ED patients who were critically ill, excluding traumas, transfers, and self-evident diagnoses.

TRENDS IN CHOLESTEROL AND LIPOPROTEINS ARE ASSOCIATED WITH ACUTE RESPIRATORY DISTRESS SYNDROME INCIDENCE AND DEATH AMONG SEPSIS PATIENTS.

Objective: Compare changes in cholesterol and lipoprotein levels occurring in septic patients with and without acute respiratory distress syndrome (ARDS) and by survivorship. Methods: We reanalyzed data from prospective sepsis studies. Cholesterol and lipoprotein levels were analyzed using univariate testing to detect changes between septic patients with or without ARDS, and among ARDS survivors compared with nonsurvivors at enrollment (first 24 h of sepsis) and 48 to 72 h later.

Racial disparities in septic shock mortality: a retrospective cohort study.

Background: Patients with septic shock have the highest risk of death from sepsis, however, racial disparities in mortality outcomes in this cohort have not been rigorously investigated. Our objective was to describe the association between race/ethnicity and mortality in patients with septic shock.

Methods: Our study is a retrospective cohort study of adult patients in the OneFlorida Data Trust (Florida, United States of America) admitted with septic shock between January 2012 and July 2018 We identified patients as having septic shock if they received vasopressors during their hospital encounter and had either an explicit International Classification of Disease (ICD) code for sepsis, or had an infection ICD code and received intravenous antibiotics.

Activating Inducible T-cell Costimulator Yields Antitumor Activity Alone and in Combination with Anti-PD-1 Checkpoint Blockade.

Unlabelled: In recent years, there has been considerable interest in mAb-based induction of costimulatory receptor signaling as an approach to combat cancer. However, promising nonclinical data have yet to translate to a meaningful clinical benefit. Inducible T-cell costimulator (ICOS) is a costimulatory receptor important for immune responses.

Expression Predicts Poor Outcomes and Mortality From Sepsis.

Unlabelled: This is a study of lipid metabolic gene expression patterns to discover precision medicine for sepsis.

Objectives: Sepsis patients experience poor outcomes including chronic critical illness (CCI) or early death (within 14 d). We investigated lipid metabolic gene expression differences by outcome to discover therapeutic targets.

Association of Early Serum Phosphate Levels and Mortality in Patients with Sepsis.

Background: Metabolic derangements in sepsis influence phosphate levels, which may predict mortality outcomes. We investigated the association between initial phosphate levels and 28-day mortality in patients with sepsis.

Methods: We conducted a retrospective analysis of patients with sepsis.

Eucalyptus bleached kraft pulp-ionic liquid inks for 3D printing of ionogels and hydrogels.

3D printing has been recently recognized as one of the most promising technologies due to the multiple options to fabricate cost-effective and customizable objects. However, the necessity to substitute fossil fuels as raw materials is increasing the research on bio-based inks with recyclable and eco-friendly properties. In this work, we formulated inks for the 3D printing of ionogels and hydrogels with bleached kraft pulp dissolved in [Emim][DMP] at different concentrations (1-4 wt%).

DHCR7 Expression Predicts Poor Outcomes and Mortality from Sepsis.

Sepsis patients experience poor outcomes including chronic critical illness (CCI) or early death (within 14 days). We investigated lipid metabolic gene expression differences by outcome to discover therapeutic targets. Secondary analysis of samples from prospectively enrolled sepsis patients and a zebrafish sepsis model for drug discovery.

Immuno-PET Monitoring of CD8 T Cell Infiltration Post ICOS Agonist Antibody Treatment Alone and in Combination with PD-1 Blocking Antibody Using a Zr Anti-CD8 Mouse Minibody in EMT6 Syngeneic Tumor Mouse.

Purpose: The presence and functional competence of intratumoral CD8 T cells is often a barometer for successful immunotherapeutic responses in cancer. Despite this understanding and the extensive number of clinical-stage immunotherapies focused on potentiation (co-stimulation) or rescue (checkpoint blockade) of CD8 T cell antitumor activity, dynamic biomarker strategies are often lacking. To help fill this gap, immuno-PET nuclear imaging has emerged as a powerful tool for in vivo molecular imaging of antibody targeting.

Physiological and Transcriptomic Analysis of Responses to Ailanthone, a Potential Bio-Herbicide.

Many plants naturally synthesize and secrete secondary metabolites that exert an allelopathic effect, offering compelling alternatives to chemical herbicides. These natural herbicides are highly important for sustainable agricultural practices. Ailanthone is the chemical responsible for the herbicidal effect of , or "tree of heaven".

Cellulose ionogels, a perspective of the last decade: A review.

Cellulose ionogels have been extensively studied due to the variability of their properties and applications. The capability of trapping an ionic liquid in a biodegradable solid matrix without losing its properties makes this type of material a promising substitute for fossil fuel-derived materials. The possibility to formulate ionogels chemically or physically, to choose between different ionic liquids, cellulose types, and the possibility to add a wide range of additives, make these ionogels an adaptable material that can be modified for each target application in many fields such as medicine, energy storage, electrochemistry, etc.

A hypolipoprotein sepsis phenotype indicates reduced lipoprotein antioxidant capacity, increased endothelial dysfunction and organ failure, and worse clinical outcomes.

Objective: Approximately one-third of sepsis patients experience poor outcomes including chronic critical illness (CCI, intensive care unit (ICU) stay > 14 days) or early death (in-hospital death within 14 days). We sought to characterize lipoprotein predictive ability for poor outcomes and contribution to sepsis heterogeneity.

Design: Prospective cohort study with independent replication cohort.

CAZymes from the thermophilic fungus Thermoascus aurantiacus are induced by C5 and C6 sugars.

Background: Filamentous fungi are excellent lignocellulose degraders, which they achieve through producing carbohydrate active enzymes (CAZymes). CAZyme production is highly orchestrated and gene expression analysis has greatly expanded understanding of this important biotechnological process. The thermophilic fungus Thermoascus aurantiacus secretes highly active thermostable enzymes that enable saccharifications at higher temperatures; however, the genome-wide measurements of gene expression in response to CAZyme induction are not understood.

Belantamab Mafodotin (GSK2857916) Drives Immunogenic Cell Death and Immune-mediated Antitumor Responses .

B-cell maturation antigen (BCMA) is an attractive therapeutic target highly expressed on differentiated plasma cells in multiple myeloma and other B-cell malignancies. GSK2857916 (belantamab mafodotin, BLENREP) is a BCMA-targeting antibody-drug conjugate approved for the treatment of relapsed/refractory multiple myeloma. We report that GSK2857916 induces immunogenic cell death in BCMA-expressing cancer cells and promotes dendritic cell activation and GSK2857916 treatment enhances intratumor immune cell infiltration and activation, delays tumor growth, and promotes durable complete regressions in immune-competent mice bearing EL4 lymphoma tumors expressing human BCMA (EL4-hBCMA).

Purification and characterization of a native lytic polysaccharide monooxygenase from Thermoascus aurantiacus.

Lytic polysaccharide monooxygenases (LPMOs) have emerged as key proteins for depolymerization of cellulose. These copper-containing enzymes oxidize C-1 and/or C-4 bonds in cellulose, promoting increased hydrolysis of the oxidized cellulose chains. The LPMO from Thermoascus aurantiacus, a thermophilic ascomycete fungus, has been extensively studied and has served as a model LPMO.

Author Correction: Design of amidobenzimidazole STING receptor agonists with systemic activity.

Change history: In this Letter, author Ana Puhl was inadvertently omitted; this error has been corrected online.An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Design of amidobenzimidazole STING receptor agonists with systemic activity.

Stimulator of interferon genes (STING) is a receptor in the endoplasmic reticulum that propagates innate immune sensing of cytosolic pathogen-derived and self DNA. The development of compounds that modulate STING has recently been the focus of intense research for the treatment of cancer and infectious diseases and as vaccine adjuvants. To our knowledge, current efforts are focused on the development of modified cyclic dinucleotides that mimic the endogenous STING ligand cGAMP; these have progressed into clinical trials in patients with solid accessible tumours amenable to intratumoral delivery.

Tumor-immune profiling of murine syngeneic tumor models as a framework to guide mechanistic studies and predict therapy response in distinct tumor microenvironments.

Mouse syngeneic tumor models are widely used tools to demonstrate activity of novel anti-cancer immunotherapies. Despite their widespread use, a comprehensive view of their tumor-immune compositions and their relevance to human tumors has only begun to emerge. We propose each model possesses a unique tumor-immune infiltrate profile that can be probed with immunotherapies to inform on anti-tumor mechanisms and treatment strategies in human tumors with similar profiles.