IDH Mutations in Glioma: Molecular, Cellular, Diagnostic, and Clinical Implications.

In 2021, the World Health Organization classified isocitrate dehydrogenase () mutant gliomas as a distinct subgroup of tumors with genetic changes sufficient to enable a complete diagnosis. Patients with an mutant glioma have improved survival which has been further enhanced by the advent of targeted therapies. enzymes contribute to cellular metabolism, and mutations to specific catalytic residues result in the neomorphic production of D-2-hydroxyglutarate (D-2-HG).

uPAR Immuno-PET in Pancreatic Cancer, Aging, and Chemotherapy-Induced Senescence.

Identifying cancer therapy resistance is a key time-saving tool for physicians. Part of chemotherapy resistance includes senescence, a persistent state without cell division or cell death. Chemically inducing senescence with the combination of trametinib and palbociclib (TP) yields several tumorigenic and prometastatic factors in pancreatic cancer models with many potential antibody-based targets.

Bedside Magnetocardiography with a Scalar Sensor Array.

Decades of research have shown that magnetocardiography (MCG) has the potential to improve cardiac care decisions. However, sensor and system limitations have prevented its widespread adoption in clinical practice. We report an MCG system built around an array of scalar, optically pumped magnetometers (OPMs) that effectively rejects ambient magnetic interference without magnetic shielding.

Association of RBC Transfusion Thresholds and Outcomes in Medical Patients With Acute Respiratory Failure Supported With Extracorporeal Membrane Oxygenation: A Single-Center Retrospective Cohort Study.

Background: The hemoglobin value to trigger RBC transfusion for patients receiving venovenous extracorporeal membrane oxygenation (ECMO) is controversial. Previous guidelines recommended transfusing to a normal hemoglobin level, but recent studies suggest that more RBC transfusions are associated with increased adverse outcomes.

Research Question: Is implementation of different institutional RBC transfusion thresholds for patients receiving venovenous ECMO associated with changes in RBC use and patient outcomes?

Study Design And Methods: This single-center retrospective study of patients receiving venovenous ECMO used segmented regression to test associations between implementation of institutional transfusion thresholds and trends in RBC use.

Examination of the PET in vivo generator Ce as a theranostic match for Ac.

Purpose: The radionuclide pair cerium-134/lanthanum-134 (Ce/La) was recently proposed as a suitable diagnostic counterpart for the therapeutic alpha-emitter actinium-225 (Ac). The unique properties of Ce offer perspectives for developing innovative in vivo investigations that are not possible with Ac. In this work, Ac- and Ce-labelled tracers were directly compared using internalizing and slow-internalizing cancer models to evaluate their in vivo comparability, progeny meandering, and potential as a matched theranostic pair for clinical translation.

Frequency and Severity of Hypoglycemia Under Conditions of Increased Hypoglycemic Risk with Insulin Efsitora Alfa Versus Insulin Glargine Treatment in Participants with Type 2 Diabetes.

Introduction: Insulin efsitora alfa (efsitora) is a basal insulin with a flat pharmacokinetic profile and long half-life, enabling weekly dosing. These attributes may provide stable glucose levels. This exploratory phase 1 study aimed to assess the hypoglycemic risk during experimental conditions that mimic situations encountered in daily life.

Effects of Tirzepatide vs Semaglutide on β-Cell Function, Insulin Sensitivity, and Glucose Control During a Meal Test.

Context: In a clinical study, tirzepatide, a glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist (GIP/GLP-1RA), provided superior glycemic control vs the GLP-1RA semaglutide. The physiologic mechanisms are incompletely understood.

Objective: This work aimed to evaluate treatment effects by model-based analyses of mixed-meal tolerance test (MMTT) data.

Exploring the PET in vivo generator Ce as a theranostic match for Ac.

Purpose: The radionuclide pair cerium-134/lanthanum-134 (Ce/La) was recently proposed as a suitable diagnostic counterpart for the therapeutic alpha-emitter actinium-225 (Ac). The unique properties of Ce offer perspectives for developing innovative in vivo investigations not possible with Ac. In this work, Ac- and Ce-labeled tracers were directly compared using internalizing and slow-internalizing cancer models to evaluate their in vivo comparability, progeny meandering, and potential as a matched theranostic pair for clinical translation.

Effect of Food Consumption on the Pharmacokinetics, Safety, and Tolerability of Once-Daily Orally Administered Orforglipron (LY3502970), a Non-peptide GLP-1 Receptor Agonist.

Introduction: We assessed the effect of the prandial state on the pharmacokinetics, safety, and tolerability of single and multiple doses of orforglipron (LY3502970), an oral, non-peptide glucagon-like peptide 1 receptor agonist (GLP-1 RA), in two studies (A and B).

Methods: Study A and study B were phase 1, randomized, crossover studies in healthy adults aged 18-65 years and 21-70 years, respectively. Participants received single (3 mg, study A) or multiple (16 mg, study B) oral doses of orforglipron under fasted and fed conditions.

Mobile Application-Based Communication Facilitation Platform for Family Members of Critically Ill Patients: A Randomized Clinical Trial.

Importance: Unmet and racially disparate palliative care needs are common in intensive care unit (ICU) settings.

Objective: To test the effect of a primary palliative care intervention vs usual care control both overall and by family member race.

Design, Setting, And Participants: This cluster randomized clinical trial was conducted at 6 adult medical and surgical ICUs in 2 academic and community hospitals in North Carolina between April 2019 and May 2022 with physician-level randomization and sequential clusters of 2 Black patient-family member dyads and 2 White patient-family member dyads enrolled under each physician.

Membrane-derived particles shed by PSMA-positive cells function as pro-angiogenic stimuli in tumors.

Cell membrane-derived particles (Mp) are rounded membrane-enclosed particles that are shed from tumor cells. Mp are formed from tumor membranes and are capable of tumor targeting and immunotherapeutic agents because they share membrane homology with parental cells; thus, they are under consideration as a drug delivery vehicle. Prostate-specific membrane antigen (PSMA), a transmembrane glycoprotein with enzymatic functionality, is highly expressed in Mp and extracellular vesicles (EV) from prostate cancer (PCa) with poor clinical prognosis.

Identifying inconsistencies in exotic pet regulations that perpetuate trade in risky species.

Regulatory inconsistencies at different jurisdictional levels have contributed to the global expansion of the exotic pet trade, with resultant increases in the spread of invasive species and pathogens. Researchers have enumerated multiple limitations and environmental risks posed by international and national rules that govern the exotic pet trade, yet little attention has focused on the regulation of the exotic pet trade within national borders. We reviewed state-level regulations that apply to the trade of vertebrate animal taxa in the United States.

Ability of the respiratory ECMO survival prediction (RESP) score to predict survival for patients with COVID-19 ARDS and non-COVID-19 ARDS: a single-center retrospective study.

The respiratory ECMO survival prediction (RESP) score is used to predict survival for patients managed with extracorporeal membrane oxygenation (ECMO), but its performance in patients with Coronavirus Disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) is unclear. We evaluated the ability of the RESP score to predict survival for patients with both non-COVID 19 ARDS and COVID-19 ARDS managed with ECMO at our institution. Receiver operating characteristic area under the curve (AUC) analysis found the RESP score reasonably predicted survival in patients with non-COVID-19 ARDS (AUC 0.

Ambient Light Resistant Shortwave Infrared Fluorescence Imaging for Preclinical Tumor Delineation via the pH Low-Insertion Peptide Conjugated to Indocyanine Green.

Shortwave infrared (900-1,700 nm) fluorescence imaging (SWIRFI) has shown significant advantages over visible (400-650 nm) and near-infrared (700-900 nm) fluorescence imaging (reduced autofluorescence, improved contrast, tissue resolution, and depth sensitivity). However, there is a major lag in the clinical translation of preclinical SWIRFI systems and targeted SWIRFI probes. We preclinically show that the pH low-insertion peptide conjugated to indocyanine green (pHLIP ICG), currently in clinical trials, is an excellent candidate for cancer-targeted SWIRFI.

Simultaneous quantitative imaging of two PET radiotracers via the detection of positron-electron annihilation and prompt gamma emissions.

In conventional positron emission tomography (PET), only one radiotracer can be imaged at a time, because all PET isotopes produce the same two 511 keV annihilation photons. Here we describe an image reconstruction method for the simultaneous in vivo imaging of two PET tracers and thereby the independent quantification of two molecular signals. This method of multiplexed PET imaging leverages the 350-700 keV range to maximize the capture of 511 keV annihilation photons and prompt γ-ray emission in the same energy window, hence eliminating the need for energy discrimination during reconstruction or for signal separation beforehand.

Efficacy and safety of oral orforglipron in patients with type 2 diabetes: a multicentre, randomised, dose-response, phase 2 study.

Background: Orforglipron, an oral, non-peptide glucagon-like peptide-1 (GLP-1) receptor agonist, is in development for type 2 diabetes and obesity. We assessed the efficacy and safety of orforglipron versus placebo or dulaglutide in participants with type 2 diabetes.

Methods: In this 26-week, phase 2, double-blind, randomised, multicentre study, participants were recruited from 45 centres (private clinics, hospitals, and research centers) in the USA, Hungary, Poland, and Slovakia.

Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity.

Background: Obesity is a major risk factor for many leading causes of illness and death worldwide. Data are needed regarding the efficacy and safety of the nonpeptide glucagon-like peptide-1 (GLP-1) receptor agonist orforglipron as a once-daily oral therapy for weight reduction in adults with obesity.

Methods: In this phase 2, randomized, double-blind trial, we enrolled adults with obesity, or with overweight plus at least one weight-related coexisting condition, and without diabetes.

Orforglipron (LY3502970), a novel, oral non-peptide glucagon-like peptide-1 receptor agonist: A Phase 1a, blinded, placebo-controlled, randomized, single- and multiple-ascending-dose study in healthy participants.

Aim: To evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple doses of orforglipron (LY3502970), an oral, non-peptide glucagon-like peptide-1 receptor agonist (GLP-1RA) in healthy participants.

Materials And Methods: This was a double-blind, placebo-controlled, Phase 1 study. Overtly healthy adults aged 18 to 65 years with body mass index of 20 to 40 kg/m and glycated haemoglobin concentration of 47.