Nemvaleukin alfa, a modified interleukin-2 cytokine, as monotherapy and with pembrolizumab in patients with advanced solid tumors (ARTISTRY-1).

Background: Nemvaleukin alfa (nemvaleukin, ALKS 4230) is a novel, engineered cytokine that selectively binds to the intermediate-affinity interleukin-2 receptor, preferentially activating CD8 T cells and natural killer cells, with minimal expansion of regulatory T cells, thereby mitigating the risk of toxicities associated with high-affinity interleukin-2 receptor activation. Clinical outcomes with nemvaleukin are unknown. ARTISTRY-1 investigated the safety, recommended phase 2 dose (RP2D), and antitumor activity of nemvaleukin in patients with advanced solid tumors.

Analysis of Concordance Between Next-Generation Sequencing Assessment of Microsatellite Instability and Immunohistochemistry-Mismatch Repair From Solid Tumors.

Purpose: The new CAP guideline published in August 2022 recommends using immunohistochemistry (IHC) to test for mismatch repair defects in gastroesophageal (GE), small bowel (SB), or endometrial carcinoma (EC) cancers over next-generation sequencing assessment of microsatellite instability (NGS-MSI) for immune checkpoint inhibitor (ICI) therapy eligibility and states there is a preference to use IHC over NGS-MSI in colorectal carcinoma (CRC).

Methods: We assessed the concordance of NGS-MSI and IHC-MMR from a very large cohort across the spectrum of solid tumors.

Results: Of the over 190,000 samples with both NGS-MSI and IHC-MMR about 1,160 were initially flagged as discordant.

SABRE-SHEATH Hyperpolarization of [1,5-C]Z-OMPD for Noninvasive pH Sensing.

Hyperpolarized (HP) C-labeled probes are emerging as promising agents to noninvasively image pH in vivo. HP [1,5-C]Z-OMPD (Z-4-methyl-2-oxopent-3-enedioic acid) in particular has recently been used to simultaneously report on kidney perfusion, filtration, and pH homeostasis, in addition to the ability to detect local tumor acidification. In previous studies, dissolution dynamic nuclear polarization was used to hyperpolarize Z-OMPD.

Anaphylactic shock during SpaceOAR Vue hydrogel procedure.

In this report, we present a unique and rare case of an intraoperative anaphylactic shock leading to cardiac arrest during the SpaceOAR Vue™ hydrogel procedure in a 70-year-old patient undergoing External Beam Radiation Therapy (EBRT) for advanced localized prostate cancer. To our knowledge, this is the first urologic case report documenting this adverse reaction associated with the placement of the SpaceOAR Vue product. We discuss the possible culprits, including the hydrogel's polyethylene glycol (PEG) and iodine content, perioperative antibiotics, and local lidocaine anesthetic, and propose relevant considerations for clinicians administering rectal hydrogel spacers.

An Autophagy-Targeting Chimera Induces Degradation of Androgen Receptor Mutants and AR-v7 in Castration-Resistant Prostate Cancer.

Genetic alterations play a pivotal role in various human diseases, particularly cancer. The androgen receptor (AR) is a crucial transcription factor driving prostate cancer (PCa) progression across all stages. Current AR-targeting therapies utilize competitive AR antagonists or pathway suppressors.

Rapid lung ventilation MRI using parahydrogen-induced polarization of propane gas.

Proton-hyperpolarized contrast agents are attractive because they can be imaged on virtually any clinical MRI scanner, which is typically equipped to scan only protons rather than heteronuclei (, anything besides protons, , C, N, Xe, Na, .). Even though the lifetime of the proton spin hyperpolarization is only a few seconds, it is sufficient for inhalation and scanning of proton-hyperpolarized gas media.

Phase II trial of multi-tyrosine kinase inhibitor ESK981 in combination with PD-1 inhibitor nivolumab in patients with metastatic castration-resistant prostate cancer.

Increasing the response rates of immune checkpoint inhibitors in patients with metastatic castration-resistant prostate cancer (mCRPC) presents a significant challenge. ESK981 is a multi-tyrosine kinase and PIKfyve lipid kinase inhibitor that augments immunotherapeutic responses. In this phase II study, ESK981 was combined with the PD-1 blocking monoclonal antibody nivolumab to test for potentially improved response rates in patients with mCRPC who have progressed on androgen receptor (AR)-targeted agents and chemotherapy.

A Novel One-Sample Mendelian Randomization Approach for Count-Type Outcomes That Is Robust to Correlated and Uncorrelated Pleiotropic Effects.

We propose two novel one-sample Mendelian randomization (MR) approaches to causal inference from count-type health outcomes, tailored to both equidispersion and overdispersion conditions. Selecting valid single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs) poses a key challenge for MR approaches, as it requires meeting the necessary IV assumptions. To bolster the proposed approaches by addressing violations of IV assumptions, we incorporate a process for removing invalid SNPs that violate the assumptions.

Developing Hyperpolarized Butane Gas for Ventilation Lung Imaging.

NMR hyperpolarization dramatically improves the detection sensitivity of magnetic resonance through the increase in nuclear spin polarization. Because of the sensitivity increase by several orders of magnitude, additional applications have been unlocked, including imaging of gases in physiologically relevant conditions. Hyperpolarized Xe gas recently received FDA approval as the first inhalable gaseous MRI contrast agent for clinical functional lung imaging of a wide range of pulmonary diseases.

An Insight into the Structure-Activity Relationship of Benzimidazole and Pyrazole Derivatives as Anticancer Agents.

Introduction: Cancer is a leading cause of death worldwide, driving the urgent need for new and effective treatments. Benzimidazole and pyrazole derivatives have gained attention for their potential as anticancer agents due to their diverse biological activities. The development of resistance in cancer cells, toxicity concerns, and inconsistent efficacy across different types of cancer are a few of the challenges.

Bioactive Potential of the Sulfated Exopolysaccharides From the Brown Microalga sp.: Antioxidant, Antimicrobial, and Antiapoptotic Profiles.

This study aims to investigate the physicochemical characteristics of the exopolysaccharides (EPS) extracted from the microalgae species sp., as well as to evaluate their antioxidant, antibacterial, and anti-apoptotic activities. The crude extracellular polysaccharides from the halophilic diatom sp.

Life's Essential 8 and Incident Cardiovascular Disease in U.S. Women With Breast Cancer.

Background: Relationships between lifestyle risk factors and cardiovascular disease (CVD) risk in women with breast cancer (BC) are underexplored.

Objectives: To evaluate the incidence of CVD in relation to the Life's Essential 8 (LE8) score among women with BC.

Methods: Data from the Women's Health Initiative were utilized.

Multiomic Characterization and Molecular Profiling of Nuclear Protein in Testis Carcinoma.

Purpose: Nuclear protein in testis carcinoma (NC) is an underdiagnosed and aggressive squamous/poorly differentiated cancer characterized by rearrangement of the gene on chromosome 15q14. Co-occurring alternations have not been fully characterized.

Methods: We analyzed the genomic and immune landscape of 54 cases of NC that underwent DNA- and RNA-based NGS sequencing (Caris).

Rapid in situ carbon-13 hyperpolarization and imaging of acetate and pyruvate esters without external polarizer.

Hyperpolarized C MRI visualizes real-time metabolic processes in vivo. In this study, we achieved high C polarization in situ in the bore of an MRI system for precursor molecules of most widely employed hyperpolarized agents: [1-C]acetate and [1-C]pyruvate ethyl esters in their perdeuterated forms, enhancing hyperpolarization lifetimes, hyperpolarized to P ≈ 28% at 80 mM concentration and P ≈ 19% at 10 mM concentration, respectively. Using vinyl esters as unsaturated Parahydrogen-Induced Polarization via Side-Arm Hydrogenation (PHIP-SAH) precursors and our novel polarization setup, we achieved these hyperpolarization levels by fast side-arm hydrogenation in acetone-d at elevated temperatures (up to 90°C) and hydrogenation pressures (up to 32 bar).

Multiomics Studies on Metabolism Changes in Alcohol-Associated Liver Disease.

Metabolic dysfunction in the liver represents a predominant feature in the early stages of alcohol-associated liver disease (ALD). However, the mechanisms underlying this are only partially understood. To investigate the metabolic characteristics of the liver in ALD, we did a relative quantification of polar metabolites and lipids in the liver of mice with experimental ALD using untargeted metabolomics and untargeted lipidomics.

The Prognostication of Surgically Resected Head and Neck Squamous Cell Carcinoma Using Pre-Therapy Neutrophil and Lymphocyte Counts.

Background: Hematological markers, such as neutrophils (ANC), lymphocyte (ALC), and neutrophil-lymphocyte ratio (NLR), may serve as indicators of systemic inflammation and immune response in head and neck squamous cell carcinoma (HNSCC). However, their prognostic significance across HNSCC subtypes remains to be fully elucidated.

Methods: We conducted a secondary analysis of a randomized clinical trial involving patients with surgically resected HNSCC with either positive margins or extranodal extension.

Through-bond and through-space radiofrequency amplification by stimulated emission of radiation.

Radio Amplification by Stimulated Emission of Radiation (RASER) is a phenomenon observed during nuclear magnetic resonance (NMR) experiments with strongly negatively polarized systems. This phenomenon may be utilized for the production of very narrow NMR lines, background-free NMR spectroscopy, and excitation-free sensing of chemical transformations. Recently, novel methods of producing RASER by ParaHydrogen-Induced Polarization (PHIP) were introduced.