Stability of microRNAs in serum and plasma reveal promise as a circulating biomarker.

Purpose: To verify the stability and reliability of circulating microRNA (miRNA) profiles in plasma and serum under different processing and storage conditions to inform future applications to circulating biomarker analyses.

Background: The development of blood-based methods for early disease detection has become increasingly desirable across various medical fields. RNA profiles have been investigated but have been a challenge due to rapid degradation of the analyte by ubiquitous RNases.

Natural born Killers: Harnessing NK cells to treat cancer.

Adoptive cellular therapy, or the collection and transfer of immune cells to patients, is emerging as a treatment option for many malignancies, especially hematologic malignancies, with a growing role in solid tumors and non-malignant conditions such as autoimmune diseases. The adoptive transfer of the innate immune cell natural killer (NK) cells is uniquely poised as a potential therapy alone or as an adjunct to other immune-targeted therapies for patients with cancer, with several advantages over other cell therapies such as T cells. We review key concepts in NK cells as a therapy for human disease and discuss key trials using NK cells in malignancy.

Implementing a PREcision meDICine Thoracic (PREDICT) service using in-house reflex testing in a large academic-community practice.

Background: Broad genomic testing is necessary to treat stage IV non-small cell lung cancer (NSCLC) patients. We describe a NSCLC precision medicine service at an academic-community practice and provide model-based estimates of the impact of a similar intervention.

Research Question: Will implementation of a precision medicine service increase NSCLC next-generation sequencing (NGS) rates, improve testing turnaround times (TAT), and increase rates of actionable genomic alterations (AGAs)?

Study Design And Methods: PREDICT (PREcision meDICine Thoracic) consisted of: 1) system-wide reflex testing of stage IV NSCLC patients by in-house solid tumor NGS focused assay and PD-L1 testing, 2) navigator, 3) molecular tumor board (MTB), 4) integrated information portal (OncoTracker) for real-time updates on samples processing, results, and treatment recommendations by the MTB.

Analysis of TERT association with clinical outcome in meningiomas: a multi-institutional cohort study.

Background: TERT promoter mutation is a rare biomarker in meningiomas associated with aberrant TERT expression and reduced progression-free survival. Although high TERT expression is characteristic of tumours with TERT promoter mutations, it has also been observed in tumours with wildtype TERT promoters. This study aimed to investigate the prevalence and prognostic association of TERT expression in meningiomas.

Real-world observations of GLP-1 receptor agonists and SGLT-2 inhibitors as potential treatments for Alzheimer's disease.

Introduction: Glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and dipeptidyl peptidase-4 (DPP-4) inhibitors have potential beneficial effects in Alzheimer's disease (AD).

Methods: We conducted pharmacoepidemiologic studies using two large-scale real-world databases. We fitted covariate-adjusted Cox models to compare the risks of AD among initiators of GLP-1 receptor agonists, SGLT-2 inhibitors, and DPP-4 inhibitors.

Systematic characterization of cell type-specific master metabolic regulators in Alzheimer's disease.

Alzheimer's disease (AD) exhibits metabolic heterogeneity; yet, the consequences on metabolic dynamics in a cell-type-specific manner and the underlying metabolite-sensor network basis remain unclear. Here, we show that neurons exhibit a striking decrease in energy and lipid-related metabolic activity, contrasted by an increase in microglial metabolism associated with neuroinflammation. To identify brain cell-type specific master metabolic regulators underlying the metabolic alterations of AD, we introduce scFUMES (ingle ell nctional tabolite-ensor), an algorithm integrating single-cell RNA sequencing, interactomics (protein-protein interactions), genomics, transcriptomics, and metabolomics from large human brain biobanks.

Immunotherapy in the Treatment of Undifferentiated Pleomorphic Sarcoma and Myxofibrosarcoma.

Undifferentiated pleomorphic sarcoma (UPS) and myxofibrosarcoma (MFS) are among the most common adult soft tissue sarcoma (STS) subtypes. Due to their high genetic complexity, heterogeneity, and lack of specific genetic alterations, no consistent molecular targets for targeted therapy have been identified for UPS and MFS. Recently, immune checkpoint inhibition (ICI) has emerged as a promising treatment modality for UPS and MFS.

In-bacteria arginylation assay.

ATE1 is an enzyme that catalyzes the post-translational arginylation of proteins by transferring arginine to acidic residues, such as aspartate and glutamate, located at the N-terminus or on side chains. This modification plays important roles in regulating protein stability and function. The mechanisms underlying substrate and site selection by ATE1 remain unclear.

Recombinant expression, purification, and characterization of human ATE1 arginyltransferase.

This chapter presents a straightforward method for expressing and purifying recombinant human Arginyl-tRNA-protein transferase 1 (ATE1) from E. coli. ATE1 is an enzyme that catalyzes the transfer of arginine from arginyl-tRNA to the N-terminal or internal Asp or Glu residues of the substrate proteins, a process that regulates protein turnover or function.

Human cytomegalovirus-encoded G protein-coupled receptor (GPCR) UL78 regulates viral reactivation.

Human cytomegalovirus (CMV) is a ubiquitous pathogen that establishes lifelong, latent infection in hematopoietic cells. Immune-competent individuals are usually asymptomatic for disease. However, immune dysregulation in latently infected individuals can result in viral reactivation, often causing further complications.

Transient gene melting governs the timing of oligodendrocyte maturation.

Cellular maturation is a crucial step for tissue formation and function, distinct from the initial steps of differentiation and cell fate specification. In the central nervous system, failure of oligodendrocyte maturation is linked to diseases such as multiple sclerosis. Here, we report a transcriptional mechanism that governs the timing of oligodendrocyte maturation.

Ten-year survival rates by PSA nadir in patients with metastatic hormone-sensitive prostate cancer: long-term survival analysis from the ECOG-ACRIN 3805 (CHAARTED) trial.

Background: The CHAARTED trial investigated the long-term survival of patients with metastatic hormone-sensitive prostate cancer (mHSPC) treated with androgen deprivation therapy (ADT) with or without docetaxel (D). This analysis focuses on 10-year overall survival (OS) stratified by disease volume and on-therapy PSA levels at 6 months.

Methods: OS was calculated using the Kaplan-Meier method from randomization to death or last known alive date.

Macrophage TBK1 signaling drives the development and outgrowth of breast cancer brain metastasis.

Tumor-associated macrophages (TAMs) are the predominant immune cells in the tumor microenvironment that promote breast cancer brain metastasis (BCBM). Here, we identify TANK-binding kinase (TBK1) as a critical signaling molecule enriched and activated in TAMs of BCBM tumors, playing an indispensable role in BCBM development and metastatic outgrowth in the brain. Mechanistically, BCBM cell-secreted matrix metalloproteinase 1 binds to protease-activated receptor 1 and integrin αVβ5 on macrophages, leading to TBK1 activation mediated by the nuclear factor-kappa B pathway.

Music Therapy in Patients Undergoing Pancreatic Surgery (MUSIC PUPS): A Mixed Methods Pilot Study.

Background: Pancreatoduodenectomy (PD) and distal pancreatectomy (DP) are painful procedures often accompanied by psychological distress. Music therapy interventions such as music-assisted relaxation and imagery (MARI) have demonstrated efficacy for acute pain but have not been examined within PD/DP. Gene expression mechanisms by which MARI may affect pain also remain poorly understood.

Challenges and opportunities on achieving an adequate delivery efficiency and immunogenicity with peptide-based anticancer vaccines.

Peptide vaccines are based on small peptide segments that contain antigenic epitopes recognizable by immune cells. Unlike traditional vaccines, they include only specific antigenic epitopes rather than entire pathogens or proteins. They are recognized, internalized, processed, and presented by antigen-presenting cells, such as dendritic cells, and subsequently presented to T cells, triggering an immune response.

Targeting CDK4 and CDK6 in hormone-dependent cancers.

FDA approval of selective CDK4/6 inhibitors (CDK4/6i) marked a groundbreaking development in cancer treatment. Decades of pre-clinical studies elucidated the route that certain cancer cells take to gain the cancer hallmark of uncontrolled proliferation, uncovering CDK4/6 as key players. Further investigation into the molecular underpinnings of this process revealed interconnected signaling between the CDK4/6 and estrogen receptor (ER) signaling axes, providing evidence that CDK4/6i would be particularly relevant in estrogen-driven cancers.

Alternative Splicing of Exon 23a in Neurofibromatosis Type 1 Pre-mRNA: Its Contribution to the Protein Structure and Function of Neurofibromin.

The neurofibromatosis type 1 (NF1) gene has 61 exons. The major alternative exon in NF1 pre-mRNA is exon 23a. Skipping and inclusion of this exon produce isoform I and isoform II neurofibromin, respectively.

Chimeric antigen receptor-engineered (CAR)-T cell therapy for metastatic prostate cancer.

Metastatic prostate cancer is associated with a significantly reduced survival rate, often indicating a more aggressive disease phenotype with diminished responsiveness to conventional therapies. Several FDA-approved treatments have demonstrated improved overall survival in men with metastatic disease. These include androgen receptor signaling inhibitors such as enzalutamide and abiraterone acetate, taxane-based chemotherapies including docetaxel and cabazitaxel, and bone-targeting radiopharmaceuticals like radium-223.

Dynamic contrast enhanced-magnetic resonance fingerprinting (DCE-MRF): A new quantitative MRI method to reliably assess tumor vascular perfusion.

Purpose: The clinical utility of conventional DCE-MRI methods is limited by the use of conventional qualitative dynamic T-weighted images, resulting in poor reproducibility. This study presents the initial implementation of a new DCE-magnetic resonance fingerprinting (DCE-MRF) methodology to provide reproducible, quantitative assessments of tumor vascular perfusion.

Methods: The DCE-MRF acquisition combines multiple T preparations, highly undersampled spiral trajectories (R = 48), a low-rank reconstruction method, and low tip angles on a 9.

The College of American Pathologists Biorepository Accreditation Program: Results from the First 10 Years.

The College of American Pathologists (CAP) Biorepository Accreditation Program (BAP) was established in 2012 with the goal of providing standardized requirements that ensure high quality for procuring, processing, storing, distributing, and computerizing information of biospecimens for scientific investigations. CAP BAP was the first biorepository accreditation program, and, since the program started in 2012, the world's second biorepository accreditation standard was issued by the International Organization for Standardization (ISO) as ISO 20387 in 2018. CAP BAP serves as an interface between several programs and draws best practices from renowned organizations.

Cell type-specific master metabolic regulators of Alzheimer's disease.

Alzheimer's disease (AD) exhibits metabolic heterogeneity; yet, the consequences on metabolic dynamics in a cell-type-specific manner and the underlying metabolite-sensor network basis remain unclear. Here, we show that neurons exhibit a striking decrease in energy and lipid-related metabolic activity, contrasted by an increase in microglial metabolism associated with neuroinflammation. To identify cell-type specific master metabolic regulators of AD underlying the metabolic alterations in AD, we introduce scFUMES (ingle ell nctional tabolite-ensor), an algorithm integrating single-cell RNA sequencing, interactomics, genomics, transcriptomics, and metabolomics from human brain biobanks.

Increasing the feasibility, impact, and equity of the Medicare Annual Wellness Visit (AWV) with a practice tailored AWV intervention: A stepped wedge clinical trial protocol.

Background: Older adults vastly underutilize evidence-based preventive health services and screenings that reduce illness, morbidity and mortality. The free-to-patient Medicare Annual Wellness Visit (AWV) is an opportunity to enhance preventive healthcare use, but also is underused.

Objectives: To evaluate the effect of a practice-tailored intervention on the sustained use of Medicare AWVs and on guideline-recommended preventive services and racial/ethnic disparities in 3 types of practice settings.

EphA2 and Ephrin-A1 Utilize the Same Interface for Both and Interactions That Differentially Regulate Cell Signaling and Function.

The 14 members of Eph receptor tyrosine kinases (RTK) bind to membrane-tethered ligand called ephrins and mediate cell contact signaling where the receptors and ligands engage on adjacent cells. Previous studies reveal that some Eph and ephrin pairs are coexpressed on the same cells, including EphA3-ephrin-A3 and EphA4/ephrin-A5, can also interact with each other . However, significant discrepancies persist as to the molecular basis and functional significance of the interactions, owning to the difficulties to directly interrogate the interactions.

Pathway polygenic risk scores (pPRS) for the analysis of gene-environment interaction.

A polygenic risk score (PRS) is used to quantify the combined disease risk of many genetic variants. For complex human traits there is interest in determining whether the PRS modifies, i.e.

The effects of dietary fat on gut microbial composition and function in a mouse model of ovarian cancer.

Objectives: The gut microbiome (GM) is pivotal in regulating inflammation, immune responses, and cancer progression. This study investigates the effects of a ketogenic diet (KD) and a high-fat/low-carbohydrate (HF/LC) diet on GM alterations and tumor growth in a syngeneic mouse model of high-grade serous ovarian cancer (EOC).

Methods: Thirty female C57BL/6 J mice injected with KPCA cells were randomized into KD, HF/LC, and low-fat/high-carbohydrate (LF/HC) diet groups.