Evolving assessment pathways for precision oncology medicines to improve patient access: a tumor-agnostic lens.

Background: Genomic and molecular alterations are increasingly important in cancer diagnosis, and scientific advances are opening new treatment avenues. Precision oncology (PO) uses a patient's genomic profile to determine optimal treatment, promising fewer side effects and higher success rates. Within PO, tumor-agnostic (TA) therapies target genomic alterations irrespective of tumor location.

Design, calibration, and performance of a uniaxial pressure cell for neutron scattering studies of quantum magnetism.

We provide an overview of a pressure cell designed to apply uniaxial pressure to single crystals for the study, by neutron scattering techniques, of strongly correlated magnetic systems and, in particular, quantum magnets. A detailed overview of the pressure cell components, their requirements, and links to the scientific and technical specifications are presented. The pressure cell is able to accommodate a 200 mm3 single crystal that can be pressurized up to 2 GPa at cryogenic temperatures.

Advancing neutron diffraction for accurate structural measurement of light elements at megabar pressures.

Over the last 60 years, the diamond anvil cell (DAC) has emerged as the tool of choice in high pressure science because materials can be studied at megabar pressures using X-ray and spectroscopic probes. In contrast, the pressure range for neutron diffraction has been limited due to low neutron flux even at the strongest sources and the resulting large sample sizes. Here, we introduce a neutron DAC that enables break-out of the previously limited pressure range.

The Prevalence of Symptom Reporting for Benign Paroxysmal Positional Vertigo in a Traumatic Brain Injury Population.

Objective: To assess the prevalence of benign paroxysmal positional vertigo (BPPV) in traumatic brain injury population.

Study Design: In this cross-sectional design, each subject completed screening for BPPV, which included subjective questioning and positional testing. Subjects were asked if they experienced dizziness with bed mobility.

Identification and Quantification of MIDD0301 Metabolites.

Background: MIDD0301 is an oral asthma drug candidate that binds GABAA receptors on airway smooth muscle and immune cells.

Objective: The objective of this study is to identify and quantify MIDD0301 metabolites in vitro and in vivo and determine the pharmacokinetics of oral, IP, and IV administered MIDD0301.

Methods: In vitro conversion of MIDD0301 was performed using liver and kidney microsomes/S9 fractions followed by quantification using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Live-Cell Imaging Shows Uneven Segregation of Extrachromosomal DNA Elements and Transcriptionally Active Extrachromosomal DNA Hubs in Cancer.

Oncogenic extrachromosomal DNA elements (ecDNA) play an important role in tumor evolution, but our understanding of ecDNA biology is limited. We determined the distribution of single-cell ecDNA copy number across patient tissues and cell line models and observed how cell-to-cell ecDNA frequency varies greatly. The exceptional intratumoral heterogeneity of ecDNA suggested ecDNA-specific replication and propagation mechanisms.

ASCL1 represses a SOX9 neural crest stem-like state in small cell lung cancer.

ASCL1 is a neuroendocrine lineage-specific oncogenic driver of small cell lung cancer (SCLC), highly expressed in a significant fraction of tumors. However, ∼25% of human SCLC are ASCL1-low and associated with low neuroendocrine fate and high MYC expression. Using genetically engineered mouse models (GEMMs), we show that alterations in in the mouse lung induce an ASCL1 state of SCLC in multiple cells of origin.

Determinants of outcome impact of vein of Marshall ethanol infusion when added to catheter ablation of persistent atrial fibrillation: A secondary analysis of the VENUS randomized clinical trial.

Background: The Vein of Marshall Ethanol for Untreated Persistent AF (VENUS) trial demonstrated that adding vein of Marshall (VOM) ethanol infusion to catheter ablation (CA) improves ablation outcomes in persistent atrial fibrillation (AF). There was significant heterogeneity in the impact of VOM ethanol infusion on rhythm control.

Objective: The purpose of this study was to assess the association between outcomes and (1) achievement of bidirectional perimitral conduction block and (2) procedural volume.

Effect of Catheter Ablation With Vein of Marshall Ethanol Infusion vs Catheter Ablation Alone on Persistent Atrial Fibrillation: The VENUS Randomized Clinical Trial.

Importance: Catheter ablation of persistent atrial fibrillation (AF) has limited success. Procedural strategies beyond pulmonary vein isolation have failed to consistently improve results. The vein of Marshall contains innervation and AF triggers that can be ablated by retrograde ethanol infusion.

Longitudinal connections and the organization of the temporal cortex in macaques, great apes, and humans.

The temporal association cortex is considered a primate specialization and is involved in complex behaviors, with some, such as language, particularly characteristic of humans. The emergence of these behaviors has been linked to major differences in temporal lobe white matter in humans compared with monkeys. It is unknown, however, how the organization of the temporal lobe differs across several anthropoid primates.

Implementation of an enhanced recovery program for lower extremity bypass.

Objective: Enhanced recovery programs (ERPs) have gained wide acceptance across multiple surgical disciplines to improve postoperative outcomes and to decrease hospital length of stay (LOS). However, there is limited information in the existing literature for vascular patients. We describe the implementation and early results of an ERP and barriers to its implementation for lower extremity bypass surgery.

MYC Drives Temporal Evolution of Small Cell Lung Cancer Subtypes by Reprogramming Neuroendocrine Fate.

Small cell lung cancer (SCLC) is a neuroendocrine tumor treated clinically as a single disease with poor outcomes. Distinct SCLC molecular subtypes have been defined based on expression of ASCL1, NEUROD1, POU2F3, or YAP1. Here, we use mouse and human models with a time-series single-cell transcriptome analysis to reveal that MYC drives dynamic evolution of SCLC subtypes.

Where is Cingulate Cortex? A Cross-Species View.

To compare findings across species, neuroscience relies on cross-species homologies, particularly in terms of brain areas. For cingulate cortex, a structure implicated in behavioural adaptation and control, a homologous definition across mammals is available - but currently not employed by most rodent researchers. The standard partitioning of rodent cingulate cortex is inconsistent with that in any other model species, including humans.

Improving Lower Extremity Bypass Patient Outcomes: Enhanced Recovery After Surgery Implementation Project.

Background: Care variation is associated with poor quality outcomes. Clinical practice guideline implementation is one method to decrease care variation and improve outcomes. Enhanced Recovery After Surgery (ERAS) is a clinical pathway encompassing best practices across the surgical patient care continuum.

MYC paralog-dependent apoptotic priming orchestrates a spectrum of vulnerabilities in small cell lung cancer.

MYC paralogs are frequently activated in small cell lung cancer (SCLC) but represent poor drug targets. Thus, a detailed mapping of MYC-paralog-specific vulnerabilities may help to develop effective therapies for SCLC patients. Using a unique cellular CRISPR activation model, we uncover that, in contrast to MYCN and MYCL, MYC represses BCL2 transcription via interaction with MIZ1 and DNMT3a.

MYC-Driven Small-Cell Lung Cancer is Metabolically Distinct and Vulnerable to Arginine Depletion.

Purpose: Small-cell lung cancer (SCLC) has been treated clinically as a homogeneous disease, but recent discoveries suggest that SCLC is heterogeneous. Whether metabolic differences exist among SCLC subtypes is largely unexplored. In this study, we aimed to determine whether metabolic vulnerabilities exist between SCLC subtypes that can be therapeutically exploited.

Formation of an r8-Dominant Si Material.

The rhombohedral phase of Si (r8-Si), a promising semiconducting material, is formed by indentation together with the body-centered cubic phase (bc8-Si). Using a novel sample preparation method, x-ray diffraction is used to determine the relative volume of these phases in indented Si and allow observation of a distorted unit cell along the direction of indentation loading. Theoretical calculations together with these observations suggest the indent contains an intrinsic compression of ∼4  GPa that stabilizes the r8 phase.

Strengthening the Health Workforce through the ECHO Stages of Participation: Participants' Perspectives on Key Facilitators and Barriers.

Introduction: Project Extension for Community Health Outcomes (ECHO) was originally developed by the University of New Mexico's Health Science Center (UNMHSC) to build the capacities of primary-care providers and to increase specialty-care access to rural and underserved populations. ECHO Colorado, a replication site at the University of Colorado Anschutz Medical Campus (CUAMC), was developed with the same purpose and to help build the health workforce of Colorado. The CUAMC and its community-based partners recognized that by reducing unnecessary referrals to the medical campus and building primary-care capacity in communities, both would increase their scope and expand overall capacity.

A suite-level review of the neutron powder diffraction instruments at Oak Ridge National Laboratory.

The suite of neutron powder diffractometers at Oak Ridge National Laboratory (ORNL) utilizes the distinct characteristics of the Spallation Neutron Source and High Flux Isotope Reactor to enable the measurements of powder samples over an unparalleled regime at a single laboratory. Full refinements over large Q ranges, total scattering methods, fast measurements under changing conditions, and a wide array of sample environments are available. This article provides a brief overview of each powder instrument at ORNL and details the complementarity across the suite.

Impact of enhanced recovery after surgery (ERAS) protocol on gastrointestinal function in gynecologic oncology patients undergoing laparotomy.

Objective: To evaluate the impact of enhanced recovery after surgery (ERAS) on postoperative gastrointestinal function in gynecologic oncology patients.

Methods: This retrospective cohort study compared gynecology oncology patients undergoing non-emergent laparotomy from 10/2016 to 6/2017 managed on an ERAS protocol to a control cohort from the year prior to ERAS implementation. Major changes to postoperative care after ERAS implementation included multimodal analgesia, early feeding, goal-directed fluid resuscitation, and early ambulation.

Acute Appendicitis: Efficient Diagnosis and Management.

Appendicitis is one of the most common causes of acute abdominal pain in adults and children, with a lifetime risk of 8.6% in males and 6.7% in females.

Diagnosis Confirmation Model: A Value-Based Pricing Model for Inpatient Novel Antibiotics.

The Diagnosis Confirmation Model (DCM) includes a dual-pricing mechanism designed to support value-based pricing of novel antibiotics while improving the alignment of financial incentives with their optimal use in patients at high risk of drug-resistant infections. DCM is a market-based model and complementary to delinked models. Policymakers interested in stimulating antibiotic innovation could consider tailoring the DCM to their reimbursement systems and incorporating it into the suite of incentives to improve the economics of antibiotics.

Impact of Performing Nonurgent Interventional Radiology Procedures on Weekends.

Most clinical services limit weekend care to urgent or emergent situations. However, providing access to nonemergent procedures on weekends may reduce length of hospital stay and unnecessary admissions. No data are available on the impact of providing nonemergent interventional radiology (IR) procedural services on weekends.