Lung Tensioning Device Coil Treatment in Patients with Severe Emphysema: A Prospective Safety and Feasibility Trial (EFFORT).

Introduction: Currently, there is a lack of bronchoscopic lung volume reduction options that do not depend on fissure integrity. Endobronchial coils have been extensively studied to address this need but exhibited variable patient response and have been discontinued. Lung tension device (LTD) coils represent the next-generation coil treatment.

Tirzepatide for Metabolic Dysfunction-Associated Steatohepatitis with Liver Fibrosis.

Background: Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease associated with liver-related complications and death. The efficacy and safety of tirzepatide, an agonist of the glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors, in patients with MASH and moderate or severe fibrosis is unclear.

Methods: We conducted a phase 2, dose-finding, multicenter, double-blind, randomized, placebo-controlled trial involving participants with biopsy-confirmed MASH and stage F2 or F3 (moderate or severe) fibrosis.

The CNS relapse in T-cell lymphoma index predicts CNS relapse in patients with T- and NK-cell lymphomas.

Little is known about risk factors for central nervous system (CNS) relapse in mature T-cell and natural killer cell neoplasms (MTNKNs). We aimed to describe the clinical epidemiology of CNS relapse in patients with MTNKN and developed the CNS relapse In T-cell lymphoma Index (CITI) to predict patients at the highest risk of CNS relapse. We reviewed data from 135 patients with MTNKN and CNS relapse from 19 North American institutions.

Discovery of Nelutroctiv (CK-136), a Selective Cardiac Troponin Activator for the Treatment of Cardiovascular Diseases Associated with Reduced Cardiac Contractility.

Cardiac myosin activation has been shown to be a viable approach for the treatment of heart failure with reduced ejection fraction. Here, we report the discovery of nelutroctiv (), a selective cardiac troponin activator intended for patients with cardiovascular conditions where cardiac contractility is reduced. Discovery of nelutroctiv began with a high-throughput screen that identified compound , a muscle selective cardiac sarcomere activator devoid of phosphodiesterase-3 activity.

Cardiac Troponin Activator Increases Cardiac Contractility in Rats.

Novel cardiac troponin activators were identified using a high throughput cardiac myofibril ATPase assay and confirmed using a series of biochemical and biophysical assays. HTS hit increased rat cardiomyocyte fractional shortening without increasing intracellular calcium concentrations, and the biological target of and was determined to be the cardiac thin filament. Subsequent optimization to increase solubility and remove PDE-3 inhibition led to the discovery of and enabled pharmacological evaluation of cardiac troponin activation without the competing effects of PDE-3 inhibition.

New genomic technologies for multi-cancer early detection: Rethinking the scope of cancer screening.

Cancers other than breast, colorectal, cervical, and lung do not have guideline-recommended screening. New multi-cancer early detection (MCED) tests-using a single blood sample-have been developed based on circulating cell-free DNA (cfDNA) or other analytes. In this commentary, we review the current evidence on these tests, provide several major considerations for new MCED tests, and outline how their evaluation will need to differ from that established for traditional single-cancer screening tests.

Detection and characterization of lung cancer using cell-free DNA fragmentomes.

Non-invasive approaches for cell-free DNA (cfDNA) assessment provide an opportunity for cancer detection and intervention. Here, we use a machine learning model for detecting tumor-derived cfDNA through genome-wide analyses of cfDNA fragmentation in a prospective study of 365 individuals at risk for lung cancer. We validate the cancer detection model using an independent cohort of 385 non-cancer individuals and 46 lung cancer patients.

Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women.

Background: Genetic testing for breast cancer susceptibility is widely used, but for many genes, evidence of an association with breast cancer is weak, underlying risk estimates are imprecise, and reliable subtype-specific risk estimates are lacking.

Methods: We used a panel of 34 putative susceptibility genes to perform sequencing on samples from 60,466 women with breast cancer and 53,461 controls. In separate analyses for protein-truncating variants and rare missense variants in these genes, we estimated odds ratios for breast cancer overall and tumor subtypes.

Risk of Distal Embolization From tPA (Tissue-Type Plasminogen Activator) Administration Prior to Endovascular Stroke Treatment.

Background And Purpose: In large artery occlusion stroke, both intravenous (IV) tPA (tissue-type plasminogen activator) and endovascular stroke treatment (EST) are standard-of-care. It is unknown how often tPA causes distal embolization, in which a procedurally accessible large artery occlusion is converted to a more distal and potentially inaccessible occlusion.

Methods: We analyzed data from a decentralized stroke telemedicine program in an integrated healthcare delivery system covering 21 hospitals, with 2 high-volume EST centers.

The Transformation of Reference Microbiology Methods and Surveillance for With the Use of Whole Genome Sequencing in England and Wales.

The use of whole genome sequencing (WGS) as a method for supporting outbreak investigations, studying microbial populations and improving understanding of pathogenicity has been well-described (1-3). However, performing WGS on a discrete dataset does not pose the same challenges as implementing WGS as a routine, reference microbiology service for public health surveillance. Challenges include translating WGS data into a useable format for laboratory reporting, clinical case management, surveillance, and outbreak investigation as well as meeting the requirement to communicate that information in an understandable and universal language for clinical and public health action.

Sensitivity to psychosocial chronic stressors and adolescents' externalizing problems: Combined moderator effects of resting heart rate and parental psychiatric history.

From the literature it is not clear whether low resting heart rate (HR) reflects low or high sensitivity to the detrimental effects of adverse environments on externalizing problems. We studied parental psychiatric history (PH), reflecting general vulnerability, as possible moderator explaining these inconsistencies. Using Linear Mixed Models, we analyzed data from 1914 subjects, obtained in three measurement waves (mean age 11, 13.

Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney.

Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals.

Unveiling the in Vivo Protein Corona of Circulating Leukocyte-like Carriers.

Understanding interactions occurring at the interface between nanoparticles and biological components is an urgent challenge in nanomedicine due to their effect on the biological fate of nanoparticles. After the systemic injection of nanoparticles, a protein corona constructed by blood components surrounds the carrier's surface and modulates its pharmacokinetics and biodistribution. Biomimicry-based approaches in nanotechnology attempt to imitate what happens in nature in order to transfer specific natural functionalities to synthetic nanoparticles.

Vascular Inflammation: A Novel Access Route for Nanomedicine.

Despite an improved understanding of its pathophysiology and a wide range of new treatments, cardiovascular disease (CVD) remains a serious public health issue and the number one cause of mortality in the United States. Conditions that promote chronic systemic inflammation, such as obesity, cancer, and autoimmune and infectious diseases, are now known to play an important role in promoting CVD by inducing the expression of endothelial adhesion molecules and chemokines; these in turn promote leukocyte adherence and infiltration, which initiates and spurs the progression of CVD. In response to this new understanding, researchers are evaluating the potential cardiovascular benefits of new-generation therapies based on endogenous molecules with anti-inflammatory properties.

Effects of Intermittent Versus Continuous Walking on Distance Walked and Fatigue in Persons With Multiple Sclerosis: A Randomized Crossover Trial.

Background And Purpose: Fatigue is a common, disabling symptom experienced by persons with multiple sclerosis (MS). Evidence shows that intermittent exercise is associated in improved performance and negligible fatigue. The purpose of this study was to examine whether subjects with MS walk greater distances with less fatigue under intermittent (INT) or continuous (CONT) walking condition.

The role of Basal cortisol in predicting change in mental health problems across the transition to middle school.

Purpose: The period in which the transition to middle school occurs is marked by major changes in social context, social rules, and scholastic responsibilities. Some adolescents thrive during this period whereas others are overwhelmed and fail to cope adequately with their changing environment. We investigated basal cortisol upon waking as a predictor of change in mental health problems across the transition to middle school.

Chronic Stress and Adolescents' Mental Health: Modifying Effects of Basal Cortisol and Parental Psychiatric History. The TRAILS Study.

Large individual differences in adolescent mental health following chronic psychosocial stress suggest moderating factors. We examined two established moderators, basal cortisol and parental psychiatric history, simultaneously. We hypothesized that individuals with high basal cortisol, assumed to indicate high context sensitivity, would show relatively high problem levels following chronic stress, especially in the presence of parental psychiatric history.

Search for gravitational waves associated with γ-ray bursts detected by the interplanetary network.

We present the results of a search for gravitational waves associated with 223 γ-ray bursts (GRBs) detected by the InterPlanetary Network (IPN) in 2005-2010 during LIGO's fifth and sixth science runs and Virgo's first, second, and third science runs. The IPN satellites provide accurate times of the bursts and sky localizations that vary significantly from degree scale to hundreds of square degrees. We search for both a well-modeled binary coalescence signal, the favored progenitor model for short GRBs, and for generic, unmodeled gravitational wave bursts.

Constraints on cosmic strings from the LIGO-Virgo gravitational-wave detectors.

Cosmic strings can give rise to a large variety of interesting astrophysical phenomena. Among them, powerful bursts of gravitational waves (GWs) produced by cusps are a promising observational signature. In this Letter we present a search for GWs from cosmic string cusps in data collected by the LIGO and Virgo gravitational wave detectors between 2005 and 2010, with over 625 days of live time.

Pds5p is an essential chromosomal protein required for both sister chromatid cohesion and condensation in Saccharomyces cerevisiae.

The PDS5 gene (precocious dissociation of sisters) was identified in a genetic screen designed to identify genes important for chromosome structure. PDS5 is an essential gene and homologues are found from yeast to humans. Pds5p function is important for viability from S phase through mitosis and localizes to chromosomes during this cell cycle window, which encompasses the times when sister chromatid cohesion exists.