Imlunestrant is an Oral, Brain-Penetrant Selective Estrogen Receptor Degrader with Potent Antitumor Activity in ESR1 Wildtype and Mutant Breast Cancer.

Targeting of the estrogen receptor (ER) by anti-estrogens is the standard-of-care for patients with ER+ HER2- advanced/metastatic breast cancer. While anti-estrogens that degrade ERα (fulvestrant) or block estrogen production (aromatase inhibitors) have improved patient outcomes, clinically important challenges remain related to drug administration, limited bioavailability, lack of brain exposure, and acquired resistance due to ESR1 mutations. These limitations indicate a need for more robust ER-targeted therapies.

A Comparison Of Mosquito Species Assemblages Sampled With Three Commonly Used Traps And A Novel Design.

In nuisance or vector mosquito management, effective sampling is a stepping stone to efficient use of resources, targeted control efforts, and successful reduction of disease transmission. Experimental evidence indicates that there are species biases for certain traps, which in turn implies that the traps used will influence the species make-up of samples collected. A comparative study between 3 CO2-baited light traps and 2 hay-infusion baited gravid traps-Centers for Disease Control and Prevention (CDC) light trap, American BioPhysics Company (ABC) light trap, Reiter-Cummings (RC) gravid trap, and a convertible gravid/light trap with a novel design-was conducted to test for species specificity of each trap type.

Changes in Probation Officer Procedural Justice and Self-Reported Recidivism.

An increasing number of studies has studied the role of procedural justice for reducing recidivism in the probation context. The objective of this study is to contribute to existing knowledge by examining (a) whether people on probation alter their perceptions of probation officer procedural justice over time and (b) the extent to which changes in procedural justice relate to recidivism. This study utilized longitudinal data from 326 adults who were released from Dutch (pre-trial) detention centers and who had contact with the Probation Service.

A vexing case of a 73-year-old man with fevers, orbital cellulitis, and asymptomatic interstitial lung disease.

VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is a rare and recently identified disease resulting from a somatic mutation in the X-linked UBA1 gene in cells of myeloid lineage. It can present in a myriad of ways with the potential to affect various organ systems, including the lungs. VEXAS is usually steroid responsive, but no strong data exists for the use of a steroid-sparing agent.

Impact of frailty on outcomes after cardiac surgery.

Objective: The study objective was to evaluate whether increasing frailty, as measured by the Clinical Frailty Scale, was associated with an increased risk of hospital mortality for patients undergoing cardiac surgery.

Methods: A retrospective binational cohort study of 46,928 patients who underwent cardiac surgery in Australia and New Zealand was conducted. The primary exposure, frailty, was measured using the Clinical Frailty Scale.

Association of vaccination status and severity of SARS-CoV-2 infections in hospitalized patients.

Vaccination is considered the most promising approach for addressing the COVID-19 pandemic. However, even vaccinated people remain at risk. In this study, we examined the association between levels of vaccination and clinical outcomes in hospitalized patients.

Redox-Active Phenanthrenequinone Molecules and Nitrogen-Doped Reduced Graphene Oxide as Active Material Composites for Supercapacitor Applications.

Carbon-based supercapacitor electrodes are generally restricted in energy density, as they rely exclusively on electric double-layer capacitance (EDLC). The introduction of redox-active organic molecules to obtain pseudocapacitance is a promising route to develop electrode materials with improved energy densities. In this work, we develop a porous nitrogen-doped reduced graphene oxide and 9,10-phenanthrenequinone composite (N-HtrGO/PQ) via a facile one-step physical adsorption method.

Development and validation of a self-report measure of perceived dehumanization from officers.

Purpose: Emerging evidence indicates that incarcerated populations' perceptions of dehumanization by officers are prevalent, yet measures of it are few, and to our knowledge, no self-report measure of dehumanization from officers exists. To fill this gap, we have developed the Perceived Dehumanization from Officers Scale (PDOS), which is designed as a brief measure to assess perception of officer treatment as dehumanizing.

Methods: In this article, we provide preliminary evidence from two studies examining the reliability and validity of the PDOS.

The Current Status and Use of Microphysiological Systems by the Pharmaceutical Industry: The International Consortium for Innovation and Quality Microphysiological Systems Affiliate Survey and Commentary.

Microphysiological systems (MPS) are comprised of one or multiple cell types of human or animal origins that mimic the biochemical/electrical/mechanical responses and blood-tissue barrier properties of the cells observed within a complex organ. The goal of incorporating these in vitro systems is to expedite and advance the drug discovery and development paradigm with improved predictive and translational capabilities. Considering the industry need for improved efficiency and the broad challenges of model qualification and acceptance, the International Consortium for Innovation and Quality (IQ) founded an IQ MPS working group in 2014 and Affiliate in 2018.

Preclinical Investigation of a Lipoglycopeptide Dry Powder Inhalation Therapy for the Treatment of Pulmonary MRSA Infection.

The increased prevalence of pulmonary methicillin-resistant (MRSA) infection in patients living with cystic fibrosis (CF) is concerning due to a correlation with reduced life expectancy and lack of available treatment options. RV94 is a next generation lipoglycopeptide designed for pulmonary delivery that preclinically demonstrated high potency against MRSA in planktonic and protected colonies and improved pulmonary clearance relative to same class molecules. Here, RV94 was formulated into a dry powder for inhalation (DPI) to investigate the localized treatment of pulmonary MRSA presented in a potentially more convenient dosage form.

Effect of Inhalation Profile on Delivery of Treprostinil Palmitil Inhalation Powder.

Treprostinil palmitil (TP), a prodrug of treprostinil, is being developed as an inhalation powder (TPIP) for the treatment of patients with pulmonary arterial hypertension (PAH) and pulmonary hypertension due to interstitial lung disease (PH-ILD). In ongoing human clinical trials, TPIP is administered via a commercially available high resistance (HR) RS01 capsule-based dry powder inhaler (DPI) device manufactured by Berry Global (formerly Plastiape), which utilizes the patient's inspiratory flow to provide the required energy to deagglomerate and disperse the powder for delivery to their lungs. In this study, we characterized the aerosol performance of TPIP in response to changes in inhalation profiles to model more realistic use scenarios, i.

A Phase 2b, Randomised, Double-blind, Placebo-controlled, Parallel-arm, Multicenter Study Evaluating the Safety and Efficacy of Tesnatilimab in Patients with Moderately to Severely Active Crohn's Disease.

Background And Aims: Tesnatilimab, a monoclonal antibody targeting NKG2D, was evaluated in Crohn's disease [CD] patients who had failed or were intolerant to biologic or conventional therapy.

Methods: TRIDENT was a phase 2b, two-part, randomised, double-blind, placebo-controlled, parallel-arm, multicenter study. In Part 1 [proof of concept], 145 patients who were biologic intolerant or refractory [Bio-IR] or had not failed biologic therapy [Bio-NF] were randomised in a 1:1 ratio to placebo subcutaneously [SC] or tesnatilimab 400 mg SC.

Do Sheriff-Coroners Underreport Officer-Involved Homicides?

Introduction: In the United States, each state sets its own standards for its death investigation system. These may require independent medical examiners and coroners or allow for the sheriff to assume the role of coroner. Motivated by the well-established fact that counts of officer-involved homicides in official data sets grossly undercount the number of these incidents, we examine the possibility that different death investigation systems may lead to different death classification outcomes.

The Reemergence of Measles.

Objectives: Present-day pathologists may be unfamiliar with the histopathologic features of measles, which is a reemerging disease. Awareness of these features may enable early diagnosis of measles in unsuspected cases, including those with an atypical presentation. Using archived tissue samples from historic patients, a unique source of histopathologic information about measles and other reemerging infectious diseases, we performed a comprehensive analysis of the histopathologic features of measles seen in commonly infected tissues during prodrome, active, and late phases of the disease.

No Ordinary Coronary: A Case Series of Two Large Coronary Artery Aneuryms Found on Chest X-Ray.

Background: Post-procedural coronary aneurysms can have high morbidity and mortality. Although found more commonly on ultrasound or computed tomography imaging, if large enough, they may appear on chest x-ray studies.

Case Reports: We present two cases of coronary artery aneurysm visible on chest x-ray study-one originating from a saphenous vein graft and the other a left anterior descending artery pseudoaneurysm 1 week post heart catheterization.

Novel Smooth Muscle Ca-Signaling Nanodomains in Blood Pressure Regulation.

Background: Ca signals in smooth muscle cells (SMCs) contribute to vascular resistance and control blood pressure. Increased vascular resistance in hypertension has been attributed to impaired SMC Ca signaling mechanisms. In this regard, transient receptor potential vanilloid 4 (TRPV4) ion channels are a crucial Ca entry pathway in SMCs.

Surface Properties and Architectures of Male Moth Trichoid Sensilla Investigated Using Atomic Force Microscopy.

The surfaces of trichoid sensilla on male moth antennae have been sculpted over evolutionary time to capture pheromone odorant molecules emitted by the females of their species and transport the molecules in milliseconds into the binding protein milieu of the sensillum lumen. The capture of pheromone molecules likely has been optimized by the topographies and spacings of the numerous ridges and pores on these sensilla. A monolayer of free lipids in the outer epicuticle covers the sensillar surfaces and must also be involved in optimal pheromone odorant capture and transport.

Futurelessness and Commitment to Institutional Rules Among People in Jail.

The current study builds on prior work examining the association between futurelessness and commitment institutional rules among correctional populations. Using cross-sectional data from a sample of 413 people incarcerated in United States jails from 2018 to 2019, this study employs Ordinary Least Squares regression to examine the association between futurelessness and commitment to institutional rules controlling for various importation and deprivation factors previously linked with institutional misconduct. Results provide support for the importance of futurelessness for commitment to institutional rules, suggesting that this finding is consistent across correctional environments.

Exodex Adam-A Reconfigurable Dexterous Haptic User Interface for the Whole Hand.

Applications for dexterous robot teleoperation and immersive virtual reality are growing. Haptic user input devices need to allow the user to intuitively command and seamlessly "feel" the environment they work in, whether virtual or a remote site through an avatar. We introduce the DLR Exodex Adam, a reconfigurable, dexterous, whole-hand haptic input device.

Healthcare Use After Buprenorphine Prescription in a Community Emergency Department: A Cohort Study.

Introduction: Recent studies from urban academic centers have shown the promise of emergency physician-initiated buprenorphine for improving outcomes in opioid use disorder (OUD) patients. We investigated whether emergency physician-initiated buprenorphine in a rural, community setting decreases subsequent healthcare utilization for OUD patients.

Methods: We performed a retrospective chart review of patients presenting to a community hospital emergency department (ED) who received a prescription for buprenorphine from June 15, 2018-June 15, 2019.

Solvent-free production of thermoplastic lignocellulose from wood pulp by reactive extrusion.

A novel acylation approach suited to rapid bulk thermoplasticization of lignocellulose without solvents was previously demonstrated by the authors in benchtop batch studies. The method relies upon a benzethonium chloride/sulfuric acid functionalizing agent at low concentrations to act as a wetting agent for the wood pulp, similar to an ionic liquid, yet binds to the lignocellulose ester as a flow aid in the final thermoplastic. The present investigation evaluates the approach in a residence time-limited (45-90 s) continuous twin-screw reactor, where intensive mixing and heat were found to yield high acylation.

Discovery and Early Clinical Development of LY3202626, a Low-Dose, CNS-Penetrant BACE Inhibitor.

The beta-site APP cleaving enzyme 1, known as BACE1, has been a widely pursued Alzheimer's disease drug target owing to its critical role in the production of amyloid-beta. We have previously reported the clinical development of LY2811376 and LY2886721. LY2811376 advanced to Phase I before development was terminated due to nonclinical retinal toxicity.

Prison Visitation and Concerns about Reentry: Variations in Frequency and Quality of Visits are Associated with Reentry Concerns among People Incarcerated in Prison.

Prior studies suggest that visitation may have an impact on successful reentry. At the same time, the impact of visitation on incarcerated people's concerns about reentry has received little empirical attention. Understanding how factors such as visitation affect concerns about reentry can provide correctional officials with policy directions on how to reduce strains and enhance successful reintegration.

Caveolar peroxynitrite formation impairs endothelial TRPV4 channels and elevates pulmonary arterial pressure in pulmonary hypertension.

Recent studies have focused on the contribution of capillary endothelial TRPV4 channels to pulmonary pathologies, including lung edema and lung injury. However, in pulmonary hypertension (PH), small pulmonary arteries are the focus of the pathology, and endothelial TRPV4 channels in this crucial anatomy remain unexplored in PH. Here, we provide evidence that TRPV4 channels in endothelial cell caveolae maintain a low pulmonary arterial pressure under normal conditions.