TAK-925 (danavorexton), an Orexin Receptor 2 Agonist, Reduces Opioid-Induced Respiratory Depression and Sedation Without Affecting Analgesia in Healthy Adult Males.

Background: Orexin neuropeptides help regulate sleep/wake states, respiration, and pain. However, their potential role in regulating breathing, particularly in perioperative settings, is not well understood. TAK-925 (danavorexton), a novel, orexin receptor 2-selective agonist, directly activates neurons associated with respiratory control in the brain and improves respiratory parameters in rodents undergoing fentanyl-induced sedation.

Effective Solutions for Caregivers of Older Adults: A Review of Systematic Reviews.

This umbrella review aims to describe caregiver interventions tested across populations of informal caregivers of older adults and to examine the effect of caregiver interventions on depression, burden, and quality of life across intervention types and care-recipient populations. PubMed, Scopus, APA PsycInfo, ABIM, Sociological Abstracts, PAIS, and EconLit databases were systematically searched. Forty systematic reviews were identified as meeting inclusion criteria.

RENEWED: A follow-up study of the opicinumab phase 2 RENEW study in participants with acute optic neuritis.

Background: The randomized, phase 2 RENEW trial (NCT01721161) evaluated efficacy/safety of opicinumab (anti-LINGO-1) versus placebo in patients with first-episode unilateral acute optic neuritis (AON). Although no significant differences in the latency recovery of visual evoked potential (VEP) were observed between opicinumab and placebo groups in the intention to treat (ITT) population, the prespecified per-protocol (PP) population showed better recovery with opicinumab than with placebo. RENEWED (NCT02657915) was a one-visit, follow-up study 2 years after the last RENEW study visit (Week 32) designed to assess the long-term electrophysiological and clinical outcomes for participants previously enrolled and having received study treatment in RENEW.

Implementing the MIRROR-TCM Randomised Control Trial During the COVID-19 Pandemic: A Mixed-Methods Evaluation.

Aim: To evaluate the implementation of the Transitional Care Model (TCM), an evidence-based, advanced practice registered nurse-led multi-component intervention, as part of a randomised controlled trial during the first year of the COVID-19 pandemic.

Design: Parallel convergent mixed-methods approach.

Methods: Data for this study were collected between June 2020 and February 2021.

Improving recovery after bowel cancer surgery: mixed methods feasibility study of a co-produced information intervention (Recover Together).

Aim: Recovery after surgery for colorectal cancer is a complex process, involving numerous physiological, emotional, social and economic challenges. Good information is a key factor for enabling patients to recover well, but there is a paucity of evidence to guide how this should be done. A new information intervention (Recover Together) comprising a booklet, an online video and an inpatient goal board has been developed.

Adherence to Guidelines and Federal Psychotropic Medication Labels for the Treatment of Medicaid-Insured Children With ADHD.

Objective: This study examined adherence to clinical practice guidelines (CPGs) and U.S. Food and Drug Administration (FDA) medication labels when prescribing psychotropic medications to Medicaid-insured children with attention-deficit hyperactivity disorder (ADHD).

Chromatographic Determination of Permeability-Relevant Lipophilicity Facilitates Rapid Analysis of Macrocyclic Peptide Scaffolds.

Hydrocarbon-determined shake-flask measurements have demonstrated great utility for optimizing lipophilicity during early drug discovery. Alternatively, chromatographic methods confer reduced experimental error and improved handling of complex mixtures. In this study, we developed a chromatographic approach for estimating hydrocarbon-water shake-flask partition coefficients for a variety of macrocyclic peptides and other bRo5 molecules including PROTACs.

Comparative effectiveness of standard vs. AI-assisted PET/CT reading workflow for pre-treatment lymphoma staging: a multi-institutional reader study evaluation.

Background: Fluorine-18 fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT) is widely used for staging high-grade lymphoma, with the time to evaluate such studies varying depending on the complexity of the case. Integrating artificial intelligence (AI) within the reporting workflow has the potential to improve quality and efficiency. The aims of the present study were to evaluate the influence of an integrated research prototype segmentation tool implemented within diagnostic PET/CT reading software on the speed and quality of reporting with variable levels of experience, and to assess the effect of the AI-assisted workflow on reader confidence and whether this tool influenced reporting behaviour.

Interventional analytics in skilled nursing facilities associated with reduced readmissions.

Objective: To assess differences in longitudinal profiles for 30-day risk-adjusted readmission rates in skilled nursing facilities (SNFs) associated with Penn Medicine's Lancaster General Hospital (LGH) that implemented an interventional analytics (IA) platform vs other LGH facilities lacking IA vs other SNFs in Pennsylvania vs facilities in all other states.

Study Design: Retrospective longitudinal analysis of CMS readmissions data from 2017 through 2022, and cross-sectional analysis using CMS quality metrics data.

Methods: CMS SNF quality performance data were aggregated and compared with risk-adjusted readmissions by facility and time period.

Improving Parental Knowledge of Medically Complex Neonates Through Scheduled Conferences.

Reports of parental dissatisfaction from incomplete or inconsistent information led to a quality improvement (QI) project to establish planned family conferences at 10 days and 1 month of life, for 50% of the medically complex neonates admitted to a neonatal intensive care unit within 1 year. A QI team instituted a system in which social workers scheduled family conferences and a neonatologist conducted the conferences. Team members tracked measures using statistical process control charts over 21 months.

The contributions of DNA accessibility and transcription factor occupancy to enhancer activity during cellular differentiation.

During gene regulation, DNA accessibility is thought to limit the availability of transcription factor (TF) binding sites, while TFs can increase DNA accessibility to recruit additional factors that upregulate gene expression. Given this interplay, the causative regulatory events in the modulation of gene expression remain unknown for the vast majority of genes. We utilized deeply sequenced ATAC-Seq data and site-specific knock-in reporter genes to investigate the relationship between the binding-site resolution dynamics of DNA accessibility and the expression dynamics of the enhancers of Cebpa during macrophage-neutrophil differentiation.

Informed Consent among Clinical Trial Participants with Different Cancer Diagnoses.

Importance: Informed consent is essential to ethical, rigorous research and is important to recruitment and retention in cancer trials.

Objective: To examine cancer clinical trial (CCT) participants' perceptions of informed consent processes and variations in perceptions by cancer type.

Design And Setting And Participants: Cross-sectional survey from mixed-methods study at National Cancer Institute-designated Northeast comprehensive cancer center.

LucFlow: A method to measure Luciferase reporter expression in single cells.

Reporter assays, in which the expression of an inert protein is driven by gene regulatory elements such as promoters and enhancers, are a workhorse for investigating gene regulation. Techniques for measuring reporter gene expression vary from single-cell or single-molecule approaches having low throughput to bulk Luciferase assays that have high throughput. We developed a Luciferase Reporter Assay using Flow-Cytometry (LucFlow), which measures reporter expression in single cells immunostained for Luciferase.

Compartment Syndrome of All Extremities in the Setting of COVID-19-Induced Systemic Capillary Leak Syndrome With Superimposed Myositis.

Three years following the pandemic's emergence, COVID-19 has continued to affect much of the symptomatic population with widely varied respiratory complaints, fevers, numerous unexpected prodromal manifestations, and unknown long-term consequences. Scattered cases involving myopathies, rhabdomyolysis, and compartment syndrome have also been reported throughout the pandemic. Some similar cases have been attributed to systemic capillary leak syndrome (SCLS).

Hospitalizations, Emergency Department Visits, and Home Health Use Among Older Adults With Sensory Loss.

This study examines healthcare resource use (hospitalizations, emergency department [ED] visits, and home health episodes) among adults 65 and older diagnosed with hearing, vision, or dual sensory loss (SL) seen in the primary care setting of an academic health system. Multivariable logistic regression models were used to examine the relationship between SL (identified using ICD-10 codes) and healthcare resource use for 45,000 primary care patients. The sample included 5.

Serum neurofilament light-chain levels and long-term treatment outcomes in relapsing-remitting multiple sclerosis patients: A post hoc analysis of the randomized CombiRx trial.

Background: CombiRx was a randomized, double-blind, placebo-controlled phase 3 trial in treatment-naive relapsing-remitting multiple sclerosis (RRMS) patients randomized to intramuscular interferon beta-1a (IM IFN beta-1a), glatiramer acetate (GA), or both therapies.

Objective: This analysis investigated changes in serum neurofilament light-chain (sNfL) levels in response to treatment and assessed baseline sNfL as a predictor of relapse.

Methods: RRMS patients treated with IM IFN beta-1a 30 µg weekly + placebo (n = 159), GA 20 mg/mL daily + placebo (n = 172), or IM IFN beta-1a + GA (n = 344) were included.

The contributions of DNA accessibility and transcription factor occupancy to enhancer activity during cellular differentiation.

The upregulation of gene expression by enhancers depends upon the interplay between the binding of sequence-specific transcription factors (TFs) and DNA accessibility. DNA accessibility is thought to limit the ability of TFs to bind to their sites, while TFs can increase accessibility to recruit additional factors that upregulate gene expression. Given this interplay, the causative regulatory events underlying the modulation of gene expression during cellular differentiation remain unknown for the vast majority of genes.

Amide-to-ester substitution as a stable alternative to N-methylation for increasing membrane permeability in cyclic peptides.

Naturally occurring peptides with high membrane permeability often have ester bonds on their backbones. However, the impact of amide-to-ester substitutions on the membrane permeability of peptides has not been directly evaluated. Here we report the effect of amide-to-ester substitutions on the membrane permeability and conformational ensemble of cyclic peptides related to membrane permeation.

Safety and pharmacodynamics of a single infusion of danavorexton in adults with idiopathic hypersomnia.

Study Objectives: Idiopathic hypersomnia (IH) is a chronic disorder characterized by excessive daytime sleepiness unexplained by another disorder or drug/medication use. Although the orexin system plays a role in sleep-wake regulation, orexin A levels in the cerebrospinal fluid are normal in people with IH. This phase 1b, randomized, placebo-controlled, crossover study aimed to investigate the safety, pharmacokinetics, and pharmacodynamics of danavorexton, a small-molecule orexin-2 receptor agonist, in adults with IH.

The study protocol to evaluate implementation of the transitional care model in four U.S. healthcare systems during the Covid-19 pandemic.

This study protocol describes the conceptual framework, design, and methods being employed to evaluate the implementation of the Transitional Care Model (TCM) as part of a randomized controlled trial. The trial, designed to examine the health and cost outcomes of at-risk hospitalized older adults, is being conducted in the context of the COVID-19 pandemic. This parallel study is guided by the Practical, Robust, Implementation and Sustainability Model (PRISM) and uses a fixed, mixed methods convergent parallel design to identify challenges encountered by participating hospitals and post-acute and community-based providers that impact the implementation of the TCM with fidelity, strategies implemented to address those challenges and the relationships between challenges, strategies, and rates of fidelity to TCM's core components over time.