Robustness Assessment of Oncology Dose-Finding Trials Using the Modified Fragility Index.

Objectives: The sample sizes of phase I trials are typically small; some designs may lead to inaccurate estimation of the maximum tolerated dose (MTD). The objective of this study was to propose a metric assessing whether the MTD decision is sensitive to enrolling a few additional subjects in a phase I dose-finding trial.

Methods: Numerous model-based and model-assisted designs have been proposed to improve the efficiency and accuracy of finding the MTD.

Deficiency of the Deubiquitinase UCHL1 Attenuates Pulmonary Arterial Hypertension.

Background: The ubiquitin-proteasome system regulates protein degradation and the development of pulmonary arterial hypertension (PAH), but knowledge about the role of deubiquitinating enzymes in this process is limited. UCHL1 (ubiquitin carboxyl-terminal hydrolase 1), a deubiquitinase, has been shown to reduce AKT1 (AKT serine/threonine kinase 1) degradation, resulting in higher levels. Given that AKT1 is pathological in pulmonary hypertension, we hypothesized that UCHL1 deficiency attenuates PAH development by means of reductions in AKT1.

A Novel, Controllable, and Efficient Method for Building Highly Hydrophobic Aerogels.

Aerogels prepared using freeze-drying methods have the potential to be insulation materials or absorbents in the fields of industry, architecture, agriculture, etc., for their low heat conductivity, high specific area, low density, degradability, and low cost. However, their native, poor water resistance caused by the hydrophilicity of their polymer matrix limits their practical application.

Systems engineering of Escherichia coli for high-level glutarate production from glucose.

Glutarate is a key monomer in polyester and polyamide production. The low efficiency of the current biosynthetic pathways hampers its production by microbial cell factories. Herein, through metabolic simulation, a lysine-overproducing E.

Early-Life Cardiovascular Risk Factor Trajectories and Vascular Aging in Midlife: A 30-Year Prospective Cohort Study.

Background: Vascular aging, as assessed by structural and functional arterial properties, is an independent predictor of cardiovascular outcomes. We aimed to explore the associations of individual cardiovascular risk factors from childhood to midlife and their accumulation over a 30-year span with vascular aging in midlife.

Methods: Using data from the ongoing cohort of Hanzhong Adolescent Hypertension study, 2180 participants aged 6 to 18 years at baseline were followed for over 30 years.

Selection of an Optimal In Vitro Model to Assess P-gp Inhibition: Comparison of Vesicular and Bidirectional Transcellular Transport Inhibition Assays.

The multidrug resistance protein 1 (MDR1) P-glycoprotein (P-gp) is a clinically important transporter. In vitro P-gp inhibition assays have been routinely conducted to predict the potential for clinical drug-drug interactions (DDIs) mediated by P-gp. However, high interlaboratory and intersystem variability of P-gp IC data limits accurate prediction of DDIs using static models and decision criteria recommended by regulatory agencies.

Associations of Long-Term Visit-to-Visit Blood Pressure Variability With Subclinical Kidney Damage and Albuminuria in Adulthood: a 30-Year Prospective Cohort Study.

Background: Recent evidence indicates that long-term visit-to-visit blood pressure variability (BPV) may be associated with risk of cardiovascular disease. We, therefore, aimed to determine the potential associations of long-term BPV from childhood to middle age with subclinical kidney damage (SKD) and albuminuria in adulthood.

Methods: Using data from the ongoing cohort of Hanzhong Adolescent Hypertension study, which recruited children and adolescents aged 6 to 18 years at baseline, we assessed BPV by SD and average real variability (ARV) for 30 years (6 visits).

Hemiretinal Asymmetry in Peripapillary Vessel Density in Healthy, Glaucoma Suspect, and Glaucoma Eyes.

Purpose: To investigate hemiretinal asymmetry in radial peripapillary capillary vessel area density (VAD) of healthy, glaucoma suspect, and glaucoma eyes of varying severity and its diagnostic utility for glaucoma.

Design: Population-based, cross-sectional study.

Methods: Optic disc scans (6 × 6 mm) were collected on optical coherence tomography angiography (OCTA) to obtain VAD and on optical coherence tomography (OCT) to measure circumpapillary retinal nerve fiber layer (RNFL) thickness.

Development and Validation of an Automatic Image-Recognition Endoscopic Report Generation System: A Multicenter Study.

Introduction: Conventional gastrointestinal (GI) endoscopy reports written by physicians are time consuming and might have obvious heterogeneity or omissions, impairing the efficiency and multicenter consultation potential. We aimed to develop and validate an image recognition-based structured report generation system (ISRGS) through a multicenter database and to assess its diagnostic performance.

Methods: First, we developed and evaluated an ISRGS combining real-time video capture, site identification, lesion detection, subcharacteristics analysis, and structured report generation.

Orphan Nuclear Receptor Nur77 Inhibits Angiotensin II-Induced Vascular Remodeling via Downregulation of β-Catenin.

Angiotensin II (Ang II) is the predominant effector peptide of the renin-angiotensin system. Ang II contributes to vascular remodeling in many cardiovascular diseases (eg, hypertension, atherosclerosis, restenosis, and aneurysm). Orphan nuclear receptor Nur77 has a crucial role in the functional regulation of vascular cells.

Pharmacokinetics and urinary excretion of eprosartan in Chinese healthy volunteers of different gender.

The study aims to evaluate the pharmacokinetics and urinary excretion of eprosartan in Chinese healthy volunteers and to study the effect of gender on pharmacokinetics of eprosartan. Twenty healthy volunteers (ten men and ten women) were recruited for an open trial and received a single dose of 600 mg eprosartan. Using a validated LC/MS/MS method, plasma and urinary concentrations of eprosartan were determined.