Matrix effect evaluation using multi-component post-column infusion in untargeted hydrophilic interaction liquid chromatography-mass spectrometry plasma metabolomics.

Metabolomics based on hydrophilic interaction liquid chromatography (HILIC) coupled with mass spectrometry (MS) is a powerful tool for polar metabolite identification and quantification to further contribute to biomarker discovery and disease mechanism elucidation. However, matrix effect (ME), which may lead to altered ionization efficiency due to co-eluting compounds, is a significant challenge during biological analysis. Therefore, ME evaluation plays a crucial role during method development.

Choice of Postintubation Sedation Strategy by Sex: A Conjoint Analysis.

Purpose: To assess if patient sex is an important attribute in physician decision-making for postintubation sedation strategies in the emergency department and intensive care units.

Methods: We designed a survey of eight fictional cases utilizing a fractional factorial design varying fictional patient sex, race/ethnicity, and history of substance use disorder. We surveyed emergency medicine and critical care fellows and attendings at three geographically diverse academic medical centers in the US.

Elexacaftor/tezacaftor/ivacaftor efficacy in intestinal organoids with rare CFTR variants in comparison to CFTR-F508del and CFTR-wild type controls.

Cystic fibrosis is a life-shortening genetic disease caused by pathological variants of the cystic fibrosis transmembrane conductance regulator gene. The CFTR modulator therapy elexacaftor, tezacaftor and ivacaftor (ETI) rescues CFTR protein function and has made a significant impact on the lives of many people with CF. In Europe, ETI is currently available for people with CF who have at least one F508del mutation whilst the effect of ETI on rare CFTR variants remains unknown, albeit that many of such variants may be restored through ETI.

Over-the-counter short-acting β-agonist purchase and asthma-related health outcomes: a post hoc analysis of the SABINA III study.

This post-hoc analysis of the SABINA III study evaluated the association of short-acting β-agonist (SABA) prescriptions and self-reported over-the-counter (OTC) SABA purchase in the previous 12 months with asthma-related outcomes using multivariable regression models in 4556 patients (mean age, 48.9 years). Of the 2810 patients prescribed ≥3 SABA canisters, 776 (27.

Predictors of treatment attendance in patients with posttraumatic stress disorder and comorbid personality disorders.

Introduction: High dropout and low treatment attendance rates among patients with posttraumatic stress disorder (PTSD) and personality disorders (PDs) continue to pose a significant challenge. Despite numerous studies focusing on enhancing treatment attendance, the identification of consistent and reliable predictors in patients with PTSD and comorbid PDs remains limited.

Objectives: This study aims to investigate a wide range of potential predictors of treatment attendance, encompassing demographic, patient-severity, treatment, and therapist-related variables in patients with PTSD and comorbid borderline and/or cluster C PDs.

Late reproduction is associated with extended female survival but not with familial longevity.

Research Question: Are age at last childbirth and number of children, as facets of female reproductive health, related to individual lifespan or familial longevity?

Design: This observational study included 10,255 female participants from a multigenerational historical cohort, the LINKing System for historical family reconstruction (LINKS), and 1258 female participants from 651 long-lived families in the Leiden Longevity Study (LLS). Age at last childbirth and number of children, as outcomes of reproductive success, were compared with individual and familial longevity using the LINKS dataset. In addition, the genetic predisposition in the form of a polygenic risk score (PRS) for age at menopause was studied in relation to familial longevity using the LLS dataset.

Borylation iridium catalysed C-H activation: a new concise route to duocarmycin derivatives.

The synthesis of the ethyl ester analogue of the ultrapotent antitumour antibiotic seco-duocarmycin SA has been achieved in eleven linear steps from commercially available starting materials. The DSA alkylation subunit can be made in ten linear steps from the same precursor. The route involves C-H activation at the equivalent of the C7 position on indole leading to a borylated intermediate 9 that is stable enough for peptide coupling reactions but can be easily converted to the free hydroxyl analogue.

Physical activity decreases in patients on the liver transplant waiting list and influences postoperative outcome-a prospective cohort study.

Background: Physical deconditioning affects patients suffering from end-stage liver disease (ESLD). Liver transplantation (LT) is the only curative option for ESLD. Growing evidence suggests that pre-habilitation is beneficial in reducing post-surgical morbidity and mortality.

Internet-based emotion regulation training aimed at reducing violent revictimization and depressive symptoms in victimized depressed patients: Results of a randomized controlled trial.

Background: Depressed patients who have become victim of violence are prone to revictimization. However, no evidence-based interventions aimed at reducing revictimization in this group exist.

Methods: This multicenter randomized controlled trial evaluated the effectiveness of an internet-based emotion regulation training (iERT) added to TAU in reducing revictimization, emotion dysregulation, and depressive symptoms in recently victimized, depressed patients compared to TAU alone.

OrgaSegment: deep-learning based organoid segmentation to quantify CFTR dependent fluid secretion.

Epithelial ion and fluid transport studies in patient-derived organoids (PDOs) are increasingly being used for preclinical studies, drug development and precision medicine applications. Epithelial fluid transport properties in PDOs can be measured through visual changes in organoid (lumen) size. Such organoid phenotypes have been highly instrumental for the studying of diseases, including cystic fibrosis (CF), which is characterized by genetic mutations of the CF transmembrane conductance regulator (CFTR) ion channel.

Technical Report: A Comprehensive Comparison between Different Quantification Versions of Nightingale Health's H-NMR Metabolomics Platform.

H-NMR metabolomics data is increasingly used to track health and disease. Nightingale Health, a major supplier of H-NMR metabolomics, has recently updated the quantification strategy to further align with clinical standards. Such updates, however, might influence backward replicability, particularly affecting studies with repeated measures.

Features of immunometabolic depression as predictors of antidepressant treatment outcomes: pooled analysis of four clinical trials.

Background: Profiling patients on a proposed 'immunometabolic depression' (IMD) dimension, described as a cluster of atypical depressive symptoms related to energy regulation and immunometabolic dysregulations, may optimise personalised treatment.

Aims: To test the hypothesis that baseline IMD features predict poorer treatment outcomes with antidepressants.

Method: Data on 2551 individuals with depression across the iSPOT-D ( = 967), CO-MED ( = 665), GENDEP ( = 773) and EMBARC ( = 146) clinical trials were used.

Exploring intrinsic variability between cultured nasal and bronchial epithelia in cystic fibrosis.

The nasal and bronchial epithelium are unified parts of the respiratory tract that are affected in the monogenic disorder cystic fibrosis (CF). Recent studies have uncovered that nasal and bronchial tissues exhibit intrinsic variability, including differences in mucociliary cell composition and expression of unique transcriptional regulatory proteins which relate to germ layer origin. In the present study, we explored whether intrinsic differences between nasal and bronchial epithelial cells persist in cell cultures and affect epithelial cell functioning in CF.

CFTR Function Restoration upon Elexacaftor/Tezacaftor/Ivacaftor Treatment in Patient-Derived Intestinal Organoids with Rare Genotypes.

Cystic fibrosis (CF) is caused by mutations in the () gene. The combination of the CFTR modulators elexacaftor, tezacaftor, and ivacaftor (ETI) enables the effective rescue of CFTR function in people with the most prevalent F508del mutation. However, the functional restoration of rare variants remains unclear.

Detection of Intracerebral Hemorrhage Using Low-Field, Portable Magnetic Resonance Imaging in Patients With Stroke.

Background: Neuroimaging is essential for detecting spontaneous, nontraumatic intracerebral hemorrhage (ICH). Recent data suggest ICH can be characterized using low-field magnetic resonance imaging (MRI). Our primary objective was to investigate the sensitivity and specificity of ICH on a 0.

Temperature Control in the Era of Personalized Medicine: Knowledge Gaps, Research Priorities, and Future Directions.

Hypoxic-ischemic brain injury (HIBI) is the leading cause of death and disability after cardiac arrest. To date, temperature control is the only intervention shown to improve neurologic outcomes in patients with HIBI. Despite robust preclinical evidence supporting hypothermia as neuroprotective therapy after cardiac arrest, there remains clinical equipoise regarding optimal core temperature, therapeutic window, and duration of therapy.

Multi-ancestry genome-wide study identifies effector genes and druggable pathways for coronary artery calcification.

Coronary artery calcification (CAC), a measure of subclinical atherosclerosis, predicts future symptomatic coronary artery disease (CAD). Identifying genetic risk factors for CAC may point to new therapeutic avenues for prevention. Currently, there are only four known risk loci for CAC identified from genome-wide association studies (GWAS) in the general population.

Diet and mitonuclear haplotype interactions affect growth rate in a slime mould.

Trait expression in metazoans is strongly influenced by the balance of macronutrients (i.e. protein, carbohydrate and fat) in the diet.