Therapeutic drug monitoring versus Bayesian AUC-based dosing for vancomycin in routine practice: a cost-benefit analysis.

Background: AUC-based dosing with validated Bayesian software is recommended as a good approach to guide bedside vancomycin dosing.

Objectives: To compare treatment and vancomycin-associated acute kidney injury (AKI) costs between Bayesian AUC-based dosing and conventional therapeutic drug monitoring (TDM) using steady-state plasma concentrations of vancomycin administered as continuous infusion in hospitalized non-critically ill patients with severe Gram-positive infection.

Methods: A cost-benefit analysis presented as a return on investment (ROI) analysis from a hospital perspective was conducted using a decision tree model (TDM versus AUC-based dosing) to simulate treatment cost (personnel, serum sampling and drug cost), vancomycin-associated AKI risk and cost up to 14 days.

Realizing zero-threshold population inversion plasmonic doping.

Lowering the population inversion threshold is key to leveraging quantum dots (QDs) for nanoscale lasing and laser miniaturization. However, optical realization of population inversion in QDs has an inherent limitation: the number of excited electrons per QD is bound by the absorbed photons. Here we show that one can break this population limit and realize near-zero threshold inversion plasmonic doping.

The role of N-methyladenosine (mA) mRNA modifications in herpesvirus infections.

Herpesviruses, a family of large enveloped DNA viruses, establish persistent infections in a wide range of hosts. This characteristic requires an intricate network of interactions with their hosts and host cells. In recent years, the interplay between herpesviruses and the epitranscriptome-chemical modifications in transcripts that may affect mRNA biology and fate-has emerged as a novel aspect of herpesvirus-host interactions.

Verruciform Acanthotic Vulvar Intraepithelial Neoplasia Harbors Recurrent Genomic Alterations Found in HPV-independent Squamous Cell Carcinoma.

The term verruciform acanthotic vulvar intraepithelial neoplasia (vaVIN) was coined to describe HPV-independent p53-wildtype lesions with characteristic clinicopathologic characteristics and association with vulvar squamous cell carcinoma (vSCC). We aimed to expand on the molecular landscape of vaVIN using comprehensive sequencing and copy number variation profiling. vaVIN diagnosis in institutional cases was confirmed by a second review, plus negative p16 and wildtype p53 by immunohistochemistry.

Deciphering the biosynthetic pathway of triterpene saponins in Prunella vulgaris.

The traditional Chinese medicinal plant Prunella vulgaris contains numerous triterpene saponin metabolites, notably ursolic and oleanolic acid saponins, which have significant pharmacological values. Despite their importance, the genes responsible for synthesizing these triterpene saponins in P. vulgaris remain unidentified.

Roads to remission: evolving treatment concepts in type 2 inflammatory diseases.

Unlabelled: Non-communicable diseases (NCDs) characterised by type 2 inflammation, including asthma, allergic rhinitis, chronic rhinosinusitis with nasal polyps, atopic dermatitis, food allergies and eosinophilic esophagitis, are increasing in prevalence worldwide. Currently, there is a major paradigm shift in the management of these diseases, towards the concept of disease modification and the treatment goal remission, regardless of severity and age. Remission as a treatment goal in chronic inflammatory NCDs was first introduced in rheumatoid arthritis, and then adopted in other non-type 2 inflammatory diseases.

Who is WithMe? EEG features for attention in a visual task, with auditory and rhythmic support.

Introduction: The study of attention has been pivotal in advancing our comprehension of cognition. The goal of this study is to investigate which EEG data representations or features are most closely linked to attention, and to what extent they can handle the cross-subject variability.

Methods: We explore the features obtained from the univariate time series from a single EEG channel, such as time domain features and recurrence plots, as well as representations obtained directly from the multivariate time series, such as global field power or functional brain networks.

Ethical considerations on surrogacy†.

Surrogacy is the assisted reproductive technology (ART) practice in which a person becomes pregnant, carries, and delivers a child on behalf of another couple/person, who are the intended parent(s). Surrogacy is an especially complex practice as the interests of the intended parents, the gestational carrier, and the future child may differ. This paper considers ethical questions related to different forms of surrogacy.

Factors associated with statural growth in pediatric kidney transplant recipients with focus on metabolic acidosis.

Background: We investigated factors associated with post-transplant growth in pediatric kidney transplant (KTx) recipients with a focus on plasma bicarbonate (HCO3) and estimated the effect of alkali treatment on growth.

Methods: In this study of the CERTAIN Registry, data were collected up to 5 years post-transplant. Generalized Additive Mixed Models were applied to assess the association between post-transplant growth and covariates.

Synchrotron XRF spectroscopy for reading salt-encrusted cuneiform tablets.

Cuneiform tablets were a primary writing medium in the ancient Near East from the late fourth millennium BCE to the first century CE. Although these clay tablets were durable for daily use, prolonged burial over millennia has made them vulnerable to salt damage. Fluctuations in temperature and humidity cause the migration of salts to the surface of the tablets, damaging them and covering the inscriptions, making the text unreadable.

Impacts of irrigation expansion on moist-heat stress based on IRRMIP results.

Irrigation rapidly expanded during the 20 century, affecting climate via water, energy, and biogeochemical changes. Previous assessments of these effects predominantly relied on a single Earth System Model, and therefore suffered from structural model uncertainties. Here we quantify the impacts of historical irrigation expansion on climate by analysing simulation results from six Earth system models participating in the Irrigation Model Intercomparison Project (IRRMIP).

The moderating and mediating role of the placenta in the association between prenatal exposure to air pollutants and birth weight: A twin study.

Prenatal exposure to air pollution has been linked to lower birth weight, yet the role of the placenta in this association is often overlooked. This study investigates whether placental characteristics act as moderators or mediators in the association between prenatal exposure to particulate matter (PM) and nitrogen dioxide (NO) and birth weight in twins. The study included 3340 twins (born 2002-2013) from the East Flanders Prospective Twin Survey.

The International Association for the Study of Lung Cancer Staging Project: The Database and Proposal for the Revision of the Staging of Pulmonary Neuroendocrine Carcinoma in the Forthcoming Ninth Edition of the TNM Classification for Lung Cancer.

Introduction: Pulmonary high-grade neuroendocrine carcinoma (NEC) includes small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC). The seventh and eighth editions of the TNM classification for lung cancer confirmed the applicability of this staging system for SCLC. With the proposal of N2 and M1c subcategories for the ninth edition classification, we assessed the applicability to NECs.

Future directions in the evaluation and management of newly diagnosed metastatic cancer.

There is a much debate regarding optimal selection in patients with metastatic cancer who should undergo local treatment (surgery or radiation treatment) to the primary tumor and/or metastases. Additionally, the optimal treatment of newly diagnosed metastatic cancer is largely unclear. Current prognostication systems to best inform these clinical scenarios are limited, as all metastatic patients are grouped together as having Stage IV disease without further incorporation of patient and disease-specific covariates that significantly impact patient outcomes.

A European Delphi Consensus on the Management of Abdominal Aortic Aneurysms in Patients with Heritable Aortic Diseases.

Objective: Abdominal aortic aneurysm (AAA) in a patient with an underlying heritable aortic disease (HAD) is rare, and evidence based recommendations for its management are lacking. This study aimed to generate a consensus from multidisciplinary specialists on the diagnosis, treatment, and surveillance of AAA associated with HAD and to define topics of interest for future research.

Methods: A Delphi consensus was designed involving European multidisciplinary specialists and reported using the ACcurate COnsensus Reporting Document (ACCORD) reporting guideline.

Stress and telomere length in leukocytes: Investigating the role of GABRA6 gene polymorphism and cortisol.

Telomere length (TL) is considered a biomarker of aging, and short TL in leukocytes is related to age and stress-related health problems. Cumulative lifetime stress exposure has also been associated with shorter TL and age-related health problems, but the mechanisms are not well understood. We tested in 108 individuals whether shorter TL in leukocytes is observed in individuals with the GABRA6 TT genotype, which has been associated with dysregulation of hypothalamic-pituitary-adrenal axis activity (the main biological stress system) compared to the CC genotype.

A participatory needs assessment to map the system dynamics of overweight related behaviours of 10-14-year-old adolescents living in an underserved neighbourhood in Amsterdam, the Netherlands.

Background: Developing interventions along with the population of interest using systems thinking is a promising method to address the underlying system dynamics of overweight. The purpose of this study is twofold: to gain insight into the perspectives of adolescents regarding: (1) the system dynamics of energy balance-related behaviours (EBRBs) (physical activity, screen use, sleep behaviour and dietary behaviour); and (2) underlying mechanisms and overarching drivers of unhealthy EBRBs.

Methods: We conducted Participatory Action Research (PAR) to map the system dynamics of EBRBs together with adolescents aged 10-14 years old living in a lower socioeconomic, ethnically diverse neighbourhood in Amsterdam East, the Netherlands.

Prospective association between breakfast consumption frequency and BMI z-score among European school-aged children. The Feel4Diabetes Study.

Background: The long-term effects of breakfast on childhood z-BMI remain inconclusive.

Objective: To prospectively assess the impact of stable and altered breakfast consumption habits on z-BMI change over two years, in school-aged children across six European countries.

Methods: Data of 6,528 children (8.

Safety and efficacy of nipocalimab in adults with generalised myasthenia gravis (Vivacity-MG3): a phase 3, randomised, double-blind, placebo-controlled study.

Background: Given burdensome side-effects and long latency for efficacy with conventional agents, there is a continued need for generalised myasthenia gravis treatments that are safe and provide consistently sustained, long-term disease control. Nipocalimab, a neonatal Fc receptor blocker, was associated with dose-dependent reductions in total IgG and anti-acetylcholine receptor (AChR) antibodies and clinically meaningful improvements in the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale in patients with generalised myasthenia gravis in a phase 2 study. We aimed to assess the safety and efficacy of nipocalimab in a phase 3 study.

Spatially restricted and ontogenically distinct hepatic macrophages are required for tissue repair.

Our understanding of the functional heterogeneity of resident versus recruited macrophages in the diseased liver is limited. A population of recruited lipid-associated macrophages (LAMs) has been reported to populate the diseased liver alongside resident Kupffer cells (KCs). However, the precise roles of these distinct macrophage subsets remain elusive.

Walking to the same winter: Urban-rural disparities in pain among middle-aged and older Chinese.

Chronic pain, as a barometer of population health, remains understudied from a socio-structural lens. This study adopts a life course perspective and integrates hukou as a potential institutional arrangement shaping pain, aiming to advance the understanding of health inequalities in China. Specifically, we examine urban-rural disparities in pain prevalence and investigate how these disparities evolve across the life course by using generalized estimating equations and the China Health and Retirement Longitudinal Study 2011-2020 (N = 16479).

Revisiting the electrophysiological correlates of valence and expectancy in reward processing - A multi-lab replication.

Two event-related brain potential (ERP) components, the frontocentral feedback-related negativity (FRN) and the posterior P300, are key in feedback processing. The FRN typically exhibits greater amplitude in response to negative and unexpected outcomes, whereas the P300 is generally more pronounced for positive outcomes. In an influential ERP study, Hajcak et al.

doubletrouble: an R/Bioconductor package for the identification, classification, and analysis of gene and genome duplications.

Summary: Gene and genome duplications are major evolutionary forces that shape the diversity and complexity of life. However, different duplication modes have distinct impacts on gene function, expression, and regulation. Existing tools for identifying and classifying duplicated genes are either outdated or not user-friendly.

Impact of reporting rapid susceptibility results in Gram negative bloodstream infections: a real world prospective study.

Purpose: Mortality and morbidity of patients with bloodstream infection (BSI) remain high despite advances in diagnostic methods and efforts to speed up reporting. This study investigated the impact of reporting rapid Minimum Inhibitory Concentration (MIC)-results in Gram negative BSIs with the ASTar system (Q-linea, Uppsala, Sweden) on the adaptation of empirically started antimicrobial therapy. We performed a real-world study during which antimicrobial susceptibility testing (AST) results were instantly reported to the treating physician in an established multidisciplinary antimicrobial stewardship setting.