"Small is beautiful" - Examining reliable determination of low-abundant therapeutic antibody glycovariants.

Glycans associated with biopharmaceutical drugs play crucial roles in drug safety and efficacy, and therefore, their reliable detection and quantification is essential. Our study introduces a multi-level quantification approach for glycosylation analysis in monoclonal antibodies (mAbs), focusing on minor abundant glycovariants. Mass spectrometric data is evaluated mainly employing open-source software tools.

Characterization of large transgene integrations in Chinese hamster ovary cells using a bioengineered mammalian transposase.

We present the first use of a bioengineered mammalian transposase system derived from Myotis lucifugus (bMLT) for integration of expression vectors into the CHO genome, focusing on GFP and trastuzumab production. Initially, CHO-K1 cells are transfected with a GFP reporter and varying amounts of bMLT DNA or mRNA. GFP expression is monitored over 17 weeks without selective pressure.

Methodological Insights on Biomarker-Based Patient Selection: A Review of Scientific Advice Procedures at the European Medicines Agency.

Biomarkers play a pivotal role in the selection and enrollment of trial participants. Particularly, predictive biomarkers help tailor medical care to individual patients; however, also prognostic biomarkers require consideration at the design stage. At the time of initiating a clinical trial, there may be uncertainty about whether a biomarker is predictive or prognostic, and the trial design may need to account for this.

High-Throughput Effect-Directed Analysis of Androgenic Compounds in Hospital Wastewater: Identifying Effect Drivers through Non-Target Screening Supported by Toxicity Prediction.

The increasing number of contaminants released into the environment necessitates innovative strategies for their detection and identification, particularly in complex environmental matrices like hospital wastewater. Hospital effluents contain both natural and synthetic hormones that might significantly contribute to endocrine disruption in aquatic ecosystems. In this study, HT-EDA has been implemented to identify the main effect-drivers (testosterone, androsterone and norgestrel) from hospital effluent using microplate fractionation, the AR-CALUX bioassay and an efficient data processing workflow.

Trends in Prescription of Stimulants and Narcoleptic Drugs in Switzerland: Longitudinal Health Insurance Claims Analysis for the Years 2014-2021.

Background: Stimulants are potent treatments for central hypersomnolence disorders or attention-deficit/hyperactivity disorders/attention deficit disorders but concerns have been raised about their potential negative consequences and their increasing prescription rates.

Objective: We aimed to describe stimulant prescription trends in Switzerland from 2014 to 2021. Second, we aimed to analyze the characteristics of individuals who received stimulant prescriptions in 2021 and investigate the link between stimulant prescriptions and hospitalization rates in 2021, using hospitalization as a potential indicator of adverse health outcomes.

Loading of CAR-T cells with magnetic nanoparticles for controlled targeting suppresses inflammatory cytokine release and switches tumor cell death mechanism.

Therapies against hematological malignancies using chimeric antigen receptors (CAR)-T cells have shown great potential; however, therapeutic success in solid tumors has been constrained due to limited tumor trafficking and infiltration, as well as the scarcity of cancer-specific solid tumor antigens. Therefore, the enrichment of tumor-antigen specific CAR-T cells in the desired region is critical for improving therapy efficacy and reducing systemic on-target/off-tumor side effects. Here, we functionalized human CAR-T cells with superparamagnetic iron oxide nanoparticles (SPIONs), making them magnetically controllable for site-directed targeting.

Exploring correlates of high psychiatric inpatient utilization in Switzerland: a descriptive and machine learning analysis.

Background: This study investigated socio-demographic, psychiatric, and psychological characteristics of patients with high versus low utilization of psychiatric inpatient services. Our objective was to better understand the utilization pattern and to contribute to improving psychiatric care.

Methods: One-hundred and twenty inpatients of the University Psychiatric Clinics (UPK) Basel, Switzerland, participated in this cross-sectional study.

Loss-of-function of DDR1 is responsible for a chondrodysplasia with multiple dislocations.

Chondrodysplasias with multiple dislocations are rare skeletal disorders characterized by hyperlaxity, joint dislocations, and growth retardation. Chondrodysplasias with multiple dislocations have been linked to pathogenic variants in genes encoding proteins involved in the proteoglycan biosynthesis. In this study, by exome sequencing analysis, we identified a homozygous nonsense variant (NM_001297654.

Conventional versus task-based package organization for out-of-hospital emergency kits: an emergency medical services simulation study.

Background: Emergency Medical Service crews are equipped with comprehensive emergency kits for routine care and to provide life-saving interventions in severely ill patients. While guidelines on contents and packing strategies of emergency kits for specific tasks and specialized situations exist, data for the design of out-of-hospital emergency kits in a general urban population is lacking. It may be possible to transfer the promising results of modern in-hospital packing strategies such as task-based package organization (TPO) to an Emergency Medical Service setting.

Magma Chamber Response to Ice Unloading: Applications to Volcanism in the West Antarctic Rift System.

Volcanic activity has been shown to affect Earth's climate in a myriad of ways. One such example is that eruptions proximate to surface ice will promote ice melting. In turn, the crustal unloading associated with melting an ice sheet affects the internal dynamics of the underlying magma plumbing system.

Mobility changes following COVID-19 stay-at-home policies varied by socioeconomic measures: An observational study in Ontario, Canada.

In Canada, lower income households and essential workers were disproportionately at risk of SARS-CoV-2. Early in the pandemic, stay-at-home restriction policies were used to limit virus transmission. There remains an evidence gap in how changes in mobility, in response to the policies, varied across socioeconomic measures in Canada.

Collaborative Outcomes Study on Health and Functioning During Infection Times (COH-FIT): Global and Risk-Group Stratified Course of Well-Being and Mental Health During the COVID-19 Pandemic in Adolescents.

Objective: To identify the COVID-19 pandemic impact on well-being/mental health, coping strategies, and risk factors in adolescents worldwide.

Method: This study was based on an anonymous online multi-national/multi-language survey in the general population (representative/weighted non-representative samples, 14-17 years of age), measuring change in well-being (World Health Organization-Five Well-Being Index [WHO-5]/range = 0-100) and psychopathology (validated composite P-score/range = 0-100), WHO-5 <50 and <29, pre- vs during COVID-19 pandemic (April 26, 2020-June 26, 2022). Coping strategies and 9 a priori- defined individual/cumulative risk factors were measured.

A Review on Ultrasound-based Methods to Image the Distribution of Magnetic Nanoparticles in Biomedical Applications.

Magnetic nanoparticles (MNPs) have gained significant attention in biomedical engineering and imaging applications due to their unique magnetic and mechanical properties. With their high magnetization and small size, MNPs serve as excitation sources for magnetically heating to destroy tumors (magnetic hyperthermia) and magnetically controlled drug carriers in magnetic drug targeting. However, effectively visualizing the distribution of MNPs during research or potential clinical use with low-cost modalities remains a critical challenge.

Patient-related characteristics or local tradition: what predicts the admission to a locked ward or the use of coercive measures in psychiatric inpatient treatment?

Prior research shows that locked doors and coercive measures are not only applied due to safety concerns, but also due to the specific local tradition of an institution. We examined the association of the use of coercive measures and the admission to a locked ward with person-related characteristics compared to the admission to a specific clinic. In this 15-year, naturalistic observational study, we examined 230,684 admissions to 14 German psychiatric inpatient clinics from Jan 1, 1998, to Dec 31, 2012.

Prognostic Value of Speckle Tracking Echocardiography-Derived Strain in Unmasking Risk for Arrhythmias in Children with Myocarditis.

Risk assessment in pediatric myocarditis is challenging, particularly when left ventricular ejection fraction (LVEF) is preserved. This study aimed to evaluate LV myocardial deformation using speckle-tracking echocardiography (STE)-derived longitudinal +strain (LS) and assessed its diagnostic and prognostic value in children with myocarditis. Retrospective STE-derived layer-specific LV LS analysis was performed on echocardiograms from patients within the multicenter, prospective registry for pediatric myocarditis "MYKKE".

Discrepancy between antibiotic pack sizes and guideline recommendations: a real-world analysis based on claims data.

Purpose: Antibiotics are often only available in predefined pack sizes, which may not align with guideline recommendations. This can result in leftover pills, leading to inappropriate self-medication or waste disposal, which can both foster the development of antibiotic resistance. The magnitude of inappropriate pack sizes is largely unknown.

Apollo: A comprehensive GPU-powered within-host simulator for viral evolution and infection dynamics across population, tissue, and cell.

Modern sequencing instruments bring unprecedented opportunity to study within-host viral evolution in conjunction with viral transmissions between hosts. However, no computational simulators are available to assist the characterization of within-host dynamics. This limits our ability to interpret epidemiological predictions incorporating within-host evolution and to validate computational inference tools.

Shared decision-making in post-coercion debriefing interventions in psychiatry - a scoping review.

Introduction: Debriefing is recommended after any coercive measure in psychiatry, but there are no wellestablished standards, and ist effectiveness remains unclear. Incorporating shared decision-making (SDM) into post-coercion debriefing interventions has potentially beneficial effects.

Methods: This scoping review provides an overview of the general characteristics of such interventions and the extent to which SDM elements are already used in such interventions.

Are integrated care models associated with improved drug safety in Swiss primary care? an observational analysis using healthcare claims data.

Background: Integrated care models (ICMs) might be an effective strategy to improve patients' quality of care. The aim of this study was to compare different ICMs such as family-doctor models, and a standard care model (SCM) regarding patients' drug safety in Swiss primary care.

Methods: We performed an observational study using health insurance claims data from patients who were continuously enrolled in an ICM or in a SCM between 2020 and 2021.

A Framework for Estimating Economic Impacts of Ecological Restoration.

Ecological restoration projects are designed to improve natural and cultural resources. Spending on restoration also stimulates economic impacts to the restoration economy through the creation or support of jobs and business activity. This paper presents accessible methods for quantifying the economic impacts supported by restoration spending and is written to be a guide and toolbox for an interdisciplinary audience of restoration practitioners and economists.