Safety, bactericidal activity, and pharmacokinetics of the antituberculosis drug candidate BTZ-043 in South Africa (PanACEA-BTZ-043-02): an open-label, dose-expansion, randomised, controlled, phase 1b/2a trial.

Background: The broad use of bedaquiline and pretomanid as the mainstay of new regimens to combat tuberculosis is a risk due to increasing bedaquiline resistance. We aimed to assess the safety, bactericidal activity, and pharmacokinetics of BTZ-043, a first-in-class DprE1 inhibitor with strong bactericidal activity in murine models.

Methods: This open-label, dose-expansion, randomised, controlled, phase 1b/2a trial was conducted in two specialised tuberculosis sites in Cape Town, South Africa.

Tamuzimod in patients with moderately-to-severely active ulcerative colitis: a multicentre, double-blind, randomised, placebo-controlled, phase 2 induction trial.

Background: Tamuzimod (VTX002) is a selective sphingosine 1-phosphate receptor 1 modulator in development for ulcerative colitis. We aimed to assess the safety and efficacy of tamuzimod in patients with moderately-to-severely active ulcerative colitis.

Methods: This double-blind, randomised, placebo-controlled, phase 2 induction trial was conducted at 122 centres across 15 countries in Asia, Europe, and North America.

From responsibility to responsibilization in stem cell research: An ethical framework.

Adopting a responsibilization approach can further improve the ethical conduct of stem cell (SC) research and applications. This approach helps align new and existing solutions for ethical implications by focusing on equipping SC researchers with the knowledge, skills, and organizational arrangements to take (co-)responsibility for the socio-ethical implications of their research.

An accurate and robust multicomponent quantitative analysis method: Molar mass coefficient method.

Multicomponent quantitative analysis (MCQA) is necessary for comprehensively characterizing the quality of complex samples, including medicines, foods. However, the limited supply of reference substances and the high costs associated with testing hinder the application of the MCQA using the external standard (ES) method. Here we propose a Molar Mass Coefficient (MMC) method for the quantification of multiple compounds with identical chromophore utilizing a single reference compound (SRC) by a UV detector.

Gut microbiome and immune checkpoint inhibitor toxicity.

Background: Multiple studies have suggested that gut microbiome may influence immune checkpoint inhibitor (ICI) efficacy, but its association with immune-related adverse events (irAEs) is less well studied. In this prospective cohort study, we assessed whether gut microbiome composition at start, or changes during ICI, are associated with severe irAEs.

Methods: Stool samples of cancer patients treated with anti-PD-1 ± anti-CTLA-4 were analyzed using 16S rRNA gene sequencing and metagenomic shotgun sequencing.

A reproducibility study on invasion in small pulmonary adenocarcinoma according to the WHO and a modified classification, supported by biomarkers.

Objectives: Evaluating invasion in non-mucinous adenocarcinoma (NMA) of the lung is crucial for accurate pT-staging. This study compares the World Health Organization (WHO) with a recently modified NMA classification.

Materials And Methods: A retrospective case-control study was conducted on small NMA pT1N0M0 cases with a 5-year follow-up.

Mitochondrial disorder diagnosis and management- what the pediatric neurologist wants to know.

Childhood-onset mitochondrial disorders are rare genetic diseases that often manifest with neurological impairment due to altered mitochondrial structure or function. To date, pathogenic variants in 373 genes across the nuclear and mitochondrial genomes have been linked to mitochondrial disease, but the ensuing genetic and clinical complexity of these disorders poses considerable challenges to their diagnosis and management. Nevertheless, despite the current lack of curative treatment, recent advances in next generation sequencing and -omics technologies have laid the foundation for precision mitochondrial medicine through enhanced diagnostic accuracy and greater insight into pathomechanisms.

An overview of plantar pressure distribution measurements and its applications in health and medicine.

Background: Measuring plantar pressure distribution is critical for understanding foot-ground interactions, providing valuable insights for diagnosing and managing various health conditions. Since its initial studies in 1984, this field has garnered increasing attention within healthcare and medicine due to its broad applications across clinical settings.

Research Question: How does measuring plantar pressure distribution affect healthcare outcomes across different age groups and health conditions?

Methods: This review thoroughly explores the literature concerning plantar pressure distribution, focusing on studies conducted from 1984 onwards.

Life cycle assessment and life cycle costing of full-scale ozonation for micropollutants removal from wastewater. Case study in the Netherlands.

Wastewater management is one of the main factors that affect drinking water quality. Therefore, the removal of micropollutant from urban wastewaters is receiving an increased attention. This study conducts a comprehensive life cycle assessment (LCA) and life cycle costing of a full-scale ozonation advanced wastewater treatment for micropollutant removal to identify the main impact contributors.

Flexible or fortified? How lichens balance defence strategies across climatic harshness gradients.

Lichens play important roles in habitat formation and community succession in polar and alpine ecosystems. Despite their significance, the ecological effects of lichen traits remain poorly researched. We propose a trait trade-off for managing light exposure based on climatic harshness.

Seasonal coastal residency and large-scale migration of two grey mullet species in temperate European waters.

Grey mullets (family Mugilidae) are widespread across coastal, brackish, and freshwater habitats, and have supported fisheries for millennia. Despite their global distribution and commercial value, little is known about their movement ecology and its role in the co-existence of sympatric mullet species. Gaps in knowledge about migratory behaviour, seasonal occurrence, and movement scales have also impeded effective management, highlighting the need for further research.

Global perspectives in acute and emergency general surgery in low and middle-income countries: a WSES project protocol for scoping review on global surgery.

Background: Around five billion people globally lack access to safe, timely, and affordable surgical facilities and care in low-income and middle-income countries (LMICs). Global initiatives have been launched, including efforts led by organizations. Also, regional efforts have shed light on the unique challenges faced by different areas within LMICs.

Enhancing work environments and reducing turnover intention: a multicenter longitudinal cohort study on differentiated nursing practices in Dutch hospitals.

Background: Addressing the growing challenge of nurse retention requires coordinated actions at national and global levels to improve recruitment, retention policies, and investments in the nursing work environment. The nursing work environment, defined as the "organizational characteristics of a work setting that facilitate or constrain professional nursing practice", is critical in influencing whether nurses decide to leave their jobs. This study investigates the impact of differentiated nursing practices - which involved tailoring roles and responsibilities based on nurses' training, skills, and experience in Dutch hospitals - and investigated their impact on the nursing work environment and turnover intention (i.

Computer-aided design and fabrication of statistically shaped nasal prostheses: A feasibility study.

Statement Of Problem: A nasal prosthesis may compensate for a partial or complete defect of the nose associated with trauma or amputation. However, the design and production is time-consuming, expensive, and expertize-dependent. Computer-generated prosthesis models and 3D printing can optimize the process.

An integrative and translational PKPD modelling approach to explore the combined effect of polymyxin B and minocycline against Klebsiella pneumoniae.

Objectives: To expand a translational pharmacokinetic-pharmacodynamic (PKPD) modelling approach for assessing the combined effect of polymyxin B and minocycline against Klebsiella pneumoniae.

Methods: A PKPD model developed based on in vitro static time-kill experiments of one strain (ARU613) was first translated to characterize that of a more susceptible strain (ARU705), and thereafter to dynamic time-kill experiments (both strains) and to a murine thigh infection model (ARU705 only). The PKPD model was updated stepwise using accumulated data.

Hypoxia Inducible Factor-dependent upregulation of Agrp in glomus type I cells of the carotid body.

Agouti-related peptide (AgRP) is a well-established potent orexigenic peptide primarily expressed in hypothalamic neurons. Nevertheless, the expression and functional significance of extrahypothalamic AgRP remain poorly understood. In this study, utilizing histological and molecular biology techniques, we have identified a significant expression of Agrp mRNA and AgRP peptide production in glomus type I cells within the mouse carotid body (CB).

Addressing Financial Toxicity From a Global Perspective: How to Advance Shared-Learning to Facilitate Change?

Financial Toxicity is a global issue requiring international efforts, but importantly, where to next?

Unlocking the multidimensionality of plantar pressure measurements for the evaluation of footwear in people with diabetes.

The offloading effectiveness of custom-made footwear for people with diabetes is assessed using plantar pressure measurements. While such pressure data is multidimensional, it is mostly analyzed using a scalar - maximum peak plantar pressure (PMax). We aimed to investigate the associations between multiple peak plantar pressure parameters for footwear assessment and determine whether this assessment depends on the chosen parameter.

Maternal pre- and postnatal stress and maternal and infant gut microbiota features.

Background: Maternal stress can have short and long term adverse (mental) health effects for the mother and her child. Previous evidence suggests that the gut microbiota may be a potential mediator and moderator for the effects of stress via various pathways. This study explored the maternal microbiota trajectory during pregnancy as well as the association between pre- and postnatal maternal stress and features of the maternal and infant gut microbiota during and after pregnancy.

The maternal body mass index and first-trimester placental (vascular) development.

Background: Maternal obesity is associated with maternal complications, including hypertensive disorders of pregnancy (HDP), and related fetal complications, such as fetal growth restriction. During pregnancy, the placenta is one of the key regulators of embryonic and fetal growth. Previous studies mainly investigated placental growth by measuring postpartum placental weight.