A Drug-Drug Interaction Study of Mobocertinib and Midazolam, a Cytochrome P450 3A Substrate, in Patients With Advanced Non-Small Cell Lung Cancer.

Mobocertinib is a kinase inhibitor designed to selectively target epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations in non-small cell lung cancer. This drug-drug interaction study assessed the effect of multiple-dose administration of mobocertinib on the pharmacokinetics (PK) of midazolam, a sensitive cytochrome P450 3A substrate. Patients with locally advanced or metastatic non-small cell lung cancer refractory/intolerant to standard available therapy were enrolled.

The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study.

Purpose: To assess the association between neoadjuvant therapy and overall survival (OS) in patients with left-sided resectable pancreatic cancer (RPC) compared to upfront surgery.

Background: Left-sided pancreatic cancer is associated with worse OS compared to right-sided pancreatic cancer. Although neoadjuvant therapy is currently seen as not effective in patients with RPC, current randomized trials included mostly patients with right-sided RPC.

Investigating socioeconomic disparities in prescribing new diabetes medications in individuals with type 2 diabetes and very high cardiovascular risk in the Netherlands.

Aims: This study aims to analyze prescription patterns of new diabetes medication and assess socioeconomic disparities in their initiation among individuals with T2DM with very high cardiovascular risk.

Methods: Individuals diagnosed with T2DM and very high cardiovascular risk were identified (N = 10,768) based on general practitioner's electronic health record data. SGLT-2is and GLP-1RAs prescription patterns were examined.

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.

FAIR Data Cube, a FAIR data infrastructure for integrated multi-omics data analysis.

Motivation: We are witnessing an enormous growth in the amount of molecular profiling (-omics) data. The integration of multi-omics data is challenging. Moreover, human multi-omics data may be privacy-sensitive and can be misused to de-anonymize and (re-)identify individuals.

Multiple Sclerosis: Glial Cell Diversity in Time and Space.

Multiple sclerosis (MS) is the most prevalent human inflammatory disease of the central nervous system with demyelination and glial scar formation as pathological hallmarks. Glial cells are key drivers of lesion progression in MS with roles in both tissue damage and repair depending on the surrounding microenvironment and the functional state of the individual glial subtype. In this review, we describe recent developments in the context of glial cell diversity in MS summarizing key findings with respect to pathological and maladaptive functions related to disease-associated glial subtypes.

WDR49-Positive Astrocytes Mark Severity of Neurodegeneration in Frontotemporal Lobar Degeneration and Alzheimer's Disease.

A subpopulation of astrocytes expressing WD Repeat Domain 49 (WDR49) was recently identified in frontotemporal lobar degeneration (FTLD) with GRN pathogenic variants. This is the first study to investigate their expression and relation to pathology in other FTLD subtypes and Alzheimer's disease (AD). In a postmortem cohort of TDP-43 proteinopathies (12 GRN, 11 C9orf72, 9 sporadic TDP-43), tauopathies (13 MAPT, 8 sporadic tau), 10 AD, and four controls, immunohistochemistry and immunofluorescence were performed for WDR49 and pathological inclusions on frontal, temporal, and occipital cortical sections.

Abatacept use for 24 weeks has a limited effect on salivary gland inflammation in Sjögren's disease patients.

Objectives: This study aimed to assess (1) effects of abatacept on salivary gland histology of Sjögren's disease (SjD) patients, (2) the predictive value of salivary gland histopathological characteristics at baseline for clinical response to abatacept treatment.

Methods: Patients (n=41) who participated in the Dutch ASAP-II and ASAP-III trials and international abatacept trial (IM101603) from whom a labial (n=13) or parotid (n=28) salivary gland biopsy was obtained at baseline and after 24 weeks of treatment with abatacept were included. Biopsies were analysed for SjD related histopathological features before and after abatacept (n=25) or placebo (n=16) treatment.

Magnetic control of soft microrobots near step-out frequency: Characterization and analysis.

Magnetically actuated soft microrobots hold promise for biomedical applications that necessitate precise control and adaptability in complex environments. These microrobots can be accurately steered below their step-out frequencies where they exhibit synchronized motion with external magnetic fields. However, the step-out frequencies of soft microrobots have not been investigated yet, as opposed to their rigid counterparts.

Run-in periods and treatment outcomes in asthma trials: A narrative review.

Background: The run-in period is an important element of randomized controlled trials, and is often used in respiratory disease trials. The design of the run-in period can greatly impact results and data interpretation, and as such should be designed carefully.

Methods: In this review, we describe the design of run-in periods across six phase 3A trials of triple therapy in asthma, and discuss how differences in run-in period design (specifically the duration, treatment, and reporting of run-in results) may have the potential to alter the interpretation of study outcomes.

Identifying Behaviours Representative of Agentic Engagement in Pre-clinical Medical Education PBL Groups Based on Literature and Observations.

Introduction: In this study we aimed to identify behaviours representative of agentic engagement in pre-clinical medical education problem-based learning (PBL) groups. Agentic engagement is defined as the proactive, intentional contributions students make to their flow of instruction. This concept, developed in secondary education, appears relevant for benefitting optimally from PBL in higher medical education.

International consensus statement on microbiome testing in clinical practice.

There is growing interest in the potential exploitation of the gut microbiome as a diagnostic tool in medicine, but evidence supporting its clinical usefulness is scarce. An increasing number of commercial providers offer direct-to-consumer microbiome diagnostic tests without any consensus on their regulation or any proven value in clinical practice, which could result in considerable waste of individual and health-care resources and potential drawbacks in the clinical management of patients. We convened an international multidisciplinary expert panel to standardise best practices of microbiome testing for clinical implementation, including recommendations on general principles and minimum requirements for their provision, indications, pre-testing protocols, method of analyses, reporting of results, and potential clinical value.

Comparing mechanical and enzymatic isolation procedures to isolate adipose-derived stromal vascular fraction: A systematic review.

The stromal vascular fraction of adipose tissue has gained popularity as regenerative therapy for tissue repair. Both enzymatic and mechanical intraoperative SVF isolation procedures exist. To date, the quest for the preferred isolation procedure persists, due to the absence of standardised yield measurements and a defined clinical threshold.

Bacterial killing and the dimensions of bacterial death.

Bacteria can be dead, alive, or exhibit slowed or suspended life forms, making bacterial death difficult to establish. Here, agar-plating, microscopic-counting, SYTO9/propidium-iodide staining, MTT-conversion, and bioluminescence-imaging were used to determine bacterial death upon exposure to different conditions. Rank correlations between pairs of assay outcomes were low, indicating different assays measure different aspects of bacterial death.

Harnessing cellular therapeutics for type 1 diabetes mellitus: progress, challenges, and the road ahead.

Type 1 diabetes mellitus (T1DM) is a growing global health concern that affects approximately 8.5 million individuals worldwide. T1DM is characterized by an autoimmune destruction of pancreatic β cells, leading to a disruption in glucose homeostasis.

Comparative Analysis of Digestion Methods for Bile Proteomics: The Key to Unlocking Biliary Biomarker Potential.

Background: Bile's potential to reflect the health of the biliary system has led to increased attention, with proteomic analysis offering deeper understanding of biliary diseases and potential biomarkers. With the emergence of normothermic machine perfusion (NMP), bile can be easily collected and analyzed. However, the composition of bile can make the application of proteomics challenging.