Nuclear Protein Aggregates Disrupt RNA Processing and Alter Biomechanics in a Muscle Cell Model of OPMD.

Aggregation of RNA-binding proteins (RBPs) is a hallmark of several age-related neuromuscular diseases. However, our understanding of how these aggregates drive dysfunction is often limited by the use of non-disease-relevant models. Oculopharyngeal muscular dystrophy (OPMD) is caused by a short alanine expansion mutation in the PABPN1 gene, which leads to nuclear aggregation of the protein.

Manipulating anthracyclines for deeper tissue penetration and implications for glycolytic tissues.

How drugs penetrate tissues is poorly understood yet important, since drugs that fail to reach their target will be ineffective. We followed the fate of anthracycline cancer drugs at high resolution by exploiting their intrinsic fluorescence. In a cell-based spheroid model, the soluble compound fluorescein penetrates the entire spheroid, unlike hydrophobic fluorescent lipids, which only enter the outermost cell layer.

Time-varying impact of established prognostic factors in resected pancreatic ductal adenocarcinoma.

Background: Prognostic factors in resected pancreatic ductal adenocarcinoma (PDAC) have been determined under the assumption that hazard ratios (HRs) remain static. However, PDAC is a dynamic disease with evolving conditional survival. The aim of this study was to determine if the impact of prognostic factors in PDAC is time-varying.

MRMAssayDB: a comprehensive integrated resource for targeted proteomics assays.

Introduction: Targeted quantitative proteomics is vital for accurate protein measurement in biological samples. Techniques like Multiple Reaction Monitoring (MRM or SRM) and Parallel Reaction Monitoring (PRM), often used with isotopically-labeled internal standards, provide absolute quantification and represent the current gold standard. However, developing and validating assays for individual proteins remains labor-intensive.

ENDOCOR: a nationwide consortium of endocarditis teams-initiating a registry for infective endocarditis within the Netherlands Heart Registration.

Background: Despite advancements in diagnostics and treatment strategies, infective endocarditis continues to carry a substantial morbidity and mortality risk. In addition, the field of infective endocarditis contains many gaps in evidence, as international guidelines are predominantly based on low-level evidence. To improve infective endocarditis care and survival rates in the Netherlands, adequate evaluation of diagnostics, treatment strategies and outcomes is essential.

Colistin resistance dynamics in under biofilm and planktonic growth.

is a major pathogen in chronic biofilm-associated lung infections, particularly in patients with cystic fibrosis. Colistin is commonly used to treat these infections, although there is little understanding of how resistance evolves when cells are grown within biofilms. The current study compared the phenotypic dynamics and genetic adaptations of colistin resistance between planktonic and biofilm-grown .

Streamlined Sample Cleanup: Small Molecule Fractionation and Extraction Via Low-Volume Polymer Monolithic Columns for In-Line Analysis.

Polymer monoliths are stationary-phase materials for liquid chromatography and solid-phase extraction. Their porous structure, tuneability and simple synthesis enable tailoring to specific analysis requirements in analytical chemistry. Typically, polymer monoliths are used to separate larger biomolecules.

Patterns and Influencing Factors in the Nurse-Patient Relationship in Hospitals' General Wards: An Integrative Review.

Background: The nurse-patient relationship is considered important in nursing theories and ethics. Yet, on general hospital wards, such relationships are often not achieved. Prior to addressing developing satisfactory nurse-patient relationships, it is essential to first understand the types of relationships that occur and the dynamics that shape them.

Cross-cultural adaptation and psychometric validation of the Indonesian version of the PTSD Checklist for DSM-5 (PCL-5) in a trauma-exposed sample of women.

The PTSD Checklist for DSM-5 (PCL-5) is the most widely used questionnaire to screen for symptoms of post-traumatic stress disorder (PTSD) in the literature and clinical contexts. This study aimed to: (1) perform a cross-cultural adaptation of PCL-5 to the Indonesian sociolinguistic context; (2) assess the psychometric validity and reliability of the adapted version; (3) examine the prevalence of PTSD in the sample using the diagnostic guidelines from DSM-5 and a cut-off score derived from empirical analysis; (4) evaluate PTSD factor structures using confirmatory factor analysis (CFA); and (5) investigate the convergent and discriminant validity of the adapted scale. The study focused on a sample of Indonesian women, including women who had experienced sexual assault, other types of trauma, or no traumatic exposure.

Do Child Gender Stereotypes Mediate Associations Between Human Fathers' Testosterone Levels and Paternal Involvement? Two Studies.

This preregistered study investigated whether human paternal testosterone levels predicted fathers' time spent with their child and their involvement in childcare and household tasks. Additionally, we examined whether associations were mediated by fathers' attitudes toward child gender stereotypes. Associations were tested in an exploratory sample (n = 70, M = 6.

Navigating Solute Carrier Transporters-A Comprehensive Review of Functionalized Small Molecule Probes for Target Identification and Characterization.

Solute carrier transporters (SLCs) are integral membrane proteins that play pivotal roles in maintaining cellular homeostasis by mediating the transport of a diverse range of substrates across cell membranes. With their involvement in fundamental physiological processes such as nutrient uptake, neurotransmitter signaling, and drug transport, SLCs have emerged as crucial players in health and disease. Dysregulation of SLC function has been implicated in a spectrum of disorders, including metabolic diseases, cancer, and neurological afflictions.

The Indo-European Cognate Relationships dataset.

The Indo-European Cognate Relationships (IE-CoR) dataset is an open-access relational dataset showing how related, inherited words ('cognates') pattern across 160 languages of the Indo-European family. IE-CoR is intended as a benchmark dataset for computational research into the evolution of the Indo-European languages. It is structured around 170 reference meanings in core lexicon, and contains 25731 lexeme entries, analysed into 4981 cognate sets.

Insulin Initiation in Type 2 Diabetes: Unraveling the Sociodemographic and Biological Dynamics using Routinely Collected Primary Care Data.

Background: Timely initiation of insulin is critical to prevent long-term complications associated with poor glycaemic control. A better understanding of the factors influencing insulin initiation is essential to guide person-centred treatment and reduce disparities. Aim To examine factors associated with insulin initiation within five years after starting metformin in adults with T2DM.

Tailoring for Health Literacy in the Design and Development of eHealth Interventions: Systematic Review.

Background: Tailoring is an important strategy to improve uptake and efficacy of medical information and guidance provided through eHealth interventions. Given the rapid expansion of eHealth, understanding the design rationale of such tailored interventions is vital for further development of and research into eHealth interventions aimed at improving health and healthy behavior.

Objective: This systematic review examines the use of health literacy concepts through tailoring strategies in digital health interventions (eHealth) aimed at improving health and how these elements inform the overall design rationale.

Older people's rehabilitation and recovery. Get up, stand up for geriatric rehabilitation.

Effective health care for older people depends on a network of interconnected services across a variety of different settings that are all well developed, organised and financed. Preventive care, long term care, palliative care, and acute care in both hospital and community settings all play important, mutually dependent roles. Rehabilitation is important for patients in each of these contexts-it can play a role in recovery after acute or subacute health problems such as a hip fracture, stroke and pneumonia.

The Environmental Impact of Cataract Surgery and Strategies for Mitigation: A Life Cycle Assessment in an Academic Hospital.

Purpose: The healthcare sector significantly contributes to environmental challenges. Cataract surgery, as one of the most frequently performed procedures worldwide, presents an opportunity to address these challenges. This study identifies the main environmental hotspots of cataract surgery and evaluates strategies to reduce its environmental impact.

Legitimacy of investigative forensic genetic genealogy under Art. 8 ECHR.

Investigative forensic genetic genealogy (iFGG) was successfully used in the United States to solve the Golden State Killer case in 2018 and in Sweden to solve the Linköping double-murder case in 2020. However, further use of iFGG in Sweden was temporarily suspended due to concerns about its legitimacy. This article evaluates the legitimacy of iFGG within what we name, the European Court of Human Rights' (ECtHR) four-fold privacy test: the preliminary interference test, the lawfulness test, the legitimate aim test, and the proportionality test.

genotypes differentially remodel the astrocytic lipid droplet-associated proteome to shape lipid droplet dynamics.

The lipids and proteins that comprise lipid droplets regulate several cellular functions including lipid storage, stress responses, and inflammation. Glial lipid droplets have been implicated in the pathogenesis and progression of Alzheimer's disease (AD), yet the mechanisms linking genetic risk to lipid droplet biology remain unclear. Here we examined how , the strongest genetic modulator of late-onset AD, impacts lipid droplet composition and dynamics.

Function focused care in hospital among nurses and patients from geriatric and neurology wards: A mixed method process evaluation.

Background: Function Focused Care is a promising approach stimulating physical activity of patients admitted to hospital. In studying the effectiveness, patients receiving Function Focused Care in Hospital were admitted 3.3 days shorter than patients receiving usual care.

In Search of Beautiful Molecules: A Perspective on Generative Modeling for Drug Design.

Generative modeling with artificial intelligence (GenAI) offers an emerging approach to discover novel, efficacious, and safe drugs by enabling the systematic exploration of chemical space and to design molecules that are synthesizable while also having desirable drug properties. However, despite rapid progress in other industries, GenAI has yet to demonstrate clear and consistent value in prospective drug discovery applications. In this Perspective, we argue that the ultimate goal of generative chemistry is not just to generate "new" or "interesting" molecules, but to generate "beautiful" molecules─those that are therapeutically aligned with the program objectives and bring value beyond traditional approaches.

Prevalence of germline pathogenic variants in 779 patients with metastatic prostate cancer.

Objective: To assess the prevalence of germline pathogenic variants (gPVs) in genes associated with female breast cancer in Dutch patients with metastatic prostate cancer (mPCa).

Patients And Methods: In this prospective multicentre cohort study (n = 15 centres), germline genetic testing of the genes BRCA1, BRCA2, ATM, CHEK2 and PALB2 was offered to patients with mPCa. We assessed the prevalence of gPVs and compared it to a reference population of 16 823 individuals who underwent genetic testing for non-oncological conditions.

Molecular mobility of extraterrestrial ices: surface diffusion in astrochemistry and planetary science.

Molecules are ubiquitous in space. They are necessary components in the creation of habitable planetary systems and can provide the basic building blocks of life. Solid-state processes are pivotal in the formation of molecules in space and surface diffusion in particular is a key driver of chemistry in extraterrestrial environments, such as the massive clouds in which stars and planets are formed and the icy objects within our solar system.