Predicting benefit from PARP inhibitors using deep learning on H&E-stained ovarian cancer slides.

Purpose: Ovarian cancer patients with a Homologous Recombination Deficiency (HRD) often benefit from polyadenosine diphosphate-ribose polymerase (PARP) inhibitor maintenance therapy after response to platinum-based chemotherapy. HR status is currently analyzed via complex molecular tests. Predicting benefit from PARP inhibitors directly on histological whole slide images (WSIs) could be a fast and cheap alternative.

Bioanalysis of protein-unbound prednisolone in serum using equilibrium dialysis followed by liquid chromatography-tandem mass spectrometry.

Introduction: High-dose systemic prednisolone is the cornerstone treatment of many autoimmune- and inflammatory diseases. Since prednisolone shows non-linear protein binding at higher serum concentrations, quantification of the unbound prednisolone concentration is important to understand prednisolone pharmacokinetics. We developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay to quantify protein-unbound prednisolone in serum.

Societal spirits in the silver streak: Unraveling complexity in drinking habits of the mature adult population.

Background: The complex interactions between an individual's drinking behavior and their social environment is crucial but understudied, particularly in mature adult populations. Our aim is to unravel these complexities by investigating how personal drinking patterns are related to those of one's social environment over time, and what the interplay is with personal factors such as occupational prestige and smoking behavior.

Method: The present study adopts an innovative graphical autoregressive (GVAR) panel network modeling approach to investigate the dynamics between personal drinking habits and social environmental factors, utilizing a comprehensive longitudinal dataset from the Framingham Heart Study with a large sample of predominantly mature adults (N = 1719-5718) connected within a social network.

Managing Friends and Foes: Sanctioning Mutualists in Mixed-Infection Nodules Trades off With Defense Against Antagonists.

Successful plant growth requires plants to minimize harm from antagonists and maximize benefit from mutualists. However, these outcomes may be difficult to achieve simultaneously, since plant defenses activated in response to antagonists can compromise mutualism function, and plant resources allocated to defense may trade off with resources allocated to managing mutualists. Here, we investigate how antagonist attack affects plant ability to manage mutualists with sanctions, in which a plant rewards cooperative mutualists and/or punishes uncooperative mutualists.

Longevity of antibody responses is associated with distinct antigen-specific B cell subsets early after infection.

Introduction: Upon infection, T cell-driven B cell responses in GC reactions induce memory B cells and antibody-secreting cells that secrete protective antibodies. How formation of specifically long-lived plasma cells is regulated via the interplay between specific B and CD4+ T cells is not well understood. Generally, antibody levels decline over time after clearance of the primary infection.

The Role of Coronary Computed Tomography Angiography in the Diagnosis, Risk Stratification, and Management of Patients with Diabetes and Chest Pain.

Coronary artery disease (CAD) affects over 200 million individuals globally, accounting for approximately 9 million deaths annually. Patients living with diabetes mellitus exhibit an up to fourfold increased risk of developing CAD compared to individuals without diabetes. Furthermore, CAD is responsible for 40 to 80 percent of the observed mortality rates among patients with type 2 diabetes.

The Rey Auditory Verbal Learning Test: adaptation into Russian and a new digital "RAVLT World".

The Rey Auditory Verbal Learning Test (RAVLT) is a classic test used to assess episodic verbal memory in research and clinical practice. We aimed to adapt the RAVLT materials into Russian, provide performance norms across the adult lifespan for the Russian adaptation, and develop a mobile application for automated RAVLT administration across languages. We created three psycholinguistically matched alternative versions of the RAVLT materials in Russian and incorporated them into a new tablet application.

Incidence and Outcomes of Patients With Mismatch Repair Deficient Rectal Cancer Operated in 2016: A Nationwide Cohort From The Netherlands.

Introduction: Data regarding the incidence and outcomes of mismatch repair deficient (dMMR) rectal cancer is limited. This study characterizes dMMR rectal cancer patients, comparing response after neoadjuvant radiotherapy and oncological outcomes to mismatch repair proficient (pMMR) rectal cancer patients.

Method: A retrospective cross-sectional cohort study was conducted in 67 Dutch centers.

Motivations for obtaining advance provision of medication abortion in the United States: a qualitative study.

Background: Advance provision of medication abortion, or the prescription of mifepristone and misoprostol before pregnancy occurs, is an unexplored care model aimed at expanding abortion access. We examine motivations for obtaining advance provision from the online telemedicine service, Aid Access, which supports people in the United States.

Methods: Between May and November 2023, we conducted semi-structured, in-depth interviews with 39 people who obtained advance provision between January 2022 and April 2023.

Impaired coagulation parameters in early RA are restored by effective antirheumatic therapy: a prospective pilot study.

Objectives: To assess the effect of treatment on haemostatic parameters in patients with early rheumatoid arthritis (RA).

Methods: Patients with newly diagnosed RA started methotrexate and were randomised to additional conventional treatment, certolizumab pegol, abatacept or tocilizumab. Several biomarkers for haemostasis were analysed including parameters of the two global haemostatic assays-overall haemostatic potential (OHP) and endogenous thrombin potential (ETP), as well as single haemostatic factors-fibrinogen, prothrombin fragment 1+2 (F1+2), D-dimer, thrombin activatable fibrinolysis inhibitor (TAFI) and clot lysis time (CLT) in 24 patients at baseline, 12 and 24 weeks after the start of the treatment.

Clonazepam repurposing in patients through conventional RCT and N-of-1 trials: an experimental strategy for orphan disease development.

Background: Clinical trials for rare disorders have unique challenges due to low prevalence, patient phenotype variability and high expectations. These challenges are highlighted by our study on clonazepam in patients, a common cause of intellectual disability. Previous studies on Arid1b-haploinsufficient mice showed positive effects of clonazepam on various cognitive aspects.

Characterization of thyroid hormone transport in a human choroid plexus papilloma cell line (HIBCPP) as an in vitro blood-cerebrospinal fluid barrier model.

Adequate levels of thyroid hormones (THs) in the fetal brain are vital for early neurodevelopment. Most of TH in fetal brain is derived from circulating thyroxine (T4), which gets locally converted into the biologically active triiodothyronine (T3) by deiodinase enzymes. One of the major routes of TH into the brain is through the blood-cerebrospinal fluid barrier (BCSFB).

More Than the Sum of Its Parts: Disrupted Core Periphery of Multiplex Brain Networks in Multiple Sclerosis.

Disruptions to brain networks, measured using structural (sMRI), diffusion (dMRI), or functional (fMRI) MRI, have been shown in people with multiple sclerosis (PwMS), highlighting the relevance of regions in the core of the connectome but yielding mixed results depending on the studied connectivity domain. Using a multilayer network approach, we integrated these three modalities to portray an enriched representation of the brain's core-periphery organization and explore its alterations in PwMS. In this retrospective cross-sectional study, we selected PwMS and healthy controls with complete multimodal brain MRI acquisitions from 13 European centers within the MAGNIMS network.

A Multinational Comparison Study of the Patient-Reported Outcomes Measurement Information System Anxiety, Depression, and Anger Item Bank in the General Population.

Objectives: This study aimed to compared Patient-Reported Outcomes Measurement Information System (PROMIS) anxiety, depression, and anger item bank among Korean, US and Dutch general population.

Methods: Between December 2021 and January 2022, we surveyed representative Korean participants (N = 2699). Then we compared the mean T-scores of PROMIS anxiety, depression, and anger full items bank among Korean, US (N = 1696) and the Dutch (N = 1002) populations.

Healthcare providers intentions to use an electronic personal health record for undocumented migrants: A qualitative exploration study in The Netherlands.

Electronic Personal Health Records (EPHRs) are potentially effective tools for improving the continuity and quality of care for migrants and refugees, and specifically for undocumented migrants (UDMs). However, little is known about the intention and preconditions of healthcare providers (HCPs) to use an EPHR for UDM in the Netherlands. Between April 2023 and June 2023, thirteen interviews, using a semi-structured topic guide, were conducted with Dutch HCPs.

Exploring the dynamics of T-cell responses: a combined approach using EdU incorporation and proliferation dye dilution assay.

Understanding antigen-specific T-cell responses is crucial for advancing immunotherapies and vaccine development. This study proposes a novel approach combining two complementary assays: the 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay (tracking proliferation over 0-48 h) and the VPD450 dye dilution assay (tracking proliferation over 4-6 days). Integrating these techniques provides additional insights into T-cell proliferation kinetics.

The performance of a lateral flow SARS-CoV-2 antibody assay and semi-autonomous SARS-CoV-2 antisense and sense RNA fluorescence in situ hybridization assay in a prospective cohort pilot study within a Dutch military population.

At the beginning of the COVID-19 pandemic, diagnostic testing was not accessible for mildly ill or asymptomatic individuals. Military operational circumstances exclude the usage of reference laboratory tests. For that reason, at the beginning of the pandemic alternative test methods were needed in order to gain insight into the SARS-CoV-2 status of military personnel.

Biologically plausible gated recurrent neural networks for working memory and learning-to-learn.

The acquisition of knowledge and skills does not occur in isolation but learning experiences amalgamate within and across domains. The process through which learning can accelerate over time is referred to as learning-to-learn or meta-learning. While meta-learning can be implemented in recurrent neural networks, these networks tend to be trained with architectures that are not easily interpretable or mappable to the brain and with learning rules that are biologically implausible.

Barriers and facilitators to implementing six monthly multi-month dispensing of antiretroviral therapy in two urban HIV clinics during the COVID-19 Era in Malawi.

Following the COVID-19 pandemic, the Malawi Government released a policy that promoted the scale-up of six-monthly multi-month dispensing (6-MMD) of antiretroviral therapy (ART) to people living with HIV in order to decrease congestion at health facilities and transmission of COVID-19. We evaluated the barriers and facilitators to implementing the scale-up of 6-MMD.We conducted a cross-sectional study and collected quantitative and qualitative data from 13 January 2022 to 5 February 2022 at two high-volume primary health facilities in urban Blantyre, Malawi.

Facilitators and barriers for the implementation of a transmural fall-prevention care pathway for older adults in the emergency department.

Background: Older adults at the emergency department (ED) with fall-related injuries are at risk of repeated falls. National guidelines state that the ED is responsible for initiating fall preventive care. A transmural fall-prevention care pathway (TFCP) at the ED can guide patients to tailored interventions.

Deciphering the role of the MALT1-RC3H1 axis in regulating GPX4 protein stability.

Ferroptosis, a unique form of iron-dependent cell death triggered by lipid peroxidation accumulation, holds great promise for cancer therapy. Despite the crucial role of GPX4 in regulating ferroptosis, our understanding of GPX4 protein regulation remains limited. Through FACS-based genome-wide CRISPR screening, we identified MALT1 as a regulator of GPX4 protein.

HIV prevention and missed opportunities among people with recently acquired HIV infection: Α protocol for a systematic review.

Background: Individuals who have recently acquired HIV represent a unique population because the time frame since HIV acquisition is relatively short and identification of missed HIV prevention opportunities is, therefore, closer to real time and less subject to recall bias. Identifying prevention measures used and missed opportunities for using them, can help stop further HIV transmission.

Objectives: This systematic review aims to synthesise current global evidence on uptake of HIV prevention methods among people with recently acquired HIV from 2007, the year that the concept of ART as a prevention method was first introduced.