Excitatory-inhibitory homeostasis and bifurcation control in the Wilson-Cowan model of cortical dynamics.

Although the primary function of excitatory-inhibitory (E-I) homeostasis is the maintenance of mean firing rates, the conjugation of multiple homeostatic mechanisms is thought to be pivotal to ensuring edge-of-bifurcation dynamics in cortical circuits. However, computational studies on E-I homeostasis have focused solely on the plasticity of inhibition, neglecting the impact of different modes of E-I homeostasis on cortical dynamics. Therefore, we investigate how the diverse mechanisms of E-I homeostasis employed by cortical networks shape oscillations and edge-of-bifurcation dynamics.

SUMO-mediated regulation of H3K4me3 reader SET-26 controls germline development in C. elegans.

Sumoylation is a posttranslational modification essential for multiple cellular functions in eukaryotes. ULP-2 is a conserved SUMO protease required for embryonic development in Caenorhabditis elegans. Here, we revealed that ULP-2 controls germline development by regulating the PHD-SET domain protein, SET-26.

ETL: From the German Health Data Lab data formats to the OMOP Common Data Model.

Objective: The German Health Data Lab is going to provide access to German statutory health insurance claims data ranging from 2009 to the present for research purposes. Due to evolving data formats within the German Health Data Lab, there is a need to standardize this data into a Common Data Model to facilitate collaborative health research and minimize the need for researchers to adapt to multiple data formats. For this purpose we selected transforming the data to the Observational Medical Outcomes Partnership Common Data Model.

Barriers and missed opportunities in PrEP uptake, use and care among men who have sex with men with recent HIV infection in the Netherlands.

Introduction: Oral pre-exposure prophylaxis (PrEP) prevents Human Immunodeficiency Virus (HIV) acquisition. In the Netherlands, PrEP is accessible through the national PrEP program (NPP) or general practitioners (GP). Still, some men who have sex with men (MSM) entering HIV care indicated having PrEP experience prior to diagnosis.

Unveiling endothelial cell border heterogeneity: VE-cadherin adherens junction stratification by deep convolutional neural networks.

Background: Systemic diseases are often associated with endothelial cell (EC) dysfunction. A key function of ECs is to maintain the barrier between the blood and the interstitial space. The integrity of the endothelial cell barrier is maintained by VE-Cadherin homophilic interactions between adjacent cells.

The influence of cognitive reserve on ERP measures of selective visual attentional processing in older adults after mild traumatic brain injury.

Objective: Older adults have an increased risk of developing persistent cognitive complaints after mild traumatic brain injury (mTBI). Yet, studies exploring which factors protect older adults with mTBI from developing such complaints are rare. It has been suggested that one such factor may be cognitive reserve (CR), but it is unknown how CR influences cognition in this patient category.

Cost-effectiveness of the SMILE intervention compared with usual care for people with severe mental illness: A randomized clinical trial.

Objectives: Only studying effectiveness of lifestyle interventions for people with severe mental illness (SMI) is insufficient for policy making. As budgets for healthcare are limited, policy makers face the problem of allocating scarce healthcare resources. Cost-effectiveness studies are needed, but currently cost-effectiveness studies of lifestyle interventions for people with SMI delivered in ambulatory care are limited.

ToF-SIMS Parallel Imaging MS/MS of Lead Soaps in Embedded Paint Cross Sections.

In the field of cultural heritage, and more specifically in oil paintings, the ability to unambiguously identify and locate metal soaps is of great interest for a better understanding of painting degradation. Here, we demonstrate the use of a Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) instrument capable of tandem mass spectrometry imaging for the unambiguous identification and localization of lead soaps in cross sections of samples of old oil paintings at high spatial resolution. It is shown that the specific fragmentation pattern of lead soaps is dictated by the loss of the lead ion and that fragmentation occurs on the hydrocarbon chains of the fatty acids.

High-Resolution Free-Breathing Chemical-Shift-Encoded MRI for Characterizing Lymph Nodes in the Upper Abdomen.

Objectives: Accurate lymph node (LN) staging is crucial for managing upper abdominal cancers. Ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging effectively distinguishes healthy and metastatic LNs through fat/water and -weighted imaging. However, respiratory motion artifacts complicate detection of abdominal LNs.

Researching gender and loneliness differently.

The majority of research on loneliness considers gender by comparing the loneliness reported by men and women. Drawing on current conceptualizations of gender and its effects, we propose alternative ways in which gender should be examined in relation to loneliness. To do so, we consider multiple gender-related factors and the role of the social environment, particularly societal ideologies about what gender is and how it should be expressed.

Fragment-to-Lead Medicinal Chemistry Publications in 2023.

This Perspective summarizes successful fragment-to-lead (F2L) studies that were published in 2023 and is the ninth installment in an annual series. A tabulated summary of the relevant articles published in 2023 is provided (17 entries from 16 articles), and a comparison of the target classes, screening methods, and overall fragment or lead property trends for 2023 examples and for the combined entries over the years 2015-2023 is discussed. In addition, we identify several trends and innovations in the 2023 literature that promise to further increase the success of fragment-based drug discovery (FBDD), particularly in the areas of NMR and virtual screening, fragment library design, and fragment linking.

Oral Glucose-Lowering Agents vs Insulin for Gestational Diabetes: A Randomized Clinical Trial.

Importance: Metformin and glyburide monotherapy are used as alternatives to insulin in managing gestational diabetes. Whether a sequential strategy of these oral agents results in noninferior perinatal outcomes compared with insulin alone is unknown.

Objective: To test whether a treatment strategy of oral glucose-lowering agents is noninferior to insulin for prevention of large-for-gestational-age infants.

Association of radiation-induced normal tissue toxicity with a high genetic risk for rheumatoid arthritis.

Purpose: Overlapping genes are involved with rheumatoid arthritis (RA) and DNA repair pathways. Therefore, we hypothesised that patients with a high polygenic risk score (PRS) for RA will have an increased risk of radiotherapy (RT) toxicity given the involvement of DNA repair.

Methods: Primary analysis was performed on 1494 prostate cancer, 483 lung cancer and 1820 breast cancer patients assessed for development of RT toxicity in the REQUITE study.

Priority Clinical Actions for Outpatient Management of Nonhospitalized Traumatic Brain Injury.

Outpatient care following nonhospitalized traumatic brain injury (TBI) is variable, and often sparse. The National Academies of Sciences, Engineering, and Medicine's 2022 report on highlighted the need to improve the consistency and quality of TBI care in the community. In response, the present study aimed to identify existing evidence-based guidance and specific clinical actions over the days to months following nonhospitalized TBI that should be prioritized for implementation in primary care.

Search for surrogate markers to predict end stage kidney disease in long term lithium users.

Background: A surrogate marker (a substitute indicator of the true outcome) is needed to predict subgroups of long-term lithium users at risk of end-stage kidney disease (ESKD). In this narrative review the aim is to determine the optimal surrogate endpoint for ESKD in long-term lithium users in a scientific context. MAIN: In a literature search in long-term lithium users, no studies on surrogate measurements on ESKD were identified.

Evaluating hypothetical prevention strategies for internalizing symptoms in the general population and at-risk children.

Objective: Specific modifiable factors (e.g., screen time [ST], sleep duration, physical activity, or social connections) are targets for reducing depression risk in adults.

Cerebral amyloid angiopathy: one single entity?

Purpose Of Review: Cerebral amyloid angiopathy (CAA) is a common brain disorder among the elderly and individuals with Alzheimer's disease, where accumulation of amyloid-ß can lead to intracerebral hemorrhage and dementia. This review discusses recent developments in understanding the pathophysiology and phenotypes of CAA.

Recent Findings: CAA has a long preclinical phase starting decades before symptoms emerge.

Prolonged grief symptoms and lingering attachment predict approach behavior toward the deceased.

Following the death of a loved one, both approach behaviors related to the deceased (i.e., engagement with feelings, memories, and/or reminders of the deceased) and the avoidance of reminders of the death are theorized to precipitate severe and persistent grief reactions, termed prolonged grief.

Depletion of TP53 in Human Pluripotent Stem Cells Triggers Malignant-Like Behavior.

Human pluripotent stem cells (hPSCs) tend to acquire genetic aberrations upon culture in vitro. Common aberrations are mutations in the tumor suppressor TP53, suspected to confer a growth-advantage to the mutant cells. However, their full impact in the development of malignant features and safety of hPSCs for downstream applications is yet to be elucidated.