Genetic Tools in Rodents to Study Cannabinoid Functions.

During the past 30 years, the endocannabinoid system (ECS) has emerged as a major signalling system in the mammalian brain regulating neurotransmission in numerous brain regions and in various cell populations. Endocannabinoids are able to regulate specific physiological functions and thus modify their behavioural manifestations and allostatic alterations of the ECS linked to different pathological conditions. As discussed in detail in other chapters of this book, endocannabinoids are involved in learning and memory, stress, and anxiety, feeding, energy balance, development, and ageing.

GWAS highlights the neuronal contribution to multiple sclerosis susceptibility.

Multiple Sclerosis (MS) is a chronic inflammatory and neurodegenerative disease affecting the brain and spinal cord. Genetic studies have identified many risk loci, that were thought to primarily impact immune cells and microglia. Here, we performed a multi-ancestry genome-wide association study with 20,831 MS and 729,220 control participants, identifying 236 susceptibility variants outside the Major Histocompatibility Complex, including four novel loci.

Demoralization's link to depression and anxiety symptoms: A network analysis.

Demoralization represents a clinical syndrome conceptualized as maladaptive coping to a stressor associated with discouragement, feelings of hopelessness, helplessness, and a loss of meaning in life. It is a prevalent comorbidity in individuals with severe physical illnesses and affects a substantial proportion of the general population when facing global stressors like the COVID-19 pandemic. The main aim of the study was to test whether demoralization and features of depression and anxiety might reflect distinct entities within the general population, specifically in older adults, and to explore symptom interconnections, using a network psychometrics approach.

Effect of protein corona on drug release behavior of PLGA nanoparticles.

Poly(lactic-co-glycolide) (PLGA) nanoparticles are highly attractive for drug delivery due to their biocompatibility, biodegradability, and potential for controlled release and targeting. Despite these outstanding properties, challenges remain for clinical translation as nanomedicines. One significant factor to address is highlighting the protein corona structure and its effect on the drug release behavior.

MirGeneDB 3.0: improved taxonomic sampling, uniform nomenclature of novel conserved microRNA families and updated covariance models.

We present a major update of MirGeneDB (3.0), the manually curated animal microRNA gene database. Beyond moving to a new server and the creation of a computational mirror, we have expanded the database with the addition of 33 invertebrate species, including representatives of 5 previously unsampled phyla, and 6 mammal species.

Mental health symptoms and burdens after a SARS-CoV-2 infection.

Background: Previous studies have found adverse effects on mental health following infection with SARS-CoV-2. This study investigates whether mental health is also impaired in unknowingly infected individuals. In addition, the relevance of the severity of the infection and the time since the onset of infection were analyzed.

Integrating carotid doppler, grey scale ultrasound, and aortic oscillometry to evaluate macroangiopathy in myositides: the MYOCARD cohort.

Objectives: To evaluate the combination of novel colour Doppler ultrasound (CDUS), greyscale ultrasound (GSUS), and oscillometric indices of macroangiopathy in patients with idiopathic inflammatory myopathies (IIM). Second, to explore the associations between these imaging markers and both patient-related and disease-related characteristics, as well as traditional cardiovascular (CV) risk factors.

Methods: We conducted CDUS to evaluate arterial compliance markers, specifically the resistance (RI) and pulsatility (PI) indices, both in the common (CCA) and internal carotid arteries (ICA) of patients with IIM and healthy controls.

Understanding European patterns of deprescribing antithrombotic medication during end-of-life care in patients with cancer.

Background: Even though antithrombotic therapy (ATT) probably has little or even negative effect on the well-being of patients with cancer near the end of life, it is often continued until death, possibly leading to excess bleeding complications, increased disease burden, reduced quality of life and higher healthcare costs.

Aim: To explore and describe European practice patterns and perspectives of healthcare professionals from different disciplines and specialties on ATT in the end-of-life care (EOLC) of patients with cancer.

Methods: We performed a two-week international cross-sectional survey study using flash-mob research methodology.

Intra-individual Differences in Pericoronary Fat Attenuation Index Measurements Between Photon-counting and Energy-integrating Detector Computed Tomography.

Rationale And Objectives: The purpose of this study was to explore intra-individual differences in pericoronary adipose tissue (PCAT) fat attenuation index (FAI) between photon-counting detector (PCD)- and energy-integrating detector (EID)-CT.

Material And Methods: Patients were prospectively enrolled for a PCD-CT research scan within 30 days of EID-CT. Both acquisitions were reconstructed using a Qr36 kernel at 0.

Nanoscale imaging and control of altermagnetism in MnTe.

Nanoscale detection and control of the magnetic order underpins a spectrum of condensed-matter research and device functionalities involving magnetism. The key principle involved is the breaking of time-reversal symmetry, which in ferromagnets is generated by an internal magnetization. However, the presence of a net magnetization limits device scalability and compatibility with phases, such as superconductors and topological insulators.

Neutralizing GDF-15 can overcome anti-PD-1 and anti-PD-L1 resistance in solid tumours.

Cancer immunotherapies with antibodies blocking immune checkpoint molecules are clinically active across multiple cancer entities and have markedly improved cancer treatment. Yet, response rates are still limited, and tumour progression commonly occurs. Soluble and cell-bound factors in the tumour microenvironment negatively affect cancer immunity.

Simple and versatile electrochemical synthesis of highly substituted 2,1-benzisoxazoles.

A sustainable, general and scalable electrochemical protocol for direct access to 3-(acylamidoalkyl)-2,1-benzisoxazoles by cathodic reduction of widely accessible nitro arenes is established. The method is characterised by a simple undivided set-up under constant current conditions, inexpensive and reusable carbon-based electrodes, and environmentally benign reaction conditions. The versatility of the developed protocol is demonstrated on 39 highly diverse examples with up to 81% yield.

Noise causes cardiovascular disease: it's time to act.

Background: Chronic transportation noise is an environmental stressor affecting a substantial portion of the population. The World Health Organization (WHO) and various studies have established associations between transportation noise and cardiovascular disease (CVD), such as myocardial infarction, stroke, heart failure, and arrhythmia. The WHO Environmental Noise Guidelines and recent reviews confirm a heightened risk of cardiovascular incidents with increasing transportation noise levels.

Modelling individual variation in human walking gait across populations and walking conditions via gait recognition.

Human walking gait is a personal story written by the body, a tool for understanding biological identity in healthcare and security. Gait analysis methods traditionally diverged between these domains but are now merging their complementary strengths to unlock new possibilities. Using large ground reaction force (GRF) datasets for gait recognition is a way to uncover subtle variations that define individual gait patterns.

Biomechanically induced regulation of Damage-Regulated Autophagy Modulator 1 in periodontal cells and tissues.

Purpose: Autophagy is an important adaptive process for mechanotransduction, in which Damage-Regulated Autophagy Modulator 1 (DRAM1) has a key function in cell fate determination. This study aimed to analyze the influence of biomechanical loading on DRAM1 expression in periodontal cells and tissues.

Methods: Human periodontal ligament (PDL) fibroblasts were stimulated with different pressure protocols, physiological load and overload, in the presence and absence of autophagy inhibitor 3-methyladenine (3-MA) and compared with untreated cells.

Pod5Viewer: a GUI for inspecting raw nanopore sequencing data.

Motivation: Oxford Nanopore Technologies recently adopted the POD5 file format for storing raw nanopore sequencing data. The information stored in these files provides detailed insights into the sequencing features and enhances the understanding of raw nanopore data. However, the process of visualizing the data can be cumbersome, especially for users without programming skills.

Electrochemical Dehydrogenative sp-Coupling Reaction of Naphthols Accessing a Polycyclic Naphthalenone Motif.

A novel polycyclic naphthalenone motif was obtained by electrochemical synthesis starting from naphthols. The process is solvent controlled, and the highly diastereoselective cyclization is due to a solvent cage. The direct, anodic dehydrogenative sp-coupling was carried out by flow electrolysis.

Enzymatic Reaction Network-Driven Polymerization-Induced Transient Coacervation.

A living cell has a highly complex microenvironment whereas numerous enzyme-driven processes are active at once. These procedures are incredibly accurate and efficient, although comparable control has not yet been established in vitro. Here, we design an enzymatic reaction network (ERN) that combines antagonistic and orthogonal enzymatic networks to produce adjustable dynamics of ATP-fueled transient coacervation.

Acute resistance to BET inhibitors remodels compensatory transcriptional programs via p300 coactivation.

Initial clinical trials with drugs targeting epigenetic modulators - such as bromodomain and extraterminal protein (BET) inhibitors - demonstrate modest results in acute myeloid leukemia (AML). A major reason for this involves an increased transcriptional plasticity within AML, which allows cells to escape the therapeutic pressure. In this study, we investigated immediate epigenetic and transcriptional responses following BET inhibition and could demonstrate that BET inhibitor-mediated release of BRD4 from chromatin is accompanied by an acute compensatory feedback that attenuates down-regulation, or even increases expression, of specific transcriptional modules.

Information needed for optimal immunization related to medical advice: an observational prospective cohort study protocol (INFORMed).

Introduction: Today, accessing information on health issues is easier than ever. However, the flood of information can make decision-making difficult. Information can influence the intention for an action, yet the action often remains unpredictable.

Which Measure of Stone Burden is the Best Predictor of Interventional Outcomes in Urolithiasis: A Systematic Review and Meta-analysis by the YAU Urolithiasis Working Group and EAU Urolithiasis Guidelines Panel.

Background And Objective: Stone size has traditionally been measured in one dimension. This is reflected in most of the literature and in the EAU guidelines. However, recent studies have shown that multidimensional measures provide better prediction of outcomes.

Protein-Specific Crowding Accelerates Aging in Protein Condensates.

Macromolecular crowding agents, such as poly(ethylene glycol) (PEG), are often used to mimic cellular cytoplasm in protein assembly studies. Despite the perception that crowding agents have an inert nature, we demonstrate and quantitatively explore the diverse effects of PEG on the phase separation and maturation of protein condensates. We use two model proteins, the FG domain of Nup98 and bovine serum albumin (BSA), which represent an intrinsically disordered protein and a protein with a well-established secondary structure, respectively.