Small Molecule Modulators of β-arrestins.

Unlabelled: β-arrestins (βarrs) are key regulators of G protein-coupled receptors (GPCRs), essential for modulating signaling pathways and physiological processes. While current pharmacological strategies target GPCR orthosteric and allosteric sites, as well as G protein transducers, comparable tools for studying βarrs are lacking. Here, we present the discovery and characterization of novel small-molecule allosteric inhibitors of βarrs through comprehensive biophysical, biochemical, pharmacological, and structural analyses.

EXtending Omalizumab Treatment Intervals in patients with Chronic spontaneous urticaria (EXOTIC): protocol of a multicentre, randomised, open-label, non-inferiority trial.

Introduction: Omalizumab, an anti-IgE monoclonal antibody, is effective in treating antihistamine-refractory chronic spontaneous urticaria (CSU). However, tapering strategies for omalizumab are currently not well-studied, and patients may be treated longer than needed. Here, we present the rationale and design of the EXtending Omalizumab Treatment Intervals in patients with Chronic spontaneous urticaria trial, a multicentre, randomised, open-label, non-inferiority clinical trial.

Chronotherapy with Cinacalcet has a striking effect on inhibition of parathyroid gland proliferation in rats with secondary hyperparathyroidism.

Secondary hyperparathyroidism (sHPT) is a significant clinical complication of CKD leading to bone abnormalities and cardiovascular disease. Current treatment based on activating the parathyroid calcium-sensing receptor (CaSR) using calcimimetics such as Cinacalcet, aims to decrease plasma PTH levels and inhibit the progression of parathyroid hyperplasia. In the present study, we found significant diurnal rhythmicity of Casr, encoding the Cinacalcet drug target in hyperplastic parathyroid glands (p = 0.

Transthoracic Echocardiography for Central Venous Catheter Tip Positioning in Children: An Observational Study Using Transesophageal Echocardiography as Reference Method.

Background: Children who need to have major surgery or are critically ill often require the insertion of a central venous catheter (CVC). To avoid serious complications, it is important to correctly position the CVC tip at the junction of the distal superior vena cava and the right atrium (cavoatrial junction). Transthoracic echocardiography (TTE) can be used to confirm the correct position of the CVC tip.

Geographic variation of recorded neurodevelopmental disorders in children and adults.

Introduction: While diagnosis rates of autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD) vary within countries at a large-scale municipal level, small neighbourhood geographic variation remains understudied. In this nationwide study, we describe the rates of ASD and ADHD diagnoses in children and adults by geographical data zones of approximately 2,500 residents across Denmark.

Methods: We included a population of children born from 1993 through 2020 and an adult population born from 1977 through 2003.

Temporal and spatial variations of urinary phthalate metabolites for adults in China (2005-2020): A synthesis of biomonitoring data.

Chinese people are experiencing phthalate exposure risks. However, temporal and regional phthalate internal exposure variations amongst Chinese have not been established. To address this gap, we integrated our 69 adult participants' bio-monitored urinary phthalate metabolite (UPM) concentration data by high-performance liquid chromatography with mass spectrometry in Xi'an and Nanjing and the data from 35 literature (total sample size: 18768).

A new effLuc/Kate dual reporter allele for tumour imaging in mice.

Genetically engineered mouse models (GEMMs) are instrumental for modelling local and systemic features of complex diseases such as cancer. Non-invasive, longitudinal cell detection and monitoring in tumors, metastases and/or the micro-environment is paramount to achieve a better spatiotemporal understanding of cancer progression and to evaluate therapies in preclinical studies. Bioluminescent and fluorescent reporters marking tumor cells or their microenvironment are valuable for non-invasive cell detection and monitoring in vivo.

A sex-specific effect of M muscarinic cholinergic autoreceptor deletion on locomotor stimulation by cocaine and scopolamine.

Objective: Acetylcholine modulates the activity of the direct and indirect pathways within the striatum through interaction with muscarinic M and M receptors. M receptors are uniquely positioned to regulate plasticity within the direct pathway and play a substantial role in reward and addiction-related behaviors. However, the role of M receptors on cholinergic neurons has been less explored.

Evaluating general practitioners' focused lung ultrasound competence and findings in patients with suspected community-acquired pneumonia in general practice.

Objectives: To evaluate general practitioners' (GPs') ability to perform focused lung ultrasound (FLUS) following a training program and assess FLUS feasibility in general practice. Also, to describe FLUS findings and evaluate GPs' ability to interpret these in adults with acute lower respiratory tract infection (LRTI) when pneumonia is suspected and assess GPs' perception of FLUS impact.

Methods: Nine GPs, using point-of-care ultrasound, completed a FLUS training program.

Epidemiology of Lymphatic Filariasis Antigen and Microfilaria in Samoa, 2019: 7-9 Months Post Triple-Drug Mass Administration.

The elimination of lymphatic filariasis (LF) as a public health problem remains an ongoing challenge in the Pacific region. This study reports on antigen (Ag) and microfilaria (Mf) prevalence in Samoa in 2019, 7-9 months after the completion of the first round of triple-drug mass drug administration (MDA). It evaluates the effectiveness of the intervention for reducing Ag prevalence to below a 2% threshold, and how this differs between 5-9-year-olds and ≥10-year-olds.

YKL-40, cardiovascular events, and mortality in individuals recently diagnosed with type 2 diabetes: A Danish cohort study.

Aims: We investigated the association of the inflammatory biomarker YKL-40 with cardiovascular events (CVEs) and mortality in individuals with type 2 diabetes.

Methods: We followed 11,346 individuals recently diagnosed with type 2 diabetes for up to 14 years. Baseline YKL-40 levels (measured in 9,010 individuals) were grouped into percentiles (0-33 %, 34-66 %, 67-90 %, and 91-100 %) and analyzed continuously (per 1 SD log increment), with comparisons to CRP (measured in 9,644 individuals).

Healthcare professionals' experiences of the change to telephone consultations in cancer care during the COVID-19 pandemic: An explorative qualitative study.

Objective: During the COVID-19 pandemic, changes were made in cancer care including increased use of teleconsultations (TCs) and restrictions for relatives to attend in-person appointments at the outpatient clinics. This study aimed to provide in-depth information on healthcare professionals' experiences of TC and the limited access for relatives during the COVID-19 pandemic in 2020.

Methods: This qualitative study was conducted at an oncological department responsible for oncological care of all patients with cancer in one of five health regions in Denmark.

Modeling the fasting blood glucose response to basal insulin adjustment in type 2 diabetes: An explainable machine learning approach on real-world data.

Introduction: Optimal basal insulin titration for people with type 2 diabetes is vital to effectively reducing the risk of complications. However, a sizeable proportion of people (30-50 %) remain in suboptimal glycemic control six months post-initiation of basal insulin. This indicates a clear need for novel titration methods that account for individual patient variability in real-world settings.

Role of Steatosis in Preventing Post-hepatectomy Liver Failure After Major Resection: Findings From an Animal Study.

Background/aim: Post-hepatectomy liver failure (PHLF) and hepatic steatosis are evident shortly after extensive partial hepatectomy (PH) in rodents. This study aimed to extrapolate the protein expression and biological pathways involved in recovering PHLF (rPHLF) and non-recovering PHLF (nrPHLF).

Methods: Rats were randomly assigned to 90% PH or sham surgery.

Metastatic risk in clear cell renal cell carcinoma: a tool incorporating sex, size, and grade.

Objective: To identify predictors of metastases, estimate the proportion of metastatic clear cell renal cell carcinoma (ccRCC) cases according to these predictors, and subsequently create a risk table showing the absolute difference in metastasis proportion for each 10 mm increase in tumour size.

Patients And Methods: Patients diagnosed with histopathological confirmed ccRCC in 2010-2018 in Denmark identified in the nationwide Danish Multidisciplinary Renal Cancer Group (DaRenCa) Study-3. Association between diagnostic variables and metastases were assessed with logistic regression analyses.

The liver-brain axis in metabolic dysfunction-associated steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects around 30% of the global population. Studies suggest that MASLD is associated with compromised brain health and cognitive dysfunction, initiating a growing interest in exploring the liver-brain axis mechanistically within MASLD pathophysiology. With the prevalence of MASLD increasing at an alarming rate, leaving a large proportion of people potentially at risk, cognitive dysfunction in MASLD is a health challenge that requires careful consideration and awareness.

Impact of nighttime human behavior on exposure to malaria vectors and effectiveness of using long-lasting insecticidal nets in the Ethiopian lowlands and highlands.

Background: Ethiopia continues to grapple with a persistent malaria burden, characterized by ongoing transmission and recurrent outbreaks. Human behavior influences both malaria exposure and the effectiveness of vector interventions, complicating malaria control efforts. Implementing tailored strategies that account for the complex interplay between human activities and vector behavior remains a challenge in both high- and low-transmission areas in Ethiopia, particularly for vulnerable highland populations and temporary labor migrants, due to lack of data.

Physical activity and incident cardiovascular disease in breast cancer survivors: the pathways study.

Purpose: Breast cancer survivors experience higher rates of cardiovascular disease (CVD) than women without breast cancer, due in part to cardiotoxic cancer treatments and shared lifestyle risk factors. Physical activity is associated with lower mortality risk in breast cancer survivors, but associations with CVD have not been examined in detail.

Methods: The Pathways Study is a prospective cohort study of 4,504 women diagnosed with invasive breast cancer between 2005 and 2013.

Clinical Profile and Treatment Adherence in Patients with Type 2 Diabetes and Chronic Kidney Disease Who Initiate an SGLT2 Inhibitor: A Multi-cohort Study.

Introduction: The clinical landscape for the treatment of patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) is rapidly evolving. As part of the FOUNTAIN platform (NCT05526157; EUPAS48148), we described and compared cohorts of adult patients with CKD and T2D initiating a sodium-glucose cotransporter 2 inhibitor (SGLT2i) before the launch of finerenone in Europe, Japan, and the United States (US).

Methods: This was a multinational, multi-cohort study of patients with T2D in five data sources: the Danish National Health Registers (DNHR) (Denmark), PHARMO Data Network (The Netherlands), Valencia Health System Integrated Database (VID) (Spain), Japan Chronic Kidney Disease Database Extension (J-CKD-DB-Ex) (Japan), and Optum's de-identified Clinformatics Data Mart Database (CDM) (US).

Vitamin D Supplementation for Treating Atopic Dermatitis in Children and Adults: A Systematic Review and Meta-Analysis.

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease affecting up to 20% of children and 10% of adults worldwide. Current research suggests a correlation between serum vitamin D level and AD severity and that vitamin D supplementation could have a potential therapeutic effect on AD.

Objectives: To conduct a systematic review and meta-analysis of studies of vitamin D supplementation for disease improvement in children and adults with AD.

Gaps between Open Science activities and actual recognition systems: Insights from an international survey.

There are global movements aiming to promote reform of the traditional research evaluation and reward systems. However, a comprehensive picture of the existing best practices and efforts across various institutions to integrate Open Science into these frameworks remains underdeveloped and not fully known. The aim of this study was to identify perceptions and expectations of various research communities worldwide regarding how Open Science activities are (or should be) formally recognised and rewarded.

Genetic Diversity and Expanded Phenotypes in Dystonia: Insights from Large-Scale Exome Sequencing.

Dystonia is one of the most prevalent movement disorders, characterized by significant clinical and etiological heterogeneity. Despite considerable heritability (~25%) and the identification of several disease-linked genes, the etiology in most patients remains elusive. Moreover, understanding the correlations between clinical manifestation and genetic variants has become increasingly complex.