Polygenic overlap with granulocyte counts identifies novel loci for clozapine metabolism and clozapine-induced agranulocytosis.

While clozapine is the most effective antipsychotic drug, its use is limited due to hematological adverse effects involving the reduction of granulocyte counts with potential life-threatening agranulocytosis. It is not yet possible to predict or prevent the risk of agranulocytosis, and the mechanisms are unknown but likely related to clozapine metabolism. Genome-wide association studies (GWASs) of clozapine metabolism and clozapine-induced agranulocytosis have identified few genetic loci.

Effects of oxytocin administration on non-social executive functions in humans: a preregistered systematic review and meta-analysis.

Background: Oxytocin has received considerable research attention for its role in affiliative behaviors, particularly regarding its pro-social effects. More recent evidence has pointed to a broader role of oxytocin signaling, which includes non-social cognitive processes. However, meta-analytic data on oxytocin's effects on non-social cognition is currently limited.

A Prospective Study on Maximal Oxygen Uptake and Cardiovascular Functions in 12-Year-Old Endurance Athletes and Their Non-Endurance-Trained Peers.

The maximal oxygen uptake (V̇O) is typically higher in endurance-trained adolescents than in non-endurance-trained peers. However, the specific mechanisms contributing to this remain unclear, as well as the impact of training during this developmental stage. This study aims to compare V̇O and cardiovascular functions between 12-year-old endurance athletes and non-endurance-trained over a 14-month period.

A Mobile Health Intervention to Support Collaborative Decision-Making in Mental Health Care: Development and Usability.

Background: Shared decision-making between clinicians and service users is crucial in mental health care. One significant barrier to achieving this goal is the lack of user-centered services. Integrating digital tools into mental health services holds promise for addressing some of these challenges.

Pellino 3 E3 ligase promotes starvation-induced autophagy to prevent hepatic steatosis.

Nutrient deprivation is a major trigger of autophagy, a conserved quality control and recycling process essential for cellular and tissue homeostasis. In a high-content image-based screen of the human ubiquitome, we here identify the E3 ligase Pellino 3 (PELI3) as a crucial regulator of starvation-induced autophagy. Mechanistically, PELI3 localizes to autophagic membranes, where it interacts with the ATG8 proteins through an LC3-interacting region (LIR).

Disease characteristics and outcomes of acute myeloid leukemia in germline deficiency (Familial Platelet Disorder with associated Myeloid Malignancy).

Familial Platelet Disorder with associated Myeloid Malignancy (FPDMM, FPD/AML, -FPD), caused by monoallelic deleterious germline variants, is characterized by bleeding diathesis and predisposition for hematologic malignancies, particularly myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Clinical data on FPDMM-associated AML (FPDMM-AML) are limited, complicating evidence-based clinical decision-making. Here, we present retrospective genetic and clinical data of the largest cohort of FPDMM patients reported to date.

Imaging-based method to quantify left ventricular diastolic pressures.

Aim: To establish an imaging-based method to quantify left ventricular (LV) diastolic pressures.

Methods/results: In 115 patients suspected of coronary artery disease, LV pressure was measured by micromanometers and images by echocardiography. LV filling pressure was measured as LV pre-atrial contraction pressure (pre-A PLV).

A Guide to Breast Cancer Research: An Introduction.

"A Guide to Breast Cancer Research: From Cells and Molecular Mechanisms to Therapy" is designed as a comprehensive reference for early career investigators and postgraduate students. This book aims to provide a broad overview of contemporary breast cancer research. It covers key areas including development and cancer, metastasis and immunology, subtypes, signalling, therapy, and resistance.

Prognostic impact of expression of CD2, CD25, and/or CD30 in/on mast cells in systemic mastocytosis: a registry study of the European Competence Network on Mastocytosis.

Expression of CD2, CD25 and/or CD30 in extracutaneous mast cells (MC) is a minor diagnostic criterion for systemic mastocytosis (SM) in the classification of the World Health Organization and International Consensus Classification. So far, it remains unknown whether expression of these antigens on MC is of prognostic significance in SM. We performed a retrospective multi-center study of patients with SM using the data set of the registry of the European Competence Network on Mastocytosis, including 5034 patients with various MC disorders.

A preliminary evaluation of a fast, low-cost, and high-throughput nucleic acid extraction method for bacterial microbiota profiling in low-microbial biomass samples.

The respiratory tract is colonized with low-density microbial communities, which have been shown to impact human respiratory health through microbiota-host interactions. However, a lack of fast and cost-effective nucleic acid extraction method for low-microbial biomass samples hinders investigation of respiratory microbiota. Here, we performed a pilot study to assess the suitability of the NAxtra nucleic acid extraction protocol for profiling bacterial microbiota in respiratory samples.

Validation of Spatial Orientation Screening questionnaire for use in memory clinic patients.

Background: Spatial orientation is required for independent mobility in society. Deficits in spatial orientation can be an early symptom of Alzheimer's disease and other dementias, and there is a need for brief assessment tools to identify impairments.

Objective: The aim of this study was to evaluate the construct and known-group validity of our newly developed Spatial Orientation Screening (SOS) questionnaire.

The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study.

Purpose: To assess the association between neoadjuvant therapy and overall survival (OS) in patients with left-sided resectable pancreatic cancer (RPC) compared to upfront surgery.

Background: Left-sided pancreatic cancer is associated with worse OS compared to right-sided pancreatic cancer. Although neoadjuvant therapy is currently seen as not effective in patients with RPC, current randomized trials included mostly patients with right-sided RPC.

Cancers attributed to modifiable factors in Norway 2016-2020.

Background: Targeting modifiable factors offers significant potential for primary cancer prevention. For public health strategies, it is essential to quantify the contribution from each factor on a national level. We estimated the contribution of 12 modifiable factors on cancer incidence in the Norwegian population.

Distinct patterns of osteoradionecrosis after photon-based radiotherapy and carbon ion radiotherapy for unresectable adenoid cystic carcinoma of the head and neck: case series from two institutions.

Background And Purpose: To present the clinical outcomes of two series of patients treated with carbon-ion radiotherapy (CIRT) and definitive photon radiotherapy (RT) for adenoid cystic carcinoma of the head and neck (HN-ACC).

Material And Methods: The first cohort of six patients was referred from Oslo University Hospital (OUS) to Centro Nazionale di Adroterapia Oncologica (CNAO, Pavia, Italy) for CIRT in 2014-2017. The second cohort included 18 patients treated with definitive photon RT at OUS in 2005-2017.

Impulse control and correlation to dopamine agonist serum concentrations in people with Parkinson's disease.

Background: Impaired impulse control is often seen in Parkinson's disease (PD) patients using dopamine agonists.

Methods: We performed a therapeutic drug monitoring study of 100 PD patients using ropinirole or pramipexole extended release. Three blood samples were collected on the same day.

Cenobamate as add-on treatment for SCN8A developmental and epileptic encephalopathy.

Objectives: Developmental and epileptic encephalopathies (DEEs) caused by pathogenic variants in SCN8A are associated with difficult-to-treat and early-onset seizures, developmental delay/intellectual disability, impaired quality of life, and increased risk of early mortality. High doses of sodium channel blockers are typically used to treat SCN8A-DEE caused by gain-of-function (GoF) variants. However, seizures are often drug resistant, and only a few patients achieve seizure freedom.

Insights into Chronic Low Back Pain Etiology: Population-based genome-wide Association Study Identifies 18 Risk Loci.

Study Design: Genome-wide association study (GWAS) meta-analysis with downstream analyses.

Objective: To explore the genetic architecture of chronic low back pain (cLBP) and identify underlying biological mechanisms that contribute to its development.

Summary Of Background Data: Chronic low back pain is prevalent and debilitating, with many cases having no identifiable biological cause.

The role of multi-modality imaging for the assessment of left atrium and left atrial appendage. A clinical consensus statement of the European Association of Cardiovascular Imaging (EACVI), European Heart Rhythm Association (EHRA) of the European Society of Cardiology (ESC).

Structural, architectural, contractile or electrophysiological alterations may occur in the left atrium (LA). The concept of LA cardiopathy is supported by accumulating scientific evidence demonstrating that LA remodeling has become a cornerstone diagnostic and prognostic marker. The structure and the function of LA and left atrial appendage (LAA) which is an integral part of the LA, are key elements for a better understanding of multiple clinical conditions, most notably atrial fibrillation (AF), cardioembolism, heart failure and mitral valve diseases.

Drones delivering automated external defibrillators for out-of-hospital cardiac arrest: A scoping review.

Unlabelled: Out-of-hospital cardiac arrest (OHCA) remains a critical health concern, where prompt access to automated external defibrillators (AEDs) significantly improves survival. This scoping review broadly investigates the feasibility and impact of dronedelivered AEDs for OHCA response.

Methods: PubMed, Cochrane, and Web of Science were searched from inception to August 6, 2024, with eligibility broadly including empirical data.

Effect of plasma levels of factor VIII according to procoagulant phospholipids on the risk of future venous thromboembolism.

Background: A high level of plasma coagulation factor (F)VIII is an established and likely causal risk factor for venous thromboembolism (VTE). Procoagulant phospholipids (PPLs) facilitate FVIII activity in coagulation.

Objectives: To assess the association between plasma levels of FVIII and risk of future VTE according to PPL clotting time (PPL), an inverse surrogate measure of plasma PPL activity.

Impact of deep or ovarian endometriosis on pelvic pain and quality of life: prospective cross-sectional ultrasound study.

Objective: To assess whether premenopausal women diagnosed with deep or ovarian endometriosis on transvaginal sonography (TVS) were more likely to suffer from dyspareunia and pelvic pain symptoms, and have a lower quality of life, compared to women without sonographically diagnosed deep or ovarian endometriosis.

Methods: This was a prospective, cross-sectional study carried out between February 2019 and October 2020 at the general gynecology clinic at University College London Hospital, London, UK. All premenopausal women aged 18-50 years, who were examined consecutively by a single experienced examiner and underwent a detailed TVS scan, were eligible for inclusion.

Fracture liaison service (FLS) is associated with lower subsequent fragility fracture risk and mortality: NoFRACT (the Norwegian capture the fracture initiative).

Unlabelled: Subsequent fracture rates and associated mortality were compared before and after the introduction of fracture liaison service (FLS). In 100,198 women and men, FLS was associated with 13% and 10% lower risk of subsequent fragility fractures and 18% and 15% lower mortality. The study suggests that FLS may prevent fractures.

Exploring the Relationship Between Humoral and Cellular T Cell Responses Against SARS-CoV-2 in Exposed Individuals From Emilia Romagna Region and COVID-19 Severity.

COVID-19 remains a significant global health problem with uncertain long-term consequences for convalescents. We investigated the relationships between anti-N protein antibody levels, severe acute respiratory syndrome (SARS)-CoV-2-associated TCR repertoire parameters, HLA type and epidemiological information from three cohorts of 524 SARS-CoV-2-infected subjects subgrouped in acute phase, seronegative and seropositive convalescents from the Emilia Romagna region. Epidemiological information and anti-N antibody index were associated with TCR repertoire data.

Nonneutralizing antibodies in Nordic persons with moderate hemophilia A and B (the MoHem study).

Background: The impact of nonneutralizing antibodies (NNAs) in moderate hemophilia is elusive.

Objectives: To explore the presence of NNAs in Nordic persons with moderate hemophilia A (MHA) and B (MHB) in relation to treatment modality, clinical outcome, history of inhibitor, and the corresponding factor VIII (FVIII)/factor IX (FIX) gene mutation.

Methods: A cross-sectional multicenter study covering persons with MHA and MHB in Sweden, Finland, and Norway.

Survival and quality of life after first-time diagnosis of brain metastases: a multicenter, prospective, observational study.

Background: A major concern in anticancer treatment (ACT) of brain metastases (BM) is exposing patients with short expected survival to treatments that negatively impact on quality of life (QoL). Such futile ACT at the end of life is time-consuming and burdensome for patients and their families and entails unnecessary healthcare costs. Refraining from ACT is challenging for both physicians and patients.