Impact of 2018 EU Risk Minimisation Measures and Revised Pregnancy Prevention Programme on Utilisation and Prescribing Trends of Medicinal Products Containing Valproate: An Interrupted Time Series Study.

Introduction: Due to established teratogenicity of valproates, the EU risk minimisation measures (RMMs) with a pregnancy prevention programme (PPP) for valproate were updated in March 2018.

Objectives: To investigate the effectiveness of the 2018 EU RMMs on valproate utilisation in five European countries/regions.

Methods: A multi-database, times series study of females of childbearing potential (12-55 years) was conducted using electronic medical records from five countries/regions (01.

Protein Biomarkers of New-Onset Heart Failure: Insights From the Heart Omics and Ageing Cohort, the Atherosclerosis Risk in Communities Study, and the Framingham Heart Study.

Background: We sought to identify protein biomarkers of new-onset heart failure (HF) in 3 independent cohorts (HOMAGE cohort [Heart Omics and Ageing], ARIC study [Atherosclerosis Risk in Communities], and FHS [Framingham Heart Study]) and assess if and to what extent they improve HF risk prediction compared to clinical risk factors alone.

Methods: A nested case-control design was used with cases (incident HF) and controls (without HF) matched on age and sex within each cohort. Plasma concentrations of 276 proteins were measured at baseline in ARIC (250 cases/250 controls), FHS (191/191), and HOMAGE cohort (562/871).

Depression, Anxiety, and Stress among Hangover-Sensitive and Hangover-Resistant Drinkers.

This study investigated potential differences in baseline (i.e., non-hangover-related) levels of depression, anxiety, and stress between individuals who are sensitive to and those resistant to hangovers after consuming alcohol.

Physical performance tasks were linked to the PROMIS physical function metric in patients undergoing hemodialysis.

Objectives: To investigate whether a multi-item performance outcome measure, the physical performance test (PPT), can be calibrated to a common scale with patient-reported outcome measures, using the Patient-Reported Outcomes Measurement Information System (PROMIS) physical function (PF) metric.

Study Design And Setting: We analyzed baseline data (N = 1,113) from the CONVINCE study, an international trial in end-stage kidney disease patients comparing high-dose hemodiafiltration with high-flux hemodialysis. Assumptions of item response theory (IRT) modelling were investigated for the combined set of the nine-item PPT and a four-item PROMIS PF short form (PROMIS-PF4a).

Blinatumomab Added to Chemotherapy in Infant Lymphoblastic Leukemia.

Background: -rearranged acute lymphoblastic leukemia (ALL) in infants is an aggressive disease with 3-year event-free survival below 40%. Most relapses occur during treatment, with two thirds occurring within 1 year and 90% within 2 years after diagnosis. Outcomes have not improved in recent decades despite intensification of chemotherapy.

Retrospective Multicenter Evaluation of the VirClia Galactomannan Antigen Assay for the Diagnosis of Pulmonary Aspergillosis with Bronchoalveolar Lavage Fluid Samples from Patients with Hematological Disease.

Galactomannan (GM) testing of bronchoalveolar lavage (BAL) fluid samples has become an essential tool to diagnose invasive pulmonary aspergillosis (IPA) and is part of diagnostic guidelines. Enzyme-linked immunosorbent assays (ELISAs) (enzyme immunoassays [EIAs]) are commonly used, but they have a long turnaround time. In this study, we evaluated the performance of an automated chemiluminescence immunoassay (CLIA) with BAL fluid samples.

Integrated Proteomics Unveils Nuclear PDE3A2 as a Regulator of Cardiac Myocyte Hypertrophy.

Background: Signaling by cAMP is organized in multiple distinct subcellular nanodomains regulated by cAMP-hydrolyzing PDEs (phosphodiesterases). Cardiac β-adrenergic signaling has served as the prototypical system to elucidate cAMP compartmentalization. Although studies in cardiac myocytes have provided an understanding of the location and properties of a handful of cAMP subcellular compartments, an overall view of the cellular landscape of cAMP nanodomains is missing.

Unexploited potential of risk factor treatment in patients with atherosclerotic cardiovascular disease.

Background: Most patients with atherosclerotic cardiovascular disease remain at (very) high risk for recurrent events due to suboptimal risk factor control.

Aims: This study aimed to quantify the potential of maximal risk factor treatment on 10-year and lifetime risk of recurrent atherosclerotic cardiovascular events in patients 1 year after a coronary event.

Methods And Results: Pooled data from six studies are as follows: RESPONSE 1, RESPONSE 2, OPTICARE, EUROASPIRE IV, EUROASPIRE V, and HELIUS.

Sleep and 24-hour rhythm characteristics in preschool children born very preterm and full term.

Study Objectives: Sleep impacts the quality of life and is associated with cardiometabolic and neurocognitive outcomes. Little is known about the sleep of preterm-born children at preschool age. We, therefore, studied sleep and 24-hour rhythms of preschool children born very preterm compared with full-term children.

Artificial intelligence to enhance clinical value across the spectrum of cardiovascular healthcare.

Artificial intelligence (AI) is increasingly being utilized in healthcare. This article provides clinicians and researchers with a step-wise foundation for high-value AI that can be applied to a variety of different data modalities. The aim is to improve the transparency and application of AI methods, with the potential to benefit patients in routine cardiovascular care.

Purified complement C3b triggers phagocytosis and activation of human neutrophils via complement receptor 1.

The complement system provides vital immune protection against infectious agents by labeling them with complement fragments that enhance phagocytosis by immune cells. Many details of complement-mediated phagocytosis remain elusive, partly because it is difficult to study the role of individual complement proteins on target surfaces. Here, we employ serum-free methods to couple purified complement C3b onto E.

Nivolumab and brentuximab vedotin with or without bendamustine for R/R Hodgkin lymphoma in children, adolescents, and young adults.

Children, adolescents, and young adults (CAYA) with relapsed/refractory (R/R) classic Hodgkin lymphoma (cHL) without complete metabolic response (CMR) before autologous hematopoietic cell transplantation (auto-HCT) have poor survival outcomes. CheckMate 744, a phase 2 study for CAYA (aged 5-30 years) with R/R cHL, evaluated a risk-stratified, response-adapted approach with nivolumab plus brentuximab vedotin (BV) followed by BV plus bendamustine for patients with suboptimal response. Risk stratification was primarily based on time to relapse, prior treatment, and presence of B symptoms.

Arterial Spin-Labeling Parameters and Their Associations with Risk Factors, Cerebral Small-Vessel Disease, and Etiologic Subtypes of Cognitive Impairment and Dementia.

Background And Purpose: Cerebral small-vessel disease may alter cerebral blood flow (CBF) leading to brain changes and, hence, cognitive impairment and dementia. CBF and the spatial coefficient of variation can be measured quantitatively by arterial spin-labeling. We aimed to investigate the associations of demographics, vascular risk factors, location, and severity of cerebral small-vessel disease as well as the etiologic subtypes of cognitive impairment and dementia with CBF and the spatial coefficient of variation.

IL-5-producing CD4 T cells and eosinophils cooperate to enhance response to immune checkpoint blockade in breast cancer.

Immune checkpoint blockade (ICB) has heralded a new era in cancer therapy. Research into the mechanisms underlying response to ICB has predominantly focused on T cells; however, effective immune responses require tightly regulated crosstalk between innate and adaptive immune cells. Here, we combine unbiased analysis of blood and tumors from metastatic breast cancer patients treated with ICB with mechanistic studies in mouse models of breast cancer.

Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses.

Background: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke.

Methods: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.

Stroke genetics informs drug discovery and risk prediction across ancestries.

Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.

Genera of phytopathogenic fungi: GOPHY 4.

This paper is the fourth contribution in the Genera of Phytopathogenic Fungi (GOPHY) series. The series provides morphological descriptions and information about the pathology, distribution, hosts and disease symptoms, as well as DNA barcodes for the taxa covered. Moreover, 12 whole-genome sequences for the type or new species in the treated genera are provided.

Toward Understanding How Staphylococcal Protein A Inhibits IgG-Mediated Phagocytosis.

IgG molecules are crucial for the human immune response against bacterial infections. IgGs can trigger phagocytosis by innate immune cells, like neutrophils. To do so, IgGs should bind to the bacterial surface via their variable Fab regions and interact with Fcγ receptors and complement C1 via the constant Fc domain.

Pelagic distribution of plastic debris (> 500 µm) and marine organisms in the upper layer of the North Atlantic Ocean.

At present, the distribution of plastic debris in the ocean water column remains largely unknown. Such information, however, is required to assess the exposure of marine organisms to plastic pollution as well as to calculate the ocean plastic mass balance. Here, we provide water column profiles (0-300 m water depth) of plastic (0.

Truncated FGFR2 is a clinically actionable oncogene in multiple cancers.

Somatic hotspot mutations and structural amplifications and fusions that affect fibroblast growth factor receptor 2 (encoded by FGFR2) occur in multiple types of cancer. However, clinical responses to FGFR inhibitors have remained variable, emphasizing the need to better understand which FGFR2 alterations are oncogenic and therapeutically targetable. Here we apply transposon-based screening and tumour modelling in mice, and find that the truncation of exon 18 (E18) of Fgfr2 is a potent driver mutation.

Time Since Stroke Onset, Quantitative Collateral Score, and Functional Outcome After Endovascular Treatment for Acute Ischemic Stroke.

Background And Objectives: In patients with ischemic stroke undergoing endovascular treatment (EVT), time to treatment and collateral status are important prognostic factors and may be correlated. We aimed to assess the relation between time to CT angiography (CTA) and a quantitatively determined collateral score and to assess whether the collateral score modified the relation between time to recanalization and functional outcome.

Methods: We analyzed data from patients with acute ischemic stroke included in the Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke Registry between 2014 and 2017, who had a carotid terminus or M1 occlusion and were treated with EVT within 6.

The Spring Distraction System for Growth-Friendly Surgical Treatment of Early Onset Scoliosis: A Preliminary Report on Clinical Results and Safety after Design Iterations in a Prospective Clinical Trial.

Background: The Spring Distraction System (SDS) is a dynamic growth-friendly implant to treat early onset scoliosis (EOS). Previous SDS studies showed promising results in terms of curve correction and complication profile. Nevertheless, complications did occur, which led to modifications in the implant design.