Humoral response 24 months after the first COVID-19 vaccination in people with HIV with and without diabetes.

People with HIV (PWH) and people with diabetes mellitus have increased risk of severe COVID-19, but little is known about humoral response to COVID-19 vaccines in PWH with DM. We investigated SARS-CoV-2 antireceptor-binding domain (anti-RBD) immunoglobulin G (IgG) geometrical concentrations and neutralizing antibody capacity (nAB) in PWH with and without diabetes mellitus. Anti-RBD IgG and nAB in COVID-19-vaccinated PWH were not associated with diabetes mellitus-status or HbA1c 24 months after the initial COVID-19 vaccination.

Independent evaluation of an 11-CpG panel for age estimation in blood.

DNA methylation patterns have emerged as reliable markers for age estimation, offering potential applications in forensic investigations, namely, in cases where there is no information about a possible suspect, in the identification of victims of mass disasters, or in immigration cases when assessing the age of individuals seeking asylum. This study aimed to evaluate the 11-CpG panel proposed by Aliferi et al. (2022) for age estimation.

Thromboinflammation in ischemic cerebrovascular patients with the JAK2V617F mutation.

Background: The JAK2V617F mutation is a driver of Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) and is also implicated in cardiovascular diseases. Thrombosis in MPN involves JAK2V617F-associated platelet activation and endothelial dysfunction, all potentially influenced by chronic inflammation. Whether the mutation affects thromboinflammatory markers similarly in non-MPN patients remains unclear.

A genome-wide association meta-analysis links hidradenitis suppurativa to common and rare sequence variants causing disruption of the Notch and Wnt/β-catenin signaling pathways.

Background: The contributions of genetic and environmental risk factors to hidradenitis suppurativa (HS) are both poorly understood.

Objective: To identify sequence variants that associate with HS and determine the contribution of environmental risk factors and inflammatory diseases to HS pathogenesis.

Methods: A genome-wide association meta-analysis of 4814 HS cases (Denmark: 1977; Iceland: 1266; Finland: 800; UK: 569; and US: 202) and 1.

Novel loci and biomedical consequences of iron homoeostasis variation.

Iron homoeostasis is tightly regulated, with hepcidin and soluble transferrin receptor (sTfR) playing significant roles. However, the genetic determinants of these traits and the biomedical consequences of iron homoeostasis variation are unclear. In a meta-analysis of 12 cohorts involving 91,675 participants, we found 43 genomic loci associated with either hepcidin or sTfR concentration, of which 15 previously unreported.

Autoantibodies targeting interferons and GM-CSF are associated with adverse outcome risk, comorbidities, and pathogen in community-acquired pneumonia.

Introduction: Cytokine autoantibodies (c-aAb) have been associated with pulmonary diseases, including severe novel coronavirus disease 2019 (COVID-19) and pulmonary alveolar proteinosis. This study aimed to determine c-aAb association with community-acquired pneumonia (CAP) etiology (SARS-CoV-2, influenza, or bacteria) and c-aAb associations with CAP-related clinical outcomes and pulmonary comorbidities.

Methods: In a cohort of 665 patients hospitalized with CAP, c-aAb targeting interferon α (IFNα), IFNβ, IFNγ, interleukin-1α (IL-1α), IL-6, IL-10, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured in plasma samples.

Temporal Dynamics of Plasma Neurofilament Light in Blood Donors With Preclinical Multiple Sclerosis.

Background And Objectives: Multiple sclerosis (MS) is a CNS disease, characterized by demyelination, inflammation, and neurodegeneration. Recent advances in technology allow measurement of the axonal damage marker neurofilament light chain in peripheral blood. Two studies have shown that patients with MS have elevated neurofilament light levels before their first symptom, but longitudinal studies are lacking.

Susceptibility to and severity of SARS-CoV-2 infection according to prescription drug use-an observational study of 46,506 Danish healthcare workers.

It is not well investigated whether exposure to specific drug classes is associated with COVID-19. We investigated the risk of SARS-CoV-2 infection and severe COVID-19 among healthcare workers according to prescription drug use. We conducted an observational study among Danish healthcare workers.

Cytokine Autoantibodies Alter Gene Expression Profiles of Healthy Donors.

Autoantibodies against cytokines (c-aAb) have been implicated in the pathophysiology of autoimmune diseases, and a variety of infections. In addition, several independent studies have detected elevated titers of c-aAb in the circulation of healthy individuals. To further understand their impact on immune responses, we measured c-aAb against IFN-α, IFN-γ, CSF2, IL-1α, IL-6, and IL-10 in the plasma of 1000 healthy individuals of the Milieu Intérieur (MI) cohort.

Cognition Assessment in Virtual Reality (CAVIR): Associations with neuropsychological performance and activities of daily living in patients with mood or psychosis spectrum disorders.

Background: More ecologically valid tools are needed to better capture daily-life cognitive impairments in patients with mood or psychosis spectrum disorders in clinical settings and cognitive treatment trials. We developed the Cognition Assessment in Virtual Reality (CAVIR) test, which assesses daily-life cognitive skills in an immersive virtual reality kitchen scenario. This study investigated the validity and sensitivity of CAVIR, including its association with activities of daily living (ADL) ability.

A partial loss-of-function variant in STAT6 protects against type 2 asthma.

Background: Signal transducer and activator of transcription 6 (STAT6) is central to type 2 (T2) inflammation, and common noncoding variants at the STAT6 locus associate with various T2 inflammatory traits, including diseases, and its pathway is widely targeted in asthma treatment.

Objective: We sought to test the association of a rare missense variant in STAT6, p.L406P, with T2 inflammatory traits, including the risk of asthma and allergic diseases, and to characterize its functional consequences in cell culture.

No association between migraine and HLA alleles in a cohort of 13,210 individuals with migraine from the Danish Blood Donor Study.

Objective: To determine the association between human leukocyte antigen (HLA) alleles and migraine, migraine subtypes, and sex-specific factors.

Background: It has long been hypothesized that inflammation contributes to migraine pathophysiology. This study examined the association between migraine and alleles in the HLA system, a key player in immune response and genetic diversity.

Developmental language disorder - heritability and genetic correlations with other disorders affecting language.

Developmental language disorder (DLD) is a neurodevelopmental disorder primarily affecting language in the absence of a known biomedical condition, which may have a large impact on a person's life and mental health. Family-based studies indicate a strong genetic component in DLD, but genetic studies of DLD are scarce. In this study we estimated the heritability of DLD and its genetic correlations with related disorders and traits in sample of >25,000 individuals from the Danish Blood Donor Study for whom we had both genotype data and questionnaire data on language disorder and language support.

A deep learning approach to prediction of blood group antigens from genomic data.

Background: Deep learning methods are revolutionizing natural science. In this study, we aim to apply such techniques to develop blood type prediction models based on cheap to analyze and easily scalable screening array genotyping platforms.

Methods: Combining existing blood types from blood banks and imputed screening array genotypes for ~111,000 Danish and 1168 Finnish blood donors, we used deep learning techniques to train and validate blood type prediction models for 36 antigens in 15 blood group systems.

Sex and Population-Specific 99th Percentiles of Troponin for Myocardial Infarction in the Danish Population (DANSPOT).

Background: Sex- and population-specific 99th percentiles of high-sensitivity cardiac troponin (hs-cTn) are recommended in guidelines although the evidence for a clinical utility is sparse. The DANSPOT trial will investigate the clinical effect of sex- and population-specific 99th percentiles of cTn. We report the 99th percentiles derived from this trial and their dependency on kidney function.

Uncovering the heritable components of multimorbidities and disease trajectories using a nationwide cohort.

Quantifying the contribution of genetics and environmental effects on disease initiation and progression, as well as the shared genetics of different diseases, is vital for the understanding of the disease etiology of multimorbidities. In this study, we leverage nationwide Danish registries to provide a granular atlas of the genetic origin of disease phenotypes for a cohort of all Danes 1978-2018 with partially known pedigree (n = 6.3 million).

Clinical implications of innate immune exhaustion in cystic fibrosis.

Objectives: Lung disease progression in people with cystic fibrosis (pwCF) varies from one individual to another. Different immunological characteristics have been suggested to explain this variation, and we hypothesised that lung capacity may be associated with the innate immune response in pwCF. In an exploratory study, we aimed to investigate potential links between the innate immune response and lung function in pwCF using the standardised immune function assay TruCulture.

Homozygosity for a stop-gain variant in CCDC201 causes primary ovarian insufficiency.

Age at menopause (AOM) has a substantial impact on fertility and disease risk. While many loci with variants that associate with AOM have been identified through genome-wide association studies (GWAS) under an additive model, other genetic models are rarely considered. Here through GWAS meta-analysis under the recessive model of 174,329 postmenopausal women from Iceland, Denmark, the United Kingdom (UK; UK Biobank) and Norway, we study low-frequency variants with a large effect on AOM.

Effects of levcromakalim in patients with migraine aura without headache: An experimental study.

Background/hypothesis: Levcromakalim has previously been shown to induce attacks of migraine with aura in certain individuals. In this study, we tested the migraine-inducing effect of levcromakalim in a cohort of participants with migraine aura without headache.

Methods: In a double-blind, randomized, placebo-controlled cross-over study, eight adult participants with migraine with aura received intravenous infusions of levcromakalim and saline.