Cyclin-dependent kinase 13 is indispensable for normal mouse heart development.

Congenital heart disease (CHD) has an incidence of approximately 1%. Over the last decade, sequencing studies including large cohorts of individuals with CHD have begun to unravel the genetic mechanisms underpinning CHD. This includes the identification of variants in cyclin-dependent kinase 13 (CDK13), in individuals with syndromic CHD.

A validated heart-specific model for splice-disrupting variants in childhood heart disease.

Background: Congenital heart disease (CHD) is the most common congenital anomaly. Almost 90% of isolated cases have an unexplained genetic etiology after clinical testing. Non-canonical splice variants that disrupt mRNA splicing through the loss or creation of exon boundaries are not routinely captured and/or evaluated by standard clinical genetic tests.

Development of a program theory for osteoporosis patient education in Denmark: a qualitative study based on realist evaluation.

Background: Osteoporosis patient education is offered in many countries worldwide. When evaluating complex interventions like these, it is important to understand how and why the intervention leads to effects. This study aimed to develop a program theory of osteoporosis patient education in Danish municipalities with a focus on examining the mechanisms of change i.

Evaluation of an mHealth App on Self-Management of Osteoporosis: Prospective Survey Study.

Background: Mobile health (mHealth) technologies can be used for disease-specific self-management, and these technologies are experiencing rapid growth in the health care industry. They use mobile devices, specifically smartphone apps, to enhance and support medical and public health practices. In chronic disease management, the use of apps in the realm of mHealth holds the potential to improve health outcomes.

Opportunistic Identification of Vertebral Compression Fractures on CT Scans of the Chest and Abdomen, Using an AI Algorithm, in a Real-Life Setting.

This study evaluated the performance of a vertebral fracture detection algorithm (HealthVCF) in a real-life setting and assessed the impact on treatment and diagnostic workflow. HealthVCF was used to identify moderate and severe vertebral compression fractures (VCF) at a Danish hospital. Around 10,000 CT scans were processed by the HealthVCF and CT scans positive for VCF formed both the baseline and 6-months follow-up cohort.

Effect of deletion of the protein kinase PRKD1 on development of the mouse embryonic heart.

Congenital heart disease (CHD) is the most common congenital anomaly, with an overall incidence of approximately 1% in the United Kingdom. Exome sequencing in large CHD cohorts has been performed to provide insights into the genetic aetiology of CHD. This includes a study of 1891 probands by our group in collaboration with others, which identified three novel genes-CDK13, PRKD1, and CHD4, in patients with syndromic CHD.

STIGMA: Single-cell tissue-specific gene prioritization using machine learning.

Clinical exome and genome sequencing have revolutionized the understanding of human disease genetics. Yet many genes remain functionally uncharacterized, complicating the establishment of causal disease links for genetic variants. While several scoring methods have been devised to prioritize these candidate genes, these methods fall short of capturing the expression heterogeneity across cell subpopulations within tissues.

The Postprandial Calcium Absorption of a Milk-Derived Calcium Permeate - The Acute RENEW Double-Blinded Randomized Controlled Cross-Over Study.

Background: Studies suggest that dairy-derived calcium supplements have additional beneficial properties compared with other calcium supplements in relation to bone health.

Objectives: We investigated the postprandial calcium absorption from a milk-derived calcium permeate (CP) compared with calcium carbonate (CC).

Methods: In this randomized double-blinded cross-over study, 10 healthy postmenopausal females (age 50-65 y) received maltodextrin (placebo), 800 mg calcium from CP or from CC provided in 6 capsules on separate days.

Genetic Screening Reveals Heterogeneous Clinical Phenotypes in Patients with Dilated Cardiomyopathy and Troponin T2 Variants.

Background: Cardiomyopathies (CMs) are a heterogeneous and severe group of diseases that shows a highly variable cardiac phenotype and an incidence of app. 1/100.000.

Aberrant phase separation and nucleolar dysfunction in rare genetic diseases.

Thousands of genetic variants in protein-coding genes have been linked to disease. However, the functional impact of most variants is unknown as they occur within intrinsically disordered protein regions that have poorly defined functions. Intrinsically disordered regions can mediate phase separation and the formation of biomolecular condensates, such as the nucleolus.

Baseline bone turnover marker levels can predict change in bone mineral density during antiresorptive treatment in osteoporotic patients: the Copenhagen bone turnover marker study.

Unlabelled: Anti-resorptive osteoporosis treatment might be more effective in patients with high bone turnover. In this registry study including clinical data, high pre-treatment bone turnover measured with biochemical markers was correlated with higher bone mineral density increases. Bone turnover markers may be useful tools to identify patients benefitting most from anti-resorptive treatment.

Exome sequencing in individuals with cardiovascular laterality defects identifies potential candidate genes.

The birth prevalence of laterality defects is about 1.1/10,000 comprising different phenotypes ranging from situs inversus totalis to heterotaxy, mostly associated with complex congenital heart defects (CHD) and situs abnormalities such as intestinal malrotation, biliary atresia, asplenia, or polysplenia. A proportion of laterality defects arise in the context of primary ciliary dyskinesia (PCD) accompanied by respiratory symptoms or infertility.

The effect of parathyroidectomy compared to non-surgical surveillance on kidney function in primary hyperparathyroidism: a nationwide historic cohort study.

Background: Patients with primary hyperparathyroidism (pHPT) and impaired kidney function (estimated glomerular filtration rate (eGFR) < 60 mL/min) are offered parathyroidectomy (PTX) to protect them from further complications. Surprisingly, two recent uncontrolled cohort studies have suggested a further decrease in kidney function following PTX. We aimed to examine the effects of PTX compared to non-surgical surveillance on kidney function in pHPT patients.

Common Genetic Variants Contribute to Risk of Transposition of the Great Arteries.

Rationale: Dextro-transposition of the great arteries (D-TGA) is a severe congenital heart defect which affects approximately 1 in 4,000 live births. While there are several reports of D-TGA patients with rare variants in individual genes, the majority of D-TGA cases remain genetically elusive. Familial recurrence patterns and the observation that most cases with D-TGA are sporadic suggest a polygenic inheritance for the disorder, yet this remains unexplored.

Effectiveness of patient education for patients with osteoporosis: a systematic review.

Unlabelled: In this systematic review, the effects of osteoporosis patient education were examined. All studies found an effect on physical function, but for the other themes, the results were inconclusive. The findings indicate a need for further research in this topic.

The emergency medical service has a crucial role to unravel the genetics of sudden cardiac arrest in young, out of hospital resuscitated patients: Interim data from the MAP-IT study.

Background: Genetics of sudden cardiac deaths (SCD) remains frequently undetected. Genetic analysis is recommended in undefined selected cases in the 2021 ERC-guideline. The emergency medical service and physicians (EMS) may play a pivotal role for unraveling SCD by saving biomaterial for later molecular autopsy.

Integrative analysis of genomic variants reveals new associations of candidate haploinsufficient genes with congenital heart disease.

Numerous genetic studies have established a role for rare genomic variants in Congenital Heart Disease (CHD) at the copy number variation (CNV) and de novo variant (DNV) level. To identify novel haploinsufficient CHD disease genes, we performed an integrative analysis of CNVs and DNVs identified in probands with CHD including cases with sporadic thoracic aortic aneurysm. We assembled CNV data from 7,958 cases and 14,082 controls and performed a gene-wise analysis of the burden of rare genomic deletions in cases versus controls.