The effect of coronary artery calcifications and radiotherapy on the risk of coronary artery disease in high-risk breast cancer patients in the DBCG RT-Nation cohort.

Background And Purpose: Radiotherapy improves outcomes for breast cancer. However, prior studies have correlated the risk of coronary artery disease (CAD) to the mean heart dose (MHD), mean dose to the left anterior descending artery (LAD_mean) and the left ventricle V5Gy (LV5). Other studies showed an increased risk of CAD for patients with pronounced coronary artery calcification (CAC) at the time of radiotherapy.

Quality assurance of internal mammary node irradiation in the DBCG IMN2 study.

Purpose/objective: The Danish Breast Cancer Group (DBCG) IMN2 study investigated the gain from internal mammary node irradiation (IMNI) in node-positive breast cancer patients. IMNI was indicated in right-sided patients, but not in left-sided. Target volume delineations were based on bony landmarks in contrast to the contemporary vessel-based ESTRO consensus guideline.

Evaluating Danish Breast Cancer Group locoregional radiotherapy guideline adherence in clinical treatment data 2008-2016: The DBCG RT Nation study.

Background And Purpose: Guideline adherence in radiotherapy is crucial for maintaining treatment quality and consistency, particularly in non-trial patient settings where most treatments occur. The study aimed to assess the impact of guideline changes on treatment planning practices and compare manual registry data accuracy with treatment planning data.

Materials And Methods: This study utilised the DBCG RT Nation cohort, a collection of breast cancer radiotherapy data in Denmark, to evaluate adherence to guidelines from 2008 to 2016.

Development of a national deep learning-based auto-segmentation model for the heart on clinical delineations from the DBCG RT nation cohort.

Background: This study aimed at investigating the feasibility of developing a deep learning-based auto-segmentation model for the heart trained on clinical delineations.

Material And Methods: This study included two different datasets. The first dataset contained clinical heart delineations from the DBCG RT Nation study (1,561 patients).

End-to-end framework for automated collection of large multicentre radiotherapy datasets demonstrated in a Danish Breast Cancer Group cohort.

Large Digital Imaging and Communications in Medicine (DICOM) datasets are key to support research and the development of machine learning technology in radiotherapy (RT). However, the tools for multi-centre data collection, curation and standardisation are not readily available. Automated batch DICOM export solutions were demonstrated for a multicentre setup.

Early-onset atrial fibrillation patients show reduced left ventricular ejection fraction and increased atrial fibrosis.

Atrial fibrillation (AF) has traditionally been considered an electrical heart disease. However, genetic studies have revealed that the structural architecture of the heart also play a significant role. We evaluated the functional and structural consequences of harboring a titin-truncating variant (TTNtv) in AF patients, using cardiac magnetic resonance (CMR).

Rare truncating variants in the sarcomeric protein titin associate with familial and early-onset atrial fibrillation.

A family history of atrial fibrillation constitutes a substantial risk of developing the disease, however, the pathogenesis of this complex disease is poorly understood. We perform whole-exome sequencing on 24 families with at least three family members diagnosed with atrial fibrillation (AF) and find that titin-truncating variants (TTNtv) are significantly enriched in these patients (P = 1.76 × 10).

Multi-ethnic genome-wide association study for atrial fibrillation.

Atrial fibrillation (AF) affects more than 33 million individuals worldwide and has a complex heritability. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis.

Genome-wide Study of Atrial Fibrillation Identifies Seven Risk Loci and Highlights Biological Pathways and Regulatory Elements Involved in Cardiac Development.

Atrial fibrillation (AF) is a common cardiac arrhythmia and a major risk factor for stroke, heart failure, and premature death. The pathogenesis of AF remains poorly understood, which contributes to the current lack of highly effective treatments. To understand the genetic variation and biology underlying AF, we undertook a genome-wide association study (GWAS) of 6,337 AF individuals and 61,607 AF-free individuals from Norway, including replication in an additional 30,679 AF individuals and 278,895 AF-free individuals.

The potential benefits from respiratory gating for breast cancer patients regarding target coverage and dose to organs at risk when applying strict dose limits to the heart: results from the DBCG HYPO trial.

Purpose: The potential benefits from respiratory gating (RG) compared to free-breathing (FB) regarding target coverage and dose to organs at risk for breast cancer patients receiving post-operative radiotherapy (RT) in the DBCG HYPO multicentre trial are reported.

Material And Methods: Patients included in the DBCG HYPO trial were randomized between 50 Gy in 25 fractions (normofractionated) versus 40 Gy in 15 fractions (hypofractionated). A tangential forward field-in-field dose planning technique was used to cover the clinical target volume (CTV) with the intent to limit dose to the left anterior descending coronary artery (LADCA) to 20 Gy and 17 Gy in the normo- and hypofractionated arms, respectively.

Generation of induced pluripotent stem cells (iPSC) from an atrial fibrillation patient carrying a PITX2 p.M200V mutation.

Atrial fibrillation (AF) is the most common sustained arrhythmia associated with several cardiac risk factors, but increasing evidences indicated a genetic component. Indeed, genetic variations of the specific PITX2 gene have been identified in patients with early-onset AF. To investigate the molecular mechanisms underlying AF, we reprogrammed to pluripotency polymorphonucleated leukocytes isolated from the blood of a patient carrying a PITX2 p.

Generation of induced pluripotent stem cells (iPSC) from an atrial fibrillation patient carrying a KCNA5 p.D322H mutation.

Atrial fibrillation (AF) is the most common sustained arrhythmia associated with several cardiac risk factors, but increasing evidences indicated a genetic component. Indeed, genetic variations of the atrial specific KCNA5 gene have been identified in patients with early-onset lone AF. To investigate the molecular mechanisms underlying AF, we reprogrammed to pluripotency polymorphonucleated leukocytes isolated from the blood of a patient carrying a KCNA5 p.

Investigation of antidepressant-like and anxiolytic-like actions and cognitive and motor side effects of four N-methyl-D-aspartate receptor antagonists in mice.

Evidence suggests that N-methyl-D-aspartate receptor (NMDAR) antagonists could be efficacious in treating depression and anxiety, but side effects constitute a challenge. This study evaluated the antidepressant-like and anxiolytic-like actions, and cognitive and motor side effects of four NMDAR antagonists. MK-801, ketamine, S-ketamine, RO 25-6981 and the positive control, citalopram, were tested for antidepressant-like and anxiolytic-like effects in mice using the forced-swim test, the elevated zero maze and the novelty-induced hypophagia test.

Effects of sertraline, duloxetine, vortioxetine, and idazoxan in the rat affective bias test.

Rationale: Affective biases seemingly play a crucial role for the onset and development of depression. Acute treatment with monoamine-based antidepressants positively influences emotional processing, and an early correction of biases likely results in repeated positive experiences that ultimately lead to improved mood.

Objectives: Using two conventional antidepressants, sertraline and duloxetine, we aimed to forward the characterization of a newly developed affective bias test (ABT) for rats.

Modelling affective pain in mice: Effects of inflammatory hypersensitivity on place escape/avoidance behaviour, anxiety and hedonic state.

Background: The place escape/avoidance paradigm (PEAP) has been used to assess the affective component of pain in rats. Using the Complete Freund's Adjuvant (CFA) model of inflammatory pain, the current study aimed at developing a mouse version of PEAP and investigating the relation between PEAP and other behavioural responses, namely anxiety-like behaviour, locomotor activity, and hedonic state.

New Method: A novel paradigm assessing the affective component of pain in mice was developed by modifying the setup known from rat studies: Animals were forced to stay 2 × 5 min in the light and the dark area of a box while being stimulated with a suprathreshold filament on the untreated or treated paw, respectively.

IKs Gain- and Loss-of-Function in Early-Onset Lone Atrial Fibrillation.

Introduction: Atrial fibrillation (AF) is the most frequent cardiac arrhythmia. The potassium current IKs is essential for cardiac repolarization. Gain-of-function mutation in KCNQ1, the gene encoding the pore-forming α-subunit of the IKs channel (KV 7.

Brugada syndrome risk loci seem protective against atrial fibrillation.

Several studies have shown an overlap between genes involved in the pathophysiological mechanisms of atrial fibrillation (AF) and Brugada Syndrome (BrS). We investigated whether three single-nucleotide polymorphisms (SNPs) (rs11708996; G>C located intronic to SCN5A, rs10428132; T>G located in SCN10A, and rs9388451; T>C located downstream to HEY2) at loci associated with BrS in a recent genome-wide association study (GWAS) also were associated with AF. A total of 657 patients diagnosed with AF and a control group comprising 741 individuals free of AF were included.

Very early-onset lone atrial fibrillation patients have a high prevalence of rare variants in genes previously associated with atrial fibrillation.

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia. Currently, 14 genes important for ion channel function, intercellular signaling, and homeostatic control have been associated with AF.

Objective: We hypothesized that rare genetic variants in genes previously associated with AF had a higher prevalence in early-onset lone AF patients than in the background population.

Screening of the ito regulatory subunit klf15 in patients with early-onset lone atrial fibrillation.

Several studies have associated mutations in genes encoding potassium channels and accessory subunits involved in cardiac repolarization with increased susceptibility of atrial fibrillation (AF). Recently, the Krüppel-like factor 15 (Klf15) was found to transcriptionally control rhythmic expression of KChIP2, a critical subunit required for generating the transient outward potassium current (Ito), and that deficiency or excess of Klf15 increased the susceptibility of arrhythmias. On this basis we hypothesized that mutations in Klf15 could be associated with AF.

Mutations in genes encoding cardiac ion channels previously associated with sudden infant death syndrome (SIDS) are present with high frequency in new exome data.

Background: Sudden infant death syndrome (SIDS) is the leading cause of death in the first 6 months after birth in the industrialized world. The genetic contribution to SIDS has been investigated intensively and to date, 14 cardiac channelopathy genes have been associated with SIDS. Newly published data from National Heart, Lung, and Blood Institute Grand Opportunity (NHLBI GO) Exome Sequencing Project (ESP) provided important knowledge on genetic variation in the background population.