Large-scale genome-wide association study of 398,238 women unveils seven novel loci associated with high-grade serous epithelial ovarian cancer risk.

Background: Nineteen genomic regions have been associated with high-grade serous ovarian cancer (HGSOC). We used data from the Ovarian Cancer Association Consortium (OCAC), Consortium of Investigators of Modifiers of (CIMBA), UK Biobank (UKBB), and FinnGen to identify novel HGSOC susceptibility loci and develop polygenic scores (PGS).

Methods: We analyzed >22 million variants for 398,238 women.

Resource constrained neural network training.

Modern applications of neural-network-based AI solutions tend to move from datacenter backends to low-power edge devices. Environmental, computational, and power constraints are inevitable consequences of such a shift. Limiting the bit count of neural network parameters proved to be a valid technique for speeding up and increasing efficiency of the inference process.

ENIGMA CHEK2gether Project: A Comprehensive Study Identifies Functionally Impaired CHEK2 Germline Missense Variants Associated with Increased Breast Cancer Risk.

Purpose: Germline pathogenic variants in CHEK2 confer moderately elevated breast cancer risk (odds ratio, OR ∼ 2.5), qualifying carriers for enhanced breast cancer screening. Besides pathogenic variants, dozens of missense CHEK2 variants of uncertain significance (VUS) have been identified, hampering the clinical utility of germline genetic testing (GGT).

How Stories Can Contribute Toward Quality Improvement in Long-Term Care.

It is important to evaluate how residents, their significant others, and professional caregivers experience life in a nursing home to improve quality of care based on their needs and wishes. Narratives are a promising method to assess this experienced quality of care as they enable a rich understanding, reflection, and learning. In the Netherlands, narratives are becoming a more substantial element within the quality improvement cycle of nursing homes.

Determining the Appropriate Support for Older Adults with Different Levels of Vitality and Health-Related Quality of Life: An Explanatory Study.

Vitality and health-related quality of life are often assessed in older adults. However, these assessments do not provide guidance on support for older adults with different levels of vitality and health-related quality of life. This guidance can be established through segmentation.

[The involvement of older adults in the residential care: dilemmas, pitfalls and potentials].

In the residential care sector we have witnessed throughout the previous decades a development from a rather paternalistic approach towards a more democratic way of care giving. In many care organizations, however, residents are still rarely involved in the daily routine. In a participatory study on a somatic care unit in the Netherlands, we examined the challenges around the involvement of residents in the care residence.

FANCM missense variants and breast cancer risk: a case-control association study of 75,156 European women.

Evidence from literature, including the BRIDGES study, indicates that germline protein truncating variants (PTVs) in FANCM confer moderately increased risk of ER-negative and triple-negative breast cancer (TNBC), especially for women with a family history of the disease. Association between FANCM missense variants (MVs) and breast cancer risk has been postulated. In this study, we further used the BRIDGES study to test 689 FANCM MVs for association with breast cancer risk, overall and in ER-negative and TNBC subtypes, in 39,885 cases (7566 selected for family history) and 35,271 controls of European ancestry.

Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers.

The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation.

Molecular characterization of an embryonal rhabdomyosarcoma occurring in a patient with Kabuki syndrome: report and literature review in the light of tumor predisposition syndromes.

Kabuki syndrome is a well-recognized syndrome characterized by facial dysmorphism and developmental delay/intellectual disability and in the majority of patients a germline variant in KMT2D is found. As somatic KMT2D variants can be found in 5-10% of tumors a tumor predisposition in Kabuki syndrome is discussed. So far less than 20 patients with Kabuki syndrome and a concomitant malignancy have been published.

Safety and Efficacy of Irradiation Boost Based on 18F-FET-PET in Patients with Newly Diagnosed Glioblastoma.

Purpose: Dual timepoint fluoro-ethyl-tyrosine (FET)-PET acquisition (10 and 60 minutes after FET injection) improves the definition of glioblastoma (GBM) location and shape. Here we evaluated the safety and efficacy of simultaneous integrated boost (SIB) planned using dual FET-PET for postoperative GBM treatment.

Patients And Methods: In this prospective pilot study (March 2017-December 2020), 17 patients qualified for FET-PET-based SIB intensity-modulated radiotherapy after resection.

Experimental demonstration of continuous quantum error correction.

The storage and processing of quantum information are susceptible to external noise, resulting in computational errors. A powerful method to suppress these effects is quantum error correction. Typically, quantum error correction is executed in discrete rounds, using entangling gates and projective measurement on ancillary qubits to complete each round of error correction.

Older Adults' Engagement in Residential Care: Pitfalls, Potentials, and the Role of ICTs.

Over the previous years, the residential care sector has gone through a transition from a rather paternalistic approach towards a more democratic way of caregiving. Nevertheless, many care organizations still find it challenging to engage their residents in the process of care. In this study, we investigated the challenges regarding the engagement of older adults in residential care.

Pathogenic neurofibromatosis type 1 (NF1) RNA splicing resolved by targeted RNAseq.

Neurofibromatosis type 1 (NF1) is caused by loss-of-function variants in the NF1 gene. Approximately 10% of these variants affect RNA splicing and are either missed by conventional DNA diagnostics or are misinterpreted by in silico splicing predictions. Therefore, a targeted RNAseq-based approach was designed to detect pathogenic RNA splicing and associated pathogenic DNA variants.

Prevalence of Germline Pathogenic Variants in Cancer Predisposing Genes in Czech and Belgian Pancreatic Cancer Patients.

(1) Background: The proportion and spectrum of germline pathogenic variants (PV) associated with an increased risk for pancreatic ductal adenocarcinoma (PDAC) varies among populations. (2) Methods: We analyzed 72 Belgian and 226 Czech PDAC patients by multigene panel testing. The prevalence of pathogenic variants (PV) in relation to personal/family cancer history were evaluated.

Supporting eating behaviour of community-dwelling older adults: co-design of an embodied conversational agent.

In order to support community-dwelling older adults with healthy eating behaviours, Embodied Conversational Agents (ECAs) may be an effective and engaging medium. However, ECAs have not yet been found to be capable of engendering behaviour change, which is partly attributed to the absence of a match with users' practices, needs and preferences. Hence, we describe a co-design process with older adults that informs both the content and the appearance of an ECA.

How Cardiac Embryology Translates into Clinical Arrhythmias.

The electrophysiological signatures of the myocardium in cardiac structures, such as the atrioventricular node, pulmonary veins or the right ventricular outflow tract, are established during development by the spatial and temporal expression of transcription factors that guide expression of specific ion channels. Genome-wide association studies have shown that small variations in genetic regions are key to the expression of these transcription factors and thereby modulate the electrical function of the heart. Moreover, mutations in these factors are found in arrhythmogenic pathologies such as congenital atrioventricular block, as well as in specific forms of atrial fibrillation and ventricular tachycardia.

Qutrit Randomized Benchmarking.

Ternary quantum processors offer significant potential computational advantages over conventional qubit technologies, leveraging the encoding and processing of quantum information in qutrits (three-level systems). To evaluate and compare the performance of such emerging quantum hardware it is essential to have robust benchmarking methods suitable for a higher-dimensional Hilbert space. We demonstrate extensions of industry standard randomized benchmarking (RB) protocols, developed and used extensively for qubits, suitable for ternary quantum logic.

Stereotactic Radiosurgery of Brain Metastasis in Patients with a Poor Prognosis: Effective or Overtreatment?

Purpose: Stereotactic radiosurgery (SRS) of brain metastasis in patients with a poor prognosis remains controversial. Here, we compared results of SRS alone to whole brain radiotherapy (WBRT) in poor-prognosis patients and defined the most important unfavorable prognostic factors related to early death after SRS alone.

Patients And Methods: In this retrospective analysis of prospective SRS data, 180 patients with brain metastases not previously treated with WBRT were analyzed.

Diagnostic yield and accuracy in a tertiary referral syncope unit validating the ESC guideline on syncope: a prospective cohort study.

Aims: To assess in patients with transient loss of consciousness the diagnostic yield, accuracy, and safety of the structured approach as described in the ESC guidelines in a tertiary referral syncope unit.

Methods And Results: Prospective cohort study including 264 consecutive patients (≥18 years) referred with at least one self-reported episode of transient loss of consciousness and presenting to the syncope unit between October 2012 and February 2015. The study consisted of three phases: history taking (Phase 1), autonomic function tests (AFTs) (Phase 2), and after 1.