Carboxyl ester lipase hybrid 1 (CEL-HYB1) haplotypes confer varying risk for chronic pancreatitis.

The CEL-HYB1 hybrid allele of the carboxyl ester lipase (CEL) gene and its pseudogene (CELP) has been associated with chronic pancreatitis (CP). Recent work indicated that amino acid positions 488 and 548 in CEL-HYB1 determined pathogenicity. Haplotype Thr488-Ile548 was associated with CP while haplotypes Thr488-Thr548 and Ile488-Thr548 were benign.

Heterogeneous force response of chromatin in isolated nuclei.

A quantitative description of nuclear mechanics is crucial for understanding its role in force sensing within eukaryotic cells. Recent studies indicate that the chromatin within the nucleus cannot be treated as a homogeneous material. To elucidate its material properties, we combine optical tweezers manipulation of isolated nuclei with multi-color fluorescence imaging of lamin and chromatin to map the response of nuclei to local deformations.

Ion-mediated condensation controls the mechanics of mitotic chromosomes.

During mitosis in eukaryotic cells, mechanical forces generated by the mitotic spindle pull the sister chromatids into the nascent daughter cells. How do mitotic chromosomes achieve the necessary mechanical stiffness and stability to maintain their integrity under these forces? Here we use optical tweezers to show that ions involved in physiological chromosome condensation are crucial for chromosomal stability, stiffness and viscous dissipation. We combine these experiments with high-salt histone depletion and theory to show that chromosomal elasticity originates from the chromatin fibre behaving as a flexible polymer, whereas energy dissipation can be explained by modelling chromatin loops as an entangled polymer solution.

Viscoelasticity of diverse biological samples quantified by Acoustic Force Microrheology (AFMR).

In the context of soft matter and cellular mechanics, microrheology - the use of micron-sized particles to probe the frequency-dependent viscoelastic response of materials - is widely used to shed light onto the mechanics and dynamics of molecular structures. Here we present the implementation of active microrheology in an Acoustic Force Spectroscopy setup (AFMR), which combines multiplexing with the possibility of probing a wide range of forces ( ~ pN to ~nN) and frequencies (0.01-100 Hz).

INHIBITION OF INTEGRIN VLA-3 AND TETRASPANIN CD151 PROTECTS AGAINST NEUTROPHIL-MEDIATED ENDOTHELIAL DAMAGE.

Background: The recruitment of neutrophils to sites of localized injury or infection is initiated by changes on the surface of endothelial cells located in proximity to tissue damage. Inflammatory mediators, such as TNF-α, increase surface expression of adhesive ligands and receptors on the endothelial surface to which neutrophils tether and adhere. Neutrophils then transit through the activated endothelium to reach sites of tissue injury with little lasting vascular injury.

Longer and better lives for patients with atrial fibrillation: the 9th AFNET/EHRA consensus conference.

Aims: Recent trial data demonstrate beneficial effects of active rhythm management in patients with atrial fibrillation (AF) and support the concept that a low arrhythmia burden is associated with a low risk of AF-related complications. The aim of this document is to summarize the key outcomes of the 9th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA).

Methods And Results: Eighty-three international experts met in Münster for 2 days in September 2023.

Generative modeling of biological shapes and images using a probabilistic -shape sampler.

Understanding morphological variation is an important task in many areas of computational biology. Recent studies have focused on developing computational tools for the task of sub-image selection which aims at identifying structural features that best describe the variation between classes of shapes. A major part in assessing the utility of these approaches is to demonstrate their performance on both simulated and real datasets.

Mechanosensitive traction force generation is regulated by the neutrophil activation state.

The generation of traction forces by neutrophils regulates many crucial effector functions responsible for host defense, such as attachment, spreading, migration, phagocytosis, and NETosis. The activation state of the cell is a strong determinant of the functional efficacy of the neutrophil; however, the effect of activation on traction force production has not yet been determined experimentally. Previously, the mapping of cellular-generated forces produced by human neutrophils via a Traction Force Microscopy (TFM) method has required a three-dimensional imaging modality to capture out-of-plane forces, such as confocal or multiphoton techniques.

A multi-institutional retrospective pooled outcome analysis of molecularly annotated pediatric supratentorial fused ependymoma.

Background: (formerly known as fused supratentorial ependymoma (fus ST-EPN) has been recognized as a novel entity in the 2016 WHO classification of CNS tumors and further defined in the recent 2021 edition. fus ST-EPN was reported to portend poorer prognosis when compared to its counterpart, ST-EPN in some previously published series. The aim of this study was to determine the treatment outcome of molecularly confirmed and conventionally treated fus ST-EPN patients treated in multiple institutions.

Optimizing biomarkers for accurate ependymoma diagnosis, prognostication, and stratification within International Clinical Trials: A BIOMECA study.

Background: Accurate identification of brain tumor molecular subgroups is increasingly important. We aimed to establish the most accurate and reproducible ependymoma subgroup biomarker detection techniques, across 147 cases from International Society of Pediatric Oncology (SIOP) Ependymoma II trial participants, enrolled in the pan-European "Biomarkers of Ependymoma in Children and Adolescents (BIOMECA)" study.

Methods: Across 6 European BIOMECA laboratories, we evaluated epigenetic profiling (DNA methylation array); immunohistochemistry (IHC) for nuclear p65-RELA, H3K27me3, and Tenascin-C; copy number analysis via fluorescent in situ hybridization (FISH) and MLPA (1q, CDKN2A), and MIP and DNA methylation array (genome-wide copy number evaluation); analysis of ZFTA- and YAP1-fusions by RT-PCR and sequencing, Nanostring and break-apart FISH.

General practitioners' perceptions on opportunistic single-time point screening for atrial fibrillation: A European quantitative survey.

Background: There is no clear guidance on how to implement opportunistic atrial fibrillation (AF) screening in daily clinical practice.

Objectives: This study evaluated the perception of general practitioners (GPs) about value and practicalities of implementing screening for AF, focusing on opportunistic single-time point screening with a single-lead electrocardiogram (ECG) device.

Methods: A descriptive cross-sectional study was conducted with a survey developed to assess overall perception concerning AF screening, feasibility of opportunistic single-lead ECG screening and implementation requirements and barriers.

Superfluid stiffness of a KTaO-based two-dimensional electron gas.

After almost twenty years of intense work on the celebrated LaAlO/SrTiOsystem, the recent discovery of a superconducting two-dimensional electron gas (2-DEG) in (111)-oriented KTaO-based heterostructures injects new momentum to the field of oxides interface. However, while both interfaces share common properties, experiments also suggest important differences between the two systems. Here, we report gate tunable superconductivity in 2-DEGs generated at the surface of a (111)-oriented KTaO crystal by the simple sputtering of a thin Al layer.

Early diagnosis and better rhythm management to improve outcomes in patients with atrial fibrillation: the 8th AFNET/EHRA consensus conference.

Despite marked progress in the management of atrial fibrillation (AF), detecting AF remains difficult and AF-related complications cause unacceptable morbidity and mortality even on optimal current therapy. This document summarizes the key outcomes of the 8th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA). Eighty-three international experts met in Hamburg for 2 days in October 2021.

Performance of an electronic health record-based predictive model to identify patients with atrial fibrillation across countries.

Background: Atrial fibrillation (AF) burden on patients and healthcare systems warrants innovative strategies for screening asymptomatic individuals.

Objective: We sought to externally validate a predictive model originally developed in a German population to detect unidentified incident AF utilising real-world primary healthcare databases from countries in Europe and Australia.

Methods: This retrospective cohort study used anonymized, longitudinal patient data from 5 country-level primary care databases, including Australia, Belgium, France, Germany, and the UK.

Loss-of-function variant in chymotrypsin like elastase 3B (CELA3B) is associated with non-alcoholic chronic pancreatitis.

Background: Genetic alterations in digestive enzymes have been associated with chronic pancreatitis (CP). Recently, chymotrypsin like elastase 3B (CELA3B) emerged as a novel risk gene. Thus, we evaluated CELA3B in two European cohorts with CP.

Preferences for and use of oral anticoagulants for stroke prevention in atrial fibrillation under real-world conditions in Germany: A survey among physicians.

In Germany, there is little real-world evidence on physicians' choice of oral anticoagulants (OACs). Our study aimed at assessing preferences for and prescribing patterns of treatment options for stroke prevention in atrial fibrillation in clinical practice in Germany. We conducted a nationwide quantitative online survey among office-based physicians in Germany.

Feasible approaches and implementation challenges to atrial fibrillation screening: a qualitative study of stakeholder views in 11 European countries.

Objectives: Atrial fibrillation (AF) screening may increase early detection and reduce complications of AF. European, Australian and World Heart Federation guidelines recommend opportunistic screening, despite a current lack of clear evidence supporting a net benefit for systematic screening. Where screening is implemented, the most appropriate approaches are unknown.