Effect of inspiratory lung volume on bronchial and arterial dimensions and ratios on chest computed tomography in patients with chronic obstructive pulmonary disease.

Background: The assessment of bronchus-artery (BA) metrics on chest CT is important for detecting airway abnormalities. It is less clear how BA metrics are dependent on lung volume.

Methods: CTs were obtained from a COPDGene substudy investigating the impact of radiation dose on lung density.

Endobronchial valve treatment improves chest-CT diaphragm configuration in COPD.

This study investigated the impact of bronchoscopic lung volume reduction treatment using endobronchial valves (EBV) on diaphragm configuration. We successfully analyzed the diaphragm index using a newly developed quantitative computed tomography (QCT) tool before and after EBV treatment in forty patients with severe emphysema. We evaluated whether changes in the diaphragm index were associated with improvements in forced expiratory volume in 1 s (FEV), residual volume (RV), Saint Georges Respiratory Questionnaire (SGRQ), and 6-min walking distance (6MWD) using Spearman's rho.

Higher small pulmonary artery and vein volume on computed tomography is associated with mortality in current and former smokers.

Background: In chronic obstructive pulmonary disease (COPD), vascular alterations have been shown to contribute to hypoxia and pulmonary hypertension, but the independent contribution of small vessel abnormalities to mortality remains unclear.

Methods: We quantified artery and vein dimensions on computed tomography (CT) down to 0.2 mm.

FIGNL1-FIRRM is essential for meiotic recombination and prevents DNA damage-independent RAD51 and DMC1 loading.

During meiosis, nucleoprotein filaments of the strand exchange proteins RAD51 and DMC1 are crucial for repairing SPO11-generated DNA double-strand breaks (DSBs) by homologous recombination (HR). A balanced activity of positive and negative RAD51/DMC1 regulators ensures proper recombination. Fidgetin-like 1 (FIGNL1) was previously shown to negatively regulate RAD51 in human cells.

Structure and position-aware graph neural network for airway labeling.

We present a novel graph-based approach for labeling the anatomical branches of a given airway tree segmentation. The proposed method formulates airway labeling as a branch classification problem in the airway tree graph, where branch features are extracted using convolutional neural networks and enriched using graph neural networks. Our graph neural network is structure-aware by having each node aggregate information from its local neighbors and position-aware by encoding node positions in the graph.

An Observational Study of Sexual Assaults in French Guiana During 2019-2020.

Introduction: Sexual violence is a major public health issue, including in French Guiana. The feeling of insecurity is significant in this part of France. Sexual violence is an important reason for consultation in forensic and emergency medicine.

HLTF disrupts Cas9-DNA post-cleavage complexes to allow DNA break processing.

The outcome of CRISPR-Cas-mediated genome modifications is dependent on DNA double-strand break (DSB) processing and repair pathway choice. Homology-directed repair (HDR) of protein-blocked DSBs requires DNA end resection that is initiated by the endonuclease activity of the MRE11 complex. Using reconstituted reactions, we show that Cas9 breaks are unexpectedly not directly resectable by the MRE11 complex.

Uncoupling programmed DNA cleavage and repair scrambles the Paramecium somatic genome.

In the ciliate Paramecium, precise excision of numerous internal eliminated sequences (IESs) from the somatic genome is essential at each sexual cycle. DNA double-strands breaks (DSBs) introduced by the PiggyMac endonuclease are repaired in a highly concerted manner by the non-homologous end joining (NHEJ) pathway, illustrated by complete inhibition of DNA cleavage when Ku70/80 proteins are missing. We show that expression of a DNA-binding-deficient Ku70 mutant (Ku70-6E) permits DNA cleavage but leads to the accumulation of unrepaired DSBs.

The relationship of fat and muscle measurements with emphysema and bronchial wall thickening in smokers.

Introduction: Differences in body composition in patients with COPD may have important prognostic value and may provide opportunities for patient-specific management. We investigated the relation of thoracic fat and muscle with computed tomography (CT)-measured emphysema and bronchial wall thickening.

Methods: Low-dose baseline chest CT scans from 1031 male lung cancer screening participants from one site were quantified for emphysema, bronchial wall thickening, subcutaneous fat, visceral fat and skeletal muscle.

Dysanapsis is differentially related to lung function trajectories with distinct structural and functional patterns in COPD and variable risk for adverse outcomes.

Background: Abnormal lung function trajectories are associated with increased risk of chronic obstructive pulmonary disease (COPD) and premature mortality; several risk factors for following these trajectories have been identified. Airway under-sizing dysanapsis (small airway lumens relative to lung size), is associated with an increased risk for COPD. The relationship between dysanapsis and lung function trajectories at risk for adverse outcomes of COPD is largely unexplored.

Bronchiectasis is associated with lower lung function in lung cancer screening participants.

Background And Objective: Bronchiectasis is a frequent incidental finding on chest computed tomography (CT), but its relevance in lung cancer screening is not fully understood. We investigated the association between bronchiectasis and respiratory symptoms, pulmonary function, and emphysema in lung cancer screening participants with and without chronic obstructive pulmonary disease (COPD).

Methods: We included 3260 (ex-)smokers from the Dutch-Belgian lung cancer screening trial (NELSON).

Structural and functional basis of inositol hexaphosphate stimulation of NHEJ through stabilization of Ku-XLF interaction.

The classical Non-Homologous End Joining (c-NHEJ) pathway is the predominant process in mammals for repairing endogenous, accidental or programmed DNA Double-Strand Breaks. c-NHEJ is regulated by several accessory factors, post-translational modifications, endogenous chemical agents and metabolites. The metabolite inositol-hexaphosphate (IP6) stimulates c-NHEJ by interacting with the Ku70-Ku80 heterodimer (Ku).

Automatic analysis of bronchus-artery dimensions to diagnose and monitor airways disease in cystic fibrosis.

Background: Cystic fibrosis (CF) lung disease is characterised by progressive airway wall thickening and widening. We aimed to validate an artificial intelligence-based algorithm to assess dimensions of all visible bronchus-artery (BA) pairs on chest CT scans from patients with CF.

Methods: The algorithm fully automatically segments the bronchial tree; identifies bronchial generations; matches bronchi with the adjacent arteries; measures for each BA-pair bronchial outer diameter (B), bronchial lumen diameter (B), bronchial wall thickness (B) and adjacent artery diameter (A); and computes B/A, B/A and B/A for each BA pair from the segmental bronchi to the last visible generation.

Emphysema subtyping on thoracic computed tomography scans using deep neural networks.

Accurate identification of emphysema subtypes and severity is crucial for effective management of COPD and the study of disease heterogeneity. Manual analysis of emphysema subtypes and severity is laborious and subjective. To address this challenge, we present a deep learning-based approach for automating the Fleischner Society's visual score system for emphysema subtyping and severity analysis.

Precision Medicine for More Oxygen (P4O2)-Study Design and First Results of the Long COVID-19 Extension.

: The coronavirus disease 2019 (COVID-19) pandemic has led to the death of almost 7 million people, however, with a cumulative incidence of 0.76 billion, most people survive COVID-19. Several studies indicate that the acute phase of COVID-19 may be followed by persistent symptoms including fatigue, dyspnea, headache, musculoskeletal symptoms, and pulmonary functional-and radiological abnormalities.

Cryo-EM structure of a DNA-PK trimer: higher order oligomerisation in NHEJ.

The ability of humans to maintain the integrity of the genome is imperative for cellular survival. DNA double-strand breaks (DSBs) are considered the most critical type of DNA lesion, which can ultimately lead to diseases including cancer. Non-homologous end joining (NHEJ) is one of two core mechanisms utilized to repair DSBs.

PAXX binding to the NHEJ machinery explains functional redundancy with XLF.

Nonhomologous end joining is a critical mechanism that repairs DNA double-strand breaks in human cells. In this work, we address the structural and functional role of the accessory protein PAXX [paralog of x-ray repair cross-complementing protein 4 (XRCC4) and XRCC4-like factor (XLF)] in this mechanism. Here, we report high-resolution cryo-electron microscopy (cryo-EM) and x-ray crystallography structures of the PAXX C-terminal Ku-binding motif bound to Ku70/80 and cryo-EM structures of PAXX bound to two alternate DNA-dependent protein kinase (DNA-PK) end-bridging dimers, mediated by either Ku80 or XLF.

Automatic bronchus and artery analysis on chest computed tomography to evaluate the effect of inhaled hypertonic saline in children aged 3-6 years with cystic fibrosis in a randomized clinical trial.

Background: SHIP-CT showed that 48-week treatment with inhaled 7% hypertonic saline (HS) reduced airway abnormalities on chest CT using the manual PRAGMA-CF method relative to isotonic saline (IS) in children aged 3-6 years with cystic fibrosis (CF). An algorithm was developed and validated to automatically measure bronchus and artery (BA) dimensions of BA-pairs on chest CT. Aim of the study was to assess the effect of HS on bronchial wall thickening and bronchial widening using the BA-analysis.