Proline substitutions in the ASIC1 β11-12 linker slow desensitization.

Desensitization is a prominent feature of nearly all ligand-gated ion channels. Acid-sensing ion channels (ASICs) undergo desensitization within hundreds of milliseconds to seconds upon continual extracellular acidification. The ASIC mechanism of desensitization is primarily due to the isomerization or "flipping" of a short linker joining the 11th and 12th β sheets in the extracellular domain.

Distribution of Solid Lung Nodules Presence and Size by Age and Sex in a Northern European Nonsmoking Population.

Background Most of the data regarding prevalence and size distribution of solid lung nodules originates from lung cancer screening studies that target high-risk populations or from Asian general cohorts. In recent years, the identification of lung nodules in non-high-risk populations, scanned for clinical indications, has increased. However, little is known about the presence of solid lung nodules in the Northern European nonsmoking population.

Effect of emphysema on AI software and human reader performance in lung nodule detection from low-dose chest CT.

Background: Emphysema influences the appearance of lung tissue in computed tomography (CT). We evaluated whether this affects lung nodule detection by artificial intelligence (AI) and human readers (HR).

Methods: Individuals were selected from the "Lifelines" cohort who had undergone low-dose chest CT.

Who is at risk of lung nodules on low-dose CT in a Western country? A population-based approach.

Background: This population-based study aimed to identify the risk factors for lung nodules in a Western European general population.

Methods: We quantified the presence or absence of lung nodules among 12 055 participants of the Dutch population-based ImaLife (Imaging in Lifelines) study (age ≥45 years) who underwent low-dose chest computed tomography. Outcomes included the presence of 1) at least one solid lung nodule (volume ≥30 mm) and 2) a clinically relevant lung nodule (volume ≥100 mm).

A quality improvement study on the effect of electronic transmission of a basic discharge medication report on medication discrepancies in patients discharged from the hospital.

Background: Medication discrepancies can occur in transitions of care because of a lack of communication between hospitals and community pharmacies. These discrepancies can lead to preventable adverse drug events (ADEs).

Aim: To investigate the effect of electronic transmission of the basic discharge medication report on unintentional medication discrepancies observed between this report and the 28-day post-discharge status in the community pharmacy.

Photomodulation of the ASIC1a acidic pocket destabilizes the open state.

Acid-sensing ion channels (ASICs) are important players in detecting extracellular acidification throughout the brain and body. ASICs have large extracellular domains containing two regions replete with acidic residues: the acidic pocket, and the palm domain. In the resting state, the acidic pocket is in an expanded conformation but collapses in low pH conditions as the acidic side chains are neutralized.

Predicted versus CT-derived total lung volume in a general population: The ImaLife study.

Predicted lung volumes based on the Global Lung Function Initiative (GLI) model are used in pulmonary disease detection and monitoring. It is unknown how well the predicted lung volume corresponds with computed tomography (CT) derived total lung volume (TLV). The aim of this study was to compare the GLI-2021 model predictions of total lung capacity (TLC) with CT-derived TLV.

CT-based emphysema characterization per lobe: A proof of concept.

Purpose: The Fleischner society criteria are global criteria to visually evaluate and classify pulmonary emphysema on CT. It may group heterogeneous disease severity within the same category, potentially obscuring clinically relevant differences in emphysema severity. This proof-of-concept study proposes to split emphysema into more categories and to assess each lobe separately, and applies this to two general population-based cohort samples to assess what information such an extension adds.

CT characteristics of solid pulmonary nodules of never smokers versus smokers: A population-based study.

Purpose: Aim was to assess CT characteristics of lung nodules in never and former smokers compared to current smokers in a population-based setting.

Method: We included individuals aged 45-60 years taking part in the ImaLife (Imaging in Lifelines) study, with at least one solid lung nodule (≥30 mm) on low-dose chest CT. Qualitative (location, shape, margin, nodule type, attached structures) and quantitative (count, diameter, volume) nodule characteristics were evaluated.

Antisense Oligonucleotide Therapy: From Design to the Huntington Disease Clinic.

Huntington disease (HD) is a fatal progressive neurodegenerative disorder caused by an inherited mutation in the huntingtin (HTT) gene, which encodes mutant HTT protein. Though HD remains incurable, various preclinical studies have reported a favorable response to HTT suppression, emphasizing HTT lowering strategies as prospective disease-modifying treatments. Antisense oligonucleotides (ASOs) lower HTT by targeting transcripts and are well suited for treating neurodegenerative disorders as they distribute broadly throughout the central nervous system (CNS) and are freely taken up by neurons, glia, and ependymal cells.

AI-Driven Model for Automatic Emphysema Detection in Low-Dose Computed Tomography Using Disease-Specific Augmentation.

The objective of this study is to evaluate the feasibility of a disease-specific deep learning (DL) model based on minimum intensity projection (minIP) for automated emphysema detection in low-dose computed tomography (LDCT) scans. LDCT scans of 240 individuals from a population-based cohort in the Netherlands (ImaLife study, mean age ± SD = 57 ± 6 years) were retrospectively chosen for training and internal validation of the DL model. For independent testing, LDCT scans of 125 individuals from a lung cancer screening cohort in the USA (NLST study, mean age ± SD = 64 ± 5 years) were used.

Qualitative Evaluation of Common Quantitative Metrics for Clinical Acceptance of Automatic Segmentation: a Case Study on Heart Contouring from CT Images by Deep Learning Algorithms.

Organs-at-risk contouring is time consuming and labour intensive. Automation by deep learning algorithms would decrease the workload of radiotherapists and technicians considerably. However, the variety of metrics used for the evaluation of deep learning algorithms make the results of many papers difficult to interpret and compare.

Molecular Investigation of Chicken Acid-Sensing Ion Channel 1 β11-12 Linker Isomerization and Channel Kinetics.

Structures of the trimeric acid-sensing ion channel have been solved in the resting, toxin-bound open and desensitized states. Within the extracellular domain, there is little difference between the toxin-bound open state and the desensitized state. The main exception is that a loop connecting the 11th and 12th β-strand, just two amino acid residues long, undergoes a significant and functionally critical re-orientation or flipping between the open and desensitized conformations.

Improved precision of noise estimation in CT with a volume-based approach.

Assessment of image noise is a relevant issue in computed tomography (CT). Noise is routinely measured by the standard deviation of density values (Hounsfield units, HU) within a circular region of interest (ROI). We explored the effect of a spherical volume of interest (VOI) on noise measurements.

Seasonal prevalence and characteristics of low-dose CT detected lung nodules in a general Dutch population.

We investigated whether presence and characteristics of lung nodules in the general population using low-dose computed tomography (LDCT) varied by season. Imaging in Lifelines (ImaLife) study participants who underwent chest LDCT-scanning between October 2018 and October 2019 were included in this sub-study. Hay fever season (summer) was defined as 1st April to 30th September and Influenza season (winter) as 1st October to 31st March.

Ultra-low-dose CT combined with noise reduction techniques for quantification of emphysema in COPD patients: An intra-individual comparison study with standard-dose CT.

Purpose: Phantom studies in CT emphysema quantification show that iterative reconstruction and deep learning-based noise reduction (DLNR) allow lower radiation dose. We compared emphysema quantification on ultra-low-dose CT (ULDCT) with and without noise reduction, to standard-dose CT (SDCT) in chronic obstructive pulmonary disease (COPD).

Method: Forty-nine COPD patients underwent ULDCT (third generation dual-source CT; 70ref-mAs, Sn-filter 100kVp; median CTDIvol 0.

Lung cancer prediction by Deep Learning to identify benign lung nodules.

Introduction: Deep Learning has been proposed as promising tool to classify malignant nodules. Our aim was to retrospectively validate our Lung Cancer Prediction Convolutional Neural Network (LCP-CNN), which was trained on US screening data, on an independent dataset of indeterminate nodules in an European multicentre trial, to rule out benign nodules maintaining a high lung cancer sensitivity.

Methods: The LCP-CNN has been trained to generate a malignancy score for each nodule using CT data from the U.

Evaluation of a novel deep learning-based classifier for perifissural nodules.

Objectives: To evaluate the performance of a novel convolutional neural network (CNN) for the classification of typical perifissural nodules (PFN).

Methods: Chest CT data from two centers in the UK and The Netherlands (1668 unique nodules, 1260 individuals) were collected. Pulmonary nodules were classified into subtypes, including "typical PFNs" on-site, and were reviewed by a central clinician.

Cardiovascular Risk Factors and Coronary Calcification in a Middle-aged Dutch Population: The ImaLife Study.

Purpose: To assess the presence of coronary artery calcium (CAC) and its association with cardiovascular risk factors and Systematic COronary Risk Evaluation (SCORE) risk in a middle-aged Dutch population.

Methods: Classic cardiovascular risk factors and CAC were analyzed in 4083 participants aged 45 to 60 years (57.9% women) from the population-based ImaLife study.

High-pitch dual-source CT for coronary artery calcium scoring: A head-to-head comparison of non-triggered chest versus triggered cardiac acquisition.

Background: To determine the effect of low-dose, high-pitch non-electrocardiographic (ECG)-triggered chest CT on coronary artery calcium (CAC) detection, quantification and risk stratification, compared to ECG-triggered cardiac CT.

Methods: We selected 1,000 participants from the ImaLife study, 50% with coronary calcification on cardiac CT. All participants underwent non-contrast cardiac CT followed by chest CT using third-generation dual-source technology.

Coupling structure with function in acid-sensing ion channels: challenges in pursuit of proton sensors.

Acid-sensing ion channels (ASICs) are a class of trimeric cation-selective ion channels activated by changes in pH within the physiological range. They are widely expressed in the central and peripheral nervous systems where they participate in a range of physiological and pathophysiological situations such as learning and memory, pain sensation, fear and anxiety, substance abuse and cell death. ASICs are localized to cell bodies and dendrites, including the postsynaptic density, and within the last 5 years several examples of proton-evoked ASIC excitatory postsynaptic currents have emerged.

Computed Tomography Screening for Early Lung Cancer, COPD and Cardiovascular Disease in Shanghai: Rationale and Design of a Population-based Comparative Study.

Rationale And Objectives: To describe the rational and design of a population-based comparative study. The objective of the study is to assess the screening performance of volume-based management of CT-detected lung nodule in comparison to diameter-based management, and to improve the effectiveness of CT screening for chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD), in addition to lung cancer, based on quantitative measurement of CT imaging biomarkers in a Chinese screening setting.

Materials And Methods: A population-based comparative study is being performed, including 10,000 asymptomatic participants between 40 and 74 years old from Shanghai urban population.

NaV1.1 and NaV1.6 selective compounds reduce the behavior phenotype and epileptiform activity in a novel zebrafish model for Dravet Syndrome.

Dravet syndrome is caused by dominant loss-of-function mutations in SCN1A which cause reduced activity of Nav1.1 leading to lack of neuronal inhibition. On the other hand, gain-of-function mutations in SCN8A can lead to a severe epileptic encephalopathy subtype by over activating NaV1.