Validation of volatile metabolites of pulmonary oxidative injury: a bench to bedside study.

Background: Changes in exhaled volatile organic compounds (VOCs) can be used to discriminate between respiratory diseases, and increased concentrations of hydrocarbons are commonly linked to oxidative stress. However, the VOCs identified are inconsistent between studies, and translational studies are lacking.

Methods: In this bench to bedside study, we captured VOCs in the headspace of A549 epithelial cells after exposure to hydrogen peroxide (HO), to induce oxidative stress, using high-capacity polydimethylsiloxane sorbent fibres.

Clusters of co-abundant proteins in the brain cortex associated with fronto-temporal lobar degeneration.

Background: Frontotemporal lobar degeneration (FTLD) is characterized pathologically by neuronal and glial inclusions of hyperphosphorylated tau or by neuronal cytoplasmic inclusions of TDP43. This study aimed at deciphering the molecular mechanisms leading to these distinct pathological subtypes.

Methods: To this end, we performed an unbiased mass spectrometry-based proteomic and systems-level analysis of the middle frontal gyrus cortices of FTLD-tau (n = 6), FTLD-TDP (n = 15), and control patients (n = 5).

Role of International Oil Companies in the Net-Zero Emission Energy Transition.

Scientific and engineering capabilities in hydrocarbon supply chains developed over decades in international oil and gas companies (IOCs) uniquely position these companies to drive rapid scale-up and transition to a net-zero emission economy. Flexible large-scale production of energy carriers such as hydrogen, ammonia, methanol, and other synthetic fuels produced with low- or zero-emission renewable power, nuclear energy, or hydrogen derived from natural gas with carbon capture and storage will enable long-distance transport and permanent storage options for clean energy. Use of energy carriers can overcome the inherent constraints of a fully electrified energy system by providing the energy and power densities, as well as transport and storage capacity, required to achieve energy supply and security in a net-zero emission economy, and over time allow optimization to the lowest cost for a consumer anywhere on the globe.

Puddle formation and persistent gaps across the non-mean-field breakdown of superconductivity in overdoped (Pb,Bi)SrCuO.

The cuprate high-temperature superconductors exhibit many unexplained electronic phases, but the superconductivity at high doping is often believed to be governed by conventional mean-field Bardeen-Cooper-Schrieffer theory. However, it was shown that the superfluid density vanishes when the transition temperature goes to zero, in contradiction to expectations from Bardeen-Cooper-Schrieffer theory. Our scanning tunnelling spectroscopy measurements in the overdoped regime of the (Pb,Bi)SrCuO high-temperature superconductor show that this is due to the emergence of nanoscale superconducting puddles in a metallic matrix.

Meeting the challenges of large-scale carbon storage and hydrogen production.

There is a pressing need to rapidly, and massively, scale up negative carbon strategies such as carbon capture and storage (CCS). At the same time, large-scale CCS can enable ramp-up of large-scale hydrogen production, a key component of decarbonized energy systems. We argue here that the safest, and most practical strategy for dramatically increasing CO storage in the subsurface is to focus on regions where there are multiple partially depleted oil and gas reservoirs.

(Cost-)effectiveness of a personalized multidisciplinary eHealth intervention for knee arthroplasty patients to enhance return to activities of daily life, work and sports - rationale and protocol of the multicentre ACTIVE randomized controlled trial.

Background: With the worldwide rising obesity epidemic and the aging population, it is essential to deliver (cost-)effective care that results in enhanced societal participation among knee arthroplasty patients. The purpose of this study is to describe the development, content, and protocol of our (cost-)effectiveness study that assesses a perioperative integrated care program, including a personalized eHealth app, for knee arthroplasty patients aimed to enhance societal participation post-surgery compared to care as usual.

Methods: The intervention will be tested in a multicentre randomized controlled trial with eleven participating Dutch medical centers (i.

Effect of tissue-grouped regulatory variants associated to type 2 diabetes in related secondary outcomes.

Genome-wide association studies have identified over five hundred loci that contribute to variation in type 2 diabetes (T2D), an established risk factor for many diseases. However, the mechanisms and extent through which these loci contribute to subsequent outcomes remain elusive. We hypothesized that combinations of T2D-associated variants acting on tissue-specific regulatory elements might account for greater risk for tissue-specific outcomes, leading to diversity in T2D disease progression.

Computed tomography-based radiomics for the differential diagnosis of pneumonitis in stage IV non-small cell lung cancer patients treated with immune checkpoint inhibitors.

Introduction: Immunotherapy-induced pneumonitis (IIP) is a serious side-effect which requires accurate diagnosis and management with high-dose corticosteroids. The differential diagnosis between IIP and other types of pneumonitis (OTP) remains challenging due to similar radiological patterns. This study was aimed to develop a prediction model to differentiate IIP from OTP in patients with stage IV non-small cell lung cancer (NSCLC) who developed pneumonitis during immunotherapy.

Monitoring of pulmonary involvement in critically ill COVID-19 patients - should lung ultrasound be preferred over CT?

Background: It is unclear if relevant changes in pulmonary involvement in critically ill COVID-19 patients can be reliably detected by the CT severity score (CTSS) and lung ultrasound score (LUSS), or if these changes have prognostic implications. In addition, it has been argued that adding pleural abnormalities to the LUSS could improve its prognostic value. The objective of this study was to compare LUSS and CTSS for the monitoring of COVID-19 pulmonary involvement through: first, establishing the correlation of LUSS (± pleural abnormalities) and CTSS throughout admission; second, assessing agreement and measurement error between raters for LUSS, pleural abnormalities, and CTSS; third, evaluating the association of the LUSS (± pleural abnormalities) and CTSS with mortality at different timepoints.

Prognostic Value of the Radiographic Assessment of Lung Edema Score in Mechanically Ventilated ICU Patients.

Introduction: The Radiographic Assessment of Lung Edema (RALE) score provides a semi-quantitative measure of pulmonary edema. In patients with acute respiratory distress syndrome (ARDS), the RALE score is associated with mortality. In mechanically ventilated patients in the intensive care unit (ICU) with respiratory failure not due to ARDS, a variable degree of lung edema is observed as well.

Patient specific intracranial neural signatures of obsessions and compulsions in the ventral striatum.

. Deep brain stimulation is a treatment option for patients with refractory obsessive-compulsive disorder. A new generation of stimulators hold promise for closed loop stimulation, with adaptive stimulation in response to biologic signals.

Protein disulfide isomerases as CSF biomarkers for the neuronal response to tau pathology.

Introduction: Cerebrospinal fluid (CSF) biomarkers for specific cellular disease processes are lacking for tauopathies. In this translational study we aimed to identify CSF biomarkers reflecting early tau pathology-associated unfolded protein response (UPR) activation.

Methods: We employed mass spectrometry proteomics and targeted immunoanalysis in a combination of biomarker discovery in primary mouse neurons in vitro and validation in patient CSF from two independent large multicentre cohorts (EMIF-AD MBD, n = 310; PRIDE, n = 771).

Polygenic risk score-based phenome-wide association study identifies novel associations for Tourette syndrome.

Tourette Syndrome (TS) is a complex neurodevelopmental disorder characterized by vocal and motor tics lasting more than a year. It is highly polygenic in nature with both rare and common previously associated variants. Epidemiological studies have shown TS to be correlated with other phenotypes, but large-scale phenome wide analyses in biobank level data have not been performed to date.

An economic evaluation of an online computer-tailored smoking cessation intervention that includes message frame-tailoring: A randomized controlled trial.

Evidence of economic evaluations of behaviour change interventions is scarce, but needed to guide policy makers' decision-making. This study economically evaluated 4 versions of an innovative online computer-tailored smoking cessation intervention. The economic evaluation from a societal perspective was embedded in a randomized controlled trial among 532 smokers using a 2 (message frame-tailoring, i.

Impact of the COVID-19 pandemic on surgical care in the Netherlands.

Background: The COVID-19 pandemic caused disruption of regular healthcare leading to reduced hospital attendances, repurposing of surgical facilities, and cancellation of cancer screening programmes. This study aimed to determine the impact of COVID-19 on surgical care in the Netherlands.

Methods: A nationwide study was conducted in collaboration with the Dutch Institute for Clinical Auditing.

Immunophenotypic aberrant hematopoietic stem cells in myelodysplastic syndromes: a biomarker for leukemic progression.

Myelodysplastic syndromes (MDS) comprise hematological disorders that originate from the neoplastic transformation of hematopoietic stem cells (HSCs). However, discrimination between HSCs and their neoplastic counterparts in MDS-derived bone marrows (MDS-BMs) remains challenging. We hypothesized that in MDS patients immature CD34CD38 cells with aberrant expression of immunophenotypic markers reflect neoplastic stem cells and that their frequency predicts leukemic progression.

Multi-Institutional Randomized Phase II Trial of Gefitinib for Previously Treated Patients With Advanced Non-Small-Cell Lung Cancer.

Purpose: To evaluate the efficacy and tolerability of two doses of gefitinib (Iressa [ZD1839]; AstraZeneca, Wilmington, DE), a novel epidermal growth factor receptor tyrosine kinase inhibitor, in patients with pretreated advanced non-small-cell lung cancer (NSCLC).

Patients And Methods: This was a randomized, double-blind, parallel-group, multicenter phase II trial. Two hundred ten patients with advanced NSCLC who were previously treated with one or two chemotherapy regimens (at least one containing platinum) were randomized to receive either 250-mg or 500-mg oral doses of gefitinib once daily.

Lung Ultrasound Prediction Model for Acute Respiratory Distress Syndrome: A Multicenter Prospective Observational Study.

Lung ultrasound (LUS) is a promising tool for diagnosis of acute respiratory distress syndrome (ARDS), but adequately sized studies with external validation are lacking. To develop and validate a data-driven LUS score for diagnosis of ARDS and compare its performance with that of chest radiography (CXR). This multicenter prospective observational study included invasively ventilated ICU patients who were divided into a derivation cohort and a validation cohort.

Electron microscopy analysis of astrocyte-synapse interactions shows altered dynamics in an Alzheimer's disease mouse model.

Introduction: Astrocyte-synapse bi-directional communication is required for neuronal development and synaptic plasticity. Astrocytes structurally interact with synapses using their distal processes also known as leaflets or perisynaptic astrocytic processes (PAPs). We recently showed that these PAPs are retracted from hippocampal synapses, and involved in the consolidation of fear memory.

Acute effects of deep brain stimulation on brain function in obsessive-compulsive disorder.

Objective: Deep brain stimulation (DBS) is an effective treatment for refractory obsessive-compulsive disorder (OCD) yet neural markers of optimized stimulation parameters are largely unknown. We aimed to describe (sub-)cortical electrophysiological responses to acute DBS at various voltages in OCD.

Methods: We explored how DBS doses between 3-5 V delivered to the ventral anterior limb of the internal capsule of five OCD patients affected electroencephalograms and intracranial local field potentials (LFPs).

A genome-wide association study of a rage-related misophonia symptom and the genetic link with audiological traits, psychiatric disorders, and personality.

Introduction: People with misophonia experience strong negative emotional responses to sounds and associated stimuli-mostly human produced-to an extent that it may cause impairment in social functioning. The exact nature of the disorder remains a matter of ongoing research and debate. Here, we investigated the genetic etiology of misophonia to understand contributing genetic factors and shed light on individual differences in characteristics that are related to the disorder.