mulea: An R package for enrichment analysis using multiple ontologies and empirical false discovery rate.

Traditional gene set enrichment analyses are typically limited to a few ontologies and do not account for the interdependence of gene sets or terms, resulting in overcorrected p-values. To address these challenges, we introduce mulea, an R package offering comprehensive overrepresentation and functional enrichment analysis. mulea employs a progressive empirical false discovery rate (eFDR) method, specifically designed for interconnected biological data, to accurately identify significant terms within diverse ontologies.

Frontoparietal network integrity supports cognitive function in pre-symptomatic frontotemporal dementia: Multimodal analysis of brain function, structure, and perfusion.

Introduction: Genetic mutation carriers of frontotemporal dementia can remain cognitively well despite neurodegeneration. A better understanding of brain structural, perfusion, and functional patterns in the pre-symptomatic stage could inform accurate staging and potential mechanisms.

Methods: We included 207 pre-symptomatic genetic mutation carriers and 188 relatives without mutations.

Innate immune response in acute critical illness: a narrative review.

Background: Activation of innate immunity is a first line of host defense during acute critical illness (ACI) that aims to contain injury and avoid tissue damages. Aberrant activation of innate immunity may also participate in the occurrence of organ failures during critical illness. This review aims to provide a narrative overview of recent advances in the field of innate immunity in critical illness, and to consider future potential therapeutic strategies.

Detecting heart failure from B-mode ultrasound characterization of arterial pulse waves.

This study investigated the sensitivity and specificity of identifying heart failure with reduced ejection fraction (HFrEF) from measurements of the intensity and timing of arterial pulse waves. Previously validated methods combining ultrafast B-mode ultrasound, plane-wave transmission, singular value decomposition (SVD), and speckle tracking were used to characterize the compression and decompression ("S" and "D") waves occurring in early and late systole, respectively, in the carotid arteries of outpatients with left ventricular ejection fraction (LVEF) < 40%, determined by echocardiography, and signs and symptoms of heart failure, or with LVEF ≥ 50% and no signs or symptoms of heart failure. On average, the HFrEF group had significantly reduced S-wave intensity and energy, a greater interval between the R wave of the ECG and the S wave, a reduced interval between the S and D waves, and an increase in the S-wave shift (SWS), a novel metric that characterizes the shift in timing of the S wave away from the R wave of the ECG and toward the D wave (all < 0.

Comprehensive allostatic load risk index is associated with increased frontal and left parietal white matter hyperintensities in mid-life cognitively healthy adults.

To date, there is a considerable heterogeneity of methods to score Allostatic Load (AL). Here we propose a comprehensive algorithm (ALCS) that integrates commonly used approaches to generate AL risk categories and assess associations to brain structure deterioration. In a cohort of cognitively normal mid-life adults (n = 620, age 51.

Robotic Distal Pancreatectomy Yields Superior Outcomes Compared to Laparoscopic Technique: A Single Surgeon Experience of 123 Consecutive Cases.

Technical limitations of laparoscopic distal pancreatectomy (LDP), in comparison to robotic distal pancreatectomy (RDP), may translate to high conversion rates and morbidity. LDP and RDP procedures performed between December 2008 and January 2023 in our tertiary referral hepatobiliary and pancreatic centres were analysed and compared with regard to short-term outcomes. A total of 62 consecutive LDP cases and 61 RDP cases were performed.

Left bundle branch pacing with and without anodal capture: impact on ventricular activation pattern and acute haemodynamics.

Aims: Left bundle branch pacing (LBBP) can deliver physiological left ventricular activation, but typically at the cost of delayed right ventricular (RV) activation. Right ventricular activation can be advanced through anodal capture, but there is uncertainty regarding the mechanism by which this is achieved, and it is not known whether this produces haemodynamic benefit.

Methods And Results: We recruited patients with LBBP leads in whom anodal capture eliminated the terminal R-wave in lead V1.

A genome-wide association study of blood cell morphology identifies cellular proteins implicated in disease aetiology.

Blood cells contain functionally important intracellular structures, such as granules, critical to immunity and thrombosis. Quantitative variation in these structures has not been subjected previously to large-scale genetic analysis. We perform genome-wide association studies of 63 flow-cytometry derived cellular phenotypes-including cell-type specific measures of granularity, nucleic acid content and reactivity-in 41,515 participants in the INTERVAL study.

Relationship between COVID-19 and ICU-Acquired Bloodstream Infections Related to Multidrug-Resistant Bacteria.

A bloodstream infection (BSI) is a severe ICU-acquired infection. A growing proportion is caused by multidrug-resistant bacteria (MDRB). COVID-19 was reported to be associated with a high rate of secondary infections.

Computerised cognitive assessment in patients with traumatic brain injury: an observational study of feasibility and sensitivity relative to established clinical scales.

Background: Online technology could potentially revolutionise how patients are cognitively assessed and monitored. However, it remains unclear whether assessments conducted remotely can match established pen-and-paper neuropsychological tests in terms of sensitivity and specificity.

Methods: This observational study aimed to optimise an online cognitive assessment for use in traumatic brain injury (TBI) clinics.

Ventilator-Associated Pneumonia in Immunosuppressed Patients.

Immunocompromised patients-including patients with cancer, hematological malignancies, solid organ transplants and individuals receiving immunosuppressive therapies for autoimmune diseases-account for an increasing proportion of critically-ill patients. While their prognosis has improved markedly in the last decades, they remain at increased risk of healthcare- and intensive care unit (ICU)-acquired infections. The most frequent of these are ventilator-associated lower respiratory tract infections (VA-LTRI), which include ventilator-associated pneumonia (VAP) and tracheobronchitis (VAT).

A mechanistic evaluation of human beta defensin 2 mediated protection of human skin barrier in vitro.

The human skin barrier, a biological imperative, is impaired in inflammatory skin diseases such as atopic dermatitis (AD). Staphylococcus aureus is associated with AD lesions and contributes to pathological inflammation and further barrier impairment. S.

Clinical validation of an artificial intelligence-assisted algorithm for automated quantification of left ventricular ejection fraction in real time by a novel handheld ultrasound device.

Aims: We sought to evaluate the reliability and diagnostic accuracy of a novel handheld ultrasound device (HUD) with artificial intelligence (AI) assisted algorithm to automatically calculate ejection fraction (autoEF) in a real-world patient population.

Methods And Results: We studied 100 consecutive patients (57 ± 15 years old, 61% male), including 38 with abnormal left ventricular (LV) function [LV ejection fraction (LVEF) < 50%]. The autoEF results acquired using the HUD were independently compared with manually traced biplane Simpson's rule measurements on cart-based systems to assess method agreement using intra-class correlation coefficient (ICC), linear regression analysis, and Bland-Altman analysis.

A Novel Handheld Echocardiography Device with Continuous-Wave Doppler Capability: Implications for the Evaluation of Aortic Stenosis Severity.

Background: The aim of this study was to evaluate the ability of a novel handheld echocardiography (HHE) device with continuous-wave Doppler (CWD) capability to measure aortic valve peak jet velocity (Vmax) and facilitate aortic stenosis (AS) severity grading.

Methods: One hundred twenty-one consecutive patients with known or suspected AS were prospectively included. All patients were scanned with the HHE device and a high-end echocardiography system (the reference standard) to obtain CWD signal across the aortic valve.

Thrombosis with thrombocytopenia after AZD1222 (ChAdOx1 nCov-19) vaccination: Case characteristics and associations.

Background: Post-marketing surveillance for COVID-19 vaccines during the pandemic identified an extremely rare thrombosis with thrombocytopenia syndrome (TTS) reported post-vaccination, requiring further characterisation to improve diagnosis and management.

Methods: We searched the AstraZeneca Global Safety Database (through April 26, 2021) for cases with co-reported thrombocytopenia and thrombosis (using standardised MedDRA queries/high-level terms) following AZD1222 (ChAdOx1 nCoV-19). Cases were adjudicated by experts as 'typical','possible', 'no' or 'unknown' according to available TTS criteria.

Highlighting uncertainty in clinical risk prediction using a model of emergency laparotomy mortality risk.

Clinical prediction models typically make point estimates of risk. However, values of key variables are often missing during model development or at prediction time, meaning that the point estimates mask significant uncertainty and can lead to over-confident decision making. We present a model of mortality risk in emergency laparotomy which instead presents a distribution of predicted risks, highlighting the uncertainty over the risk of death with an intuitive visualisation.

The clinical effectiveness and cost effectiveness of clozapine for inpatients with severe borderline personality disorder (CALMED study): a randomised placebo-controlled trial.

Background: Data from case series suggest that clozapine may benefit inpatients with borderline personality disorder (BPD), but randomised trials have not been conducted.

Methods: Multicentre, double-blind, placebo-controlled trial. We aimed to recruit 222 inpatients with severe BPD aged 18 or over, who had failed to respond to other antipsychotic medications.

Evaluating Rates of Recurrent Ischemic Stroke Among Young Adults With Embolic Stroke of Undetermined Source: The Young ESUS Longitudinal Cohort Study.

Importance: Cryptogenic strokes constitute approximately 40% of ischemic strokes in young adults, and most meet criteria for the embolic stroke of undetermined source (ESUS). Two randomized clinical trials, NAVIGATE ESUS and RESPECT ESUS, showed a high rate of stroke recurrence in older adults with ESUS but the prognosis and prognostic factors among younger individuals with ESUS is uncertain.

Objective: To determine rates of and factors associated with recurrent ischemic stroke and death and new-onset atrial fibrillation (AF) among young adults.

OCT2013, an ischaemia-activated antiarrhythmic prodrug, devoid of the systemic side effects of lidocaine.

Background And Purpose: Sudden cardiac death (SCD) caused by acute myocardial ischaemia and ventricular fibrillation (VF) is an unmet therapeutic need. Lidocaine suppresses ischaemia-induced VF, but its utility is limited by side effects and a narrow therapeutic index. Here, we characterise OCT2013, a putative ischaemia-activated prodrug of lidocaine.

Pulmonary embolism with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a common, preventable, and treatable disease. The incidence of COPD is growing annually in China, and it is a significant and growing public health burden. Multivariate analysis showed that COPD was one of the independent risk factors for the occurrence of pulmonary embolism (PE), and the incidence of PE was significantly higher in COPD patients than in normal subjects.

Comparing invasive hemodynamic responses in adenosine hyperemia versus physical exercise stress in chronic coronary syndromes.

Objectives: Adenosine hyperemia is an integral component of the physiological assessment of obstructive coronary artery disease in patients with chronic coronary syndrome (CCS). The aim of this study was to compare systemic, coronary and microcirculatory hemodynamics between intravenous (IV) adenosine hyperemia versus physical exercise stress in patients with CCS and coronary stenosis.

Methods: Twenty-three patients (mean age, 60.