Perioperative lung expansion and pulmonary outcomes after open abdominal surgery versus usual care in the USA (PRIME-AIR): a multicentre, randomised, controlled, phase 3 trial.

Background: Postoperative pulmonary complications (PPCs) are a leading cause of morbidity, death, and increased use of health-care resources. We aimed to determine whether a perioperative lung expansion bundle including individualised intraoperative management reduces PPC severity in patients undergoing major open abdominal surgery compared with usual care.

Methods: In this multicentre, randomised controlled phase 3 trial (PRIME-AIR), we enrolled adult patients (age ≥18 years) scheduled for an elective open abdominal surgery that would last at least 2 h, who were at intermediate or high risk for PPCs on the basis of their Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) score (a score of ≥26), and who had a BMI below 35 kg/m at 17 academic hospitals across ten states in the USA.

Pitfalls in performing genome-wide association studies on ratio traits.

Genome-wide association studies (GWASs) are often performed on ratios composed of a numerator trait divided by a denominator trait. Examples include body mass index (BMI) and the waist-to-hip ratio, among many others. Explicitly or implicitly, the goal of forming the ratio is typically to adjust for an association between the numerator and denominator.

EmbedGEM: a framework to evaluate the utility of embeddings for genetic discovery.

Summary: Machine learning-derived embeddings are a compressed representation of high content data modalities. Embeddings can capture detailed information about disease states and have been qualitatively shown to be useful in genetic discovery. Despite their promise, embeddings have a major limitation: it is unclear if genetic variants associated with embeddings are relevant to the disease or trait of interest.

Effects of Serratus Anterior Plane Block on Early Recovery from Thoracoscopic Lung Resection: A Randomized, Blinded, Placebo-controlled Trial.

Background: The efficacy of serratus anterior plane block for treatment of pain after minimally invasive thoracic surgery remains unclear. This trial assesses the impact of serratus anterior plane block on postoperative opioid consumption and on measures of early recovery after thoracoscopic lung resection.

Methods: Patients undergoing minimally invasive anatomic lung resection at a single center were randomized to undergo serratus anterior plane block with 40 ml injectate containing bupivacaine 0.

The mitochondrial multi-omic response to exercise training across rat tissues.

Mitochondria have diverse functions critical to whole-body metabolic homeostasis. Endurance training alters mitochondrial activity, but systematic characterization of these adaptations is lacking. Here, the Molecular Transducers of Physical Activity Consortium mapped the temporal, multi-omic changes in mitochondrial analytes across 19 tissues in male and female rats trained for 1, 2, 4, or 8 weeks.

Molecular adaptations in response to exercise training are associated with tissue-specific transcriptomic and epigenomic signatures.

Regular exercise has many physical and brain health benefits, yet the molecular mechanisms mediating exercise effects across tissues remain poorly understood. Here we analyzed 400 high-quality DNA methylation, ATAC-seq, and RNA-seq datasets from eight tissues from control and endurance exercise-trained (EET) rats. Integration of baseline datasets mapped the gene location dependence of epigenetic control features and identified differing regulatory landscapes in each tissue.

Sexual dimorphism and the multi-omic response to exercise training in rat subcutaneous white adipose tissue.

Subcutaneous white adipose tissue (scWAT) is a dynamic storage and secretory organ that regulates systemic homeostasis, yet the impact of endurance exercise training (ExT) and sex on its molecular landscape is not fully established. Utilizing an integrative multi-omics approach, and leveraging data generated by the Molecular Transducers of Physical Activity Consortium (MoTrPAC), we show profound sexual dimorphism in the scWAT of sedentary rats and in the dynamic response of this tissue to ExT. Specifically, the scWAT of sedentary females displays -omic signatures related to insulin signaling and adipogenesis, whereas the scWAT of sedentary males is enriched in terms related to aerobic metabolism.

A Bayesian network meta-analysis of 14 molecules inhibiting UV daylight-induced pigmentation.

Introduction: Hyperpigmentation disorders are very frequent, affect the quality of life and may become a psychological burden for afflicted patients. Many anti-pigmenting or depigmenting agents are available with various efficacy and almost no comparative data. 2-mercaptonicotinoyl glycine (2-MNG) was recently proposed as a viable candidate showing safe and effective results on hyperpigmentation control in vitro and in vivo.

Genetic architecture of cardiac dynamic flow volumes.

Cardiac blood flow is a critical determinant of human health. However, the definition of its genetic architecture is limited by the technical challenge of capturing dynamic flow volumes from cardiac imaging at scale. We present DeepFlow, a deep-learning system to extract cardiac flow and volumes from phase-contrast cardiac magnetic resonance imaging.

Oncogenic context shapes the fitness landscape of tumor suppression.

Tumors acquire alterations in oncogenes and tumor suppressor genes in an adaptive walk through the fitness landscape of tumorigenesis. However, the interactions between oncogenes and tumor suppressor genes that shape this landscape remain poorly resolved and cannot be revealed by human cancer genomics alone. Here, we use a multiplexed, autochthonous mouse platform to model and quantify the initiation and growth of more than one hundred genotypes of lung tumors across four oncogenic contexts: KRAS G12D, KRAS G12C, BRAF V600E, and EGFR L858R.

Evolving Perspectives on Esophagectomy Care: Clinical Update.

Recent changes in perioperative care have led to new perspectives and important advances that have helped to improve outcomes among patients treated with esophagectomy for esophageal cancer.

Objective and automatic grading system of facial signs from smartphones' pictures in South African men: Validation versus dermatologists and characterization of changes with age.

Objective: To evaluate the capacity of the automatic detection system to accurately grade, from selfie pictures, the severity of eight facial signs in South African men.

Methods: Selfie pictures (obtained from frontal and back cameras) of 281 South African men differently aged (20-70 years) were obtained and analyzed by an automatic artificial intelligence (AI)-based automatic grading system. Data were compared with the clinical gradings made by experts and dermatologists.

Sexual dimorphism and the multi-omic response to exercise training in rat subcutaneous white adipose tissue.

Subcutaneous white adipose tissue (scWAT) is a dynamic storage and secretory organ that regulates systemic homeostasis, yet the impact of endurance exercise training and sex on its molecular landscape has not been fully established. Utilizing an integrative multi-omics approach with data generated by the Molecular Transducers of Physical Activity Consortium (MoTrPAC), we identified profound sexual dimorphism in the dynamic response of rat scWAT to endurance exercise training. Despite similar cardiorespiratory improvements, only male rats reduced whole-body adiposity, scWAT adipocyte size, and total scWAT triglyceride abundance with training.

The mitochondrial multi-omic response to exercise training across tissues.

Mitochondria are adaptable organelles with diverse cellular functions critical to whole-body metabolic homeostasis. While chronic endurance exercise training is known to alter mitochondrial activity, these adaptations have not yet been systematically characterized. Here, the Molecular Transducers of Physical Activity Consortium (MoTrPAC) mapped the longitudinal, multi-omic changes in mitochondrial analytes across 19 tissues in male and female rats endurance trained for 1, 2, 4 or 8 weeks.

Deconvoluting complex correlates of COVID-19 severity with a multi-omic pandemic tracking strategy.

The SARS-CoV-2 pandemic has differentially impacted populations across race and ethnicity. A multi-omic approach represents a powerful tool to examine risk across multi-ancestry genomes. We leverage a pandemic tracking strategy in which we sequence viral and host genomes and transcriptomes from nasopharyngeal swabs of 1049 individuals (736 SARS-CoV-2 positive and 313 SARS-CoV-2 negative) and integrate them with digital phenotypes from electronic health records from a diverse catchment area in Northern California.

The genetic etiology of periodic limb movement in sleep.

Study Objectives: Periodic limb movement in sleep is a common sleep phenotype characterized by repetitive leg movements that occur during or before sleep. We conducted a genome-wide association study (GWAS) of periodic limb movements in sleep (PLMS) using a joint analysis (i.e.

Amiodarone with or without N-Acetylcysteine for the Prevention of Atrial Fibrillation after Thoracic Surgery: A Double-blind, Randomized Trial.

Background: Postoperative atrial fibrillation may identify patients at risk of subsequent atrial fibrillation, with its greater risk of stroke. This study hypothesized that N-acetylcysteine mitigates inflammation and oxidative stress to reduce the incidence of postoperative atrial fibrillation.

Methods: In this double-blind, placebo-controlled trial, patients at high risk of postoperative atrial fibrillation scheduled to undergo major thoracic surgery were randomized to N-acetylcysteine plus amiodarone or placebo plus amiodarone.

Mono- and Biallelic Protein-Truncating Variants in Alpha-Actinin 2 Cause Cardiomyopathy Through Distinct Mechanisms.

Background: ACTN2 (alpha-actinin 2) anchors actin within cardiac sarcomeres. The mechanisms linking mutations to myocardial disease phenotypes are unknown. Here, we characterize patients with novel mutations to reveal insights into the physiological function of ACTN2.