Classification of non-TCGA cancer samples to TCGA molecular subtypes using compact feature sets.

Molecular subtypes, such as defined by The Cancer Genome Atlas (TCGA), delineate a cancer's underlying biology, bringing hope to inform a patient's prognosis and treatment plan. However, most approaches used in the discovery of subtypes are not suitable for assigning subtype labels to new cancer specimens from other studies or clinical trials. Here, we address this barrier by applying five different machine learning approaches to multi-omic data from 8,791 TCGA tumor samples comprising 106 subtypes from 26 different cancer cohorts to build models based upon small numbers of features that can classify new samples into previously defined TCGA molecular subtypes-a step toward molecular subtype application in the clinic.

Structural variation of types IV-A1- and IV-A3-mediated CRISPR interference.

CRISPR-Cas mediated DNA-interference typically relies on sequence-specific binding and nucleolytic degradation of foreign genetic material. Type IV-A CRISPR-Cas systems diverge from this general mechanism, using a nuclease-independent interference pathway to suppress gene expression for gene regulation and plasmid competition. To understand how the type IV-A system associated effector complex achieves this interference, we determine cryo-EM structures of two evolutionarily distinct type IV-A complexes (types IV-A1 and IV-A3) bound to cognate DNA-targets in the presence and absence of the type IV-A signature DinG effector helicase.

Risk of Stroke or Systemic Embolism According to Baseline Frequency and Duration of Subclinical Atrial Fibrillation: Insights From the ARTESiA Trial.

Background: In the ARTESiA trial (Apixaban for the Reduction of Thromboembolism in Patients With Device-Detected Subclinical Atrial Fibrillation), apixaban, compared with aspirin, reduced stroke or systemic embolism in patients with device-detected subclinical atrial fibrillation (SCAF). Clinical guidelines recommend considering SCAF episode duration when deciding whether to prescribe oral anticoagulation for this population.

Methods: We performed a retrospective cohort study in ARTESiA.

Prediction of major arrhythmic outcomes in ischaemic cardiomyopathy: value of hibernating myocardium in positron emission tomography/computed tomography.

Aims: Known predictors of major arrhythmic events (MAEs) in patients with ischaemic cardiomyopathy (ICM) include previous MAE and left ventricular ejection fraction (LVEF) ≤ 35%. Myocardial scars detected by perfusion imaging in ICM have been linked to MAE, but the prognostic significance of hibernating myocardium (HM) is unclear. The objective was to predict MAEs from combined 13N-ammonia (NH3) and 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in ICM.

miRNAs as potential biomarkers for subclinical atherosclerosis in Sjögren's disease.

Background: MicroRNAs (miRNAs) can regulate gene expression, controlling numerous cellular processes. Dysregulation of miRNA function is linked to various diseases, making them attractive diagnostic and therapeutic targets. Examples include hsa-miR-92a-3p, hsa-miR-126-3p, hsa-miR-143-3p, hsa-miR-145-5p and hsa-miR-204-5p, which are associated with endothelial function.

A Scaled Proteomic Discovery Study for Prostate Cancer Diagnostic Markers Using Proteograph and Trapped Ion Mobility Mass Spectrometry.

There is a significant unmet need for clinical reflex tests that increase the specificity of prostate-specific antigen blood testing, the longstanding but imperfect tool for prostate cancer diagnosis. Towards this endpoint, we present the results from a discovery study that identifies new prostate-specific antigen reflex markers in a large-scale patient serum cohort using differentiating technologies for deep proteomic interrogation. We detect known prostate cancer blood markers as well as novel candidates.

Direct oral anticoagulants for stroke prevention in patients with device-detected atrial fibrillation: assessing net clinical benefit.

Subclinical, device-detected atrial fibrillation (AF) is frequently recorded by pacemakers and other implanted cardiac rhythm devices. Patients with device-detected AF have an elevated risk of stroke, but a lower risk of stroke than similar patients with clinical AF captured with surface electrocardiogram. Two randomized clinical trials (NOAH-AFNET 6 and ARTESiA) have tested a direct oral anticoagulant (DOAC) against aspirin or placebo.

Mechanisms of left ventricular systolic dysfunction in light chain amyloidosis: a multiparametric cardiac MRI study.

Background: Cardiac systolic dysfunction is a poor prognostic marker in light-chain (AL) cardiomyopathy, a primary interstitial disorder; however, its pathogenesis is poorly understood.

Purpose: This study aims to analyze the effects of extracellular volume (ECV) expansion, a surrogate marker of amyloid burden on myocardial blood flow (MBF), myocardial work efficiency (MWE), and left ventricular (LV) systolic dysfunction in AL amyloidosis.

Methods: Subjects with biopsy-proven AL amyloidosis were prospectively enrolled (April 2016-June 2021; Clinicaltrials.

Secretome profiling reveals acute changes in oxidative stress, brain homeostasis, and coagulation following short-duration spaceflight.

As spaceflight becomes more common with commercial crews, blood-based measures of crew health can guide both astronaut biomedicine and countermeasures. By profiling plasma proteins, metabolites, and extracellular vesicles/particles (EVPs) from the SpaceX Inspiration4 crew, we generated "spaceflight secretome profiles," which showed significant differences in coagulation, oxidative stress, and brain-enriched proteins. While >93% of differentially abundant proteins (DAPs) in vesicles and metabolites recovered within six months, the majority (73%) of plasma DAPs were still perturbed post-flight.

The Space Omics and Medical Atlas (SOMA) and international astronaut biobank.

Spaceflight induces molecular, cellular and physiological shifts in astronauts and poses myriad biomedical challenges to the human body, which are becoming increasingly relevant as more humans venture into space. Yet current frameworks for aerospace medicine are nascent and lag far behind advancements in precision medicine on Earth, underscoring the need for rapid development of space medicine databases, tools and protocols. Here we present the Space Omics and Medical Atlas (SOMA), an integrated data and sample repository for clinical, cellular and multi-omic research profiles from a diverse range of missions, including the NASA Twins Study, JAXA CFE study, SpaceX Inspiration4 crew, Axiom and Polaris.

Bariatric Surgery and the Long-Term Risk of Venous Thromboembolism: A Population-Based Cohort Study.

Purpose: Bariatric surgery is associated with a greater venous thromboembolism (VTE) risk in the weeks following surgery, but the long-term risk of VTE is incompletely characterized. We evaluated bariatric surgery in relation to long-term VTE risk.

Materials And Methods: This population-based retrospective matched cohort study within three United States-based integrated health care systems included adults with body mass index (BMI) ≥ 35 kg/m who underwent bariatric surgery between January 2005 and September 2015 (n = 30,171), matched to nonsurgical patients on site, age, sex, BMI, diabetes, insulin use, race/ethnicity, comorbidity score, and health care utilization (n = 218,961).

Soluble urokinase plasminogen activator receptor levels predict survival in patients with portal hypertension undergoing TIPS.

Background & Aims: Transjugular intrahepatic portosystemic shunt (TIPS) is the most effective therapy for complications of portal hypertension. However, clinical outcomes following TIPS placement vary widely between patients and identifying ideal candidates remains a challenge. Soluble urokinase plasminogen activator receptor (suPAR) is a circulating marker of immune activation that has previously been associated with liver inflammation, but its prognostic value in patients receiving TIPS is unknown.

Duration of adenosine-induced myocardial hyperaemia: insights from quantitative 13N-ammonia positron emission tomography myocardial perfusion imaging.

Aims: This study aimed to assess the impact of adenosine on quantitative myocardial blood flow (MBF) in a rapid stress-rest protocol compared with a rest-stress protocol using 13N-ammonia positron emission tomography (PET) myocardial perfusion imaging (MPI) and to gain insights into the time dependency of such effects.

Methods And Results: Quantitative MBF at rest (rMBF) and during adenosine-induced stress (sMBF) and myocardial flow reserve (MFR) were obtained from 331 retrospectively identified patients who underwent 13N-ammonia PET MPI for suspected chronic coronary syndrome and who all exhibited no perfusion defects. Of these, 146 (44.

Optimizing warfarin dosing for patients with atrial fibrillation using machine learning.

While novel oral anticoagulants are increasingly used to reduce risk of stroke in patients with atrial fibrillation, vitamin K antagonists such as warfarin continue to be used extensively for stroke prevention across the world. While effective in reducing the risk of strokes, the complex pharmacodynamics of warfarin make it difficult to use clinically, with many patients experiencing under- and/or over- anticoagulation. In this study we employed a novel implementation of deep reinforcement learning to provide clinical decision support to optimize time in therapeutic International Normalized Ratio (INR) range.

Periodic and aperiodic changes to cortical EEG in response to pharmacological manipulation.

Cortical electroencephalograms (EEGs) may help understanding of neuropsychiatric illness and new treatment mechanisms. The aperiodic component (1/) of EEG power spectra is often treated as noise, but recent studies suggest that changes to the aperiodic exponent of power spectra may reflect changes in excitation/inhibition balance, a concept linked to antidepressant effects, epilepsy, autism, and other clinical conditions. One confound of previous studies is behavioral state, because factors associated with behavioral state other than excitation/inhibition ratio may alter EEG parameters.

Quantification of right ventricular amyloid burden with 18F-florbetapir positron emission tomography/computed tomography and its association with right ventricular dysfunction and outcomes in light-chain amyloidosis.

Aims: In systemic light-chain (AL) amyloidosis, quantification of right ventricular (RV) amyloid burden has been limited and the pathogenesis of RV dysfunction is poorly understood. Using 18F-florbetapir positron emission tomography/computed tomography (PET/CT), we aimed to quantify RV amyloid; correlate RV amyloid with RV structure and function; determine the independent contributions of RV, left ventricular (LV), and lung amyloid to RV function; and associate RV amyloid with major adverse cardiac events (MACE: death, heart failure hospitalization, cardiac transplantation).

Methods And Results: We prospectively enrolled 106 participants with AL amyloidosis (median age 62 years, 55% males) who underwent 18F-florbetapir PET/CT, magnetic resonance imaging, and echocardiography.

Outcomes of Patients with a Mechanical Heart Valve and Poor Anticoagulation Control on Warfarin.

Background:  Patients with a mechanical heart valve (MHV) require oral anticoagulation. Poor anticoagulation control is thought to be associated with adverse outcomes, but data are limited.

Objective:  To assess the risks of clinical outcomes in patients with a MHV and poor anticoagulation control on warfarin.

Colchicine to Prevent Atrial Fibrillation Recurrence After Catheter Ablation: A Randomized, Placebo-Controlled Trial.

Background: Inflammation may promote atrial fibrillation (AF) recurrence after catheter ablation. This study aimed to evaluate a short-term anti-inflammatory treatment with colchicine following ablation of AF.

Methods: Patients scheduled for ablation were randomized to receive colchicine 0.

Relationship between subjectively-rated and objectively-tested physical function across six different medical diagnoses.

Objective: To quantify and compare associations and relationships between self-rated and tested assessments of mainly mobility-related physical function in different diagnoses.

Design: Six longitudinal cohort studies before and after inpatient rehabilitation.

Patients: Patients with whiplash-associated disorder (n = 71), low back pain (n = 121), fibromyalgia (n = 84), lipoedema (n = 27), lymphoedema (n = 78), and post-acute coronary syndrome (n = 64).

Thyroid Inflammation and Immunity During the COVID-19 Pandemic: A Comprehensive Review and Case Study.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the development of various vaccines. Reports have emerged suggesting a possible association between SARS-CoV-2 vaccination and the onset of thyroid diseases. This review explores the clinical aspects of thyroid disorders following SARS-CoV-2 vaccination, including a case report of a patient with concomitant subacute thyroiditis (SAT) and Graves' disease (GD) with blocking thyrotropin receptor autoantibodies (TSH-R-Ab) following SARS-CoV-2 vaccination.

[Validation and reliability testing of the "Athlete Fear Avoidance Questionnaire (AFAQ)"].

Background: Sports injuries may have severe implications for an athlete's career. Psychological factors play an important role on an athlete's journey from the injury to the return to competitive sports. These factors are often insufficiently evaluated, which may lead to prolonged downtime.

Coronary microvascular function in male physicians with burnout and job stress: an observational study.

Background: As a professional group, physicians are at increased risk of burnout and job stress, both of which are associated with an increased risk of coronary heart disease that is at least as high as that of other professionals. This study aimed to examine the association of burnout and job stress with coronary microvascular function, a predictor of major adverse cardiovascular events.

Methods: Thirty male physicians with clinical burnout and 30 controls without burnout were included.