5'-tRNA halves generated by IRE1α are linked to the ER stress response.

Transfer RNA halves (tRHs) have various biological functions. However, the biogenesis of specific 5'-tRHs under certain conditions remains unknown. Here, we report that inositol-requiring enzyme 1α (IRE1α) cleaves the anticodon stem-loop region of tRNA to produce 5'-tRHs (5'-tRH-Gly) with highly selective target discrimination upon endoplasmic reticulum (ER) stress.

APOE4/4 is linked to damaging lipid droplets in Alzheimer's disease microglia.

Several genetic risk factors for Alzheimer's disease implicate genes involved in lipid metabolism and many of these lipid genes are highly expressed in glial cells. However, the relationship between lipid metabolism in glia and Alzheimer's disease pathology remains poorly understood. Through single-nucleus RNA sequencing of brain tissue in Alzheimer's disease, we have identified a microglial state defined by the expression of the lipid droplet-associated enzyme ACSL1 with ACSL1-positive microglia being most abundant in patients with Alzheimer's disease having the APOE4/4 genotype.

Long-Term Autoimmune Inflammatory Rheumatic Outcomes of COVID-19 : A Binational Cohort Study.

Background: Some data suggest a higher incidence of diagnosis of autoimmune inflammatory rheumatic diseases (AIRDs) among patients with a history of COVID-19 compared with uninfected patients. However, these studies had methodological shortcomings.

Objective: To investigate the effect of COVID-19 on long-term risk for incident AIRD over various follow-up periods.

Clinicopathologic features and prognostic value of claudin 18.2 overexpression in patients with resectable gastric cancer.

Claudin 18.2 has emerged as a promising therapeutic target in gastric cancer based on phase 3 studies. However, clinicopathologic features associated with claudin 18.

Polymer nanoparticles deliver mRNA to the lung for mucosal vaccination.

An inhalable platform for messenger RNA (mRNA) therapeutics would enable minimally invasive and lung-targeted delivery for a host of pulmonary diseases. Development of lung-targeted mRNA therapeutics has been limited by poor transfection efficiency and risk of vehicle-induced pathology. Here, we report an inhalable polymer-based vehicle for delivery of therapeutic mRNAs to the lung.

Biliary atresia is associated with polygenic susceptibility in ciliogenesis and planar polarity effector genes.

Background & Aims: Biliary atresia (BA) is poorly understood and leads to liver transplantation (LT), with the requirement for and associated risks of lifelong immunosuppression, in most children. We performed a genome-wide association study (GWAS) to determine the genetic basis of BA.

Methods: We performed a GWAS in 811 European BA cases treated with LT in US, Canadian and UK centers, and 4,654 genetically matched controls.

APOE4/4 is linked to damaging lipid droplets in Alzheimer's microglia.

Several genetic risk factors for Alzheimer's Disease (AD) implicate genes involved in lipid metabolism and many of these lipid genes are highly expressed in glial cells. However, the relationship between lipid metabolism in glia and AD pathology remains poorly understood. Through single-nucleus RNA-sequencing of AD brain tissue, we have identified a microglial state defined by the expression of the lipid droplet (LD) associated enzyme with ACSL1-positive microglia most abundant in AD patients with the genotype.

Korean treatment recommendations for patients with axial spondyloarthritis.

We aimed to develop evidence-based recommendations for treating axial spondylarthritis (axSpA) in Korea. The development committee was constructed, key clinical questions were determined, and the evidence was searched through online databases including MEDLINE, Embase, Cochrane, KoreaMed, and Kmbase. Systematic literature reviews were conducted, quality of evidence was determined, and draft recommendations were formulated according to the Grading of Recommendations Assessment, Development, and Evaluations methodology.

Korean treatment recommendations for patients with axial spondyloarthritis.

We aimed to develop evidence-based recommendations for treating axial spondylarthritis (axSpA) in Korea. The development committee was constructed, key clinical questions were determined, and the evidence was searched through online databases including MEDLINE, Embase, Cochrane, KoreaMed, and KMbase. Systematic literature reviews were conducted, quality of evidence was determined, and draft recommendations were formulated according to the Grading of Recommendations Assessment, Development, and Evaluations methodology.

High-Throughput Microscopy Analysis of Mitochondrial Membrane Potential in 2D and 3D Models.

Recent proteomic, metabolomic, and transcriptomic studies have highlighted a connection between changes in mitochondria physiology and cellular pathophysiological mechanisms. Secondary assays to assess the function of these organelles appear fundamental to validate these -omics findings. Although mitochondrial membrane potential is widely recognized as an indicator of mitochondrial activity, high-content imaging-based approaches coupled to multiparametric to measure it have not been established yet.

Influences of Momentum Ratio on Transverse Dispersion for Intermediate-Field Mixing Downstream of Channel Confluence.

This study aims to analyze the influences of momentum ratio () and confluence angle () on the transverse dispersion in an urban scale confluence channel from the numerical simulation results using the Environmental Fluid Dynamics Code model. By changing the momentum flux and confluence angle from the simulation results, the analysis focused on the relations between the vertical variations of transverse velocity and transverse dispersion. The high momentum tributary aligned the mixing interface toward the outer bank and created a strong helical motion, which transported the contaminated water along the channel bed and inflows into the recirculation zone.

Major cardiovascular events and subsequent risk of kidney failure with replacement therapy: a CKD Prognosis Consortium study.

Aims: Chronic kidney disease (CKD) increases risk of cardiovascular disease (CVD). Less is known about how CVD associates with future risk of kidney failure with replacement therapy (KFRT).

Methods And Results: The study included 25 903 761 individuals from the CKD Prognosis Consortium with known baseline estimated glomerular filtration rate (eGFR) and evaluated the impact of prevalent and incident coronary heart disease (CHD), stroke, heart failure (HF), and atrial fibrillation (AF) events as time-varying exposures on KFRT outcomes.

Clinical Features, Neuropathology, and Surgical Outcome in Patients With Refractory Epilepsy and Brain Somatic Variants in the Gene.

Background And Objectives: The gene, located at chromosome Xp11.23, encodes for a uridine diphosphate-galactose transporter. We describe clinical, genetic, neuroimaging, EEG, and histopathologic findings and assess possible predictors of postoperative seizure and cognitive outcome in 47 patients with refractory epilepsy and brain somatic gene variants.

Associations of Fecal Short Chain Fatty Acids With Colonic Transit, Fecal Bile Acid, and Food Intake in Irritable Bowel Syndrome.

Introduction: Short-chain fatty acids (SCFAs) correlate with colonic transit time (CTT) and may influence irritable bowel syndrome (IBS) pathophysiology. However, the clinical significance of fecal SCFAs, relationships between SCFAs and other metabolites (bile acids [BAs]), and real-time diet effects on SCFAs in IBS are uncertain. The aim was to evaluate fecal SCFA associations with IBS phenotype and mechanisms and explore effects of real-time diet.

Leveraging Social Networks for the Assessment and Management of Neurological Patients.

Social networks are the persons surrounding a patient who provide support, circulate information, and influence health behaviors. For patients seen by neurologists, social networks are one of the most proximate social determinants of health that are actually accessible to clinicians, compared with wider social forces such as structural inequalities. We can measure social networks and related phenomena of social connection using a growing set of scalable and quantitative tools increasing familiarity with social network effects and mechanisms.

Differential Impact of Coronary Revascularization on Long-Term Clinical Outcome According to Coronary Flow Characteristics: Analysis of the International ILIAS Registry.

Background: Coronary pressure indices such as fractional flow reserve are the standard for guiding elective revascularization. However, considering additional coronary flow parameters could further individualize and optimize the decision on revascularization. We aimed to investigate the potentially differential prognostic associations of elective percutaneous coronary intervention (PCI) according to coronary flow properties represented by coronary flow reserve (CFR), coronary flow capacity (CFC), and baseline CFC (bCFC).

Circulating Metabolome and White Matter Hyperintensities in Women and Men.

Background: White matter hyperintensities (WMH), identified on T2-weighted magnetic resonance images of the human brain as areas of enhanced brightness, are a major risk factor of stroke, dementia, and death. There are no large-scale studies testing associations between WMH and circulating metabolites.

Methods: We studied up to 9290 individuals (50.

Direct inoculation of a biotrickling filter for hydrogenotrophic methanogenesis.

Hydrogenotrophic biomethanation in a biotrickling filter has been reported to be a proven technology for biological biogas upgrading in recent studies. However, the preparation of enriched hydrogenotrophic methanogens in a separate reactor prior to biomethanation in a trickled bed is a lengthy procedure and therefore hard to apply on an industrial scale. This study explored the direct inoculation of anaerobic biogas digestate for simultaneous enrichment of hydrogenotrophic methanogens and biofilm immobilisation in a trickled bed system.

Immunization with -Specific Antigens Bypasses T Cell Differentiation from Prior Bacillus Calmette-Guérin Vaccination and Improves Protection in Mice.

Despite the fact that the majority of people in tuberculosis (TB)-endemic areas are vaccinated with the Bacillus Calmette-Guérin (BCG) vaccine, TB remains the leading infectious cause of death. Data from both animal models and humans show that BCG and subunit vaccines induce T cells of different phenotypes, and little is known about how BCG priming influences subsequent booster vaccines. To test this, we designed a novel -specific (or "non-BCG") subunit vaccine with protective efficacy in both mice and guinea pigs and compared it to a known BCG boosting vaccine.

Compassionate Use of Remdesivir for Patients with Severe Covid-19.

Background: Remdesivir, a nucleotide analogue prodrug that inhibits viral RNA polymerases, has shown in vitro activity against SARS-CoV-2.

Methods: We provided remdesivir on a compassionate-use basis to patients hospitalized with Covid-19, the illness caused by infection with SARS-CoV-2. Patients were those with confirmed SARS-CoV-2 infection who had an oxygen saturation of 94% or less while they were breathing ambient air or who were receiving oxygen support.

Radiomics Study of Thyroid Ultrasound for Predicting Mutation in Papillary Thyroid Carcinoma: Preliminary Results.

Background And Purpose: It is not known how radiomics using ultrasound images contribute to the detection of BRAF mutation. This study aimed to evaluate whether a radiomics study of gray-scale ultrasound can predict the presence or absence of () mutation in papillary thyroid cancer.

Materials And Methods: The study retrospectively included 96 thyroid nodules that were surgically confirmed papillary thyroid cancers between January 2012 and June 2013.

Efficacy and safety of sodium zirconium cyclosilicate for hyperkalaemia: the randomized, placebo-controlled HARMONIZE-Global study.

Aims: Sodium zirconium cyclosilicate (SZC, formerly ZS-9) is a selective K binder to treat adults with hyperkalaemia. HARMONIZE-Global examined the efficacy and safety of SZC among outpatients with hyperkalaemia from diverse geographic and ethnic origins.

Methods And Results: This phase 3, randomized, double-blind, placebo-controlled study recruited outpatients with serum K ≥5.

Physiological and Clinical Assessment of Resting Physiological Indexes.

Background: Recently, resting pressure-derived indexes such as resting full-cycle ratio (RFR) and diastolic pressure ratio (dPR) have been introduced to assess the functional significance of epicardial coronary stenosis. The present study sought to investigate the agreement of RFR or dPR with other pressure-derived indexes (instantaneous wave-free ratio [iFR] or fractional flow reserve), the sensitivity of RFR or dPR for anatomic or hemodynamic stenosis severity, and the prognostic implications of RFR or dPR compared with iFR Methods: RFR and dPR were calculated from resting pressure tracings by an independent core laboratory in 1024 vessels (435 patients). The changes in resting physiological indexes according to diameter stenosis were compared among iFR, RFR, and dPR.

Approaching the adiabatic timescale with machine learning.

The control and manipulation of quantum systems without excitation are challenging, due to the complexities in fully modeling such systems accurately and the difficulties in controlling these inherently fragile systems experimentally. For example, while protocols to decompress Bose-Einstein condensates (BECs) faster than the adiabatic timescale (without excitation or loss) have been well developed theoretically, experimental implementations of these protocols have yet to reach speeds faster than the adiabatic timescale. In this work, we experimentally demonstrate an alternative approach based on a machine-learning algorithm which makes progress toward this goal.