Single-cell RNA sequencing algorithms underestimate changes in transcriptional noise compared to single-molecule RNA imaging.

Stochastic fluctuations (noise) in transcription generate substantial cell-to-cell variability. However, how best to quantify genome-wide noise remains unclear. Here, we utilize a small-molecule perturbation (5'-iodo-2'-deoxyuridine [IdU]) to amplify noise and assess noise quantification from numerous single-cell RNA sequencing (scRNA-seq) algorithms on human and mouse datasets and then compare it to noise quantification from single-molecule RNA fluorescence in situ hybridization (smFISH) for a panel of representative genes.

Postmarketing Surveillance of Inferior Vena Cava Filters Among US Medicare Beneficiaries: The SAFE-IVC Study.

Importance: Inferior vena cava filters (IVCFs) are commonly used to prevent pulmonary embolism in selected clinical scenarios, despite limited evidence to support their use. Current recommendations from professional societies and the US Food and Drug Administration endorse timely IVCF retrieval when clinically feasible. Current IVCF treatment patterns and outcomes remain poorly described.

Temporal and regional variation in the use of biologic and targeted synthetic DMARDs for rheumatoid arthritis: a nationwide cohort study.

Objective: To evaluate temporal and regional variation in biologic and targeted synthetic DMARD (b/tsDMARD) initiation for rheumatoid arthritis (RA) in England and Wales.

Methods: An observational cohort study was conducted for people with RA enrolled in the National Early Inflammatory Arthritis Audit (NEIAA) between May 2018 and April 2022 who had 12-month follow-up data. Temporal trends in escalation to b/tsDMARDs within 12 months of initial rheumatology assessment were explored, including comparisons before and after publication (July 2021) of national guidelines that lowered the threshold for b/tsDMARD initiation to include moderate-severity RA.

Association between interleukin-12 p40 subunit and risk of primary Sjögren's syndrome: a Mendelian randomization study.

Objectives: Interleukin-12 (IL-12) signalling was proposed in the immunopathogenesis of primary Sjögren's disease. The efficacy of therapies targeting this pathway is currently unclear. Herein, we investigated the associations between circulating proteins involved in the IL-12 and IL-23 signalling pathways on primary Sjögren's disease using mendelian randomization.

Quantitative comparison of single-cell RNA sequencing versus single-molecule RNA imaging for quantifying transcriptional noise.

Stochastic fluctuations (noise) in transcription generate substantial cell-to-cell variability. However, how best to quantify genome-wide noise, remains unclear. Here we utilize a small-molecule perturbation (IdU) to amplify noise and assess noise quantification from numerous scRNA-seq algorithms on human and mouse datasets, and then compare to noise quantification from single-molecule RNA FISH (smFISH) for a panel of representative genes.

Standardized Definitions for Cardiogenic Shock Research and Mechanical Circulatory Support Devices: Scientific Expert Panel From the Shock Academic Research Consortium (SHARC).

The Shock Academic Research Consortium is a multi-stakeholder group, including representatives from the US Food and Drug Administration and other government agencies, industry, and payers, convened to develop pragmatic consensus definitions useful for the evaluation of clinical trials enrolling patients with cardiogenic shock, including trials evaluating mechanical circulatory support devices. Several in-person and virtual meetings were convened between 2020 and 2022 to discuss the need for developing the standardized definitions required for evaluation of mechanical circulatory support devices in clinical trials for cardiogenic shock patients. The expert panel identified key concepts and topics by performing literature reviews, including previous clinical trials, while recognizing current challenges and the need to advance evidence-based practice and statistical analysis to support future clinical trials.

The medical device development ecosystem: Current regulatory state and challenges for future development: A review.

Background/purpose: There has been increasing emphasis on the development of new technology to mitigate unmet clinical needs in cardiovascular disease. This emphasis results in part from recognition that many devices, although being initially developed in the United States, were studied, and then eventually approved abroad before being returned to the U.S.

Expression of thioredoxin-1 in the ASJ neuron corresponds with and enhances intrinsic regenerative capacity under lesion conditioning in C. elegans.

A conditioning lesion of the peripheral sensory axon triggers robust central axon regeneration in mammals. We trigger conditioned regeneration in the Caenorhabditis elegans ASJ neuron by laser surgery or genetic disruption of sensory pathways. Conditioning upregulates thioredoxin-1 (trx-1) expression, as indicated by trx-1 promoter-driven expression of green fluorescent protein and fluorescence in situ hybridization (FISH), suggesting trx-1 levels and associated fluorescence indicate regenerative capacity.

The impact of COVID-19 on psychiatric clinical encounters among low-income racially-diverse children.

Background: There is a lack of longitudinal data to examine the impact of COVID-19 on all types of clinical encounters among United States, underrepresented BIPOC (Black, Indigenous, and people of color), children. This study aims to examine the changes in all the outpatient clinical encounters during the pandemic compared to the baseline, with particular attention to psychiatric encounters and diagnoses.

Method: This study analyzed 3-year (January 2019 to December 2021) longitudinal clinical encounter data from 3,394 children in the Boston Birth Cohort, a US urban, predominantly low-income, Black and Hispanic children.

Comparative analysis between single-cell RNA-seq and single-molecule RNA FISH indicates that the pyrimidine nucleobase idoxuridine (IdU) globally amplifies transcriptional noise.

Stochastic fluctuations (noise) in transcription generate substantial cell-to-cell variability, but the physiological roles of noise have remained difficult to determine in the absence of generalized noise-modulation approaches. Previous single-cell RNA-sequencing (scRNA-seq) suggested that the pyrimidine-base analog (5'-iodo-2'-deoxyuridine, IdU) could generally amplify noise without substantially altering mean-expression levels but scRNA-seq technical drawbacks potentially obscured the of IdU-induced transcriptional noise amplification. Here we quantify global-vs.

The effect of ethnicity on anatomic success following macular hole surgery: a multicentre cohort study.

Purpose: The purpose is to assess the effect of ethnicity on surgical macular hole closure.

Methods: A retrospective cohort study was undertaken in five UK National Health Service Hospitals. We included all patients with known ethnicity undergoing vitrectomy, internal limiting membrane peel, and gas/oil tamponade for all stages of primary full-thickness macular hole (FTMH).

'Oumuamua Is Not a Probe Sent to Our Solar System by an Alien Civilization.

'Oumuamua, the first known object of extrasolar origin seen to enter our Solar System, has multiple unusual characteristics that, taken together, are very difficult to explain with conventional astronomical entities like asteroids and comets. Consequently, it has been hypothesized that 'Oumuamua is an interstellar probe that was constructed by an alien civilization. We demonstrate that the accomplishments that can be achieved with large space telescopes/interferometers in the alien's planetary system will completely quench any motivation for construction and launch of an 'Oumuamua-like probe.

Posttraumatic Stress Symptoms and the Quality of Maternal-Child Interactions in Mothers of Preterm Infants.

Objective: The purpose of this study was to examine associations between maternal trauma exposure, posttraumatic stress symptoms, and directly observed maternal-child interactions among a diverse cohort of mother-preterm infant dyads at 12-month corrected age.

Methods: We conducted a retrospective cohort study. Maternal trauma exposure and posttraumatic stress symptoms were measured using the Modified Posttraumatic Stress Disorder Symptom Scale at baseline and 6 and 12 months.

Bioprosthetic Aortic Valve Hemodynamics: Definitions, Outcomes, and Evidence Gaps: JACC State-of-the-Art Review.

A virtual workshop was organized by the Heart Valve Collaboratory to identify areas of expert consensus, areas of disagreement, and evidence gaps related to bioprosthetic aortic valve hemodynamics. Impaired functional performance of bioprosthetic aortic valve replacement is associated with adverse patient outcomes; however, this assessment is complicated by the lack of standardization for labelling, definitions, and measurement techniques, both after surgical and transcatheter valve replacement. Echocardiography remains the standard assessment methodology because of its ease of performance, widespread availability, ability to do serial measurements over time, and correlation with outcomes.

Association between cord blood metabolites in tryptophan pathway and childhood risk of autism spectrum disorder and attention-deficit hyperactivity disorder.

Alterations in tryptophan and serotonin have been implicated in various mental disorders; but studies are limited on child neurodevelopmental disabilities such as autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). This prospective cohort study examined the associations between levels of tryptophan and select metabolites (5-methoxytryptophol (5-MTX), 5-hydroxytryptophan (5-HTP), serotonin, N-acetyltrytophan) in cord plasma (collected at birth) and physician-diagnosed ASD, ADHD and other developmental disabilities (DD) in childhood. The study sample (n = 996) derived from the Boston Birth Cohort, which included 326 neurotypical children, 87 ASD, 269 ADHD, and 314 other DD children (mutually exclusive).

Association of mitochondrial DNA content, heteroplasmies and inter-generational transmission with autism.

Mitochondria are essential for brain development. While previous studies linked dysfunctional mitochondria with autism spectrum disorder (ASD), the role of the mitochondrial genome (mtDNA) in ASD risk is largely unexplored. This study investigates the association of mtDNA heteroplasmies (co-existence of mutated and unmutated mtDNA) and content with ASD, as well as its inter-generational transmission and sex differences among two independent samples: a family-based study (n = 1,938 families with parents, probands and sibling controls) and a prospective birth cohort (n = 997 mother-child pairs).

Semantic flow and its relation to controlled semantic retrieval deficits in the narrative production of people with aphasia.

Aphasia has had a profound influence on our understanding of how language is instantiated within the human brain. Historically, aphasia has yielded an in vivo model for elucidating the effects of impaired lexical-semantic access on language comprehension and production. Aphasiology has focused intensively on single word dissociations.