Tandem Mass Spectrometry of Perfluorocarboxylate Anions: Fragmentation Induced by Reactive Species Formed From Microwave Excited Hydrogen and Water Plasmas.

Rationale: Polyfluoroalkyl substances (PFAS) like perfluorooctanoic acid have persistent environmental and physiological effects. This study investigates the degradation of CFCO (n = 1-7) with neutral radical fragmentation under oxygen attachment dissociation (OAD). Unique fragments absent from collision-induced dissociation (CID) are observed.

Efficient, specific, and combinatorial control of endogenous exon splicing with dCasRx-RBM25.

Efficient targeted control of splicing is a major goal of functional genomics and therapeutic applications. Guide (g)RNA-directed, deactivated (d)Cas CRISPR enzymes fused to splicing effectors represent a promising strategy due to the flexibility of these systems. However, efficient, specific, and generalizable activation of endogenous exons using this approach has not been previously reported.

Implementation of a Blended-Learning Perioperative Nursing Education Program in Canada.

Governmental COVID-19 mandates in Ontario, Canada, resulted in a backlog of perioperative procedures. Organization leaders were required to expand services after the pandemic; however, the ongoing nursing shortage and college-based structure of perioperative education programs complicated their response. In 2021, we developed an in-house perioperative education program using a blended-learning theory comprising online modules and videos, skills laboratory sessions, and clinical placement experiences.

Automating sedation state assessments using natural language processing.

Introduction: Common goals for procedural sedation are to control pain and ensure the patient is not moving to an extent that is impeding safe progress or completion of the procedure. Clinicians perform regular assessments of the adequacy of procedural sedation in accordance with these goals to inform their decision-making around sedation titration and also for documentation of the care provided. Natural language processing could be applied to real-time transcriptions of audio recordings made during procedures in order to classify sedation states that involve movement and pain, which could then be integrated into clinical documentation systems.

Systematic analysis of alternative exon-dependent interactome remodeling reveals multitasking functions of gene regulatory factors.

Alternative splicing significantly expands biological complexity, particularly in the vertebrate nervous system. Increasing evidence indicates that developmental and tissue-dependent alternative exons often control protein-protein interactions; yet, only a minor fraction of these events have been characterized. Using affinity purification-mass spectrometry (AP-MS), we show that approximately 60% of analyzed neural-differential exons in proteins previously implicated in transcriptional regulation result in the gain or loss of interaction partners, which in some cases form unexpected links with coupled processes.

Mechanisms underlying linear ubiquitination and implications in tumorigenesis and drug discovery.

Linear ubiquitination is a distinct type of ubiquitination that involves attaching a head-to-tail polyubiquitin chain to a substrate protein. Early studies found that linear ubiquitin chains are essential for the TNFα- and IL-1-mediated NF-κB signaling pathways. However, recent studies have discovered at least sixteen linear ubiquitination substrates, which exhibit a broader activity than expected and mediate many other signaling pathways beyond NF-κB signaling.

Metabolome-wide Mendelian randomization characterizes heterogeneous and shared causal effects of metabolites on human health.

Metabolites are small molecules that are useful for estimating disease risk and elucidating disease biology. Nevertheless, their causal effects on human diseases have not been evaluated comprehensively. We performed two-sample Mendelian randomization to systematically infer the causal effects of 1,099 plasma metabolites measured in 6,136 Finnish men from the METSIM study on risk of 2,099 binary disease endpoints measured in 309,154 Finnish individuals from FinnGen.

Pamrevlumab, a Fully Human Monoclonal Antibody Targeting Connective Tissue Growth Factor, for Non-Ambulatory Patients with Duchenne Muscular Dystrophy.

Background: Duchenne muscular dystrophy (DMD) is a neuromuscular disease stemming from dystrophin gene mutations. Lack of dystrophin leads to progressive muscle damage and replacement of muscle with fibrotic and adipose tissue. Pamrevlumab (FG-3019), a fully human monoclonal antibody that binds to connective tissue growth factor (CTGF), is in Phase III development for treatment of DMD and other diseases.

Excitation Intensity-Dependent Quantum Yield of Semiconductor Nanocrystals.

One of the key phenomena that determine the fluorescence of nanocrystals is the nonradiative Auger-Meitner recombination of excitons. This nonradiative rate affects the nanocrystals' fluorescence intensity, excited state lifetime, and quantum yield. Whereas most of the above properties can be directly measured, the quantum yield is the most difficult to assess.

Artificial intelligence in diabetic retinopathy: Bibliometric analysis.

Background: The use of artificial intelligence in diabetic retinopathy has become a popular research focus in the past decade. However, no scientometric report has provided a systematic overview of this scientific area.

Aims: We utilized a bibliometric approach to identify and analyse the academic literature on artificial intelligence in diabetic retinopathy and explore emerging research trends, key authors, co-authorship networks, institutions, countries, and journals.

Direct RNA sequencing of respiratory syncytial virus infected human cells generates a detailed overview of RSV polycistronic mRNA and transcript abundance.

To characterize species of viral mRNA transcripts generated during respiratory syncytial virus (RSV) infection, human fibroblast-like MRC-5 lung cells were infected with subgroup A RSV for 6, 16 and 24 hours. In addition, we characterised the viral transcriptome in infected Calu-3 lung epithelial cells at 48 hours post infection. Total RNA was harvested and polyadenylated mRNA was enriched and sequenced by direct RNA sequencing using an Oxford nanopore device.

Systematic exploration of dynamic splicing networks reveals conserved multistage regulators of neurogenesis.

Alternative splicing (AS) is a critical regulatory layer; yet, factors controlling functionally coordinated splicing programs during developmental transitions are poorly understood. Here, we employ a screening strategy to identify factors controlling dynamic splicing events important for mammalian neurogenesis. Among previously unknown regulators, Rbm38 acts widely to negatively control neural AS, in part through interactions mediated by the established repressor of splicing, Ptbp1.

Nuclear soluble cGAS senses double-stranded DNA virus infection.

The DNA sensor cGAS detects cytosolic DNA and instigates type I interferon (IFN) expression. Recent studies find that cGAS also localizes in the nucleus and binds the chromatin. Despite the mechanism controlling nuclear cGAS activation is well elucidated, whether nuclear cGAS participates in DNA sensing is unclear.

Opioid prescribing among new users for non-cancer pain in the USA, Canada, UK, and Taiwan: A population-based cohort study.

Background: The opioid epidemic in North America has been driven by an increase in the use and potency of prescription opioids, with ensuing excessive opioid-related deaths. Internationally, there are lower rates of opioid-related mortality, possibly because of differences in prescribing and health system policies. Our aim was to compare opioid prescribing rates in patients without cancer, across 5 centers in 4 countries.

Non-alcoholic Steatohepatitis Pathogenesis, Diagnosis, and Treatment.

There has been a rise in the prevalence of non-alcohol fatty liver disease (NAFLD) due to the popularity of western diets and sedentary lifestyles. One quarter of NAFLD patients is diagnosed with non-alcoholic steatohepatitis (NASH), with histological evidence not only of fat accumulation in hepatocytes but also of liver cell injury and death due to long-term inflammation. Severe NASH patients have increased risks of cirrhosis and liver cancer.

Improved diagnosis-medication association mining to reduce pseudo-associations.

Background And Objective: Association rule mining has been adopted to medical fields to discover prescribing patterns or relationships among diseases and/or medications; however, it has generated unreasonable associations among these entities. This study aims to identify the real-world profile of disease-medication (DM) associations using the modified mining algorithm and assess its performance in reducing DM pseudo-associations.

Methods: We retrieved data from outpatient records between January 2011 and December 2015 in claims databases maintained by the Health and Welfare Data Science Center, Ministry of Health and Welfare, Taiwan.

Obesity and Mortality Among Patients Diagnosed With COVID-19: A Systematic Review and Meta-Analysis.

Coronavirus disease 2019 (COVID-19) has already raised serious concern globally as the number of confirmed or suspected cases have increased rapidly. Epidemiological studies reported that obesity is associated with a higher rate of mortality in patients with COVID-19. Yet, to our knowledge, there is no comprehensive systematic review and meta-analysis to assess the effects of obesity and mortality among patients with COVID-19.

Clinical Characteristics and Neonatal Outcomes of Pregnant Patients With COVID-19: A Systematic Review.

Coronavirus disease 2019 (COVID-19) characterized by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created serious concerns about its potential adverse effects. There are limited data on clinical, radiological, and neonatal outcomes of pregnant women with COVID-19 pneumonia. This study aimed to assess clinical manifestations and neonatal outcomes of pregnant women with COVID-19.