Optimized chemical labeling method for isolation of 8-oxoG-modified RNA, ChLoRox-Seq, identifies mRNAs enriched in oxidation and transcriptome-wide distribution biases of oxidation events post environmental stress.

Bulk increases in nucleobase oxidation, most commonly manifesting as the guanine (G) nucleobase modification 8-oxo-7,8-dihydroguanine (8-oxoG), have been linked to several disease pathologies. Elucidating the effects of RNA oxidation on cellular homoeostasis is limited by a lack of effective tools for detecting specific regions modified with 8-oxoG. Building on a previously published method for studying 8-oxoG in DNA, we developed ChLoRox-Seq, which works by covalently functionalizing 8-oxoG sites in RNA with biotin.

Sentinel Surveillance reveals phylogenetic diversity and detection of linear plasmids harboring and among enterococci collected in the United States.

and are frequent causes of healthcare-associated infections. Antimicrobial-resistant enterococci pose a serious public health threat, particularly vancomycin-resistant enterococci (VRE), for which treatment options are limited. The Centers for Disease Control and Prevention's Division of Healthcare Quality Promotion Sentinel Surveillance system conducted surveillance from 2018 to 2019 to evaluate antimicrobial susceptibility profiles and molecular epidemiology of 205 and 180 clinical isolates collected from nine geographically diverse sites in the United States.

Complete genome sequences of four representative strains.

This report describes the complete genome sequence assemblies from four representative isolates of the human pathogen . These data provide necessary references to aid accurate sequence-based species discrimination among closely related spp. pathogens.

TolRad, a model for predicting radiation tolerance using Pfam annotations, identifies novel radiosensitive bacterial species from reference genomes and MAGs.

Unlabelled: The trait of ionizing radiation (IR) tolerance is variable between bacterium, with species succumbing to acute doses as low as 60 Gy and extremophiles able to survive doses exceeding 10,000 Gy. While survival screens have identified multiple highly radioresistant bacteria, such systemic searches have not been conducted for IR-sensitive bacteria. The taxonomy-level diversity of IR sensitivity is poorly understood, as are genetic elements that influence IR sensitivity.

The frequency and function of nucleoprotein-specific CD8 T cells are critical for heterosubtypic immunity against influenza virus infection.

Unlabelled: Cytotoxic T lymphocytes (CTLs) mediate host defense against viral and intracellular bacterial infections and tumors. However, the magnitude of CTL response and their function needed to confer heterosubtypic immunity against influenza virus infection are unknown. We addressed the role of CD8 T cells in the absence of any cross-reactive antibody responses to influenza viral proteins using an adenoviral vector expressing a 9mer amino acid sequence recognized by CD8 T cells.

Effectiveness and safety of glecaprevir/pibrentasvir for 8 weeks in the treatment of patients with acute hepatitis C: A single-arm retrospective study.

Background And Aims: No direct-acting antiviral is currently approved for acute HCV infection, delaying treatment. We investigated the effectiveness and safety of 8-week glecaprevir/pibrentasvir (G/P) in patients with acute HCV infection.

Approach And Results: This noninterventional, single-arm, retrospective chart review was designed to enroll adults/adolescents with acute HCV infection.

Functional interrogation of cellular Lp(a) uptake by genome-scale CRISPR screening.

An elevated level of lipoprotein(a), or Lp(a), in the bloodstream has been causally linked to the development of atherosclerotic cardiovascular disease and calcific aortic valve stenosis. Steady state levels of circulating lipoproteins are modulated by their rate of clearance, but the identity of the Lp(a) uptake receptor(s) has been controversial. In this study, we performed a genome-scale CRISPR screen to functionally interrogate all potential Lp(a) uptake regulators in HuH7 cells.

Carbapenem-resistant Acinetobacter baumannii complex in the United States-An epidemiological and molecular description of isolates collected through the Emerging Infections Program, 2019.

Background: Understanding the epidemiology of carbapenem-resistant A. baumannii complex (CRAB) and the patients impacted is an important step toward informing better infection prevention and control practices and improving public health response.

Methods: Active, population-based surveillance was conducted for CRAB in 9 U.

Phase 1 study of safety and tolerability of an oral contraceptive containing low-dose ethinyl oestradiol combined with glecaprevir/pibrentasvir treatment in healthy premenopausal women.

Glecaprevir/pibrentasvir (GLE/PIB) is an approved guideline-recommended chronic hepatitis C virus infection treatment. GLE/PIB coadministration with ethinyl oestradiol (EE) is not recommended in current labels owing to a Phase 1 study observing Grade ≥2 alanine aminotransferase (ALT) elevation in 2 out of 12 healthy women cotreated for 11 days with GLE/PIB and oral contraceptive (OC) containing 35 μg/250 μg EE/norgestimate. No Grade ≥2 elevation was observed with low-dose (20 μg) EE (n = 14).

Bystander Motivations and Barriers to Helping Intoxicated Peers.

We examined the prevalence of self-reported motivations and barriers to helping intoxicated peers among emerging adults (= 377; = 18.64; 75% women, 88% White) attending a Southeastern university and whether motivations and barriers differed by age, gender, race, and class standing. Respondents aged 19-24 were more likely to endorse the motivation item "Because it was your "turn" to be the helper/designated driver (DD) that night" than eighteen-year-olds.

Multimodality Cardiac Imaging and the Imaging Workforce in the United States: Diversity, Disparities, and Future Directions.

Innovations in cardiac imaging have fundamentally advanced the understanding and treatment of cardiovascular disease. These advances in noninvasive cardiac imaging have also expanded the role of the cardiac imager and dramatically increased the demand for imagers who are cross-trained in multiple modalities. However, we hypothesize that there is significant variation in the availability of cardiac imaging expertise and a disparity in the adoption of advanced imaging technologies across the United States.

Continuum of Trauma: Fear and Mistrust of Institutions in Communities of Color During the COVID-19 Pandemic.

Historical, cultural, and social trauma, along with social determinants of health (SDOH), shape health outcomes, attitudes toward medicine, government, and health behaviors among communities of color in the United States (U.S.).

Efficacy and safety of ceftazidime/avibactam in patients with infections caused by β-lactamase-producing Gram-negative pathogens: a pooled analysis from the Phase 3 clinical trial programme.

Objectives: This post hoc pooled analysis evaluated clinical and microbiological outcomes and safety in patients with infections caused by β-lactamase-producing Gram-negative pathogens across five Phase 3, randomized, controlled, multicentre trials of ceftazidime/avibactam in adults with complicated intra-abdominal infection (cIAI), complicated urinary tract infection (cUTI)/pyelonephritis and nosocomial pneumonia (NP), including ventilator-associated pneumonia (VAP).

Methods: In each trial, RECLAIM/RECLAIM 3 (cIAI), REPRISE (cIAI/cUTI), RECAPTURE (cUTI) and REPROVE (NP, including VAP) patients were randomized 1:1 to IV ceftazidime/avibactam (plus metronidazole for patients with cIAI) or comparators (carbapenems in >97% patients) for 5-21 days. Clinical and microbiological responses at the test-of-cure visit were assessed for patients with ESBLs, and/or plasmidic and/or overexpression of chromosomal AmpC, and/or serine carbapenemases without MBLs identified in baseline Gram-negative isolates by phenotypic screening and molecular characterization in the pooled microbiological modified ITT (mMITT) population.

Neural Representation of Donating Time and Money.

Volunteering and charitable donations are two common forms of prosocial behavior, yet it is unclear whether these other-benefitting behaviors are supported by the same or different neurobiological mechanisms. During an fMRI task, 40 participants (20 female-identifying; age: mean = 18.92 years, range = 18.

Spatially Controlled UV Light Generation at Depth using Upconversion Micelles.

UV light can trigger a plethora of useful photochemical reactions for diverse applications, including photocatalysis, photopolymerization, and drug delivery. These applications typically require penetration of high-energy photons deep into materials, yet delivering these photons beyond the surface is extremely challenging due to absorption and scattering effects. Triplet-triplet annihilation upconversion (TTA-UC) shows great promise to circumvent this issue by generating high-energy photons from incident lower-energy photons.

Gelation Dynamics during Photo-Cross-Linking of Polymer Nanocomposite Hydrogels.

Embedding nanomaterials into polymer hydrogels enables the design of functional materials with tailored chemical, mechanical, and optical properties. Nanocapsules that protect interior cargo and disperse readily through a polymeric matrix have drawn particular interest for their ability to integrate chemically incompatible systems and to further expand the parameter space for polymer nanocomposite hydrogels. The properties of polymer nanocomposite hydrogels depend on the material composition and processing route, which were explored systematically in this work.

The Safety and Efficacy of Dalbavancin and Active Comparator in Pediatric Patients With Acute Bacterial Skin and Skin Structure Infections.

Background: Acute bacterial skin and skin structure infections (ABSSSIs) are a significant source of morbidity in children. Dalbavancin, approved for the treatment of adults and children with ABSSSI, has a well-established safety profile in adults. We report safety and descriptive efficacy data for the treatment of ABSSSI in children.

Safety analysis of glecaprevir/pibrentasvir in patients with markers of advanced liver disease in clinical and real-world cohorts.

Chronic hepatitis C virus (HCV) infection has the greatest health impact in patients with advanced liver disease. The direct-acting antiviral (DAA) regimen glecaprevir/pibrentasvir (G/P) is approved for treatment of HCV-infected patients without cirrhosis and with compensated cirrhosis. However, events of liver decompensation/failure have been reported in patients treated with protease-inhibitor-containing DAA regimens, often in patients with advanced liver disease.

Selective Whole-Genome Amplification as a Tool to Enrich Specimens with Low Treponema pallidum Genomic DNA Copies for Whole-Genome Sequencing.

Downstream next-generation sequencing (NGS) of the syphilis spirochete Treponema pallidum subspecies (T. pallidum) is hindered by low bacterial loads and the overwhelming presence of background metagenomic DNA in clinical specimens. In this study, we investigated selective whole-genome amplification (SWGA) utilizing multiple displacement amplification (MDA) in conjunction with custom oligonucleotides with an increased specificity for the T.

Durability of sustained virological response to glecaprevir/pibrentasvir and resistance development: A long-term follow-up study.

Background And Aims: This study aimed to determine durability of sustained virologic response (SVR) in hepatitis C virus-infected participants treated with glecaprevir- and/or pibrentasvir-containing regimens.

Methods: M13-576, a rollover study, evaluated the durability of SVR in a follow-up period of approximately 3 years after hepatitis C virus genotype 1-6-infected participants received a glecaprevir- and/or pibrentasvir-containing regimen in previous phase 2/3 clinical trials. The primary efficacy endpoint was the percentage of participants maintaining SVR and the percentage of participants experiencing relapse or reinfections.

Efficacy and Safety of 8- or 12 Weeks of Glecaprevir/Pibrentasvir in Patients with Evidence of Portal Hypertension.

Introduction: High efficacy and safety of 8-week glecaprevir/pibrentasvir (G/P) therapy was seen in hepatitis C (HCV)-infected, treatment-naïve (TN), compensated cirrhosis (CC) patients in EXPEDITION-8. To provide further understanding of the efficacy of G/P treatment in HCV-infected TN patients with CC and clinical evidence of portal hypertension (PHT), this analysis focused on differences in sustained virologic response at post-treatment week 12 (SVR12) between 8-week and 12-week G/P treatment groups in patients with PHT, and on differences in safety outcomes between PHT and non-PHT groups.

Methods: Data were derived from an ad hoc subgroup analysis of the EXPEDITION-8 study for patients receiving 8 weeks of G/P therapy, and pooled patient-level data from nine clinical studies for patients receiving 12 weeks of therapy.

Adolescents Are More Likely to Help Others on Days They Take Risks and Crave Social Connections.

This study examined how adolescents' risk-taking behaviors were related to their prosocial behaviors on a daily level and how this association differed depending on adolescents' daily and average levels of sensation seeking and social craving. Adolescents (N = 212; M  = 15 years) completed daily diaries for 14 days. Adolescents were more likely to engage in prosocial behavior on days when they also took risks, but only when they also felt high levels of social craving.