SNORD80-guided 2'-O-methylation stabilizes the lncRNA GAS5 to regulate cellular stress responses.

The introns of the gene encoding the long noncoding RNA (lncRNA) GAS5 host up to 10 C/D box small nucleolar RNAs (snoRNAs). However, whether there is a regulatory and functional relationship between these snoRNAs and GAS5 is unknown. Here, we show that the expression of SNORD80, but not the other snoRNAs, parallels GAS5 expression and is regulated alongside GAS5 in response to cellular stress.

Exploiting human immune repertoire transgenic mice for protective monoclonal antibodies against antimicrobial resistant Acinetobacter baumannii.

The use of monoclonal antibodies for the control of drug resistant nosocomial bacteria may alleviate a reliance on broad spectrum antimicrobials for treatment of infection. We identify monoclonal antibodies that may prevent infection caused by carbapenem resistant Acinetobacter baumannii. We use human immune repertoire mice (Kymouse platform mice) as a surrogate for human B cell interrogation to establish an unbiased strategy to probe the antibody-accessible target landscape of clinically relevant A.

Queering genomics: How cisnormativity undermines genomic science.

Over the past century, genetics and genomics ("genomics") have contributed significantly to our knowledge of human biology and disease. Genomics has also bolstered inaccurate and harmful arguments about "essential" differences between socially defined groups. These purported differences have reinforced class hierarchies and justified the mistreatment of groups such as Black people, Indigenous people, and other people of color and/or people with disabilities.

Multicenter evaluation of the Selux Next-Generation Phenotyping antimicrobial susceptibility testing system.

The Selux Next-Generation Phenotyping (NGP) system (Charlestown, MA) is a new antimicrobial susceptibility testing system that utilizes two sequential assays performed on all wells of doubling dilution series to determine MICs. A multicenter evaluation of the performance of the Selux NGP system compared with reference broth microdilution was conducted following FDA recommendations and using FDA-defined breakpoints. A total of 2,488 clinical and challenge isolates were included; gram-negative isolates were tested against 24 antimicrobials, and gram-positive isolates were tested against 15 antimicrobials.

Accuracy of a smart bottle in measuring fluid intake by American football players during pre-season training.

Rehydration is important for athlete performance and recovery. However, it can be challenging to follow appropriate fluid replacement practices due in part to difficulties in tracking fluid intake in real time. The purpose of this study was to determine the accuracy of a smart bottle in measuring fluid intake during exercise.

Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants.

Background: Whether vaccination during pregnancy could reduce the burden of respiratory syncytial virus (RSV)-associated lower respiratory tract illness in newborns and infants is uncertain.

Methods: In this phase 3, double-blind trial conducted in 18 countries, we randomly assigned, in a 1:1 ratio, pregnant women at 24 through 36 weeks' gestation to receive a single intramuscular injection of 120 μg of a bivalent RSV prefusion F protein-based (RSVpreF) vaccine or placebo. The two primary efficacy end points were medically attended severe RSV-associated lower respiratory tract illness and medically attended RSV-associated lower respiratory tract illness in infants within 90, 120, 150, and 180 days after birth.

COPD lung studies of Nrf2 expression and the effects of Nrf2 activators.

Background: Nrf2 regulates cellular antioxidant defence in lung cells, including epithelial cells and alveolar macrophages (AM). The Nrf2/Keap-1 pathway can be modulated by activators with different modes of action; electrophilic compounds and protein-protein interaction (PPI) inhibitors. We assessed Nrf2 and Keap-1 protein and gene levels in COPD compared to controls and the effect of Nrf2 activators on COPD AM.

A smartphone sensor-based digital outcome assessment of multiple sclerosis.

Background: Sensor-based monitoring tools fill a critical gap in multiple sclerosis (MS) research and clinical care.

Objective: The aim of this study is to assess performance characteristics of the Floodlight Proof-of-Concept (PoC) app.

Methods: In a 24-week study (clinicaltrials.

Crossed cerebellar diaschisis on F-FDG PET: Frequency across neurodegenerative syndromes and association with C-PIB and F-Flortaucipir.

We used F-FDG-PET to investigate the frequency of crossed cerebellar diaschisis (CCD) in 197 patients with various syndromes associated with neurodegenerative diseases. In a subset of 117 patients, we studied relationships between CCD and cortical asymmetry of Alzheimer's pathology (β-amyloid (C-PIB) and tau (F-Flortaucipir)). PET images were processed using MRIs to derive parametric SUVR images and define regions of interest.

Association of and Clinical Variability in Alzheimer Disease With the Pattern of Tau- and Amyloid-PET.

Objective: To assess whether Alzheimer disease (AD) clinical presentation and relate to the burden and topography of β-amyloid (Aβ) and tau pathologies using in vivo PET imaging.

Methods: We studied 119 Aβ-positive symptomatic patients aged 48-95 years, including 29 patients with logopenic variant primary progressive aphasia (lvPPA) and 21 with posterior cortical atrophy (PCA). Pittsburgh compound B (PiB)-Aβ and flortaucipir (tau)-PET standardized uptake value ratio (SUVR) images were created.

Proof of Concept of a Personalized Genetic Risk Tool to Promote Smoking Cessation: High Acceptability and Reduced Cigarette Smoking.

Relatively little is known about the possible effects of personalized genetic risk information on smoking, the leading preventable cause of morbidity and mortality. We examined the acceptability and potential behavior change associated with a personalized genetically informed risk tool () among current smokers. Current smokers ( = 108) were enrolled in a pre-post study with three visits.

Low Burden Strategies Are Needed to Reduce Smoking in Rural Healthcare Settings: A Lesson from Cancer Clinics.

Rural populations face significant smoking-related health disparities, such as a higher prevalence of lung cancer and cancer mortality, higher prevalence of smoking, and lower likelihood of receiving cessation treatment than urban counterparts. A significant proportion of health disparities in rural populations could be eliminated with low-barrier, easy-access treatment delivery methods for smoking cessation. In this study, we assessed treatment engagement among patients in rural and urban settings.

International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex.

Levothyroxine in Women with Thyroid Peroxidase Antibodies before Conception.

Background: Thyroid peroxidase antibodies are associated with an increased risk of miscarriage and preterm birth, even when thyroid function is normal. Small trials indicate that the use of levothyroxine could reduce the incidence of such adverse outcomes.

Methods: We conducted a double-blind, placebo-controlled trial to investigate whether levothyroxine treatment would increase live-birth rates among euthyroid women who had thyroid peroxidase antibodies and a history of miscarriage or infertility.

Relative sarcopenia and mortality and the modifying effects of chronic kidney disease and adiposity.

Background: Conventional definitions of sarcopenia based on lean mass may fail to capture low lean mass relative to higher fat mass, that is, relative sarcopenia. The objective of this study is to determine the associations of sarcopenia and relative sarcopenia with mortality independent of co-morbidities, and whether chronic kidney disease (CKD) and adiposity alter these associations.

Methods: Dual energy X-ray absorptiometry-derived appendicular lean mass index (ALMI, kg/m ) and fat mass index (FMI, kg/m ) were assessed in 14 850 National Health and Nutrition Examination Survey participants from 1999 to 2006 and were linked to death certificate data in the National Death Index with follow-up through 2011.

Associations between [F]AV1451 tau PET and CSF measures of tau pathology in a clinical sample.

Objective: To assess the relationships between fluid and imaging biomarkers of tau pathology and compare their diagnostic utility in a clinically heterogeneous sample.

Methods: Fifty-three patients (28 with clinical Alzheimer disease [AD] and 25 with non-AD clinical neurodegenerative diagnoses) underwent β-amyloid (Aβ) and tau ([F]AV1451) PET and lumbar puncture. CSF biomarkers (Aβ, total tau [t-tau], and phosphorylated tau [p-tau]) were measured by multianalyte immunoassay (AlzBio3).

Hsp90 activator Aha1 drives production of pathological tau aggregates.

The microtubule-associated protein tau (MAPT, tau) forms neurotoxic aggregates that promote cognitive deficits in tauopathies, the most common of which is Alzheimer's disease (AD). The 90-kDa heat shock protein (Hsp90) chaperone system affects the accumulation of these toxic tau species, which can be modulated with Hsp90 inhibitors. However, many Hsp90 inhibitors are not blood-brain barrier-permeable, and several present associated toxicities.

Senescent cells: an emerging target for diseases of ageing.

Chronological age represents the single greatest risk factor for human disease. One plausible explanation for this correlation is that mechanisms that drive ageing might also promote age-related diseases. Cellular senescence, which is a permanent state of cell cycle arrest induced by cellular stress, has recently emerged as a fundamental ageing mechanism that also contributes to diseases of late life, including cancer, atherosclerosis and osteoarthritis.

Cardiovascular and Metabolic Effects of ANGPTL3 Antisense Oligonucleotides.

Background: Epidemiologic and genomewide association studies have linked loss-of-function variants in ANGPTL3, encoding angiopoietin-like 3, with low levels of plasma lipoproteins.

Methods: We evaluated antisense oligonucleotides (ASOs) targeting Angptl3 messenger RNA (mRNA) for effects on plasma lipid levels, triglyceride clearance, liver triglyceride content, insulin sensitivity, and atherosclerosis in mice. Subsequently, 44 human participants (with triglyceride levels of either 90 to 150 mg per deciliter [1.