A systematic benchmark of Nanopore long-read RNA sequencing for transcript-level analysis in human cell lines.

The human genome contains instructions to transcribe more than 200,000 RNAs. However, many RNA transcripts are generated from the same gene, resulting in alternative isoforms that are highly similar and that remain difficult to quantify. To evaluate the ability to study RNA transcript expression, we profiled seven human cell lines with five different RNA-sequencing protocols, including short-read cDNA, Nanopore long-read direct RNA, amplification-free direct cDNA and PCR-amplified cDNA sequencing, and PacBio IsoSeq, with multiple spike-in controls, and additional transcriptome-wide N-methyladenosine profiling data.

Safety, immunogenicity and effect on viral rebound of HTI vaccines combined with a TLR7 agonist in early-treated HIV-1 infection: a randomized, placebo-controlled phase 2a trial.

Building on results from the AELIX-002 trial with HIVACAT T-cell immunogen (HTI)-based vaccines, the AELIX-003 (NCT04364035) trial tested the safety of the combination of ChAdOx1.HTI (C) and MVA.HTI (M), with the TLR7 agonist vesatolimod (VES), in a double-blind, placebo-controlled, randomized clinical trial in 50 virally suppressed early-treated men with HIV-1 infection.

First-In-Human Dose Finding Study of Venadaparib (IDX-1197), a Potent and Selective PARP Inhibitor, in Patients With Advanced Solid Tumors.

Background: Venadaparib, a novel poly (ADP-ribose) polymerase (PARP) inhibitor, has demonstrated high PARP-1/2 selectivity over other PARP family members and exhibited strong PARP-trapping activity, effectively inhibiting tumor growth in homologous recombination deficient (HRD) cancer in vitro and in vivo.

Methods: This phase 1, dose-finding study evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics and anticancer efficacy of venadaparib as monotherapy in patients with advanced solid tumors that progressed after standard-of-care therapy. The study employed a conventional 3+3 design, with doses ranging from 2 mg/d to 240 mg/d.

IGLON5 Frequency in Idiopathic REM Sleep Behavior Disorder: A Multicenter Study.

Background And Objectives: Idiopathic/isolated REM sleep behavior disorder (iRBD) has been strongly linked to neurodegenerative synucleinopathies such as Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. However, there have been increasing reports of RBD as a presenting feature of serious and treatable autoimmune syndromes, particularly IGLON5. This study's objective was to investigate the frequency of autoantibodies in a large cohort of participants with iRBD.

Effects and Costs of Hepatitis C Virus Elimination for the Whole Population in China: A Modelling Study.

Background And Objective: China has the highest number of hepatitis C virus (HCV) infections in the world. However, it is unclear what levels of screening and treatment are needed to achieve the WHO 2030 hepatitis C elimination targets. We aimed to evaluate the impact of scaling up interventions on the hepatitis C epidemic and determine how and at what cost these elimination targets could be achieved for the whole population in China.

Opioid agonist treatment outcomes among individuals with a history of nonfatal overdose: Findings from a pragmatic, pan-Canadian, randomized control trial.

Background And Objectives: History of nonfatal overdose (NFO) is common among people who use opioids, but little is known about opioid agonist treatment (OAT) outcomes for this high-risk subpopulation. The objective of this study was to investigate the relative effectiveness of buprenorphine/naloxone and methadone on retention and suppression of opioid use among individuals with opioid use disorder (OUD) and history of NFO.

Methods: Secondary analysis of a pan-Canadian pragmatic trial comparing flexible take-home buprenorphine/naloxone and supervised methadone for people with OUD and history of NFO.

Five autism-associated transcriptional regulators target shared loci proximal to brain-expressed genes.

Many autism spectrum disorder (ASD)-associated genes act as transcriptional regulators (TRs). Chromatin immunoprecipitation sequencing (ChIP-seq) was used to identify the regulatory targets of ARID1B, BCL11A, FOXP1, TBR1, and TCF7L2, ASD-associated TRs in the developing human and mouse cortex. These TRs shared substantial overlap in the binding sites, especially within open chromatin.

Engineering tumor-colonizing E. coli Nissle 1917 for detection and treatment of colorectal neoplasia.

Bioengineered probiotics enable new opportunities to improve colorectal cancer (CRC) screening, prevention and treatment. Here, first, we demonstrate selective colonization of colorectal adenomas after oral delivery of probiotic E. coli Nissle 1917 (EcN) to a genetically-engineered murine model of CRC predisposition and orthotopic models of CRC.

Racial and Ethnic Differences in the Population-Attributable Fractions of Alzheimer Disease and Related Dementias.

Background And Objectives: Previous studies estimated that modifiable risk factors explain up to 40% of the dementia cases in the United States and that this population-attributable fraction (PAF) differs by race and ethnicity-estimates of future impact based on the risk factor prevalence in contemporary surveys. The aim of this study was to determine the race-specific and ethnicity-specific PAF of late-onset Alzheimer disease and related dementias (ADRDs) based on the risk factor prevalence and associations observed on the same individuals within a prospective cohort.

Methods: Data were from Multiethnic Cohort Study participants (African American, Japanese American, Latino, Native Hawaiian, and White) enrolled in Medicare Fee-for-Service.

Regurgitant volume to LA volume ratio in patients with secondary MR: the COAPT trial.

Aims: The conceptual framework of proportionate vs. disproportionate mitral regurgitation (MR) translates poorly to individual patients with heart failure (HF) and secondary MR. A novel index, the ratio of MR severity to left atrial volume (LAV), may identify patients with 'disproportionate' MR and a higher risk of events.

Clinical Benefit of Intravascular Imaging Compared With Conventional Angiography in Left Main Coronary Artery Intervention.

Background: The RENOVATE-COMPLEX-PCI (Randomized Controlled Trial of Intravascular Imaging Guidance Versus Angiography-Guidance on Clinical Outcomes After Complex Percutaneous Coronary Intervention) demonstrated that intravascular imaging-guided percutaneous coronary intervention (PCI) improved clinical outcome compared with angiography-guided PCI for patients with complex coronary artery lesions. This study aims to assess whether the prognostic benefit of intravascular imaging-guided procedural optimization persists in patients undergoing PCI for left main coronary artery disease.

Methods: Of 1639 patients enrolled in the RENOVATE-COMPLEX-PCI, 192 patients with left main coronary artery disease were selected for the current prespecified substudy.

Resistance mechanisms for Gram-negative bacteria-specific lipopeptides, turnercyclamycins, differ from that of colistin.

Bacterial resistance to antibiotics is a crisis. is among the CDC urgent threat pathogens in part for this reason. Lipopeptides known as turnercyclamycins are produced by symbiotic bacteria that normally live in marine mollusks, where they may be involved in shaping their symbiotic niche.

Single Ad26.COV2.S booster dose following two doses of BBIBP-CorV vaccine against SARS-CoV-2 infection in adults: Day 28 results of a phase 1/2 open-label trial.

Background: The inactivated COVID-19 whole-virus vaccine BBIBP-CorV has been extensively used worldwide. Heterologous boosting after primary vaccination can induce higher immune responses against SARS-CoV-2 than homologous boosting. The safety and immunogenicity after 28 days of a single Ad26.

Incidence of cognitive impairment and dementia after hospitalisation for pneumonia: a UK population-based matched cohort study.

Background: Survivors of common infections may develop cognitive impairment or dementia; however, the risk of these conditions in people hospitalised with pneumonia is not well established.

Methods: A matched cohort study was conducted using Hospital Episode Statistics (HES) data linked to the Clinical Practice Research Database (CPRD). Adults with the first International Classification of Diseases (10th Revision) code for pneumonia recorded in the HES between 1 July 2002 and 30 June 2017 were included, and up to four controls without hospitalisation for pneumonia in the CPRD were matched by sex, age and practice.

Transcatheter Mitral Valve Replacement Versus Medical Therapy for Secondary Mitral Regurgitation: A Propensity Score-Matched Comparison.

Background: Transcatheter mitral valve replacement (TMVR) is an emerging therapeutic alternative for patients with secondary mitral regurgitation (MR). Outcomes of TMVR versus guideline-directed medical therapy (GDMT) have not been investigated for this population. This study aimed to compare clinical outcomes of patients with secondary MR undergoing TMVR versus GDMT alone.

The global burden of metabolic disease: Data from 2000 to 2019.

Global estimates of prevalence, deaths, and disability-adjusted life years (DALYs) from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 were examined for metabolic diseases (type 2 diabetes mellitus [T2DM], hypertension, and non-alcoholic fatty liver disease [NAFLD]). For metabolic risk factors (hyperlipidemia and obesity), estimates were limited to mortality and DALYs. From 2000 to 2019, prevalence rates increased for all metabolic diseases, with the greatest increase in high socio-demographic index (SDI) countries.