Lymph Node Adiposity and Metabolic Dysfunction-Associated Steatotic Liver Disease.

: Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as the most common chronic liver disease, is soon to be the leading indication for liver transplantation; however, the diagnosis may remain occult for decades. There is a need for biomarkers that identify patients at risk for MASLD and patients at risk for disease progression to optimize patient management and outcomes. Lymph node adiposity (LNA) is a novel marker of adiposity identified within axillary lymph nodes on screening mammography.

Dual α-globin-truncated erythropoietin receptor knockin restores hemoglobin production in α-thalassemia-derived erythroid cells.

The most severe form of α-thalassemia results from loss of all four copies of α-globin. Postnatally, patients face challenges similar to β-thalassemia, including severe anemia and erythrotoxicity due to the imbalance of β-globin and α-globin chains. Despite progress in genome editing treatments for β-thalassemia, there is no analogous curative option for α-thalassemia.

Patterns of initial treatment and subsequent care escalation among medicare beneficiaries with neck pain: a retrospective cohort study.

Purpose: To compare long-term care escalation encounters among three care patterns for new episodes of neck pain among Medicare beneficiaries.

Methods: We examined Medicare claims spanning a four-year period for beneficiaries with new episodes of neck pain beginning in 2019. All patients were continuously enrolled under Medicare parts A, B, and D and aged 65-99 years.

Which is the better polyp detection metric: adenomas per colonoscopy or adenoma detection rate? A simulation modeling study.

We compared the ability of adenoma detection rate (ADR) and adenoma per colonoscopy (APC) to assess endoscopist detection, using statistical principles and simulations. We simulated a population of endoscopists and patients to compare the ability of ADR versus APC for capturing true endoscopist ability (TEA). We compared these rates with and without adjustment for patient and exam factors using multivariable models, and adjustment for imprecision due to low volume using empirical Bayes (shrinkage).

Consent Norms in the BDSM Community: Strong But Not Inflexible.

The BDSM community is generally regarded as having strict consent practices, such as safewords and explicit negotiations. However, no research to date has examined the flexibility of norms around these consent practices. The present study was designed to investigate the nuances of consent communication norms among BDSM practitioners, specifically the degree to which relationship context impacts the depth and nature of consent negotiations.

Gene expression responses of CF airway epithelial cells exposed to elexacaftor/tezacaftor/ivacaftor suggest benefits beyond improved CFTR channel function.

The combination of elexacaftor/tezacaftor/ivacaftor (ETI, Trikafta) reverses the primary defect in cystic fibrosis (CF) by improving CFTR-mediated Cl and HCO secretion by airway epithelial cells (AECs), leading to improved lung function and less frequent exacerbations and hospitalizations. However, studies have shown that CFTR modulators like ivacaftor, a component of ETI, have numerous effects on CF cells beyond improved CFTR channel function. Because little is known about the effect of ETI on CF AEC gene expression, we exposed primary human AEC to ETI for 48 h and interrogated the transcriptome by RNA-seq and qPCR.

Gene expression responses of CF airway epithelial cells exposed to elexacaftor/tezacaftor/ivacaftor (ETI) suggest benefits beyond improved CFTR channel function.

Unlabelled: The combination of elexacaftor/tezacaftor/ivacaftor (ETI, Trikafta) reverses the primary defect in Cystic Fibrosis (CF) by improving CFTR mediated Cl and HCO secretion by airway epithelial cells (AEC), leading to improved lung function and less frequent exacerbations and hospitalizations. However, studies have shown that CFTR modulators like ivacaftor, a component of ETI, has numerous effects on CF cells beyond improved CFTR channel function. Because little is known about the effect of ETI on CF AEC gene expression we exposed primary human AEC to ETI for 48 hours and interrogated the transcriptome by RNA-seq and qPCR.

Population-Based Estimates of the Prevalence of Children With Congenital Heart Disease and Associated Comorbidities in the United States.

Background: Congenital heart defects (CHD) are the most common birth defects and previous estimates report the disease affects 1% of births annually in the United States. To date, CHD prevalence estimates are inconsistent due to varied definitions, data reliant on birth registries, and are geographically limited. These data sources may not be representative of the total prevalence of the CHD population.

Integrated primary and community mental health care for young adults with serious mental illness: A program evaluation.

Aim: Young adults with serious mental illness (SMI) have poor physical health and high Emergency Department (ED) and hospital utilization. Integrating primary care into community mental health care may be an important form of early intervention.

Methods: Adjusted multivariable regressions assessed changes in self-reported annual primary care, ED and hospital utilization for 83 young adults with SMI enrolled in integrated care.

Repurposing the Open Global Health Library for the discovery of novel Mpro destabilizers with scope as broad-spectrum antivirals.

The SARS coronavirus 2 (SARS-CoV-2) epidemic remains globally active. The emergence of new variants of interest and variants of concern (VoCs), which are potentially more vaccine-resistant and less sensitive to existing treatments, is evident due to their high prevalence. The prospective spread of such variants and other coronaviruses with epidemic potential demands preparedness that can be met by developing fast-track workflows to find new candidates that target viral proteins with a clear and phenotype.

Relationship of Handgrip Strength and Asymmetry with Walking Ability in Older Adults with Excess Adiposity.

When low muscle mass and impaired strength and physical function coexist with excess adiposity, it is termed sarcopenic obesity (SO). Handgrip strength (HGS) is a predictor of disability and mortality. Asymmetry in HGS, particularly ≥ 10% strength differences between hands, may indicate neuromuscular dysfunction observable prior to declines in maximal strength are detectedand therefore could be incorporated to identify those at risk of physical limitations and SO.

Escuzarmycins A-D, Potent Biofungicides to Control Blotch.

A study targeting novel antifungal metabolites identified potent antifungal activity against key plant pathogens in acetone extracts of sp. strain CA-296093. Feature-based molecular networking revealed the presence in this extract of antimycin-related compounds, leading to the isolation of four new compounds: escuzarmycins A-D (-).

Prenatal AAV9-GFP administration in fetal lambs results in transduction of female germ cells and maternal exposure to virus.

Prenatal somatic cell gene therapy (PSCGT) could potentially treat severe, early-onset genetic disorders such as spinal muscular atrophy (SMA) or muscular dystrophy. Given the approval of adeno-associated virus serotype 9 (AAV9) vectors in infants with SMA by the U.S.

Dual α-globin and truncated EPO receptor knockin restores hemoglobin production in α-thalassemia-derived red blood cells.

Alpha-thalassemia is an autosomal recessive disease with increasing worldwide prevalence. The molecular basis is due to mutation or deletion of one or more duplicated α-globin genes, and disease severity is directly related to the number of allelic copies compromised. The most severe form, α-thalassemia major (αTM), results from loss of all four copies of α-globin and has historically resulted in fatality .

Increasing equity in science requires better ethics training: A course by trainees, for trainees.

Despite the profound impacts of scientific research, few scientists have received the necessary training to productively discuss the ethical and societal implications of their work. To address this critical gap, we-a group of predominantly human genetics trainees-developed a course on genetics, ethics, and society. We intend for this course to serve as a template for other institutions and scientific disciplines.

Association between Colonoscopy Sedation Type and Polyp Detection: A Registry-based Cohort Study.

Background: Colorectal cancer is a leading cause of cancer-related death. Adenomas and serrated polyps are precursors of colorectal cancer, with serrated polyps being more difficult to detect during colonoscopy. The relationship between propofol use and polyp detection remains unclear.

Clinical Trial Protocol for "Replace Cysto": Replacing Invasive Cystoscopy with Urine Testing for Non-muscle-invasive Bladder Cancer Surveillance-A Multicenter, Randomized, Phase 2 Healthcare Delivery Trial Comparing Quality of Life During Cancer Surveillance with Xpert Bladder Cancer Monitor or Bladder EpiCheck Urine Testing Versus Frequent Cystoscopy.

"Replace Cysto" is a multisite randomized phase 2 trial including 240 participants with low-grade intermediate-risk non-muscle-invasive bladder cancer, in which participants will be randomized 1:1:1 to one of two urine marker-based approaches alternating a urine marker test (Xpert Bladder Cancer Monitor or Bladder EpiCheck) with cystoscopy or to frequent scheduled cystoscopy. The primary objective is to determine whether urinary quality of life after surveillance is significantly improved in the urine marker arms. The primary outcome will be the patient-reported urinary quality of life domain score of the validated QLQ-NMIBC24 instrument, measured 1-3 d after surveillance.

Discovery of bioactive natural products of microbial origin as inhibitors of the PD-1/PD-L1 protein-protein interaction.

The PD-1/PD-L1 protein-protein interaction (PPI) controls an adaptive immune resistance mechanism exerted by tumor cells to evade immune responses. The large-molecule nature of current commercial monoclonal antibodies against this PPI hampers their effectiveness by limiting tumor penetration and inducing severe immune-related side effects. Synthetic small-molecule inhibitors may overcome such limitations and have demonstrated promising clinical translation, but their design is challenging.

The Importance, Challenges, and Possible Solutions for Sharing Proteomics Data While Safeguarding Individuals' Privacy.

Proteomics data sharing has profound benefits at the individual level as well as at the community level. While data sharing has increased over the years, mostly due to journal and funding agency requirements, the reluctance of researchers with regard to data sharing is evident as many shares only the bare minimum dataset required to publish an article. In many cases, proper metadata is missing, essentially making the dataset useless.

Prenatal delivery of a therapeutic antisense oligonucleotide achieves broad biodistribution in the brain and ameliorates Angelman syndrome phenotype in mice.

Angelman syndrome (AS), an early-onset neurodevelopmental disorder characterized by abnormal gait, intellectual disabilities, and seizures, occurs when the maternal allele of the UBE3A gene is disrupted, since the paternal allele is silenced in neurons by the UBE3A antisense (UBE3A-AS) transcript. Given the importance of early treatment, we hypothesized that prenatal delivery of an antisense oligonucleotide (ASO) would downregulate the murine Ube3a-AS, resulting in increased UBE3A protein and functional rescue. Using a mouse model with a Ube3a-YFP allele that reports on-target ASO activity, we found that in utero, intracranial (IC) injection of the ASO resulted in dose-dependent activation of paternal Ube3a, with broad biodistribution.

Uncovering the biotechnological capacity of marine and brackish water Planctomycetota.

An appealing strategy for finding novel bioactive molecules in Nature consists in exploring underrepresented and -studied microorganisms. Here, we investigated the antimicrobial and tumoral anti-proliferative bioactivities of twenty-three marine and estuarine bacteria of the fascinating phylum Planctomycetota. This was achieved through extraction of compounds produced by the Planctomycetota cultured in oligotrophic medium followed by an antimicrobial screening against ten relevant human pathogens including Gram-positive and Gram-negative bacteria, and fungi.

Naphthoquinone Derivatives from CF-097565 Display Anti-Tumour Activity in 3D Cultures of Breast Cancer Cells.

Cancer is one of the leading causes of death worldwide, with breast cancer being the second cause of cancer-related mortality among women. Natural Products (NPs) are one of the main sources for drug discovery. During a screening campaign focused on the identification of extracts from Fundación MEDINA's library inhibiting the proliferation of cancer cell lines, a significant bioactivity was observed in extracts from cultures of the fungus CF-097565.