CRISPR Dependency Screens in Primary Hematopoietic Stem Cells Identify KDM3B as a Genotype-specific Vulnerability in IDH2- and TET2-mutant Cells.

Clonal hematopoiesis (CH) is a common premalignant state in the blood and confers an increased risk of blood cancers and all-cause mortality. Identification of therapeutic targets in CH has been hindered by the lack of an ex vivo platform amenable for studying primary hematopoietic stem and progenitor cells (HSPCs). Here, we utilize an ex vivo co-culture system of HSPCs with bone marrow endothelial cells to perform CRISPR/Cas9 screens in mutant HSPCs.

Plasma Proteomics Identifies B2M as a Regulator of Pulmonary Hypertension in Heart Failure With Preserved Ejection Fraction.

Background: Pulmonary hypertension (PH) represents an important phenotype in heart failure with preserved ejection fraction (HFpEF). However, management of PH-HFpEF is challenging because mechanisms involved in the regulation of PH-HFpEF remain unclear.

Methods: We used a mass spectrometry-based comparative plasma proteomics approach as a sensitive and comprehensive hypothesis-generating discovery technique to profile proteins in patients with PH-HFpEF and control subjects.

A Test of the Self-Medication Hypothesis Using a Latent Measurement Model: Are Stress and Impaired Control over Alcohol Mediating Mechanisms of Parenting Styles on Heavy Episodic Drinking and Alcohol-Related Problems among University Students?

Introduction: The self-medication hypothesis (SMH) suggests that individuals consume alcohol to alleviate stressful emotions. Still, the underlying mechanisms between stress and heavy episodic drinking remain to be explored. Impaired control over drinking (IC) reflects a failure of self-regulation specific to the drinking context, with individuals exceeding self-prescribed limits.

Pathobiological signatures of dysbiotic lung injury in pediatric patients undergoing stem cell transplantation.

Hematopoietic cell transplantation (HCT) uses cytotoxic chemotherapy and/or radiation followed by intravenous infusion of stem cells to cure malignancies, bone marrow failure and inborn errors of immunity, hemoglobin and metabolism. Lung injury is a known complication of the process, due in part to disruption in the pulmonary microenvironment by insults such as infection, alloreactive inflammation and cellular toxicity. How microorganisms, immunity and the respiratory epithelium interact to contribute to lung injury is uncertain, limiting the development of prevention and treatment strategies.

The Mediating Role of Kynurenine Pathway Metabolites on the Relationship Between Inflammation and Muscle Mass in Oldest-Old Men.

Tryptophan (TRP) metabolites along the kynurenine (KYN) pathway (KP) have been found to influence muscle. Proinflammatory cytokines are known to stimulate the degradation of TRP down the KP. Given that both inflammation and KP metabolites have been connected with loss of muscle, we assessed the potential mediating role of KP metabolites on inflammation and muscle mass in older men.

Safety and efficacy of peptide receptor radionuclide therapy in neuroendocrine tumors: A single center experience.

Peptide receptor radionucleotide therapy (PRRT) with 177Lu-dotatate is widely used for the treatment of patients with neuroendocrine tumors (NETs). We analyzed data from 104 patients with NETs treated with 177Lu -dotatate at a US academic center between December 2017 and October 2020 to better understand patterns of long-term efficacy, safety, and toxicity in the real-world setting. 177Lu-dotatate (200 mCi) was administered every eight weeks for four doses.

Monitoring the susceptibility of Bemisia tabaci Middle East-Asia Minor 1 (Hemiptera: Aleyrodidae) to afidopyropen, cyantraniliprole, dinotefuran, and flupyradifurone in south Florida vegetable fields.

Bemisia tabaci Middle East-Asia Minor 1 (MEAM1) is a significant pest that damages a wide range of high-value vegetable crops in south Florida. This pest has demonstrated the ability to develop resistance to various insecticide groups worldwide. Monitoring the resistance levels of MEAM1 populations and maintaining baseline susceptibility data are crucial for the long-term effectiveness of insecticide management strategies.

Sex and genotype influence respiratory function under hypoxic and hypoxic-hypercapnic conditions.

The apolipoprotein E () gene has been studied due to its influence on Alzheimer's disease (AD) development and work in an mouse model recently demonstrated impaired respiratory motor plasticity following spinal cord injury (SCI). Individuals with AD often copresent with obstructive sleep apnea (OSA) characterized by cessations in breathing during sleep. Despite the prominence of genotype and sex as factors in AD progression, little is known about the impact of these variables on respiratory control.

Preclinical pharmacokinetic studies of villocarine A, an active Uncaria alkaloid.

Villocarine A is a bioactive indole alkaloid isolated from the Uncaria genus. It has demonstrated vasorelaxation activity and potential to protect the central nervous system. To identify the pharmacokinetic properties of villocarine A, a series of in vitro and in vivo studies have been performed.

Reproductive and endocrine-disrupting toxicity of pyrogallol in catfish (Clariasgariepinus).

Endocrine disruptors are synthetic or natural chemicals that can agonize/antagonize hormone receptors or can interfere with the production and secretion of hormones, leading to altered tissue histology and physiology. Pyrogallol is a contaminant widely distributed in aquatic environments that presents health risks to both humans and animals. However, the potential for endocrine disruption by pyrogallol, particularly in fish, are lacking.

Melatonin seed priming improves early establishment and water stress tolerance of peanut.

Water stress is a major cause of yield loss in peanut cultivation. Melatonin seed priming has been used to enhance stress tolerance in several crops, but not in peanut. We investigated the impact of seed priming with melatonin on the growth, development, and drought tolerance of two peanut cultivars, TUFRunner™ '511', a drought tolerant cultivar, and New Mexico Valencia A, a drought sensitive cultivar.

Setmelanotide for the treatment of acquired hypothalamic obesity: a phase 2, open-label, multicentre trial.

Background: Hypothalamic obesity resulting from hypothalamic damage might affect melanocortin signalling. We investigated the melanocortin-4 receptor agonist setmelanotide for treatment of hypothalamic obesity.

Methods: This phase 2, open-label, multicentre trial was done in five centres in the USA.

Angiogenic Gene Therapy for Refractory Angina: Results of the EXACT Phase 2 Trial.

Background: XC001 is a novel adenoviral-5 vector designed to express multiple isoforms of VEGF (vascular endothelial growth factor) and more safely and potently induce angiogenesis. The EXACT trial (Epicardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment) assessed the safety and preliminary efficacy of XC001 in patients with no option refractory angina.

Methods: In this single-arm, multicenter, open-label trial, 32 patients with no option refractory angina received a single treatment of XC001 (1×10 viral particles) via transepicardial delivery.

Deficiency of the Deubiquitinase UCHL1 Attenuates Pulmonary Arterial Hypertension.

Background: The ubiquitin-proteasome system regulates protein degradation and the development of pulmonary arterial hypertension (PAH), but knowledge about the role of deubiquitinating enzymes in this process is limited. UCHL1 (ubiquitin carboxyl-terminal hydrolase 1), a deubiquitinase, has been shown to reduce AKT1 (AKT serine/threonine kinase 1) degradation, resulting in higher levels. Given that AKT1 is pathological in pulmonary hypertension, we hypothesized that UCHL1 deficiency attenuates PAH development by means of reductions in AKT1.

Perceptions about doxycycline post-exposure prophylaxis (Doxy-PEP) as an STI-prevention strategy among gay and bisexual men (GBM) in the United States: Results from a qualitative study.

Objective: To leverage qualitative data to explore gay and bisexual men's (GBM) perceptions about doxycycline post-exposure prophylaxis (Doxy-PEP). Doxy-PEP is a novel biomedical STI-prevention strategy that helps reduce the risk of acquiring bacterial STIs. Little is known about Doxy-PEP's acceptability in the U.

Perspectives Among Health Care Providers and People with HIV on the Implementation of Long-Acting Injectable Cabotegravir/Rilpivirine for Antiretroviral Therapy in Florida.

Long-acting injectable (LAI) cabotegravir/rilpivirine (CAB/RPV) for antiretroviral therapy (ART) could benefit many people with HIV (PWH). However, its impact will largely be determined by providers' willingness to prescribe it and PWH's willingness to take it. This study explores the perceived barriers and facilitators of LAI CAB/RPV implementation among PWH and HIV care providers in Florida, a high prevalence setting.

Functional redundancy in tRNA dihydrouridylation.

Dihydrouridine (D) is a common modified base found predominantly in transfer RNA (tRNA). Despite its prevalence, the mechanisms underlying dihydrouridine biosynthesis, particularly in prokaryotes, have remained elusive. Here, we conducted a comprehensive investigation into D biosynthesis in Bacillus subtilis through a combination of genetic, biochemical, and epitranscriptomic approaches.

A Cross-Sectional Study of Grocery Shopping Factors of Importance among Food-Insecure African Americans.

The objective of this study was to (1) assess via cross-sectional survey the prevalence of food insecurity among African Americans [AAs] after their most recent grocery shopping trip, and (2) examine the grocery shopping factors of importance and characteristics of food-insecure AA grocery shoppers. Most (70.4%) were food-insecure.

Bridging the Gap: Multi-Omics Profiling of Brain Tissue in Alzheimer's Disease and Older Controls in Multi-Ethnic Populations.

Introduction: Multi-omics studies in Alzheimer's disease (AD) revealed many potential disease pathways and therapeutic targets. Despite their promise of precision medicine, these studies lacked African Americans (AA) and Latin Americans (LA), who are disproportionately affected by AD.

Methods: To bridge this gap, Accelerating Medicines Partnership in AD (AMP-AD) expanded brain multi-omics profiling to multi-ethnic donors.

Perspectives on Injectable HIV Pre-Exposure Prophylaxis: A Qualitative Study of Health Care Providers in the United States.

The introduction of injectable HIV pre-exposure prophylaxis (PrEP) has the potential to significantly change the biomedical HIV prevention landscape. However, effective implementation will require health care providers to adopt, prescribe, and administer injectable PrEP within clinical settings. This study qualitatively examined challenges and benefit of injectable PrEP implementation from the perspective of health care providers.