Single-cell analyses reveal that monocyte gene expression profiles influence HIV-1 reservoir size in acutely treated cohorts.

Elimination of latent HIV-1 is a major goal of AIDS research but the host factors determining the size of these reservoirs are poorly understood. Here, we investigated whether differences in host gene expression modulate the size of the HIV-1 reservoir during suppressive ART. Peripheral blood mononuclear cells (PBMC) from fourteen individuals initiating ART during acute infection who demonstrated effective viral suppression but varying magnitude of total HIV-1 DNA were characterized by single-cell RNA sequencing (scRNA-seq).

Spatial and single-nucleus transcriptomic analysis of genetic and sporadic forms of Alzheimer's disease.

The pathogenesis of Alzheimer's disease (AD) depends on environmental and heritable factors, with its molecular etiology still unclear. Here we present a spatial transcriptomic (ST) and single-nucleus transcriptomic survey of late-onset sporadic AD and AD in Down syndrome (DSAD). Studying DSAD provides an opportunity to enhance our understanding of the AD transcriptome, potentially bridging the gap between genetic mouse models and sporadic AD.

Hydrogen Bonding and Noncovalent Electric Field Effects in the Photoconversion of a Phytochrome.

A profound understanding of protein structure and mechanism requires dedicated experimental and theoretical tools to elucidate electrostatic and hydrogen bonding interactions in proteins. In this work, we employed an approach to disentangle noncovalent and hydrogen-bonding electric field changes during the reaction cascade of a multidomain protein, i.e.

Prospective prediction of childhood body mass index trajectories using multi-task Gaussian processes.

Background: Body mass index (BMI) trajectories have been used to assess the growth of children with respect to their peers, and to anticipate future obesity and disease risk. While retrospective BMI trajectories have been actively studied, models to prospectively predict continuous BMI trajectories have not been investigated.

Materials And Methods: Using longitudinal BMI measurements between birth and age 10 y from a mother-offspring cohort, we leveraged a multi-task Gaussian process approach to develop and evaluate a unified framework for modeling, clustering, and prospective prediction of BMI trajectories.

The prospective associations of fetal growth-related pregnancy complications with subsequent breastfeeding duration and markers of human milk production.

Background: The development of the breast for lactation occurs throughout pregnancy. It is unknown whether pregnancy complications resulting in poor fetal growth can affect breastfeeding (BF) success.

Objectives: We examined whether fetal growth-related pregnancy complications were associated with earlier BF cessation and changes in the concentrations of human milk biomarkers of low milk production.

Exploring multi-omics and clinical characteristics linked to accelerated biological aging in Asian women of reproductive age: insights from the S-PRESTO study.

Background: Phenotypic age (PhenoAge), a widely used marker of biological aging, has been shown to be a robust predictor of all-cause mortality and morbidity in different populations. Existing studies on biological aging have primarily focused on individual domains, resulting in a lack of a comprehensive understanding of the multi-systemic dysregulation that occurs in aging.

Methods: PhenoAge was evaluated based on a linear combination of chronological age (CA) and 9 clinical biomarkers in 952 multi-ethnic Asian women of reproductive age.

Innovative Microencapsulation of Polymyxin B for Enhanced Antimicrobial Efficacy via Coated Spray Drying.

This study aims to develop an innovative microencapsulation method for coated Polymyxin B, utilizing various polysaccharides such as hydroxypropyl β-cyclodextrin, alginate, and chitosan, implemented through a three-fluid nozzle (3FN) spray drying process. High-performance liquid chromatography (HPLC) analysis revealed that formulations with a high ratio of sugar cage, hydroxypropyl β-cyclodextrin (HPβCD), and sodium alginate (coded as ALGCDP) resulted in a notable 16-fold increase in Polymyxin B recovery compared to chitosan microparticles. Morphological assessments using fluorescence labeling confirmed successful microparticle formation with core/shell structures.

HIV incidence and its associated factors among young adults with multiple sexual partners in Maputo, Mozambique: a vaccine preparedness study.

Introduction: Sub-Saharan Africa has a high burden of HIV, particularly among female sex workers (FSW) and men who have sex with men (MSM). Future clinical trials to evaluate vaccines and other interventions to prevent HIV will need to enroll populations with high HIV incidence. We conducted an observational study of HIV incidence among men and women with multiple sexual partners-including MSM and FSW-in Maputo, Mozambique, in order to prepare the country to conduct future efficacy trials of candidate HIV vaccines and other HIV prevention products.

SARS-CoV-2 ferritin nanoparticle vaccines produce hyperimmune equine sera with broad sarbecovirus activity.

The rapid emergence of SARS-CoV-2 variants of concern (VoC) and the threat of future zoonotic sarbecovirus spillover emphasizes the need for broadly protective next-generation vaccines and therapeutics. We utilized SARS-CoV-2 spike ferritin nanoparticle (SpFN), and SARS-CoV-2 receptor binding domain ferritin nanoparticle (RFN) immunogens, in an equine model to elicit hyperimmune sera and evaluated its sarbecovirus neutralization and protection capacity. Immunized animals rapidly elicited sera with the potent neutralization of SARS-CoV-2 VoC, and SARS-CoV-1 pseudoviruses, and potent binding against receptor binding domains from sarbecovirus clades 1b, 1a, 2, 3, and 4.

Implementation of the psycho-existential symptom assessment scale in palliative care: Qualitative analysis of stakeholders perspectives.

Objectives: To explore 1) perspectives of feasibility, acceptability, integration and sustainability of the Psycho-existential Symptom Assessment Scale (PeSAS); 2) barriers and benefits of PeSAS in its real-world performance; and 3) clinician confidence and perceived competency in using PeSAS.

Methods: Thirty-one key stakeholders from nine palliative care services who participated in the implementation of the PeSAS were purposefully sampled and participated in semi-structured interviews. Data was managed using the Determinants Framework.

Serum metabolites and hypercholesterolemia: insights from a two-sample Mendelian randomization study.

Background: Hypercholesterolemia, a critical contributor to cardiovascular disease, is not fully understood in terms of its relationship with serum metabolites and their role in disease pathogenesis.

Methods: This study leveraged GWAS data to explore the relationship between serum metabolites and hypercholesterolemia, pinpointing significant metabolites via Mendelian Randomization (MR) and KEGG pathway enrichment analysis. Data on metabolites were sourced from a European population, with analysis focusing on individuals diagnosed with hypercholesterolemia.

Compatibility of medication admixtures in continuous subcutaneous infusions: prioritizing laboratory testing for common combinations.

Objectives: Continuous subcutaneous infusions (CSCIs) are indicated as an alternative therapy when the oral route is not viable. However, despite their widespread use in palliative care, the evidence for admixture compatibility remains a limitation. It is estimated that a significant number of admixtures used in practice are not supported by laboratory studies, which may lead to suboptimal clinical outcomes.

Prediction of differential Gag versus Env responses to a mosaic HIV-1 vaccine regimen by HLA class I alleles.

class I variation has the strongest effect genome-wide on outcome after HIV infection, and as such, an understanding of the impact of polymorphism on response to HIV vaccination may inform vaccine design. We sought associations with HIV-directed immunogenicity in the phase 1/2a APPROACH vaccine trial, which tested vaccine regimens containing mosaic inserts in Ad26 and MVA vectors, with or without a trimeric gp140 protein. While there were no allelic associations with the overall cellular immune response to the vaccine assessed by ELISpot (Gag, Pol, and Env combined), significant associations with differential response to Gag compared to Env antigens were observed.

Differences in neutralizing antibody sensitivities and envelope characteristics indicate distinct antigenic properties of Nigerian HIV-1 subtype G and CRF02_AG.

The magnitude of the HIV-1 epidemic in Nigeria is second only to the subtype C epidemic in South Africa, yet the subtypes prevalent in Nigeria require further characterization. A panel of 50 subtype G and 18 CRF02_AG Nigerian HIV-1 pseudoviruses (PSV) was developed and envelope coreceptor usage, neutralization sensitivity and cross-clade reactivity were characterized. These PSV were neutralized by some antibodies targeting major neutralizing determinants, but potentially important differences were observed in specific sensitivities (eg.

Does voluntary assisted dying impact quality palliative care? A retrospective mixed-method study.

Objectives: We aimed to explore the relationship between the pursuit of voluntary assisted dying (VAD) and the delivery of quality palliative care in an Australian state where VAD was newly available METHODS: We adopted a retrospective convergent mixed-methods design to gather and interpret data from records of 141 patients who expressed an interest in and did or did not pursue VAD over 2 years. Findings were correlated against quality domains.

Results: The mean patient age was 72.

Immunogenicity of 2 therapeutic mosaic HIV-1 vaccine strategies in individuals with HIV-1 on antiretroviral therapy.

Mosaic HIV-1 vaccines have been shown to elicit robust humoral and cellular immune responses in people living with HIV-1 (PLWH), that had started antiretroviral therapy (ART) during acute infection. We evaluated the safety and immunogenicity of 2 mosaic vaccine regimens in virologically suppressed individuals that had initiated ART during the chronic phase of infection, exemplifying the majority of PLWH. In this double-blind, placebo-controlled phase 1 trial (IPCAVD013/HTX1002) 25 ART-suppressed PLWH were randomized to receive Ad26.