An engineered immunogen activates diverse HIV broadly neutralizing antibody precursors and promotes acquisition of improbable mutations.

Elicitation of HIV broadly neutralizing antibodies (bnAbs) by vaccination first requires the activation of diverse precursors, followed by successive boosts that guide these responses to enhanced breadth through the acquisition of somatic mutations. Because HIV bnAbs contain mutations in their B cell receptors (BCRs) that are rarely generated during conventional B cell maturation, HIV vaccine immunogens must robustly engage and expand B cells with BCRs that contain these improbable mutations. Here, we engineered an immunogen that activates diverse precursors of an HIV V3-glycan bnAb and promotes their acquisition of a functionally critical improbable mutation.

The use and impact of surveillance-based technology initiatives in inpatient and acute mental health settings: a systematic review.

Background: The use of surveillance technologies is becoming increasingly common in inpatient mental health settings, commonly justified as efforts to improve safety and cost-effectiveness. However, their use has been questioned in light of limited research conducted and the sensitivities, ethical concerns and potential harms of surveillance. This systematic review aims to (1) map how surveillance technologies have been employed in inpatient mental health settings, (2) explore how they are experienced by patients, staff and carers and (3) examine evidence regarding their impact.

Anti-HIV-1 B cell antigen receptor signaling and structure.

Unlabelled: The B cell antigen receptor (BCR) complex, comprised of antigen recognition and signaling components, functions in initiating B cell activation. While structural studies have described BCR domain organization, gaps remain in our understanding of its antigen binding domain (Fab, fragment antigen-binding) disposition, and how antigen binding is sensed to initiate signaling. Here, we report antigen affinity and signaling of the immunoglobulin (Ig) class IgM and IgG BCRs and define conformational states of full-length BCRs of two human broadly neutralizing antibodies, the glycan-specific, heavy chain domain-swapped, I-shaped 2G12, and a canonical Y-shaped antibody, CH31, that recognizes the CD4-binding site on the HIV-1 Envelope protein (Env).

Cross-population validation of the PreMO risk indicator for predicting myopia onset in children.

Purpose: The Predicting Myopia Onset and progression (PreMO) risk indicator, developed using data generated from white children in the UK, incorporates age, spherical equivalent refraction (SER), axial length (AL) and parental myopia to stratify the likelihood of developing myopia. This study evaluated the PreMO's predictive accuracy using prospective datasets from independent samples of children in Hong Kong (HK) and an ethnically diverse cohort of children in the United Kingdom.

Methods: Non-myopic children (SER > -0.

Engineering immunogens that select for specific mutations in HIV broadly neutralizing antibodies.

Vaccine development targeting rapidly evolving pathogens such as HIV-1 requires induction of broadly neutralizing antibodies (bnAbs) with conserved paratopes and mutations, and in some cases, the same Ig-heavy chains. The current trial-and-error search for immunogen modifications that improve selection for specific bnAb mutations is imprecise. Here, to precisely engineer bnAb boosting immunogens, we use molecular dynamics simulations to examine encounter states that form when antibodies collide with the HIV-1 Envelope (Env).

Single-Cell Lipidomics: An Automated and Accessible Microfluidic Workflow Validated by Capillary Sampling.

We report the first demonstration of a microfluidics-based approach to measure lipids in single living cells using widely available liquid chromatography mass spectrometry (LC-MS) instrumentation. The method enables the rapid sorting of live cells into liquid chambers formed on standard Petri dishes and their subsequent dispensing into vials for analysis using LC-MS. This approach facilitates automated sampling, data acquisition, and analysis and carries the additional advantage of chromatographic separation, aimed at reducing matrix effects present in shotgun lipidomics approaches.

Atmospheric particulates over the northwestern Pacific during the late Holocene: Volcanism, dust, and human perturbation.

Mineral aerosols form a key component of Earth's dynamic biogeochemical systems, yet their composition and mass are variable in time. We reconstruct patterns in mineral aerosol flux from East Asia, the second largest global dust source, in a peat mire in northern Japan. Using geochemical fingerprinting, we show for the past ~3600 years that high but variable tephra flux dominated regional aerosol loads.

Regional/ethnic differences in ocular axial elongation and refractive error progression in myopic and non-myopic children.

Aim: To determine the regional and ethnic differences in ocular axial elongation and refractive error progression in myopic and non-myopic children.

Methods: A retrospective analysis of 15 longitudinal clinical and population-based studies was conducted in the UK, Sweden, Australia (classified as European), China, and Vietnam (classified as East Asian) between 2005 and 2021. A total of 14,593 data points from 6208 participants aged 6-16 years with spherical equivalent from +6 to -6 D were analysed.

Feasibility and Safety of a Home-based Electroencephalogram Neurofeedback Intervention to Reduce Chronic Neuropathic Pain: A Cohort Clinical Trial.

Objective: To evaluate the feasibility, safety, and potential health benefits of an 8-week home-based neurofeedback intervention.

Design: Single-group preliminary study.

Setting: Community-based.

Living With Spasticity During the COVID-19 Pandemic: A Qualitative Study of Patient, Carer and Physician Experiences.

Background: Approximately 4.4 million people in England (8% of the total population) are living with a long-term neurological condition. Within this group of vulnerable individuals, there will be individuals living with severe spasticity that requires regular outpatient treatment with botulinum toxin injection.

Safety and immunogenicity after a 30-month boost of a subtype C ALVAC-HIV (vCP2438) vaccine prime plus bivalent subtype C gp120/MF59 vaccine boost (HVTN 100): A phase 1-2 randomized double-blind placebo-controlled trial.

Induction of broad, durable immune responses is a challenge in HIV vaccine development. HVTN 100 Part A administered subtype C-containing ALVAC-HIV at months 0 and 1, and ALVAC-HIV with bivalent subtype C gp120/MF59 at months 3, 6 and 12. As IgG binding antibody and T-cell responses were similar or greater at month 12.

Isolation and characterization of IgG3 glycan-targeting antibodies with exceptional cross-reactivity for diverse viral families.

Broadly reactive antibodies that target sequence-diverse antigens are of interest for vaccine design and monoclonal antibody therapeutic development because they can protect against multiple strains of a virus and provide a barrier to evolution of escape mutants. Using LIBRA-seq (linking B cell receptor to antigen specificity through sequencing) data for the B cell repertoire of an individual chronically infected with human immunodeficiency virus type 1 (HIV-1), we identified a lineage of IgG3 antibodies predicted to bind to HIV-1 Envelope (Env) and influenza A Hemagglutinin (HA). Two lineage members, antibodies 2526 and 546, were confirmed to bind to a large panel of diverse antigens, including several strains of HIV-1 Env, influenza HA, coronavirus (CoV) spike, hepatitis C virus (HCV) E protein, Nipah virus (NiV) F protein, and Langya virus (LayV) F protein.

Challenges in Lipidomics Biomarker Identification: Avoiding the Pitfalls and Improving Reproducibility.

Identification of features with high levels of confidence in liquid chromatography-mass spectrometry (LC-MS) lipidomics research is an essential part of biomarker discovery, but existing software platforms can give inconsistent results, even from identical spectral data. This poses a clear challenge for reproducibility in biomarker identification. In this work, we illustrate the reproducibility gap for two open-access lipidomics platforms, MS DIAL and Lipostar, finding just 14.

Comparison of the immunogenicity of mRNA-encoded and protein HIV-1 Env-ferritin nanoparticle designs.

Nucleoside-modified mRNA technology has revolutionized vaccine development with the success of mRNA COVID-19 vaccines. We used modified mRNA technology for the design of envelopes (Env) to induce HIV-1 broadly neutralizing antibodies (bnAbs). However, unlike SARS-CoV-2 neutralizing antibodies that are readily made, HIV-1 bnAb induction is disfavored by the immune system because of the rarity of bnAb B cell precursors and the cross-reactivity of bnAbs targeting certain Env epitopes with host molecules, thus requiring optimized immunogen design.

Distrusting the Process: Electoral Trust, Operational Ideology, and Nonvoting Political Participation in the 2020 American Electorate.

This article explores the relationships between electoral trust, operational ideology, and nonvoting political participation (NVP) during the 2020 US presidential election cycle. We hypothesize that: (1) more liberal operational ideology is associated with more NVP, (2) less electoral trust is associated with more NVP, and (3) operational ideology moderates the negative relationship between electoral trust and NVP. Using data from the 2020 American National Election Study (N = 8,280), our contribution is threefold: We first add to previous research that indicated liberals engage in more NVP than conservatives.

Affimer reagents enable targeted delivery of therapeutic agents and RNA via virus-like particles.

Monoclonal antibodies have revolutionized therapies, but non-immunoglobulin scaffolds are becoming compelling alternatives owing to their adaptability. Their ability to be labeled with imaging or cytotoxic compounds and to create multimeric proteins is an attractive strategy for therapeutics. Focusing on HER2, a frequently overexpressed receptor in breast cancer, this study addresses some limitations of conventional targeting moieties by harnessing the potential of these scaffolds.

Approaches to improving mental healthcare for autistic people: systematic review.

Background: Autistic people have a high likelihood of developing mental health difficulties but a low chance of receiving effective mental healthcare. Therefore, there is a need to identify and examine strategies to improve mental healthcare for autistic people.

Aims: To identify strategies that have been implemented to improve access, experiences of care and mental health outcomes for autistic adults, and to examine evidence on their acceptability, feasibility and effectiveness.

Intrarater and Interrater Reliability of Quantitative Ultrasound Speed of Sound by Trained Raters at the Distal Radius in Postmenopausal Women.

Background And Purpose: Quantitative ultrasound (QUS) performed at the distal radius shows potential as an effective tool for evaluating fracture risk, especially in postmenopausal women, but the reliability of this tool has not been reported in this patient population. This study investigated the within-day intrarater and interrater reliability of trained raters performing QUS measures at the distal radius of postmenopausal community-dwelling women.

Methods: Eighteen women between the ages of 56 and 87 years were recruited from senior centers in the Greenville area of South Carolina and consented to participate.

SARS-CoV-2 Omicron XBB lineage spike structures, conformations, antigenicity, and receptor recognition.

A recombinant lineage of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant, named XBB, appeared in late 2022 and evolved descendants that successively swept local and global populations. XBB lineage members were noted for their improved immune evasion and transmissibility. Here, we determine cryoelectron microscopy (cryo-EM) structures of XBB.

Altered Inflammatory State and Mitochondrial Function Identified by Transcriptomics in Paediatric Congenital Heart Patients Prior to Surgical Repair.

Congenital heart disease (CHD) remains the most common birth defect, with surgical intervention required in complex cases. Right ventricle (RV) function is known to be a major predictor of sustained cardiac health in these patients; thus, by elucidating the divergent profiles between CHD and the control through tissue analysis, this study aims to identify new avenues of investigation into the mechanisms surrounding reduced RV function. Transcriptomic profiling, in-silico deconvolution and functional network analysis were conducted on RV biopsies, identifying an increase in the mitochondrial dysfunction genes and (padj = 4.