A design for life: Predicting cognitive performance from lifestyle choices.

Maintaining cognitive capacity through adulthood has been the target of many recent studies that have examined the influence of lifestyle choices such as exercise, diet, and sleeping habits. Many of these studies have focused on a single factor (e.g., diet) and its effect on cognitive abilities; however, humans make numerous lifestyle choices every single day, many of which interact and influence each other. Here, we investigated whether combinations of lifestyle choices can predict better or worse cognitive performance in the general population, and whether optimal combinations of choices existed depending on the cognitive domain. Specifically, we examined 20 self-reported lifestyle choices, such as playing video games, drinking alcohol, and amount of exercise taken, in a sample of almost 10,000 participants. All participants also completed 12 cognitive tests that have been shown to generate three composite cognitive domain scores pertaining to short-term memory, verbal abilities, and reasoning. Using recursive feature elimination and random forest regression, we were able to explain 9% of the variance in short-term memory scores, 8% of the variance in reasoning scores, and 7% of the variance in verbal ability scores. While the regression model provided predictive power in all three domains, these levels indicate that even when considering a large number of lifestyle choices, there remains a considerable degree of variability in predicting short-term memory, reasoning and verbal abilities. Thus, while some modifiable lifestyle factors may have an impact on cognitive capacity, there likely exists no single optimal design for life.

Engaging people with lived experiences on community advisory boards in community-based participatory research: a scoping review protocol.

INTRODUCTION: Community-based participatory research (CBPR) is a collaborative research approach that equally engages researchers and community stakeholders throughout all steps of the research process to facilitate social change and increase research relevance. Community advisory boards (CABs) are a CBPR tool in which individuals with lived experience and community organisations are integrated into the research process and ensure the work aligns with community priorities. We seek to (1) explore the best practices for the recruitment and engagement of people with lived experiences on CABs and (2) identify the scope of literature on minimising power dynamics between organisations and community members with lived experience who work on CABs together. METHODS AND ANALYSIS: This scoping review will follow the Arksey and O'Malley methodological framework, informed by Levac et al, and will be reported using a PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) diagram. Detailed and robust search strategies have been developed for Embase, Medline and PsychINFO. Grey literature references and reference lists of included articles published between 1 January 1990 and 30 March 2023 will be considered. Two reviewers will independently screen references in two successive stages of title/abstract and full-text screening. Conflicts will be decided by consensus or a third reviewer. Thematic analysis will be applied in three phases: open coding, axial coding and abstraction. Extracted data will be recorded and presented in a tabular format and/or graphical summaries, with a descriptive overview discussing how the research findings relate to the research questions. At this time, a preliminary search of peer-reviewed and grey literature has been conducted. Search results for peer-reviewed literature have been uploaded to Covidence for review and appraisal for relevance. ETHICS AND DISSEMINATION: Formal ethics approval is not required for this review. Review findings will inform ongoing and future CBPR community advisory board dynamics. REGISTRATION: The protocol has been registered prospectively on the Open Science Framework (https://doi.org/10.17605/OSF.IO/QF5D3).

Recurrent SARS-CoV-2 mutations at Spike D796 evade antibodies from pre-Omicron convalescent and vaccinated subjects.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages of the Omicron variant rapidly became dominant in early 2022 and frequently cause human infections despite vaccination or prior infection with other variants. In addition to antibody-evading mutations in the receptor-binding domain, Omicron features amino acid mutations elsewhere in the Spike protein; however, their effects generally remain ill defined. The Spike D796Y substitution is present in all Omicron sub-variants and occurs at the same site as a mutation (D796H) selected during viral evolution in a chronically infected patient. Here, we map antibody reactivity to a linear epitope in the Spike protein overlapping position 796. We show that antibodies binding this region arise in pre-Omicron SARS-CoV-2 convalescent and vaccinated subjects but that both D796Y and D796H abrogate their binding. These results suggest that D796Y contributes to the fitness of Omicron in hosts with pre-existing immunity to other variants of SARS-CoV-2 by evading antibodies targeting this site.IMPORTANCESevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved substantially through the coronavirus disease 2019 (COVID-19) pandemic: understanding the drivers and consequences of this evolution is essential for projecting the course of the pandemic and developing new countermeasures. Here, we study the immunological effects of a particular mutation present in the Spike protein of all Omicron strains and find that it prevents the efficient binding of a class of antibodies raised by pre-Omicron vaccination and infection. These findings reveal a novel consequence of a poorly understood Omicron mutation and shed light on the drivers and effects of SARS-CoV-2 evolution.

From ToyBox Study to eToyBox: Advancing Childhood Obesity Reduction in Malaysian Kindergartens.

Prevention and treatment of childhood obesity is a global concern, and in Malaysia, it is considered a national public health priority. Determinants of childhood obesity are multifactorial and include factors that directly and indirectly influence energy balance-related behaviours, including energy intake and energy expenditure. Interventions to address childhood obesity that have multiple components at different levels have been shown to be the most influential. The ToyBox-study is a childhood obesity intervention aimed at preschool-aged children and their families that had been shown to be effective in several European countries and so was chosen for adaption for the Malaysian setting. Materials were translated and adjusted for the Malaysian context and audience and implemented in kindergartens in Peninsular Malaysia and Sarawak. However, during the COVID-19 pandemic and lockdown, teaching transitioned to being online. This brought an opportunity to reach a wider audience and consider the long-term sustainability of the intervention, and thus eToybox was born. eToybox aims to bring support for healthy energy balance behaviours directly to the teachers, into kindergartens and homes, to encourage families to be active and eat healthily, and prevent or reduce obesity. Through online innovation, the Toybox Study Malaysia programme has been expanded to enhance its potential to impact the promotion of healthy lifestyles among preschoolers and their families, highlighting the importance of a holistic approach to preventing and treating childhood obesity in Malaysia.

Virome-wide detection of natural infection events and the associated antibody dynamics using longitudinal highly-multiplexed serology.

Current methods for detecting infections either require a sample collected from an actively infected site, are limited in the number of agents they can query, and/or yield no information on the immune response. Here we present an approach that uses temporally coordinated changes in highly-multiplexed antibody measurements from longitudinal blood samples to monitor infection events at sub-species resolution across the human virome. In a longitudinally-sampled cohort of South African adolescents representing >100 person-years, we identify >650 events across 48 virus species and observe strong epidemic effects, including high-incidence waves of Aichivirus A and the D68 subtype of Enterovirus D earlier than their widespread circulation was appreciated. In separate cohorts of adults who were sampled at higher frequency using self-collected dried blood spots, we show that such events temporally correlate with symptoms and transient inflammatory biomarker elevations, and observe the responding antibodies to persist for periods ranging from ≤1 week to >5 years. Our approach generates a rich view of viral/host dynamics, supporting novel studies in immunology and epidemiology.

PepSeq: a fully in vitro platform for highly multiplexed serology using customizable DNA-barcoded peptide libraries.

PepSeq is an in vitro platform for building and conducting highly multiplexed proteomic assays against customizable targets by using DNA-barcoded peptides. Starting with a pool of DNA oligonucleotides encoding peptides of interest, this protocol outlines a fully in vitro and massively parallel procedure for synthesizing the encoded peptides and covalently linking each to a corresponding cDNA tag. The resulting libraries of peptide/DNA conjugates can be used for highly multiplexed assays that leverage high-throughput sequencing to profile the binding or enzymatic specificities of proteins of interest. Here, we describe the implementation of PepSeq for fast and cost-effective epitope-level analysis of antibody reactivity across hundreds of thousands of peptides from <1 µl of serum or plasma input. This protocol includes the design of the DNA oligonucleotide library, synthesis of DNA-barcoded peptide constructs, binding of constructs to sample, preparation for sequencing and data analysis. Implemented in this way, PepSeq can be used for a number of applications, including fine-scale mapping of antibody epitopes and determining a subject's pathogen exposure history. The protocol is divided into two main sections: (i) design and synthesis of DNA-barcoded peptide libraries and (ii) use of libraries for highly multiplexed serology. Once oligonucleotide templates are in hand, library synthesis takes 1-2 weeks and can provide enough material for hundreds to thousands of assays. Serological assays can be conducted in 96-well plates and generate sequencing data within a further ~4 d. A suite of software tools, including the PepSIRF package, are made available to facilitate the design of PepSeq libraries and analysis of assay data.

COVID-19 vaccination elicits an evolving, cross-reactive antibody response to epitopes conserved with endemic coronavirus spike proteins.

The COVID-19 pandemic has triggered the first widespread vaccination campaign against a coronavirus. Many vaccinated subjects are previously naive to SARS-CoV-2; however, almost all have previously encountered other coronaviruses (CoVs), and the role of this immunity in shaping the vaccine response remains uncharacterized. Here, we use longitudinal samples and highly multiplexed serology to identify mRNA-1273 vaccine-induced antibody responses against a range of CoV Spike epitopes, in both phylogenetically conserved and non-conserved regions. Whereas reactivity to SARS-CoV-2 epitopes shows a delayed but progressive increase following vaccination, we observe distinct kinetics for the endemic CoV homologs at conserved sites in Spike S2: these become detectable sooner and decay at later time points. Using homolog-specific antibody depletion and alanine-substitution experiments, we show that these distinct trajectories reflect an evolving cross-reactive response that can distinguish rare, polymorphic residues within these epitopes. Our results reveal mechanisms for the formation of antibodies with broad reactivity against CoVs.

COVID-19 vaccination recruits and matures cross-reactive antibodies to conserved epitopes in endemic coronavirus Spike proteins.

The COVID-19 pandemic has triggered the first widespread vaccination campaign against a coronavirus. Most vaccinated subjects are naïve to SARS-CoV-2, however almost all have previously encountered other coronaviruses (CoVs) and the role of this immunity in shaping the vaccine response remains uncharacterized. Here we use longitudinal samples and highly-multiplexed serology to identify mRNA-1273 vaccine-induced antibody responses against a range of CoV Spike epitopes and in both phylogenetically conserved and non-conserved regions. Whereas reactivity to SARS-CoV-2 epitopes showed a delayed but progressive increase following vaccination, we observed distinct kinetics for the endemic CoV homologs at two conserved sites in Spike S2: these became detectable sooner, and decayed at later timepoints. Using homolog-specific depletion and alanine-substitution experiments, we show that these distinctly-evolving specificities result from cross-reactive antibodies as they mature against rare, polymorphic residues within these epitopes. Our results reveal mechanisms for the formation of antibodies with broad reactivity against CoVs.