Remotely delivered weight management for people with long COVID and overweight: the randomized wait-list-controlled ReDIRECT trial.

Long COVID (LC) is a complex multisymptom condition with no known disease-modifying treatments. This wait-list-controlled open-label trial tested whether a remotely delivered structured weight management program could improve respective LC symptoms in people living with overweight. Adults with LC (symptoms >12 weeks) and body mass index >27 kg m (>25 kg m for South Asians) were randomized (n = 234, 1:1) to control (n = 116, usual care) or the remotely delivered structured weight management (n = 118, total diet replacement (850 kcal per day) for 12 weeks, followed by food reintroduction and weight loss maintenance support) via minimization and randomization (80:20) to balance dominant LC symptom, sex, age, ethnicity and postcode-based index of multiple deprivation between groups.

Impact and cost-effectiveness of scaling up HCV testing and treatment strategies for achieving HCV elimination among people who inject drugs in England: a mathematical modelling study.

Background: England aims to reach the World Health Organization (WHO) elimination target of decreasing HCV incidence among people who inject drugs (PWID) to <2 per 100 person-years (/100pyrs) by 2030. We assessed what testing and treatment strategies will achieve this target and whether they are cost-effective.

Methods: A dynamic deterministic HCV transmission model among PWID was developed for four England regions, utilising data on the scale-up of HCV treatment among PWID in prisons, drug treatment centres (DTC, where opioid agonist therapy is provided), and any other setting (e.

Predicting the replicability of social and behavioural science claims in COVID-19 preprints.

Replications are important for assessing the reliability of published findings. However, they are costly, and it is infeasible to replicate everything. Accurate, fast, lower-cost alternatives such as eliciting predictions could accelerate assessment for rapid policy implementation in a crisis and help guide a more efficient allocation of scarce replication resources.

Massively parallel experimental interrogation of natural variants in ancient signaling pathways reveals both purifying selection and local adaptation.

The nature of standing genetic variation remains a central debate in population genetics, with differing perspectives on whether common variants are mostly neutral or have functional effects. We address this question by directly mapping the fitness effects of over 9,000 natural variants in the Ras/PKA and TOR/Sch9 pathways-key regulators of cell proliferation in eukaryotes-across four conditions in . While many variants are neutral in our assay, on the order of 3,500 exhibited significant fitness effects.

Independent volumetric internal fixation reduces posterior column acetabular fracture site motion as compared to plate/screw construct: A biomechanical analysis.

Aims & Objectives: To establish whether a suprapectineal pelvic reconstruction plate and posterior column screw (P&S) construct or a single 6.5-mm cannulated posterior column screw (PCS) construct demonstrates greater mechanical stability for fixation of acetabulum fractures involving the posterior column (PC). We hypothesized that the PCS construct would result in less fracture site motion.

Baseline Characteristics in the Remote Diet Intervention to REduce long-COVID Symptoms Trial (ReDIRECT).

Background: The persistence of symptoms for ≥12 weeks after a COVID-19 infection is known as Long COVID (LC), a condition with unclear pathophysiology and no proven treatments to date. Living with obesity is a risk factor for LC and has symptoms which may overlap with and aggravate LC.

Methods: ReDIRECT is a remotely delivered trial assessing whether weight management can reduce LC symptoms.

A general principle governing neuronal evolution reveals a human-accelerated neuron type potentially underlying the high prevalence of autism in humans.

The remarkable ability of a single genome sequence to encode a diverse collection of distinct cell types, including the thousands of cell types found in the mammalian brain, is a key characteristic of multicellular life. While it has been observed that some cell types are far more evolutionarily conserved than others, the factors driving these differences in evolutionary rate remain unknown. Here, we hypothesized that highly abundant neuronal cell types may be under greater selective constraint than rarer neuronal types, leading to variation in their rates of evolution.

Testing and Treatment Interventions in Community Settings Key to Controlling a Recent Human Immunodeficiency Virus Outbreak Among People Who Inject Drugs in Glasgow: A Modeling Study.

Background: A human immunodeficiency virus (HIV) outbreak was identified among people who inject drugs (PWID) in Glasgow in 2015, with >150 diagnoses by the end of 2019. The outbreak response involved scaling up HIV testing and improving HIV treatment initiation and retention.

Methods: We parameterized and calibrated a dynamic, deterministic model of HIV transmission among PWID in Glasgow to epidemiological data.

Immunometabolic Blood Biomarkers of Developmental Trajectories of Depressive Symptoms: Findings From the ALSPAC Birth Cohort.

Studies of longitudinal trends of depressive symptoms in young people could provide insight into aetiologic mechanism, heterogeneity and origin of common cardiometabolic comorbidities for depression. Depression is associated with immunological and metabolic alterations, but immunometabolic characteristics of developmental trajectories of depressive symptoms remain unclear. Using depressive symptoms scores measured on 10 occasions between ages 10 and 25 years in the Avon Longitudinal Study of Parents and Children (n=7302), we identified four distinct trajectories: low-stable (70% of the sample), adolescent-limited (13%), adulthood-onset (10%) and adolescent-persistent (7%).

Factors Influencing Data Quality in Electronic Health Record Systems in 50 Health Facilities in Rwanda and the Role of Clinical Alerts: Cross-Sectional Observational Study.

Background: Electronic health records (EHRs) play an increasingly important role in delivering HIV care in low- and middle-income countries. The data collected are used for direct clinical care, quality improvement, program monitoring, public health interventions, and research. Despite widespread EHR use for HIV care in African countries, challenges remain, especially in collecting high-quality data.

FHIRing up OpenMRS: Architecture, Implementation and Real-World Use-Cases in Global Health.

HL7 FHIR was created almost a decade ago and is seeing increasingly wide use in high income settings. Although some initial work was carried out in low and middle income (LMIC) settings there has been little impact until recently. The need for reliable and easy to implement interoperability between health information systems in LMICs is growing with large scale deployments of EHRs, national reporting systems and mHealth applications.

Disentangling cell-intrinsic and extrinsic factors underlying evolution.

A key goal of developmental biology is to determine the extent to which cells and organs develop autonomously, as opposed to requiring interactions with other cells or environmental factors. Chimeras have played a foundational role in this by enabling qualitative classification of cell-intrinsically vs. extrinsically driven processes.

Effectiveness of Deep Brain Stimulation in Improving Balance in Parkinson's Disease: A Systematic Review and Meta-Analysis.

Background: Balance dysfunction is a debilitating feature of advanced Parkinson's disease (PD), potentially improved by deep brain stimulation (DBS). This systematic review and meta-analysis pooled evidence from randomized controlled trials (RCTs) on DBS effectiveness in improving balance in PD.

Methods: A systematic search was conducted to identify eligible RCTs investigating the effectiveness of DBS on improving balance in people with PD.

Predictors of engagement in screening for a hepatitis C virus (HCV) treatment trial in a rural Appalachian community.

An HCV treatment trial was initiated in September 2019 to address the opioid/hepatitis C virus (HCV) syndemic in rural Kentucky. The focus of the current analysis is on participation in diagnostic screening for the trial. Initial eligibility (≥18 years of age, county resident) was established by phone followed by in-person HCV viremia testing.

Trends and factors associated with illicit drug use in South Africa: Findings from multiple national population-based household surveys, 2002-2017.

Background: Illicit drug use results in considerable global morbidity, but there is little data on its trends and factors associated with it in sub-Saharan Africa. We consider these questions using national data from South Africa for 2002-2017.

Methods: We analysed data among individuals aged 15 years or older from five national population-based household surveys in South Africa (2002-2017; n = 89,113).

Cell-type-specific -regulatory divergence in gene expression and chromatin accessibility revealed by human-chimpanzee hybrid cells.

Although gene expression divergence has long been postulated to be the primary driver of human evolution, identifying the genes and genetic variants underlying uniquely human traits has proven to be quite challenging. Theory suggests that cell-type-specific -regulatory variants may fuel evolutionary adaptation due to the specificity of their effects. These variants can precisely tune the expression of a single gene in a single cell-type, avoiding the potentially deleterious consequences of -acting changes and non-cell type-specific changes that can impact many genes and cell types, respectively.

Cancer researchers' experiences with and perceptions of research data sharing: Results of a cross-sectional survey.

Background: Despite wide recognition of the benefits of sharing research data, public availability rates have not increased substantially in oncology or medicine more broadly over the last decade.

Methods: We surveyed 285 cancer researchers to determine their prior experience with sharing data and views on known drivers and inhibitors.

Results: We found that 45% of respondents had shared some data from their most recent empirical publication, with respondents who typically studied non-human research participants, or routinely worked with human genomic data, more likely to share than those who did not.

Open Source Software in Healthcare: International Case Series from the IMIA Open Source Working Group.

In this case series, we demonstrate how open-source software has been widely adopted as the primary health information system in many low- and middle-income countries, and for government-developed applications in high-income settings. We discuss the concept of Digital Global Goods and how the general approach of releasing software developed through public funding under open-source licences could improve the delivery of healthcare in all settings through increased transparency and collaboration as well as financial efficiency.

Extended cost-effectiveness analysis of interventions to improve uptake of diabetes services in South Africa.

The rising prevalence of diabetes in South Africa (SA), coupled with significant levels of unmet need for diagnosis and treatment, results in high rates of diabetes-associated complications. Income status is a determinant of utilization of diagnosis and treatment services, with transport costs and loss of wages being key barriers to care. A conditional cash transfer (CCT) programme, targeted to compensate for such costs, may improve service utilization.

Chromatin activity identifies differential gene regulation across human ancestries.

Background: Current evidence suggests that cis-regulatory elements controlling gene expression may be the predominant target of natural selection in humans and other species. Detecting selection acting on these elements is critical to understanding evolution but remains challenging because we do not know which mutations will affect gene regulation.

Results: To address this, we devise an approach to search for lineage-specific selection on three critical steps in transcriptional regulation: chromatin activity, transcription factor binding, and chromosomal looping.

Beta-2 adrenergic receptor agonism alters astrocyte phagocytic activity and has potential applications to psychiatric disease.

Schizophrenia is a debilitating condition necessitating more efficacious therapies. Previous studies suggested that schizophrenia development is associated with aberrant synaptic pruning by glial cells. We pursued an interdisciplinary approach to understand whether therapeutic reduction in glial cell-specifically astrocytic-phagocytosis might benefit neuropsychiatric patients.

Adding a Gene Expression Profile Test to Aid Differential Diagnosis and Treatment in Aggressive Large B-Cell Lymphoma: An Early Exploratory Economic Evaluation.

Background And Objective: Adding gene expression profiles (GEPs) to the current diagnostic work-up of aggressive large B-cell lymphomas may lead to the reclassification of patients, treatment changes and improved outcomes. A GEP test is in development using TempO-Seq technology to distinguish Burkitt lymphoma (BL) and primary mediastinal large B-cell lymphoma (PMBCL) from diffuse large B-cell lymphoma (DLBCL), and to classify patients with DLBLC and to predict the benefit of (e.g.