Exploring the Ascorbate Requirement of the 2-Oxoglutarate-Dependent Dioxygenases.

In humans, the 2-oxoglutarate-dependent dioxygenases (2-OGDDs) catalyze hydroxylation reactions involved in cell metabolism, the biosynthesis of small molecules, DNA and RNA demethylation, the hypoxic response and the formation of collagen. The reaction is catalyzed by a highly oxidizing ferryl-oxo species produced when the active site non-heme iron engages molecular oxygen. Enzyme activity is specifically stimulated by l-ascorbic acid (ascorbate, vitamin C), an effect not well mimicked by other reducing agents.

Longer recreational screen time contributes to the risk of age-related macular degeneration: a UK Biobank cohort study and two-sample Mendelian randomisation.

Background: Recreational screen time (RST) has been found to be associated with cognitive decline and neurodegenerative diseases. However, the association between RST and age-related macular degeneration (AMD), an ocular neurodegenerative disease, is still unclear. We aimed to elucidate the association between RST and AMD.

Use of digital facilitation to support the use of digital services in general practice in England: An interview study with key stakeholders.

Objective: Digital services in primary care are becoming more common, yet access to and use of services can create inequities. Our aim was to explore the drivers, priorities, and evolving policy context influencing digital facilitation in primary care as reported by national, regional and local level stakeholders in England.

Methods: We conducted online semi-structured qualitative interviews with stakeholders, including those in NHS England organisations, local commissioners for health care, statutory and third sector organisations, those working within the research community, and digital platform providers.

Biomimetic Silk Nanoparticle Manufacture: Calcium Ion-Mediated Assembly.

Silk has emerged as an interesting candidate among protein-based nanocarriers due to its favorable properties, including biocompatibility and a broad spectrum of processing options to tune particle critical quality attributes. The silk protein conformation during storage in the middle silk gland of the silkworm is modulated by various factors, including the most abundant metallic ion, calcium ion (Ca). Here, we report spiking of liquid silk with calcium ions to modulate the silk nanoparticle size.

The Sikkim flood of October 2023: Drivers, causes and impacts of a multihazard cascade.

On 3 October 2023, a multihazard cascade in the Sikkim Himalaya, India, was triggered by 14.7 million m of frozen lateral moraine collapsing into South Lhonak Lake, generating an ~20 m tsunami-like impact wave, breaching the moraine, and draining ~50 million m of water. The ensuing Glacial Lake Outburst Flood (GLOF) eroded ~270 million m of sediment, which overwhelmed infrastructure, including hydropower installations along the Teesta River.

Replaying off the beaten path.

Before the hippocampus goes down memory lane, it takes a detour.

Randomizing the human genome by engineering recombination between repeat elements.

We lack tools to edit DNA sequences at scales necessary to study 99% of the human genome that is noncoding. To address this gap, we applied CRISPR prime editing to insert recombination handles into repetitive sequences, up to 1697 per cell line, which enables generating large-scale deletions, inversions, translocations, and circular DNA. Recombinase induction produced more than 100 stochastic megabase-sized rearrangements in each cell.

Ancient genomics and the origin, dispersal, and development of domestic sheep.

The origins and prehistory of domestic sheep () are incompletely understood; to address this, we generated data from 118 ancient genomes spanning 12,000 years sampled from across Eurasia. Genomes from Central Türkiye ~8000 BCE are genetically proximal to the domestic origins of sheep but do not fully explain the ancestry of later populations, suggesting a mosaic of wild ancestries. Genomic signatures indicate selection by ancient herders for pigmentation patterns, hornedness, and growth rate.

Transforming achiral semiconductors into chiral domains with exceptional circular dichroism.

Highly concentrated solutions of asymmetric semiconductor magic-sized clusters (MSCs) of cadmium sulfide, cadmium selenide, and cadmium telluride were directed through a controlled drying meniscus front, resulting in the formation of chiral MSC assemblies. This process aligned their transition dipole moments and produced chiroptic films with exceptionally strong circular dichroism. -factors reached magnitudes as high as 1.

Multiplex generation and single-cell analysis of structural variants in mammalian genomes.

Studying the functional consequences of structural variants (SVs) in mammalian genomes is challenging because (i) SVs arise much less commonly than single-nucleotide variants or small indels and (ii) methods to generate, map, and characterize SVs in model systems are underdeveloped. To address these challenges, we developed Genome-Shuffle-seq, a method that enables the multiplex generation and mapping of thousands of SVs (deletions, inversions, translocations, and extrachromosomal circles) throughout mammalian genomes. We also demonstrate the co-capture of SV identity with single-cell transcriptomes, facilitating the measurement of SV impact on gene expression.

The Management of Chronic Insomnia in Young Children: A Survey of UK General Practice.

Objectives: Chronic insomnia (CI), the most common sleep disorder in young children, is associated with negative outcomes for the child and family. This study explores the beliefs, current practice, and understanding of UK primary health care professionals (PCPs) regarding CI in children under 5 years.

Method: An online survey of UK PCPs (e.

Improving care in elderly neurosurgery initiative guideline on management of chronic subdural haematoma in older people-relevance for the geriatrician.

Chronic subdural haematoma (cSDH) is a common subtype of traumatic brain injury, typically affecting older people living with frailty and multimorbidity. Until now, no published guideline has existed internationally to guide management, perhaps explaining why the care of the older cSDH patient varies between neurosurgical centres. The Improving Care in Elderly Neurosurgery Initiative guideline is the first guideline dedicated to the care of patients with cSDH across the entire patient pathway, from initial presentation through to rehabilitation and discharge after surgery.

Incidence of ANCA associated vasculitis and polyarteritis nodosa in Norfolk, UK, from 2011-2020.

Objective: To report the annual and age-specific incidence of ANCA associated vasculitis and polyarteritis nodosa in the adult population of Norfolk County, UK.

Methods: Individuals newly diagnosed with ANCA associated vasculitis or polyarteritis nodosa between 1st Jan 2011 and 31st December 2020, residing in the postal areas of NR1-NR30 were included. Patients were classified according to the European Medicines Agency algorithm.

Plasma proteomics for risk prediction and identification of novel drug targets in systemic lupus erythematosus.

Objectives: The relationship between proteomic profiles and incident systemic lupus erythematosus (SLE) remains unclear. We aimed to identify candidate plasma proteins for SLE risk in women, discover potential treatment targets for SLE, and develop and validate a protein-based prediction model for SLE risk.

Methods: 28 220 women from the UK Biobank were randomly split into training (70%) and testing (30%) sets.

Dynamic reorganization of task-related network interactions in post-stroke aphasia recovery.

Post-stroke aphasia is a network disorder characterized by language impairments and aberrant network activation. While patients with post-stroke aphasia recover over time, the dynamics of the underlying changes in the brain remain elusive. Neuroimaging work demonstrated that language recovery is a heterogeneous process, characterized by varying activation levels in several regions of the left-hemispheric language network and the domain-general bilateral multiple-demand network.

Impact of Sensitive Skin on Quality of Life, Anxiety, and Depression: A Cross-Sectional Study.

Background: Sensitive skin (SS) is a common condition reported by many people worldwide. Patient interviews reveal that individuals with SS experience diminished quality of life, anxiety, and depression. Nonetheless, the impact of SS on mental health remains unclear.

The gonorrhoea care cascade in general practice: a descriptive study to explore gonorrhoea management utilising electronic medical records.

Background Gonorrhoea notification rates in Australia have more than doubled between 2014 and 2019. We explored gonorrhoea testing patterns and management of gonorrhoea infection in general practice. Methods We analysed de-identified electronic medical record data for individuals who attended 73 Australian general practices (72 in the state of Victoria) between January 2018 and December 2020.

Causal Association of Sleep Traits with All-Cause and Cause-Specific Mortality: A Prospective Cohort and Mendelian Randomization Study.

The study aimed to explore the association between different sleep traits and all-cause mortality as well as to validate causality in the association through mendelian randomization (MR). We analyzed 451,420 European ancestry participants from the UK Biobank. Multivariable-adjusted Cox proportional hazards model was conducted to evaluate the association between sleep traits and all-cause mortality.

Reporting of concomitant and rescue topical therapies in atopic dermatitis randomised controlled trials evaluating a systemic treatment: a scoping review.

Background: Randomised controlled trials (RCTs) evaluating new systemic treatments for atopic dermatitis (AD) have increased dramatically over the last decade. These trials often incorporate topical therapies either as permitted concomitant or rescue treatments. Differential use of these topicals post-randomisation introduces potential bias as they may nullify or exaggerate treatment responses.

Histopathology of the small airways: Similarities and differences between ageing and COPD.

Age-related lung function decline is associated with small airway closure and gas trapping. The mechanisms which cause these changes are not fully understood. It has been suggested that COPD is caused by accelerated ageing.

The diagnostic performance and optimal strategy of cone beam CT-assisted bronchoscopy for peripheral pulmonary lesions: A systematic review and meta-analysis.

Cone-beam computed tomography (CBCT) assisted bronchoscopy shows prospective advantages in diagnosing peripheral pulmonary lesions (PPLs), but its diagnostic value and potential influencing factors remain unclear. What is the clinical value and optimal strategy of CBCT-assisted bronchoscopy in diagnosing PPLs? The references were searched from PubMed, EmBase, and Web of Science. Studies reporting diagnostic yield and potential influencing factors of CBCT-assisted bronchoscopy were included.

recovered from hospital patients, livestock and dogs in Nigeria share near-identical genome sequences.

Genomic data on from the African continent are currently lacking, resulting in the region being under-represented in global analyses of infection (CDI) epidemiology. For the first time in Nigeria, we utilized whole-genome sequencing and phylogenetic tools to compare isolates from diarrhoeic human patients (=142), livestock (=38), poultry manure (=5) and dogs (=9) in the same geographic area (Makurdi, north-central Nigeria) and relate them to the global population. In addition, selected isolates were tested for antimicrobial susceptibility (=33) and characterized by PCR ribotyping (=53).

A Phase 3B, Open-Label Study to Evaluate the Immunogenicity and Safety of the Quadrivalent Meningococcal Nimenrix Vaccine When Given to Healthy Infants at 3 and 12 Months of Age.

Introduction: Infants and young children typically have the highest age-related risk of invasive meningococcal disease. The immunogenicity and safety of a single primary dose and a booster of a meningococcal A/C/W/Y tetanus toxoid conjugate vaccine (MenACWY-TT; Nimenrix) in infants were evaluated.

Methods: In this phase 3b, open-label, single-arm study, healthy 3-month-old infants received a single Nimenrix dose followed by a booster at age 12 months (1 + 1 series).