The α-globin super-enhancer acts in an orientation-dependent manner.

Individual enhancers are defined as short genomic regulatory elements, bound by transcription factors, and able to activate cell-specific gene expression at a distance, in an orientation-independent manner. Within mammalian genomes, enhancer-like elements may be found individually or within clusters referred to as locus control regions or super-enhancers (SEs). While these behave similarly to individual enhancers with respect to cell specificity, distribution and distance, their orientation-dependence has not been formally tested.

Exploring force-driven stochastic folding dynamics in mechano-responsive proteins and implications in phenotypic variation.

Single-point mutations are pivotal in molecular zoology, shaping functions and influencing genetic diversity and evolution. Here we study three such genetic variants of a mechano-responsive protein, cadherin-23, that uphold the structural integrity of the protein, but showcase distinct genotypes and phenotypes. The variants exhibit subtle differences in transient intra-domain interactions, which in turn affect the anti-correlated motions among the constituent β-strands.

Non-medicinal oral contrast in upper abdominal MRI for MR-guided radiotherapy: A scoping review.

Introduction: Using non-medicinal oral contrast agents may aid safe delivery of magnetic resonance image-guided (MR-guided) radiotherapy by improving the ability to visualise and avoid excessive radiation dose to adjacent bowel/stomach. This scoping review aims to map the literature on non-medicinal oral contrasts used in upper-abdominal diagnostic or therapeutic magnetic resonance imaging (MRI) to find potential candidates for employing in MR-guided radiotherapy and identify gaps in knowledge for further study.

Methods: A scoping review of non-medicinal oral contrast used in upper-abdominal MRI research followed a pre-defined protocol based on Arksey and O'Malley's framework.

Genome-wide association study on chronic postsurgical pain in the UK Biobank.

Background: Chronic postsurgical pain (CPSP) persists beyond the expected healing period after surgery, imposing a substantial burden on overall patient well-being. Unfortunately, CPSP often remains underdiagnosed and undertreated. To better understand the mechanism of CPSP development, we aimed to identify genetic variants associated with CPSP.

Genetically attenuated parasites show promise as a next-generation malaria vaccine.

Metabolically active, genetically attenuated Plasmodium falciparum parasite lines are promising second-generation malaria vaccine candidates. Lamers et al. and Roozen et al.

Global insight into rare disease and orphan drug definitions: a systematic literature review.

Objectives: This study sheds light on the available global definitions, classifications, and criteria used for rare diseases (RDs), ultrarare diseases (URDs), orphan drugs (ODs) and ultraorphan drugs (UODs) and provides insights into the rationale behind these definitions.

Design: A systematic literature review was conducted to identify existing definitions and the criteria used to define RDs, ODs and their subtypes.

Data Sources: Searches were performed in the PubMed/Medline, Embase, Scopus and Web of Science (Science and Social Sciences Citation Index) databases covering articles published from 1985 to 2021.

Exploratory study of patients' and carers' preferences for postdischarge surgical wound monitoring using survey and interviews.

Objectives: To explore patients' and carers' preferences for postdischarge surgical wound monitoring.

Design: Explanatory mixed methods study with an online survey followed by online interviews.

Setting: The online survey was distributed via the Cardiothoracic Interdisciplinary Research Network and cardiac surgery patient and public involvement groups in London and Leicester, UK.

How do socioeconomic inequalities and preterm birth interact to modify health and education outcomes? A narrative systematic review.

Objectives: How are socioeconomic inequalities modified by, or how do they interact with, preterm birth?

Design: Narrative systematic review of quantitative observational studies of an interaction, or effect modification, between preterm birth and socioeconomic status.

Data Sources: Five databases were searched for studies published between January 2000 and June 2020. Title and abstract were reviewed to identify articles for dual screening.

Protocol for a systematic review and individual participant data meta-analysis for risk factors for lung cancer in individuals with lung nodules identified by low-dose CT screening.

Background: Worldwide, lung cancer (LC) is the second most frequent cancer and the leading cause of cancer related mortality. Low-dose CT (LDCT) screening reduced LC mortality by 20-24% in randomised trials of high-risk populations. A significant proportion of those screened have nodules detected that are found to be benign.

Exploring the experiences of cognitive symptoms in Long COVID: a mixed-methods study in the UK.

Objective: To explore the lived experiences and extent of cognitive symptoms in Long COVID (LC) in a UK-based sample.

Design: This study implemented a mixed-methods design. Eight focus groups were conducted to collect qualitative data, and the Framework Analysis was used to reveal the experiences and impact of cognitive symptoms.

Predictors of response to low-dose amitriptyline for irritable bowel syndrome and efficacy and tolerability according to subtype: post hoc analyses from the ATLANTIS trial.

Background: Low-dose amitriptyline, a tricyclic antidepressant (TCA), was superior to placebo for irritable bowel syndrome (IBS) in the AmitripTyline at Low-dose ANd Titrated for Irritable bowel syndrome as Second-line treatment (ATLANTIS) trial.

Objective: To perform post hoc analyses of ATLANTIS for predictors of response to, and tolerability of, a TCA.

Design: ATLANTIS randomised 463 adults with IBS to amitriptyline (232) or placebo (231).

Matching model with mechanism: Appropriate rodent models for studying various aspects of diabetes pathophysiology.

Many rodent models are available for preclinical diabetes research making it a challenge for researchers to choose the most appropriate one for their experimental question. To aid in this, models have classically been categorized according to which type of diabetes they represent, and further into whether the model is induced, spontaneous or the result of genetic manipulation. This fails to capture the complexity of pathogenesis seen in diabetes in humans.

Coronary CT angiography-guided management of patients with stable chest pain: 10-year outcomes from the SCOT-HEART randomised controlled trial in Scotland.

Background: The Scottish Computed Tomography of the Heart (SCOT-HEART) trial demonstrated that management guided by coronary CT angiography (CCTA) improved the diagnosis, management, and outcome of patients with stable chest pain. We aimed to assess whether CCTA-guided care results in sustained long-term improvements in management and outcomes.

Methods: SCOT-HEART was an open-label, multicentre, parallel group trial for which patients were recruited from 12 outpatient cardiology chest pain clinics across Scotland.

Impact of SARS-CoV-2 spike antibody positivity on infection and hospitalisation rates in immunosuppressed populations during the omicron period: the MELODY study.

Background: In the UK, booster COVID-19 vaccinations have been recommended biannually to people considered immune vulnerable. We investigated, at a population level, whether the absence of detectable anti-SARS-CoV-2 spike protein IgG antibody (anti-S Ab) following three or more vaccinations in immunosuppressed individuals was associated with greater risks of infection and severity of infection.

Methods: In this prospective cohort study using UK national disease registers, we recruited participants with solid organ transplants (SOTs), rare autoimmune rheumatic diseases (RAIRDs), and lymphoid malignancies.

Stopping of adalimumab in juvenile idiopathic arthritis-associated uveitis (ADJUST): a multicentre, double-masked, randomised controlled trial.

Background: Adalimumab is an effective treatment for juvenile idiopathic arthritis-associated uveitis. Data are scarce on the effects of discontinuing adalimumab after control of the disease had been reached. We aimed to assess efficacy and safety of discontinuing treatment in patients with juvenile idiopathic arthritis-associated uveitis.

Association of statins use and genetic susceptibility with incidence of Alzheimer's disease.

Background: The effect of statins use on the incidence of Alzheimer's disease (AD) is still under debate, and it could be modified by a series of factors.

Objectives: We aimed to examine the association of statins use with the risk of cognitive impairment and AD, and assess the moderating roles of genetic susceptibility and other individual-related factors.

Design: A longitudinal study was conducted from the UK Biobank where individuals completed baseline surveys (2006-2010) and were followed (mean follow-up period: 9 years).