A multi-modal transformer for cell type-agnostic regulatory predictions.

Sequence-based deep learning models have emerged as powerful tools for deciphering the cis-regulatory grammar of the human genome but cannot generalize to unobserved cellular contexts. Here, we present EpiBERT, a multi-modal transformer that learns generalizable representations of genomic sequence and cell type-specific chromatin accessibility through a masked accessibility-based pre-training objective. Following pre-training, EpiBERT can be fine-tuned for gene expression prediction, achieving accuracy comparable to the sequence-only Enformer model, while also being able to generalize to unobserved cell states.

Competitive behaviors in Serratia marcescens are coordinately regulated by a lifestyle switch frequently inactivated in the clinical environment.

Opportunistic bacterial pathogens must compete with other bacteria and switch between host- and environment-adapted states. Type VI secretion systems (T6SSs) occur widely in gram-negative bacteria and can efficiently kill neighboring competitors. We determined the distribution of T6SSs across the genus Serratia and observed that a highly conserved antibacterial T6SS is differentially active between closely related clinical isolates of Serratia marcescens.

International Society for Pediatric and Adolescent Diabetes Clinical Practice Consensus Guidelines 2024: Insulin and Adjunctive Treatments in Children and Adolescents with Diabetes.

The International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines represent a rich repository that serves as the only comprehensive set of clinical recommendations for children, adolescents, and young adults living with diabetes worldwide. This chapter builds on the 2022 ISPAD guidelines, and updates recommendations on the principles of intensive insulin regimens, including more intensive forms of multiple daily injections with new-generation faster-acting and ultra-long-acting insulins; a summary of adjunctive medications used alongside insulin treatment that includes details on pramlintide, metformin, glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RA) and sodium-glucose cotransporter inhibitors; and key considerations with regard to access to insulin and affordability to ensure that all persons with diabetes who need insulin can obtain it without financial hardship.

New N-Alkylketonetetrahydroisoquinoline derivatives exhibits antitumor effect by HA-CD44 interaction inhibition in MDA-MB-231 breast cancer.

Molecular interactions at the cell surface, in particular between hyaluronic acid (HA) and the cluster of differentiation 44 (CD44) receptor, are crucial in several biological processes and diseases such as cancer. Thus, inhibition of the HA-CD44 interaction has become a promising therapeutic strategy. Etoposide was the only antitumor compound known to inhibit the binding of CD44 to HA, thereby disrupting key functions that drive malignancy.

Deviant sound frequency and time stimuli in auditory oddball tasks reveal persistent aberrant brain activity in patients with psychosis and symptomatic remission.

The detection of rare or deviant stimuli shares common brain circuits involved in temporal processing and salience, critical for cognitive control. Disruption in these processes may contribute to the mechanisms of the disease and explain cognitive deficits observed in psychosis and related disorders. We designed a neuroimaging study, using oddball task-based functional sequences (fMRI) and diffusion tensor imaging (DTI), comparing healthy controls (HC, n = 14, 7 females) and patients with stable psychosis (PSY, n = 20, 10 females).

Clinical outcomes of adults with intracranial grade 1 and 2 ganglioglioma.

Ganglioglioma is a rare primary brain tumour that most frequently occurs in children and young adults. They are generally low-grade and have a favourable prognosis, but there is limited literature to guide the optimal management. The aim of this study was to investigate the clinical outcomes of adults with intracranial ganglioglioma, and to determine the frequency and duration of radiological follow-up.

Circulating insulin-like growth factor-1 and the risk of multiple sclerosis: a prospective cohort study.

Background: Circulating insulin-like growth factor 1 (IGF-1) is positively associated with the risks of certain neurological disorders, including stroke, Alzheimer's disease, and Parkinson's disease. However, the association of IGF-1 with the risk of multiple sclerosis (MS) remains unclear.

Methods: A total of 348,324 participants at baseline were included from the UK biobank in this prospective study.

A miniature FUS transducer based on an acoustic Fresnel lens for integration with a surgical robot.

A new focussed ultrasound surgery (FUS) transducer for soft tissue ablation is proposed, with a miniaturised configuration that can be readily integrated with a surgical robot. The transducer fills a gap in FUS technology at this size, with capability for acoustic focus steering within a very simple transducer configuration. Miniaturisation is enabled by the incorporation of an acoustic Fresnel lens as the focussing element driven by a single piezoceramic disc.

Experiences and perspectives of patients undergoing colorectal cancer surgery: A qualitative study.

Purpose: This study aimed to explore the experiences of patients with colorectal cancer undergoing surgical treatment, capturing their perspectives from diagnosis through to post-discharge recovery.

Methods: A qualitative methodology was adopted, utilising semi-structured virtual interviews with ten patients recruited from a specialist colorectal clinic. Interviews were transcribed verbatim, and data analysed by the process of inductive thematic analysis, using interpretive description.

Sick of debt: How over-indebtedness is hampering health in rural Cambodia.

This paper evidences how many rural poor Cambodians are sick of debt. Based on original, mixed-method data (2020-2022), exploring credit provisioning in this context, the aim of this paper is to illuminate some of the conditions leading to rural Cambodians taking on debt to bolster their health, and the effects this is having on borrowers' physical, psychological, emotional and social health. Specifically, we show how the health of our participants is constrained by a range of major illnesses that many suffer from and their poor food conditions, both exacerbated by the effects of climate change.

Deep learning image registration for cardiac motion estimation in adult and fetal echocardiography via a focus on anatomic plausibility and texture quality of warped image.

Temporal echocardiography image registration is important for cardiac motion estimation, myocardial strain assessments, and stroke volume quantifications. Deep learning image registration (DLIR) is a promising way to achieve consistent and accurate registration results with low computational time. DLIR seeks the image deformation that enables the moving image to be warped to match the fixed image.

Development and psychometric properties of the Italian little developmental coordination disorder questionnaire (LDCDQ-IT).

Background: Early identification of Developmental Coordination Disorder (DCD) in children is fundamental to provide the best chance of improving their outcomes. The Little Developmental Coordination Disorder Questionnaire (LDCDQ) is a screening tool to identify preschool children who may warrant a diagnosis of DCD.

Aims: This study conducted a transcultural translation and adaptation of the Italian version of the Little Developmental Coordination Disorder Questionnaire (LDCDQ-IT) and evaluated the psychometric properties of the tool, establishing also the optimal cut-off scores.

Children with a tracheostomy: Global speech-language therapists' practice.

Purpose: Speech-language Therapists (SLTs) are specialists in communication, feeding and swallowing as core members of the paediatric tracheostomy multidisciplinary team (MDT). Inconsistent tracheostomy care leads to staff and family frustration and delayed intervention. Little is known about international SLT tracheostomy practices.

Joint exposure to multiple air pollutants and residual cardiovascular risk in hypertension.

Background: Despite the widespread availability of antihypertensive medications, residual cardiovascular risk of hypertension remained high. Limited studies have investigated the link between air pollution, particularly joint exposure to multiple air pollutants, with residual cardiovascular risk of hypertension.

Methods: 1981 hypertensive patients (≥ 18 years) from an ongoing longitudinal cohort in China, were enrolled between 2013 and 2019.

The effect of run duration, gait variable and Lyapunov exponent algorithm on the inter-session reliability of local dynamic stability in healthy young people.

Local dynamic stability (LDS) of gait has been used to differentiate between healthy and injured populations, establishing its potential as an indicator of healthy gait and a new objective measure to assess gait function following injury. For LDS to be a reliable assessment tool of healthy gait progression during rehabilitation, it must provide consistent and sensitive inter-session measures. Methodological factors such as trial duration, gait variable, and Lyapunov Exponent (LyE) algorithm can influence LDS estimation and its reliability.

The gender wage gap across life: Effects of genetic predisposition towards higher educational attainment.

Using two polygenic scores (PGS) for educational attainment in a biomedical study of all those born in a single week in Great Britain in 1958 we show that the genetic predisposition for educational attainment is associated with labour market participation and wages over the life-course for men and women. Those with a higher PGS spend more time in employment and full-time employment and, when in employment, earn higher hourly wages. The employment associations are four times larger for women than for men.

An exploration into the experiences of newly qualified midwives during their transition to practice in the UK: A systematic review.

Aim: The aim of this systematic review was to explore the experiences of newly qualified midwives (NQMs) during their transition to practice in the UK.

Background: It has been recognised that the transition from student to NQM is a time of significant change that has implications for staff recruitment and retention. Thus, the rationale for this review was that understanding the experiences of NQMs at this crucial time in their career is essential for developing systems of support to improve maternity care and no previous reviews were found on this topic based in the UK.

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.