Comprehensive Extractables and Leachables Sensitization Analysis and Practical Application of a Risk-Based Approach to Sensitization Assessment for Parenteral Drug Products.

The Extractables and Leachables Safety Information Exchange (ELSIE) Consortium added to the sensitization potency analysis of Parris et al. (2023) by including the Product Quality Research Institute (PQRI) extractable and leachable dataset (Johnson et al., 2024; Product Quality Research Institute, 2021).

IUPHAR review: Drug Repurposing in Schizophrenia - An Updated Review of Clinical Trials.

There is an urgent need for mechanistically novel and more efficacious treatments for schizophrenia, especially those targeting negative and cognitive symptoms with a more favorable side-effect profile. Drug repurposing-the process of identifying new therapeutic uses for already approved compounds-offers a promising approach to overcoming the lengthy, costly, and high-risk process of traditional CNS drug discovery. This review aims to update our previous findings on the clinical drug repurposing pipeline in schizophrenia.

Ramp Protocol for Non-linear Cerebrovascular Reactivity with Transcranial Doppler Ultrasound.

Background: Cerebrovascular reactivity (CVR) reflects the ability of cerebral blood vessels to adjust their diameter in response to vasoactive stimuli, which is crucial for maintaining brain health. Traditional CVR assessments commonly use a two-point measurement, assuming a linear relationship between cerebral blood flow (CBF) and arterial CO. However, this approach fails to capture non-linear characteristics, particularly the plateaus at extreme CO levels.

A large hypothesis-free proteomics study investigating serum inflammatory markers as biomarkers of dry eye disease.

Purpose: To test the association between serum inflammatory markers and dry eye disease (DED) using a hypothesis-free proteomic approach in a population-based cohort.

Methods: A total of 2602 unselected community-based participants (mean age 61.5 (range 21-92 years), 94.

Plasma biomarkers of endothelial function in people with depressive disorder: A systematic review and meta-analysis.

The objective of this study is to conduct a literature review and summarize existing research comparing levels of blood markers of endothelial function in people with depression with controls. We searched major databases (Embase, PubMed, Web of Science, and PsycINFO) from inception to 23.07.

Cognitive hierarchy in mood disorders and relations to daily functioning.

Cognitive impairment affects approximately 50 % of patients with mood disorders during remission, which correlates with poorer daily-life functioning. The hierarchical organization of cognitive processes may mean that some cognitive deficits, e.g.

Automated insulin delivery during the first 6 months postpartum (AiDAPT): a prespecified extension study.

Background: Clinical guidelines in the UK and elsewhere do not specifically address hybrid closed loop (HCL) use in the postpartum period when the demands of caring for a newborn are paramount. Our aim was to evaluate the safety and efficacy of HCL use during the first 6 months postpartum compared with standard care.

Methods: In this prespecified extension to a multicentre, randomised controlled trial, pregnant women with type 1 diabetes at nine UK sites were followed up for 6 months postpartum.

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.