Molecular Insights into the Adsorption of Deposit Control Additives from Hydrocarbon Fuels.

Engine deposits can reduce performance and increase emissions, particularly for modern direct-injection fuel delivery systems. Surfactants known as deposit control additives (DCAs) adsorb and self-assemble on the surface of deposit precursors to keep them suspended in the fuel. Here, we show how molecular simulations can be used to virtually screen the ability of surfactants to bind to polyaromatic hydrocarbons, comprising a major class of carbonaceous deposits.

Clonal analysis of SepSecS-specific B and T cells in autoimmune hepatitis.

Autoimmune hepatitis (AIH) is a rare chronic inflammatory liver disease characterized by the presence of autoantibodies, including those targeting O-phosphoseryl-tRNA:selenocysteine-tRNA synthase (SepSecS), also known as soluble liver antigen (SLA). Anti-SepSecS antibodies have been associated with a more severe phenotype, suggesting a key role for the SepSecS autoantigen in AIH. To analyze the immune response to SepSecS in patients with AIH at the clonal level, we combined sensitive high-throughput screening assays with the isolation of monoclonal antibodies (mAbs) and T cell clones.

ECM Modifications Driven by Age and Metabolic Stress Directly Promote the Vascular Smooth Muscle Cell Osteogenic Processes.

Background: The ECM (extracellular matrix) provides the microenvironmental niche sensed by resident vascular smooth muscle cells (VSMCs). Aging and disease are associated with dramatic changes in ECM composition and properties; however, their impact on the VSMC phenotype remains poorly studied.

Methods: Here, we describe a novel in vitro model system that utilizes endogenous ECM to study how modifications associated with age and metabolic disease impact the VSMC phenotype.

Sub-Saharan Africa's Contribution to Clinical Trials in International Acute Coronary Syndromes and Heart Failure Guidelines.

Background: There is a growing burden of acute coronary syndrome (ACS) and heart failure (HF) in sub-Saharan Africa (SSA), yet outcomes remain poor compared to high-income countries. The European Society of Cardiology (ESC) international guidelines are pivotal to the delivery of evidence-based care; however, their representation of populations from SSA remains unclear.

Objectives: The purpose of the study was to evaluate the representation of populations from SSA in randomized controlled trials (RCTs) that inform ESC ACS and HF guidelines.

Management of patients following implantable cardioverter-defibrillator therapy-The importance of a multifaceted approach.

Background: The most effective way to treat patients following a first ICD therapy is unclear. We hypothesised that following first ICD therapy, combining different treatment strategies would be associated with a reduction in the risk of subsequent therapy compared to single strategies alone.

Methods: Data was collected from consecutive patients undergoing ICD implantation at King's College Hospital between January 2009 and December 2019.

Construction of a prognostic survival model with tumor immune-related genes for breast cancer.

Background: Numerous studies have demonstrated that immune cell infiltration is a significant predictor in the prognosis of those with breast cancer. This study aimed to develop a prognostic model for undifferentiated breast cancer using immune-related markers.

Methods: Differentially expressed genes (DEGs) and prognostic factors were identified from The Cancer Genome Atlas (TCGA) database.

Lipid-mediated resolution of inflammation and survival in amyotrophic lateral sclerosis.

Neuroinflammation impacts on the progression of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder. Specialized pro-resolving mediators trigger the resolution of inflammation. We investigate the specialized pro-resolving mediator blood profile and their receptors' expression in peripheral blood mononuclear cells in relation to survival in ALS.

Multi-omics characterization of improved cognitive functions in Parkinson's disease patients after the combined metabolic activator treatment: a randomized, double-blinded, placebo-controlled phase II trial.

Parkinson's disease is primarily marked by mitochondrial dysfunction and metabolic abnormalities. We recently reported that the combined metabolic activators improved the immunohistochemical parameters and behavioural functions in Parkinson's disease and Alzheimer's disease animal models and the cognitive functions in Alzheimer's disease patients. These metabolic activators serve as the precursors of nicotinamide adenine dinucleotide and glutathione, and they can be used to activate mitochondrial metabolism and eventually treat mitochondrial dysfunction.

Decent work and nurses' work ability: A cross-sectional study of the mediating effects of perceived insider status and psychological well-being.

Background: While the benefits of decent work-employment that respects fundamental human rights, ensures fair income, guarantees workplace security, and provides social protection for families-have recently gained scholarly attention regarding job satisfaction, psychological empowerment, and work engagement, its potential to enhance nurses' work ability-defined as the ability to carry out job responsibilities-remains unaddressed. Furthermore, a gap exists in understanding the mechanisms through which decent work influences its outcomes.

Purpose: We aimed to investigate: (1) if securing decent work is associated with elevated nurses' work ability, and (2) if perceived insider status and psychological well-being mediate the association between decent work and nurses' work ability.

Association of maternal body mass index with hemodynamic and vascular alterations at 35-37 weeks' gestation.

Objective: Globally, one in four pregnant women is classified as overweight or obese, based on their prepregnancy body mass index (BMI). Obese pregnant women are at increased risk of adverse pregnancy outcomes and long-term cardiovascular disease that occurs earlier in life. This study aimed to assess maternal hemodynamic and vascular parameters at 35-37 weeks' gestation, to understand the alterations that may occur in association with increased maternal BMI and gestational weight gain, and to evaluate obesity-related pregnancy outcomes.

An exceptionally rare case of a diffuse midline glioma with concomitant H3.1 K27M and G34R mutations in the HIST1H3C (H3C3) gene.

Histone mutations (H3 K27M, H3 G34R/V) are molecular features defining subtypes of paediatric-type diffuse high-grade gliomas (HGG) (diffuse midline glioma (DMG), H3 K27-altered, diffuse hemispheric glioma (DHG), H3 G34-mutant). The WHO classification recognises in exceptional cases, these mutations co-occur. We report one such case of a 2-year-old female presenting with neurological symptoms; MRI imaging identified a brainstem lesion which was biopsied.

A policy framework for leveraging generative AI to address enduring challenges in clinical trials.

Can artificial intelligence improve clinical trial design? Despite their importance in medicine, over 40% of trials involve flawed protocols. We introduce and propose the development of application-specific language models (ASLMs) for clinical trial design across three phases: ASLM development by regulatory agencies, customization by Health Technology Assessment bodies, and deployment to stakeholders. This strategy could enhance trial efficiency, inclusivity, and safety, leading to more representative, cost-effective clinical trials.

Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis and neuromyelitis optica spectrum disorder - recommendations from ECTRIMS and the EBMT.

Autologous haematopoietic stem cell transplantation (AHSCT) is a treatment option for relapsing forms of multiple sclerosis (MS) that are refractory to disease-modifying therapy (DMT). AHSCT after failure of high-efficacy DMT in aggressive forms of relapsing-remitting MS is a generally accepted indication, yet the optimal placement of this approach in the treatment sequence is not universally agreed upon. Uncertainties also remain with respect to other indications, such as in rapidly evolving, severe, treatment-naive MS, progressive MS, and neuromyelitis optica spectrum disorder (NMOSD).

Nociplastic pain among individuals with chronic ocular surface pain: one cause for "pain without stain"?

Chronic ocular surface pain (COSP) refers to interrelated symptoms such as eye burning, aching, and irritation and can occur as an isolated condition or comorbid with numerous ocular disorders, including dry eye syndrome Treatments for COSP are largely aimed at the ocular surface and modulating pain arising from damaged corneal nerves; however, the average impact of these treatments on COSP are low to absent. A potential explanation for this is that in a subset of patients with COSP, individuals have amplified and/or dysregulated neural signaling and sensory processing within the central nervous system (CNS). As in other chronic pain conditions, this might be the pathogenic mechanism primarily responsible for maintaining pain - a phenomenon now referred to as nociplastic pain.

Effect of the prolene ripcord suture on the baerveldt tube position: A case study.

A 42 year old Afro-Caribbean man underwent Baerveldt Glaucoma Implant (BGI) surgery for silicone oil induced glaucoma. Three months following initial surgery, the 3-0 prolene ripcord suture was removed. Anterior segment OCT demonstrates the position of the intracameral portion of the tube before and after the 3/0 prolene stent suture (PSS) removal.

Assessment of the thymus in fetuses prior to spontaneous preterm birth using functional MRI.

Objectives: The aim of this study was to utilise T2* relaxometry (an indirect method of quantifying tissue oxygenation) to assess the fetal thymus in uncomplicated pregnancies throughout gestation and in a cohort of fetuses that subsequently deliver very preterm.

Methods: A control group of participants with low-risk pregnancies were recruited and retrospectively excluded if they developed any pregnancy related complications after scanning. Participants were recruited who were deemed to be at very high risk of delivery prior to 32 weeks' gestation and retrospectively excluded if they did not deliver prior to this gestation.

Assessing whether providing regular, free HIV self-testing kits reduces the time to HIV diagnosis: an internet-based, randomised controlled trial in men who have sex with men.

Background: The risk of onwards HIV transmission is strongly influenced by the interval between HIV infection and its diagnosis. The SELPHI trial examined whether this interval could be reduced by offering free HIV self-testing kits to men-who-have-sex with-men (MSM).

Setting: Internet-based RCT of MSM aged ≥16 years, resident in England/Wales, recruited via sexual and social networking sites.

Parallel EEG-fNIRS assessments of covert cognition in behaviorally non-responsive ICU patients: A multi-task feasibility study in a case of acute motor sensory axonal neuropathy.

Background: Repeat neurological assessment is standard in cases of severe acute brain injury. However, conventional measures rely on overt behavior. Unfortunately, behavioral responses may be difficult or impossible for some patients.

Predicting ALS informant distress from cognitive and behavioural change in people with ALS.

Background: The cognitive and behavioural changes that occur in around 50% of people with amyotrophic lateral sclerosis (ALS) may significantly affect people around them, contributing to heightened burden, anxiety, and depression. Despite existing evidence linking behavioural impairment to caregiver distress, the role of cognitive impairment remains less clear, with mixed findings on its impact.

Methods: This study assessed the influence of cognitive and behavioural impairments in people with ALS on the distress of their nominated informants.

Balance recovery and its link to vestibular agnosia in traumatic brain injury: a longitudinal behavioural and neuro-imaging study.

Background: Vestibular dysfunction causing imbalance affects c. 80% of acute hospitalized traumatic brain injury (TBI) cases. Poor balance recovery is linked to worse return-to-work rates and reduced longevity.

NR1D1 Inhibition Enhances Autophagy and Mitophagy in Alzheimer's Disease Models.

Alzheimer's disease (AD) is marked by extracellular beta-amyloid (Aβ) plaques and intracellular Tau tangles, leading to progressive cognitive decline and neuronal dysfunction. Impaired autophagy, a process by which a cell breaks down and destroys damaged or abnormal proteins and other substances, contributes to AD progression. This study investigated Nuclear Receptor Subfamily 1 Group D Member 1 (NR1D1) as a potential therapeutic target for modulating autophagy.

Piloting a minimum data set for older people living in care homes in England: a developmental study.

Background: We developed a prototype minimum data set (MDS) for English care homes, assessing feasibility of extracting data directly from digital care records (DCRs) with linkage to health and social care data.

Methods: Through stakeholder development workshops, literature reviews, surveys and public consultation, we developed an aspirational MDS. We identified ways to extract this from existing sources, including DCRs and routine health and social care datasets.