2,841,126 results match your criteria: "University College & Middlesex School of Medicine[Affiliation]"

Background: The associations between organisational stressors and burnout among healthcare staff working with adults with intellectual disabilities are underexplored. This study investigated rates of burnout and associated stressors among Irish healthcare workers during the COVID-19 pandemic.

Materials And Methods: A convenience sample of 329 Irish frontline staff supporting adults with intellectual disabilities completed a survey assessing personal, work-related, and client-related burnout, and organisational stressors.

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As an effective approach to mitigating urban environmental issues, New Energy Vehicles (NEVs) have become a focal point of research regarding their current development status and future prospects in China. Addressing the significant disparities in the development of the NEVs industry across different cities, this study focuses on ten typical Chinese cities and develops a novel multi-attribute decision-making (MADM) framework to evaluate the prospects of NEVs promotion in these cities. The study first establishes a comprehensive indicator system that covers key dimensions such as economy, policy support, infrastructure, technological innovation, and environment, encompassing five different types of evaluation information.

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The local environment of the active site, such as the confinement of hydronium ions within zeolite pores, significantly influences catalytic turnover, similar to enzyme functionality. This study explores these effects in the hydrolysis of guaiacols─lignin-derived compounds─over zeolites in water. In addition to the interesting catechol products, this reaction is advantageous for study due to its bimolecular hydrolysis pathway, which involves a single energy barrier and no intermediates, simplifying kinetic studies and result interpretation.

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QUEST#4X: An Extension of QUEST#4 for Benchmarking Multireference Wave Function Methods.

J Chem Theory Comput

January 2025

Qingdao Institute for Theoretical and Computational Sciences and Center for Optics Research and Engineering, Shandong University, Qingdao 266237, China.

Given a number of data sets for evaluating the performance of single reference methods for the low-lying excited states of closed-shell molecules, a comprehensive data set for assessing the performance of multireference methods for the low-lying excited states of open-shell systems is still lacking. For this reason, we propose an extension (QUEST#4X) of the radical subset of QUEST#4 ( , , 3720) to cover 110 doublet and 39 quartet excited states. Near-exact results obtained by iterative configuration interaction with selection and second-order perturbation correction (iCIPT2) are taken as benchmark to calibrate static-dynamic-static configuration interaction (SDSCI) and static-dynamic-static second-order perturbation theory (SDSPT2), which are minimal MRCI and CI-like perturbation theory, respectively.

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Triethylamine-mediated protonation-deprotonation unlocks dual-drug self assembly to suppress breast cancer progression and metastasis.

Proc Natl Acad Sci U S A

February 2025

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, People's Republic of China.

Carrier-free nanomedicines exhibited significant potential in elevating drug efficacy and safety for tumor management, yet their self assembly typically relied on chemical modifications of drugs or the incorporation of surfactants, thereby compromising the drug's inherent pharmacological activity. To address this challenge, we proposed a triethylamine (TEA)-mediated protonation-deprotonation strategy that enabled the adjustable-proportion self assembly of dual drugs without chemical modification, achieving nearly 100% drug loading capacity. Molecular dynamic simulations, supported by experiment evidence, elucidated the underlying self-assembly mechanism.

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Neomorphic leukemia-derived mutations in the TET2 enzyme induce genome instability via a substrate shift from 5-methylcytosine to thymine.

Proc Natl Acad Sci U S A

February 2025

Center for Medical Research and Innovation, Shanghai Pudong Hospital, Institutes of Biomedical Sciences, Chinese Academy of Medical Sciences (RU069), Medical College of Fudan University, Shanghai 201399, China.

Ten-eleven translocation (TET) enzymes oxidize 5-methylcytosine (mC) in DNA, contributing to the regulation of gene transcription. Diverse mutations of TET2 are frequently found in various blood cancers, yet the full scope of their functional consequences has been unexplored. Here, we report that a subset of TET2 mutations identified in leukemia patients alter the substrate specificity of TET2 from acting on mC to thymine.

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Enzyme-enzyme interactions are fundamental to the function of cells. Their atomistic mechanisms remain elusive mainly due to limitations of in-cell measurements. We address this challenge by atomistically modeling, for a total of ≈80 μs, a slice of the human cell cytoplasm that includes three successive enzymes along the glycolytic pathway: glyceraldehyde-3-phosphate dehydrogenase (GAPDH), phosphoglycerate kinase (PGK), and phosphoglycerate mutase (PGM).

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Background: Spatial data are often aggregated by area to protect the confidentiality of individuals and aid the calculation of pertinent risks and rates. However, the analysis of spatially aggregated data is susceptible to the modifiable areal unit problem (MAUP), which arises when inference varies with boundary or aggregation changes. While the impact of the MAUP has been examined previously, typically these studies have focused on well-populated areas.

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Electroencephalographic signals are obtained by amplifying and recording the brain's spontaneous biological potential using electrodes positioned on the scalp. While proven to help find changes in brain activity with a high temporal resolution, such signals are contaminated by non-stationary and frequent artefacts. A plethora of noise reduction techniques have been developed, achieving remarkable performance.

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In an era of intense brand competition, a successful logo can effectively boost consumer awareness of a company. However, existing research has not thoroughly examined the aspect of symmetry in logo design. Addressing this gap, the present study investigates the impact of logo symmetry on consumers' perceived product quality.

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Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is a neurodegenerative disease caused by mutations in the gene encoding transthyretin (TTR). Despite amyloid deposition being pathognomonic for diagnosis, this pathology in nervous tissues cannot fully account for nerve degeneration, implying additional pathophysiology for neurodegeneration, which, however, has not yet been fully elucidated. In this study, neuroinflammation in ATTRv-PN was investigated by examining nerve morphometry, the blood-nerve barrier, and macrophage infiltration in the sural nerves of ATTRv-PN patients and the sciatic nerves of a complementary mouse system, i.

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Impact of media coverage on the transmission dynamics of TB with vaccines and treatment.

PLoS One

January 2025

Department of Mathematics, College of Natural and Computational Science, Debre Berhan University, Debre Berhan, Adis Ababa, Ethiopia.

Tuberculosis (TB) is one of the deadly infectious diseases affecting millions of individuals throughout the world. The main objective of this study is to investigate the impact of media coverage on the transmission dynamics of TB with vaccine and treatment strategy using mathematical model analysis. In the qualitative analysis of the proposed model we proved the existence, uniqueness, positivity, and boundedness of the model solutions, investigated both the disease-free and endemic equilibrium points, computed the basic and effective reproduction numbers using next generation matrix approach, analyzed the stability analysis of the equilibrium points, the backward bifurcation using the Castillo-Chavez and Song theorem and we re-formulated the corresponding optimal control problem and analyzed by applying the Pontryagin's Minimum Principle.

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Youth living with HIV (YLWH) face psychosocial challenges and HIV-related stigma, which impact adherence to antiretroviral therapy (ART). This study was designed to understand better the change in mental health symptoms and experiences with stigma among YLWH in Tanzania who completed the original pilot Sauti ya Vijana (SYV), a mental health and life skills group intervention. YLWH who completed SYV and demonstrated a change of ≥2 points in either direction on their Patient Health Questionnaire PHQ-9 (depression screener) from baseline to 18 months were purposively sampled.

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Background: In recessive dystrophic epidermolysis bullosa (RDEB), complications like oesophageal strictures, hand contractures, cardiomyopathy and cutaneous squamous cell carcinoma (SCC) may develop, necessitating procedures such as oesophageal dilatation (OD), gastrostomy tube placement and hand surgery.

Objectives: To determine prevalence and age of onset of milestone events by RDEB subtype, specifically dysphagia, first OD, first gastrostomy tube, first hand surgery, cardiomyopathy, first SCC and death.

Methods: The Prospective Epidermolysis Bullosa Longitudinal Evaluation Study (PEBLES) is a register study of individuals with RDEB which records comprehensive EB- and non-EB-related health information.

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Objectives: To compare two strategies-a hydrocortisone replacement strategy and a prednisone tapering strategy-for their success in glucocorticoid discontinuation in patients with rheumatoid arthritis (RA) with low disease activity (LDA).

Methods: The Strategies for glucocorticoid TApering in Rheumatoid arthritis (STAR) study was a double- blind, double-placebo randomised controlled trial including patients with RA receiving a stable dose of glucocorticoid 5 mg/day for ≥3 months and were in LDA for ≥3 months. Patients were randomly assigned in a 1:1 ratio to either replace prednisone with 20 mg/day of hydrocortisone for 3 months, then reduce to 10 mg/day for 3 months before discontinuation or to taper prednisone by 1 mg/day every month until complete discontinuation, contingent on maintaining LDA.

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Multiple clinical trials for rheumatoid arthritis (RA) prevention have been completed. Here, we set out to report on the lessons learnt from these studies. Researchers who conducted RA prevention trials shared the background, rationale, approach and outcomes and evaluated the lessons learnt to inform the next generation of RA prevention trials.

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Objectives: The dynamics of monosodium urate (MSU) crystal changes across a range of serum urate concentrations in people with gout are unknown. This study aimed to systematically examine the relationship between serum urate and changes in dual-energy CT (DECT) urate volume in people with gout and stable serum urate concentrations.

Methods: Individual participant data were analysed from three studies of people with gout.

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RNA N6-methyladenosine (m6A) plays diverse roles in RNA metabolism and its deregulation contributes to tumor initiation and progression. Clear cell renal cell carcinoma (ccRCC) is characterized by near ubiquitous loss of followed by mutations in epigenetic regulators , , and . Mutations in , a histone H3 lysine 36 trimethylase (H3K36me3), are associated with reduced survival, greater metastatic propensity, and metabolic reprogramming.

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Stereocaulon alpinum has been found to have potential pharmaceutical properties due to the presence of secondary metabolites such as usnic acid, atranorin, and lobaric acid (LA) which have anticancer activity. On the other hand, the effect of LA on the stemness potential of colorectal cancer (CRC) cells remains unexplored, and has not yet been thoroughly investigated. In this study, we examined the inhibitory activity of LA from Stereocaulon alpinum against the stemness potential of CRC cells and investigated the possible underlying mechanisms.

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Shaping Future Medicinal Chemists: Perspectives from European Schools of Pharmacy within the GPA Network.

J Med Chem

January 2025

Centro Singular de Investigación en Química Biolóxica y Materiais Moleculares (CiQUS), Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain.

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Insight into the Mechanism of d-Glucose Accelerated Exchange in GLUT1 from Molecular Dynamics Simulations.

Biochemistry

January 2025

BHF Centre of Research Excellence, School of Medicine and Life Sciences, King's College London, London SE1 9NH, United Kingdom.

Transmembrane glucose transport, facilitated by glucose transporters (GLUTs), is commonly understood through the simple mobile carrier model (SMCM), which suggests that the central binding site alternates exposure between the inside and outside of the cell, facilitating glucose exchange. An alternative "multisite model" posits that glucose transport is a stochastic diffusion process between ligand-operated gates within the transporter's central channel. This study aims to test these models by conducting atomistic molecular dynamics simulations of multiple glucose molecules docked along the central cleft of GLUT1 at temperatures both above and below the lipid bilayer melting point.

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Functional Characterization of an Aldol Condensation Synthase PheG for the Formation of Hispidin from Phellinus Igniarius.

Adv Sci (Weinh)

January 2025

College of Pharmacy, Key Laboratory of Protection, Development and Utilization of Medicinal Resources in Liupanshan Area, Ministry of Education, Ningxia Medical University, Yinchuan, 750004, P.R. China.

Hispidin (1) is a polyphenolic compound with a wide range of pharmacological activities that is distributed in both plants and fungi. In addition to natural extraction, hispidin can be obtained by chemical or enzymatic synthesis. In this study, the identification and characterization of an undescribed enzyme, PheG, from Phellinus igniarius (P.

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A novel Ru-catalyzed radical-triggered trifunctionalization of hexenenitriles is presented, employing a strategy of remote cyano group migration and -C(sp)-H functionalization. Through remote cyano migration, the alkenyl moiety undergoes difunctionalization to the formation of a benzylic radical intermediate. This intermediate facilitates -selective C-H bond addition relative to the C-Ru bond within the Ru(III) complex, ultimately enabling trifunctionalization.

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Observations of Cherenkov-Like Radial Wake in Water Waves.

Adv Sci (Weinh)

January 2025

Key Laboratory of Ocean Observation‑Imaging Testbed of Zhejiang Province, Ocean College, Zhejiang University, Hangzhou, 310058, China.

Cherenkov radiation (CR) is a fascinating phenomenon that occurs not only in electromagnetic (EM) waves but also in water waves. The V-shaped wake formed by a moving object on the water surface results from the constructive interference of water waves of different wavelengths, similar to CR. We designed and fabricated a one-dimensional (1D) water wave crystal to analogize the behavior of moving particles in water waves.

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Aspartate Metabolism-Driven Gut Microbiota Dynamics and RIP-Dependent Mitochondrial Function Counteract Oxidative Stress.

Adv Sci (Weinh)

January 2025

Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation, Hunan international joint laboratory of Animal Intestinal Ecology and Health, Laboratory of Animal Nutrition and Human Health, College of Life Sciences, Hunan Normal University, Changsha, 410081, China.

Aspartate (Asp) metabolism-mediated antioxidant functions have important implications for neonatal growth and intestinal health; however, the antioxidant mechanisms through which Asp regulates the gut microbiota and influences RIP activation remain elusive. This study reports that chronic oxidative stress disrupts gut microbiota and metabolite balance and that such imbalance is intricately tied to the perturbation of Asp metabolism. Under normal conditions, in vivo and in vitro studies reveal that exogenous Asp improves intestinal health by regulating epithelial cell proliferation, nutrient uptake, and apoptosis.

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