Recent publications
Diffuse midline glioma, H3 K27-altered (DMG) is a fatal tumour that arises in the midline structures of the brain. When located in the pons, it is more commonly referred to as diffuse intrinsic pontine glioma (DIPG). DMG/DIPG is usually diagnosed when children are < 10 years, and it has a median overall survival of < 12 months after diagnosis. Radiological imaging is still the gold standard for DIPG diagnosis while the use of biopsy procedures led to our knowledge on its biology, such as with the identification of the canonical histone H3K27M mutation. However, the need to improve survival encourages the development of non-invasive, fast and inexpensive assays on biofluids for optimizing molecular diagnoses in DMG/DIPG. Here, we propose a rapid, new, imaging and epigenetics-based approach to diagnose DMG/DIPG in the plasma of paediatric patients.
A total of 20 healthy children (mean age: 10.5 years) and 24 children diagnosed with DMG/DIPG (mean age: 8.5 years) were recruited. Individual histones (H2A, H2B, H3, H4, macroH2A1.1 and macroH2A1.2), histone dimers and nucleosomes were assayed in biofluids by means of a new advanced flow cytometry ImageStream(X)-adapted method.
We report a significant increase in circulating histone dimers and tetramers (macroH2A1.1/H2B versus control: p value < 0.0001; macroH2A1.2/H2B versus control: p value < 0.0001; H2A/H2B versus control: p value < 0.0001; H3/H4 versus control: p value = 0.008; H2A/H2B/H3/H4 versus control: p value < 0.0001) and a significant downregulation of individual histones (H2B versus control: p value < 0.0001; H3 versus control: p value < 0.0001; H4 versus control: p value < 0.0001). Moreover, histones were also detectable in the cerebrospinal fluid (CSF) of patients with DMG/DIPG and in the supernatant of SF8628, OPBG-DIPG002 and OPBG-DIPG004 DMG/DIPG cell lines, with patterns mostly similar to each other, but distinct compared to blood plasma.
In summary, we identified circulating histone signatures able to detect the presence of DMG/DIPG in biofluids of children, using a rapid and non-invasive ImageStream(X)-based imaging technology, which may improve diagnosis and benefit the patients.
Leaders adopting TL (transformational leadership style) are capable in motivating their followers to exhibit the best possible outcomes during tough situations like COVID-19. Doctors and healthcare providers who work tirelessly to create a great balance in the helm of life and death are key players in pharmaceutical industries. Their level of satisfaction not only helps in the enhancement of the productivity of the industry but also gains customers. In order to resolve the tough situation and come up with appropriate solution, an effective TL will be the actual saviour for the pharmaceutical industry. Also, due to the invasion of COVID-19, several companies, leaders and employees were imposed to change. Leading professionals effectively built the bridge between the organizations and the customers. Thus, tracing how TL impacts OCB (organizational citizenship behaviour) and CS (customer satisfaction) is the ultimate focus of the study. In order to carry out this, the present study framed a structured questionnaire; responses were fetched from 400 respondents from the pharmaceutical business. The collected data was analysed using SPSS software and SEM to determine the relationship and the significance of the model. The overall results of the research revealed that there is a positive impact among the constructs. That is, TL has impact on CS which is mediated by OCB. Limitations and further recommendations are also addressed.
Aim
Miombo, a prominent dry forest formation, holds ecological importance for both humans and wildlife. Trees are a driving force behind miombo dynamics, thus, spatially explicit metrics of tree cover are essential for evaluating habitat characteristics, resource availability, and environmental change. We developed predictive models and maps of tree species diversity and biomass within a previously undescribed landscape.
Location
Mahale Mountains National Park (MMNP), Greater Mahale Ecosystem (GME), Tanzania.
Methods
We created models of tree density, basal area, tree species richness, and tree diversity according to the Shannon Diversity Index. We created a predictive model using an ensemble modeling approach using plot‐based data from MMNP and predictor variables derived from satellite data associated with climate, habitat structure, plant productivity, and topography. We assessed predictor importance across models and produced maps based on model predictions and compared them to land cover type and protective status.
Results
Results revealed strong positive correlations between tree metrics ( r ≥ 0.70) and substantial overlap in the selection and relative importance of predictors. Canopy height was the most important predictor across models, followed by climate and topography predictors associated with energy. Predictors derived from the soil‐adjusted vegetation index were also valuable. Model performances ranged from R ² values of 0.45 to 0.55, with tree density performing best. Maps show high tree species diversity and biomass in protected areas.
Conclusions
This study and the maps it produced provide a baseline for land management and future modeling efforts in the GME. Our results highlight the contribution of a wide variety of environmental predictors and the importance of a select few. We confirmed the importance of the current protected area network where conservation efforts align, and help sustain, an abundance and diversity of trees. Current and historical disturbance‐related predictors should be considered to address remaining unexplained variance.
Purpose
This paper presents a realist evaluation of leadership within an integrated care system (ICS) in England. This paper aims to examine which aspects of leadership are effective, for whom, how and under what circumstances.
Design/methodology/approach
Realist evaluation methodology was used, adopting prior realist review findings as the theoretical framework to refine explanations of how and why leadership within an ICS is effective. Between January and November 2023, 23 interviews with ICS leaders took place, alongside 7 meeting observations and documentary analysis. The Realist And Metanarrative Evidence Syntheses: Evolving Standards (RAMESES) guidance informed the study design, conduct and reporting.
Findings
The findings highlight two overarching infrastructural contexts influencing leadership in ICSs: the impact of the post-COVID-19 pandemic legacy and the differences between health and social care regulatory and financial environments. Findings demonstrate that ICS leaders identified a strong sense of purpose as crucial for guiding decisions and creating a psychologically safe environment for open, honest discussions, fostering calculated risk-taking. Whilst a shared vision directed priority setting, financial pressures led to siloed thinking. Leadership visibility was linked to workforce morale, with supportive leadership boosting morale amidst evolving ICS landscapes and confidence in data-driven decisions supported prevention activities. However, financial constraints hindered responsiveness and innovation in addressing health inequalities.
Originality/value
By examining ICS leadership post-COVID-19 pandemic and amidst varying regulatory and financial environments, this study contributes to the emerging literature on systems leadership and offers practical guidance for leaders navigating the complexities of integrated care.
Sample preparation is one of the most neglected areas of analytical chemistry, even though good sample preparation can be the critical factor in the success of an analytical method. Solid-phase extraction (SPE) has proven to be one of the most reliable methodologies for ensuring efficient sample extraction, pretreatment, and pre-concentration. However, the common sorbent materials used in solid-phase extraction lack specificity. Molecularly imprinted polymers (MIP) have established themselves as powerful sorbents for solid-phase extraction and overcome the lack of specificity seen for complex samples. These so-called plastic antibodies can be tailored and designed to recognize and bind to any analyte of choice. In this chapter, we aim to review the current state of the art in the use of MIPs as sorbent materials for solid-phase extraction. We will review the strategies and formats employed for MIPs used in solid-phase micro extraction (SPME). We will also discuss the advantages of using MIPs as sorbents in dispersive solid-phase extraction and how new multifunctional nanomaterials can be exploited for sample preparation. Finally, we briefly discuss the current commercial MIPs available on the market and the future direction of MIPs in sample preparation applications.
Background
Phytochemical-based synthesis of nanoparticles (NPs) is an eco-friendly approach with various biomedical applications. Betanin, a natural pigment in beetroot, has antioxidant, anti-inflammatory, and antimicrobial properties. When conjugated with zinc oxide nanoparticles (ZnO NPs), these properties are enhanced. This study aimed to synthesize betanin-ZnO nanoparticles (BE–ZnO–NPs) and evaluate their biological potential.
Methods
BE–ZnO–NPs were synthesized and characterized using UV-Visible spectroscopy, FTIR, FE-SEM, HR-TEM, EDX, XRD, DLS, and zeta potential analysis. In silico studies assessed interactions with oral pathogen proteins, and antibacterial activity was tested against Enterococcus faecalis, Candida albicans, Staphylococcus aureus and Streptococcus mutans. Antioxidant potential and cytotoxicity on KB cells were evaluated through scavenging assays, MTT assay, and qRT-PCR.
Results
Betanin synthesized ZnO NPs UV-Vis results showed surface plasmon resonance at 388 nm, and FTIR confirmed betanin role as a capping agent. FE-SEM and TEM revealed particles of 37 nm. EDX confirmed zinc content, and XRD showed a hexagonal structure. Zeta potential was − 3.3 mV, and DLS indicated a size of 38.73 nm. In silico analysis showed strong binding to E. faecalis (− 8.0 Kcal/mol). BE–ZnO–NPs demonstrated antibacterial activity at 100 µg/mL, with inhibition zones of 18 ± 0.14 mm for E. faecalis and 14 ± 0.18 mm for S. mutans. In contrast, BE demonstrated antibacterial activity at 100 µg/mL, with zone of inhibition of 10.6 ± 0.14 mm for E. faecalisand 11.4 ± 0.18 mm for S. mutans.Antioxidant assays revealed dose-dependent scavenging activity. Cytotoxicity showed an IC50 of 24.29 µg/mL, with qRT-PCR indicating apoptosis through the BCL2/BAX/P53 pathway.
Conclusions
BE–ZnO–NPs exhibited significant antibacterial and antioxidant activities and demonstrated the ability to induce apoptosis in oral cancer cells via the BCL-2/BAX/P53 signalling pathway. These findings highlight the potential of BE–ZnO–NPs as promising antimicrobial agents for tooth infections and as therapeutic agents for oral tumour treatment.
The utilization of reclaimed asphalt pavement (RAP) in flexible pavement construction and rehabilitation has gained significant traction, driven by the need to conserve limited natural resources. This study explores the effectiveness of bio-based oils derived from harvested crops as rejuvenators in asphalt mixtures containing 50% RAP. Comprehensive assessments were conducted, including penetration, softening point, viscosity and ductility tests, to determine the optimal rejuvenator dosage. Additionally, evaluations of rolling thin film oven (RTFO) aging, retained penetration and ductility, equivalent softening and breaking points, plasticity temperature range, stiffness modulus, complex modulus, and phase angle were performed. Fourier-transform infrared (FTIR) spectroscopy, Marshall immersion, and moisture susceptibility tests further validated the rejuvenator's efficacy in improving asphalt properties. The incorporation of 1.8% bio-oil significantly reduced the viscosity of the mixtures, enhancing workability. The rejuvenator effectively compensated for the loss of light components in aged binders, restoring the maximum and minimum temperature performance to levels comparable to virgin asphalt (VA). Mechanical testing revealed that bio-oil mitigated the aging effects of RAP asphalt, and the rejuvenated mixtures showed considerable improvements over both VA and non-rejuvenated RAP mixtures, where the rejuvenated specimens achieved 90.8 and 89.4% of retained strength index (RSI) values for 24- and 48-h immersion periods, respectively comparing with 88.9 and 86% post-immersion of VA for similar durations. These findings underscore the potential of bio-oil as a sustainable and eco-friendly solution for rejuvenating aged asphalts, paving the way for more sustainable asphalt production practices.
This paper investigates shore-based photovoltaic (PV)/proton exchange membrane fuel cell (PEMFC) and PV/battery renewable energy (RE) plants for cold ironing (CI) configurations. The hydrogen for PEMFCs is produced in ammonia (NH3) electrolyser by the PV panel-sourced electricity using green, blue or grey NH3 as the feedstock. The system models based on PV technology are developed using minimum, average, and maximum monthly irradiation levels. The environmental and economic analyses benchmark CI based on grid/RE electricity with onboard electricity generation using diesel and dual-fuel systems with light fuel oil (LFO) and liquefied natural gas (LNG). Results show that LNG usage in the ship electrification plant reduces equivalent carbon dioxide (CO2e) by 14.27%, sulphur oxides by 90.79%, and nearly eliminates other emissions. Using grid electricity as the CI source cuts CO2e by 58.92%, while the PV/battery system reduces it by 80.73% to 85.82%, depending on irradiation. The PV/PEMFC system with green NH3 achieves the highest CO2e reduction (99.92%–100%), while blue NH3 provides the second largest decrease (97.46%–97.54%). The grid electricity CI has the shortest payback period (PBP) at 2.06 years and a levelised cost of energy (LCOE) of 174.67 to 129-151.94–177.09-$359.89/MWh with green NH3.
Graphical abstract
Understanding observed interpersonal touch, particularly the so-called affective touch targeting the CT fibers, is essential for social interactions. Research has documented that observing other people being touched activates the same cortical areas involved in direct tactile experiences. However, observing interpersonal touch also activates an inner simulation of the movements in the observer’s motor system. Given the social and affective significance of CT-optimal touch, the present study tested the hypothesis that observing stroking touches targeting or not targeting the CT fibers system might distinctly influence motor resonance to vicarious touch. With this aim, we used single-pulse transcranial magnetic stimulation and motor-evoked potentials recording while participants observed video clips of interpersonal touch events at different stroking velocities. We found a modulation of motor system activity, particularly a decrease in corticospinal excitability, when observing CT-optimal touch as opposed to non-CT-optimal velocities, a mechanism that might aid in understanding the touchee’s feelings during vicarious interpersonal touch. Moreover, participants with higher reliance on bodily cues to be emotionally aware showed greater motor suppression for CT-optimal compared to non-CT-optimal velocities. These results shed light on the complex interplay between motor and somatosensory systems in social touch perception and emphasize the importance of affective touch in human social interactions.
The paper-based consent pathway can be associated with missing information, error, and inadequate patient comprehension. Digital consent addresses some of these limitations. However, limited research has been conducted to understand relative costs and consequences associated with adopting digital consent pathways. The aim of this study was to compare the relative costs of digital consent pathways with paper-based consent pathways in UK National Health Service (NHS) clinical practice.
A micro-costing study was conducted from the UK NHS perspective. Multi-stakeholder involvement contributed to understanding how the paper-based consent pathway varies by department and hospital setting. Sensitivity analyses were conducted to identify the key cost drivers and scenario analyses explored the effect of consent timing and hospital digital readiness. Potential advantages and disadvantages of digital consent were also considered, such as possible impacts associated with consent-related litigation.
The cost per consent episode is approximately £0.90 more expensive when completed on paper. The ordering or printing of paper consent forms, and the transportation of forms to storage and back to clinic are process steps that would not be necessary with digital consent. Sensitivity and scenario analyses indicated consultation duration had the greatest impact on the relative costs of both pathways. Per litigation claim prevented, an average of £201,590 could be saved.
Digital consent is potentially cost saving for the NHS. Consent for elective procedures is recommended in advance of the day of surgery, and digital consent used in this scenario demonstrated the greatest savings. Consultation duration was estimated to have the greatest impact on the relative costs of both pathways, which should be a focus of further investigation.
Commentary on: Weisser, B., S. Wassmann, H. G. Predel, R. E. Schmieder, A. Gillessen, T. Wilke, J. Blettenberg, O. Randerath, A. Mevius, and M. Bohm (2024). “Effect of a single pill concept on clinical and pharmacoeconomic outcomes in cardiovascular diseases.” Eur Heart J Cardiovasc Pharmacother; https://doi.org/10.1093/pvae059.
In his novel Life and Fate , Vasily Grossman imagines that we will one day engineer an artificial intelligence that will mimic humans in every way. In order to reproduce “the peculiarities of mind and soul of an average, inconspicuous human being,” however, the computer that houses it will have to be bigger than the Earth. This essay takes Grossman’s novel as the start and endpoint for a discussion about the role of the public humanities in the age of artificial intelligence (AI). The response of the humanities to the pervasive fatalism about an AI-driven future should be twofold. First, they can serve as an antidote to a credulous, amnesiac present which sees the future as already decided, with inexorable effects that we can only adapt to. Second, they can challenge the now pervasive view of intelligence as computational and algorithmic. The humanities refuse to see humans as codable, or as just part of the data stream. We should certainly study the ways in which AI is changing what it means to be human, but we should never lose sight of what is most astonishing, and uncopiable, about us.
Neuroblastoma (NB) is the most common solid extracranial neoplasm found in children and is derived from primitive sympathoadrenal neural precursor. The disease accounts for 15% of all cancer deaths in children. The mortality rate is high in patients presenting with a metastatic tumour even with extensive treatments. This signifies the need for further research towards the development of new additional therapies that can combat not only tumour growth but metastasis, especially amongst the high-risk groups. During metastasis, primary tumour cells become migratory and travel towards a capillary within the tumour. They then degrade the matrix surrounding the pericytes and endothelial cells traversing the endothelial barrier twice to establish a secondary. This led to the hypothesis that modulation of the endothelial cell junctional stability could have an influence on tumour metastasis. To test this hypothesis, agents that modulate endothelial permeability on NB cell line migration and invasion were assessed in vitro in a tissue culture model. The cAMP agonist and its antagonists were found to have no obvious effect on both SK-N-BE2C and SK-N-AS migration, invasion and proliferation. Next, NB cells were cocultured with HDMEC cells and live cell imaging was used to assess the effect of an Epac agonist on trans-endothelial cell migration of NB cells. Epac1 agonist remarkably reduced the trans-endothelial migration of both SK-N-BE2C and SK-N-AS cells. These results demonstrate that an Epac1 agonist may perhaps serve as an adjuvant to currently existing therapies for the high-risk NB patients.
Background and Aim
Professional soccer players’ self-reported dietary intakes often do not meet recommended sport nutrition guidelines. Although behaviour change models have previously explored barriers and enablers to nutritional adherence, the cultural factors influencing players’ nutritional habits also warrant investigation. Accordingly, we aimed to explore players’ perceptions of the nutrition culture within the professional soccer environment.
Methods
An interpretivist paradigm, which emphasises that reality is subjectively and socially constructed, underpins this study. Qualitative, face-to-face semi-structured interviews (comprising open-ended questions) were conducted with purposively sampled male soccer players from the English Premier League (EPL) (five British, five migrant; mean age: 26 ± 6 years; mean EPL appearances: 106 ± 129). Data were abductively analysed using thematic analysis according to Bourdieu’s concepts of habitus, capital, field and doxa practices.
Results
This study revealed five key themes: (1) players’ habitus, as shaped by familial, ethnic and religious backgrounds, influences their dietary habits; (2) social capital, via managers (head coaches), teammates and online influences, impact players’ dietary practices; (3) the increase in both soccer clubs’ and players’ economic capitals has advanced nutrition provision; (4) an unequal distribution of economic capitals has led to hierarchical practice in the performance nutrition field with personalised nutrition being somewhat enacted at the higher levels; and (5) body composition measurement is a ‘doxic’ practice in professional soccer that warrants challenge.
Conclusions
Soccer players’ habitual nutritional practices are influenced by personal upbringing and the club context, including economic resources and social capital from managers. The performance nutrition field within professional soccer is also shaped by stakeholders’ doxic beliefs surrounding the perceived optimal body composition of players, with managers exerting social capital.
Introduction
The risk of dementia in patients with stroke-heart syndrome (SHS) remains unexplored.
Patients and methods
Retrospective analysis using the TriNetX network, including patients with ischaemic stroke from 2010 to 2020. These patients were categorised into two groups: those with SHS (heart failure, myocardial infarction, ventricular fibrillation, or Takotsubo cardiomyopathy within 30 days post-stroke) and those without SHS. The primary outcome was the 1-year risk of dementia (vascular dementia, dementia in other disease, unspecified dementia, or Alzheimer’s disease). The secondary outcome was the 1-year risk of all-cause death. Cox regression analysis after 1:1 propensity score matching (PSM) was performed to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the outcomes.
Results
We included 52,971 patients with SHS (66.6 ± 14.6 years, 42.2% females) and 854,232 patients without SHS (64.7 ± 15.4 years, 48.2% females). Following PSM, 52,970 well-balanced patients were considered in each group. Patients with SHS had a higher risk of incident dementia compared to those without SHS (HR 1.28, 95%CI 1.20–1.36). The risk was the highest during the first 31 days of follow-up (HR 1.51, 95%CI 1.31–1.74) and was mainly driven by vascular and mixed forms. The increased risk of dementia in patients with SHS, was independent of oral anticoagulant use, sex and age but it was the highest in those aged <75 years compared to ⩾75 years.
Discussion and conclusion
SHS is associated with increased risk of dementia. Future studies are needed to develop innovative strategies for preventing complications associated with stroke-heart syndrome and improving the long-term prognosis of these patients.
Background/Aims
Restraint is a complex issue that is associated with multiple legal and ethical challenges. National scandals have highlighted a lack of adequate training among healthcare staff in restraint. While education should start with nurses in training, evidence suggests that the experiences of student nurses in relation to restraint has not been addressed. This study aimed to explore the lived experiences of student nurses when encountering restraint.
Methods
A qualitative methodology was used to investigate student nurse experiences of restraint. Seven semi-structured interviews were undertaken with student nurses in their second (n=3) and third year (n=4) of an undergraduate nursing degree, with a specialism in mental health nursing. Data were analysed using a thematic analysis approach.
Results
Three overarching themes were identified from the data: a ‘clinical–theory gap’, referring to a gap in students’ theoretical learning and clinical placements; ‘learning from each other’, where students felt a need for increased shared learning surrounding restraint; ‘wellbeing’, highlighting a lack of sufficient supportive and timely interventions to appropriately aid student wellbeing after witnessing restraint.
Conclusions
These findings highlight the need for improved communication between higher education institutions and clinical practice in relation to restraint. Opportunities for debriefs within higher education learning environments should be considered in order to improve student nurses’ wellbeing and experiences of their nursing degree programme.
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