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109eP Identification of potential novel therapies of leukemia
No full textBackground
Acute lymphoblastic leukemia (ALL) is characterized by the malignant proliferation of immature lymphoid progenitors, resulting in hematopoietic suppression and clinical manifestations such as anemia, immunodeficiency, and hemorrhage. Resistance to glucocorticoids (GCs), which are essential agents in the treatment of ALL, presents a significant therapeutic challenge. This study aims to investigate alternative and combinatorial treatment regimens that target the glucocorticoid receptor (GR) axis, calcium signaling, and kinase-mediated survival pathways to overcome this GC resistance.
Methods
T-cell ALL cell lines, CEM-C7 (GC-sensitive) and CEM-C1 (GC-resistant), were exposed to Perifosine, Ulixertinib, Dasatinib, dexamethasone (Dex), and calcium channel modulators (e.g., Verapamil). Cell viability was quantified via MTS assays, and apoptosis was evaluated using propidium iodide-based flow cytometry. Bioinformatic enrichment analyses were performed to identify convergence nodes across hormone-responsive and oncogenic signaling pathways.
Results
Perifosine, Ulixertinib, and Dasatinib chosen through bioinformatics analysis significantly reduced metabolic activity across both cell lines. Flow cytometry confirmed elevated apoptosis rates, with Perifosine demonstrating pronounced cytotoxicity. Combination treatments (e.g., Perifosine + Dex + Verapamil) exhibited enhanced efficacy in CEM-C1 cells, indicating more cytotoxic effects. Pathway enrichment highlighted GR signaling, PI3K-Akt, JAK-STAT, and FoxO pathways as central regulatory hubs.
Conclusions
Perifosine-based combination therapies exhibit potent anti-leukemic activity, particularly in GC-resistant phenotypes, and warrant further translational exploration. Targeting intersecting nodes in hormone and survival signaling pathways may offer a viable strategy to circumvent therapeutic resistance in ALL.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest
Exploring the discursive concept of Mental Health and Wellbeing within England's Primary Curriculum
No full textThis paper offers a discourse-focused analysis of how mental health and wellbeing are constructed within England's primary education policy. Using mixed methods that combine quantitative content analysis with discursive psychology thematic analysis, it examined statutory National Curriculum frameworks for Key Stages 1-2 and the Early Years Foundation Stage, alongside government guidance documents for primary schools. Quantitative analysis revealed a striking absence of mental health terminology from statutory frameworks, with 'mental health' appearing zero times across the frameworks. However, a thematic discourse analysis of supplementary government guidance identified three main constructions: the medicalisation of mental health, individualisation of responsibility, and the complex connection between physical and mental health. These findings highlight a paradox where mental health is absent from statutory requirements yet extensively addressed through supplementary guidance, creating a "hidden curriculum" that positions schools and educators as surveillance tools for identification and referral rather than as supportive communities. The analysis suggests that seemingly progressive mental health policies may embed problematic discourses that influence children’s and teachers' efficacy in supporting mental health in classrooms
Explainable AI–Based Semantic Retrieval from an Expert-Curated Oncology Knowledge Graph for Clinical Decision Support
No full textThe modern oncology landscape is characterised by a deluge of high-dimensional data from genomic sequencing, medical imaging, and electronic health records, negatively impacting the analytical capacity of clinicians and health practitioners. This field is not new and it has drawn significant attention from the research community. However, one of the main limiting issues is the data itself. Despite the vast amount of available data, most of it lacks scalability, quality and semantic information. This work is motivated by the data platform provided by OncoProAI, an AI-driven clinical decision support platform designed to address this challenge by enabling highly personalised, precision cancer care. The platform is built on a comprehensive knowledge graph, formally modelled as a directed acyclic graph, which has been manually populated, assessed and maintained to provide a unique data ecosystem. This enables targeted and bespoke information extraction and assessment
Epidemiology of Injury in Elite and Amateur Soccer Referees: A Systematic Review and Meta-analysis
No full textBackground
The epidemiology of injury in soccer has traditionally focused on soccer players, rather than match officials. Although injury data on referees exist, no comprehensive review has summarized injury profiles in this population.
Objective
To conduct a systematic review and meta-analysis of injury epidemiology in elite and amateur soccer referees, focusing on injury rates, types, locations, severity, and causes.
Methods
PubMed (Medline), Web of Science, Scopus, CINAHL, and SPORTDiscus, covering their entire history up to 19 April 2025 were searched. This review included prospective and retrospective studies reporting injury incidence or prevalence among football match officials, with a study period of at least one season. Studies needed to specify injury definitions and include data on injury location, type, mechanism, or severity. Both male and female officials were eligible. Systematic reviews, commentaries, and letters were excluded. Study quality and risk of bias were evaluated using the STROBE-SIIS, in addition to the Newcastle–Ottawa Scale and funnel plots. Injury incidence rates were estimated using a random effects Poisson regression, accounting for heterogeneity and moderators. Heterogeneity was assessed with the I2 statistic.
Results
A total of 17 studies were included, encompassing 3621 referees. The most frequent injuries were strains and sprains in the knee and ankle. The overall injury incidence was 2.19 injuries per 1000 h of exposure (95% CI 1.30–3.69). On-field referees experienced an incidence rate of 1.46 injuries per 1000 h of exposure (95% CI 0.76–2.81), while assistant referees had a lower rate of 0.84 per 1 h of exposure (95% CI 0.36–1.97). During matches, the injury incidence was 2.24 per 1000 h of exposure (95% CI 1.38–3.64), compared with 0.67 injuries per 1000 h of exposure during training sessions (95% CI 0.36–1.24). However, despite sensitivity analysis, there were still high levels of heterogeneity across included studies.
Conclusions
Findings noted higher injury incidence during matches compared with training, and on-field referees compared with assistants. The variation in injury profiles highlights the importance of implementing targeted preventive strategies tailored to the unique demands of refereeing. However, there is still a lack of research in this population, especially in female referees
Laser Generated MoS2 Nanomaterials and Its Applications: A Review
No full textThis review study emphasizes the significance of MoS2 nanomaterials, their manufacture, and their applications. This review examined nanomaterials and their generation processes, concentrating on laser ablation and nanomaterial production. This study advances nanomaterial synthesis and helps discover new applications by explaining the fundamental concepts and aspects affecting synthesis. Future studies should optimize laser settings, explore novel precursor materials, and understand laser-induced MoS2 synthesis pathways to enable customized nanomaterial design and engineering
The Role of Artificial Intelligence and Machine Learning in the Assessment, Diagnosis, and Prediction of Cerebral Small Vessel Disease
No full textCerebral small vessel disease (CSVD) contributes substantially to ischemic stroke and vascular cognitive impairment but remains difficult to detect with conventional diagnostics. Recent advances in artificial intelligence (AI), including machine learning (ML) and deep learning (DL), have improved neuroimaging analysis, early risk stratification, and clinical decision support in CSVD-related stroke, while raising questions about generalizability, interpretability, and ethics.
This review aims to narratively synthesize how AI supports neuroimaging analysis, early detection, clinical decision-making, and prognostication in stroke with an emphasis on CSVD, and to summarize limitations, bias, and implementation challenges.
This narrative review synthesized evidence from 122 studies. AI showed strong performance across stroke care with an emphasis on CSVD: intracerebral hemorrhage (ICH) detection on noncontrast CT (sensitivity = 93%, specificity = 92%); 18-25-minute reductions in door-to-needle time; superior prediction of 90-day disability versus clinician assessment (89% vs. 72%); reduced inter-rater variability for white matter hyperintensities (WMHs) segmentation; ~94% accuracy for enlarged perivascular spaces (EPVS) classification on MRI; and faster team notification and time-to-treatment, with mixed evidence for improved 90-day functional independence. However, performance was weaker in older and diabetic cohorts, underscoring limited generalizability, scarce prospective validation, and risks of bias.
AI augments stroke care across imaging-based diagnosis, risk stratification, and rehabilitation, with growing utility in CSVD. Translation into routine care requires robust external validation, bias mitigation, model interpretability, and clear governance around safety, liability, and cost
Bridging the Gap: Towards a theory of peer-support worker integration within early intervention psychosis services
No full textBackground
Peer Support Workers are increasingly recognised as integral components of person-centred care provision within mental health services globally, and their presence within early intervention services is expanding. The benefits that peer support workers provide are well established, but less is known about how to quickly and effectively integrate them within early intervention services to maximise their role.
Aim
This study explored barriers and enablers to effective implementation of peer support worker roles in early intervention services, through multi-stakeholder perceptions and insights involving service users, peer support workers, and clinicians.
Methods
A qualitative, multi-site study within an NHS Foundation Trust in the North-West of England was employed. Semi-structured interviews with 18 participants across the three stakeholder groups were conducted, with Normalisation Process Theory guiding the collection and interpretation of participant data to identify barriers and enablers. Data were analysed thematically using a six-phase, deductive approach.
Results
Four core themes and nine sub-themes emerged from collated participant data, providing context across Normalisation Process Theory constructs. The four core themes related to: Navigating Uncertainty and Discovering Value, Building Engagement through Trust and Relatability, Structural and Relational Conditions Shaping the Functions of PSWs, and Recognising Impact in the Absence of Formal Structures.
Conclusion
Effective integration in this context is underpinned by dynamic, relational factors. A theory of integration and logic model were developed to support policy and implementation efforts. These emphasise the need for comprehensive onboarding and evaluation mechanisms, and consideration of sustainability for these roles
Contextualising Fragments Containing Fresh Perspectives about the Spanish Settlements in Taiwan (1636–1638)
No full textThis article examines extracts relating to the period 1636–1638 in Taiwan, when the Spanish occupied two settlements in northern Taiwan, one of them being abandoned in 1637. These fragments reveal fresh perspectives on Taiwan as a stepping stone between the Philippines, the Ryukyu islands, and mainland China, giving rare first-hand accounts of the perils of journeys to these places from Taiwan’s Spanish settlements in the 1630s. The extracts also reveal fresh aspects to Spanish relationships with Taiwan’s Indigenous people. These descriptions add to arguments that the Indigenous people had a significant influence on the departure of the Spanish from the island. The fragmentary details in these texts give further evidence of the multinational exchange that took place during those years. To analyse these fragments, a thematic analysis places them at the centre of discussions, to explore what they add to existing knowledge about the settlements during those years
A feasibility study to determine whether neuromuscular adaptations to equine water treadmill exercise can be detected using synchronous surface electromyography and kinematic data.
No full textDespite a growing evidence-base on the adaptive movement patterns that horses adopt during water treadmill (WT) exercise, underlying adaptations in muscle activity remain uninvestigated. This feasibility study aimed to develop a method for the synchronous measurement of muscle activity and movement of horses during WT exercise. Combined surface electromyography (sEMG) (2000 Hz) from selected hindlimb (biceps femoris, gluteus medius, tensor fascia latae) and epaxial (longissimus dorsi) muscles and three-
dimensional kinematic (200 Hz) data from the back and pelvis of one (n=1) horse were collected during overground (OG), dry treadmill (TM), and WT walking conditions. Statistical parametric mapping evaluated differences in time- and amplitude-normalized sEMG and thoracolumbar and pelvis kinematic waveforms between conditions. Distinct, significant (p<0.05) adaptations in hindlimb and epaxial muscle activation patterns, as well as axial and pelvic kinematics, were observed in this horse across exercise conditions. Adaptive muscle activity was most pronounced in this horse during WT, compared to OG walking. These findings demonstrate the feasibility this method, which combines sEMG and motion capture technologies to synchronously quantify equine movement and muscle activation patterns during WT exercise. This justifies replication of this work in a larger sample of horses to inform evidence-based training and rehabilitation programmes
