Search Results (1,731)

The use of vein grafts in coronary artery bypass graft surgery is complicated by a high late restenosis rate resulting from the development of intimal hyperplasia. The role of changes in haemodynamics on TGFβ-driven endothelial-to-mesenchymal transition (EndMT) is not fully understood. We identified that arterial shear stress can induce TGFβ/SMAD-dependent EndMT in human umbilical vein endothelial cells (HUVECs), which was regulated by TWIST transcription factors (TWIST1&2), as the selective inhibition of TWIST1 or TWIST2 using siRNA-suppressed EndMT. We noted that brief pretreatment of HUVECs with Dexamethasone can modulate EndMT in response to shear stress. Using spatial cell sequencing in human long saphenous vein segments exposed to acute arterial flow, we identified a cluster of cells with both endothelial and smooth muscle-cell (SMC)-like phenotypes, in which TWIST2 was significantly upregulated. We validated the untargeted spatial findings in segments of veins under acute arterial flow ex vivo. We observed that Dexamethasone can suppress EndMT changes in vein segments by suppressing TGFβ/SMAD/TWIST1&2. This suggests that Dexamethasone brief pretreatment can suppress EndMT changes triggered by acute exposure of long saphenous vein segments to arterial haemodynamics by modulating the TGFβ/SMAD/TWIST1&2 pathway. Full article

Herein we report the very first experiments which were conducted in an attempt to demonstrate the ability of low-field (LF), compact benchtop NMR spectrometers to provide spectral profiles of whole human biofluids, which took place in September–November 2014, and this paper represents a 10-year (decennial) anniversary of this work. LF ¹H NMR analysis was performed on ²H₂O-reconstituted lyophilizates of urine samples (pH 7.00) collected from untreated Niemann-Pick type C1 (NPC1) disease patients and their heterozygous carrier controls (n = 3 in each case). ¹H NMR spectra were acquired on a 60 MHz Oxford Instruments Pulsar compact benchtop spectrometer with spectral filter widths of 5000 Hz, using 1000–1600 scans, and relaxation delays of 15 or 30 s. Further, 400 MHz spectra were also obtained on these samples. Following parameter optimisation, the benchtop system generated reasonable quality urinary ¹H NMR profiles containing ca. 30 signals. Benchtop ¹H NMR analysis confirmed the abnormal urinary metabolic signature of NPC1 disease, and also revealed a gastric permeability disorder in one patient (detection of upregulated urinary sucrose, verified by 400 MHz NMR analysis). Early LF NMR experiments also demonstrated that glucose was trackable in control urine samples pre-spiked with this metabolite. This paper continues with further developments made on LF NMR-based metabolomics technologies, which are systematically discussed for related investigations conducted since 2014. In conclusion, such ‘first-time’ bioanalytical information regarding spectral quality served to pave the way forward for benchtop NMR-based metabolomics investigations of biofluids, which could provide invaluable disease-engendered ‘snapshots’ of disturbances to metabolic pathways and activities, along with those of any co-linked or unlinked comorbidities. Full article

Anthropologists increasingly engage with healthcare systems, using ethnographic research as a critical tool for understanding and improving healthcare practices. The resulting interactions and collaborations between ethnographers, healthcare practitioners, and administrators often give rise to ‘frictions’—moments of tension, frustrations, misalignments, and misunderstandings. In physics, friction is the force that one object’s surface exerts over another’s to slow its motion, push back against its inherent energy and movement, and is a constant at all touchpoints between the objects, from both sides. While friction often evokes negative connotations, in this article, we look beyond frictions as obstacles, and instead explore them as productive forces that can drive transformation in the healthcare improvement field. Drawing both on the authors’ own experiences and on the work of other anthropologists, we reflect on how friction helps shed light on the dynamics of interdisciplinary work and improve collaboration. We unpack how conceptual and ethical frictions in applied ethnographic work reveal deeper structural and relational insights that would otherwise remain obscured. This article contributes to anthropological discussions on interdisciplinary collaboration and applied practice, and it offers concrete strategies for handling different kinds of friction in health-related ethnographic research. Full article

Objective: Patient information materials are sensitive and, if poorly written, can cause misunderstanding. This study evaluated and compared the readability, actionability, and quality of patient education materials on laryngology topics generated by ChatGPT, Google Gemini, and ENT UK. Methods: We obtained patient information from ENT UK and generated equivalent content with ChatGPT-4-turbo and Google Gemini 2.5 Pro for six laryngology conditions. We assessed readability (Flesch–Kincaid Grade Level, FKGL; Flesch Reading Ease, FRE), quality (DISCERN), and patient engagement (PEMAT-P for understandability and actionability). Statistical comparisons involved using ANOVA, Tukey’s HSD, and Kruskal–Wallis tests. Results: ENT UK showed the highest readability (FRE: 64.6 ± 8.4) and lowest grade level (FKGL: 7.4 ± 1.5), significantly better than that of ChatGPT (FRE: 38.8 ± 10.5, FKGL: 11.0 ± 1.5) and Gemini (FRE: 38.3 ± 8.5, FKGL: 11.9 ± 1.2) (all p < 0.001). DISCERN scores did not differ significantly (ENT UK: 21.3 ± 7.5, GPT: 24.7 ± 9.1, Gemini: 29.5 ± 4.6; p > 0.05). PEMAT-P understandability results were similar (ENT UK: 72.7 ± 8.3%, GPT: 79.1 ± 5.8%, Gemini: 78.5 ± 13.1%), except for lower GPT scores on vocal cord paralysis (p < 0.05). Actionability was also comparable (ENT UK: 46.7 ± 16.3%, GPT: 41.1 ± 24.0%, Gemini: 36.7 ± 19.7%). Conclusion: GPT and Gemini produce patient information of comparable quality and engagement to ENT UK but require higher reading levels and fall short of recommended literacy standards. Full article

We propose a new strategy for constructing Runge–Kutta (RK) methods using evolutionary computation techniques, with the goal of directly minimising global error rather than relying on traditional local properties. This approach is general and applicable to a wide range of differential equations. To highlight its effectiveness, we apply it to two benchmark problems with oscillatory behaviour: the (2+1)-dimensional nonlinear Schrödinger equation and the N-Body problem (the latter over a long interval), which are central in quantum physics and astronomy, respectively. The method optimises four free coefficients of a sixth-order, eight-stage parametric RK scheme using a novel objective function that compares global error against a benchmark method over a range of step lengths. It overcomes challenges such as local minima in the free coefficient search space and the absence of derivative information of the objective function. Notably, the optimisation relaxes standard RK node bounds ($c_i\in [0,1]$), leading to improved local stability, lower truncation error, and superior global accuracy. The results also reveal structural patterns in coefficient values when targeting high eccentricity and non-sinusoidal problems, offering insight for future RK method design. Full article

The phosphoinositide 3-kinase (PI3K)/AKT signaling pathway is a crucial regulator of cellular metabolism, proliferation, and survival. It is frequently dysregulated in metabolic, cardiovascular, and neoplastic disorders. Despite the advancements in multi-omics technology, existing methods often fail to provide real-time, pathway-specific insights for precision medicine and drug repurposing. We offer Agentic RAG-Driven Multi-Omics Analysis (ARMOA), an autonomous, hypothesis-driven system that integrates retrieval-augmented generation (RAG), large language models (LLMs), and agentic AI to thoroughly analyze genomic, transcriptomic, proteomic, and metabolomic data. Through the use of graph neural networks (GNNs) to model complex interactions within the PI3K/AKT pathway, ARMOA enables the discovery of novel biomarkers, probable candidates for drug repurposing, and customized therapy responses to address the complexities of PI3K/AKT dysregulation in disease states. ARMOA dynamically gathers and synthesizes knowledge from multiple sources, including KEGG, TCGA, and DrugBank, to guarantee context-aware insights. Through adaptive reasoning, it gradually enhances predictions, achieving 91% accuracy in external testing and 92% accuracy in cross-validation. Case studies in breast cancer and type 2 diabetes demonstrate that ARMOA can identify synergistic drug combinations with high clinical relevance and predict therapeutic outcomes specific to each patient. The framework’s interpretability and scalability are greatly enhanced by its use of multi-omics data fusion and real-time hypothesis creation. ARMOA provides a cutting-edge example for precision medicine by integrating multi-omics data, clinical judgment, and AI agents. Its ability to provide valuable insights on its own makes it a powerful tool for advancing biomedical research and treatment development. Full article

Background: Colon capsule endoscopy (CCE) has seen increased adoption since the COVID-19 pandemic, offering a non-invasive alternative for lower gastrointestinal investigations. However, inadequate bowel preparation remains a key limitation, often leading to higher conversion rates to colonoscopy. Manual assessment of bowel cleanliness is inherently subjective and marked by high interobserver variability. Recent advances in artificial intelligence (AI) have enabled automated cleansing scores that not only standardise assessment and reduce variability but also align with the emerging semi-automated AI reading workflow, which highlights only clinically significant frames. As full video review becomes less routine, reliable, and consistent, cleansing evaluation is essential, positioning bowel preparation AI as a critical enabler of diagnostic accuracy and scalable CCE deployment. Objective: This CESCAIL sub-study aimed to (1) evaluate interobserver agreement in CCE bowel cleansing assessment using two established scoring systems, and (2) determine the impact of AI-assisted scoring, specifically a TransUNet-based segmentation model with a custom Patch Loss function, on both interobserver and intraobserver agreement compared to manual assessment. Methods: As part of the CESCAIL study, twenty-five CCE videos were randomly selected from 673 participants. Nine readers with varying CCE experience scored bowel cleanliness using the Leighton–Rex and CC-CLEAR scales. After a minimum 8-week washout, the same readers reassessed the videos using AI-assisted CC-CLEAR scores. Interobserver variability was evaluated using bootstrapped intraclass correlation coefficients (ICC) and Fleiss’ Kappa; intraobserver variability was assessed with weighted Cohen’s Kappa, paired t-tests, and Two One-Sided Tests (TOSTs). Results: Leighton–Rex showed poor to fair agreement (Fleiss = 0.14; ICC = 0.55), while CC-CLEAR demonstrated fair to excellent agreement (Fleiss = 0.27; ICC = 0.90). AI-assisted CC-CLEAR achieved only moderate agreement overall (Fleiss = 0.27; ICC = 0.69), with weaker performance among less experienced readers (Fleiss = 0.15; ICC = 0.56). Intraobserver agreement was excellent (ICC > 0.75) for experienced readers but variable in others (ICC 0.03–0.80). AI-assisted scores were significantly lower than manual reads by 1.46 points (p < 0.001), potentially increasing conversion to colonoscopy. Conclusions: AI-assisted scoring did not improve interobserver agreement and may even reduce consistency amongst less experienced readers. The maintained agreement observed in experienced readers highlights its current value in experienced hands only. Further refinement, including spatial analysis integration, is needed for robust overall AI implementation in CCE. Full article

While increasingly popular for their aesthetic appeal and energy efficiency, reflective materials may also create harsh glare, disorientation, and psychological strain. Despite their prevalence in modern architectural design, the impact of these facades on mental well-being remains underexplored. Drawing from environmental psychology and perceptual science, this study assesses how different reflective materials influence both visual perception and psychological response, particularly among residents and students in Leicester. Two contrasting case studies, the reflective metal Highcross centre facade and the reflective glass Mattioli Woods PLC facade, served as focal points. Using a structured online questionnaire incorporating visual stimuli and Likert-scale questions, responses from 30 participants were analysed using descriptive and statistical analysis (i.e., one-way ANOVA) to determine differences in visual discomfort (due to brightness, glare, or shine), visual attractiveness, visual disorientation, and perception of the surroundings, as well as the associated physiological responses such as stress, tension, and mood. Results show that the Highcross Centre facade was consistently perceived as more visually discomforting and disorienting than the Mattioli Woods facade, with statistically significant differences. However, both facades were rated similarly high for visual interest, suggesting that aesthetic value can coexist with discomfort. Finally, the analysis shows that buildings’ reflective facades evoke only low levels of perceived stress, tension, or unease, with median scores remaining low overall. These findings highlight the importance of human-centred facade design, suggesting that, as cities adapt to climate change, architects and urban planners consider not only environmental performance but also perceptual and psychological effects. Full article

Urbanization, characterized by population growth and socioeconomic development, is a major driving factor of land use land cover (LULC) change. A spatio-temporal understanding of land cover change is crucial, as it provides essential insights into the pattern of urban development. This study conducted a longitudinal analysis of LULC change in order to evaluate the tradeoffs of urban growth and sustainability challenges in the Himalayan region. Landsat time-series satellite imagery from 1988 to 2024 were analyzed for two major cities in Nepal—Kathmandu metropolitan city (KMC) and Pokhara metropolitan city (PMC). The LULC classification was conducted using a machine learning support vector machine (SVM) approach. For this study period, our analysis showed that KMC and PMC witnessed urban growth of over 400% and 250%, respectively. In the next step, LULC change and urban expansion patterns were predicted based on the urban development indicator using the Cellular Automata Markov chain (CA-Markov) model for the years 2040 and 2056. Based on the CA-Markov chain analysis, the projected expansion areas of the urban area for the two future years are 282.39 km² and 337.37 km² for Kathmandu, and 93.17 km² and 114.15 km² for PMC, respectively. The model was verified using several Kappa variables (K-location, K-standard, and K-no). Based on the LULC trends, the majority of urban expansion in both the study areas has occurred at the expense of prime farmlands, which raises grave concern over the sustainability of the food supply to feed an ever-increasing urban population. This haphazard urban sprawl poses a significant challenge for future planning and highlights the urgent need for effective strategies to ensure sustainable urban growth, especially in restoring local food supply to alleviate over-reliance on long-distance transport of agro-produce in high-altitude mountain regions. The alternative planning of sustainable urban growth could involve adequate consideration for urban farming and community gardening as an integral part of the urban fabric, both at the household and city infrastructure levels. Full article

Preterm labour (PTL) affects about 11% of all deliveries world-wide. It is a major cause of perinatal morbidity and mortality. Although the precise cause is unknown in about 50% of cases, infections are thought to be a major contributing factor. These infections are more common in earlier preterm deliveries. While some women with these infections will manifest the classical features of fever, tachycardia (maternal and/or fetal), leucocytosis, raised biomarkers of infections, and uterine tenderness/irritation, others will be asymptomatic. Some of the women may develop a short/dilating cervix without any obvious contractions. Identifying such women is potentially challenging. Evidence has shown that a condensation of echogenic particles just above the cervix—amniotic fluid (AF) sludge, identified by ultrasound—is a marker for microbial invasion of the amniotic cavity (MIAC) and preterm birth (PTB) in both asymptomatic and symptomatic women (including those with a short or normal cervix). Those with a short cervix with AF sludge have a significantly greater risk of progression to PTB. Treatment with antibiotics has been shown in some but not all case series to result in a resolution of the sludge and either a delay or prevention of PTB. The widely varied results from treatment could be related to the antibiotics used and the route of administration. The use of the parenteral combination of clindamycin, a cephalosporin, and metronidazole has been shown to be more effective compared to azithromycin. Here we review the literature on the relationship between the sludge and PTB and conclude (1) that the AF sludge is an ultrasound marker of MIAC and PTL and (2) that following its diagnosis, appropriate counselling should be offered and the triple antibiotic combination offered. We suggest that randomised trials should be undertaken to determine the most efficacious antibiotic combination. Full article

Small and Medium Enterprises (SMEs) are vital to economic growth, innovation, and job creation across Sub-Saharan Africa (SSA). Women entrepreneurs are key contributors to this sector, yet they face persistent barriers to accessing finance, which constrain their business growth and broader economic participation. This study investigates the role of financial institutions in closing the financing gap for women-owned SMEs and assesses the effectiveness of various financing mechanisms, including traditional banking, micro-finance, fintech innovations, and government-backed credit schemes. Adopting a quantitative approach, this study utilises structured surveys with women SME owners across multiple SSA countries. Supplementary secondary data from sources such as the World Bank and national financial statistics provide additional context. Econometric modelling and Structural Equation Modelling (SEM) are employed to identify key factors influencing loan accessibility, such as collateral requirements, interest rates, financial literacy, and the regulatory environment. Findings reveal that high collateral demands and interest rates remain major obstacles, particularly for smaller or informal women-led enterprises. Financial literacy emerges as a critical enabler of access to credit. While fintech solutions and digital lending platforms show promise in improving access, issues around infrastructure, regulation, and trust persist. Government-backed schemes also contribute positively but are hindered by implementation inefficiencies. This study offers practical recommendations, including the need for harmonised regional credit reporting systems, gender-responsive policy frameworks, and targeted financial education. Strengthening digital infrastructure and regulatory support across SSA is essential to build inclusive, sustainable financial ecosystems that empower women entrepreneurs and drive regional development. Full article

The menstrual cycle affects the autonomic nervous system (ANS), cognition, and emotional valence in all biological women. There exists a complex relationship between hormonal fluctuations, ANS, cognition, and emotional valence during the different phases of the menstrual cycle, which includes menstruation, the follicular phase, ovulation, and the luteal phase. Hence, this narrative review is an attempt to comprehensively understand the effects of the menstrual cycle on the structural and functional integrity of the ANS. In order to provide a comprehensive understanding of the complex relationship between the menstrual cycle, hormonal fluctuations, and ANS function in biological women, this review examines key parameters, including heart rate variability (HRV), baroreflex sensitivity (BRS), muscle sympathetic nerve activity (MSNA), and pupillary light reflex (PLR), to investigate how these physiological systems are dynamically influenced by the cyclical changes in hormone levels and how these fluctuations impact various physiological and psychological outcomes, such as mood, cognition, and emotional regulation. There have been several studies previously performed to assess these parameters during different phases of the menstrual cycle. However, the results have been contradictory; therefore, this review explores possible reasons behind these inconsistent results, with likely reasons including irregularity in the menstrual cycles and differences in hormonal fluctuations between different women during similar phases of the menstrual cycle. Overall, there appears to be evidence to suggest that the menstrual cycle has both direct and indirect effects on ANS, cognition, and emotional valence, whilst measures of ANS may provide a means for assessing the effect of the menstrual cycle. Full article

Background/Objectives: Interstitial lung disease (ILD) is a frequent complication of rheumatoid arthritis (RA), representing the most common extra-articular manifestation (with a prevalence of about 10–60%) and the second cause of mortality. Spondyloarthritides (SpAs) are chronic arthritides that share with RA both a similar disease burden and similar therapeutical approaches. The evaluation of ILD is challenging, given the low sensitivity of X-ray and pulmonary function tests, and the radiation exposure linked to repetitive HRCT. Lung ultrasound (LUS) has shown potential in the evaluation of ILD in autoimmune diseases. The purpose of this study is to assess the prevalence of ILD in a cohort of SpA patients (pts) using LUS in comparison with healthy subjects (HSs). The secondary aim is to evaluate potential correlations between ILD and clinical features within the SpA cohort using LUS. Methods: Consecutive SpA out-patients were examined by LUS, applying the definition for pleural line irregularity (PLI) recently provided by the OMERACT taskforce for LUS in systemic sclerosis. Seventy-one intercostal spaces were studied (14 in the anterior chest, 27 lateral and 30 posterior) in all the pts/HS using an Esaote MyLab25 Gold US machine with a linear 7.5–10 MHz probe. A total pleural score was calculated. Each patient answered to Italian-validated PROs on respiratory function (Leicester and Saint-George), global health (SF-36) and dyspnea (mMRC scale). Clinical data on disease duration, disease onset, disease activity (at the moment of the examination) and methotrexate (MTX) or biologics treatment were collected from the medical records. Results: Seventy-three SpA pts (46 psoriatic arthritis -PsA- and 27 ankylosing spondylitis -AS-) and 56 HS were studied. No significant differences were demonstrated between groups (SpA vs. HS and PsA vs. AS) for age, sex, BMI and smoking habits. The total PLI score was significantly higher in SpA pts than in HS (p < 0.001). A positive correlation was found between the total PLI score and the PLI score from anterior, posterior and lateral chest. The posterior region of the chest showed a higher PLI score than the anterior and lateral regions. No statistically significant differences were found between PsA and AS. MTX use was not a risk factor for PLI (no differences were found between SpA MTX+ and SpA MTX- patients). PROs (Leicester, Saint-George and SF-36) were not related to the PLI total score. A significant correlation was found only between the SF36 score and the presence of PLI in the anterior chest. PROs were instead correlated with each other, showing a good concordance for absence/presence of symptoms. Disease activity, disease duration and age at disease-onset were not related to PLI total score. Smoking habit was found to be predictive of a significantly higher PLI score both in SpA patients and HSs. Conclusions: LUS examination shows a higher amount of PLI in SpA patients with respect to HSs. Smoking habit was the only clinical feature correlated to PLI on LUS examination in our population. Full article

Lord Byron’s life and poetic works have inspired musical compositions across genres even during his lifetime. The English author’s fictional characters and themes impressed nineteenth-century European composers, especially since his Byronic heroes were often conflated with their creators’ own melancholy and revolutionary personas. In contrast to Byron-inspired songs and operas, instrumental programme music has raised doubts towards a direct correlation with its poetic sources. While epigraphs help direct listeners to specific ideas, their absence has prompted dismissals of intermedial relationships, even those proposed by the composers themselves. This essay explores major connections between Hector Berlioz’s Harold in Italy, a Symphony in Four Parts with Viola Obbligato (premiered 1834), and Byron’s semi-autobiographical narrative poem Childe Harold’s Pilgrimage: A Romaunt (published 1812–1818). Although Berlioz’s titles and memoirs partially identify Byron’s Childe Harold as his inspiration, other references, including his visits to the Abruzzi mountains, his fascination with Italian folk music, his reuse of earlier material, and his reflections on brigands and solitude, have fuelled ongoing debates about the work’s programmatic content. Combining historical-biographical research, melopoetics, and musical semiotics, this essay clarifies how indefinite elements were transmitted from poetic source to musical target. Particular focus is placed on the “Harold theme”, which functions as a Byronic microcosm: a structural, thematic, and gestural condensation of Byron’s poem into music. Observing the interactions between microcosmic motifs and macrocosmic forms in Berlioz’s symphony and their poetic analogues, this study offers a new reading of how Byron’s legacy is encoded in musical terms. Full article

Green buildings are recognised for their potential to reduce energy consumption, minimise environmental impact, and improve occupants’ well-being, benefits that are especially critical in rapidly urbanising regions. However, questions remain about whether these buildings fully meet occupant comfort expectations while delivering energy efficiency. This is particularly relevant in Africa, where climate conditions and energy infrastructure challenges make sustainable building operation essential. Although interest in sustainable construction has increased, limited research has examined the real-world performance of green buildings in Africa. This study helps address that gap by evaluating indoor thermal comfort in a green-certified office building and two conventional office buildings in Abuja, Nigeria, through post-occupancy evaluation (POE). The Predicted Mean Vote (PMV) and Thermal Sensation Vote (TSV) were used to assess comfort, revealing discrepancies between predicted and actual occupant responses. In the green building, PMV indicated near-neutral conditions (0.28), yet occupants reported a slightly cool sensation (TSV: −1.1). Neutral temperature analysis showed that the TSV-based neutral temperature (26.5 °C) was 2.2 °C higher than the operative temperature (24.3 °C), suggesting overcooling. These findings highlight the importance of incorporating occupant feedback into HVAC control. Aligning cooling setpoints with comfort preferences could improve satisfaction and reduce unnecessary cooling, promoting energy-efficient building operation. Full article