University of Liverpool

Integrin-mediated cell–matrix adhesions regulate communication between cells and the extracellular matrix. In matrix-secreting cells, fibrillar adhesions (FBs) containing high levels of α5β1 integrins and the tensin3 adaptor protein are essential for fibronectin (FN) fibrillogenesis. Here, we demonstrate that tensin3 binds to four helical regions (R3, R4, R8, and R11) of talin, the principal integrin activator. Structural analysis revealed the residues critical for the tensin3–talin interaction, and mutational analysis showed that talin R8 and R11 are essential for FB formation and FN fibrillogenesis. Cellular experiments demonstrate that tensin3 binding to talin not only regulates integrin activation, but also modulates tensin3’s propensity to undergo liquid–liquid phase separation (LLPS). Formation of such LLPS condensates increased when cells were plated on soft substrates compared with stiff ones. This effect was abolished by blocking the interaction between tensin3 and talin. Our data suggest a model in which LLPS condensates provide a signaling platform involved in cellular responses to sudden changes in tissue mechanics.

IM30, the inner membrane‐associated protein of 30 kDa (also known as Vipp1) is essential for thylakoid membrane biogenesis and/or maintenance in chloroplasts and cyanobacteria. IM30 and its bacterial homolog PspA belong to the ESCRT‐III superfamily, proteins previously thought to be restricted to eukaryotes and archaea. Despite low sequence similarity, IM30 shares key structural and functional features with eukaryotic ESCRT‐IIIs, including a conserved α1–α2 helical hairpin core and the ability to form oligomeric barrel or rod assemblies that mediate membrane remodeling. Using IM30 variants, we now show that membrane binding of IM30 is driven by electrostatic interactions between the positively charged α1–α3 helical hairpin and negatively charged lipid surfaces, paralleling the role of charged helical regions in some eukaryotic ESCRT‐IIIs. This likely is followed by lateral assembly of IM30 into higher‐order barrel or rod structures on the membrane. Once assembled, α0 helices within these oligomers engage and stabilize internalized membrane tubules, mirroring membrane interaction strategies of eukaryotic ESCRT‐IIIs, which use both N‐terminal sequence motifs and charged residues on α1/α2. Thus, our findings demonstrate a conserved membrane binding and remodeling mechanism across the ESCRT‐III superfamily, underscoring an evolutionary link in membrane dynamics between pro‐ and eukaryotes.

Introduction Established (Ki-67, H3K27Me3) protein biomarkers correlate to clinically aggressive meningioma and can be quickly and easily assessed by immunohistochemistry (IHC). Novel (S100B, SCGN, ACADL, MCM2) markers have also been proposed. The aim of this study was to determine if IHC-based biomarker expression is correlated with volumetric growth rates in recurrent intracranial meningioma following primary resection. Methods This was a single-centre retrospective cohort study of adults (≥ 18 years) with surgical resection of recurrent meningioma. Serial tumour volumes were calculated on serial MRI using the ellipsoid formula. Growth rates were calculated and adjusted for time since resection. IHC was performed on paired samples from first and second resections for six markers. Associations between marker expression and tumour growth trajectories were tested using Kruskal–Wallis and linear mixed-effects models. Results Thirty-one patients were included (mean age 53.1 years, 71% female). No significant cohort differences were found in IHC expression between primary and recurrent samples (all McNemar P > 0.1). Tumours were positive for ≥ 2 novel markers in 17.2% of primary and 34.5% of recurrent samples. Neither established (Ki-67, H3K27Me3) nor novel markers predicted absolute or relative growth rates (all Kruskal–Wallis P > 0.2). Linear mixed-effects models confirmed no association between marker expression and longitudinal tumour volume trajectories (all P ≥ 0.1). Conclusion IHC expression of established or novel markers did not correlate with meningioma volumetric growth. IHC-based stratification is limited by overlapping expression patterns and inconsistent categorisation and is not recommended for routine clinical practice.

Wireless pressure insoles are emerging as portable, unobtrusive tools for gait analysis in both clinical and real-world settings. These systems incorporate pressure sensors and often inertial measurement units (IMUs), allowing for the collection of spatiotemporal, kinetic, and foot-level kinematic data. Although widely adopted, the measurement properties of wireless pressure insoles—specifically their concurrent validity and test–retest reliability—have not been systematically evaluated. This protocol outlines the methods for a systematic review and meta-analysis that will synthesise the current evidence on the psychometric properties of wireless pressure insoles during walking in healthy adults. This protocol follows the PRISMA-P 2015 guidelines and is registered in the Open Science Framework. We will include peer-reviewed journal articles that assess either the concurrent validity (i.e., simultaneous collection with a gold-standard comparator) or test–retest reliability (e.g., between-day, within-day, or between-rater reproducibility) of wireless pressure insoles during level walking in healthy adults (≥18 years). Outcomes of interest include spatiotemporal, kinematic and kinetic parameters. A comprehensive literature search will be conducted across MEDLINE, CINAHL, Scopus, Web of Science, SPORTDiscus, IEEE Xplore. Screening will be performed independently by two reviewers. Data extraction will follow a pre-piloted template and study quality will be assessed by two independent reviewers using a modified version of the Critical Appraisal of Study Design for Psychometric Articles. Where appropriate, meta-analyses will be conducted using random-effects models, with effect sizes (r, ICC) pooled and heterogeneity assessed via I². This review will provide a comprehensive synthesis of the concurrent validity and test–retest reliability of wireless pressure insoles in healthy adults, offering valuable insights for researchers, clinicians, and technology developers. While methodological heterogeneity may affect the scope of synthesis, the findings will help guide future research and clinical applications.

Background Hospice inpatient care is often considered gold standard, yet only supports a minority (Department of Health. End of life care strategy: promoting high quality care for all adults at the end of life. 2008). For example, in 2019, 84.7% of deaths in hospices in England and Wales were from cancer, while 15.3% were non-cancer (Tobin, Rogers, Winterburn, et al. BMJ Support Palliat Care. 2022;12(2):142–51). There is a lack of research into this, not least due to a ‘paucity of evidence around the factors that influence access to palliative care’ (Antonacci, Barrie, Baxter, et al. J Aging Res. 2020;2020:3921245). Aim To better understand access to UK inpatient hospice care, focussing on the reported barriers to admission. To understand who might be marginalised from care, what is considered a good death, and potential suggestions for overcoming health inequity. Methods A mixed method approach combining online survey, and interviews. Participants were recruited from three groups: providers of hospice inpatient care, referrers into that care, and the public. Surveys were analysed using univariate statistics, while interviews were interrogated reflexively, using thematic analysis. Results 132 people completed the survey. 63% of providers, 46% of the public, and 89% of referrers said access to hospice inpatient care is not equitable within the UK. 32 people were interviewed. 86% of providers, 83% of the public, and 100% of referrers believed that access is not equitable. Barriers include lack of knowledge, geography and infrastructure, referral and admission processes, recruitment and retention of clinical staff, and finance. Suggestions to overcome barriers include education, public relations, and improving statutory commissioning. The findings from the small survey also suggest who is, and is not, likely to be admitted to inpatient hospice care in the UK. Conclusion This research will help towards an understanding of who is unable to access care, why, and what can be done to overcome this. Recommendations based on these findings could contribute to the national agenda to overcome health inequities, and to the future development of hospice care.

In this study, we examined how a critical posttranscriptional regulator, the RNA‐binding protein HuR (gene name Elavl1), contributes to the development and maintenance of limb skeletal tissue. Using the Prx1‐Cre knockout model, we examined the effect of germline knockout (Elavl1KO) and limb mesenchyme‐specific knockout (MSC‐Elavl1KO) of HuR on limb development. We found that Elavl1KO disrupted the development of the limb skeleton and was associated with a loss of signaling from the apical ectodermal ridge (AER). In contrast, MSC‐Elavl1KO did not appear to affect skeletal development. Mature MSC‐Elavl1KO mice appeared healthy, but their limb skeleton exhibited abnormal bone structure in both males and females at 2.5 months of age. Osteoblasts isolated from MSC‐Elavl1KO mice exhibited lower expression of osteoblastic marker genes, and their ability to generate a mineralized matrix was markedly impaired. RNA‐Seq analysis of these osteoblasts demonstrated that loss of HuR substantially influenced their transcriptome, affecting genes associated with a wide range of cellular processes. Finally, using siRNA knockdown in the human MG63 cell line, we identified that loss of HuR leads to increased mRNA turnover of the osteoblastic transcription factor Runx2. Overall, the study has demonstrated a critical role for HuR‐mediated posttranscriptional control in skeletal development and homeostasis, but finds that its expression in mesenchyme‐derived cells only becomes critical in mature skeletal tissue.

Molecular engineering of 2D transition‐metal dichalcogenides (TMDs) is an effective strategy for tuning their electronic properties, enhancing metal‐semiconductor contacts, and modulating charge carrier dynamics. However, scalable molecular engineering for fabricating wafer‐scale 2D TMDs field‐effect transistors (FETs) has been scarcely reported. Here, improved electrical performance in monolayer (1L)‐MoS2 FETs via allylamine polymer encapsulation, achieved by a plasma‐induced molecule polymerization (PIMP) process with a low power of 5 W, is reported. Electrical measurement results confirm a weak n‐doping effect in 1L‐MoS2, with which the doping concentrations could be adjusted from 1.12 × 10¹² to 5.17 × 10¹² cm⁻². A high‐resolution transmission electron microscopy (HRTEM) image reveals an ultra‐thin and dense allylamine polymer layer with a thickness of 3.7 nm, uniformly coated on the surface of the 1L‐MoS2 under the PIMP process for 20 s. The conformal polymerized layer not only reduces the hysteresis loops of the 1L‐MoS2 FETs but also enhances environmental stability while preserving the transistor characteristics for ≈9 months. Additionally, 1L‐MoS2 FET arrays with over 5000 devices on a large scale, revealing high uniformity and reproducibility using the PIMP process, which offers a practical and scalable strategy for wafer‐scale optimization of 2D FETs, are demonstrated.

Vaso-occlusive crises (VOCs) are a hallmark of sickle cell disease (SCD). Individuals with SCD often report stigma and negative healthcare provider (HCP) attitudes when seeking treatment. This study examines health equity concerns and perceived barriers to care among adults with recurrent VOCs. A prospective survey was conducted from May to November 2022 in the US, UK, France, Germany, and Italy. Adults (≥ 18 years) with recurrent VOCs completed a health equity survey and patient-reported outcome measures (PROMs) at month 6. Participants were categorized as experiencing either unfair or fair treatment based on their response to whether they reported ever having been treated unfairly by an HCP due to their race or ethnicity. PROMs were scored, and analyses included Pearson’s Chi-squared test and two-sample t-tests. Among 110 participants, most were female (75.5%), Black/African American (93.5%), and US residents (59.1%). In the past year, 66.7% had ≥ 4 VOCs, and 85.3% used opioids. Most (68.6%) believed they would receive better care if they were of a different race/ethnicity, and 64.7% felt HCPs did not believe their symptoms. About 30% waited > 60 min for emergency department check-in, with additional delays before treatment. Key barriers included reported HCP lack of empathy (58.9%) and SCD knowledge (55.9%). Pain significantly impacted daily activities, with all outcomes worse in the Unfair treatment group. Findings highlight significant health equity concerns and barriers to care for adults with SCD and recurrent VOCs, underscoring unmet needs and the humanistic burden in this population.

Knowledge about environmental change and the evolutionary history of hominins in Arabia has been rapidly developing over the last two decades. Interdisciplinary research on humans and environments across the vast and heterogenous landmass of the Arabian Peninsula remains, however, highly spatially uneven. Here we present the results of archaeological, hydro-geological, and palaeontological research in inland northeastern Arabia, a poorly studied area with diverse landscape features including caves, palaeorivers, and chert outcrops. Hominin use of the landscape appears to be sparse in comparison to other regions of Arabia, though archaeological evidence spanning from the Lower Palaeolithic to the historic era was identified, including finds from the Middle Palaeolithic, which is the most well represented period. The caves of inland northeast Arabia contain a rich record of past climate change in the form of speleothems, as well as abundant faunal assemblages. Our survey results highlight the significant potential of these records to cast light on environmental, faunal, and cultural changes over time while demonstrating regional variation across Arabia.

Importance Incidental meningiomas are common. There is a need for a validated clinical tool to stratify patients into early intervention, serial monitoring, or safe discharge from outpatient care. Objective To externally validate the Incidental Meningioma: Prognostic Analysis Using Patient Comorbidity and Magnetic Resonance Imaging Tests (IMPACT) tool. Design, Setting, and Participants This retrospective cohort study included 33 centers in 15 countries. Adult patients diagnosed with an incidental meningioma from January 2009 to December 2010 were included, up to the point of intervention, death, or last clinical encounter. Patients with radiation-induced meningioma and NF2-related schwannomatosis were excluded. Data collection was completed on December 31, 2023. Statistical analysis was conducted between March 2024 and December 2024. Main Outcomes and Measures The primary outcome of the study was a composite end point comprising growth, symptom development, meningioma-related mortality, and end points related to loss of window of curability. Secondary end points included the occurrence of an intervention and nonmeningioma-related mortality. Results Overall, 1248 patients were included. The median (IQR) age was 66 (55-77) years and 999 were female individuals (80%). There were 945 patients (75.7%) who had 1010 treatment-naive meningiomas. During follow-up (median [IQR], 61 [17-108] months), 114 tumors (11.3%) in 113 patients (12%) progressed, 132 tumors (13.1%) in 126 patients (13.3%) underwent an intervention, and 383 patients (40.5%) died without progression or intervention, from a nonmeningioma-related cause. The 5- and 10-year progression-free survival rates were 88.1% (95% CI, 85.8%-90.5%) and 85.7% (95% CI, 83.2%-88.2%), respectively. A low-risk meningioma had a disease progression risk of 3.9%, compared with 24.2% in medium-risk meningioma, and 51.6% in high-risk meningioma (χ ² test, P < .001). Measures of external validity were adequate (Brier score = 0.12; C-statistic = 0.80; 10-year area under the curve, 0.83) and the addition of other variables in a Cox regression analysis did not confound the statistical significance of the IMPACT tool. Patients with an age-adjusted Charlson Comorbidity Index score of 6 or higher (eg, a patient aged 80 years with type 2 diabetes and a previous myocardial infarction) and a performance status of 2 to 4 (unable to carry out any work activities or in a chair/bed for 50% or more of the day) were more likely to die of other causes than to receive intervention following diagnosis. Conclusions and Relevance This cohort study found that the IMPACT tool accurately predicted the risk of incidental meningioma progression and can be used to stratify patients into early intervention, serial monitoring, or safe discharge from outpatient care.

Geopolitical risk (GPR) is a critical volatility driver in agricultural futures markets. This paper innovatively integrates the cross-quantilogram approach and TVP-VAR-BK model to construct a two-dimensional framework of “extreme shock - systematic transmission” and use daily data from January 2001 to July 2024 for analysis. Results demonstrate asymmetric responses: grains show immediate sensitivity driven by financialization, while energy-intensive commodities exhibit lagged cost-transmission effects. Core crops (corn, wheat) function as systemic risk transmitters, contrasting with vulnerable receivers. Risk spillovers concentrate predominantly in ultra-short horizons, with crises triggering connectedness surges where GPR transitions to a net receiver. Findings advocate hierarchical mitigation strategies through differentiated reserves and international coordination mechanisms.

Much of the research into white-nose disease has focused on the hibernation period, while the pathogenic fungus Pseudogymnoascus destructans is actively infecting the bat host. Previous research has found large differences between the susceptible North American Myotis lucifugus and the tolerant European Myotis myotis, suggestive of immunopathology in the former, and a beneficial lack of strong response in the latter. Here we examine gene expression in these species during both the late-hibernation period, and a month after emergence from hibernation, during healing from infection. We utilised paired sampling, collecting wing tissue that was positive and negative for fungal infection fluorescence, to examine changes in whole-transcriptome gene expression that were local to sites of infection at two timepoints: pre-emergence and 30 days post-emergence from hibernation. Positive samples were contrasted between the two timepoints to examine longitudinal changes. During the pre-emergence period, local inflammatory responses are observed in both M. myotis and M. lucifugus. Immune responses between the tolerant and susceptible species are dissimilar, favouring Th1 and Th17 cytokine responses respectively. This lends weight to immunopathology as a contributing factor to mortality in M. lucifugus. Continual immune responses may not only contribute to immunopathology and host mortality, but may also have important carry-over effects on reproduction and subsequent pre-winter fattening, affecting population viability over a longer period of time than previously considered.

Objective This service evaluation aimed to determine the prevalence of anxiety and depression and the severity of anxiety and depression symptoms experienced in irritable bowel syndrome (IBS) patients crossing the primary-secondary care interface. It also aimed to assess how routinely collected symptom scores for anxiety and depression influence clinician recognition and response in the IBS clinic. Method A retrospective review of online medical records was conducted for new patients referred to a specialist IBS clinic at a large National Health Service Teaching Hospital over 12 months. Baseline clinicodemographic data, IBS subtype and pre-existing diagnoses of anxiety and/or depression were extracted. All patients completed Generalised Anxiety Disorder-7 (GAD-7), which measures anxiety symptoms, and Patient Health Questionnaire-9 (PHQ-9), which measures depression symptoms, forms prior to clinic review. Severity scores were compared using non-parametric statistical tests (p<0.05) Results A total of 103 patients were included. Overall, 63.1% had a diagnosis of anxiety and/or depression, and most reported moderate-to-severe anxiety and depression symptoms when crossing the primary-secondary care interface. Patients with pre-existing mental health diagnoses had significantly higher GAD-7 and PHQ-9 scores (p<0.01 and p<0.001, respectively) than those without; however, there were no significant differences in symptom burden between groups (anxiety, depression or mixed disorder) on GAD-7 or PHQ-9. Elevated preclinic GAD-7 and PHQ-9 scores were acknowledged in over 80% of consultations and frequently resulted in mental-health-specific management recommendations. Conclusion Introducing preclinic screening enhances the visibility of anxiety and depression symptoms as patients cross the primary-secondary care interface, providing early insight into symptom severity.

Background and Objectives Proper stroke and bleeding risk assessment is an essential part of clinical decision‐making in patients with atrial fibrillation (AF). This study aims to determine whether the dynamic assessment of CHA 2 DS 2 ‐VASc and HAS‐BLED scores over time enhances stroke and bleeding risk prediction. Methods In this prospective longitudinal study—based on data from the Iranian Atrial Fibrillation Registry (IRAF)—patients with available CHA₂DS₂‐VASc and HAS‐BLED scores at baseline, first follow‐up (after 6 months), and second follow‐up (after 12 months) were included. Univariable and multivariable logistic regression analyses were performed to evaluate the association of CHA₂DS₂‐VASc and HAS‐BLED scores (i.e., scores at baseline, first follow‐up, and their difference defined as delta) with stroke and bleeding risk, respectively. Results A total of 529 patients (mean age 61.2 ± 14.3 years; 59.7% male) were included. CHA₂DS₂‐VASc and HAS‐BLED scores increased significantly after 6 and 12 months from recruitment. delta CHA₂DS₂‐VASc score (AUC 0.69; 95% CI: 0.54–0.84) and First follow‐up CHA₂DS₂‐VASc score (AUC 0.70; 95% CI: 0.51–0.88) achieved higher AUCs compared to baseline CHA₂DS₂‐VASc score (AUC 0.63; 95% CI: 0.44–0.82). delta HAS‐BLED score had the highest AUC (AUC 0.73; 95% CI: 0.55–0.91) compared to baseline (AUC 0.58; 95% CI: 0.43–0.74) and first follow‐up HAS‐BLED (AUC 0.60; 95% CI: 0.44–0.80) scores. Conclusions Regular reassessment of CHA₂DS₂‐VASc and HAS‐BLED scores is essential in AF patients, as stroke and bleeding risks change over time, emphasizing the need for dynamic risk stratification.

Background The integration of artificial intelligence (AI), virtual reality (VR) and haptic technologies is revolutionising dental education, offering transformative opportunities to enhance skill acquisition, ergonomic awareness and student well‐being. These tools offer immersive, repeatable and personalised learning experiences, addressing challenges such as underdeveloped manual dexterity in digitally literate students and post‐COVID disruptions in hands‐on training. Aim This letter aims to highlight the transformative potential of AI‐driven adaptive feedback paired with VR and haptic simulators in creating risk‐free environments for mastering complex procedures, while advocating for strategies to reduce clinical errors and promote sustainability by minimising reliance on physical resources. Discussion Despite their potential, barriers such as high costs, resistance to change, logistical complexities and insufficient longitudinal evidence hinder widespread adoption. These challenges perpetuate educational disparities, particularly in low‐resource regions, and necessitate targeted strategies such as cost‐effective models, faculty retraining and international collaboration. The rise of digitally native educators and global initiatives, such as the Digital, VR‐Haptic Thinkers network, signals a shift toward future‐ready curricula that prioritise equity, sustainability and innovation. As mandated by the EU's 2024 directive, digital dentistry knowledge is now a fundamental component of basic dental training. Conclusion To fully harness these technologies, stakeholders must address evidence gaps, validate cognitive benefits and align curricula with modern learner expectations. This letter calls for urgent collaboration among educators, institutions and industry to overcome barriers, ensuring dental education evolves to meet 21st‐century demands for equitable, high‐quality oral healthcare delivery.

Aim The leopard (Panthera pardus) is a generalist species inhabiting Africa and Asia, reflecting dispersal from an ancestral African range. When dispersal events occur, they can entail ecological differentiation and local adaptation. This study compares the bioclimatic niches of African and Asian leopard subspecies, to investigate whether they retained their ancestral ecology during dispersal from Africa, or adapted to novel conditions and shifted niche. Location Africa and Eurasia. Methods We assembled a database of leopard presences from public resources and associated them with bioclimatic variables to identify which are relevant in predicting the species' distribution. We constructed a species distribution model and compared distributions predicted from models based on presences from all subspecies, versus models built only using African leopard records. Finally, we used multivariate analysis to visualise the niche occupied by each subspecies in climate space, and calculated overlaps to assess ecological differentiation. Results The species distribution model trained only on African occurrences predicted most of the Asian range, but not the extension into more extreme environments such as the colder areas inhabited by several Northern Asian subspecies, and seasonal and rugged areas inhabited by Persian leopards. Niche overlaps suggest that Asian subspecies mostly retained their ancestral niche, but in some cases started to use climatic conditions that are not found in Africa. The Persian leopard is the only subspecies for which this expansion represents most of its current niche. Main Conclusions Despite some expansion into high altitude, seasonal environments in Northern Asian populations, the results suggest generally limited adaptation to novel climates after dispersal from Africa and little ecological differentiation among Asian leopard populations. This finding complements recent genetic studies that suggest limited genetic differentiation among Asian leopards. Resolving the relationships between taxonomy and biological differentiation is important due to its relevance for the conservation of the species.