University of Leeds

Psoriatic disease, encompassing psoriasis (PsO) and psoriatic arthritis (PsA), affects approximately 2 % of the global population. In the majority of cases, skin alterations occur first, followed by musculoskeletal disorders. The transition from cutaneous to synovio-entheseal disease reflects a gradual immune-driven progression from localized to systemic manifestations in most cases. Subclinical or non-specific symptoms often precede demonstrable synovitis or enthesitis, which further delays diagnosis and increases the risk of irreversible structural damage. Despite the critical importance of early detection, established risk factors for PsA are largely nonspecific, presenting challenges for precision medicine. Key amongst these is the presence of arthralgia, which usually precedes PsA development but is also common in degenerative and biomechanical problems. Recent advancements, encompassing cutting-edge imaging modalities, hold the potential to facilitate earlier and more precise detection of PsA, while groundbreaking therapeutic innovations are redefining treatment paradigms and may further integrate advanced imaging into personalized therapeutic strategies. This review explores the molecular and clinical complexity of psoriatic disease, highlights the latest developments in imaging and treatment, and considers their potential to revolutionize patient outcomes. Novel strategies promise advances in precision medicine and may pave the way for customized interventions that not only enhance the diagnosis and prognosis of psoriatic disease but also refine therapeutic decision-making. Innovative imaging techniques are essential to distinguishing psoriatic disease-related pain from alternative causes such as osteoarthritis, thereby guiding treatment continuation and optimization.

Mantle circulation in the Earth acts to remove heat from its interior and is thus a critical driver of our planet’s internal and surface evolution. Numerical mantle circulation models (MCMs) driven by plate motion history allow us to model relevant physical and chemical processes and help answer questions related to mantle properties and circulation. Predictions from MCMs can be tested using a variety of observations. Here, we illustrate how the combination of many disparate observations leads to constraints on mantle circulation across space and time. We present this approach by first describing the set-up of the example test MCM, including the parameterization of melting, and the methodology used to obtain elastic Earth models. We subsequently describe different constraints, that either provide information about present-day mantle (e.g. seismic velocity structure and surface deflection) or its temporal evolution (e.g. geomagnetic reversal frequency, geochemical isotope ratios and temperature of upper mantle sampled by lavas). We illustrate the information that each observation provides by applying it to a single MCM. In future work, we shall apply these observational constraints to a large number of MCMs, which will allow us to address questions related to Earth-like mantle circulation.

Spinal cord injury (SCI) results in significant disruption of nerve fibers responsible for transmitting signals between the brain and body, often leading to partial or complete motor, sensory, and autonomic dysfunction below the injury site. Astrocytes are an important component in scar formation, crucial for suppression of injury propagation, effective wound healing, and the regulation of neuronal plasticity. Here, we identify the role of the actin‐binding protein Drebrin (DBN) in reactive astrogliosis following SCI. SCI induces the upregulation of DBN in astrocytes, which controls immediate injury containment but also the long‐term preservation of tissue integrity and healing in the spinal cord. DBN knockout results in enlarged spinal cord lesions, increased immune cell infiltration, and neurodegeneration. Mechanistically, DBN loss disrupts the polarization of scar border‐forming astrocytes, leading to impaired encapsulation of the injury. In summary, DBN serves as a pivotal regulator of SCI outcome by modulating astrocytic polarity, which is essential for establishing a protective barrier confining the lesion site.

Although word lists have generated a great deal of attention from researchers, there has been no comprehensive review of the applications of word lists in second language learning and teaching. This article reviews the development, validation, and applications of 50 word list studies that were published and discussed in major international peer-reviewed Applied Linguistics and TESOL journals from 2013 to 2023. It shows that the methodology of word list development and validation has become more sophisticated and word list developers can see many potential applications of their lists in research and pedagogy. However, most applications of recently developed word lists have been restricted to the BNC/COCA lists developed by Paul Nation, and little is known about the degree to which most word lists have been used in pedagogical contexts. Our review indicates several directions for future research on word lists, including exploring the impact of published lists on pedagogy, replicating word list studies for learners in underrepresented contexts, and developing sustainable, low-cost methods of developing word lists to allow teachers and learners to create lists serving their own needs.

Background and purpose Endovascular treatment of wide-neck bifurcation aneurysms has historically proved difficult with variable outcomes of efficacy and safety. We assessed the short- and long-term clinical and radiologic outcomes in the real-world use of Contour neurovascular system. Materials and methods This study was a retrospective analysis of unruptured intracranial aneurysms treated with the Contour. The primary radiologic outcomes were quantified on DSA, CTA, or MRA using the modified Raymond-Roy criteria. The outcomes were defined as complete occlusion (RROC 1) and adequate occlusion (RROC 1 and RROC 2) at 6 months and 2-years. The primary safety outcome was the rate of device-related adverse events. Secondary safety outcomes included time to discharge and change in the modified Rankin scale (mRS) score at 6-month follow-up. Results 54 patients were treated with Contour from February 2017 to July 2022. 50 aneurysms underwent 6-month follow-up. 28 of 50 aneurysms treated (56%) remained completely occluded at 6-month follow-up (RROC 1), whilst 44 of 50 aneurysms treated (88%) were adequately occluded. 46 aneurysms underwent 2-year follow-up. 28 of 46 aneurysms treated (60.9%) remained completely occluded at 2-year follow-up (RROC 1), whilst 38 of 46 aneurysms (82.6%) were adequately occluded (RROC 1 and RROC2). Immediate postoperative complications occurred in 5 patients; only 1 patient (1.8%) had residual neurologic deficits at 6 months (mRS 1). Conclusions Management of wide-neck aneurysms remains difficult, with high rates of recurrence and complications. The use of the Contour demonstrated a promising and safe addition to the intravascular stock for the treatment of complex wide-neck aneurysms.

Background Over the last two decades, Nepal has experienced substantial urbanization, with an increasing number of people choosing to move to cities. Although cities offer a wealth of opportunities, it also provides significant challenges. Many of those migrating to and living in cities contend with poor conditions and live in poverty. Defining and measuring urban deprivation is challenging due to its multi-dimensional nature, encompassing various dimensions such as housing, employment, living expenses, education, healthcare, and other unique challenges associated with city life. This study draws on the ‘Domains of Urban Deprivation Framework’ and evaluates the availability, commonness, and applicability of these domains. It measures multiple urban deprivation indices relevant to the context of Nepal. Method The research will commence with a review of the availability of data covering the urban domains listed in the Urban Deprivation Framework within routine data collected in Nepal at the province, district, and municipal levels. This will involve examining existing datasets and identifying any gaps or limitations in the data that could impact the construction of the local urban deprivation indices. To understand the commonness of different urban deprivation within different urban contexts in Nepal, a Delphi survey will be conducted in two municipalities and nationally with government policymakers, community representatives, data experts/researchers, and civil society actors. In the three urban contexts, stakeholders will prioritize and weigh the indicators according to their respective urban contexts and rank domains that reflects the priorities across different geographical areas and stakeholder communities. We will compare responses across these groups of stakeholders and explore contextual differences. The composite score for each domain will be calculated by summing the weighted scores of all indices and normalizing the results to ensure that they fall within a defined range. We will then plot the deprivation indices in urban areas at the provincial, district, and municipal levels. The urban deprivation index in Nepal will provide granular data that will enable policymakers and stakeholders to explore the urban deprivation index visually and access key insights for informed decision-making and resource allocation. Ethics and dissemination Ethical approval was obtained from the Ethical Review Board of Nepal Health Research Council (Reference number: 213/2024) and the School of Medicine Research Ethics Committee at the University of Leeds, UK. The findings will be disseminated in a peer-reviewed journal and presented at conferences.

Purpose Nucleus augmentation has been proposed as an early‐stage intervention for intervertebral disc degeneration and involves the injection of a biomaterial into the nucleus to restore disc height and functionality. The aim of this work was to identify clinically relevant quantitative measures that indicate the mechanical performance of the disc following nucleus augmentation. Method Bovine tail bone‐disc‐bone units (n = 22) were mechanically tested under cyclic loading sequentially in native, artificially degenerated, and treated states. Treatment involved injection of a peptide‐glycosaminoglycan mixture into the degenerated disc to a predetermined load using a syringe driver with an integrated force sensor. The stiffness restoration of the treatment was determined by comparing the biomechanical behavior of the native state to the treated state of each disc. The stiffness restoration was then compared against clinically quantifiable parameters. Results No significant biomechanical differences were observed between the native and treated states, but both were significantly different from the degenerated state. The force delivered during injection was found to ramp to a steady state, followed by a final rapid increase; however, all measures associated with injection force poorly correlated with the level of stiffness restoration. Volume injected and change in disc height from injection had the strongest relationship to stiffness restoration. Conclusion This work showed that measuring the injection force for injectable treatments of the disc can provide lower and upper limits for delivery, but direct measures are stronger indicators of disc stiffness restoration.

Objective The SCN9A gene is primarily expressed in nociceptive pathways within the peripheral nervous system, and pathogenic variants are associated with human pain disorders. In recent years, several studies have proposed SCN9A as a monogenic cause of epilepsy. Our objective was to critically appraise the SCN9A–epilepsy gene–disease relationship. Methods We assessed “epilepsy‐associated” SCN9A variants from four sources: (1) the literature up to December 2023 (n = 27), (2) epilepsy patients referred for genetic testing at a regional service in Glasgow, UK over a 5‐year period (n = 30), (3) the Human Genetics Mutation Database (n = 25), and (4) ClinVar (n = 1546). The latter two are genome‐wide variant databases, accepting submissions from genetic laboratories and research groups. We checked whether each SCN9A variant is present in the Genome Aggregation Database (gnomAD) V4 (a reference population database for variant interpretation), and classified its pathogenicity based on the American College of Molecular Genetics and Genomics/Association of Molecular Pathologists guidelines. Results Only three SCN9A variants were classified as “likely pathogenic,” of which two were identified in healthy individuals in gnomAD. A total of 1540 of the 1546 SCN9A variants in ClinVar labeled as being associated with epilepsy were also reported in association with hereditary sensory and autonomic neuropathy. No further clinical data were provided in 1482 of these submissions. Significance There is no convincing genetic evidence to support SCN9A as a causative epilepsy gene. As such, the inclusion of SCN9A in epilepsy genetic testing panels should be reassessed. Research centers and genetic testing laboratories should be rigorous and consistent in their submissions to variant databases.

Background A predisposition to elevated food reward may hinder weight loss success during multidisciplinary interventions. However, this has not been consistently demonstrated in adults, nor at all in children. Objective To test the associations between explicit and implicit food reward and preference at baseline and prospective changes in weight and body composition in adolescents with obesity. Methods A meta‐analysis of 6 clinical trials in adolescents with obesity was undertaken using frequentist and Bayesian linear mixed models. Participants from each study took part in similar 12‐week multidisciplinary interventions. Liking and wanting for foods varying in fat content and sweet taste were assessed at enrolment, and both anthropometrics were tracked from enrolment to post‐intervention. Results In a grand sample of N = 132 adolescents with obesity, liking and wanting for high‐fat foods did not significantly predict changes in weight or fat mass. However, implicit wanting for sweet foods predicted changes in standardised body and lean mass, such that a greater wanting for sweet foods was associated with greater loss of body (p = 0.039, η²p = 0.05) and lean mass (p < 0.001, η²p = 0.13) in both frequentist and Bayesian analyses. Conclusions Baseline implicit wanting for sweet (high carbohydrate, low protein), but not energy‐dense, foods may be more strongly related to prospective changes in lean mass than fat mass during weight loss in adolescents with obesity. Further research is needed to clarify whether low protein intake can account for this effect.

Ferroelectric materials with piezoelectric and pyroelectric properties have shown promise for antimicrobial therapy by generating reactive oxygen species (ROS) under external stimuli. However, the single catalytic approaches relying on either piezoelectric or pyroelectric effect compel ferroelectric materials to yield inadequate ROS, ultimately dampening the sterilization speed and efficiency. To address the daunting issue, a dual catalytic membrane composed of BaTiO3/MgO2 and electrospun poly (lactic‐co‐glycolic acid) nanofibers is devised, which integrates both pyroelectric and piezoelectric effects of BaTiO3 by encapsulating polydopamine. The dual catalytic membrane potentiates polarization charge generation under ultrasound and near‐infrared stimulation. Subsequently, the polarized charge participates in the generation of germicidal ·OH by reacting with H2O2 from MgO2, thus achieving rapid antimicrobial activity. More intriguingly, in vitro and in vivo experiments have demonstrated that the dual catalytic membrane substantially facilitates cell proliferation and promotes the regeneration of infected wounds through bacterial slaughter, NF‐κB inflammatory pathway inhibition, pro‐angiogenesis, as well as collagen deposition. As envisaged, such a proposal provides a bright prospect for ferroelectric materials in addressing acute infections and advancing the remediation of refractory infected wounds.

In hot and arid climates, developing green roofs to improve the microclimate and thermal comfort faces challenges due to water scarcity and harsh climate conditions. To evaluate the effect of green roof types on microclimate parameters and thermal comfort, a simulation was conducted in Yazd, Iran, using the ENVI-met model. Three scenarios—intensive green roofs, extensive green roofs, and roofs without vegetation—were simulated using meteorological data from 7:00 am to 6:00 PM during the hottest period of the year. Desert-adapted plant species were included in two green roof types. The model outputs indicated that, compared to extensive green roofs and roofs without vegetation, intensive green roofs resulted in lower air temperature, mean radiant temperature, and longwave radiation. They also led to higher wind speed and relative humidity, contributing to more desirable thermal comfort. Extensive green roofs and roofs without vegetation generally showed no significant differences in the measured microclimatic parameters or thermal comfort index. As suggested by the findings of this study, intensive green roofs demonstrated superior performance in enhancing thermal comfort compared to extensive green roofs. However, during the hottest period of the year and within the measured hours, all three scenarios were classified as ‘very hot’ (PMV = 5.03) and ‘hot’ (PMV = 3.2), experiencing strong to extreme heat stress, respectively. The measured hours and distance from the roofs affected the microclimatic parameters and thermal comfort, with the intensive green roof showing the most favorable thermal comfort condition (PMV = 0.18) during 7:00–9:00 am, perceived as comfortable with no thermal stress. However, the microclimatic improvements and thermal comfort enhancements resulting from the simulated green roofs in the surrounding environment) were not significant. Considering the outcomes alongside the severe climatic conditions prevalent in the city of Yazd, characterized by high temperatures, intense radiation during the summer, and extreme water scarcity, the proposition for the construction and development of green roofs in this region is not advisable. Although green roofs aim to ameliorate the microclimate and improve thermal comfort during hot periods, their effectiveness under such harsh conditions remains limited.

Can the pretend and fanciful impinge upon reality? Over two studies (of which the second was pre-registered) we examine to what degree there is a ‘cognitive quarantine’ between the real and the imagined. We examine the permeability between real and fictive identities (using the ‘identity fusion’ construct), and establish a novel ‘cognitive porousness’ scale. We outline several theoretically relevant factors, such as emotional intensity, unpleasantness, and enjoyment which we expected to influence permeability. We also examined the Euclidean distance between one's real and one's fictive personality and moral identity. We find one's identity is influenced by the trait permeability of the participant, as well as the moral overlap between the participant and their character. This research demonstrates the tractability of examining adult pretence from a quantitative and cognitive perspective.

The UK and the USA are often said to be ‘two countries separated by a common language'. The salience of this comes into play when one considers that important reforms to union rights in the USA have never actually come into being despite being called the Employee Free Choice Act (EFCA) and the Protecting the Right to Organise (PRO) Act. By contrast, in the so-called ‘Mother of Parliaments' in the UK, a piece of what might become legislation is introduced as a Bill and, when passed through both Houses with majority support and after gaining Royal Assent, only then becomes an Act. Had EFCA and the PRO Act been passed, the situation for unions might not be as terrible as it presently is. But that is not necessarily a reason why the grass is always greener in the UK. The forthcoming Employment Rights Act 2025 covering key collective components on access rights, recognition, collective bargaining, and industrial action is a case of ‘two steps forward, one step back', highlighting the veracity of William Shakespeare's adage from Macbeth that ‘Nothing is but what is not’. It is concluded that both the UK and the USA now need a labour/labor party, which is sincerely social democratic if the fortunes of organised labour are to ever return to the promise they held out in the early post-war period.

As the world rapidly urbanises and cities become larger and more complex, understanding pedestrian dynamics is paramount. New data sources, particularly those that measure pedestrian counts (i.e. ‘footfall’), offer potential as a means of better understanding the fundamental spatio-temporal structures that characterise aggregate pedestrian behaviour. However, footfall data are often complex and influenced by a wide range of social, spatial and temporal factors, which complicates interpretation. This paper applies principal component analysis (PCA) to hourly pedestrian count data from Melbourne, Australia, to extract the key temporal signatures that underpin observed urban footfall patterns. PCA can reduce the dimensionality of noisy pedestrian flow data, revealing dominant activity patterns such as weekday commuting cycles and weekend leisure activities. By subsequently analysing pedestrian volumes through the lens of these components, we start to expose the underlying types of pedestrian activities that characterise different neighbourhoods. In addition, we can distinguish multiple overlapping activity patterns within a single location, identifying changes in urban functionality and detecting shifts in mobility trends. The impacts of external shocks, such as the COVID-19 pandemic, are particularly stark. These findings shed light on the intricacies of urban mobility and suggest that there is value in the use of PCA as a means to better understand urban dynamics.

Background and aims Magnetic actuation of endoscopes is promising—as the endoscope can be pulled from its front. Our team developed a novel Magnetic Flexible Endoscope (MFE) that uses magnetic field sensing, robotic control, and real-time image processing for colonoscopy. We conducted a Phase 1 first-in-human clinical trial to assess platform safety and tolerability. Methods Platform : The MFE contains an internal permanent magnet, camera, illumination module, and channels for instruments, insufflation/camera cleaning, irrigation, and suction. A robotic arm maneuvers a second permanent magnet coupled to the MFE. System software facilitates controlled intelligent-magnetic actuation. Experiment Five patients scheduled for screening colonoscopy (ICD-10 z12.11) were enrolled. Patients underwent standard of care colonoscopy with monitored anesthesia care. Upon withdrawal of the colonoscope, sedation was stopped, and after colonoscope removal, the MFE was inserted into the colon via the anus. The MFE was advanced through the colon while the patient was unsedated. After colon traversal, the MFE was withdrawn. Outcomes of interest included safety and tolerability of the MFE, participant sentiment via structured interview, platform usability, and robot pose data. Results All patients underwent successful standard of care colonoscopy. All patients were awake and alert for MFE colonoscopy; tolerating the exam well without discomfort, pain, or other complaint. There were no adverse events or trauma. The system was robust without software or function failure. Conclusion The MFE successfully traversed the human colon without adverse event or patient discomfort. System performance was successful without unanticipated events. This is the first time safety and tolerability of the novel platform has been demonstrated in vivo. ClinicalTrials.gov (NCT05833789)

Background Breakdown of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in basal ganglia cells through hydrolysis of diesteric bonds, primarily by PDE10A and PDE1B, is essential for normal human movement. While biallelic loss‐of‐function variants in PDE10A are known to cause hyperkinetic movement disorders, the role of PDE1B in human disease has not been characterized. Objectives We aimed to define the phenotypic and molecular characteristics of a novel autosomal recessive disorder caused by biallelic PDE1B variants. Methods Clinical phenotyping by senior geneticists and neurologists, followed by whole exome sequencing, segregation analysis (Sanger sequencing), and molecular studies, including mini‐gene splicing assays and protein studies in transfected HEK293 cells. Results Seven affected individuals from five unrelated pedigrees presented with an apparently autosomal recessive disorder characterized by hypotonia in infancy, progressing to ataxia and dystonia in early childhood, with developmental delay and intellectual disability. Biallelic PDE1B variants were identified in all affected individuals: three truncating (p.Q45*, p.Q86*, p.S298Afs*6) and three splicing variants (c.594 + 2 T>G, c.735 + 5G>A, c.837‐1G>C). Functional studies confirmed that the truncating variants caused loss of the catalytic domain, resulting in truncated or absent functional protein. Splicing variants led to exon skipping, frameshifts, and catalytic domain disruption. These findings establish a causative link between biallelic PDE1B variants and the observed clinical phenotype. Conclusions Biallelic loss‐of‐function variants in PDE1B underlie a novel early‐onset movement disorder resembling the phenotype associated with PDE10A deficiency. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Accurate preoperative segmentation of key anatomical regions on the liver surface is essential for enabling intraoperative navigation and position monitoring. However, current automatic segmentation methods face challenges due to the liver’s drastic shape variations and limited data availability. This study aims to develop a two-stream mesh convolutional network (TSMCN) that integrates both global geometric and local topological information to achieve accurate, automatic segmentation of key anatomical regions. We propose TSMCN, which consists of two parallel streams: the E-stream focuses on extracting topological information from liver mesh edges, while the P-stream captures spatial relationships from coordinate points. These single-perspective features are adaptively fused through a fine-grained aggregation (FGA)-based attention mechanism, generating a robust pooled mesh that preserves task-relevant edges and topological structures. This fusion enhances the model’s understanding of the liver mesh and facilitates discriminative feature extraction on the newly pooled mesh. TSMCN was evaluated on 200 manually annotated 3D liver mesh datasets. It outperformed point-based (PointNet++) and edge feature-based (MeshCNN) methods, achieving superior segmentation results on the liver ridge and falciform ligament. The model significantly reduced the 3D Chamfer distance compared to other methods, with particularly strong performance in falciform ligament segmentation. TSMCN provides an effective approach to liver surface segmentation by integrating complementary geometric features. Its superior performance highlights the potential to enhance AR-guided liver surgery through automatic and precise preoperative segmentation of critical anatomical regions.

Steady-state visual evoked potential (SSVEP)-based brain-computer interfaces (BCIs) can achieve high recognition accuracy with sufficient training data. Transfer learning presents a promising solution to alleviate data requirements for the target subject by leveraging data from source subjects; however, effectively addressing individual variability among both target and source subjects remains a challenge. This paper proposes a novel transfer learning framework, termed instance-based task-related component analysis (iTRCA), which leverages knowledge from source subjects while considering their individual contributions. iTRCA extracts two types of features: (1) the subject-general feature, capturing shared information between source and target subjects in a common latent space, and (2) the subject-specific feature, preserving the unique characteristics of the target subject. To mitigate negative transfer, we further design an enhanced framework, subject selection-based iTRCA (SS-iTRCA), which integrates a similarity-based subject selection strategy to identify appropriate source subjects for transfer based on their task-related components (TRCs). Comparative evaluations on the Benchmark, BETA, and a self-collected dataset demonstrate the effectiveness of the proposed iTRCA and SS-iTRCA frameworks. This study provides a potential solution for developing high-performance SSVEP-based BCIs with reduced target subject data.