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A scalable maximum-likelihood framework for near-real-time monitoring of MERS-CoV evolutionary and zoonotic dynamics
Get PDFUnderstanding the drivers of viral spillover is critical for public health, yet phylodynamic inferences can be sensitive to the analytical methods used. Here, we use a comparative framework of four independent maximum-likelihood methods to analyze 643 MERS-CoV genomes sampled through January 2024. Our results confirm that recurrent, independent zoonotic transmissions from dromedary camels are the primary driver of MERS-CoV emergence, with all spillover events tracing back to Saudi Arabia and the United Arab Emirates. While all methods consistently reconstruct viral circulation within camels on the Arabian Peninsula, they yield significant discrepancies in key epidemiological estimates, with the inferred number of camel-to-human spillover events ranging from 15 to 34 events depending on the tool used. The utility of our framework is its ability to quantify this methodological uncertainty, providing a more robust assessment of zoonotic risk than any single maximum-likelihood tool could alone. Therefore, we propose a two-tiered surveillance strategy that combines rapid real-time tracking to identify new clusters with periodic, in-depth validation using a multi-method consensus approach to guide long-term public health interventions at key human-animal interfaces
SOX2 confers tumour permissiveness in a specific skin progenitor population
Get PDFThe continuous renewal of the skin relies on stem and progenitor cells, yet their differential susceptibility to oncogenic mutations in cutaneous squamous cell carcinoma (cSCC) remains unclear. Rapid cSCC develops in melanoma patients on BRAF inhibitors due to paradoxical MAPK activation. To model this in mice, we use two complementary approaches: HRASG12V with a BRAF inhibitor to mimic paradoxical MAPK activation, and BRAFV600E, which drives MAPK hyperactivation without further treatment. We target these mutations to the interfollicular stem and differentiation-committed progenitors of the basal epidermis. While stem cells rapidly form tumours, progenitors exhibit long-latency resistance despite retaining mutations and repopulating the basal layer. Ultimately, both populations produce similar tumours, showing a shared transformation process. However, SOX2 is uniquely upregulated in progenitor-derived tumours and is expressed in 20% of human cSCC, indicating it might mark tumours arising from committed progenitors. Here, we show that SOX2 overexpression, along with MAPK activation, in progenitors induces a stem-like state and renders this otherwise resistant population permissive to rapid transformation
Rapid terrestrial weathering of the CI1 carbonaceous chondrite find Oued Chebeika 002
Get PDFAlteration of historic CI1 meteorite falls during their curation demonstrates the susceptibility of smectite-rich carbonaceous chondrites to terrestrial exposure. The discovery of Oued Chebeika 002 in Morocco in June 2024 presents a unique opportunity to document the earliest stages of weathering of a CI1 find. We studied 10–30 mg fragments that had been recovered by September 2024. Grains of quartz and feldspar were implanted into the fragments by wind action whilst on the desert floor. Gypsum is the main product of terrestrial weathering. It encrusts their outer surfaces, in one case covering 5.3% of a fragment, and has filled voids within both fractures and phyllosilicate clasts. Other products of terrestrial weathering are Ca-carbonate grains that have grown within a sand-filled fracture, and rock inhabiting fungi colonizing the surface of a fragment. Chemical weathering was facilitated by water that had been adsorbed by smectite from the humid desert air, and crystallization of gypsum was driven by evaporation from the surfaces of those fragments that were exposed to direct sunlight. The gypsum and Ca-carbonate grew over a period of 3 or 4 months, approximately between June and September 2024, whereas the time scale of fungal colonization can only be constrained to a year or less. The rapid interaction of Oued Chebeika 002 with the Earth's atmosphere, lithosphere, and biosphere underscores the importance of prompt recovery and careful curation of CI1 and other smectite-rich meteorites
MultiNFT: A Multimodal Dataset for Non-Fungible Tokens Market Analysis
No full textNon-fungible tokens (NFTs) are unique digital assets
that play an increasingly important role in decentralized markets,
supporting new forms of ownership, valuation, and exchange.
Their inherently multimodal structure, which encompasses visual
content, metadata, and trading history, has led to a growing
academic interest in modeling NFT pricing and market behavior.
However, existing research is limited by the lack of comprehensive
datasets that unify these modalities with consistent formatting
and longitudinal coverage. To address this gap, we introduce
MultiNFT, a large-scale multimodal dataset comprising 50 curated profile picture (PFP) NFT collections, including 523,020
unique assets and 2.38 million transaction records from April
2021 to September 2025. MultiNFT integrates standardized
images, structured metadata, and time-series trading data, along
with rarity scores and aesthetic features, offering a unified
foundation for multimodal learning and NFT analytics. Unlike
prior datasets that focus on visual similarity or static snapshots, MultiNFT captures evolving valuation dynamics across
market cycles and connects them to trait-level characteristics.
We demonstrate the utility of the dataset through three case
studies, including within-collection rarity-price analysis, visual
feature clustering across collections, and quantifying feature
contributions in a comprehensive pricing model. By bridging
computer vision, behavioral modeling, and financial forecasting,
MultiNFT supports a wide range of interdisciplinary research
and practical use cases. The dataset is publicly available and is
intended to promote reproducible experimentation and further
exploration of the mechanisms driving value in digital asset
ecosystems
The relationship between Connexin 43 (Cx43) and partner protein, human Discs large homologue-1 (Dlg1) during wound closure in keratinocytes
No full textPlasma membrane gap junctions, formed by connexin proteins, are responsible for direct intercellular communication between adjacent cells by allowing the exchange of ions, metabolites, secondary messengers and microRNAs. Connexin 43 (Cx43) is a widely expressed gap junction protein. Cx43 mis-expression is associated with various disease states, including chronic non-healing wounds. Loss of Cx43 from the plasma membrane is important to allow wound resolution. Cx43 expression increases, and gap junctions reform, upon wound closure. Cx43 directly interacts with Dlg1, a membrane-associated guanylate kinase (MAGUK) protein, which controls cell shape and polarity. In this study, AlphaFold3 modelling predicted an interaction between amino acids 263–269 and 302–320 of Cx43 and the SH3, HOOK and GUK domains of Dlg1. Since Dlg1 is required for maintaining Cx43 protein levels at the plasma membrane, we hypothesised that Dlg1 may regulate wound healing via its functional interaction with Cx43. Cx43 and Dlg1 relocated to the cytoplasm of cells at the wound edge in scrape wound assays and co-located in pseudopodia of cells migrating towards the wound edge in live cell imaging experiments. Scratch wound assays carried out in HaCaT cells treated with siRNA targeting Dlg1 showed that Dlg1 depletion resulted in reduced wound closure rates. This was not due to changes in cell migration, suggesting that Dlg1 controlled cell proliferation. The data demonstrate that Cx43 and Dlg1 both contribute to wound closure, but that Dlg1 has other crucial functions in migrating cells separate from its role in maintaining Cx43 at the plasma membrane
A transformer-based survival model for prediction of all-cause mortality in patients with heart failure: a multi-cohort study
Get PDFHeart failure (HF) patients have complex health profiles that existing risk models fail to capture. We developed TRisk, a Transformer-based artificial intelligence survival model for predicting mortality using routine electronic health records (EHR) in HF patients. Using UK data from 403,534 HF patients across 1,418 English general practices, we trained and validated TRisk and compared against MAGGIC-EHR, the MAGGIC model adapted for use on routine EHR by substituting variables (e.g., left-ventricular ejection fraction) that are not routinely available. External validation was conducted on 21,767 patients from USA hospitals. In the UK cohort, TRisk achieved concordance index (C-index): 0.845 (95% CI: 0.841, 0.849), outperforming MAGGIC-EHR (C-index: 0.728 [0.723, 0.733]) for 36-month mortality prediction. In subgroup analyses, TRisk demonstrated less variability in predictive performance by sex, age, and baseline characteristics compared to MAGGIC-EHR, suggesting less biased modelling. Evaluating TRisk in USA data via transfer learning yielded C-index of 0.802 (0.789, 0.816). Explainability analysis revealed TRisk captured established risk factors while identifying underappreciated ones, particularly cancers and hepatic failure, with cancers maintaining prognostic utility even a decade before baseline. TRisk provides more accurate, well-calibrated mortality prediction using routine data across international healthcare settings, demonstrating potential for improved risk stratification in patients with HF
A 3D frame element for large rotations based on the rigid-body–spring concept for analysing the failure of structures
No full textEfficient modelling of the failure process of frame structures is a challenging research topic because of the complex interaction of geometrical and material nonlinearities. Here, a 3D rigid-body–spring based frame element which has previously been shown to be energy equivalent to a continuum based reduced integration element is extended to the case of large rotations. The new model is applied successfully to classical benchmarks for buckling, bending and torsion under large rotations reported in the literature. For the new model, plastic curvature jumps localise within one element, which makes the approach suitable to model plastic hinges with a coarse mesh. The performance of the approach for failure analysis of structures involving the interplay of geometrical and material nonlinearities is further demonstrated by modelling a three-dimensional steel frame
Flipped learning in the mathematical sciences: insights, inconsistencies and gaps in the meta-analyses
Get PDFThe traditional lecture-based model of teaching in the mathematical sciences has been increasingly challenged by the adoption of flipped learning, a pedagogical approach where students engage with instructional content independently before class and participate in interactive, problem-solving activities during class sessions. By considering published meta-analyses, this paper reviews the current state of flipped learning in tertiary mathematical education focusing on its effects on student achievement, perceptions and engagement. While the literature generally supports the benefits of flipped learning, including improved performance and satisfaction, these outcomes can be inconsistent due to the varied implementation methods and diverse student cohorts. The paper concludes with recommendations for implementing flipped learning at tertiary level in the mathematical sciences along with opportunities for future research
Mechanical de-skewing enables high-resolution imaging of thin tissue slices with a mesoSPIM light-sheet microscope
Get PDFOptical clearing combined with light-sheet microscopy enables high-resolution imaging of extended tissue at scale. However, standard mesoSPIM systems are optimised for intact organs and are not suited to thin tissue slices. We present an oblique compensation scanning method using obliquely mounted samples held between refractive-index-matched slides in a 3D-printed frame. This enables mechanical de-skewing during acquisition, minimising post-processing requirements. We demonstrate feasibility in fluorescent bead phantoms and rabbit heart tissue, achieving a 4.8 × reduction in processing time and a 1.5 × improvement in axial resolution ((13.15±1.36) μm to (8.72±1.80) μm) compared to conventional z scan. The oblique compensation acquisition method extends mesoSPIM’s utility to fragile, laterally extended tissue sections
Defining the proteome of sexually committed parasites in Plasmodium falciparum
Get PDFMalaria transmission from humans to mosquitoes is essential to the parasite life cycle. In the human malaria parasite, Plasmodium falciparum, the rate of commitment to produce the sexual transmission stages, or gametocytes varies and is governed by genetic, epigenetic and environmental factors. The sexually committed parasite has so far remained elusive due to the lack of markers to efficiently isolate these parasites for subsequent functional studies including proteomic analysis of the isolated population. Here, we demonstrate that MSRP1 is a highly specific sexual commitment marker. Using this marker, we generated and validated reporter parasite lines for subsequent FACS-based isolation of sexually and asexually committed parasites. Proteomics of isolated parasites defined distinct protein signatures, including several merozoite surface proteins, indicating functional differences between the two parasite populations. This study provides a blueprint for systematic characterisation of the parasite stage at this crucial juncture in the life cycle
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