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Abstract SETANTA (Study of HEarT DiseAse and ImmuNiTy After COVID-19 in Ireland) study aimed to investigate symptom burden and incidence of cardiac abnormalities after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/COVID-19 and to correlate these results with biomarkers of immunological response and coagulation. SETANTA was a prospective, single-arm observational cross-sectional study condcuted in a primary practice setting, and prospectively registered with ClinicalTrials.gov (identifier: NCT04823182). Patients with recent COVID-19 infection (≥ 6 weeks and ≤ 12 months) were prospectively enrolled. Primary outcomes of interest were markers of cardiac injury detected by cardiac magnetic resonance imaging (CMR), which included left ventricular ejection fraction, late gadolinium enhancement and pericardial abnormalities, as well as relevant biomarkers testing immunological response and coagulopathy. 100 patients (n = 129 approached) were included, amongst which 64% were female. Mean age of the total cohort was 45.2 years. The median (interquartile range) time interval between COVID-19 infection and enrolment was 189 [125, 246] days. 83% of participants had at least one persistent symptom, while 96% had positive serology for prior SARS-CoV-2 infection. Late gadolinium enhancement, pericardial effusion, was present in 2.2% and 8.3% respectively, while left ventricular ejection fraction was below the normal reference limit in 17.4% of patients. Von Willebrand factor antigen was elevated in 32.7% of patients and Fibrinogen and D-Dimer levels were found to be elevated in 10.2% and 11.1% of patients, respectively. In a cohort of primary practice patients recently recovered from SARS-CoV-2 infection, prevalence of persistent symptoms and markers of abnormal coagulation were high, despite a lower frequency of abnormalities on CMR compared with prior reports of patients assessed in a hospital setting. Trial Registration: Clinicaltrials.gov, NCT04823182 (prospectively registered on 30th March 2021).

Abstract Candida parapsilosis is an opportunistic fungal pathogen commonly isolated from the environment and associated with nosocomial infection outbreaks worldwide. We describe here the construction of a large collection of gene disruptions, greatly increasing the molecular tools available for probing gene function in C. parapsilosis. We use these to identify transcription factors associated with multiple metabolic pathways, and in particular to dissect the network regulating the assimilation of sulphur. We find that, unlike in other yeasts and filamentous fungi, the transcription factor Met4 is not the main regulator of methionine synthesis. In C. parapsilosis, assimilation of inorganic sulphur (sulphate) and synthesis of cysteine and methionine is regulated by Met28, a paralog of Met4, whereas Met4 regulates expression of a wide array of transporters and enzymes involved in the assimilation of organosulfur compounds. Analysis of transcription factor binding sites suggests that Met4 is recruited by the DNA-binding protein Met32, and Met28 is recruited by Cbf1. Despite having different target genes, Met4 and Met28 have partial functional overlap, possibly because Met4 can contribute to assimilation of inorganic sulphur in the absence of Met28.

Abstract Biodegradability testing in soil helps to identify safe synthetic organic chemicals but is still obscured by the formation of soil-bound ‘non-extractable’ residues (NERs). Present-day methodologies using radiocarbon or stable (13C, 15N) isotope labeling cannot easily differentiate soil-bound parent chemicals or transformation products (xenoNERs) from harmless soil-bound biomolecules of microbial degraders (bioNERs). Hypothesizing a minimal retention of hydrogen in biomolecules, we here apply stable hydrogen isotope – deuterium (D) – labeling to unravel the origin of NERs. Soil biodegradation tests with D- and 13C-labeled 2,4-D, glyphosate and sulfamethoxazole reveal consistently lower proportions of applied D than 13C in total NERs and in amino acids, a quantitative biomarker for bioNERs. Soil-bound D thus mostly represents xenoNERs and not bioNERs, enabling an efficient quantification of xenoNERs by just measuring the total bound D. D or tritium (T) labeling could thus improve the value of biodegradability testing results for diverse organic chemicals forming soil-bound residues.

Abstract Iron is an essential mineral that supports numerous biological functions. Studies have reported associations between iron dysregulation and certain cardiovascular and neurodegenerative diseases, but the direction of influence is not clear. Our goal was to use computational approaches to better understand the role of genetically predicted iron levels on disease risk. We meta-analyzed genome-wide association study summary statistics for serum iron levels from two cohorts and two previous meta-analyses. We then obtained summary statistics from 11 neurodegenerative, cerebrovascular, cardiovascular or lipid traits to assess global and regional genetic correlation between iron levels and these traits. We used two-sample Mendelian randomization (MR) to estimate causal effects. Sex-stratified analyses were also carried out to identify effects potentially differing by sex. Overall, we identified three significant global correlations between iron levels and (i) coronary heart disease, (ii) triglycerides, and (iii) high-density lipoprotein (HDL) cholesterol levels. A total of 194 genomic regions had significant (after correction for multiple testing) local correlations between iron levels and the 11 tested traits. MR analysis revealed two potential causal relationships, between genetically predicted iron levels and (i) total cholesterol or (ii) non-HDL cholesterol. Sex-stratified analyses suggested a potential protective effect of iron levels on Parkinson’s disease risk in females, but not in males. Our results will contribute to a better understanding of the genetic basis underlying iron in cardiovascular and neurological health in aging, and to the eventual identification of new preventive interventions or therapeutic avenues for diseases which affect women and men worldwide.

Abstract Climate change is causing ocean warming (OW) and increasing the frequency, intensity, and duration of extreme weather events, including Marine Heat Waves (MHWs). Both OW and MHWs pose a significant threat to marine ecosystems and marine organisms, including oysters, oyster reefs and farmed oysters. We investigated the survival and growth of juveniles of two commercial species of oyster, the Sydney rock oyster, Saccostrea glomerata, and the Pacific oyster, Crassostrea gigas, to elevated seawater temperatures reflecting a moderate and an extreme MHW in context with recent MHWs and beyond. The survival and size of Pacific oysters to moderate MHWs (22–32 °C; 14 days) was greater than that for Sydney rock oysters (24–32 °C; 15 days). While survival and growth of both species was significantly impacted by extreme MHWs (29–38 °C; 5–6 days), Sydney rock oysters were found to survive greater temperatures compared to the Pacific oyster. Overall, this study found that Pacific oyster juveniles were more tolerant of a moderate MHW, while Sydney rock oyster juveniles were more resilient to extreme MHWs. These differences in thermal tolerance may have consequences for aquaculture and coexistence of both species in their intertidal and latitudinal distributions along the south-eastern Australian coastline.

Abstract HPV-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC) are recognized as distinct entities. There remains uncertainty surrounding the causal effects of smoking and alcohol on the development of these two cancer types. Here we perform multivariable Mendelian randomization (MR) to evaluate the causal effects of smoking and alcohol on the risk of HPV-positive and HPV-negative HNSCC in 3431 cases and 3469 controls. Lifetime smoking exposure, as measured by the Comprehensive Smoking Index (CSI), is associated with increased risk of both HPV-negative HNSCC (OR = 3.03, 95%CI:1.75-5.24, P = 7.00E-05) and HPV-positive HNSCC (OR = 2.73, 95%CI:1.39-5.36, P = 0.003). Drinks Per Week is also linked with increased risk of both HPV-negative HNSCC (OR = 7.72, 95%CI:3.63-16.4, P = 1.00E-07) and HPV-positive HNSCC (OR = 2.66, 95%CI:1.06-6.68, P = 0.038). Smoking and alcohol independently increase the risk of both HPV-positive and HPV-negative HNSCC. These findings have important implications for understanding the modifying risk factors between HNSCC subtypes.

Abstract Until recent events, the Antarctic was the only major geographical region in which high pathogenicity avian influenza virus (HPAIV) had never previously been detected. Here we report on the detection of clade 2.3.4.4b H5N1 HPAIV in the Antarctic and sub-Antarctic regions of South Georgia and the Falkland Islands, respectively. We initially detected H5N1 HPAIV in samples collected from brown skuas at Bird Island, South Georgia on 8th October 2023. Since this detection, mortalities were observed in several avian and mammalian species at multiple sites across South Georgia. Subsequent testing confirmed H5N1 HPAIV across several sampling locations in multiple avian species and two seal species. Simultaneously, we also confirmed H5N1 HPAIV in southern fulmar and black-browed albatross in the Falkland Islands. Genetic assessment of the virus indicates spread from South America, likely through movement of migratory birds. Critically, genetic assessment of sequences from mammalian species demonstrates no increased risk to human populations above that observed in other instances of mammalian infections globally. Here we describe the detection, species impact and genetic composition of the virus and propose both introductory routes and potential long-term impact on avian and mammalian species across the Antarctic region. We also speculate on the threat to specific populations following recent reports in the area.

Abstract Dust samples were collected from Irish homes. House Dust Mite and storage mites were separated from the dust. The microbiome and resistome of mites and originating dust were assessed using a culture-independent approach. The bacterial microbiome of mites and dust were predominantly populated by Staphylococci. There was a highly significant (P = 0.005; Spearman’s rank test) correlation between the bacterial microbiome of mites and the dust. One-hundred and eighteen antimicrobial resistance genes (ARGs) were associated with mites and 176 with dust. Both contained ARGs encoding resistance for multi drug resistances, macrolide-lincosamide-streptogramin B, mobile genetic elements, Beta-lactam, Tetracycline and Aminoglycosides. By contrast, 15 ARGs were found for a laboratory-grown strain of Dermatophagoides pteronyssinus. A significant difference (P = 0.03; t test) was found in means between the resistome of mites and the household dust from which they emanated. No significant correlations (P = 0.23 and P = 0.22; Mantel test) were observed between the microbiome and resistome of mite and dust samples. There was not a significant difference (P = 0.54; t-test) between the means of ARGs for homes with and without a history of antibiotic use.

Abstract Accurate detection and quantification of mRNA isoforms from nanopore long-read sequencing remains challenged by technical noise, particularly in single cells. To address this, we introduce Isosceles, a computational toolkit that outperforms other methods in isoform detection sensitivity and quantification accuracy across single-cell, pseudo-bulk and bulk resolution levels, as demonstrated using synthetic and biologically-derived datasets. Here we show Isosceles improves the fidelity of single-cell transcriptome quantification at the isoform-level, and enables flexible downstream analysis. As a case study, we apply Isosceles, uncovering coordinated splicing within and between neuronal differentiation lineages. Isosceles is suitable to be applied in diverse biological systems, facilitating studies of cellular heterogeneity across biomedical research applications.

Abstract Single-cell RNA sequencing predominantly employs short-read sequencing to characterize cell types, states and dynamics; however, it is inadequate for comprehensive characterization of RNA isoforms. Long-read sequencing technologies enable single-cell RNA isoform detection but are hampered by lower throughput and unintended sequencing of artifacts. Here we develop Single-cell Targeted Isoform Long-Read Sequencing (scTaILoR-seq), a hybridization capture method which targets over a thousand genes of interest, improving the median number of on-target transcripts per cell by 29-fold. We use scTaILoR-seq to identify and quantify RNA isoforms from ovarian cancer cell lines and primary tumors, yielding 10,796 single-cell transcriptomes. Using long-read variant calling we reveal associations of expressed single nucleotide variants (SNVs) with alternative transcript structures. Phasing of SNVs across transcripts enables the measurement of allelic imbalance within distinct cell populations. Overall, scTaILoR-seq is a long-read targeted RNA sequencing method and analytical framework for exploring transcriptional variation at single-cell resolution.

Abstract We report the first cryoEM structure of the Hendra henipavirus nucleoprotein in complex with RNA, at 3.5 Å resolution, derived from single particle analysis of a double homotetradecameric RNA-bound N protein ring assembly exhibiting D14 symmetry. The structure of the HeV N protein adopts the common bi-lobed paramyxoviral N protein fold; the N-terminal and C-terminal globular domains are bisected by an RNA binding cleft containing six RNA nucleotides and are flanked by the N-terminal and C-terminal arms, respectively. In common with other paramyxoviral nucleocapsids, the lateral interface between adjacent Ni and Ni+1 protomers involves electrostatic and hydrophobic interactions mediated primarily through the N-terminal arm and globular domains with minor contribution from the C-terminal arm. However, the HeV N multimeric assembly uniquely identifies an additional protomer-protomer contact between the Ni+1 N-terminus and Ni−1 C-terminal arm linker. The model presented here broadens the understanding of RNA-bound paramyxoviral nucleocapsid architectures and provides a platform for further insight into the molecular biology of HeV, as well as the development of antiviral interventions.

Abstract Animal regeneration involves coordinated responses across cell types throughout the animal body. In endosymbiotic animals, whether and how symbionts react to host injury and how cellular responses are integrated across species remain unexplored. Here, we study the acoel Convolutriloba longifissura, which hosts symbiotic Tetraselmis sp. green algae and can regenerate entire bodies from tissue fragments. We show that animal injury causes a decline in the photosynthetic efficiency of the symbiotic algae, alongside two distinct, sequential waves of transcriptional responses in acoel and algal cells. The initial algal response is characterized by the upregulation of a cohort of photosynthesis-related genes, though photosynthesis is not necessary for regeneration. A conserved animal transcription factor, runt, is induced after injury and required for acoel regeneration. Knockdown of Cl-runt dampens transcriptional responses in both species and further reduces algal photosynthetic efficiency post-injury. Our results suggest that the holobiont functions as an integrated unit of biological organization by coordinating molecular networks across species through the runt-dependent animal regeneration program.

Abstract The availability of protein measurements and whole exome sequence data in the UK Biobank enables investigation of potential observational and genetic protein-cancer risk associations. We investigated associations of 1463 plasma proteins with incidence of 19 cancers and 9 cancer subsites in UK Biobank participants (average 12 years follow-up). Emerging protein-cancer associations were further explored using two genetic approaches, cis-pQTL and exome-wide protein genetic scores (exGS). We identify 618 protein-cancer associations, of which 107 persist for cases diagnosed more than seven years after blood draw, 29 of 618 were associated in genetic analyses, and four had support from long time-to-diagnosis ( > 7 years) and both cis-pQTL and exGS analyses: CD74 and TNFRSF1B with NHL, ADAM8 with leukemia, and SFTPA2 with lung cancer. We present multiple blood protein-cancer risk associations, including many detectable more than seven years before cancer diagnosis and that had concordant evidence from genetic analyses, suggesting a possible role in cancer development.

Abstract Circulating proteins can reveal key pathways to cancer and identify therapeutic targets for cancer prevention. We investigate 2,074 circulating proteins and risk of nine common cancers (bladder, breast, endometrium, head and neck, lung, ovary, pancreas, kidney, and malignant non-melanoma) using cis protein Mendelian randomisation and colocalization. We conduct additional analyses to identify adverse side-effects of altering risk proteins and map cancer risk proteins to drug targets. Here we find 40 proteins associated with common cancers, such as PLAUR and risk of breast cancer [odds ratio per standard deviation increment: 2.27, 1.88-2.74], and with high-mortality cancers, such as CTRB1 and pancreatic cancer [0.79, 0.73-0.85]. We also identify potential adverse effects of protein-altering interventions to reduce cancer risk, such as hypertension. Additionally, we report 18 proteins associated with cancer risk that map to existing drugs and 15 that are not currently under clinical investigation. In sum, we identify protein-cancer links that improve our understanding of cancer aetiology. We also demonstrate that the wider consequence of any protein-altering intervention on well-being and morbidity is required to interpret any utility of proteins as potential future targets for therapeutic prevention.

Abstract This study investigates the humoral and cellular immune responses and health-related quality of life measures in individuals with mild to moderate long COVID (LC) compared to age and gender matched recovered COVID-19 controls (MC) over 24 months. LC participants show elevated nucleocapsid IgG levels at 3 months, and higher neutralizing capacity up to 8 months post-infection. Increased spike-specific and nucleocapsid-specific CD4+ T cells, PD-1, and TIM-3 expression on CD4+ and CD8+ T cells were observed at 3 and 8 months, but these differences do not persist at 24 months. Some LC participants had detectable IFN-γ and IFN-β, that was attributed to reinfection and antigen re-exposure. Single-cell RNA sequencing at the 24 month timepoint shows similar immune cell proportions and reconstitution of naïve T and B cell subsets in LC and MC. No significant differences in exhaustion scores or antigen-specific T cell clones are observed. These findings suggest resolution of immune activation in LC and return to comparable immune responses between LC and MC over time. Improvement in self-reported health-related quality of life at 24 months was also evident in the majority of LC (62%). PTX3, CRP levels and platelet count are associated with improvements in health-related quality of life.

The widespread and abundant brooding brittle-star (Amphipholis squamata) is a simultaneous hermaphrodite with a complex mitochondrial phylogeography of multiple divergent overlapping mtDNA lineages, high levels of inbreeding or clonality and unusual sperm morphology. We use exon-capture and transcriptome data to show that the nuclear genome comprises multiple (greater than 3) divergent (π > 6%) expressed components occurring across samples characterized by highly divergent (greater than 20%) mitochondrial lineages, and encompassing several other genera, including diploid dioecious species. We report a massive sperm genome size in A. squamata, an order of magnitude larger than that present in other brittle-stars, and consistent with our SNP-based measure of greatly elevated ploidy. Similarity of these genetic signatures to well-known animal systems suggests that A. squamata (and related taxa) is a hybrid polyploid asexual complex of variable subgenome origins, ploidy and reproductive mode. We discuss enigmatic aspects of A. squamata biology in this light. This putative allopolyploid complex would be the first to be reported from the phylum Echinodermata.

Abstract Despite progress towards malaria reduction in Peru, measuring exposure in low transmission areas is crucial for achieving elimination. This study focuses on two very low transmission areas in Loreto (Peruvian Amazon) and aims to determine the relationship between malaria exposure and proximity to health facilities. Individual data was collected from 38 villages in Indiana and Belen, including geo-referenced households and blood samples for microscopy, PCR and serological analysis. A segmented linear regression model identified significant changes in seropositivity trends among different age groups. Local Getis-Ord Gi* statistic revealed clusters of households with high (hotspots) or low (coldspots) seropositivity rates. Findings from 4000 individuals showed a seropositivity level of 2.5% (95%CI: 2.0%-3.0%) for P. falciparum and 7.8% (95%CI: 7.0%-8.7%) for P. vivax, indicating recent or historical exposure. The segmented regression showed exposure reductions in the 40–50 age group (β1 = 0.043, p = 0.003) for P. vivax and the 50–60 age group (β1 = 0.005, p = 0.010) for P. falciparum. Long and extreme distance villages from Regional Hospital of Loreto exhibited higher malaria exposure compared to proximate and medium distance villages (p

Abstract Here, we establish a CT-radiomics based method for application in invasive, orthotopic rodent brain tumour models. Twenty four NOD/SCID mice were implanted with U87R-Luc2 GBM cells and longitudinally imaged via contrast enhanced (CE-CT) imaging. Pyradiomics was employed to extract CT-radiomic features from the tumour-implanted hemisphere and non-tumour-implanted hemisphere of acquired CT-scans. Inter-correlated features were removed (Spearman correlation > 0.85) and remaining features underwent predictive analysis (recursive feature elimination or Boruta algorithm). An area under the curve of the receiver operating characteristic curve was implemented to evaluate radiomic features for their capacity to predict defined outcomes. Firstly, we identified a subset of radiomic features which distinguish the tumour-implanted hemisphere and non- tumour-implanted hemisphere (i.e, tumour presence from normal tissue). Secondly, we successfully translate preclinical CT-radiomic pipelines to GBM patient CT scans (n = 10), identifying similar trends in tumour-specific feature intensities (E.g. ‘glszm Zone Entropy’), thereby suggesting a mouse-to-human species conservation (a conservation of radiomic features across species). Thirdly, comparison of features across timepoints identify features which support preclinical tumour detection earlier than is possible by visual assessment of CT scans. This work establishes robust, preclinical CT-radiomic pipelines and describes the application of CE-CT for in-depth orthotopic brain tumour monitoring. Overall we provide evidence for the role of pre-clinical ‘discovery’ radiomics in the neuro-oncology space.

Abstract Genomic regions associated with ripening time (RPT) and soluble solids concentration (SSC) were mapped using a pedigreed population including multiple F1 and F2 families from the Clemson University peach breeding program (CUPBP). RPT and SSC QTLs were consistently identified in two seasons (2011 and 2012) and the average datasets (average of two seasons). A target region spanning 10,981,971–11,298,736 bp on chromosome 4 of peach reference genome used for haplotype analysis revealed four haplotypes with significant differences in trait values among different diplotype combinations. Favorable alleles at the target region for both RPT and SSC were determined and a DNA test for predicting RPT and SSC was developed. Two Kompetitive Allele Specific PCR (KASP) assays were validated on 84 peach cultivars and 163 seedlings from the CUPBP, with only one assay (Ppe.RPT/SSC-1) needed to predict between early and late-season ripening cultivars and low and high SSC. These results advance our understanding of the genetic basis of RPT and SSC and facilitate selection of new peach cultivars with the desired RPT and SSC.

Abstract Surveillance of endemic pathogens is essential for disease control, providing an evidence base for policy and advice. Bovine Herpes Virus Type 1 (BoHV-1), the causative agent of Infectious Bovine Rhinotracheitis (IBR), has been found to have high seroprevalence within the Irish cattle population. The aim of the present study was to establish seroprevalence levels for culled cattle in Ireland aged

Zoonotic disease dynamics in wildlife hosts are rarely quantified at macroecological scales due to the lack of systematic surveys. Non-human primates (NHPs) host Plasmodium knowlesi, a zoonotic malaria of public health concern and the main barrier to malaria elimination in Southeast Asia. Understanding of regional P. knowlesi infection dynamics in wildlife is limited. Here, we systematically assemble reports of NHP P. knowlesi and investigate geographic determinants of prevalence in reservoir species. Meta-analysis of 6322 NHPs from 148 sites reveals that prevalence is heterogeneous across Southeast Asia, with low overall prevalence and high estimates for Malaysian Borneo. We find that regions exhibiting higher prevalence in NHPs overlap with human infection hotspots. In wildlife and humans, parasite transmission is linked to land conversion and fragmentation. By assembling remote sensing data and fitting statistical models to prevalence at multiple spatial scales, we identify novel relationships between P. knowlesi in NHPs and forest fragmentation. This suggests that higher prevalence may be contingent on habitat complexity, which would begin to explain observed geographic variation in parasite burden. These findings address critical gaps in understanding regional P. knowlesi epidemiology and indicate that prevalence in simian reservoirs may be a key spatial driver of human spillover risk.

Abstract Modulation of autophagy, specifically its inhibition, stands to transform the capacity to effectively treat a broad range of cancers. However, the clinical efficacy of autophagy inhibitors has been inconsistent. To delineate clinical and epidemiological features associated with autophagy inhibition and a positive oncological clinical response, a retrospective analysis of patients is conducted treated with hydroxychloroquine, a known autophagy inhibitor. A direct correlation between smoking status and inhibition of autophagy with hydroxychloroquine is identified. Recognizing that smoking is associated with elevated circulating levels of carbon monoxide (CO), it is hypothesized that supplemental CO can amplify autophagy inhibition. A novel, gas‐entrapping material containing CO in a pre‐clinical model is applied and demonstrated that CO can dramatically increase the cytotoxicity of autophagy inhibitors and significantly inhibit the growth of tumors when used in combination. These data support the notion that safe, therapeutic levels of CO can markedly enhance the efficacy of autophagy inhibitors, opening a promising new frontier in the quest to improve cancer therapies.

Summary: Fungal β-glucans are major drivers of trained immunity which increases long-term protection against secondary infections. Heterogeneity in β-glucan source, structure, and solubility alters interaction with the phagocytic receptor Dectin-1 and could impact strategies to improve trained immunity in humans. Using a panel of diverse β-glucans, we describe the ability of a specific yeast-derived whole-glucan particle (WGP) to reprogram metabolism and thereby drive trained immunity in human monocyte-derived macrophages in vitro and mice bone marrow in vivo. Presentation of pure, non-soluble, non-aggregated WGPs led to the formation of the Dectin-1 phagocytic synapse with subsequent lysosomal mTOR activation, metabolic reprogramming, and epigenetic rewiring. Intraperitoneal or oral administration of WGP drove bone marrow myelopoiesis and improved mature macrophage responses, pointing to therapeutic and food-based strategies to drive trained immunity. Thus, the investment of a cell in a trained response relies on specific recognition of β-glucans presented on intact microbial particles through stimulation of the Dectin-1 phagocytic response.

Abstract Multiple sclerosis (MS), a chronic neurodegenerative disease driven by damage to the protective myelin sheath, is currently incurable. Today, all clinically available treatments modulate the immune-mediated symptoms of the disease but they fail to stop neurodegeneration in many patients. Remyelination, the regenerative process of myelin repair by oligodendrocytes, which is considered a necessary step to protect demyelinated axons and stop neuronal death, is impaired in MS patients. One of the major obstacles to finding effective remyelinating drugs is the lack of biomimetic drug screening platforms that enable quantification of compounds’ potential to stimulate 3D myelination in the physiologically relevant axon-like environment. To address this need, we built a unique myelination drug discovery platform, by expanding our previously developed technology, artificial axons (AAs), which enables 3D-printing of synthetic axon mimics with the geometry and mechanical properties closely resembling those of biological axons. This platform allows for high-throughput phenotypic myelination assay based on quantification of 3D wrapping of myelin membrane around axons in response to compounds. Here, we demonstrate quantification of 3D myelin wrapping by rat oligodendrocytes around the axon mimics in response to a small library of known pro-myelinating compounds. This assay shows pro-myelinating activity for all tested compounds consistent with the published in vitro and in vivo data, demonstrating predictive power of AA platform. We find that stimulation of myelin wrapping by these compounds is dose-dependent, providing a facile means to quantify the compounds’ potency and efficacy in promoting myelin wrapping. Further, the ranking of relative efficacy among these compounds differs in this 3D axon-like environment as compared to a traditional oligodendrocyte 2D differentiation assay quantifying area of deposited myelin membrane. Together, we demonstrate that the artificial axons platform and associated phenotypic myelin wrapping assay afford direct evaluation of myelin wrapping by oligodendrocytes in response to soluble compounds in an axon-like environment, providing a predictive tool for the discovery of remyelinating therapies.

Abstract Single cell spatial interrogation of the immune-structural interactions in COVID −19 lungs is challenging, mainly because of the marked cellular infiltrate and architecturally distorted microstructure. To address this, we develop a suite of mathematical tools to search for statistically significant co-locations amongst immune and structural cells identified using 37-plex imaging mass cytometry. This unbiased method reveals a cellular map interleaved with an inflammatory network of immature neutrophils, cytotoxic CD8 T cells, megakaryocytes and monocytes co-located with regenerating alveolar progenitors and endothelium. Of note, a highly active cluster of immature neutrophils and CD8 T cells, is found spatially linked with alveolar progenitor cells, and temporally with the diffuse alveolar damage stage. These findings offer further insights into how immune cells interact in the lungs of severe COVID-19 disease. We provide our pipeline [Spatial Omics Oxford Pipeline (SpOOx)] and visual-analytical tool, Multi-Dimensional Viewer (MDV) software, as a resource for spatial analysis.

Abstract Biomarkers for early detection of breast cancer may complement population screening approaches to enable earlier and more precise treatment. The blood proteome is an important source for biomarker discovery but so far, few proteins have been identified with breast cancer risk. Here, we measure 2929 unique proteins in plasma from 598 women selected from the Karolinska Mammography Project to explore the association between protein levels, clinical characteristics, and gene variants, and to identify proteins with a causal role in breast cancer. We present 812 cis-acting protein quantitative trait loci for 737 proteins which are used as instruments in Mendelian randomisation analyses of breast cancer risk. Of those, we present five proteins (CD160, DNPH1, LAYN, LRRC37A2 and TLR1) that show a potential causal role in breast cancer risk with confirmatory results in independent cohorts. Our study suggests that these proteins should be further explored as biomarkers and potential drug targets in breast cancer.

Abstract Obesity is a well-recognized risk factor for severe influenza infections but the mechanisms underlying susceptibility are poorly understood. Here, we identify that obese individuals have deficient pulmonary antiviral immune responses in bronchoalveolar lavage cells but not in bronchial epithelial cells or peripheral blood dendritic cells. We show that the obese human airway metabolome is perturbed with associated increases in the airway concentrations of the adipokine leptin which correlated negatively with the magnitude of ex vivo antiviral responses. Exogenous pulmonary leptin administration in mice directly impaired antiviral type I interferon responses in vivo and ex vivo in cultured airway macrophages. Obese individuals hospitalised with influenza showed dysregulated upper airway immune responses. These studies provide insight into mechanisms driving propensity to severe influenza infections in obesity and raise the potential for development of leptin manipulation or interferon administration as novel strategies for conferring protection from severe infections in obese higher risk individuals.

Abstract Aberrant expansion of KRT5+ basal cells in the distal lung accompanies progressive alveolar epithelial cell loss and tissue remodelling during fibrogenesis in idiopathic pulmonary fibrosis (IPF). The mechanisms determining activity of KRT5+ cells in IPF have not been delineated. Here, we reveal a potential mechanism by which KRT5+ cells migrate within the fibrotic lung, navigating regional differences in collagen topography. In vitro, KRT5+ cell migratory characteristics and expression of remodelling genes are modulated by extracellular matrix (ECM) composition and organisation. Mass spectrometry- based proteomics revealed compositional differences in ECM components secreted by primary human lung fibroblasts (HLF) from IPF patients compared to controls. Over-expression of ECM glycoprotein, Secreted Protein Acidic and Cysteine Rich (SPARC) in the IPF HLF matrix restricts KRT5+ cell migration in vitro. Together, our findings demonstrate how changes to the ECM in IPF directly influence KRT5+ cell behaviour and function contributing to remodelling events in the fibrotic niche.

Abstract Chimeric antigen receptor (CAR) T cells have transformed the treatment landscape for hematological malignancies. However, CAR T cells are less efficient against solid tumors, largely due to poor infiltration resulting from the immunosuppressive nature of the tumor microenvironment (TME). Here, we assessed the efficacy of Lewis Y antigen (LeY)-specific CAR T cells in patient-derived xenograft (PDX) models of prostate cancer. In vitro, LeY CAR T cells directly killed organoids derived from androgen receptor (AR)-positive or AR-null PDXs. In vivo, although LeY CAR T cells alone did not reduce tumor growth, a single prior dose of carboplatin reduced tumor burden. Carboplatin had a pro-inflammatory effect on the TME that facilitated early and durable CAR T cell infiltration, including an altered cancer-associated fibroblast phenotype, enhanced extracellular matrix degradation and re-oriented M1 macrophage differentiation. In a PDX less sensitive to carboplatin, CAR T cell infiltration was dampened; however, a reduction in tumor burden was still observed with increased T cell activation. These findings indicate that carboplatin improves the efficacy of CAR T cell treatment, with the extent of the response dependent on changes induced within the TME.

East African lakes support the food and water security of millions of people. Yet, a lack of continuous long-term water quality data for these waterbodies impedes their sustainable management. While satellite-based water quality retrieval methods have been developed for lakes globally, African lakes are typically underrepresented in training data, limiting the applicability of existing methods to the region. Hence, this study aimed to (1) assess the accuracy of existing and newly developed water quality band algorithms for East African lakes and (2) make satellite-derived water quality information easily accessible through a Google Earth Engine application (app), named LAndsat water QUality retrieval tool for east African lakes (LAQUA). We collated a dataset of existing and newly collected in situ surface water quality samples from seven lakes to develop and test Landsat water quality retrieval models. Twenty-one published algorithms were evaluated and compared with newly developed linear and quadratic regression models, to determine the most suitable Landsat band algorithms for chlorophyll-a, total suspended solids (TSS), and Secchi disk depth (SDD) for East African lakes. The three-band algorithm, parameterised using data for East African lakes, proved the most suitable for chlorophyll-a retrieval (R2 = 0.717, p < 0.001, RMSE = 22.917 μg/L), a novel index developed in this study, the Modified Suspended Matter Index (MSMI), was the most accurate for TSS retrieval (R2 = 0.822, p < 0.001, RMSE = 9.006 mg/L), and an existing global model was the most accurate for SDD estimation (R2 = 0.933, p < 0.001, RMSE = 0.073 m). The LAQUA app we developed provides easy access to the best performing retrieval models, facilitating the use of water quality information for management and evidence-informed policy making for East African lakes.

The National Oceanic and Atmospheric Administration’s (NOAA) Center for Satellite Applications and Research (STAR) facilitates and enables societal benefits from satellite oceanography, supporting operational and experimental satellite missions, developing new and improved ocean observing capabilities, engaging users by developing and distributing fit-for-purpose data, applications, tools, and services, and curating, translating, and integrating diverse data products into information that supports informed decision making. STAR research, development, and application efforts span from passive visible, infrared, and microwave observations to active altimetry, scatterometry, and synthetic aperture radar (SAR) observations. These efforts directly support NOAA’s operational geostationary (GEO) and low Earth orbit (LEO) missions with calibration/validation and retrieval algorithm development, implementation, maintenance, and anomaly resolution, as well as leverage the broader international constellation of environmental satellites for NOAA’s benefit. STAR’s satellite data products and services enable research, assessments, applications, and, ultimately, decision making for understanding, predicting, managing, and protecting ocean and coastal resources, as well as assessing impacts of change on the environment, ecosystems, and climate. STAR leads the NOAA Coral Reef Watch and CoastWatch/OceanWatch/PolarWatch Programs, helping people access and utilize global and regional satellite data for ocean, coastal, and ecosystem applications.

Abstract Malaysia has reported no indigenous cases of P. falciparum and P. vivax for over 3 years. When transmission reaches such low levels, it is important to understand the individuals and locations where exposure risks are high, as they may be at greater risk in the case of a resurgence of transmission. Serology is a useful tool in low transmission settings, providing insight into exposure over longer durations than PCR or RDT. We ran blood samples from a 2015 population-based survey in northern Sabah, Malaysian Borneo on a multiplex bead assay. Using supervised machine learning methods, we characterised recent and historic exposure to Plasmodium falciparum and P. vivax and found recent exposure to P. falciparum to be very low, with exposure to both species increasing with age. We performed a risk-factor assessment on environmental, behavioural, demographic and household factors, and identified forest activity and longer travel times to healthcare as common risk-factors for exposure to P. falciparum and P. vivax. In addition, we used remote-sensing derived data and geostatistical models to assess environmental and spatial associations with exposure. We created predictive maps of exposure to recent P. falciparum in the study area and showed 3 clear foci of exposure. This study provides useful insight into the environmental, spatial and demographic risk factors for P. falciparum and P. vivax at a period of low transmission in Malaysian Borneo. The findings would be valuable in the case of resurgence of human malarias in the region.

Abstract Respiratory viruses that were suppressed through previous lockdowns during the COVID-19 pandemic have recently started to co-circulate with SARS-CoV-2. Understanding the clinical characteristics and symptomatology of different respiratory viral infections can help address the challenges related to the identification of cases and the understanding of SARS-CoV-2 variants' evolutionary patterns. Flu Watch (2006–2011) and Virus Watch (2020–2022) are household community cohort studies monitoring the epidemiology of influenza, respiratory syncytial virus, rhinovirus, seasonal coronavirus, and SARS-CoV-2, in England and Wales. This study describes and compares the proportion of symptoms reported during illnesses infected by common respiratory viruses. The SARS-CoV-2 symptom profile increasingly resembles that of other respiratory viruses as new strains emerge. Increased cough, sore throat, runny nose, and sneezing are associated with the emergence of the Omicron strains. As SARS-CoV-2 becomes endemic, monitoring the evolution of its symptomatology associated with new variants will be critical for clinical surveillance.

The COVID-19 pandemic forced many educators out of their traditional settings and into web-based learning environments. Zoos were no different, and throughout the pandemic they strived to reach their supporters using different approaches. By adapting quickly and using outreach activities and online learning, zoos continued to serve society through the pandemic. This study examined whether an in-person educational interaction with zoological specimens can enhance cognitive learning and increase primary-level students’ attitudes towards animals and science. Additionally, attention was drawn to the effectiveness of online learning methods for young pupils. A total of 165 paired questionnaires from primary-level students in three schools were analysed. Findings indicate significant positive increases in attitude but not in learning achievements. Thus, zoological specimens can be utilised for enhancing scientific attitudes in primary-level students. The effect of a face-to-face lesson on learning compared with online methods was positive but the difference was not statistically significant. This, taken together with a significant positive effect of a face-to-face lesson on attitude improvements, is sufficient to determine the importance of a traditional learning environment for students of this educational level. Additionally, gender differences relating to scientific attitudes and understanding are not apparent at primary level but this may become more apparent at secondary level. This research may be used for further investigations into the relationship between age, gender, and scientific learning. It may also be used to support studies examining the effectiveness of zoo outreach programs in schools versus zoo visits.

Abstract Only praziquantel is available for treating schistosomiasis, a disease affecting more than 200 million people. Praziquantel-resistant worms have been selected for in the lab and low cure rates from mass drug administration programs suggest that resistance is evolving in the field. Thioredoxin glutathione reductase (TGR) is essential for schistosome survival and a validated drug target. TGR inhibitors identified to date are irreversible and/or covalent inhibitors with unacceptable off-target effects. In this work, we identify noncovalent TGR inhibitors with efficacy against schistosome infections in mice, meeting the criteria for lead progression indicated by WHO. Comparisons with previous in vivo studies with praziquantel suggests that these inhibitors outperform the drug of choice for schistosomiasis against juvenile worms.

Abstract There is tremendous variation in life-history strategies among anadromous salmonids. Species that enter the ocean environment at small sizes ( 90% of all parasites lost by 16 days post-infection (dpi). Rejection was concomitant with host epithelial granulomatous infiltrations that initially targeted the embedded frontal filament (4 dpi) and the entire parasite by 10 dpi. Illumina sequencing, followed by functional enrichment analysis, revealed a concerted defense response in the fin within 1 dpi that included multiple innate and adaptive immunity components. Strikingly, early indications of an allergic-type inflammatory response were associated with chitin sensing pathways orchestrated by early overexpression of the IgE-receptor, fcer1g. Additionally, there was profound overexpression of several classes of c-type lectin receptors, including dectin-2, mincle, and dc-sign at 1 dpi onward. These profiles and upregulation of cellular effector markers were corroborated by histopathological evaluation, revealing the simultaneous presence of mast cell/eosinophilic granular cells, sacciform cells, macrophages/histiocytes, and granulocytes in fin. At 10 dpi and concurrent with parasite expulsion, there was evidence of immunoregulation in addition to tissue remodelling pathways. At 16 dpi, the response was effectively abrogated. Simultaneous profiling of the parasite transcriptome revealed early induction of chitin metabolism and immunomodulation, toxin production and ECM degradation; however, after 7 dpi, these were replaced with overexpression of stress and immune defense genes. These data present the first evidence for Coho salmon demonstrating chitin- and sugar moiety-sensing as key drivers of salmon louse rejection.

Abstract Over 15% of probands in a large cohort of more than 1500 inherited retinal degeneration patients present with a clinical diagnosis of Stargardt disease (STGD1), a recessive form of macular dystrophy caused by biallelic variants in the ABCA4 gene. Participants were clinically examined and underwent either target capture sequencing of the exons and some pathogenic intronic regions of ABCA4, sequencing of the entire ABCA4 gene or whole genome sequencing. ABCA4 c.4539 + 2028C > T, p.[= ,Arg1514Leufs*36] is a pathogenic deep intronic variant that results in a retina-specific 345-nucleotide pseudoexon inclusion. Through analysis of the Irish STGD1 cohort, 25 individuals across 18 pedigrees harbour ABCA4 c.4539 + 2028C > T and another pathogenic variant. This includes, to the best of our knowledge, the only two homozygous patients identified to date. This provides important evidence of variant pathogenicity for this deep intronic variant, highlighting the value of homozygotes for variant interpretation. 15 other heterozygous incidents of this variant in patients have been reported globally, indicating significant enrichment in the Irish population. We provide detailed genetic and clinical characterization of these patients, illustrating that ABCA4 c.4539 + 2028C > T is a variant of mild to intermediate severity. These results have important implications for unresolved STGD1 patients globally with approximately 10% of the population in some western countries claiming Irish heritage. This study exemplifies that detection and characterization of founder variants is a diagnostic imperative.

Abstract Glioblastoma (GBM) is the most frequent malignant primary tumor of the CNS in adults, with a median survival of 14.6 months after diagnosis. The effectiveness of GBM therapies remains poor, highlighting the need for new therapeutic alternatives. In this work, we evaluated the effect of 4-methylumbelliferone (4MU), a coumarin derivative without adverse effects reported, in combination with temozolomide (TMZ) or vincristine (VCR) on U251, LN229, U251-TMZ resistant (U251-R) and LN229-TMZ resistant (LN229-R) human GBM cells. We determined cell proliferation by BrdU incorporation, migration through wound healing assay, metabolic and MMP activity by XTT and zymography assays, respectively, and cell death by PI staining and flow cytometry. 4MU sensitizes GBM cell lines to the effect of TMZ and VCR and inhibits metabolic activity and cell proliferation on U251-R cells. Interestingly, the lowest doses of TMZ enhance U251-R and LN229-R cell proliferation, while 4MU reverts this and even sensitizes both cell lines to TMZ and VCR effects. We showed a marked antitumor effect of 4MU on GBM cells alone and in combination with chemotherapy and proved, for the first time, the effect of 4MU on TMZ-resistant models, demonstrating that 4MU would be a potential therapeutic alternative for improving GBM therapy even on TMZ-refractory patients.

BackgroundChronic neuropsychological sequelae following SARS-CoV-2 infection, including depression, anxiety, fatigue, and general cognitive difficulties, are a major public health concern. Given the potential impact of long-term neuropsychological impairment, it is important to characterize the frequency and predictors of this post-infection phenotype.MethodsThe Epidemiology, Immunology, and Clinical Characteristics of Emerging Infectious Diseases with Pandemic Potential (EPICC) study is a longitudinal study assessing the impact of SARS-CoV-2 infection in U.S. Military Healthcare System (MHS) beneficiaries, i.e. those eligible for care in the MHS including active duty servicemembers, dependents, and retirees. Four broad areas of neuropsychological symptoms were assessed cross-sectionally among subjects 1-6 months post-infection/enrollment, including: depression (Patient Health Questionnaire-9), anxiety (General Anxiety Disorder-7), fatigue (PROMIS® Fatigue 7a), and cognitive function (PROMIS® Cognitive Function 8a and PROMIS® Cognitive Function abilities 8a). Multivariable Poisson regression models compared participants with and without SARS-CoV-2 infection history on these measures, adjusting for sex, ethnicity, active-duty status, age, and months post-first positive or enrollment of questionnaire completion (MPFP/E); models for fatigue and cognitive function were also adjusted for depression and anxiety scores.ResultsThe study population included 2383 participants who completed all five instruments within six MPFP/E, of whom 687 (28.8%) had at least one positive SARS-CoV-2 test. Compared to those who had never tested positive for SARS-CoV-2, the positive group was more likely to meet instrument-based criteria for depression (15.4% vs 10.3%, pConclusionsParticipants with a history of SARS-CoV-2 infection were up to twice as likely to report cognitive impairment and fatigue as the group without prior SARS-CoV-2 infection. These findings underscore the continued importance of preventing SARS-CoV-2 infection and while time since infection/enrollment was not significant through 6 months of follow-up, this highlights the need for additional research into the long-term impacts of COVID-19 to mitigate and reverse these neuropsychological outcomes.

Background and aimsMetabolic dysfunction associated steatotic liver disease (MASLD) increases the risk of incident chronic kidney disease (CKD). However, the relative risk of CKD associated with increasing hepatic fibrosis, and consequent mortality risk, remains underexplored in real-world cohorts. In this study, we sought to establish whether hepatic fibrosis is associated with increased CKD risk and explore differences in mortality risk in a cohort of people living with MASLD, contingent on liver fibrosis and CKD status.MethodsThis was an observational study of people who underwent routine liver function testing in Tayside, Scotland. MASLD was defined as: elevated ALT (>30 U/L) or GGT (>73 U/L); presence of diabetes, and/or hypertension, and/or obesity; weekly alcohol consumption ResultsIn our cohort (n = 2,046), 1,448 (70.8%) people had MASLD without fibrosis and 598 (29.2%) with fibrosis; 161 (11.1%) and 117 (19.6%) respectively also had CKD. After excluding individuals with structural, autoimmune, or malignant CKD (n = 22), liver fibrosis (n = 593; 18.9% with CKD) was associated with increased CKD risk (aRR = 1.31, 1.04-1.64, p = 0.021). Increased mortality risk was observed for those with liver fibrosis (aHR = 2.30, 1.49-3.56, p = ConclusionsLiver fibrosis was an independent risk factor for CKD in this cohort of people living with MASLD. Furthermore, those with MASLD with liver fibrosis had higher risk for mortality and this risk was further elevated among those with co-morbid CKD. Given the increased risk of CKD, and consequent mortality risk, among people living with MASLD fibrosis, renal function screening should be considered within liver health surveillance programmes and guidelines.

ObjectiveTo assess whether case finding for depression among people aged 65 and above improves mental health.DesignOpportunistic evaluation using a regression discontinuity analysis with data from a randomised controlled trial.SettingThe REFORM trial, a falls prevention study that recruited patients from NHS podiatry clinics.Participants1010 community-dwelling adults over the age of 65 with at least one risk factor for falling (recent previous fall or fear of falling).InterventionLetter sent to patient's General Practitioner if they scored 10 points or above on the 15-item Geriatric Depression Scale (GDS-15) informing them of the patient's risk of depression.Main outcome measureGDS-15 score six months after initial completion of GDS-15.Results895 (88.6%) of the 1010 participants randomised into REFORM had a valid baseline and six-month GDS-15 score and were included in this study. The mean GDS-15 baseline score was 3.5 (SD 3.0, median 3.0, range 0-15); 639 (71.4%) scored 0-4, 204 (22.8%) scored 5-9 indicating mild depression, and 52 (5.8%) scored 10 or higher indicating severe depression. At six months follow-up, those scoring 10 points or higher at baseline had, on average, a reduction of 1.08 points on the GDS-15 scale (95% confidence interval -1.83 to -0.33, p = 0.005) compared to those scoring less than 10, using the simplest linear regression model.ConclusionCase finding of depression in podiatry patients based on a GDS-15 score of 10 or more followed by a letter to their General Practitioner significantly reduced depression severity. Whether this applies to all older patients in primary care is unknown. Further research is required to confirm these findings. Regression discontinuity analyses could be prespecified and embedded within other existing research studies.

The detection of temperature by the human sensory system is life-preserving and highly evolutionarily conserved. Platelets are sensitive to temperature changes and are activated by a decrease in temperature, akin to sensory neurons. However, the molecular mechanism of this temperature-sensing ability is unknown. Yet, platelet activation by temperature could contribute to numerous clinical sequelae, most importantly to reduced quality of ex vivo-stored platelets for transfusion. In this multidisciplinary study, we present evidence for the expression of the temperature-sensitive ion channel transient receptor potential cation channel subfamily member 8 (TRPM8) in human platelets and precursor cells. We found the TRPM8 mRNA and protein in MEG-01 cells and platelets. Inhibition of TRPM8 prevented temperature-induced platelet activation and shape change. However, chemical agonists of TRPM8 did not seem to have an acute effect on platelets. When exposing platelets to below-normal body temperature, we detected a cytosolic calcium increase which was independent of TRPM8 but was completely dependent on the calcium release from the endoplasmic reticulum. Because of the high interindividual variability of TRPM8 expression, a population-based approach should be the focus of future studies. Our study suggests that the cold response of platelets is complex and TRPM8 appears to play a role in early temperature-induced activation of platelets, while other mechanisms likely contribute to later stages of temperature-mediated platelet response.

IntroductionIncreasing numbers of people are living with stroke, due to population ageing and improved survival, leading to a need for evidence to inform future policy decision-making. This study aimed to engage with stakeholders in Ireland to identify priorities for stroke services development.MethodsA sequential mixed methods design was used. Phase 1 (qualitative) was exploratory, involving initial priority gathering via an online qualitative survey and interviews, with stroke survivors, family/main carers, and professionals working in stroke care. Framework analysis was used to generate a long-list of improvements to stroke services. Phase 2 involved a quantitative survey, where stakeholders selected five priority improvements from the long-list. Results were discussed in a stakeholder meeting.ResultsIn-depth interviews were completed with 18 survivors, 13 carers and 8 professionals, while 80 professionals took part in a qualitative survey (phase 1). Priority areas of care were identified and a long-list of 45 priority improvements was generated. In phase 2, 34 survivors, 19 family carers and 42 professionals completed a survey. The highest priority improvements (selected by >20% of respondents) were access to specialist neuro-rehabilitation, ongoing support for life after stroke, recruitment/retention of specialist staff, improved information and support for health system navigation, and access to specialist acute care. Stroke survivors/carers prioritised exploring ways to improve access for strokes with atypical presentation, while professionals prioritised specialist inpatient rehabilitation and early supported discharge. Neither group prioritised stroke prevention. Based on discussions in the stakeholder meeting (n = 12), it was decided that support for mental health should also be included as a priority.DiscussionThe development of stroke services benefits from exploring the priorities of those receiving and delivering stroke care. Findings emphasise the need for equitable access to high quality adequately-staffed services, particularly post-discharge, that are easy to navigate, with good communication, and effective information provision.

Abstract A significant proportion of the infant gut microbiome is considered to be acquired from the mother during and after birth. Thus begins a lifelong and dynamic relationship with microbes that has an enduring impact on host health. Based on a cohort of 135 mother-infant (F = 72, M = 63) dyads (MicrobeMom: ISRCTN53023014), we investigated the phenomenon of microbial strain transfer, with a particular emphasis on the use of a combined metagenomic-culture-based approach to determine the frequency of strain transfer involving members of the genus Bifidobacterium, including species/strains present at low relative abundance. From the isolation and genome sequencing of over 449 bifidobacterial strains, we validate and augment metagenomics-based evidence to reveal strain transfer in almost 50% of dyads. Factors important in strain transfer include vaginal birth, spontaneous rupture of amniotic membranes, and avoidance of intrapartum antibiotics. Importantly, we reveal that several transfer events are uniquely detected employing either cultivation or metagenomic sequencing, highlighting the requirement for a dual approach to obtain an in-depth insight into this transfer process.

Abstract We have developed a high-throughput computational method to predict the superconducting transition temperature in stable hexagonal M $$_2$$ 2 AX phases, and applied it to all the known possible choices for M (M: Sc, Ti, V, Cr, Mn, Fe, Y, Zr, Nb, Mo, Lu, Hf and Ta). We combine this with the best candidates for A (A: Al, Cu, Ge and Sn ) and X (X: C and N) from our previous work, and predict T $$_c$$ c for 60 M $$_2$$ 2 AX-phase materials, 53 of which have never been studied before. From all of these, we identify Cr $$_2$$ 2 AlN as the best candidate for the highest T $$_c$$ c , and confirm its high T $$_c$$ c with more detailed density functional theory electron-phonon coupling calculations. Our detailed calculations predict $$T_c$$ T c = 14.8 K for Cr $$_2$$ 2 AlN, which is significantly higher than any $$T_c$$ T c value known or predicted for any material in the M $$_2$$ 2 AX family to date.

Abstract Eye movement data has been extensively utilized by researchers interested in studying decision-making within the strategic setting of economic games. In this paper, we demonstrate that both deep learning and support vector machine classification methods are able to accurately identify participants’ decision strategies before they commit to action while playing games. Our approach focuses on creating scanpath images that best capture the dynamics of a participant’s gaze behaviour in a way that is meaningful for predictions to the machine learning models. Our results demonstrate a higher classification accuracy by 18% points compared to a baseline logistic regression model, which is traditionally used to analyse gaze data recorded during economic games. In a broader context, we aim to illustrate the potential for eye-tracking data to create information asymmetries in strategic environments in favour of those who collect and process the data. These information asymmetries could become especially relevant as eye-tracking is expected to become more widespread in user applications, with the seemingly imminent mass adoption of virtual reality systems and the development of devices with the ability to record eye movement outside of a laboratory setting.

Henipaviruses such as Nipah virus (NiV) cause severe encephalitis with high fatality rates in humans. NiV fusion (F) glycoprotein is a key target of the host immune response. Here, Byrne et al. isolate ten neutralizing antibodies against NiV prefusion F and provide a structural analysis of the antibodies and defined eight neutralization-sensitive epitopes on NiV F.