Huge automatically extracted training sets for multilingual Word Sense Disambiguation

We release to the community six large-scale sense-annotated datasets in multiple language to pave the way for supervised multilingual Word Sense Disambiguation. Our datasets cover all the nouns in the English WordNet and their translations in other languages for a total of millions of sense-tagged sentences. Experiments prove that these corpora can be effectively used as training sets for supervised WSD systems, surpassing the state of the art for low- resourced languages and providing competitive results for English, where manually annotated training sets are accessible. The data is available at trainomatic. org

Analysis of colorectal cancers in British Bangladeshi identifies early onset, frequent mucinous histotype and a high prevalence of RBFOX1 deletion

PMCID: PMC3544714This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

From Andes to Amazon: assessing branched tetraether lipids as tracers for soil organic carbon in the Madre de Dios River system

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Kirkels, F. M. S. A., Ponton, C., Galy, V., West, A. J., Feakins, S. J., & Peterse, F. From Andes to Amazon: assessing branched tetraether lipids as tracers for soil organic carbon in the Madre de Dios River system. Journal of Geophysical Research-Biogeosciences, 125(1), (2020): e2019JG005270, doi:10.1029/2019JG005270.We investigate the implications of upstream processes and hydrological seasonality on the transfer of soil organic carbon (OC) from the Andes mountains to the Amazon lowlands by the Madre de Dios River (Peru), using branched glycerol dialkyl glycerol tetraether (brGDGT) lipids. The brGDGT signal in Andean soils (0.5 to 3.5 km elevation) reflects air temperature, with a lapse rate of −6.0 °C/km elevation (r 2 = 0.89, p < 0.001) and −5.6 °C/km elevation (r 2 = 0.89, p < 0.001) for organic and mineral horizons, respectively. The same compounds are present in river suspended particulate matter (SPM) with a lapse rate of −4.1 °C/km elevation (r 2 = 0.82, p < 0.001) during the wet season, where the offset in intercept between the temperature lapse rates for soils and SPM indicates upstream sourcing of brGDGTs. The lapse rate for SPM appears insensitive to an increasing relative contribution of 6‐methyl isomer brGDGTs produced within the river. River depth profiles show that brGDGTs are well mixed in the river and are not affected by hydrodynamic sorting. The brGDGTs accumulate relative to OC downstream, likely due to the transition of particulate OC to the dissolved phase and input of weathered soils toward the lowlands. The temperature‐altitude correlation of brGDGTs in Madre de Dios SPM contrasts with the Lower Amazon River, where the initial soil signature is altered by changes in seasonal in‐river production and variable provenance of brGDGTs. Our study indicates that brGDGTs in the Madre de Dios River system are initially soil derived and highlights their use to study OC sourcing in mountainous river systems.The brGDGT analyses were supported by NWO‐Veni grant 863.13.016 to F.P. This material is based upon work supported by the US National Science Foundation under grant EAR‐1227192 to A. J. W. and S. J. F. for the river fieldwork and lipid purification. In Perú, we thank the Servicio Nacional de Áreas Naturales Protegidas por el Estado (SERNANP) and personnel of Manu and Tambopata National Parks for logistical assistance and permission to work in the protected areas. We thank the Explorers' Inn and the Pontifical Catholic University of Perú (PUCP), as well as the Amazon Conservation Association for the use of the Tambopata and Wayqecha Research Stations, respectively. For river fieldwork assistance, we thank M. Torres, A. Robles, and A. Cachuana. Soil samples were contributed by Andrew Nottingham and Patrick Meir. Logistical support was provided by Y. Malhi, J. Huaman, W. Huaraca Huasco, and other collaborators as part of the Andes Biodiversity and Ecosystems Research Group ABERG (www.andesresearch.org). We thank Dominika Kasjaniuk for technical support at Utrecht. Two anonymous reviewers have provided valuable comments that have helped to improve this manuscript. Geochemical and brGDGT data are available in the PANGAEA Data Repository (Kirkels et al., 2019) and can be accessed at https://doi.pangaea.de/10.1594/PANGAEA.90617

High temperatures in the terrestrial mid-latitudes during the early Palaeogene

The early Paleogene (56–48 Myr) provides valuable information about the Earth’s climate system in an equilibrium high pCO2 world. High ocean temperatures have been reconstructed for this greenhouse period, but land temperature estimates have been cooler than expected. This mismatch between marine and terrestrial temperatures has been difficult to reconcile. Here we present terrestrial temperature estimates from a newly calibrated branched glycerol dialkyl glycerol tetraether-based palaeothermometer in ancient lignites (fossilized peat). Our results suggest early Palaeogene mid-latitude mean annual air temperatures of 23–29 °C (with an uncertainty of ± 4.7 °C), 5–10 °C higher than most previous estimates. The identification of archaeal biomarkers in these same lignites, previously observed only in thermophiles and hyperthermophilic settings, support these high temperature estimates. These mid-latitude terrestrial temperature estimates are consistent with reconstructed ocean temperatures and indicate that the terrestrial realm was much warmer during the early Palaeogene than previously thought

Hydroclimate in the Pamirs Was Driven by Changes in Precipitation‐Evaporation Seasonality Since theLast Glacial Period

The Central Asian Pamir Mountains (Pamirs) are a high‐altitude region sensitive to climatic change, with only few paleoclimatic records available. To examine the glacial‐interglacial hydrological changes in the region, we analyzed the geochemical parameters of a 31‐kyr record from Lake Karakul and performed a set of experiments with climate models to interpret the results. δD values of terrestrial biomarkers showed insolation‐driven trends reflecting major shifts of water vapor sources. For aquatic biomarkers, positive δD shifts driven by changes in precipitation seasonality were observed at ca. 31–30, 28–26, and 17–14 kyr BP. Multiproxy paleoecological data and modelling results suggest that increased water availability, induced by decreased summer evaporation, triggered higher lake levels during those episodes, possibly synchronous to northern hemispheric rapid climate events. We conclude that seasonal changes in precipitation‐evaporation balance significantly influenced the hydrological state of a large waterbody such as Lake Karakul, while annual precipitation amount and inflows remained fairly constant

Remodelling of microRNAs in colorectal cancer by hypoxia alters metabolism profiles and 5-fluorouracil resistance

AN, HT and AP are Constance Travis post-graduate fellows. NS is a Barts and The London post-doctoral fellow. SMD is a Bowel & Cancer Research post-doctoral fellow. TS is supported by a Grant-in-Aid for scientific research on Innovative Areas, Japan (No. 22134007 to T.S.), and the Yamagata Prefectural Government and City of Tsuruoka

Epigenetic and metabolic reprogramming of fibroblasts in Crohn's disease strictures reveals histone deacetylases as therapeutic targets.

BACKGROUND & AIMS: No effective therapeutic intervention exists for intestinal fibrosis in Crohn's disease [CD]. We characterised fibroblast subtypes, epigenetic and metabolic changes, and signalling pathways in CD fibrosis to inform future therapeutic strategies. METHODS: We undertook immunohistochemistry, metabolic, signalling pathway and Epigenetic [Transposase-Accessible Chromatin using sequencing] analyses associated with collagen production in CCD-18Co intestinal fibroblasts and primary fibroblasts isolated from stricturing [SCD] and non-stricturing [NSCD] CD small intestine. SCD/ NSCD fibroblasts were cultured with TGFβ and valproic acid [VPA]. RESULTS: Stricturing CD was characterised by distinct histone deacetylase [HDAC] expression profiles, particularly HDAC1, HDAC2, and HDAC7. As a proxy for HDAC activity, reduced numbers of H3K27ac+ cells were found in SCD compared to NSCD sections. Primary fibroblasts had increased extracellular lactate [increased glycolytic activity] and intracellular hydroxyproline [increased collagen production] in SCD compared to NSCD cultures. The metabolic effect of TGFβ-stimulation was reversed by the HDAC inhibitor VPA. SCD fibroblasts appear "metabolically primed" and responded more strongly to both TGFβ and VPA. Treatment with VPA revealed TGFβ-dependent and independent Collagen-I production in CCD-18Co cells and primary fibroblasts. VPA altered the epigenetic landscape with reduced chromatin accessibility at the COL1A1 and COL1A2 promoters. CONCLUSIONS: Increased HDAC expression profiles, H3K27ac hypoacetylation, a significant glycolytic phenotype, and metabolic priming, characterise SCD-derived as compared to NSCD fibroblasts. Our results reveal a novel epigenetic component to Collagen-I regulation and TGFβ-mediated CD fibrosis. HDAC inhibitor therapy may 'reset' the epigenetic changes associated with fibrosis

Long-term monitoring in primary care for chronic kidney disease and chronic heart failure: a multi-method research programme

Background: Long-term monitoring is important in chronic condition management. Despite considerable costs of monitoring, there is no or poor evidence on how, what and when to monitor. The aim of this study was to improve understanding, methods, evidence base and practice of clinical monitoring in primary care, focusing on two areas: chronic kidney disease and chronic heart failure. Objectives: The research questions were as follows: does the choice of test affect better care while being affordable to the NHS? Can the number of tests used to manage individuals with early-stage kidney disease, and hence the costs, be reduced? Is it possible to monitor heart failure using a simple blood test? Can this be done using a rapid test in a general practitioner consultation? Would changes in the management of these conditions be acceptable to patients and carers? Design: Various study designs were employed, including cohort, feasibility study, Clinical Practice Research Datalink analysis, seven systematic reviews, two qualitative studies, one cost-effectiveness analysis and one cost recommendation. Setting: This study was set in UK primary care. Data sources: Data were collected from study participants and sourced from UK general practice and hospital electronic health records, and worldwide literature. Participant: The participants were NHS patients (Clinical Practice Research Datalink: 4.5 million patients), chronic kidney disease and chronic heart failure patients managed in primary care (including 750 participants in the cohort study) and primary care health professionals. Interventions: The interventions were monitoring with blood and urine tests (for chronic kidney disease) and monitoring with blood tests and weight measurement (for chronic heart failure). Main outcome measures: The main outcomes were the frequency, accuracy, utility, acceptability, costs and cost-effectiveness of monitoring. Results: Chronic kidney disease: serum creatinine testing has increased steadily since 1997, with most results being normal (83% in 2013). Increases in tests of creatinine and proteinuria correspond to their introduction as indicators in the Quality and Outcomes Framework. The Chronic Kidney Disease Epidemiology Collaboration equation had 2.7% greater accuracy (95% confidence interval 1.6% to 3.8%) than the Modification of Diet in Renal Disease equation for estimating glomerular filtration rate. Estimated annual transition rates to the next chronic kidney disease stage are ≈ 2% for people with normal urine albumin, 3–5% for people with microalbuminuria (3–30 mg/mmol) and 3–12% for people with macroalbuminuria (> 30 mg/mmol). Variability in estimated glomerular filtration rate-creatinine leads to misclassification of chronic kidney disease stage in 12–15% of tests in primary care. Glycaemic-control and lipid-modifying drugs are associated with a 6% (95% confidence interval 2% to 10%) and 4% (95% confidence interval 0% to 8%) improvement in renal function, respectively. Neither estimated glomerular filtration rate-creatinine nor estimated glomerular filtration rate-Cystatin C have utility in predicting rate of kidney function change. Patients viewed phrases such as ‘kidney damage’ or ‘kidney failure’ as frightening, and the term ‘chronic’ was misinterpreted as serious. Diagnosis of asymptomatic conditions (chronic kidney disease) was difficult to understand, and primary care professionals often did not use ‘chronic kidney disease’ when managing patients at early stages. General practitioners relied on Clinical Commissioning Group or Quality and Outcomes Framework alerts rather than National Institute for Health and Care Excellence guidance for information. Cost-effectiveness modelling did not demonstrate a tangible benefit of monitoring kidney function to guide preventative treatments, except for individuals with an estimated glomerular filtration rate of 60–90 ml/minute/1.73 m2, aged < 70 years and without cardiovascular disease, where monitoring every 3–4 years to guide cardiovascular prevention may be cost-effective. Chronic heart failure: natriuretic peptide-guided treatment could reduce all-cause mortality by 13% and heart failure admission by 20%. Implementing natriuretic peptide-guided treatment is likely to require predefined protocols, stringent natriuretic peptide targets, relative targets and being located in a specialist heart failure setting. Remote monitoring can reduce all-cause mortality and heart failure hospitalisation, and could improve quality of life. Diagnostic accuracy of point-of-care N-terminal prohormone of B-type natriuretic peptide (sensitivity, 0.99; specificity, 0.60) was better than point-of-care B-type natriuretic peptide (sensitivity, 0.95; specificity, 0.57). Within-person variation estimates for B-type natriuretic peptide and weight were as follows: coefficient of variation, 46% and coefficient of variation, 1.2%, respectively. Point-of-care N-terminal prohormone of B-type natriuretic peptide within-person variability over 12 months was 881 pg/ml (95% confidence interval 380 to 1382 pg/ml), whereas between-person variability was 1972 pg/ml (95% confidence interval 1525 to 2791 pg/ml). For individuals, monitoring provided reassurance; future changes, such as increased testing, would be acceptable. Point-of-care testing in general practice surgeries was perceived positively, reducing waiting time and anxiety. Community heart failure nurses had greater knowledge of National Institute for Health and Care Excellence guidance than general practitioners and practice nurses. Health-care professionals believed that the cost of natriuretic peptide tests in routine monitoring would outweigh potential benefits. The review of cost-effectiveness studies suggests that natriuretic peptide-guided treatment is cost-effective in specialist settings, but with no evidence for its value in primary care settings. Limitations: No randomised controlled trial evidence was generated. The pathways to the benefit of monitoring chronic kidney disease were unclear. Conclusions: It is difficult to ascribe quantifiable benefits to monitoring chronic kidney disease, because monitoring is unlikely to change treatment, especially in chronic kidney disease stages G3 and G4. New approaches to monitoring chronic heart failure, such as point-of-care natriuretic peptide tests in general practice, show promise if high within-test variability can be overcome

Trans-Amazon Drilling Project (TADP): origins and evolution of the forests, climate, and hydrology of the South American tropics

This article presents the scientific rationale for an ambitious ICDP drilling project to continuously sample Late Cretaceous to modern sediment in four different sedimentary basins that transect the equatorial Amazon of Brazil, from the Andean foreland to the Atlantic Ocean. The goals of this project are to document the evolution of plant biodiversity in the Amazon forests and to relate biotic diversification to changes in the physical environment, including climate, tectonism, and the surface landscape. These goals require long sedimentary records from each of the major sedimentary basins across the heart of the Brazilian Amazon, which can only be obtained by drilling because of the scarcity of Cenozoic outcrops. The proposed drilling will provide the first long, nearly continuous regional records of the Cenozoic history of the forests, their plant diversity, and the associated changes in climate and environment. It also will address fundamental questions about landscape evolution, including the history of Andean uplift and erosion as recorded in Andean foreland basins and the development of west-to-east hydrologic continuity between the Andes, the Amazon lowlands, and the equatorial Atlantic. Because many modern rivers of the Amazon basin flow along the major axes of the old sedimentary basins, we plan to locate drill sites on the margin of large rivers and to access the targeted drill sites by navigation along these rivers

Small-molecule Wnt inhibitors are a potential novel therapy for intestinal fibrosis in Crohns disease

Intestinal fibrosis and stricture formation is an aggressive complication of Crohns disease (CD), linked to increased morbidity and costs. The present study investigates the contribution of Wingless-Int-1 (Wnt) signalling to intestinal fibrogenesis, considers potential cross-talk between Wnt and transforming growth factor β1 (TGFβ) signalling pathways, and assesses the therapeutic potential of small-molecule Wnt inhibitors. β-catenin expression was explored by immunohistochemistry (IHC) in formalin-fixed paraffin embedded (FFPE) tissue from patient-matched nonstrictured (NSCD) and strictured (SCD) intestine (n=6 pairs). Functional interactions between Wnt activation, TGFβ signalling, and type I collagen (Collagen-I) expression were explored in CCD-18Co cells and primary CD myofibroblast cultures established from surgical resection specimens (n=16) using small-molecule Wnt inhibitors and molecular techniques, including siRNA-mediated gene knockdown, immunofluorescence (IF), Wnt gene expression arrays, and western blotting. Fibrotic SCD tissue was marked by an increase in β-catenin-positive cells. In vitro, activation of Wnt-β-catenin signalling increased Collagen-I expression in CCD-18Co cells. Conversely, ICG-001, an inhibitor of β-catenin signalling, reduced Collagen-I expression in cell lines and primary CD myofibroblasts. TGFβ increased β-catenin protein levels but did not activate canonical Wnt signalling. Rather, TGFβ up-regulated WNT5B, a noncanonical Wnt ligand, and the Wnt receptor FZD8, which contributed directly to the up-regulation of Collagen-I through a β-catenin-independent mechanism. Treatment of CCD-18Co fibroblasts and patient-derived myofibroblasts with the FZD8 inhibitor 3235-0367 reduced extracellular matrix (ECM) expression. Our data highlight small-molecule Wnt inhibitors of both canonical and noncanonical Wnt signalling, as potential antifibrotic drugs to treat SCD intestinal fibrosis. They also highlight the importance of the cross-talk between Wnt and TGFβ signalling pathways in CD intestinal fibrosis