13 research outputs found

    Large expert-curated database for benchmarking document similarity detection in biomedical literature search

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    Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

    Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

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    SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

    Beyond climate envelopes:bio-climate modelling accords with observed 25-year changes in seabird populations of the British Isles

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    Aim: Climate envelope models (CEMs) are used to assess species’ vulnerabilityto predicted changes in climate, based on their distributions. Extinction risk,however, also depends on demographic parameters. Accordingly, we use CEMsfor 18 seabird species to test three hypotheses: (i) population sizes are larger inareas where CEMs fitted using distribution data predict more suitable climate;(ii) the presence of this relationship (Hypothesis i) is related to a species’ foraging ecology; and (iii) species whose distributions and population sizes conformed most closely to indices of climatic suitability in the mid-1980sexperienced the largest population changes following climatic change between1986 and 2010.Location: Europe.Methods: Climate envelope models fitted at a 50-km resolution using Europeanclimatic and distribution data were applied using local climatic data tocalculate local climatic suitability indices (CSIs) for 18 species within the BritishIsles. We then investigated the relationship between CSI and population size ata 10-km resolution and related both the presence of this relationship and goodness-of-fit metrics from the European models to changes in population size (1986–2010).Results: Local population sizes were significantly positively related to local CSIin 50% of species, providing support for Hypothesis (i), and these 50% of specieswere independently considered to be most vulnerable to changes in foodavailability at sea in support of Hypothesis (ii). Those species whose distributionsand populations most closely conformed to indices of climatic suitabilityshowed the least favourable subsequent changes in population size, over a period in which mean climatic suitability decreased for all species, in support ofHypothesis (iii).Main conclusions: Climate influences the population sizes of multiple seabirdspecies in the British Isles. We highlight the potential for outputs of CEMs fittedwith coarse resolution occupancy data to provide information on both localabundance and sensitivity to future climate changes

    Keramische Nanokomposite: Optimierung des Syntheseverfahrens im Sinne einer Durchsatzerhoehung und Qualitaetsverbesserung Abschlussbericht

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    SIGLEAvailable from TIB Hannover: F00B1308 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Bildung und Forschung, Berlin (Germany)DEGerman

    A-Ring Dihalogenation Increases the Cellular Activity of Combretastatin-Templated Tetrazoles

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    The combretastatins have been investigated for their antimitotic and antivascular properties, and it is widely postulated that a 3,4,5-trimethoxyaryl A-ring is essential to maintain potent activity. We have synthesized new tetrazole analogues (<b>32</b>–<b>34</b>), demonstrating that 3,5-dihalogenation can consistently increase potency by up to 5-fold when compared to the equivalent trimethoxy compound on human umbilical vein endothelial cells (HUVECs) and a range of cancer cells. Moreover, this increased potency offsets that lost by installing the tetrazole bridge into combretastatin A-4 (<b>1</b>), giving crystalline, soluble compounds that have low nanomolar activity, arrest cells in G<sub>2</sub>/M phase, and retain microtubule inhibitory activity. Molecular modeling has shown that optimized packing within the binding site resulting in increased Coulombic interaction may be responsible for this improved activity
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