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

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

Effect of calcium from dairy and dietary supplements on faecal fat excretion: a meta-analysis of randomized controlled trials.

Summary Observational studies have found that dietary calcium intake is inversely related to body weight and body fat mass. One explanatory mechanism is that dietary calcium increases faecal fat excretion. To examine the effect of calcium from dietary supplements or dairy products on quantitative faecal fat excretion, we performed a systematic review with meta-analysis. We included randomized, controlled trials of calcium (supplements or dairy) in healthy subjects, where faecal fat excretion was measured. Meta-analyses used random-effects models with changes in faecal fat excreted expressed as standardized mean differences, as the studies assessed the same outcome but measured in different ways. An increased calcium intake resulted in increased excretion of faecal fat by a standardized mean difference of 0.99 (95% confidence intervals: 0.63-1.34; P < 0.0001; expected to correspond to approximately 2g day(-1)) with moderate heterogeneity (I(2) = 49.5%) indicating some inconsistency in trial outcomes. However, the dairy trials showed homogeneous outcomes (I(2)=0%) indicating consistency among these trials. We estimated that increasing the dairy calcium intake by 1241 mg day(-1) resulted in an increase in faecal fat of 5.2 (1.6-8.8) g day(-1). In conclusion, dietary calcium has the potential to increase faecal fat excretion to an extent that could be relevant for prevention of weight (re-)gain. Long-term studies are required to establish its potential contribution

Appetite sensations and substrate metabolism at rest, during exercise, and recovery: impact of a high-calcium meal

The aim of this study was to investigate the effects of the calcium content of a high-carbohydrate, pre-exercise meal on substrate metabolism and appetite sensations before, during, and after exercise. Nine active males participated in 2 trials in a double-blind, randomised, crossover design. After consuming a high carbohydrate (1.5 g.kg(-1) of body mass) breakfast with a calcium content of either 3 (control trial) or 9 mg.kg(-1) of body mass (high milk-calcium (CAL)), participants ran at 60\% peak oxygen uptake for 60 min. Following exercise, a recovery drink was consumed and responses were investigated for a further 90 min. Blood and expired gas were sampled throughout to determine circulating substrate and hormone concentrations and rates of substrate oxidation. Visual analogue scales were also administered to determine subjective appetite sensations. Neither whole-body lipid oxidation nor non-esterified fatty acid availability differed between trials. The area under the curve for the first hour following breakfast consumption was 16\% (95\% confidence interval: 0\%-35\%) greater for fullness and 10\% (95\% confidence interval: 2\%-19\%) greater for insulin in the CAL trial but these differences were transient and not apparent later in the trial. This study demonstrates that increasing the calcium content of a high carbohydrate meal transiently increases insulinemia and fullness but substrate metabolism is unaffected

Synthesis and biological evaluation of disubstituted N6- cyclopentyladenine analogues: The search for a neutral antagonist with high affinity for the adenosine A1 receptor

Novel 3,8- and 8,9-disubstituted N6-cyclopentyladenine derivatives were synthesised in moderate overall yield from 6-chloropurine. The derivatives were made in an attempt to find a new neutral antagonist with high affinity for adenosine A1 receptors. N6-Cyclopentyl-9- methyladenine (N-0840) was used as a lead compound. Binding affinities of the new analogues were determined for human adenosine A1 and A 3 receptors. Their intrinsic activity was assessed in [ 35S]GTPγS binding experiments. Elongation of the 9-methyl of N-0840 to a 9-propyl substituent was very well tolerated. A 9-benzyl group, on the other hand, caused a decrease in adenosine A1 receptor affinity. Next, the 8-position was examined in detail, and affinity was increased with appropriate substitution. Most derivatives were A1-selective and 20 of the new compounds (6-9, 15-21, 23-26, 28, 31, 33, 35, and 36) had higher adenosine A1 receptor affinity than the reference substance, N-0840. Compound 31 (N6-cyclopentyl-8-(N-methylisopropylamino)-9- methyladenine, LUF 5608) had the highest adenosine A1 receptor affinity, 7.7 nM. In the [35S]GTPγS binding experiments, derivatives 5, 14, 22, 23, 25, 26, 33 and 34 did not significantly change basal [35S]GTPγS binding, thus behaving as neutral antagonists. Moreover, four of these compounds (23, 25, 26, and 33) displayed a 4- to 10-fold increased adenosine A1 receptor affinity (75-206 nM) compared to N-0840 (852 nM). In summary, we synthesised a range of N-0840 analogues with higher affinity for adenosine A1 receptors. In addition, four new derivatives, LUF 5666 (23), LUF 5668 (25), LUF 5669 (26) and LUF 5674 (33), behaved as neutral antagonists when tested in [ 35S]GTPγS binding studies. Thus, these compounds have improved characteristics as neutral adenosine A1 receptor antagonists. © 2003 Elsevier Ltd. All rights reserved