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

The Antinociceptive Properties of the Corydalis <i>yanhusuo</i> Extract

<div><p>Corydalis <i>yanhusuo</i>. W.T. extracts (YHS) are widely used for the treatment of pain and inflammation. There are a few studies that assessed the effects of YHS in pain assays; however, none of these studies has systematically compared its activities in the different pain animal modes namely: acute, inflammatory and chronic pain. Furthermore, little is known about the mechanism of YHS activity in these assays. The aim of this study was to systematically evaluate the antinociceptive properties of YHS by testing it in four standardized pain assays and to investigate its mechanism. YHS antinociceptive properties were analyzed in the tail flick, the formalin paw licking, the von Frey filament and the hot box assays after spinal nerve ligation, which monitors acute nociceptive, persistent inflammatory and chronic neuropathic pain, respectively. YHS pharmacological profile was determined by screening it against a battery of G-protein coupled receptors and its mechanism of action was studied using knock-out mice. Our study shows that YHS, at a non-sedative dose, increases the tail flick latency in the tail flick assay without resulting in development of tolerance. YHS also decreases paw licking time in the formalin assay. Further, YHS increases paw withdraw threshold and latency in the von Frey filament and the hot box assays, respectively. <i>In vitro</i>, YHS exhibits prominent dopamine receptor antagonistic properties. In dopamine D2 receptor knockout mice, its antinociceptive effects are attenuated in acute and neuropathic pain but not inflammatory pain assays. Our results therefore indicate that YHS effectively attenuates acute, inflammatory and neuropathic pain, without causing tolerance. The effects on acute and neuropathic pain, but not inflammatory pain, are at least partially mediated through dopamine D2 receptor antagonism. Since YHS is a dietary supplement commercially available in the United States, our data suggest that it might be a candidate for alternative pain treatment.</p></div

A novel analgesic isolated from a traditional Chinese medicine.

BackgroundCurrent pain management is limited, in particular, with regard to chronic pain. In an attempt to discover novel analgesics, we combined the approach developed to characterize traditional Chinese medicine (TCM), as part of the "herbalome" project, with the reverse pharmacology approach aimed at discovering new endogenous transmitters and hormones.ResultsIn a plant used for centuries for its analgesic properties, we identify a compound, dehydrocorybulbine (DHCB), that is effective at alleviating thermally induced acute pain. We synthesize DHCB and show that it displays moderate dopamine receptor antagonist activities. By using selective pharmacological compounds and dopamine receptor knockout (KO) mice, we show that DHCB antinociceptive effect is primarily due to its interaction with D2 receptors, at least at low doses. We further show that DHCB is effective against inflammatory pain and injury-induced neuropathic pain and furthermore causes no antinociceptive tolerance.ConclusionsOur study casts DHCB as a different type of analgesic compound and as a promising lead in pain management

A novel analgesic isolated from a traditional Chinese medicine.

BackgroundCurrent pain management is limited, in particular, with regard to chronic pain. In an attempt to discover novel analgesics, we combined the approach developed to characterize traditional Chinese medicine (TCM), as part of the "herbalome" project, with the reverse pharmacology approach aimed at discovering new endogenous transmitters and hormones.ResultsIn a plant used for centuries for its analgesic properties, we identify a compound, dehydrocorybulbine (DHCB), that is effective at alleviating thermally induced acute pain. We synthesize DHCB and show that it displays moderate dopamine receptor antagonist activities. By using selective pharmacological compounds and dopamine receptor knockout (KO) mice, we show that DHCB antinociceptive effect is primarily due to its interaction with D2 receptors, at least at low doses. We further show that DHCB is effective against inflammatory pain and injury-induced neuropathic pain and furthermore causes no antinociceptive tolerance.ConclusionsOur study casts DHCB as a different type of analgesic compound and as a promising lead in pain management

Effects of YHS in D2KO mice assessed in the tail flick and formalin paw licking assays.

<p>(A) Effects of YHS (200 mg/kg) in D2KO mice assessed in the tail flick assay (n = 10). Tail-flick latencies were measured 120 min following drug administration. One-way ANOVA indicated a significant drug effect (F_3,36 = 12.53, P < 0.0001) followed by Bonferroni post hoc test: YHS vs vehicle, *** <i>P</i> < 0.001, N.S., not significant; KO vs WT, ^## <i>P</i> < 0.01. (B) Effects of YHS (200 mg/kg) in D2KO mice assessed in the formalin paw licking assay (n = 6). One-way ANOVA indicated significant drug effects in both Phase I (F_3,20 = 8.751, P = 0.0007) and Phase II (F_3,20 = 19.01, P < 0.0001) followed by Bonferroni post hoc test: YHS vs vehicle, *<i>P</i> < 0.05, **<i>P</i> < 0.01, *** <i>P</i> < 0.001; KO vs WT, N.S., not significant.</p

Effects of YHS in D2KO mice assessed in the von Frey filaments and hot box assays.

<p>(A) Effects of YHS (200 mg/kg) in WT mice assessed in the von Frey filaments assay after SNL (n = 10). Paw withdraw thresholds were measured 60 minutes after drug administration. Two way ANOVA revealed a significant treatment effect (F_3,36 = 12.81, P < 0.0001) and time effect (F_1,36 = 7.244, P = 0.0107) followed by Bonferroni post hoc test: contralateral vs. ipsilateral, **<i>P</i> < 0.01, *** <i>P</i> < 0.001, N.S., not significant; YHS vs vehicle, ^# <i>P</i> < 0.05. (B) Effects of YHS (200 mg/kg) in D2KO mice assessed in the von Frey filaments assay after SNL (n = 10). Paw withdraw thresholds were measured 60 minutes after drug administration. Two way ANOVA revealed a significant treatment effect (F_3,36 = 17.00, P < 0.0001) and time effect (F_1,36 = 6.340, P = 0.0164) followed by Bonferroni post hoc test: contralateral vs. ipsilateral, *<i>P</i> < 0.05, **<i>P</i> < 0.01; YHS vs vehicle, ^# <i>P</i> < 0.05, N.S., not significant. (C) Paw withdraw threshold (PWT) difference between contralateral (Contra) and ipsilateral (Ipsi) paws in WT and D2KO mice assessed in the von Frey filaments assay 60 minutes after YHS (200 mg/kg) administration (n = 10): t = 2.281, <i>P</i> = 0.0349. Unpaired student t test, KO vs WT, *<i>P</i> < 0.05. (D) Effects of YHS (200 mg/kg) in WT mice assessed in the hot box assay after SNL (n = 10). Paw withdraw latencies were measured 60 minutes after drug administration. Two way ANOVA revealed a significant treatment effect (F_3,36 = 66.27, P < 0.0001), time effect (F_1,36 = 34.40, P < 0.0001) and drug x time interaction (F_3,36 = 19.38, P < 0.0001) followed by Bonferroni post hoc test: contralateral vs. ipsilateral, *<i>P</i> < 0.05, *** <i>P</i> < 0.001; YHS vs vehicle, ^### <i>P</i> < 0.001, N.S., not significant. (E) Effects of YHS (200 mg/kg) in D2KO mice assessed in the hot box assay after SNL (n = 9–10). Paw withdraw latencies were measured 60 minutes after drug administration. Two way ANOVA revealed a significant treatment effect (F_3,34 = 75.99, P < 0.0001), time effect (F_1,34 = 25.25, P < 0.0001) and drug x time interaction (F_3,34 = 6.119, P = 0.0019) followed by Bonferroni post hoc test: contralateral vs. ipsilateral, *** <i>P</i> < 0.001; YHS vs vehicle, ^### <i>P</i> < 0.001, N.S., not significant. (F) Paw withdraw latency (PWL) difference between contralateral (Contra) and ipsilateral (Ipsi) paws in WT and D2KO mice assessed in the hot box assay 60 minutes after YHS (200 mg/kg) administration (n = 9–10): t = 1.394, <i>P</i> = 0.1812. Unpaired student t test, N.S., not significant.</p

Antinociceptive effects of YHS in acute, inflammatory and neuropathic pain models.

<p>(A) Antinociceptive effects of YHS (100–500 mg/kg) in the tail flick assay (n = 7–9). Two way ANOVA revealed significant drug effects (F_6,49 = 38.26, P < 0.0001), time effect (F_4,196 = 59.93, P < 0.0001) and drug x time interaction (F_24,196 = 14.15, P < 0.0001) followed by Bonferroni post hoc test: drug vs vehicle, *<i>P</i> < 0.05, **<i>P</i> < 0.01, *** <i>P</i> < 0.001. (B) Comparison between YHS (500 mg/kg) and the mixture of l-THP (1 mg/kg) and DHCB (1 mg/kg) in the tail flick assay (n = 8–9). Tail-flick latencies were measured 60 min following drug administration. One way ANOVA revealed a significant drug effect (F_2,22 = 42.85, P < 0.0001) followed by Bonferroni post hoc test: drug vs vehicle, *** <i>P</i> < 0.001, N.S., not significant; YHS vs L-THP+DHCB, ^### <i>P</i> < 0.001. (C) Time course of the antinociceptive effects of YHS (200 mg/kg) in the formalin paw licking assay (n = 6–7). Two way ANOVA revealed significant drug effects (F_2,17 = 36.59, P < 0.0001) and time effect (F_9,153 = 10.22, P < 0.0001) followed by Bonferroni post hoc test: drug vs vehicle, *<i>P</i> < 0.05, **<i>P</i> < 0.01, *** <i>P</i> < 0.001. (D) Cumulative effects of the antinociceptive effects of YHS (200 mg/kg) in the formalin paw licking assay (n = 6–7). One-way ANOVA indicated significant drug effects in both Phase I (F_2,17 = 34.92, P < 0.0001) and Phase II (F_2,17 = 31.68, P < 0.0001) followed by Dunnett’s post hoc tests: drug vs vehicle, **<i>P</i> < 0.01, *** <i>P</i> < 0.001. (E) Antinociceptive effects of YHS (200 mg/kg) in the von Frey filament assay after spinal nerve ligation (n = 10). Two way ANOVA revealed a significant treatment effect (F_3,36 = 11.42, P < 0.0001) followed by Bonferroni post hoc test: contralateral vs. ipsilateral, *** <i>P</i> < 0.001. (F) Antinociceptive effects of YHS (200 mg/kg) in the hot box assay after spinal nerve ligation (n = 10). Two way ANOVA revealed a significant treatment effect (F_3,36 = 31.06, P < 0.0001) and drug x time interaction (F_9,108 = 3.045, P = 0.0028) followed by Bonferroni post hoc test: *<i>P</i> < 0.05, *** <i>P</i> < 0.001.</p