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Find video protocols related to scientific articles indexed in Pubmed.
Tramadol and O-Desmethyl Tramadol Clearance Maturation and Disposition in Humans: A Pooled Pharmacokinetic Study.
Clin Pharmacokinet
PUBLISHED: 09-27-2014
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We aimed to study the impact of size, maturation and cytochrome P450 2D6 (CYP2D6) genotype activity score as predictors of intravenous tramadol disposition.
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Intake of St. John's wort improves the glucose tolerance in healthy subjects that ingest metformin compared to metformin alone.
Br J Clin Pharmacol
PUBLISHED: 09-20-2014
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Our object was to investigate the steady-state pharmacokinetic and pharmacodynamic interaction between the antidepressive herbal medicine St. John's wort (SJW) and the antidiabetic drug metformin.
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CYP2C19*17 increases the clopidogrel-mediated platelet inhibition but does not alter the pharmacokinetics of the active metabolite of clopidogrel.
Clin. Exp. Pharmacol. Physiol.
PUBLISHED: 08-12-2014
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The purposes were to determine the impact of CYP2C19*17 on the pharmacokinetics and pharmacodynamics of the active metabolite of clopidogrel and the pharmacokinetics of proguanil. Thus, we conducted an open-label, two-phase cross-over study in 31 healthy male volunteers (11 CYP2C19*1/*1, 11 CYP2C19*1/*17 and 9 CYP2C19*17/*17). In phase A, the pharmacokinetics of the derivatized active metabolite of clopidogrel (CAMD) and the platelet function were determined after administration of a single oral dose of 600 mg clopidogrel (Plavix(®) ). In phase B, the pharmacokinetics of proguanil and its metabolites, cycloguanil and 4-chlorphenylbiguanide, were determined in 29 of the 31 subjects after a single oral dose of 200 mg proguanil given as the combination drug Malarone(®) . Statistically significant correlations between the area under the time-concentration curve (AUC0-? ) of CAMD on the one hand and both the absolute ADP-induced P2Y12 -activated platelet aggregation (PRU) (r=-0.60, p=0.0007) and the percent inhibition of aggregation (r=0.59, p=0.0009) on the other hand were found. Besides, the CYP2C19*17/*17 and CYP2C19*1/*17 genotype groups had statistically significantly higher percent inhibition of platelet aggregation compared to the group of CYP2C19*1/*1 subjects (geometric mean of 84%, 73% and 63%, respectively, p=0.014). Neither the PRU, the exposure to CAMD nor the pharmacokinetic parameters of proguanil, cycloguanil and 4-chlorphenylbiguanide showed any statistically significant differences between the genotype groups. In conclusion, carriers of CYP2C19*17 display higher percent inhibition of platelet aggregation but do not have significantly lower absolute P2Y12 -activated platelet aggregation or higher exposure of the active metabolite after a single oral administration of 600 mg clopidogrel. This article is protected by copyright. All rights reserved.
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Design and fabrication of memory devices based on nanoscale polyoxometalate clusters.
Nature
PUBLISHED: 06-26-2014
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Flash memory devices-that is, non-volatile computer storage media that can be electrically erased and reprogrammed-are vital for portable electronics, but the scaling down of metal-oxide-semiconductor (MOS) flash memory to sizes of below ten nanometres per data cell presents challenges. Molecules have been proposed to replace MOS flash memory, but they suffer from low electrical conductivity, high resistance, low device yield, and finite thermal stability, limiting their integration into current MOS technologies. Although great advances have been made in the pursuit of molecule-based flash memory, there are a number of significant barriers to the realization of devices using conventional MOS technologies. Here we show that core-shell polyoxometalate (POM) molecules can act as candidate storage nodes for MOS flash memory. Realistic, industry-standard device simulations validate our approach at the nanometre scale, where the device performance is determined mainly by the number of molecules in the storage media and not by their position. To exploit the nature of the core-shell POM clusters, we show, at both the molecular and device level, that embedding [(Se(iv)O3)2](4-) as an oxidizable dopant in the cluster core allows the oxidation of the molecule to a [Se(v)2O6](2-) moiety containing a {Se(v)-Se(v)} bond (where curly brackets indicate a moiety, not a molecule) and reveals a new 5+ oxidation state for selenium. This new oxidation state can be observed at the device level, resulting in a new type of memory, which we call 'write-once-erase'. Taken together, these results show that POMs have the potential to be used as a realistic nanoscale flash memory. Also, the configuration of the doped POM core may lead to new types of electrical behaviour. This work suggests a route to the practical integration of configurable molecules in MOS technologies as the lithographic scales approach the molecular limit.
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Mitigation of methane emission from an old unlined landfill in Klintholm, Denmark using a passive biocover system.
Waste Manag
PUBLISHED: 01-21-2014
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Methane generated at landfills contributes to global warming and can be mitigated by biocover systems relying on microbial methane oxidation. As part of a closure plan for an old unlined landfill without any gas management measures, an innovative biocover system was established. The system was designed based on a conceptual model of the gas emission patterns established through an initial baseline study. The study included construction of gas collection trenches along the slopes of the landfill where the majority of the methane emissions occurred. Local compost materials were tested as to their usefulness as bioactive methane oxidizing material and a suitable compost mixture was selected. Whole site methane emission quantifications based on combined tracer release and downwind measurements in combination with several local experimental activities (gas composition within biocover layers, flux chamber based emission measurements and logging of compost temperatures) proved that the biocover system had an average mitigation efficiency of approximately 80%. The study showed that the system also had a high efficiency during winter periods with temperatures below freezing. An economic analysis indicated that the mitigation costs of the biocover system were competitive to other existing greenhouse gas mitigation options.
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Macroecological evidence for competitive regional-scale interactions between the two major clades of mammal carnivores (Feliformia and Caniformia).
PLoS ONE
PUBLISHED: 01-01-2014
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Geographical gradients in species diversity are often explained by environmental factors such as climate and productivity. Biotic interactions play a key role in evolutionary diversification and may therefore also affect diversity patterns, but this has rarely been assessed. Here, we investigate whether negative competitive interactions shape the diversity patterns of the two major mammalian clades of carnivores, the suborders Caniformia (dogs and allies) and Feliformia (cats and allies) within the order Carnivora. We specifically test for a negative effect of feliform species richness on caniform species richness by a natural experiment, The Great American Interchange, which due to biogeographic lineage history and climate patterns caused tropical South America to be colonized by most caniform families, but only one feliform family. To this end we used regression modelling to investigate feliform and caniform richness patterns and their determinants with emphasis on contrasting the Old and New World tropics. We find that feliform richness is elevated in the Old World Tropics, while caniform richness is elevated in the New World Tropics. Models based on environmental variables alone underpredict caniform richness and overpredict feliform richness in the New World and vice versa in the Old World. We further show that models including feliform richness as a predictor for caniform species richness significantly improve predictions at the continental scale, albeit not at finer scales. Our results are consistent with a negative effect of feliforms on regional-scale caniform diversification within the tropics, probably indicating that niche space occupancy by the one clade constrains diversification in the other in the build-up of regional faunas, while negative interactions at smaller scales may be unimportant due to niche differentiation within the regional faunas.
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[Ketamine for treatment of acute depression].
Ugeskr. Laeg.
PUBLISHED: 09-10-2013
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In clinical trials a single dose of the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has shown a rapid antidepressant effect in patients with treatment-resistant depression and bipolar depression. The implications of glutaminergic mechanisms in depression and the rapid effect of a single dose of ketamine could open new pathways to understand the pathophysiology of depression and the development of novel rapid-acting antidepressant drugs.
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A gene-gene interaction between polymorphisms in the OCT2 and MATE1 genes influences the renal clearance of metformin.
Pharmacogenet. Genomics
PUBLISHED: 07-23-2013
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The aim of this study was to determine the association between the renal clearance (CL(renal)) of metformin in healthy Caucasian volunteers and the single-nucleotide polymorphism (SNP) c.808G>T (rs316019) in OCT2 as well as the relevance of the gene-gene interactions between this SNP and (a) the promoter SNP g.-66T>C (rs2252281) in MATE1 and (b) the OCT1 reduced-function diplotypes.
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A cytochrome P450 phenotyping cocktail causing unexpected adverse reactions in female volunteers.
Eur. J. Clin. Pharmacol.
PUBLISHED: 06-11-2013
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A four-drug cytochrome P450 (CYP) phenotyping cocktail was developed to rapidly and safely determine CYP2D6, CYP2C19, CYP2C9 and CYP1A2 enzyme activity and phenotype.
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[Weight loss pills purchased on the internet as the cause of ventricular fibrillation].
Ugeskr. Laeg.
PUBLISHED: 03-14-2013
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We present a case regarding a 25-year-old woman who had been taking unauthorized weight loss pills prior to a sudden cardiac arrest from which she was resuscitated by paramedics. Her initial electrocardiogram revealed a prolonged corrected QT-interval (QTc). During admission she developed torsades de pointes and was treated with magnesium sulphate and temporary pacing. An electrophysiological study, a coronary angiogram and genetic testing for long QT syndrome all revealed normal results. After cessation of the pills the QTc normalized, and two weeks later she was discharged.
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Inhibitory effect of oral contraceptives on CYP2C19 activity is not significant in carriers of the CYP2C19*17 allele.
Clin. Exp. Pharmacol. Physiol.
PUBLISHED: 03-13-2013
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(1) The purpose of the present study was to examine whether cytochrome P450 2C19 (CYP2C19) in carriers of the CYP2C19*17 allele is inhibited in vivo by oral contraceptives (OC). (2) Retrospective CYP2C19 phenotyping according to omeprazole : 5-OH-omeprazole molar 3 h plasma metabolic ratios (MR) from a population (n = 222) genotyped as CYP2C19*1/*1, CYP2C19*1/*17 and CYP2C19*17/*17 was analysed. Furthermore, 30 women genotyped as CYP2C19*1/*1 (n = 11), CYP2C19*1/*17 (n = 11) and CYP2C19*17/*17 (n = 8) were prospectively CYP2C19 phenotyped during the administration of OC and again after a minimum 5 days break from OC. (3) We found a significantly higher MR in the CYP2C19*1/*1 genotype group that took OC (n = 48) compared with women who did not take OC (n = 31; geometric mean 1.37 vs. 0.83, respectively; P < 0.05). However, in the CYP2C19*1/*17 genotype group, the geometric means of the MR in the 37 women taking OC and the 20 women not taking OC were 0.67 and 0.46, respectively (P > 0.05). In the CYP2C19*1/*1 panel of the prospective cross-over study, we found a significantly higher MR while women were taking the OC compared with the MR during the OC break (geometric mean 1.21 vs. 0.91, respectively; P = 0.0123). However, in the CYP2C19*1/*17 group, the geometric means of the MR with and without OC were 0.77 and 0.65, respectively, compared with 1.05 and 0.79, respectively, in the CYP2C19*17/*17 group (P = 0.20 and 0.17, respectively). (4) In conclusion, we have shown that OC intake inhibits CYP2C19 in homozygous carriers of the CYP2C19 wild type but that the inhibition is not significant in heterozygous and homozygous carriers of the CYP2C19*17 allele.
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Label-free segmentation of Co-cultured cells on a nanotopographical gradient.
Nano Lett.
PUBLISHED: 01-02-2013
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The function and fate of cells is influenced by many different factors, one of which is surface topography of the support culture substrate. Systematic studies of nanotopography and cell response have typically been limited to single cell types and a small set of topographical variations. Here, we show a radical expansion of experimental throughput using automated detection, measurement, and classification of co-cultured cells on a nanopillar array where feature height changes continuously from planar to 250 nm over 9 mm. Individual cells are identified and characterized by more than 200 descriptors, which are used to construct a set of rules for label-free segmentation into individual cell types. Using this approach we can achieve label-free segmentation with 84% confidence across large image data sets and suggest optimized surface parameters for nanostructuring of implant devices such as vascular stents.
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Regulation of CYP2C19 expression by estrogen receptor ?: implications for estrogen-dependent inhibition of drug metabolism.
Mol. Pharmacol.
PUBLISHED: 07-30-2010
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Cytochrome P4502C19 (CYP2C19) is an important drug-metabolizing enzyme involved in the biotransformation of, for example, proton pump inhibitors and antidepressants. Several in vivo studies have shown that the CYP2C19 activity is inhibited by oral contraceptives, which can cause important drug interactions. The underlying molecular mechanism has been suggested to be competitive inhibition. However, the results presented here indicate that estradiol derivatives down-regulate CYP2C19 expression via estrogen receptor (ER) ?, which interacts with the newly identified ER-binding half site [estrogen response element (ERE)] at the position -151/-147 in the CYP2C19 promoter. In gene reporter experiments in Huh-7 hepatoma cells, the activity of the luciferase construct carrying a 1.6-kb long CYP2C19 promoter fragment cotransfected with ER? was down-regulated upon treatment with 17?-estradiol (EE) or 17?-ethinylestradiol (ETE) at half-maximum concentrations of 10(-7) and 10(-8) M, respectively. Mutations introduced into the ERE half site -151/-147 significantly inhibited these ligand-dependent effects. Electrophoretic mobility shift assays and quantitative chromatin immunoprecipitation experiments revealed that estrogen receptor ? binds to this element. A significant suppression of CYP2C19 transcription by female sex steroids was confirmed by reverse transcription polymerase chain reaction after hormonal treatment of human hepatocytes. Inhibition experiments using a stable human embryonic kidney 293 CYP2C19 cell line revealed competitive inhibition at much higher concentrations of EE and ETE compared with those required for transcriptional inhibition. These results indicate that both EE and ETE inhibit CYP2C19 expression via an ER?-dependent regulatory pathway, thus providing a new insight into the molecular mechanism behind the inhibitory effect of oral contraceptives on CYP2C19 activity.
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Linkage disequilibrium between the CYP2C19*17 allele and wildtype CYP2C8 and CYP2C9 alleles: identification of CYP2C haplotypes in healthy Nordic populations.
Eur. J. Clin. Pharmacol.
PUBLISHED: 06-03-2010
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To determine the distribution of clinically important CYP2C genotypes and allele frequencies in healthy Nordic populations with special focus on linkage disequilibrium.
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The transcription factor GATA-4 regulates cytochrome P4502C19 gene expression.
Life Sci.
PUBLISHED: 02-24-2010
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Cytochrome P4502C19 (CYP2C19) is an important enzyme involved in the metabolism of antiulcer drugs and antidepressants. However, despite the well documented drug-dependent variability of CYP2C19 expression, the mechanisms underlying the regulation of the enzyme remain unknown. In this study we investigated whether the transcription factor family GATA is involved in the regulation of CYP2C19 gene expression.
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Two separate dose-dependent effects of paroxetine: mydriasis and inhibition of tramadols O-demethylation via CYP2D6.
Eur. J. Clin. Pharmacol.
PUBLISHED: 02-17-2010
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To investigate paroxetines putative dose-dependent impact on pupil reaction and inhibition of the O-demethylation of tramadol.
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New insights into the regulation of CYP2C9 gene expression: the role of the transcription factor GATA-4.
Drug Metab. Dispos.
PUBLISHED: 12-07-2009
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CYP2C9 is an important drug-metabolizing enzyme that metabolizes, e.g., warfarin, antidiabetics, and antiphlogistics. However, the endogenous regulation of this enzyme is largely unknown. In this study, we examined the role of GATA transcription factors in the gene expression of CYP2C9. We investigated four putative GATA binding sites within the first 200 base pairs of CYP2C9 promoter at the positions I: -173/-170, II: -167/-164, III: -118/-115, and IV: -106/-103. Luciferase activity driven by a wild-type CYP2C9 promoter construct was strongly up-regulated in Huh-7 cells upon cotransfection with expression plasmids for GATA-2 and GATA-4, whereas mutations introduced into GATA binding site III or I and II reduced this induction to a significant extent. Electrophoretic mobility shift assays revealed specific binding of GATA-4 and GATA-6 to the oligonucleotides containing GATA binding sites I and II. Furthermore, the association of GATA-4 with CYP2C9 promoter was confirmed by chromatin immunoprecipitation assays in HepG2 cells. Taken together, these data strongly suggest an involvement of liver-specific transcription factor GATA-4 in the transcriptional regulation of CYP2C9.
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Degradation of the potato glycoalkaloid alpha-solanine in three agricultural soils.
Chemosphere
PUBLISHED: 04-01-2009
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The toxic glycoalkaloids produced by the potato plant (Solanum tuberosum L.) have previously been found in upper soil from a potato field during several months. Further insight into the fate of the glycoalkaloids is needed, as only little information about their degradation in soil is available. Degradation of the glycoalkaloid, alpha-solanine, has been followed for 42d in three agricultural soils with common texture and carbon contents. A similar degradation pattern was found in all soils, and the kinetics was well described by a sum of two first-order equations. Overall, degradation rates for the initial first reaction were in the range 0.22-1.64d(-1). Estimated half-lives were in the range 1.8-4.1d for the three top soils at 15 degrees C; the fastest degradation was observed in the sandy soil. The major proportion of alpha-solanine in the sandy soil was degraded by the fast process, while the proportion was lower for the two other soils. Fast degradation appeared to be related to the presence of low amount of sorbents. Additionally, degradation was followed at 5 degrees C in A- and C-horizon soil from the sandy location, and for both horizons the half-lives were of similar length (4.7-8.7d). For the slow process, degradation rates were in the range 0.000-0.123d(-1), and residuals were still present in all soils and all temperatures at the end of the experiment (d 42). Overall, fast degradation was found in both top- and subsoil even at low temperatures, and the risk for alpha-solanine leaching to the groundwater appears to be low.
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The hypoalgesic effect of oxycodone in human experimental pain models in relation to the CYP2D6 oxidation polymorphism.
Basic Clin. Pharmacol. Toxicol.
PUBLISHED: 02-27-2009
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Oxycodone is O-demethylated by CYP2D6 to oxymorphone which is a potent micro-receptor agonist. The CYP2D6 oxidation polymorphism divides the Caucasian population in two phenotypes: approximately 8% with no enzyme activity, poor metabolizers (PM) and the remainder with preserved CYP2D6 activity, extensive metabolizers (EM). The objective of the study was to determine if the analgesic effect of oxycodone in human experimental pain depends on its metabolism to oxymorphone. The analgesic effect of oxycodone was evaluated in a randomized, placebo-controlled, double-blinded, crossover experiment including 33 (16 EM and 17 PM) healthy volunteers. Pain tests were performed before and 1, 2, 3 and 4 hr after medication and included pain detection and tolerance thresholds to single electrical sural nerve stimulation, pain summation threshold to repetitive electrical sural nerve stimulation and the cold pressor test with rating of discomfort and pain-time area under curve (AUC(0-2 min.)). For single sural nerve stimulation, there was a less pronounced increase in thresholds on oxycodone in pain detection (9% vs. 20%, P = 0.02, a difference of 11%, CI: 2%-20%) and pain tolerance thresholds (15% vs. 26%, P = 0.037, a difference of 10%, CI: 1%-20%) for PM compared with EM. In the cold pressor test, there was less reduction in pain AUC on oxycodone for PM compared with EM (14% vs. 26%, P = 0.012, a difference of 12%, CI: 3%-22%). The plasma oxymorphone/oxycodone ratio was significantly lower in PM compared with EM (P < 0.001). Oxycodone analgesia seems to depend both on oxycodone itself and its metabolite oxymorphone.
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A dual gradient assay for the parametric analysis of cell-surface interactions.
Small
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Cellular response to microgrooves is addressed using a new assay format, comprising orthogonal gradients of continuously varied groove pitch and depth. Dual layer etch masks are created using a combination of micropatterning and plasma polymer deposition. A silicon substrate with a constant groove width of 8 ?m and with ridge width increasing from 8 ?m in 0.5 ?m steps across 10 mm is fabricated by photolithography. A plasma-polymerized hexane film which is 120 nm thick at one end of these grooves, and 10 nm at the other, is deposited under a diffusion mask. Reactive etching of the patterned sample transfers a gradient of groove pitch and groove depth into the silicon substrate. A silicon master with a gradient of groove depth spanning more than two orders of magnitude (less than 10 nm to over 1000 nm) is used to create an injection molding inlay for mass replication of the screening topography. Polycarbonate replicas are molded for use in cell culture studies, and the functionality of the topography as a high-throughput screening platform is investigated. The response of MDCK, h-TERT fibroblasts, and LE2 endothelial cells is examined, in terms of attachment and morphological response to the variation in topographical cues, with the aim of pinpointing the optimal combination of groove pitch and depth to elicit a tailored response from each cell type. When the range of topographical features screened on a single substrate is considered, this new assay represents a significant step forward in the parametric design and analysis of topographical cues at the biomaterial interface.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.