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Find video protocols related to scientific articles indexed in Pubmed.
[Clinical features and microsurgical treatment of spinal intramedullary cavernoma].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 08-22-2014
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To explore the clinical features and microsurgical treatment of spinal intramedullary cavernomas (SICs).
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Bradykinin stimulates IL-6 production and cell invasion in colorectal cancer cells.
Oncol. Rep.
PUBLISHED: 07-30-2014
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Bradykinin (BK) has been reported to be involved in the progression of many types of cancer. In the present study, we investigated a possible role of BK in colorectal cancer cell invasion and migration. Invasion and migration assays showed that BK treatment promoted the invasion and migration of colorectal cancer cells. Further experiments showed that BK treatment stimulated ERK1/2 activation and IL-6 production. Two bradykinin receptors, bradykinin B1 receptor (B1R) and bradykinin B2 receptor (B2R), were significantly expressed in all the tested colorectal cancer cells. Repression of B2R, but not B1R, attenuated the BK-mediated invasion and migration, and inhibited ERK1/2 activation and IL-6 production. Moreover, blocking of the ERK pathway decreased the BK-mediated IL-6 production. In addition, IL-6 repression suppressed the effects of BK on colorectal cancer cell invasion and migration. Taken together, the present study demonstrated that BK increases IL-6 production via B2R and the ERK pathway, thereby contributing to the invasion and migration of colorectal cancer cells. Thus, our findings may provide benefits for the treatment of colorectal cancer.
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Facile chemoenzymatic strategies for the synthesis and utilization of S-adenosyl-(L)-methionine analogues.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 03-11-2014
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A chemoenzymatic platform for the synthesis of S-adenosyl-L-methionine (SAM) analogues compatible with downstream SAM-utilizing enzymes is reported. Forty-four non-native S/Se-alkylated Met analogues were synthesized and applied to probing the substrate specificity of five diverse methionine adenosyltransferases (MATs). Human MAT?II was among the most permissive of the MATs analyzed and enabled the chemoenzymatic synthesis of 29 non-native SAM analogues. As a proof of concept for the feasibility of natural product "alkylrandomization", a small set of differentially-alkylated indolocarbazole analogues was generated by using a coupled hMAT2-RebM system (RebM is the sugar C4'-O-methyltransferase that is involved in rebeccamycin biosynthesis). The ability to couple SAM synthesis and utilization in a single vessel circumvents issues associated with the rapid decomposition of SAM analogues and thereby opens the door for the further interrogation of a wide range of SAM utilizing enzymes.
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Hypoxia-inducible factor-1? C1772T polymorphism and cancer risk: a meta-analysis including 18,334 subjects.
Cancer Invest.
PUBLISHED: 02-27-2014
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Studies on HIF 1? C1772T (P582S) polymorphism revealed a genetic susceptibility to malignant tumors, however, the results were conflicting. We conducted a meta-analysis utilizing 29 eligible case-control studies to analyze the data concerning the association between the HIF-1? C1772T polymorphism and cancer risks. There was statistical association between the HIF-1? CT/TT genotype and cancer risk (OR = 1.28, 95% CI = 1.06-1.54, P(heterogeneity) < .00001). The stability of these observations was confirmed by a one-way sensitivity analysis. Our findings suggested that CT/TT genotype was associated with increased risks of prostate cancer. Besides, the HIF-1? C1772T polymorphism most likely contributes to susceptibility to malignant tumors, especially in American population.
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H6 influenza viruses pose a potential threat to human health.
J. Virol.
PUBLISHED: 02-05-2014
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Influenza viruses of the H6 subtype have been isolated from wild and domestic aquatic and terrestrial avian species throughout the world since their first detection in a turkey in Massachusetts in 1965. Since 1997, H6 viruses with different neuraminidase (NA) subtypes have been detected frequently in the live poultry markets of southern China. Although sequence information has been gathered over the last few years, the H6 viruses have not been fully biologically characterized. To investigate the potential risk posed by H6 viruses to humans, here we assessed the receptor-binding preference, replication, and transmissibility in mammals of a series of H6 viruses isolated from live poultry markets in southern China from 2008 to 2011. Among the 257 H6 strains tested, 87 viruses recognized the human type receptor. Genome sequence analysis of 38 representative H6 viruses revealed 30 different genotypes, indicating that these viruses are actively circulating and reassorting in nature. Thirty-seven of 38 viruses tested in mice replicated efficiently in the lungs and some caused mild disease; none, however, were lethal. We also tested the direct contact transmission of 10 H6 viruses in guinea pigs and found that 5 viruses did not transmit to the contact animals, 3 viruses transmitted to one of the three contact animals, and 2 viruses transmitted to all three contact animals. Our study demonstrates that the H6 avian influenza viruses pose a clear threat to human health and emphasizes the need for continued surveillance and evaluation of the H6 influenza viruses circulating in nature.
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Upregulation of neuregulin-1 reverses signs of neuropathic pain in rats.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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Peripheral nerve injury can result in neuropathic pain, a chronic condition of unclear cause often poorly responsive to current treatments. One possibility is that nerve injury disrupts large A-fiber-mediated inhibition of C-fiber-evoked responses in spinal dorsal horn neurons, leading to central sensitization. A recent study provided a potential molecular mechanism; large dorsal root ganglion (DRG) neurons secrete neuregulin-1 (NRG1), which binds to erbB4 receptors on interneurons and promotes GABA release to inhibit C-fiber-evoked nociceptive transmission. Thus, reduced NRG1 expression following nerve injury could induce chronic pain by disinhibition. We examined if DRG expression of NRG1 is in fact reduced in a rat model of neuropathic pain and if exogenous NRG1 alleviates behavioral signs of this condition.
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H7N9 influenza viruses are transmissible in ferrets by respiratory droplet.
Science
PUBLISHED: 07-18-2013
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A newly emerged H7N9 virus has caused 132 human infections with 37 deaths in China since 18 February 2013. Control measures in H7N9 virus-positive live poultry markets have reduced the number of infections; however, the character of the virus, including its pandemic potential, remains largely unknown. We systematically analyzed H7N9 viruses isolated from birds and humans. The viruses were genetically closely related and bound to human airway receptors; some also maintained the ability to bind to avian airway receptors. The viruses isolated from birds were nonpathogenic in chickens, ducks, and mice; however, the viruses isolated from humans caused up to 30% body weight loss in mice. Most importantly, one virus isolated from humans was highly transmissible in ferrets by respiratory droplet. Our findings indicate nothing to reduce the concern that these viruses can transmit between humans.
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Chromosomal circularization of the model Streptomyces species, Streptomyces coelicolor A3(2).
FEMS Microbiol. Lett.
PUBLISHED: 05-07-2013
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Streptomyces linear chromosomes frequently cause deletions at both ends spontaneously or by various mutagenic treatments, leading to chromosomal circularization and arm replacement. However, chromosomal circularization has not been confirmed at a sequence level in the model species, Streptomyces coelicolor A3(2). In this work, we have cloned and sequenced a fusion junction of a circularized chromosome in an S. coelicolor A3(2) mutant and found a 6-bp overlap between the left and right deletion ends. This result shows that chromosomal circularization occurred by nonhomologous recombination of the deletion ends in this species, too. At the end of the study, we discuss on stability and evolution of Streptomyces chromosomes.
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Investigating Mithramycin deoxysugar biosynthesis: enzymatic total synthesis of TDP-D-olivose.
Chembiochem
PUBLISHED: 08-25-2011
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Mixnmatch: Enzymatic total synthesis of TDP-D-olivose was achieved, starting from TDP-4-keto-6-deoxy-D-glucose, by combining three pathway enzymes with one cofactor-regenerating enzyme. The results also revealed that MtmC is a bifunctional enzyme that can perform a 4-ketoreduction necessary for D-olivose biosynthesis besides the previously found C-methyltransfer for D-mycarose biosynthesis.
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A dog-associated primary pneumonic plague in Qinghai Province, China.
Clin. Infect. Dis.
PUBLISHED: 02-04-2011
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Primary pneumonic plague (PPP) caused by Yersinia pestis is the most threatening clinical form of plague. An outbreak was reported in July 2009 in Qinghai Province, China.
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Protective efficacy of H7 subtype avian influenza DNA vaccine.
Avian Dis.
PUBLISHED: 06-05-2010
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Highly pathogenic avian influenza viruses (HPAIV) have historically caused disastrous damage to the poultry industry, and recently they have shown their zoonotic potential by causing human infections and deaths. Control and prevention of HPAIV are therefore important issues for both veterinary and human public health. In this study, we constructed a plasmid, pCAGGoptiH7, encoding a codon-optimized HA gene of the H7N1 avian influenza virus A/FPV/Rostock/34 (RK/34). To evaluate the vaccine efficacy of pCAGGoptiH7, groups of specific-pathogen-free (SPF) chickens were intramuscularly inoculated with one or two doses of 100 microg, 50 microg, or 10 microg of the plasmid in 3-wk intervals. Four weeks after the single vaccination or 2 wk after the second dose, all chickens were challenged with 100CLD50 (chicken lethal dose) of highly pathogenic RK/34. After the single dose vaccination, only 90% of chickens were protected in all of the pCAGGoptiH7-immunized groups, although all of the chickens immunized generated detectable HI antibodies. After the second dose of vaccination, HI antibodies increased sharply, and chickens in the 100-microg and 50-microg pCAGGoptiH7-immunized groups were completely protected from virus challenge (no disease signs, no virus shedding, and no deaths). Low titers of virus shedding were detected in two out of ten chickens inoculated with two doses of 10-microg pCAGGoptiH7, although no disease or death was observed. These results provide a strong argument for the continued evaluation of this vaccine in field trials.
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The G243D mutation (afsB mutation) in the principal sigma factor sigmaHrdB alters intracellular ppGpp level and antibiotic production in Streptomyces coelicolor A3(2).
Microbiology (Reading, Engl.)
PUBLISHED: 05-20-2010
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Deficient antibiotic production in an afsB mutant, BH5, of Streptomyces coelicolor A3(2) was recently shown to be due to a mutation (G243D) in region 1.2 of the primary sigma factor sigma(HrdB). Here we show that intracellular ppGpp levels during growth, as well as after amino acid depletion, in the mutant BH5 are lower than those of the afsB(+) parent strain. The introduction of certain rifampicin resistance (rif) mutations, which bypassed the requirement of ppGpp for transcription of pathway-specific regulatory genes, actII-ORF4 and redD, for actinorhodin and undecylprodigiosin, respectively, completely restored antibiotic production by BH5. Antibiotic production was restored also by introduction of a new class of thiostrepton-resistance (tsp) mutations, which provoked aberrant accumulation of intracellular ppGpp. Abolition of ppGpp synthesis in the afsB tsp mutant Tsp33 again abolished antibiotic production. These results indicate that intracellular ppGpp level is finely tuned for successful triggering of antibiotic production in the wild-type strain, and that this fine tuning was absent from the afsB mutant BH5, resulting in a failure to initiate antibiotic production in this strain.
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Dogs are highly susceptible to H5N1 avian influenza virus.
Virology
PUBLISHED: 03-25-2010
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Replication of avian influenza viruses (AIVs) in dogs may facilitate their adaptation in humans; however, the data to date on H5N1 influenza virus infection in dogs are conflicting. To elucidate the susceptibility of dogs to this pathogen, we infected two groups of 6 beagles with 10(6) 50% egg-infectious dose of H5N1 AIV A/bar-headed goose/Qinghai/3/05 (BHG/QH/3/05) intranasally (i.n.) and intratracheally (i.t.), respectively. The dogs showed disease symptoms, including anorexia, fever, conjunctivitis, labored breathing and cough, and one i.t. inoculated animal died on day 4 post-infection. Virus shedding was detected from all 6 animals inoculated i.n. and one inoculated i.t. Virus replication was detected in all animals that were euthanized on day 3 or day 5 post-infection and in the animal that died on day 4 post-infection. Our results demonstrate that dogs are highly susceptible to H5N1 AIV and may serve as an intermediate host to transfer this virus to humans.
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ScoC regulates bacilysin production at the transcription level in Bacillus subtilis.
J. Bacteriol.
PUBLISHED: 10-02-2009
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Bacillus subtilis mutants with high expression of the bacilysin operon ywfBCDEFG were isolated. Comparative genome sequencing analysis revealed that all of these mutants have a mutation in the scoC gene. The disruption of scoC by genetic engineering also resulted in increased expression of ywfBCDEFG. Primer extension and gel mobility shift analyses showed that the ScoC protein binds directly to the promoter region of ywfBCDEFG. Our results indicate that the transition state regulator ScoC, together with CodY and AbrB, negatively regulates bacilysin production in B. subtilis.
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A novel insertion mutation in Streptomyces coelicolor ribosomal S12 protein results in paromomycin resistance and antibiotic overproduction.
Antimicrob. Agents Chemother.
PUBLISHED: 05-20-2009
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We identified a novel paromomycin resistance-associated mutation in rpsL, caused by the insertion of a glycine residue at position 92, in Streptomyces coelicolor ribosomal protein S12. This insertion mutation (GI92) resulted in a 20-fold increase in the paromomycin resistance level. In combination with another S12 mutation, K88E, the GI92 mutation markedly enhanced the production of the blue-colored polyketide antibiotic actinorhodin and the red-colored antibiotic undecylprodigiosin. The gene replacement experiments demonstrated that the K88E-GI92 double mutation in the rpsL gene was responsible for the marked enhancement of antibiotic production observed. Ribosomes with the K88E-GI92 double mutation were characterized by error restrictiveness (i.e., hyperaccuracy). Using a cell-free translation system, we found that mutant ribosomes harboring the K88E-GI92 double mutation but not ribosomes harboring the GI92 mutation alone displayed sixfold greater translation activity relative to that of the wild-type ribosomes at late growth phase. This resulted in the overproduction of actinorhodin, caused by the transcriptional activation of the pathway-specific regulatory gene actII-orf4, possibly due to the increased translation of transcripts encoding activators of actII-orf4. The mutant with the K88E-GI92 double mutation accumulated a high level of ribosome recycling factor at late stationary phase, underlying the high level of protein synthesis activity observed.
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Inactivation of KsgA, a 16S rRNA methyltransferase, causes vigorous emergence of mutants with high-level kasugamycin resistance.
Antimicrob. Agents Chemother.
PUBLISHED: 04-21-2009
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The methyltransferases RsmG and KsgA methylate the nucleotides G535 (RsmG) and A1518 and A1519 (KsgA) in 16S rRNA, and inactivation of the proteins by introducing mutations results in acquisition of low-level resistance to streptomycin and kasugamycin, respectively. In a Bacillus subtilis strain harboring a single rrn operon (rrnO), we found that spontaneous ksgA mutations conferring a modest level of resistance to kasugamycin occur at a high frequency of 10(-6). More importantly, we also found that once cells acquire the ksgA mutations, they produce high-level kasugamycin resistance at an extraordinarily high frequency (100-fold greater frequency than that observed in the ksgA(+) strain), a phenomenon previously reported for rsmG mutants. This was not the case for other antibiotic resistance mutations (Tsp(r) and Rif(r)), indicating that the high frequency of emergence of a mutation for high-level kasugamycin resistance in the genetic background of ksgA is not due simply to increased persistence of the ksgA strain. Comparative genome sequencing showed that a mutation in the speD gene encoding S-adenosylmethionine decarboxylase is responsible for the observed high-level kasugamycin resistance. ksgA speD double mutants showed a markedly reduced level of intracellular spermidine, underlying the mechanism of high-level resistance. A growth competition assay indicated that, unlike rsmG mutation, the ksgA mutation is disadvantageous for overall growth fitness. This study clarified the similarities and differences between ksgA mutation and rsmG mutation, both of which share a common characteristic--failure to methylate the bases of 16S rRNA. Coexistence of the ksgA mutation and the rsmG mutation allowed cell viability. We propose that the ksgA mutation, together with the rsmG mutation, may provide a novel clue to uncover a still-unknown mechanism of mutation and ribosomal function.
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Activation of dormant bacterial genes by Nonomuraea sp. strain ATCC 39727 mutant-type RNA polymerase.
J. Bacteriol.
PUBLISHED: 04-03-2009
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There is accumulating evidence that the ability of actinomycetes to produce antibiotics and other bioactive secondary metabolites has been underestimated due to the presence of cryptic gene clusters. The activation of dormant genes is therefore one of the most important areas of experimental research for the discovery of drugs in these organisms. The recent observation that several actinomycetes possess two RNA polymerase beta-chain genes (rpoB) has opened up the possibility, explored in this study, of developing a new strategy to activate dormant gene expression in bacteria. Two rpoB paralogs, rpoB(S) and rpoB(R), provide Nonomuraea sp. strain ATCC 39727 with two functionally distinct and developmentally regulated RNA polymerases. The product of rpoB(R), the expression of which increases after transition to stationary phase, is characterized by five amino acid substitutions located within or close to the so-called rifampin resistance clusters that play a key role in fundamental activities of RNA polymerase. Here, we report that rpoB(R) markedly activated antibiotic biosynthesis in the wild-type Streptomyces lividans strain 1326 and also in strain KO-421, a relaxed (rel) mutant unable to produce ppGpp. Site-directed mutagenesis demonstrated that the rpoB(R)-specific missense H426N mutation was essential for the activation of secondary metabolism. Our observations also indicated that mutant-type or duplicated, rpoB often exists in nature among rare actinomycetes and will thus provide a basis for further basic and applied research.
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Baeyer-Villiger C-C bond cleavage reaction in gilvocarcin and jadomycin biosynthesis.
J. Am. Chem. Soc.
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GilOII has been unambiguously identified as the key enzyme performing the crucial C-C bond cleavage reaction responsible for the unique rearrangement of a benz[a]anthracene skeleton to the benzo[d]naphthopyranone backbone typical of the gilvocarcin-type natural anticancer antibiotics. Further investigations of this enzyme led to the isolation of a hydroxyoxepinone intermediate, leading to important conclusions regarding the cleavage mechanism.
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Cooperation of two bifunctional enzymes in the biosynthesis and attachment of deoxysugars of the antitumor antibiotic mithramycin.
Angew. Chem. Int. Ed. Engl.
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Two bifunctional enzymes cooperate in the assembly and the positioning of two sugars, D-olivose and D-mycarose, of the anticancer antibiotic mithramycin. MtmC finishes the biosynthesis of both sugar building blocks depending on which MtmGIV activity is supported. MtmGIV transfers these two sugars onto two structurally distinct acceptor substrates. The dual function of these enzymes explains two essential but previously unidentified activities.
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The correlations between the expression of FGFR4 protein and clinicopathological parameters as well as prognosis of gastric cancer patients.
J Surg Oncol
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Fibroblast growth factor receptor 4 (FGFR4) was seldom investigated in gastric cancer (GC). The purpose of the study was to elucidate the expression of FGFR4 protein in GC and related clinical significance.
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Elucidation of post-PKS tailoring steps involved in landomycin biosynthesis.
Org. Biomol. Chem.
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The functional roles of all proposed enzymes involved in the post-PKS redox reactions of the biosynthesis of various landomycin aglycones were thoroughly studied, both in vivo and in vitro. The results revealed that LanM2 acts as a dehydratase and is responsible for concomitant release of the last PKS-tethered intermediate to yield prejadomycin (10). Prejadomycin (10) was confirmed to be a general pathway intermediate of the biosynthesis. Oxygenase LanE and the reductase LanV are sufficient to convert 10 into 11-deoxylandomycinone (5) in the presence of NADH. LanZ4 is a reductase providing reduced flavin (FMNH) co-factor to the partner enzyme LanZ5, which controls all remaining steps. LanZ5, a bifunctional oxygenase-dehydratase, is a key enzyme directing landomycin biosynthesis. It catalyzes hydroxylation at the 11-position preferentially only after the first glycosylation step, and requires the presence of LanZ4. In the absence of such a glycosylation, LanZ5 catalyzes C5,6-dehydration, leading to the production of anhydrolandomycinone (8) or tetrangulol (9). The overall results provided a revised pathway for the biosynthesis of the four aglycones that are found in various congeners of the landomycin group.
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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.

Video X seems to be unrelated to Abstract Y...

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.