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Find video protocols related to scientific articles indexed in Pubmed.
The HER2 peptide nelipepimut-S (E75) vaccine (NeuVax™) in breast cancer patients at risk for recurrence: correlation of immunologic data with clinical response.
Immunotherapy
PUBLISHED: 06-05-2014
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Nelipepimut-S (formerly known as E75) is an immunogenic peptide from the HER2 protein that is highly expressed in breast cancer. The NeuVax™ (Galena, OR, USA) vaccine, nelipepimut-S plus granulocyte-macrophage colony-stimulating factor, is designed for the prevention of clinical recurrences in high risk, disease-free breast cancer patients. Although cancer vaccines such as NeuVax represent promising approaches to cancer immunotherapy, much remains to be elucidated regarding their mechanisms of action: particularly given that multiple cancer vaccine trials have failed to demonstrate a correlation between immunologic data and clinical outcome. Here, we briefly discuss our clinical trial experience with NeuVax focusing on immunologic response data and its implication on how the immune system may be affected by this peptide vaccine. Most importantly, we demonstrate the potential capability of certain immunologic assays to predict clinical benefit in our trials.
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Treatment of complex medical emergencies in a forward deployed setting: a case of out-of-hospital cardiac arrest.
Mil Med
PUBLISHED: 02-05-2014
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The Joint Trauma System in Afghanistan, while designed for the care of injured patients, can provide timely, multimodal, coordinated care for nontraumatic medical emergencies as patients are evacuated from theater. To illustrate this, a case of out-of-hospital cardiac arrest is presented. The patient was able to receive all recommended components of postcardiac arrest care in a timely, coordinated manner at four different medical treatment facilities and while traveling over 8,600 miles with critical care provided en route.
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Neurological outcome scale for traumatic brain injury: III. Criterion-related validity and sensitivity to change in the NABIS hypothermia-II clinical trial.
J. Neurotrauma
PUBLISHED: 08-02-2013
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The neurological outcome scale for traumatic brain injury (NOS-TBI) is a measure assessing neurological functioning in patients with TBI. We hypothesized that the NOS-TBI would exhibit adequate concurrent and predictive validity and demonstrate more sensitivity to change, compared with other well-established outcome measures. We analyzed data from the National Acute Brain Injury Study: Hypothermia-II clinical trial. Participants were 16-45 years of age with severe TBI assessed at 1, 3, 6, and 12 months postinjury. For analysis of criterion-related validity (concurrent and predictive), Spearmans rank-order correlations were calculated between the NOS-TBI and the glasgow outcome scale (GOS), GOS-extended (GOS-E), disability rating scale (DRS), and neurobehavioral rating scale-revised (NRS-R). Concurrent validity was demonstrated through significant correlations between the NOS-TBI and GOS, GOS-E, DRS, and NRS-R measured contemporaneously at 3, 6, and 12 months postinjury (all p<0.0013). For prediction analyses, the multiplicity-adjusted p value using the false discovery rate was <0.015. The 1-month NOS-TBI score was a significant predictor of outcome in the GOS, GOS-E, and DRS at 3 and 6 months postinjury (all p<0.015). The 3-month NOS-TBI significantly predicted GOS, GOS-E, DRS, and NRS-R outcomes at 6 and 12 months postinjury (all p<0.0015). Sensitivity to change was analyzed using Wilcoxons signed rank-sum test of subsamples demonstrating no change in the GOS or GOS-E between 3 and 6 months. The NOS-TBI demonstrated higher sensitivity to change, compared with the GOS (p<0.038) and GOS-E (p<0.016). In summary, the NOS-TBI demonstrated adequate concurrent and predictive validity as well as sensitivity to change, compared with gold-standard outcome measures. The NOS-TBI may enhance prediction of outcome in clinical practice and measurement of outcome in TBI research.
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AE37: a novel T-cell-eliciting vaccine for breast cancer.
Expert Opin Biol Ther
PUBLISHED: 09-06-2011
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Immunotherapy, including vaccines targeting the human EGFR2 (HER-2/neu) protein, is an active area of investigation in combatting breast cancer. Several vaccines are currently undergoing clinical trials, most of which are CD8(+) T-cell-eliciting vaccines. AE37 is a promising primarily CD4(+) T-cell-eliciting HER-2/neu breast cancer vaccine currently in clinical trials.
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Clinical trial results of the HER-2/neu (E75) vaccine to prevent breast cancer recurrence in high-risk patients: from US Military Cancer Institute Clinical Trials Group Study I-01 and I-02.
Cancer
PUBLISHED: 06-23-2011
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The authors conducted exploratory phase 1-2 clinical trials vaccinating breast cancer patients with E75, a human leukocyte antigen (HLA) A2/A3-restricted HER-2/neu (HER2) peptide, and granulocyte-macrophage colony-stimulating factor. The vaccine is given as adjuvant therapy to prevent disease recurrence. They previously reported that the vaccine is safe and effective in stimulating expansion of E75-specific cytotoxic T cells. Here, they report 24-month landmark analyses of disease-free survival (DFS).
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Diffusion tensor imaging of the perforant pathway zone and its relation to memory function in patients with severe traumatic brain injury.
J. Neurotrauma
PUBLISHED: 04-27-2011
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Based on the importance of the perforant pathway (PP) for normal hippocampal function, the vulnerability of temporal structures, and significant memory impairment in patients with traumatic brain injury (TBI), we investigated in vivo changes in the PP zone, hippocampus, and temporal lobe white and gray matter using diffusion tensor imaging (DTI) and volumetric analysis, and any specific relations with memory performance (Verbal Selective Reminding Test, Rey-Osterrieth Complex Figure Test), in 14 patients with severe TBI. Compared to a demographically-similar control group, our patients had significantly decreased fractional anisotropy (FA) and higher apparent diffusion coefficient (ADC) for the PP zone bilaterally, and higher ADC bilaterally in the hippocampus. Volumetric analysis revealed significantly decreased volumes in both hippocampi and temporal gray matter bilaterally. Consistent long-term retrieval (CLTR) and delayed recall were significantly related to (1) right and left PP zone ADC, (2) left hippocampus ADC, and (3) left hippocampal volume. Nonverbal memory (immediate and delayed recall) was significantly associated with (1) right and left PP zone ADC, (2) left hippocampal volume, and (3) gray (immediate recall) and white (immediate recall, bilaterally; delayed recall, left) matter temporal volumes. Advanced neuroimaging analysis can detect in vivo changes in the PP zone and temporal structures in patients with severe TBI, with these changes being highly associated with memory impairment.
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Comparison of different HER2/neu vaccines in adjuvant breast cancer trials: implications for dosing of peptide vaccines.
Expert Rev Vaccines
PUBLISHED: 02-22-2011
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We have performed multiple adjuvant clinical trials using immunogenic peptides from the HER2/neu protein (AE37/E75/GP2) plus (GM-CSF) given intradermally to breast cancer patients. Four trials were performed with similar dose-escalation design with increasing doses of peptide (AE37/E75/GP2) and varying amounts of GM-CSF. Dose reductions (DRs) were made for significant local and/or systemic toxicity by decreasing GM-CSF for subsequent inoculations. Ex vivo and in vivo immunologic responses were used to compare groups. Of 132 patients, 39 required DR (30 for robust local reactions [DR-L]). DR patients, particularly DR-L, had greater immune responses both ex vivo and in vivo. Postvaccine delayed-type hypersensitivity in DR-L patients compared with all others was larger for E75 (p = 0.001), AE37 (p = 0.077) and GP2 (p = 0.076). All three peptide vaccines were safe and well-tolerated. These findings have led to a clinically relevant optimal vaccine dosing strategy, which may be applicable to other peptide-based cancer vaccines.
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Folate receptor ?: a storied past and promising future in immunotherapy.
Hum Vaccin
PUBLISHED: 02-01-2011
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Folate receptor alpha (FR ?) is a membrane-bound transport protein with several features which make it an attractive target for cancer immunotherapy. FR ? is largely shielded from the immune system in normal tissue but exposed while expressed on a variety of malignancies; it is functionally active in cancer pathogenesis; and it is immunogenic. A variety of different immunotherapeutic methods targeting FR ? are being explored to treat cancer. Passive immunotherapy includes monoclonal antibodies, antibodies modified to deliver treatments, and modified T cell therapy. Active immunotherapy has focused on using FR ? to increase the immunogenicity of cancer or to generate active FR ?-directed immunity through a range of vaccination techniques. We will review the rationale behind targeting immunotherapy to FR ? and cover the various techniques designed to do this. Folate receptor alpha (FR?) is a unique tumor-associated antigen (TAA) with many characteristics that make it an attractive target for immunotherapy in cancer. Many different immunotherapeutic modalities utilizing FR? are being explored to treat cancer. The research is in various stages: some are just beyond conception, others have been tried and abandoned, and others still are progressing through human clinical trials. This review will cover immunotherapeutic methods, both active and passive, that target FR?.
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Very early hypothermia induction in patients with severe brain injury (the National Acute Brain Injury Study: Hypothermia II): a randomised trial.
Lancet Neurol
PUBLISHED: 12-17-2010
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The inconsistent effect of hypothermia treatment on severe brain injury in previous trials might be because hypothermia was induced too late after injury. We aimed to assess whether very early induction of hypothermia improves outcome in patients with severe brain injury.
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The temporal stem in traumatic brain injury: preliminary findings.
Brain Imaging Behav
PUBLISHED: 09-14-2010
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The temporal stem (TS) of the temporal lobe is a major white matter (WM) region containing several major pathways that connect the temporal lobe with the rest of the brain. Because of its location, it may be particularly vulnerable to shear-strain effects resulting from traumatic brain injury (TBI). A case vignette is presented in a patient with severe brain injury and focal TS pathology. Also, 12 severe TBI subjects unselected for TS pathology were compared to demographically matched, neurologically-intact controls using diffusion tensor imaging (DTI) to examine white matter tracts associated with the TS, including the inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), arcuate fasciculus (AF), cingulum bundle (CB) and the uncinate fasciculus (UF). For each tract, fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were computed and compared between the two groups and also examined in relationship to memory performance in the TBI subjects. Significant FA and ADC differences were observed in all tracts in the TBI patients compared to controls, with several relationships with memory outcome noted in the IFOF, ILF and AF. Based on these preliminary findings, the potential role of TBI-induced WM disconnection involving the TS is discussed as well as the relationship of TS damage to neurobehavioral outcome. The need for future studies specifically examining the role of TS injury in TBI is emphasized.
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Use of booster inoculations to sustain the clinical effect of an adjuvant breast cancer vaccine: from US Military Cancer Institute Clinical Trials Group Study I-01 and I-02.
Cancer
PUBLISHED: 04-28-2010
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The authors are conducting clinical trials of the HER-2/neu E75-peptide vaccine in clinically disease-free breast cancer (BC) patients. Their phase 1-2 trials revealed that the E75 + granulocyte-macrophage colony-stimulating factor (GM-CSF) vaccine is safe and effective in stimulating clonal expansion of E75-specific CD8(+) T cells. They assessed the need for and response to a booster after completion of primary vaccination series.
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Circulating regulatory T cells (CD4+CD25+FOXP3+) decrease in breast cancer patients after vaccination with a modified MHC class II HER2/neu (AE37) peptide.
Vaccine
PUBLISHED: 04-26-2010
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Regulatory T cells (T(Reg)), CD4(+)CD25(+)FOXP3(+), are implicated in suppressing tumor immune responses. We analyzed peripheral blood lymphocytes (PBL) from breast cancer patients receiving a modified HLA class II HER2/neu peptide (AE37) vaccine for T(Reg) cells and correlated their levels with vaccine-specific immune responses. The mean CD4(+)CD25(+)FOXP3(+) T(Reg) cells decreased in patients with vaccination with no significant difference in serum TGF-? levels. IFN-? ELISPOT and DTH increased after vaccination with a good correlation between T(Reg) cell reduction and size of DTH to AE37. The T(Reg) cell reduction and associated immune response suggest that AE37 may be clinically useful.
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Serum IL-6: a candidate biomarker for intracranial pressure elevation following isolated traumatic brain injury.
J Neuroinflammation
PUBLISHED: 03-11-2010
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Increased intracranial pressure (ICP) is a serious, life-threatening, secondary event following traumatic brain injury (TBI). In many cases, ICP rises in a delayed fashion, reaching a maximal level 48-96 hours after the initial insult. While pressure catheters can be implanted to monitor ICP, there is no clinically proven method for determining a patients risk for developing this pathology.
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The Neurological Outcome Scale for Traumatic Brain Injury (NOS-TBI): I. Construct validity.
J. Neurotrauma
PUBLISHED: 03-10-2010
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The Neurological Outcome Scale for Traumatic Brain Injury (NOS-TBI) is a measure adapted from the National Institutes of Health Stroke Scale (NIHSS), and is intended to capture essential neurological deficits impacting individuals with traumatic brain injury (TBI) (see Wilde et al., 2010 ). In the present study we evaluate the measures construct validity via comparison with a quantified neurological examination performed by a neurologist. Spearman rank-order correlation between the NOS-TBI and the neurological examination was rho = 0.76, p < 0.0001, suggesting a high degree of correspondence (construct validity) between these two measures of neurological function. Additionally, items from the NOS-TBI compared favorably to the neurological examination items, with correlations ranging from 0.60 to 0.99 (all p < 0.0001). On formal neurological examination, some degree of neurological impairment was observed in every participant in this cohort of individuals undergoing rehabilitation for TBI, and on the NOS-TBI neurological impairment was evident in all but one participant. This study documents the presence of measurable neurological sequelae in a sample of patients with TBI in a post-acute rehabilitation setting, underscoring the need for formal measurement of the frequency and severity of neurological deficits in this population. The results suggest that the NOS-TBI is a valid measure of neurological functioning in patients with TBI.
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Feasibility of the Neurological Outcome Scale for Traumatic Brain Injury (NOS-TBI) in adults.
J. Neurotrauma
PUBLISHED: 03-10-2010
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This article describes the design and initial implementation of the Neurological Outcome Scale for Traumatic Brain Injury (NOS-TBI) as an adaptation of the National Institutes of Health Stroke Scale (NIHSS), specifically for clinical and research use in patients with TBI, including (1) the addition of items specific to TBI, (2) adjustment to the scoring algorithm to allow quantification of deficits in patients who are comatose/vegetative or agitated, and (3) the reassignment of items (i.e., limb ataxia) that are problematic in TBI as supplemental items. The feasibility of using the NOS-TBI is discussed and limitations of the scale are highlighted. This scale offers (1) a cost-effective, brief, practicable, standardized, and quantifiable method of communicating and analyzing neurological deficits in a way that traditional neurological assessment alone cannot currently provide, and (2) a measure that non-physicians can administer. The NOS-TBI may serve a role in clinical practice in patients with TBI similar to the way the NIHSS has functioned for patients following stroke, by serving as a tool for initial stratification of injury severity, and as an outcome measure in clinical trials.
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Serum ceruloplasmin and copper are early biomarkers for traumatic brain injury-associated elevated intracranial pressure.
J. Neurosci. Res.
PUBLISHED: 01-22-2010
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High intracranial pressure (ICP) is a prominent secondary pathology after traumatic brain injury (TBI) and is a major contributor to morbidity and mortality. Currently, there are no clinically proven methods for predicting which TBI patients will develop high ICP. In the present study, we examined whether the serum levels of the copper-binding protein ceruloplasmin are differentially altered in patients with elevated ICP (> or =25 mmHg) vs. those whose ICP remained below 20 mmHg throughout the study period. Consistent with its role as an acute-phase reactant, we found that ceruloplasmin levels were significantly increased by 3 days post-TBI compared with healthy volunteers. However, prior to this delayed increase, ceruloplasmin levels during the first 24 hr following injury were found to be significantly reduced in patients who subsequently developed high ICP. This decrease was found to have prognostic accuracy in delineating TBI patients based on their ICP status (cutoff of 140 microg/ml; sensitivity: 87%, specificity: 73%), Likewise, low total serum copper (below 1.32 microg/ml) was also found to be predictive of high ICP (sensitivity 86%, specificity 73%). These results suggest that initial serum ceruloplasmin/copper levels may have diagnostic value in predicting patients at risk for developing high intracranial pressure.
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Incidence rates of exocrine and endocrine pancreatic cancers in the United States.
Cancer Causes Control
PUBLISHED: 01-15-2010
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Descriptive studies of pancreatic cancer incidence have been sparse particularly in terms of tumor histology and stage. The purpose of this study was to examine the incidence rate trends of exocrine and endocrine pancreatic cancers by demographic and tumor characteristics using data from the Surveillance, Epidemiology, and End Results (SEER) program from 1977 to 2005. During this period, the incidence of exocrine pancreatic cancer generally decreased whereas the incidence of endocrine pancreatic cancer increased. This difference in trends by histology was evident across age, gender, and racial groups. It was also evident among different racial/ethnic groups using data from 1992 to 2005. Variation in trends was observed by stage. The incidence of exocrine cancers declined for all stages except regional. Endocrine cancer incidence increased for all tumor stages, and the increase was most prominent for localized tumors. When exocrine tumors were stratified by tumor subsite, the incidence of cancers in the tail and body regions increased while the incidence in other regions decreased. While better detection and classification of tumors through improved diagnostic procedures may be related to these changing trends, etiologic factors warrant study.
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Clinical and immunologic responses of HLA-A3+ breast cancer patients vaccinated with the HER2/neu-derived peptide vaccine, E75, in a phase I/II clinical trial.
J. Am. Coll. Surg.
PUBLISHED: 08-26-2009
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We have treated disease-free breast cancer patients with an HER2/neu-derived peptide, E75, as an adjuvant vaccine. E75 was originally described as HLA-A2-restricted and has been previously tested in this population. Based on computer modeling, E75 is predicted to bind to HLA-A3, and preclinical data support this. We conducted a clinical trial of E75 in HLA-A3(+), A2(-) (A3) patients.
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Multicenter trial of early hypothermia in severe brain injury.
J. Neurotrauma
PUBLISHED: 02-28-2009
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The North American Brain Injury Study: Hypothermia IIR (NABIS:H IIR) is a randomized clinical trial designed to enroll 240 patients with severe brain injury between the ages of 16 and 45 years. The primary outcome measure is the dichotomized Glasgow Outcome Scale (GOS) at 6 months after injury. The study has the power to detect a 17.5% absolute difference in the percentage of patients with a good outcome with a power of 80%. All patients are randomized by waiver of consent unless family is immediately available. Enrollment is within 2.5 h of injury. Patients may be enrolled in the field by emergency medical services personnel affiliated with the study or by study personnel when the patient arrives at the emergency department. Patients who do not follow commands and have no exclusion criteria and who are enrolled in the hypothermia arm of the study are cooled to 35 degrees C as rapidly as possible by intravenous administration of up to 2 liters of chilled crystalloid. Those patients who meet the criteria for the second phase of the protocol (primarily a post-resuscitation GCS 3-8 without hypotension and without severe associated injuries) are cooled to 33 degrees C. Patients enrolled in the normothermia arm receive standard management at normothermia. As of December 2007, 74 patients had been randomized into phase II of the protocol. Patients in the hypothermia arm reached 35 degrees C in 2.7 +/- 1.1 (SD) h after injury and reached 33 degrees C at 4.4 +/- 1.5 h after injury.
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Overcoming cancer immune tolerance and escape.
Clin. Cancer Res.
PUBLISHED: 02-04-2009
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Although HER2/neu-targeted cancer vaccines have shown initial promise in the adjuvant setting, a therapeutic vaccine remains elusive due to the tumor escape mechanisms of established cancer. As described by Seavey et al. in this issue of CCR, a Listeria-delivered vaccine may help overcome immune tolerance, leading to an effective therapeutic vaccine.
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Early induction of hypothermia for evacuated intracranial hematomas: a post hoc analysis of two clinical trials.
J. Neurosurg.
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The authors hypothesized that cooling before evacuation of traumatic intracranial hematomas protects the brain from reperfusion injury and, if so, further hypothesized that hypothermia induction before or soon after craniotomy should be associated with improved outcomes.
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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.