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Find video protocols related to scientific articles indexed in Pubmed.
Stability of preclinical models of aggressive renal cell carcinomas.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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Renal-cell carcinomas (RCC) are often resistant to conventional cytotoxic agents. Xenograft models are used for in vivo preclinical studies and drug development. The validity of these studies is highly dependent on the phenotypic and genotypic stability of the models. Here we assessed the stability of six aggressive human RCC xenografted in nude/NMRI mice. We compared the initial samples (P0), first (P1) and fifth (P5) passages for the following criteria: histopathology, immunohistochemistry for CK7, CD10, vimentin and p53, DNA allelic profiles using 10 microsatellites and CGH-array. Next we evaluated the response to sunitinib in primary RCC and corresponding xenografted RCC. We observed a good overall stability between primary RCC and corresponding xenografted RCC at P1 and P5 regarding histopathology and immunohistochemistry except for cytokeratin 7 (one case) and p53 (one case) expression. Out of 44 groups with fully available microsatellite data (at P0, P1 and P5), 66% (29 groups) showed no difference from P0 to P5 while 34% (15 groups) showed new or lost alleles. Using CGH-array, overall genomic alterations at P5 were not different from those of initial RCC. The xenografted RCC had identical response to sunitinib therapy compared to the initial human RCC from which they derive. These xenograft models of aggressive human RCC are clinically relevant, showing a good histological and molecular stability and are suitable for studies of basic biology and response to therapy.
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Phase II trial of palliative radiotherapy for hepatocellular carcinoma and liver metastases.
J. Clin. Oncol.
PUBLISHED: 09-23-2013
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To evaluate the feasibility and response of liver radiotherapy (RT) in improving symptoms and quality of life in patients with hepatocellular carcinoma (HCC) or liver metastases (LM).
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Lung stereotactic body radiation therapy (SBRT) delivered over 4 or 11 days: a comparison of acute toxicity and quality of life.
Radiother Oncol
PUBLISHED: 06-25-2013
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The optimal duration over which lung SBRT should be delivered is unknown. We conducted a randomized pilot study in patients treated with four fractions of lung SBRT delivered over 4 or over 11 days.
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Psychometric validation of the functional assessment of cancer therapy-brain (FACT-Br) for assessing quality of life in patients with brain metastases.
Support Care Cancer
PUBLISHED: 05-15-2013
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This study aimed to test the reliability, psychometric, and clinical validity of the use of the Functional Assessment of Cancer Therapy-Brain (FACT-Br) in patients with brain metastases.
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Hypofractionated stereotactic radiotherapy in five daily fractions for post-operative surgical cavities in brain metastases patients with and without prior whole brain radiation.
Technol. Cancer Res. Treat.
PUBLISHED: 04-24-2013
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Our purpose was to report efficacy of hypofractionated cavity stereotactic radiotherapy (HCSRT) in patients with and without prior whole brain radiotherapy (WBRT). 32 surgical cavities in 30 patients (20 patients/21 cavities had no prior WBRT and 10 patients/11 cavities had prior WBRT) were treated with image-guided linac stereotactic radiotherapy. 7 of the 10 prior WBRT patients had "resistant" local disease given prior surgery, post-operative WBRT and a re-operation, followed by salvage HCSRT. The clinical target volume was the post-surgical cavity, and a 2-mm margin applied as planning target volume. The median total dose was 30 Gy (range: 25-37.5 Gy) in 5 fractions. In the no prior and prior WBRT cohorts, the median follow-up was 9.7 months (range: 3.0-23.6) and 15.3 months (range: 2.9-39.7), the median survival was 23.6 months and 39.7 months, and the 1-year cavity local recurrence progression- free survival (LRFS) was 79 and 100%, respectively. At 18 months the LRFS dropped to 29% in the prior WBRT cohort. Grade 3 radiation necrosis occurred in 3 prior WBRT patients. We report favorable outcomes with HCSRT, and well selected patients with prior WBRT and "resistant" disease may have an extended survival favoring aggressive salvage HCSRT at a moderate risk of radiation necrosis.
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Effects of ROI Placement on PET-Based Assessment of Tumor Response to Therapy.
Int J Mol Imaging
PUBLISHED: 01-15-2013
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Purpose. Quantitative PET response assessment during therapy requires regions of interest (ROI). Commonly, a fixed-size ROI is placed at the maximum uptake point in the pretreatment study. For intratreatment, the ROI is placed either at the maximum uptake point (ROIpeak) or at the same location as the pretreatment ROI (ROIsame). We have evaluated the effects of the ROI placement on response assessment. Methods. PET scans of 15 head and neck cancer patients were used to evaluate the effects of the two ROI methods on response assessment. Results. The average intratreatment ROIpeak uptake was 13.4% higher than the ROIsame uptake (range -14% to 38%). The average relative change in ROIpeak uptake was 7.9% lower than ROIsame uptake (range -5% to 36%), resulting in ambiguous tumour classification in 19% of the tumours. Conclusion. Quantitative PET response assessment using a fixed-size ROI is sensitive the ROI placement. The difference between ROIpeak and ROIsame could be substantial resulting in ambiguous response assessment. Although the fixed-size ROI is simple to implement, it is also prone to the limitations and should be used with caution. Clinical trial data are necessary to establish reliable thresholds for fixed-size ROI techniques and to evaluate their efficacy for response assessment.
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Automatic Segmentation of Lung Carcinoma Using 3D Texture Features in 18-FDG PET/CT.
Int J Mol Imaging
PUBLISHED: 01-06-2013
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Target definition is the largest source of geometric uncertainty in radiation therapy. This is partly due to a lack of contrast between tumor and healthy soft tissue for computed tomography (CT) and due to blurriness, lower spatial resolution, and lack of a truly quantitative unit for positron emission tomography (PET). First-, second-, and higher-order statistics, Tamura, and structural features were characterized for PET and CT images of lung carcinoma and organs of the thorax. A combined decision tree (DT) with K-nearest neighbours (KNN) classifiers as nodes containing combinations of 3 features were trained and used for segmentation of the gross tumor volume. This approach was validated for 31 patients from two separate institutions and scanners. The results were compared with thresholding approaches, the fuzzy clustering method, the 3-level fuzzy locally adaptive Bayesian algorithm, the multivalued level set algorithm, and a single KNN using Hounsfield units and standard uptake value. The results showed the DTKNN classifier had the highest sensitivity of 73.9%, second highest average Dice coefficient of 0.607, and a specificity of 99.2% for classifying voxels when using a probabilistic ground truth provided by simultaneous truth and performance level estimation using contours drawn by 3 trained physicians.
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Prevalence and spectrum of microsatellite alterations in nonmuscle invasive bladder cancers.
Am J Cancer Res
PUBLISHED: 03-11-2011
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We aimed to identify interesting deleted chromosomal regions for bladder cancer diagnosis and carcinogenesis, and to evaluate the association between loss of heterozygosity (LOH) and clinico-pathological parameters. Microsatellite analysis was performed on urine sediment and tumor tissue from 43 consecutive patients with superficial transitional cell carcinoma (TCC) and from 42 consecutive controls. Informative cases were scored as LOH or allelic loss (AL) according to the decrease of the allelic-imbalance ratio. The prevalence of LOH and AL was 39.5% and 86%, respectively. Chromosome 9 was the most frequently altered, especially at 9p (35%). The total number of microsatellite alterations per analysis was correlated with age, grade, stade and EAU classification. The locus 17p13.1 was strongly associated with high-stage (p=0.01) and high-grade tumors (p=0.02). Specificity and sensitivity of LOH was 100% and 39.3% for diagnosis of malignant urinary disease. Specificity and sensitivity of AL was 73.8% and 88%, respectively. Allelic losses are a frequent and early event in bladder cancer, especially at 9p. Thanks to its high specificity, LOH may serve as a complementary tool for non invasive diagnosis of bladder cancer. Further study is warranted to evaluate the prognostic value of LOH on recurrence, progression and muscle invasion.
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The prognostic value of FGFR3 mutational status for disease recurrence and progression depends on allelic losses at 9p22.
Am J Cancer Res
PUBLISHED: 02-16-2011
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Developing molecular markers that define high-risk lesions is clinically critical for improving the prognosis determination of the tumors and their treatment. We decided to focus on the two pathways involving FGFR3 and allelic losses at 9p22 to identify a potential combined role in predicting tumor recurrence, progression and/or muscle. Microsatellite and mutational FGFR3 status analyses was performed in tumor tissue of 58 patients in a prospective unicentre study. The results of microsatellite and FGFR3 analyses were dichotomized as follows: loss of heterozygos-ity (LOH) versus retention of heterozygosity (ROH) on the one hand; mutant FGFR3 (mtFGFR3) versus wild-type FGFR3 (wtFGFR3) on the other hand. The combined 9p22/FGFR3 status was strongly correlated with stage (p=0.001) and grade (p<0.001) whereas the single FGFR3 mutational status was not able to predict recurrence, progression or muscle invasion. The survival curves corresponding to each combined status (mtFGFR3/ROH, wtFGFR3/ROH, mtFGFR3/LOH, wtFGFR3/LOH) were significantly different for recurrence (p=0.008), progression (p=0.046) and progression to muscle invasive disease (p=0.004). In case of 9p22 LOH, the FGFR3 mutational status was strongly associated with different clinical outcomes. In a multivariate model, the combined wtFGFR3/9p22 LOH status remained significant in predicting oncologic outcomes. FGFR3 mutations strongly characterize tumors with low malignant potential and favourable clinical outcome in case of allelic losses at 9p22, whereas its prognostic value becomes null or slightly inverts in case of allelic stability. Thus, our findings may also lead to further experiments in order to study interactions between FGFR3 and genes located at 9p22, as CDKN2A.
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Functional imaging using diffuse optical spectroscopy of neoadjuvant chemotherapy response in women with locally advanced breast cancer.
Clin. Cancer Res.
PUBLISHED: 04-20-2010
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Functional imaging with tomographic near-infrared diffuse optical spectroscopy (DOS) can measure tissue concentration of deoxyhemoglobin (Hb), oxyhemoglobin (HbO2), percent water (%water), and scattering power (SP). In this study, we evaluated tumor DOS parameters and described their relationship to clinical and pathologic outcome in patients undergoing neoadjuvant therapy for locally advanced breast cancer.
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Accelerated hypofractionated radiotherapy for early-stage non-small-cell lung cancer: long-term results.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 04-10-2010
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To retrospectively review the results of a single-institution series of accelerated hypofractionated radiotherapy for early-stage non-small-cell lung cancer (NSCLC) in patients who are medically inoperable or who refuse surgery.
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Determination of angptl4 mRNA as a diagnostic marker of primary and metastatic clear cell renal-cell carcinoma.
PLoS ONE
PUBLISHED: 04-06-2010
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We have previously shown that angiopoietin-like 4 (angptl4) mRNA, a hypoxia-inducible gene, is highly expressed in clear cell renal-cell carcinoma (ccRCC), the most common subtype of RCC for which no specific marker is available. We here investigated whether angptl4 mRNA 1) could be a useful diagnostic and/or prognostic marker of ccRCC in a large and comprehensive retrospective series, 2) induction is dependent on the VHL status of tumors.
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Prognostic value of loss of heterozygosity at chromosome 9p in non-muscle-invasive bladder cancer.
Urology
PUBLISHED: 02-15-2010
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To investigate the prognostic value of loss of heterozygosity (LOH) at chromosome 9p in patients with non-muscle-invasive bladder cancer (NMI-BC).
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Association between a high number of isolated lymph nodes in T1 to T4 N0M0 colorectal cancer and the microsatellite instability phenotype.
Arch Surg
PUBLISHED: 01-20-2010
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Stage I or II colorectal carcinomas with microsatellite instability (MSI) are characterized by more isolated lymph nodes in the resected specimen than their counterparts with microsatellite stability (MSS).
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Functional imaging of neoadjuvant chemotherapy response in women with locally advanced breast cancer using diffuse optical spectroscopy.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 12-08-2009
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Functional imaging with tomographic near infrared diffuse optical spectroscopy (DOS) can quantitatively measure tissue parameters such as the concentration of deoxy-hemoglobin (Hb), oxy-hemoglobin (HbO2), percent water (%water), and scattering power (SP). The purpose of this study was to evaluate the correlation between DOS functional parameters with pathologic outcomes. Patients with locally advanced breast cancer undergoing neoadjuvant chemotherapy or chemoradiotherapy were recruited to this study (n = 10). Five scans were conducted per patient: a baseline scan was taken up to 3 days prior to treatment and at 1 week, 4 weeks, 8 weeks, and after neoadjuvant treatment prior to surgery. At each scan the patient lay prone with the breast suspended between immobilization plates in optical coupling medium. Pulsed near-infrared laser light was used to scan the breast at four different wavelengths and data was used for tomographic reconstruction. Volume-of-interest (VOI) weighted tissue Hb, HbO2, %water, and SP corresponding to the tumour was calculated and compared to clinical and pathological response as determined from full mount mastectomy pathology. For all 10 patients the tumour-based VOI was significantly different than background tissue for all functional parameters (p<0.001). Five patients had a good clinical and pathologic response. Four patients were considered non-responders. One patient initially had a poor clinical response to chemotherapy but after a change in chemotherapy had a good clinical and radiographic response. Responders and non-responders were significantly different for all of the functional parameters (p<0.05) at the 4-week scan. In the 5 patients with a good response the mean drop in Hb, HbO2, %water, and SP from baseline to the 4-week scan was 70.4% (SD = 18.6), 66.5% (SD = 24.5), 59.6% (SD = 30.9), and 60.7% (SD = 29.2), respectively. In contrast, the 4 non-responders had a mean drop of 17.7% (SD = 9.8), 18.0% (SD = 20.8), 15.4% (SD = 11.7), and 12.6% (SD = 10.2), for Hb, HbO2, %water and SP, respectively. Functional imaging using tomographic diffuse optical spectroscopy parameters of Hb, HbO2, %water and SP could be used as an early detector of final clinical and pathologic tumor response. This could be evaluated in the future to assess responses and potentially adjust chemotherapy regimins.
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Diffuse optical imaging for monitoring treatment response in breast cancer patients.
Conf Proc IEEE Eng Med Biol Soc
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The necessity for a non-invasive and inexpensive imaging modality to both diagnose and monitor treatment response has lead to renewed interest in the potential of optical imaging. The aim of this study was to investigate the potential of diffuse optical spectroscopy for monitoring of patients with locally advanced breast cancer undergoing neoadjuvant chemotherapy. Fifteen women receiving neoadjuvant treatment for breast cancer had the affected breast scanned 5 times: before, 1 week, 4 weeks, and 8 weeks following initiation of the treatment and prior to surgery. Data was collected using a commercial optical system at four different wavelengths (690 nm, 730 nm, 780 nm, and 830 nm) and used to create three dimensional tomographic images. Mean measured values of deoxyhemoglobin (Hb), oxyhemoglobin (HbO(2)), and water in the entire breast were obtained and integrated over the entire breast volume to calculate the integrated optical index for each parameter. Volume-of-interest weighted tissue Hb, HbO(2), and water corresponding to the tumor were also calculated. Patient response to the treatment was evaluated from clinical and pathological response using whole-mount pathology after mastectomy.
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A meta-analysis of the relationship between FGFR3 and TP53 mutations in bladder cancer.
PLoS ONE
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TP53 and FGFR3 mutations are the most common mutations in bladder cancers. FGFR3 mutations are most frequent in low-grade low-stage tumours, whereas TP53 mutations are most frequent in high-grade high-stage tumours. Several studies have reported FGFR3 and TP53 mutations to be mutually exclusive events, whereas others have reported them to be independent. We carried out a meta-analysis of published findings for FGFR3 and TP53 mutations in bladder cancer (535 tumours, 6 publications) and additional unpublished data for 382 tumours. TP53 and FGFR3 mutations were not independent events for all tumours considered together (OR?=?0.25 [0.18-0.37], p?=?0.0001) or for pT1 tumours alone (OR?=?0.47 [0.28-0.79], p?=?0.0009). However, if the analysis was restricted to pTa tumours or to muscle-invasive tumours alone, FGFR3 and TP53 mutations were independent events (OR?=?0.56 [0.23-1.36] (p?=?0.12) and OR?=?0.99 [0.37-2.7] (p?=?0.35), respectively). After stratification of the tumours by stage and grade, no dependence was detected in the five tumour groups considered (pTaG1 and pTaG2 together, pTaG3, pT1G2, pT1G3, pT2-4). These differences in findings can be attributed to the putative existence of two different pathways of tumour progression in bladder cancer: the CIS pathway, in which FGFR3 mutations are rare, and the Ta pathway, in which FGFR3 mutations are frequent. TP53 mutations occur at the earliest stage of the CIS pathway, whereas they occur would much later in the Ta pathway, at the T1G3 or muscle-invasive stage.
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Diffuse optical spectroscopy evaluation of treatment response in women with locally advanced breast cancer receiving neoadjuvant chemotherapy.
Transl Oncol
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The aim of this study was to investigate the potential of diffuse optical spectroscopy for monitoring of patients with locally advanced breast cancer (LABC) undergoing neoadjuvant chemotherapy. Fifteen women receiving treatment for LABC had the affected breast scanned before; 1 week, 4 weeks, and 8 weeks after treatment initiation; and before surgery. Optical properties related to tissue microstructure and biochemical composition were obtained. Clinical and pathologic tumor response was evaluated using whole-mount pathology after mastectomy. Patients who responded to treatment demonstrated an initial increase followed by a drop in optical parameters measured in the whole breast, whereas nonresponding patients demonstrated only a drop in the same parameters 1 week after treatment initiation. Responding patients demonstrated a significant increase of 17% ± 7%, 8% ± 8%, 10% ± 7%, 11% ± 11%, and 16% ± 15% in deoxygenated hemoglobin, oxygenated hemoglobin, total hemoglobin concentrations, water percentage, and tissue optical index, 1 week after treatment initiation, respectively. In contrast, nonresponding patients had a decrease of 14% ± 9%, 18% ± 7%, 17% ± 7%, 29% ± 7%, and 32% ± 9% in their corresponding optical parameters. Deoxygenated hemoglobin concentration (with 100% sensitivity, 83% specificity) and water percentage (with 75% sensitivity, 100% specificity) were found to be the best predictors of treatment response at 1 week after starting treatment. The results of this study suggest that optical parameters can be potentially used to predict and monitor patients responses to neoadjuvant chemotherapy and can form a basis for the customization of treatments in which inefficacious treatments can be switched to more efficacious therapies.
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FAN1 mutations cause karyomegalic interstitial nephritis, linking chronic kidney failure to defective DNA damage repair.
Nat. Genet.
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Chronic kidney disease (CKD) represents a major health burden. Its central feature of renal fibrosis is not well understood. By exome sequencing, we identified mutations in FAN1 as a cause of karyomegalic interstitial nephritis (KIN), a disorder that serves as a model for renal fibrosis. Renal histology in KIN is indistinguishable from that of nephronophthisis, except for the presence of karyomegaly. The FAN1 protein has nuclease activity and acts in DNA interstrand cross-link (ICL) repair within the Fanconi anemia DNA damage response (DDR) pathway. We show that cells from individuals with FAN1 mutations have sensitivity to the ICL-inducing agent mitomycin C but do not exhibit chromosome breakage or cell cycle arrest after diepoxybutane treatment, unlike cells from individuals with Fanconi anemia. We complemented ICL sensitivity with wild-type FAN1 but not with cDNA having mutations found in individuals with KIN. Depletion of fan1 in zebrafish caused increased DDR, apoptosis and kidney cysts. Our findings implicate susceptibility to environmental genotoxins and inadequate DNA repair as novel mechanisms contributing to renal fibrosis and CKD.
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Whole-brain radiation therapy of brain metastasis.
Prog Neurol Surg
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The purpose of this report was to review the role of whole brain radiotherapy (WBRT) in the management of brain metastases. In particular, we review the role of WBRT as a prophylactic therapy, and the role of surgery and stereotactic radiousurgery (SRS) with respect to WBRT, by discussing the relevant randomized controlled trials. WBRT is associated with toxicities and this may influence the decision to use WBRT and, therefore, we review both the acute side effects of WBRT and the more serious late side effects of neurocognitive impairment and leukoencephalopathy. As patients are living longer with brain metastases the role of WBRT is moving forward; however, using modern radiation technology we may be able to reduce the morbidity of this therapy. We present an extreme case of re-re-treatment WBRT with hippocampal sparing and simultaneous integrated boosts to multiple lesions as one of the future directions under evaluation.
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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.