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Find video protocols related to scientific articles indexed in Pubmed.
Parallel microfluidic chemosensitivity testing on individual slice cultures.
Lab Chip
PUBLISHED: 10-02-2014
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There is a critical unmet need to tailor chemotherapies to individual patients. Personalized approaches could lower treatment toxicity, improve the patient's quality of life, and ultimately reduce mortality. However, existing models of drug activity (based on tumor cells in culture or animal models) cannot accurately predict how drugs act in patients in time to inform the best possible treatment. Here we demonstrate a microfluidic device that integrates live slice cultures with an intuitive multiwell platform that allows for exposing the slices to multiple compounds at once or in sequence. We demonstrate the response of live mouse brain slices to a range of drug doses in parallel. Drug response is measured by imaging of markers for cell apoptosis and for cell death. The platform has the potential to allow for identifying the subset of therapies of greatest potential value to individual patients, on a timescale rapid enough to guide therapeutic decision-making.
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Hypertriglyceridemia, lipemia, and elevated liver enzymes associated with prolonged propofol anesthesia for craniotomy.
Ther Drug Monit
PUBLISHED: 09-16-2014
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: Lipemic blood was noted in the surgical field by a neurosurgeon after 12.5 hours of anesthesia consisting of infusions of propofol (total dose, 14,956 mcg) and remifentanil (total dose, 25,091 mcg). For most of that time, the rate of propofol was 120-160 mcg·kg-1·min-1 and never exceeded 160 mcg·kg-1·min-1. Lipemia was confirmed by allowing a sample of the patient's blood to settle in a syringe. The triglyceride concentration was 15.8 mmol/L. There was no metabolic acidosis or other indications of propofol infusion syndrome. Postoperatively, liver enzymes were elevated (peak aspartate aminotransferase, 420 units/L) but returned to nearly normal within 5 days. The patient recovered from surgery uneventfully. Reports of intraoperative lipemia during propofol anesthesia are very rare but raise concerns about the safety of prolonged propofol infusion.
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Periostin is a novel therapeutic target that predicts and regulates glioma malignancy.
Neuro-oncology
PUBLISHED: 08-19-2014
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Periostin is a secreted matricellular protein critical for epithelial-mesenchymal transition and carcinoma metastasis. In glioblastoma, it is highly upregulated compared with normal brain, and existing reports indicate potential prognostic and functional importance in glioma. However, the clinical implications of periostin expression and function related to its therapeutic potential have not been fully explored.
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Patient-specific metrics of invasiveness reveal significant prognostic benefit of resection in a predictable subset of gliomas.
PLoS ONE
PUBLISHED: 01-01-2014
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Malignant gliomas are incurable, primary brain neoplasms noted for their potential to extensively invade brain parenchyma. Current methods of clinical imaging do not elucidate the full extent of brain invasion, making it difficult to predict which, if any, patients are likely to benefit from gross total resection. Our goal was to apply a mathematical modeling approach to estimate the overall tumor invasiveness on a patient-by-patient basis and determine whether gross total resection would improve survival in patients with relatively less invasive gliomas.
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Hemangiopericytoma: Radical resection remains the cornerstone of therapy.
J Clin Neurosci
PUBLISHED: 08-13-2013
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Hemangiopericytomas (HPC) are mesenchymal tumors with a propensity towards chronicity and metastasis. This study aimed to reflect a single institution experience with both World Health Organization (WHO) grade II and III HPC. Pathology records from the years 1990-2013 at the University of Washington were searched to identify tumors unequivocally classified as HPC. Electronic chart review was then utilized to collect pertinent patient data. Of the WHO grade II HPC, there were four men and two women (average age 52years) while the grade III HPC group had eight men and two women (average age 51years). Sixty-six percent of WHO grade II tumors were located in the middle or posterior fossa as compared to none of the grade III tumors. Survival analysis revealed a significant survival benefit for patients who underwent complete resection (223months) versus those with subtotal resection (138months, p<0.05). Factors such as age, sex, the use of up-front radiation, and whether the patient had a recurrence did not show statistical significance related to overall survival or progression free survival. Radiation in the form of external beam radiotherapy given at the time of the first recurrence did trend towards improved progression free survival (56months) compared to those patients who were not radiated (22months, p=0.09) All patients with radical resection went on to never have a recurrence. Our results indicate that HPC are tumors with limited response to radiation and best treated with aggressive resection. Future studies will determine whether molecular-based therapies may provide added adjuvant benefit.
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The impact of age on oncogenic potential: tumor-initiating cells and the brain microenvironment.
Aging Cell
PUBLISHED: 05-06-2013
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Paradoxically, aging leads to both decreased regenerative capacity in the brain and an increased risk of tumorigenesis, particularly the most common adult-onset brain tumor, glioma. A shared factor contributing to both phenomena is thought to be age-related alterations in neural progenitor cells (NPCs), which function normally to produce new neurons and glia, but are also considered likely cells of origin for malignant glioma. Upon oncogenic transformation, cells acquire characteristics known as the hallmarks of cancer, including unlimited replication, altered responses to growth and anti-growth factors, increased capacity for angiogenesis, potential for invasion, genetic instability, apoptotic evasion, escape from immune surveillance, and an adaptive metabolic phenotype. The precise molecular pathogenesis and temporal acquisition of these malignant characteristics is largely a mystery. Recent studies characterizing NPCs during normal aging, however, have begun to elucidate mechanisms underlying the age-associated increase in their malignant potential. Aging cells are dependent upon multiple compensatory pathways to maintain cell cycle control, normal niche interactions, genetic stability, programmed cell death, and oxidative metabolism. A few multi-functional proteins act as critical nodes in the coordination of these various cellular activities, although both intracellular signaling and elements within the brain environment are critical to maintaining a balance between senescence and tumorigenesis. Here, we provide an overview of recent progress in our understanding of how mechanisms underlying cellular aging inform on glioma pathogenesis and malignancy.
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Converging paths to progress for skull base chordoma: Review of current therapy and future molecular targets.
Surg Neurol Int
PUBLISHED: 01-01-2013
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Chordomas of the skull base are rare locally aggressive neoplasms with a predilection for encapsulating critical neurovascular structures, bony destruction and irregular growth patterns, and from which patients succumb to recurrence and treatment failures.
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Seed, soil, and beyond: The basic biology of brain metastasis.
Surg Neurol Int
PUBLISHED: 01-01-2013
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First invoked by Paget, the seed and soil hypothesis suggests that the successful growth of metastatic cells depends on the interactions and properties of cancer cells (seeds) and their potential target organs (soil). In the context of the seed and soil hypothesis this review examines recent advances in the understanding of molecular and cellular features that permit transformed epithelial cells to gain access to the blood stream (intravasation), survive their journey through the blood stream, and ultimately traverse through the microvasculature of target organs (extravsation) to deposit, survive, and grow in a foreign tissue environment. In addition to a review of the clinical and experimental evidence supporting the seed and soil theory to cancer metastasis, additional concepts highlighted include: (i) The role of cancer stem-like cells as putative cells of metastatic origin (the "seeds"); (ii) the mechanism of epithelial to mesenchymal transition (EMT) in driving epithelial cell conthose molecules do no blood stream to avoid anoikis, or anchorage independent cell death; and (iv) the reverse process of EMT, or mesenchymal to epithelial transition (MET), which promotes conversion back to the parent cell morphology and growth of macrometastsis in the target organ. The unique biology of metastases once established in the brain, and in particular the "sanctuary" role that the brain microenvironment plays in promoting metastatic growth and treatment resistance, will also be examined. These issues are of more than academic interest since as systemic therapies gradually improve local tumor control, the relative impact of brain metastasis will inexorably play a proportionally greater role in determining patient morbidity and mortality.
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Increased re-entry into cell cycle mitigates age-related neurogenic decline in the murine subventricular zone.
Stem Cells
PUBLISHED: 09-28-2011
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Although new neurons are produced in the subventricular zone (SVZ) of the adult mammalian brain, fewer functional neurons are produced with increasing age. The age-related decline in neurogenesis has been attributed to a decreased pool of neural progenitor cells (NPCs), an increased rate of cell death, and an inability to undergo neuronal differentiation and develop functional synapses. The time between mitotic events has also been hypothesized to increase with age, but this has not been directly investigated. Studying primary-cultured NPCs from the young adult and aged mouse forebrain, we observe that fewer aged cells are dividing at a given time; however, the mitotic cells in aged cultures divide more frequently than mitotic cells in young cultures during a 48-hour period of live-cell time-lapse imaging. Double-thymidine-analog labeling also demonstrates that fewer aged cells are dividing at a given time, but those that do divide are significantly more likely to re-enter the cell cycle within a day, both in vitro and in vivo. Meanwhile, we observed that cellular survival is impaired in aged cultures. Using our live-cell imaging data, we developed a mathematical model describing cell cycle kinetics to predict the growth curves of cells over time in vitro and the labeling index over time in vivo. Together, these data surprisingly suggest that progenitor cells remaining in the aged SVZ are highly proliferative.
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Aging neural progenitor cells have decreased mitochondrial content and lower oxidative metabolism.
J. Biol. Chem.
PUBLISHED: 09-07-2011
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Although neurogenesis occurs in discrete areas of the adult mammalian brain, neural progenitor cells (NPCs) produce fewer new neurons with age. To characterize the molecular changes that occur during aging, we performed a proteomic comparison between primary-cultured NPCs from the young adult and aged mouse forebrain. This analysis yielded changes in proteins necessary for cellular metabolism. Mitochondrial quantity and oxygen consumption rates decrease with aging, although mitochondrial DNA in aged NPCs does not have increased mutation rates. In addition, aged cells are resistant to the mitochondrial inhibitor rotenone and proliferate in response to lowered oxygen conditions. These results demonstrate that aging NPCs display an altered metabolic phenotype, characterized by a coordinated shift in protein expression, subcellular structure, and metabolic physiology.
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HIF induces human embryonic stem cell markers in cancer cells.
Cancer Res.
PUBLISHED: 06-28-2011
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Low oxygen levels have been shown to promote self-renewal in many stem cells. In tumors, hypoxia is associated with aggressive disease course and poor clinical outcomes. Furthermore, many aggressive tumors have been shown to display gene expression signatures characteristic of human embryonic stem cells (hESC). We now tested whether hypoxia might be responsible for the hESC signature observed in aggressive tumors. We show that hypoxia, through hypoxia-inducible factor (HIF), can induce an hESC-like transcriptional program, including the induced pluripotent stem cell (iPSC) inducers, OCT4, NANOG, SOX2, KLF4, cMYC, and microRNA-302 in 11 cancer cell lines (from prostate, brain, kidney, cervix, lung, colon, liver, and breast tumors). Furthermore, nondegradable forms of HIF?, combined with the traditional iPSC inducers, are highly efficient in generating A549 iPSC-like colonies that have high tumorigenic capacity. To test potential correlation between iPSC inducers and HIF expression in primary tumors, we analyzed primary prostate tumors and found a significant correlation between NANOG-, OCT4-, and HIF1?-positive regions. Furthermore, NANOG and OCT4 expressions positively correlated with increased prostate tumor Gleason score. In primary glioma-derived CD133 negative cells, hypoxia was able to induce neurospheres and hESC markers. Together, these findings suggest that HIF targets may act as key inducers of a dynamic state of stemness in pathologic conditions.
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Fast bound pool fraction imaging of the in vivo rat brain: association with myelin content and validation in the C6 glioma model.
Neuroimage
PUBLISHED: 09-08-2010
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Cross-relaxation imaging (CRI) is a quantitative magnetic resonance technique that measures the kinetic parameters of magnetization transfer between protons bound to water and protons bound to macromolecules. In this study, in vivo, four-parameter CRI of normal rat brains (N=5) at 3.0 T was first directly compared to histology. The bound pool fraction, f, was strongly associated with myelin density (Pearsons r=0.99, p<0.001). The correlation persisted in separate analyses of gray matter (GM; r=0.89, p=0.046) and white matter (WM; r=0.97, p=0.029). Subsequently, a new time-efficient approach for solely capturing the whole-brain parametric map of f was proposed, validated with histology, and used to estimate myelin density. Since the described approach for the rapid acquisition of f applied constraints to other CRI parameters, a theoretical analysis of error was performed. Estimates of f in normal and pathologic tissue were expected to have <10% error. A comparison of values for f obtained from the traditional four-parameter fit of CRI data versus the proposed rapid acquisition of f was within this expected margin for in vivo rat brain gliomas (N=4; mean±SE; 3.9±0.2% vs. 4.0±0.2%, respectively). In both whole-brain f maps and myelin density maps, replacement of normal GM and WM by proliferating and invading tumor cells could be readily identified. The rapid, whole-brain acquisition of the bound pool fraction may provide a reliable method for detection of glioma invasion in both GM and WM during animal and human imaging.
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Imaging features of invasion and preoperative and postoperative tumor burden in previously untreated glioblastoma: Correlation with survival.
Surg Neurol Int
PUBLISHED: 04-28-2010
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A paucity of data exists concerning the prognostic usefulness of preoperative and postoperative imaging after resection of glioblastoma multiforme (GBM). This study aimed to connect outcome with imaging features of GBM.
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Quantitative proteomic analysis of oligodendrogliomas with and without 1p/19q deletion.
J. Proteome Res.
PUBLISHED: 03-27-2010
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Approximately 50-80% of oligodendrogliomas demonstrate a combined loss of chromosome 1p and 19q. Chromosome 1p/19q deletion, appearing early in tumorigenesis, is associated with improved clinical outcomes, including response to chemotherapy and radiation. Although many hypotheses have been proposed, the molecular mechanisms underlying improved clinical outcomes with 1p/19q deletion in oligodendrogliomas have not been characterized fully. To investigate the molecular differences between oligodendrogliomas, we employed an unbiased proteomic approach using microcapillary liquid chromatography mass spectrometry, along with a quantitative technique called isotope-coded affinity tags, on patient samples of grade II oligodendrogliomas. Following conventional biochemical separation of pooled tumor tissue from five samples of undeleted and 1p/19q deleted grade II oligodendrogliomas into nuclei-, mitochondria-, and cytosol-enriched fractions, relative changes in protein abundance were quantified. Among the 442 total proteins identified, 163 nonredundant proteins displayed significant changes in relative abundance in at least one of the three fractions between oligodendroglioma with and without 1p/19q deletion. Bioinformatic analyses of differentially regulated proteins supported the potential importance of metabolism and invasion/migration to the codeleted phenotype. A subset of altered proteins, including the pro-invasive extracellular matrix protein BCAN, was further validated by Western blotting as candidate markers for the more aggressive undeleted phenotype. These studies demonstrate the utility of proteomic analysis to identify candidate biological motifs and molecular mechanisms that drive differential malignancy related to 1p19q phenotypes. Future analysis of larger patient samples are warranted to further refine biomarker panels to predict biological behavior and assist in the identification of deleted gene products that define the 1p/19q phenotype.
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Multiportal endoscopic approaches to the central skull base: a cadaveric study.
World Neurosurg
PUBLISHED: 03-19-2010
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There has been marked evolution in techniques in skull base surgery including the development of minimally invasive endoscopic supraorbital, transnasal, and more recently, transorbital approaches. These have been typically described as isolated, rather than concerted approaches. It is possible that rather than using these approaches alone, they could be combined with transnasal approaches to provide improved manipulation angles, shorter working distances, and optimal visualization of the pathology. The primary objective of this study is therefore to determine whether these pathways can be combined in "multiportal" approaches to further improve the surgeons ability to access and manipulate pathology in the central anterior cranial fossa.
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TWIST1 promotes invasion through mesenchymal change in human glioblastoma.
Mol. Cancer
PUBLISHED: 02-23-2010
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Tumor cell invasion into adjacent normal brain is a mesenchymal feature of GBM and a major factor contributing to their dismal outcomes. Therefore, better understandings of mechanisms that promote mesenchymal change in GBM are of great clinical importance to address invasion. We previously showed that the bHLH transcription factor TWIST1 which orchestrates carcinoma metastasis through an epithelial mesenchymal transition (EMT) is upregulated in GBM and promotes invasion of the SF767 GBM cell line in vitro.
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A syngeneic glioma model to assess the impact of neural progenitor target cell age on tumor malignancy.
Aging Cell
PUBLISHED: 05-31-2009
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Human glioma incidence, malignancy, and treatment resistance are directly proportional to patient age. Cell intrinsic factors are reported to contribute to human age-dependent glioma malignancy, but suitable animal models to examine the role of aging are lacking. Here, we developed an orthotopic syngeneic glioma model to test the hypothesis that the age of neural progenitor cells (NPCs), presumed cells of glioma origin, influences glioma malignancy. Gliomas generated from transformed donor 3-, 12-, and 18-month-old NPCs in same-aged adult hosts formed highly invasive glial tumors that phenocopied the human disease. Survival analysis indicated increased malignancy of gliomas generated from older 12- and 18-month-old transformed NPCs compared with their 3-month counterparts (median survival of 38.5 and 42.5 vs. 77 days, respectively). This study showed for the first time that age of target cells at the time of transformation can affect malignancy and demonstrated the feasibility of a syngeneic model using transformed NPCs for future examination of the relative impacts of age-related cell intrinsic and cell-extrinsic factors in glioma malignancy.
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Quantitative analysis of mitotic Olig2 cells in adult human brain and gliomas: implications for glioma histogenesis and biology.
Glia
PUBLISHED: 05-14-2009
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The capacity of adult human glial progenitor cells (AGPs), to proliferate and undergo multipotent differentiation, positions them as ideal candidate cells of origin for human gliomas. To investigate this potential role we identified AGPs as mitotically active Olig2 cells in nonneoplastic adult human brain and gliomas. We conservatively estimated that one in 5,000 human temporal lobe neocortical gray or subcortical white matter cells is mitotic. Extrapolating from a mean Olig2/Mib-1 labeling index (LI) of 52% and total cell number of 100 billion, we estimated the overall prevalence of mitotic Olig2 AGPs in nonneoplastic human brain parenchyma at 10 million. These data identify a large reservoir of Olig2 AGPs which could be potential targets for human gliomagenesis. The vast majority of mitotic cells in Grade II and Grade III gliomas of all histologic subtypes expressed Olig2 (mean LI 75%) but rarely S100B (LI 0.6%), identifying the Olig2 cell as a distinct contributor to the proliferating cell population of human gliomas of both oligodendroglial and astrocytic lineages. In the most malignant Grade IV glioma, or glioblastoma multiforme (GBM), the prevalence of Olig2/Mib-1 cells was significantly decreased (24.5%). The significantly lower Olig2/Mib-1 LI in GBMs suggests that a decrease in the prevalence of Olig2 cells to the total mitotic cell pool accompanies increasing malignancy. The novel framework provided by this quantitative and comparative analysis supports future studies to examine the histogenetic role of Olig2 AGPs in adult gliomas, their potential contribution to the tumor stroma and the molecular role of Olig2 in glioma pathogenesis.
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A rare case of gamma knife-induced smoking cessation in a patient with a vestibular schwannoma.
Br J Neurosurg
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We report a rare case of a patient with a vestibular schwanomma who underwent gamma knife irradiation and subsequently lost unilateral taste sensation. As a result, the patient ceased smoking.
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Increased age of transformed mouse neural progenitor/stem cells recapitulates age-dependent clinical features of human glioma malignancy.
Aging Cell
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Increasing age is the most robust predictor of greater malignancy and treatment resistance in human gliomas. However, the adverse association of clinical course with aging is rarely considered in animal glioma models, impeding delineation of the relative importance of organismal versus progenitor cell aging in the genesis of glioma malignancy. To address this limitation, we implanted transformed neural stem/progenitor cells (NSPCs), the presumed cells of glioma origin, from 3- and 18-month-old mice into 3- and 20-month host animals. Transplantation with progenitors from older animals resulted in significantly shorter (P ? 0.0001) median survival in both 3-month (37.5 vs. 83 days) and 20-month (38 vs. 67 days) hosts, indicating that age-dependent changes intrinsic to NSPCs rather than host animal age accounted for greater malignancy. Subsequent analyses revealed that increased invasiveness, genomic instability, resistance to therapeutic agents, and tolerance to hypoxic stress accompanied aging in transformed NSPCs. Greater tolerance to hypoxia in older progenitor cells, as evidenced by elevated HIF-1 promoter reporter activity and hypoxia response gene (HRG) expression, mirrors the upregulation of HRGs in cohorts of older vs. younger glioma patients revealed by analysis of gene expression databases, suggesting that differential response to hypoxic stress may underlie age-dependent differences in invasion, genomic instability, and treatment resistance. Our study provides strong evidence that progenitor cell aging is responsible for promoting the hallmarks of age-dependent glioma malignancy and that consideration of progenitor aging will facilitate development of physiologically and clinically relevant animal models of human gliomas.
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Radiation associated tumors following therapeutic cranial radiation.
Surg Neurol Int
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A serious, albeit rare, sequel of therapeutic ionizing radiotherapy is delayed development of a new, histologically distinct neoplasm within the radiation field.
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A Case of Nodular Fasciitis Causing Compressive Optic Neuropathy.
Ophthal Plast Reconstr Surg
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A 16-year-old girl with worsening vision, new OD visual field deficits, and tumor in right orbital apex underwent biopsy and surgical excision. Orbital imaging revealed an apical tumor causing bony erosion. Histopathology confirmed the diagnosis of nodular fasciitis. This is a rare diagnosis, and one that can mimic a neoplastic process. To the authors knowledge, this is the first case of nodular fasciitis in the deep orbit and the first case of nodular fasciitis causing an optic neuropathy.
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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.

How does it work?

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.