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Method Enables Nanoscale Mapping of Protein Interactions on Live Cells [Techniques]

A new method called MicroMapping can identify nanoscale protein–protein interactions on live cells.




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Epigenetic Therapy Can Suppress Premetastatic Changes in the Lung [Metastasis]

Low-dose adjuvant epigenetic therapy (AET) reduced metastasis and promoted survival in mouse models.




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Non-Stem Cells Seed Colorectal Cancer Metastases and Gain Stem Traits [Metastasis]

LGR5 cells seed colorectal cancer metastases and produce stemlike LGR5+ outgrowth-promoting cells.




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Gastrin Blocks Symmetric Stem-Cell Division and Gastric Tumorigenesis [Gastric Cancer]

Symmetric division of stem cells positive for gastrin receptor CCK2R is linked to gastric cancer.




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Comparative single-cell RNA sequencing (scRNA-seq) reveals liver metastasis-specific targets in a patient with small intestinal neuroendocrine cancer [RESEARCH REPORT]

Genomic analysis of a patient's tumor is the cornerstone of precision oncology, but it does not address whether metastases should be treated differently. Here we tested whether comparative single-cell RNA sequencing (scRNA-seq) of a primary small intestinal neuroendocrine tumor to a matched liver metastasis could guide the treatment of a patient's metastatic disease. Following surgery, the patient was put on maintenance treatment with a somatostatin analog. However, the scRNA-seq analysis revealed that the neuroendocrine epithelial cells in the liver metastasis were less differentiated and expressed relatively little SSTR2, the predominant somatostatin receptor. There were also differences in the tumor microenvironments. RNA expression of vascular endothelial growth factors was higher in the primary tumor cells, reflected by an increased number of endothelial cells. Interestingly, vascular expression of the major VEGF receptors was considerably higher in the liver metastasis, indicating that the metastatic vasculature may be primed for expansion and susceptible to treatment with angiogenesis inhibitors. The patient eventually progressed on Sandostatin, and although consideration was given to adding an angiogenesis inhibitor to her regimen, her disease progression involved non-liver metastases that had not been characterized. Although in this specific case comparative scRNA-seq did not alter treatment, its potential to help guide therapy of metastatic disease was clearly demonstrated.




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BRAF V600E-mutated metastatic pediatric Wilms tumor with complete response to targeted RAF/MEK inhibition [RESEARCH REPORT]

Wilms tumor (WT) is the most common renal malignancy of childhood and accounts for 6% of all childhood malignancies. With current therapies, the 5-yr overall survival (OS) for children with unilateral favorable histology WT is greater than 85%. The prognosis is worse, however, for the roughly 15% of patients who relapse, with only 50%–80% OS reported in those with recurrence. Herein, we describe the extended and detailed clinical course of a rare case of a child with recurrent, pulmonary metastatic, favorable histology WT harboring a BRAF V600E mutation. The BRAF V600E mutation, commonly found in melanoma and other cancers, and previously undescribed in WT, has recently been reported by our group in a subset of epithelial-predominant WT. This patient, who was included in that series, presented with unilateral, stage 1, favorable histology WT and was treated with standard chemotherapy. Following the completion of therapy, the patient relapsed with pulmonary metastatic disease, that then again recurred despite an initial response to salvage chemotherapy and radiation. Next-generation sequencing (NGS) on the metastatic pulmonary nodule revealed a BRAF V600E mutation. After weighing the therapeutic options, a novel approach with dual BRAF/MEK inhibitor combination therapy was initiated. Complete radiographic response was observed following 4 months of therapy with dabrafenib and trametinib. At 12 months following the start of BRAF/MEK combination treatment, the patient continues with a complete response and has experienced minimal treatment-related side effects. This represents the first case, to our knowledge, of effective treatment with BRAF/MEK molecularly targeted therapy in a pediatric Wilms tumor patient.




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Objectively-Measured Light-Intensity Physical Activity and Risk of Cancer Mortality: A Meta-analysis of Prospective Cohort Studies

Background:

The impact of light-intensity physical activity (LPA) in preventing cancer mortality has been questioned. To address this concern, the present meta-analysis aimed to quantify the association between objectively-measured LPA and risk of cancer mortality.

Methods:

We conducted a systematic literature search in PubMed and Scopus to January 2020. Prospective cohort studies reporting the association between objectively-measured LPA using activity monitors (e.g., accelerometers) and risk of cancer mortality in the general population were included. The summary hazard ratios (HR) per 30 min/day of LPA and 95% confidence intervals (CI) were obtained using a random-effects model. Dose–response analysis was used to plot their relationship.

Results:

Five prospective cohort studies were included, in which the definition of LPA based on accelerometer readings was mainly set within 100 to 2,100 counts/min. The summary HR for cancer mortality per 30 min/day of LPA was 0.86 (95% CI, 0.79–0.95; I2 < 1%), and the association between LPA and risk reduction in cancer mortality was linearly shaped (Pnonlinearity = 0.72). LPA exhibited a comparable magnitude of risk reduction in cancer mortality of moderate-to-vigorous physical activity regardless of equal time-length (0.87 per 30 min/day vs. 0.94 per 30 min/day, Pinteraction = 0.46) or equal amount (0.74 vs. 0.94 per 150 metabolic equivalents-min/day, Pinteraction = 0.11). Furthermore, replacing sedentary time by LPA of 30 min/day decreased the risk of cancer mortality by 9%.

Conclusions:

Objectively-measured LPA conferred benefits in decreasing the risk of cancer mortality.

Impact:

LPA should be considered in physical activity guidelines to decrease the risk of cancer mortality.




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Red and Processed Meat, Poultry, Fish, and Egg Intakes and Cause-Specific and All-Cause Mortality among Men with Nonmetastatic Prostate Cancer in a U.S. Cohort

Background:

Research on the relationship of meat, fish, and egg consumption and mortality among prostate cancer survivors is limited.

Methods:

In the Cancer Prevention Study-II Nutrition Cohort, men diagnosed with nonmetastatic prostate cancer between baseline in 1992/1993 and 2015 were followed for mortality until 2016. Analyses of pre- and postdiagnosis intakes of red and processed meat, poultry, fish, and eggs included 9,286 and 4,882 survivors, respectively. Multivariable-adjusted RRs and 95% confidence intervals (CI) were estimated using Cox proportional hazards models.

Results:

A total of 4,682 and 2,768 deaths occurred during follow-up in pre- and postdiagnosis analyses, respectively. Both pre- and postdiagnosis intakes of total red and processed meat were positively associated with all-cause mortality (quartile 4 vs. 1: RR = 1.13; 95% CI, 1.03–1.25; Ptrend = 0.02; RR = 1.22; 95% CI, 1.07–1.39; Ptrend = 0.03, respectively), and both pre- and postdiagnosis poultry intakes were inversely associated with all-cause mortality (quartile 4 vs. 1 RR = 0.90; 95% CI, 0.82–0.98; Ptrend = 0.04; RR = 0.84; 95% CI, 0.75–0.95; Ptrend = 0.01, respectively). No associations were seen for prostate cancer–specific mortality, except that higher postdiagnosis unprocessed red meat intake was associated with lower risk.

Conclusions:

Higher red and processed meat, and lower poultry, intakes either before or after prostate cancer diagnosis were associated with higher risk of all-cause mortality.

Impact:

Our findings provide additional evidence that prostate cancer survivors should follow the nutrition guidelines limiting red and processed meat consumption to improve overall survival. Additional research on the relationship of specific meat types and mortality is needed.




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Prospective Association of Energy Balance Scores Based on Metabolic Biomarkers with Colorectal Cancer Risk

Background:

Energy balance–related factors, such as body mass index (BMI), diet, and physical activity, may influence colorectal cancer etiology through interconnected metabolic pathways, but their combined influence is less clear.

Methods:

We used reduced rank regression to derive three energy balance scores that associate lifestyle factors with combinations of prediagnostic, circulating levels of high-sensitivity C-reactive protein (hsCRP), C-peptide, and hemoglobin A1c (HbA1c) among 2,498 participants in the Cancer Prevention Study-II Nutrition Cohort. Among 114,989 participants, we verified 2,228 colorectal cancer cases. We assessed associations of each score with colorectal cancer incidence and by tumor molecular phenotypes using Cox proportional hazards regression.

Results:

The derived scores comprised BMI, physical activity, screen time, and 14 food groups, and explained 5.1% to 10.5% of the variation in biomarkers. The HR and 95% confidence interval (CI) for quartile 4 versus 1 of the HbA1c+C peptide–based score and colorectal cancer was 1.30 (1.15–1.47), the hsCRP-based score was 1.35 (1.19–1.53), and the hsCRP, C-peptide, and HbA1c-based score was 1.35 (1.19–1.52). The latter score was associated with non-CIMP tumors (HRQ4vsQ1: 1.59; 95% CI: 1.17–2.16), but not CIMP-positive tumors (Pheterogeneity = 0.04).

Conclusions:

These results further support hypotheses that systemic biomarkers of metabolic health—inflammation and abnormal glucose homeostasis—mediate part of the relationship between several energy balance–related modifiable factors and colorectal cancer risk.

Impact:

Results support cancer prevention guidelines for maintaining a healthful body weight, consuming a healthful diet, and being physically active. More research is needed on these clusters of exposures with molecular phenotypes of tumors.




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Harnessing Population Pedigree Data and Machine Learning Methods to Identify Patterns of Familial Bladder Cancer Risk

Background:

Relatives of patients with bladder cancer have been shown to be at increased risk for kidney, lung, thyroid, and cervical cancer after correcting for smoking-related behaviors that may concentrate in some families. We demonstrate a novel approach to simultaneously assess risks for multiple cancers to identify distinct multicancer configurations (multiple different cancer types that cluster in relatives) surrounding patients with familial bladder cancer.

Methods:

This study takes advantage of a unique population-level data resource, the Utah Population Database (UPDB), containing vast genealogy and statewide cancer data. Familial risk is measured using standardized incidence risk (SIR) ratios that account for sex, age, birth cohort, and person-years of the pedigree members.

Results:

We identify 1,023 families with a significantly higher bladder cancer rate than population controls (familial bladder cancer). Familial SIRs are then calculated across 25 cancer types, and a weighted Gower distance with K-medoids clustering is used to identify familial multicancer configurations (FMC). We found five FMCs, each exhibiting a different pattern of cancer aggregation. Of the 25 cancer types studied, kidney and prostate cancers were most commonly enriched in the familial bladder cancer clusters. Laryngeal, lung, stomach, acute lymphocytic leukemia, Hodgkin disease, soft-tissue carcinoma, esophageal, breast, lung, uterine, thyroid, and melanoma cancers were the other cancer types with increased incidence in familial bladder cancer families.

Conclusions:

This study identified five familial bladder cancer FMCs showing unique risk patterns for cancers of other organs, suggesting phenotypic heterogeneity familial bladder cancer.

Impact:

FMC configurations could permit better definitions of cancer phenotypes (subtypes or multicancer) for gene discovery and environmental risk factor studies.




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Projected Reductions in Absolute Cancer-Related Deaths from Diagnosing Cancers Before Metastasis, 2006-2015

Background:

New technologies are being developed for early detection of multiple types of cancer simultaneously. To quantify the potential benefit, we estimated reductions in absolute cancer–related deaths that could occur if cancers diagnosed after metastasis (stage IV) were instead diagnosed at earlier stages.

Methods:

We obtained stage-specific incidence and survival data from the Surveillance, Epidemiology, and End Results Program for 17 cancer types for all persons diagnosed ages 50 to 79 years in 18 geographic regions between 2006 and 2015. For a hypothetical cohort of 100,000 persons, we estimated cancer-related deaths under assumptions that cancers diagnosed at stage IV were diagnosed at earlier stages.

Results:

Stage IV cancers represented 18% of all estimated diagnoses but 48% of all estimated cancer-related deaths within 5 years. Assuming all stage IV cancers were diagnosed at stage III, 51 fewer cancer-related deaths would be expected per 100,000, a reduction of 15% of all cancer-related deaths. Assuming one third of metastatic cancers were diagnosed at stage III, one third diagnosed at stage II, and one third diagnosed at stage I, 81 fewer cancer-related deaths would be expected per 100,000, a reduction of 24% of all cancer-related deaths, corresponding to a reduction in all-cause mortality comparable in magnitude to eliminating deaths due to cerebrovascular disease.

Conclusions:

Detection of multiple cancer types earlier than stage IV could reduce at least 15% of cancer-related deaths within 5 years, affecting not only cancer-specific but all-cause mortality.

Impact:

Detecting cancer before stage IV, including modest shifts to stage III, could offer substantial population benefit.




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Genomics Methods for Xenopus Embryos and Tissues

High-throughput sequencing methods have created exciting opportunities to explore the regulatory landscape of the entire genome. Here we introduce methods to characterize the genomic locations of bound proteins, open chromatin, and sites of DNA–DNA contact in Xenopus embryos. These methods include chromatin immunoprecipitation followed by sequencing (ChIP-seq), a combination of DNase I digestion and sequencing (DNase-seq), the assay for transposase-accessible chromatin and sequencing (ATAC-seq), and the use of proximity-based DNA ligation followed by sequencing (Hi-C).




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[PERSPECTIVES] Myeloid Cells in Metastasis

Metastatic disease is the leading cause of death in patients with solid cancers. The progression to metastasis is a multistep process that involves detachment of tumor cells from their constraining basement membrane at the primary site, migration and intravasation into the circulation, survival in the circulation, extravasation into the secondary organ, and survival and growth at the secondary site. During these steps, tumor and immune cells interact and influence each other both within the tumor microenvironment and systemically. In particular, myeloid cells such as monocytes, macrophages, neutrophils, and myeloid-derived suppressor cells (myeloid regulatory cells) have been shown to play important roles in the metastatic process. These interactions open new avenues for targeting cancer metastasis, especially given the increasing interest in development of cancer immunotherapies. In this review, we describe the currently reported pathways and mechanisms involved in myeloid cell enhancement of the metastatic cascade.




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[PERSPECTIVES] Brain Metastasis Organotropism

Brain metastases are associated with poor prognosis irrespective of the primary tumor they originate from. Current treatments for brain metastases are palliative, and patients with symptomatic brain metastasis have a one-year survival of <20%. Lung cancer, breast cancer, and melanoma have higher incidences of brain metastases compared with other types of cancers. However, it is not very clear why some cancers metastasize to the brain more frequently than others. Studies thus far suggest that brain-specific tropism of certain types of cancers is defined by a winning combination of the following factors: unique genetic subtypes of primary tumors or its subclones enabling detachment, dissemination, blood–brain barrier penetration, plus proliferation and survival in hypoxic low-glucose microenvironment; specific transcriptomic and epigenetic changes of colony-forming metastatic cells, allowing their outgrowth; favorable metastasis-permissive microenvironment of the brain created by interactions of cancer cells and cells in the brain through triggering inflammation, recruiting myeloid-derived suppressor cells, and promoting metabolic adaptation; immunosuppression resulting in the failure of adaptive immune response to recognize or kill cancer cells in the brain. Here, we briefly review recent advances in understanding brain metastasis organotropism and outline directions for future research.




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Advanced ADC Histogram, Perfusion, and Permeability Metrics Show an Association with Survival and Pseudoprogression in Newly Diagnosed Diffuse Intrinsic Pontine Glioma: A Report from the Pediatric Brain Tumor Consortium [FUNCTIONAL]

BACKGROUND AND PURPOSE:

Diffuse intrinsic pontine glioma is a lethal childhood brain cancer with dismal prognosis and MR imaging is the primary methodology used for diagnosis and monitoring. Our aim was to determine whether advanced diffusion, perfusion, and permeability MR imaging metrics predict survival and pseudoprogression in children with newly diagnosed diffuse intrinsic pontine glioma.

MATERIALS AND METHODS:

A clinical trial using the poly (adenosine diphosphate ribose) polymerase (PARP) inhibitor veliparib concurrently with radiation therapy, followed by maintenance therapy with veliparib + temozolomide, in children with diffuse intrinsic pontine glioma was conducted by the Pediatric Brain Tumor Consortium. Standard MR imaging, DWI, dynamic contrast-enhanced perfusion, and DSC perfusion were performed at baseline and approximately every 2 months throughout treatment. ADC histogram metrics of T2-weighted FLAIR and enhancing tumor volume, dynamic contrast-enhanced permeability metrics for enhancing tumors, and tumor relative CBV from DSC perfusion MR imaging were calculated. Baseline values, post-radiation therapy changes, and longitudinal trends for all metrics were evaluated for associations with survival and pseudoprogression.

RESULTS:

Fifty children were evaluable for survival analyses. Higher baseline relative CBV was associated with shorter progression-free survival (P = .02, Q = 0.089) and overall survival (P = .006, Q = 0.055). Associations of higher baseline mean transfer constant from the blood plasma into the extravascular extracellular space with shorter progression-free survival (P = .03, Q = 0.105) and overall survival (P = .03, Q = 0.102) trended toward significance. An increase in relative CBV with time was associated with shorter progression-free survival (P < .001, Q < 0.001) and overall survival (P = .004, Q = 0.043). Associations of longitudinal mean extravascular extracellular volume fraction with progression-free survival (P = .03, Q = 0.104) and overall survival (P = .03, Q = 0.105) and maximum transfer constant from the blood plasma into the extravascular extracellular space with progression-free survival (P = .03, Q = 0.102) trended toward significance. Greater increases with time were associated with worse outcomes. True radiologic progression showed greater post-radiation therapy decreases in mode_ADC_FLAIR compared with pseudoprogression (means, –268.15 versus –26.11, P = .01.)

CONCLUSIONS:

ADC histogram, perfusion, and permeability MR imaging metrics in diffuse intrinsic pontine glioma are useful in predicting survival and pseudoprogression.




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Intermixed Dimethyl-Sulfoxide-Based Nonadhesive Liquid Embolic Agents Delivered Serially via the Same Microcatheter for Cerebral AVM Treatment [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

Conventional nonadhesive liquid embolic agents currently are the criterion standard for endovascular embolization of cerebral AVMs. However, inadequate distal penetration into the nidus and unstable proximal plug formation are the major limitations of this approach and of the currently available embolic materials. The aim of this study was to evaluate the hypothetic efficacy of combining liquid embolic agents with different properties and viscosities for use in endovascular embolization of cerebral AVMs.

MATERIALS AND METHODS:

From March 2018 to March 2019, sixteen patients with cerebral AVMs (12 women, 4 men; age range, 33–61 years) underwent endovascular embolization with combined liquid embolic agents delivered serially via a single microcatheter. The procedure consists of initial embolization with PHIL 30%, followed by Menox 18 through the same microcatheter. According to the Spetzler-Martin scale, 11 (68.75%) AVMs were grades I–II, 4 (25%) were grade III, and 1 (6.25%) was grade IV. Angiographic, technical, and clinical outcomes were analyzed independently.

RESULTS:

Combined PHIL and Menox embolization through the same microcatheter via 21 pedicles was performed in these 16 patients. Once the length of the reflux reached approximately 2 cm, PHIL 30% was switched to Menox 18. Antegrade flow and distal penetration of the serially applied liquid embolic agents were observed in all 16 cases. The ability to completely control the flow of the materials and avoid any dangerous proximal reflux was noted in all performed embolizations. The estimated average size reduction of the treated AVMs was 85%, ranging from 50% to 100%. Complete embolization was achieved in 10/16 or 62.5% of the cases. There was no procedure-related complication during or after the embolization. No mortality or postprocedural clinical worsening was seen. Clinical success and complete obliteration were confirmed with at least 1 follow-up angiography in 10/16 patients.

CONCLUSIONS:

Serial delivery of nonadhesive liquid embolic agents via the same microcatheter was safe and effective in our study and may be a potential technique for routine AVM treatment. However, further investigations are required to validate the safety and the efficacy of the method.




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Is Histologic Thrombus Composition in Acute Stroke Linked to Stroke Etiology or to Interventional Parameters? [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

Detailed insight into the composition of thrombi retrieved from patients with ischemic stroke by mechanical thrombectomy might improve pathophysiologic understanding and therapy. Thus, this study searched for links between histologic thrombus composition and stroke subtypes and mechanical thrombectomy results.

MATERIALS AND METHODS:

Thrombi from 85 patients who had undergone mechanical thrombectomy for acute ischemic stroke between December 2016 and March 2018 were studied retrospectively. Thrombi were examined histologically. Preinterventional imaging features, stroke subtypes, and interventional parameters were re-analyzed. Statistical analysis was performed with the Kruskal-Wallis test, Mann-Whitney U test, or Spearman correlation as appropriate.

RESULTS:

Cardioembolic thrombi had a higher percentage of macrophages and a tendency toward more platelets than thrombi of large-artery atherosclerotic stenosis (P = .021 and .003) or the embolic stroke of undetermined source (P = .037 and .099) subtype. Thrombi prone to fragmentation required the combined use of contact aspiration and stent retrieval (P = .021) and were associated with an increased number of retrieving maneuvers (P = .001), longer procedural times (P = .001), and a higher lymphocyte content (P = .035).

CONCLUSIONS:

We interpreted the higher macrophage and platelet content in cardioembolic thrombi compared with large-artery atherosclerotic stenosis or embolic stroke of undetermined source thrombi as an indication that the latter type might be derived from an atherosclerotic plaque rather than from an undetermined cardiac source. The extent of thrombus fragmentation was associated with a more challenging mechanical thrombectomy and a higher lymphocyte content of the thrombi. Thus, thrombus fragmentation not only might be caused by the recanalization procedure but also might be a feature of a lymphocyte-rich, difficult-to-retrieve subgroup of thrombi.




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Suspected Metallic Embolization Distal to Coiled Intracranial Aneurysms Detectable by Susceptibility-Weighted MR Imaging [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

After endovascular coiling of intracranial aneurysms, round dark parenchymal lesions believed to be particulate metal are sometimes encountered in MR imaging studies of the brain. We used SWI to assess the frequency of such occurrences, in addition to exploring likely causes and clinical implications.

MATERIALS AND METHODS:

We reviewed 700 MR imaging studies performed between September 2018 and March 2019 at our institution as follow-up monitoring of coiled intracranial aneurysms. Any sizeable (>5 mm) rounded dark-signal lesions encountered were presumed to be metallic. The magnitudes and locations of such lesions were recorded. In patients with these lesions, pertinent procedural documentation was screened for devices used, including coils, microcatheters, microguidewires, and stents. Medical records were also examined to determine whether any related symptoms ensued.

RESULTS:

Twenty patients (2.8%) exhibited a total of 25 lesions on SWI. Diameters ranged from 5 to 11 mm (median, 8 mm). All except 2 lesions were located in brain regions downstream from aneurysms, but all lesions occupied vascular territories of vessels used to place guiding catheters. Other than the Synchro 14, which was routinely deployed, no device was regularly used in patients with SWI-detectable lesions; and none of the affected patients developed focal neurologic symptoms as a consequence.

CONCLUSIONS:

Although the origins remain unclear, distal embolization of particulate metal distal to coiled cerebral aneurysms is occasionally observed on follow-up MR imaging studies. Such lesions, however, seem to have no apparent clinical impact.




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Discrimination between Glioblastoma and Solitary Brain Metastasis: Comparison of Inflow-Based Vascular-Space-Occupancy and Dynamic Susceptibility Contrast MR Imaging [FUNCTIONAL]

BACKGROUND AND PURPOSE:

Accurate differentiation between glioblastoma and solitary brain metastasis is of vital importance clinically. This study aimed to investigate the potential value of the inflow-based vascular-space-occupancy MR imaging technique, which has no need for an exogenous contrast agent, in differentiating glioblastoma and solitary brain metastasis and to compare it with DSC MR imaging.

MATERIALS AND METHODS:

Twenty patients with glioblastoma and 22 patients with solitary brain metastasis underwent inflow-based vascular-space-occupancy and DSC MR imaging with a 3T clinical scanner. Two neuroradiologists independently measured the maximum inflow-based vascular-space-occupancy–derived arteriolar CBV and DSC-derived CBV values in intratumoral regions and peritumoral T2-hyperintense regions, which were normalized to the contralateral white matter (relative arteriolar CBV and relative CBV, inflow-based vascular-space-occupancy relative arteriolar CBV, and DSC-relative CBV). The intraclass correlation coefficient, Student t test, or Mann-Whitney U test and receiver operating characteristic analysis were performed.

RESULTS:

All parameters of both regions had good or excellent interobserver reliability (0.74~0.89). In peritumoral T2-hyperintese regions, DSC-relative CBV (P < .001), inflow-based vascular-space-occupancy arteriolar CBV (P = .001), and relative arteriolar CBV (P = .005) were significantly higher in glioblastoma than in solitary brain metastasis, with areas under the curve of 0.94, 0.83, and 0.72 for discrimination, respectively. In the intratumoral region, both inflow-based vascular-space-occupancy arteriolar CBV and relative arteriolar CBV were significantly higher in glioblastoma than in solitary brain metastasis (both P < .001), with areas under the curve of 0.91 and 0.90, respectively. Intratumoral DSC-relative CBV showed no significant difference (P = .616) between the 2 groups.

CONCLUSIONS:

Inflow-based vascular-space-occupancy has the potential to discriminate glioblastoma from solitary brain metastasis, especially in the intratumoral region.




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Brain Metastases: Insights from Statistical Modeling of Size Distribution [ADULT BRAIN]

BACKGROUND AND PURPOSE:

Brain metastases are a common finding on brain MRI. However, the factors that dictate their size and distribution are incompletely understood. Our aim was to discover a statistical model that can account for the size distribution of parenchymal metastases in the brain as measured on contrast-enhanced MR imaging.

MATERIALS AND METHODS:

Tumor volumes were calculated on the basis of measured tumor diameters from contrast-enhanced T1-weighted spoiled gradient-echo images in 68 patients with untreated parenchymal metastatic disease. Tumor volumes were then placed in rank-order distributions and compared with 11 different statistical curve types. The resultant R2 values to assess goodness of fit were calculated. The top 2 distributions were then compared using the likelihood ratio test, with resultant R values demonstrating the relative likelihood of these distributions accounting for the observed data.

RESULTS:

Thirty-nine of 68 cases best fit a power distribution (mean R2 = 0.938 ± 0.050), 20 cases best fit an exponential distribution (mean R2 = 0.957 ± 0.050), and the remaining cases were scattered among the remaining distributions. Likelihood ratio analysis revealed that 66 of 68 cases had a positive mean R value (1.596 ± 1.316), skewing toward a power law distribution.

CONCLUSIONS:

The size distributions of untreated brain metastases favor a power law distribution. This finding suggests that metastases do not exist in isolation, but rather as part of a complex system. Furthermore, these results suggest that there may be a relatively small number of underlying variables that substantially influence the behavior of these systems. The identification of these variables could have a profound effect on our understanding of these lesions and our ability to treat them.




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MR Thermometry in Cerebrovascular Disease: Physiologic Basis, Hemodynamic Dependence, and a New Frontier in Stroke Imaging [ADULT BRAIN]

SUMMARY:

The remarkable temperature sensitivity of the brain is widely recognized and has been studied for its role in the potentiation of ischemic and other neurologic injuries. Pyrexia frequently complicates large-vessel acute ischemic stroke and develops commonly in critically ill neurologic patients; the profound sensitivity of the brain even to minor intraischemic temperature changes, together with the discovery of brain-to-systemic as well as intracerebral temperature gradients, has thus compelled the exploration of cerebral thermoregulation and uncovered its immutable dependence on cerebral blood flow. A lack of pragmatic and noninvasive tools for spatially and temporally resolved brain thermometry has historically restricted empiric study of cerebral temperature homeostasis; however, MR thermometry (MRT) leveraging temperature-sensitive nuclear magnetic resonance phenomena is well-suited to bridging this long-standing gap. This review aims to introduce the reader to the following: 1) fundamental aspects of cerebral thermoregulation, 2) the physical basis of noninvasive MRT, and 3) the physiologic interdependence of cerebral temperature, perfusion, metabolism, and viability.




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Sở hữu ngay Shophouse Metro Star mặt tiền Song Hành Xa Lộ Hà Nội giá chỉ 70 triệu/m2 Lh: 0933836751

Chỉ cần thanh toán 15% sở hữu ngay Shophouse Metro Star.- Chiết khấu lên đến 10%.- Cam kết cho thuê 111,305 triệu/tháng trong 3 năm.- Cam kết mua lại sau 24 tháng với lợi nhuận 22%.- Shophouse Metro Star vị trí vàng cửa ngõ khu Đông.- Nằm ngay mặt tiền Song Hành, Xa Lộ Hà Nội, li...




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Duy nhất 1 căn Shophouse 90m2 GĐ1 của CĐT mặt tiền đường Xa Lộ Hà Nội Q9, đối diện ga Metro số 10

- Chủ đầu tư mở bán giai đoạn 1 duy nhất còn 1 căn diện tích 90m2 Shophouse Metro Star góc 2 mặt tiền tiện kinh doanh hoặc cho thuê sau này. - Shophouse Metro Star nằm đối diện trạm metro số 10 tuyến số 1 có cầu bộ hành kết nối trực tiếp vào tầng 2 của trung tâm thương mại của dự án. - Hiện tại tuyến Metro số 1 đã hoàn thiện hơn 70% tiến độ, dự kiến sẽ đi vào vận hành vào cuối ...




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Shophouse Metro Star, hot nhất khu Đông, cầu bộ hành nối liền tầng 2 của dự án vào nhà ga số 10

Lấy cảm hứng từ Myeongdong - khu phố mua sắm, giải trí nổi tiếng bậc nhất Seoul Một Myeongdong Hàn Quốc sẽ được tái hiện sống động ngay tại khu Đông Sài Gòn hứa hẹn tạo nên không gian sầm uất của phố thị rực rỡ.Tập trung hàng trăm thương hiệu thời trang nổi tiếng, không gian ẩm t...




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Thiết kế phòng giặt tiện nghi, phong cách giúp xua tan mệt mỏi

Không cần quá cầu kỳ, kiểu cách, một vài ý tưởng thiết kế phòng giặt gọn gàng, đẹp mắt không chỉ giúp công việc giặt giũ hàng ngày bớt nhàm chán, mệt mỏi mà còn mang đến cho bạn tinh thần thoải mái, đầy hứng khởi.




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Central Metropolitan

Gia Lâm Central Metropolitan là dự án nhà phố thương mại được đầu tư bởi Công Ty Xây Dựng Cổ Phần Đầu Tư Và Phát Triển Xây Dựng 1 Hà Nội tại thị trấn Trâu Quỳ, huyện Gia Lâm, Hà Nội.




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Metro Star Project In Ho Chi Minh City

If you are looking for commercial properties in HCMC with rental guarantee 10% per year and buy back interest 22% in 2 years, you HAVE TO CHECK METRO STAR SHOPHOUSE. Please read on:Metro Star is located on two fronts of Hanoi and Nam Hoa Highway, in the most crowded and vibrant...




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6 guiding parameters to upgrade your workplace environment in the digital economy

Prof. Jason Pomeroy talks about the rise of the digital economy and its impact on the workplace.




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TP.HCM: Xin chủ trương bố trí vốn giải phóng mặt bằng tuyến metro 2

Phó Chủ tịch UBND TP.HCM Võ Văn Hoan vừa có chỉ đạo về việc tháo gỡ khó khăn, vướng mắc nhằm đẩy nhanh tiến độ triển khai các dự án đầu tư công trọng điểm.




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TP.HCM: Đề xuất làm metro Bến Thành - Tân Kiên vốn 68.000 tỷ đồng

UBND TP.HCM vừa gửi Bộ Kế hoạch và Đầu tư xem xét, trình Thủ tướng dự án Metro Bến Thành - Tân Kiên (số 3A) với chiều dài 20km, tổng mức đầu tư 68.000 tỷ đồng.




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Hot! 3-storey shophouse for sale in Thao Dien D2, 300m2, near metro station - Call +84 948 522 889

- Sublease investor commits to profit within 6 years , plan price 25$/m2 - Area: 191.2m2 - Price: $1,060,000 -The Developer is the company of Fraser Singapore which is very famous in other countries because this is the first project in Vietnam so the Developer sells with not much...




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Never Rarely Sometimes Always – Movie Review

Never Rarely Sometimes Always – Movie Review Rating: A- (Great) Trailer/Thumbnail Courtesy Universal Pictures Getting pregnant can be a tricky event for any teenager and how they approach this can often depend on their environment. In exploring the topic, director/writer Eliza Hittman has opted for a realistic portrayal. The journey taken by Autumn and her […]

The post Never Rarely Sometimes Always – Movie Review appeared first on The Scene Magazine.




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How a flawed mentality led to Silicon Valley’s meteoric rise

In the memoir Uncanny Valley, Anna Wiener examines the collective hyperconfidence that has enabled the tech sector’s meteoric growth




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US military face recognition system could work from 1 kilometre away

The US Special Operations Command is developing a portable face-recognition system designed to identify people 1 kilometre away. It could also be used by law enforcement




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Liquid metal that floats on water could make transformable robots

A lightweight liquid metal alloy that is less dense than water could be used to make exoskeletons and transformable flexible robots




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Teenager Ran Away to Be With Boy She Met on Dating Site. A Week Later She Was Dead.

Moorcraft Police Department/Meade County Sheriff’s Office

A South Dakota teenager has admitted to slaying a 16-year-old girl who “ran away” from home to live with him after they met on an online dating website, authorities said.

Michael Campbell, 17, pleaded guilty to first-degree manslaughter on Thursday for the death of Shayna Ritthaler, a 16-year-old from Moorcroft, Wyoming, who was reported missing from a local coffee shop on Oct. 3. Less than a week later, her body was found in the basement bedroom of Campbell’s home.

“We got into an argument and then I shot her,” Campbell said during a change-of-plea hearing on Thursday, before referring to the teenager as his girlfriend, according to the Associated Press. “I shot her in the head.”

Read more at The Daily Beast.




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Meth, Murder, and Madness: The System That Buried Ahmaud Arbery

Photo Illustration by Lyne Lucien/The Daily Beast/Getty

SAVANNAH, Georgia—Allegations Friday that a Georgia district attorney blocked police officers from arresting the killers of 25-year-old Ahmaud Arbery were just the latest blow to a local law enforcement apparatus that has been rocked by a series of troubling and deadly scandals.

Brunswick DA Jackie Johnson’s office allegedly prevented the Glynn County Police Department from arresting Travis and Gregory McMichael in connection with the shooting death of Arbery, an unarmed black man, in late February, the Atlanta Journal-Constitution reported. Johnson has recused herself from that case. But one Glynn County commissioner suggested she personally intervened in early plans to make arrests “to protect her friend” Gregory McMichael. McMichael was a former cop and investigator in the Brunswick DA’s office for 25 years who had reportedly investigated Arbery in the past. 

It is far from the first time the office—and local law enforcement more generally—had come under scathing scrutiny. 

Read more at The Daily Beast.




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Here's A Metal Cover Of The Cantina Band Song

I bloody love me some Figrin D'an and the Modal Nodes. So for Star Wars Day I thought it would be funny to see if a decent cover of their most famous tune existed. It does. Oh how it does. More »
    




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How to watch the Quadrantids, the first meteor shower of 2020

The Quadrantid meteor shower has a short peak period that lasts only a few hours, so midnight on 3 January is the best time to view in the UK




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Have we really found an alien protein inside a meteorite?

A team of researchers say they have discovered a protein molecule inside a meteorite, the first extraterrestrial example ever found, but others are sceptical




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Comet 67P is hiding nitrogen that could solve a solar system mystery

The Rosetta spacecraft’s measurements of comet 67P have revealed a hidden source of nitrogen that may help us learn how giant planets – and even life – formed




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Interstellar comet Borisov may be breaking up as it exits solar system

The first-ever interstellar comet is showing signs of brightening, suggesting it may have been heated up as it passed near to the sun




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Tiny meteorite found in Antarctica came from an unknown asteroid

A tiny meteorite found in Antarctica doesn’t match any asteroid or comet we know of. Instead, it must have come from a mystery parent body that’s full of water




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Interstellar comet Borisov came from a cold and distant home star

The interstellar comet Borisov, which flew past Earth in December, is full of carbon monoxide ice that implies its home star is smaller and colder than our sun




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RoMeLa's Newest Robot Is a Curiously Symmetrical Dynamic Quadruped

With four legs but no back or front, ALPHRED 2 can run, jump, and punch through boards in any direction




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The Ultimate Optimization Problem: How to Best Use Every Square Meter of the Earth's Surface

Lucas Joppa, founder of Microsoft's AI for Earth program, is taking an engineering approach to environmental issues




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RuPaul’s Drag Race Recap: #Methmentum

Given the overall strength of this top six, it’s surprising how messy these one-queen shows turn out to be.




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RPGCast – Episode 367: “Cheaters Sometimes Prospers”

Chris enters the confessional and spills the beans about what evil deeds he’s been up to in Fallout 4 and Tales of Zestiria. Alex Dances...




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RPG Cast – Episode 524: “Overhead Isometricy Game”

Alex, Johnathan, and Chris run through the past two weeks of news, bemoan the lack of time to play games, and then commit to not trying to play anything new. Ring Fit Adventure wins RPG of the year. But seriously, why isn't Shining Force II on that thing?




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Cosmetic surgery conundrum: is it OK to speculate about Jared Kushner and Botox?

The ‘haunted doll’ look of Donald Trump’s son-in-law has attracted a lot of attention. When people comment on famous women and surgery there is often a backlash, but should the same apply here?

What has happened to Jared Kushner’s face?
Richard, by email

People get a little antsy about the subject of cosmetic surgery: they don’t like to be asked if they have had it, and public speculation over whether someone else has had it is generally considered to be de trop. I don’t really get this. Maybe it’s because I am 100% the world’s worst liar, but pretending to not see that someone’s face has completely changed is a form of magical thinking that is just beyond my capabilities.

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