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[PERSPECTIVES] PTEN Nuclear Functions

For years, clinical and basic researchers have been aware of the presence of PTEN in the nucleus in cell culture, animal models, and both healthy and diseased human tissues. Despite the early recognition of nuclear PTEN, the understanding of the mechanisms of its nuclear localization, function in the nucleus, and importance in biology and human disease has been lacking. Over the last decade, emerging concepts for the complex involvement of nuclear PTEN in a variety of processes, including genome maintenance and DNA repair, cell-cycle control, gene expression, and DNA replication, are illuminating what could prove to be the key path toward a full understanding of PTEN function in health and disease. Dysregulation of nuclear PTEN is now considered an important aspect of the etiology of many pathologic conditions, prompting reconsideration of the therapeutic approaches aimed at countering the consequences of PTEN deficiency. This new knowledge is fueling the development of innovative therapeutic modalities for a broad spectrum of human conditions, from cancer and metabolic diseases, to neurological disorders and autism.




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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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Radiomics Study of Thyroid Ultrasound for Predicting BRAF Mutation in Papillary Thyroid Carcinoma: Preliminary Results [FUNCTIONAL]

BACKGROUND AND PURPOSE:

It is not known how radiomics using ultrasound images contribute to the detection of BRAF mutation. This study aimed to evaluate whether a radiomics study of gray-scale ultrasound can predict the presence or absence of B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutation in papillary thyroid cancer.

MATERIALS AND METHODS:

The study retrospectively included 96 thyroid nodules that were surgically confirmed papillary thyroid cancers between January 2012 and June 2013. BRAF mutation was positive in 48 nodules and negative in 48 nodules. For analysis, ROIs from the nodules were demarcated manually on both longitudinal and transverse sonographic images. We extracted a total of 86 radiomics features derived from histogram parameters, gray-level co-occurrence matrix, intensity size zone matrix, and shape features. These features were used to build 3 different classifier models, including logistic regression, support vector machine, and random forest using 5-fold cross-validation. The performance including accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve, of the different models was evaluated.

RESULTS:

The incidence of high-suspicion nodules diagnosed on ultrasound was higher in the BRAF mutation–positive group than in the mutation–negative group (P = .004). The radiomics approach demonstrated that all classification models showed moderate performance for predicting the presence of BRAF mutation in papillary thyroid cancers with an area under the curve value of 0.651, accuracy of 64.3%, sensitivity of 66.8%, and specificity of 61.8%, on average, for the 3 models.

CONCLUSIONS:

Radiomics study using thyroid sonography is limited in predicting the BRAF mutation status of papillary thyroid carcinoma. Further studies will be needed to validate our results using various diagnostic methods.




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Anoxic Brain Injury Detection with the Normalized Diffusion to ASL Perfusion Ratio: Implications for Blood-Brain Barrier Injury and Permeability [FUNCTIONAL]

BACKGROUND AND PURPOSE:

Anoxic brain injury is a result of prolonged hypoxia. We sought to describe the nonquantitative arterial spin-labeling perfusion imaging patterns of anoxic brain injury, characterize the relationship of arterial spin-labeling and DWI, and evaluate the normalized diffusion-to-perfusion ratio to differentiate patients with anoxic brain injury from healthy controls.

MATERIALS AND METHODS:

We identified all patients diagnosed with anoxic brain injuries from 2002 to 2019. Twelve ROIs were drawn on arterial spin-labeling with coordinate-matched ROIs identified on DWI. Linear regression analysis was performed to examine the relationship between arterial spin-labeling perfusion and diffusion signal. Normalized diffusion-to-perfusion maps were generated using a custom-built algorithm.

RESULTS:

Thirty-five patients with anoxic brain injuries and 34 healthy controls were identified. Linear regression analysis demonstrated a significant positive correlation between arterial spin-labeling and DWI signal. By means of a combinatory cutoff of slope of >0 and R2 of > 0.78, linear regression using arterial spin-labeling and DWI showed a sensitivity of 0.86 (95% CI, 0.71–0.94) and specificity of 0.82 (95% CI, 0.66–0.92) for anoxic brain injuries. A normalized diffusion-to-perfusion color map demonstrated heterogeneous ratios throughout the brain in healthy controls and homogeneous ratios in patients with anoxic brain injuries.

CONCLUSIONS:

In anoxic brain injuries, a homogeneously positive correlation between qualitative perfusion and DWI signal was identified so that areas of increased diffusion signal showed increased ASL signal. By exploiting this relationship, the normalized diffusion-to-perfusion ratio color map may be a valuable imaging biomarker for diagnosing anoxic brain injury and potentially assessing BBB integrity.




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Hippocampal Sclerosis Detection with NeuroQuant Compared with Neuroradiologists [FUNCTIONAL]

BACKGROUND AND PURPOSE:

NeuroQuant is an FDA-approved software that performs automated MR imaging quantitative volumetric analysis. This study aimed to compare the accuracy of NeuroQuant analysis with visual MR imaging analysis by neuroradiologists with expertise in epilepsy in identifying hippocampal sclerosis.

MATERIALS AND METHODS:

We reviewed 144 adult patients who underwent presurgical evaluation for temporal lobe epilepsy. The reference standard for hippocampal sclerosis was defined by having hippocampal sclerosis on pathology (n = 61) or not having hippocampal sclerosis on pathology (n = 83). Sensitivities, specificities, positive predictive values, and negative predictive values were compared between NeuroQuant analysis and visual MR imaging analysis by using a McNemar paired test of proportions and the Bayes theorem.

RESULTS:

NeuroQuant analysis had a similar specificity to neuroradiologist visual MR imaging analysis (90.4% versus 91.6%; P = .99) but a lower sensitivity (69.0% versus 93.0%, P < .001). The positive predictive value of NeuroQuant analysis was comparable with visual MR imaging analysis (84.0% versus 89.1%), whereas the negative predictive value was not comparable (79.8% versus 95.0%).

CONCLUSIONS:

Visual MR imaging analysis by a neuroradiologist with expertise in epilepsy had a higher sensitivity than did NeuroQuant analysis, likely due to the inability of NeuroQuant to evaluate changes in hippocampal T2 signal or architecture. Given that there was no significant difference in specificity between NeuroQuant analysis and visual MR imaging analysis, NeuroQuant can be a valuable tool when the results are positive, particularly in centers that lack neuroradiologists with expertise in epilepsy, to help identify and refer candidates for temporal lobe epilepsy resection. In contrast, a negative test could justify a case referral for further evaluation to ensure that false-negatives are detected.




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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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Fundamentals for Creating a Shoppable Interactive Video for eCommerce

(function () { var vjs = videojs("hapyak-player-225918-6090"); vjs.one("loadedmetadata", function () { hapyak.viewer({ apiKey: "dd426e8a5f6c45db9ca6", projectId: 225918, plugins: { annotationSources: {"brightcove.cuepoints": true} }, resetVariables: true, player: […]

The post Fundamentals for Creating a Shoppable Interactive Video for eCommerce appeared first on e-Learning Feeds.




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Twitter was once a fun place – now it is heading towards destruction

Twitter used to be full of cat memes and had a culture of sharing. Now, I pay a company to make sure my presence on the site is extremely limited, writes Annalee Newitz




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The coronavirus crisis could fundamentally alter the internet

The covid-19 pandemic has many of us stuck at home. The result could completely reshape how we use the internet, writes Annalee Newitz




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Calculator Hacked for Cheating Includes a Secret OLED Screen, Wifi, and Even a Chat Function

But can you still write "BOOBS" on it?




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RPGCast – Episode 348: “You Know, That Funny Thing I Said”

Chris has to resist the lure of the bratwurst to record a show. Anna Marie has to match 3. Alice has to deliver missiles…wait…she didn’t...




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RPGCast – Episode 435: “This Deck Was Funded With Miniskirts”

The RPG Cast crew gets tempted to buy all the collector’s editions today. We also then find out all the release dates. Now excuse us...




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RPGCast – Episode 497: “Git Gud Or Git A Refund”

A slightly smaller show doesn’t mean any less action, news, or hilariously questionable jibes for this week’s RPGCast. We learn we cannot, in fact, git...



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Soundgarden countersue Chris Cornell's widow over fundraising show

Soundgarden have claimed Chris Cornell's widow used charity money for personal purposes.







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Biden campaign signs joint fundraising agreement with DNC

Joe Biden's campaign has signed a joint fundraising agreement with the DNC that will help Democrats close the gap with President Donald Trump's massive war chest.




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A role reversal for the function of certain circadian network neurons

A new study y reveals surprising findings about the function of circadian network neurons that undergo daily structural change. The research could lead to a better understanding of how to address circadian rhythm disruptions in humans and facilitate preventing a host of associated health problems, including increased risk for cancer and metabolic syndrome.




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Gamer who died of coronavirus has Nintendo 'Animal Crossing' funeral

The life of a New York video game enthusiast who died from complications of the coronavirus was celebrated with a virtual service on Nintendo’s hit video game: “Animal Crossing: New Horizons.”




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Explainer: Fed funds futures market sees negative rates by next April

The fed funds futures market is pricing in negative U.S. interest rates next year, a scenario the Federal Reserve has said it wants to avoid as many doubt that it would be an effective tool to stimulate growth.




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Home Office announces awareness campaign and £2m funding to tackle domestic abuse amid lockdown

Read our live coronavirus updates HERE




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Donald Trump to halt World Health Organisation funding over handling of coronavirus pandemic

Following our live Covid-19 updates HERE




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Piers Morgan donates £10,000 to war veteran, 99, walking to fundraise for NHS during coronavirus pandemic

Follow our live coronavirus updates HERE Coronavirus: the symptoms




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Bill Gates condemns Trump&apos;s &apos;dangerous&apos; decision to stop WHO funding during coronavirus crisis

Read our live updates on coronavirus HERE Coronavirus: The symptoms




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US records highest daily coronavirus death toll yet as Donald Trump threatens to cut WHO funding

Coronavirus: the symptoms Live updates here




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Why has Donald Trump frozen WHO funding during the coronavirus crisis?

Coronavirus: The symptoms




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How to donate to Captain Tom Moore&apos;s NHS fundraiser

Coronavirus: the symptoms Read our live updates here




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Captain Tom Moore completes final fundraising lap for NHS as donations soar past £12m

Follow our live coronavirus updates HERE Coronavirus: The symptoms




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Royals send thank you letters to hero Captain Tom Moore, 99, after fundraiser for NHS hits £15 million

The Duke of Cambridge and his stepmother the Duchess of Cornwall have both written to Captain Tom Moore, 99, to congratulate him on smashing his NHS fundraising target.




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Captain Tom Moore hits £18 million in NHS fundraiser as Prince William donates to cause

Read our live coronavirus updates HERE




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Tom Moore could receive Spitfire flypast for 100th birthday as coronavirus fundraiser passes £21 million

The 99-year-old war veteran has raised an incredible £21 million for charity




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Funerals can go ahead with close family present, Government confirms

Funerals must be allowed to take place to enable families to mourn their loved ones, the Government has said.




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Fundraising hero Captain Tom Moore&apos;s charity cover on course for number one

Captain Tom Moore and Michael Ball are on course to score a number one single for their cover of You'll Never Walk Alone.




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Fundraising hero Captain Tom Moore to open NHS Nightingale hospital in Yorkshire

New field hospital in Harrogate to provide 500 extra beds for Covid-19 patients




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NHS fundraising hero Captain Tom Moore sent &apos;tens of thousands&apos; of birthday cards

War veteran Captain Tom Moore, who has raised £28 million for the NHS by walking lengths of his garden, has been sent tens of thousands of cards ahead of his 100th birthday.




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WHO chief brushes off calls for resignation and urges US to reconsider funding freeze

The head of the World Health Organisation has brushed off calls for his resignation as he told the US to reconsider freezing its funding.




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Ryanair will not issue refunds to customers until &apos;coronavirus crisis is over&apos;, airline confirms

Ryanair has told passengers it will not pay refunds for cancelled flights until the coronavirus crisis "is over".




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London filmmaker claps for 24 hours straight to raise funds for NHS

Jack Peagam is livestreaming the event on Facebook




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Labour proposes legislation for fast-tracked fund for domestic abuse services hit by Covid-19 crisis

Labour has proposed legislation to deliver a dedicated fast-tracked fund for domestic abuse services affected by the coronavirus crisis.




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Newham stabbing: Double tragedy as NHS worker knifed to death in east London days before father&apos;s funeral

A young NHS worker was stabbed to death in east London just days before his father's funeral.




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Captain Tom Moore made honorary Colonel to mark 100th birthday as his NHS fundraiser nears £30m

Captain Tom Moore has been appointed as an honorary colonel to mark his 100th birthday after raising almost £30 million for the NHS by walking laps of his garden.




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Airlines should be able to issue vouchers instead of cash refunds for cancelled flights, EU members say

Airlines should be able to issue vouchers instead of cash refunds for cancelled flights, according to 12 EU member states who have requested a change in the rules to help carriers.




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Captain Tom Moore&apos;s NHS fundraising campaign hits £30m as birthday wishes flood in

Captain Tom Moore has now raised a staggering £30m for the NHS in its battle against coronavirus as he celebrates his 100th birthday.




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New York funeral home put bodies in trucks after running out of space

Police were called to a funeral home in New York after a bad smell coming from the street outside turned out to be from hundreds of bodies kept inside trucks.




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Colonel Tom Moore&apos;s NHS fundraiser closes after veteran raises £32 million by walking lengths of garden

The appeal by NHS fundraiser Colonel Tom Moore topped £32 million as it closed at midnight.




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Westbourne Park bus depot falls silent then bursts into applause for driver&apos;s funeral cortege

Bus drivers paid their respects to a colleague who died with coronavirus symptoms as his funeral cortege passed through the depot where he had worked for almost 20 years.




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Government announces £76m funding for domestic abuse after lockdown spike

Robert Jenrick has announced a package of more than £76 million in new funding "to support the most vulnerable in society".




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Government demands Turkey refund or replace &apos;unusable&apos; PPE after 400,000 gowns impounded

The Government is requesting a refund or replacement for 400,000 medical gowns flown over from Turkey which were later deemed "unusable".




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Downing Street says JustGiving will want to &apos;reflect&apos; on &apos;£300K fee&apos; for Captain Tom Moore&apos;s fundraiser

Downing Street has said JustGiving will want to "reflect" on fees taken for processing Captain Tom Moore's £32 million fundraiser for NHS charities.