Background:

Pancreatic cancer is the third leading cause of cancer death in the United States, and 80% of patients present with advanced, incurable disease. Risk markers for pancreatic cancer have been characterized, but combined models are not used clinically to identify individuals at high risk for the disease.

Background:

We assessed the ability to supplement existing epidemiologic/etiologic studies with data on treatment and clinical outcomes by linking to publicly available cancer registry and administrative databases.

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.

Skeletal muscle wasting is a devastating consequence of cancer that contributes to increased complications and poor survival, but is not well understood at the molecular level. Herein, we investigated the role of Myocilin (Myoc), a skeletal muscle hypertrophy-promoting protein that we showed is downregulated in multiple mouse models of cancer cachexia. Loss of Myoc alone was sufficient to induce phenotypes identified in mouse models of cancer cachexia, including muscle fiber atrophy, sarcolemmal fragility, and impaired muscle regeneration. By 18 months of age, mice deficient in Myoc showed significant skeletal muscle remodeling, characterized by increased fat and collagen deposition compared with wild-type mice, thus also supporting Myoc as a regulator of muscle quality. In cancer cachexia models, maintaining skeletal muscle expression of Myoc significantly attenuated muscle loss, while mice lacking Myoc showed enhanced muscle wasting. Furthermore, we identified the myocyte enhancer factor 2 C (MEF2C) transcription factor as a key upstream activator of Myoc whose gain of function significantly deterred cancer-induced muscle wasting and dysfunction in a preclinical model of pancreatic ductal adenocarcinoma (PDAC). Finally, compared with noncancer control patients, MYOC was significantly reduced in skeletal muscle of patients with PDAC defined as cachectic and correlated with MEF2c. These data therefore identify disruptions in MEF2c-dependent transcription of Myoc as a novel mechanism of cancer-associated muscle wasting that is similarly disrupted in muscle of patients with cachectic cancer.Significance:This work identifies a novel transcriptional mechanism that mediates skeletal muscle wasting in murine models of cancer cachexia that is disrupted in skeletal muscle of patients with cancer exhibiting cachexia.

Determining mechanisms of resistance to αPD-1/PD-L1 immune-checkpoint immunotherapy is key to developing new treatment strategies. Cancer-associated fibroblasts (CAF) have many tumor-promoting functions and promote immune evasion through multiple mechanisms, but as yet, no CAF-specific inhibitors are clinically available. Here we generated CAF-rich murine tumor models (TC1, MC38, and 4T1) to investigate how CAFs influence the immune microenvironment and affect response to different immunotherapy modalities [anticancer vaccination, TC1 (HPV E7 DNA vaccine), αPD-1, and MC38] and found that CAFs broadly suppressed response by specifically excluding CD8+ T cells from tumors (not CD4+ T cells or macrophages); CD8+ T-cell exclusion was similarly present in CAF-rich human tumors. RNA sequencing of CD8+ T cells from CAF-rich murine tumors and immunochemistry analysis of human tumors identified significant upregulation of CTLA-4 in the absence of other exhaustion markers; inhibiting CTLA-4 with a nondepleting antibody overcame the CD8+ T-cell exclusion effect without affecting Tregs. We then examined the potential for CAF targeting, focusing on the ROS-producing enzyme NOX4, which is upregulated by CAF in many human cancers, and compared this with TGFβ1 inhibition, a key regulator of the CAF phenotype. siRNA knockdown or pharmacologic inhibition [GKT137831 (Setanaxib)] of NOX4 “normalized” CAF to a quiescent phenotype and promoted intratumoral CD8+ T-cell infiltration, overcoming the exclusion effect; TGFβ1 inhibition could prevent, but not reverse, CAF differentiation. Finally, NOX4 inhibition restored immunotherapy response in CAF-rich tumors. These findings demonstrate that CAF-mediated immunotherapy resistance can be effectively overcome through NOX4 inhibition and could improve outcome in a broad range of cancers.Significance:NOX4 is critical for maintaining the immune-suppressive CAF phenotype in tumors. Pharmacologic inhibition of NOX4 potentiates immunotherapy by overcoming CAF-mediated CD8+ T-cell exclusion.Graphical Abstract:http://cancerres.aacrjournals.org/content/canres/80/9/1846/F1.large.jpg.See related commentary by Hayward, p. 1799

Although genome-wide association studies (GWAS) have identified more than 100 colorectal cancer risk loci, most of the biological mechanisms associated with these loci remain unclear. Here we first performed a comprehensive expression quantitative trait loci analysis in colorectal cancer tissues adjusted for multiple confounders to test the determinants of germline variants in established GWAS susceptibility loci on mRNA and long noncoding RNA (lncRNA) expression. Combining integrative functional genomic/epigenomic analyses and a large-scale population study consisting of 6,024 cases and 10,022 controls, we then prioritized rs174575 with a C>G change as a potential causal candidate for colorectal cancer at 11q12.2, as its G allele was associated with an increased risk of colorectal cancer (OR = 1.26; 95% confidence interval = 1.17–1.36; P = 2.57 × 10–9). rs174575 acted as an allele-specific enhancer to distally facilitate expression of both FADS2 and lncRNA AP002754.2 via long-range enhancer–promoter interaction loops, which were mediated by E2F1. AP002754.2 further activated a transcriptional activator that upregulated FADS2 expression. FADS2, in turn, was overexpressed in colorectal cancer tumor tissues and functioned as a potential oncogene that facilitated colorectal cancer cell proliferation and xenograft growth in vitro and in vivo by increasing the metabolism of PGE2, an oncogenic molecule involved in colorectal cancer tumorigenesis. Our findings represent a novel mechanism by which a noncoding variant can facilitate long-range genome interactions to modulate the expression of multiple genes including not only mRNA, but also lncRNA, which provides new insights into the understanding of colorectal cancer etiology.Significance:This study provides an oncogenic regulatory circuit among several oncogenes including E2F1, FADS2, and AP002754.2 underlying the association of rs174575 with colorectal cancer risk, which is driven by long-range enhancer–promoter interaction loops.Graphical Abstract:http://cancerres.aacrjournals.org/content/canres/80/9/1804/F1.large.jpg.

Consistently, the field of genetic counseling has advocated that parents be advised to defer elective genetic testing of minors until adulthood to prevent a range of potential harms, including stigma, discrimination, and the loss of the child's ability to decide for him- or herself as an adult. However, consensus around the policy of "defer-when-possible" obscures the extent to which this norm is currently under siege. Increasingly, routine use of full or partial genome sequencing challenges our ability to control what is discovered in childhood or, when applied in a prenatal context, even before birth. The expansion of consumer-initiated genetic testing services challenges our ability to restrict what is available to minors. As the barriers to access crumble, medical professionals should proceed with caution, bearing in mind potential risks and continuing to assess the impact of genetic testing on this vulnerable population.

BACKGROUND AND PURPOSE:

The massa intermedia is a normal midline transventricular thalamic connection. Massa intermedia aberrations are common in schizophrenia, Chiari II malformation, X-linked hydrocephalus, Cornelia de Lange syndrome, and diencephalic-mesencephalic junction dysplasia, among others. We have noticed that massa intermedia abnormalities often accompany other midline malformations. The massa intermedia has never been formally evaluated in a group of exclusively pediatric patients, to our knowledge. We sought to compare and contrast the prevalence, size, and location of the massa intermedia in pediatric patients with and without congenital midline brain abnormalities.

BACKGROUND AND PURPOSE:

In the medicolegal literature, notching of the corpus callosum has been reported to be associated with fetal alcohol spectrum disorders. Our purpose was to analyze the prevalence of notching of the corpus callosum in a fetal alcohol spectrum disorders group and a healthy population to determine whether notching occurs with increased frequency in the fetal alcohol spectrum disorders population.

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.

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.

SUMMARY:

Use of mechanical thrombectomy for stroke has increased since the publication of trials describing outcome improvement when used in the anterior circulation. These results, however, cannot be directly translated to the posterior circulation. While a high NIHSS score has demonstrated an association with poor outcomes in posterior stroke, the NIHSS is weighted toward hemispheric disease, and complex scores potentially delay definitive imaging diagnosis. We performed a retrospective analysis to ascertain whether any rapidly obtainable demographic or clinical and imaging data have a correlation with patient outcome postthrombectomy. Seventy-three cases were audited between September 2010 and October 2017. Presenting with a Glasgow Coma Scale score of >13 meant that the odds of reaching the primary end point of functional independence (defined as a 90-day modified Rankin Scale score of 0–2) were 5.70 times greater; similarly, presenting with a posterior circulation ASPECTS of >9 resulted in the odds of reaching the primary end point being 4.03 times greater. Older age correlated to a lower odds of independence (0.97, p = .04).

Competition ushers in new era to recognise the country’s standout real estate projects and senior leaders.

शनि कर्म के देवता हैं और आपके किए गए कार्य का फल जरूर देते हैं। शनिदेव को मनाने के लिए किए जाने वाले सनातनी उपाय को करके आप कुंडली के उन दोषों को दूर कर सकते हैं जिनके कारण आपको कष्ट उठाने पड़ते हैं।

Bloober Team has announced psychological horror game, The Medium, for Xbox Series X and Windows PC via Steam. It will launch this holiday season and be available on Xbox Game Pass.

"Every one of our games has a central theme that drives its creative and technological design," said Bloober Team CEO Piotr Babieno.

"In The Medium, we focus on perspective and perception. When you change your point of view, you discover that things are more complicated and nuanced than you initially thought. The Medium is our most ambitious game ever and we can’t wait to show you how we’re translating this vision into a psychological horror."

View the reveal trailer below:

Here is an overview of the game:

Become a medium living in two different worlds: the real one and the spirit one. Haunted by the vision of a child’s murder, you travel to an abandoned hotel resort, which many years ago became the stage of an unthinkable tragedy. There you begin your search for difficult answers.

As a medium with access to both worlds, you have a wider perspective and can see more clearly that there’s no one simple truth to what others perceive. Nothing is what it seems, everything has another side.

The Medium features a “dual” soundtrack by Bloober Team’s Arkadiusz Reikowski and legendary composer Akira Yamaoka of Silent Hill fame.

A life-long and avid gamer, William D'Angelo was first introduced to VGChartz in 2007. After years of supporting the site, he was brought on in 2010 as a junior analyst, working his way up to lead analyst in 2012. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel dedicated to gaming Let's Plays and tutorials. You can contact the author at wdangelo@vgchartz.com or on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/443420/psychological-horror-game-the-medium-announced-for-xbox-series-x-and-pc/

An analysis of the media consumption habits of people in the US shows that fake news makes up a tiny fraction of what they watch or read every day

An image-editing program designed by researchers at Abode uses AI to let you quickly transform the shape of objects in images and change the lighting

BRITAIN'S summer holiday destinations will face some of the biggest economic hits of the coronavirus pandemic with fears of massive job losses in coastal communities, a study has claimed.

A military exercise in Australia demonstrates how small drones can airdrop critical medical supplies to soldiers in combat

New York City study shows that drones could deliver life-saving medical supplies several minutes before an ambulance arrives

Bosch SoundSee combines deep learning with mobile microphone arrays to identify problems on the ISS before they happen

The makers of Blair Witch, Observer and Layers of Fear today announced a new psychological horror game - The Medium.

FIFA 20 Team Of The Season So Far continues this week, hopefully with the release of the La Liga FUT Squad. Here some predictions on who might be included, plus when they'll be announced.

FIFA 20 Team Of The Season So Far continues this week, hopefully with the additional release of the Portuguese Liga Nos FUT Squad. Here some predictions on who might be included, plus when they'll be announced.

FIFA 20 Team Of The Season So Far continues this week, hopefully with the release of the Bundesliga FUT Squad. Here some predictions on who might be included, plus when they'll be announced.

We hope you’re not sick of Fire Emblem: Three Houses from last week, because we’ve got even more this episode. We discuss strategies for raising professor rank and recruiting, in case you need some tips. We also cover a variety of games and their official release dates. Finally, our briefs are more like long underwear this week.

Platform sandals meet 40-denier tights as rock’n’roll goes bourgeois at Paris fashion week

At his Celine catwalk show on Friday night, the designer Hedi Slimane distilled what looks to be the most compelling trend of this season of fashion shows. Working title: rock’n’roll bourgeois.

Slim knee-length dresses were worn with slinky chain belts; towering platform sandals with sensible 40-denier semi-sheer tights; slim bootcut velvet trousers worn with Princess-line above-the-knee coats. This was a masterclass in Parisian allure: take one part Avenue Montaigne privilege, and mix with one part backstage pass. Shaken, not stirred.

Study highlights industry failures and calls for shift in consumer attitudes

The fashion industry needs to fundamentally change in order to mitigate the environmental impact of fast fashion, experts have said.

Clothes rental, better recycling processes, pollution control technology and the innovative use of offcuts are among measures that could help, they said.

Choose soft and cosy or short and sassy. Staying in gives you a great excuse to wear PJs all day

Researchers have developed a set of recommendations to manage the mental health of frontline medical workers during viral outbreaks, such as COVID-19.

Miniature devices that could be developed into safe, high-resolution imaging technology, with uses such as helping doctors identify potentially deadly cancers and treat them early, have been created.

Staff of the magazine that kicked off the French New Wave say its new elite owners pose a threat to editorial independence

The mass resignation of the staff of Cahiers du Cinéma, the film journal that launched the French New Wave, has reignited debate in France about the possibility of critical independence in a society whose major stakeholders frequently operate in several spheres.

On Thursday, the 15 staff writers and editors announced their resignation, saying they believed its new owners posed a threat to the magazine’s cherished independence.

There has been talk for some time now about easing labour laws, already seen in industry circles as being too rigid and acting as a drag on growth, specifically to facilitate emerging from the lockdown. And it’s not just a question of emerging from it, there’s also the issue of surviving what looks like being a brutal and prolonged global economic downturn. It was reported on Friday that ordinances were being issued in some states.

Neil Ferguson, whose modelling has informed the UK's coronavirus strategy, says that the need for intensive care beds will come close to, but not exceed, national capacity

With all the unknowns about covid-19, any numbers you hear about death tolls or how long restrictions will last should be taken not just with a pinch of salt but with a sack of it

Metabolites from urine or blood samples can be used to predict how much a baby will grow six months ahead of time, which could improve interventions for chronic malnutrition

The covid-19 pandemic has led to rushed guidelines for doctors making treatment decisions, and has encouraged more people to make advance decisions on CPR and ventilation

The speed limit on Spadina Crescent from Avenue H to Windsor Street should be reduced to 40km per hour, writes Don Greer.

The Simpsons has done it again, this time predicting the COVID-19 pandemic and murder hornets. Here are some other instances of The Simpsons predicting the future.

LIVERPOOL midfielder Georginio Wijnaldum will be pivotal for Jurgen Klopp at Manchester City..

The 'Hello' singer turned 32 on Tuesday (05.05.20) and when she took to Instagram to thank fans for their well-wishes on her special day

Justin Bieber discussed his experiences during the latest episode of his and wife Hailey's Facebook Watch series, The Biebers on Watch.

The apparent Democratic nominee called for an immediate $13 minimum wage increase for essential workers and criticized President Trump for viewing these front-liners as “disposable."

Meat production this week is up about 3 percent compared with the previous week, according to market reports by SiriusXM’s Rural Radio. That’s still off by as much as a third from a year ago. The numbers are causing some retailers to ration fresh meat purchases or risk selling out their entire supplies. The beef,... Continue Reading

Asian giant hornet, which became more active in the state in April, is the world’s largest and can kill humans with multiple stings

• Alarm over deaths of bees from rapidly spreading viral disease
  

Researchers and citizens in Washington state are on a careful hunt for invasive “murder hornets”, after the insect made its first appearance in the US.

The Asian giant hornet is the world’s largest and can kill humans. But it is most dangerous for the European honeybee, which is defenseless in the face of the hornet’s spiky mandibles, long stinger and potent venom.

नये साल के लिए यह सबसे अच्छा वेट लॉस टिप्स है.