We present a unique case of a single patient presenting with two mutationally distinct, PD-L1⁺ diffuse large B-cell lymphomas (DLBCLs). One of these DLBCLs demonstrated exceptionally high mutational burden (eight disease-associated variants and 41 variants of undetermined significance) with microsatellite instability (MSI) and an acquired PMS2 mutation with loss of PMS2 protein expression, detected postchemotherapy. This report, while highlighting the extent of possible tumor heterogeneity across separate clonal expansions as well as possible syndromic B-cell neoplasia, supports the notion that, although rare, PD-L1 expression and associated states permissive of high mutational burden (such as mismatch repair gene loss of function/MSI) should be more routinely considered in DLBCLs. Appropriate testing may be predictive of outcome and inform the utility of targeted therapy in these genetically diverse and historically treatment-refractory malignancies.

Metastatic porocarcinomas (PCs) are vanishingly rare, highly aggressive skin adnexal tumors with mortality rates exceeding 70%. Their rarity has precluded the understanding of their disease pathogenesis, let alone the conduct of clinical trials to evaluate treatment strategies. There are no effective agents for unresectable PCs. Here, we successfully demonstrate how functional precision medicine was implemented in the clinic for a metastatic PC with no known systemic treatment options. Comprehensive genomic profiling of the tumor specimen did not yield any actionable genomic aberrations. However, ex vivo drug testing predicted pazopanib efficacy, and indeed, administration of pazopanib elicited remarkable clinicoradiological response. Pazopanib and its class of drugs should be evaluated for efficacy in other cases of PC, and the rationale for efficacy should be determined when PC tumor models become available. A functional precision medicine approach could be useful to derive effective treatment options for rare cancers.

Shetland Library and the National Library of Scotland have been praised for "providing optimist for the future."

This week we finally figure out if Dark Souls ripped off Breath of the Wild. We also get really worked up over Bethesda. When is Game Pass coming to PS5, again?

The post RPG Cast – Episode 557: “PS5 Crunchwrap Supreme!” appeared first on RPGamer.

Matt makes twenty slices of toast. Josh is still fighting sewer rat six. Kelley's dog is NOT a baby. And Chris saves E3 with the power of...no...he can't do it. No GEX allowed.

The post RPG Cast – Episode 684: “Remember What I Said at the Fazoli’s Drive Thru?” appeared first on RPGamer.

Sam puts magnets on her arms. Kelley sits down to play Diablo 4 with a proper English muffin. Chris gets hit with a pie for money. And Phil has the cast roll a head-petting check.

The post RPG Cast – Episode 686: “Head Harem” appeared first on RPGamer.

Deller on politics, music and his film Everybody in the Place, now showing at The Vinyl Factory's Reverb exhibition.

The post Interview: Jeremy Deller appeared first on Fact Magazine.

Capcom has updated its list of Platinum Titles, games that have sold over one million units as of September 30, 2024. The list includes 122 games with sales over one million units, 64 over two million units, 14 over five million units, and six over 10 million units sold.

Resident Evil 4 remake sold 400,000 units to bring lifetime sales to eight million units, Resident Evil 2 remake sold 300,000 units to bring sales to 14.5 million units, and Resident Evil 3 remake sold 200,000 units to bring lifetime sales to 9.2 million units. 

Resident Evil 7: biohazard sold 300,000 units to bring lifetime sales to 14 million units and Resident Evil Village sold 400,000 units to bring sales to 10.5 million units.

Monster Hunter Rise sold 600,000 units in the quarter to bring lifetime sales to 16 million units. Monster Hunter Rise: Sunbreak sold 400,000 units to bring lifetime sales to 8.8 million units.

Monster Hunter: World sold 400,000 units in the quarter to bring lifetime sales to 20.9 million units, while the Iceborne expansion sold 600,000 units for a total of 14 million units.

Dragon's Dogma 2 sold 300,000 units in the quarter to bring lifetime sales to 3.3 million units. Street Fighter 6 sold 400,000 units in the quarter to bring lifetime sales to 4.1 million units. Devil May Cry 5 sold 300,000 units to bring sales to 8.7 million units. 

Check out the complete list below:

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 and taking over the hardware estimates in 2017. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel. You can contact the author on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/463020/capcom-updates-its-best-sellers-list-monster-hunter-world-at-209m-re4-remake-at-8m-more/

Remedy's Alan Wake 2 has now "recouped most of its development and marketing expenses", CEO Tero Virtala has announced in a business review for January-September 2024. Speaking as somebody who would quite like there to be more Alan Wake games - or at least, moderately weird and pretty decent blockbuster singleplayer horror games - I am both pleased by this news and a little troubled that Remedy's eldritch forest fable (which came out in October 2023) has yet to break even.

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Like a plague doctor delicately administering another handful of leeches, Ice Pick Lodge have shared a bit more about the recently announced Pathologic 3, explaining how their plans for the cult epidemic-battling series have progressed since the release of Pathologic 2.

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The Elder Scrolls: Legends, the free-to-play card game set in Bethesda's fantasy world, has been removed from sale on Steam. Its servers will shut down for good on January 30th, 2025, after which it will no longer be playable. The closure comes five years after the game was last updated.

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Sunday is cancelled. Book for now!

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We’re still a week away from Blizzard’s Warcraft 30th Anniversary Direct next Wednesday the 13th of November, but art from an apparent remaster of 1995 real time strategy game Warcraft II: Tides Of Darkness has leaked online, via Xibbly user Stiven. It’s a thin one, as far as leaks go, but does show what looks to be cover, logo art, and a Battle.net icon. Thanks for the spot, Percy Coswald Gamer.

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The water column is hazy as an unusual remotely operated vehicle glides over the seafloor in search of a delicate tilt meter deployed three years ago off the west side of Vancouver Island. The sensor measures shaking and shifting in continental plates that will eventually unleash another of the region’s 9.0-scale earthquakes (the last was in 1700). Dwindling charge in the instruments’ loggers threatens the continuity of the data.

The 4-metric-ton, C$8-million (US $5.8-million) remotely operated vehicle (ROV) is 50 meters from its target when one of the seismic science platforms appears on its sonar imaging system, the platform’s hard edges crystallizing from the grainy background like a surgical implant jumping out of an ultrasound image. After easing the ROV to the platform, operators 2,575 meters up at the Pacific’s surface instruct its electromechanical arms and pincer hands to deftly unplug a data logger, then plug in a replacement with a fresh battery.

This mission, executed in early October, marked an exciting moment for Josh Tetarenko, director of ROV operations at North Vancouver-based Canpac Marine Services. Tetarenko is the lead designer behind the new science submersible and recently dubbed it Jenny in homage to Forrest Gump, because the fictional character named all of his boats Jenny. Swapping out the data loggers west of Vancouver Island’s Clayoquot Sound was part of a weeklong shakedown to test Jenny’s unique combination of dexterity, visualization chops, power, and pressure resistance.

Jenny is only the third science ROV designed for subsea work to a depth of 6,000 meters.

By all accounts Jenny sailed through. Tetarenko says the worst they saw was a leaky O-ring and the need to add some spring to a few bumpers. “Usually you see more things come up the first time you dive a vehicle to those depths,” says Tetarenko.

Jenny’s successful maiden cruise is just as important for Victoria, B.C.–based Ocean Networks Canada (ONC), which operates the NEPTUNE undersea observatory. The North-East Pacific Time-series Undersea Networked Experiments array boasts thousands of sensors and instruments, including deep-sea video cameras, seismometers, and robotic rovers sprawled across this corner of Pacific. Most of these are connected to shore via an 812-kilometer power and communications cable. Jenny was custom-designed to perform the annual maintenance and equipment swaps that have kept live data streaming from that cabled observatory nearly continuously for the past 15 years, despite trawler strikes, a fault on its backbone cable, and insults from corrosion, crushing pressures, and fouling.

NEPTUNE remains one of the world’s largest installations for oceanographic science despite a proliferation of such cabled observatories since it went live in 2009. ONC’s open data portal has over 37,000 registered users tapping over 1.5 petabytes of ocean data—information that’s growing in importance with the intensification of climate change and the collapse of marine ecosystems.

Over the course of Jenny’s maiden cruise, her operators swapped devices in and out at half a dozen ONC sites, including at several of NEPTUNE’s five nodes and at one of NEPTUNE’s smaller sister observatories closer to Vancouver.

Inside Jenny

ROV Jenny aboard the Valour, Canpac’s 50-meter offshore workhorse, ahead of October’s NEPTUNE observatory maintenance cruise.Ocean Networks Canada

What makes Jenny so special?

• Jenny is only the third science ROV designed for subsea work to a depth of 6,000 meters.
• Motion sensors actively adjust her 7,000-meter-long umbilical cable to counteract topside wave action that would otherwise yank the ROV around at depth and, in rough seas, could damage or snap the cable.
• Dual high-dexterity manipulator arms are controlled by topside operators via a pair of replica mini-manipulators that mirror the movements.
• Each arm is capable of picking up objects weighing about 275 kilograms, and the ROV itself can transport equipment weighing up to 3,000 kg.
• 11 high-resolution cameras deliver 4K video, supported by 300,000 lumens of lighting that can be tuned to deliver the soft red light needed to observe bioluminescence.
• Dual multibeam sonar systems maximize visibility in turbid water.

Meghan Paulson, ONC’s executive director for observatory operations, says the sonar imaging system will be particularly invaluable during dives to shallower sites where sediments stirred up by waves and weather can cut visibility from meters to centimeters. “It really reduces the risk of running into things accidentally,” says Paulson.

To experience the visibility conditions for yourself, check out recordings of the live video broadcast from the NEPTUNE maintenance cruise. Tetarenko says that next year they hope to broadcast not only the main camera feed but also one of the sonar images.

3D video could be next, according to Canpac ROV pilot and Jenny codesigner, James Barnett. He says they would need to boost the computing power installed topside, to process that “firehose of data,” but insists that real-time 3D is “definitely not impossible.” Tetarenko says the science ROV community is collaborating on software to help make that workable: “3D imagining is kind of the very latest thing that’s being tested on lots of ROV systems right now, but nobody’s really there yet.”

More Than Science

Expansion of the cabled observatory concept is the more certain technological legacy for ONC and NEPTUNE. In fact, the technology has evolved beyond just oceanography applications.

ONC tapped Alcatel Submarine Networks (ASN) to design and build the Neptune backbone and the French firm delivered a system that has reliably delivered multigigabit Ethernet plus 10 kilovolts of direct-current electricity to the deep sea. Today ASN deploys a second-generation subsea power and communications networking solution, developed with the Norwegian international energy company Equinor.

ASN’s “Direct Current/Fiber Optic” or DC/FO system provides the 100-km backbone for the ARCA subsea neutrino observatory near Sicily, in addition to providing control systems for a growing number of offshore oil and gas installations. The latter include projects led by Equinor and BP where DC/FO networks drive the subsea injection of captured carbon dioxide and monitor its storage below the seabed. Future oil and gas projects will increasingly rely on the cables’ power supply to replace the hydraulic lines that have traditionally been used to operate machinery on the seafloor, according to Ronan Michel, ASN’s product line manager for oil and gas solutions.

Michel says DC/FO incorporates important lessons learned from the Neptune installation. And the latter’s existence was a crucial prerequisite. “The DC/FO solution would probably not exist if Neptune Canada would not have been developed,” says Michel. “It probably gave confidence to Equinor that ASN was capable to develop subsea power and coms infrastructure.”

One fan has been rebuilding Final Fantasy 8 but it's not going quickly enough for some people who suggested they cut out things like relationships to focus on the game.

Online group Girls Who Chase has created a global community of women who head into severe weather to record images, report damage and help scientists understand the impact of storms to be better prepared

One Arsenal star is on the list of the top ten Premier League players for increased transfer value in 2019.

How private is your internet address? Very, says the Supreme Court of Canada. Police can’t just walk into a company and demand a suspect’s IP address by saying a Canadian resident doesn’t have an expectation of privacy of that information, the court ruled today. An IP address is vital enough that every resident expects it […]

Depending on PC config you may see up to a 30fps uplift with anti-tamper tech ditched.

A woman's brain was scanned throughout her pregnancy, adding to the growing body of evidence that dramatic remodelling takes place in preparation for motherhood

A better understanding of what happens to our bodies when we get fitter can unlock ways to speed up the journey – and it might be simpler than you think

Trump would face little to no resistance in confirming his picks for Supreme Court justices in the majority-GOP Congress, but Alito has no plans to step down.

<a href="https://bluetechker.com/" rel="nofollow ugc">Blue Techker</a> Nice post. I learn something totally new and challenging on websites

Computer scientist and meteorologist Amy McGovern has studied the technology for two decades, and she weighs in with some answers

Here's how the aerial acrobats are able to survive on a nearly all-sugar diet, fly higher than many helicopters can and migrate over the open ocean

King Charles has led Remembrance Sunday commemorations at the Cenotaph.

Mark Stibbe was one of John Smyth's victims. He's a former vicar and is now an author.

I’ve been hearing a lot about IPTV lately. There’s no denying that it’s shaken up the way we consume content. From streaming live sports events to watching your favorite shows on demand, IPTV services have become incredibly popular. But let’s be honest: with so many different subscription options out there, it can get a little […]

The post Is a Premium IPTV Subscription Worth the Extra Cost? appeared first on Chart Attack.

The Supreme Court dealt a major legal blow to former White House Chief of Staff Mark Meadows on Tuesday, refusing to move the Georgia election interference charges against him to federal court.

Susan Holt, who repeatedly emphasized her differences with the prime minister leading up to last month’s election, was on more welcoming terms Tuesday after their first official meeting in Fredericton.

An Ottawa high school principal has apologized for playing an Arabic song about peace during a Remembrance Day ceremony after facing swift backlash from critics calling it inappropriate and hurtful to members of the Jewish community.

In a 5-4 decision, the Supreme Court struck down a key provision of the Voting Rights Act of 1965, stating that the legislation was based on now outdated data. The ruling removes the coverage formula that required federal oversight for voting processes in nine states.

In a 5-4 decision in U.S. v. Windsor, the Supreme Court ruled the federal Defense Of Marriage Act unconstitutional. The court rules that supporters of California's Proposition 8 case did not have standing to bring the case to court, which means same-sex marriages in California may resume.

1. Swiggy’s reclusive CEO Sriharsha Majety makes rare public appearance at IPO listing ceremony  Hindustan Times
2. Zomato gives ‘Jai and Veeru’ vibes with special meme for rival Swiggy on IPO day  Hindustan Times
3. JM Financial gives Swiggy its first 'buy' tag, sees 20% upside from IPO price  Moneycontrol
4. Swiggy IPO: 9 execs who will become richer by Rs 50 crore or more  The Times of India
5. ‘You and I…’: Zomato welcomes Swiggy on Dalal Street post stock market listing  India Today

Starring Tamannaah Bhatia, Jimmy Shergill, and Avinash Tiwary, ‘Sikandar Ka Muqaddar’ is directed by Neeraj Pandey

‘Horizon Zero Dawn Remastered’ elevates a classic with breathtaking visuals, smooth performance, and a gripping narrative on PS5 and PC

Top-ranked Jannik Sinner made it two wins in two matches before his home fans at the ATP Finals, beating Taylor Fritz 6-4, 6-4 on Tuesday. Earlier, Daniil Medvedev moved back into contention with a 6-2, 6-4 victory over Alex De Minaur.

Balatro from developer LocalThunk and publisher Playstack is finally coming to mobile later this month on iOS, Android, and also …

Continue reading "‘Balatro’ Is Coming to Apple Arcade and Also iOS as a Standalone Premium Release Beginning September 26th"

Combining DNA analysis, archeological techniques, and historical records overturns some assumptions of the people of Pompeii.

Protect your dog from ticks with these easy steps for safe removal and prevention. Learn how to spot, remove, and keep ticks at bay.

The ‘Scream Queens’ actor revealed her white co-star made a ‘weighted’ reference to Martin Luther King

We all need to be fully aware who has access to our health data, when they can access it, what it’s being used for and the potential implications.

The post My Health Record: Remain in or opt out? appeared first on Star Observer.

Two congruent angles are simply pairs of angles with equal measures. You can find congruent angles examples in hundreds of everyday objects.