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The BlackBerry-Esque Smartphone With a Full Keyboard Just Launched on Kickstarter
This Android smartphone with a tactile QWERTY keyboard has already raised over $2.1 million.
Bioresorbable microneedles track organ health
Nature Reviews Bioengineering - An article in Nature Biomedical Engineering reports a bioresorbable flexible microneedle sensor array for continuous monitoring of organ function for at least 7...
DOE Chancellor finds Albany allies supportive of smaller class size fixes
Schools Chancellor Kamar Samuels wants the full four-year extension of mayoral control passed in the state budget.
Crystal Etienne: Florida’s school choice debate isn’t ignoring evidence, it’s asking for it
Critics argue school choice expansion lacks full data and accountability
Marathon has sold 1.2M copies across Steam, PS5, and Xbox
Alinea Analytics estimates show that Marathon has generated gross revenues of $55M via 1.2M copies sold on Steam, PS5, and Xbox: Looking at the split between Steam, PS5, and Xbox, Steam is clearly the main platform for Marathon, accounting for a little under 70% of the audience (800K copies sold). Meanwhile, PS5 takes about 19% (217K) and Xbox (including console, PC, and cloud) accounts for a bit over 11% or 133K. Marathon is technically a first-party Sony title, so seeing the home console struggle to break 20% of the volume is a notable data point for the ongoing platform-agnostic debate. PlayStation Studios online games will almost certainly continue being multiplatform (despite Sony reportedly pulling back on PC releases). Subscribe for free to get the most accurate games estimates in your inbox twice a week 🫶 Subscribe As for Marathon, the consensus among hardcore players who pushed through the awkward onboarding phase – myself included – is that it’s fantastic. The gunplay, aesthetic, and presentation are among the best in the shooter genre. A great game doesn’t always equal an immediate hit, though, as shown by our estimates. Things are looking lukewarm right now. But this might be one of those marathon-not-a-sprint situations. Had to, didn’t I? Why wasn’t Marathon a hit on the same level as Arc Raiders? One topic that came up in a lot of conversations at GDC this year was why Marathon hasn’t hit the same stratosphere as Arc Raiders. On paper, they’re both extraction shooters, and Marathon has the Bungie pedigree – the house that built the gold standard for gunplay in Halo and Destiny. Marathon’s neon-futuristic aesthetic also distinguishes itself from the gritty realism of Tarkov or the post-apocalyptic hope of ARC Raiders. But vibes can only get you so far for first impressions if the onboarding feels like a brick wall. Marathon is a sweaty PvP-focused experience with a first-time user experience and UI that I can only describe as dreadful. Players are dropped into a complex ecosystem where the UI, though visually striking, is functionally uninformative, forcing users to manually hover over nondescript, identical icons just to identify basic gear or weapon mods. This lack of clarity is compounded by punishing mechanics like a severe heat gauge for movement and a scarcity of vital resources, all without a clear tutorial or a low-stakes mode to learn the ropes. Most people – even top streamers and veteran shooter players – have no idea what’s going on in Marathon at first. Arc is on the complete other end of the spectrum. As we covered here and here, Arc Raiders offers a more collaborative, approachable loop where players often work together toward shared goals. And the objectives are instantly clear. To many players, this contrast only emphasised Marathon’s issues, especially during the testing period. Players understand the Arc Raiders loop within 30 minutes, while Marathon acts as a massive filter, chewing up newcomers and spitting them out before they can experience the depth of Bungie’s signature gunplay. What I’m getting at here is that the poor first-time user experience of Marathon’s Server Slam likely stifled launch sales, while the opposite was true for Arc. Let’s look at the pre-launch copies sold for each game during their respective Server Slams (launch-aligned) : Looking at the trajectory: Arc Raiders saw a massive 80% jump in copies sold during its three-day Server Slam (day -13 to -11). Players jumped in, realised the water was fine, and immediately opened their wallets. Marathon, meanwhile, saw a 49% increase in the four days following its Slam (Day -7 to -3). At the time of each game’s respective launch, Arc Raiders had nearly double the Steam footprint of Marathon – and word of mouth only continued to grow. Bungie could have had more time to fix the onboarding process had the beta happened earlier. But Marathon launched three days after the beta finished. These factors limited the launch sales quite a bit, I reckon. Marathon has found a niche audience, though Despite the friction-heavy start, the data suggests that those who survived Marathon’s onboarding are loving life. We’ve been tracking cross-platform DAUs, and while there’s the expected post-launch leakage, many players are sticking with it. After peaking at 478K total DAUs on its first Saturday, Marathon has settled into a respectable rhythm, holding 345K DAUs as of yesterday and averaging 380K DAUs across the weekend. Steam continues to do the heavy lifting here, consistently accounting for the lion’s share of the daily players. Players have been putting in the hours, too: On Steam, Marathon’s average playtime has climbed to 27.8 hours, significantly outpacing the console averages on PS5 (16.5h) and Xbox (17.3h). Even more telling than the averages: 22% of the Steam audience has surged past the 50-hour mark, and nearly 7% have already logged over 100 hours. Subscribe for free to get the most accurate games estimates in your inbox twice a week 🫶 Subscribe This data suggests that once the Bungie magic clicks, it hooks players deeper than the average extraction shooter. There’s also started to be a shift in the game’s discourse. Marathon launched as one of those games that’s cool to hate. But as Marathon’s 100-hour club grows, we’re seeing conversations around its mechanical merit outweigh the negativity. Several high-profile creators, who were initially vocal critics, have spent the last week coming around on the mechanical depth of the endgame. It’s a subtle but positive signal; the hate train is losing steam, and a new narrative about the game is emerging. Bungie faithfuls unite Another interesting metric in Marathon’s first few weeks is who, exactly, is playing. Bungie leans heavily on its prestige as the “makers of Halo and Destiny,” in its marketing, and that message has clearly hit the mark. On Steam, the gravity (hammer) of Bungie’s previous work is unavoidable. A staggering 78.2% of Marathon players also played Destiny 2. The trend carries across other platforms, with 74.2% of PS5 players and 82.7% of Xbox players also having played Destiny 2. The Halo legacy lives on, it seems. More on that in a bit. While Destiny 2 went free to play, these numbers still represent a high-intent migration of a fanbase that trusts Bungie’s specific brand of kinetic gunplay and cryptic world-building. The Xbox data adds another layer of legacy. About 85.7% of Marathon players on Xbox have played Halo Infinite, while over half of the Steam audience has spent time in Halo Infinite and 36.1% in the Master Chief Collection (a paid collection of the old Bungie-made legacy games). Interestingly, we see a 55.9% overlap with ARC Raiders on Steam. Overlap is even higher there on PlayStation (60.5%) and Xbox (66.5%). And there’s also significant crossover with Helldivers 2 on all platforms, too. Subscribe for free to get the most accurate games estimates in your inbox twice a week 🫶 Subscribe Bungie has found some of its fans with Marathon, and the challenge now is keeping this engaged in a high-stakes PvP environment when they’ve spent the last decade primarily enjoying the power fantasies of PvE. On that note… Go the full 26 miles? Or cut and run? Time for some could’ve, should’ve, would’ve. These things would have improved Marathon’s performance at launch: A more robust onboarding process, perhaps in the form of a short single-player/PvE campaign. We know Bungie fans love this stuff. A traditional arena-based mode akin to Destiny’s Crucible could have been a bridge for the cautious players who’d have been otherwise deterred by the Server Slam. It’s also a great palate cleanser after getting merked. Introducing a dedicated PvE environment would have similarly diversified the conversation and lowered the barrier for the Bungie faithful who found the pure PvP extraction loop too abrasive. PvE is safer than PvP these days. There’s an argument that a thin PvE mode would have just felt like a budget Destiny, potentially hurting the brand more. But given how dire the FTUE is, I think it would have been a net positive. Any kind of tutorialised loop that demystifies the stakes, really. While there is merit in a studio sticking firmly to a singular creative vision, and going all in on the hardcore extraction loop. Less forgiving is the technical reality is that the user interface and first-time user experience (FTUE) were not at a commercial standard for launch. Subscribe for free to get the most accurate games estimates in your inbox twice a week 🫶 Subscribe In a landscape where player time is oversaturated and the most contested currency, a flawed FTUE is a critical failure point. But it’s not all doom and gloom, as Marathon has an incredible, unique gameplay loop, suggesting that financial success is still attainable if Bungie can pivot effectively. Bungie and PlayStation now face a difficult strategic crossroads, though – one within a challenging games market. They could: Double down on Marathon with a long-term Rainbow Six Siege- or No Man’s Sky-style recovery plan, which is something I heard Last Stand Media’s Chris Maldonado mention last week. While this could be a sunk-cost fallacy in action, it could eventually yield the audience the game’s mechanical depth deserves. Shift focus toward the inevitable Destiny 3 or another project, mitigating the escalating opportunity cost and cutting their losses, so to speak. Doing both is an expensive proposition, given the high overhead and burn rate of operating out of Bellevue, Washington. With Sony recently demonstrating a lower threshold for underperforming studios and projects, the margin for error has vanished. Whatever happens, the next six months will determine whether Marathon becomes a cornerstone of Sony’s live-service portfolio or a cautionary tale of vision exceeding accessibility. I’m hoping it’s the former, because Marathon rocks. As always, hit subscribe to get updates on Marathon and other relevant games. Subscribe Want to get your hands on our data for yourself – for free? We’re offering a free trial of our platform for games companies. Send us a message here, or reply to this email, and we’ll set you up. The last word Reply to this email – or reach out here – if you have any feedback for the newsletter – or want to request a game for us to cover. [Alinea Analytics boasts the most accurate PC and console estimates in the business. Game makers use our platform to understand their audience, keep an eye on the competition, monitor sales trends, and spot new opportunities. We equip game studios and financial institutions with accurate data and the confidence to make smarter, data-driven decisions. Want to talk about all things games market data? We’d love to chat!]
My unsung hero of science: Buckminster Fuller, the architect who wanted to redesign the world (and inspired a nanosized one)
Few 20th-century scientific figures are as hard to classify as Buckminster Fuller.
Apple takes aim at Google Workspace and Microsoft 365 with new hosted business email
The new Apple Business platform is expanding beyond device management. It now includes fully integrated email, calendar, and directory services for business domain.
Lee’s Summit weighs permit for seasonal inflatable sports dome
Lee's Summit City Council discusses inflatable high school sports complex with full-size pitch.
MLB Opening Day 2026: How to watch every game, including Yankees vs. Giants, full four-day schedule, streaming info and more
We’re Suing the Trump Administration for Removing Science, History from Our National Parks
We cannot fully understand our country and climate without publicly accessible and accurate historical and scientific information.
We disagreed on politics. We agreed on wine. That was enough.
At the Virginia Governor’s Cup Gala in Richmond earlier this month, a very dapper gentleman approached me and introduced himself. In his light-colored suit and bowtie, he looked very Southern in a classical sense, the sort of Virginia Gentleman you used to see south of the Rappahannock as recently as my college days. “I’m a longtime reader and fan of your writing, if not your politics,” he said. His comment was the proverbial iron fist in a velvet glove, simultaneously conveying praise and disapproval while establishing boundaries. Man, I wish we still discoursed like this instead of shouting bromides and insults to try and “own” our opponents with a funny meme and a furrowed brow. Subscribe “Well, we’ll always have wine to share together,” I said, and thanked him for his kind words. We clinked glasses, exchanged pleasantries about the delicious gold medal-winning wines being poured that evening, and went our separate ways. Our exchange reminded me that more unites us than divides us. Wine brings people together to share a meal and a few hours of joy despite our differences.1 That’s why I refer to the wine community — including readers and consumers — rather than the wine industry. Together, we are so much more than production, distribution and sales statistics. A few minutes later the evening’s awards ceremony began. Applause grew as the 12 winemakers who made the top-scoring wines for the Governor’s Case took the stage, including a loud cheer for Jonathan Wheeler of Trump Winery and his 2018 Blanc de Noir sparkling wine. All the winemakers on stage had reason to be proud, Wheeler perhaps more so. Trump Winery was the only winery to win six gold medals in the competition this year. (Wineries are limited to six entries.) Two of Wheeler’s ciders also won gold medals in a separate competition. When you cover the labels and take the sour taste of politics off your palate, the wines are pretty darn good.2 Then Gov. Abigail Spanberger, newly elected Democrat and Virginia’s first female governor, was introduced to great applause to announce which of the 12 wines had won the Governor’s Cup. She spoke for a few minutes about the importance of wine to Virginia’s economy and tourism and the international acclaim Virginia wine has received. Just two weeks earlier, she gave the Democrats’ response to Trump’s State of the Union speech, but this night wasn’t about politics. That didn’t stop several people in the crowd from speculating on the irony should she have to present the trophy to Trump Winery. In the end, Valley Road Vineyards was displayed on the screen behind Spanberger as the winning winery. Blue Bee Cidery in Richmond took top honors for that category. The crowd cheered a female governor presenting the state’s highest trophy to a female winemaker and then resumed the evening’s festivities, united by their mutual love of wine. A whiff of politics couldn’t dim the cheer of celebration and a community united by its love of wine. In Memoriam: Michel Rolland The global wine community lost a giant March 20, with the passing of Michel Rolland. He was 78. Rolland was the original “flying winemaker,” a globe-trotting consultant who helped Bordeaux regain its mojo in the 1970s and then shaped the rise of Napa Valley cult Cabernet as consultant to Simi, Harlan, Newton, Screaming Eagle, Araujo, Dalle Valle and other wineries. He was instrumental in Argentina’s rise to prominence and even had his own winery, Clos de los Siete, in a partnership with other wine families. Rolland’s career arc paralleled that of Robert Parker, the world’s most influential critic. Parker championed many of the wines Rolland consulted on, helping build his reputation and demand for his services. It also made him a target for Parker’s critics. As W. Blake Gray wrote on Wine-Searcher in his excellent tribute to Rolland: Rolland created the type of wines Parker loved: rich body, plenty of fruit, soft tannins. He sometimes faced the accusation of creating a generic international style of red wine, where the great wines he made in Argentina were indistinguishable from the great wines he made in France. Rolland chafed at that critique, as did many of his fans. He was credited with championing green harvesting and leaf pulling, as well as careful selection of grapes in the winery, practices we nearly universally think of today for high-quality winemaking. “Michel was an incredible innovator who changed how wine was made and how grapes were grown,” Napa Valley winemaker Aaron Pott wrote on Facebook. “His work has transformed the wine trade. He created new ways of looking at wine, tasting wine, evaluating ripeness and quality. … This was not just a man with a ‘style’ that he imposed on vineyards but a man that understood how to make great wine from great sites.” Rolland started his consulting company in 1973 in Libourne, in Bordeaux, with his wife, Dany. Both had graduated the year before from Bordeaux’s Institute d’Oenologie. The couple sold their majority share in the business in 2020, according to Wine Spectator. Over his career, Rolland reportedly worked with more than 100 wineries in 20 countries. He even made it to Virginia, where he consulted for Kluge Estate in the mid-2000s. (Kluge Estate is now Trump Winery.) Reader feedback, please! Last week, I did my first WineLine Live! with Dr. Laura Catena of Catena Zapata winery in Argentina. We enjoyed a fascinating discussion about her efforts to preserve the genetic heritage of old vineyards in Mendoza. I conceived of WineLine Live! for paid subscribers, as a thank you for your financial support. And while only a few people joined live, the video now has more views than I have paid subscribers, so I guess that’s pretty good. Even so, I’m considering opening future installments to anyone on Substack to reach a broader audience. So my questions to you: Should these be public? And what format do you prefer? Live gives a chat feature with the potential for viewers to interact with me and the guest, while a video post would just be that. Another alternative is a podcast, which would just be audio, without video of my chins. Please let me know in the comments. Leave a comment In the Glass A few wines I’ve enjoyed recently: Bonny Doon Vineyard Take Me to Your Liter, Le Cigare Volant, Red Wine of the Earth. 2023, Central Coast, CA. Blend of Grenache, Syrah Cinsaut and Petite Sirah. Delightful wine with expressive red fruit flavors, casual drinking. Doon lovers of a certain age will remember Randall Grahm’s Big House Red; this is more in that style than his original Le Cigare Volant, modeled after Chateauneuf du Pape. The liter bottle makes it an even better value. I see this online at about $15. Great value. Albert Bichot Bourgogne Pinot Noir Origines 2023. 13% - Textbook pinot noir and an excellent, affordable entry (regional) Burgundy. Wine Enthusiast Top 100 Wines of 2025. $24 at Total Wine & More. Loma Larga Pinot Noir 2021 “Coastal Cool Climate Wine”, Valle de Casablanca, Chile. An older sample, showing beautifully. Spicy and fruit forward. I’m seeing widely varied pricing online, from $18-$32. At the lower end, it’s a terrific value. 13.5% Dr. Loosen Riesling Dry 2016, Mosel, Germany. Found this “in the stack.” And it stacked up well, shedding some of its youthful acidity for opulent Riesling character, including a hint of the mineral oil older Riesling often features. A great value, as I’m seeing it as low as $14 online. 12% abv. Red Tail Ridge Blau Franc Blend 2024, Sans Oak, Finger Lakes. 13.4% abv. The name is a neat portmanteau of Blaufrankisch and Cabernet Franc, thus Blau Franc. The blend is 50-50, no oak involved. The Blau dominates on the palate, with the spicy caraway seed (think New York deli rye bread). The Franc adds body. The result is juicy, energetic and joyful. Sokol Blosser Estate Rosé of Pinot Noir 2025, Dundee Hills, Willamette Valley, Oregon. This first rosé of 2025 was a welcome respite to our cold, snowy winter here in the Mid-Atlantic. Oh man, I needed this! Bright and energetic, exuberant even, it perks up the mood and goes down fast. 13%. Certified B Corp. Ingredient and nutrition labeling, and in a modest way that doesn’t occupy a lot of label space. (Since it’s not required, presumably there are no minimum font size requirements.) More wineries should follow this example. Dave McIntyre's WineLine is a reader-supported publication. To receive new posts and support my work, consider becoming a free or paid subscriber. Subscribe Thanks for reading Dave McIntyre's WineLine! This post is public so feel free to share it. Share 1 Some restraint may be required. 2 Especially the bubblies.
How Pixar Got the Science Right in Hoppers
Meet the researcher who informed the writers about beaver behavior and threats to their habitat
Ecological and demographic drivers of Oropouche virus transmission
Nature Health - Nationwide analysis of 30,086 confirmed Oropouche virus cases in Brazil between 2014 and 2025 shows that rural municipalities had over 11-fold-higher incidence than urban areas and...
An ode to Olympic sports
Under the current cash-grabbing model, universities are harmfully disregarding the fundamental purpose of collegiate athletics.
Manor Township Democratic committee person kicked off May 19 primary ballot
Kirk Barrett, a candidate for a Manor Township seat on the Lancaster County Democratic Committee, has successfully kicked the incumbent’s name off the ballot for the upcoming May 19 primary.
Senior Playgrounds Are the Latest Healthy Aging Trend With Real Benefits
They're full of low-impact equipment for seniors to get their bodies moving and keep their minds active.
Mills says federal abortion investigation is ‘political’
In particular, the federal government says it wants to find out if Maine “is unlawfully coercing entities covered by Federal health care conscience protection laws to provide, pay for, or provide coverage of abortion.”
2026 MLB standings predictions: Expert picks for every division, full projections as baseball season begins
Here are the predictions from our CBS Sports MLB staff for the 2026 season
New C8 Corvette Grand Sport Makes Surprise Debut at 12 Hours of Sebring
The first mid-engined Grand Sport dons a widebody and red hashmarks, with the car's full reveal coming later this week.
Exclusive: Prenuvo expands full-body MRI protocol. What's new?
Prenuvo is launching a new bloodwork component to complement its full-body MRIs. Here's what to know.
How to beat Gigantamax Pikachu: Best Counters & Guide
Gigantamax Pikachu is a Tier 6 Max Battle in Pokémon GO. It will cost 800 Max Particles to participate in this Max Battle, which will only be consumed if you defeat Pikachu successfully. Gigantamax Pikachu can be shiny from Max Battles. Being an type, it is only weak to type moves. Pikachu can be caught […]
Doubts from key Republicans on surgeon general test MAHA’s political power
Casey Means faces pushback from some Republicans over her refusal to forcefully recommend vaccines.
Crimson Desert now launches on Intel Arc, Pearl Abyss changes course
Pressure matters: Crimson Desert now boots on Intel Arc, full optimization still pending Pearl Abyss has changed its position on Intel Arc support in
Palm Beach County high school sports weekly schedule for March 23-28
High school sports are back in full swing in Palm Beach County. See the full schedule for baseball, softball, lacrosse and more.
Leeds 0-0 Brentford
Paul: Leeds played as if they are frightened of losing rather than trying to win. Chris: Good point in the end - they are a good side pushing for a European place and have good players. Hopefully in the final run-in we will see more of Daniel James, Wilfried Gnonto and Noah Okafor, especially in the home games, to create more goals and keep us in the Premier League.
Tribune All-Area girls' basketball team full of winners
2025-26 Tribune All-Area girls' basketball team features a group of winners, boasting a ton of talent on the hardwood.
California Politics 360 Full Episode | Sexual abuse allegations against César Chávez
Civil rights leader Dolores Huerta broke her silence, saying she was also sexually abused by Chávez. It led to the birth of two children, a secret she kept for 60 years.
Crimson Desert March 23 Update 1.00.03 Released
Pearl Abyss has just released Title Update 1.00.03 for Crimson Desert and shared its full patch notes.
Science diplomacy, research and global health
Nature Microbiology - As a young scientist from the global south, engaging in science diplomacy has brought greater purpose and meaning to my career, writes Delfina Fernandes Hlashwayo.
Science diplomacy, research and global health
Nature Microbiology - As a young scientist from the global south, engaging in science diplomacy has brought greater purpose and meaning to my career, writes Delfina Fernandes Hlashwayo.
Art and science collide in alumna’s artwork
Juliet Fiss, an RIT imaging science alumna, uses algorithms and formulas to create artwork, including a piece at RIT’s Carlson Center.
French Local Elections Are Yardstick for Far Right. Initial Results Are Mixed.
France’s municipal elections ended on Sunday evening. Full results were not expected for hours, but the first projections suggested the far right may not have made major gains.
Full 7-round Arizona Cardinals mock draft simulation
We have a new 7-round mock draft for the Arizona Cardinals.
Your Thymus and Your Healthspan
Our thymus gland plays a central role in the development or our immune system, specifically for supporting T cell development (how these cells got their name, maturation and differentiation in the thymus) and discriminating between self and foreign, non-self antigen proteins with production of dendritic cells. As we age, our thymus gland shrinks—the process known as involution—with progressive change from spongy to fatty tissue, with loss of functionality. But this process, with respect to timeline and extent, markedly varies from one person to the next. And to make things even more complicated, our thymus gland anatomy and precise location in the chest also is highly variable. So the famous Frank Netter diagrams from the 1960s (such as at left below) don’t capture the remarkable heterogeneity that a random set of 12 chest CT scans (below at right). What I consider as 2 landmark papers in Nature this week (here and here) used AI to quantify health of the thymus in 2 large cohorts, and then correlate the metric to a broad array of health outcomes. In this edition of Ground Truths, I’m going to cover three questions: (1) How was thymus health determined by AI?; (2) How is thymus health linked to key clinical outcomes? and (3) Are there ways we can promote a healthy (aka rejuvenate) thymus gland in our later years? Subscribe 1. How was thymus health determined by AI? This was accomplished by extensive work developing and validating an AI pipeline for 2 stages, the first for localization and segmentation of the thymus bed, and the second to quantify a digital marker, termed the thymic health score. There’s a lot to this algorithmic development, so I won’t go into all the details, but just provide a rudimentary outline of what was done. The 1st stage used supervised learning with 2 radiologists reviewing 2,461 chest CT scans. That work trained a 3D U-Net model to automatically identify the thymic bed’s 3D cropped region using center of mass coordinates, which reached 99.8% accuracy. The 2nd stage used a foundation model that was pre-trained with SwAV (which stands for Swapping Assignment between multiple Views), a self-supervised model, that generated a high-dimensional thymus representation of 4,096 features. That compares to the radiology reductionist and subjective scoring of 0 to 3 where 0 means the thymus is fully degenerated and fatty, and 3 is considered dense, intact glandular soft tissue. Notably, the self-supervised learning (SSL) performance was superior to supervised (AUC ~0.75 vs 0.55, respectively) reflecting the shallowness of the 0-3 classifier vs SSL’s holistic, self-taught AI. The thymic health score ranged from 0 to 100, with the highest number indexed to fully preserved thymic health. The algorithmic work extended to explainability with both Shapely value distribution, meaning the model was holistic not relying on any “magic” pixel, and occlusion sensitivity, demonstrating the model’s performance was not affected by ribs, sternum, lung tissue, but rather focused on the thymic bed directly. Below are a few saliency maps from the occlusion sensitivity that indicate the thymic bed focus, not affected by neighboring structures, using the jet color scale. Now the AI was ready for processing ~25,000 CT scans, each over 30 MB files, from the 2 large participant cohorts to provide a thymic health score, it did so in less than 14 hours, which is less than 2 seconds per scan! Share 2. How is thymus health linked to key clinical outcomes? The two cohorts were the National Lung Screening Trial, NLST (N=25,031) and the Framingham Heart Study, FHS (N=2,581) each with baseline demographics and long term follow up of >12 years for health outcomes. From the NSLT, you can see below that increased age and body-mass index were correlated to reduced thymic health. And, overall, men had reduced thymic health scores compared with women. There are a lot of graphs in the paper for outcomes, for both the NLST and FHS cohorts. To simplify the major outcomes, below is a composite Figure with striking reduction of all-cause mortality and for the different causes of death. The results were consistent between the 2 cohorts. For example, the cardiovascular mortality hazard ratio average was 0.57 in NLST and 0.38 in FHS (weighted to be 0.53 for the aggregate). The reduction of mortality also extended to digestive diseases and pulmonary disease (data not shown below). Lung cancer incidence was reduced by 36% for high vs low thymic health (Figure below, with a panel -incidence and b panel-mortality, adjusted for age, sex, BMI, smoking status). Notably, there was a smoker’s paradox: lower incidence and improved survival for lung cancer in smokers who had a high thymus health score. Smoking was associated with lower thymic scores whereas alcohol was not. Higher thymic health was linked to higher HDL cholesterol, lower triglycerides, lower fasting blood glucose, and lower systolic and diastolic blood pressure. Inflammation biomarkers, such as C-reactive protein and interleukin-6, were elevated in the people with lower thymic health scores. In their second paper, the same team looked at the relationship between thymic score and outcomes for 3,476 patients receiving cancer immunotherapy. The non-small cell lung cancer progression-free survival was reduced in patients with low thymic health score. A parallel relationship for survival was seen for other types of cancer including melanoma, breast, and kidney with a 44% lower risk among high thymic scores (Figure). A similar pattern was seen with different immune checkpoint inhibitors. The thymus health score outperformed programmed death ligand-1 (PD-L1)and tumor mutation burden (TMB) assay of the tumor and was an independent prognostic marker of progression-free survival. In this dataset, a direct connect with thymus score and adaptive immune function was noted with a correlation before cancer treatment for both T-cell diversity and thymus T-cell production (a metric known as T cell receptor excision circles). Thymus Removal Study There is a highly relevant citation about thymus function before moving onto ways to rejuvenate it. In 2023, a very important study of thymus removal during cardiothoracic surgery was published, with 1146 patients undergoing thymus removal vs 1146 matched controls (mean age 55 years). The adverse outcomes for thymus removal were striking, with a 2.9 higher risk of all-cause mortality and doubling of cancer incidence, 1.5 fold increase in cancer mortality, and 1.5-fold increase in autoimmune diseases. The immune function showed marked compromise after thymus removal, as reflected by CD4+ and CD8+ T cells (Figure below) Share Ground Truths 3. Are there ways we can promote a healthy (aka rejuvenate) thymus gland in our later years? In recent months we’ve learned a lot about the process of thymus involution and the pathways by which this may be modulated. Thymus involution is primarily due to loss to thymus epithelial cells (TECs) and there are 2 subtypes with different functions: the cortical, responsible for positive selection of T cells, and the medullary, for negative selection. When adipose tissue infiltrates the thymus, thymic adipocytes are pro-inflammatory, knocking out T-cell output. Likewise, systemic inflammation, or “inflammaging,” from smoking, obesity, and chronic stress promote thymic adipocytes. Now, from preclinical studies, we know about key pathways that account for these processes. Historically, back in 2014, FOXN1 was recognized as a single master transcription factor essential for TEC function, with studies in mice with forced FOXN1 upregulation leading to thymus regeneration. That laid the foundation for potential regrowth of quiescent thymus cells. It took awhile to find pathways to accomplish this goal and to even refute its role as the master regulator. The Liver-Thymus Axis Feng Zhang and his team recently showed that injection of an mRNA vaccine to the liver encoding DLL1, IL-7 and FLT3-L in combination, factors known to support thymopoiesis (Figure), successfully enhanced immune function in aged mice. However, the effect was transient. The FGF21 Story Two reports in 2025 addressed the thymus gland’s production of FGF21, a growth factor (fibroblast growth factor 21) and its control of thymus involution. This growth factor is also produced by the liver, but it doesn’t have impact on the thymus in aged rodent models. In contrast, The liver’s hepatocyte growth factor (HGF) has been shown to reverse senescent TEC structural changes. Growth hormone stimulates production of insulin growth factor-1 (IGF-1) in the liver and the thymus. Two small studies in human participants (TRIIM, for Thymus Regeneration, Immunorestoration, and Insulin Mitigation) of 6 and 50 people, respectively, treated with combined human growth hormone, metformin and DHEA, suggested the potential of slowing epigenetic aging and improving thymus mass and function. But the combination of drugs, small sample, and lack of controls make conclusions murky. Increased thymus FGF21 led to increased CD8 T cells in old mice and extended healthspan and improved physical performance. Building on the previous FOXN1 data, ablation of β-klotho, the obligatory co-receptor for FOXN1, accelerated thymic aging. The benefit to FGF21 was confirmed in a companion paper using an FGF21 knock-in mouse model showing thymus enlargement and increased TECs throughout the lifespan. (schematic Figure below). The accompanying editorial for these 2 papers speculated: “The proposed link between age-associated thymus involution and organismal aging is intriguing, and suggests we might seek to achieve systemic rejuvenation by counteracting thymic involution.” Other Factors Lessons from the Axolotl (Mexican Salamander) In an elegant set of experiments of the axolotl (Figure), known for its complete thymus regeneration after total surgical removal, mediators were identified. Surprisingly FOXN1 was dispensable. But midkine, a growth factor, appeared to be the driver, the initiator of thymus cell growth, survival, and repair. Other components that contributed were Postn+ (periostin-expressing mesenchymal niches) and Ccl19, a chemokine protein from the bloodstream. RANK and RANKL RANK (receptor activator of nuclear factor κB its ligand (RANKL) have been considered key regulators of medullary TECs. In a study of both aged mice and human thymus cell cultures, their key role was confirmed, with multiple benefits of resorting TEC function, recruitment of progenitor cells, and T cell development. Subscribe Summing Up This body of work strongly supports the health of the thymus gland as a critical regulator of human healthspan, not just a correlate or link. The new landmark studies are reinforced by the regenerative biology experimental models that have shown, via an array of mediators, that healthspan of aged mice is at least in part dependent on thymus gland function and its critical role for maintaining adaptive immunity. It sure seems that we’d be better off having an immune reservoir of naive T cells instead of a profile in older adults of exhausted, low quality, memory T cells, with a senescent phenotype. It is striking that we ignored the importance of the thymus gland for many decades. A wake-up call was the results of the thymectomy matched control study reviewed here, with the opposite of high thymic health score improved health outcomes. The convergence of AI and healthspan here is notable. The exceptional and laborious work for developing and validating (no less explaining) the AI to quantify thymus health set the foundation for probing the connect the major health outcomes in two cohorts with extensive follow-up. We’ve never had a way to meaningfully quantify the thymus gland before, so this represents important leverage of supervised, self-supervised, and transformer models. The study wouldn’t have been possible without AI. And it begs the question as to whether there are ways we can maintain our thymus at a high health score. But it’s not so simple to rejuvenate our thymus. There are multiple risks including the induction of autoimmunity, increasing the risk of cancer, and inducing a pro-inflammatory state. For example, factors that increase TEC proliferation could compromise the medulllary negative selection process and leak out auto-reactive (self-attacking) T cells. Thymic cells could be induced to proliferate, but we know, for example, that growth hormone and IGF-1 are associated with an increase risk of cancer. If thymus rejuvenation doesn’t clear out the accumulated senescent cells in older adults, then inflammation within the gland could block the production of TECs. Keeping these risks in mind, we now have identified many ways to keep our thymus healthy as we age that undoubtedly will be tested in clinical trials going forward. Ultimately, the benefit-to-risk tradeoffs will be defined. In the meantime, we have desperately needed an immunome. As I’ve stressed in multiple prior Ground Truths, we have no test in the clinic to assess a patient’s immune status! It was very encouraging for me to get an email from Hugo Aerts, the senior author of the landmark papers in the days after they were published: “I also wanted to say that your Substack on “Why We Need an Immunome” was inspiring for this work. We found it a very compelling perspective and greatly enjoyed reading it.” Just having an assessment of a person’s immune status via a chest CT scan, with millions of these performed per year, might help in guiding the right immunotherapy for cancer (e.g. more intensive, combinations for those with low thymic health scores) and help define people who are increased risk for age-related diseases of cancer, cardiovascular, and neurodegenerative. The main theme of Super Agers is that we now have many layers of data (genetics, proteins, biomarkers, organ clocks that can be integrated via multimodal AI) for us to define a person’s specific risk decades before one of these age-related diseases leads to symptoms, enabling prevention. From the new studies this week, we can add thymus health score as yet another way to understand a person’s risk, a window into their adaptive immune system and healthspan. And perhaps someday we will be able to safely rejuvenate the thymus, or maintain its health through one’s life, and use the thymus health score to monitor. NB: I wrote this post (No A.I.) A Quick Poll Loading... ********************************************************************* Thanks to Ground Truths subscribers (now > 200,000) from every US state and 212 countries. Your subscription to these free essays and podcasts makes my work in putting them together worthwhile. Please join! If you found this interesting PLEASE share it! Share Ground Truths Paid subscriptions are voluntary and all proceeds from them go to support Scripps Research. They do allow for posting comments and questions, which I do my best to respond to. Please don’t hesitate to post comments and give me feedback. Let me know topics that you would like to see covered. Leave a comment Many thanks to those who have contributed—they have greatly helped fund our summer internship programs for the past two years. It enabled us to accept and support 47 summer interns in 2025! We aim to accept even more of the several thousand who will apply for summer 2026.
Oscar-Winning Alumnus Returns to Pasadena’s ArtCenter for Entertainment Design Expo
One week after winning the Academy Award for Best Animated Feature, KPop Demon Hunters co-director Chris Appelhans returns today to ArtCenter College of Design, the Pasadena campus where he studied illustration, for the college’s third annual Entertainment Design Expo. The expo, known as ENTX, opens the Hillside Campus to the public for a full day of gallery exhibitions, game playtesting, animation screenings and interactive experiences featuring work from more than 200 ArtCenter students and alumni. General admission is free with advance registration. Two industry panels — including Appelhans’s talk — require $15 tickets. Appelhans, who graduated from ArtCenter with a bachelor of fine arts in 2002, co-directed KPop Demon Hunters with Maggie Kang. The animated film, produced by Sony Pictures Animation and released on Netflix, became the streaming platform’s most-watched film in history, according to Netflix, and swept awards season with wins at the Golden Globes, the Annie Awards and the Grammys before taking the Oscar on March 15. His talk and audience Q&A is scheduled from noon to 1 p.m. in the Ahmanson Auditorium. Doors open at 11:30 a.m. The film’s ArtCenter ties extend beyond its co-director. Art director Angela Sung, cinematographer Gary H. Lee, visual development artist Celine Kim and painter Simon Baek are all ArtCenter graduates who worked on the production, according to the college. The free portions of ENTX include a concept design showcase, a production design gallery, a model gallery, a stop motion studio preview, an alumni gallery and a KPop Demon Hunters fan art gallery. Visitors can also playtest games designed by ArtCenter students. An Animation Shorts Showcase runs from 2 to 3 p.m. and includes “Boy, I’m Scared,” a capstone short by ArtCenter graduate Lindsey Tenaglia that was named a semifinalist for the 2025 Student Academy Awards in the animation category. Also screening
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Scientists twisted a mysterious superconductor and got a shocking result
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Today’s Papers – Italy’s World Cup mission, Napoli’s comeback
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New dispute emerges around Subnautica 2’s early access release
Lawyers for the ousted—and now partially reinstated—leadership team of Unknown Worlds, the studio behind Subnautica 2, are crying foul over news that the game will be released into early access in May. The release announcement earlier this week was made improperly, potentially “damaging the game and sowing additional confusion among the Subnautica community,” the lawyers said in a letter sent on Tuesday to Vice Chancellor Lori Will of Delaware’s Court of Chancery. In their letter, the lawyers also floated the idea of asking Will to find Krafton in contempt of the court’s ruling. The letter was sent just one day after Will’s bombshell ruling that publisher Krafton had breached its contract with Unknown Worlds’ executive team, when it fired them last June. The new issue isn’t necessarily the May early access timeframe, but how the news was announced. The letter and Krafton’s response have not been previously reported. A quick recap of prior events: Subnautica 2 is an unreleased, underwater survival adventure and the most-wishlisted game on Steam. Last year, longtime Unknown Worlds CEO Ted Gill, along with studio co-founders Charlie Cleveland and Max McGuire, were fired by Krafton. They swiftly sued, saying the publisher had terminated them to avoid paying out up to $250 million in potential performance-based bonuses. The studio leaders had hoped to earn that with an early access release of the game, which Krafton had blocked. The publisher argued in court that Subnautica 2 wasn’t ready, which the ousted execs disputed. On Monday, Will ruled that Krafton had violated its contract, firing the execs to avoid the performance payouts, and that it had to reinstate Gill and give him full authority over any early access release for Subnautica 2. On Tuesday, IGN reported on a new memo issued that day to Unknown Worlds staff by Steve Papoutsis, the executive Krafton had put in charge of Unknown Worlds after the 2025 firings. In the note, Papoutsis said that Subnautica 2 had passed a key development milestone “last week” and that he and Krafton had determined the game “is ready for Early Access release in May.” This news appeared to catch the lawyers for Gill, Cleveland and McGuire by surprise. On Tuesday night, they sent a letter to Will expressing “serious concerns” about whether it would be possible to forge an agreement with Krafton consistent with the judge’s order. Papoutsis’ memo was a problem, they wrote. He didn’t have the authority to declare anything about Subnautica 2’s release. As of 9am ET on Monday, March 16, the effective date of Will’s order, Papoutsis wasn’t CEO of Unknown Worlds. Gill was. And, per Will’s order, only Gill could make Subnautica 2 release decisions. They continued: Krafton self-servingly announced the launch without any regard to its impact on the game, the team, or the community—let alone this Court’s Opinion. Announcing the release of a game is momentous, and it is typically accompanied by significant marketing activity, fanfare, and community coordination. And most importantly, the announcement is carefully designed to maximize excitement for the game. That entire process was supposed to be driven by Mr. Gill. However, in defiance of the Court’s Opinion, Krafton has now taken that away, further damaging the game and sowing additional confusion among the Subnautica community. The lawyers speculated that Krafton had “intentionally leaked” Papoutsis’ memo and then issued an official statement to confirm the leak. Game File is a reader-supported publication. My reporting is only possible through support from readers like you. To support my work, consider becoming a free or paid subscriber. Subscribe On Wednesday, lawyers for Krafton defended their client in their own letter to vice chancellor Will, saying nothing they did violated her order nor showed contempt: Papoutsis’s message was simply celebrating the UW employees’ efforts toward a past event: Krafton’s pre-Opinion determination that Subnautica 2 was ready for Early Access release. There was nothing improper about conveying the results of the milestone review or thanking the development team for their dedication and talent. They added that Gill could still make his own call about Subnautica 2’s release: In his role as CEO, Gill will be able to assess independently his views on the state of Subnautica 2 and the appropriate release schedule; nothing in Papoutsis’s message alters Gill’s authority or discretion. Vice chancellor Will has not responded to the letters and doesn’t necessarily have to. Both parties were previously ordered by Will to confer this week and submit a proposed judgment consistent with her ruling. The letter from Gill’s attorney’s this week doesn’t indicate whether he would or would not support a May release for Subnautica 2. But it could limit his options. And, if Gill’s lawyers are right, the lack of marketing fanfare around the leak of the May date could dull the launch of the game. Any harm to Subnautica 2’s launch is an extra sensitive issue given the context of the legal dispute: millions of dollars of payouts are on the line, tethered to the scale of the game’s initial performance. In her ruling on Monday, Will noted that there was obvious “bad blood” between Gill’s side and Krafton but that the two would need to work together: “They can—and must—act in good faith to navigate their remaining contractual relationship.” Item 2: A new kind of couch co-op game A highlight of GDC each year is the Alt.Ctrl showcase that features games played with extremely experimental controllers. Perusing this year’s offerings last Friday, I found a game controlled with giant scissors, another with big toothbrushes and one that amounted to dumpster diving. My favorite was Pivot, a co-op game about collectively maneuvering a couch. It was developed by students at the University of Utah’s masters of arts and engineering games program. Players lift and tilt the physical couch in order to control the position of a virtual one. That virtual one is moving through an obstacle course on-screen, while being pursued by a giant skull. Developer Nishant Verma told me at GDC that the couch is made of styrofoam (this became more evident as I watched!) and that the name was a riff on an episode of the sitcom Friends. Item 3: In brief… 🚫 Ubisoft is laying off more than 100 workers at its Red Storm studio, as the North Carolina location known for decades for its Tom Clancy games, ceases in-house game development, VGC reports. 👀 On Monday, Nvidia’s revealed its DLSS 5 AI-driven graphics technology that purports to improve game graphics… and it has been roasted about it by the media and the online gaming public for the remainder of the week. The tech changed the faces of characters in footage from Resident Evil Requiem, Hogwarts Legacy and EA Sports FC, drawing accusations of giving carefully art-directed games the generic look of AI “slop.” Nvidia CEO Jensen Huang had said on Monday that “DLSS 5 is the GPT moment for graphics—blending handcrafted rendering with generative AI to deliver a dramatic leap in visual realism while preserving the control artists need for creative expression.” By mid-week, Huang was telling Tom’s Hardware that the new tech’s critics were “completely wrong” because game-makers could still “fine-tune the generative AI” to suit their game’s aesthetics.
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