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Chuck Schumer’s Other Challenge Is Geographic | WSJ Politics Newsletter for March 25
Plus, a MAGA rebellion in Arkansas and the DHS-funding standoff continues
Anderson to get new youth behavioral health campus with $24.7M grant
A Redding nonprofit received a $24.7 million state grant to build a behavioral health campus in Anderson for vulnerable youth. Find out more.
California's Ro Khanna was riding high, then came the billionaires
As he lays the groundwork for a presidential bid, Ro Khanna couldn’t ask for a more perfect opportunity to burnish his credentials than a fight with billionaires.
Exclusive | Domain Capital Raises $768 Million Fund to Tap Surging Entertainment Demand
The firm is expanding its entertainment investments with a new artist-management venture and financing agreements with major studios.
The labor leader behind California’s billionaire tax showdown
For decades, Dave Regan has used California’s direct democracy system in a relentless campaign to shore up union power — and his own. But his newest mission is on an entirely different scale.
Kentucky basketball assembled a $22 million roster. The results never matched the price.
Kentucky is making a bold move that could signal where the future of college sports is headed.
Qualified Health raises $125 million, as it helps more health systems build and manage AI tools
Qualified Health, which helps health systems build and manage artificial intelligence tools, has raised $125 million.
Epstein accountant, lawyer explain finances in Congress testimony
Jeffrey Epstein's longtime lawyer Darren Indyke and accountant Richard Kahn manage Epstein's $630 million estate without salaries.
Some Meta executives could make billions under new pay package
AI competition is heating up as Meta plans new pay increases. CEO Mark Zuckerberg isn't included in the plan.
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.
New Mexico jury says Meta harms children's mental health and safety, violating state law
The jury agreed that Meta engaged in "unconscionable" trade practices that unfairly took advantage of the vulnerabilities of and inexperience of children. Jurors found there were thousands of violations, each counting separately toward a penalty of $375 million.
Rural health care providers can now apply for $50M to stabilize access - New round of health care funding builds on record $146M investment - Office of the Governor
SANTA FE – New Mexico’s rural health care providers can now apply for a share of $50 million in health care funding as part of the State of New Mexico’s three-year, $146 million investment that has helped recruit more than 800 health care workers to underserved communities. The funding comes from New Mexico’s Rural Health […]
Scientists discover mirror of our solar system in 2 exoplanets forming around a star
Astronomers have spotted two planets forming around a distant infant star, offering a time capsule into see what the solar system looked like billions of years ago.
Epic Games Laying Off 1,000+ Employees, Swears AI Is Not to Blame
The company behind Fortnite, the Epic Game Store, and the Unreal Engine is also implementing a $500 million cost savings plan.
Tua Tagovailoa eager for fresh start, quarterback battle with Atlanta Falcons
Tagovailoa owed $54 million by Miami Dolphins in 2026
Paranovus sells 14.3M shares at 35 cents to raise $5M
A single institutional investor agreed to buy the shares, with closing set for about March 25. Paranovus says net proceeds will fund working capital.
'Mystery Science Theater' Set to Make Comeback After Fans Raise Over $5 Million to Fund New Episodes
RiffTrax and Shout! Studios announced a Kickstarter campaign to create new episodes of 'Mystery Science Theater 3000.' 'MST3K' has existed in different iterations from 1988 to the present day.
Billionaire OpenAI investor Vinod Khosla thinks 80% of jobs could vanish by 2030, and that ‘fear of AI’ put American politics in a chokehold
“The single biggest issue I believe in the 2028 presidential election will be fear of AI,” the Khosla Ventures founder said.
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!]
NEA Business Notes: RightFiber expands into North Texas - Talk Business & Politics
Jonesboro-based RightFiber is expanding its 100% fiber optic internet with a more than $50 million investment in north Texas. RightFiber brings speeds up to 5 gigabytes to homes and up...
NYC Health + Hospitals/Gotham Health Receives Over $1 Million from Queens Borough President Donovan Richards Jr. to Enhance Patient Care Across Queens - NYC Health + Hospitals
Queens, NY — NYC Health + Hospitals/Gotham Health today announced a significant investment of over $1 million from Queens Borough President Donovan
Antoine Griezmann to join Orlando City in MLS when Atletico Madrid season ends: Why 35-year-old is still great
Griezmann, a World Cup winner with France in 2018, joins an influx of star players like Lionel Messi and Son Heung-min in MLS
AI compressed billions of years of evolution into seconds to create 'Lego-like robots' that can recover even when they lose limbs
Modular robots are easily expandable, know when they're upside down or stuck, and can march forward across all kinds of terrain.
Epic Games to Layoff 1,000 and Cut $500 Million Amid 'Fortnite' Slump
Epic Games will cut 1,000 staffers and another $500 million in costs amid a slump in engagement with 'Fortnite,' CEO Tim Sweeney confirmed in a memo.
Covid Relief Loans Are Haunting Small Businesses
The Small Business Administration lent $378 billion to keep businesses afloat. Getting paid back is proving difficult.
The Morning After: WWDC 2026 is happening June 8th
The biggest news stories this morning: Wing expands its drone delivery service to the Bay Area, Billionaire OnlyFans owner Leonid Radvinsky has died from cancer at 43, Apple will reportedly start stuffing ads into the Maps app.
Avalon’s New Challenges, Opportunities in Life Science Investing
LA JOLLA – As Avalon BioVentures wraps up deploying its very first fund, the $135 million ABV1, the early stage focused venture capital firm is already lookin
Pro Padel League raises $15 million as investors bet on sport’s U.S. growth
The Pro Padel League has raised $15 million in new funding as it looks to accelerate its next phase of growth in the U.S.
Pacers Sports & Entertainment Launches Fieldhouse Media Network, Delivering First-Of-Its-Kind Global Media Channel for Partners
Deloitte and Yieldmo help PS&E to grow market size through first-party fan data while producing convertible ROI INDIANAPOLIS (March 24, 2026) – Pacers Sports & Entertainment today launched the Fieldhouse Media Network, a first-of-its-kind global AI-powered media platform built on authenticated sports fandom, giving brands measurable access to one of the most engaged audiences – the fan. Developed in collaboration with Deloitte and Yieldmo, the network leverages Yieldmo’s Ymax.ai, an advertising platform with a dedicated sports vertical, and Converge™ by Deloitte for Sports fan data platform built on Deloitte Ascend™ to activate first-party, authenticated data from approximately 250 million sports and entertainment fans worldwide in a privacy-safe, cookieless […]
Pacers Sports & Entertainment Launches Fieldhouse Media Network, Delivering First-Of-Its-Kind Global Media Channel for Partners
Deloitte and Yieldmo help PS&E to grow market size through first-party fan data while producing convertible ROI INDIANAPOLIS (March 24, 2026) – Pacers Sports & Entertainment today launched the Fieldhouse Media Network, a first-of-its-kind global AI-powered media platform built on authenticated sports fandom, giving brands measurable access to one of the most engaged audiences – the fan. Developed in collaboration with Deloitte and Yieldmo, the network leverages Yieldmo’s Ymax.ai, an advertising platform with a dedicated sports vertical, and Converge™ by Deloitte for Sports fan data platform built on Deloitte Ascend™ to activate first-party, authenticated data from approximately 250 million sports and entertainment fans worldwide in a privacy-safe, cookieless […]
Nintendo cuts Switch 2 production amid weakening console sales
Output is reportedly being reduced from six million to four million units, despite the console’s record debut.
New Maine law seeks to help parents afford childcare costs
Since 2019, the state has spent more than $145 million in state and federal funds on childcare and early education programs, according to the governor’s office.
Ice In New Orleans, Floods In Los Angeles: Businesses’ Risk Reality
Extreme weather is reshaping business risk management, from billion‑dollar storm losses to unexpected climate events that disrupt operations.
Blount: Online sports betting proposal has little support in Senate, would cost casino industry
Sen. David Blount, chairman of the Gaming Committee in the Senate, says a proposal to legalize online sports betting lacks support in the Senate, and could harm the state's casino tourism industry, which provides thousands of jobs and millions in state revenue. Blount also discusses proposed, and recently enacted, changes to the Public Employee Retirement System, and proposals to increase tax credits for private schools.
CelebrateOne secures $3.39M grant to fund for maternal health in Columbus
CelebrateOne secured a $3.39 million grant to fund 15 organizations expanding maternal health services in Franklin County.
We’ve Been Underestimating Flying Foxes
Australia used to incinerate the large fruit bats, but research suggests they bring hundreds of millions of dollars in benefits to the country’s economy.
We’ve Been Underestimating Flying Foxes
Australia used to incinerate the large fruit bats, but research suggests they bring hundreds of millions of dollars in benefits to the country’s economy.
Play the Tiny Takeover drop
Tiny Takeover has officially stormed Minecraft! New versions of baby mobs are causing cuteness overload across biomes and builds. Pack your golden dandelions, craft name tags, and get ready to collect, cuddle, and coo over our new tiny rascals.
'Dhurandhar' Powers India's Record $2.18 Billion 2025
'Dhurandhar' headlines a record $2.18 billion film year as India's M&E sector grows 9% to $29.63 billion in 2025, per the annual FICCI-EY report.
Scientists found a rhino in the Arctic and it changes everything
Scientists have uncovered a new species of rhinoceros in the Canadian High Arctic, revealing that rhinos once lived far farther north than expected. The fossil, dating back 23 million years, is unusually complete and has helped reshape ideas about how these animals migrated between continents. Evidence suggests rhinos crossed from Europe to North America more recently than scientists once thought.
The Business of Bull Riding: CEO Sean Gleason Opens Up His PBR Playbook
Under Gleason, the Cowtown-based Professional Bull Riders has evolved into a made-for-TV, multibillion-dollar sports property.
Insulin pills may soon replace daily injections
For over a century, scientists have chased the dream of insulin pills, but the digestive system kept destroying the drug before it could work—forcing millions of patients to rely on daily injections. Now, researchers at Kumamoto University have developed a clever workaround using a tiny peptide that helps insulin slip through the intestinal wall.
Political traffic signals: waiting for the light to change on the Hill
Congress faces a steep political battle over a $200 billion Iran war spending request, with Trump sending mixed signals on whether the funds are needed.
Someone has publicly leaked an exploit kit that can hack millions of iPhones
Leaked "DarkSword" exploits published to GitHub allow hackers and cybercriminals to target iPhone users running old versions of iOS with spyware, according to cybersecurity researchers.
Travis Kelce reportedly re-ups with Chiefs on a 3-year, $54.7 million deal, but there's a catch
Trump’s Political Risk Insurance Plan for Ships in the Gulf Could Benefit China, Says Democratic Senator
President Trump’s $20 billion plan to provide political risk insurance for ships aimed at unblocking the Strait of Hormuz could end up ultimately
Microsoft-backed startup raises $40 million for advanced chipmaking equipment tech
Lace, a Norway-headquartered chipmaking equipment startup which is backed by Microsoft, has raised $40 million in funding to further develop a technology that could enable significant advances in semiconductor design and manufacturing, the company said on Monday.
Microsoft-backed startup raises $40 million for advanced chipmaking equipment tech
Lace, a Norway-headquartered chipmaking equipment startup which is backed by Microsoft, has raised $40 million in funding to further develop a technology that could enable significant advances in semiconductor design and manufacturing, the company said on Monday. To make cutting-edge chips, manufacturers such as Taiwan Semiconductor Manufacturing Co and Intel employ a process called lithography that uses light to draw complex circuits that form the foundation of advanced artificial intelligence chips. Manufacturers use light-based lithography systems made by the Dutch company ASML - which dominates the market - as they race to shrink chip components and squeeze in more features to boost the computing horsepower on a limited area of silicon.
Trump admin dumps Biden-era wind projects for billion-dollar investment in US oil
The Trump Department of the Interior secured a landmark agreement with energy giant TotalEnergies to redirect nearly $1 billion away from "unreliable" and "ideological" wind projects.
Grub Lab: $6 Million Raised To Bring Sports And Entertainment IP To Independent Restaurants Nationwide
Grub Lab, an Australia-founded restaurant technology startup, announced it has raised $6 million in funding from Quantaco to accelerate its expansion across the United States and support a national rollout tied to major sports leagues and entertainment studios. The company is positioning itself as a modern solution to help independent restaurants compete for family dining traffic through interactive, branded experiences.
We both lost our jobs. So we started a company.
After being laid off in 2020, my husband and I launched Larroudé from home. Today, the shoe brand employs 600 people and generates millions.
Cencora to buy retina business of EyeSouth Partners for $1.1 billion
Drug distributor Cencora said on Monday it would buy the retina business of eye care network EyeSouth Partners for $1.1 billion, expanding its eye care unit.
Sony Is Said to Near $1 Billion Home Entertainment Deal With TCL
Sony Group Corp. is nearing a binding agreement to sell a majority stake in its home entertainment business to Chinese rival TCL Electronics Holdings Ltd. in a deal that may be valued at about $1 billion, according to people familiar with the matter.
A Look At PENN Entertainment (PENN) Valuation As Expansion Projects And New Financing Move Ahead
Expansion plans and fresh financing reshape the PENN Entertainment story PENN Entertainment (PENN) has put expansion and balance sheet moves front and center, with new casino and hotel projects in Aurora and Columbus alongside a fresh US$600 million senior notes offering. See our latest analysis for PENN Entertainment. Despite the new projects and financing, PENN’s 1 year total shareholder return of 21.21% and 5 year total shareholder return of 86.08% sit well behind peers. A recent 4.99% 1...
The 'Nail Test': Why This $54 Billion Innovation Is Terrifying Western Auto Executives
BYD says it's fixed yet another major problem with EVs.
'A towering figure in French politics': reactions to Lionel Jospin's death pour in
Lionel Jospin, Socialist prime minister of France from 1997 to 2002, has died.
Ambani's Reliance Jio: businesses and investors of the IPO-bound firm
Indian billionaire Mukesh Ambani's Reliance Jio Platforms is gearing up to file papers seeking regulatory approvals for a Mumbai listing, in what is likely to be the biggest-ever stock offering in the country.
David Gallo opens up about why AI data centers, private equity are good for his company
After Katrina, David Gallo led his family's company, Gallo Mechanical, through a geographic expansion that helped grow the company to nearly $500 million in revenues and more than 700 employees. Last year, he led the 80-year-old business through a sale to a private equity firm. In this week's Talking Business, he explains why it was a good thing
Scientists See Converging Evidence of Antarctic Ice Retreat
A sediment core spanning millions of years and new modeling studies point to significant ice retreat under temperatures similar to today.
Delivery Hero to Sell Taiwan Business to Grab
The German food-delivery company said it would sell Foodpanda as part of a strategic review for $600 million in cash.
Grab Strikes $600 Million Deal for Foodpanda Taiwan Business
Grab Holdings Ltd. agreed to buy Delivery Hero SE’s Foodpanda operations in Taiwan for $600 million, a deal that marks its first foray outside of its Southeast Asian home market.
Funding for populist-right ‘media-political complex’ exceeded £170m in five years, research finds
Handful of billionaires gave huge sums in particular to media organisations that boosted rightwing politicians, says Liam Byrne MP
Executive Council seeks greater role in half-billion-dollar rural health initiative
New Hampshire executive councilors are seeking a greater role in a $640 million rural health initiative after initially delaying approval and securing more oversight.
Iranian Missile Strikes Are Costing Big Oil Billions in Lost Revenue
Damaged energy infrastructure is likely to take years to come back online, but a surge in oil-and-gas prices is helping to offset some of the lost production for now.
'Project Hail Mary' blasts off to record-breaking $80 million, becomes 2026's best premiere
'Project Hail Mary' burned through the outer layer of box office projections this weekend, reaching an astounding $80 million in its domestic premiere and $141 million worldwide.
‘Project Hail Mary’ blasts off with $80.5 million, a best for Amazon MGM, and the year
Studio estimates on Sunday say Amazon MGM's “Project Hail Mary” has topped the North American box office charts with $80.5 million in ticket sales — the second biggest ever for a non-franchise film.
Educational Service Center awarded Teach Computer Science 2.0 Grant
The Educational Service Center of the Western Reserve has been awarded $584,614 through the Ohio Teach Computer Science 2.0 State Grant, a competitive initiative funded by the Ohio Department of Higher Education. As part of an $8 million…
Israel Thought It Could Spur Rebellion Inside Iran. That Hasn’t Happened.
President Trump’s hopes that an Israeli plan to ignite an internal uprising against Iran’s theocratic government could bring the war to a swift end have so far been dashed.
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.
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