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Which tiny will take over?
Take on the first of two challenges in the Tiny Takeover drop and earn adorable rewards together! Choose a side: land or water! Then name as many baby mobs you can on land OR in water using name tags between Mar 27, 8 AM PT to Mar 30, 10 AM PT!
The Entertainment Report: Paul McCartney, C2E2, and ‘Project Hail Mary’
Cindy Pearlman Gaber, senior writer for the New York Times and entertainment columnist for the Las Vegas Review-Journal, joins Bob Sirott to talk about movies to see this weekend, HallmarkR…
South Carolina nonprofit considering new entertainment complex
The South Carolina Entertainment and Music Hall of Fame is considering developing a new complex to showcase the arts the Palmetto State has to offer.
NYS assembly majority leader questions proposals from Buffalo Mayor Sean Ryan
Crystal Peoples-Stokes said there are some concerns with Ryan's plan to cover the city's budget gap.
Ability to remain positive during conflict associated with better overall mental health in young children
Staying positive in stressful situations is a sign of resilience in young children — and it protects against mental health problems.An examination of how young children reacted to challenging and stressful situations by the Arizona State University Department of Psychology has found that those who were able to maintain positive emotions during an argument with their parents experienced fewer mental health problems, such as anxiety, depressive symptoms, behavioral outbursts and attention deficit hyperactivity disorder behaviors.
Saros has been made easier than Returnal due to player feedback, though creative director claims its still "a very challenging game"
According to Saros' creative director, the game has been made easier thanks to player complaints around Returnal not having auto saves or multiple save slots.
Wayfound.ai CEO transforms engineers into AI managers
Wayfound.ai, led by CEO Tatyana Mamut, uses AI agents to transform software development, challenging the traditional SaaS model.
See Louisiana’s ‘Vote for the Crook’ election through the eyes of 8 new Hall of Fame inductees
The eight inductees to the 2026 class of the Louisiana Political Hall of Fame played a role in the epic 1991 governor’s race between Edwin Edwards and David Duke.
Now in power, Nepal’s rapper-politician Balen Shah faces new challenge
Shah was a rebel — crude and different from the politicians who previously led Nepal. How will he be in office?
'Growth' for Republic of Ireland despite Prague pain
Republic of Ireland boss Heimir Hallgrimsson says there are plenty of reasons to be optimistic following his side's World Cup play-off shootout defeat by the Czech Republic.
Challenges for downtown Buffalo businesses continue
BUFFALO, N.Y. (WIVB) — Business in downtown Buffalo continues to be a big topic. On Wednesday, Public Espresso announced it is closing its cafes — including a Washington Street location…
Kennedy’s Vaccine Agenda Hits Roadblocks, Diminishing His Clout
Health Secretary Robert F. Kennedy Jr.’s vaccine skepticism is posing challenges for the Trump administration. Top health jobs are unfilled, and a court has blocked his vaccine schedule changes.
Democratic US Sen. John Hickenlooper qualifies for Colorado primary by petition, will skip assembly
U.S. Sen. John Hickenlooper has qualified for Colorado’s Democratic primary after the first-term incumbent submitted enough valid petition signatures to make the ballot, state officials said. Hickenlooper is facing primary challenges from state Sen. Julie Gonzales, D-Denver, and university professor Karen Breslin, who are both vying for spots in the June 30 primary at the […]
Vermont Sports Hall of Fame adds two members to 2026 induction class
South Burlington tennis legend Jake Agna and 1909 University of Vermont grad Fenwick Watkins join 2026 Vermont Sports Hall of Fame induction class.
LGBT People Experience Widespread Concerns and Challenges When it Comes to Health Care Affordability
This analysis highlights the health care affordability challenges facing LGBT adults, a growing population that faces health related disparities. Findings from KFF Health Tracking Polls show that LGBT adults face more widespread concerns with affording basic necessities, including health care, compared to non-LGBT adults.
Pomegranate Market owners discuss challenges of transitioning family business
This entrepreneurial father-son duo opened up about transitioning the family business, as well as their vision for the future of Pomegranate Market.
Healthcare Priorities in Governors’ 2026 State of the State Addresses
Across the country, Governors from coast to coast made healthcare a centerpiece of their 2026 legislative addresses—identifying common challenges around rural access, workforce shortages, rising costs, and behavioral health, and charting a range of ambitious courses to address them. Rural Access Gaps Rural and remote communities have experienced losses in critical healthcare infrastructure, inherently decreasing […]
Arts and Entertainment Agenda: March 27-April 3
Limitless Mountain Challenge, March 28 Challenge Aspen’s “Limitless Mountain Challenge” runs 8 a.m. to 4 p.m. March 28 at Snowmass Mountain. The all-abilities ski and snowboard event supports adaptive recreation, with a downhill ski and...
Federal ruling on UF case deals blow to state law limiting faculty dispute appeals
Court filings showed multiple professors were denied arbitration after challenging terminations and performance reviews under the law.
How the youngest female CEO in the Fortune 500 navigates political turmoil
Sarah London is leading Centene through political challenges like Medicaid cuts.
Hershey Entertainment & Resorts Celebrates 2025 Partners of the Year
Hershey Entertainment & Resorts (HE&R) recently named its 2025 Partners of the Year at Town Hall meetings across several properties. Throughout the 2025 calendar year, team members were nominated by their peers or supervisors for “Team Member of the Month” recognition for embodying HE&R's Core Values: Devoted to the Legacy, Selfless Spirit o...
York County sheriff candidate’s eligibility challenged
The Maine Secretary of State’s Office will issue a ruling following a hearing on Friday.
Campaign hopes to boost business at Marshall restaurants impacted by water outage
A shop local campaign aims to help Marshall restaurants that were forced to shut down during the recent water main break and boil water notice. The city of Marshall, Marshall […]
Why politics, money, and construction capacity will limit any European turn toward nuclear power generation
The EU wants to reestablish the nuclear power supply it once had, when nuclear provided about a third of the bloc’s electricity supply. But Europe's industrial capacity, financial challenges, and politics are major obstacles to a European nuclear renaissance.
Questions on Trinity Health's move to Brighton? Townhall on March 31
Trinity Health Livingston is moving all operations from its legacy campus at 620 Byron Road to a new hospital at 7555 Grand River Ave.
Fatal collision highlights air traffic control challenges at LaGuardia
New York’s airports pose difficulties for an air traffic system already under strain.
MacPherson to challenge Mercado Kim for District 14 seat
MacPherson to challenge Mercado Kim in primary
Melania Trump shares the spotlight with a robot at an education and technology event
Melania Trump and the humanoid walked slowly side by side along the red carpet from the opposite end of a White House hallway.
Postal Service to implement first-ever fuel surcharge amid mounting fuel costs, financial challenges
USPS is reportedly planning its first-ever 8% fuel surcharge on packages starting in April as the agency faces a cash crisis and mounting financial losses.
"The Hall of Fame Knocks: Class of 2026" nominated for Sports Emmy | Pro Football Hall of Fame
“The Hall of Fame Knocks: Class of 2026” has been nominated in the Outstanding Edited Sports Special category as part of the 2026 Sports Emmy Awards.
Providing quality, access to health care in rural Indonesia | Harvard T.H. Chan School of Public Health
Leni Siagian, MPH ’26, wants to ensure care for those who face challenges getting it.
Some East Grand Forks businesses must register with city to sell low-potency hemp products
Changes in requirements from the state Office of Cannabis Management mean businesses selling these products must now be licensed with the OCM and registered with their local cities.
Top climate scientist Kate Marvel just resigned from NASA. Here's why
Climate scientist Kate Marvel talked to Scientific American about her decision to leave NASA amid federal government turmoil and funding challenges
Partnership in Action: Reimagining Climate and Health Funding Together
Climate Communities Network members explore funding strategies to sustain community-based climate and health work amid shifting challenges.
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
SW FL Business Hall of Fame honors four new leaders. Read about them
Junior Achievement of Southwest Florida inducted four new laureates into its Business Hall of Fame on March 24.
SW FL Business Hall of Fame honors four new leaders. Read about them
Junior Achievement of Southwest Florida inducted four new laureates into its Business Hall of Fame on March 24.
Poll: 1 in 3 Adults Are Turning to AI Chatbots for Health Information, Equaling the Share Who Use Social Media for Health
About a third (32%) of adults nationally say they have turned to artificial intelligence (AI) chatbots in the past year for health information, a new KFF Tracking Poll on Health Information and Trust finds. Most who turned to AI for health information say they were in search of quick and immediate advice, though challenges affording and accessing health care also play a role, particularly for younger adults.
Imaging manufacturer Guerbet faces financial challenges following recent FDA warning
Regulators recently scolded the France-based pharmaceutical firm for safety issues that occurred at its plant in Raleigh, North Carolina, which produces imaging contrast agents.
#46 | IT/Digital Solutions Business | Scope
From Recognition to Resolution—One-Stop Solutions for Digital Challenges
Mamdani uses fast food feast to bring attention to worker rights
“City Hall’s first-ever mukbang. Here we are," he said.
ICE detains longtime Kearney business owner and entrepreneur
Immigration and Customs Enforcement detained a Kearney business owner on March 11. Carlos Godinez, the owner of Nick’s Gyros for the past 15 years, is currently at the Hall County Department of Corrections on an ICE hold.
Pentagon will remove media offices after judge reinstates NYT's press credentials
The U.S. Defense Department will remove media offices from the Pentagon after a federal judge sided with The New York Times in a lawsuit challenging limits on reporters' access to the building, a department official announced Monday.
Royal Challengers Cricket Buy to Be Blackstone's First Sports Deal
Cricket team Royal Challengers is sold to investor group that includes Blackstone, Bolt Ventures, Aditya Birla Group and The Times of India Group
TDN Business Hour: The Global Thoroughbred Market
Mark Taylor, Marshall Gramm, Anthony Trimarchi and Case Clay join the TDN Business Hour podcast hosted by Najja Thompson.
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!]
UC Berkeley’s Lawrence Hall of Science to host Earth Day celebration, month of events
The Lawrence Hall of Science, University of California, Berkeley’s public science center, will host its third annual Earth Day Celebration on April 26,
Communicating Across Disciplines in Climate Change Litigation
Climate change litigation must climb many mountains to advance justice and reshape human behaviors for the well-being of people and our planet. On this long, arduous journey, litigants, lawyers, scientific witnesses, and judges face challenges of communicating across disciplines. UCS’s new resourc
Talking politics at work may support employee well‑being
Study challenges the conventional wisdom about avoiding talking politics at work, showing that it can sometimes benefit employee well-being.
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
Football Hall of Fame to Honor St. John’s Alumnus Who Led Landmark Sports Statistics Firm
A St.
Arbitration case could bring change to NCAA's 'messy middle'
Why Nebraska's recent challenge could have wide-ranging salary cap implications.
New Fathers Face Mental Health Challenges, Study Finds
By Dennis Thompson HealthDay ReporterTUESDAY, March 24, 2026 (HealthDay News) — New fathers might be proud poppas, but their mental health might be shaky as they adapt to their increased responsibilities, a new study says. Men have a 30% increased risk of depression and stress disorders by the end ...
Alabama High School Sports Hall of Fame inducts 12 coaches, administrators in Class of 2026
Inductees selected from slate of 60 nominees.
Latest stats show stress and lack of physical activity are rising, putting heart health at risk
As people navigate higher levels of stress and spend more of their day sitting, finding time to move can feel challenging. Less than half of adults and fewer than one in five children in the U.S. get ...
Ron DeSantis, Nikki Haley tie for 3rd in New Hampshire GOP 2028 poll, far behind Marco Rubio, JD Vance
New polling shows another run for the Governor may be challenging.
Veterinary Science Certificate Program promotes early steps on career path
Rural communities face a growing shortage of veterinary professionals, creating challenges for pet owners and livestock producers alike.
Takeaways from arguments in the Supreme Court case that could end grace periods for mail-in ballots
The Supreme Court’s conservative majority appeared dubious of state laws that allow the counting of mail ballots that arrive at election offices after Election Day as justices heard oral arguments in a challenge to Mississippi’s five-day grace period for mail ballots.
Federal judge sides with Wisconsin in transgender health care suit
A U.S. judge ruled in favor of Wisconsin and 20 other states challenging a Trump administration declaration that tried to limit care for trans youth.
Lenoir-Rhyne Sports Hall of Fame Nominations Due April 1
HICKORY, N.C. - Nominations for the Lenoir-Rhyne Sports Hall of Fame are due by Wednesday, April 1. The 2026 Hall of Fame ceremony will take place on Saturday, September 19, prior to Lenoir-Rhyne's 6:00 p.m. football game vs. Mars Hill.
Cardinal Health Appoints Patricia A. Hemingway Hall as Board Chair
/PRNewswire/ -- Cardinal Health (NYSE: CAH) today announced that its Board of Directors has appointed Patricia A. Hemingway Hall to succeed Gregory B. Kenny as...
Executive Director of SnoCo Sports to be Inducted to the Sports ETA Hall of Fame
Tammy Dunn, Executive Director of the SnoCo Sports Commission, is to be inducted into the Sports ETA Hall of Fame on April 22, 2026.
I tested ChatGPT vs. Perplexity with the same 5 prompts — the winner surprised me
AI Madness Round 1: The Heavyweight meets the Challenger in our first round of Tom's Guide AI Madness
Socialist Emmanuel Grégoire elected Paris mayor in runoff vote
Emmanuel Grégoire has won the Paris mayoral race and takes over from fellow Socialist Anne Hidalgo. On Sunday, he sealed the moment by riding a city bike to City Hall.
How Obama’s Strategist Discouraged Biden From Running in 2016
In a new set of oral histories, David Plouffe, President Barack Obama’s political adviser, described how he urged Vice President Joseph R. Biden Jr. not to challenge Hillary Clinton for the nomination.
The Christian Science Monitor Daily for March 23, 2026
Rethink the news: Reducing news to hard lines and side-taking leaves a lot of the story untold. Progress comes from challenging what we hear and considering different views.
Kansas coach Bill Self non-committal if he'll return next year due to health concerns
Hall of Fame Kansas basketball coach Bill Self said after a crushing loss to St. John's that he hasn't decided if he'll be back next season or retire.
Scientists Open Moon Rocks Locked Away Since 1972 – and Find Something Totally Unexpected
Decades after being sealed away, Apollo-era lunar samples are revealing unexpected chemical signatures that challenge long-standing assumptions about the Moon’s composition.
Analyst reveals high expectations for 49ers after free agency spree
Could the 49ers really challenge in 2026?
Two-thirds of workers are burned out—here's what science says about how to tackle it
Burnout is at an all-time high, with some studies saying two-thirds of employees now cite job burnout as a major challenge. Overwork and chronic stress do not just drain energy, they can erode health, ...
Opinion | Jesse Jackson, the Prophet Who Became a Politician
He challenged black Americans in the 1960s and ’70s, then retreated into victimhood and grievance.
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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