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Amusement Entertainment Management Client Wins 2026 FEC of the Year
Star Lanes Polaris of Columbus, Ohio proudly accepted The American Amusement Machine Association’s (AAMA) 2026 Family Entertainment Center Location of the Year Award during the AAMA President…
Glyphosate: A story of science, risk, and nuance
In the summer of 2014, a California groundskeeper named Dewayne Johnson started noticing patches of raw, weeping skin spreading across his body. He had spent years applying Roundup, Monsanto’s glyphosate-based herbicide, for a school district, sometimes drenched in it when equipment malfunctioned. By 2014, he had a diagnosis: non-Hodgkin’s lymphoma. In 2018, a jury awarded him $289 million in damages, later reduced on appeal. Tens of thousands of lawsuits followed. The story hasn’t quieted down. It’s all over the internet, swinging between “this will kill you, buy organic” and “relax, you’re fear-mongering.” Some of that recent chatter stems from an Executive Order protecting glyphosate and its production, which set off intense infighting within the MAHA movement. Some of it reflects a deeper truth: Americans genuinely care about harmful chemicals in their environment (see poll below). And the conversation isn’t going anywhere, with a Supreme Court case involving Monsanto set for this April. Glyphosate (the active ingredient in Roundup) is one of the most widely used herbicides in the world. But does glyphosate cause cancer? And how much exposure is actually risky? With so much mistrust in institutions and corporations (and some genuine conflicts of interest), making sense of the actual scientific evidence is genuinely hard. Here is a translation of what the scientific evidence actually says. Does glyphosate cause harm? Glyphosate is an herbicide that kills most plants it contacts rather than targeting specific species. It works by blocking an enzyme pathway (EPSPS) that plants and many microorganisms need to produce essential amino acids. Without those amino acids, the plant can’t grow and dies. Glyphosate was first developed by Monsanto in the 1970s and became ubiquitous after the company introduced “Roundup Ready” crops in the 1990s. In 2024, Bayer removed glyphosate from residential Roundup-branded products due to litigation pressure. But today it is still the most widely used herbicide in the world. Farmers also discovered they could spray it directly on crops like oats, lentils, beans, and peas just before harvest to dry them out faster and make harvesting easier. Because of its widespread use, it’s obviously really important to understand if it’s harmful to humans. The key principle: The dose makes the poison The most important concept in toxicology is that “the dose makes the poison.” Sixteenth-century physician Paracelsus articulated what remains the foundational principle of toxicology: sola dosis facit venenum. Water will kill you if you drink enough of it. Aspirin saves lives at 81 milligrams and causes internal bleeding at higher chronic doses. So, at what dose is glyphosate poisonous? The LD50 in rats (the dose that kills half the test animals) is around 5,600 mg/kg body weight. Table salt is roughly 3,000 mg/kg. By that classic measure, glyphosate is less acutely toxic than salt. But some people are exposed to a lot of glyphosate through their work. And among the general public, there are many questions about low-dose, cumulative exposure from multiple sources over long periods. Does glyphosate cause health problems? Cancer Correlation maps are striking, with one analysis finding that 60% of counties that spray the most glyphosate have non-Hodgkin’s lymphoma rates above the national average. But correlation alone doesn’t establish cause, which is why animal and human studies matter. In animals: Rat studies are typically what most fear is rooted in, but most people don’t know the study details on the dosage given to rats. A pooled analysis of the 13 most rigorous rat studies found evidence that very high doses, around 55,000 times greater than typical food residue exposure, can cause certain cancers. In humans: One of the strongest studies followed 55,000 herbicide users over 20 years and found no overall increased cancer risk. There was one signal: among those with the highest use, rates of acute myeloid leukemia (AML) appeared elevated. A broader meta-analysis of 18 human studies also found no overall cancer risk, though a separate meta-analysis focused specifically on non-Hodgkin lymphoma found that people with high cumulative glyphosate exposure faced a 41% higher relative risk compared to those with low or no exposure. These human studies are observational studies (randomized controlled trials would be unethical), and meta-analyses are only as reliable as the studies they pool. But the story seems consistent: at very high exposure levels, there may be some cancer risk. But that’s about as far as the science currently takes us. Emerging research: gut and reproductive health Gut: Because glyphosate targets a pathway that exists in some gut bacteria, scientists have questioned whether it could affect the microbiome. In mice, a 2023 University of Iowa study found that glyphosate altered gut bacterial composition and raised markers of intestinal inflammation. A 2024 systematic review found similar patterns: disrupted gut bacteria and problems with the mucus layer that protects the intestinal wall in mice. Whether this translates to humans is an open question. The human gut is highly variable and resistant, and we don't yet have strong studies confirming the same effects in people. Reproductive health: Animal studies have found that glyphosate-based herbicides can interfere with reproductive hormones, including disrupting egg cell development in mice and reducing the number of eggs available in sheep’s ovaries. However, the doses used in these experiments were high, so it’s not yet clear whether the same effects would occur in humans. On the human side, a 2021 pilot study led by Mount Sinai researchers tested urine samples from pregnant women across the U.S. and found glyphosate in 95% of them. The study also found a possible connection between higher glyphosate exposure during pregnancy and a subtle physical difference measured in female newborns. That said, some connections weren’t statistically reliable and this was a small study. The researchers themselves said more and larger studies are needed before drawing firm conclusions. What do regulators say about glyphosate safety? In 2015, the International Agency for Research on Cancer (IARC), part of the World Health Organization, classified glyphosate as "probably carcinogenic to humans" (Group 2A). The classification is worth taking seriously. But, there’s an important distinction: IARC classifies hazard, meaning the potential to cause harm under some conditions. It does not assess risk, which accounts for actual exposure levels and the real-world probability of harm. The U.S. EPA, the European Food Safety Authority, Health Canada, and regulatory agencies in Australia and Japan have all concluded that glyphosate is “unlikely to be carcinogenic to humans” at realistic exposure levels. They’re asking a different question: given how much of this people actually encounter, what is the probability of harm? Your actual exposure is what determines your actual risk. What does glyphosate mean for your daily life? At the grocery store: Food residues are small. The EPA’s acceptable daily intake is 1.75 mg/kg of body weight per day. To hit that threshold from oatmeal alone, a 150-pound adult would need to eat roughly 50 pounds of oats every day. But this calculation addresses only one pathway (food), and we don’t yet have robust tools to measure people’s actual total exposure. If reducing exposure matters to you, organic certification prohibits synthetic herbicides, and organic oat products generally test at lower or undetectable levels. Either way, a diet rich in whole grains, conventional or organic, is far better for your health than one that omits them out of fear of residues. On the farm: Occupational exposure is orders of magnitude higher than consumer exposure. Farmers and farm workers who mix, load, and apply glyphosate-based herbicides, especially without protective equipment, face meaningfully different risk profiles. Proper PPE isn’t optional. Integrated weed management strategies that rotate chemical modes of action are also worth taking seriously, both for health and for long-term effectiveness. If you live near a farm: Spray drift is real. Concentrations near field edges can spike during and after application, particularly on windy days. This is an area where I think public health could really step up and empower rural communities with buffer zones, rather than placing the onus on individuals. But for now, knowing your local agricultural calendar and keeping windows closed during application are the first steps. Bottom line Dewayne Johnson was exposed to glyphosate at levels most people will never encounter, and a jury decided he deserved compensation. That outcome is not evidence that the oatmeal in your pantry is dangerous. But it is a reminder that the dose, the context, and the person doing the exposing all matter enormously. Glyphosate is a chemical tool with benefits, trade-offs, and genuine open scientific questions. Learning to hold that complexity without collapsing into panic or dismissal is, honestly, one of the most useful and hardest things to do in navigating modern health science. Love, YLE Your Local Epidemiologist (YLE) is founded and operated by Dr. Katelyn Jetelina, MPH PhD—an epidemiologist, wife, and mom of two little girls. Hannah Totte, MPH, is an epidemiologist and YLE Community Manager. YLE reaches more than 425,000 people in over 132 countries with one goal: “Translate” the ever-evolving public health science so that people will be well-equipped to make evidence-based decisions. This newsletter is free to everyone, thanks to the generous support of fellow YLE community members. To support the effort, subscribe or upgrade below: Subscribe
Trump Retained Classified Documents Because Of His ‘Business Interests,’ Jack Smith Alleged
Trump allegedly showed a classified map to people aboard his private plane, Smith found during his investigation.
PHOTO RELEASE: Gottheimer Tours Atlantic Health’s Newton Medical Center
Above: Congressman Gottheimer Tours Newton Medical Center NEWTON, NJ — U.S. Congressman Josh Gottheimer (NJ-5) toured Atlantic Health System’s Newton Medical Center and met with hospital leadership to discuss improving access to health care, supporting our health care workers, and ensuring New Jersey families continue to receive the high-quality care they deserve. During the visit, Gottheimer […]
Fox Sports Host weighs in on the Chiefs acquiring QB Justin Fields
During a recent media appearance, Fox Sports Host Nick Wright weighed in on the Kansas City Chiefs acquiring quarterback Justin Fields | @EdEastonJr
Concern on campus as legal sports gambling grows during March Madness
Legal sports gambling is flooding broadcasts with ads during major sporting events like March Madness and reaching a younger audience.
Sports Illustrated Stadium to host fan events during FIFA World Cup
Sports Illustrated Stadium will host fan events — unaffiliated with the 2026 FIFA World Cup — during the world's largest sporting event.
How to stream all Yankees games in 2026 if you don't have cable TV
Here's how to watch all New York Yankees games during the 2026 season.
IPS Students Showcase Data Science Skills with Pascal Siakam at Arsenal Tech
Pascal Siakam of the Indiana Pacers will visit Indianapolis Public Schools (IPS) on Thursdaay, March 26 to celebrate student achievements in the ‘Data Dunkers’ program. Driven by a partnership between the PS43 Foundation and Dell Technologies, this initiative leverages basketball to teach foundational STEM and data analysis skills. During the event, Siakam will meet with… Read More »IPS Students Showcase Data Science Skills with Pascal Siakam at Arsenal Tech
Volunteers honor local sports leader Jim Morris during March Madness preparations
Hundreds of volunteers spread out across Indianapolis Tuesday to help prepare the city for next week's NCAA Men's Final Four basketball games.
Hubert Davis out as North Carolina men's basketball coach after five seasons
North Carolina fired men’s basketball coach Hubert Davis after five seasons during which the Tar Heels won but not at the consistent level of the program’s storied history.
Why your brain may be sabotaging your balance as you age
Balance problems in aging and Parkinson’s may come from the body working too hard, not too little. Scientists found that the brain and muscles become overactive during even minor disturbances, yet this actually weakens balance recovery. At the same time, muscles can stiffen against each other, making movement less stable. This unexpected pattern could help predict who is more likely to fall.
March Madness 2025: CBS Sports sets viewership records during most-watched first NCAA Tournament weekend ever
The NCAA Tournament delivered on action during its first weekend, and viewers were tuning in by the droves
Ex-Abercrombie & Fitch CEO said doctors "better find me incompetent"
The prison recording emerged during a three-day competency hearing over the ability of Michael Jefferies to stand trial for sex trafficking.
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!]
“SNL” alum calls out cast members who break into laughter during sketches: 'It doesn't work'
Kevin Nealon doesn't seem to be a fan of the recent Ryan Gosling episode.
'SNL' alum calls out cast members who break into laughter during sketches: 'It doesn't work'
Former 'Weekend Update' anchor Kevin Nealon isn't a fan of 'SNL' cast members breaking during sketches.
Nine Brody School of Medicine students match to ECU Health for residency training
Fourth-year medical students from the Brody School of Medicine learned where they will take on residency during Match Day.
Change is ‘long overdue’ at Homeland Security. Can Markwayne Mullin bring it?
Newly confirmed Homeland Security Secretary Markwayne Mullin told senators during his confirmation hearing that he wanted to keep the department out of the headlines. That won’t be easy.
Personnel note: Natalie Brown departs RSA, heads back to Senate as Danny Burgess Senior Aide
'During her time with us, she added significant value to our clients and brought a level of direction and strategy to our Session approach and appropriations process.'
Stony Brook Southampton Educators Earn Suffolk County Recognition for Science, Sustainability and Service
Suffolk County Legislator Ann E. Welker recognized educators from Stony Brook Southampton during the March 10 general meeting of the Suffolk County Legislature and the Women of Distinction luncheon, both held in Riverhead, NY. Wendy Pearson, vice president for strategic initiatives at Stony Brook University and executive director for Stony Brook Southampton, received a 2026 Woman
Earth’s Strangest Magnetic Era: Scientists Decode the Ediacaran Mystery
Ancient rocks reveal that Earth’s magnetic field during the Ediacaran may not have been chaotic after all.
Supreme Court to scrutinize former policy of turning away asylum seekers at southern border
The Supreme Court on Tuesday will consider the legality of a policy championed by President Donald Trump during his first term that prevented scores of migrants arriving at the southern border from starting the process of applying for asylum.
Nintendo Cuts Switch 2 Output by Over 30% on Weak Holiday Sales
Nintendo Co. is cutting back the production of Switch 2 after demand for the $450 gaming console trailed the company’s expectations during the year-end holiday season, particularly in the US.
Businesses in the mountains trading ski rentals for bike rentals during warm spring
Entertainment district ordinance repeal not on council agendas despite Ward 7 councilmember claims
Norman City Council will not see an ordinance repeal related to the Rock Creek Entertainment District during Tuesday’s city council meeting, despite a statement from a council member that it
Trump makes a detour to Elvis Presley’s Graceland in Memphis during Iran war
Trump took the side trip to Elvis Presley’s home while in Memphis for an event on crime
SCOTUS conservatives signal readiness to curb late-arriving mail ballots
Conservative Supreme Court justices appeared skeptical during oral arguments of allowing states to continue counting late-arriving mail-in ballots. A decision is expected in June.
iPhone Air Said to Be Roughly Twice as Popular as iPhone 16 Plus
While it certainly has its critics, the iPhone Air appears to have validated Apple's decision to retire the iPhone Plus, if new results from an independent analysis are anything to go by. Crowdsourced Speedtest data published by Ookla suggests the iPhone Air captured 6.8 percent of iPhone 17 generation samples in the U.S. during the fourth quarter of 2025, up from the 2.9 percent share the iPhone 16 Plus managed in the same launch window a year earlier.
Seven most intriguing offensive additions during the 2026 NFL free agency period
Kyler Murray joining Kevin O'Connell with the Vikings, plus more interesting offensive moves
Stamford cites serious health violations at nine entities in January
Of the more than 30 Stamford businesses inspected in January, nine were cited for serious violations during health inspections, reports show.
Volunteer US and UK fighters in Ukraine face hidden health crises, new study suggests
Former soldiers who have served as volunteer fighters in Ukraine experience high levels of mental and physical health difficulties yet are rarely able to access the health care they need, either during ...
Norman City Council to consider ordinance repeal related to Rock Creek Entertainment District
Norman City Council will consider repealing an ordinance related to the Rock Creek Entertainment District during its Tuesday meeting, according to a council member’s social media post.
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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