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Amazon all-day delivery test could reshape logistics
As part of the plan, Amazon benchmarked similar services from Walmart, Instacart, DoorDash, and UberEats, internal document shows.
O'Connor touts business opportunities at latest tech summit held in Pittsburgh
Mayor Corey O’Connor sees himself as Pittsburgh’s biggest promoter, which is why he’s been making dozens of calls to sell people on settling...
Shop the 34 best deals on earbuds, chargers and smart lights for spring Prime Day
Amazon’s Big Spring Sale is officially live. I used my decade of experience covering deals and the latest electronics to find my favorite tech discounts.
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
Meta layoffs hit Reality Labs, recruiting divisions
Meta's latest wave of job cuts follow years of the company pushing to become more efficient and going all in on AI.
I didn’t pay attention to politics. Then my house fell down
This Overland Park independent voter is reminded of his father’s advice, and applies it to our democracy. | Opinion
Sub Pop has signed its latest Seattle band, Telehealth
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Sibanye Lawyer Assassination Alarms South African Business
The assassination this week of a labor lawyer working for Sibanye Stillwater Ltd. in downtown Johannesburg has prompted a protest from South Africa’s business fraternity.
Four from Greater Grand Forks on Top 25 Women in Business list
Prairie Business contest honors exceptional professionals in the region
About 40 'No Kings' protests planned across Tennessee. See when and where
In total, organizers estimate about 3,000 events nationwide, surpassing previous 'No Kings' mobilizations since the movement gained traction on President Trump’s birthday in June 2025.
Growing Southern Nevada’s health care economy
Last week The Lincy Institute, the Vegas Chamber, the Vegas Chamber Leadership Foundation, and the Nevada Health and Bioscience Corporation hosted a symposium on the future of Southern Nevada’s health care economy. Today, health care is the fastest-growing sector in the regional economy having added more than 42,000 jobs since 2016. Yet, despite this growth […]
The week in politics (March 25, 2026)
On Wednesday's show: We discuss the latest developments in politics in our weekly roundup. And we consider whether Texas is too big.
Health Care Roundup: Market Talk
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Upset winner Gray Davis on California's last wide-open governor's race
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They gave her business a lifeline, then froze all her money
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Yankees’ Netflix debut is latest example of sports’ complicated TV landscape
Fans have never had more access to live sports on TV. But it comes with costs, like navigating a maze of networks and new subscription fees.
Mohamed Salah: Who is the Premier League's greatest forward?
As Mohamed Salah announces he will leave Liverpool this summer, BBC Sport asks you to rank the best forwards in Premier League history.
Superstar Connor McDavid hits multiple milestones in Utah
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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.
8 new emojis arrive in Apple iOS 26.4 update for iPhone users
Along with eight new emojis, the latest Apple iPhone and iPad software update includes new Apple Music features such as AI-generated playlists.
Entertainment Poll: Who is the highest paid (annually), active athlete on the planet?
Test your knowledge!
Commentary: When conservation becomes entertainment
My parents love to tell the story about the time I protested going to the aquarium when I was eight years old.
KY leader testifies in support of bill to expand Mammoth Cave National Park
Two Kentucky lawmakers on Capitol Hill are pushing to expand the sprawling park through legislation.
Apple's M5 Pro & M5 Max easily beat the RTX 5090 in PugetBench creator benchmarks
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Residents, business owners express mixed reaction about roadway project underway in Trussville
A major roadway project along Highway 11 is entering its final phase in Trussville, with city leaders acknowledging temporary inconveniences while emphasizing long-term traffic relief in one of the area’s fastest-growing corridors.
Paul George ready to be 'the focal guy' for shorthanded 76ers upon return from suspension
George apologized Tuesday for his failed drug test and how it affected his team's momentum
Fact check: The lies Trump is using to sell his latest attack on mail-in voting
CNN debunks four of Trump’s most frequently repeated false claims about mail‑in voting.
iOS 27 Siri Overhaul: Standalone App, New Design, Dynamic Island Integration and Ask Siri Button
Apple is testing a standalone Siri chatbot app for iOS 27, reports Bloomberg's Mark Gurman. Apple plans to debut a chatbot version of Siri that will compete with Claude and ChatGPT, and the new Siri could be accessible through a dedicated app. Gurman previously said that Apple was not going to develop a standalone Siri app, but it appears plans have changed.
‘The Price Is Right’ Contestant Loses Big After Listening to Audience
'You're not risking anything by going forward.'
‘The Price Is Right’ Contestant Loses Big After Listening to Audience
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Episode 68, Science for Success, Tissue testing and Potassium
By Dusty Sonnenberg, CCA, Field Leader, a project of the Ohio Soybean Council and Soybean Check-off In Episode 68, Dusty visits with soybean researchers involved in the Science for Success program. Science for Success provides timely, cutting-edge best management practices by coordinating the uni
Apple Plans AI Reboot With Siri App, New Look and ‘Ask Siri’ Button in iOS 27
Apple Inc. is testing a standalone app for its Siri voice assistant alongside a new “Ask Siri” feature that will work across the company’s software, part of a broader artificial intelligence overhaul.
76ers' Paul George blamed mental health for banned substance use
The Sixers' Paul George, who was suspended 25 games for a failed drug test, is set to return Wednesday when Philadelphia faces the Boston Celtics.
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!]
32 incredible wildlife images from the Nature Photography Contest
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Candle-Making Business Is the Latest Pop-Up to Join Downtown Revitalization Effort
Visitors on Saturday, March 28 can receive a free gift.
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American Airports Are Latest Washington Battlefield | WSJ Politics Newsletter for March 24
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Using multiple AI health tools could pose reliability risks
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French Business-Activity Gauge Hits Five-Month Low on Iran
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Brent crude oil back over $100 a barrel as optimism over Middle East de-escalation fades
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On the road with antiprotons: CERN runs delicate test on transporting ultrasensitive antimatter
Scientists at CERN plan to take some antiprotons out for a spin in a never-tried-before test drive.
Scientists take antimatter on first road trip as they study how to transport ultra-sensitive cargo
Scientists at CERN are taking some antiprotons out for a spin in a never-tried-before test drive.
On the Road With Antiprotons: CERN Runs Delicate Test on Transporting Ultrasensitive Antimatter
GENEVA (AP) — Scientists in Geneva are taking some antiprotons out for a spin — a very delicate one — in a truck, in a never-tried-before test drive. If this so-called antimatter comes into contact with actual matter — even for a fraction of an instant — it will be annihilated in a quick flash of ...
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Milledgeville teen runs car detailing business in school, wins $1,000 in chamber contest
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Trump Claims Victory on Memphis Crime as His Crackdown Draws Protests
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Special election on Tuesday will test whether national political winds reach Florida
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DarkSword exploit leaks on GitHub
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Democratic and Republican Party officials face internal backlash after primaries
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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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