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MinnPost analysis: How Minnesota’s remarkable response to Operation Metro Surge changed politics
The pushback to Operation Metro Surge impacted policy and congressional politics, it’s also redefined how Americans relate to immigrants.
IPL 2026: Sai Sudharsan scripts history, shatters Chris Gayle’s 13-year record
Gujarat Titans opener Sai Sudharsan has rewritten IPL history, surpassing Chris Gayle for the most runs after 50 matches with 2178 runs. He also recently became the fastest to 2000 runs in just 47 innings. Sudharsan's consistent performances, including a century and three fifties in his last four innings, highlight his remarkable rise.
Meredith Eicher’s clients come for strategy. They stay for the truth.
Executive coach Meredith Eicher draws on a remarkable journey of reinvention to help business leaders grow through honesty, accountability and empathy. From accounting practice to CEO peer coaching, her work centers on human transformation and second chances.
King Charles Did Something Remarkable Today. That Should Worry All of Us.
This is not cause for celebration.
Graphene kills harmful bacteria “superbugs” but spares human cells
Scientists have uncovered how graphene oxide pulls off a remarkable trick: it hunts down and destroys harmful bacteria while leaving human cells completely unharmed. By targeting a molecule found only in bacterial membranes, this ultra-thin carbon-based material acts with laser-like precision—offering a powerful new alternative to traditional antibiotics. Even more exciting, it works against drug-resistant “superbugs,” promotes faster wound healing, and keeps its antibacterial strength even after repeated washing.
Republicans often ignore Trump’s socialistic moves. Spirit Airlines could test that
For more than a year, Republicans in Washington have largely stood by as President Donald Trump staged a series of remarkable government interventions into private business.
Crooked Letter Sports: There’s a draft in here
We take a look at what the 2026 NFL Draft might look like for Mississippi’s top prospects, and what the New Orleans Saints need to do to continue their rebuild. Plus, baseball heats up as the Big 3 get back on track and the Braves jump out to a truly remarkable start.
Ancient DNA reveals a hidden Neanderthal group frozen in time
A remarkable genetic breakthrough has uncovered what may be one of the clearest snapshots yet of a Neanderthal “community” living together 100,000 years ago in what is now Poland. The findings reveal that these individuals shared genetic ties with Neanderthals spread across Europe and the Caucasus, hinting at widespread ancient lineages that later disappeared.
Stanford's sports teams capture an NCAA championship for a 50th straight year
STANFORD, Calif. (AP) — Dick Gould has been around Stanford sports long enough as a tennis player and coach — a remarkable run of seven decades — that he clearly remembers some down years for the university's sports programs.
Every step in making tea transforms its molecules: here is the science behind what makes a great cup - Futura-Sciences
Tea is the world’s most popular beverage after water. Whether we are talking about matcha, Earl Grey, or oolong, every true tea comes from the leaves of a single plant species: Camellia sinensis. Any other infusion is technically an herbal tea, or tisane. What makes this one plant so remarkable...
Editorial: 11 Sports Director Gerry Sandusky retires
After more than four remarkable decades in broadcasting, WBAL-TV 11 Sports Director Gerry Sandusky is stepping away from the microphone.
Gina Procaccio to be Inducted to the Philadelphia Sports Hall of Fame
PHILADELPHIA—Villanova women's track & field and cross country head coach Gina Procaccio earned a top honor on Thursday morning when she was announced as part of the 23rd inductee class to the Philadelphia Sports Hall of Fame. Procaccio will be recognized along with other top athletes, coaches, contributors, and teams whose legacies have shaped the rich history of Philadelphia sports when the 2026 Inductee Class is celebrated on Thursday, November 5, 2026, at Live! Casino & Hotel Event Center. The public is invited to join in honoring these remarkable individuals and teams.
Padres closer Mason Miller is 'one of the most remarkable things about our sport right now'
Manchester United vs Leeds – Match preview and team news
Manchester United host Leeds United on Monday night to conclude the Premier League action of the matchweek.The Red Devils have enjoyed a remarkable transformation under Michael Carrick since January. ...
Astronomers detect mega-laser beam signal from 8 billion light-years away
Science News: One of the most remarkable discoveries made by astronomers in recent years is the identification of an extremely strong \"mega-laser\" signal that has t.
‘Her recovery literally is miraculous’: Walmart Heart celebrates Church Hill girl after series of health issues
KINGSPORT, Tenn. (WJHL) — The Church Hill community gathered at Walmart in Kingsport on Saturday to support a girl who has made a remarkable recovery after facing serious health issues. Charleigh M…
“AI polls” are fake polls
A few weeks after Donald Trump’s second presidential win, I took the train up from London (where I was living at the time) to Oxford to attend a conference on polls and forecasts of the 2024 election. Most of the attendees were pollsters or academics, but I also watched presentations from Aaru and Electric Twin, two companies that do what is interchangeably called synthetic sampling, silicon sampling, or synthetic audiences. Stripped of startup jargon, that means they use large language models (LLMs) to simulate responses to public opinion polls by having AI agents take on the role of survey respondents. I had already heard of Aaru thanks to some articles with eye-catching headlines like “No people, no problem: AI chatbots predict elections better than humans” in the months leading up to Election Day. The founders were making some big, some might even say far-fetched claims, such as: “within two years, we will simulate the entire globe — from the way crops are grown in Ukraine to how that impacts production of oil in Iraq, trade through the strait of Malacca, and elections for the mayor of Baltimore.” When Semafor asked Aaru’s cofounders — Cameron Fink and Ned Koh — about my boss, they said “we respect all those who came before us.” Nate (as he so often does) shared his thoughts on Twitter: Fink and Koh were relatively good-natured about this back-and-forth when we spoke at Oxford. They even offered to mail me one of the t-shirts featuring Nate’s quote they apparently had made. I never took them up on the offer, which I now somewhat regret. These synthetic sampling companies fell off my radar for a while, but they do still exist. In fact, Aaru recently received a $1 billion valuation. Is what they’re doing anywhere close to the most important frontier in AI development? Not by a longshot, especially when Anthropic just developed a model so adept at exploiting software vulnerabilities that it’s only being released to 40 companies. Still, silicon sampling is increasingly finding its way into public polling. Axios reported in March that “a majority of people trust their own doctors and nurses” based on findings from Aaru — without mentioning that the “people” in that sentence were actually LLMs. Around the same time, the Public Sentiment Institute “boosted” their online sample of 373 real survey respondents with 114 AI agents.1 (Spoiler alert: even the co-founder of Electric Twin doesn’t think that’s a particularly defensible approach.) Polling companies like Qualtrics and Ipsos are also developing synthetic data panels. So, what should we make of these … “polls”? Let’s get one thing out of the way: whatever they are, they’re not polls in the way that term is usually defined. Subscribe You can’t replace polls with AI On one hand, using LLMs to essentially make up fake survey respondents sort of sounds like the dumbest idea ever, one that will at best imperfectly replicate real polls while introducing all sorts of biases. On the other hand, with LLMs improving at a remarkable, perhaps even alarming rate, maybe that means I’m a dinosaur at the ripe old age of 24 because I still want to rely on polls that talk to actual people. I’m not going to argue that synthetic samples are completely useless. In fact, as I’ll return to later, there is evidence that some techniques can replicate topline survey results quickly and cheaply. But the marketing from certain companies can be slightly optimistic. “No traditional poll will exist by the time the next general election occurs,” said Fink in 2024. We’re just 206 days away from the midterms, and based on the fact that I still have to collect a bunch of polls every day, I’d say he should have run that prediction by a sample of AI agents before the interview.2 To see why synthetic samples can’t replace polls, here’s a quick primer on how they work. The simplest version of these models involves taking a LLM (like ChatGPT or Claude), giving it a demographic profile (e.g., a white, college-educated woman who lives in Utah and makes $70k a year), and then asking it to respond to a survey question. You repeat that process a few thousand times using different demographic profiles and end up with a sample of synthetic survey responses. The actual models used by private companies are more sophisticated than this, usually because they incorporate more hypothesized demographic characteristics for each agent and provide them with extra information. Aaru, for example, feeds agents a diet of news and information they’d be likely to consume, while Electric Twin incorporates their customers’ proprietary data about the audience they’re trying to replicate. The way Ben Warner, the co-founder of Electric Twin, explained it to me was “we have a large amount of data on […] for instance, 5,000 people. Can we make an accurate prediction of how they would respond to another question?” Still, it should be obvious why synthetic samples can’t replace polls. Polling is fundamentally a data collection process. We might use surveys to make predictions by feeding them into election forecasts, but the main purpose of a poll isn’t prediction, it’s gathering new data about what people think and how they feel. Silicon sampling, on the other hand, produces no new data. It’s simply a model: you input LLM training data, demographic prompts, and a bunch of other information, and it spits out a prediction for what a poll would say. We love models here, but models aren’t polls. That difference is an important philosophical sticking point for most pollsters I talk to. “I think politics should stay away from [synthetic sampling], because we’re trying to […] represent the voice of the people,” said Natalie Jackson, a vice president at GQR Insights. Democratic pollster John Hagner told me: “I think I’m just incredibly skeptical of this idea. I don’t think it’s research. At that point, you’re asking the machine to tell you what you already believe.” Hagner has seen some presentations of early synthetic sampling experiments, but so far, “if it’s being used in a campaign, people are keeping it incredibly quiet.”3 But Eli, I hear you saying, aren’t polls themselves increasingly governed by modeling decisions? Indeed they are: pollsters’ choices on which sampling method to use, how to define their likely voter models, and how to weight their samples can and do lead to dramatic differences in the results they publish. Aaru even referenced these limitations in the methodology statement included with that maternal mortality “poll” — although I’m using the term “methodology statement” loosely here, because it doesn’t really explain how the model works at all. We can ignore the (frankly preposterous) implication that synthetic sampling isn’t subject to a separate set of biases. The important point is that there’s still a meaningful difference between using weighting and other statistical techniques on actual polling data and using a model to predict what a poll would say. The latter is far closer to election forecasts or techniques like MRP — potentially useful models, but not a replacement for polls.4 To be fair, other synthetic sampling companies are perfectly happy with the distinction between polls and models. Warner compared polling and synthetic sampling to different tools in a toolbox. “The mistake I think we make is we think that these new tools should either work in exactly the same way or somehow replace these old tools,” he said. “Rather than thinking of it as, okay, so we’ve always had the hammer, we’ve always had the screwdriver, now we’ve got a saw. But don’t use a saw to try [to] do the job of a hammer.” A quick comment from Nate Eli didn’t ask me for a comment — rather rude of him, don’t you think? But since I’m editing this story, I figured I’d add a few quick thoughts rather than putting words in his mouth. Beyond the frequently misleading marketing, what bothers me about the AI “poll” hype is that as AI tools make statistical inference cheaper and/or better (note that these are not synonyms) that actually increases the comparative value of collecting original data. You might be able to train a model to make a reasonable estimate of what some hard-to-reach poll respondent would say — say, a young Black man who voted for Trump. (Such a person checks a number of boxes for a voter who is usually hard to reach in surveys.) Indeed, this is closely related to what models like the Silver Bulletin forecast already do. They essentially smooth out the kinks in noisy survey data by making inferences based on past voting patterns or national polls or surveys of other states. But you don’t actually know what these voters think unless you’re reaching them directly. If there’s a shift in opinion among this subgroup, you’re not going to detect it. So if I were running a campaign, I’d invest more in going the extra mile to find a representative sample of those voters. And then I’d hire some smart quants — or Claude? — to figure out the implications for campaign strategy based on proprietary data that my competitors didn’t have access to. -Nate Silver Are these models any good? If synthetic surveys are just a new type of model, the next obvious question is whether the models are at least accurate. The answer very much depends on who you ask. On one end of the spectrum, you have the maximalist argument that synthetic sampling is more accurate than actual polls. “It’s an incredibly challenging problem to go to someone and say ‘hey, we’re going to be more accurate at predicting human behavior than you, even when you talk to your customers directly’,” Koh recently told CNBC. In his view, synthetic sampling isn’t a saw to polling’s hammer, it’s “magic.” There’s certainly evidence that synthetic samples can replicate certain survey toplines. But if Aaru does have any examples of their approach outperforming the polls, they’re keeping those to themselves.5 Aaru’s 2024 election model, for example, had Kamala Harris leading in Michigan, Nevada, Pennsylvania, and Wisconsin on November 4th. And although they’ve since taken down their forecast page, they gave Harris a 50.5 percent chance of winning the race on November 2nd.6 After the election, Fink told Semafor he was happy enough with those results because they were “within margin of error,” a term that is completely meaningless when applied to a “sample” of AI agents. And of course, Aaru says their models have improved since 2024, so supposedly now they’d be more accurate than the polls? Still, their stronger argument is on cost: “We are significantly faster and cheaper than traditional polling, and still more accurate,” said Fink. The first two claims are undeniably true, but the third brings us to the opposite end of the spectrum. Both Jackson and Hagner are skeptical that these models are reliable for anything beyond replicating common survey toplines. “I just […] don’t think the machines are what we want when we’re looking for nuanced views. My example on this is people in Arizona and Nevada in 2024 who voted for Trump and voted for expanding abortion in their states on ballot initiatives,” said Jackson. Hagner identified another issue. Maybe the synthetic respondents, like sycophantic LLMs, are inhuman in one important way: they’re too nice. “The reports that have come through at the meetings that I’ve been at are that the early experiments on this, they cannot get respondents to be as racist or sexist or, frankly, as negative as human respondents,” he said. Academic research mostly agrees on this point. While there are some papers that show promising results when using LLMs to replicate polling data, most show that LLMs suffer from various quirks like producing too few “don’t know” responses and can seriously overpredict the favorability of politicians like Donald Trump and Kamala Harris. They also seem to struggle with too little variation between demographic subgroups, so the difference in predicted opinion between Democrats and Republicans, for example, is too small. When I asked Warner about these studies, his response to these papers was that just because academics can’t get synthetic sampling to work doesn’t mean that the technique doesn’t work in general. “Actually, the argument is, okay, yours does not [work]. That does not mean […] for this complex set of machinery, which uses a lot of investment, a lot of time, a lot of money, you can’t get it to work.” Cards on the table, I’m somewhat sympathetic to this argument because academics aren’t exactly great at making election forecasts. Usually, the people with skin in the game are the most accurate. Warner’s argument is that the approach Electric Twin takes — which includes, for example, making multiple predictions for each synthetic respondent using different models and prompts and subsequently averaging those to get a final prediction in a sort of ensemble forecast — produces better results than the simpler academic models. Warner shared a comparison between his method and the method from a recent academic paper with me, and Electric Twin was indeed able to get more accurate replication. But even still, he acknowledged that synthetic sampling “is not a crystal ball.” “If you asked me, do I think using other data sources will be more accurate than asking somebody who they will vote for, I would probably say no. But if you asked me ‘would your system be useful for our turnout modeling today?’ I would say yes.” For better or worse, it looks like the method is already getting more popular in the market research world. Most of the clients Aaru touts these days are businesses like EY and McDonald’s. And AI will probably begin to pop up in other parts of the political polling process. Pollsters are already using it to code open-ended survey responses, and some firms, like YouGov, are testing using LLMs to ask survey respondents questions. More worryingly, one danger to actual polls is that AI agents can be used to infiltrate online surveys. Most online polls use various checks to prevent that from happening, but there’s conflicting evidence on how effective those filters are and how prevalent AI agents currently are in online panels. If those agents ever become impossible to detect, it might spell the end of online polling, but the solution isn’t to replace all of your respondents with ChatGPT. Silver Bulletin is a reader-supported publication. To receive new posts and support our work, consider becoming a subscriber. Subscribe 1 That particular poll obviously doesn’t meet Silver Bulletin standards for aggregation. But we exclude all Public Sentiment Institute polls from our averages because we classify them as an amateur polling firm. 2 You could argue that Fink meant the next presidential election, but (a) I’m also confident we’ll still have real polls in 2028 and (b) in that case he should have asked an LLM to define “general election.” 3 Quick caveat: that’s reporting from a Democratic pollster. It’s possible that Republicans are more willing to use AI in political campaigns. 4 Indeed, Silver Bulletin does not include “polls” produced by MRP in our forecasts or averages, and we think it’s extremely misleading when their practitioners describe them in a way that suggests original data had been collected among a large number of states or Congressional districts. 5 A recent report from Aaru and EY did show two examples of a synthetic estimate being closer than a survey to a real-world benchmark — but I’d take those findings with a grain of salt because the report reads more like an ad and didn’t involve any sort of prediction being made ahead of time. 6 For comparison, our odds for Harris on the same day were 48.2 percent.
'Docs said I'll never walk': How this woman reversed her health with Indian food and is now baking healing cakes
Mira, born as Pallavi Kumar Aggarwal in Patna, has led a life full of remarkable turns. She studied fashion design, ventured into print modelling, and.
Will Trump get a worse Iran deal than Obama? Here’s what to know
The contrasts are remarkable.
When The Boardroom Wakes Up To Climate Risk In Health Care
Over the past five years, I have watched a remarkable shift in how healthcare executives approach the impact and risk of a warming world and extreme weather.
Scientists found a “lost world” of animals that shouldn’t exist yet
A remarkable fossil discovery in southwest China is rewriting the story of how complex animal life began, showing that many key animal groups appeared millions of years earlier than scientists once believed. Dating back over 540 million years, the fossils reveal a surprisingly diverse and advanced ecosystem from the late Ediacaran period—before the famous Cambrian explosion. Among the finds are early relatives of starfish, worm-like creatures, and even ancestors of animals with backbones, suggesting that the roots of modern life were already taking shape.
Scientists found a protein that drives brain aging — and how to stop it
Scientists have uncovered a powerful new clue in the mystery of brain aging: a single protein called FTL1. In aging mice, higher levels of this protein weakened connections between brain cells and led to memory decline. But when researchers reduced FTL1, something remarkable happened — the brain began to recover, rebuilding lost connections and restoring memory performance.
MXene breakthrough boosts conductivity 160x with perfect atomic order
A new breakthrough is transforming MXenes—ultra-thin, high-tech materials—into something far more powerful and precise. Researchers have developed a cleaner, more controlled way to build these materials using molten salts and iodine, eliminating the messy chemical processes that once left their surfaces disordered. The result is a perfectly arranged atomic structure that lets electrons flow with remarkable ease, boosting conductivity by up to 160 times.
Sharing her passion for science
By Danielle Rush Communications Specialist, Indiana University Kokomo Hisako Masuda, Indiana University Kokomo professor of biochemistry, was honored by the Indiana Academy of Science (IAS) as its 2026 Distinguished Scholar. The award is given to an individual who is recognized by the IAS as having an exceptional record of scholarship. Recipients are selected from nominations submitted to its awards committee. “I was surprised,” said Masuda, who joined IU Kokomo’s faculty in 2013. “I feel there are many good scientists in the Academy, so I wasn’t expecting it at all.” Patrick Motl, dean of the School of Sciences, said the Academy recognizes up to one member per year, and that Masuda is the second or third IU Kokomo faculty member to receive the commendation. “Clearly this speaks to the strength of Dr. Masuda’s accomplishments in research and scholarship and that her work stands out amongst her peers in Indiana,” said Motl, who received the award in 2019. “Many of the institutions that participate in the IAS are undergraduate institutions or primarily undergraduate institutions, but even having that caveat, Dr. Masuda has built and maintains a very active research program in her lab, working exclusively with undergraduates. She is passionate about science and can share that passion with her students. To carry on a quality research program with so many students involved in so many projects is truly remarkable and I am glad that the IAS acknowledged that for Dr. Masuda.” The IAS specifically commended her for involving more than 50 undergraduates in her research in bacterial metabolism, genomics, and their phenotypic plasticity at IU Kokomo, and publishing 23 articles with many student co-authors. Masuda’s current work primarily focuses on biodegradation and chemical repurposing of nylon. Using soil bacteria, her lab studies bacterial biodegradation of nylon and other environmental pollutants. She applies principles of green chemistry while developing a method to convert nylon waste into other nontoxic polymers. In collaborative work with health scientists, her lab investigates gut microbiomes of Indiana native birds as well as human subjects in a clinical study. She became interested in converting plastic waste while earning her Ph.D. at Rutgers University, working on methods to remove environmental waste not using chemicals or other intrusive methods. She learned about Nylon 11, which is used in pipes for transferring oil, interior components for cars, catheters, and in other industrial hard plastics. Nylon 11 is nontoxic, she added, so it is safe to include students in the research. “Those are considered to be nonbiodegradable, and have to go to a landfill,” she said. “I thought if we could come up with a way to biodegrade it, that would make some kind of impact.” Eventually, she wants to develop a product that would convert nylon waste to something useful, and to reduce waste and microplastics in the environment. “That would be my goal at some point, that we can make that change, and also make people more aware of their use of plastics,” she said. “I hope students stop to think about what we can do as scientists to address issues currently impacting us.” She appreciates the IAS for its support of scientific research at Indiana institutions, and IU Kokomo and the School of Sciences for providing funding for students to attend the Academy’s annual meeting. She added that IU Kokomo has also supported her research with funding from the School of Sciences and Academic Affairs. “Without that, I couldn’t do my research,” she said. Masuda has also earned a Senior Research Grant from the IAS, IU Kokomo’s Distinguished Research Award, and the IU Kokomo Junior Faculty Annual Research Award. She is a Fellow of the Indiana Academy of Science. Education is KEY at Indiana University Kokomo.
BUSINESS BRIEFS: BTG’s Playhouse Project receives $500,000; Berkshire HorseWorks receives $18,500; BCC Assistant Professor receives $5,000; Berkshire County Arc receives $80,000; NBT Bank donates $29,000; Egremont Water Commission receives $33,225; MountainOne distributes $363,200
“Like so many people in the Berkshires, I have deep personal memories of the Stockbridge Playhouse and the transformative experiences it made possible,” said Gilson Family Foundation board member Mary Gilson Spina. “Supporting its restoration is about honoring that legacy while ensuring future generations have the same opportunity to experience the magic of live theatre in this remarkable space.”
CEO Letter to Shareholders 2025
Dear Shareholders, 2025 was a remarkable year for Amer Sports and our teammates, partners, and shareholders. It gives me great pleasure to share with you some winning moments from the last 12 months…
24 new deep-sea species found including a rare new branch of life
In a remarkable deep-sea breakthrough, researchers have discovered 24 new species of amphipods in the Pacific’s Clarion-Clipperton Zone—including a rare, entirely new superfamily. The findings reveal previously unknown branches of life and push the boundaries of how deep these creatures are known to live.
Mohamed Salah's Remarkable Career At Liverpool, Broken Down In Numbers
A by-the-numbers look at Mohamed Salah's time at Liverpool after he announced he will be leaving the club at the end of this season.
Brookdale Student Leana Vitale Turns Passion for Science into Research Success
Leana Vitale is proving that curiosity, determination, and hard work can open remarkable doors. A Brookdale student graduating this spring with two associate degrees in biology and chemistry, she has already distinguished herself as an
Science Through Shadows: How Astronomical Alignments Reveal the Universe
When one celestial object passes in front of another, it can cast a shadow that travels across space – and sometimes across Earth. These moments of alignment, known as eclipses, occultations, and transits, allow scientists to study distant objects in remarkable ways. By observing how light changes when an object briefly blocks another, astronomers can measure sizes and shapes, detect atmospheres, and refine the orbits of asteroids and planets.
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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Suds & Science
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