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Walmart prepares Google TV Streamer clone, may start selling its own Google TV sets too
Walmart is preparing new Google TV products including a set top box, likely a sequel to Onn 4K Pro, as...
Some East Grand Forks businesses must register with city to sell low-potency hemp products
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Meta and Google liable for social media harm to children’s mental health in landmark US case
Jury awards at least $3mn in damages with Instagram owner to pay the majority
Google launches Lyria 3 Pro music generation model
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Xiaomi's EV business defies industry slump with standout profitability
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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
Scion of historic Fargo business dies at 98
Robert B. Herbst, who ran Fargo's Herbst department store for decades, is being remembered for his humor, passion for the outdoors, and devotion to family.
American Express Launches New Graphite™ Business Cash Unlimited Card, Kicking Off the Most Significant Year for Commercial Product Expansion in Company History
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Amex Makes Its Biggest Commercial Bet in Years With ‘Business Membership’
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Ilia Malinin seeks his 'redemption' at World Figure Skating Championships
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Pulitzer winner 'Fairview' is a little cloudy in its L.A. premiere
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In politics, common decency still matters
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Sphere Entertainment (SPHR) Stock Trades Up, Here Is Why
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Public health alert issued for this ground beef product. Here's why.
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Broadview mayor demands closure of ICE facility, reimbursement of village, business losses
The suburban mayor asked the feds to pay back $700,000 in costs to the villlage associated with Operation Midway Blitz and for economic losses suffered by nearby businesses.
Broadview mayor demands closure of ICE facility, reimbursement of village, business losses
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Health Ring Oura Interviews Banks for IPO as Soon as This Year
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Kent Alterman & Sarah Babineau’s Good Walk Entertainment Inks First-Look Deal With Sony Pictures Television
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Public health alert issued for ground beef product; possible foreign material contamination
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US business activity slips to 11-month low in March amid Iran war, S&P Global survey shows
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Health alert issued for ground beef sold in Pennsylvania
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Facts About Small Business: Family Farm Statistics 2026
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Report: Nintendo Is Slashing Switch 2 Production By A Third
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Apnimed Announces Strategic Monetization of Shionogi-Apnimed Sleep Science (SASS) Joint Venture Stake for $150M and Royalties, Strengthening Focus on its Wholly-Owned OSA Program, AD109
/PRNewswire/ -- Apnimed, Inc., a pharmaceutical company developing an oral drug product candidate, AD109, that is designed to address a root cause of...
Nintendo cuts Switch 2 production amid weakening console sales
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Colorado football lands mid-tier in ESPN's returning production metric
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Public Health Alert For Ground Beef—‘Do Not Consume’
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What’s That Building? South portico of the Griffin Museum of Science and Industry
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Nintendo reportedly adjusting Switch 2 production after weak holiday sales
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Trump’s ultimatum to Iran was almost up. Then he found an offramp
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Nintendo Cuts Switch 2 Output by Over 30% on Weak Holiday Sales
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We disagreed on politics. We agreed on wine. That was enough.
At the Virginia Governor’s Cup Gala in Richmond earlier this month, a very dapper gentleman approached me and introduced himself. In his light-colored suit and bowtie, he looked very Southern in a classical sense, the sort of Virginia Gentleman you used to see south of the Rappahannock as recently as my college days. “I’m a longtime reader and fan of your writing, if not your politics,” he said. His comment was the proverbial iron fist in a velvet glove, simultaneously conveying praise and disapproval while establishing boundaries. Man, I wish we still discoursed like this instead of shouting bromides and insults to try and “own” our opponents with a funny meme and a furrowed brow. Subscribe “Well, we’ll always have wine to share together,” I said, and thanked him for his kind words. We clinked glasses, exchanged pleasantries about the delicious gold medal-winning wines being poured that evening, and went our separate ways. Our exchange reminded me that more unites us than divides us. Wine brings people together to share a meal and a few hours of joy despite our differences.1 That’s why I refer to the wine community — including readers and consumers — rather than the wine industry. Together, we are so much more than production, distribution and sales statistics. A few minutes later the evening’s awards ceremony began. Applause grew as the 12 winemakers who made the top-scoring wines for the Governor’s Case took the stage, including a loud cheer for Jonathan Wheeler of Trump Winery and his 2018 Blanc de Noir sparkling wine. All the winemakers on stage had reason to be proud, Wheeler perhaps more so. Trump Winery was the only winery to win six gold medals in the competition this year. (Wineries are limited to six entries.) Two of Wheeler’s ciders also won gold medals in a separate competition. When you cover the labels and take the sour taste of politics off your palate, the wines are pretty darn good.2 Then Gov. Abigail Spanberger, newly elected Democrat and Virginia’s first female governor, was introduced to great applause to announce which of the 12 wines had won the Governor’s Cup. She spoke for a few minutes about the importance of wine to Virginia’s economy and tourism and the international acclaim Virginia wine has received. Just two weeks earlier, she gave the Democrats’ response to Trump’s State of the Union speech, but this night wasn’t about politics. That didn’t stop several people in the crowd from speculating on the irony should she have to present the trophy to Trump Winery. In the end, Valley Road Vineyards was displayed on the screen behind Spanberger as the winning winery. Blue Bee Cidery in Richmond took top honors for that category. The crowd cheered a female governor presenting the state’s highest trophy to a female winemaker and then resumed the evening’s festivities, united by their mutual love of wine. A whiff of politics couldn’t dim the cheer of celebration and a community united by its love of wine. In Memoriam: Michel Rolland The global wine community lost a giant March 20, with the passing of Michel Rolland. He was 78. Rolland was the original “flying winemaker,” a globe-trotting consultant who helped Bordeaux regain its mojo in the 1970s and then shaped the rise of Napa Valley cult Cabernet as consultant to Simi, Harlan, Newton, Screaming Eagle, Araujo, Dalle Valle and other wineries. He was instrumental in Argentina’s rise to prominence and even had his own winery, Clos de los Siete, in a partnership with other wine families. Rolland’s career arc paralleled that of Robert Parker, the world’s most influential critic. Parker championed many of the wines Rolland consulted on, helping build his reputation and demand for his services. It also made him a target for Parker’s critics. As W. Blake Gray wrote on Wine-Searcher in his excellent tribute to Rolland: Rolland created the type of wines Parker loved: rich body, plenty of fruit, soft tannins. He sometimes faced the accusation of creating a generic international style of red wine, where the great wines he made in Argentina were indistinguishable from the great wines he made in France. Rolland chafed at that critique, as did many of his fans. He was credited with championing green harvesting and leaf pulling, as well as careful selection of grapes in the winery, practices we nearly universally think of today for high-quality winemaking. “Michel was an incredible innovator who changed how wine was made and how grapes were grown,” Napa Valley winemaker Aaron Pott wrote on Facebook. “His work has transformed the wine trade. He created new ways of looking at wine, tasting wine, evaluating ripeness and quality. … This was not just a man with a ‘style’ that he imposed on vineyards but a man that understood how to make great wine from great sites.” Rolland started his consulting company in 1973 in Libourne, in Bordeaux, with his wife, Dany. Both had graduated the year before from Bordeaux’s Institute d’Oenologie. The couple sold their majority share in the business in 2020, according to Wine Spectator. Over his career, Rolland reportedly worked with more than 100 wineries in 20 countries. He even made it to Virginia, where he consulted for Kluge Estate in the mid-2000s. (Kluge Estate is now Trump Winery.) Reader feedback, please! Last week, I did my first WineLine Live! with Dr. Laura Catena of Catena Zapata winery in Argentina. We enjoyed a fascinating discussion about her efforts to preserve the genetic heritage of old vineyards in Mendoza. I conceived of WineLine Live! for paid subscribers, as a thank you for your financial support. And while only a few people joined live, the video now has more views than I have paid subscribers, so I guess that’s pretty good. Even so, I’m considering opening future installments to anyone on Substack to reach a broader audience. So my questions to you: Should these be public? And what format do you prefer? Live gives a chat feature with the potential for viewers to interact with me and the guest, while a video post would just be that. Another alternative is a podcast, which would just be audio, without video of my chins. Please let me know in the comments. Leave a comment In the Glass A few wines I’ve enjoyed recently: Bonny Doon Vineyard Take Me to Your Liter, Le Cigare Volant, Red Wine of the Earth. 2023, Central Coast, CA. Blend of Grenache, Syrah Cinsaut and Petite Sirah. Delightful wine with expressive red fruit flavors, casual drinking. Doon lovers of a certain age will remember Randall Grahm’s Big House Red; this is more in that style than his original Le Cigare Volant, modeled after Chateauneuf du Pape. The liter bottle makes it an even better value. I see this online at about $15. Great value. Albert Bichot Bourgogne Pinot Noir Origines 2023. 13% - Textbook pinot noir and an excellent, affordable entry (regional) Burgundy. Wine Enthusiast Top 100 Wines of 2025. $24 at Total Wine & More. Loma Larga Pinot Noir 2021 “Coastal Cool Climate Wine”, Valle de Casablanca, Chile. An older sample, showing beautifully. Spicy and fruit forward. I’m seeing widely varied pricing online, from $18-$32. At the lower end, it’s a terrific value. 13.5% Dr. Loosen Riesling Dry 2016, Mosel, Germany. Found this “in the stack.” And it stacked up well, shedding some of its youthful acidity for opulent Riesling character, including a hint of the mineral oil older Riesling often features. A great value, as I’m seeing it as low as $14 online. 12% abv. Red Tail Ridge Blau Franc Blend 2024, Sans Oak, Finger Lakes. 13.4% abv. The name is a neat portmanteau of Blaufrankisch and Cabernet Franc, thus Blau Franc. The blend is 50-50, no oak involved. The Blau dominates on the palate, with the spicy caraway seed (think New York deli rye bread). The Franc adds body. The result is juicy, energetic and joyful. Sokol Blosser Estate Rosé of Pinot Noir 2025, Dundee Hills, Willamette Valley, Oregon. This first rosé of 2025 was a welcome respite to our cold, snowy winter here in the Mid-Atlantic. Oh man, I needed this! Bright and energetic, exuberant even, it perks up the mood and goes down fast. 13%. Certified B Corp. Ingredient and nutrition labeling, and in a modest way that doesn’t occupy a lot of label space. (Since it’s not required, presumably there are no minimum font size requirements.) More wineries should follow this example. Dave McIntyre's WineLine is a reader-supported publication. To receive new posts and support my work, consider becoming a free or paid subscriber. Subscribe Thanks for reading Dave McIntyre's WineLine! This post is public so feel free to share it. Share 1 Some restraint may be required. 2 Especially the bubblies.
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Trump Delays Threat to Iran, but War Negotiations Are in Early Stage
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Apple has six new products that could launch soon, per rumors
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Top business leader demands end to stalemate over City Council's pick for zoning chair
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Trump Poised to Skip CPAC For First Time in a Decade
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Apple Reportedly Preparing 'Biggest Set of iPhone Revamps' Ever
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A surprising foam discovery could change everyday products
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Trump orders War Dept to postpone strikes on Iranian energy sites, citing 'productive' talks to end war
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Turning coal to medicines: Chinese scientists bring a 160-year-old dream to life
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Iranian Missile Strikes Are Costing Big Oil Billions in Lost Revenue
Damaged energy infrastructure is likely to take years to come back online, but a surge in oil-and-gas prices is helping to offset some of the lost production for now.
Man who bought $75 worth of Apple products from a stranger in a car park realizes he might be sitting on a small fortune
A tech enthusiast who bought a bunch of used Apple products off a stranger in a car park was left pleasantly surprised by the haul
Business closed after new Ohio law banning intoxicating hemp products went into effect
Senate Bill 56 grants law enforcement the authority to remove intoxicating THC products from unlicensed retail locations,
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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A DOWNTOWN CHICO MERCHANT IS EXPRESSING CONCERN OVER THE IMPACT OF STREET CLOSURES FOR EVENTS -- ON THEIR BUSINESS. ACTION NEWS NOW REPORTER BELLA BARBOSA REPORTS FROM DOWNTOWN CHICO { "@context": "https://schema.org", "@type": "VideoObject", "name": "Downtown Road Closure Dilemma", "description": "A DOWNTOWN CHICO MERCHANT IS EXPRESSING CONCERN OVER THE IMPACT OF STREET CLOSURES FOR EVENTS -- ON THEIR BUSINESS. ACTION NEWS NOW REPORTER BELLA BARBOSA REPORTS FROM DOWNTOWN CHICO", "thumbnailUrl": "https://bloximages.newyork1.vip.townnews.com/actionnewsnow.com/content/tncms/assets/v3/editorial/c/47/c47e26d6-03c3-5f35-bf49-37925ab603d7/69bdedc4eb57d.image.jpg", "uploadDate": "2026-03-20T17:45:00-07:00", "contentUrl": "https://cdn.field59.com/KHSL/1774053903-6e1ef36dd09fbebf020833aee86b60da3b3cca3f_fl9-720p.mp4" } CHICO, Calif. - A downtown Chico business owner is voicing concerns about the impact of street closures for events on local shops. Leann Powell, owner of The Peddler’s Closet, expressed concern about events closing down streets downtown and bringing in food trucks and other shops’ products that directly compete with the brick-and-mortar stores in downtown Chico.Powell said an upcoming event held on a Saturday has brought up concerns for her and other business owners downtown, due to it being a busy day for businesses. "We're already struggling, and then to bring in more businesses on top of our businesses and shut our streets down is absolutely devastating," said Powell.Powell noted a decline in business during events like the Thursday Night Market, where street closures allow outside vendors to set up shop. She shared that while organizers for these types of events often offer booths to local businesses, it does not alleviate the burden."I don't really feel like that's a solution because you're bringing in other businesses, you're shutting the streets down. Yes, we can go down and set up a space, but then you've gotta pay somebody to run that space, plus run your own business for the day, and it's really not, it's really not helpful for us," said Powell.Applying for a street closure permit in Chico involves approval from the Public Works Department, the Chief of Police, and the Fire Chief. Permits can be denied only under a handful of circumstances, such as interference with first responders, previously scheduled construction, or existing permits for the same space.Mayor Kasey Reynolds addressed the issue, saying the city council has tasked staff with reviewing the municipal code for street closure permits with the goal of finding ways to minimize negative impacts on local businesses during events.Reynolds mentioned that any recommended changes might require further direction from the city council, depending on the extent of any changes recommended. googletag.cmd.push(function() { googletag.display('ad-1514992'); });
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