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Science funding loosens but uncertainty remains at NKU
NKU researchers face uncertainty after federal cuts to NIH, NSF and NASA funding disrupt grants, labs and student research opportunities.
Drinking Raw Milk Is Risky. Should People Be Able to Buy It Anyway?
Several states are considering bills that would expand access to unpasteurized milk. MAHA supporters say consumers should have the right to choose.
‘Canadians don’t want to come here any more’: anger over Trump squeezes US border businesses
Shops and restaurants once bustling with tourists now struggle for survival as Canadians think twice about crossing the border
Lewis Steele reveals Liverpool’s top target to replace Mohamed Salah
Liverpool Transfer News: Yan Diomande Heavily LinkedIn the latest Media Matters episode from Anfield Index, Dave Davis and Lewis Steele explored Liverpool’s forward planning, with Yan Diomande among...
New Funding Models Needed As Global Health Faces Growing Financial Strain
Global health is facing a funding crisis. Aid is shrinking, debt is rising, and the needs are only increasing. According to Christoph Benn of the Joep Lange
Global Health Needs Rethink As Systems Fall Behind
Global health leaders say the world needs to rethink how it approaches health, arguing that outdated systems, narrow thinking, and lack of coordination are
Kim Kardashian's New Energy Drink Promises No Jitters. Does It Live Up to the Hype?
Kim Kardashian has released a new "healthy" energy drink called Update, which contains paraxanthine instead of caffeine. We asked experts about paraxanthine vs. caffeine in Update and how it stacks up against traditional energy drinks.
Braiding science, stories and indigeneity with Robin Wall Kimmerer’s ReadUP talk
Half an hour before the start, BC Aud was already overflowing. Attendees pressed shoulder to shoulder along stairways to hear Robin Wall Kimmerer, an author and environmental activist. Click the link to read the recap of her events on campus.
27 Must-Haves For People Who Consider Leaving Their Bed A Personal Tragedy
Some may call it bed-rotting, but I think of it as self-care. ✨
Popular sugar substitute linked to brain damage and stroke risk
A widely used sugar substitute found in everything from keto snacks to diet drinks may not be as harmless as it seems. New research shows that erythritol can disrupt brain blood vessel cells, reducing their ability to relax, increasing harmful oxidative stress, and impairing the body’s ability to break down clots. These changes create conditions that could raise stroke risk, even at typical consumption levels.
Can a new heart health metric identify fracture risk in postmenopausal women? Study finds link
Postmenopausal women face a high risk of bone fractures. Due to declines in estrogen levels, which can lead to an increased risk of osteoporosis, even a low-impact fall can result in a serious hip, back, ...
Parkinson's Link to Gut Bacteria Hints at Unexpectedly Simple Treatment
Inching closer to the full picture.
Business Lookahead: Gauging the war's impact
STORY: From a worrying drop in stocks to a surge in energy prices from the war in the Middle East to key data on jobs and trade, these are the stories to watch in business and finance in the coming week. ::Look Ahead::War impactThe first quarter is ending with financial markets at the mercy of geopolitics.The Iran war has wiped roughly $7 trillion off global stocks since it erupted.With oil prices up nearly 70% year to date, suddenly interest rates are heading up, rather than down, and energy-hungry AI does not look like such a slam-dunk anymore.Meanwhile, gold has plunged 16% after being nearly unstoppable since the start of 2025.We’ll see whether markets roll on or rollover as the second quarter begins.::Job growth in focusThe U.S. jobs report for March comes out Friday.It will offer a crucial view into the economy's health as investors gauge fallout from the energy price surge.Monthly payrolls are seen rising by 48,000, according to a Reuters poll. February's surprisingly weak report caught Wall Street off guard, showing nonfarm payrolls fell by 92,000 while the unemployment rate increased to 4.4%.Uncertainty over the Iran war is also clouding the economic forecasts for the Federal Reserve, with Wall Street pulling back on expectations for U.S. interest rate cuts this year as the oil price surge fuels concerns about rising inflation.Other U.S. data in the coming week includes retail sales for February and reports on manufacturing and services activity.::Chip checkSouth Korea releases its trade data for March on Wednesday.It will provide an early indicator of how the global economy is holding up in the face of the war and the resulting shock to energy prices. Korea's export-heavy economy is a bellwether for global trade and one of the first to report data from the previous month.Its manufacturing fortunes are of even greater interest than usual, not just because of its dependence on Middle Eastern energy imports, but also because its world-leading DRAM chips are of critical importance to the AI sector and currently in short supply too. ::Inflation assessmentAnd flash euro zone inflation for March is due on Tuesday. After long hovering around the 2% mark, higher energy prices are now expected to push headline inflation up, as they did in 2022. The question is, how large and sustained any jump in inflation might be.Early data is not painting a pretty picture. Private sector growth in the euro zone slowed sharply in March, with input costs rising to their highest in more than three years and supply chains being significantly disrupted.Money markets are now heavily pricing in a rate hike which was almost unthinkable before the Iran war.
Oregon business leaders urge Gov. Kotek to think bigger with prosperity council effort
A leading Oregon business group is urging Gov. Tina Kotek’s economic advisers to act with greater ambition if they want to attract businesses into the state and reignite the state’s […]
New movies to watch this weekend: See 'They Will Kill You' in theaters, rent 'Send Help,' stream 'Pretty Lethal' on Prime Video
Check out "Mike & Nick & Nick & Alice" on Hulu — or sink your teeth into some horror.
One type of alcoholic drink linked to lower death risk, study finds
While experts advise avoiding alcohol altogether, a new study says that, among those who imbibe a low or moderate amount, there is a decrease in serious health risks and one type of alcoholic drink…
Sports Betting Linked to Rising Credit Card and Auto Loan Delinquencies
A new Fed study finds that the expansion of legal betting is driving declines in household financial stability, particularly among younger consumers.
All-new Star Fox and Zelda: Ocarina of Time remake reportedly set for Switch 2 release this year
Nintendo reportedly has great plans to tap into (and benefit from) our nostalgia this year.
Ashley Benson Signs With Strand Entertainment (EXCLUSIVE)
Ashley Benson has inked with Strand Entertainment for management. She continues to be repped by IAG and Hansen, Jacobson, Teller.
Iran-linked hackers have breached FBI Director Kash Patel’s personal emails
Hackers connected to the Iranian government accessed FBI Director Kash Patel’s personal email and posted materials — including photos and documents — taken from his account, a person familiar with the hack confirmed to CNN.
Amazon is practically giving away smart home devices — 31 deals from Blink, Fire TV, Echo and more
Grab these best-selling devices starting at $17
Your stereotypes about Gen Z aren’t just inaccurate. They’re hurting your business
Welcome to Fast Company Daily, our daily newsletter on LinkedIn, featuring a free article selected each day by our editors as well as a roundup of great advice on careers, hiring, innovation, and technology. Visit fastcompany.
AitM Phishing Targets TikTok Business Accounts Using Cloudflare Turnstile Evasion
AitM phishing hijacks TikTok Business accounts via Cloudflare Turnstile evasion as SVG malware linked to BianLian targets Venezuela.
Health Rounds: Researchers find biomarker that could lead to improved schizophrenia treatments
Researchers have identified a biomarker linked to schizophrenia that could lead to new treatments to tackle symptoms of the debilitating mental disorder not addressed by current medicines.
An engineer with multiple side hustles found the most passive one: ATMs
William Butterton doesn't believe in passive income, but he thinks he's found the closest thing: ATMs.
19th-Century Blues: When Science Killed God and Made Some Englishmen Sad
With the Royal Navy ruling the waves, Queen Victoria safely on her throne, science explaining a confusing world, and British missionaries, explorers, and armies turning the map pink you’d think tha…
Italian regulator launches probe into LVMH, Sephora for unfair commercial practices
The Italian competition authority AGCM said on Friday it had launched two investigations into LVMH-owned entities in Italy, citing unfair commercial practices linked to the premature use of adult cosmetics among minors.
The nation’s cartoonists on the week in politics
Every week political cartoonists throughout the country and across the political spectrum apply their ink-stained skills to capture the foibles, memes, hypocrisies and other head-slapping events in the world of politics. The fruits of these labors are hundreds of cartoons that entertain and enrage readers of all political stripes. Here's an offering of the best of this week's crop, picked fresh off the Toonosphere. Edited by Matt Wuerker.
Measles case confirmed in Multnomah County linked to Gresham WinCo exposure
Multnomah County health officials are investigating one confirmed case of measles linked to a known exposure site at a WinCo grocery store in Gresham.
Mexican hotspot ‘Canta Corazon’ brings entertainment, unique drinks to Wynwood - WSVN 7News | Miami News, Weather, Sports
Deco people are the kind of people looking to turn a regular night out into something way more fun. Good thing Wynwood’s got a newRead More
Oregon business leaders urge Gov. Kotek to think bigger with prosperity council effort
In a letter, the business leaders ended up laying out several priority areas but offered few specific proposals.
One type of alcoholic drink linked to lower death risk, study finds
While experts advise avoiding alcohol altogether, a new study says that, among those who imbibe a low or moderate amount, there is a decrease in serious health risks and one type of alcoholic drink…
Windows 11 KB5079391 out with features, direct download links for offline installers (.msu)
Windows 11 KB5079391 is available as an optional update, and there are several notable improvements. One change that stands out is support for 1000 Hz refresh rate monitors; another is the ability to turn Smart App Control (SAC) on or off without reinstalling the OS. Microsoft has also posted direct download links for KB5079391 offline […]
American Airlines in talks with Starlink, Amazon for Wi-Fi upgrade, weighs return of seatback screens
American Airlines is considering a big upgrade to its in-flight entertainment and internet providers, including potentially bringing back seatback screens.
18 million-year-old fossils of ape found in Africa, but in an unexpected place
The ancestor of apes was long thought to come from East Africa, but newly discovered fossils in Egypt may prompt a rethink.
The Celsius Stock Selloff Shows How Costco Can Impact Any Business
Investors are digesting news that Costco has launched its own energy drink line.
Chargers Daily Links: Thursday Open Thread
Your source for all Chargers and NFL news from around the web.
Iran war's environmental toll could leave damage and health risks for decades, experts say
The Iran war is unleashing a toxic mix of chemicals, heavy metals and other pollutants that threaten everything from agriculture to drinking water to people’s health.
Iran war's environmental toll could leave damage and health risks for decades, experts say
The Iran war is unleashing a toxic mix of chemicals, heavy metals and other pollutants that threaten everything from agriculture to drinking water to people’s health.
Good Morning, Nashville! Talking Immigration Data Politics at Vanderbilt University
After a busy day on Capitol Hill yesterday, I landed in Nashville, Tennessee, last night for an exciting two days on campus at Vanderbilt University. Carwil Bjork-James, an anthropologist whose creative use of database construction to support critical scholarship resonates strongly with my own work, generously invited me to give a talk today about the politics of immigration data and to join a Wikipedia edit-a-thon tomorrow on the topic of immigrant detention. I encourage you to check out Carwil’s database project “Ultimate Consequences” about political deaths in Bolivia after 1982, and his book The Sovereign Street: Making Revolution in Urban Bolivia. My talk today is titled “Untangling the Messy Politics of Immigrant Detention Data.” I’ll focus on how immigrant detention data (not just detention centers themselves) become sites of controversy—from the collection and classification choices that shape what we can know, to the strategic withholding and distortion of data for political ends. Drawing on research spanning multiple administrations, I’ll trace how current data controversies in the second Trump administration connect to long-standing tensions in how we measure, interpret, and communicate about immigration. My goal is to move beyond simple partisan narratives and offer a practical guide for anyone working with immigration data to explore both the pitfalls to avoid and the creative opportunities for more transparent, rigorous public communication about immigration realities. If you are on campus, please stop by. Tomorrow I will join Carwil and Vanderbilt students for a Wikipedia Edit-a-Thon to edit and update Wikipedia entries related to immigrant detention with the latest robust information and data. This event is designed to orient participants into how to edit on Wikipedia, provide them with data-driven starter templates on detention facilities, and allow each person to produce an initial article on one element of the network of ICE facilities or one death in custody this year. The workshop is also a demonstration of how to use open data sources to build public knowledge—something I am deeply passionate about. Thank you to Vanderbilt University, the Spatial Histories series, and Carwil for hosting me. I would love to be a part of conversations and workshops related to immigration data on your campus. Students are really eager these days to have informed, critical, and data-driven explorations of our current immigration system. Reach out anytime if you want to discuss the possibility of bringing me to your campus. Subscribe
Political commentary on religious radio, and what listeners think about it
Most religious radio listeners say keeping up with news and politics isn't a major reason they tune in. Still, some stations have a heavy focus on political commentary.
Coca-Cola Bottler Raising Euro Bonds to Buy Africa Business
Coca-Cola HBC Finance BV is raising at least €1.5 billion ($1.7 billion) of debt on Thursday to help fund an acquisition of another drinks bottling firm.
The fastest-growing and fastest-shrinking US cities
New Census Bureau data showed which cities experienced population growth from July 2024 to July 2025. Several Southern metros grew the fastest.
Radio, TV, newspaper, digital: Women in regional media
Worcester Magazine's annual Women Making History special feature focuses on movers, shapers and thinkers in the region's news and entertainment media.
Saros Looks Like Returnal, But Feels Unlike Anything Else Housemarque Has Made
A three-hour hands-on shows that the Helsinki-based studio is poised to deliver another memorable PlayStation 5 exclusive.
Weekly Entertainment Report for Southern NH, March 26-29: Live music and lively arts
Live music and the lively arts connects us to the human experience. Go forth and enjoy what is waiting for you.
Why Vince Vaughn thinks late-night TV 'stopped being funny'
Vince Vaughn shared his hot take on the state of late-night television during an appearance on Theo Von's "This Past Weekend" podcast.
Can Lifestyle Changes Over a Lifetime Protect Brain Health?
University of Miami researchers link long‑term exercise, diet, and social engagement to better cognition with aging.
New studies of old dogs help scientists understand where they came from
Using the oldest dog genes studied so far, scientists are finding more evidence that our furry friends have been our companions for thousands of years. Scientists think dogs descended from an ancient...
Biden political priorities impeded Iran negotiations, former secretary of state admits
Former Secretary of State Antony Blinken admitted that midterm elections complicated the Biden administration's push for a stronger Iran nuclear deal.
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
Partnership in Action: Reimagining Climate and Health Funding Together
Climate Communities Network members explore funding strategies to sustain community-based climate and health work amid shifting challenges.
Amazon Prime Day 'Big Spring Sale' Introduces Major Discounts on AirPods, iPads, AirTag, and Much More
Amazon this week is hosting a "Big Spring Sale," which includes deals and offers on everything from Apple devices to clothes, kitchen electronics, furniture, and much more. The new event is set to run through March 31, so you'll have a few days of discounts to shop, with new markdowns appearing every day. Note: MacRumors is an affiliate partner with some of these vendors. When you click a link and make a purchase, we may receive a small payment, which helps us keep the site running.
Random: "Blink Twice If You Need Help" - The Internet Dunks On Ex-WWE CEO For Claiming PSP Was "The Beginning Of Life On The Go"
"What the f**k are you talking about, Linda"
Science Mill offers three special events in April
Sharing news, features, and sports with the Dripping Springs community. Support local news and subscribe here: linktr.ee/drippingspringsnews.
German Business Outlook Sinks as Iran War Puts Recovery ‘on Ice’
Germany’s business outlook soured as higher energy prices due to the Iran war threaten to derail its nascent economic revival.
‘Hard to say no’ – Jan Virgili talks possible Barcelona return
The winger has been linked with a summer return.
Scientists Call for a Complete Rethink of Alzheimer’s Treatment
New insights suggest that Alzheimer’s cannot be tackled through a single pathway, as its roots extend across molecular, genetic, and systemic processes.
This Unique Diet Could Slow Your Brain Aging by Over 2 Years, Study Suggests
Food for thought.
Scientists discover why this deadly lung cancer keeps coming back
Scientists have discovered that losing a key protein in small cell lung cancer triggers inflammation that actually helps tumors grow and spread. Even more surprising, it pushes cancer cells into a more aggressive, neuron-like state linked to relapse.
Scientists just discovered bees and hummingbirds are drinking alcohol
Flower nectar often contains small amounts of alcohol, meaning pollinators like hummingbirds are drinking it all day long. Despite consuming human-equivalent amounts, they show no signs of intoxication—suggesting a surprising evolutionary tolerance.
Instagram and Facebook are pushing deeper into shopping and ads
Meta unveiled a slew of new shopping and advertising updates to woo brands and creators. Influencers can soon earn a commission from affiliate links.
Your Poop Schedule Says a Lot About Your Overall Health, Study Reveals
It matters more than you think.
Trump sinks to record low approval rating due to Iran war in new poll
President Donald Trump's approval rating dropped to 36%, its lowest level since his return to the White House, according to a new Reuters/Ipsos poll.
Drought could fuel the rise of antibiotic-resistant superbugs as climate change worsens, new research suggests
A warming world may see more antibiotic-resistant bacteria, according to new research that shows a link between aridity and antibiotic resistance today.
Andre Iguodala says winning NBA Finals MVP with Warriors meant ‘nothing' to him
Former Warriors forward Andre Iguodala revealed why winning NBA Finals MVP with Golden State in 2015 wasn't as meaningful to him as one might think.
Did Scientists Overestimate AI’s Ability To Think Like Humans?
A new wave of AI research is attempting to tackle one of psychology’s oldest questions: whether the human mind can be unified under a single theory.
Trump touts ‘significant’ Iran ‘present’ linked to Strait of Hormuz as deal talks heat up
President Donald Trump said Iran gave the U.S. a 'significant' oil and gas gift tied to the Strait of Hormuz, saying Iran is ready to make a deal on nuclear weapons.
Billionaire OpenAI investor Vinod Khosla thinks 80% of jobs could vanish by 2030, and that ‘fear of AI’ put American politics in a chokehold
“The single biggest issue I believe in the 2028 presidential election will be fear of AI,” the Khosla Ventures founder said.
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!]
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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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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. 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