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Exit polls suggest lead for Merz's SPD in key west German state
Far-right Alternative for Germany party (AfD) looks set for a record score in western Germany
Student researchers bring Kentucky State University science to Posters-at-the-Capitol
With lawmakers just steps away, three Kentucky State University undergraduates presented research on cattle health, soil amendments and food safety at the Capitol Annex on March 5, bringing student-led agricultural […]
Kentucky Gov. Beshear takes jabs at JD Vance in his home state of Ohio
Kentucky Gov. Andy Beshear, speaking in JD Vance’s home state of Ohio on Saturday, tore into the vice president, questioning his Appalachian roots and telling voters they “deserve better.”
Nevada Wins Temporary Ban on Sports Betting on Kalshi
The prediction-market platform must obtain state gambling licenses and prohibit users under 21 to offer such contracts, a state court said.
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.
Southern Living names top small towns, Florida snags 5 spots
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Mississippi State Health Officer Dr. Daniel Edney, a Vaccine Proponent, Is Under Consideration to Lead the CDC
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Kentucky vs. Iowa State odds, time, March Madness predictions: 2026 NCAA Tournament picks from proven model
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Top 5 states with the highest number of safe hospitals, according to new report
Tom Steyer explains why he should be California's next governor
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California sheriff seizes 650,000 ballots in defiance of state officials over election count dispute
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The best seafood restaurant in every state, according to Yelp
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Scientists twisted a mysterious superconductor and got a shocking result
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Neighbors say Indian Springs revival could do KCK ‘more good than that stadium’
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Boys' basketball coach of the year: Mike LeDuc of Damien
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Lancaster County public sales: March 22, 2026
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The Times' final top 25 high school boys' basketball rankings
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Southland girls' basketball final rankings for 2025-26 seaosn
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Where to watch Oklahoma vs. Michigan State in March Madness Second Round: Time, TV Channel
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Alaska Sports Scoreboard: March 21, 2026
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GALLERY: Moments from Iowa State’s 9-7 win over Houston
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Mt. Vernon withstands 'nightmare' scenario, punches ticket to state finals
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Former OSU athletes talk mental health at Scioto County Mindset Matters Summit
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March Madness live updates, scores: No. 3 Gonzaga battling No. 11 Texas; Duke, Michigan, Michigan State bound for Sweet 16
Warriors provide exciting injury update on Moses Moody
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Illinois State, Wake Forest battle for NIT quarterfinal spot
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Top 5 states with the highest number of safest hospitals, according to new report
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Jaebri'an Autry ends Detroit Renaissance career with heartbreak
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Gov. Stein announces $8.5 million for WNC small business recovery after Helene
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Robert Mueller, former FBI director and special counsel in Trump-Russia probe, dies
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Former FBI chief, Robert Mueller, dead at 81
Robert Mueller oversaw the probe into alleged Russian interference in the 2016 United States election.
Here’s how Va. lawmakers suggest the next state budget handle federal health care funding fallout
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NCDHHS launches new program looking to expand number of mental health providers in state
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Big money flows into state attorney general races as legal battles shape American politics
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Big money flows into state attorney general races as legal battles shape American politics
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Big Money Flows Into State Attorney General Races as Legal Battles Shape American Politics
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Sign on shuttered Keizer store accuses Bricks & Minifigs of Lego theft
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RFK Jr. Touts Food as Medicine. He Often Overstates the Science, Experts Say.
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The State That Decided to Topple a Political Giant
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Maternal and Infant Health in State Rural Health Transformation Proposals Set Promising Priorities in an Uncertain Landscape
Visit the post for more.
[VIDEO] Lucy Wang Featured in Business Interview TV Series
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Political tug of war over Iranian women's soccer team prompts criticism in Australia
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Here’s how Va. lawmakers suggest the next state budget handle federal health care funding fallout
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Where to watch Michigan State vs. Colorado State in March Madness First Round: Time, TV Channel
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How New Mexico Became an Obamacare Success Story
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Set appropriate state guidelines for critical surveillance technology
I admit it: I’m worried. I’m hearing a lot about surveillance in the public arena. I hear cameras are capturing my car’s license plate wherever I drive, my face as I go in and out of stores and health facilities, and that it’s all used to compile detailed information about me. I read news articles […]
Political tug of war over Iranian women's soccer team prompts criticism in Australia
MELBOURNE, Australia (AP) — The United States and Australia’s political tug of war against Iran over the fates of seven members of the Iranian women’s soccer squad appears to have ended with the depleted team returning home minus the two players who defected last week.
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Illinois Gov JB Pritzker on key Dem win in his state and 2028 speculation
Trump administration probes states that mandate health insurance coverage for abortion
The Trump administration said Thursday that it has launched investigations into 13 states that require state-regulated health insurance plans to cover abortion.
Trump administration probes states that mandate health insurance coverage for abortion
The Trump administration said Thursday that it has launched investigations into 13 states that require state-regulated health insurance plans to cover abortion.
Senate Dems propose their own $200M ‘CT option’ health care bill
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New dispute emerges around Subnautica 2’s early access release
Lawyers for the ousted—and now partially reinstated—leadership team of Unknown Worlds, the studio behind Subnautica 2, are crying foul over news that the game will be released into early access in May. The release announcement earlier this week was made improperly, potentially “damaging the game and sowing additional confusion among the Subnautica community,” the lawyers said in a letter sent on Tuesday to Vice Chancellor Lori Will of Delaware’s Court of Chancery. In their letter, the lawyers also floated the idea of asking Will to find Krafton in contempt of the court’s ruling. The letter was sent just one day after Will’s bombshell ruling that publisher Krafton had breached its contract with Unknown Worlds’ executive team, when it fired them last June. The new issue isn’t necessarily the May early access timeframe, but how the news was announced. The letter and Krafton’s response have not been previously reported. A quick recap of prior events: Subnautica 2 is an unreleased, underwater survival adventure and the most-wishlisted game on Steam. Last year, longtime Unknown Worlds CEO Ted Gill, along with studio co-founders Charlie Cleveland and Max McGuire, were fired by Krafton. They swiftly sued, saying the publisher had terminated them to avoid paying out up to $250 million in potential performance-based bonuses. The studio leaders had hoped to earn that with an early access release of the game, which Krafton had blocked. The publisher argued in court that Subnautica 2 wasn’t ready, which the ousted execs disputed. On Monday, Will ruled that Krafton had violated its contract, firing the execs to avoid the performance payouts, and that it had to reinstate Gill and give him full authority over any early access release for Subnautica 2. On Tuesday, IGN reported on a new memo issued that day to Unknown Worlds staff by Steve Papoutsis, the executive Krafton had put in charge of Unknown Worlds after the 2025 firings. In the note, Papoutsis said that Subnautica 2 had passed a key development milestone “last week” and that he and Krafton had determined the game “is ready for Early Access release in May.” This news appeared to catch the lawyers for Gill, Cleveland and McGuire by surprise. On Tuesday night, they sent a letter to Will expressing “serious concerns” about whether it would be possible to forge an agreement with Krafton consistent with the judge’s order. Papoutsis’ memo was a problem, they wrote. He didn’t have the authority to declare anything about Subnautica 2’s release. As of 9am ET on Monday, March 16, the effective date of Will’s order, Papoutsis wasn’t CEO of Unknown Worlds. Gill was. And, per Will’s order, only Gill could make Subnautica 2 release decisions. They continued: Krafton self-servingly announced the launch without any regard to its impact on the game, the team, or the community—let alone this Court’s Opinion. Announcing the release of a game is momentous, and it is typically accompanied by significant marketing activity, fanfare, and community coordination. And most importantly, the announcement is carefully designed to maximize excitement for the game. That entire process was supposed to be driven by Mr. Gill. However, in defiance of the Court’s Opinion, Krafton has now taken that away, further damaging the game and sowing additional confusion among the Subnautica community. The lawyers speculated that Krafton had “intentionally leaked” Papoutsis’ memo and then issued an official statement to confirm the leak. Game File is a reader-supported publication. My reporting is only possible through support from readers like you. To support my work, consider becoming a free or paid subscriber. Subscribe On Wednesday, lawyers for Krafton defended their client in their own letter to vice chancellor Will, saying nothing they did violated her order nor showed contempt: Papoutsis’s message was simply celebrating the UW employees’ efforts toward a past event: Krafton’s pre-Opinion determination that Subnautica 2 was ready for Early Access release. There was nothing improper about conveying the results of the milestone review or thanking the development team for their dedication and talent. They added that Gill could still make his own call about Subnautica 2’s release: In his role as CEO, Gill will be able to assess independently his views on the state of Subnautica 2 and the appropriate release schedule; nothing in Papoutsis’s message alters Gill’s authority or discretion. Vice chancellor Will has not responded to the letters and doesn’t necessarily have to. Both parties were previously ordered by Will to confer this week and submit a proposed judgment consistent with her ruling. The letter from Gill’s attorney’s this week doesn’t indicate whether he would or would not support a May release for Subnautica 2. But it could limit his options. And, if Gill’s lawyers are right, the lack of marketing fanfare around the leak of the May date could dull the launch of the game. Any harm to Subnautica 2’s launch is an extra sensitive issue given the context of the legal dispute: millions of dollars of payouts are on the line, tethered to the scale of the game’s initial performance. In her ruling on Monday, Will noted that there was obvious “bad blood” between Gill’s side and Krafton but that the two would need to work together: “They can—and must—act in good faith to navigate their remaining contractual relationship.” Item 2: A new kind of couch co-op game A highlight of GDC each year is the Alt.Ctrl showcase that features games played with extremely experimental controllers. Perusing this year’s offerings last Friday, I found a game controlled with giant scissors, another with big toothbrushes and one that amounted to dumpster diving. My favorite was Pivot, a co-op game about collectively maneuvering a couch. It was developed by students at the University of Utah’s masters of arts and engineering games program. Players lift and tilt the physical couch in order to control the position of a virtual one. That virtual one is moving through an obstacle course on-screen, while being pursued by a giant skull. Developer Nishant Verma told me at GDC that the couch is made of styrofoam (this became more evident as I watched!) and that the name was a riff on an episode of the sitcom Friends. Item 3: In brief… 🚫 Ubisoft is laying off more than 100 workers at its Red Storm studio, as the North Carolina location known for decades for its Tom Clancy games, ceases in-house game development, VGC reports. 👀 On Monday, Nvidia’s revealed its DLSS 5 AI-driven graphics technology that purports to improve game graphics… and it has been roasted about it by the media and the online gaming public for the remainder of the week. The tech changed the faces of characters in footage from Resident Evil Requiem, Hogwarts Legacy and EA Sports FC, drawing accusations of giving carefully art-directed games the generic look of AI “slop.” Nvidia CEO Jensen Huang had said on Monday that “DLSS 5 is the GPT moment for graphics—blending handcrafted rendering with generative AI to deliver a dramatic leap in visual realism while preserving the control artists need for creative expression.” By mid-week, Huang was telling Tom’s Hardware that the new tech’s critics were “completely wrong” because game-makers could still “fine-tune the generative AI” to suit their game’s aesthetics.
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