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Corsair Cove Is Available Today With Xbox Game Pass, And Here's What The Reviews Are Saying
"Undoubtedly one of the best strategy games of recent years"
Kone overtakes Barella to become Serie A’s most expensive midfielder
The season has started off on the right foot for Roma, who are still undefeated in their first six league and Champions League matches. Among the key players is undoubtedly French midfielder Manu Kon�...
"To coach Steph Curry who is undoubtedly the greatest …
"To coach Steph Curry who is undoubtedly the greatest …
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.
Raskin says its more important for Democrats to address healthcare
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Building the beat: How New Orleans can grow the business behind the music
People dance to the music of the TBC Brass Band Photo by Michael DeMocker / The Times-Picayune This week New Orleans hosts the annual Cutting Edge CE Conference, which brings together members of the music industry, musicians, lawyers and others to learn about and discuss the latest changes in the business of making, producing and selling music. googletag.cmd.push(function() { googletag.display('ad-1492300'); }); The conference comes as AI and streaming are causing upheavals in the industry. Meanwhile, we’ve seen at least a partial collapse of the global festival industrial complex which has long been a key financial lifeline for many artists.All of that can feel a bit removed from life in New Orleans. After all, we are a city filled with music. On any given day or night, there are dozens of shows across the city, ranging from jazz and blues to hip-hop, bounce and house. Whereas in other cities kids dream of being the star of their local sports team, in New Orleans more often than not they dream of leading their own band.And music is a huge part of our economy. Before New Orleans was known as a foodie destination, it was already drawing millions of visitors from around the globe to experience our jazz, soul and funk scenes firsthand.But the reality is, if you want to make it big, you’re probably going to end up leaving the city. We’ve seen major performers like Lil Wayne, Master P and Jon Batiste (though he’s back on the Northshore) decamp to Los Angeles, Miami and New York. Likewise, up-and-coming musicians like Greer Grimsely, $leazy EZ and Lucky Daye have also left town in search of more profitable pastures.Meanwhile, our local universities train some of the best producers and engineers in the business — only to see them head to one of the big music industry cities after graduation.It’s not a new phenomenon, though the reasons have changed over the years. Like a lot of early jazz musicians, Louis Armstrong famously left New Orleans, first for Chicago before ultimately settling in New York City. But while those early migrations had more to do with racism, in today’s day and age, musicians end up leaving because New Orleans doesn’t have the industry infrastructure necessary to sustain the kind of growth and, well, success, a lot of folks dream of.It’s a hard, but very real, truth. Artists have to go to Nashville for publishing, Los Angeles for production, Atlanta to join a label or New York for representation. That, in turn, is a drain not only on the city’s talent pool but on money that could be staying here at home.Not being an industry town inevitably makes it that much harder for musicians who don’t leave to get the recognition and success they deserve. It also undoubtedly plays a part in keeping the wages working musicians in New Orleans make at their gigs here lower than in places like Austin or Nashville.That’s not to say we don’t have any of the infrastructure needed to make New Orleans a music industry town. We’ve got live music venues, studios, record labels, management companies, copyright attorneys ... all the various building blocks are there. We just haven’t ever built upon that solid foundation. googletag.cmd.push(function() { googletag.display('ad-1492297'); }); The question is how do we do that in a way that supports our existing industry and artists, respects our cultural traditions and ensures the wealth generated is equitably distributed so it isn’t just C-suite executives who end up reaping the benefits. And the time to start figuring out the answers is now: next year the legislature will focus on taxes and spending, making it vital that New Orleans leaders have a plan to try and secure funding to help grow our industry.So we asked a group of New Orleanians to give us their thoughts, ranging from industry attorneys and venue operators to working musicians and cultural advocates. Their answers point toward turning New Orleans into a music industry city without leaving musicians behind or abandoning what makes us the greatest music city on earth.If a dusty city like Austin can transform itself into a major hub not just for music but the industry behind it, surely the birthplace of jazz — and pretty much all modern music by extension — can figure it out as well. +3 Mailbox Money: The Recording Academy’s Reid Wick on supporting, and growing, New Orleans’ music industry Reid Wick has been a part of the New Orleans music landscape from virtually every angle. He'… California Dreaming: Pell discusses his time in L.A. and how New Orleans can help young musicians In 2015, New Orleans-born rapper Pell decided to make the move to Los Angeles. He was fresh … +2 Up from the street: To build a stronger music industry, support community first. At MaCCNO, most of our team aren’t just advocates, we’re also working musicians. Here are a … +2 Live and direct: Public investment in independent venues is key to a robust music economy. I’ve spent most of my adult life looking at the New Orleans music business from every side o… +2 Helping Hand: New Orleans doesn’t need more talent. It needs more infrastructure. People love to call New Orleans a music town. And they’re right. +2 \We out here: New Orleans doesn't need to be Austin. It's already a music industry city. +2 Futureshock: New Olreans has the music talent. Now it needs the innovation. New Orleans has long been known as a place for music creation and innovation. People travel … .donate-gambit-article-module-container { text-align: center; padding: 10px; /* background-color: #24da6d; */ background-color: rgb(153, 0, 0); margin-bottom: 20px; } .donate-gambit-article-module-title { font-weight: bold; color: #fff; } .donate-gambit-article-module-copy { color: #fff !important; font-size: 16px; } .donate-gambit-article-module-button { background-color: black; width: 50%; border-color: black; font-size: 16px; } .donate-gambit-article-module-button:hover { background-color: black; } @media only screen and (max-width: 600px) { .donate-gambit-article-module-button { font-size: 14px; width: 100%; } .donate-gambit-article-module-copy { font-size: 14px; } } BECOME A GAMBIT MEMBER AND JOIN OUR KREWE TODAY For more than 40 years, Gambit has covered New Orleans, for New Orleans. We’ve stood up to city hall with you, cheered the Saints with you, danced in the streets with you and cried over our collective loss with you. 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Blackhawks Trade Pitch Lands Sabres Former First-Round Pick
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Blackhawks Trade Pitch Lands Flames $30M Skilled Winger
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Maple Leafs Coach’s Dilemma Emerges Before NHL Season
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🚨Breaking news: Mbappé brings big news to Xabi Alonso
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Did any cat breeds develop naturally?
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Patriots Fans Claim Tom Brady Is Sabotaging Drake Maye
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Who for captain? Miley or Murphy?
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