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Leeds 0-0 Brentford
Paul: Leeds played as if they are frightened of losing rather than trying to win. Chris: Good point in the end - they are a good side pushing for a European place and have good players. Hopefully in the final run-in we will see more of Daniel James, Wilfried Gnonto and Noah Okafor, especially in the home games, to create more goals and keep us in the Premier League.
Your Thymus and Your Healthspan
Our thymus gland plays a central role in the development or our immune system, specifically for supporting T cell development (how these cells got their name, maturation and differentiation in the thymus) and discriminating between self and foreign, non-self antigen proteins with production of dendritic cells. As we age, our thymus gland shrinks—the process known as involution—with progressive change from spongy to fatty tissue, with loss of functionality. But this process, with respect to timeline and extent, markedly varies from one person to the next. And to make things even more complicated, our thymus gland anatomy and precise location in the chest also is highly variable. So the famous Frank Netter diagrams from the 1960s (such as at left below) don’t capture the remarkable heterogeneity that a random set of 12 chest CT scans (below at right). What I consider as 2 landmark papers in Nature this week (here and here) used AI to quantify health of the thymus in 2 large cohorts, and then correlate the metric to a broad array of health outcomes. In this edition of Ground Truths, I’m going to cover three questions: (1) How was thymus health determined by AI?; (2) How is thymus health linked to key clinical outcomes? and (3) Are there ways we can promote a healthy (aka rejuvenate) thymus gland in our later years? Subscribe 1. How was thymus health determined by AI? This was accomplished by extensive work developing and validating an AI pipeline for 2 stages, the first for localization and segmentation of the thymus bed, and the second to quantify a digital marker, termed the thymic health score. There’s a lot to this algorithmic development, so I won’t go into all the details, but just provide a rudimentary outline of what was done. The 1st stage used supervised learning with 2 radiologists reviewing 2,461 chest CT scans. That work trained a 3D U-Net model to automatically identify the thymic bed’s 3D cropped region using center of mass coordinates, which reached 99.8% accuracy. The 2nd stage used a foundation model that was pre-trained with SwAV (which stands for Swapping Assignment between multiple Views), a self-supervised model, that generated a high-dimensional thymus representation of 4,096 features. That compares to the radiology reductionist and subjective scoring of 0 to 3 where 0 means the thymus is fully degenerated and fatty, and 3 is considered dense, intact glandular soft tissue. Notably, the self-supervised learning (SSL) performance was superior to supervised (AUC ~0.75 vs 0.55, respectively) reflecting the shallowness of the 0-3 classifier vs SSL’s holistic, self-taught AI. The thymic health score ranged from 0 to 100, with the highest number indexed to fully preserved thymic health. The algorithmic work extended to explainability with both Shapely value distribution, meaning the model was holistic not relying on any “magic” pixel, and occlusion sensitivity, demonstrating the model’s performance was not affected by ribs, sternum, lung tissue, but rather focused on the thymic bed directly. Below are a few saliency maps from the occlusion sensitivity that indicate the thymic bed focus, not affected by neighboring structures, using the jet color scale. Now the AI was ready for processing ~25,000 CT scans, each over 30 MB files, from the 2 large participant cohorts to provide a thymic health score, it did so in less than 14 hours, which is less than 2 seconds per scan! Share 2. How is thymus health linked to key clinical outcomes? The two cohorts were the National Lung Screening Trial, NLST (N=25,031) and the Framingham Heart Study, FHS (N=2,581) each with baseline demographics and long term follow up of >12 years for health outcomes. From the NSLT, you can see below that increased age and body-mass index were correlated to reduced thymic health. And, overall, men had reduced thymic health scores compared with women. There are a lot of graphs in the paper for outcomes, for both the NLST and FHS cohorts. To simplify the major outcomes, below is a composite Figure with striking reduction of all-cause mortality and for the different causes of death. The results were consistent between the 2 cohorts. For example, the cardiovascular mortality hazard ratio average was 0.57 in NLST and 0.38 in FHS (weighted to be 0.53 for the aggregate). The reduction of mortality also extended to digestive diseases and pulmonary disease (data not shown below). Lung cancer incidence was reduced by 36% for high vs low thymic health (Figure below, with a panel -incidence and b panel-mortality, adjusted for age, sex, BMI, smoking status). Notably, there was a smoker’s paradox: lower incidence and improved survival for lung cancer in smokers who had a high thymus health score. Smoking was associated with lower thymic scores whereas alcohol was not. Higher thymic health was linked to higher HDL cholesterol, lower triglycerides, lower fasting blood glucose, and lower systolic and diastolic blood pressure. Inflammation biomarkers, such as C-reactive protein and interleukin-6, were elevated in the people with lower thymic health scores. In their second paper, the same team looked at the relationship between thymic score and outcomes for 3,476 patients receiving cancer immunotherapy. The non-small cell lung cancer progression-free survival was reduced in patients with low thymic health score. A parallel relationship for survival was seen for other types of cancer including melanoma, breast, and kidney with a 44% lower risk among high thymic scores (Figure). A similar pattern was seen with different immune checkpoint inhibitors. The thymus health score outperformed programmed death ligand-1 (PD-L1)and tumor mutation burden (TMB) assay of the tumor and was an independent prognostic marker of progression-free survival. In this dataset, a direct connect with thymus score and adaptive immune function was noted with a correlation before cancer treatment for both T-cell diversity and thymus T-cell production (a metric known as T cell receptor excision circles). Thymus Removal Study There is a highly relevant citation about thymus function before moving onto ways to rejuvenate it. In 2023, a very important study of thymus removal during cardiothoracic surgery was published, with 1146 patients undergoing thymus removal vs 1146 matched controls (mean age 55 years). The adverse outcomes for thymus removal were striking, with a 2.9 higher risk of all-cause mortality and doubling of cancer incidence, 1.5 fold increase in cancer mortality, and 1.5-fold increase in autoimmune diseases. The immune function showed marked compromise after thymus removal, as reflected by CD4+ and CD8+ T cells (Figure below) Share Ground Truths 3. Are there ways we can promote a healthy (aka rejuvenate) thymus gland in our later years? In recent months we’ve learned a lot about the process of thymus involution and the pathways by which this may be modulated. Thymus involution is primarily due to loss to thymus epithelial cells (TECs) and there are 2 subtypes with different functions: the cortical, responsible for positive selection of T cells, and the medullary, for negative selection. When adipose tissue infiltrates the thymus, thymic adipocytes are pro-inflammatory, knocking out T-cell output. Likewise, systemic inflammation, or “inflammaging,” from smoking, obesity, and chronic stress promote thymic adipocytes. Now, from preclinical studies, we know about key pathways that account for these processes. Historically, back in 2014, FOXN1 was recognized as a single master transcription factor essential for TEC function, with studies in mice with forced FOXN1 upregulation leading to thymus regeneration. That laid the foundation for potential regrowth of quiescent thymus cells. It took awhile to find pathways to accomplish this goal and to even refute its role as the master regulator. The Liver-Thymus Axis Feng Zhang and his team recently showed that injection of an mRNA vaccine to the liver encoding DLL1, IL-7 and FLT3-L in combination, factors known to support thymopoiesis (Figure), successfully enhanced immune function in aged mice. However, the effect was transient. The FGF21 Story Two reports in 2025 addressed the thymus gland’s production of FGF21, a growth factor (fibroblast growth factor 21) and its control of thymus involution. This growth factor is also produced by the liver, but it doesn’t have impact on the thymus in aged rodent models. In contrast, The liver’s hepatocyte growth factor (HGF) has been shown to reverse senescent TEC structural changes. Growth hormone stimulates production of insulin growth factor-1 (IGF-1) in the liver and the thymus. Two small studies in human participants (TRIIM, for Thymus Regeneration, Immunorestoration, and Insulin Mitigation) of 6 and 50 people, respectively, treated with combined human growth hormone, metformin and DHEA, suggested the potential of slowing epigenetic aging and improving thymus mass and function. But the combination of drugs, small sample, and lack of controls make conclusions murky. Increased thymus FGF21 led to increased CD8 T cells in old mice and extended healthspan and improved physical performance. Building on the previous FOXN1 data, ablation of β-klotho, the obligatory co-receptor for FOXN1, accelerated thymic aging. The benefit to FGF21 was confirmed in a companion paper using an FGF21 knock-in mouse model showing thymus enlargement and increased TECs throughout the lifespan. (schematic Figure below). The accompanying editorial for these 2 papers speculated: “The proposed link between age-associated thymus involution and organismal aging is intriguing, and suggests we might seek to achieve systemic rejuvenation by counteracting thymic involution.” Other Factors Lessons from the Axolotl (Mexican Salamander) In an elegant set of experiments of the axolotl (Figure), known for its complete thymus regeneration after total surgical removal, mediators were identified. Surprisingly FOXN1 was dispensable. But midkine, a growth factor, appeared to be the driver, the initiator of thymus cell growth, survival, and repair. Other components that contributed were Postn+ (periostin-expressing mesenchymal niches) and Ccl19, a chemokine protein from the bloodstream. RANK and RANKL RANK (receptor activator of nuclear factor κB its ligand (RANKL) have been considered key regulators of medullary TECs. In a study of both aged mice and human thymus cell cultures, their key role was confirmed, with multiple benefits of resorting TEC function, recruitment of progenitor cells, and T cell development. Subscribe Summing Up This body of work strongly supports the health of the thymus gland as a critical regulator of human healthspan, not just a correlate or link. The new landmark studies are reinforced by the regenerative biology experimental models that have shown, via an array of mediators, that healthspan of aged mice is at least in part dependent on thymus gland function and its critical role for maintaining adaptive immunity. It sure seems that we’d be better off having an immune reservoir of naive T cells instead of a profile in older adults of exhausted, low quality, memory T cells, with a senescent phenotype. It is striking that we ignored the importance of the thymus gland for many decades. A wake-up call was the results of the thymectomy matched control study reviewed here, with the opposite of high thymic health score improved health outcomes. The convergence of AI and healthspan here is notable. The exceptional and laborious work for developing and validating (no less explaining) the AI to quantify thymus health set the foundation for probing the connect the major health outcomes in two cohorts with extensive follow-up. We’ve never had a way to meaningfully quantify the thymus gland before, so this represents important leverage of supervised, self-supervised, and transformer models. The study wouldn’t have been possible without AI. And it begs the question as to whether there are ways we can maintain our thymus at a high health score. But it’s not so simple to rejuvenate our thymus. There are multiple risks including the induction of autoimmunity, increasing the risk of cancer, and inducing a pro-inflammatory state. For example, factors that increase TEC proliferation could compromise the medulllary negative selection process and leak out auto-reactive (self-attacking) T cells. Thymic cells could be induced to proliferate, but we know, for example, that growth hormone and IGF-1 are associated with an increase risk of cancer. If thymus rejuvenation doesn’t clear out the accumulated senescent cells in older adults, then inflammation within the gland could block the production of TECs. Keeping these risks in mind, we now have identified many ways to keep our thymus healthy as we age that undoubtedly will be tested in clinical trials going forward. Ultimately, the benefit-to-risk tradeoffs will be defined. In the meantime, we have desperately needed an immunome. As I’ve stressed in multiple prior Ground Truths, we have no test in the clinic to assess a patient’s immune status! It was very encouraging for me to get an email from Hugo Aerts, the senior author of the landmark papers in the days after they were published: “I also wanted to say that your Substack on “Why We Need an Immunome” was inspiring for this work. We found it a very compelling perspective and greatly enjoyed reading it.” Just having an assessment of a person’s immune status via a chest CT scan, with millions of these performed per year, might help in guiding the right immunotherapy for cancer (e.g. more intensive, combinations for those with low thymic health scores) and help define people who are increased risk for age-related diseases of cancer, cardiovascular, and neurodegenerative. The main theme of Super Agers is that we now have many layers of data (genetics, proteins, biomarkers, organ clocks that can be integrated via multimodal AI) for us to define a person’s specific risk decades before one of these age-related diseases leads to symptoms, enabling prevention. From the new studies this week, we can add thymus health score as yet another way to understand a person’s risk, a window into their adaptive immune system and healthspan. And perhaps someday we will be able to safely rejuvenate the thymus, or maintain its health through one’s life, and use the thymus health score to monitor. NB: I wrote this post (No A.I.) A Quick Poll Loading... ********************************************************************* Thanks to Ground Truths subscribers (now > 200,000) from every US state and 212 countries. Your subscription to these free essays and podcasts makes my work in putting them together worthwhile. Please join! If you found this interesting PLEASE share it! Share Ground Truths Paid subscriptions are voluntary and all proceeds from them go to support Scripps Research. They do allow for posting comments and questions, which I do my best to respond to. Please don’t hesitate to post comments and give me feedback. Let me know topics that you would like to see covered. Leave a comment Many thanks to those who have contributed—they have greatly helped fund our summer internship programs for the past two years. It enabled us to accept and support 47 summer interns in 2025! We aim to accept even more of the several thousand who will apply for summer 2026.
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The Crown adds to market share dominance despite lower production for the last two years running.
Cunningham on target as depleted Pistons down Raptors
Cade Cunningham finished with 28 points as the Detroit Pistons shrugged off the suspensions of Jalen Duren and Isaiah Stewart to cruise past the Toronto Raptors 113-95 on Wednesday.But the absence of the two Pistons centers had little effect on Detroit as they coasted to a wire-to-wire victory in Toronto.
From gifting a hat to tossing them onto the rink, a history of hat tricks in sports
Hat tricks have a rich history in hockey, but it didn't start there. For NPR's Word of the Week, we trace the term's some 150-year-history and why it's particularly special on the hockey rink.
The Super Bowl Halftime Shows Are Sending A Message — And It’s One That Shouldn’t Be Ignored
After statement-making performances from Bad Bunny and Kendrick Lamar, there’s a new standard for stepping onto the global stage. But will it last?
A Democrat’s victory in a Louisiana legislative race got national attention. Here’s why.
Democrats weren’t sure if they could hold onto state House District 60, an Iberville Parish-based seat long represented by their party.
BeWhere and Examinetics Transform Occupational Health with Low Power 5G Asset Tracking
Toronto, Ontario--(Newsfile Corp. - February 9, 2026) - BeWhere Holdings Inc. (TSXV: BEW) (OTCQB: BEWFF), a leader in low-power 5G IoT asset tracking, is pleased to announce the release of a new case study featuring Examinetics, a leading provider of mobile occupational health services in the US.The new case study highlights how Examinetics has used BeWhere's compact BeMini asset trackers to improve the management of high-value portable medical testing equipment. The deployment keeps track of...
Bad Bunny Delivers Party, Not Politics, During Super Bowl Halftime
Super Bowl LX halftime show headliner Bad Bunny, just like pregame performer Green Day, paused the political commentary during the title game.
Green Day Avoids Politics During Super Bowl LX Pregame Show
Green Day played it safe Sunday at Levi’s Stadium, less than 48 hours after taking aim at U.S. President Donald Trump.
Revealed: The new Defiler stomps onto the battlefield
Wield six legs of absolute devastation on the battlefield.
A Look At Madison Square Garden Entertainment (MSGE) Valuation After Quarterly Earnings Beat Expectations
Q2 earnings outperformance puts MSGE in focus Madison Square Garden Entertainment (MSGE) has moved onto more investor watchlists after its latest quarterly results, where revenue, net income and earnings per share all came in above analyst expectations. See our latest analysis for Madison Square Garden Entertainment. The stronger than expected Q2 numbers sit alongside a solid recent run in the shares, with a 30 day share price return of 10.62% and a 90 day share price return of 23.50%. Over...
Record-Breaking One-Off Bugatti Brouillard Could Become the Most Expensive Bugatti Ever
A one-off aimed at a historic record Bugatti’s latest one-off, the Brouillard, steps onto the hypercar stage with the quiet confidence of a record-breaker. The brand’s tradition of bespoke excellence meets a bold new aesthetic, positioning this unique commission to potentially become the marque’s most expensive creation. Built on the proven underpinnings of the Chiron/Mistral architecture, yet transformed by distinctive craft, the Brouillard is both homage and innovation. A name born from equestrian legend More than a century ago, a striking white horse captivated Ettore Bugatti in Molsheim. That equine myth now informs the car’s name and its sensory identity. The result is an automotive portrait of athletic grace—surfaces that read like muscle, curves that suggest motion, and details that quietly speak of discipline and heritage. Embroidered horse motifs on door panels and seat backs echo the story, while a miniature glass sculpture of the steed crowns the shifter. Sculptural design with purpose The Brouillard’s silhouette favors sinuous surfaces over hard creases, allowing light to glide over its form like a tendon under skin. Aerodynamics inform elegance: an integrated ducktail replaces a deployable wing, cleansing the airflow and boosting stability at speed. Its stance is athletic, its volumes taut, and its visual language unmistakably Bugatti. “Sculptural, organic forms—like a tendon beneath the skin—hide immense power behind noble simplicity,” said design chief Frank Heyl, capturing the car’s philosophy in a single stroke. Craft elevated to an art The cabin embraces craftsmanship at an uncommon level. Custom-woven textiles from Paris introduce a discreet tartan pattern, while green-tinted carbon fiber nods to the exterior’s hue. A glazed roof creates a cathedral atmosphere, bathing the cockpit in natural light. A central spine appears to flow from exterior to interior, emphasizing continuity and structure. Highlights include: Custom textiles with subtle tartan motifs Green-tinted carbon fiber matched to the exterior finish A “cathedral” glass roof that elevates cabin ambience A sculptural centerline linking outside to inside Bespoke embroidery and glass equine detail W16 power at its absolute apex Under the sculpted skin, the final evolution of Bugatti’s 8.0‑liter, quad‑turbo W16 delivers a thunderous 1,600 hp at 7,050 rpm and 1,600 Nm of torque. This represents the pinnacle of nearly two decades of Bugatti engineering, honed to an ultimate state. The lightweight monocoque blends carbon fiber with aluminum, holding mass to around 1,900 kg for poise and control. Experts suggest the Brouillard could surpass the 282 mph (454 km/h) achieved by the Mistral, aided by more aerodynamic bodywork and the fixed ducktail. Whether or not it sets a new benchmark, its intent is clear: relentless speed paired with refinement. Exclusivity with an exacting timeline The commissioning process is intensive, with roughly 18 months of development leading to a 2027 delivery. Bugatti’s program limits itself to no more than two creations per year, ensuring focus and rarity. Each example leaves the atelier as a singular vision, shaped to the client’s collection and the brand’s ethos. An unveiling is planned for Monterey Car Week 2025, placing the Brouillard amid the world’s most discerning enthusiasts. Its patron is a European collector deeply invested in the Bugatti universe, from historic and modern cars to Carlo Bugatti furniture and Rembrandt Bugatti bronzes. A valuation poised to make history While Bugatti has not disclosed an official price, informed estimates place the Brouillard between €10 million and €30 million. Context matters: a series Mistral begins near €5 million, while the Brouillard adds profound personalization, sculptural changes, and a pace of production that keeps scarcity front and center. In an arena where uniqueness drives value, the path to a brand record is unmistakably open. What it signals for the marque The Brouillard crystallizes Bugatti’s dual identity: traditional savoir‑faire intertwined with boundary-pushing performance. It exhibits a narrative soul—the white horse of Molsheim—woven into modern materials and world-class aerodynamics. As a rolling statement, it reaffirms that the Bugatti idea is larger than speed alone; it is about story, craft, and the courage to pursue an ideal to its logical limit.
Atrium Health offers heart screenings in Macon, Eatonton during American Heart Month
Atrium Health Navicent is celebrating American Heart Month by hosting a series of AngioScreen events in Macon and Eatonton.
How does brain rot shape our politics?
Absurdist internet slang and content dubbed “brain rot” has become increasingly prevalent online in recent years, shaping public interactions and modern politics.
Alexandria Ocasio-Cortez Steps Onto a Wider Stage
The progressive lawmaker is taking a larger role in Democratic politics, supporting moderate candidates and helping drive the party’s economic message. Now she is planning a major trip abroad.
'Burping' Your Home Really Could Be Good For Your Health, Says Expert
The Germans might be onto something.
San Jose’s first Entertainment Zone opening for Super Bowl weekend
Fans can take their drinks out onto the streets around San Pedro Square this weekend, which will be filled with music, activities and a Super Bowl LX watch party.
Bad Bunny doesn’t need the NFL as much as the NFL needs him
The National Football League is not new to global superstars nor controversy. The Puerto Rican superstar’s selection as the halftime show performer has come with both – but will also bring more eyes from around the world onto the sport in a way the league has been craving.
This paper-thin chip turns invisible light into a steerable beam
Researchers have built a paper-thin chip that converts infrared light into visible light and directs it precisely, all without mechanical motion. The design overcomes a long-standing efficiency-versus-control problem in light-shaping materials. This opens the door to tiny, highly efficient light sources integrated directly onto chips.
Curiosity Blog, Sols 4788-4797: Welcome Back from Conjunction
Written by Alex Innanen, Atmospheric Scientist at York University, Toronto
Microsoft actually does something useful, adds Sysmon to Windows
: After years of bolting AI onto everything, Redmond remembers admins exist
Scientists just mapped the hidden structure holding the Universe together
Astronomers have produced the most detailed map yet of dark matter, revealing the invisible framework that shaped the Universe long before stars and galaxies formed. Using powerful new observations from NASA’s James Webb Space Telescope, the research shows how dark matter gathered ordinary matter into dense regions, setting the stage for galaxies like the Milky Way and eventually planets like Earth.
Maple Leafs' Fraser Minten trade has aged horribly
Toronto might want this one back.