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  • ‘World Models,’ an Old Idea in AI, Mount a Comeback

    ‘World Models,’ an Old Idea in AI, Mount a Comeback

    The latest ambition of artificial intelligence research — particularly within the labs seeking “artificial general intelligence,” or AGI — is something called a world model: a representation of the environment that an AI carries around inside itself like a computational snow globe. The AI system can use this simplified representation to evaluate predictions and decisions before applying them to its real-world tasks. The deep learning luminaries Yann LeCun (of Meta), Demis Hassabis (of Google DeepMind) and Yoshua Bengio (of Mila, the Quebec Artificial Intelligence Institute) all believe world models are essential for building AI systems that are truly smart, scientific and safe.

    The fields of psychology, robotics and machine learning have each been using some version of the concept for decades. You likely have a world model running inside your skull right now — its how you know not to step in front of a moving train without needing to run the experiment first.

    So does this mean that AI researchers have finally found a core concept whose meaning everyone can agree upon? As a famous physicist once wrote: Surely youre joking. A world model may sound straightforward — but as usual, no one can agree on the details. What gets represented in the model, and to what level of fidelity? Is it innate or learned, or some combination of both? And how do you detect that its even there at all?

    It helps to know where the whole idea started. In 1943, a dozen years before the term “artificial intelligence” was coined, a 29-year-old Scottish psychologist named Kenneth Craik published an influential monograph in which he mused that “if the organism carries a ‘small-scale model’ of external reality … within its head, it is able to try out various alternatives, conclude which is the best of them … and in every way to react in a much fuller, safer, and more competent manner.” Craiks notion of a mental model or simulation presaged the “cognitive revolution” that transformed psychology in the 1950s and still rules the cognitive sciences today. What’s more, it directly linked cognition with computation: Craik considered the “power to parallel or model external events” to be “the fundamental feature” of both “neural machinery” and “calculating machines.”

    The nascent field of artificial intelligence eagerly adopted the world-modeling approach. In the late 1960s, an AI system called SHRDLU wowed observers by using a rudimentary “block world” to answer commonsense questions about tabletop objects, like “Can a pyramid support a block?” But these handcrafted models couldn’t scale up to handle the complexity of more realistic settings. By the late 1980s, the AI and robotics pioneer Rodney Brooks had given up on world models completely, famously asserting that “the world is its own best model” and “explicit representations … simply get in the way.”

    It took the rise of machine learning, especially deep learning based on artificial neural networks, to breathe life back into Craik’s brainchild. Instead of relying on brittle hand-coded rules, deep neural networks could build up internal approximations of their training environments through trial and error and then use them to accomplish narrowly specified tasks, such as driving a virtual race car. In the past few years, as the large language models behind chatbots like ChatGPT began to demonstrate emergent capabilities that they weren’t explicitly trained for — like inferring movie titles from strings of emojis, or playing the board game Othello — world models provided a convenient explanation for the mystery. To prominent AI experts such as Geoffrey Hinton, Ilya Sutskever and Chris Olah, it was obvious: Buried somewhere deep within an LLM’s thicket of virtual neurons must lie “a small-scale model of external reality,” just as Craik imagined.

    The truth, at least so far as we know, is less impressive. Instead of world models, today’s generative AIs appear to learn “bags of heuristics”: scores of disconnected rules of thumb that can approximate responses to specific scenarios, but don’t cohere into a consistent whole. (Some may actually contradict each other.) It’s a lot like the parable of the blind men and the elephant, where each man only touches one part of the animal at a time and fails to apprehend its full form. One man feels the trunk and assumes the entire elephant is snakelike; another touches a leg and guesses it’s more like a tree; a third grasps the elephant’s tail and says it’s a rope. When researchers attempt to recover evidence of a world model from within an LLM — for example, a coherent computational representation of an Othello game board — they’re looking for the whole elephant. What they find instead is a bit of snake here, a chunk of tree there, and some rope.

    Of course, such heuristics are hardly worthless. LLMs can encode untold sackfuls of them within their trillions of parameters — and as the old saw goes, quantity has a quality all its own. That’s what makes it possible to train a language model to generate nearly perfect directions between any two points in Manhattan without learning a coherent world model of the entire street network in the process, as researchers from Harvard University and the Massachusetts Institute of Technology recently discovered.

    So if bits of snake, tree and rope can do the job, why bother with the elephant? In a word, robustness: When the researchers threw their Manhattan-navigating LLM a mild curveball by randomly blocking 1% of the streets, its performance cratered. If the AI had simply encoded a street map whose details were consistent — instead of an immensely complicated, corner-by-corner patchwork of conflicting best guesses — it could have easily rerouted around the obstructions.

    Given the benefits that even simple world models can confer, it’s easy to understand why every large AI lab is desperate to develop them — and why academic researchers are increasingly interested in scrutinizing them, too. Robust and verifiable world models could uncover, if not the El Dorado of AGI, then at least a scientifically plausible tool for extinguishing AI hallucinations, enabling reliable reasoning, and increasing the interpretability of AI systems.

    That’s the “what” and “why” of world models. The “how,” though, is still anyones guess. Google DeepMind and OpenAI are betting that with enough “multimodal” training data — like video, 3D simulations, and other input beyond mere text — a world model will spontaneously congeal within a neural network’s statistical soup. Meta’s LeCun, meanwhile, thinks that an entirely new (and non-generative) AI architecture will provide the necessary scaffolding. In the quest to build these computational snow globes, no one has a crystal ball — but the prize, for once, may just be worth the AGI hype.

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  • Humans inherited Neanderthal genes that limit our muscle activity

    Humans inherited Neanderthal genes that limit our muscle activity

    Most of us carry a small trace of Neanderthal ancestry and, in some cases, that legacy sits in our legs. A single change in a muscle enzyme can subtly throttle how hard muscles can work under pressure.

    People outside Africa typically carry about 2 percent Neanderthal DNA in their genomes, a result of ancient interbreeding between populations. That shared history still influences traits today, including how our muscles manage energy during all out effort.

    What the enzyme variant does


    In an influential 2017 study, lead author Dominik Macak from the Max Planck Institute for Evolutionary Anthropology (MPI EVA), and colleagues, focused on AMPD1. This is an enzyme that helps skeletal muscle recycle energy-rich molecules during effort.

    In their new study, they show that Neanderthals carried a version of AMPD1 with lower activity than the typical modern human form.

    The team expressed both versions of the enzyme in cells and measured activity in a controlled setup. The Neanderthal version showed about a quarter less activity in test tubes, and when the change was engineered into mice, total AMPD activity measured in leg muscle extracts dropped sharply.

    How the muscle enzyme reached modern humans

    The variant appears in all sequenced Neanderthals and is absent in other primates, which points to a change specific to that lineage. Some modern humans carry the Neanderthal-derived form because of archaic introgression, the movement of DNA across populations through interbreeding.

    Today, the gene for this variant enzyme is found most often in Europe and Western Asia at modest frequencies. The pattern is consistent with gene flow into early modern humans who met Neanderthals around 50,000 years ago, interbred and then spread across Eurasia.

    From bench to muscle

    The lab assays matter because AMPD1 sits in a critical energy pathway known as the purine nucleotide cycle. When muscles need ATP (the molecule that provides power for cellular activities in all living organisms) in a hurry, AMPD1 helps pull the chemical levers that keep ATP production humming.

    In practice, the variant’s impact shows up most clearly when muscles are pushed. Mouse muscle carrying the engineered change showed large decreases in measured AMPD activity in extracts. In addition, prior case reports hint at reduced enzyme activity in rare human carriers with combined AMPD1 defects.

    Neanderthal muscle enzyme and sport

    The research also looked at athletic outcomes by using a well-known human knockout allele of AMPD1 as a stand in for reduced enzyme function. That analysis covered more than a thousand elite athletes across endurance and power disciplines.

    “Carrying one dysfunctional AMPD1 allele confers approximately a 50 percent lower probability of achieving elite athletic performance,” wrote Macak. The sentence sums up where the enzyme matters most, at the razor’s edge where physiology meets peak performance.

    Health signals to watch

    Reduced AMPD1 activity is common in clinic genetics, yet many carriers feel fine most of the time. The clinical picture of myoadenylate deaminase deficiency (MAD) ranges from exercise-induced cramps and early fatigue to no symptoms, a pattern known as incomplete penetrance.

    Large data resources add nuance. Biobank analyses suggest a small increase in risk for varicose veins among people with AMPD1 variants that reduce activity, although replication across cohorts is mixed and the absolute risk increase is modest.

    Why the Neanderthal muscle enzyme stuck around

    If reduced enzyme activity can hinder elite performance, why did the variant enzyme persist. One likely factor is relaxed purifying selection, which occurs when a gene becomes less crucial for day-to-day survival across a population.

    Another possibility is that culture and technology reduced the constant demand for extreme muscle output. If everyday life did not require maximum sprint power or heavy loads, then a small energetic inefficiency would be tolerated.

    What counts as a meaningful effect

    The findings do not imply that someone with the variant cannot excel at sports or live a healthy life. Most carriers have no obvious health problems, and plenty of other genes and training factors shape performance.

    Still, the enzyme’s role appears during stress. When energy turnover spikes, AMPD1 helps buffer the system, and slightly less activity can tip the balance in high stakes settings like championship level competition.

    A closer look at enzyme chemistry

    To keep terms clear, an enzyme is a protein catalyst that speeds up chemical reactions in cells. Purine molecules are key building blocks for DNA and RNA, and they also form ATP, the energy currency that pays for muscle contractions.

    An allele is one version of a gene among alternatives, and the Neanderthal-derived allele in AMPD1 swaps one amino acid in a position that helps the enzyme’s subunits stick together. That subtle change lowers catalytic efficiency without removing the protein entirely.

    A bigger shift in energy chemistry

    This is not the first sign that energy metabolism took a different path in humans when compared to other primates. Earlier work found that modern humans carry a unique change in another enzyme, ADSL, which tunes the same pathway and is linked to lower purine levels in key tissues, especially the brain.

    Together, these threads suggest that parts of our energy machinery became less dependent on certain purine reactions over evolutionary time. The Neanderthal AMPD1 story adds a muscle-specific chapter and ties it directly to present day physiology.

    Where this leaves us

    The signal here is not alarm, it is perspective. Daily life proceeds as usual for almost everyone who carries the muscle enzyme variant. However, a centuries-old interbreeding event still leaves a fingerprint on who is more likely to reach the top tier of sport.

    This work also emphasizes why population history matters in medicine and performance science. Small shifts in enzyme activity, inherited across tens of thousands of years, can still modulate outcomes when humans are pushed to the limit.

    The study is published in Nature Communications.

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  • Racket Rivals Codes (September 2025)

    Racket Rivals Codes (September 2025)

    Update: added new Racket Rivals codes on September 2, 2025

    Being a fan of legends like Lin Dan and Saina Nehwal, I’ve always loved playing badminton in real life. But as time went on, I wanted a digital smash fest, and Roblox Racket Rivals serves exactly that. You dive into a badminton world where rackets, skills, and awakenings decide your fate. To make things easier, we’ve rounded up the latest Racket Rivals codes that hand out free lucky spins, awakening spins, and other goodies. Use them to snag top-tier rackets, awakenings, and build the ultimate loadout.

    All New Racket Rivals Codes

    • sorryreboot: 1 Lucky Spin (NEW)
    • SL3EPY: 1 Awakening Spin (NEW)

    Expired Racket Rivals Codes

    Right now, there are no expired codes in the game, so I would suggest that you get the rewards from the existing ones before they go away.

    Fans of all sorts of anime sports games might enjoy Volleyball Legends, Basketball Zero, while soccer fans can dive into Blue Lock Rivals. For some fresh experiences, check out our Roblox game codes master list. Want some RPG action? Get into Type Soul or Blox Fruits.

    How to Redeem Racket Rivals Codes

    Scoring some points in Racket Rivals is easy, but before you get faster, you must learn how to get the free rewards. Follow the step-by-step process below and redeem the codes for Racket Rivals:

    • Launch the Racket Rivals app on Roblox.
    • Open the Shop menu from the bottom of the screen.
    • Select the Codes option on the top right of the ‘Shop’ menu.
    • Input a working code and click the Submit button.

    How to Get More Racket Rivals Codes

    When it comes to gathering the latest codes, we follow the title of the anime. Yes, if you are looking for the codes right as they arrive, our page is your best option. We frequently update the codes list with the new ones and move the expired ones. So, bookmark this page and stay on top of the codes always.

    If you still want to hunt down all the codes for Racket Rivals, yourself, follow the official social media accounts for the game. The best place to find them is the Racket Rivals Discord server. The new codes are often shared in the update-logs channel. However, the moderators compile the codes and post them in the showcase channel as well.

    Want more updates about the game and some more freebies? You can follow the ⨯ Small World Games Roblox community and get more rewards.

    Ishan Adhikary

    A gaming nerd who covers all things video games. Spending time playing games and writing about them was always a dream. Thanks to Beebom, I live it. Once I am done gaming, I write. Once I am done writing, I game. You feel me.


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  • Scientists Uncover Hidden Megathrust That Could Trigger Massive Earthquakes

    Scientists Uncover Hidden Megathrust That Could Trigger Massive Earthquakes

    Scientists have captured the first detailed images of the Queen Charlotte fault system offshore Haida Gwaii, revealing that the region has the potential to unleash powerful megathrust earthquakes. Credit: SciTechDaily.com

    Scientists used advanced hydrophone technology to image the Queen Charlotte fault, confirming its potential for destructive megathrust earthquakes.

    New research on the Queen Charlotte fault system has produced the first images of its subsurface structure off the coast of Haida Gwaii, confirming that northern British Columbia is capable of generating megathrust earthquakes.

    These types of earthquakes occur where one tectonic plate is forced beneath another—in this case, the Pacific plate being driven under the North American plate—and they are known for producing both intense shaking and tsunamis.

    Advanced hydrophone technology

    An international team of scientists from American and Canadian institutions, including Dalhousie University, collected the data using a 15-kilometre-long hydrophone streamer. This instrument, equipped with thousands of underwater microphones, was towed through the region to capture seismic signals and map the deep structure of Earth’s crust.

    Map Showing Queen Charlotte Fault and Surrounding Tectonic Plates
    Map of the study area, showing the location of the Queen Charlotte Fault (QCF) in relation to the Pacific (PAC), North America (NA), Yakutat (YAK), Explorer (EXP) and Juan De Fuca (JdF) tectonic plates. Credit: 10.1126/sciadv.adt3003

    The findings, published in Science Advances, present the first definitive evidence that the Pacific plate is beginning to collide with and subduct beneath the North American plate in the Haida Gwaii area. In practical terms, this means the region has the potential to generate earthquakes capable of both strong ground shaking and destructive tsunamis.

    In fact, the Queen Charlotte fault system represents the greatest seismic hazard in Canada, producing the country’s largest recorded earthquake in 1949.

    “This region is actively becoming a subduction zone, so understanding the fault structure here tells us about the early stages of subduction zone development,” says lead author Collin Brandl, a postdoctoral research scientist at the Lamont-Doherty Earth Observatory, part of the Columbia Climate School.

    “Our study provides the first direct observations of the Haida Gwaii thrust, the “megathrust” of this system, which can help improve hazard analysis in the region, better preparing residents for future earthquakes and tsunamis.”

    Reference: “Seismic imaging reveals a strain-partitioned sliver and nascent megathrust at an incipient subduction zone in the northeast Pacific” by Collin C. Brandl, Lindsay L. Worthington, Emily C. Roland, Maureen A. L. Walton, Mladen R. Nedimović, Andrew C. Gase, Olumide Adedeji, Jose Castillo Castellanos, Benjamin J. Phrampus, Michael G. Bostock, Kelin Wang and Sarah Jaye Oliva, 18 July 2025, Science Advances.
    DOI: 10.1126/sciadv.adt3003

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  • Earth’s violent birth: What it takes to make a living world

    Earth’s violent birth: What it takes to make a living world

    Earth today is teeming with life. We have oceans, breathable air, and the perfect combination of chemical ingredients necessary for living organisms to thrive. But when Earth first started forming, it lacked some of the most fundamental elements required for life.

    So how did our world transition from being barren and inhospitable to what it is today?


    A team of scientists just found new clues that show Earth’s original mix of elements was complete surprisingly early – only a short time after the solar system came together.

    Formation of the solar system

    When the solar system began to form billions of years ago, it emerged from a gigantic cloud of gas and dust. This cloud contained important elements such as hydrogen, carbon, and sulfur – chemicals essential for life.

    Not everything in the solar system was equally formed, though. The inner zone, the region nearest the Sun, was extremely hot.

    Due to this heat, most of the life-critical components never condensed into solid form. Instead, they remained in the form of gas and didn’t persist long enough to become part of the rocky material that formed the tiny inner worlds such as Mercury, Venus, Earth, and Mars.

    As a result, early Earth was built mostly from dry, rocky stuff. It missed out on a lot of the “wet” ingredients that came from the cooler, outer parts of the solar system.

    The puzzle of life on Earth

    Scientists have long wondered when Earth picked up the materials that would one day allow life to appear. If the inner solar system didn’t have them, then they had to come from somewhere else. And if they came later, when exactly did that happen?

    That’s what scientists at the University of Bern’s Institute of Geological Sciences wanted to know. They analyzed rocks from ancient Earth and meteorites, using radioactive isotopes to calculate time with astonishing accuracy.

    “A high-precision time measurement system based on the radioactive decay of manganese-53 was used to determine the precise age. This isotope was present in the early solar system and decayed to chromium-53 with a half-life of around 3.8 million years,” said Dr. Pascal Kruttasch, who led the study.

    The team’s method allowed them to measure ages with less than a million years of error – even on materials that are billions of years old.

    “These measurements were only possible because the University of Bern has internationally recognized expertise and infrastructure for the analysis of extraterrestrial materials and is a leader in the field of isotope geochemistry,” noted Klaus Mezger, co-author of the study.

    Earth’s chemistry was locked in fast

    The team found that Earth’s chemical signature – the unique mix of elements that made up the young planet – was complete in less than 3 million years after the solar system formed.

    “Our solar system formed around 4,568 million years ago. Considering that it only took up to 3 million years to determine the chemical properties of Earth, this is surprisingly fast,” said Kruttasch.

    “Thanks to our results, we know that the proto-Earth was initially a dry rocky planet. It can therefore be assumed that it was only the collision with Theia that brought volatile elements to Earth and ultimately made life possible there,” explained Kruttasch.

    The collision that changed everything

    Scientists have long believed that Earth was hit by a planet-sized object called Theia early in its history. This impact is also what likely created the Moon.

    However, this study adds something new: evidence that Theia may have delivered the materials that made Earth capable of supporting life.

    Theia likely formed farther from the Sun, where cooler temperatures allowed water and other volatiles to collect. When it slammed into Earth, it didn’t just shake things up – it may have delivered the very elements we needed to build oceans, an atmosphere, and the chemistry of life.

    “The Earth does not owe its current life-friendliness to a continuous development, but probably to a chance event – the late impact of a foreign, water-rich body. This makes it clear that life-friendliness in the universe is anything but a matter of course,” said Mezger.

    What this means for other planets

    If Earth only became habitable thanks to a lucky collision, that has big implications for other planets – both in our solar system and beyond.

    Even if a rocky planet forms in the right zone around its star, it might not be enough. The timing and location of volatile delivery, plus the exact kind of collision, may all play a role. And those things don’t happen everywhere.

    It’s possible that many planets stay dry forever. Others might get hit too hard or too often. Earth’s path may not be typical – it may be one of the rare cases where the right ingredients arrived at the right time, in just the right way.

    Understanding Earth’s massive collision

    We still don’t fully understand what happened during that massive collision between proto-Earth and Theia. Kruttasch and his team want to explore the event further.

    “So far, this collision event is insufficiently understood. Models are needed that can fully explain not only the physical properties of the Earth and moon, but also their chemical composition and isotope signatures,” Kruttasch said.

    In other words, scientists still need to untangle the chemistry of Earth and its satellite. The Moon and Earth share strikingly similar chemical fingerprints – a mystery that challenges the idea of a foreign body like Theia delivering the missing ingredients for life.

    If Theia really formed farther from the Sun, where water and volatile elements were abundant, why don’t those differences show up more clearly in the Moon’s composition?

    Future research could help answer that question – and may also help us figure out how common this kind of planet-forming “recipe” is in the universe.

    The full study was published in the journal Science Advances.

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  • François Ozon Talks Golden Lion Contender ‘The Stranger’

    François Ozon Talks Golden Lion Contender ‘The Stranger’

    Prolific French director François Ozon touched down in Venice on Tuesday with his adaptation of Albert  Camus’s absurdist classic The Stranger about a French expat living in colonial 1930s French Algeria who indifferently kills a local man.

    It is the third fiction adaption of the novella after the 1967 version by Luchino Visconti, starring Marcello Mastroianni, and 2001 Turkish film Fate, which played in Cannes Un Certain Regard.

    Anticipation is riding high on the Lido as to whether Ozon has pulled it off with his black-and-white adaptation, starring Benjamin Voisin as protagonist Meursault and Rebecca Varder as his lover.

    At the press conference for the Golden Lion contender, Ozon revealed he had hit on the idea of adapting The Stranger after failing to secure financing for a project following a young man in the wake of a failed suicide attempt.

    The director said that like most people in France, he had read the novella when he was a high school student, but had found fresh meaning when he came back to it later in later life.  

    “Maybe I understood it a little better than when I read it as a teenager and at the same time there were a lot of things that I didn’t understand in the book that fascinated me,” said Ozon.

    “I started in a somewhat carefree way and at the same time a little anxious because everyone around me was saying to me, ‘It’s my favorite book. I’m curious to see what you’re going to do’. That put pressure on.”

    Ozon said he decided very quickly that he would revisit the story with a modern perspective rather than – as Visconti had done – with gaze of the time of its writing in 1939 and publication in 1942 when France still occupied Algeria.  

    “The most important thing right away is the first sentence of the book, which is extremely well-known and everyone remembers, ‘Mother is dead, maybe it was yesterday’,” said Ozon.

    “But in fact, it wasn’t this sentence that shocked me today, that surprised me. It was rather a sentence that appears in the second part of the book, when Meursault returns to prison and says, ‘I killed an Arab’.”

    “I said to myself, there you go, this is the key to my adaptation. Contextualize this story about French colonization and try to understand Meursault’s character by following Camus’s book as faithfully as possible.”

    Ozon said his decision to making the film in black and white was both artistic and financial.

    “Since it’s a philosophical book, it seemed to me that black and white was ideal for telling this story, being free of color, it’s a form of purity… it was also a financial choice. It’s not an American blockbuster and I didn’t have the means to recreate the 1930s in Algiers, so it allowed me to simplify a lot of the sets,” he explained.

    The film was shot in color and then converted into black and white. Ozon said the end result was a pleasant surprise.

    “It makes everything absolutely magnificent and awakens the cinephile in us because all of a sudden, when I saw Rebecca in a white swimsuit on the beach, I said to myself, it’s Elizabeth Taylor in Suddenly, Last Summer, or Benjamin walking in the streets, I had the impression of seeing James Stewart or Cary Grant.”

    Ozon, who has delivered a film every year for the past decade, was asked where his drive came from at a time when it was increasingly hard to get feature films financed and over the line.

    “There’s a quote from Camus: ‘To create is to live twice’.  Well, to make a film is to live twice. Journalists often say to me, ‘You can’t have time to live because you’re always making films,” said Ozon.

    “On the contrary, I believe that I live twice as much because I make films… to create, to tell a story, to work with a team, because it’s truly a collective effort, is the most powerful thing.”

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  • Bath’s Holburne museum to unveil ‘art chamber’ of Renaissance masterpieces | Museums

    Bath’s Holburne museum to unveil ‘art chamber’ of Renaissance masterpieces | Museums

    Beneath the Georgian city of Bath, a gleaming treasury of Renaissance masterpieces created for kings, queens, church leaders and scientists is about to be unveiled.

    Based on the idea of the Renaissance kunstkammer – an art chamber – the basement room at the Holburne Museum is crammed with scores of exquisite pieces of silverware, paintings, bronzes and ceramics.

    They include an astonishing model of a silver ship, a rare mechanical celestial globe and a bronze vessel likely to have belonged to Henry VIII.

    A bronze vessel likely to have belonged to Henry VIII. Photograph: Adrian Sherratt/The Guardian

    “It’s wonderful having pieces here that you’d usually see in places like the Met in New York or the British Museum,” said Chris Stephens, director of the Holburne.

    The treasures were collected over many decades by the Schroder family, who made their fortune as merchants and bankers, and have been loaned to the Holburne for at least 20 years.

    A £2m gallery has been created out of two store rooms to show off the objects, which have never been brought together in one place before.

    The relationship between the Holburne and the Schroders began about five years ago when the family’s art curator wondered if the museum would like to borrow a few of the family’s Renaissance paintings.

    Stephens boldly asked if they could possibly loan all of them. “I thought they’d say no but they were delighted and we turned my office into a gallery for them.”

    The family then offered the Holburne other Renaissance treasures and the idea of creating Bath’s very own kunstkammer emerged.

    Stephens said: “The key decision was to have everything in there together, not to separate the different art forms. That created the sense of the kunstkammer, the Renaissance idea in which wealthy people would bring together exotic items from around the world.”

    Among the highlights of the collection is a celestial globe commissioned in the 16th century by one of the earliest modern astronomers, Wilhelm IV of Hesse-Kassel.

    A celestial globe commissioned in the 16th century. ‘It’s like those apps of the night sky you get that tell you which stars you are looking at.’ Photograph: Adrian Sherratt/The Guardian

    When it was wound up, the globe turned to show the position of constellations. “It’s like those apps of the night sky you get that tell you which stars you are looking at,” Stephens said. “It was made in the 1570s. To have that level of precision and complexity and so many moving points is awesome.”

    The silver ship – the Schwarzenberg Nef – was created in about 1580. It is a ceremonial ewer – a pitcher or jug – that could be filled with drink through a hole in the deck with the spout concealed within the bow. “It’s miraculous,” said Stephens, pointing out details such as the rigging billowing out with the weight of a crew member and the hefty chicken on a plate in the captain’s cabin.

    It is not certain that Henry VIII handled the bronze cup that appears in another cabinet, but the signs are that it was his – one of his inventories describes such a vessel weighing exactly the same as this one.

    Most of the objects were collected in the late 19th and early 20th centuries. They have been held at various homes and offices owned by members of the Schroder family.

    The only collection comparable to Bath’s new kunstkammer, Stephens said, was the Waddesdon Bequest in the British Museum, a collection of Renaissance treasures collected by Baron Ferdinand Rothschild. “What’s really exciting is to see all these objects brought together in one place. It’s extraordinary, really.”

    The Schroder Gallery opens to the public on 10 September 2025

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  • Webb’s Search for Habitable Worlds

    Webb’s Search for Habitable Worlds

    Episode description: 

    Some exoplanets—like a gas giant with rain made of glass and 5,000-mile-per-hour winds—sound like worlds dreamed up by a science fiction writer. But they’re real. From light-years away, scientists can uncover details about planets orbiting distant stars and even ask whether some exoplanets could support life. Néstor Espinoza, an astronomer at the Space Telescope Science Institute, explains how NASA’s James Webb Space Telescope is revealing new details about exoplanets, especially rocky worlds like Earth.  

    [Music: Curiosity by SYSTEM Sounds] 

    HOST JACOB PINTER: You’re listening to NASA’s Curious Universe. I’m your host, Jacob Pinter.  

    Imagine a movie that starts like this: 

    [Muisic: Into the Void by Gage Boozan] 

    The camera pans up, and we see a spaceship. It’s sailing toward to an alien planet. The planet is cobalt blue, and it’s gigantic—bigger than any planet in our own solar system. It even has water vapor. But the explorers in the spaceship know they have to be careful because this planet’s atmosphere is basically blow-torched, with a rain of molten glass whipping in winds of more than 5,000 miles an hour. So the spaceship keeps flying, and as the movie continues we see other bizarre worlds.  

    There’s a planet that orbits a small, red star. It’s unknown if the planet has life. But if it does, that red starlight could make plants here red or purple—even black. We also glimpse a rogue planet. Somehow this one broke free from its star. It roams the galaxy alone and in perpetual darkness, never to see another sunrise.  

    Well, here’s the big plot twist: all of these planets are real. Hollywood didn’t make them up. They’re called exoplanets, a whole assortment of planets beyond our solar system, orbiting faraway stars.  

    NÉSTOR ESPINOZA:  If you go outside and you just pick a random star, chances are that star has a planet orbiting around it.  

    JACOB: Néstor Espinoza is an astronomer at the Space Telescope Science Institute. 

    NÉSTOR: If they have rocky planets, do the atmospheres look like, you know, the Earth’s or Mars or Venus, or something else completely? We have no idea. We just started exploring them. It sounded science fiction up to five years ago. Now it’s science. It’s not science fiction anymore, which is pretty fun. (laughs) 

    [Music: Move As I Move by Jan Telegra] 

    JACOB: Now, these exoplanets are too far away for our spacecraft to visit. But we have tools to study them, including the James Webb Space Telescope. Webb is a huge telescope in space, a million miles from Earth, studying the cosmos in ways that we just can’t from Earth’s surface. NASA leads the international partnership that built Webb, and the Space Telescope Science Institute handles its science and operations for NASA. That means Néstor was there in Webb’s first moments, watching engineers take Webb for a test drive. Néstor planned to use Webb’s data to prove whether exoplanet science was something he could really do with this mission. And almost instantly, he got his answer from the universe. 

    NÉSTOR: Like, I got that answer within like 15 minutes, and it was, like a complete “Yes,” and I already knew it was going to be beyond what we were expecting. The signal was just so much better, like nothing I have ever seen. From that moment, I knew, like, this is going to make everyone crazy. 

    JACOB: But getting that cosmic “yes” was only the beginning. Before it launched, scientists around the world knew what Webb was supposed to be able to do. Now they were waiting to hear how it really performed. Néstor sifted through the data, making sure Webb could capture as much detail as the world hoped. 

    NÉSTOR: Doing exoplanet science with James Webb—it’s not that straightforward. Typically, just, you know—you want to look at a star with James Webb, point at a star, you get your data, and that’s it. With exoplanet data, you have to massage the data a little bit more in order to extract the signals that you want, because they’re very tiny signals. 

    JACOB: So what makes exoplanet data so tricky? 

    [Music: Results Take Time by Paul Richard O’Brien] 

    Imagine traveling far, far away from own solar system and trying to look back at Earth. From out here, the Sun is a speck—just one of many. As we try to zoom in on the Sun, we run into a problem. It’s really bright—so much brighter than Earth. There’s just no hope of seeing the faint glow of our own home planet. But there is a way we can detect it.  

    Whenever a planet passes in front of the Sun, the Sun would appear just a little bit dimmer. And since planets radiate their own energy, when they disappear behind the Sun, we could detect that too. That tiny bit of information may not sound like much. But with careful study, scientists can use it to figure out details like a planet’s temperature and what chemicals are in its atmosphere. 

    Since the first discovery of an exoplanet in the 1990s, scientists have catalogued thousands of these planets all across our galaxy. Some of them are exotic worlds in classifications like “hot Jupiters” or “sub-Neptune” gas giants. Néstor’s research focuses on rocky planets like Earth, and if you’re thinkin’ what I’m thinkin’, the next step is to ask, Could these rocky planets also show signs of life? 

    Now, rocky planets are smaller, and that makes them harder to study. NASA is already planning for a future telescope called the Habitable Worlds Observatory, specifically designed to hunt for signs of life. In the meantime, Néstor says Webb is giving us a lot to work with. 

    JACOB: It’s a big universe out there, and there’s a lot of stuff to study. What made you say, this is the thing that I want to spend my life looking at? 

    NÉSTOR: So from when I was a kid—I think everyone has gone through this stage in which you’re like, kind of obsessed with, like, aliens, right? Either from movies and like E.T. and stuff like that. Or Star Wars, for instance—big fan of Star Wars. I remember—I think that’s when started. My mom brought me to these—for some reason, they redid the original Star Wars movies, episodes, you know, four through six, and they put it in the movies. And my mom had only one free day in her week. She worked a lot. We were basically just my mom and I. She had one day free and the week, and she said, We’re going to spend the whole day and we’re gonna see the three episodes. I was, like, eleven.  

    JACOB: Back to back to back?  

    NÉSTOR: Back to back! It was nuts. I was like, I have no idea what this movie is about. I’ll just go. And it blew my mind too, right? This thing of seeing Tattoine with two suns. What?! This thing could exist out there? You know, planets that are covered in ice, planets that are like Earth or desert planets. And I thought that was nuts. So that really kick started the thing, like that little seed, and that just grew. I never thought I could actually be a scientist. So I come from Chile. And in Chile, I don’t know—science was not a thing that I knew one could do. From TV, I thought, There’s scientists out there, but it’s done by folks at NASA and other places. But I’m, like, very far away from that. So at some point, my physics teacher just grabbed me and she told me, “You know, I’ve seen you with these bright eyes in physics, and you like this astronomy thing a lot. You know you can be a scientist, right?” This was when I was 15, and I was like, but you—really? You can get paid for, like, doing science, for, like, discovering new things? That sounded completely nuts. It’s like someone paying you to play video games, right?  

    JACOB: Right. 

    NÉSTOR: And she was like, yeah, that’s a career, and you can study it here. And that also blew my mind. I was like, what? So that’s when I figured out that I wanted to be an astronomer. So that that was the kind of the path to science and me and the path to exoplanets: physics teachers, moms, and Star Wars. 

    JACOB: So, I wonder if you can fill in the blank in this sentence for me: James Webb is teaching us _____ about exoplanets.   

    NÉSTOR: Ooh. There’s no single word, really, because it’s revolutionizing the field, really. We are starting to see maybe the first hints of evidence of atmospheres around rocky exoplanets. That was well beyond our capabilities three years ago before the launch of James Webb. This is really the next frontier. Like, if we want to get and eventually detect life out there, the first question is, Does this rocky planet have an atmosphere or not? And we can see that in our solar system, even. So, you know, Mercury has, like, a very thin, almost non-existent atmosphere. Now that’s because it’s just too close to the sun, right? Poor planet.  

    JACOB: Sure. It’s getting baked all the time.  

    NÉSTOR: Exactly. Poor planet. You can bake a pizza in the thing if you want. But then it doesn’t have a substantial atmosphere, as you know, the one we have on Earth, the one that Venus has. And stars out there are also very different. We’re used to this beautiful Sun that we see every day, but there are stars of all sizes and colors out there. And in fact, one of the things that impresses the public I think the most is, when you ask them, “What do you think is the average star out there? How does it look like?” And everyone tells you, like, Ah, it looks like the Sun. And the answer is, no, that it’s not like the Sun. It’s actually a star that is kind of 10 percent the size of the Sun. So much smaller. That makes it much redder. And then you have to be closer to that star in order to feel the same heat, because it’s smaller, it’s colder. Just like a heater. So those stars really outnumber all the rest of the stars. Those are the majority of the stars out there. So we also know that rocky planets—actually most of the rocky planets—live around these small stars. We’re trying to explore, how does the average rocky planet out there look like, which orbits these small stars? Which is very alien. Like, if you imagine the sky on these things, it’s completely different. Like, you are used to this orange star coming up. Imagine now, like a very small star coming up. It’s red—like, very, very red. So if there’s plants or something like that, on these rocks—on these planets, they might look completely different. They might absorb completely different light. They might look completely different. So figuring out these alien worlds, it’s this exciting thing that James Webb is allowing us to do. 

    JACOB: The thing that the James Webb Space Telescope, I think, is the most famous for, is that it is looking back to cosmic dawn and sort of the very first galaxies and so on. And in a lot of ways, that’s what it was designed to do. So what makes those tools that it has also really useful for studying exoplanets? 

    NÉSTOR: That’s an excellent question. So what you do is that you wait until the planet passes in front of the star from your point of view on Earth. And when the planet passes—if you’re lucky enough to see that passage—some of the starlight passes through the atmosphere of the planet and interacts with it. And those little signals are the ones that we detect with James Webb, and we’re able to extract, like some sort of, like cosmic detective part, right, which is, see which light got absorbed by the atmosphere of the planet. What we’re trying to do is see which part of that starlight is being eaten up by the molecules in the atmosphere, and different molecules like to eat different colors of light. They have different diets. So if you want to detect sodium, for instance—you know, your classic salt—you typically go to what we call optical wavelengths, which are light that we can see. Like, you and I can see. Like the color of your shirt, the color of your pants. That’s light, colors of light that we can see. But there’s many other colors out there. In particular, James Webb is what we call an infrared telescope. So it’s able to detect light, which is called infrared light. It’s past—like way redder than the reddest you could see, that we cannot see. Our eyes just can’t detect that. In the infrared, it’s exactly where the molecules that we’re most excited about—like, you know, water; carbon dioxide, which is a big thing on the rocky planets on the solar system; methane—all of these molecules, their diets of light are based on infrared light. So if you want to detect those molecules, you have to go to the infrared, right? And that’s what makes James Webb so unique. You have this big bucket of light that is very stable, and it’s able to look at exactly the colors of light on which these very important molecules are absorbing. 

    JACOB: Do you think you could take me on a little tour of some of the exoplanets you study? Like, I don’t know—can we pretend that we’re visiting? And can you tell me what we see and what it even might be like to actually go there and be on the surface or be in that atmosphere or something? 

    NÉSTOR: Totally. Yeah, I can do that. So right now we don’t have a solid detection, but I can make a case for this. I think I’m going to put as an example case one planetary system that is very dear to my heart because I’ve been working a lot on that, and it’s called the TRAPPIST-1 system.  

    [Music: Designing the Future by Carl David Harms] 

    So in order to travel to the TRAPPIST-1 system, we have to take a rocket and travel like several tens—like a couple tens of light-years. That means that if we threw a little laser, it will take, like, 20 to 30 years to get there. So the first alien thing about this system is that the star is crazy small. The star is the size of Jupiter, which is like, What?! A star can be that small? The answer is yes, they can be that small. And this system doesn’t have, you know, one, two, or three, four rocky exoplanets going around. It has seven rocky exoplanets going around the star. The other alien thing about this system is that all these planets orbit very tightly packed together. So they are in orbits that are—in an orbit that it’s smaller than the orbit of Mercury. All these seven planets are packed in an orbit that is very, very small. The other alien part about this TRAPPIST-1 system—as I told you, seven planets. Two or three of those planets are in what we call the habitable zone of this system, which is a distance from its star, in which it’s not too hot and not too cold, such that if they had atmospheres like we have on Earth, they could sustain liquid water in their surfaces. And that’s pretty exciting, because it means, you know, maybe life is there. Even more, because the system is so tightly packed, if we, you know, we were traveling to this thing, if we were to go and land on one of these planets and you looked up in the sky, you could actually see the other planets as, like, big moons. So if you have a friend in this other habitable planet, you can call them and say, “Hey, there’s a storm coming your way in like three hours,” right? Which is nuts, right? The fact that it’s so packed means that you can see the planets in the sky, the other planets in the sky. So that would be, you know, a beautiful sight, 

    JACOB: Even better than Tatooine, right?   

    NÉSTOR: Even better! Right? So that’s the whole thing with this field. It’s like, you think you have seen cool stuff in science fiction? Wait until you see the science data, right? That’s crazy! 

    JACOB: This is maybe going to ask you to take your scientist hat off and put your prediction hat on. But do you think that we’ll find signs of life on an exoplanet—I don’t know, within your lifetime?  

    NÉSTOR: I surely hope so. Signs? Yes, I think we would be able within my lifetime, especially with what we have lined up in the future. So will we be able to detect these biosignatures within my lifetime, between like 30 years, 40 years from now? I think the answer is probably yes. Will we be able to claim unambiguously that that’s aliens, like, walking on that planet? Probably not. But that’s where our scientific community gets together to try to figure out what alternative scenarios will produce this particular signal?  

    JACOB: Right.  

    NÉSTOR: And I’m very confident that we will get to very good answers with that. Like the scientific community—once it focuses on a problem, it’s very good at figuring out how to make that happen. You just mentioned, for instance, that the James Webb Space Telescope was made basically for the deep universe, trying to figure out the first galaxies and so on. So they really thought very hard and how to make that with James Webb. That is the beauty of the Habitable Worlds Observatory. It’s the first time in history of humankind that we’re saying we’re going to build a big mission, big telescope, and this is going to be based on trying to figure out this—you know, actually get the signatures of possibilities of life out there in other planets. And that’s a very exciting—again, it’s a very exciting time to be alive, to be in this era in which we are jumping into try to figure out there’s life out there. It’s like, it’s never happened before. It’s amazing.   

    JACOB: I was thinking about when you said that you grew up and didn’t know that being a scientist was an option. What advice do you have for someone who is interested in science but also may not realize that that is a real career path? 

    NÉSTOR: Yeah. So what I would say—well, first of all that it is a real career path (laughs). It’s a thing you can do. So first thing is that there’s not a linear career path. You don’t have to be like a total genius that gets into physics, top grades, and then you go and do amazing discoveries. That’s just not how it works for the majority of us. If you have an interest and an excitement for this, that is like 60, 70 percent of the way. That is, if you’re really excited about this stuff, then this is a career path for you. It’s not going to be easy, like, I can tell you that from the very beginning, but it’s going to be totally worth it. I would also say that—and this is sometimes underlooked—that, yes, your excitement and for the science and so on is really important, but also having a support system is really important. I told you that basically it was my mom and I, and that support from my mom and from my friends and so on was key for me to going through this. I mean, if it weren’t for them, I would not be here. The final advice that I have for people that want to do science is that I know people have this concept of scientists being like these white-coated folks that are just in their own labs and the whiteboard, right? And they’re alone, lone wolves.  

    JACOB: Oh yeah. I’ve seen it in the movies. 

    NÉSTOR: Right! “Eureka! I solved cancer, whatever.” That’s not how science works. Science is a very, very collaborative environment. Like, my native language is Spanish, so I had to learn how to speak English and how to communicate effectively and so on. That is also very important. If you’re hearing all of this and you say, Wow, you have to do a lot of stuff, you can do it. If you’re excited about this stuff, you can be that scientist.   

    JACOB: I have one last question for you, and then we’ll get you out of here. Since our show is called Curious Universe, what are you still curious about? 

    NÉSTOR: Well, I’m curious about these atmospheres around rocky planets, for—in particular, if the atmospheres survived around the TRAPPIST-1 exoplanets. If they did and we find the system that it’s in the habitable zone of their stars, that has an atmosphere that we can characterize in detail, that would be such an amazing moment in humanity. Like, yes, we have this chance to figure out if life might be in this planet. That is the thing that has made me the most curious. And the overreaching kind of bigger question to that is, how frequent is life out there? The reality is that we don’t know. Maybe life is like this very rare, very niche thing that we were very lucky to have here on Earth, right? In our galaxy—in the hundreds of billions of stars in our galaxy—is there another one that has life? Not only life—intelligent life, technology out there? Is there more advanced technology out there, perhaps? That has me very, very curious. That would be one of the questions if I had, like, a genie that could answer any question that would be—give me the number, right? How many? And that will solve so many questions in my mind about the universe out there.  

    [Music: Exoplanet by Jeff Penny] 

    But the very fact that we’re talking about this—and you folks are thinking, that you’re hearing this, you’re thinking, That’s an interesting question, and that’s an interesting question that we could get answered—that is amazing. Because we are not in the realm of science fiction anymore. This is science, and we are putting telescopes out there to get these answers. 

    JACOB: Néstor Espinoza is an astronomer at the Space Telescope Science Institute. And I just want to give you a quick update. Since I talked to Néstor, we have a little bit more information about TRAPPIST-1, the planetary system that Néstor is really excited about. Using the Webb telescope, scientists determined that TRAPPIST 1-d—which is one of the planets in that system—does not have an Earth-like atmosphere. We’re still learning more about that planet, and the six other rocky planets orbiting the same star.  

    If you liked this episode, you will love NASA’s documentary Cosmic Dawn. Cosmic Dawn reveals the incredible true story of the James Webb Space Telescope with never-before-seen footage from the creation, construction, and launch of this remarkable telescope. See the film at nasa.gov/cosmicdawn.  

    And you can find the latest news from the Webb telescope and much more information at nasa.gov/webb. 

    This is NASA’s Curious Universe. This episode was written and produced by Emma Brambila. Our executive producer is Katie Konans. The Curious Universe team also includes Christian Elliott and of course, Padi Boyd. Krystofer Kim designed our show art. Our theme song was composed by Matt Russo and Andrew Santaguida of SYSTEM Sounds.  

    As always, if you enjoyed this episode of NASA’s Curious Universe, please let us know. Leave us a review. Share the show with a friend. And remember, you can “follow” NASA’s Curious Universe in your favorite podcast app to get a notification each time we post a new episode 

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  • Everton fan’s relief as missing season-ticket seat issue resolved

    Everton fan’s relief as missing season-ticket seat issue resolved

    A lifelong Everton fan who found her allocated season ticket-seat at the club’s new Hill Dickinson stadium did not exist, said the club have “redeemed themselves” after resolving the issue.

    Cathy Clarke, from Liverpool, had previously described her shock when she attended the Blues’ first home game, only to discover a metal panel and railing in the space where her seat should have been.

    A week after raising the issue online, the club finally contacted her and offered her and her family a private tour of the ground and helped them to select four new seats.

    “They’ve sorted it out and we have seats together – that’s all we wanted,” she said. “We are really pleased.”

    Cathy, a season ticket-holder of 30 years, had been looking forward to the first Premier League game at Everton’s new ground since her family secured their season tickets earlier this year.

    It was the first time Cathy, her husband, her son and her nephew – who are all season ticket-holders, had been able to sit together, because it had not been possible at Goodison Park.

    But when she located the space where her seat should have been in the new stadium, there was only a metal railing – and no seat.

    In the following week, Cathy repeatedly tried to raise the issue with the club, but was unable to reach anyone who might resolve the issue.

    But after sharing her plight online, the club finally contacted the family.

    “We just wanted someone to listen to us, and Everton accepted the issue and a lack of communication,” she said.

    “They had to scour the ground – and they were able to give us a few options, and I appreciate the time they took doing that.

    “We have comparable seats in a different part of the ground but we are really happy with what we’ve got now – so we are over the moon!

    “They have redeemed themselves in our eyes. We are very happy with the outcome and I’m looking forward to sitting in my seat for the Aston Villa game.”

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  • OncLive’s August Roundup of Key FDA Approvals in Oncology: 3 Decisions to Know

    OncLive’s August Roundup of Key FDA Approvals in Oncology: 3 Decisions to Know

    FDA Approval Roundup: August

    Below is your guide to all the oncologic therapeutic options that were cleared by the FDA in August 2025. The roundup provides everything you need to know, right at your fingertips—all the topline data that supported the decisions and expert insights contextualizing what they mean for clinical practice.

    Indication: The FDA has granted accelerated approval to dordaviprone (Modeyso; formerly ONC201) for use in adult and pediatric patients at least 1 year of age with H3K27M-mutant diffuse midline glioma who have progressive disease after previous therapy. This marks the first systemic therapy approved for this biomarker-defined subset of diffuse midline glioma.

    Supporting Data: The regulatory decision was based on pooled findings from 5 open-label, nonrandomized US trials: ONC006 (NCT02525692), ONC013 (NCT03295396), ONC014 (NCT03416530), ONC018 (NCT03134131), and ONC016 (NCT05392374). Among 50 patients treated with monotherapy, the objective response rate (ORR) was 22% (95% CI, 12%-36%), with a median duration of response (DOR) of 10.3 months (95% CI, 7.3-15.2). Notably, 73% of responders maintained a response for at least 6 months, and 27% maintained a response for at least 12 months. Additional analyses showed 46.7% of evaluable patients achieved corticosteroid dose reduction of 50% or higher, and 20.6% had improved performance scores.

    Clinical Significance: Dordaviprone represents a first-in-class protease activator that establishes a long-awaited treatment option for patients with H3K27M-mutant diffuse midline glioma, a population with limited therapeutic options and poor prognosis. The decision underscores the value of biomarker testing for H3K27M mutations and opens the door for further drug development in primary brain tumors.

    In a recent interview with OncLive®, Timothy F. Cloughesy, MD, of UCLA Health Jonsson Comprehensive Cancer Center, discussed the significance of the approval: “[Diffuse midline glioma] is a particularly difficult tumor to manage. Having a therapy available is just a huge win for our field.”

    OTHER RELATED COVERAGE

    • In an episode of OncLive On Air, Patrick Y. Wen, MD, of Dana-Farber Cancer Institute and Harvard Medical School, discussed the significance of this accelerated approval across patient age groups, key efficacy and safety data that supported the decision, and the importance of biomarker testing in this population.
    • In a past interview, Yoshie Umemura, MD, of Ivy Brain Tumor Center, further discussed the development of ONC201 in H3K27M-mutant diffuse midline glioma.
    • In another OncLive On Air episode, Stephen Bagley, MD, MSCE, of Penn Medicine, spotlighted the exploration of ONC201 in the phase 3 ACTION trial (NCT05580562) in H3K27M-mutant diffuse midline gliomas and explained why clinicians should consider the trial for patients.
    • This Clinical Trial Spotlight offers additional insight into the ACTION trial, in which dordaviprone aims to improve upon standard-of-care (SOC) radiotherapy in H3K27M-mutant glioma.
    • In a past interview, Ashley Sumrall, MD, FACP, of Atrium Health Carolinas Medical Center and University of North Caroline at Chapel Hill, discussed the unmet needs for patients with gliomas, impacts that disease classification evolutions have had on diagnosis and management of the disease, and ongoing research with ONC201 in this area.
    • Ilyas Sahin, MD, of the University of Florida College of Medicine, previously shared preclinical data from a study examining the combination of milademetan and ONC201 in solid tumors with MDM2 overexpression.

    Indication: Accelerated approval was also awarded to zongertinib (Hernexeos) for the treatment of adult patients with unresectable or metastatic nonsquamous non–small cell lung cancer (NSCLC) harboring HER2 TKD-activating mutations, as detected by an FDA-approved test, after previous systemic therapy.

    Supporting Data: The decision was supported by data from the phase 1 Beamion LUNG-1 trial (NCT04886804). Among evaluable patients who had received previous platinum-based chemotherapy without prior HER2-targeted TKIs or antibody-drug conjugates (ADCs; n = 71), the ORR was 75% (95% CI, 63%-83%) with a 6-month DOR rate of 58%. In patients previously treated with chemotherapy and a HER2-targeted ADC(n = 34), the ORR was 44% (95% CI, 29%-61%) and the 6-month DOR rate was 27%. Safety was manageable, with mostly grade 1/2 treatment-related adverse effects (TRAEs; diarrhea, 51%; rash, 27%); only 1 patient experienced a grade 3 or higher TRAE. No cases of treatment-related interstitial lung disease were reported.

    Clinical Significance: Zongertinib provides an important new targeted therapy option for patients with HER2-mutant NSCLC, a population with historically limited treatment choices. The high response rates, particularly in those who had not previously received a HER2-directed agent, highlight the drug’s potential to redefine the treatment paradigm for this biomarker-driven subset. Its ongoing evaluation in the phase 3 Beamion LUNG-2 trial (NCT06151574) will clarify its role vs SOC regimens.

    “It’s the first time that we’re seeing a HER2-targeting therapy that captures these most common exon 20 insertion mutations in HER2 with a specificity that doesn’t overlap with EGFR. We don’t see a lot of the on-target [adverse] effects [AEs] on the skin or in the gastrointestinal tract,” Martin F. Dietrich, MD, PhD, of The US Oncology Network Cancer Care Centers of Brevard and University of Central Florida College of Medicine, said in a recent interview.

    ALSO APPROVED: The regulatory agency cleared the Oncomine™ Dx Target Test as a companion diagnostic for the identification of patients with unresectable or metastatic nonsquamous NSCLC whose tumors have HER2 TKD–activating mutations and could benefit from zongertinib.

    OTHER RELATED COVERAGE

    • In a recent OncLive On Air episode, Ticiana Leal, MD, of Emory University School of Medicine, and Misako Nagasaka, MD, PhD, of University of California, Irvine School of Medicine, discussed the significance of the approval, spotlighted key efficacy and safety data from Beamion LUNG-1, and unpacked where zongertinib currently fits into the paradigm.
    • In the same month, the National Comprehensive Cancer Network updated their Clinical Practice Guideline in Oncology for the treatment of patients with NSCLC to include zongertinib tablets as a preferred subsequent therapy option for patients with advanced or metastatic HER2-mutant disease who have not previously received systemic therapy.
    • Among the Clinical Trials to Watch in 2025, the phase 3 Beamion Lung-2 study (NCT06151574) is evaluating zongertinib vs with the KEYNOTE-189 (NCT02578680) regimen in patients with HER2-mutated NSCLC.
    • In a previous interview, Joshua K. Sabari, MD, of New York University Grossman School of Medicine and Perlmutter Cancer Center, spotlighted key efficacy data from Beamion LUNG-1.
    • John V. Heymach, MD, PhD, of The University of Texas MD Anderson Cancer Center, further discussed the potential role of zongertinib in HER2-mutated advanced NSCLC.
    • For a Bridging the Gaps in Lung Cancer: 6-Month Update to the 2025 Winter Lung Cancer Conference, Benjamin P. Levy, MD, and Misty D. Shields, MD, PhD, explained how emerging data on novel HER2-targeted agents, such as zongertinib, show promise for advanced NSCLC.

    Indication: The FDA cleared a 3-month, 21-mg subcutaneous depot formulation of leuprolide mesylate (Camcevi ETM) for the palliative treatment of adult patients with advanced prostate cancer.

    Supporting Data: The approval was supported by findings from a global, open-label, single-arm phase 3 trial (NCT03261999). In the intention-to-treat population (n = 144), 97.9% (95% CI, 93.5%-99.3%) of patients achieved the primary end point of sustained serum testosterone suppression to castration levels (≤50 ng/dL) by day 28 and maintained through day 168. Among evaluable patients (n = 143), 98.6% achieved castration by day 28, with a mean testosterone concentration of 17.8 ng/dL; no mean increase was observed following the second injection. Safety was manageable, with the most common AEs being hot flushing (24%), hypertension (11%), weight gain (8%), and injection site hemorrhage (6%).

    Clinical Significance: This approval expands the Camcevi portfolio by offering a shorter 3-month dosing option alongside the 6-month, 42-mg formulation that was previously approved in 2021. The availability of multiple depot schedules provides greater flexibility in androgen deprivation therapy delivery, potentially improving convenience and alignment with patient and clinician treatment preferences in advanced prostate cancer management.

    OTHER RELATED COVERAGE

    OTHER NOTEWORTHY DECISIONS

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