Background: Informal caregivers of people living with dementia often experience high rates of caregiver burnout while providing care. Although there are many websites and mobile apps available to help caregivers, many do not use digital tools. The Olera platform was developed to be an easily adoptable web-based support tool, connecting caregivers with long-term services and supports, financial assistance, and educational resources. The platform was developed based on the Build-Measure-Learn framework with input from caregiver needs assessments and usability studies. Objective: This study aims to evaluate the quantitative and qualitative feedback of informal caregivers of people living with dementia on the second iteration of the Olera platform. The primary objective was to assess caregivers’ acceptance of this caregiving platform. The secondary objective was to use qualitative methods to explore (1) the study cohort’s challenges in daily caregiving to determine and compare them with prior literature, (2) their experience when using the Olera platform, and (3) their attitudes toward integrating artificial intelligence in caregiver services for future studies and platform development. Methods: Caregivers were recruited through various sources and screened for eligibility through an initial survey. Participants used the platform for 4 weeks and completed a survey with an adapted Technology Acceptance Survey (TAS) and qualitative open-ended questions at the end of the testing period. TAS responses were summarized with descriptive statistics, while ANOVAs, tests, and linear regressions were used to compare the differences in the overall TAS scores by caregiver characteristics. Qualitative feedback data on the platform’s usefulness were analyzed via a thematic analysis framework approach. Results: A total of 65 caregivers in the United States completed the study, with a mean age of 59.9 (SD 9.8) years. The majority were female (61/65, 95.3%), non-Hispanic or Latino White (45/65, 69.2%), and the adult child of their care recipient (42/65, 64.6%). Evaluation of the Olera platform showed a high acceptance rate, with each TAS item scoring above 5.0 and an overall TAS score of 5.83 (SD 0.85) out of 7. Higher platform use frequency was associated with higher TAS ratings in technology acceptance (=7.88, <.001). Thematic analyses elicited the caregiving challenges, evaluation of the Olera platform, and feedback on artificial intelligence–assisted support. Conclusions: The Olera platform is an example of a beneficial web-based tool, though key features were requested to be included in the next iteration. Additionally, data supported prior findings regarding informal caregiver challenges and the insufficiency of conventional support mechanisms, indicating a need for more innovative digital solutions. Future research and development efforts using the Build-Measure-Learn approach are necessary to further iterate the platform’s key features, enhance the tool, involve more informal caregivers in its improvements, and serve as a model for customizable, person-centered online care support. International Registered Report Identifier (IRRID): RR2-10.2196/64127
It’s not easy to transplant a whole human eye. The surgery is difficult. And the eyes themselves start to degenerate as soon as they’ve left the body. When surgeons attempted it a few years ago, the newly-transplanted eye wasn’t able to see.
But researchers believe they might have a solution: a device that maintains and revives freshly removed eyeballs using a technique called perfusion. Perfusion works by providing surgically-removed organs with some of the oxygen and nutrients they typically get when they’re inside a body. Treated eyes don’t degrade as quickly, and appear to retain the ability to transmit electrical signals, and potentially see. The device could one day make eye transplantations a viable possibility.
“It’s really cool,” says Shannon Tessier at Massachusetts General Hospital, who was not involved in the research but studies perfusion of other organs. “It could be a new frontier for retina preservation.”
Pia Cosma at the Centre for Genomic Regulation at the Barcelona Institute of Science and Technology in Spain and her colleagues have spent years developing their device. The Eye-in-a-Care-Box (ECaBox), as they call it, delivers an oxygen-rich supply of fluid through the artery that normally supplies the eye with blood.
The eye itself sits on a “bed,” and excess fluids are drained away. And while the device itself is sealed to maintain a specific temperature and pressure, a clear window on its side allows researchers to study and image the eye while it’s inside.
Cosma and her colleagues started experimenting with pig eyes, which are anatomically similar to human eyes but easier to get hold of (the team got theirs from a local slaughterhouse).
Pig eyes that are kept at room temperature outside of the device start to degenerate pretty quickly. The team found that cells in the eye shrank, and the eyes started to lose their structure. Cooling the organs didn’t help preserve them, either—the eyes degenerated within 24 hours even when they were kept at 4°C (39°F).
But eyes kept in the EcABox fared much better. 24 hours later, tests suggested the prefused eyes were “significantly more viable” than eyes that hadn’t been maintained in the device.
The perfused eyes also seemed to be able to respond to light, suggesting they might technically be able to see if they were transplanted. Untreated pig eyes lost this ability as soon as they were removed from the animal. But it came back after about 15 minutes of perfusion, according to the scientists behind the work. A few of the treated eyes kept going for 10 hours or more.
Cosma and her colleagues described the work in a preprint article that has not yet been peer reviewed, and did not want to comment on the work.
After success with the pig eyes, the team members then tested their device on human eyes. They first collected 12 eyes from six people who had died. In each case, one of each pair of eyes was put in the device, while the other was not. Again, the perfused eyes did better—and their retinas were preserved.
Cosma and her colleagues hope that their device could offer scientists a new way to study eye treatments—one that doesn’t involve experimenting on living animals. They also hope that, with some improvements, the ECaBox might provide a way to maintain and revive donated human eyes for whole-eye transplantation.
Whole-eye transplants have been attempted in the past, mostly in research animals, with limited success. In May 2023, a team at NYU Langone transplanted an eye along with part of a face to a man who had survived a high-voltage electrical accident that resulted in the loss of much of the left side of his face, including his left eye, two years earlier. Although the man recovered well, he wasn’t able to see out of the transplanted eye.
We won’t know whether eyes treated in the ECaBox could do any better until they have been transplanted, says Tessier.
In the meantime, Cosma and her colleagues plan to use a newer version of their device to collect more human eyes for research. “We are planning to develop a portable, surgery-room ECaBox to minimize [degradation] in heart-beating donor eyes, when they become available,” they write.
As the parent of two little girls, I often think about how their childhood is different from mine. The seven-year-old is learning about AI at school. The five-year-old is given internet-based homework every week. And they are both absolutely repulsed by the idea of smoking.
That was not the prevailing sentiment when I was young. My parents smoked. The customers at our family’s restaurant smoked. Cartoon characters smoked. My friends and I would buy little cigarette-box-shaped packets of sugary white sticks and pretend to smoke in the playground. Smoking was a central part of our culture.
Which is why the UK’s recent passing of a generational sales ban on tobacco products feels like such a big deal. As part of the Tobacco and Vapes Act 2026, retailers are prohibited from selling tobacco products to anyone born after January 1, 2009, in perpetuity. It doesn’t matter when those people turn 18—or 38 or 68, for that matter. It will always be illegal to sell to anyone born after that date.
This is what’s described as an “endgame” approach. While many tobacco control strategies—such as taxation or gory imagery—aim to reduce consumption, policies like the UK’s are designed to eliminate it entirely. It’s a new approach, and no one knows whether it will work.
The Maldives was the first country to implement a generational smoking ban, in November last year. It’s too soon to say how that has panned out.
Nor do we know if these laws will even last. In 2022, New Zealand passed a similar generational sales ban as part of a broader anti-smoking law. But it was never enacted—the law was repealed by a new government in February 2024.
In the UK, both major parties support the ban. But Nigel Farage, whose right-wing party has seen a recent surge in support, has promised that “the generational smoking ban will not last long if Reform gets the chance to start rebuilding our mismanaged country.”
Chris Bostic, an attorney and former policy director for the advocacy group Action on Smoking and Health, says he and his colleagues began promoting the idea of a generational ban in the United States 11 years ago. Back then, they struggled to win support, even from major health charities. “People said we were crazy … [and] that this was impossible,” he says. Opponents argued that bans would infringe on personal freedoms.
“The public health argument is: Well, what about freedom from addiction?” says Britta Matthes, a tobacco control researcher at the University of Bath in the UK. Most people who smoke began when they were teenagers, want to quit, and wish they’d never started. Tobacco is arguably the most harmful consumer product of all time. It will kill half its users who don’t quit, according to the World Health Organization.
It also kills people who don’t smoke. Of the 7 million who die from tobacco every year, 1.6 million are nonsmokers who were exposed to secondhand smoke, according to the WHO.
Generational sales bans are a long-term strategy that will only protect future smokers. Most experts agree that people who already smoke should be a main consideration for any policy, and that a multipronged approach is probably the best way to go. Janet Hoek at the University of Otago, who has explored tobacco control policies in New Zealand, believes that enforcing very low limits on nicotine levels and banning filters—an environmental scourge that does not make smoking safer, as many people believe—might be a “powerful combination,” for example.
But preventing teenagers from starting to smoke in the first place is an enticing prospect, even among the majority of people who smoke. And it’s starting to look a lot less radical.
The US has quietly been making progress on a smaller scale. Since 2021, Brookline, a town in the Boston area, has banned the sale of tobacco products to anyone born after January 1, 2000. The idea has spread. Today there are 23 towns in Massachusetts with similar bans, says Bostic. Nine towns across Minnesota, New York, and California have implemented other endgame policies.
The UK law has normalized the idea more than ever, he adds. His colleagues are already fielding calls from health agencies around the world. “People [are] saying, Wow I can’t believe the UK just did this—can we do this here?” he says.
Norms change. Like many other millennials, I vividly remember my first night out after a ban on indoor smoking took effect. My clothes didn’t stink! My hair still felt clean! And my throat wasn’t scratchy the next morning! Now that’s just normal. I hope a tobacco-free world can be the new normal for my kids.
University of Southern California (USC) researchers have paired a biological discovery with an engineering feat to create more faithful, reproducible kidney organoid structures, grown from human pluripotent stem cells (hPSCs). By mapping the developing human kidney, the scientists identified a previously unrecognized developmental axis that helps organize the kidney’s nephrons, which are their filtering units. The team then engineered Wnt-secreting “synthetic organizer” cells to recreate aspects of this developmental environment in organoids.
Their advance makes the organoids more reliable models for studying disease and evaluating potential therapies, while supporting long-term efforts to generate transplantable kidney tissue. “It is important that we’re starting to get good reproducibility from organoid models that can lead to robust preclinical models of cell function and disease to benefit patients,” said Nils Lindström, PhD, assistant professor of stem cell biology and regenerative medicine at the Keck School of Medicine of USC. Lindström is co-corresponding author of the team’s published report in Science, titled “Patterning human kidney organoids with synthetic Wnt-secreting organizers.” In their paper, the researchers reported, “Our findings link a spatial organizing geometry in the developing human kidney to controllable engineering in vitro.”
“Stem cell–derived organoids have emerged as systems for modeling organ development and generating complex tissue structures in vitro,” the authors wrote. Over the past decade, organoid work has relied on cells’ ability to self-organize into tissue-like structures, often in response to adding chemicals and proteins that act broadly in the whole organoid. “Although this capacity enables organoids to recapitulate many developmental programs, it limits experimental control over tissue architecture, often producing structures that vary between cultures and are difficult to engineer reproducibly,” the team continued. “Understanding how to impose spatial patterning in organoid systems is therefore an important challenge.”
In embryos, spatial patterning is often organized by localized signalling centers, known as developmental organizers. But how organizing geometry is controlled in the developing kidney, and whether it can be recreated in vitro, hasn’t been known.
For their reported study, the team combined spatial transcriptomics of the developing human kidney with synthetic engineering. “We mapped this organizing geometry in developing human kidneys and tested whether a minimal cue of localized WNT signaling could restore spatial control of nephron patterning in organoids,” they explained.
The project began by making tools to copy developmental signals. Postdoctoral researcher Fokion Glykofrydis, PhD, in the Morsut lab, engineered a “synthetic organizer” cell that secreted a Wnt protein that their spatial transcriptomics and other analyses indicated was involved in spatial patterning during kidney development. Graduate student Connor Fausto from the Lindström lab proposed an experiment to test how this Wnt-secreting cell would affect organoid nephrons.
The experiments revealed that the synthetic organizer enabled two key processes essential for building organs: controlling the identity of cells and influencing the shape of developing structures. The synthetic organizer serves as a localized and targeted source that secretes controllable amounts of specific Wnt proteins within the organoid itself. These are key signals that help shape the developing kidney. This creates a signaling environment much more similar to a naturally developing kidney and gives researchers a way to control where and how kidney structures form.
Co-corresponding author Leonardo Morsut, PhD, associate professor of stem cell biology and regenerative medicine, and biomedical engineering at the Keck School of Medicine and USC Viterbi School of Engineering, said, “With our approach, we are trying to control self-organization, and work with it as opposed to try to completely override it.”
Lindström expected Wnt to trigger nephrons to change their identity into cells capable of forming connections with the urine drainage system. What surprised him was that the nephrons also changed shape and elongated toward the source of the Wnt signal, which doesn’t happen when signals are delivered uniformly to the whole organoid. Compared with the developmental process seen in traditional kidney organoids, this elongation toward the Wnt source is more similar to what happens in a naturally developing kidney.
“A single, localized signal did two things at once. It changed what the cells became and physically pulled the tubules toward the source,” Lindström said. “You would not see that with a uniform chemical bath of signals.” Engineered WNT-secreting cellular organizers introduced into kidney organoids restored organizing geometry, the authors noted, “… biasing distal nephron differentiation and orienting nephron morphogenesis toward the signal source, which demonstrates that developmental signaling geometry can be reconstructed synthetically to control tissue patterning.”
The team identified a previously unrecognized axis, a direction along which the developing kidney organizes itself. Developmental biologists have long known about the nephron’s classic “proximal-distal (PD) axis,” which runs from its blood-filtering end to its urine-drainage end. The new axis is defined instead by how close each part of the nephron sits to the collecting duct, the tube system that drains urine and releases Wnt signals during development. Those signals tell the nephron what shape to take and which way to point.
“The study shows that there’s an undiscovered axis that sets up how a nephron looks and forms,” said Lindström. “It’s not every day that you find something new in human development at that level.”
Most kidney organoids contain only nephrons and lack the collecting duct that supplies this local Wnt signal, so they have no such axis and organize in a radially symmetrical pattern. By mapping how kidney cells respond to Wnt at specific locations in the developing kidney, the team recreated that environment in organoids with the synthetic organizer, producing structures that are both more developmentally faithful and more reproducible.
“Introducing tunable WNT-secreting synthetic organizers (SOs) in organoids restored canonical WNT responses, biased distal nephron differentiation, and oriented nephron morphogenesis toward the WNT source,” the investigators stated in summary. The combined results, they suggested, “… demonstrate that the spatial geometry observed in vivo can be reconstructed synthetically to control early nephron patterning and morphogenesis … Synthetic organizers provide a modular way to restore missing spatial interactions without reconstructing the entire collecting duct lineage, complementing approaches that rebuild collecting duct–to–nephron cellular interactions.”
For Morsut, the synthetic organizer is one of several tools his lab is building to control how tissues form, and the one he is most excited about, because it steers development in a way that is powerful but not intrusive. “The synthetic organizer is just a little cluster of cells that don’t build anything themselves,” said Morsut. “But they produce a powerful field that aligns the stem cells and gives them a direction.”
Synthetic organizers offer a modular strategy to reintroduce spatial signaling interactions that are often absent in conventional organoid cultures, the team suggested. “This approach should be broadly applicable to other organoid systems in which spatial signaling environments play instructive roles during development, providing a framework for linking developmental biology with the rational engineering of tissue architecture.
Aligning cells is something embryos do repeatedly as they build themselves, Morsut noted, and the study shows it can now be put to work in an engineering setting, steering the process toward a desired outcome. “At the beginning of my talks, I always show a video of embryonic development,” said Morsut. “You start from a single cell, and you get to a complete organism, and that’s as close to magic as it gets. Now, we open a possibility of controlling this magic technology for building organs. This study shows that we can do that, and I’m excited to see what others will do in other contexts.”
Elevance Health has sued the U.S. government, alleging that federal efforts to recalculate its Medicare Advantage quality ratings didn’t align with a recent court ruling, costing the health insurer $115 million.
The lawsuit, filed Wednesday in U.S. District Court for the Southern District of Georgia, represents a new tier of drama in the Medicare Advantage program, which is the alternative to traditional Medicare that is run by private insurers.
The suit centers on star ratings, which are supposed to measure the quality of a health plan’s care and customer service. Plans that meet certain quality thresholds get extra taxpayer-funded bonuses and rebates.
During the 2026 BIO International convention in San Diego, GEN sat down with Aki Ko, CEO of Elixirgen Therapeutics, to discuss the company’s multi-platform technology development efforts. The company, which was founded in 2017, is developing what it believes are breakthrough technologies that target telomere biology disorders (TBD) and aging as well as mRNA-based therapies.
Its therapy for addressing telomere biology disorders, based on its proprietary ZSCAN4 approach, is the furthest to the clinic. The biotech company will also target other aging-related diseases with the technology. Meanwhile, its efforts in the mRNA space are currently focused on Duchenne Muscular Dystrophy (DMD), although there are plans to pursue other targets there as well.
Ko founded the company with CSO Minoru Ko, MD, PhD, in 2017. Elixirgen’s 15 employees are based in Baltimore in its office space in the Johns Hopkins Medical campus, although there is no affiliation with the university. This location offers some advantages to the company, according to Ko. Specifically, “we have a wet lab and an animal lab” that has “helped us go from in vivo to in vitro very quickly to test concepts or optimize formulations and things like that.”
Recently, Elixirgen announced an option agreement with Japan’s Nippon Shinyaku focused on DMD. Under the terms of the agreement, Elixirgen will be responsible for the development of an asset dubbed EXG-7001, a locally administered, full-length dystrophin mRNA therapeutic that is currently in preclinical development for the treatment of DMD.
As part of the deal, Nippon Shinyaku will provide funding for the developmental costs of the therapy. Meanwhile, Elixirgen will receive an upfront payment and is eligible to receive additional development and sales-based milestone payments if the option were to be exercised. Also, Nippon Shinyaku may obtain exclusive worldwide rights to commercialize EXG-7001.
“Current approaches for treating DMD focus on delivering or restoring an incomplete dystrophin protein, and there still remains a significant unmet need for a therapy that can successfully deliver a full-length dystrophin protein,” Ko said in comments about the announcement. “By design, EXG-7001 has the potential to deliver the full-length, complete dystrophin protein that is missing in DMD patients, regardless of their genetic mutation.”
EXG-7001 leverages one of Elixirgen’s core technologies. The company has developed a platform for delivering mRNA-based therapies that it claims addresses the major delivery limitations of current methods. “The key features are that it is a lipid nanoparticle-free, localized mRNA therapeutics platform,” Ko explained to GEN. With this approach, “we’re avoiding some of the complications of gene therapies and delivering genes systemically by going local” and avoiding liver accumulation, which remains “a big issue” for mRNA therapeutics.
The system has two components. The first component, called RNA tether, is designed to ensure that the RNA stays in the tissue that is injected without migrating to the liver. The second component is the mRNA cargo itself, which the company calls Bobcat®mRNA. Though the lead indication for this technology is DMD, there are other diseases involving large genes that the company could target.
“We’re able to express the full length protein as mRNA as a single strand” and “it stays where you administer it, which is kind of unusual,” Ko said. Combining RNA tether and Bobcat makes it possible to express large genes and localize them to target tissues even without accumulation in the liver. Preclinical data has demonstrated its effectiveness in mice with no safety concerns associated with administration or treatment. “A full length dystrophin being given to kind of key muscles could potentially change quality of life,” particularly for the non-ambulatory population, Ko said.
Beyond EXG-7001, Elixigen has other candidates in its pipeline that are much closer to the clinic. Its lead candidate is currently in Phase I/II testing at Cincinnati Children’s Hospital Medical Center. This is an ex vivo cell therapy based on the company’s ZSCAN4 technology, which is designed to extend the telomeres of stem cells in “a controlled way” using a telomerase-independent mechanism. EXG-34217 is comprised of autologous CD34+ hematopoietic stem cells that have been treated ex vivo with EXG-001, a non-integrating, non-transmissible, temperature-sensitive Sendai virus vector encoding human ZSCAN4.
The features of that technology were identified by the company’s CSO and his team while he worked at the National Institutes of Health’s National Institute on Aging. In 2024, the U.S. Food and Drug Administration granted Rare Pediatric Disease Designation to the treatment, dubbed EXG-34217, for the treatment of patients with dyskeratosis congenita and related telomere biology disorders.
“Telomeres obviously have a relationship with aging, and there are in fact genetic diseases associated with short telomeres and telomerase mutations,” CEO Ko told GEN at BIO. People with TBDs are “born with shorter telomeres typically, but also have a mutation in their telomerase so they are not necessarily maintaining them either.” The result is a type of premature aging, so conditions like bone marrow failure and cytopenia happen earlier in the life of the patient. In fact, “bone marrow failure is one of the largest issues” affecting both adults and young children, CEO Ko said.
One treatment option in these cases is allogeneic hematopoietic stem cell transplantation (HSCT), he continued. However, people with short telomeres have more fragile genomes that are less resistant to chemotherapy and radiotherapy and are at greater risk of cancer even after HSCT treatment. In an ideal scenario, it would be possible to postpone or avoid HSCT for these patients, and the company’s ZSCAN4-based therapy could make it possible to do that.
The treatment is currently being tested in adult and pediatric patients in Cincinnati. “We started in adults because this is first-in-human,” but the disease is also very severe in children, Ko said. “Our target ultimately is to make sure as many people with TBDs can get this if they need it.” Early clinical results published in 2025 in a paper in NEJM Evidenceshow durable telomere extension overall with no treatment-related safety concerns observed over a 24-month and 5-month period after infusion. The trial has been going on for some time, and “we have a lot of longer-term data now” and are “looking toward potential accelerated approval.”
But targeting TBDs is just one indication. “Short telomeres manifest in many different ways,” Ko said. Other potential targets for the company’s technology are aging-related diseases, including things like idiopathic pulmonary fibrosis.
To date, Elixirgen has raised roughly $34 million from existing investors.
At the 74th American Society for Mass Spectrometry (ASMS) Conference in San Diego, the obvious story was hardware. Vendors showcased faster acquisition, higher sensitivity, alternative fragmentation, spatial workflows, and software ecosystems. New or highlighted platforms and workflows came from Waters, Thermo Fisher Scientific, Sciex, Bruker, Biognosys, and Evosep.
But after several days of talks, posters, hallway conversations, and interviews with senior figures in mass spectrometry (MS)-based proteomics, the deeper story was not simply that instruments are getting better. The field is beginning to look past the instrument. The mass spectrometer is still central, but the question is shifting: what has to happen around it for proteomics to become clinically useful, scalable, trusted, and routine?
Beyond the instrument
Jennifer Van Eyk, PhD, professor of cardiology, biomedical sciences, pathology, and laboratory medicine, and director of the Advanced Clinical Biosystems Research Institute at Cedars-Sinai Health Science University, put it most directly: “I think mass spec is no longer the limitation. We have the sensitivity, the throughput, and the accuracy at discovery and targeted levels.”
Jennifer Van Eyk, PhD [Gustav Ceder]
That is a remarkable statement in a field long defined by instrument performance. Van Eyk was not saying that MS innovation is finished. She pointed to continuing gains in quantitation, protein structure, conformational analysis, post-translational modifications (PTMs), top-down proteomics, and protein dynamics. But for clinical impact, she argued, the next bottlenecks are increasingly sample preparation, data analysis, standardization, harmonization, and quality control.
Joshua Coon, PhD, professor of biomolecular chemistry at the University of Wisconsin-Madison and the Pyle Chair at the Morgridge Institute for Research, saw instrument speed as the force opening new applications. Faster scanning mass analyzers are allowing deeper proteome coverage, more post-translational modification (PTM) measurements, and shorter runs. Ryan Kelly, PhD, professor of chemistry and biochemistry at Brigham Young University, framed the same shift as a throughput problem. “Now the mass spec is so fast that we need to figure out how to feed it faster,” he said. In plasma proteomics, Coon said, faster instruments, nanoparticle-based enrichment, and improved chromatography are moving the field from hundreds
Joshua Coon, PhD [Gustav Ceder]
toward thousands of detectable proteins in blood.
John R. Yates III, PhD, the John Lytton Young Endowed Chair in the department of integrative structural and computational biology at Scripps Research, highlighted electron activation dissociation methods and the possibility that high-throughput workflows could push MS deeper into plasma and population-level studies. He described targeted affinity platforms as powerful for “known knowns” because they measure targets defined in advance. “But with mass spectrometry,” he added, “you can look for unknown unknowns, which is where the gold lies.”
John R. Yates III, PhD [Gustav Ceder]
The point cuts to the heart of where the field now stands, and a recurring ASMS tension. The future of proteomics is not a choice between platforms. It is a division of labor. Targeted affinity technologies have become central to large-scale plasma proteomics and population studies. MS remains uniquely powerful for unbiased discovery, tissue proteomics, complex sample matrices, protein modifications, structural diversity, and biology that is not yet named.
From depth to trust
If the first era of modern proteomics was about seeing more, the next may be about measuring better. Devin Schweppe, PhD, assistant professor in the Department of Genome Sciences at the University of Washington, described the current moment as a “duality.” Instruments can now deliver deep coverage, and computational tools are making interpretation faster. Together, he said, they are creating “a comfort level with trusting the data.”
Devin Schweppe, PhD [Gustav Ceder]
Trust came up repeatedly. For discovery biology, a strong signal can be enough to generate a hypothesis. For clinical practice, it is not. Van Eyk said clinical-grade assays are “way harder than people think they are.” A research study can iterate. A clinical assay has to deliver the same measurement today, in five weeks, in six months, and years later. Once a test is locked, “you can’t go, ‘Oh no, we should have had this extra protein in there,’” she said. “It’s done.”
This distinction matters across assay types. Targeted MS methods such as multiple reaction monitoring (MRM) and parallel reaction monitoring (PRM) can provide absolute quantification, but only for preselected proteins. Data-independent acquisition (DIA), meanwhile, has moved discovery proteomics closer to translation by improving reproducibility and scalability. DIA is still often used for relative quantification, but its ability to capture patterns across tens or hundreds of proteins may become important as clinical decision-making moves beyond single biomarkers and reference intervals.
The field is responding to these demands. David Kotol, PhD, R&D manager at ProteomEdge, discussed an independently validated nine-protein plasma panel designed to improve emergency department triage and imaging decisions for patients with suspected venous thromboembolism, compared with D-dimer alone.
David Kotol, PhD [Gustac Ceder]
Kotol described a shift “from relative protein measurements toward robust, multiplexed absolute quantification.” He emphasized stable isotope-labeled protein standards added early in sample preparation to monitor digestion efficiency, downstream analytical variation, and multi-peptide quantification. These standards cannot remove variation introduced during sample collection, handling, or storage. But they can make the analytical workflow more transparent and transferable.
The clinical gap
Mathieu Lavallée-Adam, PhD, associate professor in the department of biochemistry, microbiology and immunology and director of the specialization in bioinformatics at the University of Ottawa, gave the least glamorous answer to what still blocks clinical translation. “My answer is going to be boring,” he said. “It’s going to be education.”
Mathieu Lavallée-Adam, PhD [Gustav Ceder]
Lavallée-Adam argued that many clinicians and biomedical researchers still do not fully understand what modern MS can do. Too often, the outside view is still: give me a list of differentially expressed proteins. But MS-based proteomics has moved beyond lists, into proteoforms, structural information, PTMs, protein dynamics, and flexible acquisition. “We’re past that now,” he said. “The main barrier is our inability to communicate the possibilities that we offer.”
Sasha Singh, PhD, assistant professor of medicine at Harvard Medical School, associate scientist at Brigham and Women’s Hospital, and director of proteomics research at the Center for Interdisciplinary Cardiovascular Sciences (CICS), described this translation role from inside a hospital environment. “That’s actually my role at the hospital,” Singh said. “I am a liaison between the technology and the application scientist.”
Sasha Singh, PhD [Gustav Ceder]
The translation is becoming harder because proteomics is diversifying. End users often need to distinguish among discovery MS, which can provide broad relative quantification; targeted MS, which can provide absolute concentrations for selected proteins; and targeted affinity proteomics, which can scale well for plasma cohorts but is limited by predefined assays and available binding reagents. Singh added that different technologies may produce profiles that do not fully overlap. Rather than treating that as a failure, she suggested it reveals something real: the circulation contains many subproteomes, and different technologies enrich different views.
AI with guardrails
No 2026 conference escapes artificial intelligence (AI), and ASMS was no exception. But the mood among the researchers was cautious rather than breathless.
Lavallée-Adam said agent-based AI was dominating conversations in his part of the field. The dream is seductive: put a sample on an instrument, ask an AI agent to maximize protein identifications or optimize a method, and let it select the best protocol. But he drew a clear line between potential and reality. “Are such agents really driving change? It’s unclear at this point,” he said. “I think it’s unproven.”
Still, AI-assisted acquisition strategies are entering workflows. Lavallée-Adam’s group works on real-time MS data acquisition, where software analyzes data as it is acquired and adapts the run to the biological question. Instead of measuring the same abundant proteins repeatedly, the system can decide it has seen enough and move on to new targets. In that sense, AI becomes less a magical oracle than an instrument assistant.
Faster instruments are generating more data, and faster analysis is needed to keep up. Schweppe also argued that open-source tools remain essential because they let laboratories build on one another’s work rather than rebuild it.
More than abundance
Much of the clinical proteomics effort is focused on plasma because it is minimally invasive and suitable for screening, longitudinal sampling, and routine monitoring. But even in blood, researchers are learning that plasma is only part of the story.
Roman Fischer, PhD, associate professor and head of the Discovery Proteomics Facility at the Target Discovery Institute, University of Oxford, pushed the conversation back toward biology. Plasma alone does not capture the full circulating system, he noted. Peripheral blood mononuclear cells, extracellular vesicles, microvesicles, and other compartments may contain disease-relevant information that conventional workflows miss. “We have to be more sophisticated in addressing the compartments of the blood,” Fischer said.
Roman Fischer, PhD [Gustav Ceder]
He also pointed to the proteoform problem. A single gene can give rise to many transcripts, isoforms, modified proteins, and glycosylated forms. These differences may affect activity, localization, disease pathways, and therapy response. Capturing that diversity is not possible with targeted affinity assays alone. It requires deeper characterization of the proteome, not only quantification.
Yates offered a clinical example. His group has been developing protein-footprinting approaches that can detect conformational changes in proteins in blood. In one transthyretin amyloid cardiomyopathy project, he said, abundance alone was not the answer. The important signal was how the protein folded or misfolded. That kind of assay moves proteomics beyond proteins going up or down, into structural disease biology.
Van Eyk’s work on remote sampling devices pointed to another future: patient-collected blood samples that make longitudinal cardiovascular studies easier, more inclusive, and better matched to real clinical questions.
In the background was a broader translational arc: discovery, verification, clinical validation, health economics, and access. Plasma proteomics highlights included Lekha Sleno, PhD, professor at Université du Québec à Montréal, who is combining nanoparticle enrichment with isotope-enabled targeted proteomics, and a CinderBio breakfast seminar featuring Fredrik Edfors, PhD, assistant professor at KTH Royal Institute of Technology and SciLifeLab, and Simion Kreimer, PhD, senior research project advisor in the Proteomics and Metabolomics Core at Cedars-Sinai Health Science University.
The seminar focused on accelerated plasma proteomics, rapid digestion workflows, stable isotope standards, Human Protein Atlas resources, and faster enzyme workflows that can reduce lead times. The common message was that sample preparation, quantification, and validation may become as decisive as instrument resolution.
The next bottleneck
ASMS 2026 was not short on technical spectacle. High-resolution instruments, electron-based fragmentation, narrow-window DIA, rapid acquisition, MS imaging, top-down workflows, and AI-enabled software all had their moment. But the most interesting conversations were less about spectacle than maturity.
Proteomics is no longer trying only to prove that it can see more. It is trying to prove that it can measure consistently, explain biology more deeply, support drug development, fit into clinical laboratories, and eventually improve patient decisions.
That means the next bottleneck is distributed across the ecosystem: sample preparation, standards, software, education, reimbursement, clinical menus, regulatory validation, open tools, and the ability to translate technical power into something a clinician can use.
Longer term, integrated proteomics, other omics, imaging, clinical data, and AI may support not only single biomarkers, but interpretable molecular patterns, longitudinal trajectories, and digital-twin-like models of patient biology.
The field spent decades making proteins visible. The next challenge is making proteomic measurements dependable enough to act on.
A set of blood-based circular RNAs (circRNAs) could change how we diagnose and monitor Alzheimer’s disease, providing a simple, noninvasive test that can detect the disease with remarkable accuracy and predict its progression years before symptoms appear.
Washington University School of Medicine researchers analyzed blood samples from 1,221 individuals, including people with Alzheimer’s disease and cognitively healthy participants, making it one of the largest investigations of blood circRNAs in Alzheimer’s to date. The findings, published in a Nature Medicine study, identified 34 circRNAs whose combined expression patterns accurately distinguished Alzheimer’s disease from healthy aging.
Unlike conventional RNA molecules, circRNAs form single-stranded closed loops that resist degradation and are abundant in the brain. Their stability and ability to cross the blood-brain barrier make them attractive candidates for blood-based biomarkers that reflect changes occurring in the brain.
The research indicated that a predictive model built from the 34 circRNAs achieved an area under the curve (AUC) of 0.945 for identifying biomarker-confirmed Alzheimer’s disease, outperforming the widely used plasma biomarker pTau217 (AUC 0.877). When circRNA measurements were combined with pTau217, diagnostic performance increased further to an AUC of 0.977.
Beyond diagnosis, the circRNA signature demonstrated exceptional ability to predict disease progression. Individuals with elevated circRNA scores were nearly three times more likely to progress to symptomatic Alzheimer’s disease than those with lower scores. The model also outperformed pTau217 in forecasting progression and remained highly specific for Alzheimer’s, showing limited predictive ability for other neurodegenerative disorders such as Parkinson’s disease, frontotemporal dementia, and dementia with Lewy bodies.
Importantly, the findings were independently replicated in two additional cohorts, including 551 participants from the Knight Alzheimer’s Disease Research Center and 1,767 participants enrolled in the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease (A4) study. This independent validation demonstrates that the circRNA signature is robust across multiple populations and study designs.
The researchers also found evidence that circRNA changes begin approximately two to four years before the onset of clinical symptoms, suggesting that these molecules may capture biological processes closely linked to the transition from silent pathology to cognitive decline. Such biomarkers could become increasingly valuable as disease-modifying therapies enter clinical practice, where monitoring ongoing neurodegeneration is just as important as detecting amyloid pathology.
The work builds on intellectual property protected by patent PCT/US2026/017857, “Blood Circular RNA as a Noninvasive Biomarker of Alzheimer’s Disease,” which Circular Genomics has licensed. The company, based in San Diego, California, is developing next-generation molecular blood biomarker diagnostics for precision neurology. The patent covers the use of blood circRNA signatures for the diagnosis and monitoring of Alzheimer’s disease and supports continued development of clinically deployable blood tests.
While the authors emphasize that larger prospective studies are still needed before widespread clinical implementation, the findings position blood circRNAs as a promising new class of biomarkers for Alzheimer’s disease. By combining high diagnostic accuracy with strong prediction of disease progression using a simple blood sample, circRNA-based testing could help identify patients earlier, improve clinical trial enrollment, and provide physicians with new tools to monitor disease over time.
Researchers at the University of Texas MD Anderson Cancer Center have identified a strategy to reverse resistance to standard treatment in BRAF-mutant advanced melanoma. Their findings, published today in Nature Communications, support using a biomarker-guided approach to improve outcomes for patients with treatment-resistant melanoma.
“Patients whose melanoma has stopped responding to standard therapies currently have very few effective treatment options,” said Vashisht Gopal Yennu Nanda, PhD, associate professor of melanoma medical oncology and translational molecular pathology at UT MD Anderson. “Our findings could help address this critical need for these patients by guiding clinicians toward combinations tailored to each individual’s tumors.”
About 50% of melanoma tumors carry BRAF mutations that drive uncontrolled tumor growth. Although the standard of care, consisting of a combination of BRAF and MEK inhibitors, is initially effective in most patients, about 80% will develop resistance within two years. In many cancers, but especially in melanoma, acquired resistance is often driven by the tumor increasing production of proteins from the BCL2 family, which block apoptosis and support the survival of cancer cells.
Yennu Nanda and colleagues tested the effects of adding a BCL2 inhibitor drug to the standard two-drug regimen in patient-derived xenograft models, which were established using melanoma tumors that had acquired resistance to standard therapy. Results showed that tumors that expressed high levels of BCL2 responded well to the triple combination, reversing resistance and inducing a complete tumor regression.
However, tumors that expressed high levels of MCL1—another protein from the BCL2 family—did not respond to this combination. In these tumors, the researchers tested an alternative treatment course adding an experimental MCL1 inhibitor to standard treatment, which successfully led to complete tumor regression.
“Targeted therapy works by shutting down the main signal driving melanoma growth, but tumors often have backup systems that keep them alive,” said Yennu Nanda. “By identifying which protein a tumor relies on for survival, we may be able to match patients to drug combinations tailored to their specific tumor biology.”
MCL1 inhibitors have previously shown promising antitumor activity, but early clinical trials flagged concerning heart-related side effects that have prevented them from moving through clinical development and receiving approval. In this study, however, the combination of an MCL1 inhibitor with standard BRAF-MEK inhibitors seemed to protect cardiac cells from the harmful effects associated with these experimental drugs.
“We did not anticipate that pairing these drugs would reduce MCL1 inhibitor toxicity,” said Michael A. Davies, MD, PhD, chair of melanoma medical oncology at UT MD Anderson. “If this finding is confirmed in clinical trials, it could give a second life to a class of drugs that has struggled to advance through development. It also reinforces that the most effective combinations are those that eliminate cancer while sparing healthy tissue.”
Building on these findings, the researchers are now working on analyzing tumor samples from a recent Phase II clinical trial in melanoma patients who received standard treatment and a BCL2 inhibitor, with the goal of studying whether MCL1 expression can predict clinical response. Down the line, their goal is to design clinical trials where melanoma patients are matched with drug combinations based on the expression of BCL2 or MCL1 biomarkers.
This is today’s edition of The Download, our weekday newsletter that provides a daily dose of what’s going on in the world of technology.
LLMs are stuck in a groupthink groove. This startup is trying to get them out.
Open up your chatbot of choice—Claude, ChatGPT, Gemini—and type “Give me a random number between 1 and 10.” You’re going to get 7. Almost always.
That won’t work every time—but if it did for you, you may wonder if I have superpowers. I don’t.
The truth is that most large language models are stuck in a rut. They are far more predictable and far less creative in their responses than you might expect. That’s fine for tasks like coding or research, but groupthink is a problem when you’re brainstorming or planning your next vacation.
The Australian startup Springboards has a solution. It built an LLM called Flint, which has been trained to come up with a wider variety of responses than mainstream LLMs to open-ended questions such as “Where should I go in Europe?”
I’ve combed the internet to find you today’s most fun/important/scary/fascinating stories about technology.
1 Scientists say they have built a cell from scratch for the first time Built with lab-made DNA, it can feed, grow, and multiply. (CNN) + It brings us closer to creating synthetic life. (Quanta) + And is arguably the greatest feat of bioengineering yet. (New Scientist $) + But also raises concerns over the dangers of synthetic biology. (NYT $) + Mirror organisms could threaten life on Earth. (MIT Technology Review)
2 OpenAI has proposed giving the Trump administration a 5% stake Talks over a public ownership deal come amid rising political pressure.(FT $) + OpenAI also proposed other US AI giants providing a 5% stake. (CNBC) + That could include Anthropic, Google, and Meta. (Bloomberg $) + President Trump says he wants the public to have a stake in AI. (BBC)
3 Singapore has seized a $42 million mansion tied to Nvidia chip smuggling It was seized as part of an investigation into alleged illegal trading. (BBC) + Days earlier, Supermicro’s Taiwan offices were raided in the probe. (FT $)
4 Anthropic’s Fable 5 is back online But queries posing security risks may be routed to less powerful models. (Axios) + Anthropic restored access yesterday after the US lifted an export ban. (BBC) + But the battle over how to tame AI has just begun. (WSJ $) + Anthropic has launched a new AI science product. (MIT Technology Review)
5 Meta is building its own cloud infrastructure business It’s exploring two ways of monetizing AI compute and models. (Bloomberg $) + One is selling access to models hosted on Meta’s infrastructure. (CNBC) + The other is selling “raw” computing power. (TechCrunch)
6 PlayStation will stop releasing games on discs in 2028 Future PS5 games will be digital-only releases. (Verge) + The news comes days after reports that GTA VI will have no disc. (BBC) + It’s put a nail in physical media’s coffin. (Wired $)
7 A low-cost Chinese AI model is catching up with US giants on their home turf Western customers are drawn to GLM-5.2’s cheap but powerful model. (Reuters $) + Chinese open-source models are spreading fast. (MIT Technology Review)
8 Google has lost its fight against a record €4.1 billion EU antitrust fine It was charged in 2018 for using Android to block rivals. (CNBC)
9 The UN has launched an “AI for Good” commission Salesforce CEO Benioff and Rwandan President Kagame will co-chair it. (Axios)
10 People prefer AI impersonators over politicians The study’s findings raise alarm bells around potential public deception. (404 Media)
Quote of the day
“If AI overdelivers, it will impact financial stability. If AI underdelivers, it will impact financial stability.”
—Torsten Slok from Apollo Global Management shares common concerns about AI at the European Central Bank’s annual conference, Reuters reports.
One More Thing
America was winning the race to find Martian life. Then China jumped in.
In July 2024, after more than three years on Mars, the Perseverance rover came across a peculiar rocky outcrop. Instead of the usual crystals or sedimentary layers, this one had spots. Those specks were the best hint yet of alien life.
NASA began a new mission to bring the rocks back to Earth to study. But now, just over a year and a half later, the project is on life support. As a result, those oh-so-promising rocks may be stuck out there forever.
This also means that, in the race to find evidence of alien life, America has effectively ceded its pole position to its greatest geopolitical rival: China. Beijing is now moving full steam ahead with its own version of NASA’s mission.
