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User Acceptance of Remote Care Assist, a Telecare System for Home Care Among Care and Nursing Staff: Cross-Sectional Pilot Study

Background: Demographic and epidemiological changes are increasing pressure on health and long-term care systems, underscoring the need for digital innovations. Remote Care Assist is a digital system that enables home care staff to connect with care experts for exchange and support via real-time video calls. Although technology acceptance is crucial for successful implementation, little is known about how care staff’s expected benefits for care recipients influence acceptance in professional home care. Objective: This study examined predictors of user acceptance of the Remote Care Assist among home care staff, with a particular focus on the role of staff’s expectations of benefits for home care service users. Methods: Technology acceptance data were collected from staff in home care organizations in Austria and Luxembourg. Among 337 survey respondents, 139 participants who reported using Remote Care Assist at least once per month over a period of 5-6.5 months were included in the acceptance analysis (45 care experts and 94 on-site care staff). Partial least squares structural equation modeling was used to test a contextualized technology acceptance model. Results: Technology acceptance was measured by “Behavioral Intention to Use” the Remote Care Assist. “Behavioral Intention to Use” was positively associated with “Expected Benefit for Home Care Service Users” (EBC; =0.506, 95% CI 0.364 to 0.658; <.001), “Perceived Usefulness (PU)” for care staff (=0.314, 95% CI 0.151 to 0.460; <.001), and “Perceived Ease of Use” (PEOU; =0.130, 95% CI 0.038 to 0.231; =.01). “EBC” (=0.415, 95% CI 0.276 to 0.537; <.001), “Perceived Efficiency” (=0.396, 95% CI 0.267 to 0.531; <.001), and “PEOU” (=0.170, 95% CI 0.083 to 0.266; =.001) were positively associated with “PU” for care staff. “PU” also positively mediated the associations of “EBC” (=0.130, 95% CI 0.061 to 0.194; =.001) and “PEOU” (=0.053, 95% CI 0.017 to 0.101; =.02) with “Behavioral Intention to Use.” “Reliable Functionality” was not significantly associated with “PU.” Conclusions: This study suggests that the technology acceptance of a digital system for enhancing professional exchange between different staff groups in home care is shaped not only by established predictors of acceptance, such as PU and PEOU, but also by a currently neglected predictor, namely care staff’s expectations that the technology will benefit home care service users, which plays an important role in technology acceptance. In addition to usability and workflow support, successful implementation strategies for digital technologies should clearly communicate the technology’s potential benefits for care staff, care service users, and the broader care ecosystem.
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Wearable Sensor–Derived Gait Parameters Across Self-Reported Physical Activity Levels in Individuals With Knee Osteoarthritis and Healthy Controls: Pilot Cross-Sectional Validation Study

Background: Wearable inertial measurement units (IMUs) offer scalable, objective gait assessment, but detailed stride-level validation against motion capture and their ability to reflect physical activity (PA)–related gait differences in knee osteoarthritis (KOA) remain incompletely characterized. Objective: This study aimed to evaluate the technical validity of foot-mounted IMU–derived gait parameters compared with optical motion capture in individuals with KOA and healthy controls. As a secondary exploratory aim, we assessed whether IMU-derived gait parameters differed across self-reported PA levels. Methods: In this pilot cross-sectional validation study, 20 participants (KOA: n=10, 50%; healthy controls: n=10, 50%) completed 3 standardized walking conditions (self-paced, fast-paced, and endurance-equivalent). IMU-derived gait parameters were compared with motion capture at the stride level (≥5000 strides) using Pearson correlation, intraclass correlation coefficients (ICCs), mean absolute error, root mean square error, and Bland-Altman analysis. Participants completed the Stanford Brief Activity Survey to categorize PA level. Secondary analyses emphasized effect sizes and 95% CIs given the pilot design. Feasibility was assessed by protocol completion, data completeness, and tolerability. Results: IMU-derived gait speed demonstrated strong agreement with motion capture (=0.99; ICC=0.98, 95% CI 0.95‐0.99; mean absolute error=0.07 m/s; bias=0.01 m/s; 95% limits of agreement −0.14 to 0.16 m/s). Stride length and cadence showed similarly high agreement (ICC range 0.96‐0.97). All participants completed the protocol with minimal adverse events. Exploratory analyses suggested that participants reporting higher PA demonstrated directionally faster gait speed and longer stride length, with small-to-moderate effect sizes, whereas inactive participants exhibited higher stance-related rhythm parameters. Conclusions: Foot-mounted IMUs demonstrated strong stride-level agreement with motion capture across walking conditions, supporting technical validity in both KOA and healthy populations. Exploratory findings suggest that wearable-derived gait parameters may reflect activity-related differences; however, larger longitudinal studies are required to confirm these preliminary signals.
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Clinical Evaluation of the Clinical Reasoning Process of Large Language Models in Nephrology: Comparative Evaluation Study

This study evaluates the dynamic clinical reasoning of 4 leading large language models in complex nephrology cases, demonstrating that while Gemini 2.5 Pro achieved the highest reasoning scores and computational efficiency, all tested models excelled at static data synthesis but shared vulnerabilities in formulating nuanced differential diagnoses and in prospective clinical planning.
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Engineered Islets Could Eliminate Need for Immunosuppression in Type 1 Diabetes

Researchers at the University of Missouri School of Medicine have developed a method to transplant insulin-producing islets for type 1 diabetes (T1D) treatment that illuminate the need for immunosuppressive drugs. The approach, details of which are published in JCI Insight, uses ex vivo engineering of donor islets with immune-regulating molecules that reduce both innate and adaptive immune rejection after transplantation. By adding thrombomodulin (TM) and CD47 to the surface of islets, the team created a localized immune-modulating barrier that allowed transplanted cells to survive and function while still responding to glucose and producing insulin.

“Immunosuppressant medications affect and weaken the whole body, so we instead focused on how we could improve our delivery of the transplanted islets,” said study senior author Haval Shirwan, PhD, a professor of molecular microbiology and immunology at University of Missouri. “We provided islets with a protective shield consisting of two molecules that help the transplants evade rejection from the immune system, a solution that lengthens the survival of islet cells with minimal side effects.”

To create the islets, the researchers used a surface-engineering approach known as a ProtEx platform. Islets were biotinylated and then coated with streptavidin-fused immune ligands (SA-TM and SA-CD47), allowing transient display of immune-regulating proteins without genetic modification. The purpose of this design was to reduce early inflammatory injury and block immune cell activation signals that normally lead to graft destruction following transplantation.

To discover whether these engineered cells reduced immune response, the cells were testing in allogenic mouse models. The data showed that in eight of the 11 mice tested the grafts survived from 120 to 330 days without resulting immunosuppression. By comparison unmodified islets were rejected quickly in the mouse models with survival time averaging 12 days.

The team also showed that islets engineered with only one of the molecules had limited benefit, while islets with both TM and CD47 produced the strongest effect. In recipients receiving modified islets, normal blood glucose levels were achieved in more than 72% of the mice, and the grafts maintained glucose-responsive insulin secretion.

The inclusion of two different molecules on the islets served different purposes. TM was used to reduce early inflammatory and coagulation-driven damage that occurs immediately after transplantation, while CD47 signaled to immune cells to inhibit phagocytosis and dampen adaptive immune activation.

“The double-engineered islets generated a localized tolerogenic immune environment characterized by low frequencies of inflammatory innate immune cells and increased frequencies of M2 macrophages, myeloid-derived suppressor cells, and CD4+FoxP3+ T regulatory cells,” the researchers wrote.

This new approach builds on the team’s prior work which showed that single-molecule engineering of islets with either CD47 or TM could partially improve graft survival. Earlier studies demonstrated that CD47 signaling reduced immune cell–mediated killing and that TM reduced early inflammatory injury linked to coagulation and cytokine release.

Importantly, the researchers noted that the engineering process does not impair islet function, viability, or metabolic activity, which can frequently happen as a result of cell engineering. Because the proteins are displayed transiently on the islet surface rather than permanently encoded, the methods does not produce long-term genetic alteration but still reshapes early immune responses during transplantation.

The researchers said that additional work now needs to evaluate the safety and effectiveness of these cells in humans and to determine whether the approach can reduce or eliminate the need for multiple donor islet sources, which are needed in current approaches due to early immune loss. The study also suggests that the modular nature of the platform could allow additional immune-regulating molecules to be added to further improve outcomes or tailor responses in different patients.

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Human Hookworm Engineered to Produce, Secrete Anti-Tetrodotoxin Antibody Into Preclinical Host Bloodstream

Hookworms, intestinal parasites that infect hundreds of millions of people in under-resourced tropical regions around the globe, have evolved to survive inside the human gut for years, secreting molecules that enable co-existence with their hosts. Now, researchers at Washington University School of Medicine in St. Louis have harnessed that biological mechanism for potential human benefit, engineering a human hookworm parasite, Ancylostoma ceylanicum, to produce and deliver a drug within a living host.

Headed by Makedonka Mitreva, PhD, the Gordon R. Miller Professor in the John T. Milliken Department of Medicine’s Division of Infectious Diseases at WashU Medicine, the investigators report what they say is the first successful genetic modification of the human hookworm, which they engineered to produce an antibody that neutralizes tetrodotoxin (TTX), a deadly neurotoxin produced by pufferfish and other marine animals. The team’s preclinical study demonstrated that the modified hookworms colonized an animal host, and secreted the antitoxin into the host bloodstream, partially inactivating the toxin. They say the findings demonstrate that this drug production and delivery approach could potentially offer a long-term solution for multiple indications, including continuous treatment for chronic conditions, or for exposure to toxins in remote settings.

“The hookworm has spent millions of years perfecting how to assure long-term survival inside a human host and how to get molecules out of its body and into ours,” said Mitreva. “We asked: What if we could add one more molecule to the roughly 1,000 things the worm already secretes, something therapeutically useful to people? This study shows that’s not just a concept. It works.”

Mitreva and colleagues reported on their study in Nature Communications, in a paper titled “Transgenic hookworm secretes anti-tetrodotoxin human single chain antibody.” In their paper the team concluded that their achievement, “… represents a critical step towards the development of a transgenic human hookworm pharmaceutical biofactory platform with the potential to continuously, safely, and effectively deliver biologics in situ within patients.”

“Hookworms have evolved to survive for years within the human host while minimally disrupting host homeostasis, and controlled human infections with hookworms are safe and well-tolerated in clinical settings, bolstering their potential for utility as pharmaceutical biofactories,” the authors wrote.

Hookworms have already been studied as treatments for inflammatory bowel diseases such as ulcerative colitis, based on evidence that the anti-inflammatory molecules the worms secrete can dampen the immune responses that drive those conditions. Mitreva’s team set out to build on that foundation by engineering the worm to secrete a therapeutic of the researchers’ choosing, rather than relying solely on what the parasite produces naturally.

The appeal of hookworms as a long-term drug production and delivery platform stems from a quirk of their biology. When a person is infected with a controlled number of hookworm larvae, which can be administered orally as a pill or through the skin like a lotion, the worms migrate to the small intestine and take up residence, often for years. Because they cannot multiply inside the host, the number of worms stays fixed, and the infection remains controlled. If the infection ever needs to be cleared, a single dose of an oral anti-parasitic drug eliminates the hookworms within 24 hours.

To adapt hookworms for therapeutic use, Mitreva and her team drew on more than two decades of hookworm genomics research conducted at WashU Medicine. This depth of data helped them understand the organism’s biology from the cellular to the genetic level, allowing them to locate a viable site in the genome to insert the new gene carrying instructions for making the new antitoxin. The antibody selected for the team’s reported proof-of-concept study neutralizes tetrodotoxin, a paralyzing and potentially lethal toxin with no antidote.

The project presented significant technical hurdles: gene-editing tools that work in other organisms had not been adapted for hookworms, and no one had previously achieved stable genetic modification in the species. Critically, they had to ensure the insertion wouldn’t disrupt surrounding gene activity and would prompt the worm to secrete the antitoxin out into the host.

The team reported that blood collected from hamsters infected with the genetically modified hookworms partially neutralized tetrodotoxin, whereas blood from animals infected with unmodified worms had no neutralizing capability. Mitreva noted that the level of neutralization achieved in this initial study, while significant, likely represents only a fraction of what the platform can ultimately deliver. They wrote in summary “Here, we report on methodological, technical, and conceptual advances, demonstrating successful bioengineering of a human hookworm, Ancylostoma ceylanicum, to produce and secrete a human single-chain antibody, s16-HuScFv, that neutralizes tetrodotoxin (TTX).”

Several components of what she calls a “configurable chassis” are still being optimized to increase the amount of therapeutic protein produced and secreted. Because the worm resides in the gut and a substantial portion of what it secretes remains there, rather than entering the bloodstream, the researchers expect that concentrations of therapeutic molecules in the intestine may be substantially higher than what was detected in circulation in this study, making the platform suitable for gut-directed therapies.

In their paper the team wrote, “Building on the foundation that experimental human hookworm infection has been shown to be safe and well tolerated, here we present technological, methodological, and conceptual advances that have enabled the establishment of a genetically modified and tractable model system that can produce and deliver biologics … Taken together, this transgenic human hookworm platform highlights a promising approach in biotechnology that has the potential to significantly advance how we conceptualize disease treatment and prevention. Technologically, it also constitutes a notable advance in functional genomics for hookworms and helminths more broadly.”

Mitreva added, “What we demonstrated here is that the concept works end to end—you can insert a gene, the worm produces the protein, the protein gets out of the worm, and it is functionally active in the host. From that starting point, we can optimize the platform and think carefully about which diseases stand to benefit most from a delivery system that is continuous, targeted and long-lasting. That’s a fundamentally different kind of pharmaceutical biofactory platform, and we think it opens possibilities that are very hard to achieve with any other platform.”

Gut inflammatory diseases, including Crohn’s disease and ulcerative colitis, and food allergies are among the conditions Mitreva sees as strong candidates for future development. Diseases requiring small but sustained therapeutic concentrations, where compliance with repeated injections or infusions is a barrier, may also be well-suited to the platform. “Given the availability of controlled human infections, our disease-agnostic bioengineered hookworm platform offers a next-generation approach to address a suite of chronic human diseases, and with a single-dose administration, could potentially produce and deliver biologic medicines within the human host for years,” the authors wrote.

Although natural hookworm infection may cause only mild digestive symptoms in healthy adults, chronic infection with large numbers of hookworms can be dangerous for children, pregnant people and malnourished or otherwise vulnerable individuals. Infection can lead to anemia, poor growth and development, pregnancy complications and, in extreme untreated cases, heart problems or death.

This underscores the importance of keeping the infection strictly controlled for therapeutic use, Mitreva noted, which is possible because of the worms’ inability to reproduce without spending part of their life cycle in soil. “… as research progresses, it will be essential to ensure that these transgenic organisms do not have unintended ecological or human health impacts, maintaining a balance between innovation and safety,” the authors stated.

Mitreva noted that biocontainment strategies, such as engineering the worms to be unable to produce eggs, are under consideration to protect hosts and their environments as the platform advances. “Future studies can also address biocontainment of the genetically modified organism (GMO) by engineering suicide genes and/or inducible promoters into the transgene,” the team suggested.

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Small Molecules to Big Partnership: Incyte, Genesis Expand AI Collaboration to $1B+

Drug collaborations don’t always work out as planned. Sometimes they work out better.

When Incyte agreed last year to partner with artificial intelligence (AI) platform developer Genesis Molecular AI to research, discover, and develop at least two small molecule treatments, they designed a collaboration that would generate at least up to $620 million for Genesis, whose foundation models for molecular AI are designed to power agentic drug design and development.

The companies now say they made enough progress over the past 15 months to expand their AI-based drug collaboration to encompass at least five targets—with a potential payoff for Genesis that has ballooned to over $1 billion.

Behind that expansion, Incyte and Genesis say, is the promise shown so far by the two initial targets, both selected by Incyte as called for in the initial strategic collaboration. One is a “very hard-to-drug, novel target” for which the companies worked to create novel, first-in-class chemical matter, while the other is a target that other companies have sought to make druggable without success, Pablo J. Cagnoni, MD, Incyte’s president and global head of R&D, told GEN.

“Novel targets create problems for obvious reasons. You don’t have any chemical matter that you know to start with. The collaboration with Genesis has jump-started that program significantly,” Cagnoni said of the first target. “You need a crystal structure, you need to know which particular site in the target you need to bind, and then you need to start making chemical substance against it.”

“It’s easy to make chemical matter, it’s really hard to make medicines—so that was the optimization step that Genesis really helped us do,” Cagnoni added.

The second target, he explained, required not only high potency and very high selectivity, but unique pharmaceutical and pharmacokinetic properties. The companies were able to incorporate those and other properties for the target with help from Genesis’s generative and predictive AI platform, Genesis Exploration of Molecular Space (GEMS).

GEMS integrates AI and physics into models designed to generate and optimize drug molecules. GEMS’ generative diffusion model for structure prediction, Pearl—short for “Placing Every Atom in the Right Location”—was unveiled in an October 26 preprint showing it to have surpassed AlphaFold 3 and other open source baseline models on the public protein-ligand co-folding benchmark Runs N’ Poses (14.5% improvement) and the docking and molecular generation benchmark PoseBusters (14.2% improvement).

‘Substantial progress’

“By being able to optimize multiple parameters at the same time with the help of the GEMS platform and our colleagues at Genesis, we were able to really make substantial progress that was eluding us with other technology,” Cagnoni said. “The collaboration with Genesis has allowed us to make significant progress on the path to an IND. We’re not quite there, but we’re getting pretty close to that.”

The two targets, he said, represented opposite ends of the drug discovery spectrum: “For one, we had something that started to look like a drug but wasn’t good enough. For the other one, we had a great target and no drugs. So, taking a view of those two ends of the spectrum, convinced me that we had to expand this, make it as broad as possible, and that’s why we put in place a new collaboration.”

As with their initial collaboration, the companies aren’t yet revealing the targets or therapeutic areas in which they are working, though Cagnoni said they fall within one of Incyte’s three current therapeutic areas of interest: hematology, oncology, and inflammation and autoimmunity, a narrower niche within the traditional I&I (inflammation and immunology) focus area.

Through the expanded collaboration, Incyte will use its proprietary experimental data to train Genesis’ GEMS platform, with the aim of accelerating drug development across multiple programs.

Options beyond five targets

Incyte will select at least five new targets to develop with Genesis, with options to nominate additional collaboration targets over time. Incyte will have exclusive rights to develop and commercialize treatments developed through the collaboration.

“We know what properties a priori we need to optimize for, always with some caveats,” Feinberg said. “We almost always know that we need to achieve potency, selectivity, a wide variety of ADME [absorption, distribution, metabolism, and excretion] properties. Usually, in a given program, something like 30 or so different ADME assays are routinely run to some degree of frequency. This can often feel like playing whack-a-mole, instead of the serious engineering task of multi-parameter optimization.”

“Our aim,” he added, “is to render the drug discovery process as much like the latter and as little like the former.”

Incyte has agreed to pay Genesis $120 million upfront—to consist of $80 million cash and a $40 million purchase of Genesis’ equity—and unspecified recurring research funding to support AI model training and inference computing. Incyte has also agreed to pay genesis up to $232 million in payments per target, tied to achieving preclinical and clinical development, regulatory, and sales milestones.

The collaboration is the second AI-focused partnership announced by Incyte in late May. A day before the Genesis expansion announcement, Incyte said it had launched a separate strategic collaboration with Edison Scientific to employ its Kosmos AI platform for discovery and development work—namely enabling continuous learning from translational and clinical data, real-time synthesis of evidence and predictive models of therapeutic performance.

Incyte and Edison disclosed the focus of their initial project: “high-impact” use cases in target discovery and validation and translational biology, where Edison’s AI capabilities will be embedded within Incyte’s research workflows. The companies said they aim to support more efficient exploration of experimental, clinical, and biomarker data with the potential to expand across Incyte’s broader R&D organization.

As for Incyte’s collaboration with Genesis, if Genesis achieves all milestones across the five initial targets of the expanded partnership, including multiple indications and major territories, Incyte will pay the company more than $1 billion—as long as the aggregate peak annual net sales of the five products exceed specified milestones. Payments could grow to “several” billion dollars depending on how many additional collaboration targets are nominated, and how many milestones are achieved.

Genesis is also eligible to receive royalties on sales of any approved collaboration products.

Stanford spinout

Genesis spun out in 2019 from the Stanford University lab of Vijay Pande, PhD, co-founder and managing partner of the venture capital firm VZVC and a former general partner at Andreessen Horowitz (a16z) and founding general partner of its bio funds. Feinberg was a graduate student in Pande’s lab who co-invented and co-authored key peer-reviewed papers detailing deep learning technologies.

In 2020, Genesis won a $52 million Series A financing. The company has grown since then to raise $340 million, most of that consisting of $200 million Series B financing completed three years later, plus the $40 million strategic investment Incyte made in Genesis equity as part of the companies’ expanded partnership.

In addition to a16z, Genesis’ investors have included NVentures, the venture capital arm of AI chip giant Nvidia, which has expanded in recent years into biopharma among other industries.

Incyte is the fourth and latest biopharma giant to partner with Genesis on an AI-focused drug discovery and development collaboration applying GEMS. Genesis garnered $35 million upfront in launching its partnership with Gilead Sciences in 2024, and earlier announced past collaborations with Eli Lilly and Genentech, a Member of the Roche Group.

“Our mission at Genesis is to create AI technologies that enable creating drugs that otherwise would not be possible,” Evan Feinberg, PhD, Genesis’ founder and CEO, told GEN. “And thanks to working with really, really elite drug discovery teams, like what Incyte has, we’re able to work on a wide spectrum of very important problems in drug discovery.”

That work, he asserted, requires discerning the uniqueness of each potential target.

“Every target is really its own special snowflake in some way. Every drug target really entails its own challenges, oftentimes requires its own special approach,” Feinberg said. “Over the past year, we were able to work on two very different programs, that each have their own challenges, and thereby enable us to adapt and deploy our GEMS AI platform in these very different settings, bringing one of those two targets much closer to IND, and for the other target finding the first-in-class chemical matter, which was a very exciting year of work.

“Now we’re excited to address the challenges ahead with this, expanded partnership together,” Feniberg added.

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New Antibiotic, Manikomycin, Acts on Novel Ribosomal Target

Traditionally, antibiotic discovery has involved the isolation of natural products from fungi and bacteria—largely actinomycetes. However, the perception that antibiotic-producing actinomycetes have yielded all they can, with little left to give, has motivated a recent shift toward novel antibiotic discovery processes.

However, a new study from researchers at McMaster University presents the isolation of a novel antibiotic from Streptomyces rimosus that showed efficacy against multiple bacteria, including multidrug-resistant Enterobacteriaceae. In addition, the compound—known as manikomycin—is the first antibacterial agent known to target the E-site in the large ribosomal subunit, opening the door to an entirely new class of treatments.

“Not a single antibiotic prescribed in clinics today does what manikomycin does,” says Gerry Wright, PhD, professor in the department of biochemistry and biomedical sciences at McMaster University in Ontario, Canada. “Not azithromycin, not tetracycline—none of them. So, we’ve not only found a brand-new drug candidate, but we’ve also established a brand-new target in bacteria that could potentially be exploited with other new drugs.”

This work, published in Nature in the paper, “A natural depsipeptide antibiotic binds the E-site of the bacterial ribosome.”

This discovery marks the fourth new antibiotic candidate from the Wright lab in just over a year, underscoring a promising new approach to drug discovery at a time when antibiotic resistance is a growing global threat.

Given that many antibiotics used today target the ribosome, bacteria have evolved broad defense strategies against them. However, a drug targeting a different part of the ribosome will not face the same resistance mechanisms.

Manikomycin binds in the E-site of the large subunit of the bacterial ribosome, the authors write, “preventing entry of the 3′ end of the tRNA into the E-site and effectively hindering the translocation step of protein synthesis in a sequence-context-specific manner.”

“Even newly discovered drugs that attack those same old targets may quickly face resistance,” says Wright. “But, over the history of medicine, we’ve put absolutely no selective pressure on this particular target, so bacteria have no existing resistance mechanisms for manikomycin.”

The discovery of manikomycin builds on work that began more than 75 years ago, when scientists first discovered that the soil bacterium Streptomyces rimosus produced oxytetracycline, a powerful new drug that would help usher medicine into the antibiotic age.

While the breakthrough was one of several like discoveries made in the mid-1900s, S. rimosus and related bacteria have long since been abandoned as a potential source of new antibiotics.

“There is an overwhelming perception in science that these bacteria have been mined completely dry—that we’ve found all there is to find,” Wright says. “Our lab has found that this is not at all the case.”

Wright’s group, working with collaborators at the University of Illinois Chicago and the University of Hamburg in Germany, used an advanced fractionation method to uncover the new antibiotic. By filtering out oxytetracycline and other abundant compounds from the chemical mixtures produced by S. rimosus, the researchers were able to isolate scarcer molecules that had gone unnoticed over the years.

“There is likely so much still to be discovered through fractionation,” says Manpreet Kaur, PhD, a postdoctoral fellow in Wright’s lab. “Revisiting the extracts of even-well studied bacteria like Streptomyces may lead to similar discoveries in the future.”

Wright’s team is now advancing manikomycin toward clinical development. They have already shown that the new antibiotic is not toxic to human cells, and that it works well in a lab-controlled model of infection—key milestones on the early development pathway.

The team is now working on optimizing the drug’s “residency time”—or how long it stays active in the body—and have produced 60 different derivatives with plans to push the best one forward.

“We’re excited about this molecule’s potential,” Wright says. “There’s a clear path forward, and we may even be able to expand its spectrum so that it eventually affects even more bacteria, too.”

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New Tumor Survival Mechanism Revealed in Aggressive ALT Cancers

Researchers at the University of Pittsburgh have uncovered an unexpected relationship between two of the genome’s most distinct chromosomal structures, revealing how aggressive cancers that rely on the alternative lengthening of telomeres (ALT) pathway may adapt to sustain their growth.

The study, published in Nature, shows that centromeric DNA sequences and chromatin components become incorporated into telomeres in ALT-positive cancers, creating a previously unrecognized genomic signature that appears to help maintain telomere integrity. The findings provide new insight into how cancers driven by ALT evolve and may ultimately reveal vulnerabilities that could be therapeutically exploited.

“Telomeres and centromeres are not known to interact,” said senior author Roderick O’Sullivan, PhD, professor of pharmacology and chemical biology at the University of Pittsburgh and UPMC Hillman Cancer Center. “They’re not known to occupy the same regions of the genome. This is a really bizarre and unique event that is being captured in this specifically pathogenic context.”

ALT, or alternative lengthening of telomeres, is a specialized telomere maintenance mechanism used by approximately 5% to 10% of cancers. Unlike most tumors, which reactivate telomerase to extend telomeres and achieve replicative immortality, ALT-positive tumors rely on recombination-based mechanisms to lengthen chromosome ends. ALT is particularly enriched in aggressive subsets of sarcomas, gliomas, pancreatic neuroendocrine tumors, and other mesenchymal-derived cancers.

Although ALT has long been associated with genome instability and epigenetic dysregulation, researchers had not previously identified specific genomic rearrangements generated during ALT activation.

In the new study, O’Sullivan and colleagues discovered that centromeric DNA repeats become inserted into telomeric regions specifically in ALT cancer cell lines and primary pediatric neuroblastoma samples. The findings challenge a long-standing assumption that telomeres and centromeres remain physically and functionally separated within the nucleus.

“Centromeres and telomeres typically occupy exclusive nuclear territories,” said co-corresponding author Yael Nechemia-Arbely, PhD. “When we first saw the results, I was very skeptical. It took a long time and a lot of quantification and looking at it from many different angles to convince us that this was real.”

The investigators traced the phenomenon to loss of ATRX, a chromatin-remodeling protein frequently mutated in ALT-positive cancers and widely used as a biomarker of ALT status. Loss of ATRX has long been linked to telomere dysfunction, but the new work suggests it may simultaneously destabilize centromeric regions, creating conditions that enable interactions between two chromosomal domains that are normally kept apart.

“What we think is going on is that when ATRX is gone, you’ve not only destabilized telomeres, but you’ve also destabilized centromeres,” O’Sullivan said. “Now you have these two exposed domains that either through chance or necessity are interacting, and the ultimate byproduct of that transaction is the insertion of DNA repeats from the centromere into the telomere.”

The researchers found that epigenetic dysregulation caused by ATRX loss, together with DNA hypomethylation, promoted acquisition of these centromeric chromatin signatures at telomeres.

Ragini Bhargava, PhD, co-corresponding author of the study, said the findings expand current understanding of how ALT-associated telomeres evolve. “For a long time, the field viewed ALT as telomeres recombining with other telomeres,” Bhargava said. “What this study is showing is that when you lose ATRX, telomeres become prone not only to recombination within telomeres but also with other parts of the genome. One of those regions is the centromere, which should be highly protected and spatially very far away from telomeres.”

The team also demonstrated that the centromeric material incorporated into telomeres is not merely a passive byproduct of genome instability. Functional experiments showed that disrupting HJURP-mediated deposition of CENP-A compromised telomere integrity, impaired ALT activity, and triggered aberrant telomeric mitotic DNA synthesis. Those results suggest that centromeric chromatin becomes functionally integrated into the telomere maintenance machinery of ALT cancers.

“What’s interesting is that the DNA repeats from the centromere are actually doing something,” O’Sullivan said. “They’re bringing machinery to the telomere, and somehow the telomere is adapting and using that to protect itself so that the cancer cell can keep growing.”

The work points to a previously unrecognized form of interchromosomal communication that may help explain how ALT-positive tumors survive despite extensive genomic instability.

Clinically, the findings are not yet ready to translate into a therapeutic strategy, the authors cautioned. However, they may eventually provide new biomarkers or reveal dependencies unique to ALT-driven tumors.

“We have a documentation of something within the series of events that happens as these cells become highly detrimental,” O’Sullivan said. “This is a new signature of that process.”

Because proteins involved in centromere function are essential for normal cellular processes, directly targeting the newly identified pathway may prove challenging. Nevertheless, the researchers believe the discovery opens a new area of investigation into ALT biology.

“In my view, this is the beginning,” O’Sullivan said. “There could be other machinery that these centromere proteins are bringing that will provide a vulnerability that could be targeted.”

The findings suggest that aggressive ALT-positive cancers have evolved an unexpected strategy for preserving chromosome ends, co-opting centromeric DNA and chromatin to reinforce telomere function. In doing so, they reveal a previously hidden connection between two of the genome’s most fundamental structures and provide new insight into how cancer cells sustain limitless growth.

 

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Veracyte Launches Test Identifying Breast Cancer Patients Who Don’t Need Chemo

Buoyed by the remarkable results of the OPTIMA trial presented at the ASCO Annual Meeting, Veracyte this week announced the U.S. launch of the Prosigna Breast Risk of Recurrence (ROR) test, a genomic test for patients diagnosed with early-stage hormone-receptor positive (HR+) breast cancer. 

“Prosigna is the only test proven to be predictive for chemotherapy benefit in a Phase III prospective trial for patients with up to nine positive lymph nodes, including premenopausal women, all of whom were recommended to receive ovarian suppression,” Phillip G. Febbo, MD, chief scientific and medical officer at Veracyte, told Inside Precision Medicine. 

The Prosigna test determines a patient’s ROR score and estimates the 10-year probability of distant recurrence. It thus help guide treatment decisions, including predicting whether high risk patients are likely to benefit from chemotherapy or may safely achieve optimal outcomes with endocrine therapy alone, helping clinicians to make personalized care plans for their patients. 

Prosigna will be available to order starting June 8, 2026.

“Every patient diagnosed with breast cancer deserves answers they can trust about what their cancer means and what comes next,” said John Leite, PhD, chief commercial officer, Veracyte​.

“Prosigna gives patients and their oncologists a deeper understanding of their individual risk of recurrence, and, for many, whether chemotherapy will truly benefit them or whether they can safely avoid it. That kind of personalized insight can bring greater confidence and reassurance as patients navigate decisions that will shape their care and future health.”

In the U.S., more than 225,000 new HR+/HER2- breast cancer cases are diagnosed each year. When breast cancer is diagnosed early and treated appropriately, five-year survival rates reach 92%.

“For decades, clinical staging just comprised tumor size and nodal status together with pathology. This was the standard approach to determining whether patients with HR+/HER2- breast cancer need chemotherapy. Many node-positive patients routinely receive chemotherapy as standard of care,” Febbo said.

He added, “And yet, chemotherapy is likely to only benefit a relatively small fraction of these patients.” 

The OPTIMA trial uses the Prosigna test to guide therapy and testing. Those patients with a low Prosigna ROR (<60) can safely avoid chemotherapy. OPTIMA shows that tumor biology, as evaluated by the Prosigna test, provides information beyond traditional clinical factors.

Prosigna is based on the PAM50 genomic classifier, which classifies tumors into four intrinsic subtypes. Prosigna, the company said in a press release, “uniquely combines intrinsic subtypes and proliferation score with clinical pathological factors into a single comprehensive analysis to calculate a patient’s Risk of Recurrence (ROR) score and predict 10-year probability of distant recurrence.”  

Veracyte’s portfolio includes multiple cancer types, including tests for prostate cancer (Decipher Prostate), bladder cancer (Decipher Bladder and TrueMRD for muscle invasive bladder cancer monitoring), and others. The company said, “Prosigna’s intrinsic subtyping data positions us well for future expansion. While ROR scoring is specific to HR+/HER2- disease, the underlying intrinsic subtyping information spans all breast cancer types.” 

More than 225,000 new HR+/HER2- breast cancer cases are diagnosed annually, with approximately 75,000 patients having node-positive disease annually. The OPTIMA trial demonstrated that more than two-thirds of clinically high-risk patients (68%) can safely avoid chemotherapy—a significant population previously assumed to require treatment based solely on nodal status. 

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Nanotube Sensor Provides Chemical Imaging for Earlier Detection of Bladder Cancer Recurrence

Researchers at the Massachusetts Institute of Technology (MIT) have developed a catheter-based nanosensor that can detect the recurrence of bladder cancer at an earlier stage by identifying a biomarker released by tumors directly within the bladder. The technology, detailed in Nature Nanotechnology, combines carbon nanotube sensors with a rotating optical imaging device to create what researchers describe as a three-dimensional chemical imaging platform capable of locating cancer-associated biomarkers within tissue.

“It’s like a camera for molecules instead of light,” said Michael Strano, PhD, a professor of chemical engineering at MIT and senior author of the study. “If you have a billion nanosensors in an array, you can use them to make a chemical image that helps you locate their source.”

Roughly 85,000 people in the U.S. are diagnosed with bladder cancer each year, and more than half of patients experience recurrence within five years. The disease also carries among the highest lifetime treatment costs because patients require ongoing surveillance.

The new method addresses a major challenge in detecting bladder cancer recurrence, which currently relies on urinalysis to look for signs cancer has returned. Using urine for detection is hindered since biomarkers of cancer recurrence are diluted, degraded, and are often cleared shortly after they are released by the new tumor.

To address this, the MIT researchers targeted the matrix protein 22 (NMP-22), an FDA-approved biomarker for bladder cancer. While it is possible to detect NMP-22 in urine, the shortcomings of that method often mean that the cancer is often only found at a later stage of development.

To overcome this gap, the MIT team looked for a way to develop a sensor that could work inside the bladder. Their device consists of a urinary catheter coated with specialized nanosensors that detect the presence of NMP-22. A miniature rotating ball lens embedded in the catheter tip emits laser light and collects fluorescent signals generated by the nanotubes when they interact with the target biomarker.

Over the past decade, Strano’s laboratory has focused on developing carbon nanotube-based sensors that can identify specific molecules. The team customizes nanotubes for each application by applying different polymer coatings that function as “synthetic antibodies,” enabling them to bind to disease biomarkers. Previous development efforts in the lab have yielded sensors capable of detecting molecules such as hydrogen peroxide, riboflavin, and viral proteins.

For the bladder cancer application, researchers engineered a phospholipid-containing a synthetic polymer that selectively recognizes NMP-22. The project was partly motivated by earlier computational modeling conducted by the team, which suggested that placing sensors near an emerging bladder tumor could produce “a more than 50,000-fold increase in detection limit by minimizing biomarker dilution and degradation.” That finding pointed toward the potential advantages of measuring biomarkers at their source rather than after they enter urine.

In experimental testing, the platform achieved a 182-fold signal enhancement compared with biofluid sampling. The new technology was tested in multiple ways. The researchers first tested the nanosensors against six bladder cancer cell lines and healthy fibroblast cells and found distinct sensor responses associated with cancer-cell apoptosis. The team also used the chemotherapy drug gemcitabine to induce cancer cell death in vitro and monitored the resulting release of biomarkers. siRNA analysis confirmed that NMP-22 was a major contributor to the detected signals.

Researchers then evaluated the platform in porcine bladder models using a catheter coated with the specially designed nanotubes. Using a rotating ball lens system, they generated chemical maps showing the location of biomarker sources and demonstrated detection at distances up to two centimeters from the source. The researchers also reported a simulated tumor resolution of 16 square millimeters.

The chemical imaging capability is a unique attribute of the new method and the information it can provide should be very useful for treating recurrent cancer. “If you are scanning over a region of tissue, you would like to know not just that there is a signal indicating that a tumor is there, but also its location so that you can treat it or perform a biopsy,” Strano said. “Before an early-stage tumor breaks through the urothelium so that it’s visible, it’s under the surface but still emitting chemical signals that can be imaged.”

While the study focused on bladder cancer, the researchers indicated that the underlying platform may have broader applications. By replacing the nanosensors with versions designed to recognize other biomarkers, the system could potentially be adapted for additional cancers or for diseases affecting the cardiovascular or gastrointestinal systems.

“The beauty of polymer chemistry is that if we understand the molecular structures of target biomarkers and the design principles of binding sites, we can develop new sensors tailored to different diseases,” said lead author Wonjun Yim, PhD.

Future work will focus on expanding the range of detectable analytes, developing multiplexed sensor arrays, conducting omics-based biomarker validation studies, and improving optical engineering. The researchers also aim to miniaturize the imaging system and integrate the technology into cystoscopes already used in clinical practice.

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