Tag: Academic research

Posted on

StockWatch: Revolution’s Phase III Pancreatic Cancer Data Dazzles Investors, Analysts

Pancreatic cancer is one of the most difficult cancers to treat, with an overall five-year survival rate of 13%, according to the American Cancer Society, stretching from 3% for metastatic (Stage 4) to 44% for localized (Stages 1 and 2).

Dismal odds such as these explain the enthusiastic response of investors when Revolution Medicine (NASDAQ: RVMD), a developer of RAS-addicted cancer therapies, announced dazzling data from its Phase III RASolute 302 trial (NCT06625320) evaluating its once-daily oral daraxonrasib in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) who had been previously treated.

In the trial’s overall (intent-to-treat) study population, daraxonrasib showed a median overall survival (OS) of 13.2 months, nearly double the 6.7 months demonstrated for standard-of-care chemotherapy, with a hazard ratio (HR) of 0.40 (p < 0.0001). Daraxonrasib also presented what Revolution called a manageable safety profile and no new safety signals.

“These results represent a potentially transformative advance for patients and underscore daraxonrasib’s potential to redefine the treatment landscape. We are moving with urgency toward global regulatory submissions and remain committed to rapidly advancing this therapy for patients with a broad range of RAS-addicted cancers, Revolution’s CEO and chairman Mark A. Goldsmith, MD, PhD, said in a statement.

Investors and analysts largely agreed with Goldsmith. Revolution’s stock reacted to the data release by soaring 54% this past week, starting with a 41% surge that sent the share price soaring from $96.43 on April 10 to $136.30 on April 13. Since then, the stock has jumped another 12%, reaching $152.54 at Wednesday’s closing bell. Profit-taking by investors led to a 2% slide on Thursday (to $149.27) and a 0.43% dip on Friday (to $148.63).

“Our base case from stats sim [statistics simulation] was 11 vs. 7 mos, and based on our investor discussions, OS >12 months (and/or >6 mos delta vs. chemo) should drive meaningful stock upside,” Faisal Khurshid, an equity analyst with Jefferies, correctly predicted in an April 13 research note.

A “clear win” scenario, Khurshid explained, would show daraxonrasib with an OS of greater than 11 to 12 months, and/or a daraxonrasib difference vs. chemo of >4–6 months, and/or an HR of <0.5–0.6.

“Best-case outcome”

“The disclosed data materially exceeds these expectations,” Khurshid declared. “This is by any measure a best-case outcome for RVMD [emphasis in original]. Darax’s performance was roughly in line with the Ph1 experience, and chemo only slightly outperformed historical benchmarks.”

Revolution’s positive data sets the bar high for other cancer treatment developers—including Erasca (NASDAQ: ERAS), which is expected by the end of the first half to announce initial monotherapy data from its Phase I trial (NCT06983743) assessing ERAS-0015, a RAS-targeting molecule, in patients with RAS-mutant solid tumors.

Khurshid’s colleague at Jefferies, Maury Raycroft, PhD, noted Erasca has said it believes a >10% improvement in response rates in PDAC or non-small cell lung cancer compared to daraxonrasib could support ERAS-0015 as being differentiated from Revolution’s candidate, as would improvement in two or more safety/tolerability attributes, such as rash, gastrointestinal diseases, and stomatitis.

“Given the efficacy seen in ERAS’ 8 mg cohort and escalation to 40 mg, we remain (+)ve on the pot’l for stronger activity at higher doses,” Raycroft wrote in an April 13 research note. “That said, improved safety may be a key differentiator, particularly to enable combinations, especially as the competitive benchmark in PDAC continues to move higher.”

At Leerink Partners, Jonathan Chang, PhD, senior managing director, emerging oncology, and a senior research analyst, raised the firm’s 12-month share price target 28%, from $115 to $147, “to reflect greater conviction in pipeline opportunities.”

“Although RAS pathway drug development is highly competitive, we continue to believe encouraging clinical data from the innovative RAS(ON) platform, coupled with the large addressable population of RAS-dependent cancers, support a positive long-term outlook for RVMD,” Chang wrote.

Leerink colleague Andrew Berens, MD, senior managing director, targeted oncology, and a senior research analyst, observed that daraxonrasib could set a standard for positive data that several RAS-based cancer drug developers are working to improve upon, citing:

  • Adlai Nortye (NASDAQ: ANL): Its panRAS inhibitor AN9025 shares the same method of action as daraxonrasib but with potentially greater potency and durability. The company’s pipeline also includes AN4035, a panRAS antibody-drug conjugate.
  • BridgeBio Oncology Therapeutics (NASDAQ: BBOT): Its BBO-11818, a pan KRAS ON/OFF inhibitor, has shown efficacy signals in early PDAC clinical studies. “The more targeted ON/OFF approach may lead to greater potency and less toxicity.”
  • Immuneering (NASDAQ: IMRX): Its atebimetinib showed 64% OS at 12 months as a first-line pancreatic cancer treatment in updated data announced January 7.

“Not insurmountable”

“Dara[xonrasib] sets a high bar that is not insurmountable. The data for dara look encouraging, with a clear benefit over SOC [standard-of-care] chemo, but could leave room for other novel approaches to improve on efficacy and/or tolerability,” Berens wrote. “We think dara could be the first targeted therapy for RAS mutant PDAC patients and potentially become the 2L SOC, establishing RAS inhibitors as key backbone therapies in PDAC.”

That could lead to more RAS-based combination therapies, which Berens said has favorable implications for Tango Therapeutics (NASDAQ: TNGX)’s vopimetostat, an oral, selective PRMT5 inhibitor being studied in combinations with either daraxonrasib and another Revolution RAS(ON) cancer candidate, zoldonrasib, in a Phase I/II trial (NCT05732831).

Revolution said it plans to present its data at the American Society of Clinical Oncology’s 2026 ASCO Annual Meeting, set for May 29–June 2 in Chicago. Data will also be presented to regulators as Revolution files a New Drug Application (NDA) with the FDA, which has selected daraxonrasib for its Commissioner’s National Priority Voucher (CNPV).

Launched in October by FDA Commissioner Martin A. Makary, MD, CNPV is a pilot program that awards vouchers to drug developers whose work is deemed to address a health crisis in the United States, deliver more innovative cures, address unmet public health needs, and increase domestic drug manufacturing as a national security issue. In return, the vouchers entitle companies to reviews of their final applications within a target timeframe of 1–2 months rather than the current 10–12 months.

The stock surge boosted Revolution’s market capitalization (share price times the number of outstanding shares) to approximately $30 billion. That’s the midpoint of the $28 billion to $32 billion acquisition that Merck & Co. (NYSE: MRK) was pursuing for Revolution in January, according to the Financial Times. That prospective deal reportedly collapsed after the companies failed to agree on the value of daraxonrasib and Revolution’s other cancer-fighting candidates.

Merck never commented on its pursuit of Revolution, while AbbVie (NYSE: ABBV) flatly denied an earlier report that it sought to acquire the cancer drug developer. All the acquisition talk surrounding Revolution landed the company on GEN’s updated A-List Top 10 Takeover Targets of 2026, published March 9.

Cashing in

Revolution quickly cashed in on its positive data and stock surge, first proposing a $1 billion public offering of stock and debt, then doubling the size to $2 billion. The $2 billion offering consisted of concurrent public offerings of 10,563,381 shares of common stock at $142 per share (approximately $1.5 billion in gross proceeds) and $500 million of 0.50% convertible senior notes due 2033. Revolution also granted underwriters of the common stock offering a 30-day option to purchase up to an additional 1,584,506 shares.

J.P. Morgan, TD Cowen, and Guggenheim Securities are book-running managers for the stock and note offering, with LifeSci Capital acting as lead manager.

Daraxonrasib (formerly RMC-6236) is an oral RAS(ON) multi-selective, non-covalent inhibitor designed to target cancers driven by a variety of common RAS mutations, including PDAC, non-small cell lung cancer (NSCLC), and colorectal cancer. It is now under study in four global Phase III registrational trials—three in PDAC, the other in NSCLC. Daraxonrasib has been granted the FDA’s Breakthrough Therapy and Orphan Drug designations for the treatment of patients with previously treated metastatic PDAC harboring G12 mutations.

The RASolute 302 trial is a 501-patient global, randomized, registrational clinical study designed to evaluate the efficacy and safety of daraxonrasib as a monotherapy in patients with previously treated metastatic PDAC. Patients were randomized to receive either an oral dose of 300 mg daraxonrasib once daily or investigator’s choice of standard of care cytotoxic chemotherapy. The trial enrolled patients with metastatic PDAC harboring a wide range of RAS variants, including those with RAS G12 mutations (such as G12D, G12V, and G12R), as well as patients without an identified tumor RAS mutation (wild type).

Primary endpoints of RASolute 302 are OS and progression-free survival (PFS), as well as OS in patients with tumors harboring RAS G12 mutations. Secondary endpoints include PFS and OS in all enrolled patients (the intent-to-treat population) encompassing patients with and without identified tumor RAS mutations, as well as objective response rate, duration of response, and patient-reported quality of life.

Kailera makes history with $625M IPO

The “sign of life” StockWatch reported on last week when Avalyn Pharma filed paperwork for an initial public offering (IPO) is blooming this spring into a full blown comeback for IPOs, paced by what market watchers called the largest-ever public offering for a U.S. biotech—the eye-popping $625 million IPO carried out by Kailera Therapeutics—with at least two other companies submitting paperwork for filings of their own.

Kailera is a developer of therapies for obesity and weight management based on glucagon-like peptide receptor 1 (GLP-1) agonists, alone or in combination with glucose-dependent insulinotropic polypeptide (GIP) receptor agonists. The company priced an IPO on Thursday that generated $489.7 million in net proceeds through the sale of 39,062,500 shares of common stock at $16 per share—the high end of the pricing range of $14–$16.

On Kailera’s first full day of trading on Friday, investors showered the company with buys, propelling a 72% leap that sent shares to a high of $27.50 before the stock settled for a 62.5% gain, closing at an even $26.

The company earlier anticipated $458.7 million in net proceeds based on a $15 per share IPO price—though any $1 increase to the IPO price would increase what Kailera netted from the offering by an additional $31 million, according to an amended Form S-1 registration statement filed April 13 with the U.S. Securities and Exchange Commission (SEC).

Net proceeds could ultimately be even higher, since Kailera has granted its underwriters a 30-day option to purchase up to an additional 5,859,375 shares at the IPO price minus underwriting discounts and commissions. J.P. Morgan, Jefferies, Leerink Partners, TD Cowen, and Evercore ISI are joint book-running managers for the offering, with William Blair acting as lead manager.

Pipeline development

Kailera said the IPO plus its cash, cash equivalents, and marketable securities would give the company resources that it intended to spend on developing its four clinical-phase pipeline candidates, all in-licensed for $100 million upfront from Jiangsu Hengrui Pharmaceuticals (Shanghai Stock Exchange: 600276):

  • Ribupatide, the company’s lead product and a once-weekly injectable GLP-1/GIP receptor dual agonist peptide, including to fund three ongoing global Phase III KaiNETIC clinical trials into the second quarter of 2028 (more than $625 million, the estimate based on the $15 share price)
  • Oral ribupatide, a once-daily oral tablet formulation of ribupatide, including the funding of planned Phase III trials into the second quarter of 2028 (more than $150 million)
  • KAI-7535, a once-daily oral small molecule GLP-1 receptor agonist, including through the completion of a planned Phase II clinical trial (more than $50 million)
  • Other R&D activities, including development of KAI-4729, a once-weekly injectable GLP-1/GIP/glucagon receptor tri-agonist, as well as for working capital and other general corporate purposes (Remaining proceeds, not quantified)

Kailera gained exclusive global rights outside Greater China to Jiangsu Hengrui’s GLP-1 portfolio in 2024. That year, Kailera was launched with a $400 million Series A financing co-led by Atlas Venture, Bain Capital Life Sciences, and RTW Investments. Last October, Kailera garnered an additional $600 million in Series B financing led by a new investor, Bain Capital Private Equity.

“Our obesity-first approach seeks to capitalize on and improve upon proven science to advance product candidates which have the potential to maximize weight loss and address other critical needs in the current therapeutic landscape and to provide options, including oral options and alternative mechanisms, for people living with obesity no matter where they are in their treatment journey,” Kailera stated in its amended registration statement.

Kailera has adjusted the value of its cash and equivalents plus marketable securities from $652.728 million to a pro forma $1.142 billion in assets, reflecting the conversion of all outstanding preferred shares into common stock upon closing of the offering, plus an amended and restated certificate of incorporation.

Kailera’s IPO has surpassed the previous record-high among U.S. biotechs, the $604 million offering of Moderna (NASDAQ: MRNA) in December 2018, two years before the messenger RNA (mRNA) vaccine developer won FDA emergency authorization for its COVID-19 vaccine.

In the works

At least two other biotechs have filed Form S-1 registration statements for future IPOs in recent days, without disclosing how many shares they plan to raise or their offering prices.

  • Seaport Therapeutics is a developer of treatments for depression, anxiety, and other debilitating neuropsychiatric disorders based on its GlyphTM platform, a lymphatic-targeting prodrug technology designed to enhance a drug’s oral bioavailability and reduce side effects by bypassing first-pass metabolism. “Through our differentiated approach, we identify clinically validated mechanisms with established efficacy and safety profiles that have historically been limited by high first-pass metabolism, low bioavailability, and/or side effects,” Seaport stated in its Form S-1
  • Hemab Therapeutics, a developer of subcutaneous treatments for rare blood coagulation disorders, said its lead candidate, sutacimig (HMB-001), is a bispecific antibody in Phase I/II trials for the prophylactic treatment of Glanzmann thrombasthenia and Phase II studies for the prophylactic treatment of Factor VII deficiency. Another therapeutic candidate, HMB-002, is a monovalent antibody in Phase I/II trials for the subcutaneous prophylactic treatment of Von Willebrand disease. “We are building a franchise designed to address select coagulation disorders where we believe advances in biology, drug modality, and care delivery have the potential to meaningfully improve disease management,” Hemab stated in its Form S-1.

Leaders and laggards

  • MeiraGTx (NASDAQ: MGTX) shares yo-yoed, rising 26% from $8.97 to $11.29 Tuesday, after the company announced plans to present three-year data from its Phase I AQUAx trial (NCT04043104) evaluating AAV-hAQP1 in Grade 2/3 radiation-induced xerostomia. MeiraGTx reported “clinically meaningful” improvements in xerostomia symptoms, such as the average XQ score improving by 17 points (39.5%) at month 12, bilaterally treated participants reporting greater improvement than those treated unilaterally (21 points vs 13 points), and 75% of bilaterally-treated patients reporting transformative (≥10 point) improvement at month 12. After dipping 0.4% to $11.25 Wednesday, shares slumped 16% to $9.48 Thursday as MeiraGTx priced an approximately $100 million offering of 11,111,111 shares at $9 per share. Proceeds plus existing cash and cash equivalents are expected to fund commercial launches of AAV-hAQP1 and botaretigene sparoparvovec (“bota-vec”), a gene therapy for XLRP that MeiraGTx agreed to acquire from Johnson & Johnson (NYSE: JNJ) for $25 million cash upfront, a $50 million one-time payment tied to achieving specified regulatory and commercial milestones, plus a “mid-teens” royalty on global net sales starting on or after July 1, 2029.
  • Travere Therapeutics (NASDAQ: TVTX) shares soared 37% from $30.70 to $42.13 Tuesday after the rare disease drug developer won full FDA approval for Filspari® (sparsentan) in a second rare kidney disease. Filspari has become the first and only treatment for focal segmental glomerulosclerosis (FSGS), specifically to reduce proteinuria in adults and younger patients ages eight years and older with FSGS without nephrotic syndrome. Filspari won FSGS approval based on positive data from the Phase III DUPLEX trial (NCT03493685), where researchers reported a statistically significant 46% reduction in proteinuria from baseline to Week 108 in patients treated with Filspari vs. 30% for those treated with standard of care maximum labeled dose irbesartan, marketed by Sanofi (Euronext Paris: SAN) as Avapro®. Filspari first won FDA approval in 2023 to slow kidney function decline in adults with primary immunoglobulin A nephropathy (IgAN) who are at risk for disease progression.

The post StockWatch: Revolution’s Phase III Pancreatic Cancer Data Dazzles Investors, Analysts appeared first on GEN – Genetic Engineering and Biotechnology News.

Posted on

10x Genomics Unveils Atera Spatial Platform at AACR Meeting

The genomics community’s long wait for 10x Genomics’ highly anticipated news is finally over. On Saturday night, at the Hard Rock Café Hotel in San Diego—across the street from the American Association for Cancer Research (AACR) conference—the company hosted the “Impossible” party to announce its new spatial instrument—the Atera.

Serge Saxonov, PhD, CEO of 10x Genomics, walking onto the stage to thunderous applause, noted that there is “a gap between what we need to see and what we have been able to measure.” The Atera, which enables whole-transcriptome spatial biology at scale, “obliterates the typical trade offs” that come with existing spatial tools, he said.

“This is the biggest launch in our history. I am the most excited I’ve ever been about any product, or any product category, across the board,” Saxonov told GEN. “It has been a long time in development, and it is what we have known the world needs for a long time. I think it will fundamentally change how we measure and understand biology, and it really puts research on a new trajectory. It is really exciting to be at a place now where we can deliver it to the world.”

Nuts and bolts

Atera offers more plex, throughput, and sensitivity than 10x Genomics’ Xenium—enabling whole-transcriptome at scale. More specifically, when compared to Xenium, Atera has four times the throughput, six times higher plex capacity for targeted assays, 3.6x higher plex, and 2–3x sensitivity for whole transcriptome assays.

10x Genomics Atera
10x Genomics Atera

The price for Atera is $495,000, and the instrument measures roughly 53” x 36” x 64” or (4.42 ft × 3 ft × 5.33 ft). Orders are currently being taken, and the instrument will be available in the second half of this year.

The instrument can run up to 800 1 cm2 whole transcriptome samples (FFPE and fresh frozen) per year, with flexible run configurations, and a greater than 5 cm² imageable area per slide (for greater than 2,000 mm² total tissue per run when using all four slides.)

There are 18,000-genes on the Atera WTA (whole transcriptome) with stackable customization of 1,000-gene Atera Select panels available now, and optional stacking of up to three 1,000-gene panels coming in the future.

“Spatial genomics with whole-transcriptome profiling capabilities is the ultimate approach to measure single cells in their tissue context,” Holger Heyn, PhD, ICREA professor at the Centro Nacional de Análisis Genómico (CNAG) and member of the Human Cell Atlas, added. “All other lower-plexity approaches have been just a warm-up phase leading to this application.”

Jasmine Plummer, PhD, associate member of the St. Jude Faculty and director of the Center for Spatial OMICs points out that the whole transcriptome, while exciting, can bring a big “sticker shock” for many researchers because it will require a lot more probes in contrast to a sequencing-based platform, where a library accesses all of the genes.

The instrument uses standard glass microscopy slides, which is exciting to Plummer. In the past, she said, slides have posed a challenge when coordinating with other researchers, and using regular slides will be more “pathology friendly.”

An end to tradeoffs? 

Existing spatial technologies, which are still relatively nascent in genomics, have been constrained by tradeoffs between plex, resolution, and throughput. Researchers have had to make choices and prioritize.

“In general, with the landscape as it is today, there is a tradeoff,” Nick Banovich, PhD, VP of scientific development at TGen, and professor of bioinnovation and genome sciences division and director of the Center for Spatial Multi-Omics (COSMO), told GEN. “The closer you walk toward whole transcriptome, the lower the per gene sensitivity.”

“The most exciting thing [about Atara],” he continued, “is that there is still quite good sensitivity with whole transcriptome breadth. That’s the huge advantage of this system; there is no tradeoff anymore.”

However, this launch comes just over three years after Xenium’s launch. Purchasing a new instrument so soon may pose a challenge. Plummer notes: “In this economy, with the uncertainty of scientific funding, it is concerning to ask customers—many of whom just landed a machine—to spend another several hundred thousand dollars.”

Why AACR?

Oncology is one of the most exciting, most promising applications of spatial, especially in the near term, noted Saxonov. This is, in large part, because the work exists across the spectrum—from basic discovery to translation to clinical applications. Spatial is unambiguously important, he asserted.

Unveiling at AACR “just made a lot of sense.”

In addition to the party, the company will host a digital launch event on Tuesday, April 21. Within the AACR program, a presentation from the German Cancer Research Center (DKFZ) will include data generated on the platform, highlighting Atera’s ability to uncover cancer biology not accessible with legacy approaches. Researchers distinguished multiple malignant and stem cell states across disease stages, within a single colorectal tumor sample, and mapped how these populations interact with the surrounding immune microenvironment. The data reveal a more complex immune landscape that could inform future therapeutic strategies and drug development. In addition, two posters (#7116, #6216) will include data from Atera.

The future

10x Genomics said that Atera will play a role in advancing large data studies. For example, the company noted that Atera will enable the goal of the Human Cell Atlas (HCA) as it continues its mission to map every cell type in the human body.

“With the Human Cell Atlas entering its next phase of generating spatially resolved atlases, whole-transcriptome approaches will be the workhorse for data generation,” Heyn told GEN.

“I am excited to see the Atara platform being launched now,” he added. “It is very timely as we ramp up production for the Human Cell Atlas 2.0 phase.”

Atera’s future

The company presented a roadmap with future plans at the AACR event, highlighting spatial proteomics, automation, base by base sequencing (a de novo sequencing assay) and software improvements.

Atera, Saxonov told GEN, is a fundamental platform that the company will continue enabling. It lays the groundwork for the next decade of research and work. This point in time, he said, feels similar to the early days of next generation sequencing (NGS). And although the company will continue to develop its other platforms and product lines, Atera has “massive amounts of headroom to keep building on top of it. It is the convergence of all these different technology stacks and different fields onto one.”

“What the platform can do right out of the gate is exciting. And all the things that it can do in the future will be really, really exciting,” he asserted.

The post 10x Genomics Unveils Atera Spatial Platform at AACR Meeting appeared first on GEN – Genetic Engineering and Biotechnology News.

Posted on

RSV Vaccination in Late Pregnancy Reduces Infant Hospitalizations

Results from a large U.K. study show that vaccination against respiratory syncytial virus (RSV) at least two weeks before giving birth has a significant protective effect against hospitalization for this infection in babies born to these mothers.

As reported at the congress of the European Society of Clinical Microbiology and Infectious Diseases in Munich this week, the researchers found that vaccination reduced a baby’s risk of being admitted to hospital with serious RSV lung infections in the first months of life by around 80% versus no vaccination.

Notably, the benefit from vaccination increased if mothers were vaccinated at least four weeks before the baby was born, although even if they received the vaccine 10-13 days before delivery the risk of hospitalization for their babies in subsequent months still went down by 50%.

“As the largest study to date examining the impact of this vaccine on infant hospitalization, these findings provide robust evidence that vaccination offers substantial protection against severe illness in young infants,” commented lead author and UK Health Security Agency epidemiologist Matt Wilson in a press statement.

“We found a clear relationship between timing and protection, with effectiveness increasing as the interval between vaccination and birth lengthens, reaching close to 85% when vaccination occurs at least four weeks before delivery.”

After a national RSV vaccination campaign for pregnant women began in the U.K. in September 2024, around 55% coverage was reached by December of the same year. In total, 289,399 infants born between September 2024 and March 2025 were included in the cohort of which around 55% were vaccinated via maternal exposure. Vaccination was considered ‘full’ if mothers received it at least 14 days before giving birth.

The team followed up the babies for around three months after birth to monitor for RSV-associated lower respiratory tract infections requiring hospitalization, which affected a total of 4,594 babies.

Overall, unvaccinated babies had around seven times the rate of RSV‑related hospital admissions compared with babies whose mothers were vaccinated during pregnancy. Preterm infants also benefitted significantly from the vaccine.

“These findings are particularly important for preterm infants, who are among the most vulnerable to severe RSV infection,” said Wilson. “With sufficient time between vaccination and birth, we saw good levels of protection in these babies. Giving the vaccination early in the third trimester, as recommended by the World Health Organization, could protect most preterm infants.”

The post RSV Vaccination in Late Pregnancy Reduces Infant Hospitalizations appeared first on Inside Precision Medicine.

Posted on

Tunneling Neurons in Adult Bird Brains Provide New Insights into Neurogenesis

Despite its small size—it could sit in the palm of your hand—the zebra finch is a remarkable learner. A songbird native to Australia, it’s renowned for its ability to pick up new songs. That talent has made it a favorite of scientists studying how animal brains imprint new skills, particularly vocal learning, or the capacity to perfect new sounds.

Researchers at Boston University, working with scientists at the Max Planck Institute for Biological Intelligence and the MRC Laboratory of Molecular Biology, have now discovered another quirk to the zebra finch brain—one that could also have implications for understanding our own. In a study that looked at the bird’s brain in unprecedented detail, the scientists uncovered new insights into neurogenesis—the birth, migration, and maturation of neurons—that may help the brain learn, add new skills, and restore and repair itself.

Observing the finch brain using a high-powered microscope, the researchers watched as new neurons made their way through the brain en route to bolstering existing circuits and connections. The expectation was that these neurons would step around established brain structures, including more mature brain cells, to better preserve them. Instead, the investigators saw the neurons tunnel right through. According to the BU-led team, the findings could help explain human vulnerability to a range of brain disorders. The researchers also noted that cell tunneling is used by some metastatic cancer cells.

“We found that in songbirds, new neurons in the adult brain behave like explorers forging a path through a dense jungle,” said Benjamin Scott, PhD, a BU College of Arts & Sciences assistant professor of psychological and brain sciences and the study’s corresponding author. That may help them learn new things or repair damage, but it could come with a cost to existing cells and memories—and that might be why neurogenesis is, in humans, something that doesn’t seem to extend beyond the womb. “This potentially disruptive behavior may help explain why humans and other mammals have limited capacity to regenerate brain tissue in adulthood,” commented Scott, “leaving us more vulnerable to neurodegenerative disorders such as Alzheimer’s disease.”

Scott is senior and corresponding author of the team’s published paper in Current Biology, titled “Songbird connectome reveals tunneling of migratory neurons in the adult striatum,” in which the researchers commented that their collective findings “… suggest that migrating neurons may physically reshape the mature circuit to reach their targets, revealing an unexpected degree of structural and functional plasticity in the adult brain.”

At birth our brains have pretty much all the neurons they are ever going to have. Other organs—from your skin to your heart—might get frequent cell updates, but the brain is working on version 1.0. That’s true for most mammals, but not for fish, reptiles, and birds—their brains get a regular refresh.

“This raises two questions,” said Scott, who’s also affiliated with BU’s centers for neurophotonics, photonics, and systems neuroscience. “Why do other species have high rates of neurogenesis throughout life and why is it so restricted in humans? And is there something we can learn from their biology that we might be able to harness in future?”

Scott typically studies the neural circuits that control behavior in humans and other mammals, but chose the zebra finch to investigate neurogenesis because it has a reputation as a champion species—it’s really good at generating new neurons. “Songbirds are valuable model organisms for the study of neuron migration in the adult brain,” the authors wrote. “In these species, new neurons integrate into brain regions that control complex learned behaviors, where they establish synapses with mature neurons and respond to sensory stimuli.”

However, the team pointed out, a key question is how these new neurons interact with mature circuit structures in the brain. “It is not known whether neurons pursue migratory routes that flexibly avoid these structural obstacles or deform surrounding tissue to reach their targets,” they wrote. “While prior studies have examined the molecular mechanisms and functional consequences of adult neurogenesis, few have investigated the physical interactions between migrating neurons and their surrounding microenvironment.”

For their newly reported study the team used electron microscopy (EM)-based connectomics to examine how migrating neurons interact with mature circuit elements. “We applied a new tool to study this process [neurogenesis] called electron microscopy-based connectomics—basically a really high-powered microscope—to image these cells at a very high resolution,” Scott explained. “Our first hope was just to say, what does this look like at a detail we couldn’t see before?”

Their resulting data revealed intricate interactions between migratory neurons in the adult striatum and their environment, but also showed up the tunneling neurons. “Our findings support a model in which migrating neurons disperse throughout dense neural tissue in multiple directions, making various contacts with surrounding structures,” the team wrote in summary. “In addition, our data reveal a previously undescribed form of neuron migration in which new neurons cause deformities in nearby neurons and synapses.”

The authors say that, to their knowledge, tunneling migration by neurons hasn’t previously been reported in the vertebrate nervous system. It’s possible that this is due to the constraints of study methods used, but it’s also possible that tunneling is a specialization of neurogenesis in birds.

If these new neurons are deforming brain tissue, commented Scott, are they also disrupting memories along the way? And, if neurogenesis comes with a cost, how does that balance against the brain’s capacity for learning new things and repairing after injury? And as the authors pointed out, “Interestingly, tunneling-like behavior has been described in metastatic cancer cells, which navigate confined spaces by actively deforming their microenvironments. Tunneling may therefore reflect a conserved strategy adopted by specialized migratory cell types in dense tissues.”

Scott has two—as yet untested—hypotheses for what the findings might mean for the human brain. The first is that our brains evolved to limit neurogenesis after birth as a form of protection—a way of making sure determined neurons couldn’t barge through mature connections and damage memory storage. “There is an alternative framing that is more optimistic,” he also noted. “Our discovery of tunneling shows how cells can move without glia scaffolds.”

These are the structures that operate as highways for migrating neurons. “Most glia scaffolds are lost in humans after birth, and this loss was thought to be an obstacle for neurogenesis in the adult brain,” says Scott. “However, our work shows that new neurons in the bird do not need this glia scaffold. This is exciting because it means that brain repair may not require specialized glia scaffolds.” That opens the door for scientists to explore potential stem-cell therapies that would spark neurogenesis in humans.

In summary, the authors wrote, “These results reveal the value of applying EM connectomics to adult neurogenesis and suggest that migratory neurons may dramatically perturb the existing functional circuits as they migrate and integrate. Furthermore, they reveal the remarkable structural flexibility of mature neural circuits.”

In current studies, Scott and the team in his BU Laboratory of Comparative Cognition are digging into the biology driving neurogenesis to uncover which genes are regulating the process. Much of the work merges ideas and tools from biomedical engineering and neuroethology, the study of the mechanisms underpinning animal behavior.

“Right now, we’re using a technique called single-cell RNA sequencing to identify genes that are expressed by these new neurons as they migrate,” said Scott. “We want to know what other cells they’re talking to as they move and how they are speaking to these different cells.” That’ll help them figure out whether neurons warn other cells they’re traveling through and how they know where to stop and integrate with a current circuit.

“We share a lot with our animal relatives on this planet,” noted Scott. And, while the term “bird brain” might be an insult, by learning more about the biology of songbird brains, he says, we could learn some remarkable things about our own.

The post Tunneling Neurons in Adult Bird Brains Provide New Insights into Neurogenesis appeared first on GEN – Genetic Engineering and Biotechnology News.

Posted on

Use of Wearable Devices to Augment Traditional Measurements of Postoperative Outcomes Following Total Joint Arthroplasty: Systematic Review

Background: Wearable devices enabling remote monitoring by surgeons of their patients have gained prominence around total joint arthroplasty (TJA), offering continuous patient data to identify those not meeting postoperative goals, thereby facilitating timely interventions. While multiple studies highlight the utility of these devices in tracking postoperative progress, a standardized approach to their application is lacking. This review aims to synthesize existing literature on the use of wearable device-tracked activity for monitoring TJA outcomes. Objective: We examined the current literature to evaluate how wearable devices are used in monitoring and improving patient rehabilitation and outcomes following TJA. Methods: A systematic review was conducted following Cochrane methodology. A literature search of all available literature was performed in April 2024 and identified 102 studies to undergo full-text review. Systematic reviews, duplicate papers, and theoretical papers were excluded. Ultimately, 35 studies met the selection criteria. Results: The review revealed that 32 of 35 (91.4%) studies used wearable devices to monitor step counts. A total of 21 (60%) studies incorporated joint-specific patient-reported outcome measures, though the specific measures varied. Further, 9 studies used standardized performance-based outcome measures, which also differed across studies. Finally, 7 (20%) studies collected sleep data; however, the methods and outcomes for sleep measurement were inconsistent among these studies. Conclusions: Remote monitoring via wearable devices offers a novel approach to tracking outcomes in TJA patients. Although the use of these devices in perioperative care is expanding, significant variability exists in the data reported across studies. Wearable monitoring is often integrated with patient-reported outcome measures and standardized functional assessments, yet the optimal data parameters that best correlate with established outcome metrics remain undefined. Additionally, data collected by wearables has not yet been shown to predict patient recovery or satisfaction. Further research is essential to refine these data parameters and the development of postoperative protocols that leverage wearable devices to enhance patient compliance and improve clinical outcomes. Trial Registration: PROSPERO CRD420261346230; https://www.crd.york.ac.uk/PROSPERO/view/CRD420261346230
<img src="https://jmir-production.s3.us-east-2.amazonaws.com/thumbs/84cacc21227b2261fe37fe6071778bab" />

Posted on

Preliminary Usability Assessment of a Rule-Based Digital Self-Monitoring Platform for Patients With Brain Tumors Toward Digital Early Warning Systems: Pilot Feasibility Study

<strong>Background:</strong> Postoperative follow-up after brain tumor surgery is typically limited to intermittent clinic visits, leaving subtle neurological or general deterioration between visits underrecognized. Digital self-monitoring platforms may help fill this gap, but evidence in neuro-oncology is scarce, particularly regarding how patient-reported symptom trajectories can feed into future data-driven early warning systems. <strong>Objective:</strong> This study aimed to evaluate the feasibility, use patterns, and preliminary usability of a smartphone or web-based self-monitoring system for patients after brain tumor surgery and to explore simple rule-based digital alerts as a first step toward an advanced digital early warning framework. <strong>Methods:</strong> We conducted a single-center prospective pilot study including adults discharged after brain tumor surgery who had access to a smartphone and could use a web app. Participants completed brief symptom surveys consisting of 51 binary items across 7 symptom domains, with an automatically calculated daily total score and score history visualization. Feasibility was assessed by enrollment, retention, submission counts, and submission rates. A total of 4 interpretable alert rules based on current score, short-term worsening, new-onset symptom combinations, and persistence across domains were evaluated using each patient’s last 3 submissions as the analytic unit. Clinical deterioration was defined a priori as objective decline in performance status, new neurological deficit, radiologic progression, or clinically significant laboratory changes. Rule performance metrics and bootstrap CIs were computed. Usability and acceptability were evaluated using the System Usability Scale and additional adherence-related items. <strong>Results:</strong> Of 64 enrolled patients, 30 (47%) with ≥3 submissions formed the analysis cohort (median age 57, IQR 47.2–64.5 years; n=12.9, 43% malignant tumors); 6 (20%) experienced clinical deterioration during follow-up. Patients contributed a median of 8.5 submissions (mean 19.03, SD 30.12) at 1.7 surveys per week on average, indicating sustained but heterogeneous engagement. The best-performing rule, based on net short-term score increase, achieved an area under the receiver operating characteristic of 0.88, with sensitivity 0.83, specificity 0.92, and accuracy 0.90 on the last-window dataset, outperforming rules based solely on current score or multidomain persistence. Among 23 app users who completed the System Usability Scale, the mean score was 84.0, reflecting high perceived usability; higher-frequency users reported stronger perceived usefulness and habit-driven use. <strong>Conclusions:</strong> This pilot study demonstrates that a smartphone or web-based self-monitoring platform for patients with brain tumor is feasible and well accepted and that simple, transparent rules applied to longitudinal symptom scores show potential to capture early signals of clinical deterioration. However, given the small sample size, these predictive metrics are preliminary and require rigorous validation in larger, independent cohorts. These findings support further development of integrated digital early warning systems that combine patient-reported trajectories with clinical and physiological data to enhance postoperative neurosurgical care.
Posted on

Involving Health Care Professionals in the Human-Centered Design of a Digital Platform for Work-Focused Health Care: Lessons From a Mixed Methods Study

<strong>Background:</strong> Effective collaboration throughout the full cycle of care is essential for value-based health care. In the Netherlands, occupational health care and curative health care traditionally operate as 2 separate sectors. As a consequence, effective communication and robust collaboration between professionals working in these sectors are lacking. Digital collaborative care platforms (ie, digital systems that facilitate communication and collaboration between health care professionals) are recognized as a promising solution to address the fragmentation of work-focused health care (health care that supports people on long-term sick leave in staying at or returning to work). A human-centered design (HCD) approach can help ensure that such platforms align with professionals’ needs by involving them throughout the design process. <strong>Objective:</strong> This study examines the experiences of (work-focused) health care professionals, including occupational physicians, insurance physicians, medical specialists, and general practitioners, during the design phase of a real-world HCD process for developing a digital platform to support collaborative care. The study specifically focused on understanding how these professionals perceive this collaborative approach. <strong>Methods:</strong> A mixed method study design was employed, combining observations of 17 design sessions with semistructured interviews with health care professionals as intended users of the platform. Observational data captured session dynamics, while interview data provided deeper insights into professionals’ experiences with the participatory HCD approach. <strong>Results:</strong> Health care professionals were generally motivated to contribute, driven by professional interest, social encouragement, or a desire to improve practice. They valued the open and informal atmosphere of the design sessions and described their role as actively sharing practical experiences and identifying bottlenecks in current practice. Participants emphasized the importance of clear goals, good preparation, and iterative involvement for meaningful engagement. Barriers identified included limited session time, constraints of virtual interaction, and uncertainty about the commercial context of the platform. Some professionals felt unsure about the relevance of their input or experienced limited interaction, especially when the session’s purpose was unclear. Others noted that the use of a mock-up platform as a conversational foundation, familiarity with similar system interfaces, and well-guided, structured discussions facilitated their input. Positive experiences included a sense of impact through involvement in the design process, note-taking as part of active user engagement, and a safe environment for open and constructive feedback. Participants recommended a clearer explanation of the platform’s broader aims in advance, enhanced participant preparation, and opportunities for multidisciplinary co-creation in future sessions. <strong>Conclusions:</strong> Health care professionals valued being part of the collaborative design process, but their engagement and perceived contribution were highly dependent on how the design sessions were facilitated. Structuring design sessions with clear expectations, preparatory tools, and opportunities for follow-up can support more effective, foundational co-creation in digital platform development for collaboration among professionals providing work-focused health care.
Posted on

Impact of Prescribed and Self-Selected Music Interventions on Stress, Sleep, Heart Rate Variability, and Brain Connectivity in Surgeons Using 7-Tesla Functional Magnetic Resonance Imaging and Wearable Actigraphy: Multimodal Feasibility Randomized Controlled Trial

<strong>Background:</strong> Stress, sleep deprivation, and burnout are significant safety risks for acute care surgeons, negatively impacting performance, well-being, and clinical outcomes. <strong>Objective:</strong> This pilot randomized controlled trial aimed to measure neurophysiological effects of prescribed music (PM) and self-selected music (SSM) on surgeon stress, burnout, and neurophysiological responses using a multimodal protocol that integrated functional magnetic resonance imaging (fMRI), wearable biosensor monitoring, and psychological self-assessments. <strong>Methods:</strong> Full-time attending surgeons at a quaternary care hospital were invited to participate in a 3-armed trial (1:1:1 block allocation). Intervention groups were instructed to listen to 30 minutes (minimum 15 minutes) of either PM or SSM daily at bedtime for 6 weeks, reflecting real-world conditions. PM comprised original compositions based on elements promoting perceived relaxation from a prior study. The control arm avoided music in the 30 minutes before bed. Allocation was concealed from the recruiting investigator; the fMRI technicians, the statistician, and lead investigators were blinded until analyses were completed. Functional connectivity patterns were measured using fMRI at baseline and 6 weeks while participants listened to simulated intensive care unit noise, PM, and SSM. Secondary outcomes included continuous actigraphy for sleep quality and self-reported anxiety, sleep quality, and burnout using validated scales (State-Trait Anxiety Inventory, Pittsburgh Sleep Quality Index, and Maslach Burnout Inventory). <strong>Results:</strong> A total of 22 surgeons were assessed; demands of fMRI and data collection schedule led 3 to decline and 2 (allocated to PM) not to finish baseline measures; 6 PM, 5 SSM, and 6 controls received allocated intervention; 2 PM participants were withdrawn for nonadherence and missing follow-up data and 1 control missed follow-up collection due to scheduling (final analysis set after missing data: PM: n=4, SSM: n=5, control: n=5). One control participant experienced transient vertigo in fMRI. Trends in fMRI data indicated that both intervention groups experienced less negative emotional arousal and anxiety, with physical tension reduced in the PM group. The PM group exhibited reduced stress response in the frontal lobes when exposed to intensive care unit alarms, suggesting diminished attentional response to the high-stress auditory environment, compared to control. However, lack of statistical significance and baseline variability entail cautious interpretation. Observations of sleep quality were mixed, and no statistically significant differences in stress surveys were observed. <strong>Conclusions:</strong> Both music interventions trended toward positive changes in neurophysiological responses, suggesting potential benefits in reducing surgeon stress. However, due to the small sample, mixed or nonsignificant results, and the exploratory nature of this study, findings should be considered preliminary. Further research with larger, diverse cohorts is required to confirm trends, refine both the intervention approach and recruitment strategies, and determine whether objective compositional elements or personally selected music drive the mechanisms of potential positive effects. <strong>Trial Registration:</strong> ClinicalTrials.gov NCT05980429; https://clinicaltrials.gov/study/NCT05980429
Posted on

Exploring Influencing Factors of Medication Adherence Among Chinese Patients With Alzheimer Disease: Delphi Study Informing Future Artificial Intelligence–Supported Interventions

Background: Alzheimer disease (AD) affects cognition, treatment adherence, family connections, and health care resource allocation. Most patients with AD have low adherence to medication therapy due to the limitations associated with cognitive impairment. Therefore, increasing the involvement of patients and their family members in medication management is important to improve treatment outcomes and reduce the burden of care. Objective: This study explores the potential application of artificial intelligence (AI) in medication management for Chinese patients with early- to mid-stage AD focusing on enhancing medication adherence. The study first predicts and evaluates key factors through an online Delphi study, which provides a basis for their subsequent incorporation into the AI model as input variables to enable prediction of medication-taking behaviors. Since AI research in medication management for this population is still undeveloped, this paper further explores the multiple potentials of AI from a theoretical view, including drug dosage optimization, multidrug interaction detection, and family education support. It will provide a preliminary direction and theoretical basis for the development of an intelligent medication management system in the future. Methods: The exploratory online Delphi study with no modification predicted the key factors influencing medication adherence. Based on the results, the study confirmed the potential of AI to improve adherence. Participation by 12 experts in 3 rounds systematically assessed the core elements influencing patients’ adherence to their medication. Results: Family care, social support, environmental factors, emotional support, and patient behaviors were identified as the primary factors influencing medication adherence among Chinese patients with AD. These factors were validated and ranked through iterative Delphi rounds, with family care and social support receiving the highest importance scores. The Wilcoxon signed-rank test indicated no significant difference between rounds (=.06), supporting the stability of the consensus. These findings establish a foundational set of variables for AI systems that predict and enhance medication adherence. Conclusions: This study highlights the critical factors affecting medication adherence by Chinese patients with AD. It was designed as an exploratory online Delphi study to identify and prioritize key influencing factors, rather than to validate a specific AI-based system, and the findings provide a theoretical foundation for future AI-informed interventions. The results also indicate theoretical potential roles for AI in supporting medication management, such as optimizing drug dosage, detecting multidrug interactions, and enhancing family education.
<img src="https://jmir-production.s3.us-east-2.amazonaws.com/thumbs/ac6c696cb235dbc4abc952c4a3cb9283" />