Background: Society faces multiple challenges, including lifestyle diseases and global climate change. Framing health education within sustainable development may enhance motivation for behavior change because proenvironmental behaviors, as well as healthy behaviors, often rely on the same behavior change principles. Combining these perspectives may therefore reinforce health behaviors and climate-friendly choices. Objective: This pilot study aims to explore changes in dietary intake, diet-related carbon footprint, and physical activity among office workers receiving sustainable plus healthy lifestyle (sustainable lifestyle arm) or healthy lifestyle education (healthy lifestyle arm) alone. It also aims to assess the feasibility of the intervention functions, including workshop attendance rate, participants’ dietary goals, social support, and facilitators and barriers to behavior change. Methods: A 2-armed participant-blinded cluster randomized study, including an experimental intervention arm (sustainable lifestyle; n=19) and a control intervention arm (healthy lifestyle; n=14), was conducted in Sweden. The study lasted 8 weeks and included 6 workplace-based workshops and was framed by the behavioral change wheel and the socioecological model. Diet, carbon footprint, and physical activity were assessed using the web-based questionnaires Meal-Q and Active-Q. Attendance rate, individual goals, social support, and facilitators and barriers were assessed using printed questionnaires. Results: The reduction of total diet-related carbon dioxide equivalents (COe) was 0.8 kg and 0.4 kg per day for the sustainable and healthy lifestyle arm, respectively. Also, there was a statistically significant interaction between time and lifestyle when the carbon footprint was expressed as a qualitative aspect of diet, that is, COe kg per 1000 kcal per day (=.05). Moreover, the intake of vitamin C, a marker for fruits and vegetables, increased to 8.0 and 12.5 mg per 1000 kcal per day for the sustainable and healthy lifestyle arms, respectively. In addition, total sedentary time decreased by 0.4 hours per day in the sustainable lifestyle arm, but not in the healthy lifestyle arm. This indicates that the educational workshops in respective arms had different impacts on health behavior over time. Minor differences were found in dietary goals, with the sustainable lifestyle arm setting more goals related to ecological and vegetarian foods. No differences were seen between arms regarding barriers or facilitators. Conclusions: This study suggests that embedding healthy lifestyle recommendations within a sustainable development context may be an efficient way to reduce carbon footprint and increase healthy behavior among office workers. Given the ongoing global epidemic of metabolic diseases, climate change, and environmental degradation, promoting a sustainable lifestyle in a workplace context has the potential to counteract these trends. Trial Registration: ClinicalTrials.gov NCT06698094; https://clinicaltrials.gov/study/NCT06698094
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Barriers and Facilitators in the Implementation of the Systematic Medical Appraisal, Referral, and Treatment (SMART) Mental Health Digital Intervention in Rural India: Mixed Methods Process Evaluation Study
<strong>Background:</strong> An estimated 150 million people have mental health care needs in India, but only 15% are able to access care. Depression and anxiety contribute to a large proportion of mental morbidity. The Systematic Medical Appraisal, Referral, and Treatment (SMART) Mental Health trial used a mobile-based clinical decision support system for primary care doctors and community health workers (CHWs) to identify and treat people at risk of depression, anxiety disorders, and self-harm. A community-based antistigma campaign was also delivered. The intervention led to improved remission rates for depression and anxiety and lower stigma scores. <strong>Objective:</strong> A process evaluation assessed (1) implementation fidelity, barriers, and facilitators; (2) perceptions of doctors and CHWs on the use of SMART Mental Health; and (3) the causal pathways that led to trial outcomes. <strong>Methods:</strong> A mixed methods evaluation combining backend program data and qualitative data was conducted. A total of 38 focus group discussions and 37 key informant interviews were conducted with primary doctors, CHWs, government officials, local community leaders, and research project staff. The data were coded and analyzed using a framework analysis approach based on the UK Medical Research Council guidance on process evaluations and the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework. <strong>Results:</strong> The intervention had high implementation fidelity. Across clusters, the median proportion of participants with at least 1 CHW follow-up was 98% (IQR 96.6%-100%). The referral rate for a psychiatrist was low (224/1697, 13.2%), and only 23.6% (53/224) of those referred visited the psychiatrist. The median exposure to antistigma audiovisual content was 84% (IQR 65.7%-95.9%). At the community level, key implementation barriers included cultural inhibitions in seeking mental health care and the unavailability of patients due to competing demands. Proximity and tight social connections between CHWs and their communities were important facilitators in seeking medical help. Doctor and CHW training, mentoring, and feedback provided by program staff were important facilitators to support the use of the digital health components by the health workforce. <strong>Conclusions:</strong> A complex intervention that included both community-based antistigma and clinical digital health interventions achieved high implementation fidelity. Key areas to consider for maintenance of such interventions include (1) the need for sustained community-based strategies to address stigma and other cultural barriers; (2) health workforce strengthening policies, including supportive supervision for CHWs and doctors to increase capability in the use of mental health digital health tools; and (3) strategies to improve access to specialist care for those with more complex care needs. <strong>Trial Registration:</strong> Clinical Trial Registry India CTRI/2018/08/015355; https://tinyurl.com/5r63suxp
Macrophages Use Cell Volume Changes to Sense Danger and Amplify Inflammation
Macrophages are often described as the immune system’s first responders, but new work suggests they are also remarkably attuned to the physical state of their environment. A study published in the Journal of Cell Biology titled “Disruption of macrophage cell volume drives inflammatory responses and type I interferon signaling” reveals that shifts in cell volume act as a previously underappreciated danger signal—one that can rewire macrophage gene expression, heighten antiviral defenses, and intensify inflammatory responses.
The research, led by Jack Green, PhD, and colleagues at the University of Manchester, centers on the Volume‑Regulated Anion Channel (VRAC), a protein complex that helps cells maintain osmotic balance. When VRAC is missing, macrophages lose the ability to correct swelling under hypo‑osmotic stress. “Cell volume disruption induced type I interferon signaling through a DNA- and TBK1-dependent mechanism, but independent of cGAS and 2′3′-cGAMP transport,” the authors wrote. That loss of control, the team found, is far more consequential than a simple biophysical hiccup. It fundamentally alters how macrophages interpret threats.
Green noted that although earlier studies hinted at a connection between cell volume and inflammatory signaling, the underlying biology remained murky. “Despite the reported indications that cell volume and VRAC are involved in inflammatory signaling, the basic biological mechanisms of how the regulation of cell volume shapes inflammation were unknown,” he said. To probe that gap, the team examined VRAC‑deficient macrophages exposed to mild osmotic stress.
The swelling triggered broad reprogramming of gene expression, including the induction of antiviral and proinflammatory pathways. Many of the most strongly upregulated genes belonged to type I interferon signaling cascades or nucleic acid–sensing systems. First author James Cook frames the finding succinctly: “Together, these findings suggest that cell volume acts as an additional layer of danger sensing in macrophages that shapes and tunes the nature of immune responses to pathogens.”
That prediction held up in functional assays. When challenged with Influenza A virus, VRAC‑deficient macrophages mounted a more potent antiviral response than their wild‑type counterparts. The heightened sensitivity extended beyond viral infection. In mouse models of systemic hyperinflammation, animals lacking VRAC showed elevated levels of a key inflammatory mediator, indicating that dysregulated cell volume can exacerbate cytokine‑driven pathology in vivo.
Rather than responding solely to biochemical cues, these cells appear to fold physical perturbations—such as osmotic imbalance—into their danger‑sensing logic. Green argued that this perspective may help explain why inflammatory diseases can escalate unpredictably when tissue conditions shift. “Understanding disruptions in the tissue microenvironment leading to alterations in cell volume is therefore an important consideration in our understanding of inflammation and disease pathogenesis,” he concluded, adding that “future studies will reveal the potential for regulating VRAC‑dependent cell volume changes in macrophages in disease.”
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Fraudulent citations, blamed on AI hallucinations, are becoming more common in research papers
Citations in academic papers are intended to ground research in the work that preceded it, over time creating something of a family tree explaining the roots of ideas, protocols, and studies.
But a growing number of these citations lead to dead ends. “Fabricated” citations that do not reference real papers are spreading in the literature, polluting the public record of science, a new study published Thursday in the Lancet shows. Tools using generative AI are likely to blame, say the Columbia University researchers who authored the paper.
From Sequence to Patient in Under 12 Months: A Case Study in Advancing Complex Cancer Immunotherapies
Joseph Shultz
Vice President of Technical Development and Manufacturing
Ottimo Pharma
Panelist
Joseph Shultz
Joseph Shultz is the vice president of technical development and manufacturing at Ottimo Pharma. His more than 30 years in the industry span development, manufacturing, quality, and technology development. He has held influential positions at Amgen, Novartis Pharma, the Battelle Memorial Institute, Evelo Biosciences, and Resilience. He initiated the technologies and led the strategies that resulted in next-generation biomanufacturing plants at both Amgen and Novartis.
Imroz Ghangas
Vice President of Commercial Sales
Asimov
Panelist
Imroz Ghangas
Imroz Ghangas and his team drive partnerships to advance Asimov’s genetic design platform and AI capabilities. With over 25 years in biotech, Imroz has evolved from process development scientist to commercial leader, bridging technical innovation with scalable solutions. His expertise spans bioprocess development and platform integration, with deep knowledge of biomanufacturing workflows from gene to drug product. He leverages his technical foundation to accelerate the adoption of next-generation bioprocessing technologies.
Broadcast Date:
- Time:
Complex biologics such as bifunctional antibodies are opening new therapeutic possibilities in oncology, but these molecules present significant challenges for manufacturing teams. Non-standard architectures can often translate to low expression and difficult developability, making cell line development a critical bottleneck between a promising sequence and a viable clinical candidate.
In this GEN webinar, Joseph Shultz (vice president of technical development and manufacturing, Ottimo Pharma) and Imroz Ghangas (vice president of commercial sales, Asimov) discuss strategies for achieving high-performing clonal titers and advancing a dual-paratopic cancer immunotherapy from sequence to dosed patient in under a year. Attendees will learn about the unique attributes of Ottimo’s molecule and how a specialist partnership with Asimov accelerated the program. The presenters will also introduce the CHO Edge System, which combines Asimov’s proprietary GS knock-out CHO host, hyperactive transposase, library of characterized genetic elements, and AI-driven genetic design tools to routinely deliver clonal titers of 8-12 g/L.
A live Q&A session will follow the presentation offering you a chance to pose questions to our expert panelists.
Produced with support from:
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G-Link CAR-T Delivery Platform Showcased at ASGCT
Vyriad reports that it will showcase its latest CAR T delivery technology platform, G-Link, through a schedule of presentations, technical sessions, and exhibition activities at ASGCT. The modular plug-and-play protein adapter developed in collaboration with Menachem Rubenstein, PhD, of the Weizmann Institute allows drug developers to cap and retarget existing lentiviral vectors for in vivo delivery, according to the company.
By leveraging G-Link, wild-type lentiviral vectors can be reprogrammed for in vivo applications without the need for intensive vector re-engineering, effectively shortening development timelines for next-generation CAR T and other cell therapies, notes a company spokesperson, who adds that G-Link can also be used to simplify ex vivo CAR T manufacturing and significantly improve T cell transduction efficiency without redesigning vectors.
“I believe that G-Link can address some of the most persistent challenges in in vivo delivery and we are excited to unveil it at ASGCT this year,” says Stephen Russell, PhD, CEO of Vyriad. “Our participation this year underscores our clear mission: to replace complex, weeks-long manufacturing cycles with precise, off-the-shelf immunotherapies. With G-Link, we aim to foster collaborations that will define the next generation of in vivo cell therapies.”
Vyriad’s VV169 in vivo CAR T program will progress into clinical development later this year, while the G-Link platform will advance towards clinical translation later in the future, continues Russell.
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Key takeaways from WHO briefing on hantavirus cruise ship outbreak
The MV Hondius, the cruise ship that has garnered global attention because of an apparent outbreak of person-to-person spread hantavirus infections, is on the move. At the request of Tedros Adhanom Ghebreyesus, the World Health Organization’s director-general, Spain has agreed to let the ship dock off Tenerife, in the Canary Islands. The ship is expected to arrive on Sunday.
This outbreak — the first time hantavirus has been suspected of transmitting on a cruise ship — is an evolving situation. It’s also one that is going to take weeks to resolve, because of the long incubation period of hantaviruses. And it could be months before scientists piece together how the virus got on the boat and whether all the subsequent cases were people infected through contact with other people or whether rodents — which are known to carry hantaviruses — that were on board played any part.
Human Antibodies Identified That Have Potential To Prevent and Treat Measles Virus
Scientists at La Jolla Institute for Immunology (LJI) say they are the first in the world to characterize human monoclonal antibodies (mAbs) capable of neutralizing measles virus (MeV). The antibodies, derived from the memory B immune cells of an individual who had previously received the MMR vaccine years previously, bind to key hemaggglutinin (H) and fusion (F) surface virus proteins, preventing viral entry into host cells.
The researchers, headed by Erica Ollmann Saphire, PhD, LJI professor, president, and CEO, say the new panel of human antibodies may form the basis for future medical therapies against measles infection. In their newly reported study the team showed that an infusion of the antibodies resulted in 500-fold lower viral load in a rodent model of measles infection.
“These antibodies work as prophylaxis—to protect from initial infection—and they work after viral exposure as a treatment to fight measles infection, said Saphire. “It may be possible to give someone an infusion of these antibodies and deliver the immune response they wish they had.”
In their study (“Human neutralizing antibodies targeting the measles virus hemagglutinin and fusion surface proteins”) reported in Cell Host & Microbe, the team concluded “Characterization of these fully human mAbs provides avenues for prophylactic or therapeutic intervention against re-emerging MeV.”
Measles virus is “… a highly transmissible paramyxovirus, can cause severe complications and death, particularly in infants and young children,” the authors wrote. “A live-attenuated vaccine derived from a genotype A MeV strain provides vaccinees with lifelong immunity and protective antibodies against all 24 MeV genotypes in circulation.”
However, in recent years, decreased vaccination rates have led to deadly measles outbreaks across the U.S. and around the world. This sharp rise in measles cases is especially dangerous for the millions of people who cannot receive a measles vaccine. While the measles vaccine is incredibly safe and effective, it does contain a live, weakened virus. This means that people who have compromised immune systems, such as those who are pregnant or receiving chemotherapy, including children, cannot receive the vaccine. The very young are also at risk. Infants must wait until they are 12 months old to be vaccinated, and most children in the U.S. aren’t fully vaccinated against measles until they are six years of age.
“There are a growing number of people that can’t be vaccinated or haven’t been fully vaccinated,” said Saphire. “The very same people who can’t be vaccinated or can’t be vaccinated yet, are the same people for whom a measles virus infection would be the most severe—or be lethal.”
Until recently, enough people were vaccinated against measles virus that the risk of exposure for this unvaccinated group was very low. Unfortunately, that community protection—herd immunity, is no longer. LJI scientists are on a mission to find treatment options for the most vulnerable.
There are currently no measles-specific therapies to help patients. The new study shows that monoclonal antibody therapies may may be a feasible option. Monoclonal antibody treatments contain many copies of a neutralizing antibody, and are widely used for a variety of infectious diseases. Even infants receive monoclonal antibody therapies each year to prevent respiratory syncytial virus (RSV).
To design a monoclonal antibody treatment for measles, researchers need a clear picture of how human antibodies fight the virus. However, as they noted, “Despite the global presence of MeV and widespread use of the vaccine, few studies have mapped the human antibody response. We do not yet know how human antibodies, from either measles vaccination or natural infection, recognize and protect against the virus.”
Saphire and her colleagues began by harnessing an imaging technique, cryo-electron microscopy (cryo-EM), to capture the first-ever glimpses of how antibodies bind to the measles virus. They started by examining mouse antibodies, and published that work in a recent paper. That initial study showed where measles virus is vulnerable to antibody attack. The mouse antibodies, the researchers showed, latched onto the virus fusion protein, to block viral entry into a cell.
To find out whether human antibodies could do the same thing, the researchers analyzed blood from a clinical research volunteer. “We evaluated 15 MMR-vaccinated donors for their polyclonal MeV responses to identify individuals with vaccine-induced, protective, circulating antibodies,” they explained. The 56-year-old female volunteer they selected had been vaccinated against measles many years before, and already had antibodies ready to fight measles virus. This individual “… demonstrated the highest polyclonal response and the most H- and F-reactive memory B cells.”
From the one blood sample, the LJI scientists isolated antibodies that bind to the measles virus fusion protein, along with other antibodies that bind to the virus hemagglutinin protein. They then captured 3D images of these antibodies bound together with the measles virus. “We found that these antibodies are exceptionally potent,” said study first author, LJI Instructor Dawid Zyla, PhD. “Two orders of magnitude better than comparable molecules reported at conferences.”
Measles virus is a shape-shifting virus. When it meets a human cell, it unfolds to reveal viral machinery that fuses with the host cell membrane. The new study shows that antibodies targeting the fusion protein work by locking the protein in place, leaving the virus unable to shape shift and infect a host cell. The next step was to test these antibodies in a preclinical animal model. Study collaborators at The Ohio State University carried out key experiments in cotton rats. They found that all four lead antibodies reduced viral load when given either before measles exposure or within 24 to 48 hours after measles virus infection. One antibody, designated 3A12, which binds to a site on the F protein, rendered the circulating virus actually undetectable.
While more work needs to be done, the researchers see these antibodies as promising tools in the fight against measles. Their new images of the antibody structures provide the materials needed to make the world’s first before- or after exposure treatment for measles virus. “Now we know what we’re aiming for, and we have the antibodies we need,” said Saphire.
In their paper the authors stated, “The protective mAbs identified here target four distinct, non-competing epitopes, and may be combined as cocktail therapies to enhance treatment potency, maintain durable protection, and reduce the risk of viral escape.… these human mAbs themselves, which recognize conserved sites and inhibit measles by complementary mechanisms, represent a basis to develop a treatment that is urgently needed as measles virus infections surge globally.”
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Oral Small-Molecule GLP-1s Linked to Deep Brain Activity and Reduced Cravings in Mice
Interest in glucagon-like peptide 1 receptor agonists (GLP-1s) continues to surge due to their effectiveness in reducing body weight and improving metabolic outcomes. This includes interest in small molecule oral GLP-1s which are more bioavailable and more easily manufactured than their injectable counterparts.
Now data from a new study in mice performed by scientists at the University of Virginia shows that this emerging class of weight-loss drugs suppress hedonic eating by modulating a reward circuit deep in the brain that is separate from previously described mechanisms that broadly affect appetite. The scientists believe that this pathway could be an avenue by which GLP-1s treat other dysfunctions in reward processing such as substance use disorders.
Details of the National Institutes of Health-funded study were published this week in a Nature paper titled “A brain reward circuit inhibited by next-generation weight-loss drugs in mice.” In it, the team reported that they investigated the small-molecule GLP-1s including Eli Lilly’s recently approved drug orforglipron, also known by the brand name Foundayo, as well as danuglipron, an oral GLP-1 that was being developed by Pfizer until the company decided to discontinue its development in 2025.
Previous studies that explored the effects of larger peptide GLP-1s such as semaglutide in the brain have found that they suppress hunger-driven eating by engaging networks in the hypothalamus and hindbrain. What has been less clear is the mechanism by which small-molecule GLP-1s work. “As the accessibility of these medications continues to rise and patient uptake increases, it’s crucial that we understand the neural mechanisms underlying the effects we’re seeing,” said Lorenzo Leggio, MD, PhD, clinical director of NIH’s National Institute on Drug Abuse.
The current study gets scientists one step closer to that goal. According to the paper, the scientists first used gene editing to modify the GLP-1 receptors of mice to make them more humanlike. They then administered orforglipron or danuglipron to the mice, and identified brain regions where the drugs induced activity. The results showed that in addition to inducing activity in familiar pathways, the drugs also triggered the central amygdala, a region associated with desire that is deeper in the brain than scientists previously thought GLP-1s could directly reach. Further testing showed that once activated, the central amygdala reduced the release of dopamine into key hubs of the brain’s reward circuitry during hedonic feeding.
“We’ve known that GLP-1 drugs suppress feeding behavior driven by energy demand,” said co-corresponding author Ali Guler, PhD, a professor of biology at the University of Virginia. “Now it seems oral small-molecule GLP-1s also dial back eating for pleasure by engaging a brain reward circuit.”
Given the effect of these drugs on eating for pleasure, future studies could explore whether small-molecule GLP-1s can also suppress cravings for other addictive substances. It is a question that the team hopes to explore in follow up studies focused specifically on substance use disorder.
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Reduced Glaucoma Risk Connected to Migraine Medication Use
Individuals with migraines have been known to have a higher risk of glaucoma development, and a new study published in Neurology suggests that use of preventative medication for migraines may be connected with reduced instance of glaucoma development.
“Glaucoma is a leading cause of blindness, and evidence has linked migraine with an increased risk of glaucoma, with both conditions affecting the capacity of the blood vessels in the brain to alter blood flow in response to stimuli,” said the study lead, Chien-Hsiang Weng, MD, clinical associate professor at Brown University.
Weng and his team surmised that drugs that help to regulate blood vessel function to prevent migraines may also help prevent the development of glaucoma. The researchers focused on assessing the efficacy of calcitonin gene-related peptide inhibitors (CGRPi), which included six medications: erenumab, fremanezumab, galcanezumab, eptinezumab, atogepant, and rimegepant.
“Since CGRP inhibitors help regulate blood vessel contraction and inflammation in the nervous system, there has been hope that these drugs could benefit eye health in people at risk of glaucoma,” said Weng.
In this retrospective cohort study, the researchers collected data from a healthcare database including individuals who were prescribed migraine prevention drugs with at least one refill between 2018 and 2024. These individuals were tracked for three years to identify glaucoma diagnoses.
The researchers analyzed data from over 73 thousand participants, 36,822 of which were prescribed drugs from the CGRPi group to prevent migraine, and an equivalent number of people prescribed non-CGRPi drugs (including valproate, topiramate, flunarizine, candesartan, lisinopril, metoprolol, propranolol, nadolol, amitriptyline and venlafaxine). To prevent confounding the data, the researchers point out that “Crossovers were not allowed, and the non-CGRPi group included only individuals who never used CGRPi.”
Primary analysis using the Cox proportional hazards model showed that within the first three years from the first prescription of the migraine medication, 153 people (0.42%) in the CGRPi group developed glaucoma, compared to 223 people (0.61%) of those in the non-CGRPi group.
When adjusted for glaucoma risk factors including migraine frequency, history of high blood pressure, and age, individuals taking CGRPi drugs have a 25% lower risk of developing glaucoma compared with those taking the non-CGRPi drugs.
Not all CGRPi drugs showed equal effectiveness in reducing the risk of developing glaucoma. The authors specify that “only users of monoclonal antibody CGRPi show a reduced risk of glaucoma compared with non-CGRPi users (HR 0.77; 95% CI 0.61–0.98).”
Additionally, not all participants responded to the CGRPi medications equally. “The reduced risk of glaucoma associated with CGRPi is also observed in older adults, women, and those with chronic migraine or migraine without aura.”
This study presented a broad overview of the comparison of the potential effectiveness of two drug groups in preventing glaucoma. While this study shows a promising correlation between reduced risk of developing glaucoma when some individuals use specific CGRPi drugs, more directed and focused studies would be required to confirm a causative impact of CGRPi treatment reducing glaucoma risk.
“Further studies are needed to confirm these results, but the findings may help us better understand both migraine and glaucoma,” confirmed Weng.
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