WASHINGTON — An influential progressive think tank is proposing that Democrats assert more federal government control over hospitals and private insurers to make health care more affordable.
Democrats have set out to gather ideas for overhauling the health care system in preparation for potentially regaining control of Congress and the presidency. Democrats see themselves in a “blue sky moment” following Republicans’ big cuts to health care funding, and they want to give themselves plenty of time to devise a fresh approach so they’re ready to strike if and when they get the chance.
The Trump administration will not be asking the Supreme Court to take up its fight to slash federal support for funding that the nation’s science enterprise relies on for basic operating costs. The deadline to do so came and went this week without a petition from Trump’s Department of Justice, effectively ending the 14-month standoff over a controversial policy to drastically reduce the rate of reimbursement for “indirect costs” on federal grants.
The legal battle between the administration and the research community started last February, when the National Institutes of Health abruptly announced it would cap payments for research overhead at 15%. Three lawsuits opposing the caps were immediately filed by state attorneys general and organizations representing private and public universities, hospitals, and academic medical centers.
Under the previous policy, these institutions would negotiate with the NIH for individual rates — to cover expenses not directly linked to the goals of a particular project, like facility upkeep and salaries for grant management staff. Many of the nation’s most elite research institutions typically receive 50% or more of their direct research expenses to cover indirect costs.
Neuroblastoma is the most common tumor among children under a year of age, and while in its gentlest form neuroblastoma can regress on its own, it can also take an aggressive form, with high-risk neuroblastoma carrying a five-year survival rate of about 40%.
Researchers at The Hebrew University of Jerusalem have now discovered a mechanistic explanation for how neuroblastoma sustains itself and identified a potential approach to severing that mechanism, by inhibiting nitric oxide (NO) production to suppress mTOR signaling. The collective results from work in human neuroblastoma cells and experiments in a mouse xenograft model showed that inhibiting the enzyme neuronal nitric oxide synthase (nNOS) to inhibit NO production suppressed mTOR signaling and slowed tumor growth.
Professor Haitham Amal, PhD, head of The Laboratory of Neuromics, Cell Signaling, and Translational Medicine, is senior and co-corresponding author of the team’s published paper in Brain Medicine, titled “Targeting nNOS suppresses AKT–TSC–mTOR signaling and inhibits neuroblastoma growth.” In their paper the team concluded “Inhibition of nNOS suppresses mTOR signaling, reduces cellular malignancy, and attenuates tumor growth in vivo, identifying the nNOS-mTOR axis as a promising therapeutic target in neuroblastoma.”
Neuroblastoma accounts for roughly 28% of all cancers diagnosed in infants across Europe and the United States. “Neuroblastoma (NB) refers to a spectrum of neuroblastic tumors that originate from the neural crest cells during fetal development,” the authors wrote. “Neuroblastoma is predominantly a pediatric malignancy, with approximately 97% of cases occurring in children.”
NBs can range from spontaneous regression to maturation to an aggressive, deadly metastatic disease. And as the investigators noted, “Despite major advances in multimodal therapy, high-risk neuroblastoma remains associated with poor prognosis, frequent relapse, and therapy resistance, underscoring the need for a better understanding of the signaling pathways that regulate tumor cell survival, differentiation, and metabolic adaptation.”
Nitric oxide (NO) is an essential regulator of carcinogenesis in various tumors, including NB, the authors pointed out. “Nitric oxide (NO) is a ubiquitous free radical signaling molecule produced in multiple organs and tissues), such as those of the central and peripheral nervous systems.” But at elevated concentrations NO becomes reactive, generating nitrogen species that chemically modify proteins through a process called S-nitrosylation. That modification has been implicated in every stage of cancer progression.
The relationship between nitric oxide and tumors is not simple. Very high concentrations can damage DNA and trigger apoptosis. Lower, sustained levels appear to do the opposite, promoting survival and metastasis. Amal and colleagues had previously demonstrated that nitric oxide drives glioblastoma progression. The question that remained was whether the same enzyme, neuronal nitric oxide synthase, was performing a similar service for neuroblastoma, and if so, through which downstream pathway. The answer turned out to be mTOR.
The team attacked nNOS from two directions. They treated human SH-SY5Y neuroblastoma cells with BA-101, a selective pharmacological inhibitor, at 100 μM for 24 hours. Separately, they silenced the nNOS gene with small interfering RNA. The reasoning was that if a drug and a genetic tool produce the same result, you are looking at biology, not pharmacological noise.
The experiments produced the same result. BA-101 reduced NADPH-diaphorase activity, the standard readout of NOS function, by 35-40%. Genetic silencing cut it by 45-50%. Nitrite levels, a stable proxy for nitric oxide production, fell 65-70% with BA-101 and 55-60% with siRNA. Colony formation, the most direct measure of proliferative capacity, dropped significantly after both BA-101 treatment (p < 0.001) and nNOS silencing (p < 0.01). The cells were losing their ability to multiply.
What followed downstream was systematic. Protein tyrosine nitration, measured by 3-nitrotyrosine immunoreactivity, fell sharply after BA-101 treatment (p < 0.01) and nNOS silencing (p < 0.001). The chemical signature of nitrosative stress was fading.
The results then confirmed that AKT phosphorylation decreased (p < 0.01 with BA-101; p < 0.05 with siRNA), while total AKT remained unchanged. Phosphorylation of mTOR itself declined under both conditions (p < 0.01 each). The downstream mTORC1 substrate ribosomal protein S6 followed (p < 0.05 with BA-101; p < 0.01 with siRNA).
And here, the most telling detail, that TSC2, a master negative regulator of mTOR signaling, rose significantly under both treatments (p < 0.05). Removing the nitric oxide signal had allowed the cell’s own braking system to re-engage. In summary, the authors noted, “Pharmacological inhibition of nNOS with BA-101 (100 μM, 24 h) or genetic silencing of nNOS with siRNA caused upregulation of the key negative regulator TSC2 and decreased phosphorylation of AKT, mTOR, and RPS6, indicating suppression of mTOR pathway activity.”
Synaptophysin, a neuroendocrine tumor marker used to gauge the malignant identity of neuroblastoma cells, decreased significantly with BA-101 (p < 0.01) and nNOS knockdown (p < 0.05). The tumor cells were not merely growing more slowly. They were becoming, at a molecular level, less recognizably cancerous. In summary, the investigators noted, “Our results show that inhibition of NO production in the human NB cell line (SH-SY5Y cells), either by pharmacological intervention using the selective nNOS inhibitor BA-101 (41) or by genetic ablation using the specific siRNA, successfully suppressed NB malignancy.”
Schematic model illustrating the NO-mTOR signaling axis in neuroblastoma. Under basal/pathological conditions (left panel), and nNOS inhibition (right panel). [Haitham Amal]
But if blocking nitric oxide suppresses mTOR signaling, then flooding the cell with nitric oxide should amplify it. The researchers tested this by exposing SH-SY5Y cells to SNAP, a nitric oxide donor, at 200 μM for 24 hours. This converse experiment produced the converse result. 3-nitrotyrosine rose (p < 0.05), and TSC2 fell (p < 0.01). Phosphorylation of AKT, mTOR, and RPS6 all increased (p < 0.05 for each).
The team then tested their findings in a xenograft mouse model of neuroblastoma, treated with BA-101. “Importantly, to extend these findings to an in vivo context, we further assessed the impact of pharmacological nNOS inhibition on tumor growth in a xenograft NB model,” they stated. The investigators found that while tumors in control animals grew to approximately 1.5 cm in their largest dimension, the treated tumors did not. Final tumor volume and weight were dramatically reduced in the BA-101 group. ‘Quantitative analysis revealed a dramatic decrease in the final tumor volume and weight in the BA-101-treated group (p < 0.001) compared with controls,” they noted.
Body weight did not differ significantly between groups, suggesting that the compound was tolerated without gross systemic toxicity. In summary, the authors wrote, “Our finding demonstrate that the pro-tumorigenic effects of nNOS in SH-SY5Y involve activation of themTOR signaling pathway.” Importantly, both genetic inhibition of nNOS using siRNA and pharmacological inhibition with BA-101 effectively suppressed mTOR pathway activation and reduced malignant properties of NB cells, highlighting the therapeutic relevance of targeting nNOS signaling. “These findings indicate that pharmacological inhibition of nNOS effectively suppresses xenograft tumor progression, highlighting the critical role of nNOS-derived NO in promoting neuroblastoma growth in vivo.”
“The magnitude of the in vivo suppression caught our attention,” said Amal, the study’s corresponding author, who holds appointments at the Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, and the Rosamund Stone Zander and Hansjoerg Wyss Translational Neuroscience Center at Boston Children’s Hospital, Harvard Medical School. “We had demonstrated the role of nitric oxide in glioblastoma previously, but the consistency of the neuroblastoma results across every assay, from protein phosphorylation to colony formation to xenograft growth, points to nNOS as something more than a contributor. It appears to be a central driver of the signaling that sustains this tumor.”
Added first author Shashank Kumar Ojha, PhD, first author of the study and a researcher at the Institute for Drug Research, The Hebrew University of Jerusalem, added, “What convinced me was the concordance between the pharmacological and genetic approaches. When BA-101 and siRNA independently produce the same pattern of effects across NADPH-diaphorase activity, nitrosative stress markers, mTOR pathway phosphorylation, and clonogenic growth, you can be confident the biology is real. That reproducibility is what gives you a therapeutic hypothesis worth testing further.”
The authors acknowledged limitations to their study. The in vitro work relied on a single cell line, SH-SY5Y, which cannot capture the full genetic heterogeneity of neuroblastoma or the complexity of the tumor microenvironment. The chemical identity of BA-101 is currently undisclosed pending patent issuance, which means independent replication by other laboratories must wait. Whether nitrosative stress directly underlies its functional impairment, or whether an intermediary mechanism is involved, remains an open question that the authors explicitly flag for future investigation. “Future studies using patient-derived cells, organoids, or genetically engineered mouse models will be important to further validate and extend these observations,” they stated. Nevertheless, the authors suggest, the limitations do not diminish the central discovery of a druggable nNOS–mTOR axis.
mTOR inhibitors such as rapalogs and catalytic mTOR inhibitors have shown limited efficacy as monotherapies in neuroblastoma, undermined by feedback activation and resistance mechanisms. The present study suggests the potential for a different attack strategy. Rather than targeting mTOR at the lock, intervene upstream at the hand that turns the key. By reducing nitric oxide-dependent mTOR activation, nNOS inhibition may sidestep the compensatory pathways that have frustrated direct mTOR blockade. “Collectively, these results identify the nNOS-mTOR axis as a key driver of neuroblastoma progression and suggest that nNOS inhibition represents a promising strategy for NB treatment,” they concluded.
Background: Passive smartphone sensing shows promise for suicide prevention, but behavioral metadata (GPS, screen time, and accelerometry) often lacks the contextual information needed to detect acute psychological distress. Analyzing what people actually see, read, and type on their phones—rather than just usage patterns—may provide more proximal signals of risk. Objective: This study aimed to test whether vision-language models (VLMs) applied to passively captured smartphone screenshots can predict momentary suicidal ideation (SI). Methods: Seventy-nine adults with past month suicidal thoughts or behaviors completed ecological momentary assessments (EMA) over 28 days while screenshots were captured every 5 seconds during active phone use. We fine-tuned open-source VLMs (Qwen2.5-VL [Alibaba Cloud], LFM2-VL [Liquid AI]), and text-only models (Qwen3 [Alibaba Cloud]) to predict SI from screenshots captured in the 2 hours preceding each EMA. We evaluated performance with temporal and subject holdouts. Results: The analytic sample comprised 2.5 million screenshots from 70 participants. Temporal holdout models achieved strong discrimination at the EMA level (AUC=0.83; AUPRC=0.77), with image-based models outperforming text-only models (AUC=0.83 vs 0.79; 95% CI 0.003-0.07). Subject holdout generalization was near chance (AUC≈0.50), though a simple lexical screening method retained modest discrimination (AUC=0.62). Smaller models performed comparably to larger models, supporting feasible on-device deployment. Conclusions: Screen content predicts short-term SI with clinically meaningful accuracy when models are personalized but does not generalize across individuals. These findings support a 2-stage clinical architecture, coarse lexical screening for new patients, with personalized VLM-based monitoring after a calibration period. On-device inference may enable privacy-preserving deployment.
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Stanford researchers have developed a urine test that can accurately predict which patients with bladder cancer will respond to standard surgery and immunotherapy treatments. In a study published in Cell, they report that this DNA test takes into account background mutations caused by aging that existing tests may otherwise mistake for cancer.
“Our test can detect minimal residual disease non-invasively after bladder cancer treatment, while accounting for mutations present in normal urothelium that have complicated prior studies,” said Joseph C. Liao, MD, professor of urology and senior author of the study. “For the first time, we were able to distinguish patients likely cured by [immunotherapy] from those cured by surgery.”
Even when detected in early stages, bladder cancer has a high relapse rate. Patients with non-muscle invasive bladder cancer (NMIBC), whose tumors are still confined to the inner layers of the bladder, are typically treated with surgery. Those with higher risk profiles are then given a bacillus Calmette Guerin (BCG) immunotherapy, which can significantly reduce recurrence risk after surgery.
However, while some patients respond well to surgery without immunotherapy, others may end up relapsing even after receiving BCG immunotherapy. Until now, there was no reliable way to predict which patients will respond to each of these treatments, making it difficult for physicians and patients alike to make informed clinical decisions.
The molecular test developed by Liao and colleagues analyzes urine tumor DNA in urine samples to detect the presence of tumor DNA and predict whether a patient will respond to standard surgery or BCG treatment. Importantly, the test was designed to account for the “field effect,” a phenomenon where even healthy people can carry cancer-associated mutations in the bladder’s lining, with these mutations becoming increasingly common as the person ages.
“By correcting for the field effect, a known confounder of mutation-based bladder cancer detection, we improved the specificity of urine tumor DNA liquid biopsies,” said William Y. Shi, MD/PhD student at Stanford School of Medicine and lead author of the study. “This allowed us to molecularly distinguish the relative contributions of surgery and BCG to disease control.”
The researchers evaluated the urine test in a cohort of 261 NMIBC patients who underwent surgery and BCG treatment. Results revealed three distinct molecular patterns of treatment response. These included surgery responders, for whom tumor DNA disappeared after surgery; BCG responders, who showed tumor DNA after surgery that was eliminated with the immunotherapy; and non-responders who saw tumor DNA levels remain stable or even increase after both treatments.
“The ability to distinguish responders from non-responders to the two treatments also allowed us to study which molecular properties make tumors more likely to benefit from each therapy,” said Max Diehn, MD, PhD, professor of radiation oncology and senior author of the study.
The study also revealed distinct molecular patterns driving response to surgery and response to BCG immunotherapy. On the one hand, patients who relapsed after surgery had tumors with genetic activity linked to cell growth and invasion. On the other hand, tumors who responded to BCG had a higher mutation burden and tended to have features that made them more visible to the immune system.
Following validation in a larger patient cohort, this urine test could help spare patients who respond well to surgery from receiving an unnecessary course of immunotherapy. In particular, BCG supply has suffered from shortages for the past decade, leaving many patients waiting for longer than necessary. In the face of shortages, a predictive test could help prioritize those who are most likely to benefit from it.
For patients who are unlikely to respond to both surgery and BCG, the urine test could also prove valuable in escalating treatment early on. In the study, the test was able to identify recurrence risk in patients for whom routine cystoscopy exams appeared normal, meaning it could be able to detect relapse earlier than the current standard.
“These kinds of predictive biomarkers are critical,” said Eila C. Skinner, MD, professor of urology and chair of Stanford’s Department of Urology. “We have new treatments that are costly and carry risk of side effects. We would love to personalize therapy to ensure each patient receives the best treatment for their individual cancer.”
Salk Institute scientists have developed a biological platform for studying mitochondrial DNA in physiology, adaptation, disease mechanisms, and therapeutic development. Headed by Ronald Evans, PhD, professor and director of the Gene Expression Laboratory and holder of the March of Dimes Chair in Molecular and Developmental Biology at Salk, the team has already used the platform to generate a library of 155 mitochondrial DNA mutant cell lines and reveal correlations between mouse development and mitochondrial function. They suggest that the platform, library, and findings will accelerate therapeutic development for mitochondrial disorders, as well as help scientists treat mitochondrial dysfunction in other diseases and conditions like cancer or aging.
“Mitochondrial DNA accumulates mutations at a high rate, and more than 260 inherited disease-causing mtDNA mutations have been identified in humans,” said Evans. “Until now, a lack of models representing this diversity has limited mechanistic insight and therapeutic development. Our new platform will allow scientists to investigate mitochondrial DNA variation in health, disease, and evolution, which will enable therapeutic innovation for mitochondrial disorders.”
Evans is co-corresponding author of the team’s published paper in PNAS, titled “A scalable embryonic stem cell–based platform for efficient generation of mitochondrial DNA mutant mice,” in which they concluded that their new platform, “… opens the door to mechanistic dissection of how mtDNA variation influences metabolism, adaptation, and disease, and provides a strategically valuable foundation for accelerating therapeutic development through genetically precise mitochondrial disease models.”
Some of your most important life partners are the mitochondria that power all your cells. You and these little cellular powerhouses are in a 1.5-billion-year-old evolutionary relationship—but mitochondria brought some baggage. Mitochondria brought their own DNA with them when they joined with the bigger, more complex cells so long ago, and today that mitochondrial DNA influences human health. Mitochondrial DNA does the extremely important job of creating the proteins needed for energy production—but it also has an especially high rate of mutation, and those mutations can accumulate thanks to inefficient repair mechanisms. Because mitochondria are essential parts of every cell, their dysfunction can lead to body-wide dysfunction, with especially devastating impact on high-energy organs like the brain and heart. Without enough power in your cells, symptoms like migraines, muscle weakness, and loss of hearing or sight can begin to manifest.
“Mitochondria are central to energy metabolism and cellular signaling, and mutations in mitochondrial DNA (mtDNA) can disrupt these processes and contribute to human disease,” the authors wrote. “Mitochondrial DNA (mtDNA) accumulates mutations at a high rate, and more than 260 pathogenic germline mtDNA mutations have been identified in humans, producing diverse and often tissue-specific disorders.”
The chronic and broad impact of mitochondrial dysfunction makes it especially important to study. However, trying to pinpoint the outcome of specific mitochondrial DNA mutations has for many years been a slow, arduous process for many years. “… progress in defining how mtDNA variation influences adaptation, pathophysiology, and disease susceptibility has been limited by the lack of suitable animal models,” the team continued. “Researchers would create mouse models one-by-one with different mitochondrial DNA mutations, with just one model sometimes taking years,” said Salk staff scientist Weiwei Fan, PhD. This was a problem that Fan had noted early in his scientific career and set his mind to as a PhD student.
The new Salk model is a scalable, embryonic stem-cell (ES)-based platform creating mice with mutations to their mitochondrial DNA. “This new work is all building off an original platform I generated during my PhD,” says Fan, first and co-corresponding author of the study. “That platform was inefficient—it took a long time to generate just one mitochondrial DNA mutant. With some technological improvements and modifications, this new platform is much more efficient and can create dozens of mutants with far greater ease.”
A playful representation of a mitochondrion moving into a larger cell, bringing with it the “baggage” of mutated mitochondrial DNA. Researchers at the Salk Institute developed a new platform for studying that mutated mitochondrial DNA, helping explain the ways it influences human health. [Salk Institute]
The authors explained, “… we developed a scalable ES cell–based platform that integrates mtDNA mutagenesis, cybrid technology, high-sensitivity mutation detection, and optimized mouse transgenesis.” The platform starts with a protein, called mitochondrial DNA polymerase, generating randomly mutated mitochondrial DNA. That mutated mitochondrial DNA is then transferred into stem cells, which can be integrated with mouse embryos to create mice for study. Once one of these mice is established, researchers can investigate the specific symptoms of their specific mitochondrial DNA mutation and the mechanisms by which those symptoms arise—insight that can be used to design targeted therapies down the line. “Optimized ES cell–embryo aggregation enables robust contribution of mtDNA mutant ES cells to host embryos, producing chimeric mice with germline transmission,” the investigators noted.
Using this platform, the Salk team generated a library of 155 mitochondrial DNA mutation cell lines, each with its own distinct impact on mitochondrial performance. “Using this platform, we generate a library of 155 donor fibroblast lines carrying distinct homoplasmic single-nucleotide mtDNA mutations that produce diverse mitochondrial phenotypes, including impaired oxidative phosphorylation, increased reactive oxygen species, and altered mitochondrial membrane potential,” they stated. They then used that library to validate that the cells could be used to generate mice with single mitochondrial DNA mutations. These mice allowed them to find a strong correlation between mitochondrial function and early embryonic development, suggesting a baseline energy level is required for normal development.
“Our library is a huge milestone and is very diverse, with a scale of diversity similar to the known human disease-causing mutation diversity of around 260,” said Fan. “And with this collection of mutant cells, we can not only look at inherited mutations but also at ones that occur based on other stresses like environmental cues or aging.” The authors added, “Together, the advances outlined in this study establish a powerful and generalizable platform for systematically modeling the functional diversity of human mtDNA mutations and polymorphisms in vivo.”
The new platform and library are cracking open the world of mitochondrial DNA. With the ability to generate mitochondrial DNA mutants more rapidly, therapeutic development for mitochondrial disease and dysfunction will come more rapidly, too. The mouse models are already a huge step forward for the field, but the researchers are also eager to move into human models in a more human-relevant context.
“The majority of human diseases come with or cause mitochondrial dysfunction,” said Evans. “Progress in this field has been limited, but this new platform is going to fuel so much important research that points to therapeutic approaches to combat mitochondrial diseases, as well as diseases or conditions associated with mitochondrial dysfunction like cancer or aging.”
In their paper the team concluded, “The library provides a unique and comprehensive resource for modeling the diversity of human mtDNA variation in vitro and can also be used to generate in vivo models through ES-cybrid technology … By enabling the generation of both pathogenic and physiologically relevant mtDNA variants—including those resembling somatic mutations associated with aging and cancer—this platform substantially expands the toolkit available to mitochondrial researchers.”
Researchers from Ohio State University have developed a gene therapy that promotes blood vessel growth following nerve graft surgery. A study published today in Science Advances reports a significant improvement in both nerve growth and muscle strength in treated mice.
Peripheral nerve injury can cause long-term disability, weakness, numbness, or loss of function. While nerve grafts can help repair some of these injuries by regrowing damaged nerves and reconnecting any gaps left by the original injury, many patients still can’t fully recover mobility or feeling.
The new approach developed at Ohio State combines traditional nerve graft surgery with a gene therapy delivered using quick electrical pulses to the nerve drafts. This technique, known as tissue nanotransfection (TNT) is used to introduce three genes (Etv2, Fli1 and Foxc2) into graft cells that promote the formation of new blood vessels.
“This study is the first to combine TNT with nerve graft surgery,” said Daniel Gallego-Perez, PhD, professor of biomedical engineering at Ohio State and senior author of the study. “While healing nerves do need oxygen and nutrients, blood vessels do much more than just deliver supplies—they help guide and support the repair process. By helping the body quickly grow new blood vessels, our approach creates a healthier environment that allows nerves to heal more effectively.”
In a mouse model of peripheral nerve injury, mice treated with the gene therapy grew more blood vessels than those only receiving a conventional nerve graft surgery. The treatment did not just help nerves regrow and reconnect, but also improved function and general health outcomes in mice.
“We saw improvements not just under the microscope, but in real function like stronger muscle contractions and better grip strength,” said Amy Moore, MD, chair of Ohio State’s Department of Plastic and Reconstructive Surgery and interim dean of the university’s College of Medicine. “The findings from this study advance our ability to reconstruct long nerve gaps and restore function to limbs with devastating nerve injuries.”
Moore noted that this approach could make a significant difference when treating severe, complex nerve injuries common among military services injured in training or combat. The treatment is being developed as part of the Military Medicine Program at Ohio State, which focuses on offering surgical reconstruction and pain management care for wounded service members.
Development of the gene therapy will continue with studies in larger animals before human trials can begin. Next, the research team plans to investigate how long the benefits of the treatment last.
This novel approach could one day become part of routine nerve graft surgery, adding a simple short step to significantly improve the outcomes of a well-established procedure. Salazar-Puerta added: “This is designed to fit into the operating room and is a single treatment that could have lasting benefits.”
Background: The United Nations’ third Sustainable Development Goal emphasizes ensuring healthy lives and promoting well-being (WB) for all, which requires effective assistive technology (AT) for persons with disabilities. In low- and middle-income countries (LMICs), however, AT remains largely inaccessible, and high abandonment rates indicate that many existing solutions fail to meet users’ needs. To improve AT design and effectiveness, a deeper understanding of users’ lived experiences and the ways AT influences WB is essential. Objective: This study aimed to explore how technology creates opportunities or barriers in the daily lives of persons with visual disabilities in LMICs and how it affects their WB. Methods: We conducted a qualitative narrative study guided by deductive qualitative analysis, using the capability approach (CA) and disadvantage theory (DT) as theoretical frameworks. Nineteen adults with visual disabilities from Cali, Colombia, participated in in-depth, semistructured interviews. A focus group (n=5) deepened the exploration of shared experiences. Data analysis followed three stages: (1) deductive coding using Nussbaum list of central capabilities and key CA constructs (functionings, conversion factors, and agency); (2) recoding through DT concepts (insecure functioning, corrosive disadvantages, and fertile functionings); and (3) inductive analysis to capture emergent sociocultural themes. Results: AT shaped both opportunities and constraints in participants’ lives. While functionings such as employment, mobility, and affiliation were highly valued, they often remained insecure due to systemic barriers. Corrosive disadvantages—such as unemployment, exclusion, and limited spatial autonomy—undermined multiple capabilities simultaneously. Conversely, fertile functionings such as equitable employment, adaptive sports, and access to well-designed AT supported agency and resilience. The inductive analysis revealed 3 interconnected themes: the aspiration to explore and expand movement, the desire to appear attractive, and the adoption of nonconfrontational strategies to maintain social harmony. These findings highlight how emotional, aesthetic, and cultural dimensions shape the experience and meaning of AT. Conclusions: While AT research in LMICs often emphasizes availability, it rarely addresses how social norms, structural violence, and fear affect meaningful use. The combined CA and DT lens reveals that AT can either enable or constrain WB depending on how it aligns with users’ lived contexts. Designing for fertile functionings—those that support agency, safety, and resilience—is essential. Participatory, context-sensitive design must prioritize not only functionality, but also aesthetic dignity, cultural relevance, and emotional security. Including the voices—and silences—of persons with disabilities in the Global South is crucial for transforming AT from a mere tool into a catalyst for real freedom and WB.
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![Schematic model illustrating the NO-mTOR signaling axis in neuroblastoma. Under basal/pathological conditions (left panel), and nNOS inhibition (right panel). [Haitham Amal]](https://www.genengnews.com/wp-content/uploads/2026/04/Low-Res_Amal-Figure1-2026-Screenshot-2026-04-01-at-11.41.51-300x153.jpg)
![A playful representation of a mitochondrion moving into a larger cell, bringing with it the "baggage" of mutated mitochondrial DNA. Researchers at the Salk Institute developed a new platform for studying that mutated mitochondrial DNA, helping explain the ways it influences human health. [Salk Institute]](https://www.genengnews.com/wp-content/uploads/2026/04/Low-Res_26_03_Evans_PR_PNAS_04-300x232.jpg)