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Nature Medicine, Published online: 29 June 2026; doi:10.1038/s41591-026-04516-1
We developed a tool, Talos, for automated reanalysis of genomic data from patients with a rare disease and show that frequent reanalysis can be delivered at scale and low cost. Talos is open source, thereby enabling broad adoption by the clinical and research communities.
Nature Medicine, Published online: 29 June 2026; doi:10.1038/s41591-026-04544-x
Author Correction: SEZ6-targeting antibody−drug conjugate ABBV-706 in advanced small cell lung cancer and solid tumors: a phase 1 trial
Methylphenidate is a stimulant medication used to treat symptoms of ADHD. It helps the brain regulate attention, focus, and impulsive behaviors.
It’s one of the two stimulants widely used in ADHD medications. Methylphenidate is the active ingredient in Ritalin and Concerta, among others. The other commonly used stimulant, amphetamine, is the active ingredient in Adderall and Vyvanse, among others. Both stimulants work by increasing levels of dopamine and norepinephrine, chemicals in the brain that control attention, focus, and impulsivity. If a child doesn’t do well on the first stimulant medication they try, they may respond better to a different formulation of that type or the other type of stimulant.
Methylphenidate is somewhat less powerful than amphetamine and tends to have milder side effects.
If your child is under 12 and has just been diagnosed with ADHD, a doctor is likely to prescribe a methylphenidate medication first, to see how well the medication reduces their ADHD symptoms, and whether the side effects are problematic.
Methylphenidate is also many doctors’ first choice for younger children because it has been used to treat ADHD much longer than amphetamine. Ritalin (methylphenidate-based) was FDA approved in 1955, while Adderall (amphetamine-based) wasn’t approved until 1996. In countries outside the United States, amphetamine-based ADHD medications are less widely approved than those based on methylphenidate.
The two stimulants target the same brain chemicals but work slightly differently, says Paul Mitrani, MD, PhD, a child and adolescent psychiatrist at the Child Mind Institute. Methylphenidate increases the levels of dopamine and norepinephrine by blocking what’s called reuptake — the process by which nerve cells reabsorb these chemicals after they’ve been released. As Dr. Mitrani describes it, methylphenidate “enhances” the norepinephrine and dopamine the brain naturally releases by making the chemicals stay around longer. It boosts the stimulation the brain is already getting from whatever activity the child is engaged in.
Amphetamine, on the other hand, not only blocks reuptake but stimulates the release of more dopamine and norepinephrine, which is why it’s considered stronger. “Adding stimulation with amphetamine sometimes helps,” he notes. “But sometimes that added stimulation is too much, and it increases side effects the child experiences.”
There is individual variation in how children respond to the two stimulants. So if methylphenidate doesn’t give the desired symptom relief or produces problematic side effects, it’s recommended practice to try amphetamine, or vice versa. Research shows that 70 percent of children with ADHD respond to a trial of methylphenidate. More than 90 percent will have a beneficial response to one of the stimulants if both methylphenidate and amphetamine are tried. Studies also show that approximately 41 percent respond equally well to both types of stimulant.
Children can also vary in their response to different formulations of the same stimulant, which affect the rate at which the medication goes into the bloodstream. For instance, a short-acting form of Ritalin will kick in quickly and last for 3-4 hours, while Concerta, a delayed-release formula, lasts as long as 10-12 hours. It’s very common for kids to try several before finding the best fit.
Methylphenidate and amphetamine have the same side effects, though they may be less intense with the former.
The most common side effect of stimulants is appetite suppression. It can be especially concerning with long-acting forms of the medication, which are often preferred to get better coverage through the school day. Kids who take a long-acting stimulant in the morning tend to lose their appetite for lunch and may not be interested in eating until after dinnertime.
When this is a problem, Dr. Mitrani notes that taking a shorter-acting form of the medication can help. “For instance, Concerta is a methylphenidate medication that lasts for a long time and can suppress appetite for 10–12 hours.” An alternative might be a medication that lasts for 6–8 hours, such as Metadate CD or Ritalin LA. Some children with more pronounced problems with appetite will do better on a short-acting dose in the morning and then another after lunch, he adds, since it gives them a break during the day where they can eat better.
Kids who take stimulant medication can have trouble falling asleep. This can happen when a long-acting medication or an afternoon dose of a short-acting medication wears off and they get restless or hyperactive around bedtime. Difficulty falling asleep can get better after a few weeks, but if it doesn’t, it may be helpful to change either the timing or the type of the medication that is given. It’s also important to explore whether there are other contributors to sleep challenges, such as worry, screen time too close to bedtime, or lack of a consistent evening routine that helps kids calm down.
Stimulant medications can generate agitation and irritability, which can be especially problematic in kids who are already anxious. For children with anxiety, this can be another reason to start treatment with methylphenidate, because amphetamines can feel more activating.
But Dr. Mitrani notes that treating ADHD can also reduce anxiety: “Some kids are so stressed about school — because they can’t pay attention or arealways getting in trouble — that when you treat the ADHD, they are better able to manage the demands of school and become less anxious.”
That reduction in school anxiety can also affect what happens when they get home from school. “When there is anxiety, it’s like kids are holding it together at school, and then they come home after a stressful day and just let it out,” he says. “So if the school day is less stressful, you may also see that come down at the end of the day.”
Some children report that stimulant medications seem to dull their personality. Dr. Mitrani suggests that this may be connected to the medication stimulating the prefrontal cortex, the part of the brain that not only manages attention and focus, but also helps regulate emotions and impulse control in other brain areas. “Enhanced control of the emotional part of the brain can cause this feeling of dullness,” he notes. “Some people will even say they feel depressed, that they’re just not like themselves because they don’t have the same energy or personality.”
If this happens to a child on methylphenidate, Dr. Mitrani will recommend trying an amphetamine or a non-stimulant medication.
Some families report that their child is irritable or emotional after school or at the end of the day, when the stimulant medication is wearing off. Dr. Mitrani notes that this can coincide with the child being hungry after missing lunch. It can also be connected to the medication level dropping too quickly, and strategies that create a more gradual decrease may help take it away. For example, he might suggest adding a small dose of short-acting form of the stimulant a half hour before the morning medication wears off.
Dr. Mitrani usually starts a child on a short-acting form of methylphenidate for two reasons: as a quick test to see if the child will experience side effects and to have an opportunity to try it twice in a day, to have more chances to assess for positive changes.
He recommends starting the medication on a weekend or a break from school and giving the child some tasks that are challenging for them because of their ADHD, like reading or something else that requires concentration, such as cleaning their room or doing household chores. “After lunch you want to try it again, to have another time point to check on. Because if you only give one dose of the medication, you don’t know if the child’s behavior was a result of the medication or some other factor. The more data points that we have, or more trials, the more information we get.”
He recommends keeping the child on short-acting doses for at least several days before trying a longer-acting formula.
Practice guidelines for psychiatrists recommend starting children on a low dose to assess any side effects the child might experience and gradually increasing it over 1-2 weeks with careful monitoring of response until you reach the minimum dose that will give the best symptom relief.
There is a great deal of variation in how children respond to these medications, so starting with an “average” effective dose, even adjusted by body weight, would be under-medicating some kids and overmedicating others.
For instance, for a 6- or 7-year-old child, a common starting dose of a short-acting medication might be about 2.5 mg, going up to 5 mg if more is needed for symptom relief and side effects are not an issue, Dr. Mitrani says.
Liquid versions of either stimulant have an advantage when it comes to getting exactly the right dose, he notes: “You can do, 1 milliliter, 1.5, 1.6, depending on the syringe.”
Long-acting formulations that come in capsules can be especially frustrating, he adds — since they come in set doses and can’t be opened and divided effectively, because the beads inside are made to be triggered at different time periods.
Dr. Mitrani stresses that small differences in the formulation of a medication can make a difference in a child’s reaction.
For instance, Focalin (dexmethylphenidate) is a refined form of methylphenidate. Standard methylphenidate medications contain two mirror-image forms, or isomers, but most of the benefit comes from one of them. Focalin contains only this more active isomer. For some children, it works better, causes fewer side effects, or feels smoother.
He also notes that variations in the release patterns among long-acting formulations can affect a child’s experience. “Take Concerta, which has a unique mechanism for the extended release,” he explains. “There are three phases: a really immediate phase, then a regular Ritalin kind of phase and, then a slow extrusion of the remaining methylphenidate throughout the day that helps it last as long as 12 hours.”
By contrast, he describes Ritalin LA, which tends to last for 6-8 hours, as “50-50” — 50 percent of the dose is immediate released and the other half is delayed release. Other formulations are “40-60” or “30-70.” “These subtle differences can result in some kids responding better to one than the other, while other kids can do well on any of them.”
So even within the methylphenidate group, there may be reason to try a child on number of different formulations to get the best fit. And, of course, other reasons for trying different versions are limits on what insurance covers —which can change suddenly — and what’s available because of shortages. “And that can be really frustrating for families,” he says. “What I hear is, ‘My child was on Concerta or on Metadate CD and they made me switch to this one and now my kid’s not doing as well.’ “
When families cannot get a medication that has been working, finding another medication that’s available, that’s effective, and that insurance will approve can be a lot of hoops to jump through, he adds.
The post Treating ADHD With Methylphenidate (Ritalin, Concerta) appeared first on Child Mind Institute.
Background: Office work is increasingly carried out outside conventional office settings, particularly during and after the COVID-19 pandemic. This highlights the need to understand the complexity of aspects that may influence health across different office work environments. Objective: This study aimed to (1) identify aspects that office workers perceive as supporting or hindering their health during office work, and (2) formulate novel questions about office work for quantitative studies. Methods: In February 2021, we conducted a digitally distributed photovoice study in Sweden, in which a convenience sample of 17 office workers from 5 companies took photos and provided written comments on what they perceived as supporting or hindering their health in places where they performed office work. For objective 1, we carried out both qualitative formal analysis and analysis without a theoretical frame, as well as quantified the content of the photos and comments. The identified aspects and their interactions were summarized in a visual framework. For objective 2, findings from the photovoice study were used to adapt selected items from the 2019 Swedish Work Environment Survey, capturing office work performed across multiple settings. Results: Of a total of 63 photos, 70% (44/63) were taken at home, 24% (15/63) in an office, and 6% (4/63) outdoors. The comments on photos taken in conventional office settings largely highlighted health-promoting aspects, while the interpretations of home office photos showed greater variability regarding their impact on health. We identified 9 aspects and categorized them into two groups: (1) environmental perspective, including space, ergonomic, technical, and aesthetic-sensuous aspects and (2) behavioral perspective, including flexibility, focus, breaks-recovery, physical activity, and eating habits. Whether the aspects supported or hindered health depended on the environment where office work was performed and the employees’ living conditions. Our visual framework illustrates how these two perspectives interact with each other, bridged by space and flexibility. The study also resulted in a battery of multiple-choice questions about work in offices, at home, in public places, and outdoors that can be used in future research to better capture variation in modern work arrangements. Conclusions: This study extends the notion that office environments play a central role in supporting employee health by suggesting that this also applies to home offices. The results emphasize the need for tailored health-promoting interventions that account for the diverse environments in which office work is performed and for individual needs. The developed visual framework for analyzing health-promoting work environments for office workers and the battery of survey questions can contribute to future research and the advancement of sustainable, health-promoting office environments.
<img src="https://jmir-production.s3.us-east-2.amazonaws.com/thumbs/5ec51afe1b4c20241033ac2a6da36395" />
Helminth parasites of the Schistosoma genus cause roughly 290,000 deaths annually, primarily in tropical and subtropical regions. In addition, an estimated 250 million people are currently chronically infected with Schistosoma parasites—with an additional 800 million people at risk of getting the infection—making schistosomiasis second only to malaria among the world’s deadliest tropical parasitic diseases.
The larvae, which live in fresh water, penetrate the skin and develop into adults. Schistosomiasis can be found in nearly 80 countries and is common in sub-Saharan Africa.
Now, new research shows promise for a vaccine being tested to prevent and treat schistosomiasis. SchistoShield® (Sm-p80 + GLA-SE) is a leading vaccine candidate for schistosomiasis that has successfully completed Phase I (USA) and Phase Ib (Africa) safety and immunogenicity clinical trials. Findings in a new report suggest that the vaccine triggered an adaptive immune effector and memory responses.
This work is published in npj Vaccines in the paper, “Schistosomiasis vaccine SchistoShield® induces functional immune memory responses in U.S. and African populations.”
Afzal Siddiqui, PhD, director of the Center for Tropical Medicine and Infectious Diseases and chair of the Department of Immunology and Molecular Microbiology at the TTUHSC School of Medicine has devoted decades to creating SchistoShield.
In this study, samples taken from people who’ve received trial doses of the vaccine in both the United States and Africa now demonstrate the vaccine’s effectiveness. Using Peripheral Blood Mononuclear Cells (PBMCs) obtained from intercontinental Phase I and Phase Ib trial participants, the team analyzed adaptive immune effector and memory responses to SchistoShield.
“The SchistoShield vaccine,” Siddiqui notes, “induced robust cell-mediated effector and memory responses, hallmarks of a potentially efficacious vaccine against schistosome/helminth parasites.”
More specifically, the paper reports results demonstrating that “the vaccine induced pronounced effector and memory T-cell responses. Upon recall with Sm-p80 antigen, cytokines including IFN-γ, TNF-α, IL-17A, IL-9, and granzyme B were produced, indicating the generation of functionally heterogeneous CD4 T-helper and cytotoxic lymphocyte responses. Consistent with T-helper responses that promote humoral immunity, Sm-p80 antigen-specific antibody-secreting plasmablasts were detected in vaccinated volunteers who were tracked longitudinally.”
“The people we have vaccinated, in both the U.S. and in Africa, have the memory response, both B-cell and T-cell-based,” Siddiqui said. “The vaccine is doing what it is supposed to. But always remember that these trials are very small 50 to 100 people. Now it has to go to thousands of people. So that’s where we are moving into.”
Schistosomiasis is considered a “neglected disease” because it predominantly affects impoverished communities in tropical and subtropical regions. There’s only one drug available to treat people, but it does not prevent re-infection. Through his efforts, and the support of TTUHSC, federal grants and national and international charitable and non-profit groups, Siddiqui has been able to develop SchistoShield as a humanitarian effort, rather than making it for profit.
“Our purpose from the beginning has been to expand access to care,” Lori Rice-Spearman, PhD, president of TTUHSC said. “Dr. Siddiqui’s work reflects that commitment through research that could help address a disease affecting millions of people around the world.”
The post Schistosomiasis Vaccine Shows Strong Immune Memory in Early Clinical Trials appeared first on GEN – Genetic Engineering and Biotechnology News.
Neurodegenerative diseases affect tens of millions of people worldwide. A new study published in Cell Death Discovery titled, “Sustained dysregulation of iron and glutathione homeostasis induces chronoferroptosis, a persistent ferroptotic adaptation in neuronal cells,” points to iron accumulation as a key target in the effort to predict, prevent, and treat neurodegenerative diseases.
“Resilience has become a huge topic of discussion when it comes to Alzheimer’s disease and other neurodegenerative disorders, trying to make the brain more resilient in the face of stressors that contribute to neurodegeneration,” said Pam Maher, PhD, co-corresponding author and a research professor at the Salk Institute. “Our study reveals that cells lose resilience when iron hits a certain level, making neurons more susceptible to stressors that damage or even kill them.”
Found in dark leafy greens, starchy cereals, lean meats, seafood, and other common foods, iron helps red blood cells develop, carries oxygen, makes hormones, and engages in key functions across the immune system and energy production.
“It’s one of the most important minerals in the body,” says co-corresponding author Nawab John Dar, PhD, a postdoctoral researcher in Maher’s lab. “So, it isn’t the iron itself that is a problem with age. It is this accumulation of iron over time that is the problem.”
The authors suggest iron buildup is caused by a failure in iron export machinery. Using a human-derived nerve cell line, the study generated a progressive model of iron accumulation in neuronal cells. They compared the effects of both acute (between six and eight hours) and chronic (nine days) exposure to iron and found the chronoferroptosis pathway.
Traditionally, ferroptosis was considered an iron-dependent cell death pathway related to lipid peroxidation. “It is like the cellular equivalent of when a cooking oil or nut goes bad. The fats in that oil or nut have undergone peroxidation,” explains Maher.
Chronoferroptosis adds the dimension of time to ferroptosis. The pathway does not necessarily end in cell death, but rather, ferroptosis can act as a cellular stress pathway.
“We think these coordinated alterations in iron-handling and antioxidant defense proteins make chronically exposed neurons vulnerable to neurodegenerative pathology,” said Dar. “Entering this state of chronoferroptosis may set neurons up for age-related failure.”
“It’s not the amount of iron that seals the fate of these cells,” Dar continued. “It’s the amount of time they spend under stress.”
Researchers aspire to detect when iron accumulation starts stressing neurons to develop new interventions for addressing iron imbalances to keep neurons resilient.
“It’s not something we worked on in this paper, but our lab has developed several compounds to inhibit this pathway,” says Maher. “This could really be a promising therapeutic route for boosting neuron resilience and staving off neurodegeneration as we grow older.”
The post Iron Accumulation Drives Neurodegeneration via Chronic Stress Pathway appeared first on GEN – Genetic Engineering and Biotechnology News.
Rinn Advanced Therapies, Ireland’s national research center for personalized immune cell therapies, signed a Memorandum of Understanding (MOU) with CCRM, which focuses on cell and gene therapy development and commercialization. The agreement outlines a strategic collaboration to explore establishing a CCRM-affiliated advanced therapies hub in Ireland.
The proposed initiative, referred to as CCRM Ireland, is designed to position Ireland as a key node within CCRM’s global network of advanced therapies hubs and further strengthen Ireland’s expertise in next-generation biomedicine. CCRM’s global network comprises CCRM in Canada, CCRM Australia, and CCRM Nordic in Sweden.
“The idea of collaborating with CCRM to establish CCRM Ireland is very attractive because of our shared commitment to improving patient outcomes,” said Sakis Mantalaris, PhD, director of Rinn Advanced Therapies. “By combining Rinn Advanced Therapies’ focus on novel personalized immune cell therapeutics with CCRM’s global platform, CCRM Ireland can accelerate the translation of cutting-edge science into accessible, high-quality treatments.”
Through this collaboration, Rinn Advanced Therapies will lead the evaluation of how Ireland’s integrated ecosystem—spanning academia, health care, biomanufacturing and research—can be aligned with CCRM’s model for accelerating the development of advanced therapies. The partnership will explore how to advance the design and clinical translation and delivery of personalized immune cell therapies, while also leveraging Ireland’s biopharmaceutical manufacturing skills.
CCRM Ireland would potentially support investment, venture creation and commercialization pathways, following CCRM Canada’s proven model.
“As cell and gene therapies move from scientific promise to clinical reality, no single organization, region or country can build this industry alone,” says Michael May, president and CEO, CCRM. “CCRM’s global hubs are designed to connect world-class research, manufacturing expertise, capital and talent into a coordinated network that accelerates the development and commercialization of advanced therapies.
By creating hubs around the world, and in the spirit of the Prime Minister of Canada’s call for middle-power countries to work together, with CCRM Ireland, we can help innovators overcome barriers to scale, strengthen local ecosystems and, most importantly, bring life-changing treatments to patients faster.”
Rinn Advanced Therapies brings together a network that includes universities, hospitals, and national organizations with a shared mission to develop and deliver personalized immune cell therapies that are more effective, accessible and affordable for patients.
CCRM will contribute its expertise in establishing and operating advanced therapies hubs, drawing on its experience in Canada and its growing international network. This includes proven frameworks in governance, GMP manufacturing, quality systems and commercialization.
The post CCRM Ireland Would Be Established to Hasten Translation of Advanced Therapies Into Patient Treatments appeared first on GEN – Genetic Engineering and Biotechnology News.
India-based Shilpa Biologicals commissioned an antibody–drug conjugate (ADC) GMP manufacturing facility, purpose-built and designed to meet global regulatory approval standards including U.S. FDA, EMA, and other major health authority requirements. The facility is fully operational, with GMP qualification protocols now underway.
According to Sridevi Khambhampaty, CEO, Shilpa Biologicals, “The manufacturing of highly potent compounds has been a core pillar of Shilpa’s identity, and this ADC drug substance facility adds a new sophisticated dimension to the capabilities of the Shilpa group. We now offer global biotech and pharma partners a uniquely integrated ADC facility built with the knowledge of our existing high potency manufacturing excellence.”
“India has the scientific talent and now, with this facility, the infrastructure to be a serious and trusted partner in global ADC drug substance manufacturing,” said Vishnukant Bhutada, managing director, Shilpa Medicare. “We are ready to partner with the world’s leading oncology innovators.”
The post Shilpa Commissions Integrated ADC Drug Substance GMP Manufacturing Facility appeared first on GEN – Genetic Engineering and Biotechnology News.
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Imagine coming in to work to learn that a new underling will report to you. The worker is not a person but an AI tool—one that your company nonetheless calls Alex, an “employee” with a title and defined responsibilities. How well do you think you would work with Alex?
If you’re anything like the managers recently studied by Emma Wiles, a Boston University business professor, treating Alex as a “coworker” and not a software tool would lead you to do a worse job. Wiles found that people caught 18% fewer errors when the work was said to have come from an agentic “AI employee” rather than a chatbot. It turns out that what’s in a name matters. A lot.
This is an alarming glimpse of the future Silicon Valley is hurling us toward. Last year Nvidia’s CEO, Jensen Huang, talked about workplaces of “digital humans.” Since April, Microsoft, OpenAI, Anthropic, and Google have all released new tools oriented toward managing teams of AI agents, many of which are explicitly advertised as digital colleagues with the flexibility and cognitive power of actual humans. And nearly a third of the 1,261 managers who participated in Wiles’s study said their companies already frame AI agents as employees (23% even list them on org charts).
The technical progress of agentic AI is not all hot air, of course. Agents, which can effectively be thought of as AI tools programmed to work in a loop until they achieve a goal, have become measurably better at more complicated tasks. But it’s a huge leap to refer to these tools as coworkers or employees, and doing so will set unrealistic expectations for what AI can do while leaving the human employees supposedly responsible for them worse off.
That’s partially because, Wiles’s research suggests, it inverts our sense of who’s in charge. When an AI tool was framed as an employee, participants in the study saw themselves as less responsible for its output. They were also 44% more likely to escalate its questionable work to a manager for further review rather than trusting their own corrections (thus negating the time-saving purpose of using the AI agent in the first place).
That matters far beyond office culture: As AI agents are embedded into health care, warfare, education, and government, there’s a growing risk they’ll become a convenient place to dump blame for failures that are instead the product of bad human decisions, incentives, and oversight (recall how the bomb strike on a girls’ school in Iran was popularly blamed on Claude, when all signs point to a cascade of human errors).
“AI agents right now are being marketed as things that can replace humans, and I think that’s just a losing proposition,” says Daron Acemoglu, an economist at MIT who won the Nobel Prize in 2024 and studies AI’s impact on the economy. “They should instead be optimized so that they can improve human capabilities, which is not what they have [been] at the moment.”
What could that look like? Consider a new effort at Stanford, where researchers presented 1,500 workers in 104 jobs with information about what tasks AI could potentially do in their work and then asked what would actually be most helpful and productive. Workers did want automation in certain areas: Law clerks thought AI could help ensure that adequate progress was being made across cases, for example. But often the tasks that tech experts deemed most suitable for AI—like verifying customer credit ratings for sales reps—were what the actual workers said they definitely did not want or need an agent to do.
Which brings us back to Alex. Calling Alex an employee is easy—and convenient, especially when something goes wrong—but it’s a branding exercise. It doesn’t make the tool more fit for the job, and as Wiles’s research shows, it makes the humans around it worse at theirs. And recall that they are the ones with the agency that AI is trying to replicate. They deserve better than Alex.