The mysterious case of Eli Lilly’s obesity drug

Who got exclusive access to Eli Lilly’s highly anticipated obesity candidate? Why are drugmakers spending so much money on acquisitions? And are hair loss drugs a good investment?

We discuss all that and more on this week’s episode of “The Readout LOUD,” STAT’s biotech podcast. We bring on our colleague Lizzy Lawrence to discuss her scoop that Lilly and the Food and Drug Administration have allowed one person to receive the pharma company’s obesity candidate, retatrutide, through the FDA’s “compassionate use” program.

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Imaging Technique Scans Entire Donor Livers for Transplant Viability

A new imaging approach to assess donor livers before transplantation could provide a much more comprehensive view of the condition of the whole organ, complementing conventional pathology tests that are typically restricted to localized areas. 

In a study published in Science Translational Medicine, researchers at the University of Oklahoma used polarization-sensitive optical coherence tomography (PS-OCT) to noninvasively measure multiple relevant parameters across the entire surface of donor livers. Using polarized light, this imaging technique was able to detect signs of steatosis, fibrosis, inflammation, and necrosis in donor livers—all of which are critical indicators of transplant viability. 

“PS-OCT offers a noninvasive assessment of liver viability by quantifying hepatic parameters across the entire donor liver, effectively complementing current pathological analysis,” write the authors of the study, led by Qinggong Tang, PhD, associate professor of biomedical engineering at the University of Oklahoma. “These results suggest that PS-OCT provides a robust approach to assessing donor liver viability, which could potentially decrease the discard rate of high-risk livers, thereby expanding the donor pool.”

Liver transplants are limited by a shortage of viable donor livers, which is driven by a high demand for donor livers and high rates of organ discard. In the U.S. alone, there are over 9,000 people on the liver transplant waitlist, which has driven healthcare providers to progressively expand the criteria used to evaluate potential donors. 

Assessing whether a donor liver is viable for transplantation currently relies on biopsies. However, these are invasive procedures that only provide information about the specific location within the liver the sample was taken from. As a result, this approach can sometimes miss critical signs of damage or disease elsewhere in the organ, potentially increasing the risk of transplanting a compromised liver. 

Tang and colleagues first evaluated the performance of PS-OCT imaging in discarded human donor livers, comparing the results to biopsies and functional tests. Using a machine learning algorithm to analyze the imaging data enabled the identification of key signs of injury and disease with 80% accuracy compared to conventional pathology assessments. The team then scanned five viable donor livers slated for transplantation and stratified them into different risk categories, accurately predicting clinical outcomes a week after transplantation. 

While biopsy tests can take several days to give back results, PS-OCT scans can produce a complete picture of the condition of the entire liver within about 15 minutes, offering a fast and noninvasive tool to assess multiple markers of transplant viability. Although the imaging technique is not intended to replace current evaluation methods, it could significantly reduce sampling error and add valuable information when screening potential donors. Ultimately, improving the assessment of donor livers could address the urgent need for increasing transplant numbers while simultaneously improving clinical outcomes for transplant recipients. 

The post Imaging Technique Scans Entire Donor Livers for Transplant Viability appeared first on Inside Precision Medicine.

Evaluating Source-Based Large Language Models for Preclinical Dermatology Education: Comparative Study

Background: Large language models (LLMs) have gained increasing popularity in medical education, with evidence supporting their educational value when framed through the lens of cognitive load theory. Source-based LLMs, which explicitly ground responses in user-uploaded material via retrieval-augmented generation algorithms, may offer additional educational value by using student-developed materials to conceptualize new areas of learning within a familiar framework. This has applications for areas like medical education in dermatology, which could benefit from inclusive sources and enhanced education to alleviate health care gaps. However, no prior studies have examined whether the inclusion of student-authored notes alters the response characteristics of a source-based LLM when responding to medical questions. Objective: This study aims to conduct an observational, comparative performance evaluation study assessing the accuracy, response reproducibility, and intermodel response similarity of freely available LLMs on text-only step 1 dermatology questions, and to explore whether providing extensive student-generated notes to a source-based LLM alters these performance characteristics. Methods: In December 2024, 4 LLMs were evaluated: NotebookLM (NLM) with uploaded preclerkship study guides (NLM w/ Notes), NLM with an uploaded blank sheet of paper (NLM w/o Notes), ChatGPT-4o Mini, and Google Gemini 1.5 Flash. Each model completed 3 trials of 121 text-based United States Medical Licensing Examination (USMLE) step 1 dermatology questions from the AMBOSS question bank. They were evaluated for overall majority-consensus accuracy, accuracy by question difficulty, intertrial reproducibility, and agreement in answer choice selection between models. Differences were analyzed through a Cochran omnibus test and subsequent pairwise McNemar tests with Benjamini-Hochberg correction. Response reproducibility and intermodel agreement were analyzed through Fleiss κ statistics with 95% CI. Results: ChatGPT-4o Mini achieved the highest overall majority-consensus accuracy (102/121, 84.3%). NLM w/ Notes demonstrated the highest intertrial reproducibility (Fleiss κ=0.927, 95% CI 0.875‐0.978) and strong performance on lower-difficulty questions but comparatively reduced accuracy on higher-difficulty items. NLM w/o Notes exhibited significantly higher omission rates (38/363, 10.5% vs ≤7/363, 1.92% for other models) than other tested LLMs. Sensitivity analysis excluding omissions increased NLM w/o Notes’ accuracy from 66.9% (81/121) to 77.8% (77/99), matching NLM w/ Notes’ accuracy of 74.4% (90/121). Intermodel agreement was significantly higher between NLM w/ Notes and ChatGPT-4o Mini compared to NLM w/o Notes and Gemini 1.5 Flash. Conclusions: Provision of student-generated notes substantially increased response reproducibility in a source-based LLM, likely reflecting consistent retrieval of similar source excerpts across trials. However, note-grounding appeared to constrain performance on higher-difficulty questions, suggesting a retrieval-augmented generation algorithm retrieval error when question stems excluded characteristic “keywords” present in lower-difficulty items. The results highlight potential challenges of a student-level, cognitive load theory–grounded educational LLM that must deal with notes not curated by experts, balance source use and internal reasoning, and meaningfully appraise uploaded sources to assess a student’s individual learning gaps.
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Mental Illness Shows Context-Specific Genetic Effects

Many DNA variants linked with neuropsychiatric disorders (NPD) that do not code for proteins depend on neuronal activation, a study suggests.

The findings, in Science, highlight the power of cell stimulation to reveal context-specific “hidden” genetic effects in conditions such as schizophrenia.

They suggest that genetic regulation is not fully revealed by measuring gene expression alone.

Instead, gene activity—at least in the brain—may depend on context and the physiological state of neurons.

“Liang et al. demonstrate that the genetic processes that underlie neuropsychiatric disease are heavily determined by a dynamic physiological environment rather than by fixed cellular conditions,” said Biao Zheng, PhD, and Panos Roussos, PhD, from Icahn School of Medicine at Mount Sinai in New York, in a Perspective article accompanying the study.

They added: “To understand disease genetics, we might need to study the genome in motion and not at rest.”

Genome-wide association studies have revealed hundreds of genetic loci associated with mental illness, with more than 280 identified for schizophrenia alone.

But many of these DNA regions do not encode proteins and their impact is often subtle and difficult to detect.

To investigate further, Lifan Liang, PhD, from the University of Chicago, and co-workers studied gene expression and chromatin accessibility in single neurons derived from induced pluripotent stem cells collected from a hundred human donors.

The single-cell multi-omics study involved assessing transcriptional and epigenomic profiles before and after neurons were activated through potassium-induced depolarization.

The team found that much of the activity in regulatory DNA regions only became apparent with neuronal stimulation.

Both the number of detectable expression quantitative trait loci (eQTLs)—genetic variants associated with differences in gene expression—and chromatin accessibility QTLs (caQTLs)—DNA variants associated with differences in chromatin accessibility—rose after neuronal stimulation.

Shared and cell type-specific transcription factors worked together, possibly through regulatory cascades, to drive cell type-specific neuronal responses to stimuli.

eQTLs after stimulation had substantially weaker overlap with brain eQTL catalogs derived from postmortem tissue compared with eQTLs before stimulation.

This suggested that many relationships between regulatory DNA activity and gene expression become detectable only during neuronal activation and could be missed by traditional tissue-based studies.

A higher number of caQTLs were associated with neuropsychiatric disease compared with eQTLs, suggesting that disease-associated genetic variants could have detectable effects on regulatory DNA even when downstream changes in gene expression were not obvious.

Supporting this, chromatin accessibility and transcriptional responses to neuronal activation often occurred at different times.

Regulatory regions associated with genes that respond rapidly to neuronal stimulation often remained accessible after transcription subsided. By contrast, some late response genes exhibited accessible chromatin before their expression was induced.

When taken together, these observations implied that chromatin accessibility can be an indication of both prior and future transcriptional potential.

“We identified thousands of cell type–specific and activity-dependent quantitative trait loci for gene expression (eQTLs) and chromatin accessibility (caQTLs), helping prioritize NPD risk variants and genes that manifested functional effects only upon neuronal stimulation,” the researchers asserted.

They added: “Our work provides mechanistic insights on neuron subtype–specific activity-dependent gene regulation, substantially expanding the repertoire of context-specific causal variants and genes for NPD and other brain traits.”

The post Mental Illness Shows Context-Specific Genetic Effects appeared first on Inside Precision Medicine.

STAT+: Cassidy proposes bill to rein in 340B drug discount program

WASHINGTON — The chair of the Senate health committee introduced a bill to restrict a federal drug discount program known as 340B that has been lucrative for nonprofit hospitals.

The bill by Sen. Bill Cassidy (R-La.) comes as hospitals face attacks on their bottom lines, especially in Medicaid. The tax bill that Republicans passed last summer significantly decreased the federal government’s share of Medicaid costs and is expected to reduce the number of people on Medicaid. Hospitals also face the prospect of legislation that would lower hospital payments to levels charged by doctor offices, an idea known as site-neutral payments. 

The 340B program also has received scrutiny, and it could be a target for lowering health care spending in future legislation. Cassidy has been looking into the 340B program for years, including an investigation into the company that contracts with the government to be the program’s vendor and a hearing in October.

Continue to STAT+ to read the full story…

Supreme Court ruling blocks thousands of lawsuits against maker of Roundup weedkiller

WASHINGTON — The Supreme Court sided with the maker of Roundup weedkiller Thursday in a ruling expected to block thousands of lawsuits alleging it failed to warn people the product could cause cancer.

The case came before the justices after a tidal wave of litigation that included some multibillion-dollar verdicts against the global agrochemical manufacturer Bayer, a Germany-based company that acquired Roundup when it bought its original producer Monsanto in 2018.

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Angry Kids: Dealing With Explosive Behavior

When a child — even a small child — melts down and becomes aggressive, they can pose a serious risk to themselves and others, including parents and siblings.

It’s not uncommon for kids who have trouble handling their emotions to lose control and direct their distress at a caregiver — screaming and cursing, throwing dangerous objects, or hitting and biting. It can be a scary, stressful experience for you and your child, too. Children often feel sorry after they’ve worn themselves out and calmed down.

So what are you to do?

It’s helpful to first understand that behavior is communication. A child who is so overwhelmed that they are lashing out is a distressed child. They don’t have the skill to manage their feelings and express them in a more mature way. They may lack language, impulse control, or problem-solving abilities.

Sometimes parents see this kind of explosive behavior as manipulative. But kids who lash out are usually unable to handle frustration or anger in a more effective way — say, by talking and figuring out how to achieve what they want.

Nonetheless, how you react when a child lashes out has an effect on whether they will continue to respond to distress in the same way or learn better ways to handle feelings so they don’t become overwhelming.

Behavioral techniques for anger management

Here are some pointers to help kids learn techniques to regulate their emotions:

  • Stay calm. Faced with a raging child, it’s easy to feel out of control and find yourself yelling at them. But when you shout, you have less chance of reaching them. Instead, you will only be making them more aggressive and defiant. As hard as it may be, if you can stay calm and in control of your own emotions, you can be a model for your child and teach them to do the same thing.
  • Don’t give in. Don’t encourage them to continue this behavior by agreeing to what they want in order to make it stop.
  • Praise appropriate behavior. When they have calmed down, praise them for pulling themselves together. And when they do try to express their feelings verbally, calmly, or try to find a compromise on an area of disagreement, praise them for those efforts.
  • Help them practice problem-solving skills. When your child is not upset is the time to help them try out communicating their feelings and coming up with solutions to conflicts before they escalate into aggressive outbursts. You can ask them how they feel and how they think you might solve a problem.
  • Time-outs and reward systems. Time-outs for nonviolent misbehavior can work well with children younger than 7 or 8 years old. When using time-outs, be sure to be consistent with them and balance them with other, more positive forms of attention. If a child is too old for time-outs, you want to move to a system of positive reinforcement for appropriate behavior — points or tokens toward something they want.
  • Avoid triggers. Vasco Lopes, PsyD, a clinical psychologist, says most kids who have frequent meltdowns do it at very predictable times, like homework time, bedtime, or when it’s time to stop playing, whether it’s Legos or video games. The trigger is usually being asked to do something they don’t like, or to stop doing something they do like. Time warnings (“we’re going in 10 minutes”), breaking tasks down into one-step directions (“first, put on your shoes”), and preparing your child for situations (“please ask to be excused before you leave Grandma’s table”) can all help avoid meltdowns.

What kind of tantrum is it?

How you respond to a tantrum also depends on its severity. The first rule in handling nonviolent tantrums is to ignore them as often as possible, since even negative attention, like telling the child to stop, can be encouraging.

But when a child is getting physical, ignoring is not recommended since it can result in harm to others as well as your child. In this situation, Dr. Lopes advises putting the child in a safe environment that does not give them access to you or any other potential rewards.

Critics of time-outs argue that they can be emotionally isolating for kids, but research shows that they are effective and do not cause children harm. (For more on the debate around time-outs, read our full article on the topic.) However, it’s very important to use them as just one technique in a nurturing, supportive parenting strategy. Be sure to balance use of time outs with lots of praise for kids’ positive behaviors. It’s also important to manage your own stress so that kids can learn how to regulate their emotions from your positive example.

If the child is young (usually 7 or younger), try placing them in a time out chair. If they won’t stay in the chair, take them to a backup area where they can calm down on their own without anyone else in the room. Again, for this approach to work there shouldn’t be any toys or games in the area that might make it rewarding.

Your child should stay in that room for one minute and must be calm before they are allowed out. Then they should come back to the chair for time out. “What this does is gives your child an immediate and consistent consequence for their aggression and it removes all access to reinforcing things in their environment,” explains Dr. Lopes.

If you have an older child who is being aggressive and you aren’t able to carry them into an isolated area to calm down, Dr. Lopes advises removing yourself from their vicinity. This ensures that they are not getting any attention or reinforcement from you and keeps you safe. In extreme instances, it may be necessary to call 911 to ensure your and your child’s safety.

Help with behavioral techniques

If your child is doing a lot of lashing out — enough that it is frequently frightening you and disrupting your family — it’s important to get some professional help. There are good behavioral therapies that can help you and your child get past the aggression, relieve your stress, and improve your relationship. You can learn techniques for managing their behavior more effectively, and they can learn to rein in disruptive behavior and enjoy a much more positive relationship with you.

  • Parent-child interaction therapy (PCIT). PCIT has been shown to be very helpful for children between the ages of 2 and 7. The parent and child work together through a set of exercises while a therapist coaches parents through an ear piece. You learn how to pay more attention to your child’s positive behavior, ignore minor misbehaviors, and provide consistent consequences for negative and aggressive behavior, all while remaining calm.
  • Parent management training (PMT). PMT teaches similar techniques as PCIT, though the therapist usually works with parents, not the child.
  • Collaborative and Proactive Solutions (CPS). CPS is a program based on the idea that explosive or disruptive behavior is the result of lagging skills rather than, say, an attempt to get attention or test limits. The idea is to teach children the skills they lack to respond to a situation in a more effective way than throwing a tantrum.

Figuring out explosive behavior

Tantrums and meltdowns are especially concerning when they occur more often, more intensely, or past the age in which they’re developmentally expected — those terrible twos up through preschool. As a child gets older, aggression becomes more and more dangerous to you, and the child. And it can become a big problem for them at school and with friends, too.

If your child has a pattern of lashing out it may be because of an underlying problem that needs treatment. Some possible reasons for aggressive behavior include:

  • ADHD: Kids with ADHD are frustrated easily, especially in certain situations, such as when they’re supposed to do homework or go to bed.
  • Anxiety: An anxious child may keep their worries secret, then lash out when the demands at school or at home put pressure on them that they can’t handle. Often, a child who “keeps it together” at school loses it with one or both parents.
  • Undiagnosed learning disability: When your child acts out repeatedly in school or during homework time, it could be because the work is very hard for them.
  • Sensory processing issues: Some children have trouble processing the information they are taking in through their senses. Things like too much noise, crowds and even “scratchy” clothes can make them anxious, uncomfortable, or overwhelmed. That can lead to actions that leave you mystified, including aggression.
  • Autism: Children with autism spectrum disorder are often prone to meltdowns when they are frustrated or faced with unexpected change. They also often have sensory issues that make them anxious and agitated.

Given that there are so many possible causes for emotional outbursts and aggression, an accurate diagnosis is key to getting the help you need. You may want to start with your pediatrician. They can rule out medical causes and then refer you to a specialist. A trained, experienced child psychologist or psychiatrist can help determine what, if any, underlying issues are present.

When behavioral plans aren’t enough

Professionals agree, the younger you can treat a child, the better. But what about older children and even younger kids who are so dangerous to themselves and others that behavioral techniques aren’t enough to keep them and others around them safe?

  • Medication. Medication for underlying conditions such as ADHD and anxiety may make your child more reachable and teachable. Kids with extreme behavior problems are often treated with antipsychotic medications like Risperdal or Abilify. But these medications should be partnered with behavioral techniques.
  • Holds. Parent training may, in fact, include learning how to use safe holds on your child so that you can keep both them and yourself out of harm’s way.
  • Residential settings. Children with extreme behaviors may need to spend time in a residential treatment facility — sometimes, but not always, in a hospital setting. There, they receive behavioral and, most likely, pharmaceutical treatment. Therapeutic boarding schools provide consistency and structure around the clock, seven days a week. The goal is for the child to internalize self-control so they can come back home with more appropriate behavior with you and the world at large.
  • Day treatment. With day treatment, a child with extreme behavioral problems lives at home but attends a school with a strict behavioral plan. Such schools should have trained staff prepared to safely handle crisis situations.

Explosive children need calm, confident parents

It can be challenging work for parents to learn how to handle an aggressive child with behavioral approaches, but for many kids it can make a big difference. Parents who are confident, calm, and consistent can be very successful in helping children develop the anger management skills they need to regulate their own behavior.

This may require more patience and willingness to try different techniques than you might with a typically developing child, but when the result is a better relationship and happier home, it’s well worth the effort.

Frequently Asked Questions

How can you deal with children’s anger?

One way to handle a child’s anger is to stay calm when they lose their temper. Controlling your emotions sets an example for the child. You can praise them when they express their feelings calmly and when they calm themselves down after an explosion. Adults who are confident, calm, and consistent help children develop the skills to regulate their behavior.

How do I teach a child to control their anger?

In parent-child interaction therapy, a therapist coaches parents on how to pay more attention to positive behavior, ignore minor misbehaviors, and provide consistent consequences for negative and aggressive behavior, all while remaining calm. Other forms of therapy also center on teaching the parent how to model emotional stability.

How can I calm a child down when angry?

Stay calm and ensure they are in a safe space. Yelling can escalate aggression. Speak in a steady voice, avoid giving in, and use time-outs to prevent meltdowns. When they calm down, praise them for it and for expressing their emotions appropriately. If they are frequently aggressive, behavioral therapy may help.

How do I help a child with anger issues?

Children who lash out often lack the skills to manage emotions. Identifying triggers, teaching problem-solving, and using praise or rewards can encourage better behavior. Time-outs work for younger kids, while older ones may need structured reinforcement. If outbursts are severe, you might need professional help. Programs like parent-child interaction therapy (PCIT), parent management training (PMT), or collaborative and practical solutions (CPS) can help.

The post Angry Kids: Dealing With Explosive Behavior appeared first on Child Mind Institute.

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<![CDATA[Phase 3 data show adjunctive seltorexant eases depression and insomnia with lessened weight gain and somnolence.]]>