Early protein and calorie supplements lead to fewer high-risk newborns

One of the main reasons why compounds fail is that they actually don't work in the patients they are tested in. We may have picked the wrong target since although we've actually created a molecule that, for example, inhibits the activity of the protein in the disease, it may actually turn out that over activity of that e protein isn't as important as we thought it was in that disease. The other reasons molecules fail now is primarily unexpected toxicity. You could take a molecule all the way through to phase 3 trials – the biggest trials in patients – and suddenly find that in your long-term, two-year carcinogenicity studies in animals, that you've got something that is quite cancer-provoking, so you have to stop development. Those are the two reasons: efficacy and toxicity. Somehow, we've got to find a way of trying to increase the chances of success or making the process less costly and leaner.

Uncertainty and model limitations are critical in safety assessment. There is clearly greater potential for animal or human harm from an incorrect safety assessment than from making the wrong molecule in early discovery, although uncertainty matters in both contexts. It is important to distinguish different types of uncertainty. Aleatoric uncertainty reflects irreducible randomness in a task, while epistemic uncertainty is model-related, such as hallucinations or lack of knowledge. For LLM systems, we use multiple methods to measure consistency and we have built fact-checking approaches in which a separate LLM independently verifies the primary engine's outputs. For QSAR models, including our SAR work around seizure liability, we can use statistical metrics such as confidence intervals to quantify and communicate uncertainty. Understanding that uncertainty exists and communicating it in both safety and discovery is critical. Uncertainty metrics tell us where potential blind spots may exist in our modelling allowing us to take action to improve over time. This applies to both safety and discovery. The aim is not to pretend AI removes uncertainty, but to make uncertainty visible so scientists can make better-informed decisions. Download the Full PDF to Revisit James McDonagh's Insights on AI in Drug Safety Discovery

Daily, if you eat a balanced diet that includes healthy foods, you technically should not need a vitamin supplement. A healthy diet incorporates lean proteins, healthy fats, grains, fruits, and vegetables. But if you do not have a balanced diet, you may be considering hair, skin, and nail vitamins. Some people prefer supplements, sometimes choosing a multivitamin that can supply all of your essential minerals and vitamins. But taking too much of vitamins or unnecessary supplements is wasteful because the body gets rid of excess vitamins and minerals or, worse, it can be dangerous. The following is a guide to choosing which vitamins you may want to consider supplementing and when. Deficiencies in the nutrients that keep the skin, hair, and nails healthy can cause changes over time. For example, not enough intake of vitamins A and E, along with not enough biotin, can cause scaly and rough skin patches, eczema, and hair loss. If there is a deficiency, vitamins will help. However, if there is no deficiency, there is no clear evidence that supplements will make a difference. No research studies concluded that supplements treat or prevent age-related, natural hair damage or loss or lead to healthier skin. Two studies in the early 1990s did suggest that a biotin supplement may cause the hair to become stronger and strengthen weak nails. However, the studies were small and not reproduced.

We are now testing the drug in patients with earlier-stage pancreatic cancer, prescribing it while their tumors are still operable and before their cancer spreads.

More specifically, the study showed that the female patient produced very few cathelicidins, which is a natural toxin found in the immune cells of the lungs needed to fight tuberculosis. In most people infected by tuberculosis, tuberculosis bacteria attack the immune cells of the lungs. The immune cells fight the bacteria by eating them. But the tuberculosis bacterium has developed various evasive mechanisms that reduce the immune cells’ ability to digest and thus to kill the Mtb. “You could say that the tuberculosis bacterium has developed a way to lull the immune cells to sleep. This enables the disease the hide inside the immune cells, making it invisible to other parts of the immune system,” Martin Kongsbak-Wismann explains. This is where vitamin D enters the picture. Because vitamin D is able to counteract the soporific effect of the tuberculosis bacteria by making the immune cells produce more of the cathelicidin toxin. “Cathelicidin is like a microscopic needle that is able to pierce the tuberculosis bacteria. And when it does, it weakens the bacteria’s soporific effect on the immune cells. This restores the immune cells’ ability to kill tuberculosis bacteria,” says Martin Kongsbak-Wismann and adds: “We were amazed by the effect of vitamin D. In immune cells from healthy control subjects, vitamin D improved the cells’ ability to fight Mtb, whereas in the female patient’s immune cells we saw no response to vitamin D. This shows that vitamin D is key to the immune system’s ability to fight Mtb and prevent tuberculosis.” Al-Jaberi, F.A.H., et al. (2022) Reduced vitamin D-induced cathelicidin production and killing of Mycobacterium tuberculosis in macrophages from a patient with a non-functional vitamin D receptor: A case report. Frontiers in Immunology. doi.org/10.3389/fimmu.2022.1038960.