Algorithmovigilance, lessons from pharmacovigilance.

Artificial Intelligence (AI) systems are increasingly being deployed across various high-risk applications, especially in healthcare. Despite significant attention to evaluating these systems, post-deployment incidents are not uncommon, and effective mitigation strategies remain challenging. Drug safety has a well-established history of assessing, monitoring, understanding, and preventing adverse effects in real-world usage, known as pharmacovigilance.

Do machine learning methods lead to similar individualized treatment rules? A comparison study on real data.

Identifying patients who benefit from a treatment is a key aspect of personalized medicine, which allows the development of individualized treatment rules (ITRs). Many machine learning methods have been proposed to create such rules. However, to what extent the methods lead to similar ITRs, that is, recommending the same treatment for the same individuals is unclear.

Metformin does not compromise energy status in human skeletal muscle at rest or during acute exercise: A randomised, crossover trial.

5´AMP-activated protein kinase (AMPK) is a mediator of a healthy metabolic phenotype in skeletal muscle. Metformin may exacerbate the energy disturbances observed during exercise leading to enhanced AMPK activation, and these disturbances may provoke early muscular fatigue. We studied acute (1 day) and short-term (4 days) effects of metformin treatment on AMPK and its downstream signaling network, in healthy human skeletal muscle and adipose tissue at rest and during exercise, by applying a randomized blinded crossover study design in 10 lean men.

Deletion of skeletal muscle SOCS3 prevents insulin resistance in obesity.

Obesity is associated with chronic low-grade inflammation that contributes to defects in energy metabolism and insulin resistance. Suppressor of cytokine signaling (SOCS)-3 expression is increased in skeletal muscle of obese humans. SOCS3 inhibits leptin signaling in the hypothalamus and insulin signal transduction in adipose tissue and the liver.

Estimation of the dissociation rate of unlabelled ligand-receptor complexes by a 'two-step' competition binding approach.

Background And Purpose: Because the in vivo effectiveness of ligands may also be determined by the rate by which they dissociate from their target receptors, drug candidates are being increasingly screened for this kinetic property. The dissociation rate of unlabelled ligand-receptor complexes can be estimated indirectly from their ability to slow the association of subsequently added radioligand molecules.

Experimental Approach: We used the 'two-step competition' binding approach consisting of pre-incubating the receptor preparation with a wide range of ligand concentrations, washing off free ligand molecules, adding radioligand and monitoring its receptor binding after a fixed time.