Altered expression of aromatase and estrogen receptors in adipose tissue from men with obesity or type 2 diabetes.

Objective: Obesity and insulin resistance in men are linked to decreased testosterone and increased estradiol (E2) levels. Aromatase (ARO) converts testosterone into E2, and this occurs mainly in adipose tissue in men. E2 acts through estrogen receptors ESR1 and ESR2, and they potentially affect development of type 2 diabetes (T2D).

Estimating an Elephant Population Size Through Local Ecological Knowledge.

In planning and monitoring measures to protect wildlife in an area, it is important to have a reliable baseline estimate of population size and trends. There has been minimal published information on a small population of elephants, a keystone and endangered species, in a large area west of Etosha National Park in Namibia, known locally as the Northern Highlands. It is a highly remote, mountainous area in which it is difficult to count elephants.

Enabled Discovery of KAI-11101, a Preclinical DLK Inhibitor for the Treatment of Neurodegenerative Disease and Neuronal Injury.

Dual leucine zipper kinase (DLK), expressed primarily in neuronal cells, is a regulator of neuronal degeneration in response to cellular stress from chronic disease or neuronal injury. This makes it an attractive target for the treatment of neurodegenerative diseases such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis, and neuronal injury, such as chemotherapy-induced peripheral neuropathy. Here, we describe the discovery of a potent, selective, brain-penetrant DLK inhibitor, KAI-11101 ().

Discovery of a Novel Mutant-Selective Epidermal Growth Factor Receptor Inhibitor Using an Enabled Drug Discovery Platform.

Despite the success of first, second, and third generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for non-small cell lung cancer with classical EGFR mutations (L858R or Exon 19 deletions), disease progression occurs due to the acquisition of T790M and C797S resistance. Herein, we report a physics-based computationally driven lead identification approach that identified structurally unique imidazo[3.2-]pyrazoles as reversible and wild-type-sparing EGFR TKIs of classical mutations bearing both T790M and C797S.

Concentration of spending and share of specialty drug spending in Medicare Part D over a 10-year period.

Background: In 2021, Medicare Part D gross prescription drug spending amounted to $216 billion, a number that has more than doubled over the last 10 years. Spending in Medicare Part D is concentrated on a small number of drugs, and spending on specialty drugs has increased in recent years. However, the extent to which concentration in Part D spending has changed over time and the drivers of this change have not been described.