Discovery of BBO-8520, a first-in-class direct and covalent dual inhibitor of GTP-bound (ON) and GDP-bound (OFF) KRASG12C.

Approved inhibitors of KRASG12C prevent oncogenic activation by sequestering the inactive, GDP-bound (OFF) form rather than directly binding and inhibiting the active, GTP-bound (ON) form. This approach provides no direct target coverage of the active protein. Expectedly, adaptive resistance to KRASG12C (OFF)-only inhibitors is observed in association with increased expression and activity of KRASG12C(ON).

Provision of inguinal hernia surgery in first-referral hospitals across low- and middle-income countries: Secondary analysis of an international cohort study.

Introduction: Surgical care in first-referral hospitals (FRHs) in low- and middle-income countries (LMICs) is poorly characterized. Inguinal hernia repair can act as a good tracer condition. This study aimed to evaluate the variation in hernia repair across different hospital types in LMICs.

National phosphorus planning for food and environmental security.

The dependence of countries on phosphorus fertilisers derived from phosphate rock to maintain crop yields and ensure food security is well established. Yet, exposure of national food systems to constrained reserves of phosphate rock and supply chain complexities still pose risks to farmers' access to this critical nutrient in many countries. Whilst phosphorus scarcity can threaten food security, suboptimal fertiliser use and poor wastewater treatment can lead to pollution of freshwaters and coasts, causing eutrophication.