Converting IMPROVE bleeding and VTE risk assessment models into a fast-and-frugal decision tree for optimal hospital VTE prophylaxis.

Current hospital venous thromboembolism (VTE) prophylaxis for medical patients is characterized by both underuse and overuse. The American Society of Hematology (ASH) has endorsed the use of risk assessment models (RAMs) as an approach to individualize VTE prophylaxis by balancing overuse (excessive risk of bleeding) and underuse (risk of avoidable VTE). ASH has endorsed IMPROVE (International Medical Prevention Registry on Venous Thromboembolism) risk assessment models, the only RAMs to assess short-term bleeding and VTE risk in acutely ill medical inpatients.

Claspin haploinsufficiency leads to defects in fertility, hyperplasia and an increased oncogenic potential.

Claspin is an adaptor protein required for ATR-dependent phosphorylation of CHK1 during S-phase following DNA replication stress. Claspin expression is highly variable in cancer, with low levels frequently correlating with poor patient survival. To learn more about the biological consequences of reduced Claspin expression and its effects on tumorigenesis, we investigated mice with a heterozygous knockout of the Clspn gene.

A prometaphase mechanism of securin destruction is essential for meiotic progression in mouse oocytes.

Successful cell division relies on the timely removal of key cell cycle proteins such as securin. Securin inhibits separase, which cleaves the cohesin rings holding chromosomes together. Securin must be depleted before anaphase to ensure chromosome segregation occurs with anaphase.

Aneuploidy in Oocytes Is Prevented by Sustained CDK1 Activity through Degron Masking in Cyclin B1.

Successful mitosis requires that cyclin B1:CDK1 kinase activity remains high until chromosomes are correctly aligned on the mitotic spindle. It has therefore been unclear why, in mammalian oocyte meiosis, cyclin B1 destruction begins before chromosome alignment is complete. Here, we resolve this paradox and show that mouse oocytes exploit an imbalance in the ratio of cyclin B1 to CDK1 to control CDK1 activity; early cyclin B1 destruction reflects the loss of an excess of non-CDK1-bound cyclin B1 in late prometaphase, while CDK1-bound cyclin B1 is destroyed only during metaphase.