A human-like glutaminase-free asparaginase is highly efficacious in ASNS leukemia and solid cancer mouse xenograft models.

L-asparaginase (L-ASNase) is crucial in treating pediatric acute lymphoblastic leukemia (ALL), but its use is hampered by side effects from the immunogenicity and L-glutaminase (L-GLNase) co-activity of FDA-approved bacterial L-ASNases, often leading to treatment discontinuation and poor outcomes. The toxicity of these L-ASNases makes them especially challenging to use in adult cancer patients. To overcome these issues, we developed EBD-200, a humanized guinea pig L-ASNase with low Km and no L-GLNase activity, eliminating glutamine-related toxicity.

SNMF: Integrated Learning of Mutational Signatures and Prediction of DNA Repair Deficiencies.

Motivation: Many tumours show deficiencies in DNA damage response (DDR), which influence tumorigenesis and progression, but also expose vulnerabilities with therapeutic potential. Assessing which patients might benefit from DDR-targeting therapy requires knowledge of tumour DDR deficiency status, with mutational signatures reportedly better predictors than loss of function mutations in select genes. However, signatures are identified independently using unsupervised learning, and therefore not optimised to distinguish between different pathway or gene deficiencies.

The antiviral JNJ-A07 significantly reduces dengue virus transmission by mosquitoes when delivered via blood-feeding.

Dengue virus (DENV) is the most widespread mosquito-borne virus worldwide, but no antiviral therapies are available yet. The pan-serotype DENV inhibitor JNJ-A07 has shown potent activity in a mouse model. It remains unknown whether an antiviral drug ingested by mosquitoes could inhibit virus replication and thus reduce transmission to other hosts.

Fasciotomy for Chronic Exertional Compartment Syndrome of the Deep Posterior Lower Leg Compartment: A Prospective Study.

Objective: Patients with lower leg deep posterior chronic exertional compartment syndrome (dp-CECS) experience exercise-induced calf pain and tightness. Retrospective studies suggest that outcome after a fasciotomy is suboptimal. This prospective case series determined success rates of a fasciotomy and identified factors predicting outcome.

ZEB2 drives intra-tumor heterogeneity and skin squamous cell carcinoma formation with distinct EMP transition states.

About 5% of patients with cutaneous squamous cell carcinoma (cSCC) have a poor prognosis which is associated with a loss of tumor differentiation, invasion and metastasis, all of which are linked to the process of epithelial-to-mesenchymal plasticity (EMP). Here, we showed that the EMP-associated transcription factor ZEB2 drives cSCC heterogeneity which resembles biphasic carcinosarcoma-like tumors. Single cell RNA sequencing revealed distinct subpopulations ranging from fully epithelial (E) to intermediate (EM) to fully mesenchymal (M), associated with the gradual loss of cell surface markers EPCAM, CDH1, ITGB4, and CD200.