A perspective review on the systematic implementation of ctDNA in phase I clinical trial drug development.

Circulating tumour DNA (ctDNA) represents an increasingly important biomarker for the screening, diagnosis and management of patients in clinical practice in advanced/metastatic disease across multiple cancer types. In this context, ctDNA-based comprehensive genomic profiling is now available for patient management decisions, and several ctDNA-based companion diagnostic assays have been approved by regulatory agencies. However, although the assessment of ctDNA levels in Phase II-III drug development is now gathering momentum, it remains somewhat surprisingly limited in the early Phase I phases in light of the potential opportunities provided by such analysis.

Genetically Distinct Acute Megakaryoblastic Leukemia following Low Hypodiploid B-Lymphoblastic Leukemia linked by Mutation.

We report a case of acute myeloid leukemia with megakaryoblastic differentiation (AMKL) that developed after an initial B-lymphoblastic leukemia (B-ALL) with low hypodiploidy. Although the AMKL was initially thought either to be a phenotypic change from the original B-ALL or to have arisen as a result of treatment (acute myeloid leukemia, post cytotoxic therapy, AML-pCT [WHO]; AML, therapy related [ICC]), genetic evaluation of both the AMKL and the B-ALL suggest that neither of these considerations was correct. Rather, the AMKL did not harbor the most common genetic hallmark of AML-pCT-rearrangement of and was genetically distinct from the B-ALL.

Optimizing infant neuroimaging methods to understand the neurodevelopmental impacts of early nutrition and feeding.

There is strong evidence proper nutrition is imperative for healthy infant neurodevelopment, providing the neural foundations for later cognition and behavior. Over the first years of life infants are supported by unique sources of nutrition (e.g.

Differential effects of acute stress on spatial learning and memory in the open-field tower maze across the female estrous cycle.

The purpose of the present investigation was to test how acute stress and levels of circulating estrogens together influence acquisition and retention of spatial learning, as well as explorative behaviors in female rats. We used the hippocampus-dependent Open-field Tower Maze (OFTM) task to assess acquisition followed by a retention test (reacquisition) that was given 48 h later. Immediately prior to acquisition, experimental rats were exposed to an acute restraint stress and were trained under bright lights.