Low-Frequency Oscillations in Mid-rostral Dorsolateral Prefrontal Cortex Support Response Inhibition.

Executive control of movement enables inhibiting impulsive responses critical for successful navigation of the environment. Circuits mediating stop commands involve prefrontal and basal ganglia structures with fMRI evidence demonstrating increased activity during response inhibition in the dorsolateral prefrontal cortex (dlPFC)-often ascribed to maintaining task attentional demands. Using direct intraoperative cortical recordings in male and female human subjects, we investigated oscillatory dynamics along the rostral-caudal axis of dlPFC during a modified Go/No-go task, probing components of both proactive and reactive motor control.

Tumor-agnostic transcriptome-based classifier identifies spatial infiltration patterns of CD8+T cells in the tumor microenvironment and predicts clinical outcome in early-phase and late-phase clinical trials.

Background: The immune status of a patient's tumor microenvironment (TME) may guide therapeutic interventions with cancer immunotherapy and help identify potential resistance mechanisms. Currently, patients' immune status is mostly classified based on CD8+tumor-infiltrating lymphocytes. An unmet need exists for comparable and reliable precision immunophenotyping tools that would facilitate clinical treatment-relevant decision-making and the understanding of how to overcome resistance mechanisms.

Matching by OS Prognostic Score to Construct External Controls in Lung Cancer Clinical Trials.

External controls (eControls) leverage historical data to create non-randomized control arms. The lack of randomization can result in confounding between the experimental and eControl cohorts. To balance potentially confounding variables between the cohorts, one of the proposed methods is to match on prognostic scores.

Circulating tumor DNA: Opportunities and challenges for pharmacometric approaches.

To support further development of model-informed drug development approaches leveraging circulating tumor DNA (ctDNA), we performed an exploratory analysis of the relationships between treatment-induced changes to ctDNA levels, clinical response and tumor size dynamics in patients with cancer treated with checkpoint inhibitors and targeted therapies. This analysis highlights opportunities for pharmacometrics approaches such as for optimizing sampling design strategies. It also highlights challenges related to the nature of the data and associated variability overall emphasizing the importance of mechanistic modeling studies of the underlying biology of ctDNA processes such as shedding, release and clearance and their relationships with tumor size dynamic and treatment effects.

Unexpected scaffold rearrangement product of pirenzepine found in commercial samples.

Pharmacovigilance aims at a better understanding of the molecular events triggered by medications to prevent adverse effects, which despite significant advances in our analytical repertoire plague the use of drugs until today. In this study, we find that clinically prescribed and commercially available pirenzepine may not be the correct compound. Pirenzepine can undergo an unexpected scaffold rearrangement from the pharmaceutical active ingredient (API) to a previously uncharacterized benzimidazole.