These data support the lack of dose or exposure dependency in pembrolizumab OS for melanoma and NSCLC between 2 and 10 mg/kg. An association of pembrolizumab CL with OS potentially reflects catabolic activity as a marker of disease severity versus a direct PK-related impact of pembrolizumab on efficacy. Similar data from other trials suggest such patterns of exposure-response confounding may be a broader phenomenon generalizable to antineoplastic mAbs..

Transcranial direct current stimulation (tDCS)1 has been reported to be a promising technique for consciousness improvement for patients with disorders of consciousness (DOC).2 However, there has been no direct electrophysiological evidence to demonstrate the efficacy of tDCS on patients with DOC. Therefore, we aim to measure the cortical excitability changes induced by tDCS in patients with DOC, to find electrophysiological evidence supporting the therapeutic efficacy of tDCS on patients with DOC. In this study, we enrolled sixteen patients with DOC, including nine vegetative state (VS)3 and seven minimally conscious state (MCS)4 (six females and ten males). TMS-EEG was applied to assess cortical excitability changes after twenty minutes of anodal tDCS of the left dorsolateral prefrontal cortex. Global cerebral excitability were calculated to quantify cortical excitability in the temporal domain: four time intervals (0–100, 100–200, 200–300, 300-400 ms). Then local cerebral excitability in the significantly altered time windows were investigated (frontal, left/right hemispheres, central, and posterior). Compared to baseline and sham stimulation, we found that global cerebral excitability increased in early time windows (0–100 and 100-200 ms) for patients with MCS; for the patients with VS, global cerebral excitability increased in the 0-100 ms interval but decreased in the 300-400 ms interval. The local cerebral excitability was significantly different between MCS and VS. The results indicated that tDCS can effectively modulate the cortical excitability of patients with DOC; and the changes in excitability in temporal and spatial domains are different between patients with MCS and those with VS.

No abstract

Alterations in brain connectivity have been extensively reported in autism spectrum disorder (ASD), while their effects on the topology of brain network are still unclear. This study investigated whether and how the brain networks in children with ASD were abnormally organized with resting state EEG. Temporal synchronization analysis was first applied to capture the aberrant brain connectivity. Then brain network topology was characterized by three graph analysis methods including the commonly-used weighted and binary graph, as well as minimum spanning tree (MST). Whole brain connectivity in ASD group was found to be significantly reduced in theta and alpha band compared to typically development children (TD). Weighted graph found significantly decreased path length together with marginally significantly decreased clustering coefficient in ASD in alpha band, indicating a loss of small-world architecture to a random network. Such abnormal network topology was also demonstrated in the binary graph. In MST analysis, children with ASD showed a significant lower leaf fractions with a decrease trend of tree hierarchy in the alpha band, suggesting a shift towards line-like decentralized organization in ASD. The altered brain network may offer an insight into the underlying pathology of ASD and possibly serve as a biomarker that may aid in diagnosis of ASD.

No abstract