Pediatric high-grade glioma (HGG) is a devastating disease with a two-year survival of less than 20%1. We analyzed 127 pediatric HGGs, including diffuse intrinsic pontine gliomas (DIPGs) and non-brainstem HGGs (NBS-HGGs) by whole genome, whole exome, and/or transcriptome sequencing. We identified recurrent somatic mutations in ACVR1 exclusively in DIPG (32%), in addition to the previously reported frequent somatic mutations in histone H3, TP53 and ATRX in both DIPG and NBS-HGGs2-5. Structural variants generating fusion genes were found in 47% of DIPGs and NBS-HGGs, with recurrent fusions involving the neurotrophin receptor genes NTRK1, 2, or 3 in 40% of NBS-HGGs in infants. Mutations targeting receptor tyrosine kinase/RAS/PI3K signaling, histone modification or chromatin remodeling, and cell cycle regulation were found in 68%, 73% and 59%, respectively, of pediatric HGGs, including DIPGs and NBS-HGGs. This comprehensive analysis provides insights into the unique and shared pathways driving pediatric HGG within and outside the brainstem.

A facile synthetic protocol for the production of neomycin B derivatives with various modifications at the 5″ position has been developed. Structural activity relationship (SAR) against aminoglycoside resistant bacteria equipped with various aminoglycoside-modifying enzymes (AME's) was investigated. Enzymatic and molecular modeling studies reveal that the superb substrate promiscuity of AME's allows the resistant bacteria to cope with diverse structural modifications despite the observation that several derivatives show enhanced antibacterial activity than the parent neomycin. Surprisingly, when testing synthetic neomycin derivatives against other human pathogens, two leads exhibit prominent activity against both Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) that are known to exert high level of resistance against clinically used aminoglycosides. These findings can be extremely useful in developing new aminoglycoside antibiotics against resistant bacteria. Our result also suggests that new biological and antimicrobial activities can be obtained by chemical modifications of old drugs.

Background: Brain-computer interface (BCI) has been regarded as a newly developing intervention in promoting motor recovery in stroke survivors. Several studies have been performed in chronic stroke to explore its clinical and subclinical efficacy. However, evidence in subacute stroke was poor, and the longitudinal sensorimotor rhythm changes in subacute stroke after BCI with exoskeleton feedback were still unclear. Materials and Methods: Fourteen stroke patients in subacute stage were recruited and randomly allocated to BCI group (n = 7) and the control group (n = 7). Braincomputer interface training with exoskeleton feedback was applied in the BCI group three times a week for 4 weeks. The Fugl-Meyer Assessment of Upper Extremity (FMA-UE) scale was used to assess motor function improvement. Brain-computer interface performance was calculated across the 12-time interventions. Sensorimotor rhythm changes were explored by event-related desynchronization (ERD) changes and topographies. Results: After 1 month BCI intervention, both the BCI group (p = 0.032) and the control group (p = 0.048) improved in FMA-UE scores. The BCI group (12.77%) showed larger percentage of improvement than the control group (7.14%), and more patients obtained good motor recovery in the BCI group (57.1%) than did the control group (28.6%). Patients with good recovery showed relatively higher online BCI performance, which were greater than 70%. And they showed a continuous improvement in offline BCI performance and obtained a highest value in the last six sessions of interventions during BCI training. However, patients with poor recovery reached a platform in the first six sessions of interventions and did not improve any more or even showed a decrease. In sensorimotor rhythm, patients with good recovery showed an enhanced ERD along with time change. Topographies showed that the ipsilesional hemisphere presented stronger activations after BCI intervention.