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"Lin, Tim"
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Instantaneous effects of prefrontal transcranial magnetic stimulation on brain oxygenation: A systematic review
•Provides a thorough understanding of brain activation during/immediately after prefrontal TMS.•The prefrontal cortex, insula, striatum, anterior cingulate and thalamus are engaged.•The target engagement (local and remote regions) is inconsistent among studies.
This systematic review investigates how prefrontal transcranial magnetic stimulation (TMS) immediately influences neuronal excitability based on oxygenation changes measured by functional magnetic resonance imaging (fMRI) or functional near-infrared spectroscopy (fNIRS). A thorough understanding of TMS-induced excitability changes may enable clinicians to adjust TMS parameters and optimize treatment plans proactively. Five databases were searched for human studies evaluating brain excitability using concurrent TMS/fMRI or TMS/fNIRS. Thirty-seven studies (13 concurrent TMS/fNIRS studies, 24 concurrent TMS/fMRI studies) were included in a qualitative synthesis. Despite methodological inconsistencies, a distinct pattern of activated nodes in the frontoparietal central executive network, the cingulo-opercular salience network, and the default-mode network emerged. The activated nodes included the prefrontal cortex (particularly dorsolateral prefrontal cortex), insula cortex, striatal regions (especially caudate, putamen), anterior cingulate cortex, and thalamus. High-frequency repetitive TMS most consistently induced expected facilitatory effects in these brain regions. However, varied stimulation parameters (e.g., intensity, coil orientation, target sites) and the inter- and intra-individual variability of brain state contribute to the observed heterogeneity of target excitability and co-activated regions. Given the considerable methodological and individual variability across the limited evidence, conclusions should be drawn with caution.
Journal Article
Trofinetide for the treatment of Rett syndrome: a randomized phase 3 study
Rett syndrome is a rare, genetic neurodevelopmental disorder. Trofinetide is a synthetic analog of glycine–proline–glutamate, the N-terminal tripeptide of the insulin-like growth factor 1 protein, and has demonstrated clinical benefit in phase 2 studies in Rett syndrome. In this phase 3 study (
https://clinicaltrials.gov
identifier
NCT04181723
), females with Rett syndrome received twice-daily oral trofinetide (
n
= 93) or placebo (
n
= 94) for 12 weeks. For the coprimary efficacy endpoints, least squares mean (LSM) change from baseline to week 12 in the Rett Syndrome Behaviour Questionnaire for trofinetide versus placebo was −4.9 versus −1.7 (
P
= 0.0175; Cohen’s
d
effect size, 0.37), and LSM Clinical Global Impression–Improvement at week 12 was 3.5 versus 3.8 (
P
= 0.0030; effect size, 0.47). For the key secondary efficacy endpoint, LSM change from baseline to week 12 in the Communication and Symbolic Behavior Scales Developmental Profile Infant–Toddler Checklist Social Composite score was −0.1 versus −1.1 (
P
= 0.0064; effect size, 0.43). Common treatment-emergent adverse events included diarrhea (80.6% for trofinetide versus 19.1% for placebo), which was mostly mild to moderate in severity. Significant improvement for trofinetide compared with placebo was observed for the coprimary efficacy endpoints, suggesting that trofinetide provides benefit in treating the core symptoms of Rett syndrome.
Results from the LAVENDER phase 3 study demonstrate that trofinetide, a synthetic analog of glycine–proline–glutamate, provides significant therapeutic benefits in the core symptoms of Rett syndrome
Journal Article
Non-Invasive Brain Stimulation Effects on Biomarkers of Tryptophan Metabolism: A Scoping Review and Meta-Analysis
Abnormal activation of the kynurenine and serotonin pathways of tryptophan metabolism is linked to a host of neuropsychiatric disorders. Concurrently, noninvasive brain stimulation (NIBS) techniques demonstrate high therapeutic efficacy across neuropsychiatric disorders, with indications for modulated neuroplasticity underlying such effects. We therefore conducted a scoping review with meta-analysis of eligible studies, conforming with the PRISMA statement, by searching the PubMed and Web of Science databases for clinical and preclinical studies that report the effects of NIBS on biomarkers of tryptophan metabolism. NIBS techniques reviewed were electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), and transcranial direct current stimulation (tDCS). Of the 564 search results, 65 studies were included with publications dating back to 1971 until 2022. The Robust Bayesian Meta-Analysis on clinical studies and qualitative analysis identified general null effects by NIBS on biomarkers of tryptophan metabolism, but moderate evidence for TMS effects on elevating serum serotonin levels. We cannot interpret this as evidence for or against the effects of NIBS on these biomarkers, as there exists several confounding methodological differences in this literature. Future controlled studies are needed to elucidate the effects of NIBS on biomarkers of tryptophan metabolism, an under-investigated question with substantial implications to clinical research and practice.
Journal Article
Cucurbitacin B inhibits Th17 cell differentiation via the suppression of the JAK/STAT pathway and alleviates collagen-induced arthritis in mice
Objective:
Rheumatoid arthritis (RA) is a chronic autoimmune disease with limited treatment options and associated side effects or resistance. This study aims to investigate the therapeutic potential of the natural compound cucurbitacin B (CuB) in RA treatment.
Methods:
We utilized a collagen-induced arthritis (CIA) mouse model to evaluate the effects of CuB. Arthritis scores, histological damage, and pro-inflammatory cytokine expression (TNF-α, IL-17A) were assessed. In addition, network pharmacology analysis was performed to explore CuB’s molecular mechanisms, focusing on Th17 cell differentiation, IL-17 signaling, and the JAK-STAT pathway.
Results:
CuB significantly reduced arthritis severity, decreased histological damage, and lowered the expression of pro-inflammatory cytokines in CIA mice. CuB was found to inhibit STAT3 phosphorylation and reduce the proportion of Th17 cells in the spleen, indicating its potential anti-inflammatory effects.
Conclusion:
These findings suggest that cucurbitacin B may serve as a promising novel therapeutic agent for rheumatoid arthritis by targeting key inflammatory pathways.
Journal Article
Effects of Transcranial Pulse Stimulation of the Primary Motor Cortex on Motor Performance in Healthy Adults: A Randomized Crossover Pilot Study
Aims We aimed to investigate the behavioral aftereffects of a novel noninvasive brain stimulation technique—transcranial pulse stimulation (TPS)—applied over the right motor cortex (rM1) in healthy adults. Methods Thirty‐four healthy adults underwent a randomized, subject‐ and analyst‐ blind, crossover trial, receiving active TPS over the rM1 or control TPS over the vertex in two sessions 24 h apart. Motor performance was assessed using the Nine‐Hole Peg Test (NHPT) and the Simple Reaction Time Task (SRTT) before, immediately after, and every 10 min for 40 min after each session. A linear mixed model and post hoc analyses were applied to evaluate the effects. Results No significant interaction effect (stimulation condition × time) was found. The left‐hand NHPT performance significantly improved from 10 min post‐TPS onward in both conditions (ps ≤ 0.002). Conclusion A single session of rM1‐TPS does not yield significant improvements in motor dexterity compared to vertex‐TPS. Future well‐powered studies with a sham control condition and multiple stimulation sessions are needed to investigate the aftereffects using a combination of neurophysiological and neuroimaging approaches. Trial Registration This study was registered in ClinicalTrial.gov in April 2024 (NCT06312930) A single session of transcranial pulse stimulation (TPS) at the right primary motor cortex (rM1) does not improve hand dexterity compared to vertex stimulation. A similar practice effect was observed for both stimulations from 10 to 40 min post‐stimulation.
Journal Article
Scalable Fabrication of Si-Graphene Composite as Anode for Li-ion Batteries
A facile and scalable method is reported to fabricate Si-graphene nanocomposite as anode material for Li-ion batteries (LIBs) with high capacity and capacity retention performance. The Si-graphene electrode showed an initial discharge capacity of 1307 mAh g−1 at a current rate of 0.1C. At the 25th cycle, the electrode retained a discharge capacity of 1270 mAh g−1, with an excellent capacity retention of 97%. At the 50th cycle, the electrode still retained high capacity retention of 89%. The improved capacity retention of Si-graphene anode compared with Si anode is attributed to the mechanical flexibility of graphene that compromises the volume expansion of Si during the lithiation/delithiation process. The electrochemical impedance measurement further confirms the enhanced electrical conductivity and the denser solid-electrolyte-interface of the Si-graphene electrode. This fabrication approach is cost-effective and easy to scale up compared to known techniques, making it a promising candidate for commercializing Si-based anode for LIBs.
Journal Article
A New Keynesian Model with Robots: Implications for Business Cycles and Monetary Policy
This paper examines the effects of labor-replacing capital, referred to as robots, on business cycle dynamics using a New Keynesian model with a role for both traditional and robot capital. This study finds that shocks to the price of robots have effects on wages, output, and employment that are distinct from shocks to the price of traditional capital. Further, the inclusion of robots alters the response of employment and labor’s share to total factor productivity and monetary policy shocks. The presence of robots also weakens the correlation between human labor and output and the correlation between human labor and labor’s share. The paper finds that monetary policymakers would need to place a greater emphasis on output stabilization if their objective is to minimize a weighted average of output and inflation volatility. Moreover, if policymakers have an employment stabilization objective apart from their output stabilization objective, they would have to further focus on output stabilization due to the deterioration of the output-employment correlation.
Journal Article