Search

The emergence of rapidly spreading variants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) poses a major challenge to vaccines' protective efficacy. Intramuscular (IM) vaccine administration induces short-lived immunity but does not prevent infection and transmission. New vaccination strategies are needed to extend the longevity of vaccine protection, induce mucosal and systemic immunity and prevent viral transmission. The intranasal (IN) administration of the VSV–ΔG–spike vaccine candidate directly to mucosal surfaces yielded superior mucosal and systemic immunity at lower vaccine doses. Compared to IM vaccination in the K18–hACE2 model, IN vaccination preferentially induced mucosal IgA and T-cells, reduced the viral load at the site of infection, and ameliorated disease-associated brain gene expression. IN vaccination was protective even one year after administration. As most of the world population has been vaccinated by IM injection, we demonstrate the potential of a heterologous IM + IN vaccination regimen to induce mucosal immunity while maintaining systemic immunity. Furthermore, the IM + IN regimen prevented virus transmission in a golden Syrian hamster co-caging model. Taken together, we show that IN vaccination with VSV–ΔG–spike, either as a homologous IN + IN regimen or as a boost following IM vaccination, has a favorable potential over IM vaccination in inducing efficient mucosal immunity, long-term protection and preventing virus transmission. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults. This study aimed to construct immune-related long non-coding RNAs (lncRNAs) signature and radiomics signature to probe the prognosis and immune infiltration of GBM patients. Methods: We downloaded GBM RNA-seq data and clinical information from The Cancer Genome Atlas (TCGA) project database, and MRI data were obtained from The Cancer Imaging Archive (TCIA). Then, we conducted a cox regression analysis to establish the immune-related lncRNAs signature and radiomics signature. Afterward, we employed a gene set enrichment analysis (GSEA) to explore the biological processes and pathways. Besides, we used CIBERSORT to estimate the abundance of tumor-infiltrating immune cells (TIICs). Furthermore, we investigated the relationship between the immune-related lncRNAs signature, radiomics signature and immune checkpoint genes. Finally, we constructed a multifactors prognostic model and compared it with the clinical prognostic model. Results: We identified four immune-related lncRNAs and two radiomics features, which show the ability to stratify patients into high-risk and low-risk groups with significantly different survival rates. The risk score curves and Kaplan–Meier curves confirmed that the immune-related lncRNAs signature and radiomics signature were a novel independent prognostic factor in GBM patients. The GSEA suggested that the immune-related lncRNAs signature were involved in L1 cell adhesion molecular (L1CAM) interactions and the radiomics signature were involved signaling by Robo receptors. Besides, the two signatures was associated with the infiltration of immune cells. Furthermore, they were linked with the expression of critical immune genes and could predict immunotherapy's clinical response. Finally, the area under the curve (AUC) (0.890,0.887) and C-index (0.737,0.817) of the multifactors prognostic model were greater than those of the clinical prognostic model in both the training and validation sets, indicated significantly improved discrimination. Conclusions: We identified the immune-related lncRNAs signature and tradiomics signature that can predict the outcomes, immune cell infiltration, and immunotherapy response in patients with GBM. [ABSTRACT FROM AUTHOR]

To investigate potential correlations between the susceptibility values of certain brain regions and the severity of disease or neurodevelopmental status in children with autism spectrum disorder (ASD), 18 ASD children and 15 healthy controls (HCs) were recruited. The neurodevelopmental status was assessed by the Gesell Developmental Schedules (GDS) and the severity of the disease was evaluated by the Autism Behavior Checklist (ABC). Eleven brain regions were selected as regions of interest and the susceptibility values were measured by quantitative susceptibility mapping. To evaluate the diagnostic capacity of susceptibility values in distinguishing ASD and HC, the receiver operating characteristic (ROC) curve was computed. Pearson and Spearman partial correlation analysis were used to depict the correlations between the susceptibility values, the ABC scores, and the GDS scores in the ASD group. ROC curves showed that the susceptibility values of the left and right frontal white matter had a larger area under the curve in the ASD group. The susceptibility value of the right globus pallidus was positively correlated with the GDS-fine motor scale score. These findings indicated that the susceptibility value of the right globus pallidus might be a viable imaging biomarker for evaluating the neurodevelopmental status of ASD children., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Efficient treatment of anthrax-related meningitis in patients poses a significant therapeutic challenge. Previously, we demonstrated in our anthrax meningitis rabbit model that ciprofloxacin treatment is ineffective with most of the treated animals succumbing to the infection. Herein we tested the efficacy of doxycycline in our rabbit model and found it highly effective. Since all of our findings are based on a rabbit model, we test the efficacy of ciprofloxacin or doxycycline in a specific central nervous system (CNS) model developed in non-human primates (NHPs). Similar to rabbits, ciprofloxacin treatment was ineffective, while doxycycline protected the infected rhesus macaques ( n = 2) from the lethal CNS Bacillus anthracis infection. To test whether the low efficacy of Ciprofloxacin is an example of low efficacy of all fluoroquinolones or only this substance, we treated rabbits that were inoculated intracisterna magna (ICM) with levofloxacin or moxifloxacin. We found that in contrast to ciprofloxacin, levofloxacin and moxifloxacin were highly efficacious in treating lethal anthrax-related meningitis in rabbits and NHP (levofloxacin). We demonstrated (in naïve rabbits) that this difference probably results from variances in blood-brain-barrier penetration of the different fluoroquinolones. The combined treatment of doxycycline and any one of the tested fluoroquinolones was highly effective in the rabbit CNS infection model. The combined treatment of doxycycline and levofloxacin was effective in an inhalation rabbit model, as good as the doxycycline mono-therapy. These findings imply that while ciprofloxacin is highly effective as a post-exposure prophylactic drug, using this drug to treat symptomatic patients should be reconsidered.

Background and Objective: Diffusion tensor imaging (DTI) has been implemented in a breadth of scientific investigations of optic neuropathies, though it has yet to be fully adopted for diagnosis or prognosis. This is potentially due to a lack of standardization and weak replication of results. The aim of this investigation was to review DTI results from studies specific to three distinct optic neuropathies in order to probe its current clinical utility., Methods: We reviewed the DTI literature specific to primary open-angle glaucoma (POAG), optic neuritis (ON), and traumatic optic neuropathy (TON) by systematically searching the PubMed database on March 1 st , 2023. Four distinct DTI metrics are considered: fractional anisotropy (FA), along with mean diffusivity (MD, axial diffusivity (AD), and radial diffusivity (RD). Results from within-group, between-group, and correlational studies were thoroughly assessed., Key Content and Findings: POAG studies most consistently report a decrease in FA, especially in the optic radiations, followed in prevalence by an increase in RD and then MD, whilst AD yields conflicting results between studies. It is notable that there is not an equal distribution of investigated DTI metrics, with FA utilized the most, followed by MD, RD, and AD. Studies of ON are similar in that the most consistent findings are specific to FA, RD, and MD. These results are specific to the optic nerve and radiation since only one study measured the intermediary regions. More studies are needed to assess the effect that ON has on the tracts of the visual system. Finally, only three studies assessing DTI of TON have been performed to date, displaying low to moderate replicability of results. To improve the level of agreement between studies assessing each optic neuropathy, an increased level of standardization is recommended., Conclusions: Both POAG and ON studies have yielded some prevalent DTI findings, both for contrast and correlation-based assessments. Although the clinical need is high for TON, considering the limitations of the current diagnostic tools, too few studies exist to make confident conclusions. Future use of standardized and longitudinal DTI, along with the foreseen methodological and technical improvements, is warranted to effectively study optic neuropathies., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-779/coif). J.D.M. and A.S. report that this study was supported by a grant from the U.S. Department of Defense CDMRP Vision Research Program (Award No. W81XWH1910853). The other authors have no conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)