•The MT-DTI deep learning model was used to identify potent drugs for SARS-CoV-2.•Atazanavir, remdesivir, and Kaletra were predicted to inhibit SARS-CoV-2.•Rapamycin and tiotropium bromide may also ...be effective for SARS-CoV-2.
The infection of a novel coronavirus found in Wuhan of China (SARS-CoV-2) is rapidly spreading, and the incidence rate is increasing worldwide. Due to the lack of effective treatment options for SARS-CoV-2, various strategies are being tested in China, including drug repurposing. In this study, we used our pre-trained deep learning-based drug-target interaction model called Molecule Transformer-Drug Target Interaction (MT-DTI) to identify commercially available drugs that could act on viral proteins of SARS-CoV-2. The result showed that atazanavir, an antiretroviral medication used to treat and prevent the human immunodeficiency virus (HIV), is the best chemical compound, showing an inhibitory potency with Kd of 94.94 nM against the SARS-CoV-2 3C-like proteinase, followed by remdesivir (113.13 nM), efavirenz (199.17 nM), ritonavir (204.05 nM), and dolutegravir (336.91 nM). Interestingly, lopinavir, ritonavir, and darunavir are all designed to target viral proteinases. However, in our prediction, they may also bind to the replication complex components of SARS-CoV-2 with an inhibitory potency with Kd < 1000 nM. In addition, we also found that several antiviral agents, such as Kaletra (lopinavir/ritonavir), could be used for the treatment of SARS-CoV-2. Overall, we suggest that the list of antiviral drugs identified by the MT-DTI model should be considered, when establishing effective treatment strategies for SARS-CoV-2.
Diffusion tensor imaging (DTI), and fractional-anisotropy (FA) maps in particular, have shown promise in predicting areas of tumor recurrence in glioblastoma. However, analysis of peritumoral edema, ...where most recurrences occur, is impeded by free-water contamination. In this study, we evaluated the benefits of a novel, deep-learning-based approach for the free-water correction (FWC) of DTI data for prediction of later recurrence. We investigated 35 glioblastoma cases from our prospective glioma cohort. A preoperative MR image and the first MR scan showing tumor recurrence were semiautomatically segmented into areas of contrast-enhancing tumor, edema, or recurrence of the tumor. The 10th, 50th and 90th percentiles and mean of FA and mean-diffusivity (MD) values (both for the original and FWC-DTI data) were collected for areas with and without recurrence in the peritumoral edema. We found significant differences in the FWC-FA maps between areas of recurrence-free edema and areas with later tumor recurrence, where differences in noncorrected FA maps were less pronounced. Consequently, a generalized mixed-effect model had a significantly higher area under the curve when using FWC-FA maps (AUC = 0.9) compared to noncorrected maps (AUC = 0.77,
< 0.001). This may reflect tumor infiltration that is not visible in conventional imaging, and may therefore reveal important information for personalized treatment decisions.
Purpose
White matter tractography reconstructions using conventional diffusion tensor imaging (DTI) near cerebrospinal fluid (CSF) spaces are often adversely affected by CSF partial volume effects ...(PVEs). This study evaluates the ability of free water elimination (FWE) DTI methods to minimize the PVE of CSF for deterministic tractography applications.
Materials and Methods
Ten healthy individuals were scanned with "traditional," FLAIR (fluid‐attenuated inversion recovery), and FWE DTI scans. The fornix, corpus callosum, and cingulum bundles were reconstructed using deterministic tractography. The FWE DTI scan was performed twice to separately match total acquisition time (long FWE) and number of measurements (encoding directions, short FWE) to the FLAIR and "traditional" DTI scans. PVE resolution was determined based on reconstructed tract volume. All reconstructions underwent blinded review for anatomical correctness, symmetry, and completeness.
Results
Reconstructions of the fornix demonstrated that the FWE and FLAIR scans produce more complete, anatomically plausible reconstructions than "traditional" DTI. Additionally, the tract reconstructions using FWE‐DTI were significantly larger than when FLAIR was used with DTI (P < 0.0005). FLAIR and the FWE methods led to signal‐to‐noise ratio (SNR) reductions of 33% and 11%, respectively, compared with conventional DTI. The long and short FWE acquisitions did not significantly (P ≥ 0.31) differ from one another for any of the reconstructed tracts.
Conclusion
The FWE diffusion model overcomes CSF PVE without the time, SNR, and volumetric coverage penalties inherent to FLAIR DTI. J. MAGN. RESON. IMAGING 2015;42:1572–1581.
To noninvasively evaluate the three-dimensional collagen fiber architecture of porcine meniscus using diffusion MRI, meniscal specimens were scanned using a 3D diffusion-weighted spin-echo pulse ...sequence at 7.0 T. The collagen fiber alignment was revealed in each voxel and the complex 3D collagen network was visualized for the entire meniscus using tractography. The proposed automatic segmentation methods divided the whole meniscus to different zones (Red-Red, Red-White, and White-White) and different parts (anterior, body, and posterior). The diffusion tensor imaging (DTI) metrics were quantified based on the segmentation results. The heatmap was generated to investigate the connections among different regions of meniscus. Strong zonal-dependent diffusion properties were demonstrated by DTI metrics. The fractional anisotropy (FA) value increased from 0.13 (White-White zone) to 0.26 (Red-Red zone) and the radial diffusivity (RD) value changed from 1.0 × 10
mm
/s (White-White zone) to 0.7 × 10
mm
/s (Red-Red zone). Coexistence of both radial and circumferential collagen fibers in the meniscus was evident by diffusion tractography. Weak connections were found between White-White zone and Red-Red zone in each part of the meniscus. The anterior part and posterior part were less connected, while the body part showed high connections to both anterior part and posterior part. The tractography based on diffusion MRI may provide a complementary method to study the integrity of meniscus and nondestructively visualize the 3D collagen fiber architecture.
•Mentalization, represented by self-reflective function with stress perception level identified two clusters, hyper-mentalization, and hypo-mentalization•Hypo-mentalization is linked to poorer mental ...health and lower resilience.•Neuroimaging reveals brain structural differences correlated with mentalization toward mental health conditions•An interplay of psychological resilience and mentalization interacted with mental health conditions was observed•The importance of balanced intrapersonal and interpersonal factors in promoting resilience correlated with mentalization
We aim to investigate the interplay between mentalization, brain microstructure, and psychological resilience as potential protective factors against mental illness.
Four hundred and twenty-six participants (mean age 40.12±16.95; 202 males, 224 females), without psychiatric or neurological history, completed assessments: Dissociative Process Scale (DPS), Peace of Mind (PoM), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Resilience Scale for Adults (RSA), and Magnetic Resonance Imaging (MRI) structures with selected region of interests, and Diffusion Tensor Imaging (DTI) maps from various tracts in the right hemisphere and connection to the frontal areas, including anterior thalamic radiation (ATR), Cingulum (hippocampus) (CH), Corticospinal tract (CST), Superior longitudinal fasciculus (SLF), Inferior fronto-occipital fasciculus (IFOF), and Uncinate fasciculus (UF) were analyzed.
Two clusters, representing hypomentalization (HypoM) and hypermentalization (HyperM), were identified based on DPS, CPSS, and RFQ responses. One-way ANOVA showed no significant age or gender differences between clusters. The HypoM group exhibited lower PoM scores, higher BDI and BAI scores, and lower RSA scores (ps< 0.05). Structural brain metric comparison showed significant differences in GMV in the right caudal middle frontal gyrus (rcMFG), right superior frontal gyrus (rsFG) and right frontal pole (rFP) between groups. In addition, the HyperM individuals with a higher risk of depression and a higher ratio of intrapersonal to interpersonal factors of resilience were found with reduced GMV on the rcMFG. Additionally, analyses of DTI metrics revealed significant differences between two groups in rATR and rSLF in terms of fractional anisotropy (FA) values; rATR, rCST, rUF, rSLF, rCH and rIFF in terms of mean diffusivity (MD) values; and rATR, rCH, rCST, and rUF in terms of radial diffusivity (RD) (corrected p = 0.05). Moreover, the positive correlation between different domains of resilience and white matter (WM) integrity implied further enhancement of intrapersonal or interpersonal resilience factors that are different for people with different mentalization.
The findings underscore the importance of considering both intrapersonal and interpersonal factors in understanding the interactions between psychological resilience and mental health conditions relevant to brain mechanisms.
Summary
Objective
The epilepsy‐aphasia spectrum (EAS) is a heterogeneous group of age‐dependent childhood disorders characterized by sleep‐activated discharges associated with infrequent seizures and ...language, cognitive, and behavioral deficits. Defects in the GRIN2A gene, encoding a subunit of glutamate‐gated N‐methyl‐d‐aspartate (NMDA) receptors, represent the most important cause of EAS identified so far. Neocortical or thalamic lesions were detected in a subset of severe EAS disorders, and more subtle anomalies were reported in patients with so‐called “benign” phenotypes. However, whether brain structural alterations exist in the context of GRIN2A defects is unknown.
Methods
Magnetic resonance diffusion tensor imaging (MR‐DTI) was used to perform longitudinal analysis of the brain at 3 developmental timepoints in living mice genetically knocked out (KO) for Grin2a. In addition, electroencephalography (EEG) was recorded using multisite extracellular electrodes to characterize the neocortical activity in vivo.
Results
Microstructural alterations were detected in the neocortex, the corpus callosum, the hippocampus, and the thalamus of Grin2a KO mice. Most MR‐DTI alterations were detected at a specific developmental stage when mice were aged 30 days, but not at earlier (15 days) or later (2 months) ages. EEG analysis detected epileptiform discharges in Grin2a KO mice in the third postnatal week.
Significance
Grin2a KO mice replicated several anomalies found in patients with EAS disorders. Transient structural alterations detected by MR‐DTI recalled the age‐dependent course of EAS disorders, which in humans start during childhood and show variable outcome at the onset of adolescence. Together with the epileptiform discharges detected in young Grin2a KO mice, our data suggested the existence of early anomalies in the maturation of the neocortical and thalamocortical systems. Whereas the possible relationship of those anomalies with sleep warrants further investigations, our data suggest that Grin2a KO mice may serve as an animal model to study the neuronal mechanisms of EAS disorders and to design new therapeutic strategies.
Amyloid-beta and tau are key molecules in the pathogenesis of Alzheimer’s disease, but it remains unclear how these proteins interact to promote disease. Here, by combining cross-sectional and ...longitudinal molecular imaging and network connectivity analyses in living humans, we identified two amyloid-beta/tau interactions associated with the onset and propagation of tau spreading. First, we show that the lateral entorhinal cortex, an early site of tau neurofibrillary tangle formation, is subject to remote, connectivity-mediated amyloid-beta/tau interactions linked to initial tau spreading. Second, we identify the inferior temporal gyrus as the region featuring the greatest local amyloid-beta/tau interactions and a connectivity profile well suited to accelerate tau propagation. Taken together, our data address long-standing questions regarding the topographical dissimilarity between early amyloid-beta and tau deposition.
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•Network flow-based model identifies tau propagation hubs in inferior temporal gyri•Remote Aβ-tau interactions in entorhinal cortex may trigger initial tau spreading•Local Aβ-tau interactions in inferior temporal gyrus may promote tau propagation•Connectivity-based model addresses the spatial incongruity between early Aβ and tau
Lee et al. show that the natural history of AD traverses a critical period that begins once Aβ emerges within entorhinal cortex (EC)-connected regions, continues as tau spreads from the EC into connected mesial temporal and limbic regions, and may end once Aβ and tau interact within the inferior temporal gyrus propagation hubs, whose connections are well suited to facilitate widespread neocortical tau propagation.
Stroke or cerebrovascular accident (CVA) is a sudden occurrence, focal and non-convulsive neurologic deficit 1. In recent analysis (N=1541), spontaneous intracerebral haemorrhage (ICH), patients with ...intermediate Glasgow Coma Scale (GCS) between 9 to 12 may benefit from surgery, whereas those with higher or lower GCS may not 2.
According to WHO, every-year there were 10.3 million new cases and, overall high prevalence of 67% Ischemic strokes (IC) (Fig. 1) were observed in Middle East countries. Also, the incidence rate for females were high when compared to male 3.
The tissue plasminogen activator (tPA) is the only approved medication for IS, which must be administered within a three-hour space from the onset of symptoms for recovering results. Unfortunately, only 3- 5 percent reach the hospital in time, and the actual use of tPA is considerably low. This tPA also carries risk of increased intracranial hemorrhage so it is not used for haemorrhagic stroke 4. Management with surgery opted as least priority, because surgery benefits some and harms others 2.
The integration of stereotactic diffusion tensor imaging (DTI) tractography (Fig. 2) with Gamma Knife radiosurgery (GKRS) has increased therapeutic potential and safety 5. The procedure affects white matter tracts (predominantly the optic radiation and fasciculus - arcuate) are more vulnerable to radiation during stereotactic radiosurgery.
Integration of stereotactic tractography into Single-fraction stereotactic radiosurgery (SF-SRS) represents a promising tool for preventing the surgical complications in white matter tracts 6.
We report the design concept and fabrication of MRI phantoms, containing blocks of aligned microcapillaires that can be stacked into larger arrays to construct diameter distribution phantoms or ...fractured, to create a “powder-averaged” emulsion of randomly oriented blocks for vetting or calibrating advanced MRI methods, that is, diffusion tensor imaging, AxCaliber MRI, MAP-MRI, and multiple pulsed field gradient or double diffusion-encoded microstructure imaging methods. The goal was to create a susceptibility-matched microscopically anisotropic but macroscopically isotropic phantom with a ground truth diameter that could be used to vet advanced diffusion methods for diameter determination in fibrous tissues. Two-photon polymerization, a novel three-dimensional printing method is used to fabricate blocks of capillaries. Double diffusion encoding methods were employed and analyzed to estimate the expected MRI diameter. Susceptibility-matched microcapillary blocks or modules that can be assembled into large-scale MRI phantoms have been fabricated and measured using advanced diffusion methods, resulting in microscopic anisotropy and random orientation. This phantom can vet and calibrate various advanced MRI methods and multiple pulsed field gradient or diffusion-encoded microstructure imaging methods. We demonstrated that two double diffusion encoding methods underestimated the ground truth diameter.
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