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BACKGROUND: The neurobiological pathogenesis of major depression disorder (MDD) remains largely controversial. Previous literatures with limited sample size utilizing group-level structural covariance networks (SCN) commonly generated mixed findings regarding the topology of brain networks. METHODS: We analyzed T1 images from a high-powered multisite sample including 1173 patients with MDD and 1019 healthy controls (HCs). We used regional gray matter volume to construct individual SCN by utilizing a novel approach based on the interregional effect size difference. We further investigated MDD-related structural connectivity alterations using topological metrics. RESULTS: Compared to HCs, the MDD patients showed a shift toward randomization characterized by increased integration. Further subgroup analysis of patients in different stages revealed this randomization pattern was also observed in patients with recurrent MDD, while the first-episode drug naïve patients exhibited decreased segregation. Altered nodal properties in several brain regions which have a key role in both emotion regulation and executive control were also found in MDD patients compared with HCs. The abnormalities in inferior temporal gyrus were not influenced by any specific site. Moreover, antidepressants increased nodal efficiency in the anterior ventromedial prefrontal cortex. CONCLUSIONS: The MDD patients at different stages exhibit distinct patterns of randomization in their brain networks, with increased integration during illness progression. These findings provide valuable insights into the disruption in structural brain networks that occurs in patients with MDD and might be useful to guide future therapeutic interventions.
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A fast and accurate sampling method is in high demand, in order to bridge the large gaps between molecular dynamic simulations and experimental observations. Recently, an integrated tempering enhanced sampling (ITS) method has been proposed and successfully applied to various biophysical examples, significantly accelerating conformational sampling. The mathematical validation for its effectiveness has not been elucidated yet. Here we show that the integrated tempering enhanced sampling method can be viewed as a reformulation of the infinite switching limit of the simulated tempering method over a mixed potential. Moreover, we demonstrate that the efficiency of simulated tempering molecular dynamics improves as the frequency of switching between the temperatures is increased, based on the large deviation principle of empirical distributions. Our theory provides the theoretical justification of the advantage of ITS. Finally, we illustrate the utility of the infinite switching simulated tempering method through several numerical examples.
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BACKGROUND: Previous neuroimaging studies have extensively demonstrated many signs of functionally spontaneous local neural activity abnormalities in bipolar disorder (BD) patients using resting-state functional magnetic resonance imaging (rs-fMRI). However, how to identify the changes of voxel-wise whole-brain functional connectivity pattern and its corresponding functional connectivity changes remain largely unclear in BD patients. The current study aimed to investigate the voxel-wise changes of functional connectivity patterns in BD patients using publicly available data from the UCLA CNP LA5c Study. METHODS: A total of 45 BD patients and 115 healthy control subjects were finally included and whole-brain functional connectivity homogeneity (FcHo) was calculated from their rs-fMRI. Moreover, the alterations of corresponding functional connectivity were subsequently identified using seed-based resting-state functional connectivity analysis. RESULTS: Individuals with BD exhibited significantly lower FcHo values in the left middle temporal gyrus (MTG) when compared with controls. Functional connectivity findings further indicated decreased functional connectivities between left MTG and cluster 1 (left superior temporal gyrus, extend to middle temporal gyrus, rolandic operculum), cluster 2 (right postcentral, extend to right precentral) in BD patients. The mean FcHo values of left MTG were positively correlated with insomnia, middle scores and appetite increase scores. The mean functional connectivities of left MTG to cluster 1 were negatively correlated with grandiose delusions scores. While the functional connections between left MTG with cluster 2 were negatively correlated with delusions of reference and positively correlated with insomnia, middle scores in BD patients. CONCLUSIONS: Our findings suggested that abnormal FcHo and functional connections in those areas of the brain involving DMN and SMN networks might play a crucial role in the neuropathology of BD.
Asunto(s)
Trastorno Bipolar , Trastornos del Inicio y del Mantenimiento del Sueño , Trastorno Bipolar/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Mapeo Encefálico/métodos , Humanos , Imagen por Resonancia Magnética/métodos , NeuroimagenRESUMEN
OBJECTIVE: To investigate the association between rs185983011 single-nucleotide polymorphisms (SNP) of apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3G (APOBEC3G) and the susceptibility to chronic hepatitis B. METHODS: The blood samples were collected from 186 healthy subjects and 159 patients with chronic hepatitis B. The rs185983011 SNP was detected and genotyped by sequencing with Sanger's method to analyze the relationship between rs185983011 SNP and chronic hepatitis B. RESULTS: Only C/C and C/T genotypes of the alleles of rs185983011 SNP were found in the tested subjects, and the C/C genotype was predominant (97.7%). The distribution frequencies of rs185983011 SNP genotypes and alleles showed no significant difference between healthy subjects and patients with chronic hepatitis B (P>0.05). CONCLUSION: The predominant genotype of rs185983011 SNP of APOBEC3G is C/C in the tested subjects, and rs185983011 SNP does not appear to associate with the susceptibility to chronic hepatitis B.