Similarities and differences of functional connectivity in drug-naïve, first-episode adolescent and young adult with major depressive disorder and schizophrenia

Major depressive disorder (MDD) and schizophrenia (SZ) are considered two distinct psychiatric disorders. Yet, they have considerable overlap in symptomatology and clinical features, particularly in the initial phases of illness. The amygdala and prefrontal cortex (PFC) appear to have critical roles in these disorders; however, abnormalities appear to manifest differently. In our study forty-nine drug-naïve, first-episode MDD, 45 drug-naïve, first-episode SZ, and 50 healthy control (HC) participants from 13 to 30 years old underwent resting-state functional magnetic resonance imaging. Functional connectivity (FC) between the amygdala and PFC was compared among the three groups. Significant differences in FC were observed between the amygdala and ventral PFC (VPFC), dorsolateral PFC (DLPFC), and dorsal anterior cingulated cortex (dACC) among the three groups. Further analyses demonstrated that MDD showed decreased amygdala-VPFC FC and SZ had reductions in amygdala-dACC FC. Both the diagnostic groups had significantly decreased amygdala-DLPFC FC. These indicate abnormalities in amygdala-PFC FC and further support the importance of the interaction between the amygdala and PFC in adolescents and young adults with these disorders. Additionally, the alterations in amygdala-PFC FC may underlie the initial similarities observed between MDD and SZ and suggest potential markers of differentiation between the disorders at first onset

Systematic Identification of Synergistic Drug Pairs Targeting HIV

The systematic identification of effective drug combinations has been hindered by the unavailability of methods that can explore the large combinatorial search space of drug interactions. Here we present a multiplex screening method named MuSIC (Multiplex Screening for Interacting Compounds), which expedites the comprehensive assessment of pair-wise compound interactions. We examined ~500,000 drug pairs from 1000 FDA-approved or clinically tested drugs and identified drugs that synergize to inhibit HIV replication. Our analysis reveals an enrichment of anti-inflammatory drugs in drug combinations that synergize against HIV, indicating HIV benefits from inflammation that accompanies its infection. Multiple drug pairs identified in this study, including glucocorticoid and nitazoxanide, synergize by targeting different steps of the HIV life cycle. As inflammation accompanies HIV infection, our findings indicate that inhibiting inflammation could curb HIV propagation. MuSIC can be applied to a wide variety of disease-relevant screens to facilitate efficient identification of compound combinations

Ab initio Gamow shell-model calculations for dripline nuclei

We developed a Gamow shell model based on first principles and successfully applied it to the nuclei around driplines. Herein, we review the theoretical and technical developments of this method. Starting from the realistic nuclear forces, the model uses the Berggren basis, which contains bound, resonant, and scattering continuum states. Therefore, the Gamow shell model can handle the coupling to the continuum. In the complex-momentum plane, we used many-body perturbation theory (i.e., so-called Q^-box folded diagrams) to derive the Hamiltonian for the valence space. Subsequently, the shell-model calculations, which included the resonance and continuum effects, were performed. Therefore, such ab initio calculations can describe the weakly bound properties of nuclei near driplines and unbound resonance properties of nuclei beyond driplines. In this study, the symmetry breaking between oxygen isotopes and their mirror nuclei is discussed, and the important continuum effects on the excitation spectra of neutron-rich carbon isotopes are analyzed

An Automatic Segmentation Method of Cerebral Arterial Tree in TOF-MRA Based on DBCNet

Arterial tree region segmentation from medical images of the brain is an early step in the diagnosis and evaluation of many cerebrovascular diseases. Most of the existing region segmentation methods rely on manual assistance. In this paper, we propose an automatic brain arterial tree partitioning method based on a dual branch connected network (DBCNet), which can partition the arterial tree in time of flight-magnetic resonance angiography (TOF-MRA) into six main regions. The branch feature decoupling module and the global and local feature fusion module based on Swin Transformer mechanism were used for DBCNet. The two-step training strategy of localization followed by segmentation was used for training. In this study, 111 cases of TOF-MRA data were used, of which 81 cases as the training set, 20 cases as the validation set, and 10 cases as the test set. The average Dice coefficient of the model on the test set was 74.72% and 95% Haus dorff distance (HD95) was 3.89 mm. Compared with other advanced segmentation networks, the network reported in this paper can segment each major region more accurately with robustness

Porcine HMGCR Inhibits Porcine Circovirus Type 2 Infection by Directly Interacting with the Viral Proteins

Porcine circovirus type 2 (PCV2) is the etiological agent of porcine circovirus diseases and porcine circovirus-associated diseases (PCVDs/PCVADs). However, the pathogenesis of PCV2 is not fully understood. We previously found that 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) is negatively associated with PCV2 infection in vitro and in vivo. HMGCR inhibits the early stages of PCV2 infection, while PCV2 infection induces the phosphorylation of HMGCR to inactivate the protein. In this study, we investigated the possibility that adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK), and protein phosphatase 2 (PP2A) participate in HMGCR-mediated inhibition of PCV2 infection and the interaction of porcine HMGCR with PCV2 proteins. The results showed that AMPK activity fluctuated in cells during the early stage of PCV2 infection, while PP2A had little effect on PCV2 infection and HMGCR activity. Furthermore, PCV2 infection may enhance or maintain the level of phosphorylated HMGCR by directly interacting with the protein in PK-15 cells. These findings may provide a better understanding of PCV2 pathogenesis, and HMGCR may be a novel PCV2 antiviral target

Correction: Voxel-Based Morphometry in Individuals at Genetic High Risk for Schizophrenia and Patients with Schizophrenia during Their First Episode of Psychosis.

[This corrects the article DOI: 10.1371/journal.pone.0163749.]

Demographic and clinical data of participants.

<p>Demographic and clinical data of participants.</p

The correlation between the strength of these functional connectivities and the FA Value of the fornix within each group.

<p>The correlation between the strength of these functional connectivities and the FA Value of the fornix within each group.</p