Brain-Driven Representation Learning Based on Diffusion Model

Interpreting EEG signals linked to spoken language presents a complex challenge, given the data's intricate temporal and spatial attributes, as well as the various noise factors. Denoising diffusion probabilistic models (DDPMs), which have recently gained prominence in diverse areas for their capabilities in representation learning, are explored in our research as a means to address this issue. Using DDPMs in conjunction with a conditional autoencoder, our new approach considerably outperforms traditional machine learning algorithms and established baseline models in accuracy. Our results highlight the potential of DDPMs as a sophisticated computational method for the analysis of speech-related EEG signals. This could lead to significant advances in brain-computer interfaces tailored for spoken communication

REX-1 Expression and p38 MAPK Activation Status Can Determine Proliferation/Differentiation Fates in Human Mesenchymal Stem Cells

BACKGROUND: REX1/ZFP42 is a well-known embryonic stem cell (ESC) marker. However, the role of REX1, itself, is relatively unknown because the function of REX1 has only been reported in the differentiation of ESCs via STAT signaling pathways. Human mesenchymal stem cells (hMSCs) isolated from young tissues and cancer cells express REX1. METHODOLOGY/PRINCIPAL FINDING: Human umbilical cord blood-derived MSCs (hUCB-MSCs) and adipose tissue-derived MSCs (hAD-MSCs) strongly express REX1 and have a lower activation status of p38 MAPK, but bone marrow-derived MSCs (hBM-MSCs) have weak REX1 expression and higher activation of p38 MAPK. These results indicated that REX1 expression in hMSCs was positively correlated with proliferation rates but inversely correlated with the phosphorylation of p38 MAPK. In hUCB-MSCs, the roles of REX1 and p38 MAPK were investigated, and a knockdown study was performed using a lentiviral vector-based small hairpin RNA (shRNA). After REX1 knockdown, decreased cell proliferation was observed. In REX1 knocked-down hUCB-MSCs, the osteogenic differentiation ability deteriorated, but the adipogenic potential increased or was similar to that observed in the controls. The phosphorylation of p38 MAPK in hUCB-MSCs significantly increased after REX1 knockdown. After p38 MAPK inhibitor treatment, the cell growth in REX1 knocked-down hUCB-MSCs almost recovered, and the suppressed expression levels of CDK2 and CCND1 were also restored. The expression of MKK3, an upstream regulator of p38 MAPK, significantly increased in REX1 knocked-down hUCB-MSCs. The direct binding of REX1 to the MKK3 gene was confirmed by a chromatin immunoprecipitation (ChIP) assay. CONCLUSIONS/SIGNIFICANCE: These findings showed that REX1 regulates the proliferation/differentiation of hMSCs through the suppression of p38 MAPK signaling via the direct suppression of MKK3. Therefore, p38 MAPK and REX-1 status can determine the cell fate of adult stem cells (ASCs). These results were the first to show the role of REX1 in the proliferation/differentiation of ASCs

Long-term risks of complicated grief and insomnia in student survivors of the Sewol ferry disaster in South Korea: A four-year observational follow-up study

Background: The Sewol ferry disaster in April 2014 resulted in the drowning of 304 people. Of the 325 students on board, 250 died and 75 were rescued. The measure of stress caused by bereavement and sleep problems is common and can be a chronic health concern for disaster survivors. The aim of this study was to determine longitudinal predictive factors of complicated grief and insomnia among student survivors of the disaster. Methods: This study centered on 67 student survivors who were enrolled in the disaster registry after graduating from high school. The self-report data as presented by the participants were collected at baseline (27 months after the disaster, T1) and again at two years later (51 months after the disaster, T2). Thirty-one participants completed both T1 and T2 surveys. The noted predictive variables, in this case, were event-related rumination, coping strategy, social support, attachment, meaning in life, and adverse childhood experiences. The outcome variables were complicated grief and insomnia. Results: Dysfunctional coping (T1) was positively associated with complicated grief (T2) (coefficient = 0.070; p<0.001). Intrusive rumination (T1) (coefficient = -0.114; p<0.001), social support (T1) (coefficient = -0.031; p<0.001), and meaning in life – search (T1) (coefficient = -0.082; p<0.001) were negatively associated with insomnia (T2). In contrast, dysfunctional coping (T1) (coefficient = 0.041; p = 0.012), adverse childhood experiences (T1) (coefficient = 0.280; p = 0.007), and insomnia (T1) (coefficient = 0.166; p<0.001) were positively associated with insomnia (T2). Conclusions: Dysfunctional coping influenced how student survivors of the Sewol ferry disaster suffered from complicated grief and insomnia over time. In this case, the findings from the current study indicate that interventions that target coping strategies should be provided to improve the resolution of grief and sleep among survivors. [Ethiop.J. Health Dev. 2020;34(Special issue-3):97-106] Keywords: Sewol ferry disaster, student survivors, coping strategy, complicated grief, insomni

Repeated Gene Transfection Impairs the Engraftment of Transplanted Porcine Neonatal Pancreatic Cells

BackgroundPreviously, we reported that neonatal porcine pancreatic cells transfected with hepatocyte growth factor (HGF) gene in an Epstein-Barr virus (EBV)-based plasmid (pEBVHGF) showed improved proliferation and differentiation compared to those of the control. In this study, we examined if pancreatic cells transfected repeatedly with pEBVHGF can be successfully grafted to control blood glucose in a diabetes mouse model.MethodsNeonatal porcine pancreatic cells were cultured as a monolayer and were transfected with pEBVHGF every other day for a total of three transfections. The transfected pancreatic cells were re-aggregated and transplanted into kidney capsules of diabetic nude mice or normal nude mice. Blood glucose level and body weight were measured every other day after transplantation. The engraftment of the transplanted cells and differentiation into beta cells were assessed using immunohistochemistry.ResultsRe-aggregation of the pancreatic cells before transplantation improved engraftment of the cells and facilitated neovascularization of the graft. Right before transplantation, pancreatic cells that were transfected with pEBVHGF and then re-aggregated showed ductal cell marker expression. However, ductal cells disappeared and the cells underwent fibrosis in a diabetes mouse model two to five weeks after transplantation; these mice also did not show controlled blood glucose levels. Furthermore, pancreatic cells transplanted into nude mice with normal blood glucose showed poor graft survival regardless of the type of transfected plasmid (pCEP4, pHGF, or pEBVHGF).ConclusionFor clinical application of transfected neonatal porcine pancreatic cells, further studies are required to develop methods of overcoming the damage for the cells caused by repeated transfection and to re-aggregate them into islet-like structures

Dual Therapy with Cidofovir and Mirtazapine for Progressive Multifocal Leukoencephalopathy in a Sarcoidosis Patient

Background: Progressive multifocal leukoencephalopathy (PML) is a demyelinating central nervous system disease caused by JC virus (JCV) reactivation in immunocompromised patients. The disease course of PML is often progressive, fatal and at present, there are few reports on successful treatment outcomes. Case Report: A 45-year-old man with systemic sarcoidosis presented with rapidly progressive dementia and right hemiparesis. The patient was diagnosed with PML as confirmed via brain biopsy and JCV PCR. With a combination treatment of cidofovir and mirtazapine, there was significant improvement of neurological symptoms without measurable functional deficit. Conclusion: This case suggests that dual therapy with cidofovir and mirtazapine might be an effective treatment option in PML patients with sarcoidosis

Hu.4-1BB-Fc fusion protein inhibits allergic inflammation and airway hyperresponsiveness in a murine model of asthma

Purpose4-1BB (CD 137) is a costimulatory molecule expressed on activated T-cells. Repression by 4-1BB is thought to attenuate Th2-mediated allergic reactions. The aim of this study was to investigate the effect of 4-1BB on allergic airway inflammation in a murine asthma model.MethodsBALB/c mice were sensitized to and challenged with ovalbumin (OVA). Hu.4-1BB-Fc was administered 1 day before the first OVA sensitization or 1 day after the second OVA sensitization. Following antigen challenge, airway responsiveness to methacholine was assessed and bronchoalveolar lavage (BAL) fluid was analyzed. Total immunoglobulin (Ig) E, OVA-specific IgE, IgG1, and IgG2a levels in sera were measured by enzyme-linked immunosorbent assay. Lung pathology was also evaluated.ResultsIn mice treated with Hu.4-1BB-Fc before the first OVA sensitization, there was a marked decrease in airway hyperresponsiveness, total cell count, and eosinophil count in the BAL fluid. In addition, Hu.4-1BB-Fc treatment decreased serum OVA-specific IgG1 levels and increased serum IgG2a level significantly compared with the corresponding levels in mice sensitized to and challenged with OVA. Hu.4-1BB-Fc-treated mice also showed suppressed peribronchial and perivascular inflammatory cell infiltration. In contrast, treatment with Hu.4-1BB-Fc 1 day after sensitization had no effect on airway hyperresponsiveness and showed less suppression of inflammation in lung tissue.ConclusionAdministration of Hu.4-1BB-Fc can attenuate airway inflammation and hyperreactivity in a mouse model of allergic airway inflammation. In addition, administration before sensitization may be more effective. These findings suggest that 4-1BB may be a useful therapeutic molecule against asthma

Two pediatric cases with hematuria, normal renal function and positive antineutrophil cytoplasmic antibodies

Antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis requires prompt diagnosis and treatment, since renal function at the time of diagnosis is significantly associated with renal outcomes. Here, we report two pediatric patients with ANCA-positive glomerulonephritis initially presenting with hematuria, mild proteinuria, and normal renal function. The first patient with a high myeloperoxidase-ANCA titer (>134 IU/mL) was diagnosed with rapidly progressive glomerulonephritis based on renal biopsy and treated with immunosuppressive therapy after 10 months of follow-up. The second patient with a low myeloperoxidase-ANCA titer (11 IU/mL) maintained normal kidney function without medication. Two cases showed different clinical course according to ANCA titer

Growth characteristics and productivity of cold-tolerant “Kowinearly” Italian ryegrass in the northern part of South Korea

The objective of this research is to evaluate differences in growth characteristics and productivity between Kowinearly and Florida 80 Italian ryegrass varieties in regions with severely cold winters. This research was carried out in Suwon (in central South Korea) and Yonchun (in northern South Korea) during the 2002 2006 growing seasons. Kowinearly is a diploid variety with green leaf colour and a semi prostrate growth habit in autumn and a semi-erect one in spring. There were differences among the varieties in terms of cold tolerance, heading date, and forage yield in Yonchun. The winter field survival of Kowinearly was 85%, while that of Florida 80 was 43%. The dry matter yield of Kowinearly in Yonchun was 9,662 kg/ha, which was 31% more than that of Florida 80. In Suwon, the heading date of Kowinearly was May 7, which was 2 days later than that of Florida 80. In Yonchun, Kowinearly’s heading date was May 12, 1 day earlier than that of Florida 80. These results indicate that Kowinearly has good cold tolerance, and that in spring, it starts growth earlier than Florida 80, because of its higher cold tolerance.Keywords: Italian ryegrass, Kowinearly, cold tolerance, new variety, forage cro

Piceatannol, Natural Polyphenolic Stilbene, Inhibits Adipogenesis via Modulation of Mitotic Clonal Expansion and Insulin Receptor-dependent Insulin Signaling in Early Phase of Differentiation

Piceatannol, a natural stilbene, is an analog and a metabolite of resveratrol. Despite a well documented health benefit of resveratrol in intervention of the development of obesity, the role of piceatannol in the development of adipose tissue and related diseases is unknown. Here, we sought to determine the function of piceatannol in adipogenesis and elucidate the underlying mechanism. We show that piceatannol inhibits adipogenesis of 3T3-L1 preadipocytes in a dose-dependent manner at noncytotoxic concentrations. This anti-adipogenic property of piceatannol was largely limited to the early event of adipogenesis. In the early phase of adipogenesis, piceatannol-treated preadipocytes displayed a delayed cell cycle entry into G2/M phase at 24 h after initiation of adipogenesis. Furthermore, the piceatannol-suppressed mitotic clonal expansion was accompanied by reduced activation of the insulin-signaling pathway. Piceatannol dose-dependently inhibited differentiation mixture-induced phosphorylation of insulin receptor (IR)/insulin receptor substrate-1 (IRS-1)/Akt pathway in the early phase of adipogenesis. Moreover, we showed that piceatannol is an inhibitor of IR kinase activity and phosphatidylinositol 3-kinase (PI3K). Our kinetics study of IR further identified a Km value for ATP of 57.8 μm and a Ki value for piceatannol of 28.9 μm. We also showed that piceatannol directly binds to IR and inhibits IR kinase activity in a mixed noncompetitive manner to ATP, through which piceatannol appears to inhibit adipogenesis. Taken together, our study reveals an anti-adipogenic function of piceatannol and highlights IR and its downstream insulin signaling as novel targets for piceatannol in the early phase of adipogenesis