• Fisheries and Aquatic Sciences
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• v.25 no.3
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• pp.117-139
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• 2022

Synucleinopathies such as Parkinson's disease (PD) are incurable neurodegenerative conditions characterised by the abnormal aggregation of α-synuclein protein in neuronal cells. In PD, fibrillary synuclein aggregation forms Lewy bodies and Lewy neurites in the substantia nigra and cortex on the brain. Dementia with Lewy bodies and multiple system atrophy are also associated with α-synuclein protein abnormalities. α-synuclein is one of three synuclein proteins, and while its precise function is still unknown, one hypothesis posits that α-synuclein propagates from the enteric nervous system through the vagus nerve and into the brain, resulting in synucleinopathy. Studies on synucleinopathies should thus encompass not only the central nervous system but must necessarily include the gut and microbiome. The zebrafish (Danio rerio) is a well-established model for human neuronal pathologies and have been used in studies ranging from genetic models of hereditary disorders to neurotoxin-induced neurodegeneration as well as gut-brain-axis studies. There is significant genetic homology between zebrafish and mammalian vertebrates which is what makes the zebrafish so amenable to modelling human conditions but in the case of synucleinopathies, the zebrafish notably does not possess an α-synuclein homolog. Synuclein orthologs are present in the zebrafish however, and transgenic zebrafish that carry human α-synuclein have been generated. In addition, the zebrafish is a highly advantageous model and ideal replacement for reducing the use of mammalian models. This review discusses the application of the zebrafish as a model for synucleinopathies in efforts to further understand synuclein function and explore therapeutic strategies.

• Proceedings of the Korean Society of Computer Information Conference
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• 2021.07a
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• pp.313-315
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• 2021

Timely and accurate diagnosis of lung diseases using Chest X-ray images has been gained much attention from the computer vision and medical imaging communities. Although previous studies have presented the capability of deep convolutional neural networks by achieving competitive binary classification results, their models were seemingly unreliable to effectively distinguish multiple disease groups using a large number of x-ray images. In this paper, we aim to build an advanced approach, so-called Ensemble Knowledge Distillation (EKD), to significantly boost the classification accuracies, compared to traditional KD methods by distilling knowledge from a cumbersome teacher model into an ensemble of lightweight student models with parallel branches trained with ground truth labels. Therefore, learning features at different branches of the student models could enable the network to learn diverse patterns and improve the qualify of final predictions through an ensemble learning solution. Although we observed that experiments on the well-established ChestX-ray14 dataset showed the classification improvements of traditional KD compared to the base transfer learning approach, the EKD performance would be expected to potentially enhance classification accuracy and model generalization, especially in situations of the imbalanced dataset and the interdependency of 14 weakly annotated thorax diseases.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5451-5454
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• 2012

Objective: The objective of this study was to evaluate the association of MDR1 gene polymorphisms with susceptibility to hepatocellular carcinoma (HCC). Methods: A total of 689 HCC patients and 680 cancer-free subjects were enrolled. Human MDR1 gene polymorphisms were investigated by created restriction site-polymerase chain reaction (CRS-PCR) and DNA sequencing methods. Multiple logistic regression models were applied to estimate the association between MDR1 gene polymorphisms and susceptibility to HCC. Results: We detected a novel c.4125A>C polymorphism and our findings suggested that this variant was significantly associated with susceptibility to HCC. A significantly increased susceptibility to HCC was noted in the homozygote comparison (CC versus AA: OR=1.621, 95% CI 1.143-2.300, ${\chi}^2$=7.4095, P=0.0065), recessive model (CC versus AC+AA: OR=1.625, 95% CI 1.167-2.264, ${\chi}^2$=8.3544, P=0.0039) and allele contrast (C versus A: OR=1.185, 95% CI 1.011-1.389, ${\chi}^2$=4.4046, P=0.0358). However, no significant increase was observed in the heterozygote comparison (AC versus AA: OR=0.995, 95% CI 0.794-1.248, ${\chi}^2$=0.0017, P=0.9672) and dominant model (CC+AC versus AA: OR=1.106, 95% CI 0.894-1.369, ${\chi}^2$=0.8560, P=0.3549). Conclusions: These findings suggest that the c.4125A>C polymorphism of the MDR1 gene might contribute to susceptibility to HCC in the Chinese population. Further work will be necessary to clarify the relationship between the c.4125A>C polymorphism and susceptibility to HCC on larger populations of diverse ethnicity.

• BMB Reports
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• v.48 no.1
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• pp.13-18
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• 2015

Alzheimer's disease severely compromises cognitive function. One of the mechanisms to explain the pathology of Alzheimer's disease has been the hypotheses of amyloid-pore/channel formation by complex $A{\beta}$-aggregates. Clinical studies suggested the moderate alcohol consumption can reduces probability developing neurodegenerative pathologies. A recent report explored the ability of ethanol to disrupt the generation of complex $A{\beta}$ in vitro and reduce the toxicity in two cell lines. Molecular dynamics simulations were applied to understand how ethanol blocks the aggregation of amyloid. On the other hand, the in silico modeling showed ethanol effect over the dynamics assembling for complex $A{\beta}$-aggregates mediated by break the hydrosaline bridges between Asp 23 and Lys 28, was are key element for amyloid dimerization. The amyloid pore/ channel hypothesis has been explored only in neuronal models, however recently experiments suggested the frog oocytes such an excellent model to explore the mechanism of the amyloid pore/channel hypothesis. So, the used of frog oocytes to explored the mechanism of amyloid aggregates is new, mainly for amyloid/pore hypothesis. Therefore, this experimental model is a powerful tool to explore the mechanism implicates in the Alzheimer's disease pathology and also suggests a model to prevent the Alzheimer's disease pathology.

• 한국약용작물학회:학술대회논문집
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• 2011.09a
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• pp.31-45
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• 2011

The amyloid ${\beta}$-peptide ($A{\beta}$), which originates from the proteolytic cleavage of amyloid precursor protein (APP), plays a central role in the pathogenesis of Alzheimer's disease (AD). Mounting evidence indicates that different species of $A{\beta}$, such as $A{\beta}$ oligomers and fibrils, may contribute to AD pathogenesis via distinct mechanisms at different stages of the disease. Importantly, elevation and accumulation of soluble $A{\beta}$ oligomers closely correlate with cognitive decline and/or disease progression in animal models of AD. In agreement with these studies, oligomers of $A{\beta}$ have been shown to directly affect synaptic plasticity, a neuronal process that is known to be essential for memory formation. Our previous studies showed that $A{\beta}$ induces the breakdown of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), a phospholipid that regulates key aspects of neuronal function. PI(4,5)P2 breakdown was found to be a key step toward synaptic and memory dysfunction in a mouse model of AD. To this end, we seek to identify small molecules that could elevate the levels of PI(4,5)P2 and subsequently block $A{\beta}$ oligomer-induced breakdown of PI(4,5)P2 and synaptic dysfunction.. We found that (20S)Rg3, an active triterpene glycoside from heat-processed ginseng, serves as an agonist for phosphatidylinositol 4-kinase IIalpha (PI4KIIalpha), which is a lipid kinase that mediates a rate-limiting step in PI(4,5)P2 synthesis. Consequently, (20S)Rg3 stimulates PI(4,5)P2 synthesis by directly stimulating the activity of PI4KIIalpha. Interestingly, treatment of a mouse model of AD with (20S)Rg3 leads to reversal of memory deficits. Our data suggest that the PI(4,5)P2-promoting effects of (20S)Rg3 may help mitigate the cognitive symptoms associated with AD.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3893-3900
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• 2015

It's known that having multiple sexual partners is one of the risk factors of human papillomavirus (HPV) infection which is a major cause of cervical cancer. However, it is not clear whether the number of sexual partners is an independent risk factor for cervical cancer. We identified relevant studies by searching the databases of MEDLINE, PubMed and ScienceDirect published in English from January 1980 to January 2014. We analyzed those studies by combining the study-specific odds ratios (ORs) using random-effects models. Forty-one studies were included in this meta-analysis. We observed that the number of sexual partners was associated with the occurrence of non-malignant cervical disease (OR=1.82, 95%CI 1.63-2.00) and invasive cervical carcinoma (OR=1.77, 95%CI 1.50-2.05). Subgroup analyses revealed that the association remained significant after controlling for HPV infection (OR=1.52, 95%CI 1.21-1.83 for non-malignant disease; OR=1.53, 95%CI 1.30-1.76 for invasive cervical carcinoma). We found that there was a non-linear relation of the number of sexual partners with both non-malignant cervical disease and invasive cervical carcinoma. The risk of both malignant and non-malignant disease is relatively stable in women with more than 4-7 sexual partners. Furthermore, the frequency-risk of disease remained significant after controlling for HPV infection.The study suggested that h aving multiple sexual partners, with or without HPV infection, is a potential risk factor of cervical cancer.

• The korean journal of orthodontics
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• v.50 no.2
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• pp.86-97
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• 2020

Objective: To propose a three-dimensional (3D) method for evaluating temporomandibular joint (TMJ) changes during Twin-block treatment. Methods: Seventeen patients with Class II division 1 malocclusion treated using Twin-block and nine untreated patients with a similar malocclusion were included in this research. We collected their cone beam computed tomography (CBCT) data from before and 8 months after treatment. Segmentations were constructed using ITK-SNAP. Condylar volume and superficial area were measured using 3D Slicer. The 3D landmarks were identified on CBCT images by using Dolphin software to assess the condylar positional relationship. 3D models of the mandible and glenoid fossa of the patients were constructed and registered via voxel-based superimposition using 3D Slicer. Thereafter, skeletal changes could be visualized using 3DMeshMetric in any direction of the superimposition on a color-coded map. All the superimpositions were measured using the same scale on the distance color-coded map, in which red color represents overgrowth and blue color represents resorption. Results: Significant differences were observed in condylar volume, superficial area, and condylar position in both groups after 8 months. Compared with the control group (CG), the Twin-block group exhibited more obvious condyle-fossa modifications and joint positional changes. Moreover, on the color-coded map, more obvious condyle-fossa modifications could be observed in the posterior and superior directions in the Twin-block group than in the CG. Conclusions: We successfully established a 3D method for measuring and evaluating TMJ changes caused by Twin-block treatment. The treatment produced a larger condylar size and caused condylar positional changes.

• Journal of Gastric Cancer
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• v.21 no.3
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• pp.279-297
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• 2021

Purpose: Various changes in nutrition, metabolism, immunity, and psychological status occur through multiple mechanisms after gastrectomy. The purpose of this study was to predict disease status after gastrectomy by analyzing diseases pattern that occur or change after gastrectomy. Materials and Methods: A retrospective cohort study was conducted using nationwide claims data. Patients with gastric cancer who underwent gastrectomy or endoscopic resection were included in the study. Eighteen target diseases were selected and categorized based on their underlying mechanism. The incidence of each target disease was compared by dividing the study sample into those who underwent gastrectomy (cases) and those who underwent endoscopic resection for early gastric cancer (controls). The cases were matched with controls using propensity score matching. Thereafter, Cox proportional hazard models were used to evaluate intergroup differences in disease incidence after gastrectomy. Results: A total of 97,634 patients who underwent gastrectomy (84,830) or endoscopic resection (12,804) were included. The incidence of cholecystitis (P<0.0001), pancreatitis (P=0.034), acute kidney injury (P=0.0083), anemia (P<0.0001), and inguinal hernia (P=0.0007) were higher after gastrectomy, while incidence of dyslipidemia (P<0.0001), vascular diseases (ischemic heart disease, stroke, and atherosclerosis; P<0.0001, P<0.0001, and P=0.0005), and Parkinson's disease (P=0.0093) were lower after gastrectomy. Conclusions: This study identifies diseases that may occur after gastrectomy in patients with gastric cancer.

• Journal of Microbiology and Biotechnology
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• v.32 no.9
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• pp.1168-1177
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• 2022

Parkinson's disease (PD) is the second-most prevalent neurodegenerative disease and is characterized by dopaminergic neuronal death in the midbrain. Recently, the association between alterations in PD pathology and the gut microbiota has been explored. Microbiota-targeted interventions have been suggested as a novel therapeutic approach for PD. Agathobaculum butyriciproducens SR79^T (SR79) is an anaerobic bacterium. Previously, we showed that SR79 treatment induced cognitive improvement and reduced Alzheimer's disease pathologies in a mouse model. In this study, we hypothesized that SR79 treatment may have beneficial effects on PD pathology. To investigate the therapeutic effects of SR79 on PD, 6-hydroxydopamine (6-OHDA)-induced mouse models were used. D-Amphetamine sulfate (d-AMPH)-induced behavioral rotations and dopaminergic cell death were analyzed in unilateral 6-OHDA-lesioned mice. Treatment with SR79 significantly decreased ipsilateral rotations induced by d-AMPH. Moreover, SR79 treatment markedly activated the AKT/GSK3β signaling pathway in the striatum. In addition, SR79 treatment affected the Nrf2/ARE signaling pathway and its downstream target genes in the striatum of 6-OHDA-lesioned mice. Our findings suggest a protective role of SR79 in 6-OHDA-induced toxicity by regulating the AKT/Nrf2/ARE signaling pathway and astrocyte activation. Thus, SR79 may be a potential microbe-based intervention and therapeutic strategy for PD.

• Journal of Veterinary Science
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• v.25 no.1
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• pp.13.1-13.9
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• 2024

Background: Foot-and-mouth disease (FMD) is a highly contagious viral disease in livestock that has tremendous economic impact nationally. After multiple FMD outbreaks, the South Korean government implemented a vaccination policy for efficient disease control. However, during active surveillance by quarantine authorities, pig farms have reported an insufficient antibody positivity rate to FMD. Objective: In this study, the spatial and temporal trends of insufficiency among pig farms were analyzed, and the effect of the number of government veterinary officers was explored as a potential preventive factor. Methods: Various data were acquired, including national-level surveillance data for antibody insufficiency from the Korea Animal Health Integrated System, the number of veterinary officers, and the number of local pig farms. Temporal and geographical descriptive analyses were conducted to overview spatial and temporal trends. Additionally, logistic regression models were employed to investigate the association between the number of officers per pig farm with antibody insufficiency. Spatial cluster analysis was conducted to detect spatial clusters. Results: The results showed that the incidence of insufficiency tended to decrease in recent years (odds ratio [OR], 0.803; 95% confidence interval [95% CIs], 0.721-0.893), and regions with a higher density of governmental veterinary officers (OR, 0.942; 95% CIs, 0.918-0.965) were associated with a lower incidence. Conclusions: This study implies that previously conducted national interventions would be effective, and the quality of government-provided veterinary care could play an important role in addressing the insufficient positivity rate of antibodies.