1.Machine Learning-assisted Quantitative Mapping of Intracortical Axonal Plasticity Following a Focal Cortical Stroke in Rodents
Hyung Soon KIM ; Hyo Gyeong SEO ; Jong Ho JHEE ; Chang Hyun PARK ; Hyang Woon LEE ; Bumhee PARK ; Byung Gon KIM
Experimental Neurobiology 2023;32(3):170-180
Stroke destroys neurons and their connections leading to focal neurological deficits. Although limited, many patients exhibit a certain degree of spontaneous functional recovery. Structural remodeling of the intracortical axonal connections is implicated in the reorganization of cortical motor representation maps, which is considered to be an underlying mechanism of the improvement in motor function. Therefore, an accurate assessment of intracortical axonal plasticity would be necessary to develop strategies to facilitate functional recovery following a stroke. The present study developed a machine learning-assisted image analysis tool based on multi-voxel pattern analysis in fMRI imaging. Intracortical axons originating from the rostral forelimb area (RFA) were anterogradely traced using biotinylated dextran amine (BDA) following a photothrombotic stroke in the mouse motor cortex. BDA-traced axons were visualized in tangentially sectioned cortical tissues, digitally marked, and converted to pixelated axon density maps. Application of the machine learning algorithm enabled sensitive comparison of the quantitative differences and the precise spatial mapping of the post-stroke axonal reorganization even in the regions with dense axonal projections. Using this method, we observed a substantial extent of the axonal sprouting from the RFA to the premotor cortex and the peri-infarct region caudal to the RFA. Therefore, the machine learningassisted quantitative axonal mapping developed in this study can be utilized to discover intracortical axonal plasticity that may mediate functional restoration following stroke.
2.SARS‑CoV‑2 Omicron variant causes brain infection with lymphoid depletion in a mouse COVID‑19 model
Na Yun LEE ; Youn Woo LEE ; Seung‑Min HONG ; Dain ON ; Gyeong Min YOON ; See‑He AN ; Ki Taek NAM ; Jun‑Young SEO ; Jeon‑Soo SHIN ; Yang‑Kyu CHOI ; Seung Hyun OH ; Jun‑Won YUN ; Ho Young LEE ; Kang‑Seuk CHOI ; Je Kyung SEONG ; Jun Won PARK
Laboratory Animal Research 2023;39(2):165-171
Background:
The Omicron variant has become the most prevalent SARS-CoV-2 variant. Omicron is known to induce milder lesions compared to the original Wuhan strain. Fatal infection of the Wuhan strain into the brain has been well documented in COVID-19 mouse models and human COVID-19 cases, but apparent infections into the brain by Omicron have not been reported in human adult cases or animal models. In this study, we investigated whether Omicron could spread to the brain using K18-hACE2 mice susceptible to SARS-CoV-2 infection.
Results:
K18-hACE2 mice were intranasally infected with 1 × 105 PFU of the original Wuhan strain and the Omicron variant of SARS-CoV-2. A follow-up was conducted 7 days post infection. All Wuhan-infected mice showed > 20% body weight loss, defined as the lethal condition, whereas two out of five Omicron-infected mice (40%) lost > 20% body weight. Histopathological analysis based on H&E staining revealed inflammatory responses in the brains of these two Omicron-infected mice. Immunostaining analysis of viral nucleocapsid protein revealed severe infection of neuron cells in the brains of these two Omicron-infected mice. Lymphoid depletion and apoptosis were observed in the spleen of Omicron-infected mice with brain infection.
Conclusion
Lethal conditions, such as severe body weight loss and encephalopathy, can occur in Omicron-infected K18-hACE2 mice. Our study reports, for the first time, that Omicron can induce brain infection with lymphoid depletion in the mouse COVID-19 model.
3.Acoustic and Magnetic Stimuli-Based Three-Dimensional Cell Culture Platform for Tissue Engineering
Ju Yeon SEO ; Song Bin PARK ; Seo Yeon KIM ; Gyeong Jin SEO ; Hyeon-Ki JANG ; Tae-Jin LEE
Tissue Engineering and Regenerative Medicine 2023;20(4):563-580
In a conventional two-dimensional (2D) culture method, cells are attached to the bottom of the culture dish and grow into a monolayer. These 2D culture methods are easy to handle, cost-effective, reproducible, and adaptable to growing many different types of cells. However, monolayer 2D cell culture conditions are far from those of natural tissue, indicating the need for a threedimensional (3D) culture system. Various methods, such as hanging drop, scaffolds, hydrogels, microfluid systems, and bioreactor systems, have been utilized for 3D cell culture. Recently, external physical stimulation-based 3D cell culture platforms, such as acoustic and magnetic forces, were introduced. Acoustic waves can establish acoustic radiation force, which can induce suspended objects to gather in the pressure node region and aggregate to form clusters. Magnetic targeting consists of two components, a magnetically responsive carrier and a magnetic field gradient source. In a magnetic-based 3D cell culture platform, cells are aggregated by changing the magnetic force. Magnetic fields can manipulate cells through two different methods: positive magnetophoresis and negative magnetophoresis. Positive magnetophoresis is a way of imparting magnetic properties to cells by labeling them with magnetic nanoparticles. Negative magnetophoresis is a label-free principle-based method. 3D cell structures, such as spheroids, 3D network structures, and cell sheets, have been successfully fabricated using this acoustic and magnetic stimuli-based 3D cell culture platform. Additionally, fabricated 3D cell structures showed enhanced cell behavior, such as differentiation potential and tissue regeneration. Therefore, physical stimuli-based 3D cell culture platforms could be promising tools for tissue engineering.
4.Demand for Priorities for Preventing Occupational Diseases among Farmers
Ae-Rim SEO ; Ji-Youn KIM ; Bokyoung KIM ; Gyeong-Ye LEE ; Kyungsu KIM ; Ki-Soo PARK
Journal of Agricultural Medicine & Community Health 2023;48(4):239-250
Objective:
This study was a preliminary study for the prevention programs for farmers' occupational diseases. It selected the priorities recognized by farmers, such as occupational diseases, and also identifies the effectiveness and feasibility of prevention programs among diseases recognized by farmers. Therefore, we plan to use it as basis data for future farmer safety and health programs.Method: The subjects of the study were farmers living in the region, selected through a snowball recruitment method, and a total of 671 people were targeted. The priority selection method was the Basic Priority Rating System (BPRS) method, and among the occupational diseases, programs to prevent musculoskeletal diseases, cardiovascular and respiratory diseases, and pesticide poisoning were surveyed on the effectiveness and feasibility of farmers.
Results:
Among occupational diseases, the highest priority was musculo-skeletal disease, followed by respiratory disease and pesticide poisoning. Among the programs for musculoskeletal disease, 'use of agricultural work convenience equipment and auxiliary tools' had the highest perceived effectiveness and feasibility. Among the five programs for pesticide poisoning, ‘equipment of protective equipment such as pesticide protective clothing/glove’ had the highest effectiveness at 67.4%, and ‘compliance with pesticide use instructions’ had the highest level of feasibility at 64.3%. Among the four programs to prevent respiratory diseases, ‘wearing a dust mask or gas mask’ was the highest at 65.5% in terms of both effectiveness and feasibility.
Conclusion
When carrying out safety and health programs for farmers, the priorities recognized by farmers should be taken into consideration, and the program contents should also be developed taking into account the size of effect and feasibility recognized by farmers.
5.Validation of Cancer Diagnosis Based on the National Health Insurance Service Database versus the National Cancer Registry Database in Korea
Min Soo YANG ; Minae PARK ; Joung Hwan BACK ; Gyeong Hyeon LEE ; Ji Hye SHIN ; Kyuwoong KIM ; Hwa Jeong SEO ; Young Ae KIM
Cancer Research and Treatment 2022;54(2):352-361
Purpose:
This study aimed to assess the feasibility of operational definitions of cancer patients in conducting cancer-related studies using the claims data from the National Health Insurance Service (NHIS).
Materials and Methods:
Cancer incidence data were obtained from the Korean Central Cancer Registry, the NHIS primary diagnosis, and from the rare and intractable disease (RID) registration program.
Results:
The operational definition with higher sensitivity for cancer patient verification was different by cancer type. Using primary diagnosis, the lowest sensitivity was found in colorectal cancer (91.5%; 95% confidence interval [CI], 91.7 to 92.0) and the highest sensitivity was found in breast cancer (97.9%; 95% CI, 97.8 to 98.0). With RID, sensitivity was the lowest in liver cancer (91.9%; 95% CI, 91.7 to 92.0) and highest in breast cancer (98.1%; 95% CI, 98.0 to 98.2). In terms of the difference in the date of diagnosis in the cancer registration data, > 80% of the patients showed a < 31-day difference from the RID definition.
Conclusion
Based on the NHIS data, the operational definition of cancer incidence is more accurate when using the RID registration program claims compared to using the primary diagnosis despite the relatively lower concordance by cancer type requires additional definitions such as treatment.
6.XperCT-guided Intra-cisterna Magna Injection of Streptozotocin for Establishing an Alzheimer’s Disease Model Using the Cynomolgus Monkey (Macaca fascicularis)
Junghyung PARK ; Jinyoung WON ; Chang-Yeop JEON ; Kyung Seob LIM ; Won Seok CHOI ; Sung-hyun PARK ; Jincheol SEO ; Jiyeon CHO ; Jung Bae SEONG ; Hyeon-Gu YEO ; Keonwoo KIM ; Yu Gyeong KIM ; Minji KIM ; Kyung Sik YI ; Youngjeon LEE
Experimental Neurobiology 2022;31(6):409-418
Till date, researchers have been developing animal models of Alzheimer’s disease (AD) in various species to understand the pathological characterization and molecular mechanistic pathways associated with this condition in humans to identify potential therapeutic treatments. A widely recognized AD model that mimics the pathology of human AD involves the intracerebroventricular (ICV) injection with streptozotocin (STZ).However, ICV injection as an invasive approach has several limitations related to complicated surgical procedures. Therefore, in the present study, we created a customized stereotaxic frame using the XperCT-guided system for injecting STZ in cynomolgus monkeys, aiming to establish an AD model. The anatomical structures surrounding the cisterna magna (CM) were confirmed using CT/MRI fusion images of monkey brain with XperCT, the c-arm cone beam computed tomography. XperCT was used to determine the appropriate direction in which the needle tip should be inserted within the CM region. Cerebrospinal fluid (CSF) was collected to confirm the accurate target site when STZ was injected into the CM.Cynomolgus monkeys were administered STZ dissolved in artificial CSF once every week for 4 weeks via intracisterna magna (ICM) injection using XperCT-guided stereotactic system. The molecular mechanisms underlying the progression of STZ-induced AD pathology were analyzed two weeks after the final injection. The monkeys subjected to XperCT-based STZ injection via the ICM route showed features of AD pathology, including markedly enhanced neuronal loss, synaptic impairment, and tau phosphorylation in the hippocampus. These findings suggest a new approach for the construction of neurodegenerative disease models and development of therapeutic strategies.
7.Awareness of the Prevention of Work-Related Diseases among Farmers - Based on Qualitative Research Methods
Ae-Rim SEO ; Ji-Youn KIM ; Bokyoung KIM ; Gyeong-Ye LEE ; Ki-Soo PARK
Journal of Agricultural Medicine & Community Health 2022;47(4):211-219
Objective:
This study was conducted to investigate the awareness of work-related disease prevention of farmers.Method: As a research method, a qualitative focus group interview was conducted in 18 participants.
Results:
Prevention and management services for work-related diseases of farmers mostly are based on research from other fields and so are not highly effective because their content is not relevant to agricultural work. It has been suggested that such program designers be required to have some appropriate related knowledge, and that incentives and a certification system for participation in such education be established. To analyze work-related diseases of farmers, fields of prevention, diagnosis, treatment, and rehabilitation should be created. They demanded the designation of hospitals and the actualization of compensation for farmers' safety insurance. The work-related diseases to address were include musculoskeletal diseases, pesticide poisoning-related diseases (cardiovascular disease, respiratory disease), psychiatric diseases such as depression, and allergic diseases. However, this must have been the result of the harmful factors they felt during agricultural work. And for farmer patients diagnosed with work-related diseases, it was said to strengthen farmer safety insurance.
Conclusion
In order to increase the safely and health effects of agricultural work, it is necessary to prevent and manage work-related diseases of farmers. Projects should be developed in consideration of cultural and economic barriers of farmers and the characteristics of the work.
8.A Drug-Induced Sarcoidosis-Like Reaction in Lung Cancer Patient Treated with Nivolumab and Ipilimumab: A Case Report and Literature Review
Soo Hyung KIM ; Seo Gyeong LEE ; Ji Yoon KIM ; Hyun Jeong JU ; Gyong Moon KIM ; Ji Hae LEE
Korean Journal of Dermatology 2022;60(3):182-185
Immune checkpoint inhibitor (ICI), including programmed cell death protein 1 and cytotoxic T-lymphocyte-associated protein 4 inhibitors, has emerged as a pillar in the management of advanced malignancies. A drug-induced sarcoidosis-like reaction (DISR) is a rare cutaneous adverse event of ICI. A 47-year-old male presented with one-month history of a solitary erythematous nodule on his forehead. He had been diagnosed with metastatic adenocarcinoma of the lung and was treated with nivolumab and ipilimumab for three months. Histological findings revealed multinucleated giant cells forming non-caseating granulomas with moderate peripheral lymphocyte infiltration in the dermis. Also, new hilar lymphadenopathy of the lung was identified in a systemic evaluation. Given the temporal relationship with ICI treatment, the final diagnosis was ICI-induced sarcoidosis-like reaction. To our knowledge, this is the first report of a case of DISR that developed following ICI treatment in the dermatologic literature in Korea.
9.Nutrition and Psychosocial Factors were associated with Possible Sarcopenia in the Rural Elderly
Bokyoung KIM ; Gyeong-Ye LEE ; Ae-Rim SEO ; Mi-Ji KIM ; Sung-Hyo SEO ; Ki-Soo PARK
Journal of Agricultural Medicine & Community Health 2022;47(2):90-98
Objective:
This study aimed to provide basic data for preventing and managing sarcopenia by identifying the relationship between sarcopenia, malnutrition, and psychosocial factors among the elderly in the community.
Methods:
The study included 1,019 subjects aged 60 and over. “Possible sarcopenia” was defined by low handgrip strength with or without reduced physical performance. Nutrition was evaluated according to the mini nutrition assessment (MNA), and the psychosocial factors examined were self-efficacy, social isolation, fear of falling, and social capital (trust and participation). A logistic regression analysis was also performed on the relationship between risk of malnutrition, psychosocial factors, and sarcopenia.
Results:
MNA was significantly associated with social participation (OR = 1.747, p <0.001), fear of falling (OR = 2.905, p <0.001), and self-efficacy (high/low, OR = 0.654, p = 0.011). In model 3, which included both MNA and psychosocial factors, sarcopenia was significantly associated with MNA (OR = 2.529, p <0.001) and fear of falling (OR = 1.544, p = 0.045). Compared with the low self-efficacy group, the high group (OR = 0.589, p = 0.009) was significant. The factors related to possible sarcopenia include risk of malnutrition, fear of falls, and low self-efficacy.
Conclusion
It will be necessary to improve self-efficacy so that individuals feel they can do activities of daily living themselves and to reduce their fear of falling through muscle strength and balance exercises.Finally, it is also necessary to increase regular participation in community social activities.

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