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.

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.

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.

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.

Background: Although there are growing demands for stem cell-based therapy for companion animals in various diseases, a few clinical trials have been reported. Moreover, most of them are the results from only one or a few times of stem cell injection. Objectives: The aim of this study is to describe a long-term treatment with allogeneic adipose-derived stem cells (ASCs) in a dog with rheumatoid arthritis (RA), which is a rare canine disease. Methods: The dog with RA received intravascular injection of allogeneic ASCs derived from two healthy donors once a month for 11 months. To assess therapeutic effects of ASCs, orthopedic examination and clinical evaluation was performed. Cytokines of tumor necrosis factor-α and interleukin-6 in the plasma were measured using ELISA analysis. Results: Despite this repeated and long-term administration of allogeneic ASCs, there were no side effects such as immunorejection responses or cell toxicity. The orthopedic examination score for the dog decreased after ASCs treatment, and the clinical condition of the dog and owner’s satisfaction were very good Conclusions Although ASCs has been suggested as one of the options for RA treatment because of its anti-inflammatory and immunosuppressive functions, it has never been used to treat RA in dogs. The present report describes a case of canine RA treated with allogeneic ASCs for long-term in which the dog showed clinical improvement without adverse effects.

Purpose: This study analyzed the relationship between degree of disability and edema index [extracellular water/total body water (ECW/TBW) ratio] values in a rural population of older adult patients with osteopenia, sarcopenia, or osteosarcopenia (OS). Materials and Methods: This study used data from the Namgaram-2 cohort. The degree of disability was measured using the World Health Organization Disability Assessment Schedule (WHODAS) 12, and ECW/TBW ratio was calculated using bioelectrical impedance analysis. Based on ECW/TBW ratio, the participants were stratified into normal (<0.391) and abnormal (≥0.391) groups, and the mean WHODAS 12 scores were compared between the two groups. Multiple regression analysis corrected for demographic factors, smoking history, hypertension, diabetes, and serological test results was also conducted. Results: Significant differences in mean WHODAS 12 scores were observed in the healthy group (5.8±7.4 vs. 9.2±9.7, p=0.008), the osteopenia only group (7.4±8.7 vs. 12.9±12.0, p<0.001), and the OS group (16.0±13.2 vs. 23.1±17.1, p=0.004). However, no significant difference in mean WHODAS 12 score was observed in the sarcopenia only group (14.9±13.4 vs. 20.7±14.8, p= 0.051). There were significant differences in ECW/TBW ratio values between the abnormal and normal groups in the osteopenia only group (B=4.646 and p=0.001), the sarcopenia only group (B=5.097 and p=0.016), and the OS group (B=5.653 and p=0.043). Conclusion This study found that the degree of disability is related to the edema index in older patients with osteopenia, sarcopenia, or OS. Since the edema index indicates the nutritional status of an individual, proper nutrition and fluid intake are important to reduce disability.

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.

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.

Leukemia cutis (LC) is a cutaneous condition caused by leukemia cells leaching into the skin, with various clinical manifestations. At times, skin lesions called aleukemic LC occur before leukemia cells appear in the bone marrow or peripheral blood. Proper diagnosis of such a condition is important for early detection, treatment, and prognosis of leukemia. In general, LC is usually associated with an unfavorable prognosis. Herein, we report a case of a 65-year-old male with LC who presented with multiple papular lesions on the trunk and extremities. Histopathological examination of the lesions revealed LC of the monocytic type. Additional laboratory tests of the peripheral blood were normal, but a bone marrow biopsy demonstrated a high proportion of leukemic cells. In conclusion, we present this case to highlight that early diagnosis and accurate management are crucial for the prognosis of patients affected with leukemia, especially when skin lesions are the first clinical symptom.