Objective: : Although Republic of Korea is an advanced country in medical technology with a successful treatment rate for serious diseases, such as cancer, and has improved technology for highly difficult surgery, many excellent medical doctors and physicians are struggling due to the recent unreasonable medical environment. Specialization in brain tumor surgery also faces challenges in Republic of Korea, including low financial incentives, legal threats, and limited career prospects. In response, the Korean Brain Tumor Society (KBTS) formed the Future Strategy Committee to assess these obstacles and propose solutions. Methods: : A survey was conducted among the KBTS members to understand their perceptions and concerns across different career stages. Results: : The findings revealed a decline in interest among chief residents in brain tumor surgery, owing to limited job opportunities and income prospects. Neurosurgical fellows expressed neutral satisfaction but highlighted challenges, such as low patient numbers and income. Faculty members with varying levels of experience echoed similar concerns, emphasizing the need for improved financial incentives and job stability. Despite these challenges, the respondents expressed dedication to the field and suggested strategies for improvement. Conclusion : The KBTS outlines a vision that focuses on practical excellence, comprehensive research, professional education, responsibilities, and member satisfaction. Addressing these challenges requires collaborative efforts among healthcare institutions, professional societies, and policymakers to support brain tumor specialists and enhance patient care.

Objective: : Although Republic of Korea is an advanced country in medical technology with a successful treatment rate for serious diseases, such as cancer, and has improved technology for highly difficult surgery, many excellent medical doctors and physicians are struggling due to the recent unreasonable medical environment. Specialization in brain tumor surgery also faces challenges in Republic of Korea, including low financial incentives, legal threats, and limited career prospects. In response, the Korean Brain Tumor Society (KBTS) formed the Future Strategy Committee to assess these obstacles and propose solutions. Methods: : A survey was conducted among the KBTS members to understand their perceptions and concerns across different career stages. Results: : The findings revealed a decline in interest among chief residents in brain tumor surgery, owing to limited job opportunities and income prospects. Neurosurgical fellows expressed neutral satisfaction but highlighted challenges, such as low patient numbers and income. Faculty members with varying levels of experience echoed similar concerns, emphasizing the need for improved financial incentives and job stability. Despite these challenges, the respondents expressed dedication to the field and suggested strategies for improvement. Conclusion : The KBTS outlines a vision that focuses on practical excellence, comprehensive research, professional education, responsibilities, and member satisfaction. Addressing these challenges requires collaborative efforts among healthcare institutions, professional societies, and policymakers to support brain tumor specialists and enhance patient care.

Objective: : Although Republic of Korea is an advanced country in medical technology with a successful treatment rate for serious diseases, such as cancer, and has improved technology for highly difficult surgery, many excellent medical doctors and physicians are struggling due to the recent unreasonable medical environment. Specialization in brain tumor surgery also faces challenges in Republic of Korea, including low financial incentives, legal threats, and limited career prospects. In response, the Korean Brain Tumor Society (KBTS) formed the Future Strategy Committee to assess these obstacles and propose solutions. Methods: : A survey was conducted among the KBTS members to understand their perceptions and concerns across different career stages. Results: : The findings revealed a decline in interest among chief residents in brain tumor surgery, owing to limited job opportunities and income prospects. Neurosurgical fellows expressed neutral satisfaction but highlighted challenges, such as low patient numbers and income. Faculty members with varying levels of experience echoed similar concerns, emphasizing the need for improved financial incentives and job stability. Despite these challenges, the respondents expressed dedication to the field and suggested strategies for improvement. Conclusion : The KBTS outlines a vision that focuses on practical excellence, comprehensive research, professional education, responsibilities, and member satisfaction. Addressing these challenges requires collaborative efforts among healthcare institutions, professional societies, and policymakers to support brain tumor specialists and enhance patient care.

Objective: : Although Republic of Korea is an advanced country in medical technology with a successful treatment rate for serious diseases, such as cancer, and has improved technology for highly difficult surgery, many excellent medical doctors and physicians are struggling due to the recent unreasonable medical environment. Specialization in brain tumor surgery also faces challenges in Republic of Korea, including low financial incentives, legal threats, and limited career prospects. In response, the Korean Brain Tumor Society (KBTS) formed the Future Strategy Committee to assess these obstacles and propose solutions. Methods: : A survey was conducted among the KBTS members to understand their perceptions and concerns across different career stages. Results: : The findings revealed a decline in interest among chief residents in brain tumor surgery, owing to limited job opportunities and income prospects. Neurosurgical fellows expressed neutral satisfaction but highlighted challenges, such as low patient numbers and income. Faculty members with varying levels of experience echoed similar concerns, emphasizing the need for improved financial incentives and job stability. Despite these challenges, the respondents expressed dedication to the field and suggested strategies for improvement. Conclusion : The KBTS outlines a vision that focuses on practical excellence, comprehensive research, professional education, responsibilities, and member satisfaction. Addressing these challenges requires collaborative efforts among healthcare institutions, professional societies, and policymakers to support brain tumor specialists and enhance patient care.

Purpose: We hypothesized that a radiomics approach could be employed to classify children with growth hormone deficiency (GHD) and idiopathic short stature (ISS) on sella magnetic resonance imaging (MRI). Accordingly, we aimed to develop a radiomics prediction model for differentiating GHD from ISS and to evaluate the diagnostic performance thereof. Materials and Methods: Short stature pediatric patients diagnosed with GHD or ISS from March 2011 to July 2020 at our institution were recruited. We enrolled 312 patients (GHD 210, ISS 102) with normal sella MRI and temporally split them into training and test sets (7:3). Pituitary glands were semi-automatically segmented, and 110 radiomic features were extracted from the coronal T2-weighted images. Feature selection and model development were conducted by applying mutual information (MI) and a light gradient boosting machine, respectively. After training, the model’s performance was validated in the test set. We calculated mean absolute Shapley values for each of the selected input features using the Shapley additive explanations (SHAP) algorithm. Volumetric comparison was performed for GHD and ISS groups. Results: Ten radiomic features were selected by MI. The receiver operating characteristics curve of the developed model in the test set was 0.705, with an accuracy of 70.6%. When analyzing SHAP plots, root mean squared values had the highest impact in the model, followed by various texture features. In volumetric analysis, sagittal height showed a significant difference between GHD and ISS groups. Conclusion Radiomic analysis of sella MRI may be able to differentiate between GHD and ISS in clinical practice for short-statured children.

Huntington’s disease (HD) is a dominantly inherited neurodegenerative disorder caused by abnormally expanded CAG repeats in the huntingtin gene. The huntingtin gene mutation leads to the progressive degeneration of striatal GABAergic medium spiny neurons (MSN) and reduces the level of brain-derived neurotrophic factor (BDNF) in HD patient’s brain. BDNF is an essential neurotrophic factor for the cortico-striatal synaptic activity and the survival of GABAergic neurons. In this study, we transplanted BDNF-overexpressing human neural stem cells (HB1.F3.BDNF) into the contra-lateral side of unilateral quinolinic acid (QA)-lesioned striatum of HD rat model. The results of in vivo transplantation were monitored using various behavioral tests, 4.7 T animal magnetic resonance imaging (MRI) and immunohistochemical staining. We observed that the QA-lesioned rats receiving HB1.F3.BDNF cells exhibited significant behavioral improvements in the stepping, rotarod and apomorphine-induced rotation tests. Interestingly, contralaterally transplanted cells were migrated to the QA-lesioned striatum and the size of lateral ventricle was reduced. Histological analyses further revealed that the transplanted cells, which had migrated to the QA lesion site, were differentiated into the cells of GABAergic, MSN-type neurons expressing DARPP-32, and neural networks were established between the transplanted cells and the host brain, as revealed by retrograde tracing. Finally, there was a significant reduction of inflammatory response in HB1.F3.BDNF-transplanted HD animal model, compared with vehicle-transplanted group. Taken together, these results suggest that HB1.F3.BDNF can be an effective therapeutic strategy to treat HD patients in the future.

Alzheimer's Disease (AD) is a progressive neurodegenerative disease, which is pathologically defined by the accumulation of amyloid plaques and hyper-phosphorylated tau aggregates in the brain. Mitochondrial dysfunction is also a prominent feature in AD, and the extracellular Aβ and phosphorylated tau result in the impaired mitochondrial dynamics. In this study, we generated an induced pluripotent stem cell (iPSC) line from an AD patient with amyloid precursor protein (APP) mutation (Val715Met; APP-V715M) for the first time. We demonstrated that both extracellular and intracellular levels of Aβ were dramatically increased in the APP-V715M iPSC-derived neurons. Furthermore, the APP-V715M iPSC-derived neurons exhibited high expression levels of phosphorylated tau (AT8), which was also detected in the soma and neurites by immunocytochemistry. We next investigated mitochondrial dynamics in the iPSC-derived neurons using Mito-tracker, which showed a significant decrease of anterograde and retrograde velocity in the APP-V715M iPSC-derived neurons. We also found that as the Aβ and tau pathology accumulates, fusion-related protein Mfn1 was decreased, whereas fission-related protein DRP1 was increased in the APP-V715M iPSC-derived neurons, compared with the control group. Taken together, we established the first iPSC line derived from an AD patient carrying APP-V715M mutation and showed that this iPSC-derived neurons exhibited typical AD pathological features, including a distinct mitochondrial dysfunction.
Alzheimer Disease ; Amyloid ; Brain ; Carisoprodol ; Humans ; Immunohistochemistry ; Mitochondrial Dynamics ; Neurites ; Neurodegenerative Diseases ; Neurons ; Pathology ; Plaque, Amyloid ; Pluripotent Stem Cells

Disease modeling of Alzheimer's disease (AD) has been hampered by the lack of suitable cellular models while animal models are mainly based on the overexpression of AD-related genes which often results in an overemphasis of certain pathways and is also confounded by aging. In this study, we therefore developed and used induced pluripotent stem cell (iPSC) lines from a middle-aged AD patient with a known presenilin 1 (PSEN1) mutation (Glu120Lys; PS1-E120K) and as a control, an elderly normal subject. Using this approach, we demonstrated that the extracellular accumulation of Aβ was dramatically increased in PS1-E120K iPSC-derived neurons compared with the control iPSC line. PS1-E120K iPSC-derived neurons also exhibited high levels of phosphorylated tau, as well as mitochondrial abnormalities and defective autophagy. Given that the effect of aging is lost with iPSC generation, these abnormal cellular features are therefore indicative of PSEN1-associated AD pathogenesis rather than primary changes associated with aging. Taken together, this iPSC-based approach of AD modeling can now be used to better understand AD pathogenesis as well as a tool for drug discovery.
Aged ; Aging ; Alzheimer Disease* ; Autophagy ; Cerebellar Ataxia* ; Drug Discovery ; Humans ; Models, Animal ; Neurons ; Pluripotent Stem Cells ; Presenilin-1 ; Stem Cells

Induced pluripotent stem cells (iPSCs) generated from somatic cells of patients can provide immense opportunities to model human diseases, which may lead to develop novel therapeutics. Huntington's disease (HD) is a devastating neurodegenerative genetic disease, with no available therapeutic options at the moment. We recently reported the characteristics of a HD patient-derived iPSC carrying 72 CAG repeats (HD72-iPSC). In this study, we investigated the in vivo roles of HD72-iPSC in the YAC128 transgenic mice, a commonly used HD mouse model carrying 128 CAG repeats. To do this, we transplanted HD72-iPSC-derived neural precursors into the striatum of YAC128 mice bilaterally and observed a significant behavioral improvement in the grafted mice. Interestingly, the transplanted HD72-iPSC-derived neural precursors formed GABAeric neurons efficiently, but no EM48-positive protein aggregates were detected at 12 weeks after transplantation. Taken together, these results indicate no HD pathology was developed from the grafted cells, or no transmission of HD pathology from the host to the graft occurred at 12 weeks post-transplantation.
Animals ; GABAergic Neurons ; Humans ; Huntington Disease* ; Induced Pluripotent Stem Cells ; Mice ; Mice, Transgenic ; Neurons ; Pathology ; Pluripotent Stem Cells* ; Transplants

The transplantation of neural precursor cells (NPCs) is known to be a promising approach to ameliorating behavioral deficits after stroke in a rodent model of middle cerebral artery occlusion (MCAo). Previous studies have shown that transplanted NPCs migrate toward the infarct region, survive and differentiate into mature neurons to some extent. However, the spatiotemporal dynamics of NPC migration following transplantation into stroke animals have yet to be elucidated. In this study, we investigated the fates of human embryonic stem cell (hESC)-derived NPCs (ENStem-A) for 8 weeks following transplantation into the side contralateral to the infarct region using 7.0T animal magnetic resonance imaging (MRI). T2- and T2*-weighted MRI analyses indicated that the migrating cells were clearly detectable at the infarct boundary zone by 1 week, and the intensity of the MRI signals robustly increased within 4 weeks after transplantation. Afterwards, the signals were slightly increased or unchanged. At 8 weeks, we performed Prussian blue staining and immunohistochemical staining using human-specific markers, and found that high percentages of transplanted cells migrated to the infarct boundary. Most of these cells were CXCR4-positive. We also observed that the migrating cells expressed markers for various stages of neural differentiation, including Nestin, Tuj1, NeuN, TH, DARPP-32 and SV38, indicating that the transplanted cells may partially contribute to the reconstruction of the damaged neural tissues after stroke. Interestingly, we found that the extent of gliosis (glial fibrillary acidic protein-positive cells) and apoptosis (TUNEL-positive cells) were significantly decreased in the cell-transplanted group, suggesting that hESC-NPCs have a positive role in reducing glia scar formation and cell death after stroke. No tumors formed in our study. We also performed various behavioral tests, including rotarod, stepping and modified neurological severity score tests, and found that the transplanted animals exhibited significant improvements in sensorimotor functions during the 8 weeks after transplantation. Taken together, these results strongly suggest that hESC-NPCs have the capacity to migrate to the infarct region, form neural tissues efficiently and contribute to behavioral recovery in a rodent model of ischemic stroke.
Animals ; Apoptosis ; Cell Differentiation ; *Cell Movement ; Embryonic Stem Cells/cytology/metabolism/*transplantation ; Glial Fibrillary Acidic Protein/genetics/metabolism ; Humans ; Infarction, Middle Cerebral Artery/metabolism/pathology/physiopathology/*surgery ; Male ; Neural Stem Cells/cytology/metabolism/*transplantation ; *Psychomotor Performance ; Rats ; Rats, Sprague-Dawley ; Receptors, CXCR4/genetics/metabolism