Background: and Purpose Visual perceptual learning (VPL) may improve visual field defects (VFDs) after chronic stroke, but the optimal training duration and location remain unknown. This prospective study aimed to determine the efficacy of 8 weeks of VFD-customized visual discrimination training in improving poststroke VFDs. Methods: Prospectively enrolled patients with poststroke VFDs initially received no training for 8 weeks (no-training phase). They subsequently underwent our customized VPL program that included orientation-discrimination tasks in individualized blind fields and central letterdiscrimination tasks three times per week for 8 weeks (training phase). We analyzed the luminance detection sensitivity and deviation as measured using Humphrey visual field tests before and after the no-training and training phases. The vision-related quality of life was assessed at baseline and at a 16-week follow-up using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25). Results: Changes in mean total deviation (MTD) scores were greater during the training phase than during the no-training phase (defective hemifield, p=0.002; whole field, p=0.004). The MTD scores improved during the training phase (defective hemifield, p=0.004; whole field, p=0.016), but not during the no-training phase (defective hemifield, p=0.178; whole field, p=0.178). The difference between the improved and worsened areas (≥6 dB changes in luminance detection sensitivity) was greater during the training phase than during the no-training phase (p=0.009). The vision-specific social functioning subscore of the NEI-VFQ-25 improved after the 16-week study period (p=0.040). Conclusions Our 8-week VFD-customized visual discrimination training protocol may effectively improve VFDs and vision-specific social functioning in chronic stroke patients.

Background: and Purpose The additive effects of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) remain unclear. We aimed to investigate the efficacy and safety of IVT prior to MT depending on the location of M1 occlusion. Methods: We reviewed the cases of patients who underwent MT for emergent large-vessel occlusion of the M1 segment. Baseline characteristics as well as clinical and periprocedural variables were compared according to the location of M1 occlusion (i.e., proximal and distal M1 occlusion). The main outcome was the achievement of functional independence (modified Rankin Scale score, 0–2) at 3 months after stroke. The main outcomes were compared between the proximal and distal groups based on the use of IVT before MT. Results: Among 271 patients (proximal occlusion, 44.6%; distal occlusion, 55.4%), 33.9% (41/121) with proximal occlusion and 24.7% (37/150) with distal occlusion underwent IVT prior to MT. Largeartery atherosclerosis was more common in patients with proximal M1 occlusion; cardioembolism was more common in those with distal M1 occlusion. In patients with proximal M1 occlusion, there was no association between IVT before MT and functional independence. In contrast, there was a significant association between the use of IVT prior to MT (odds ratio=5.30, 95% confidence interval=1.56–18.05, P=0.007) and functional independence in patients with distal M1 occlusion. Conclusion IVT before MT was associated with improved functional outcomes in patients with M1 occlusion, especially in those with distal M1 occlusion but not in those with proximal M1 occlusion.

Background: and Purpose The accurate prediction of functional outcomes in patients with acute ischemic stroke (AIS) is crucial for informed clinical decision-making and optimal resource utilization. As such, this study aimed to construct an ensemble deep learning model that integrates multimodal imaging and clinical data to predict the 90-day functional outcomes after AIS. Methods: We used data from the Korean Stroke Neuroimaging Initiative database, a prospective multicenter stroke registry to construct an ensemble model integrated individual 3D convolutional neural networks for diffusion-weighted imaging and fluid-attenuated inversion recovery (FLAIR), along with a deep neural network for clinical data, to predict 90-day functional independence after AIS using a modified Rankin Scale (mRS) of 3–6. To evaluate the performance of the ensemble model, we compared the area under the curve (AUC) of the proposed method with that of individual models trained on each modality to identify patients with AIS with an mRS score of 3–6. Results: Of the 2,606 patients with AIS, 993 (38.1%) achieved an mRS score of 3–6 at 90 days post-stroke. Our model achieved AUC values of 0.830 (standard cross-validation [CV]) and 0.779 (time-based CV), which significantly outperformed the other models relying on single modalities: b-value of 1,000 s/mm2 (P<0.001), apparent diffusion coefficient map (P<0.001), FLAIR (P<0.001), and clinical data (P=0.004). Conclusion The integration of multimodal imaging and clinical data resulted in superior prediction of the 90-day functional outcomes in AIS patients compared to the use of a single data modality.

Purpose: Current faculty development (FD) programs are mostly limited to medical education and often lack a comprehensive and systematic structure. Therefore, the present study aimed to explore the current status and needs of FD programs in medical schools to provide a basis for establishing FD strategies. Methods: We conducted an online survey of medical school FD staff and professors regarding FD. Frequency, regression, and qualitative content analyses were conducted. FD programs were categorized into the classification frameworks. Results: A total of 17 FD staff and 256 professors at 37 medical schools participated. There are gaps between the internal and external FD programs offered by medical schools and their needs, and there are gaps between the programs the professors participated in and their needs. Recent internal and external FD programs in medical schools have focused on educational methods, student assessment, and education in general. Medical schools have a high need for leadership and self-development, and student assessment. Furthermore, professors have a high need for leadership and self-development, and research. The number of participants, topics, and needs of FD programs varied depending on the characteristics of individual professors. Conclusion Medical schools should expand their FD programs to meet the needs of individuals and the changing demands of modern medical education. The focus should be on comprehensive and responsive programs that cover various topics, levels, and methods. Tailored programs that consider professors’ professional roles, career stages, and personal interests are essential for effective FD.

BACKGROUND: Parkinson’s disease (PD) is one of the most prevalent neurodegenerative diseases, following Alzheimer’s disease. The onset of PD is characterized by the loss of dopaminergic neurons in the substantia nigra. Stem cell therapy has great potential for the treatment of neurodegenerative diseases, and human nasal turbinate-derived stem cells (hNTSCs) have been found to share some characteristics with mesenchymal stem cells. Although the Hippo signaling pathway was originally thought to regulate cell size in organs, recent studies have shown that it can also control inflammation in neural cells. METHODS: Dopaminergic neuron-like cells were differentiated from SH-SY5Y cells (DA-Like cells) and treated with 1-Methyl-4-phenylpyridinium iodide to stimulate Reactive oxidative species (ROS) production. A transwell assay was conducted to validate the effect of hNTSCs on the Hippo pathway. We generated an MPTP-induced PD mouse model and transplanted hNTSCs into the substantia nigra of PD mice via stereotaxic surgery. After five weeks of behavioral testing, the brain samples were validated by immunoblotting and immunostaining to confirm the niche control of hNTSCs. RESULTS: In-vitro experiments showed that hNTSCs significantly increased cell survival and exerted anti-inflammatory effects by controlling ROS-mediated ER stress and hippocampal signaling pathway factors. Similarly, the in-vivo experiments demonstrated an increase in anti-inflammatory effects and cell survival rate. After transplantation of hNTSCs, the PD mouse model showed improved mobility and relief from PD symptoms. CONCLUSION hNTSCs improved the survival rate of dopaminergic neurons by manipulating the hippocampal pathway through Yes-associated protein (YAP)/transcriptional coactivator with a PDZ-binding motif (TAZ) by reducing inflammatory cytokines. In this study, we found that controlling the niche of hNTSCs had a therapeutic effect on PD lesions.

Background: and Purpose We investigated the impact of comorbidity burden on troponin elevation, with separate consideration of neurological conditions, in patients with acute ischemic stroke (AIS). Methods: This prospective, observational cohort study consecutively enrolled patients with AIS for 2 years. Serum cardiac troponin I was repeatedly measured, and disease-related biomarkers were collected for diagnosis of preassigned comorbidities, including atrial fibrillation (AF), ischemic heart disease (IHD), myocardial hypertrophy (MH), heart failure (HF), renal insufficiency (RI), and active cancer. The severity of neurological deficits and insular cortical ischemic lesions were assessed as neurological conditions. Adjusted associations between these factors and troponin elevation were determined using a multivariate ordinal logistic regression model and area under the receiver operating characteristic curve (AUC). Cox proportional hazards model was used to determine the prognostic significance of comorbidity beyond neurological conditions. Results: Among 1,092 patients (66.5±12.4 years, 63.3% male), 145 (13.3%) and 335 (30.7%) had elevated (≥0.040 ng/mL) and minimally-elevated (0.040–0.010 ng/mL) troponin, respectively. In the adjusted analysis, AF, MH, HF, RI, active cancer, and neurological deficits were associated with troponin elevation. The multivariate model with six comorbidities and two neurological conditions exhibited an AUC of 0.729 (95% confidence interval [CI], 0.698–0.759). In Cox regression, AF, IHD, and HF were associated with adverse cardio-cerebrovascular events, whereas HF and active cancer were associated with mortality. Conclusion Troponin elevation in patients with AIS can be explained by the burden of comorbidities in combination with neurological status, which explains the prognostic significance of troponin assay.

Background: and Purpose We investigated the impact of stroke etiology on the endovascular treatment (EVT) procedure and clinical outcome of posterior circulation stroke (PCS) patients with EVT compared to anterior circulation stroke (ACS) patients. Methods: We retrospectively analyzed ischemic stroke patients who underwent EVT between January 2012 and December 2020. Enrolled ACS and PCS patients were compared according to etiologies (intracranial arterial steno-occlusion [ICAS-O], artery-to-artery embolic occlusion [AT-O], and cardioembolic occlusion [CA-O]). EVT procedure and favorable clinical outcomes at 3 months (modified Rankin Scale 0–2) were compared between the ACS and PCS groups for each etiology. Results: We included 419 patients (ACS, 346; PCS, 73) including 88 ICAS-O (ACS, 67; PCS, 21), 66 AT-O (ACS, 50; PCS, 16), and 265 CA-O (ACS, 229; PCS, 36) patients in the study. The onset-to-recanalization time was longer in the PCS group than in the ACS group (median 628.0 minutes vs. 421.0 minutes, P=0.01). In CA-O patients, the door-to-puncture time was longer, whereas the puncture-to-recanalization time was shorter in the PCS group than in the ACS group. The proportions of successful recanalization and favorable clinical outcomes were similar between the ACS and PCS groups for all three etiologies. Low baseline National Institutes of Health Stroke Scale (NIHSS) scores and absence of intracerebral hemorrhage at follow-up imaging were associated with favorable clinical outcomes in both groups, whereas successful recanalization (odds ratio, 11.74; 95% confidence interval, 2.60 to 52.94; P=0.001) was only associated in the ACS group. Conclusions The proportions of successful recanalization and favorable clinical outcomes were similar among all three etiologies between PCS and ACS patients who underwent EVT. Initial baseline NIHSS score and absence of hemorrhagic transformation were related to favorable outcomes in the PCS and ACS groups, whereas successful recanalization was related to favorable outcomes only in the ACS group.

Purpose: Epidermal growth factor receptor kinase domain duplication (EGFR-KDD) is a rare and poorly understood oncogenic mutation in non–small cell lung cancer (NSCLC). We aimed to investigate the acquired resistance mechanism of EGFR-KDD against EGFR-TKIs. Materials and Methods: We identified EGFR-KDD in tumor tissue obtained from a patient with stage IV lung adenocarcinoma and established the patient-derived cell line SNU-4784. We also established several EGFR-KDD Ba/F3 cell lines: EGFR-KDD wild type (EGFR-KDDWT), EGFR-KDD domain 1 T790M (EGFR-KDDD1T), EGFR-KDD domain 2 T790M (EGFR-KDDD2T), and EGFR-KDD both domain T790M (EGFR-KDDBDT). We treated the cells with EGFR tyrosine kinase inhibitors (TKIs) and performed cell viability assays, immunoblot assays, and ENU (N-ethyl-N-nitrosourea) mutagenesis screening. Results: In cell viability assays, SNU-4784 cells and EGFR-KDDWT Ba/F3 cells were sensitive to 2nd generation and 3rd generation EGFR TKIs. In contrast, the T790M-positive EGFR-KDD Ba/F3 cell lines (EGFR-KDDT790M) were only sensitive to 3rd generation EGFR TKIs. In ENU mutagenesis screening, we identified the C797S mutation in kinase domain 2 of EGFR-KDDBDT Ba/F3 cells. Based on this finding, we established an EGFR-KDD domain 1 T790M/domain 2 cis-T790M+C797S (EGFR-KDDT/T+C) Ba/F3 model, which was resistant to EGFR TKIs and anti-EGFR monoclonal antibody combined with EGFR TKIs. Conclusion Our study reveals that the T790M mutation in EGFR-KDD confers resistance to 1st and 2nd generation EGFR TKIs, but is sensitive to 3rd generation EGFR TKIs. In addition, we identified that the C797S mutation in kinase domain 2 of EGFR-KDDT790M mediates a resistance mechanism against 3rd generation EGFR TKIs.

Background: and Purpose This study aimed to investigate the applicability of deep learning (DL) model using diffusion-weighted imaging (DWI) data to predict the severity of aphasia at an early stage in acute stroke patients. Methods: We retrospectively analyzed consecutive patients with aphasia caused by acute ischemic stroke in the left middle cerebral artery territory, who visited Asan Medical Center between 2011 and 2013. To implement the DL model to predict the severity of post-stroke aphasia, we designed a deep feed-forward network and utilized the lesion occupying ratio from DWI data and established clinical variables to estimate the aphasia quotient (AQ) score (range, 0 to 100) of the Korean version of the Western Aphasia Battery. To evaluate the performance of the DL model, we analyzed Cohen’s weighted kappa with linear weights for the categorized AQ score (0–25, very severe; 26–50, severe; 51–75, moderate; ≥76, mild) and Pearson’s correlation coefficient for continuous values. Results: We identified 225 post-stroke aphasia patients, of whom 176 were included and analyzed. For the categorized AQ score, Cohen’s weighted kappa coefficient was 0.59 (95% confidence interval [CI], 0.42 to 0.76; P<0.001). For continuous AQ score, the correlation coefficient between true AQ scores and model-estimated values was 0.72 (95% CI, 0.55 to 0.83; P<0.001). Conclusions DL approaches using DWI data may be feasible and useful for estimating the severity of aphasia in the early stage of stroke.