Chimeric antigen receptor (CAR)-T cell therapy, which has demonstrated remarkable efficacy in hematologic malignancies, is being extended to the treatment of refractory solid tumors, including brain tumors. Lymphodepletion (LD) is an essential preconditioning process that enhances CAR-T efficacy by promoting CAR-T cell expansion and persistence in the body, and has become a standard regimen for hematologic cancers. Recent clinical results of CAR-T therapy for solid tumors, including brain tumors, have shown that cyclophosphamide/fludarabine-based preconditioning has potential benefits and is gradually becoming adopted in solid tumor CAR-T trials. Furthermore, some CAR-T trials for solid tumors are attempting to develop LD regimens optimized specifically for solid tumors, distinct from the standard LD regimens used in hematologic cancers. In contrast, CAR-T therapy targeting brain tumors frequently employs locoregionally repeated administration in tumors or cerebrospinal fluid, resulting in less frequent use of LD compared to other solid tumors. Nevertheless, several clinical studies suggest that LD may still provide potential benefits for CAR-T expansion and improvement in clinical responses in systemic CAR-T administration. The studies presented in this review suggest that while LD can be beneficial for enhancing CAR-T efficacy, considerations must be made regarding its compatibility with the CAR-T administration route, potential excessive activation based on CAR-T structural characteristics, and target expression in normal organs. Additionally, given the unique characteristics of brain tumors, optimized selection of LD agents, as well as dosing and regimens, may be required, highlighting the need for further research.

Chimeric antigen receptor (CAR)-T cell therapy, which has demonstrated remarkable efficacy in hematologic malignancies, is being extended to the treatment of refractory solid tumors, including brain tumors. Lymphodepletion (LD) is an essential preconditioning process that enhances CAR-T efficacy by promoting CAR-T cell expansion and persistence in the body, and has become a standard regimen for hematologic cancers. Recent clinical results of CAR-T therapy for solid tumors, including brain tumors, have shown that cyclophosphamide/fludarabine-based preconditioning has potential benefits and is gradually becoming adopted in solid tumor CAR-T trials. Furthermore, some CAR-T trials for solid tumors are attempting to develop LD regimens optimized specifically for solid tumors, distinct from the standard LD regimens used in hematologic cancers. In contrast, CAR-T therapy targeting brain tumors frequently employs locoregionally repeated administration in tumors or cerebrospinal fluid, resulting in less frequent use of LD compared to other solid tumors. Nevertheless, several clinical studies suggest that LD may still provide potential benefits for CAR-T expansion and improvement in clinical responses in systemic CAR-T administration. The studies presented in this review suggest that while LD can be beneficial for enhancing CAR-T efficacy, considerations must be made regarding its compatibility with the CAR-T administration route, potential excessive activation based on CAR-T structural characteristics, and target expression in normal organs. Additionally, given the unique characteristics of brain tumors, optimized selection of LD agents, as well as dosing and regimens, may be required, highlighting the need for further research.

Chimeric antigen receptor (CAR)-T cell therapy, which has demonstrated remarkable efficacy in hematologic malignancies, is being extended to the treatment of refractory solid tumors, including brain tumors. Lymphodepletion (LD) is an essential preconditioning process that enhances CAR-T efficacy by promoting CAR-T cell expansion and persistence in the body, and has become a standard regimen for hematologic cancers. Recent clinical results of CAR-T therapy for solid tumors, including brain tumors, have shown that cyclophosphamide/fludarabine-based preconditioning has potential benefits and is gradually becoming adopted in solid tumor CAR-T trials. Furthermore, some CAR-T trials for solid tumors are attempting to develop LD regimens optimized specifically for solid tumors, distinct from the standard LD regimens used in hematologic cancers. In contrast, CAR-T therapy targeting brain tumors frequently employs locoregionally repeated administration in tumors or cerebrospinal fluid, resulting in less frequent use of LD compared to other solid tumors. Nevertheless, several clinical studies suggest that LD may still provide potential benefits for CAR-T expansion and improvement in clinical responses in systemic CAR-T administration. The studies presented in this review suggest that while LD can be beneficial for enhancing CAR-T efficacy, considerations must be made regarding its compatibility with the CAR-T administration route, potential excessive activation based on CAR-T structural characteristics, and target expression in normal organs. Additionally, given the unique characteristics of brain tumors, optimized selection of LD agents, as well as dosing and regimens, may be required, highlighting the need for further research.

Objective: To evaluate the diagnostic performance of a deep learning algorithm for the automated detection of developmental dysplasia of the hip (DDH) on anteroposterior (AP) radiographs. Materials and Methods: Of 2601 hip AP radiographs, 5076 cropped unilateral hip joint images were used to construct a dataset that was further divided into training (80%), validation (10%), or test sets (10%). Three radiologists were asked to label the hip images as normal or DDH. To investigate the diagnostic performance of the deep learning algorithm, we calculated the receiver operating characteristics (ROC), precision-recall curve (PRC) plots, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) and compared them with the performance of radiologists with different levels of experience. Results: The area under the ROC plot generated by the deep learning algorithm and radiologists was 0.988 and 0.988–0.919, respectively. The area under the PRC plot generated by the deep learning algorithm and radiologists was 0.973 and 0.618– 0.958, respectively. The sensitivity, specificity, PPV, and NPV of the proposed deep learning algorithm were 98.0, 98.1, 84.5, and 99.8%, respectively. There was no significant difference in the diagnosis of DDH by the algorithm and the radiologist with experience in pediatric radiology (p = 0.180). However, the proposed model showed higher sensitivity, specificity, and PPV, compared to the radiologist without experience in pediatric radiology (p < 0.001). Conclusion The proposed deep learning algorithm provided an accurate diagnosis of DDH on hip radiographs, which was comparable to the diagnosis by an experienced radiologist.

Objective: To evaluate the diagnostic performance of a deep learning algorithm for the automated detection of developmental dysplasia of the hip (DDH) on anteroposterior (AP) radiographs. Materials and Methods: Of 2601 hip AP radiographs, 5076 cropped unilateral hip joint images were used to construct a dataset that was further divided into training (80%), validation (10%), or test sets (10%). Three radiologists were asked to label the hip images as normal or DDH. To investigate the diagnostic performance of the deep learning algorithm, we calculated the receiver operating characteristics (ROC), precision-recall curve (PRC) plots, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) and compared them with the performance of radiologists with different levels of experience. Results: The area under the ROC plot generated by the deep learning algorithm and radiologists was 0.988 and 0.988–0.919, respectively. The area under the PRC plot generated by the deep learning algorithm and radiologists was 0.973 and 0.618– 0.958, respectively. The sensitivity, specificity, PPV, and NPV of the proposed deep learning algorithm were 98.0, 98.1, 84.5, and 99.8%, respectively. There was no significant difference in the diagnosis of DDH by the algorithm and the radiologist with experience in pediatric radiology (p = 0.180). However, the proposed model showed higher sensitivity, specificity, and PPV, compared to the radiologist without experience in pediatric radiology (p < 0.001). Conclusion The proposed deep learning algorithm provided an accurate diagnosis of DDH on hip radiographs, which was comparable to the diagnosis by an experienced radiologist.

OBJECTIVES: The aim of this study was to analyze research and development projects in mental health services in Korea, using priority evaluation of mental health promotion policies to determine direction of the service. METHODS: An online survey was conducted that targeted experts in the mental health service regarding promotion of mental health in Korea in 2016. The survey was based on 32 policy projects that resulted from 12 strategies according to 4 policy objectives. RESULTS: Analysis of 32 mental health projects were assessed regarding the possibility of technology development success, magnitude of the ripple effect, and necessity of a national response. It was observed that 3 policy projects relevant to suicide, had a high relative priority. This was followed by policies for improvement of health insurance and the medical benefit cost system, and policies for reinforcement of crisis psychological support such as those for disaster victims. CONCLUSION: The prioritization of mental health services should place an emphasis on promotion of a healthy mental lifestyle, rehabilitation support for patients with serious mental illness, and reinforcement of social safety networks for suicide prevention.
Disaster Victims ; Health Promotion ; Humans ; Industrial Development ; Insurance, Health ; Korea ; Life Style ; Mental Health Services* ; Mental Health* ; Rehabilitation ; Social Change* ; Suicide

Empathy is the ability to identify with or make a vicariously experience of another person's feelings or thoughts based on memory and/or self-referential mental simulation. The default mode network in particular is related to self-referential empathy. In order to elucidate the possible neural mechanisms underlying empathy, we investigated the functional connectivity of the default mode network in subjects from a general population. Resting state functional magnetic resonance imaging data were acquired from 19 low-empathy subjects and 18 medium-empathy subjects. An independent component analysis was used to identify the default mode network, and differences in functional connectivity strength were compared between the two groups. The low-empathy group showed lower functional connectivity of the medial prefrontal cortex and anterior cingulate cortex (Brodmann areas 9 and 32) within the default mode network, compared to the medium-empathy group. The results of the present study suggest that empathy is related to functional connectivity of the medial prefrontal cortex/anterior cingulate cortex within the default mode network. Functional decreases in connectivity among low-empathy subjects may reflect an impairment of self-referential mental simulation.
Empathy ; Functional Neuroimaging ; Gyrus Cinguli ; Magnetic Resonance Imaging ; Memory ; Prefrontal Cortex

Th17 cells promote inflammatory reactions, whereas regulatory T (Treg) cells inhibit them. Thus, the Th17/Treg cell balance is critically important in inflammatory diseases. However, the molecular mechanisms underlying this balance are unclear. Here, we demonstrate that casein kinase 2 (CK2) is a critical determinant of the Th17/Treg cell balance. Both the inhibition of CK2 with a specific pharmacological inhibitor, CX-4945, and its small hairpin RNA (shRNA)-mediated knockdown suppressed Th17 cell differentiation but reciprocally induced Treg cell differentiation in vitro. Moreover, CX-4945 ameliorated the symptoms of experimental autoimmune encephalomyelitis and reduced Th17 cell infiltration into the central nervous system. Mechanistically, CX-4945 inhibited the IL-6/STAT3 and Akt/mTOR signaling pathways. Thus, CK2 has a crucial role in regulating the Th17/Treg balance.
Casein Kinase II* ; Casein Kinases* ; Caseins* ; Central Nervous System ; Encephalomyelitis, Autoimmune, Experimental ; In Vitro Techniques ; RNA, Small Interfering ; T-Lymphocytes, Regulatory* ; Th17 Cells

In the previous experiments, we reported that ethanol extract of Gastrodiae Rhizoma, the dried tuber of Gastrodia ElataBlume (Orchidaceae) increased pentobarbital-induced sleeping behaviors. These experiments were undertaken to know whether 4-hydroxybenzaldehyde (4-HBD), is one of the major compounds of Gastrodiae Rhizoma increases pentobarbital-induced sleeping behaviors and changes sleep architectures via activating GABA(A)-ergic systems in rodents. 4-HBD decreased locomotor activity in mice. 4-HBD increased total sleep time, and decreased of sleep onset by pentobarbital (28 mg/kg and 40 mg/kg). 4-HBD showed synergistic effects with muscimol (a GABA(A) receptor agonist), shortening sleep onset and enhancing sleep time on pentobarbital-induced sleeping behaviors. On the other hand, 4-HBD (200 mg/kg, p.o.) itself significantly inhibited the counts of sleep-wake cycles, and prolonged total sleep time and non-rapid eye movement (NREM) in rats. Moreover, 4-HBD increased intracellular Cl- levels in the primary cultured cerebellar cells. The protein levels of glutamic acid decarboxylase (GAD) and GABA(A) receptors subunits were over-expressed by 4-HBD. Consequently, these results demonstrate that 4-HBD increased NREM sleep as well as sleeping behaviors via the activation of GABA(A)-ergic systems in rodents.
Animals ; Ethanol ; Eye Movements* ; Gastrodia* ; Glutamate Decarboxylase ; Hand ; Mice ; Motor Activity ; Muscimol ; Pentobarbital ; Rats ; Receptors, GABA-A ; Rodentia*

OBJECTIVES: The multimodal telepresence systems have been adopted in a variety of applications, such as telemedicine, space or underwater teleoperation and videoconference. Multimedia, one of the telepresence systems, has been used in various fields including entertainment, education and communication. The degree of subjective telepresence is defined as the probability that a person perceives to be physically in the remote place when he/she experiences a multisensory feedback from the multimedia. The current study aimed to explore the neural mechanism of telepresence related to multisensory feedback in patients with schizophrenia. METHODS: Brain activity was measured using functional magnetic resonance imaging while fifteen healthy controls and fifteen patients with schizophrenia were experiencing filmed referential conversation at various distances (1 m, 5 m and 10 m). Correlations between the image contrast values and the telepresence scores were analyzed. RESULTS: Subjective telepresence was not significantly different between the two groups. Some significant correlations of brain activities with the telepresence scores were found in the left postcentral gyrus, bilateral inferior frontal gyri, right fusiform gyrus, and left superior temporal sulcus. There were no main effects of group and distance. CONCLUSION: These results suggest that patients with schizophrenia experience telepresence as appropriately as healthy people do when exposed to multimedia. Therefore, patients with schizophrenia would have no difficulty in immersing themselves in multimedia which may be used in clinical training therapies.
Brain ; Humans ; Hypogonadism ; Magnetic Resonance Imaging ; Mitochondrial Diseases ; Multimedia ; Ophthalmoplegia ; Schizophrenia ; Telemedicine ; Videoconferencing