Sustaining Surface Lithiophilicity of Ultrathin Li-Alloy Coating Layers on Current Collector for Zero-Excess Li-Metal Batteries.

Zero-excess Li-metal batteries (ZE-LMBs) have emerged as the ultimate battery platform, offering an exceptionally high energy density. However, the absence of Li-hosting materials results in uncontrolled dendritic Li deposition on the Cu current collector, leading to chronic loss of Li inventory and severe electrolyte decomposition, limiting its full utilization upon cycling. This study presents the application of ultrathin (≈50 nm) coatings comprising six metallic layers (Cu, Ag, Au, Pt, W, and Fe) on Cu substrates in order to provide insights into the design of Li-depositing current collectors for stable ZE-LMB operation. In contrast to non-alloy Cu, W, and Fe coatings, Ag, Au, and Pt coatings can enhance surface lithiophilicity, effectively suppressing Li dendrite growth, thereby improving Li reversibility. Considering the distinct Li-alloying behaviors, particularly solid-solution and/or intermetallic phase formation, Pt-coated Cu current collectors maintain surface lithiophilicity over repeated Li plating/stripping cycles by preserving the original coating layer, thereby attaining better cycling performance of ZE-LMBs. This highlights the importance of selecting suitable Li-alloy metals to sustain surface lithiophilicity throughout cycling to regulate dendrite-less Li plating and improve the electrochemical stability of ZE-LMBs.

Cyclin Y regulates spatial learning and memory flexibility through distinct control of the actin pathway.

Spatial learning and memory flexibility are known to require long-term potentiation (LTP) and long-term depression (LTD), respectively, on a cellular basis. We previously showed that cyclin Y (CCNY), a synapse-remodeling cyclin, is a novel actin-binding protein and an inhibitory regulator of functional and structural LTP in vitro. In this study, we report that Ccny knockout (KO) mice exhibit enhanced LTP and weak LTD at Schaffer collateral-CA1 synapses in the hippocampus. In accordance with enhanced LTP, Ccny KO mice showed improved spatial learning and memory. However, although previous studies reported that normal LTD is necessary for memory flexibility, Ccny KO mice intriguingly showed improved memory flexibility, suggesting that weak LTD could exert memory flexibility when combined with enhanced LTP. At the molecular level, CCNY modulated spatial learning and memory flexibility by distinctively affecting the cofilin-actin signaling pathway in the hippocampus. Specifically, CCNY inhibited cofilin activation by original learning, but reversed such inhibition by reversal learning. Furthermore, viral-mediated overexpression of a phosphomimetic cofilin-S3E in hippocampal CA1 regions enhanced LTP, weakened LTD, and improved spatial learning and memory flexibility, thus mirroring the phenotype of Ccny KO mice. In contrast, the overexpression of a non-phosphorylatable cofilin-S3A in hippocampal CA1 regions of Ccny KO mice reversed the synaptic plasticity, spatial learning, and memory flexibility phenotypes observed in Ccny KO mice. Altogether, our findings demonstrate that LTP and LTD cooperatively regulate memory flexibility. Moreover, CCNY suppresses LTP while facilitating LTD in the hippocampus and negatively regulates spatial learning and memory flexibility through the control of cofilin-actin signaling, proposing CCNY as a learning regulator modulating both memorizing and forgetting processes.

Modulating Ionic Transport and Interface Chemistry via Surface-Modified Silica Carrier in Nano Colloid Electrolyte for Stable Cycling of Li-Metal Batteries.

Tailoring the Li+ microenvironment is crucial for achieving fast ionic transfer and a mechanically reinforced solid-electrolyte interphase (SEI), which administers the stable cycling of Li-metal batteries (LMBs). Apart from traditional salt/solvent compositional tuning, this study presents the simultaneous modulation of Li+ transport and SEI chemistry using a citric acid (CA)-modified silica-based colloidal electrolyte (C-SCE). CA-tethered silica (CA-SiO2 ) can render more active sites for attracting complex anions, leading to further dissociation of Li+ from the anions, resulting in a high Li+ transference number (≈0.75). Intermolecular hydrogen bonds between solvent molecules and CA-SiO2 and their migration also act as nano-carrier for delivering additives and anions toward the Li surface, reinforcing the SEI via the co-implantation of SiO2 and fluorinated components. Notably, C-SCE demonstrated Li dendrite suppression and improved cycling stability of LMBs compared with the CA-free SiO2 colloidal electrolyte, hinting that the surface properties of the nanoparticles have a huge impact on the dendrite-inhibiting role of nano colloidal electrolytes.

Is spiritual well-being related to survival time of inpatients with advanced cancer? An East Asian cohort study.

OBJECTIVES: It has been suggested that psychosocial factors are related to survival time of inpatients with cancer. However, there are not many studies examining the relationship between spiritual well-being (SWB) and survival time among countries. This study investigated the relationship between SWB and survival time among three East Asian countries. METHODS: This international multicenter cohort study is a secondary analysis involving newly admitted inpatients with advanced cancer in palliative care units in Japan, South Korea, and Taiwan. SWB was measured using the Integrated Palliative Outcome Scale (IPOS) at admission. We performed multivariate analysis using the Cox proportional hazards model to identify independent prognostic factors. RESULTS: A total of 2,638 patients treated at 37 palliative care units from January 2017 to September 2018 were analyzed. The median survival time was 18.0 days (95% confidence interval [CI] 16.5-19.5) in Japan, 23.0 days (95% CI 19.9-26.1) in Korea, and 15.0 days (95% CI 13.0-17.0) in Taiwan. SWB was a significant factor correlated with survival in Taiwan (hazard ratio [HR] 1.27; 95% CI 1.01-1.59; p = 0.04), while it was insignificant in Japan (HR 1.10; 95% CI 1.00-1.22; p = 0.06), and Korea (HR 1.02; 95% CI 0.77-1.35; p = 0.89). SIGNIFICANCE OF RESULTS: SWB on admission was associated with survival in patients with advanced cancer in Taiwan but not Japan or Korea. The findings suggest the possibility of a positive relationship between spiritual care and survival time in patients with far advanced cancer.

Comparison of Objective Prognostic Score and Palliative Prognostic Score performance in inpatients with advanced cancer in Japan and Korea.

OBJECTIVE: Accurate prognostication is important for patients and their families to prepare for the end of life. Objective Prognostic Score (OPS) is an easy-to-use tool that does not require the clinicians' prediction of survival (CPS), whereas Palliative Prognostic Score (PaP) needs CPS. Thus, inexperienced clinicians may hesitate to use PaP. We aimed to evaluate the accuracy of OPS compared with PaP in inpatients in palliative care units (PCUs) in three East Asian countries. METHOD: This study was a secondary analysis of a cross-cultural, multicenter cohort study. We enrolled inpatients with far-advanced cancer in PCUs in Japan, Korea, and Taiwan from 2017 to 2018. We calculated the area under the receiver operating characteristics (AUROC) curve to compare the accuracy of OPS and PaP. RESULTS: A total of 1,628 inpatients in 33 PCUs in Japan and Korea were analyzed. OPS and PaP were calculated in 71.7% of the Japanese patients and 80.0% of the Korean patients. In Taiwan, PaP was calculated for 81.6% of the patients. The AUROC for 3-week survival was 0.74 for OPS in Japan, 0.68 for OPS in Korea, 0.80 for PaP in Japan, and 0.73 for PaP in Korea. The AUROC for 30-day survival was 0.70 for OPS in Japan, 0.71 for OPS in Korea, 0.79 for PaP in Japan, and 0.74 for PaP in Korea. SIGNIFICANCE OF RESULTS: Both OPS and PaP showed good performance in Japan and Korea. Compared with PaP, OPS could be more useful for inexperienced physicians who hesitate to estimate CPS.

Evaluation of design, mechanical properties, and torque/force generation of heat-treated NiTi glide path instruments.

BACKGROUND: Recently, various kinds of heat-treated nickel-titanium (NiTi) glide path instruments have been manufactured. This study aimed to investigate design, phase transformation behavior, mechanical properties of TruNatomy Glider (#17/02), V Taper 2H (#14/03), and HyFlex EDM (#15/03) and compare torque/force generated during simulated glide path preparation with them. METHODS: The designs and phase-transformation behaviors of the instruments were examined via scanning electron microscopy (n = 3) and differential scanning calorimetry (n = 2). Their bending (n = 15), torsional (n = 15), and cyclic fatigue resistances (n = 15) were tested. The ultimate strength and distortion angle were obtained from torsional resistance test. The number of cycles to failure (NCF) was calculated from cyclic fatigue resistance test. The preparation of the glide path was simulated using a double-curved artificial canal (n = 15), and the maximum torque and screw-in forces were measured. Data except NCF was compared between brands with one-way ANOVA with Tukey's honestly significant difference test. NCF was analyzed via Kruskal-Wallis and Mann-Whitney U tests. RESULTS: TruNatomy Glider had the greatest number of threads. TruNatomy Glider showed progressive taper, while V Taper 2H and HyFlex EDM had constant taper. The austenitic transformation-finish temperatures of all the instruments were above body temperature. V Taper 2H demonstrated significantly lower ultimate strength, higher distortion angle, and a higher number of cycles to failure compared with HyFlex EDM and TruNatomy Glider (p < 0.05). The maximum torque generated during preparing glide path was lowest for V Taper 2H, and the maximum screw-in force was lowest for HyFlex EDM (p < 0.05). TruNatomy Glider generated the highest torque and screw-in force during the apical preparation. CONCLUSIONS: V Taper 2H #14/03 showed superior cyclic fatigue resistance and lower ultimate strength. TruNatomy Glider generated greater clockwise torque and screw-in force during apical preparation. The mechanical properties, torque, and screw-force was affected by design of heat-treated glide path instruments. Cervical pre-flaring prior to glide path instrument is recommended.

Factors related to spiritual well-being in the last days of life in three East Asian countries: An international multicenter prospective cohort study.

BACKGROUND: Some factors associated with spiritual well-being in dying patients have previously been reported. However, there has been no cross-cultural study comparing factors related to spiritual well-being. The current investigation may shed light on this under-investigated area through a comparison of diverse factors. AIM: We aimed to (1) examine factors associated with spiritual well-being in the last days and (2) compare those factors across three East Asian countries. DESIGN: This is an international multicenter prospective cohort study. SETTING/PARTICIPANTS: Newly admitted inpatients with far advanced cancer in palliative care units in Japan, Korea and Taiwan were enrolled. Each patient was classified into one of two groups based on spiritual well-being score in the last days of life. Univariate and multivariate analyses were performed to identify the factors related to better spiritual well-being score in each country. RESULTS: A total of 1761 patients treated at 37 palliative care units from January 2017 to September 2018 were analyzed. Seven variables were significant in Japan, three in Korea, and five in Taiwan. "Good death scale [acceptance]," "fatigue" and "expressed wish for hastened death" were unique in Japan. "Visit from a pastoral care worker within 48 h of death" was unique in Korea. "Patient's preferences for place of death," "dyspnea" and "continuous deep sedation" were unique in Taiwan. CONCLUSIONS: This study found novel factors related to spiritual well-being in the last days of life, several of which differed according to country. Recognition of factors associated with spiritual well-being can improve the quality of palliative care.

Molecular crosstalk between cancer and neurodegenerative diseases.

The progression of cancers and neurodegenerative disorders is largely defined by a set of molecular determinants that are either complementarily deregulated, or share remarkably overlapping functional pathways. A large number of such molecules have been demonstrated to be involved in the progression of both diseases. In this review, we particularly discuss our current knowledge on p53, cyclin D, cyclin E, cyclin F, Pin1 and protein phosphatase 2A, and their implications in the shared or distinct pathways that lead to cancers or neurodegenerative diseases. In addition, we focus on the inter-dependent regulation of brain cancers and neurodegeneration, mediated by intercellular communication between tumor and neuronal cells in the brain through the extracellular microenvironment. Finally, we shed light on the therapeutic perspectives for the treatment of both cancer and neurodegenerative disorders.

Ccny knockout mice display an enhanced susceptibility to kainic acid-induced epilepsy.

Cyclin Y (CCNY) is a member of cyclin superfamily proteins involved in the regulation of the cell cycle in proliferating cells. Intriguingly, CCNY is highly expressed in terminally differentiated neuronal cells of multiple brain regions and acts as a postsynaptic protein, which plays an inhibitory role in long-term potentiation. However, the pathophysiological significance of CCNY in the nervous system remains largely unexplored. In this study, we revisited our RNA-sequencing (RNA-seq) data obtained from cultured hippocampal neurons virally overexpressing or depleting CCNY. Using RNA-seq-based bioinformatic disease analysis and synaptic gene ontology analysis, we identified that numerous genes associated with epilepsy (e.g. Chrna4, Gabrd, Nhlrc1, Reln, Samd12, Slc6a1, etc.) or neurodegenerative diseases (e.g. Psen1, Pdyn, Ndrg1, etc.) are affected by the level of CCNY expression. In agreement with the RNA-seq-based disease analysis, we found that Ccny knockout (KO) mice are more susceptible to kainic acid-induced epilepsy than wild-type mice. In addition, some epilepsy-associated genes that are regulated by CCNY levels were further validated in the brain of Ccny KO mice at the mRNA and protein levels. Collectively, our findings indicate that CCNY shifts the expression profile of epilepsy-associated genes and exerts a protective effect against kainic acid-induced epilepsy, suggesting CCNY as a potential pharmaceutical candidate for the treatment of epilepsy.

Chronophin coordinates cell leading edge dynamics by controlling active cofilin levels.

Cofilin, a critical player of actin dynamics, is spatially and temporally regulated to control the direction and force of membrane extension required for cell locomotion. In carcinoma cells, although the signaling pathways regulating cofilin activity to control cell direction have been established, the molecular machinery required to generate the force of the protrusion remains unclear. We show that the cofilin phosphatase chronophin (CIN) spatiotemporally regulates cofilin activity at the cell edge to generate persistent membrane extension. We show that CIN translocates to the leading edge in a PI3-kinase-, Rac1-, and cofilin-dependent manner after EGF stimulation to activate cofilin, promotes actin free barbed end formation, accelerates actin turnover, and enhances membrane protrusion. In addition, we establish that CIN is crucial for the balance of protrusion/retraction events during cell migration. Thus, CIN coordinates the leading edge dynamics by controlling active cofilin levels to promote MTLn3 cell protrusion.

Validity of Rapid Antibody Testing for COVID-19 Vaccine in Homeless People.

(1) Background: There is a paucity of data regarding the validity of rapid antibody testing for SARS-CoV-2 vaccine response in homeless people worldwide. The objective of this study was to evaluate a rapid SARS-CoV-2 IgM/IgG antibody detection kit as a qualitative screen for vaccination in homeless people. (2) Methods: This study included 430 homeless people and 120 facility workers who had received one of BNT162b2, mRNA-1273, AZD1222/ChAdOx1, or JNJ-78436735/AD26.COV2.5 vaccines. They were tested for IgM/IgG antibodies to the SARS-CoV-2 spike protein with the STANDARD™ Q COVID-19 IgM/IgG Plus Test (QNCOV-02C). ELISA/competitive inhibition ELISA (CI-ELISA) was subsequently run to assess the validity of the serological antibody test. (3) Results: The sensitivity of homeless people was 43.5%. The status of homelessness was related to a lower agreement between serological antibody testing and CI-ELISA (adjusted OR (aOR), 0.35; 95% CI, 0.18-0.70). However, the Heterologous boost vaccine presented higher agreement between serological antibody testing and CI-ELISA (adjusted OR (aOR), 6.50; 95% CI, 3.19-13.27). (4) Conclusions: This study found weak agreement between the rapid IgG results and confirmatory CI-ELISA testing in homeless people. However, it can be used as a screening test for the acceptance of homeless people with heterologous boost vaccination in facilities.

Automated detection of intracranial aneurysms using skeleton-based 3D patches, semantic segmentation, and auxiliary classification for overcoming data imbalance in brain TOF-MRA.

Accurate and reliable detection of intracranial aneurysms is vital for subsequent treatment to prevent bleeding. However, the detection of intracranial aneurysms can be time-consuming and even challenging, and there is great variability among experts, especially in the case of small aneurysms. This study aimed to detect intracranial aneurysms accurately using a convolutional neural network (CNN) with 3D time-of-flight magnetic resonance angiography (TOF-MRA). A total of 154 3D TOF-MRA datasets with intracranial aneurysms were acquired, and the gold standards were manually drawn by neuroradiologists. We also obtained 113 subjects from a public dataset for external validation. These angiograms were pre-processed by using skull-stripping, signal intensity normalization, and N4 bias correction. The 3D patches along the vessel skeleton from MRA were extracted. Values of the ratio between the aneurysmal and the normal patches ranged from 1:1 to 1:5. The semantic segmentation on intracranial aneurysms was trained using a 3D U-Net with an auxiliary classifier to overcome the imbalance in patches. The proposed method achieved an accuracy of 0.910 in internal validation and external validation accuracy of 0.883 with a 2:1 ratio of normal to aneurysmal patches. This multi-task learning method showed that the aneurysm segmentation performance was sufficient to be helpful in an actual clinical setting.

Structural and Chemical Evolutions of Li/Electrolyte Interfaces in Li-Metal Batteries: Tracing Compositional Changes of Electrolytes under Practical Conditions.

Despite the promises in high-energy-density batteries, Li-metal anodes (LMAs) have suffered from extensive electrolyte decomposition and unlimited volume expansion owing to thick, porous layer buildup during cycling. It mainly originates from a ceaseless reiteration of the formation and collapse of solid-electrolyte interphase (SEI). This study reveals the structural and chemical evolutions of the reacted Li layer after different cycles and investigates its detrimental effects on the cycling stability under practical conditions. Instead of the immediately deactivated top surface of the reacted Li layer, the chemical nature underneath the reacted Li layer can be an important indicator of the electrolyte compositional changes. It is found that cycling of LMAs with a lean electrolyte (≈3 g Ah-1 ) causes fast depletion of salt anions, leading to the dynamic evolution of the reacted Li layer structure and composition. Increasing the salt-solvent complex while reducing the non-solvating diluent retards the rate of depletion in a localized high-concentration electrolyte, thereby demonstrating prolonged cycling of Li||NMC622 cells without compromising the Li Coulombic efficiencies and high-voltage stability.

Efficacy and Safety of Korean Herbal Medicine for Patients with Post-Accident Syndrome, Persistent after Acute Phase: A Pragmatic Randomized Controlled Trial.

This is a pragmatic, two-armed, parallel, single-center, randomized controlled clinical trial for comparative evaluation between the effectiveness of integrated Korean medicine (IKM) and herbal medicine treatment with that of IKM monotherapy (control) for post-accident syndrome persistent after the acute phase. Participants were randomized into Herbal Medicine (HM, n = 20) and Control groups (n = 20) to receive the allocated treatment of 1-3 sessions/week for 4 weeks. Intention-to-treat analysis was conducted. The Difference of Numeric Rating Scale (NRS) change of overall post-accident syndromes from baseline to week 5 for the two groups was 1.78 (95% CI: 1.08-2.48; p < 0.001). Regarding secondary outcomes, a significant decrease compared to the baseline values was confirmed for NRS of musculoskeletal, neurological, psychiatric complaints and general symptoms of post-accident syndromes. In a survival analysis based on the recovery criteria of "patients with a reduction in the NRS of overall post-accident syndromes of ≥50%," the HM group showed a shorter time to recovery than the control group during the 17-week study period (p < 0.001 by the log-rank test). IKM combined with herbal medicine treatment significantly improved the quality of life by relieving somatic pain and alleviating the overall post-accident syndrome persistent after the acute phase; this effect was maintained for at least 17 weeks.

Diagnosis of Current Flow Patterns Inside Fault-Simulated Li-Ion Batteries via Non-Invasive, In Operando Magnetic Field Imaging.

With the growing popularity of Li-ion batteries in large-scale applications, building a safer battery has become a common goal of the battery community. Although the small errors inside the cells trigger catastrophic failures, tracing them and distinguishing cell failure modes without knowledge of cell anatomy can be challenging using conventional methods. In this study, a real-time, non-invasive magnetic field imaging (MFI) analysis that can signal the battery current-induced magnetic field and visualize the current flow within Li-ion cells is developed. A high-speed, spatially resolved MFI scan is used to derive the current distribution pattern from cells with different tab positions at a current load. Current maps are collected to determine possible cell failures using fault-simulated batteries that intentionally possess manufacturing faults such as lead-tab connection failures, electrode misalignment, and stacking faults (electrode folding). A modified MFI analysis exploiting the magnetic field interference with the countercurrent-carrying plate enables the direct identification of defect spots where abnormal current flow occurs within the pouch cells.

Validation of Modified Models of Objective Prognostic Score in Patients With Advanced Cancer.

Background: The objective prognostic score (OPS) needs to be modified to reflect practical palliative care circumstances. Objectives: We aimed to validate modified models of OPS with few or no laboratory tests for patients with advanced cancer. Design: An observational study was performed. Setting/Subjects: A secondary analysis of an international, multicenter cohort study of patients in East Asia was performed. The subjects were inpatients with advanced cancer in the palliative care unit. Measurements: We developed two modified OPS (mOPS) models to predict two-week survival: mOPS-A consisted of two symptoms, two objective signs, and three laboratory results, while mOPS-B consisted of three symptoms, two signs, and no laboratory data. We compared the accuracy of the prognostic models using sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC). Calibration plots for two-week survival and net reclassification indices (NRIs) were compared for the two models. Survival differences between higher and lower score groups of each model were identified by the log-rank test. Results: We included a total of 1796 subjects having median survival of 19.0 days. We found that mOPS-A had higher specificity (0.805-0.836) and higher AUROCs (0.791-0.797). In contrast, mOPS-B showed higher sensitivity (0.721-0.725) and acceptable AUROCs (0.740-0.751) for prediction of two-week survival. Two mOPSs showed good concordance in calibration plots. Considering NRIs, replacing the original OPS with mOPSs improved overall reclassification (absolute NRI: 0.47-4.15%). Higher score groups of mOPS-A and mOPS-B showed poorer survival than those of lower score groups (p < 0.001). Conclusions: mOPSs used reduced laboratory data and had relatively good accuracy for predicting survival in advanced cancer patients receiving palliative care.

Methimazole-induced bullous systemic lupus erythematosus: a case report.

Bullous systemic lupus erythematosus (SLE) is a kind of LE-non-specific bullous skin disease that is rarely induced by a medication. We describe the first case of bullous SLE to develop after administration of methimazole. A 31-yr-old woman presented with generalized erythematous patches, multiple bullae, arthralgia, fever, conjunctivitis, and hemolytic anemia. Biopsy of her bulla showed linear deposition of lgG, lgA, C3, fibrinogen, and C1q at dermo-epidermal junction. She was diagnosed as bullous SLE and treated with prednisolone, dapsone, hydroxychloroquine, and methotrexate. Our experience suggests that SLE should be considered as a differential diagnosis when bullous skin lesions develop in patients being treated for hyperthyroidism.

Bone suppression on pediatric chest radiographs via a deep learning-based cascade model.

BACKGROUND AND OBJECTIVE: Bone suppression images (BSIs) of chest radiographs (CXRs) have been proven to improve diagnosis of pulmonary diseases. To acquire BSIs, dual-energy subtraction (DES) or a deep-learning-based model trained with DES-based BSIs have been used. However, neither technique could be applied to pediatric patients owing to the harmful effects of DES. In this study, we developed a novel method for bone suppression in pediatric CXRs. METHODS: First, a model using digitally reconstructed radiographs (DRRs) of adults, which were used to generate pseudo-CXRs from computed tomography images, was developed by training a 2-channel contrastive-unpaired-image-translation network. Second, this model was applied to 129 pediatric DRRs to generate the paired training data of pseudo-pediatric CXRs. Finally, by training a U-Net with these paired data, a bone suppression model for pediatric CXRs was developed. RESULTS: The evaluation metrics were peak signal to noise ratio, root mean absolute error and structural similarity index measure at soft-tissue and bone region of the lung. In addition, an expert radiologist scored the effectiveness of BSIs on a scale of 1-5. The obtained result of 3.31 ± 0.48 indicates that the BSIs show homogeneous bone removal despite subtle residual bone shadow. CONCLUSION: Our method shows that the pixel intensity at soft-tissue regions was preserved, and bones were well subtracted; this can be useful for detecting early pulmonary disease in pediatric CXRs.

Myristoylation-dependent palmitoylation of cyclin Y modulates long-term potentiation and spatial learning.

Many psychiatric disorders accompany deficits in cognitive functions and synaptic plasticity, and abnormal lipid modifications of neuronal proteins are associated with their pathophysiology. Lipid modifications, including palmitoylation and myristoylation, play crucial roles in the subcellular localization and trafficking of proteins. Cyclin Y (CCNY), enriched in the postsynaptic compartment, acts as an inhibitory modulator of functional and structural long-term potentiation (LTP) in the hippocampal neurons. However, cellular and molecular mechanisms underlying CCNY-mediated inhibitory functions in the synapse remain largely unknown. Here, we report that myristoylation located CCNY to the trans-Golgi network (TGN), and subsequent palmitoylation directed the myristoylated CCNY from the TGN to the synaptic cell surface. This myristoylation-dependent palmitoylation of CCNY was required for the inhibitory role of CCNY in excitatory synaptic transmission, activity-induced dynamics of AMPA receptors and PSD-95, LTP, and spatial learning. Furthermore, spatial learning significantly reduced palmitoyl- and myristoyl-CCNY levels, indicating that spatial learning lowers the synaptic abundance of CCNY. Our findings provide mechanistic insight into how CCNY is clustered adjacent to postsynaptic sites where it could play its inhibitory roles in synaptic plasticity and spatial learning.

Long-Term Follow-Up of Patients with Neck Pain Associated with Ossification of the Posterior Longitudinal Ligament Treated with Integrative Complementary and Alternative Medicine: A Retrospective Analysis and Questionnaire Survey.

Purpose: Integrative Korean medicine treatment (KMT) is a conservative treatment approach for the ossification of the posterior longitudinal ligament (OPLL) in Korea; nonetheless, relevant studies focusing on KMT for OPLL are lacking. A multicenter retrospective analysis of patient medical records and a questionnaire survey were conducted to investigate the effectiveness of integrative KMT in patients with OPLL treated for neck pain. Patients and Methods: A total of 78 inpatients radiologically diagnosed with OPLL and treated for neck pain at four Korean medicine hospitals from April 1, 2016, to December 31, 2019, were enrolled. The primary index was an improvement in the numeric rating scale (NRS) score for neck pain, whereas the secondary outcome indices were improvements in the NRS score for arm pain, neck disability index (NDI) score, and EuroQol 5-dimension 5-level (EQ-5D-5L) score. Results: At discharge, the NRS score for neck pain, NRS score for arm pain, and NDI score decreased by 2.47 (95% confidence interval [CI], -2.81 to -2.14), 1.32 (95% CI, -1.73 to -0.91), and 16.02 (95% CI, -18.89 to -13.15), respectively, as compared with the scores at admission (p < 0.001). The EQ-5D-5L score increased by 0.12 (95% CI, 0.09 to 0.16) as compared with the score at admission (p < 0.001). This trend was also evident during follow-up. With respect to Patient Global Impression of Change evaluation, 33 (61.1%) patients claimed to have very much improved, whereas 17 (31.5%) patients reported to have much improved. Conclusion: Inpatients with OPLL who received integrative KMT showed improvements in neck pain, arm pain, the NDI, and quality of life, which were retained throughout the follow-up period.