This retrospective study investigated the clinical and angiographic characteristics of ruptured true posterior communicating artery (PCoA) aneurysms in comparison with junctional PCoA aneurysms ...presenting with a subarachnoid hemorrhage.
The medical records and radiological data of 93 consecutive patients who underwent three-dimensional rotational angiography and surgical or endovascular treatment for a ruptured junctional or true PCoA aneurysm over an 8-year period were examined.
The maximum diameter of the ruptured true PCoA aneurysm (n=13, 14.0%) was significantly smaller than that of the ruptured junctional PCoA aneurysms (n=80, 4.45±1.44 vs. 7.68±3.36 mm, p=0.001). In particular, the incidence of very small aneurysms <4 mm was 46.2% (six of 13 patients) in the ruptured true PCoA aneurysm group, yet only 2.5% (two of 80 patients) in the ruptured junctional PCoA aneurysm group. Meanwhile, the diameter of the PCoA was significantly larger in the true PCoA aneurysm group than that in the junctional PCoA aneurysm group (1.90±0.57 vs. 1.15±0.49 mm, p<0.001). In addition, the ipsilateral PCoA/P1 ratio was significantly larger in the true PCoA aneurysm group than that in the group of a junctional PCoA aneurysm (mean PCoA/P1 ratio±standard deviation, 2.67±1.22 vs. 1.14±0.88; p<0.001). No between-group difference was identified for the modified Fisher grade, clinical grade at admission, and 3-month modified Rankin Scale score.
A true PCoA aneurysm was found to be associated with a larger PCoA and ruptured at a smaller diameter than a junctional PCoA aneurysm. In particular, the incidence of a ruptured aneurysm with a very small diameter <4 mm was significantly higher among the patients with a true PCoA aneurysm.
Fatigue failure under cyclic deformation remains longstanding challenge in the flexible interconnect for the long term application. In this study, we design Cu–Ag alloy interconnects with excellent ...fatigue resistance by adopting nanovoid structures acquired by a simple post-annealing process. Nanovoids are generated during Ag agglomeration in the Cu matrix because of the low solubility of Ag in Cu, which enhances the fatigue property of a Cu–Ag alloy deposited on a polyimide film. The effect of high-density nanovoids located at the triple junction of the Cu and Ag grain boundaries on the mechanical fatigue lifetime is investigated by microstructure analysis (HAADF, HR-TEM and ASTAR™-coupled TEM). The fatigue damage of the Cu–Ag alloy has been observed to originate from grain boundary decohesion, unlike typical long fatigue cracks and extrusions. This can be attributed to the uniform distribution of nanovoids, which leads to stress concentration relief and consequently reduces the level of deformation.
The coiled-coil domain containing 50 (CCDC50) protein is a phosphotyrosine-dependent signalling protein stimulated by epidermal growth factor. It is highly expressed in neuronal cells in the central ...nervous system; however, the roles of CCDC50 in neuronal development are largely unknown. In this study, we showed that the depletion of CCDC50-V2 impeded the neuronal development process, including arbor formation, spine density development, and axonal outgrowth, in primary neurons. Mechanistic studies revealed that CCDC50-V2 positively regulated the nerve growth factor receptor, while it downregulated the epidermal growth factor receptor pathway. Importantly, JNK/c-Jun activation was found to be induced by the CCDC50-V2 overexpression, in which the interaction between CCDC50-V2 and JNK2 was also observed. Overall, the present study demonstrates a novel mechanism of CCDC50 function in neuronal development and provides new insight into the link between CCDC50 function and the aetiology of neurological disorders.
Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are two representative chronic inflammatory demyelinating disorders of the central nervous system. We aimed to determine and ...compare the alterations of white matter (WM) connectivity between MS, NMOSD, and healthy controls (HC). This study included 68 patients with relapsing-remitting MS, 50 with NMOSD, and 26 HC. A network-based statistics method was used to assess disrupted patterns in WM networks. Topological characteristics of the three groups were compared and their associations with clinical parameters were examined. WM network analysis indicated that the MS and NMOSD groups had lower total strength, clustering coefficient, global efficiency, and local efficiency and had longer characteristic path length than HC, but there were no differences between the MS and NMOSD groups. At the nodal level, the MS group had more brain regions with altered network topologies than did the NMOSD group when compared with the HC group. Network alterations were correlated with Expanded Disability Status Scale score and disease duration in both MS and NMOSD groups. Two distinct subnetworks that characterized the disease groups were also identified. When compared with NMOSD, the most discriminative connectivity changes in MS were located between the thalamus, hippocampus, parahippocampal gyrus, amygdala, fusiform gyrus, and inferior and superior temporal gyri. In conclusion, MS patients had greater network dysfunction compared to NMOSD and altered short connections within the thalamus and inferomedial temporal regions were relatively spared in NMOSD compared with MS.
Design and fabrication of reliable electrodes is one of the most important challenges in flexible devices, which undergo repeated deformation. In conventional approaches, mechanical and electrical ...properties of continuous metal films degrade gradually because of the fatigue damage. The designed incorporation of nanoholes into Cu electrodes can enhance the reliability. In this study, the electrode shows extremely low electrical resistance change during bending fatigue because the nanoholes suppress crack initiation by preventing protrusion formation and damage propagation by crack tip blunting. This concept provides a key guideline for developing fatigue‐free flexible electrodes.
Nanohole‐structured fatigue‐damage‐free metal electrode is developed using a nanorod polymer substrate to realize highly stable flexible devices. The nanohole metal electrode shows almost no degradation of the electrical resistance during repeating bending deformation because of the suppression of damage initiation and propagation.
To secure the reliability of flexible electronics, the effect of multicomponent stress on the device properties during complex mechanical deformation needs to be thoroughly understood. The electrical ...resistances of metal interconnects are investigated by in situ monitoring at different twisting angles and with different pattern positions. As the twisting angle increased, the electrical resistance increased earlier. Furthermore, in the line pattern located far from the central axis, severe electrical degradation and fatigue damage formation were observed. Multicomponent stress evolution during twisting was analyzed by the finite-element simulation method. For easy practical application for estimating the representative twisting strain, an analytic solution of twisting deformation was formulated and compared with the simulation. Using the equivalent strain, the fatigue lifetime was fitted, and the exponents were obtained for lifetime expectation. This systematic study provides the guidelines for highly reliable flexible devices and the tools for determining the expected fatigue lifetime.
The composite autonomic symptom scale-31 (COMPASS-31) is a self-rated questionnaire that evaluates diverse autonomic symptoms. In the present study, we developed the Korean version of the COMPASS-31 ...(K-COMPASS-31) with appropriate translation, and verified its reliability and internal and external validity in patients with Parkinson's disease (PD). The original COMPASS-31 was translated independently into Korean by two bilingual neurologists. Test-retest reliability was evaluated at a 2-week interval. We investigated the correlations between the K-COMPASS-31, the scale for outcomes in PD-autonomic (SCOPA-AUT), and the results of an autonomic function test (AFT), respectively. A total of 90 patients with PD (47 females; mean age, 63.4 ± 10.8 years) were enrolled. The K-COMPASS-31 showed excellent test-retest reliability (intra-class correlation coefficient = 0.874, p < 0.001) and internal validity (Cronbach's alpha-coefficient = 0.878). The COMPASS-31 was positively correlated with SCOPA-AUT (r = 0.609, p < 0.001) and the results of the AFT. In conclusion, the K-COMPASS-31 showed excellent reliability and validity for the assessment of autonomic symptoms in PD patients. The K-COMPASS-31 is an easy-to-repeat and widely used tool for investigating autonomic dysfunction in various neurologic disorders and enables comparison of autonomic dysfunction among neurologic disorders. We recommend the K-COMPASS-31 as a valid instrument for use in clinical practice for patients with PD.
Cancer therapy using immune checkpoint inhibitor antibodies has markedly shifted the paradigm of cancer treatment. However, methods completely eliminating the effector function of these ...signal-regulating antibodies is urgently required. The heterogeneity of glycan chains in antibodies limits their use as therapeutic agents due to their variability; thus, the development of uniform glycan chains is necessary. Here, we subjected the anti-programmed cell death protein (PD)-1 antibody nivolumab, a representative immune checkpoint inhibitor, to GlycoDelete (GD) engineering to remove the antibody-dependent cellular cytotoxicity (ADCC) of the antibody, leaving only one glycan in the Fc. Glyco-engineered CHO cells were prepared by overexpressing endo-β-N-acetyl-glucosaminidase (Endo T) in CHO cells, in which N-acetyl-glucosaminyl-transferase I was knocked out using Cas9. GD IgG1 nivolumab and GD IgG4 nivolumab were produced using GD CHO cells, and glycan removal was confirmed using mass spectrometry. Target binding and PD-1 inhibition was not altered; however, ADCC decreased. Furthermore, the IgG4 form, determined to be the most suitable form of GD nivolumab, was produced in a plant GD system. The plant GD nivolumab also reduced ADCC without affecting PD-1 inhibitory function. Thus, CHO and plant GD platforms can be used to improve signal-regulating antibodies by reducing their effector function.
PurposeThe composite autonomic symptom scale-31 (COMPASS-31) is a self-rated questionnaire that evaluates diverse autonomic symptoms. In the present study, we developed the Korean version of the ...COMPASS-31 (K-COMPASS-31) with appropriate translation, and verified its reliability and internal and external validity in patients with Parkinson's disease (PD).MethodsThe original COMPASS-31 was translated independently into Korean by two bilingual neurologists. Test-retest reliability was evaluated at a 2-week interval. We investigated the correlations between the K-COMPASS-31, the scale for outcomes in PD-autonomic (SCOPA-AUT), and the results of an autonomic function test (AFT), respectively.ResultsA total of 90 patients with PD (47 females; mean age, 63.4 ± 10.8 years) were enrolled. The K-COMPASS-31 showed excellent test-retest reliability (intra-class correlation coefficient = 0.874, p < 0.001) and internal validity (Cronbach's α-coefficient = 0.878). The COMPASS-31 was positively correlated with SCOPA-AUT (r = 0.609, p < 0.001) and the results of the AFT.ConclusionsIn conclusion, the K-COMPASS-31 showed excellent reliability and validity for the assessment of autonomic symptoms in PD patients. The K-COMPASS-31 is an easy-to-repeat and widely used tool for investigating autonomic dysfunction in various neurologic disorders and enables comparison of autonomic dysfunction among neurologic disorders. We recommend the K-COMPASS-31 as a valid instrument for use in clinical practice for patients with PD.
N-glycans influence the activity of antibody drugs such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Thus, glycan profiling is considered a ...critical quality attribute (CQA) and requires routine and comprehensive monitoring. In this report, we validate the new glycan profiling method called Rapi-Fluor method, which reduced the sample preparation time and increased the FLR and MS intensities compared with conventional 2-AB method. Optimized glycan release, labeling, hydrophilic interaction liquid chromatography (HILIC) enrichment, and HILIC separation resulted in low variation and short preparation time. The method evaluated for human IgG standard varied from 100 µg/mL to 4000 µg/mL in 25 µL of water. The determination of coefficient (r2 > 0.9992), recovery (88.992% ~ 111.198%), limit of detection (LOD < 193.274 µg/mL), limit of quantification (LOQ < 585.679 µg/mL), and precision (Intra-day < 2.317%RSD and Inter-day < 4.287%RSD) were evaluated with four major glycans from antibody drugs. In addition, the method was used for glycan profiling of five different commercial antibodies. The method yielded precise results for IgG glycan analysis and demonstrated effective glycan profiling of commercial antibody drugs.
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•This paper reports validation of Rapi-Flour method for glycan profiling of antibody.•The method requires short preparation time and gives high signal compared to conventional method.•The method was applied to commercial antibody drugs and showed easier way to profile the glycan from antibody drugs.
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