bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aconiti Lateralis Radix Praeparata Lipid-Soluble Alkaloids Alleviates IL-1β-Induced Inflammation of Human Fibroblast-Like Synoviocytes in Rheumatoid Arthritis by Inhibiting NF-κB and MAPKs Signaling Pathways and Inducing Apoptosis
Authors: Guo Chaocheng , He Linfeng , Hu Naihua , Zhao Xingtao , Gong Lihong , Wang Cheng , Peng Cheng , Li Yunxia 
Published: September 2021

Abstract
Background: Fuzi lipid-soluble alkaloids (FLA) is the main bioactive components extracted from the traditional Chinese medicine Aconiti Lateralis Radix Praeparata (“Fuzi” in Chinese), which has promising analgesic and anti-inflammatory effects. However, the effects and the underlying mechanisms of FLA on rheumatoid arthritis (RA) have not been studied. The present study aimed to explore the anti-arthritic effects of FLA and its underlying mechanisms. Methods: To standardize the FLA, UPLC-HR-MS was used for quantitative and qualitative analysis of the representative alkaloids. Cell viability was measured by MTT. The anti-inflammatory activity of FLA was examined by analyzing the expression levels of inflammatory mediators such as TNF-α, IL-6, MMP-1, MMP-3, PGE2, and COX-2 using ELISA and RT-PCR analysis. The Annexin V-FITC/PI double staining method was used to detect the apoptosis of HFLS-RA and analyzed by flow cytometry. Western blot analysis was used to analyze the expression of NF-κB, MAPKs and mitochondrial apoptosis pathway related proteins. Results: FLA had a significant inhibitory effect on the proliferation of HFLS-RA induced by IL-1β, which was accompanied by decreased expression levels of TNF-α, IL-6, MMP-1, MMP-3, COX-2 and PGE2. Remarkably, FLA inhibited the activation of NF-κB and MAPKs signaling pathways in IL-1β-induced HFLS-RA, as well as inducing HFLS-RA apoptosis through the mitochondrial apoptosis pathway. Conclusions: FLA inhibited the expression and synthesis of inflammatory mediators by inhibiting the activation of NF-κB and MAPKs signaling pathways in HFLS-RA, and induced apoptosis of HFLS-RA via the mitochondrial apoptosis pathway.
Statistical Supervised Learning With Engineering Data: A Case Study of Low Frequency Noise Measured On Semiconductor Devices
Authors: Gamiz ML , Kalen Anton , Nozal-Cañadas Rafael , Raya-Miranda Rocio 
Published: September 2021

Abstract
Our practical motivation is the analysis of potential correlations between spectral noise current and threshold voltage from common on-wafer MOSFETs. The usual strategy leads to the use of standard techniques based on Normal linear regression easily accessible in all statistical software (both free or commercial). However, these statistical methods are not appropriate because the assumptions they lie on are not met. More sophisticated methods are required. A new strategy based on the most novel nonparametric techniques which are data-driven and thus free from questionable parametric assumptions is proposed. A backfitting algorithm accounting for random effects and nonparametric regression is designed and implemented. The nature of the correlation between threshold voltage and noise is examined by conducting a statistical test, which is based on a novel technique that summarizes in a color map all the relevant information of the data. The way the results are presented in the plot makes it easy for a non-expert in data analysis to understand what is underlying. The good performance of the method is proven through simulations and it is applied to a data case in a field where these modern statistical techniques are novel and result very efficient.
Optimization of Anti-ADAMTS13 Antibodies for the Treatment of ADAMTS13-Related Bleeding Disorder in Patients Receiving Circulatory Assist Device Support
Authors: Ito Toshihiro , Minamitani Takeharu , Hayakawa Masaki , Otsubo Ryota , Akiba Hiroki , Tsumoto Kouhei , Matsumoto Masanori , Yasui Teruhito 
Published: September 2021

Abstract
ADAMTS13 (a disintegrin-like and metalloproteinase with thrombospondin type-1 motif 13)-related bleeding disorder has been frequently observed as a life-threatening clinical complication in patients carrying a circulatory assist device. Currently, treatment modalities for the bleeding disorder are very limited and not always successful. To address the unmet medical need, we constructed humanized antibodies of mouse anti-ADAMTS13 antibody A10 (mA10) by using complementarity-determining region (CDR) grafting techniques with human antibody frameworks, 8A7 and 16E8. The characteristics of the two humanized A10 antibodies, namely A10/8A7 and A10/16E8, were assessed in vitro and in silico. Among the two humanized A10 antibodies, the binding affinity of A10/16E8 to ADAMTS13 was comparable to that of mA10 and human-mouse chimeric A10. In addition, A10/16E8 largely inhibited the ADAMTS13 activity in vitro. The results indicated that A10/16E8 retained the binding affinity and inhibitory activity of mA10. To compare the antibody structures, we performed antibody structure modeling and structural similarity analysis in silico. As a result, A10/16E8 showed higher structural similarity to mA10, compared with A10/8A7, suggesting that A10/16E8 retains a native structure of mA10 as well as its antigen binding affinity and activity. A10/16E8 has great potential as a therapeutic agent for ADAMTS13-related bleeding disorder.
Low- versus high-concentration intravenous immunoglobulin for children with Kawasaki disease in the acute phase
Authors: Suzuki Takanori , Michihata Nobuaki , Yoshikawa Tetsushi , Saito Kazuyoshi , Matsui Hiroki , Fushimi Kiyohide , Yasunagaa Hideo 
Published: September 2021

Abstract
Purpose: Few studies have compared the effects of low-concentration (5%) and high-concentration (10%) intravenous immunoglobulin (IVIG) preparations for patients with Kawasaki disease (KD) in the acute phase. The purpose of this study was to compare outcomes between low- and high-concentration IVIG preparations in children with KD, using a national inpatient database in Japan.Method: We used the Diagnostic Procedure Combination database to identify patients with KD treated with IVIG from April 2012 to March 2020. We identified those receiving high- and low-concentration IVIG preparations as an initial treatment. The outcomes included the proportions of patients with coronary artery abnormalities (CAAs) and IVIG resistance, length of stay, and medical costs. Propensity score-matched analyses were conducted to compare the outcomes between the two groups. Instrumental variable analyses were performed to confirm the results.Result: We identified 48,046 patients with KD and created 4:1 propensity score-matched pairs between the low- and high-concentration IVIG groups. There was a significant difference in the percentage with IVIG resistance between the two groups (20.6% vs 24.1%; risk difference, 3.5% [95% confidence interval, 2.3-4.7]; p < 0.001). However, there was no significant difference in CAAs (1.6% vs 1.6%; risk difference, 0.013% [95% confidence interval, −0.34 to 0.37]; p = 0.953). The instrumental variable analyses showed similar results.Conclusions: The proportion of CAAs did not differ significantly between those receiving low- and high-concentration IVIG. To confirm the results of this study, prospective studies adjusting for duration of IVIG administration and duration of observation are needed.
Fate of residual tumor after subtotal-resected, previously-irradiated vestibular schwannoma: Long-term follow-up of a single institutional series
Authors: Byun Joonho , Song Sang Woo , Kim Young-Hoon , Hong Chang Ki , Kim Jeong Hoon 
Published: September 2021

Abstract
Background

The fate of residual tumor after salvage surgery for recurrent vestibular schwannoma (VS) after radiosurgery has not been elucidated. We reviewed our surgical series of salvage surgery for recurrent VS and the natural history of the residual tumor after salvage surgery.
Methods

This study enrolled 14 patients who were received salvage surgical resection in our institute and were followed-up for > 12 months.
Results

There were 3 male and 11 female patients with a median age of 55 years (range: 16–70). The pre-SRS tumor volume was a median 6591 mm3. All patients were treated by GKS. The median duration from GKS to surgery was 52 months (range: 10–116). Solid tumor growth was observed in 6 (42.9%) patients and cyst formation was observed in 8 patients (57.1%). Subtotal resection was performed in 13 (92.9%) patients and gross total resection was only achieved in one (7.1%) patient. Postoperative facial paresis occurred in 5 (35.7%) patients. Postoperative surgical complications occurred in 2 (14.3%) patients. After salvage resection for irradiated VS, no patient showed tumor progression or recurrence during the follow-up period (13 subtotal resection and 1 total resection). In addition, 2 patients in the subtotal resection group showed residual tumor shrinkage after salvage surgery during the follow-up period
Conclusion

The behavior of residual tumors after salvage surgery for irradiated VS was stable. Adjuvant treatment for these residual tumors may not be necessary.
The Origins of Human Complex Arithmetic Abilities: Involvement of Evolutionarily Ancient Brain Circuits
Authors: Saban William , Sklar Asael Y. , Hassin Ran R. , Gabay Shai 
Published: September 2021

Abstract
Humans exhibit complex arithmetic skills, often attributed to the exceptional enlargement of neocortical regions during evolution. However, the past decade has provided ample evidence that the functional domain of the subcortex extend well beyond basic functions. Using a sensitive behavioral method, for the first time, we explored the contributions of lower-order visual monocular channels to symbolic arithmetic operations, addition and subtraction. The pattern of results from 4 different experiments provides converging evidence for a causal relation between mental arithmetic and primitive subcortical regions. The results have major implications for our understanding of the neuroevolutionary development of general numerical abilities–subcortical regions, which are shared across different species, are essential to complex numerical operations. In a bigger conceptual framework, these findings and others call for a shift from the modal view of the exclusive role of the neocortex in high-level cognition to a view that emphasizes the interplay between subcortical and cortical brain networks.
Isolation of Rhizosheath and Analysis of Microbial Community Structure Around Roots of Stipa Grandis
Authors: Zhu Ai-Min , Wu Qian , Liu Hai-Li , Sun Hai-lian , Han Guo-Dong 
Published: September 2021

Abstract
Background：The root zone microbial structure is particularly complex for plants with rhizosheaths, which may play an important role in the future agricultural sustainable development. However, one of the important reasons for restricting our study of rhizosheath microbial structure is that there is no definite method for rhizosheath separation. The aim of this study was to explore the isolation methods of rhizosheath and the diversity characteristics of microorganisms around the rhizosphere. In this study, we isolated the rhizosheath of Stipa grandis, a dominant species in desert steppe, and the microorganisms in the roots, root epidermis, rhizosheath, rhizosphere soil were extracted and sequenced by 16SrRNA and ITS.Results:The bacterial alpha diversity index was in the order rhizosphere soil > rhizosheath>root epidermis>endophytic, and the fungal alpha diversity index wasrhizosphere soil and rhizosheath> root epidermisand endophytic. There were significant differences in bacterial community structure between the root epidermis and endophytic, rhizosheath, rhizosphere soil. Different from bacterial community structure, the community structure of root epidermis fungi was similar to endophytic, but significantly different from rhizosheath and rhizosphere soil.Our method is feasible for separating plant rhizosheath and root epidermis.Conclusions：We suggest that the root epidermiscan act as the interface between the host plant root and the external soil environment.We will have to re-examine the biological and ecological significance of root sheath and microorganisms in rhizosheath, as well as the mechanism of its close relationship with plant root epidermis.This study will provide theoretical and technical guidance for the isolation of plant rhizosheath and the study of microorganisms in it.
Dysfunctional ER-mitochondrion Crosstalk Leads to Subsequent ER Stress-induced Neuronal Apoptosis and Neurological Deficits in an Experimental Rodent Model of Severe Head Injury
Authors: Chen Xin , Mi Liang , Gu Gang , Gao Xiangliang , Shi Mingming , Chai Yan , Chen Fanglian , Yang Weidong , Zhang Jianning 
Published: September 2021

Abstract
Introduction: Previous studies have shown proper interorganelle communication between the endoplasmic reticulum (ER) and mitochondria (ER-mitochondrion crosstalk) is crucial for cellular homeostasis. Mitochondria-associated membranes (MAMs) provide an excellent platform and play an essential role in different signaling pathways to maintain cellular viability. However, the time course and potential pathological effects of this ER-mitochondrion physical and functional tethering in traumatic brain injury (TBI) remain unknown. We tested the hypothesis that dysfunctional ER-mitochondrion crosstalk at the acute phase of injury results in ER stress-induced neuronal apoptosis and neurological deficits in a mouse model of TBI. Methods: Male C57BL/6 mice were subjected to severe TBI (sTBI) using a controlled cortical impact (CCI) device. Transmission electron microscopy, western blot, immunofluorescence staining, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL), and MitoSOX assays were used to analyze posttraumatic ER-mitochondrion physical contact, Ca2+ transfer from the ER to mitochondria, mitochondrial reactive oxygen species (ROS) production, the unfolded protein response (UPR), the neuroinflammatory response and ER stress-mediated apoptosis in the perilesional cortex. The brain water content (BWC) and Evans blue dye extravasation were used to assess the blood-brain barrier (BBB) integrity, and a modified neurological severity score (mNSS) to evaluate neurological function in mice. Results: We showed sTBI led to significant MAM reorganization in the mouse cerebral cortex during the first 24 hr after injury. Enhanced ER-mitochondrion crosstalk peaked at 6 hr post injury and was significantly correlated with increased ER-mitochondrion Ca2+ transfer, mitochondrial ROS overproduction, elevated ER stress and UPR levels, and augmented levels of proinflammatory cytokines. In vivo experimental downregulation of PACS2, a protein essential for ER-mitochondrion tethering, restored mitochondrial Ca2+ homeostasis and alleviated mitochondrial oxidative stress by downregulating the IP3R1-GRP75-VDAC1 axis, inhibited ER stress and suppressed the inflammatory response through the PERK/eIF2α/ATF4/CHOP signaling pathway, blocked Caspase 12-dependent ER stress-mediated apoptosis, and reduced BBB permeability, resulting in significantly improved neurological function in mice subjected to sTBI. Conclusions: These results indicate that dysfunctional ER-mitochondrion crosstalk at the acute stage of injury might be primarily involved in the neuronal apoptosis and neurological deficits following sTBI, and specific modulation of ER-mitochondrion crosstalk might be a novel promising therapeutic strategy for sTBI.
Detection of EGFR Mutation Distribution and Transcriptional Variants in IDH-wildtype High-grade Gliomas using a Next-generation Sequencing Oncopanel
Authors: Higa Nayuta , Akahane Toshiaki , Hamada Taiji , Yonezawa Hajime , Uchida Hiroyuki , Makino Ryutaro , Watanabe Shoji , Takajo Tomoko , Yokoyama Seiya , Kirishima Mari , Fujio Shingo , Hanaya Ryosuke , Tanimoto Akihide , Yoshimoto Koji 
Published: September 2021

Abstract
Purpose: To detect the epidermal growth factor receptor gene (EGFR) mutation profile and transcriptional variants in high-grade gliomas (HGGs), we sequenced EGFR and evaluated the EGFR splicing profile using a next-generation sequencing (NGS) oncopanel. Methods: We analyzed 124 HGGs—10 grade Ⅲ IDH-wildtype anaplastic astrocytomas (AAs) and 114 grade Ⅳ IDH-wildtype glioblastomas (GBMs). Results: The EGFR mutations were observed in 6.0% of grade Ⅳ GBMs and in 33% of grade Ⅲ AAs. Four cases harbored missense mutations in the EGFR kinase domain (L747A, S768I, V774M, and T790M). A total of 25% of the GBMs showed EGFR amplification. Moreover, 27% of the EGFR mutations occurred in the kinase domain. EGFRvⅢ positivity was detected in 8.0% of EGFR-amplified GBMs. We identified two other EGFR variants in GBM cases with deletions of exons 6–7 (Δe 6-7) (one case) and exons 2–14 (Δe 2-14) (two cases). Interestingly, in one case, the initial EGFRvIII mutation transformed into an EGFR Δe 2-14 mutation during recurrence. The frequency of EGFR alterations in our cohort was lower but the frequency of EGFR mutations in the kinase domain in our cohort was higher than that in The Cancer Genome Atlas and Memorial Sloan Kettering Cancer Center cohorts. Conclusions: We suggested that the EGFR gene profiles of GBM differ among cohorts and identified rare EGFR variants with longitudinal and temporal transformations of EGFRvⅢ.
Carboxyl Methyl Cellulose@Guar Gum@ CuO Nanoparticle as Effective Adsorbent for the Removal of Dye From Aqueous Solution
Authors: Naeini Ali Hosseinian , kalaee mohammad Reza , Moradi Omid , Khajavi Ramin , Abdouss Majid 
Published: September 2021

Abstract
In the present study, the study and fabrication of inorganic organic nanocomposites with Guar gam and Carboxy methyl cellulose biopolymer substrates. The synthesis nanocomposite of CMC/GG/CuO-3 is biodegradable and biocompatible, and also has a significant efficiency in removing malachite green (MG) dye from aqueous solution. Properties were evaluated by XRD, FTIR, SEM, EDX and BET analysis. Important and influential parameters on the adsorption process such as adsorbent amount, initial dye concentration, pH and contact time on the removal efficiency of contaminants from aqueous solutions were investigated. Maximum removal efficiency and adsorption capacity were 92.4% and 18.6 mg/g, respectively. In order to analyze the mechanism of experimental data, two First-order and Second-order kinetic models were used, which followed the second-order kinetics with R2=1. Also, the study of Freundlich and Langmuir isotherms showed that the isotherm model of Freundlich follows the R2=0.94, which indicates the non-uniformity of adsorption on the adsorbent surface.
Micro-grooving of brittle materials using textured diamond grinding wheels shaped by an integrated nanosecond laser system
Authors: Geng Zongchao , Tong Zhen , Zhong Wenbin , Huang Guoqin , Cui Changcai , Xu Xipeng , Jiang Xiangqian 
Published: September 2021

Abstract
The freeform surfaces including both the aspherical and prismatic concave/convex have been widely utilized in optical, electronical, and biomedical areas. Most recently, it is reported that grinding with structured wheels provides new possibility to generate patterns on hard and brittle materials. This paper reports the latest research progress on micro-grooving glass ceramic using laser structured bronze bond diamond grinding wheels. A nanosecond pulse laser is firstly integrated into an ultra-precision machine tool and used for the in-line conditioning of super abrasive grinding wheels, i.e. truing, dressing, and profiling/texturing. Meanwhile, an offset compensation method, considering the shifting depth of focus (DoF) at different laser irradiation position, is proposed to accurately generate various profiles on the periphery of the grinding wheels. Three types of patterns (riblets, grooves, and pillars) are successfully fabricated on the ceramic substrate using the laser textured grinding wheels. The results indicate that the integrated laser system offers high flexibility and accuracy in shaping super abrasive grinding wheels, and the grinding using textured grinding wheels provide a promising solution to generate functional structures on hard and brittle materials.
Deep Learning Approach for Evaluating Lumbar Intervertebral Disc Degeneration: Achieving High Accurate Segmentation for Quantitative Analysis on MRI
Authors: Zheng Hua-dong , Sun Yue-li , Kong De-wei , Yin Meng-chen , Chen Jiang , Lin Yong-peng , Ma Xue-feng , Wang Hong-shen , Yuan Guangjie , Yao Min , Cui Xue-jun , Tian Yingzhong , Wang Yongjun 
Published: September 2021

Abstract
Purpose: Using deep learning and image processing technology, a standardized automatic segmentation and quantitation network of lumbar disc degeneration based on T2MRI was proposed to help residents accurately evaluate the intervertebral disc (IVD) degeneration.Materials and Methods: A semantic segmentation network (BianqueNet) consist of self-attention mechanism skip connection module and deep feature extraction module was proposed to achieve high-precision segmentation of IVD related areas. A quantitative method was used to calculate the signal intensity difference (∆SI) in IVD, average disc height (DH), disc height index (DHI), and disc height-to-diameter ratio (DHR). Quantitative ranges for these IVD parameters in a larger population was established among the 1051 MRI images collected from four hospitals around China.Results: The average dice coefficients of BianqueNet for vertebral bodies and intervertebral discs segmentation are 97.04% and 94.76%, respectively. This procedure was suitable for different MRI centers and different resolution of lumbar spine T2MRI (ICC=.874~.958). These geographic parameters of IVD degeneration have a significant negative correlation with the modified Pfirrmann Grade, while signal intensity in IVD degeneration had excellent reliability according to the modified Pfirrmann Grade (macroF1=90.63%~92.02%).Conclusion: we developed a fully automated deep learning-based lumbar spine segmentation network, which demonstrated strong versatility and high reliability to assist residents on IVD degeneration evaluating by means of IVD degeneration quantitation.Implication for Patient Care: Deep learning–based approaches have the potential to maximize diagnostic performance for detecting disc degeneration and assessing risk of disc herniation while reducing subjectivity, variability, and errors due to distraction and fatigue associated with human interpretation.
The pocketome of G protein-coupled receptors reveals previously untargeted allosteric sites
Authors: Kolb Peter , Hedderich Janik , Persechino Margherita , Becker Katharina , Heydenreich Franziska , Gutermuth Torben , Bouvier Michel , Bünemann Moritz 
Published: September 2021

Abstract
G protein-coupled receptors do not only feature the orthosteric pockets, where most endogenous agonists bind, but also a multitude of other allosteric pockets that have come into the focus as potential binding sites for synthetic modulators. We have investigated 557 GPCR structures to better characterise such pockets by exhaustively docking small molecular probes in silico and converting the ensemble of binding locations to pocket-defining volumes. Our analysis confirmed all previously identified pockets and revealed nine previously untargeted sites. In order to test for the feasibility of functional modulation of receptors through binding of a ligand to such sites, we mutated residues in two sites in two model receptors. Moreover, we analysed the correlation of inter-residue contacts with the activation states of receptors and showed that contact patterns closely correlated with activation indeed coincide with these sites.