bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Anesthesia Beginning at On-hours Versus Off-hours on Outcomes in Patients Undergoing Hip Surgery: A Retrospective, Propensity Score–matched Cohort Study
Authors: Wu Jiayi , Zhang Shuang , Wu Xi , Mei Wei
Published: September 2021

Objective: To explore the impact of the begin time of anesthesia on in-hospital mortality and early prognosis of patients undergoing hip surgery.Methods: All patients who had hip surgery between January 1, 2015, and December 31, 2020, were evaluated in this retrospective cohort study. The primary outcome was in-hospital mortality. Secondary outcomes were: (1) postoperative hospital length of stay (postoperative LOS) and total LOS; (2) ICU admission; (3) the ratio of postoperative complications, including renal dysfunction, anemia, hypotension, deep vein thrombosis (DVT), arrhythmia, coronary artery disease (CAD) or heart failure, pulmonary infection, electrolyte disturbance, hyoxemia and delirium; (4) intraoperative outcomes, including blood loss, urine volume, concentrated red blood cells (CRBC), fresh frozen plasma (FFP), equilibrium liquid, colloidal solution, intraoperative sufentanil, and using vasoactive drugs. A propensity score–matched analysis was used to adjust for confounders to make baseline characteristics more similar within the cohort. Results: We identified 1,843 patients, of whom 1,727 had anesthesia begun at on-hours and 116 had anesthesia begun at off-hours. Before propensity score matching (PSM), in-hospital mortality (risk ratio, 19.85; 95% CI, 4.39-89.78; P <0.001), postoperative LOS (11 days [8-16] vs. 9 days [7-14]; P =0.001) and total LOS (16 days [12-25.3] vs. 14 days [12-19]; P =0.020), the proportion of ICU admission (risk ratio, 4.70; 95% CI, 1.84-12.01; P <0.001), hypotension (risk ratio, 5.96; 95% CI, 1.84-19.29; P =0.004), pulmonary infection (risk ratio, 4.74; 95% CI, 1.98-11.33; P <0.001) and hyoxemia (risk ratio, 5.32; 95% CI, 1.88-15.03; P <0.001) was higher in the off-hours group. Intraoperative CRBC (0 U [0-2] vs. 0 U [0-0]; P <0.001), FFP (0 mL [0-37.5] vs. 0 mL [0-0]; P <0.001) and the intraoperative dosage of sufentanil (24.5 vs. 19.3 μg; P =0.003) was higher in the off-hours group. After PSM, 110 patients in the on-hours group were matched to similar patients in the off-hours group. Intraoperative CRBC (0 U [0-2] vs. 0 U [0-0]; P =0.040) and FFP (0 mL [0-0] vs. 0 mL [0-0]; P =0.015) was higher in the off-hours group. And postoperative renal dysfunction (risk ratio, 1.67; 95% CI, 0.86-3.21; P =0.050) and hyoxemia (4.5% vs. 0%; P =0.060) had a tendency to be different.Conclusion: Off-hours anesthesia for hip surgery is associated with statistically significant increases in intraoperative CRBC, FFP, and possibly associated with higher ratio of postoperative renal dysfunction and hyoxemia. These findings suggest that off-hours anesthesia, possibly by affecting the anesthetist’s judgment and decision making, could cause potential risks for hip surgery patients, which requires further exploration.
An Ifnar1 allele impairs the colonization of gut bacteria
and promotes tuberculosis
Authors: Chen Lingming , Zhang Guoliang , Li Guobao , Wang Wei , Ge Zhen-Huang , Yang Yi , He Xing , Liu Zhi , Zhang Zhiyi , Mai Qiongdan , Chen Yiwei , Chen Zixu , Pi Jiang , Yang Shuai , Cui Jun , Liu Haipeng , Shen Ling , Zeng Lingchan , Zhou Lin , Chen Xinchun , Ge Baoxue , Chen Zheng W. , Zeng Gucheng
Published: September 2021

Both host genetics and gut microbiome have important effects on human health, yet how host genetics regulates gut bacteria and further determines disease susceptibility remains unclear. Here, we find that gut microbiome pattern of active tuberculosis (TB) patients is characterized by a reduction of core species found across healthy controls, particularly Akkermansia muciniphila (A. muciniphila). Oral treatments of A. muciniphila or palmitoleic acid, an A. muciniphila-derived metabolite, strongly inhibit TB infection through epigenetically inhibiting TNF-α. We use three independent cohorts comprising 6512 individuals and identify that single-nucleotide polymorphism rs2257167 “G” allele of type I interferon (IFN-I) receptor 1 (Ifnar1) contributes to stronger IFN-I signaling, impaired colonization and abundance of A. muciniphila, reduced production of palmitoleic acid, higher TNF-α, and much severer TB disease in humans and transgenic mice. Thus, host genetics are critical in modulating structure and functions of gut microbiome and gut microbial metabolites, which further determines disease susceptibility.
Selected Physico-Chemical Properties of Composite Scaffolds of Sintered Submicrocrystalline Corundum and Bioglass
Authors: Staniewicz-Brudnik Barbara , Karolus Malgorzata , Cholewa-Kowalska Katarzyna , Skrabalak Grzegorz , Laszkiewicz-Łukasik Jolanta , Drukała Justyna , Stalińska Joanna , Dziedzic Katarzyna
Published: September 2021

Presented paper contains description and interpretation of the results of selected physicochemical and structural properties of two types of composite sinters. They were constituted of a mixture of sintered microcrystalline corundum and bioglass CaO-P2O5-SiO2-Na2O system intended for scaffolds to cell culture of human chondrocytes. The composites contained a mixture of both above-mentioned components in the volumetric proportion of 50:50 (W5) and 30:70 (W7). They were obtained using powder metallurgy by free sintering in air atmosphere. Phase analysis of composites and verification of theoretical identification using X-ray diffraction were performed. The same phases were found in both cases (Al2O3 SiO2 CaAl2Si2O8, Ca3 (PO4)2, Ca2Al4O7 and NaAlSiO4. Microscopic tests of composite surfaces were performed and some differences were found. W5 sample was not completely covered with bioglass, whilst W7 sample was completely covered with bioglass with few fine pores. Tests of surface topography confirmed the presence of large and small pores. Composite surfaces immersed for 30 days in artificial blood plasma were tested and then electron microscopy analysis was performed. It was found that no significant changes occurred on the surface of the W5 composite, probably partial corrosion of the glass happened. Spherical forms characteristic of HA-hydroxyapatites were observed on the surface of sample W7. Human chondrocyte cells were seeded on both types of sinters and proliferation assay was performed on them with positive results.
Recollision of excited electron in below-threshold nonsequential double ionization
Authors: Hao Xiaolei , Bai Yuxing , Li Chan , Zhang Jingyu , Li Weidong , Yang Weifeng , Liu Mingqing , Chen Jing
Published: September 2021

Consensus has been reached that recollision, as the most important post-tunneling process, is responsible for nonsequential double ionization process in intense infrared laser field, however, its effect has been restricted to interaction between the first ionized electron and the residual ion so far. Here we identify the key role of recollision of the second ionized electron, which is enhanced by the stronger Coulomb potential of the higher valence residual ion, in the below-threshold nonsequential double ionization process by introducing a Coulomb-corrected quantum-trajectories method, which enables us to well reproduce the experimentally observed cross-shaped and anti-correlated patterns in correlated two-electron momentum distributions, and also the transition between these two patterns. Being significantly enhanced relatively by the recapture process which is also attributed to the stronger Coulomb potential of the residual ion, recolliding trajectories of the second electron excited by the first- or third-return recolliding trajectories of the first electron produce the cross-shaped or anti-correlated distributions, respectively. And the transition is induced by the increasing contribution of the third return with increasing pulse duration. Our work provides a new insight into atomic ionization dynamics and paves the new way to imaging of ultrafast dynamics of atoms and molecules in intense laser field.
Quantitative Glycoproteomics Analysis Identifies Novel FUT8 Targets and Signaling Networks Critical for Breast Cancer Cell Invasiveness
Authors: Tu Cheng-Fen , Li Fu-An , Li Ling-Hui , Yang Ruey-Bing
Published: September 2021

BackgroundWe recently showed that fucosyltransferase 8 (FUT8)-mediated core fucosylation of transforming growth factor-β receptor enhances its signaling and promotes breast cancer invasion and metastasis. However, the complete FUT8 target glycoproteins and their downstream signaling networks critical for breast cancer progression remain largely unknown.MethodWe performed quantitative glycoproteomics with two highly invasive breast cancer cell lines to unravel a comprehensive list of core-fucosylated glycoproteins by comparison to parental wild-type and FUT8-knockout counterpart cells. In addition, Ingenuity Pathway Analysis (IPA) was performed to highlight the most enriched biological functions and signaling pathways mediated by FUT8 targets. Novel FUT8 target glycoproteins with biological interest were functionally studied and validated by using LCA (Lens culinaris agglutinin) blotting and LC-MS/MS (liquid chromatography-tandem mass spectrometry) analysis.ResultsLoss-of-function studies demonstrated that FUT8 knockout suppressed the invasiveness of highly aggressive breast carcinoma cells. Quantitative glycoproteomics identified 140 common target glycoproteins. Ingenuity Pathway Analysis (IPA) of these target proteins gave a global and novel perspective on signaling networks essential for breast cancer cell migration and invasion. In addition, we showed that core fucosylation of integrin αvβ5 or IL6ST is crucial for breast cancer cell adhesion to vitronectin or enhanced cellular signaling to interleukin 6 and oncostatin M, two cytokines implicated in the breast cancer epithelial–mesenchymal transition and metastasis.ConclusionsOur report reveals a comprehensive list of core-fucosylated target proteins and provides novel insights into signaling networks crucial for breast cancer progression. These findings will assist in deciphering the complex molecular mechanisms and developing diagnostic or therapeutic approaches targeting these signaling pathways in breast cancer metastasis.
Melatonin Inhibits the Ferroptotic Pathway in Rat Bone Marrow Mesenchymal Stem Cells by Activating the PI3K-AKT-mTOR Signaling Axis to Attenuate Steroid-induced Osteoporosis
Authors: li meng , yang ning , hao li , zhou wei , li lei , liu lei , fang fang , xu lei , yao gang , zhu chen , xu wei , fang shiyuan
Published: September 2021

ObjectivesSteroid-induced osteoporosis (SIOP) is a secondary osteoporosis, which is a systemic bone disease characterized by low bone mass, bone microstructure damage, increased bone fragility, and easy fracture. However, the specific mechanism remains unclear. Glucocorticoid-induced death of osteoblasts and bone marrow mesenchymal stem cells (BMSCs) is an important factor in SIOP. Ferroptosis is an iron-dependent programmed cell death that differs from apoptosis, cell necrosis, and autophagy, which can be induced by many factors. Herein, we aimed to explore whether glucocorticoids (GCs) cause ferroptosis in BMSCs and determine possible treatment pathways and mechanisms of action. Melatonin (MT), a hormone secreted by the pineal gland, displays strong antioxidant abilities to scavenge free radicals and alleviates ferroptosis in many tissues and organs. MethodsIn this study, we used high-dose dexamethasone (DEX) to observe whether glucocorticoids induced ferroptosis in BMSCs. We then assessed whether MT can inhibit the ferroptotic pathway, thereby providing early protection against GC-induced SIOP, and investigated the signaling pathways involved.ResultsIn vitro experiments showed that MT intervention significantly improved GC-induced ferroptosis in BMSCs and significantly improved SIOP in vivo. Pathway analysis showed that MT improves ferroptosis by activating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) axis. MT upregulates expression of PI3K, which is an important regulator of ferroptosis resistance. PI3K activators mimic the anti-ferroptosis effect of MT, but after blocking the PI3K pathway, the effect of MT is weakened. Obviously, MT can protect against SIOP induced by GC. Notably, even after GC-induced ferroptosis begins, MT can confer protection against SIOP. Conclusion﻿Our research confirms that GC-induced ferroptosis is closely related to SIOP. Melatonin can inhibit ferroptosis by activating the PI3K-AKT-mTOR signaling pathway, thereby reducing the occurrence of steroid-induced osteoporosis. Therefore, MT may provide a novel strategy for preventing and treating SIOP.
Stay Out of the Blast Radius: Influence of Surgical Masks on Virtual Pedestrian Interactions
Authors: Bühler Marco A. , Lynch Sean D. , Bhojwani Trineta , Zidan Ahlam , Fiset Félix , McFadyen Bradford J. , Lamontagne Anouk
Published: September 2021

To combat the global pandemic caused by COVID-19, a series of mitigation strategies have been proposed by governments around the world. While responses varied across different governing bodies, recommendations such as social distancing and the use of facial masks were nearly universal. Considering that even with restrictions in place, walking in community environments remained an important component of everyday life, these public health recommendations, as well as the anxiety generated by the pandemic, are likely to have influenced pedestrian interactions. In this study, we have examined the effect of facial masks and anxiety related to community ambulation in the context of the COVID-19 pandemic. Using virtual reality, obstacle circumvention strategies in response to approaching pedestrians with and without facial masks were measured in a sample of 11 healthy young individuals. Additionally, a questionnaire was developed and used to gain insights into the participant's behaviours during and after a strict period of restrictions that were in effect before the summer of 2020. Results showed that participants maintained a larger obstacle clearance when virtual pedestrians wore a facial mask. The extent of obstacle clearance was also positively associated with anxiety towards community ambulation in the context of the pandemic. Our findings provide evidence that mask-wearing results in an increase in physical distancing during pedestrian interactions, which may help to reduce the risk of infection. Furthermore, results demonstrate the effects of social context and psychological status on pedestrian interactions and highlight the potential of virtual reality simulations to study locomotion in natural community settings.
Bevacizumab in Combination with Paclitaxel and Platinum for Previously Treated Advanced Thymic Epithelial Tumor
Authors: Wang Chang-Lu , Gao Lan-Ting , Lyu Chang-Xing , Zhang Qin , Zeng Wan-Qin , Fang Wen-Tao , Zhu Lei , Fu Xiao-Long
Published: September 2021

BackgroundThere are no optimal regimens for advanced thymic epithelial tumors (TETs) when front-line chemotherapy fails. In this study, we aimed to assess the activity of Bevacizumab in combination with routine chemotherapeutic regimen.MethodsPatients with advanced TETs who had failed after previous chemotherapy were enrolled in this study. Paclitaxel (160mg/m2) or cisplatin (70mg/m2) and carboplatin (area under the curve, 6) plus Bevacizumab (7.5mg/kg) were intravenously injected on day 1.The treatment was repeated every 3 weeks until the disease progressed or intolerable toxicities occurred.ResultsBetween March 2018 and August 2020, a total of 49 patients (21 thymoma and 28 thymic carcinoma) received the new treatment. There were 28 men and 21 women with a median age of 50 years (range: 21-73 years).The median number of cycles was 3 (range: 1-6) per patient. The objective response rate (ORR) for all patients was 43% (21/49). The ORRs for thymoma and thymic carcinoma were 24% and 57%, respectively. The median progression free survival for thymoma and thymic carcinoma were 6 and 8 months, respectively. Hematological toxicities were the main side effects.ConclusionsPaclitaxel and platinum plus Bevacizumab showed promising effect in refractory or relapsed advanced TETs without severe toxicity. Even applied as salvage therapy, this regimen resulted in better ORR than the front-line chemotherapy.
Improvement of Surface Quality and Machining Depth of µ-ECDM Performances Using Mixed Electrolyte at Different Polarity
Authors: MALLICK BIJAN , SARKAR B R , DOLOI B , BHATTACHARYYA B
Published: September 2021

The production of miniature parts and various shape of micro-profile by electrochemical discharge micro-machining process (µ-ECDM) draw challenging attention to the researchers. Parametric influences as well as comparative analysis on machining depth (MD) and surface roughness (Ra) has been propounded using NaOH and KOH at the ratio of 1:0, 3:1, 1:1, 1:3 and 0:1 with their varying concentration(wt.%), and applied voltage (V), pulse frequency(Hz) and duty ratio (%)in straight as well as in reverse polarity using template guided stainless steel (SS) cylindrical tool with motion and spring feed mechanism for fabrication of different shapes of micro-channel like Zig-Zag, ‘Y’ shaped on glass by µ-ECDM process. Tool electrode wear rate (TEWR) has been reduced using mixed electrolyte and reversed polarity. The SEM analysis has been performed to identify the micro-crack and uncut debris into micro-channel. Machining depth has been increased up to 1850 µm with better surface quality using mixed electrolyte of NaOH:KOH::3:1 at direct polarity of 50 V and lower TEWR is found using NaOH:KOH::1:3 as electrolyte at reverse polarity.
Association of Dyslipidemia With Nucleoside Analogue Treatment in HBeAg-Positive Chronic Hepatitis B Patients
Authors: Xia Ziqiang , Zheng Juzeng , Zheng Liang , Zheng Endian , Zou Zhuolin , Sheng Xiong , Wu Jinming
Published: September 2021

BackgroundThe prevalence of dyslipidemia in China is increasing annually. Current studies suggest that dyslipidemia affects the antiviral efficacy of hepatitis C virus (HCV) therapies. Recent studies have shown that serum lipids influence the response rates of chronic hepatitis B patients receiving PEGylated interferon-alpha (Peg IFN-a) treatment. However, the role of dyslipidemia in the efficacy of nucleoside (acid) analogues in chronic hepatitis B patients has not been determined. Methods From January 2010 to December 2013, data from 179 treatment-naive patients with chronic hepatitis B (CHB) who were hepatitis B e antigen (HBeAg)-positive and visited the first affiliated hospital of Wenzhou Medical University were collected. Amongst them, 68 patients were diagnosed with CHB complicated with dyslipidemia (dyslipidemia group) whilst 111 patients comprised the lipid control group. Three treatment strategies were performed amongst the 179 CHB patients over a 5 year period. Treatments included combination therapy of lamivudine (LAM) plus adefovir dipivoxil (ADV), telbivudine (LdT) monotherapy or entecavir (ETV) monotherapy. Serum assessments, blood biochemistry, HBV serological markers, HBV DNA before treatment and HBeAg serological conversion and virological responses at different time points after treatment were compared between the two groups. Measurement data were compared using τ tests, whilst enumeration data were compared using c2 tests. Correlation analysis was performed using binary Logistic regression analysis. Results The rates of HBeAg seroconversion in the dyslipidemia group at years 1, 2, 3 and 4 were 10.3%, 13.2%, 17.6% and 22.1%, respectively, which were not significantly lower than those of the lipid control group 11.7%, 16.2%, 18.0% and 33.3%, (c2 = 0.085, 0.293, 0.004 and 2.601, respectively; R > 0.05). However, the rates of HBeAg seroconversion in the dyslipidemia group were significantly lower than those of the lipid control group at year 5 (27.9% vs 43.2%, c2 =4.216, R<0.05). Univariate logistic regression analysis showed significant differences in sex PTA, ALT, AST, CR and LDL-C. Multivariate regression analysis demonstrated that dyslipidemia (OR=1.993, R=0.038), and male gender (OR=2.317, R=0.029) were risk factors associated with HBeAg seroconversion.Conclusions During antiviral therapy, dyslipidemia affects HBeAg seroconversion in CHB patients treated with nucleoside (acid) analogues but does not affect the virological response.
Augmented EPR Effect Post IRFA to Enhance the Therapeutic Efficacy of Arsenic Loaded ZIF-8 Nanoparticles on Residual HCC Progression
Authors: Chen Xuehua , Wang Hao , Chen Hui , Chen Ziman , Chen Jiaxin , Huang Yongquan , Li Dan , Su Zhongzhen
Published: September 2021

BackgroundInsufficient radiofrequency ablation (IRFA) can promote the local recurrence and distal metastasis of residual hepatocellular carcinoma (HCC), which makes clinical treatment extremely challenging. In this study, the malignant transition of residual tumors after IRFA was explored. Then, arsenic-loaded zeolitic imidazolate framework-8 nanoparticles (As@ZIF-8 NPs) were constructed, and their therapeutic effect on residual tumors was studied. ResultsOur data showed that IRFA can dramatically promote the proliferation, induce the metastasis, activate the epithelial-mesenchymal transition (EMT) and accelerate the angiogenesis of residual tumors. Interestingly, we found, for the first time, that extensive angiogenesis after IRFA can augment the enhanced permeability and retention (EPR) effect and enhance the enrichment of ZIF-8 nanocarriers in residual tumors. Encouraged by this unique finding, we successfully prepared As@ZIF-8 NPs with good biocompatibility and confirmed that they were more effective than free arsenic trioxide (ATO) in sublethal heat-induced cell proliferation suppression, apoptosis induction, cell migration and invasion inhibition, and EMT reversal in vitro. Furthermore, compared with free ATO, As@ZIF-8 NPs exhibited remarkably increased therapeutic effects by repressing residual tumor growth and metastasis in vivo.Conclusions﻿This work provides a new paradigm for the treatment of residual HCC after IRFA.
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

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

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

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

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

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

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

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

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

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

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

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

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.
Evaluation efficacy of amniotic membrane in the treatment of neonatal Extravasation: a pilot study
Authors: Kadivar Maliheh , amini maryam , afshani maryam , nasrabadi Seyed ali hashemi , mirnia kayvan
Published: September 2021

The authors have requested that this preprint be removed from Research Square.
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

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.
A stretchable micrometer with enhanced performance for intermediate Reynolds numbers
Authors: Fallahi Hedieh , Zhang Jun , Nicholls Jordan , Singha Pradip , Nguyen Nhat-Khuong , Ooi Chin Hong , Nguyen Nam-Trung
Published: September 2021

Chemical reactions in microscale require good mixing at a relatively low flowrate. However, mixing in microscale faces the major challenge of stable laminar flow associated with the low Reynolds number, the relative ratio between inertial force and viscous force. For low Reynolds numbers of less than unity, mixing occurs due to molecular diffusion. For high Reynolds number of more than several tens, chaotic advection enhances mixing. However, in the intermediate regime, mixing is not efficient. This paper reports a stretchable micromixer with dynamically tuneable channel dimensions. Periodically stretching the device changes the channel geometry and the curvature induced secondary Dean flows. The dynamically evolving secondary and main flows in the mixing channel result in chaotic advection and enhance mixing. The concept was demonstrated in a stretchable micromixer with a serpentine channel. We evaluated the performance of this stretchable micromixer both experimentally and numerically. At the intermediate range of Reynolds numbers from 4 to 17, the periodically stretched micromixer showed a better mixing efficiency than the non-stretched counterpart. Therefore, our stretchable micromixer is a potential candidate for applications where precious reagents need to be mixed at relatively low flow rate conditions.