bluuebunny/crossref_metadata_2025_split huggingface dataset:
Flagellin synergistically enhances anti-tumor effect of EGFRvIII peptide in a glioblastoma-bearing mouse brain tumor model
Authors: Choi Jin Myung , Lim Sa-Hoe , Liu Zhi-Peng , Rhee Joon Haeng , Yoon Mee Sun , Min Jung-Joon , Jung Shin 
Published: November 2021

Abstract
Purpose

Glioblastoma (GBM) is the most aggressive type of brain tumor with heterogeneity and strong invasive ability. Treatment of GBM has not improved significantly despite the progress of immunotherapy and classical therapy. Epidermal growth factor receptor variant III (EGFRvIII), one of GBM-associated mutants, is regarded as an ideal therapeutic target in EGFRvIII-expressed GBM patients because it is a tumor-specific receptor expressed only in tumors. Flagellin B (FlaB) originated from Vibrio vulnificus is known as a strong adjuvant that enhance innate and adaptive immunity in various vaccine models. This study performed whether FlaB synergistically could enhance the anti-tumor effect of EGFRvIII peptide (PEGFRvIII).
Methods

EGFRvIII-GL261/Fluc cells were used for glioblastoma-bearing mouse brain model and cell-bearing mice were inoculated with PBS, FlaB alone, PEGFRvIII alone, and PEGFRvIII plus FlaB. Survival rate through tumor growth was investigated by MRI. T cell population was examined by flow cytometry analysis. Both cleaved caspase-3 and CD8+ lymphocytes were shown by immunohistochemistry (IHC) staining.
Results

The PEGFRvIII plus FlaB group showed delayed tumor growth and increased survival rate when compared to other treatment groups. As an evidence of apoptosis, cleaved caspase-3 expression and DNA disruption were more increased in the PEGFRvIII plus FlaB group than in other groups. In addition, the PEGFRvIII plus FlaB group showed more increased CD8+ T cells and decreased Treg cells than other treatment groups in the brain.
Conclusion

FlaB can enhance the anti-tumor effect of PEGFRvIII by increasing CD8+ T cell response in a mouse brain GBM model.
Cotinine Levels Influence the Risk of Rupture of Brain Aneurysms
Authors: Missori Paolo , Ambrosone Angela , Currà Antonio , Paolini Sergio , Incarbone Giorgio , Amabile Elena , Biraschi Francesco , Diana Francesco , Peschillo Simone 
Published: November 2021

Abstract
The relationship between nicotine levels in smokers and brain aneurysm has never been determined. To assess the levels of cotinine in smoker patients with ruptured and unruptured brain aneurysm and the risk of aneurysm rupture we quantified cotinine levels in smoker patients with ruptured or unruptured brain aneurysms. We identified a control group of smokers and nonsmokers without brain aneurysm. Out of 182 participants cerebral aneurysms were statistically significantly associated with smoking (P<0.001) and female sex (P=0.006). Cotinine levels were significantly correlated with both the presence (P=0.009) and the rupture (P=0.002) of brain aneurysms. Compared with nonsmokers, smokers had a 5-fold higher risk of having a brain aneurysm (OR, 5.72; 95% CI, 2.96–11.07; P<0.001). The risk of rupture of brain aneurysms increased by 50% with each cotinine unit and was 4-fold higher with cotinine levels between 4 and 6 (OR, 3.75; 95% CI, 1.48–9.53; P=0.005). With increasing age, the cotinine level decreased (P <0.001, rho= –0.28), declining by 2% with each year of age. In the whole population, the probability of a ruptured aneurysm in patients with cotinine levels between 4 and 6 was higher than in those with levels between 0 and 3 (OR, 5.55; 95% CI, 1.08–28.5; P=0.040). Our results suggest that high cotinine levels in smokers with brain aneurysm, rather than size, are significantly associated with high rupture risk. Cotinine levels decrease with age, possibly reducing the risk of formation and rupture of a brain aneurysm.
Identification of Key Ischemic Stroke Genes by Computational Systems Biology
Authors: Yue Rongting , Dutta Abhishek 
Published: November 2021

Abstract
Stroke is one of the leading causes of death in humans. Even if patients survive from stroke, they may suffer sequelae such as disability. Treatment for strokes remains unsatisfactory due to an incomplete understanding of its mechanisms. This study investigates Ischemic Stroke (IS), a primary subtype of stroke, through analyses based on microarray data. Limma (in R)derives differentially expressed genes, and the protein-protein interaction (PPI) network is mapped from the database. Gene co-expression patterns are obtained for clustering gene modules by the Weighted Correlation Network Analysis (WGCNA), and genes with high connectivity in the significantly co-expressed modules are selected as key regulators. Common hubs are identified as Cdkn1a, Nes and Anxa2. Based on our analyses, we hypothesize that these hubs might play a key role in the onset and progression of IS. Result suggests the potential of identifying unexplored key regulators by the systemic method used in this work. Further analyses aim at expanding candidate genes for screening biomarkers for IS, and experimental validation is required on identified potential hubs.
Mobility network reveals the impact of spatial vaccination heterogeneity on COVID‐19
Authors: Yuan Yuan , Jahani Eaman , Zhao Shengjia , Ahn Yong-Yeol , Pentland Alex 
Published: November 2021

Abstract
Massive vaccination is one of the most effective epidemic control measures. Because one’s vaccination decision is shaped by social processes (e.g., socioeconomic sorting and social contagion), the pattern of vaccine uptake tends to show strong social and spatial heterogeneity, such as urban-rural divide and clustering. Examining through network perspectives, here we quantify the impact of spatial vaccination heterogeneity on COVID outbreaks and offer policy recommendations on location-based vaccination campaigns. Leveraging fine-grained mobility data and computational models, we investigate two network effects—the “hub effect” (hubs in the mobility network usually have higher vaccination rates) and the “homophily effect” (neighboring places tend to have similar vaccination rates). Applying Bayesian deep learning and fine-grained epidemic simulations, we show a negative effect of homophily and a positive effect of highly vaccinated hubs on reducing COVID-19 case counts; these two effects are estimated to jointly increase the total cases by approximately 10% in the U.S. Moreover, inspired by these results, we propose a vaccination campaign strategy that targets a small number of regions with the largest gain in protective power. Our simulation shows that we can reduce the number of cases by 20% by only vaccinating an additional 1% of the population. Our study suggests that we must examine the interplay between vaccination patterns and mobility networks beyond the overall vaccination rate, and that accurate location-based targeting can be equally if not more important than improving the overall vaccination rate.
Lattice fluctuation induced pseudogap in quasi-one-dimensional Ta2NiSe5
Authors: He Yu , Chen Cheng , Chen Xiang , Tang Weichen , Li Zhenglu , Wang Siqi , Ding Suhan , Jozwiak Chris , Bostwick Aaron , Rotenberg Eli , Hashimoto Makoto , Lu Donghui , Ruff Jacob , Louie Steven , Birgeneau Robert , Chen Yulin , Wang Yao 
Published: November 2021

Abstract
In conventional solid-state systems, the development of an energy gap is often associated with a broken symmetry. However, strongly correlated materials can exhibit energy gaps without any global symmetry breaking -- the so-called pseudogap, most notably in the Mott insulating state1 and the fluctuating superconducting or charge density wave states. To date, lattice induced pseudogap remains elusive. With angle-resolved photoemission spectroscopy (ARPES) and single crystal x-ray diffraction, we identify a pseudogap in the quasi-1D excitonic insulator candidate Ta2NiSe5. Strong lattice contribution is revealed by the pervasive diffuse scattering well above the transition temperature and the negative electronic compressibility in the pseudogap state. Combining first-principles and microscopic model calculations, we show that inter-band electron-phonon coupling can create fluctuating phonon-mediated electron-hole pairing or hybridization. This suppresses the spectral weight on the Fermi surface, causing a metal-to-insulator-like transition without breaking the global symmetry. Our work establishes the precedence of a pseudogap with a lattice origin, highlighting Ta2NiSe5 as a room-temperature platform to study lattice-induced charge localization and low dimensional fluctuations.
Dietary Exposure to Antibiotic Residues Facilitates Metabolic Disorder by Altering the Gut Microbiota and Bile Acid Composition
Authors: Chen Rou-An , Wu Wei-Kai , Panyod Suraphan , Liu Po-Yu , Chuang Hsiao-Li , Chen Yi-Hsun , Lyu Qiang , Hsu Hsiu-Ching , Lin Tzu-Lung , Shen Ting-Chin , Yang Yu-Tang , Zou Hsin-Bai , Huang Huai-Syuan , Lin Yu-En , Chen Chieh-Chang , Ho Chi-Tang , Lai Hsin-Chih , Wu Ming-Shiang , Hsu Cheng-Chih , Sheen Lee-Yan 
Published: November 2021

Abstract
Low dose antibiotic residues in food potentially contribute to obesity and metabolic dysfunction. However, the effect of chronic exposure to very low-dose antibiotic residue (~1000-fold lower than the therapeutic dose) on gut microbiota and host metabolism is poorly understood. Herein the effect of exposure to a residual dose of tylosin—an antibiotic growth promoter—on host metabolism and gut microbiota is explored in a mouse model. Theoretical maximal daily intake (TMDI) dose of tylosin facilitates high-fat diet-induced obesity, induces insulin resistance, and perturbs gut microbiota composition. Moreover, obesity-related phenotypes are transferrable to germ-free recipient mice following fecal microbiota transplantation. Tylosin TMDI exposure restricted to early life is sufficient to induce metabolic complications, alter the abundance of specific bacteria related to host metabolic homeostasis later in life, and modify the composition of short-chain fatty acids and bile acids. Finally, tylosin TMDI exposure induces lasting metabolic consequences via elevating the ratio of primary to secondary bile acids and its downstream FGF15 signaling pathway. Hence, exposure to very low doses of antibiotic residues, whether continuously or in early life, can exert long-lasting effects on host metabolism by altering gut microbiota and their metabolites.
Identification of hub genes and networks in cisplatin-induced acute kidney injury
Authors: Yang Lingyun , Xu Jinwen , Liu Xunwei , Cheng Yun , Zhou Hongxia , Zhao Liping 
Published: November 2021

Abstract
Acute kidney injury induced by cisplatin poses a serious health hazard to patients. Thus, this study was undertaken to elucidate key signaling pathways and hub genes relevant for therapeutic intervention involved in cisplatin-induced acute kidney injury(CI-AKI) by bioinformatics. We identified differentially expressed genes(DEGs) by R language on GSE106993 and GSE153625 datasets, downloaded from Gene Expression Omnibus (GEO). GO enrichment analysis and KEGG analysis were used to identify the main functions of common differential genes. The STRING database was used to construct protein-protein interaction (PPI) networks and hub genes were selected by Cytoscape. TransmiR v2.0 database and miRWalk2.0 database were used to construct transcription factor (TF)/microRNA (miRNA)/mRNA networks. Chinese herbal medicines targeting hub genes were screened by the ETMC database. 817 up-regulated genes and 769 down-regulated genes were obtained in CI-AKI model. Tumor necrosis factor(TNF) signaling pathway, P53 signaling, and metabolic signaling pathway are important pathways in CI-AKI. 8 hub genes were identified through PPI (Trp53、Egf、Stat3、Jun、Casp3、Cdh1、Ptgs2、Cat). We also constructed TF/microRNA/mRNA regulatory networks, including 2 TFs, 4 miRNAs and 214 mRNAs. The results of ETMC database analysis showed that Sang-Ye and Ban-Xia could be used for the treatment of CI-AKI. In this study, we identified 8 hub genes and 3 important signaling pathways in CI-AKI model by bioinformatics analysis, which provide targets for the treatment of CI-AKI. And the two Chinese herbal medicines obtained from our research, Sang-Ye and Ban-Xia, are expected to be used for the treatment of CI-AKI. Meanwhile, the TF/miRNA/mRNA networks we constructed are helpful to the further study of the mechanism of CI-AKI.
Value of Variation of End-Tidal Carbon Dioxide for Predicting Fluid Responsiveness During the Passive Leg Raising Test in Patients with Mechanical Ventilation: A Systematic Review and Meta-Analysis
Authors: Huang Haijun , Wu Chenxia , Shen Qinkang , Fang Yixin , Xu Hua 
Published: November 2021

Abstract
Background: The variation of end-tidal carbon dioxide(ΔEtCO2) has have been extensively studied with respect to its value in predicting fluid responsiveness, but the results are conflicting. This meta-analysis aimed to explore the value of ΔEtCO2 for predicting fluid responsiveness during the passive leg raising(PLR) test in patients with mechanical ventilation. Methods: PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched up to November 2021. The diagnostic odds ratio (DOR), sensitivity, and specificity were calculated. The summary receiver operating characteristic curve was estimated, and the area under the curve (AUROC) was calculated. We performed meta-regression analysis for heterogeneity exploration and sensitivity analysis for the publication bias.Results: Overall, 298 patients were included in this review, of whom 149 (50%) were fluid responsive. The cutoff values of ΔEtCO2 varied across studies, ranging from 5% to 5.8% or absolute increase 2mmHg. Heterogeneity between studies was assessed with an overall Q = 4.098, I2 = 51%, and P = 0.064. The pooled sensitivity and specificity for the overall population were 0.79 (95% CI: 0.72–0.85) and 0.90 (95% CI: 0.77–0.96), respectively. The DOR was 35 (95% CI: 12–107) (Fig. 4). The pooled AUROC was 0.81 (95% CI: 0.77–0.84). On meta-regression analysis, the number of patients was sources of heterogeneity. The sensitivity analysis showed that the pooled DOR ranged from 21 to 140 and the pooled AUC ranged from 0.92 to 0.96 when one study was omitted.Conclusions: This study was the first meta-analysis to evaluate the diagnostic accuracy of ΔEtCO2 in predicting fluid responsiveness during PLR test in patients with mechanical ventilation. This study confirmed that the ΔEtCO2 performed well in predicting fluid responsiveness in patients with mechanical ventilation.
Vitamin C Improves Microvascular Reactivity and Peripheral Tissue Perfusion in Septic Shock Patients
Authors: Lavillegrand Jean-Rémi , Raia Lisa , Urbina Tomas , Hariri Geoffroy , Gabarre Paul , Bonny Vincent , Bigé Naïke , Baudel Jean-Luc , Bruneel Arnaud , Dupre Thierry , Guidet Bertrand , Maury Eric , Oufella Hafid Ait 
Published: November 2021

Abstract
Background
Vitamin C has potential protective effects through anti-oxydant and anti-inflammatory properties. However, the effect of Vitamin C supplementation on microvascular function and peripheral tissue perfusion in human sepsis remains unknown. We aimed to determine vitamin C effect on microvascular endothelial dysfunction and peripheral tissue perfusion in septic shock patients.
Methods
Patients with septic shock were prospectively included after initial resuscitation. Bedside peripheral tissue perfusion and skin microvascular reactivity in response to acetylcholine iontophoresis in the forearm area were measured before and 1 hour after intravenous Vitamin C supplementation (40 mg/kg). Norepinephrine dose was not modified during the studied period.
Results
We included 30 patients with septic shock. SOFA score was 11 [8–14], SAPS II was 66 [54-79] and in-hospital mortality was 33%. Half of these patients had vitamin C deficiency at inclusion. Vitamin C supplementation strongly improved microvascular reactivity (AUC 2263 [430-4246] vs 5362 [1744-10585] UI, p=0.0004). In addition, Vitamin C supplementation improved mottling score (p=0.06), finger-tip (p=0.0003) and knee capillary refill time (3.7 [2.6-5.5] vs 2.9 [1.9-4.7] s, p<0.0001), as well as and central-to-periphery temperature gradient (6.1 [4.9-7.4] vs 4.6 [3.4-7.0] °C, p<0.0001). The beneficial effects of Vitamin C were observed both in patients with or without Vitamin C deficiency.
Conclusion
In resuscitated septic shock patients, vitamin C supplementation improved peripheral tissue perfusion and microvascular reactivity whatever plasma levels of vitamin C.
The Effect of Heat Treatment on Microstructure, Microhardness and Pitting Corrosion of Ti6Al4V Produced by Electron Beam Melting Additive Manufacturing Process
Authors: Xiu Mingzhen , Tan Yong Teck , Raghavan Srinivasan , Goh Min Hao , Nai Mui Ling Sharon 
Published: November 2021

Abstract
There has been limited studies on corrosion behaviour of post-processed Electron Beam Melted (EBM) Ti6Al4V, given that the factors affecting corrosion resistance of AM Ti6Al4V remain unclear. This paper proposes using heat treatment method to improve the pitting corrosion resistance of EBM Ti6Al4V. Different treatment profiles alter the microstructure of EBM Ti6Al4V. A clear trend is observed between microhardness and α lath width. As-printed EBM Ti6Al4V exhibits an inferior pitting potential, while heat treatment provided a significant improvement in the corrosion resistance. This study finds that the β phase fraction is a better indicator than the α lath width for pitting corrosion resistance. Solution air-cooled & ageing heat treated EBM Ti6Al4V exhibits good mechanical and corrosion properties, and even performs better than commercial cast Ti6Al4V.
Annual variability in sound acorn production was regulated by a generalist seed predator weevil in Quercus serrata
Authors: Hirayama Kimiko , Mizo Kenta , Tatsuno Manaka , Yoshikawa Mizuki , Tachikawa Chieri 
Published: November 2021

Abstract
Highly variable and synchronous seed production within a population (‘masting’) could be from either synchronised high annual variability in floral initiation (‘flower masting’) or synchronised floral abortion until maturity (‘fruit maturation masting’). We investigated the demographic processes of the female organs from flowering to seed maturity, including each type of insect damage identified, in Quercus serrata in six individuals within a stand from 2014 to 2020, western Japan. Although the annual production of sound acorns was significantly correlated with that of female flowers, the annual variability in sound acorn production within an individual was significantly higher and their synchrony increased, compared to those of female flowers. The annual production of female flowers was positively correlated with the temperature difference in April between the previous and flowering years. However, their fluctuation was low, which was neither affected by seed and flower production in the previous year nor contributed to predator starvation. Key-factor analyses revealed that reproductive loss due to oviposition and sap suction by Mechoris ursulus , a generalist seed predator weevil for oak species, was the largest and most important factor that contributed to the annual variation in the total pre-dispersal loss of Q. serrata . The survival rate from female flowers to sound acorns was strongly predicted by the temperature in June, corresponding to the emergence of adult M. ursulus . This study suggests that highly variable and synchronous sound seed production can be proximately regulated by seed predation when the main predator is a generalist.
New Metabolic Health Definition Might Not Be a Reliable Predictor for Mortality in the Nonobese Chinese Population
Authors: Wang Ziqiong , Li Liying , Zhang Muxin , Ruan Haiyan , Zhu Ye , Wei Xin , Wei Jiafu , Chen Xiaoping , He Sen 
Published: November 2021

Abstract
Background

A new metabolic health (MH) definition was proposed recently. We aimed to investigate the association between the new MH definition and all-cause mortality (ACM) in a nonobese Chinese population.
Methods

A total of 1157 participants with 15-year of follow-up were included for the present analysis. The association between MH and ACM were analyzed by Cox regression models with overlap weighting according to propensity score (PS) as primary analysis.
Results

At baseline, 920 (79.5%) participants were categorized as MH and 237 (20.5%) participants were categorized as metabolic unhealth (MUH) by this new definition. During follow-up, ACM occurred in 30 participants with mortality rate at 1.85% in MH group and 5.49% in MUH group, respectively. In the crude sample, Kaplan-Meier (K-M) analysis demonstrated a significantly lower ACM in MH group when compared to MUH group (log-rank p = 0.002). However, in multivariable Cox analysis, MH was not significantly associated with reduced ACM when compared to MUH with HR at 0.92 (95% CI: 0.32-2.64, p = 0.875). Moreover, overlap weighting-adjusted K-M analysis showed that the cumulative incidence of ACM was not significantly different between MH and MUH groups (adjusted p = 0.589). In the primary multivariable Cox analysis with overlap weighting, the HR for ACM was 0.70 (95% CI: 0.24-2.06, p = 0.519) in MH group in reference to MUH group. Additional PS analyses yielded similar results.
Conclusion

The new MH definition was not significantly associated with ACM in non-obese Chinese people. Further investigations are needed.
Comparative effectiveness and safety of homologous two-dose ChAdOx1 versus heterologous vaccination with ChAdOx1 and BNT162b2: a cohort analysis
Authors: Prieto-Alhambra Daniel , Hermosilla Eduardo , Coma Ermengol , Xie Junqing , Feng Shuo , Cabezas Carmen , Méndez-Boo Leonardo , Fina Francesc , Ballo Elisabet , Martínez Montserrat , Medina-Peralta Manuel , Argimon Josep Maria 
Published: November 2021

Abstract
Small trials have suggested that heterologous vaccination with first-dose ChAdOx1 and second-dose BNT162b2 may generate a better immune response than homologous vaccination with two doses of ChAdOx1. We used linked data from Catalonia (Spain), where those aged <60 who received a first dose of ChAdOx1 could choose between ChAdOx1 and BNT162b2 for their second dose. Comparable cohorts were obtained after exact-matching 14,325/17,849 (80.3%) people receiving heterologous vaccination to 14,325/149,386 (9.6%) receiving homologous vaccination by age, sex, region, and date of second dose. Of these, 238 (1.7%) in the heterologous and 389 (2.7%) in the homologous groups developed COVID-19 between 1st June 2021 and 11th October 2021. The resulting hazard ratio (95% confidence interval) was 0.61 [ 0.52-0.71 ], favouring heterologous vaccination, with a Number Needed to Treat of 94.9 [ 71.8 - 139.8 ]. The two groups had similar testing rates and safety outcomes. Sensitivity and negative control outcome analyses confirmed these findings. In conclusion, we demonstrate that a heterologous vaccination schedule with ChAdOx1 followed by BNT162b2 was more efficacious than and similarly safe to homologous vaccination with two doses of ChAdOx1. Most of the infections in our study occurred when Delta was the predominant SARS-CoV-2 variant in Spain. These data agree with previous phase 2 randomised trials.