bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of hub genes of endothelial cells in glioblastoma-A prognostic model for GBM patients integrating single cell RNA sequencing and bulk RNA sequencing
Authors: Zhao SongYun , Ji Wei , Shen YiFan , Fan YuanSheng , Huang Jin , Huang Hui , Cheng Chao , Shao Junfei 
Published: June 2022

Abstract
Background：Glioblastoma multiforme (GBM) is one of the most common malignancies in the world and many studies have used traditional high-throughput RNA sequencing (bulk RNA-seq) data to explore its potential prognostic markers. However, it is unable to detect specific cellular and molecular changes in tumour cells. The aim of this study was to use single cell RNA-seq (scRNA-seq) to discover marker genes in endothelial cells and to construct a prognostic model for GBM patients in combination with traditional RNA-seq data.Methods：Bulk RNA-seq data were downloaded from The Cancer Genome Atlas (TCGA) and The China Glioma Genome Atlas (CGGA) databases. 10x scRNA-seq data for GBM were obtained from the Gene Expression Omnibus (GEO) database. The uniform manifold approximation and projection (UMAP) was used for downscaling and cluster identification. Key modules and differentially expressed genes (DEGs) were identified by weighted gene correlation network analysis (WGCNA). Non-negative matrix decomposition (NMF) algorithm was used to identify different subtypes based on DEGS. And Cox regression analysis was used to build prognostic models. Finally, differences in mutational landscape, immune cell abundance, immune checkpoint inhibitors (ICIs)-associated genes, immunotherapy effects and enriched pathways were also investigated between different risk groups.RESULT：The analysis of scRNA-seq data from eight samples revealed 13 clusters and four cell types. After applying differential analysis, endothelial cells were identified as the most important significant cell type. In addition, we explored potential neoangiogenic pathways in GBM after controlling for phenotypic differences between GBM and normal brain tissue ECs at the single cell level. Overall, through differential analysis, WGCNA and screening of endothelial cell marker genes, we identified 157 DEGs for the construction of prognostic models. In addition, based on DEGs,the NMF algorithm identified two clusters with different prognostic and immunological features observed. We finally built a prognostic model based on the expression levels of four of these key genes. Higher risk scores were significantly associated with poorer survival outcomes and were associated with low mutation rates in IDH genes and upregulation of immune checkpoints such as PD-L1 and CD276. The CGGA cohort served as an external validation cohort for our findings.Conclusion：We built and validated a 4-gene signature for GBM using 10 scRNA-seq and bulk RNA-seq data in this work. We believe our findings will provide greater insight into the characteristics of ECs in GBM and provide potential prognostic biomarkers to design rational treatment plans.
Potential significance of Nrf2-ROS-MMP-9 axis in blood cerebrospinal fluid barrier dysfunction induced by lanthanum chloride
Authors: Zhang Lijin , Sun Jing , Yan Licheng , Li Shuang , Wang Weixuan , Wu Lei , He Bin , Zhang Yanshu 
Published: June 2022

Abstract
Lanthanum (La) can cause brain barrier injured and lead to the cognitive impairment. Yet, fewer research about La induced the blood cerebrospinal fluid barrier (BCSFB) dysfunction. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key regulator of the cellular antioxidant defense system in preventing the exogenous chemicals associated with the accumulation of reactive oxygen species (ROS). Matrix metalloproteinase 9 (MMP9) is proteases that degrades the extracellular matrix as well as tight junctions between choroid plexus epithelial cells (CPECs) and have been implicated in BCSFB in neurodegenerative diseases. This study was aimed to explore the significance of Nrf2-ROS-MMP9 axis in BCSFB dysfunction induced by lanthanum chloride (LaCl3). Z310 cells, rat choroid plexus epithelial cells were treated with 0 mM, 0.125 mM, 0.25 mM, 0.5 mM LaCl3 for 24 h respectively, and meanwhile cotreated with tert-Butylhydroquinone (tBHQ). LaCl3 decreased the transepithelial electrical resistance (TEER) of BCSFB model in vitro, caused reduction of Z310 cells survival rate and elevation of necrosis rate, which closely related to the overproduction of ROS in cells. More intriguingly, Nrf2 pathway downregulated caused by LaCl3 given rise to improving the activation of MMP9 following excessive degradation tight junction proteins including occludin, zonula occludens-1/2, etc. in Z310 cells. But the expression of MMP9 can be alleviated possibly by tBHQ through upregulating Nrf2 pathway. Consequently, this study highlighted an innovative perspective that Nrf2-ROS-MMP-9 axis was likely the potential mechanism of La led to the BCSFB dysfunction.
Development of an immune-related gene prognostic risk model and identification of an Immune infiltration signature in the tumor microenvironment of colon cancer
Authors: Hao MengDi , Li HuiMin , Yi Meng , Wang Kun , Liu Yin , Liang XiaoQing , Ding Lei 
Published: June 2022

Abstract
Background: Colon cancer is a common and highly malignant tumor. Its incidence is increasing rapidly with poor prognosis. At present, immunotherapy is a rapidly developing treatment for colon cancer. The aim of this study was to construct a prognostic risk model based on immune genes for early diagnosis and accurate prognostic prediction of colon cancer.Results: A total of 477 DE immune genes (180 up-regulated and 297 down-regulated) were detected. We developed and validated twelve immune gene models for colon cancer, including SLC10A2, FABP4, FGF2, CCL28, IGKV1-6, IGLV6-57, ESM1, UCN, UTS2, VIP, IL1RL2, NGFR. The model was proved to be an independent prognostic variable with good prognostic ability. A total of 68 DE TFs (40 up-regulated and 23 down-regulated) were obtained. The regulation network between TF and immune genes was plotted by using TF as source node and immune genes as target node. In addition, Macrophage, Myeloid Dendritic cell and CD4+ T cell increased with the increase of risk score.Conclusions: We developed and validated twelve immune gene models for colon cancer, including SLC10A2, FABP4, FGF2, CCL28, IGKV1-6, IGLV6-57, ESM1, UCN, UTS2, VIP, IL1RL2, NGFR. This model can be used as a tool variable to predict the prognosis of colon cancer.
Evidence for Vestibular Sensory Reweighting and Improvement in Dynamic Posturography after Computerized Vestibular Retraining for Stable Unilateral Vestibular Deficit
Authors: David Eytan A. , Shahnaz Navid 
Published: June 2022

Abstract
Balance deficits increase the risk of falls and compromise quality of life. This single group, interventional study assesses a computerized vestibular retraining protocol in patients with objectively determined unilateral peripheral vestibular deficits. Participants received twelve twice-weekly sessions of vestibular retraining guided by an interactive display. Objective posturography tests and questionnaires were administered before and after retraining. We enrolled 13 participants (5 females and 8 males) with a median age of 51 years (range 18 to 67). After retraining, the median change in sensory organization test (SOT) composite scores was 8.8 (95% CI, 0.6 to 19.1). The SOT visual (median change of 0.12 [-0.09 to 0.30]) and vestibular (0.10 [-0.06 to 0.25]) ratios improved but there was no change in the somatosensory or visual preference ratios. Participants with moderate-to-severe disability at baseline (n=7), as measured by Dizziness Handicap Inventory, had a larger magnitude of improvement (SOT composite 14.6 [7.0 to 36.9]; visual ratio 0.16 [0.09 to 0.39]; vestibular ratio 0.12 [0.08 to 0.28]). We found that computerized vestibular retraining is associated with improvement in dynamic balance performance for individuals with stable unilateral vestibular deficits, consistent with sensory substitution to vestibular organs. Posturography improvements correlated with reduced perceived fall risk. Clinicaltrials.gov registration NCT04875013; 06/05/2021
Preparation of ultra-flame retardant wood materials with mechanical reinforcement and water resistance through biomimetic mineralization of carbonated apatite
Authors: Meng Dan , Wang Kaihao , Wang Shuheng , Qiu Yong , Gu Xiaoyu , Sun Jun , Li Hongfei , Zhang Sheng 
Published: June 2022

Abstract
The preparation of wood products with mechanical reinforcement, flame retardancy, and water resistance is still a problem to be solved. In this work, carbonated apatite (CAp) was biomimetically mineralized in wood vessel by the method of gradient impregnation. The CAp@wood75G sample with the weight gain of 75% showed the greatest bending strength due to the formation of organic-inorganic composites. With the high bending strength, the CAp@wood75G sample exhibited elevated limiting oxygen index (LOI) of 60.4% and passed the UL-94 V-0. In cone calorimetry, the peak of heat release rate and total heat release for CAp@wood75G sample were lessened by 68.2% and 53.1% respectively, compared with that of natural wood sample. Furthermore, the LOI of CAp@wood75G was still as high as 38.4% with V-0 rating after immersed in water for 24 h. Furthermore, the flame retardant mechanism was explored and generalized. The CAp was decomposed to produced CO2 and H2O to dilute the combustible gases in the air, and catalyzed wood to form the barrier of heat and oxygen during burning. Moreover, CAp produced inorganic salts which played the protective layer role. To conclude, this efficient processing method by bioinspired mineralization was eco-friendly and effective.
Evaluation of a novel fully automated and ELISA- based assays for detecting anti- SARS- CoV-2 neutralizing antibodies
Authors: Zedan Hadeel T. , Yassine Hadi M. , Al-Sadeq Duaa W. , Liu Na , Qotba Hamda , Nicolai Eleonora , Pieri Massimo , Bernardini Sergio , Abu-Raddad Laith J. , Nasrallah Gheyath K. 
Published: June 2022

Abstract
Background: Rapid and accurate measurement of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2)-specific neutralizing antibodies (nAbs) is paramount for monitoring immunity in infected and vaccinated subjects. The current gold standard relies on pseudovirus neutralization tests which require sophisticated skills and facilities. Alternatively, recent competitive immunoassays measuring anti-SARS-CoV-2 nAbs are proposed as a quick and commercially available surrogate virus neutralization test (sVNT). Here, we report the performance evaluation of three sVNTs, including two ELISA-based assays and a novel automated bead-based immunoassay for detecting nAbs against SARS-CoV-2. Method: The performance of three sVNTs, including GenScript cPass, Dynamiker, and Mindray NTAb was assessed in samples collected from SARS-CoV-2 infected patients (n=160), COVID-19 vaccinated individuals (n=163), and pre-pandemic controls (n=70). Samples were collected from infected patients and vaccinated individuals 2-24 weeks after symptoms onset or second dose administration. Correlation analysis with pseudovirus neutralization test (pVNT) and immunoassays detecting anti-SARS-CoV-2 binding antibodies was performed. Receiver operating characteristic (ROC) curve analysis was generated to assess the optimal threshold for detecting nAbs by each assay. Results: All three sVNTs showed an excellent performance in terms of specificity (100%) and sensitivity (100%, 97.0%, and 97.1% for GenScript, Dynamiker, and Mindray, respectively) in samples collected from vaccinated subjects. GenScript demonstrated the strongest correlation with pVNT (r=0.743, R2=0.552), followed by Mindray (r=0.718, R2=0.515) and Dynamiker (r=0.608, R2=0.369). Correlation with anti-SARS-CoV-2 binding antibodies was variable, but the strongest correlations were observed between anti-RBD IgG antibodies and Mindray (r=0.952, R2=0.907). ROC curve analyses demonstrated excellent performance for all three sVNT assays in both groups, with an AUC ranging between 0.99 and 1.0 (p <0.0001). Also, it was shown that the manufacturer’s recommended cutoff values could be modified based on the tested cohort without significantly affecting the sVNT performance.Conclusion: The sVNT provides a rapid, low-cost, and scalable alternative to conventional neutralization assays for measuring and expanding nAbs testing across a wide range of research and clinical settings. Also, it could aid in evaluating actual protective immunity at the population level and assessing vaccine effectiveness to lay a foundation for boosters’ requirements.
Viral Load Rebound in Placebo and Nirmatrelvir-Ritonavir Treated COVID-19 Patients is not Associated with Recurrence of Severe Disease or Mutations
Authors: Soares Holly , Baniecki Mary Lynn , Cardin Rhonda , Leister-Tebbe Heidi , Zhu Yuao , Guan Shunjie , Hyde Craig , He Wen , Wang Zhenyu , Hao Li , Perrin B. Scott , Bao Weihang , Chan Phylinda , Damle Bharat , Menon Sandeep , Hammond Jennifer , Anderson Annaliesa 
Published: June 2022

Abstract
Nirmatrelvir-ritonavir was developed for the treatment of COVID-19 and has shown efficacy in a Phase 2/3 study of high risk patients (EPIC-HR1). Monitoring for the emergence of viral resistance and recurrence of symptoms is a critical component of any antiviral drug development. As part of the study of viral resistance, a sub-analysis was conducted to examine viral load rebound (VLR) following nirmatrelvir-ritonavir treatment in the EPIC-HR study. Nasopharyngeal or nasal swabs were collected from all study participants at Day 1, Day 3, Day 5, Day 10, and Day 14, and analyzed for viral RNA load and next generation viral sequencing. Two categories of viral load rebound were considered including present/persistent and transient. In EPIC-HR, the proportion of present/persistent VLR was low, occurring at 1.73% (17/980) vs 2.32% (23/990) and for transient VLR 2.35% (23/980) vs 4.65% (46/990) in placebo vs nirmatrelvir-ritonavir participants, respectively. VLR occurred in both treatment arms and was not associated with low nirmatrelvir exposure, hospitalization or death, severe symptom relapse, serological status, or Mpro gene/cleavage treatment emergent mutations. In summary, viral load rebounds are likely a phenomena COVID-19 disease course and nirmatrelvir-ritonavir continue to be an important treatment option for high risk COVID-19 patients.
Studies in Gyromitra II: Cryptic speciation in the Gyromitra gigas species complex; rediscovery of G. ussuriensis and G. americanigigas sp. nov.
Authors: Miller Andrew N. , Dirks Alden C. , Filippova Nina , Popov Eugene , Methven Andrew S. 
Published: June 2022

Abstract
Taxa in the Gyromitra gigas species complex were previously studied and their taxonomy resolved. During ongoing studies in this group, cryptic speciation was discovered in G. gigas. Sequences of the ITS and LSU regions from 75 specimens were included in maximum likelihood and Bayesian phylogenetic analyses to establish species boundaries and resolve species relationships. Sequence similarity comparisons were also conducted between the two ribosomal markers and between the ITS1 and ITS2 regions. Gyromitra gigas sensu stricto and two additional species were discovered within the G. gigas clade. Gyromitra ussuriensis was rediscovered as a distinct taxon and removed from synonymy under G. gigas. It occurs in central and eastern Asia, whereas G. gigas occurs mostly in Europe but also extends into central Asia. A neotype is designated for G. ussuriensis. A new species, Gyromitra americanigigas, is described and illustrated from eastern North America. Although morphology and the LSU exhibited little variation among the three species, the ITS1 and ITS2 regions displayed similar interspecific sequence variability around 0.5–1%, which is sufficient for species identification at the molecular level.
Experimental study of the influence of swing grinding parameters on machining surface quality of large-width Cam
Authors: Sun Li , Dong Baojiang , Lu Jie , Zhou Honggen , Chen Jianzhi , Li Guochao 
Published: June 2022

Abstract
Large-width Cam has been widely used in high-power marine diesel engines, due to its well strength, wear-resisting, and service life. Unlike the traditional cam, the large-width Cam must be ground by swing grinding process to avoid grinding defects caused by high machining temperature. As the influence of swing grinding parameters on machining surface quality has not been clearly clarified, experimental study was discussed in the paper. The orthogonal experiment was designed and based on which the residual stress, surface roughness and hardness were analyzed. The results showed that, the grinding depth and the cam speed, have a relatively great influence on the residual stress compared with grinding wheel swing frequency and swing amplitude. The grinding wheel frequency has the greatest influence on the hardness of the cam surface and the increment of it will increase the hardness of the Cam.
Microbiostratigraphy of Miocene Guri Member of Mishan Formation in the Bandar Abbas area, SE Zagros, Iran
Authors: Gholamalian Hossein , Rameshgar Reyhaneh , Sharif-Abad Fatemeh Lotfi , Azizi Mahsa 
Published: June 2022

Abstract
Three sections of Guri Member of Mishan Formation in the Bandar Abbas area are investigated for foraminifer biostratigraphy and lithostratigraphic correlation. The base of Guri Member conformably overlies Gachsaran and\or Razak Formation, the top overlain by marly member. Thirty four foraminifer species are identified and prove the age of Burdigalian for Guri Member in the Gery Sheikh and Anguran sections and Burdigalian – Langhan range in the Bāz section. Two assemblage zones are recognized based on distribution range of species. Correlation to other sections shows the eastward marine progression and age change from the Burdigalian in the west to Burdigalian – Langhian in the east of Bandar Abbas area.
Resting-state EEG functional networks organization and individual differences in the task-unrelated thoughts: Greater Mind-Wanderers exhibit weaker default mode network integration
Authors: Krukow Paweł , Jonak Kamil 
Published: June 2022

Abstract
When performing cognitively demanding tasks, we all sometimes experience a momentary distractions or our stream of consciousness is intercepted by personal associations. This phenomenon is called Mind Wandering (MW) and it became a subject of neuroscientific investigations. Off-task thoughts can be analyzed during task performance, but currently MW is also understood as a dimension of individual differences in cognitive processing. We wanted to recognize the intrinsically-organized functional networks which could be considered as the neuronal basis for the MW dispositional variability. To achieve this goal we have recruited a group of normal adults, the group was eventually divided in half on the basis of participants scores on the scale measuring dispositional MW. Next, these groups were compared regarding arrangement of preselected intrinsic functional networks which were reconstructed on the basis of multi-channel signal-source resting-state EEG. It appeared that subjects who tend to mind wander often exhibited decreased synchronization within the default mode network, and simultaneously strengthened connectivity between ‘on-task’ networks of diverse functional specificity. Such within- and between networks integrity patterns might suggest that greater Mind Wanderers have atypical organization of resting-state brain activity which may translate into attenuated resources needed to maintain attentional control in task-related conditions.
A research method to improve the quality of box-type thin-walled parts by combining parameter optimization and i nverse-deformation design
Authors: Zhai Haorui , Chang Ying , Li Xiaodong , Xiong Xin , Zhu Wuwei , Li Chuqing , Wang Yongqing 
Published: June 2022

Abstract
In this paper, a five-part study on the molding quality of box-type thin-walled injection molded parts with volume shrinkage and warpage deformation was conducted. In the first part, the molding parameters: filling time, plastic temperature, mold temperature (C), holding time (D), maximum holding pressure (E), and cooling time (F) were selected, and a six-factor, five-level L25 (5 6 ) orthogonal experimental design (OED) was designed. Then, the optimal combination of molding parameters was optimized by using gray correlation (GC) theory analysis. In the second part, the six molding parameters from the first part were further optimized based on the Box Behnken Design (BBD) response surface method (RSM) and BP neural network (BPNN) training, and the results showed that the fitted regression model after BPNN training had a smaller prediction error. In the third part, the regression models fitted with BBD and BPNN-BBD are further optimized globally. The optimization search method uses the NSGA-II genetic optimization algorithm. And comparing the above four optimization methods found that BPNN-BBD-NSGA-II prediction error < BPNN-BBD prediction error < BBD-NSGA-II prediction error < BBD prediction error. The fourth part is based on the anti-deformation design (ADD) theory. The NX/Moldex3D global optimization platform is created to finally almost completely eliminate warpage deformation of box-type thin-walled injection molded parts. In the last part, a trial mold verification analysis was performed, and the molding quality data was obtained by using optical scanning instruments, and the GOM software was used to compare and analyze the deviation values of each appearance surface and the flatness values.
Applying the CRISPR-Cas9 system to targeted transgene integration in the development of recombinant lepidopteran insect cells
Authors: Matsuda Takuya , Togami Shinya , Masumi-Koizumi Kyoko , Kahar Prihardi , Katsuda Tomohisa , Yamaji Hideki 
Published: June 2022

Abstract
The clustered regularly interspaced short palindromic repeats-CRISPR-associated protein 9 (CRISPR-Cas9) system is a widely used genome editing tool, but its application for the development of stably transformed lepidopteran insect cells for recombinant protein production has been limited. In the present study, we applied the CRISPR-Cas9 system to the targeted transgene knock-in to efficiently develop recombinant insect cells. A double-strand break (DSB) in a target site of the genome of Trichoplusia ni BTI-TN-5B1-4 (High Five) cells was detected by T7 endonuclease assay after the cells were transfected with a plasmid for genome editing by employing a U6-4 promoter derived from T. ni to drive guide RNA (gRNA). Genomic DNA analysis via PCR confirmed the integration of a transgene into a target site of the High Five cell genome. The length of the homology arm affected the genome editing efficiency, and the use of a 500-bp version proved to be optimal. Via the co-transfection of High Five cells with gRNA-Cas9 plasmid and a donor vector harboring a reporter gene and the neomycin resistance gene, 21 clones of stably transformed cells were established. In 19 of those clones a site-specific knock-in of the reporter gene at the target site was confirmed, which indicates that an exogenous gene can be efficiently integrated into a target site of the High Five cell genome via the CRISPR-Cas9 system, though transcriptional hot spots in the genome should be identified to establish highly productive recombinant cells.