bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overcoming Chemoresistance to Vemurafenib in Melanoma via Targeted Inhibition of PCK1 Using 3-mercaptopropionic Acid
Authors: Ren Ming , Wang Lu , Deng Xin-Yi , Gao Zi-Xu , Wang Qiang , Tao Meng-Yuan , Shen Kang-Jie , Ding Yi-Teng , Qian Le-Qi , Wei Chuan-Yuan , Gu Jian-Ying 
Published: May 2021

Abstract
Background:BRAF inhibitors are the mainstay treatment for melanoma with the V600E mutation, but its resistance to BRAFi remains a clinical challenge. Therefore, it is necessary to explore the mechanism of BRAFi resistance and develop new therapeutic targets. Methods:We established an A2058 melanoma cell line with acquired resistance to vemurafenib in vitro. RNA sequencing was used to identify the target gene and signaling pathway which were related to the resistance.A series of in vitro assays were applied to confirm the function of PCK1, including test of scratch,transwell,cell viability,flow cytometry,sphere formation,western blot and ROS detection.Western blot was taken to identify the activation of PI3K/Akt pathway.We constructed the subcutaneous xenograft model of melanoma,and the mice were randomly injected with DMSO,vemurafenib,and combination of vemurafenib and 3-mercaptopropionic acid.Finally, tumor size,ROS in tissue,and immunohistochemistry were analyzed to validate the findings.Results:We identified that the activation of PI3K/Akt pathway led to the overexpression of phosphoenolpyruvate carboxykinase 1, a key enzyme of gluconeogenesis. An elevated PCK1 level induced intracellular metabolic reprogramming, thereby lowering oxidative stress contributed to the chemoresistance to vemurafenib. 3-mercaptopropionic acid , an antihyperglycemic agent, could inhibit the viability of PCK1 then bring oxidative damage to drug-resistant cells. As a result, 3-mercaptopropionic acid sensitized the cells to the killing effect of vemurafenib, exerting a synergistic anti-tumor effect in combination with vemurafenib. Conclusions:Our study demonstrates that the PI3K/Akt-PCK1-ROS axis plays an important role in BRAFi-resistant melanoma and that using the antihyperglycemic agent 3-MPA is a feasible strategy to restore its therapeutic sensitivity.
High Voc Fullerene-Free Organic Photovoltaics Composed of PTB7 and Axially-Substituted Silicon Phthalocyanines
Authors: Vebber Mario , Rice Nicole A. , Brusso Jaclyn L. , Lessard Benoît H. 
Published: May 2021

Abstract
While the efficiency of organic photovoltaics (OPV) has improved drastically in the past decade, such devices rely on exorbitantly expensive materials that are unfeasible for commercial applications. Moreover, examples of high voltage single-junction devices, which are necessary for several applications, particularly low-power electronics and rechargeable batteries, are lacking in literature. Alternatively, silicon phthalocyanines (R2-SiPc) are inexpensive, industrially scalable organic semiconductors, having a minimal synthetic complexity (SC) index, and are capable of producing high voltages when used as acceptors in OPVs. In the present work, we have developed high voltage OPVs composed of Poly({4,8-bis[(2-ethylhexyl)oxy]benzo[1,2-b:4,5-b′]dithiophene-2,6-diyl}{3-fluoro-2-[(2-ethylhexyl)carbonyl] thieno [3,4 b]thiophenediyl}) (PTB7) and an SiPc derivative ((3BS)2-SiPc). Interestingly, while changes to the solvent system had a strong effect on performance, the PTB7:3BS-SiPc active layer were robust to spin speed, annealing and components ratio. This invariance is a desirable characteristic for industrial production. All PTB7:(3BS)2-SiPc devices produced high open circuit voltages between 1.0 and 1.07 V, while maintaining 80% of the overall efficiency, when compared to their fullerene-based counterpart.
Comparison of In-hospital Mortality Prognostic Accuracy of the pSOFA Score and SIRS Criteria Among Children With Infection Admitted to Pediatric Intensive Care Units: A Retrospective Multi-center Cohort Study
Authors: Zhao Chun , Xin Meiyun , Li Jing , Zhao Jinfang , Wang Yujuan , Wang Wei , Gao Qian , Chen Jie , Wang Qiwei , Jin Youpeng 
Published: May 2021

Abstract
Background: The sepsis version 3.0 highlights the co-existence of infection with organ dysfunction, assessed by the Sequential Organ Failure Assessment (SOFA) score. However, the prognostic accuracy of the Pediatric SOFA score (pSOFA) for in-hospital mortality was not fully validated. We compared the performance of the pSOFA with the SIRS criteria as predictors of in-hospital mortality in children with infectious disease and evaluate whether the pSOFA is suitable to be used in pediatric intensive care units (PICU) in Shandong Province, China.Methods::A retrospective multicenter cohort study was conducted on children hospitalized with confirmed or suspected infection, between January 2011 and December 2019, in three PICUs of three tertiary care hospitals in Shandong Province. The maximum pSOFA score and SIRS criteria within the first 24 hr of PICU admission were calculated. Univariate and multivariate logistic regressions were conducted to analyze the risk factors for in-hospital mortality. Three sub-components of the pSOFA score with relatively good predictive value were identified according to the Yuden Index and formed a simple-pSOFA score. The efficiency and diagnostic ability of these scores were compared by measuring the area under the receiver operating characteristic curve (AUROC) and Delong’s test.Results: 1092 patients were included and the overall in-hospital mortality was 23.4%. Multivariate logistic regressions showed that high 24h pSOFA score, bloodstream as the main infection site, and the need for MV were the risk factors for in-hospital mortality. The AUROC analysis verified that simple-pSOFA had the best diagnostic ability in predicting in-hospital mortality of infected children compared with the 24h pSOFA score and SIRS criteria. The sensitivity and specificity of 24h pSOFA score ≥2 were the highest, 97.6% and 78.9%, respectively.Conclusions: The pSOFA score was superior to SIRS criteria in identifying children with infection and a high risk of mortality, but it is expensive and time-consuming to complete the pSOFA score. Simple-pSOFA score is superior to pSOFA score in early identification of infected children with a high risk of death, but further validation studies with a larger size is needed.
A geometric progression on the mass of elementary fermions
Authors: Mishulan Li-Gong 
Published: May 2021

Abstract
The Standard Model of particle physics contains three generations of elementary fermions, which have prominent mass hierarchies. Through careful analysis of the observational data on the mass of elementary fermions, we determine that an intrinsic pattern does exist. A geometric progression is proposed to describe the mass distribution of elementary fermions, and using the observational data of neutrino oscillations, we can estimate the neutrino masses for all three generations. At the same time, we propose a hypothesis about the mass distribution of elementary fermions and explore the quantum physical mechanism of the origin of the elementary fermions masses hierarchies.
Biomechanical Role of Fibula in Lower Limbs: a Fracture Mechanics Analysis
Authors: Shao Bin , Xing Jianqiang , Liu Dong , Wang Dawei , Zhao Bei , Wang Tingguang , Mu Weidong 
Published: May 2021

Abstract
Background Fibular grafting is widely used in the treatment of various bone nonunion and bone defect because of its good therapeutic effect. Besides, partial fibular resection has also been used as a treatment for fibular tumors, injuries, etc. However, fibula plays an important role in the biomechanics of the lower limbs. Some experts have used cadaver specimens to study these aspect. In this study, the biomechanical effects of fibula in lower limbs were researched based on mechanics analysis.Methods The CT image data of a middle-aged male normal knee joint were selected. The tibia and fibula were extracted by CT-bone function in Mimics software, and the 3D model of tibia and fibula was obtained. The model was imported into 3-matic and LS-DYNA software to smooth the surface, mesh, define material properties, set failure parameters and interface properties, and set vertical loads and boundary conditions. The tibial fractures in both models were calculated to evaluate the biomechanical role of the fibula in the lower leg.Results The validity of the model was verified, and the fibula load condition was similar to the previous references. In the model with fibula support, the fracture load of the tibia was 78.5KN, the initial fracture time was 0.67164S, and the complete fracture time was 0.73225S. The fibula distributes about 7% of the load on the lower leg. In the fibula defect model, the fracture load of tibia was 73.5KN, the initial fracture time was 0.54034S, and the complete fracture time was 0.61105S.Conclusions Fibula plays an irreplaceable biomechanical role in the process of lower limb load-bearing, which is worthy of clinical attention. Meanwhile, LS-DYNA can be used as an effective tool for bone fracture and numerical analysis.
Relationship Between Hyperuricemia and Apolipoprotein AI in Chinese Healthy People: a Cohort Study
Authors: Duan Yan , Chang Xiaona , Ding Xiaoyu , An Yu , Wang Guang , Liu Jia 
Published: May 2021

Abstract
Background: Hyperuricemia is an independent risk factor for various cardiovascular diseases. However the association of plasma uric acid and Apolipoprotein AI among Chinese healthy people is still unclear.Aims: To evaluate the relationship between blood uric acid and Apolipoprotein AI level in Chinese healthy people. Method; A total of 3501 normal healthy subjects who were undergone physical examination were divided into hyperuricemia (HUA) group and normouricemia (NUA) group.Result: Apo AI (1.33±0.21 vs. 1.47±0.26) and HDL-c (1.12±0.27 vs. 1.36±0.33)decreased significantly in HUA group than NUA group. LDL-C(2.81±0.77 vs. 2.69±0.73),Apo B(0.96±0.20 vs. 0.89±0.20), FBG(5.48±0.48 vs. 5.36±0.48) and HOMA-IR(2.75（1.92-3.91）vs. 2.18（1.50-3.12）) was significantly higher in HAU group than NUA group. Increased plasma UA was correlated with decreased HDL-c(r=-0.289, P<0.01 ) and Apo AI(r=-0.236, p<0.01) .Conclusion: Hyperuricemia was associated with decreased plasma Apolipoprotein AI and HDL-c. Inhibiting Apolipoprotein AI may be one of the mechanisms of UA involved in the progression of cardiovascular disease.
Landscape-scale Remote Sensing and Classification of Pond and Lake Habitat Diversity in a Tropical City
Authors: Teo Hoong Chen , Hill Matthew J. , Lechner Alex M. , Teo Fang Yenn , Gibbins Christopher N. 
Published: May 2021

Abstract
Ponds and lakes are common freshwater habitats in urban landscapes, and often have a high biodiversity and conservation value. The importance of landscape-scale conservation of pond networks has recently been recognised, yet the categorisation and classification of pond network spatial structures is missing. Developing spatial methods and tools to characterise and understand pond networks is a critical first step to accurately conserve pond habitats and inhabiting species. This paper presents an inventory of ponds and lakes in Greater Kuala Lumpur, Malaysia, characterising their distribution, abundance and type. Remote sensing was first employed to map and characterise these habitats, followed by multivariate cluster analysis to classify and develop a typology of the ponds identified. Physicochemical data was collected from a sample (n=60) of ponds to compare with the remotely sensed pond classification. Results demonstrated that multi-source remote sensing can be highly accurate and effective in inventorying ponds and lakes of varying sizes. A total of 1013 ponds and lakes were identified within the Greater Kuala Lumpur region and were found to be highly environmentally heterogeneous. Typology clusters were driven by land cover rather than local physicochemical variables demonstrating that specific remotely-sensed variables may be sufficient proxies for certain chemical variables. Landscape-scale conservation and management of pond networks should utilise remote sensing tools, to establish pond network structure, and to maintain wide environmental heterogeneity among pond habitats. Incorporating remote sensing tools into pond conservation will ensure that effective pond conservation can be achieved and biodiversity protection can be maximised.
Competency Development for Military Nursing: Developing the Competency Framework for Global Health
Authors: Ma Huijuan , Cheng Zhen , Tan Jing , Luo Yu 
Published: May 2021

Abstract
Background: As military nurses are required to maintain high level of clinical expertise and currency for short-notice deployments of global health missions, competency assessment and capability building is a basic paradigm of military nursing. However, research focusing on the competencies of military nurses is limited.Methods: A two-phased procedure was implemented. In phase 1, the competency framework was developed by scoping review and crosschecking the common used competency framework of nurses. During phase 2, two rounds of a Delphi process were carried out and a penal of experts used a 5-point Likert scale to rate their level of agreement with the competency statement. Results: Experts of military nursing and military medicine responded to the first round (n = 19), and the second round (n = 19). The final competency framework consisted of 67 competencies and was classified into five domains: clinical nursing knowledge and skills, military nursing knowledge and skills, professional ability, management ability, and comprehensive quality. Conclusion: The competency framework developed in this study lays solid foundation for competency-based education of a competent nursing team to play a significant role in the global health.
Protective Effect of SCUBE1 on Oxidative Stress-induced Apoptosis in Human Ovarian Granulosa Cells
Authors: Fu Huijiao , Cai Xuzi , Liu Qiwen , Yang Wei , Wang Xuefeng 
Published: May 2021

Abstract
Background: Apoptosis of ovarian granulosa cells (GCs) is a sign of follicular atresia. This study aimed to explore the role and mechanism of signal peptide, CUB domain, epidermal growth factor-like protein1 (SCUBE1) in protecting GCs from apoptosis induced by hydrogen peroxide (H2O2). Results: SCUBE1 was expressed in women of all ages and had the highest expression level in the ovaries in multiple organs and tissues of KM mouse. In vitro cell experiments show that SCUBE1 pretreatment reduced H2O2-induced apoptosis and improved cell viability. SCUBE1 also blocked the production of ROS in cells and improved mitochondrial membrane potential. After SCUBE1 pretreatment, anti-apoptotic protein Bcl-2 expression was upregulated, whereas the expression of the pro-apoptotic proteins Bax, Bax/Bcl-2, Caspase-3, and p53 were downregulated. Analysis of the impact of SCUBE1 (c.1169C >G, p.P390R) mutation from the aspect of mutation pathogenicity; protein stability; and gene haplotype insufficiency, indicated that the p.P390R mutation is significantly pathogenic.Conclusions: This is the first time that the potential role of SCUBE1 in protecting GCs from H2O2-induced damage by blocking the production of ROS, increasing the mitochondrial membrane potential and regulating apoptosis-related proteins, attributing to POI, is studied. SCUBE1 (c.1169C >G, p.P390R) mutation has significant pathogenicity but the specific harm needs to be confirmed by further studies.
Trans-apical Aortic Valve Implantation for Quadricuspid Aortic Valve With Aortic Regurgitation Using J-valve System: A Case Report
Authors: Luo Chaodi , Jiang Yi , Yan Yang , Han Dan 
Published: May 2021

Abstract
Background: Quadricuspid aortic valve (QAV) is a rare congenital heart defect usually accompanied with different hemodynamic abnormalities. Due to the rarity of QAV, treatment and prognosis of QAV patients with aortic regurgitation still remain challenging. We here present the first case of a patient with severe QAV regurgitation who underwent successful treatment and performed favorable prognosis with transapical aortic valve implantation (TAVI) using J-Valve system.Case presentation: A 62-year-old man experienced intermittent palpitation, shortness of breath and chest pain. Echocardiography revealed congenital QAV with massive aortic regurgitation and mild aortic stenosis, left ventricular enlargement. Aortic valve replacement was successfully performed with TAVI using J-Valve system. The postoperation and follow-up was uneventful.Conclusion: Transapical aortic valve implantation (TAVI) using J-Valve system has emerged as a new high success rate method for treatment of high-risk patients with simple non-calcified aortic valve insufficiency.
Clinical characteristics and outcomes of neonates with polymicrobial ventilator-associated pneumonia in the intensive care unit
Authors: Wang Hsiao-Chin , Tsai Ming-Horng , Chu Shih-Ming , Liao Chen-Chu , Lai Mei-Yin , Chiang Ming-Chou , Fu Ren-Huei , Hsu Jen-Fu , Huang Hsuan-Rong 
Published: May 2021

Abstract
Background: Ventilator associated pneumonia (VAP) caused by more than one microorganisms is not uncommon and may be potentially challenging, but the relevant data is scarce in ventilated neonates. We aimed to investigate the clinical characteristics and outcomes of polymicrobial VAP in the neonatal intensive care unit (NICU).Methods: All neonates with definite diagnosis of VAP from a tertiary level neonatal intensive care unit (NICU) in Taiwan between October 2017 and September 2020 were prospectively observed and enrolled for analyses. All clinical features, therapeutic interventions and outcomes were compared between the polymicrobial VAP and monomicrobial VAP episodes. Multivariate regression analyses were used to find the independent risk factors for treatment failure. Results: Among 236 episodes of neonatal VAP, 60 (25.4%) were caused by more than one microorganisms. Polymicrobial VAP episodes were more likely to be associated with multidrug-resistant pathogens (53.3% versus 34.7%, P = 0.014), more often occurred in later days of life and in neonates with prolonged intubation and underlying bronchopulmonary dysplasia. Otherwise most clinical characteristics of polymicrobial VAP were similar to those of monomicrobial VAP. The therapeutic responses and treatment outcomes were also comparable between these two groups, although modification of therapeutic antibiotics were significantly more common in polymicrobial VAP episodes than monomicrobial VAP episodes (63.3% versus 46.2%; P<0.001). None of any specific pathogens was significantly associated with worse outcomes. Instead, it is the severity of illness, including presence of concurrent bacteremia, septic shock, and requirement of high-frequency oscillatory ventilator and underlying neurological sequelae that are independently associated with treatment failure.Conclusions: Polymicrobial VAP accounted for 25.4% of all neonatal VAP in the NICU, and frequently occurred in neonates with prolonged intubation and underlying bronchopulmonary dysplasia. In our cohort, most clinical features, therapeutic responses and final outcomes of neonates with monomicrobial and polymicrobial VAP did not differ significantly.
Bio-mimetic synthesis of catalytically active nano-silver using Bos taurus (A-2) urine
Authors: Sarvalkar Prashant D , Mandavkar Rutuja R , Nimbalkar Mansingraj S , Sharma Kiran K , Patil Pramod S , Prasad Neeraj R , Kamble Ganesh S 
Published: May 2021

Abstract
Bio-molecules present in liquid metabolic waste of an Indian cow are effectively used to reduce silver (Ag) ions into Ag nanoparticles (Ag NPs) in one step. This bio-inspired electron transfer to Ag ion for the formation of base Ag metal is fairly prompt and facile. These nanoparticles act as a positive catalyst for various organic transformation reactions. The X-RD pattern of the synthesized product confirmed the formation of Ag nanoparticles. The bio-mimetic Ag NPs show potential activity for degradation of dyes under study. Herein, we have successfully carried out several reduction reactions of nitro groups using Ag nanoparticles as a heterogeneous nanocatalyst.
Prognostic Significance of NBEAL2 in Liver hepatocellular carcinoma
Authors: Wen Yanghui , Su Hui , Wang Wuke , Ren Feng , Jiang Haitao , Wang Jie , Xiang Jianjian , Chen Yunjie 
Published: May 2021

Abstract
Background: NBEAL2 is a member of the BEACH domain–containing protein (BDCP) family and little is known about the relationship between NBEAL2 and malignancy.Methods: We downloaded the Gene expression profiles and clinical data of Liver hepatocellular carcinoma(LIHC) form the Cancer Genome Atlas (TCGA) dataset. The expression difference of NBEAL2 in LIHC tissues and adjacent nontumor tissues was analyzed by R software. The relationship between NBEAL2 expression and clinicopathological parameters was evaluate by Chi-square test. The effect of NBEAL2 expression on survival were assessed by Kaplan–Meier survival analysis and Cox proportional hazards regression model. GSEA was used to explore the potential molecular mechanism of NBEAL2 in LIHC.Results: Up-regulation of NBEAL2 expression was detected in the LIHC tissue compared with adjacent nontumor tissues(P < 0.001). The chi-square test showed that no significant correlation between the expression level of NBEAL2 and various clinicopathological parameters (including T, N and M classifications) were detected. The Kaplan–Meier curves suggested that lower NBEAL2 expression was related with poor prognosis. The results of Multivariate analysis revealed that a lower expression of NBEAL2 in LIHC was an independent risk of poor overall survival (HR, 8.873; 95% CI, 1.159-67.936; P = 0.035). GSEA suggested that multiple tumor-related metabolic pathways were evidently enriched in samples with the low-NBEAL2 expression phenotype. Conlusion: NBEAL2 might act as an tumor suppressor gene in the progression of LIHC but the precise role of NBELA2 in LIHC needs further vertification.
Identification of Tumor Microenvironment-Related Genes in Kidney Renal Clear Cell Carcinoma Patients via Bioinformatic Analysis
Authors: Zheng Rongjiong , SHao Yaosen , Wang Mingming , Tang Yeli , Hu Meiling 
Published: May 2021

Abstract
BackgroundTumor microenvironment has been implicated in the development and progression of cancers. However, the prognostic significance of tumor microenvironment-related genes in kidney renal clear cell carcinoma (KIRC) remains unclear. MethodsIn this study, we obtained and analyzed gene expression profiles from The Cancer Genome Atlas database. Stromal and immune scores were calculated based on the ESTIMATE algorithm. ResultsIn the discovery series of 537 patients, we identified a list of differentially expressed genes which was significantly associated with prognosis in KIRC patients. Protein-protein interaction networks and functional enrichment analysis were both performed, indicating that these identified genes were related to the immune response. ConclusionsThe tumor microenvironment-related genes could serve as the potential biomarkers for KIRC.