bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Prognostic Biomarkers of Potential Hub Genes in Urothelial Carcinoma and Function in Microenvironment
Authors: Chu Wei , Zhang Bing , Gong Haifeng , Zhao Qianqian , Chen Jun , Ji Hong 
Published: July 2021

Abstract
Background: Urothelial carcinoma (UC) is the most common histological type of urinary system. In the past decades, despite the advances in UC diagnosis and therapy, there are still challenges to improve the overall survival (OS) of UC patients. PD-L1 inhibitor and PD-1 inhibitor have been approved for treating invasive UC, however, only about 20% of patients with metastatic UC show clinical benefits from immune checkpoint inhibitors. Therefor, bioinformatics tools were utilized to screen prognostic-related biomarkers, and analyze their relationship with immunocyte in UC, hoping to provide new ideas for the clinical treatment of UC patients.Methods: Three gene expression profiles (i.e. GSE32548, GSE32894 and GSE48075) were selected from GEO, and divide them into invasive and superficial UC group for study. NetworkAnalyst tool was used to construct gene regulatory network of DEGs, while DAVID and Metascape were utilized to perform GO/KEGG enrichment analysis of DEGs. The hub genes were screened by STRING and cytoscape, and the ONCOMINE, GEPIA, UALCAN, cBioPortal and HPA databases were used to analyze the expression differences at the DNA, RNA, protein levels and prognostic of UC. TIMER was used to analyze the relationship between hub genes and immunocyte infiltration.Results: In total, 63 DEGs were identified from the GEO database of UC, of which 31 and 32 were up-and down-regulated. GO/KEGG pathway analysis identified DEGs were mainly enriched in the collagen catabolic process, extracellular matrix (ECM) organization, ECM structural constituent and ECM-receptor interaction. Nine hub genes (i.e. COL1A1, COL1A2, COL3A1, COL5A2, MMP9, POSTN, SPP1, VCAN and THBS2) upregulated in invasive UC compared with superficial UC were identified. cBioportal database analysis showed that 35% of UC patients presented genetic variants in the hub genes, of which amplification and deletion mutations were the most common. ONCOMINE and UALCAN database analysis showed that the mRNA expression of all hub genes in invasive UC was significantly higher than that in superficial UC and normal tissues. HPA database analysis showed that there was up-regulation of COL3A1, SPP1, POSTN and VCAN protein in UC tissues than in normal tissues. GEPIA showed that COL1A2, COL3A1, THBS2, and VCAN were positively correlated with the OS rate among patients with UC (P < 0.05). UALCAN showed that UC patients with high expression of COL1A1, COL1A2, COL5A2 and POSTN had a poorer prognosis (P < 0.05). TRRUST database analysis indicated that there was a significant correlation between the expression of the hub genes and the infiltration of CD4+T cells, CD8+T cells, macrophages, neutrophils and dendritic cells. Conclusion: Hub genes played important roles in pathogenesis and treatment prognosis of UC and they can provides new biomolecular predictions for immunotherapy and prognosis judgment of UC.
Characterization and Mutagenesis of a Novel Mycobacterium Smegmatis -Derived Glutamate Decarboxylase Active at Neutral pH
Authors: Li Yudi , Chen Guiying , Ge Fanglan , Dang Ting , Ren Yao , Shi Fengfei , Chen Hongjin , li wei 
Published: July 2021

Abstract
γ-aminobutyric acid (GABA) has various physiological functions and is widely used in medicine, food, and other fields. Glutamate decarboxylase (GAD) is a key enzyme that catalyzes the decarboxylation of L-glutamate to synthesize GABA. However, the industrial application of microorganism-derived GAD is limited by its rapid loss of enzymatic activity with pH approaching neutrality. In this study, a novel glutamate decarboxylase, GAD MSM, from Mycobacterium smegmatis was overexpressed and purified. On the basis of homologous modeling and substrate molecular docking, several GAD MSM mutants were constructed, and their enzymatic properties were analyzed. The results showed that the optimal pH of wild-type GAD MSM is 5.4; at pH 6.2, 22.8% enzymatic activity was retained; the T211 amino acid residue and C-terminal deletion mutant GAD MSMΔC showed relatively high catalytic activity in a pH range of 5.0–7.0. The V max and K m values of GAD MSMΔC were 14.69 and 5.70, respectively, at pH 5.5, and 9.87 and 6.17, respectively, at pH 7.0. Compared with the wild-type GAD, GAD MSMΔC still maintained higher affinity and enzymatic activity of the substrate, maintaining 78.5% of the highest enzymatic activity even at pH 7.0, which is the highest reported activity retention for GAD under neutral pH condition. Therefore, GAD MSMΔC can be used for the transformation of high-yielding strains and industrial production of GABA.
The Pandemic Stressor Scale – Factorial Validity and Reliability of a Measure of Stressors During a Pandemic
Authors: Lotzin Annett , Ketelsen Ronja , Zrnic Irina , Lueger-Schuster Brigitte , Böttche Maria , Schäfer Ingo 
Published: July 2021

Abstract
Background: This study aimed to assess the factorial validity and reliability of the Pandemic Stressor Scale (PaSS), a new measure to assess the severity of distress for different stressors relevant during a pandemic or epidemic. Methods: The PaSS was administered in N = 2760 German participants. Exploratory factor analysis was used to extract factors. The factor structure obtained in the German sample was examined in N = 1021 Austrian participants using confirmatory factor analysis. χ², RMSEA, SRMR, CFI, TLI were assessed as global goodness of fit indices for two models (Model 1: nine-factor model; Model 2: nine-factor model combined with a second-order general factor). We additionally assessed factor loadings, communalities, factor reliability, discriminant validity as local fit indices. Internal consistency, item discrimination, and item difficulty were assessed as additional test quality criteria.Results: The results of the exploratory factor analysis suggested a nine-factor solution with factor loadings accounting for 50.4% of the total variance (Factor 1 ‘Problems with Childcare’, Factor 2 ‘Work-related Problems’, Factor 3 ‘Restricted Face-to-Face Contact’, Factor 4 ‘Burden of Infection ‘, Factor 5 ‘Crisis Management and Communication’, Factor 6 ‘Difficult Housing Condition’, Factor 7 ‘Fear of Infection’, Factor 8 ‘Restricted Access to Resources’, Factor 9 ‘Restricted Activity’). The confirmatory factor analysis showed a sufficient global fit for both tested models (Model 1: χ² (369, N =1021) = 1443.28, p < .001, RMSEA = .053, SRMR = .055, CFI = .919, TLI = .904; Model 2: χ² (396, N = 1021) = 1948.51, p < .001, RMSEA = .062, SRMR = .074, CFI = .883, TLI = .871). The results of the chi-square difference test indicated a significantly better model-fit of Model 1 compared to Model 2 (∆χ² (27, N = 1021) = 505.23, p < .001). Local goodness of fit indices were comparable for both tested models. We found good factor reliabilities for all factors and moderate to large factor loadings of the items as indicators. In Model 2, four first-order factors showed small factor loadings on the second-order general factor. Conclusion: The Pandemic Stressor Scale showed sufficient factorial validity for the nine measured domains of stressors during the current COVID-19 pandemic.
PEX-168 Improves Insulin Resistance, Inflammatory Response and Adipokines in Simple Obese Mice: A Mechanistic Exploration
Authors: Guo Zeyuan , Wu Yuting , Sun Xiaofang 
Published: July 2021

Abstract
Background：Polyethylene glycol losenatide (PEX-168) is a new antidiabetic drug; as such, there are not yet any reports on its weight loss effect. Therefore, this trial was designed to investigate the effect of PEX-168 on simple obese mice.Methods：Thirty healthy male C57BL/6 mice were randomly selected and divided into a control group (NC) and an obesity model group. The high-fat diet-induced simple obesity mice were divided into a model control group (HF) and three intervention groups. The intervention groups were injected with different doses of PEX-168 intraperitoneally once a week for 12 weeks (low (LD), medium (MD) and high (HD)). Fasting blood glucose (FBG), body weight and food intake were measured from 1 to 12 weeks after PEX-168 injection. The serum insulin (INS), C-reactive protein (CRP), chemerin and omentin levels were measured after 12 weeks.Results：Compared with the HF group, the low dose of PEX-168 reduced the body weight of the mice in a short period of time (8 weeks), and the mice in the LDand HD groups showed a significant decrease in body weight (P < 0.05). The low dose of PEX-168 could effectively improve the blood glucose and insulin resistance index (Homa-IR) of the mice (FBG P < 0.05 INS, Homa-IR P < 0.001), but there was no significant difference between different doses (P > 0.05). CRP levels in the HD and LD groups were significantly improved (P < 0.05). The levels of serum chemerin and omentin in the intervention groups were also significantly improved (P < 0.01), but there was no significant difference between the different doses (P > 0.05).Conclusion：PEX-168 significantly reduced the body weight of simple obese mice and prevented the development of diabetes. PEX-168 may regulate the expression of chemerin and omentin mainly through its hypoglycaemic effect, and the weight-reducing effect of PEX-168 is unlikely to be the reason for the changes in both.
Isotopic signature in integration with hydrochemistry to infer the groundwater quality in alluvial aquifer, Jhajjar district, Haryana, NCR, India
Authors: Kumari Rina , Kumar Sudhir , Rao Mavidanam Someshwar , Mukherjee Saumitra , Sen Ratan 
Published: July 2021

Abstract
In many Asian megacities, millions of human inhabitants are dependent on groundwater for fulfilling daily water demand due to lack of public water supply and infrastructure. Many of these megacities are situated on alluvial plains which are more susceptible to contamination also. The present study has been carried out in Jhajjar District, Haryana, a part of Indo-Gangetic Plain, India. Indo-Gangetic plain, harbour one of the most productive alluvial aquifer of the world and plays an important role in Indian economy. After green revolution, in a large part of Indo-Gangetic plain groundwater salinization and contamination has been reported. In past few decades, groundwater in Jhajjar district is continuously degraded by fluoride, sulphate, chloride, salinity, etc. problems. So, the present study aims to assess the groundwater quality of the alluvial aquifer of Jhajjar district using integrated approach. Hydrochemistry in integration with stable isotopes (δ18O and δD), GIS and multivariate statistical analysis has been to decipher the sub-surface geochemical processes taking place. Twenty-one groundwater samples were collected and a total 14 hydro-chemical parameter and water stable isotopes (δ18O and δD) has been analyzed. Hierarchical clustering of hydro-chemical and isotopic data classified the water in three groups, varying from fresh to brackish/salt waters. Sampling location with higher salinity is showing enriched fluoride signature. Depletion in water level, insufficient flushing with freshwater is affecting fresh-saline water interface which favors the dissolution and mobilization of salts from the unsaturated zone as well as pollution in aquifer. Understanding the recharge processes and the groundwater dynamics is critical to assess the vulnerability and protection of groundwater resources.
Theta Burst Stimulation in Adults with Symmetric and Asymmetric Visual Acuity
Authors: Tuna Ana Rita , Lc Nuno Pinto , Fernandes Andresa , Brardo Francisco Miguel , Pato Maria Vaz 
Published: July 2021

Abstract
Purpose: Theta Burst Stimulation can influence adult neuro-visual response in imbalanced visual pathways, possibly by influencing cortical excitability. Our objective was to compare suppressive imbalance (SI) and visual acuity (VA) after applying repetitive Transcranial Magnetic Stimulation (TMS) between groups of subjects with normal binocular vision, visual asymmetry and amblyopia. Methods: Thirty – five volunteers between 19 and 51 years of age, were split into three groups: 6 volunteers with asymmetric VA (group A); 19 amblyopes (group B); and 10 subjects with normal binocular vision (group C). VA and SI of all groups were evaluated before and after a single session of continuous theta-burst stimulation (cTBS) or placebo stimulation over the right occipital cortex. Results: In both groups A and B we found a significant VA improvement in the non-dominant eye after cTBS (p=0.04 and p=0.01, respectively). In SI evaluation, group A and group B also revealed a significant improvement after the cTBS session (p=0.03 and p=0.01, respectively).Finally, in the group of volunteers with normal binocular vision and for placebo groups A and B, there were no significant differences in VA and SI after cTBS. Conclusions: Amblyopic and visually asymmetric individuals improved VA and SI of the non-dominant eye after cTBS when compared to baseline and to placebo stimulation. These enhancements were not found in the group of volunteers with normal binocular vision. We can therefore reasonably assume that cTBS may interfere with the visual system of subjects that present some kind of asymmetry, possibly by improving neuronal imbalances.
Contamination Level, Source Identification And Health Risk Assessment of Potentially Toxic Elements In Drinking Water Sources of Mining And Non-Mining Areas of Khyber Pakhtunkhwa, Pakistan
Authors: Bhatti Zahid , Ishtiaq Muhammad , Khan Said , nawab javed , Khan Sardar , Baig Shams , Muhammad Ihsan , Din Zia , Khan Asad , Ghani Junaid 
Published: July 2021

Abstract
Accelerated mining activities have increased water contamination with potentially toxic elements (PTEs) and their associated human health risk in developing countries. The current study investigated the distribution of PTEs, their potential sources and health risk assessment in both ground and surface water sources in mining and non–mining areas of Khyber Pakhtunkhwa, Pakistan. Water samples (n=150) were taken from selected sites and were analyzed for six PTEs (Ni, Cr, Zn, Cu, Pb and Mn). Among PTEs, Cr showed high mean concentration (497) μg L–1, followed by Zn (414) μg L–1 in mining area, while Zn showed lowest mean value (4.44) μg L–1 in non-mining areas. Elevated concentrations of Ni, Cr and moderate level of Pb in ground and surface water of Mohmand District exceeded the permissible limits set by WHO (2017). Multivariate statistical analyses showed that pollution sources of PTEs were mainly from mafic-ultramafic rocks, acid mine drainage, open dumping of mine-wastes and mine tailings. The hazard quotient (HQ) was highest for children relatively to adults, but not higher than the US-EPA limits. The hazard index (HI) for ingestions of all selected PTEs were lower than the threshold value (HIing <1), except Mohmand District which showed (HI >1) in mining areas through ingestion. Moreover, the carcinogenic risk (CR) values exceeded the threshold limits for Ni and Cr set by the US-EPA (1.0E−04 to 1.0E−06). In order to protect the drinking water sources of the study areas from more contamination, the management techniques and policy for mining operations need to be implemented.
Potential Contribution of the Uterine Microbiome in Early Missed Abortion
Authors: shu junjun , Lin ShiXin , Wu Yu , Gong Dan , Zou Xia , Zhu Hong , Gao Jun 
Published: July 2021

Abstract
BackgroundMissed abortion is a kind of pregnancy failure caused by various reasons. The etiology is complicated, and the incidence of miscarriage is increasing in recent years. Previous studies shown microbiota contributes to multi-systemic function, whereas the relationship between microbiota and early missed abortion remains unknown. This study aimed to explore the composition of uterine microbiota in missed abortion and the potential role.MethodsWe enrolled 19 patients diagnosed with missed abortion and 12 healthy pregnant who subsequently had 6-8th week pregnant. All samples were taken from the endometrial fluid by a special disposable endometrial sampler. After samples were collected, DNA was extracted and amplified. The high-throughput next-generation sequencing (MiSeq) of the 16S rDNA V3-V4 region was used to identify the present of microbiota. The α-diversity of microbiota data was used to reflect species richness and evenness within bacterial populations, β-diversity was used to reflect the shared diversity between bacterial populations, and Nonmetric Multidimensional Scaling based on Weighted Unifrac distance. Statistical was determined by use of multiple testing, including the generalized mixed-effects model.ResultsThe microbiome sequencing (16S rDNA V3-V4 region) revealed that low abundance microbiome was detected in uterine cavity of patients with missed abortion and normal pregnancy. The diversity of intrauterine microflora in patients with missed abortion was higher than that in patients with induced abortion in normal pregnancy. There was no significant difference in alpha diversity between the two groups, but a significant difference was observed in beta diversity. PCoA moment array analysis did not show significant differences. Proteobacteria and Firmicutes in missed abortion patients were significantly more than those in normal pregnancy group.ConclusionThere are low abundance of microflora in uterine cavity of missed abortion patients, and the diversity of microflora is higher than that of normal pregnancy patients. Also, Proteobacteria and Firmicutes may be potential biological markers in missed abortion. New observations may prompt further investigations to understand the potential mechanism of microbiology on pathologic human pregnancy in the future.SubjectsMicrobiology, Molecular Biology, Gynecology and Obstetrics, missed abortion, Female Reproductive Tract,
Trend Analysis of Regulatory Approval Pathways and Major Shifts in Pivotal Clinical Trial Designs for Antineoplastic Drugs Approved by the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) From 2004 to 2019.
Authors: Hirai Takehiro , Suzuki Asuka , Yamori Takao , Matsuura Masaaki 
Published: July 2021

Abstract
BackgroundThe Japanese Pharmaceuticals and Medical Devices Agency (PMDA) was established in 2004. Since then, various pieces of legislation, notices, and guidelines have been issued, and the regulatory approval pathways for domestic drugs have been diversified. However, the effects of these measures have not been fully examined. We examined the impact of these measures on the approval of antineoplastic drugs and the design of pivotal clinical trials for efficacy assessment by the PMDA. MethodsWe collected data on the antineoplastic drugs approved by the PMDA in fiscal years 2004–2019. We extracted the approval review pathways and the pivotal clinical trial designs from the PMDA review reports, and analyzed them to identify patterns. ResultsIn total, 387 indications in oncology were approved by the PMDA in fiscal years 2004–2019, or 365 indications excluding multiple regulatory pathways. The number of approved indications generally increased year on year (p < 0.001). The largest number of approved indications was under the Orphan Drug Designation (31%, 114/365) and this continues to increase (p < 0.001). In the 288 indications for which clinical trial data were submitted for review, the pivotal clinical trial designs changed significantly (p < 0.001) after the guideline on clinical evaluation for antineoplastic drugs was revised in 2006. ConclusionThe number of indications in oncology approved by the PMDA has been increasing over the past 16 years, alongside changes in regulatory pathways. The 2006 guideline on clinical evaluation had a particular impact on pivotal clinical trial designs.
A scenario analysis of Chinese Carbon Neutral based on STIRPAT &amp; System Dynamic model
Authors: Wen Lei , Zhang Jie , Li Zhao 
Published: July 2021

Abstract
With the statement of Chinese government on energy saving in 2020 at the United Nations General Assembly, carbon neutral was widely spread as a new concept. As a big country, China has the responsibility and obligation to make its own contribution to global climate change. This paper aims to explore and find effective ways for China to achieve carbon neutrality by 2060. We identify the main factors affecting carbon emissions by STIRPAT model, combined with the scenarios analysis we divide the year 2020 to 2060 into three stages： year 2020-2030 is Carbon Peak stage, year 2030-2050 is Rapid Emission Reduction stage, year 2050-2060 is Complete Carbon Neutralization stage. At each stage, three development models, high, medium and low level, were established. A total of 27 different scenarios in three stages. A system dynamics model was established to simulate the effects of carbon emission factors and changes in carbon sinks in different scenarios. Finally, 8 paths were found which in line with Chinese current goal of achieving carbon neutrality with treating reach Carbon peak in 2030 as an additional filter condition. Comparing per capita GDP levels in different scenarios, we eventually find that keep economic development at a low level in the first stage, a high level in the second stage and a medium level in the finally stage, the point where net carbon emissions are less than zero for the first time will appear between year 2056-2057.By then, the per capita GDP will reach 144,500 yuan (based on year 2000), nearly four times 2000’s. In all, these findings are helpful for policymakers to implement reasonable policies to achieve carbon emission peaking & carbon neutral in China.
Planar photonic chips with tailored angular transmission for high-contrast-imaging devices
Authors: Kuai Yan , Chen Junxue , Zou Gang , Lakowicz Joseph , Zhang Douguo 
Published: July 2021

Abstract
A limitation of standard brightfield microscopy is its low contrast images, especially for thin specimens of weak absorption, and biological species with refractive indices very close in value to that of their surroundings. Here, we demonstrate, using a planar photonic chip with tailored angular transmission as the sample substrate, a standard brightfield microscopy can provide both darkfield and total internal reflection (TIR) microscopy images with one experimental configuration. The image contrast is enhanced without altering the specimens and the microscope configurations. This planar chip consists of several multilayer sections with designed photonic band gaps and a central region with dielectric nanoparticles, which does not require top-down nanofabrication and can be fabricated in a large scale. The photonic chip eliminates the need for a bulky condenser or special objective to realize darkfield or TIR illumination. Thus, it can work as a miniaturized high-contrast-imaging device for the developments of versatile and compact microscopes.